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X-Ray Fused With Magnetic Resonance Imaging (XFM) to Target Endomyocardial Injections Validation in a Swine Model of Myocardial Infarction
Abstract
Magnetic resonance imaging (MRI) permits 3-dimensional (3D) cardiac imaging with high soft tissue contrast. X-ray fluoroscopy provides high-resolution, 2-dimensional (2D) projection imaging. We have developed real-time x-ray fused with MRI (XFM) to guide invasive procedures that combines the best features of both imaging modalities. We tested the accuracy of XFM using external fiducial markers to guide endomyocardial cell injections in infarcted swine hearts.
Endomyocardial injections of iron-labeled mesenchymal stromal cells admixed with tissue dye were performed in previously infarcted hearts of 12 Yucatan miniswine (weight, 33 to 67 kg). Features from cardiac MRI were displayed combined with x-ray in real time to guide injections. During 130 injections, operators were provided with 3D surfaces of endocardium, epicardium, myocardial wall thickness (range, 2.6 to 17.7 mm), and infarct registered with live x-ray images to facilitate device navigation and choice of injection location. XFM-guided injections were compared with postinjection MRI and with necropsy specimens obtained 24 hours later. Visual inspection of the pattern of dye staining on 2,3,5-triphenyltetrazolium chloride-stained heart slices agreed (kappa=0.69) with XFM-derived injection locations mapped onto delayed hyperenhancement MRI and the susceptibility artifacts seen on the postinjection T2*-weighted gradient echo MRI. The distance between the predicted and actual injection locations in vivo was 3.2+/-2.6 mm (n=64), and 75% of injections were within 4.1 mm of the predicted location.
Three-dimensional to two-dimensional registration of x-ray and MR images with the use of external fiducial markers accurately targets endomyocardial injection in a swine model of myocardial infarction.
... Since from the current perspective, X-ray imaging (XR) will remain limited in providing volumetric soft-tissue or functional information, complementary modalities like Echocardiography (U/S), computed tomography (CT) or magnetic resonance imaging (MRI) will likely be utilized to facilitate improved interventional guidance. The fusion of CT [3,4] and MRI5678 data with XR has been introduced successfully to facilitate intracardiac procedures [4,5,8] . Registration of the involved modalities is performed by fidicual or anatomic landmarks visible in both modalities [3,7], by manually aligning the MRI-derived 3D model with the fluoroscopy data [5], or by optical tracking [6] with accuracies in the 1–5 mm range [3,567. ...
... Since from the current perspective, X-ray imaging (XR) will remain limited in providing volumetric soft-tissue or functional information, complementary modalities like Echocardiography (U/S), computed tomography (CT) or magnetic resonance imaging (MRI) will likely be utilized to facilitate improved interventional guidance. The fusion of CT [3,4] and MRI5678 data with XR has been introduced successfully to facilitate intracardiac procedures [4,5,8] . Registration of the involved modalities is performed by fidicual or anatomic landmarks visible in both modalities [3,7], by manually aligning the MRI-derived 3D model with the fluoroscopy data [5], or by optical tracking [6] with accuracies in the 1–5 mm range [3,567. ...
... Compensation of respiration-induced motion components, however, need more deliberate techniques such as following a reference marker attached to the heart such as reference catheters introduced into the coronary sinus or means to follow the diaphragm over time as possible with a simple A-line U/S device [28] or directly from the XR image [29]. However, even without motion compensation, the fusion of pre-interventional data and XR fluoroscopy showed promising results [4,5,8]. In conclusion, it is demonstrated that the fusion of preinterventional U/S-derived data with interventional XR images is feasible at an overall accuracy better than 2 mm. ...
Objective
Cardiovascular intervention guidance requires knowledge of heart function relative to its blood supply or venous drainage. Functional and vascular anatomic data are usually generated on different imaging systems, so fusion of the data is necessary to simultaneously visualize the results for intervention planning and guidance. The objective of this work is to establish the feasibility of fusing volumetric ultrasound (U/S) data with three-dimensional (3D) X-ray imaging data for visualization of cardiac morphology, function and coronary venous drainage.
Methods
Temporally resolved U/S volume data was registered with the 3D reconstruction of vascular structures derived from X-ray modeling and reconstruction. U/S image registration was obtained by optical tracking fiducial markers with simultaneous X-ray imaging. The proposed technique was applied to phantom data for accuracy assessment of the registration process and to biventricular pacemaker implantation as clinical example.
Results
Fusion of U/S data with 3D X-ray reconstruction data produced an RMS registration error below 2 mm.
Conclusion
Preliminary clinical feasibility of U/S-derived data synchronously with X-ray derived 3D coronary venography was established. This technique can be applied for fusion of functional U/S data with 3D anatomic X-ray data of the coronary veins during a biventricular pacemaker implantation procedures.
... In this paper, we are concerned with a technique known as X-ray fused with MRI ͑XFM͒, [9][10][11][12][13][14][15] also known as XMR, in which live X-ray fluoroscopy ͑XF͒ projection images are displayed along with a previously gathered roadmap 3D MR image. In this paper, we present a novel, fully automatic method to register the two modalities. ...
... While previous publications 9,12,13,21 have presented the XFM system as applied to endomyocardial injections, 9 mitral cerclage annuloplasty, 21 and the closure of ventricular septal defects 13 ͑VSDs͒ in a swine model, none have presented the computational method that achieves the automatic registration. In early works, 9,21 the procedure was minimally automated and required extensive, time-consuming, interaction by a skilled human operator to localize the MR and X-ray markers by manual examination of the data. ...
... While previous publications 9,12,13,21 have presented the XFM system as applied to endomyocardial injections, 9 mitral cerclage annuloplasty, 21 and the closure of ventricular septal defects 13 ͑VSDs͒ in a swine model, none have presented the computational method that achieves the automatic registration. In early works, 9,21 the procedure was minimally automated and required extensive, time-consuming, interaction by a skilled human operator to localize the MR and X-ray markers by manual examination of the data. A more recent work 13 used a promising predecessor 22,23 of the method that we present in this paper. ...
In X-ray fused with MRI, previously gathered roadmap MRI volume images are overlaid on live X-ray fluoroscopy images to help guide the clinician during an interventional procedure. The incorporation of MRI data allows for the visualization of soft tissue that is poorly visualized under X-ray. The widespread clinical use of this technique will require fully automating as many components as possible. While previous use of this method has required time-consuming manual intervention to register the two modalities, in this article, the authors present a fully automatic rigid-body registration method.
External fiducial markers that are visible under these two complimentary imaging modalities were used to register the X-ray images with the roadmap MR images. The method has three components: (a) The identification of the 3D locations of the markers from a full 3D MR volume, (b) the identification of the 3D locations of the markers from a small number of 2D X-ray fluoroscopy images, and (c) finding the rigid-body transformation that registers the two point sets in the two modalities. For part (a), the localization of the markers from MR data, the MR volume image was thresholded, connected voxels were segmented and labeled, and the centroids of the connected components were computed. For part (b), the X-ray projection images, produced by an image intensifier, were first corrected for distortions. Binary mask images of the markers were created from the distortion-corrected X-ray projection images by applying edge detection, pattern recognition, and image morphological operations. The markers were localized in the X-ray frame using an iterative backprojection-based method which segments voxels in the volume of interest, discards false positives based on the previously computed edge-detected projections, and calculates the locations of the true markers as the centroids of the clusters of voxels that remain. For part (c), a variant of the iterative closest point method was used to find correspondences between and register the two sets of points computed from MR and X-ray data. This knowledge of the correspondence between the two point sets was used to refine, first, the X-ray marker localization and then the total rigid-body registration between modalities. The rigid-body registration was used to overlay the roadmap MR image onto the X-ray fluoroscopy projections.
In 35 separate experiments, the markers were correctly registered to each other in 100% of the cases. When half the number of X-ray projections was used (10 X-ray projections instead of 20), the markers were correctly registered in all 35 experiments. The method was also successful in all 35 experiments when the number of markers was (retrospectively) halved (from 16 to 8). The target registration error was computed in a phantom experiment to be less than 2.4 mm. In two in vivo experiments, targets (interventional devices with pointlike metallic structures) inside the heart were successfully registered between the two modalities.
The method presented can be used to automatically register a roadmap MR image to X-ray fluoroscopy using fiducial markers and as few as ten X-ray projections.
... For instance, the tissue presented in Echo is inherently characterized by a specific spatial distribution of speckles rather than a specific distribution of gray scales that exist in MRI and CT (Sandoval and Dillenseger, 2013). Gilardi et al. (1998) PET, SPECT Myo Surface-based rigid reg ASD Savi et al. (1995) Echo, PET Myo Landmark-based rigid reg MSD Mäkelä et al. (2003) MRI, PET, Echo LV, RV, Myo Landmark and seg-based reg Region energy De Silva et al. (2006) MRI, X-ray LV, RV, Myo Landmark-based rigid reg MSD Baka et al. (2013) CT, X-ray CA Landmark-based rigid reg 2D-3D distance Aksoy et al. (2013) CT, X-ray CA Landmark-based rigid reg 2D-3D distance Döring et al. (2013) Echo, CSA Myo Landmark-based reg N/A Smith et al. (2014) PET, SPECT Myo Landmark-based reg N/A Tayebi et al. (2015) CT, X-rayAI CA Landmark-based affine reg RMSE Faber et al. (1991) MRI, SPECT LV Point set based rigid reg MD Sinha et al. (1995) MRI, PET Myo Point set based rigid reg MSD Santarelli et al. (2001) MRI, SPECT Myo Point set based non-rigid reg MSD Sturm et al. (2003) MRI ...
Multi-modality cardiac imaging plays a key role in the management of patients with cardiovascular diseases. It allows a combination of complementary anatomical, morphological and functional information, increases diagnosis accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. Fully-automated processing and quantitative analysis of multi-modality cardiac images could have a direct impact on clinical research and evidence-based patient management. However, these require overcoming significant challenges including inter-modality misalignment and finding optimal methods to integrate information from different modalities. This paper aims to provide a comprehensive review of multi-modality imaging in cardiology, the computing methods, the validation strategies, the related clinical workflows and future perspectives. For the computing methodologies, we have a favored focus on the three tasks, i.e., registration, fusion and segmentation, which generally involve multi-modality imaging data, either combining information from different modalities or transferring information across modalities. The review highlights that multi-modality cardiac imaging data has the potential of wide applicability in the clinic, such as trans-aortic valve implantation guidance, myocardial viability assessment, and catheter ablation therapy and its patient selection. Nevertheless, many challenges remain unsolved, such as missing modality, modality selection, combination of imaging and non-imaging data, and uniform analysis and representation of different modalities. There is also work to do in defining how the well-developed techniques fit in clinical workflows and how much additional and relevant information they introduce. These problems are likely to continue to be an active field of research and the questions to be answered in the future.
... Modality Target MRI, X-ray LV normalized gradient field based rigid reg NCC Kolbitsch et al. (2017) MRI, PET Myo motion field based affine reg + FFD NCC Gouveia et al. (2017) CT, X-ray CA regression based rigid reg N/A Atehortúa et al. (2020) MRI, Echo Myo salient image based Eulerian and nonrigid reg NCC Savi et al. (1995) Echo, PET Myo landmark-based rigid reg MSD Mäkelä et al. (2003) MRI, PET, Echo LV, RV, Myo landmark and seg based reg region energy Walimbe et al. (2003) Echo, SPECT Myo landmark-based 2D-3D reg MI De Silva et al. (2006) MRI, X-ray LV, RV, Myo landmark-based rigid reg MSD Baka et al. (2013) CT, X-ray CA landmark-based rigid reg 2D-3D distance Aksoy et al. (2013) CT, X-ray CA landmark-based rigid reg 2D-3D distance Döring et al. (2013) Echo, CSA Myo landmark-based reg N/A Smith et al. (2014) PET, SPECT Myo landmark-based reg N/A Tayebi et al. (2015) CT, X-rayAI CA landmark-based affine reg RMS Khalil et al. (2017c) CT, Echo LA landmark-based rigid reg NMI Faber et al. (1991) MRI, SPECT LV point set based rigid reg MD Sinha et al. (1995) MRI Modality-invariant anatomical landmarks, surfaces (contours or point clouds) or labels can also be used to define the transformation from one image to the other due to their inherent correspondences with original images. For example, Savi et al. (1995); Döring et al. (2013); Smith et al. (2014) employed the landmarks being identified in multi-modality images for registration. ...
Multi-modality cardiac imaging plays a key role in the management of patients with cardiovascular diseases. It allows a combination of complementary anatomical, morphological and functional information, increases diagnosis accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. Fully-automated processing and quantitative analysis of multi-modality cardiac images could have a direct impact on clinical research and evidence-based patient management. However, these require overcoming significant challenges including inter-modality misalignment and finding optimal methods to integrate information from different modalities. This paper aims to provide a comprehensive review of multi-modality imaging in cardiology, the computing methods, the validation strategies, the related clinical workflows and future perspectives. For the computing methodologies, we have a favored focus on the three tasks, i.e., registration, fusion and segmentation, which generally involve multi-modality imaging data, \textit{either combining information from different modalities or transferring information across modalities}. The review highlights that multi-modality cardiac imaging data has the potential of wide applicability in the clinic, such as trans-aortic valve implantation guidance, myocardial viability assessment, and catheter ablation therapy and its patient selection. Nevertheless, many challenges remain unsolved, such as missing modality, combination of imaging and non-imaging data, and uniform analysis and representation of different modalities. There is also work to do in defining how the well-developed techniques fit in clinical workflows and how much additional and relevant information they introduce. These problems are likely to continue to be an active field of research and the questions to be answered in the future.
... Although it was first reported over a decade ago, only recently has FI started to play an increasing role in 3D guidance of cardiac catheterizations [54][55][56][57]. It has been mostly, but not exclusively, reported in those clinical situations where pre-intervention CT/MRI is commonly performed e.g. ...
Pediatric cardiology is eminently dependent on imaging for the accurate diagnosis and treatment of congenital and structural heart disease. The understanding of the three-dimensionality of the normal and pathological inner structures of the heart, their dynamic spatial inter-relationships and the influences on flow are critical to planning and performing interventions. Advances in computer technology have made three-dimensional reconstructions readily available and the quality of these reconstructions has improved to such an extent that they can be used both pre-procedurally and intra-procedurally to plan and guide interventions. However, the three-dimensional data is generally displayed within a two-dimensional screen, which restricts the image to a single plane of view, precludes interaction directly with the image and hampers the perception of depth. The experience of true depth perception in a three-dimensional medical image, free from the confines of a two-dimensional display, is a refreshingly new experience that for the first time allows the operator to intuitively comprehend and interact with the patient-specific anatomy.
... 17,95 Novel catheters and guidewires have made possible targeted intramyocardial injection of progenitor stem cells in myocardial infarction in animal models. 109,[157][158][159] Using real-time CMR and direct apical access in porcine hearts, prosthetic aortic valves were implanted in the beating heart. 160 This breakthrough application may allow CMR guidance of minimally invasive extra-anatomic bypass and beating-heart valve repair. ...
Diagnostic and interventional cardiac catheterization is routinely used in the diagnosis and treatment of congenital heart disease. There are well-established concerns regarding the risk of radiation exposure to patients and staff, particularly in children given the cumulative effects of repeat exposure. Magnetic resonance imaging (MRI) offers the advantage of being able to provide better soft tissue visualization, tissue characterization, and quantification of ventricular volumes and vascular flow. Initial work using MRI catheterization employed fusion of x-ray and MRI techniques, with x-ray fluoroscopy to guide catheter placement and subsequent MRI assessment for anatomical and hemodynamic assessment. Image overlay of 3D previously acquired MRI datasets with live fluoroscopic imaging has also been used to guide catheter procedures.Hybrid x-ray and MRI-guided catheterization paved the way for clinical application and validation of this technique in the assessment of pulmonary vascular resistance and pharmacological stress studies. Purely MRI-guided catheterization also proved possible with passive catheter tracking. First-in-man MRI-guided cardiac catheter interventions were possible due to the development of MRI-compatible guidewires, but halted due to guidewire limitations.More recent developments in passive and active catheter tracking have led to improved visualization of catheters for MRI-guided catheterization. Improvements in hardware and software have also increased image quality and scanning times with better interactive tools for the operator in the MRI catheter suite to navigate through the anatomy as required in real time. This has expanded to MRI-guided electrophysiology studies and radiofrequency ablation in humans. Animal studies show promise for the utility of MRI-guided interventional catheterization. Ongoing investment and development of MRI-compatible guidewires will pave the way for MRI-guided diagnostic and interventional catheterization coming into the mainstream.
... Experts can combine anatomical knowledge with extensive experience of interpreting X-ray images and projective geometry, this is, however, time-consuming, has a learning curve, and is highly userdependent. Manual registration can be simplified by using fiducial markers [4,13]. Fiducials can also be used in optical tracking-based registration [14,15], but these approaches require the preoperative scan to be acquired directly before the intervention and changes to the clinical workflow need to be introduced, which are often not feasible. ...
Purpose:
In cardiac interventions, such as cardiac resynchronization therapy (CRT), image guidance can be enhanced by involving preoperative models. Multimodality 3D/2D registration for image guidance, however, remains a significant research challenge for fundamentally different image data, i.e., MR to X-ray. Registration methods must account for differences in intensity, contrast levels, resolution, dimensionality, field of view. Furthermore, same anatomical structures may not be visible in both modalities. Current approaches have focused on developing modality-specific solutions for individual clinical use cases, by introducing constraints, or identifying cross-modality information manually. Machine learning approaches have the potential to create more general registration platforms. However, training image to image methods would require large multimodal datasets and ground truth for each target application.
Methods:
This paper proposes a model-to-image registration approach instead, because it is common in image-guided interventions to create anatomical models for diagnosis, planning or guidance prior to procedures. An imitation learning-based method, trained on 702 datasets, is used to register preoperative models to intraoperative X-ray images.
Results:
Accuracy is demonstrated on cardiac models and artificial X-rays generated from CTs. The registration error was [Formula: see text] on 1000 test cases, superior to that of manual ([Formula: see text]) and gradient-based ([Formula: see text]) registration. High robustness is shown in 19 clinical CRT cases.
Conclusion:
Besides the proposed methods feasibility in a clinical environment, evaluation has shown good accuracy and high robustness indicating that it could be applied in image-guided interventions.
... The process 30 is time consuming and highly user dependent. Fiducial markers which are visible in both modalities can be placed on the patient for matching [3], or on the components of the imaging system for tracking [4]. This solves the registration problem, but introduces workflow challenges and requires the MRI to be acquired directly before the procedure which is not feasible for most hospitals. ...
A key component of image guided interventions is the registration of pre-operative and intra-operative images. Classical registration approaches rely on cross-modality information; however, in modalities such as MRI and X-ray there may not be sufficient cross-modality information. This paper proposes a fundamentally different registration approach which uses adjacent anatomical structures with superabundant vessel reconstruction and dynamic outlier rejection. In the targeted clinical scenario of cardiac resynchronization therapy (CRT) delivery, preoperative, non contrast-enhanced, MRI is registered to intraoperative, contrasted X-ray fluoroscopy. The adjacent anatomical structures are the left ventricle (LV) from MRI and the coronary veins reconstructed from two contrast-enhanced X-ray images. The novel concept of superabundant vessel reconstruction is introduced to bypass the standard reconstruction problem of establishing one-to-one correspondences. Furthermore, a new dynamic outlier rejection method is proposed, to enable globally optimal point set registration. The proposed approach has been qualitatively and quantitatively evaluated on phantom, clinical CT angiography with ground truth and clinical CRT data. A novel evaluation method is proposed for clinical CRT data based on previously implanted artificial aortic and mitral valves. The registration accuracy in 3D was 2.94 mm for the aortic and 3.86 mm for the mitral valve. The results are below the required accuracy identified by clinical partners to be the half-segment size (16.35 mm) of a standard American Heart Association (AHA) 16 segment model of the LV.
... Originally, the meshes and the motion model are given in MR coordinates. Both coordinate systems are registered manually based on multi-modal skin markers, which have been shown to yield accurate registration [7], [40]. ...
In X-ray fluoroscopy, static overlays are used to visualize soft tissue. We propose a system for cardiac and respiratory motion compensation of these overlays. It consists of a 3-D motion model created from real-time MR imaging. Multiple sagittal slices are acquired and retrospectively stacked to consistent 3-D volumes. Slice stacking considers cardiac information derived from the ECG and respiratory information extracted from the images. Additionally, temporal smoothness of the stacking is enhanced. Motion is estimated from the MR volumes using deformable 3-D/3-D registration. The motion model itself is a linear direct correspondence model using the same surrogate signals as slice stacking. In X-ray fluoroscopy, only the surrogate signals need to be extracted to apply the motion model and animate the overlay in real time. For evaluation, points are manually annotated in oblique MR slices and in contrast-enhanced X-ray images. The 2-D Euclidean distance of these points is reduced from 3:85 mm to 2:75 mm in MR and from 3:0 mm to 1:8 mm in X-ray compared to the static baseline. Furthermore, the motion-compensated overlays are shown qualitatively as images and videos.
... The Helix and Stilletto have been tested in multiple large animal studies. Both types of catheters are guided by three-dimensional MRI coregistered onto X-ray fluoroscopy [72][73][74] (Fig. 3.4). The Helix has been used for three-dimensional ultrasound-guided injections [75], and the Stilletto has been modified for real-time MRI-guided injections [76]. ...
Cell delivery and retention properties are inextricably linked to the therapeutic capabilities of mesenchymal stromal cells (MSCs). An assortment of noninvasive, minimally invasive, and invasive delivery approaches are being explored, particularly for heart disease treatment. Cellular imaging labels may be used to track cells in the short and medium terms. Regulatory officials typically review how cells are administered and their fate. This chapter reviews common delivery and tracking approaches as it pertains to cell-based therapy.
... 5 In 2006, our team applied XFM to guide preclinical transcatheter interventions, including direct antegrade crossing and delivery of a ventricular septal defect closure device, 6 and to guide endomyocardial injections. 7 In 2015, Grant et al reported the use of XFM guidance for closure of a leftventricle-to-right-atrium shunt. 8 The mature XFM system has since been used in clinical procedures, including bypass graft angiography, right ventricular free-wall mass biopsy, and iliac and femoral artery recanalization and stenting. ...
Background:
A patient with a history of cancer in remission and congestive heart failure with no acute symptoms presented for a follow-up echocardiogram. The scan revealed a new echodense mass filling his right ventricular apex. An endomyocardial biopsy guided by x-ray fused with magnetic resonance (MR) imaging (XFM) was performed. This case report outlines the steps of XFM image preparation involving MR image acquisition, processing, and coregistration with x-ray fluoroscopy.
Discussion:
In cases of focal pathology or cardiac masses, endomyocardial biopsy can be challenging because x-ray fluoroscopy guidance offers limited visualization of soft-tissue structures. XFM overcomes this issue by overlaying high-resolution MR images onto x-ray fluoroscopy images.
Conclusion:
This case report illustrates the clinical use of XFM for endomyocardial biopsy of an apical right ventricular mass and provides a practical, step-by-step description of MR image acquisition, processing, and coregistration with fluoroscopy, as performed by the MR technologist.
... X-ray combined with magnetic resonance imaging is referred to as co-registration or XFM and uses MR images to enhance X-ray fluoroscopic procedures. This multimodality approach has been used in various X-ray procedures such as biopsy of the myocardial free wall [51] or repair of membranous ventricular septal defects with significantly decreased examination time and radiation exposure in animal studies [52,53]. Finally, in clinical EP studies, CMR roadmaps have been already combined with electroanatomic mapping [44]. ...
Cardiovascular magnetic resonance ( CMR ) has the inherent capability to perform tissue characterization, assessment of disease severity, myocardial inflammation, ventricular function, perfusion and fibrosis without radiation exposure. All these advantages of CMR can be perfectly well applied in interventional cardiovascular magnetic resonance ( iCMR ) providing high‐quality images during interventional procedures. CMR , as an innovating imaging technique, can (1) provide reliable information about the pattern of myocardial perfusion‐fibrosis in both ischemic and non‐ischemic heart disease and (2) guide the traditional interventional procedures. iCMR , by using excellent tissue imaging, can create a surrogate for direct visualization and offer multiplanar views and real‐time functional imaging without ionizing radiation. These images can facilitate the utilization of interventional procedures and promote the innovation of new interventional approaches.
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... As an interim step to performing cardiovascular interventions from start to finish in the MRI scanner, pre-acquired MR images can be "fused" with X-ray fluoroscopy. External fiduciary markers [1] or internal anatomic structures [2] are used to co-register MR overlays of chosen 3D structures onto the fluoroscopic images. In the field of electrophysiology, co-registration of CT or MRI images with electroanatomic maps to improve catheter navigation in three dimensions has been applied for many years. ...
Interventional cardiovascular magnetic resonance (iCMR) promises to enable radiation-free catheterization procedures and to enhance contemporary image guidance for structural heart and electrophysiological interventions. However, clinical translation of exciting pre-clinical interventions has been limited by availability of devices that are safe to use in the magnetic resonance (MR) environment. We discuss challenges and solutions for clinical translation, including MR-conditional and MR-safe device design, and how to configure an interventional suite. We review the recent advances that have already enabled diagnostic MR right heart catheterization and simple electrophysiologic ablation to be performed in humans and explore future clinical applications.
... Ionization can also be performed using a focused beam of protons in a technique called particle induced X-ray emission (PIXE). All of these techniques are performed in high-vacuum environments, so steps such as cryopreservation or careful drying must be taken to protect biological samples or specimen degassing that can reduce the performance of the instrument (de Silva et al., 2006;George et al., 2011;Ramsay et al., 2011;Weekley et al., 2013). ...
Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. AD represents a complex neurological disorder which is best understood as the consequence of a number of interconnected genetic and lifestyle variables, which culminate in multiple changes to brain structure and function. At a molecular level, metal dyshomeostasis is frequently observed in AD due to anomalous binding of metals such as Iron (Fe), Copper (Cu) and Zinc (Zn), or impaired regulation of redox-active metals which can induce the formation of cytotoxic reactive oxygen species and neuronal damage. Neuroimaging of metals in a variety of intact brain cells and tissues is emerging as an important tool for increasing our understanding of the role of metal dysregulation in AD. Several imaging techniques have been used to study the cerebral metallo-architecture in biological specimens to obtain spatially resolved data on chemical elements present in a sample. Hyperspectral techniques, such as particle-induced X-ray emission (PIXE), energy dispersive X-ray spectroscopy (EDS), X-ray fluorescence microscopy (XFM), synchrotron X-ray fluorescence (SXRF), secondary ion mass spectrometry (SIMS), and laser ablation inductively coupled mass spectrometry (LA-ICPMS) can reveal relative intensities and even semi-quantitative concentrations of a large set of elements with differing spatial resolution and detection sensitivities. Other mass spectrometric and spectroscopy imaging techniques such as laser ablation electrospray ionisation mass spectrometry (LA ESI-MS), MALDI imaging mass spectrometry (MALDI-IMS), and Fourier transform infrared spectroscopy (FTIR) can be used to correlate changes in elemental distribution with the underlying pathology in AD brain specimens. The current review aims to discuss the advantages and challenges of using these emerging elemental and molecular imaging techniques, and highlight clinical achievements in AD research using bioimaging techniques.
... 9,10 The possibility of integrating pre-procedural MRI images with live X-ray fluoroscopy circumvents these limitations. 11 Alternatively, the location and extent of the infarct region could be derived from computed tomography (CT) or 18 F-FDG positron emission tomography (PET) in MRI-incompatible patients. ...
Biological therapies for ischaemic heart disease require efficient, safe, and affordable intramyocardial delivery. Integration of multiple imaging modalities within the fluoroscopy framework can provide valuable information to guide these procedures. We compared an anatomo-electric method (LARCA) with a non-fluoroscopic electromechanical mapping system (NOGA(®)). LARCA integrates selective three-dimensional-rotational angiograms with biplane fluoroscopy. To identify the infarct region, we studied LARCA-fusion with pre-procedural magnetic resonance imaging (MRI), dedicated CT, or (18)F-FDG-PET/CT.
We induced myocardial infarction in 20 pigs by 90-min LAD occlusion. Six weeks later, we compared peri-infarct delivery accuracy of coloured fluospheres using sequential NOGA(®)- and LARCA-MRI-guided vs. LARCA-CT- and LARCA-(18)F-FDG-PET/CT-guided intramyocardial injections. MRI after 6 weeks revealed significant left ventricular (LV) functional impairment and remodelling (LVEF 31 ± 3%, LVEDV 178 ± 15 mL, infarct size 17 ± 2% LV mass). During NOGA(®)-procedures, three of five animals required DC-shock for major ventricular arrhythmias vs. one of ten during LARCA-procedures. Online procedure time was shorter for LARCA than NOGA(®) (77 ± 6 vs. 130 ± 3 min, P < 0.0001). Absolute distance of injection spots to the infarct border was similar for LARCA-MRI (4.8 ± 0.5 mm) and NOGA(®) (5.4 ± 0.5 mm). LARCA-CT-integration allowed closer approximation of the targeted border zone than LARCA-PET (4.0 ± 0.5 mm vs. 6.2 ± 0.6 mm, P < 0.05).
Three-dimensional -rotational angiography fused with multimodal imaging offers a new, cost-effective, and safe strategy to guide intramyocardial injections. Endoventricular procedure times and arrhythmias compare favourably to NOGA(®), without compromising injection accuracy. LARCA-based fusion imaging is a promising enabling technology for cardiac biological therapies.
... The field of image-guided interventions is still evolving as techniques in medical imaging and computing power continue to improve. For example, a growing potential application for image-guided intervention in the heart is stem cell implantation therapy [141], [153], [160]. Trans-catheter endomyocardial injection may be an important route for delivery of emerging biological therapies to treat myocardium supplied by an occluded epicardial coronary artery. ...
Minimally invasive and less invasive procedure is becoming more and more common in medical therapy. Image guidance is an indispensable component in minimally invasive procedures by providing critical information about the position of the target sites and the optimal manipulation of the devices, while the field of view is limited to naked eyes due to the small incision. Registration is one of the enabling technologies for computer-aided image guidance, which brings high-resolution pre-operative data into the operating room to provide more realistic information about the patient's anatomy. In this paper, we survey the recent advances in registration techniques applied to minimally and/or less invasive therapy, including a wide variety of therapies in surgery, endoscopy, interventional cardiology, interventional radiology, and hybrid procedures. The registration approaches are categorized into several groups, including projection-to-volume, slice-to-volume, video-to-volume, and volume-to-volume registration. The focus is on recent advances in registration techniques that are specifically developed for minimally and/or less invasive procedures in the following medical specialties: neuroradiology and neurosurgery, cardiac applications, and thoracic-abdominal interventions.
... Using myocardial borders derived from a navigator-and cardiac-gated whole heart CMR at 1.5T fused with real-time X-ray fluoroscopy, barium sulfate impregnated microcapsules were delivered to the pericardial space in swine on a clinical angiographic system (Figure 9) [173]. These studies build upon X-ray fused with MRI (XFM) techniques [174,175] developed in preclinical applications [176] for ultimate translation to pediatric and adult cardiac interventions [177,178]. ...
In the past ten years, the concept of injecting stem and progenitor cells to assist with rebuilding damaged blood vessels and myocardial tissue after injury in the heart and peripheral vasculature has moved from bench to bedside. Non-invasive imaging can not only provide a means to assess cardiac repair and, thereby, cellular therapy efficacy but also a means to confirm cell delivery and engraftment after administration. In this first of a two-part review, we will review the different types of cellular labeling techniques and the application of these techniques in cardiovascular magnetic resonance and ultrasound. In addition, we provide a synopsis of the cardiac cellular clinical trials that have been performed to-date.
... that would otherwise be poorly visible. Transcatheter endomyocardial injection delivers biological materials for therapeutic purposes [4]. There, exact device placement is important for high efficacy and minimal risk. ...
Rigid registration is a key requirement to overlay anatomical structures from pre-operative magnetic resonance (MR) images onto live X-ray fluoroscopic images. Clinical applications are for instance radio frequency catheter ablation and transcatheter endomyocardial injection. We present a method for fully automatic marker-based detection and registration. The algorithm locates the markers in the MR volumetric data set automatically by combining homomorphic unsharp masking, adaptive thresholding, region growing, and shape analysis. In the X-ray images, the markers are localized in several 2-D images and then their 3-D positions are reconstructed. The 2-D X-ray localization is performed using adaptive thresholding and template matching. The 3-D X-ray marker positions are established using back projection. Rigid registration between the two 3-D point sets is performed by an iterative closest point algorithm. The 3-D registration error using a flat panel detector X-ray system is on average 1.5 ± 1.8 mm. The novelty of our approach is the incorporation of bundle adjustment to reduce the 2-D overlay errors. Bundle adjustment reduces the 2-D X-ray marker localization error from 0.6 ± 0.8 mm to 0.4 ± 0.5 mm. The target registration error of our proposed method evaluated on eight datasets is on average 1.4±3.5 mm. These targets were not used during registration. Accordingly, anatomical structures from MR are positioned more accurately.
... Attempts have been made to overcome the limitations of X-ray imaging by integrating pre-procedural MR images. This technology is often referred to as XFM, and the first such system for endomyocardial injections was proposed in [33]. Point based registration was performed by using X-ray/MR visible markers ( " fiducials " ) placed on the chest. ...
... A solution to some of the disadvantages of MRI, such as lack of MR compatible devices, poor physiological monitoring and limited temporal resolution for real-time interventions, would be to combine MRI with x-ray interventional techniques for stem cell delivery (Figure 4). Fusion of myocardial anatomy and viability maps from MRI in a swine infarction model have been used to target injections to the infarct borders using an x-ray fused with a MR registration platform [97]. ...
Despite rapid translation of stem cell therapy into clinical practice, the treatment of cardiovascular disease using embryonic stem cells, adult stem and progenitor cells or induced pluripotent stem cells has not yielded satisfactory results to date. Noninvasive stem cell imaging techniques could provide greater insight into not only the therapeutic benefit, but also the fundamental mechanisms underlying stem cell fate, migration, survival and engraftment in vivo. This information could also assist in the appropriate choice of stem cell type(s), delivery routes and dosing regimes in clinical cardiovascular stem cell trials. Multiple imaging modalities, such as MRI, PET, SPECT and CT, have emerged, offering the ability to localize, monitor and track stem cells in vivo. This article discusses stem cell labeling approaches and highlights the latest cardiac stem cell imaging techniques that may help clinicians, research scientists or other healthcare professionals select the best cellular therapeutics for cardiovascular disease management.
... The rapid evolution of minimally invasive vascular and cardiac interventions is shaping the demand for high temporal and spatial resolution imaging that offers safety, accuracy, flexibility and functionality. Recent improvements in signal processing, tissue characterization and angiographic integration allowed MR-guidance in complex interventional procedures, which require optimal spatial resolution and orienta- tion [1, 2]. MR fluoroscopy offers rapid acquisition, reconstruction and display of 3D images. ...
Vascular and cardiac disease remains a leading cause of morbidity and mortality in developed and emerging countries. Vascular and cardiac interventions require extensive fluoroscopic guidance to navigate endovascular catheters. X-ray fluoroscopy is considered the current modality for real time imaging. It provides excellent spatial and temporal resolution, but is limited by exposure of patients and staff to ionizing radiation, poor soft tissue characterization and lack of quantitative physiologic information. MR fluoroscopy has been introduced with substantial progress during the last decade. Clinical and experimental studies performed under MR fluoroscopy have indicated the suitability of this modality for: delivery of ASD closure, aortic valves, and endovascular stents (aortic, carotid, iliac, renal arteries, inferior vena cava). It aids in performing ablation, creation of hepatic shunts and local delivery of therapies. Development of more MR compatible equipment and devices will widen the applications of MR-guided procedures. At post-intervention, MR imaging aids in assessing the efficacy of therapies, success of interventions. It also provides information on vascular flow and cardiac morphology, function, perfusion and viability. MR fluoroscopy has the potential to form the basis for minimally invasive image-guided surgeries that offer improved patient management and cost effectiveness.
... Although CMR requires a substantially longer image acquisition time than ACT, there is no ionizing radiation and the functional information obtained by CMR is available. Several investigators have described techniques for the registration of CMR images with biplane fluoroscopy to allow the use of this 3D dataset for roadmapping (46)(47)(48)(49). Much future work will be required to determine the optimal application of these new strategies in transcatheter evaluation and treatment of congenital heart disease. ...
This study sought to retrospectively evaluate our initial experience using angiographic computed tomography (ACT) in a pediatric cardiac catheterization laboratory.
ACT provides cross-sectional CT images from a rotational angiography run using a C-arm mounted flat-panel detector in the interventional suite. A 3-dimensional (3D) angiographic image can be created from the CT volume set and used in real time during the procedure. To our knowledge, its use has never previously been described for congenital heart disease.
3D reconstructions were created and we retrospectively reviewed cases during our first year of ACT use. Images obtained were independently evaluated to determine their diagnostic utility. Radiation dose reduction protocols were defined using phantom testing and radiation dose calculation.
ACT was used during 41 cardiac catheterizations in patients at a median age of 5.1 years (range: 0.4 to 58.8 years) for evaluation of: right ventricular outflow tract (RVOT)/central pulmonary arteries (PAs) in 20; cavopulmonary connection (CPC) in 11; pulmonary veins in 5; distal PAs in 4; and other locations in 5. Four subjects had 2 anatomic areas studied by ACT. The mean contrast volume for ACT was 1.2 ± 0.4 ml/kg. Diagnostic-quality imaging was obtained in 71% of cases: 13/20 RVOT/central PAs; 9/11 CPC; 4/5 pulmonary veins; 2/4 distal PAs; and 4/5 others. In 12 cases, ACT contributed to clinical outcomes beyond standard angiography. Radiation dose reduction protocols allowed ACT to be comparable in exposure to a standard biplane cineangiogram.
Diagnostic-quality imaging can be obtained using ACT in 71% of cases without a significant increase in contrast or radiation exposure. In certain cases, ACT provides additional anatomic detail and may aid complex catheter manipulations. Future work is needed to continue to define applications of this new technology.
... improvements in needle model for intramyocardial injection which promote cell dispersion and limit immediate washout) [161][162][163][164] as well as the use of a detailed imaging technique that facilitates a better characterization of target organs thereby improving cell delivery. 164,165 In addition, proper imaging techniques are required to be regulated so that specific clinical results can be evaluated in a uniformed manner (e.g. the use of MRI instead of angiography or echocardiography for assessing LV dimensions and systolic function). 1 ...
An immediate reperfusion therapy after acute myocardial infarction (AMI) is a prerequisite to prevent further cardiac damage and minimize ventricular remodelling. Although a rigorous and sophisticated set of therapeutic procedure has been applied in the disease management, mortality rate has yet unchanged during the last twenty years. This fact necessitates an alternative or adjuvant therapy that is critically safe and capable of repairing the injured vascular as well as regenerating the infarcted myocardium without omitting the ethical considerations. Stem cell therapy could be the answer. It has gained major basic and clinical research interest, ever since its discovered potential to repair the injured vascular in 1997. Multiple cell types across lineages have been shown to be able to transdifferentiate into mature functioning cardiomyocytes either in vitro through similar phenotypical and genotypical characteristics or in vivo by regenerating the infarcted myocardium and improve contractile function. Although the exact repairing mechanisms are still in a major debate, numerous clinical trials have demonstrated favorable effects toward the use of autologous stem cells in AMI patients with considerably low side effects. Despite the relatively novel discovery, stem cell therapy offers a promising prospect to confer a better protection, prevent later complications, and perhaps reduce the mortality among patients with ischemic heart disease. This ultimate outcome would likely be achieved through a stringent and coordinated of either basic and clinical research.
Micro-endomyocardial biopsy (micro-EMB) is a novel catheter-based biopsy technique, aiming to increase flexibility and safety compared to conventional EMB. The technique was developed and evaluated in healthy swine. Therefore, the ability to detect disease related tissue changes could not be evaluated. The aim of the present pilot study was to investigate the ability to detect disease related gene expression changes using micro-EMB. Myocardial infarction was induced in three swine by coronary artery balloon occlusion. Micro-EMB samples (n = 164) were collected before, during, and after occlusion. RNA-sequencing was performed on 85 samples, and 53 of these were selected for bioinformatic analysis. A large number of responding genes was detected from the infarcted area (n = 1911). The early responding genes (n = 1268) were mostly related to apoptosis and inflammation. There were fewer responding genes two days after infarction (n = 6), which were related to extra-cellular matrix changes, and none after 14 days. In contrast to the infarcted area, samples harvested from a non-infarcted myocardial region showed considerably fewer regulated genes (n = 33). Deconvolution analysis, to estimate the proportion of different cell types, revealed a higher proportion of fibroblasts and a reduced proportion of cardiomyocytes two days after occlusion compared to baseline (p < 0.02 and p < 0.01, respectively. S5 File). In conclusion, this pilot study demonstrates the capabilities of micro-EMB to detect local gene expression responses at an early stage after ischemia, but not at later timepoints.
Magnetic resonance image guidance for cardiovascular interventions has grown in recent years from a research tool to translation into clinical practice. The scope of improved visualization of cardiovascular anatomy, tissue characterization, physiologic information, and reduced ionizing radiation from cardiovascular magnetic resonance (CMR) is attractive compared to conventional fluoroscopic cardiac catheterization techniques. This is particularly relevant to a pediatric population who are more at risk from radiation, and more likely to need repeat interventions in the future.
Industry support has increased the development of interventional CMR systems. New generation scanners allow for faster scanning protocols, which translate into improved catheter visualization and tracking. The platforms for interacting with these images are also more intuitive. CMR conditional hardware in the form of catheters and guidewires is more available, although more work is still needed in this area.
These advances are balanced with the need to maintain safety issues in a CMR environment and any risks from heating. While there is some limitation in the available hardware options for sole CMR guidance, x-ray fused with CMR allows physiologic testing in the assessment of pulmonary avascular resistance as an example. There is now a growing body of early human experience or interventional cases, electrophysiology testing, and radiofrequency ablation in the CMR environment. These are discussed in the chapter.
Objectives
The aim of this study was to characterize the clinical safety profile of transendocardial injection catheters (TIC) reported in the published literature.
Background
Transendocardial delivery is a minimally invasive approach to deliver potential therapeutic agents directly into the myocardium. The rate of adverse events across TIC is uncertain.
Methods
A systematic search was performed for trial publications using TIC. Procedure-associated adverse event data were abstracted, pooled and compared across catheters for active treatment and placebo injected patients. The transendocardial injection associated serious adverse events (TEI-SAE) was defined as the composite of death, myocardial infarction, stroke or transient ischemic attack within 30 days and cardiac perforation causing death or requiring evacuation, serious intraprocedural arrhythmias and serious coronary artery or peripheral vascular complications.
Results
The search identified 4 TIC systems: a helical needle (HN), an electro-anatomically tracked straight needle (EAM-SN), a straight needle without tracking elements (SN), and a curved needle (CN). Of 1789 patients who underwent transendocardial injections, the combined TEI-SAE was 3.5% across all catheters, and 1.4%, 3.3%, 7.1%, and 8.3% for HN, EAM-SN, SN and CN, respectively. However, TIC procedure duration and post procedural cardiac biomarker levels were reported in only 24% and 36% of published trials, respectively.
Conclusions
Transendocardial injection is associated with varied TEI-SAE but the data are very limited. The HN catheter appeared to be associated with lower TEI-SAE, versus other catheters. Procedure duration and post procedure cardiac biomarker levels were under-reported. Clearly, standardized, procedure-related event reporting for trials involving transcatheter delivery would improve our understanding of complications across different systems.
Objectives
To determine whether X‐ray fused with MRI (XFM) is beneficial for select transcatheter congenital heart disease interventions.
Background
Complex transcatheter interventions often require three‐dimensional (3D) soft tissue imaging guidance. Fusion imaging with live X‐ray fluoroscopy can potentially improve and simplify procedures.
Methods
Patients referred for select congenital heart disease interventions were prospectively enrolled. Cardiac MRI data was overlaid on live fluoroscopy for procedural guidance. Likert scale operator assessments of value were recorded. Fluoroscopy time, radiation exposure, contrast dose, and procedure time were compared to matched cases from our institutional experience.
Results
Forty‐six patients were enrolled. Pre‐catheterization, same day cardiac MRI findings indicated intervention should be deferred in nine patients. XFM‐guided cardiac catheterization was performed in 37 (median age 8.7 years [0.5–63 years]; median weight 28 kg [5.6–110 kg]) with the following prespecified indications: pulmonary artery (PA) stenosis (n = 13), aortic coarctation (n = 12), conduit stenosis/insufficiency (n = 9), and ventricular septal defect (n = 3). Diagnostic catheterization showed intervention was not indicated in 12 additional cases. XFM‐guided intervention was performed in the remaining 25. Fluoroscopy time was shorter for XFM‐guided intervention cases compared to matched controls. There was no significant difference in radiation dose area product, contrast volume, or procedure time. Operator Likert scores indicated XFM provided useful soft tissue guidance in all cases and was never misleading.
Conclusions
XFM provides operators with meaningful three‐dimensional soft tissue data and reduces fluoroscopy time in select congenital heart disease interventions.
Fluoroscopy is a common imaging modality in medicine for guidance of minimally invasive interventions due to its high temporal and spatial resolution and the good visibility of interventional devices and bones. To counteract its lack of 3-D information and soft-tissue contrast, the X-ray images can be enhanced with overlays. This constitutes a medical application of augmented reality technology. Most commonly, the overlays are static. Due to inevitable respiratory and cardiac motion of the patient when imaging chest or abdomen, the images and the overlays frequently are inconsistent. In this thesis, two methods for compensating this involuntary motion are presented. In the first method, a respiratory signal is estimated from a 2-D+t X-ray image sequence using unsupervised learning. The robustness of respiratory signal extraction to common disturbances occurring in interventional imaging is increased by patchbased processing and illumination invariance. The respiratory signal is used as prior information in the subsequent motion estimation step. Due to transparency effects in X-ray, conventional registration methods are not applicable for motion estimation. Thus, a novel surrogate-driven layered motion model is proposed to estimate the respiratory motion from the X-ray sequence. The motion model is incorporated in an energy formulation that is solved with an efficient graphics processing unit (GPU) implementation of primal-dual optimization. In the second method, pre-operative magnetic resonance imaging (MRI) enables 3-D imaging with good soft-tissue contrast. Real-time 2-D+t slice images are acquired and stacked to 3-D+t volumes using a Markov random field (MRF). The MRF enforces similar surrogate signals in slices that are assigned to each other as well as temporal smoothness of the assignment. The surrogate signal for respiratory motion is estimated from the MRI images, while the cardiac surrogate signal is derived from electrocardiography (ECG). In the MRI volumes, conventional 3-D/3-D registration is used to estimate the patient motion. In both methods, the surrogate signals and the estimated motions are combined in a motion model, which is then used for motion compensation in X-ray. For evaluation, experiments are conducted on pig and patient data. Compared to static overlays, the residual apparent motion in the X-ray images is reduced by 13% using the X-ray-based motion model and by 40% using the MRI-based motion model. The runtime of applying the motion model during the procedure is sufficient for real-time processing at common fluoroscopy frame rates. Two alternative methods with different properties are proposed in this thesis. Xray-based motion compensation requires no pre-procedural processing, but is more complex during the procedure and is limited to respiratory motion. MRI-based motion compensation can also handle cardiac motion, but needs to be transferred from MRI to X-ray. The choice of motion model depends on the requirements of the clinical application. To this end, the X-ray-based motion model is implemented in a prototype and is evaluated clinically.
This chapter reviews the technological advances in catheter ablation of atrial fibrillation (AF). Pulmonary veins isolation (PVI) and electroanatomical mapping (EAM) remain the mainstays of AF ablation. The chapter summarizes the advantages, disadvantages, and potential complications of energy source and catheter during AF ablation. Based on randomized controlled trials, AF ablation is considered an important part of management as a class I level of evidence A in patients with paroxysmal AF, particularly in those refractory to antiarrhythmic therapy. Furthermore, randomized controlled trials have shown that catheter ablation is superior to medical rate control. New mapping and imaging systems and catheters have improved the success rate of AF ablation procedures. The goal of the strategies for catheter ablation of atrial fibrillation is to maintain sinus rhythm and prevent AF recurrence without significant damage to collateral tissue.
Objectives
With emergence of targeted cell transplantation and gene therapy, there is a need for minimally invasive tissue access to facilitate delivery of therapeutic substrate. The objective of this study is demonstrate the suitability of an endovascular device able to directly access tissue and deliver therapeutic agent to the heart, kidney, and pancreas without need to seal the penetration site.
Methods
In vivo experiments were performed in 30 swine, including subgroups with follow‐up to evaluate complications. The previously described trans‐vessel wall (VW) device was modified to be sharper, and not require tip detachment to seal the VW. Injections into targets in the heart (n=13, 24‐hour follow‐up n=5, 72‐hour follow‐up n=3), kidney (n=8, 14‐day follow‐up n=3), and pancreas (n=5), were performed. Some animals were used for multiple organ injections. Follow‐up consisted of clinical monitoring, angiography, and necropsy. Transvenous (in heart) and transarterial approaches (in heart, kidney, and pancreas) approaches were used. Injections were targeted towards the subepicardium, endomyocardium, pancreas head and tail, and kidney subcapsular space and cortex.
Results
Injections were successful in target organs, visualized by intraparenchymal contrast on fluroscopy and by necropsy. No serious complications (defined as heart failure or persistent arrhythmia, hemorrhage requiring treatment, or acute kidney injury) were encountered over a total of 157 injections.
Conclusions
The trans‐VW device can achieve superselective injections to the heart, pancreas, and kidney for delivery of therapeutic substances without tip detachment. All parts of these organs including the subepicardium, pancreas tail, and renal subcapsular space can be efficiently reached.
This article is protected by copyright. All rights reserved.
Because of great strides in medical care, survival into adulthood has become a common expectation in patients suffering from nearly all forms of congenital heart disease. As this aging population expands, the utilization of cardiac magnetic resonance imaging in their care continues to grow. Magnetic resonance technology has developed exponentially over the last 2 decades, and several advanced techniques for imaging adults with congenital heart disease have moved from the purely research arena into routine clinical care. In particular, 4-dimensional phase-contrast imaging allows comprehensive hemodynamic assessment, myocardial characterization quantifies fibrosis, stress magnetic resonance imaging detects vulnerable myocardium and hemodynamic reserve, and 3-dimensional modeling enables preinterventional planning, all of which are now widespread in their applications.
In the past several decades, there has been great interest in the transplantation of stem cells to recapitulate organs with limited regenerative capacity. During this same period, the ability to image stem cells by labeling with MRI-visible contrast agents has proved to be an enabling technology for determining the engraftment and fate of these cells. A natural extension of MR-labeling of stem cells is the delivery of stem cells using MR interventional techniques. While the development of these interventional techniques is hindered in part by the need to develop user-friendly imaging interfaces, MR-compatible devices, and advanced physiologic monitoring capabilities, limited clinical trials with MR-labeled stem cells have been performed that suggest MR interventional techniques will offer a safe and more effective method to deliver the stem cell therapies.
Hybrid X-ray/MRI systems facilitate complex minimally invasive procedures by providing information about anatomy and physiology from the MRI while using all of the tools available for X-ray fluoroscopy. Combining two modalities, such as X-ray and MRI, presents some significant challenges not encountered in the individual imaging labs alone. In this chapter we will discuss opportunities and limitations when operating a hybrid X-ray/MRI laboratory. Equipment, tools and resources, as well as clinical applications that benefit from a hybrid setting, are also reviewed.
Cardiovascular disease has reached epidemic proportions worldwide. Cell-based therapy for advanced heart and vascular disease may offer new hope for those afflicted. Although a variety of cell types are under investigation, mesenchymal stromal/stem cells (MSCs) have compelling features that offer advantages as an off-the-shelf therapy. These cells are multipotent, anti-inflammatory, and immunoprivileged and can incite regenerative growth factors via paracrine mechanisms. Animal studies and clinical trials are underway to characterize these cells and demonstrate efficacy for acute and chronic heart disease. This chapter reviews the current understanding of MSCs for heart disease, preclinical and clinical experience to date, delivery methods under investigation, and exciting new approaches to boost therapeutic efficiency.
Cardiac mapping is a perfect example of the evolution of science and practice in medicine and its related changes and future perspectives. Over the past decade multi-modality and multi-dimensional imaging and its applications in diagnostic and interventional electrophysiology - such as cardiac computed tomography, cardiac magnetic resonance imaging and positron emission tomography - have transformed current practice in a way that was previously unimaginable. Furthermore, the combination of these techniques with image integration and fusion on one hand and development of large number of pharmaceuticals and tracers on the other has taken mapping and imaging beyond the whole body, to subcellular levels.This review discusses some aspects of the advances in the modalities used for accurate diagnosis and equally effective therapies that have resulted in improvements in basic and clinical electrophysiology and its outcomes. Furthermore, the potential future outlook and expectations are briefly discussed to provide a picture of what the future holds in this field.
This study sought to demonstrate transcatheter deployment of a circumferential device within the pericardial space to modify tricuspid annular dimensions interactively and to reduce functional tricuspid regurgitation (TR) in swine.
Functional TR is common and is associated with increased morbidity and mortality. There are no reported transcatheter tricuspid valve repairs. We describe a transcatheter extracardiac tricuspid annuloplasty device positioned in the pericardial space and delivered by puncture through the right atrial appendage. We demonstrate acute and chronic feasibility in swine.
Transatrial intrapericardial tricuspid annuloplasty (TRAIPTA) was performed in 16 Yorkshire swine, including 4 with functional TR. Invasive hemodynamics and cardiac magnetic resonance imaging (MRI) were performed at baseline, immediately after annuloplasty and at follow-up.
Pericardial access via a right atrial appendage puncture was uncomplicated. In 9 naïve animals, tricuspid septal-lateral and anteroposterior dimensions, the annular area and perimeter, were reduced by 49%, 31%, 59%, and 24% (p < 0.001), respectively. Tricuspid leaflet coaptation length was increased by 53% (p < 0.001). Tricuspid geometric changes were maintained after 9.7 days (range, 7 to 14 days). Small effusions (mean, 46 ml) were observed immediately post-procedure but resolved completely at follow-up. In 4 animals with functional TR, severity of regurgitation by intracardiac echocardiography was reduced.
Transatrial intrapericardial tricuspid annuloplasty is a transcatheter extracardiac tricuspid valve repair performed by exiting the heart from within via a transatrial puncture. The geometry of the tricuspid annulus can interactively be modified to reduce severity of functional TR in an animal model.
Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
The aim of this work is to provide the necessary methods to register and fuse the endo-epicardial signal intensity (SI) maps extracted from contrast-enhanced magnetic resonance imaging (ceMRI) with X-ray coronary angiograms using an intrinsic registration-based algorithm to help pre-planning and guidance of catheterization procedures.
C-arm fluoroscopy units provide continuously updating X-ray video images
during surgical procedure. The modality is widely adopted for its low
cost, real-time imaging capabilities, and its ability to display
radio-opaque tools in the anatomy. It is, however, important to correct
for fluoroscopic image distortion and estimate camera parameters, such
as focal length and camera center, for registration with 3D CT scans in
fluoroscopic imageguided procedures. This paper describes a method for
C-arm calibration and evaluates its accuracy in multiple C-arm units and
in different viewing orientations. The proposed calibration method
employs a commerciallyavailable unit to track the C-arm and a
calibration plate. The method estimates both the internal calibration
parameters and the transformation between the coordinate systems of
tracker and C-arm. The method was successfully tested on two C-arm units
(GE OEC 9800 and GE OEC 9800 Plus) of different image intensifier sizes
and verified with a rigid airway phantom model. The mean
distortion-model error was found to be 0.14 mm and 0.17 mm for the
respective C-arms. The mean overall system reprojection error (which
measures the accuracy of predicting an image using tracker coordinates)
was found to be 0.63 mm for the GE OEC 9800.
Reliable transbronchial access of peripheral lung lesions is desirable
for the diagnosis and potential treatment of lung cancer. This procedure
can be difficult, however, because accessory devices (e.g., needle or
forceps) cannot be reliably localized while deployed. We present a
fluoroscopic image-guided intervention (IGI) system for tracking such
bronchoscopic accessories. Fluoroscopy, an imaging technology currently
utilized by many bronchoscopists, has a fundamental shortcoming - many
lung lesions are invisible in its images. Our IGI system aligns a
digitally reconstructed radiograph (DRR) defined from a pre-operative
computed tomography (CT) scan with live fluoroscopic images. Radiopaque
accessory devices are readily apparent in fluoroscopic video, while
lesions lacking a fluoroscopic signature but identifiable in the CT scan
are superimposed in the scene. The IGI system processing steps consist
of: (1) calibrating the fluoroscopic imaging system; (2) registering the
CT anatomy with its depiction in the fluoroscopic scene; (3) optical
tracking to continually update the DRR and target positions as the
fluoroscope is moved about the patient. The end result is a continuous
correlation of the DRR and projected targets with the anatomy depicted
in the live fluoroscopic video feed. Because both targets and
bronchoscopic devices are readily apparent in arbitrary fluoroscopic
orientations, multiplane guidance is straightforward. The system tracks
in real-time with no computational lag. We have measured a mean
projected tracking accuracy of 1.0 mm in a phantom and present results
from an in vivo animal study.
This paper presents the evaluation of the use of multimodality skin markers for the registration of cardiac magnetic resonance (MR) image data to x-ray fluoroscopy data for the guidance of cardiac electrophysiology procedures. The approach was validated using a phantom study and 3 patients undergoing pulmonary vein (PV) isolation for the treatment of paroxysmal atrial fibrillation. In the patient study, skin markers were affixed to the patients' chest and used to register pre-procedure cardiac MR image data to intra-procedure fluoroscopy data. Registration errors were assessed using contrast angiograms of the left atrium that were available in 2 out of 3 cases. A clinical expert generated "gold standard" registrations by adjusting the registration manually. Target registration errors (TREs) were computed using points on the PV ostia. Ablation locations were computed using biplane x-ray imaging. Registration errors were further assessed by computing the distances of the ablation points to the registered left atrial surface for all 3 patients. The TREs were 6.0 & 3.1mm for patients 1 & 2. The mean ablation point errors were 6.2, 3.8, & 3.0mm for patients 1, 2, & 3. These results are encouraging in the context of a 5mm clinical accuracy requirement for this type of procedure. We conclude that multimodality skin markers have the potential to provide anatomical image integration for x-ray guided cardiac electrophysiology procedures, especially if coupled with an accurate respiratory motion compensation strategy.
Modern reperfusion strategies and advances in pharmacological management have resulted in an increasing proportion of patients
surviving after an acute myocardial infarction (AMI). Cell transplantation has been developed as a potential treatment for
these patients. Multiple clinical trials have been conducted with various cell types to restore function in AMI patients.
Although some clinical trials have provided a signal that cell therapy improves cardiac function after AMI, parallel experimental
investigations of the mechanisms involved have shattered the concept of adult stem cell plasticity and have highlighted instead
the importance of paracrine effects. The data that have created this scientific roller-coaster ride, which has generated excitement
and confusion, are reviewed in this chapter.
KeywordsMyocardial infarction-Bone marrow stem cells-Clinical trials-Bone marrow cells-Heart failure-Cell therapy
Stem cell therapies offer potential therapeutic alternatives for coronary artery disease, myocardial infarction, and heart
failure. To a lesser extent, stem cell transplantations are used for experimental treatment of congenital heart conditions,
atherosclerotic peripheral arterial disease, and other cardiovascular pathologies. The efficacy of stem cell transplants on
the aforementioned diseases has been inconsistent, and the specific regenerative mechanisms by which stem cells work are not
well understood. Thus, a reliable and efficient method of cell tracking and monitoring would be beneficial. The different
imaging strategies and modalities for cell tracking, as well as the latest approaches to cell labeling in this field, are
reviewed in the hope that this will foster a better understanding of the best methods to treat cardiovascular diseases with
cellular therapeutics.
KeywordsHeart diseases–Stem cell transplantation and imaging–Magnetic resonance imaging–Single photon emission computed tomography–Positron emission tomography–Optical imaging–Bioluminescence
Live 3D trans-esophageal echocardiography (TEE) and X-ray fluoroscopy provide complementary imaging information for guiding
minimally invasive cardiac interventions. X-ray fluoroscopy is most commonly used for these procedures due to its excellent
device visualization. However, its challenges include the 2D projection nature of the images and poor soft tissue contrast,
both of which are addressed by the use of live 3D TEE imaging. We propose to integrate 3D TEE imaging with X-ray fluoroscopy,
providing the capability to co-visualize both the interventional devices and cardiac anatomy, by accurately registering the
images using an electro-magnetic tracking system. Phantom trials validating the proposed registration scheme indicate an average
accuracy of 2.04 mm with a standard deviation of 0.59 mm. In the future, this system may benefit the guidance and navigation
of interventional cardiac procedures such as mitral valve repair or patent foramen ovale closure.
Despite preclinical promise, the progress of cell-based therapy to clinical cardiovascular practice has been slowed by several challenges and uncertainties that have been highlighted by the conflicting results of human trials. Most telling has been the revelation that current strategies fall short of achieving sufficient retention and engraftment of cells to meet the ambitious objective of myocardial regeneration. This has sparked novel research into the refinement of cell biology and delivery to overcome these shortcomings. Within this context, molecular imaging has emerged as a valuable tool for providing noninvasive surveillance of cell fate in vivo. Direct and indirect labelling of cells can be coupled with clinically relevant imaging modalities, such as radionuclide single photon emission computed tomography and positron emission tomography, and magnetic resonance imaging, to assess their short- and long-term distributions, along with their viability, proliferation and functional interaction with the host myocardium. This review details the strengths and limitations of the different cell labelling and imaging techniques and their potential application to the clinical realm. We also consider the broader, multifaceted utility of imaging throughout the cell therapy process, providing a discussion of its considerable value during cell delivery and its importance during the evaluation of cardiac outcomes in clinical studies.
X-ray magnetic resonance fusion (XMRF) allows for use of 3D data during cardiac catheterization. However, to date, technical requirements have limited the use of this modality in clinical practice. We report on a new internal-marker XMRF method that we have developed and describe how we used XMRF during cardiac catheterization in congenital heart disease.
XMRF was performed in a phantom and in 23 patients presenting for cardiac catheterization who also needed cardiac MRI for clinical reasons. The registration process was performed in < 5 minutes per patient, with minimal radiation (0.004 to 0.024 mSv) and without contrast. Registration error was calculated in a phantom and in 8 patients using the maximum distance between angiographic and 3D model boundaries. In the phantom, the measured error in the anteroposterior projection had a mean of 1.15 mm (standard deviation, 0.73). The measured error in patients had a median of 2.15 mm (interquartile range, 1.65 to 2.56 mm). Internal markers included bones, airway, image artifact, calcifications, and the heart and vessel borders. The MRI data were used for road mapping in 17 of 23 (74%) cases and camera angle selection in 11 of 23 (48%) cases.
Internal marker-based registration can be performed quickly, with minimal radiation, without the need for contrast, and with clinically acceptable accuracy using commercially available software. We have also demonstrated several potential uses for XMRF in routine clinical practice. This modality has the potential to reduce radiation exposure and improve catheterization outcomes.
To validate a multi-modality image fusion approach to guide catheter-based, targeted transendocardial therapeutic delivery in a swine myocardial infarction (MI) model.
Biologic agents such as stem cells may curb post MI adverse ventricular remodeling if delivered by a transendocardial catheter directly into the infarct border. 3D visualization of the infarct and other cardiac surfaces is required to perform this task. We propose registering and overlaying magnetic resonance imaging (MRI) roadmaps onto live x-ray fluoroscopy (XRF) to guide targeted transendocardial delivery.
Custom software was used to register and overlay MRI models of the endocardium and infarct on live XRF by aligning common endocardial border features. In a swine MI model, transendocardial injections of co-localizing imaging labels were performed, targeting a 20 mm perimeter around the infarct. Directed targeting error (DTE) was defined as the difference between the predicted injection site-to-infarct distance calculated by the image fusion system, to the actual distance determined by postprocedure in vivo MRI. The mobile image fusion system was designed to be vendor-independent for imaging systems and transendocardial catheters.
Transendocardial injections were performed in all animals without complications. Mean DTE was 0.9 ± 5.0 mm (n = 8 swine). Time to register the images and establish a high quality roadmap was less than 12 min in all animals. Custom imaging tools to display injection sites and distribution were useful adjuncts during targeted injection procedures.
Multi-modality image fusion is a feasible and accurate platform technology to guide transendocardial injections precisely to the discrete infarct border.
Cardiovascular disease affects millions of Americans each year. Interventional guidance systems are being developed as treatment options for some of the more delicate procedures, including targeted stem cell therapy. As advanced systems for such types of interventional guidance are being developed, electromagnetic (EM) tracking is coming in demand to perform navigation. To use this EM tracking technology, a calibration is necessary to register the tracker to the imaging system. In this paper we investigate the calibration of an X-ray imaging system to EM tracking. Two specially designed calibration phantoms have been designed for this purpose, each having a rigidly attached EM sensor. From a clinical usability point-of-view, we propose to divide this calibration problem into two steps: i) in initial calibration of the EM sensor to the phantom design using an EM tracked needle to trace out grooves in the phantom surface and ii) segmentation from X-ray images and 3D reconstruction of beads embedded in the phantom in a known geometric pattern. Combining these two steps yields and X-ray-to-EM calibration accuracy of less than 1 mm when overlaying an EM tracked needle on X-ray images.
Minimally invasive cardiac procedures have been investigated to reduce the risks associated with open heart surgery. With the assistance of improvements in engineering technologies such as medical imaging, surgical navigation, and robotic devices, more cardiac surgeries can be performed in a minimally invasive fashion. We have surveyed these state-of-the-art engineering technologies and the minimally invasive cardiac procedures that are benefited from these technologies.
Clinical and basic scientific studies of stem cell-based therapies have shown promising results for cardiovascular diseases. Despite a rapid transition from animal studies to clinical trials, the mechanisms by which stem cells improve heart function are yet to be fully elucidated. To optimize cell therapies in patients will require a noninvasive means to evaluate cell survival, biodistribution and fate in the same subject over time. Cell labeling offers the ability to image distinct cell lineages in vivo and investigate the efficacy of these therapies using standard noninvasive imaging techniques. In this article, we will discuss the most promising cell labeling techniques for translation to clinical cardiovascular applications.
A catheter-based left ventricular (LV) endocardial mapping procedure using electromagnetic field energy for positioning of the catheter tip was designed to acquire simultaneous measurements of endocardial voltage potentials and myocardial contractility. We investigated such a mapping system to distinguish between infarcted and normal myocardium in an animal infarction model and in patients with coronary artery disease.
Measurements of LV endocardial unipolar (UP) and bipolar (BP) voltages and local endocardial shortening were derived from dogs at baseline (n=12), at 24 hours (n=6), and at 3 weeks (n=6) after occlusion of the left anterior descending coronary artery. Also, 12 patients with prior myocardial infarction (MI) and 12 control patients underwent the LV endocardial mapping study for assessment of electromechanical function in infarcted versus healthy myocardial regions. In the canine model, a significant decrease in voltage potentials was noted in the MI zone at 24 hours (UP, 42. 8+/-9.6 to 29.1+/-12.2 mV, P=0.007; BP, 11.6+/-2.3 to 4.9+/-1.2 mV, P<0.0001) and at 3 weeks (UP, 41.0+/-8.9 to 13.9+/-3.9 mV, P<0.0001; BP, 11.2+/-2.8 to 2.4+/-0.4 mV, P<0.0001). No change in voltage was noted in zones remote from MI. In patients with prior MI, the average voltage was 7.2+/-2.7 mV (UP)/1.4+/-0.7 mV (BP) in MI regions, 17.8+/-4.6 mV (UP)/4.5+/-1.1 mV (BP) in healthy zones remote from MI, and 19.7+/-4.4 mV (UP)/5.8+/-1.0 mV (BP) in control patients without prior MI (P<0.001 for MI values versus remote zones or control patients). In the canine model and patients, local endocardial shortening was significantly impaired in MI zones compared with controls.
These preliminary data suggest that infarcted myocardium could be accurately diagnosed and distinguished from healthy myocardium by a reduction in both electrical voltage and mechanical activity. Such a diagnostic electromechanical mapping study might be clinically useful for accurate assessment of myocardial function and viability.
In MRI tagging, magnetic tags-spatially encoded magnetic saturation planes-are created within tissues acting as temporary markers. Their deformation pattern provides useful qualitative and quantitative information about the functional properties of underlying tissue and allows non-invasive analysis of mechanical function. The measured displacement at a given tag point contains only unidirectional information; in order to track the full 3D motion, these data have to be combined with information from other orthogonal tag sets over all time frames. Here, we provide a method to describe the motion of the heart using a four-dimensional tensor product of B-splines. In vivo validation of this tracking algorithm is performed using different tagging sets on the same heart. Using the validation results, the appropriate control point density was determined for normal cardiac motion tracking. Since our motion fields are parametric and based on an image plane based Cartesian coordinate system, trajectories or other derived values (velocity, acceleration, strains ...) can be calculated for any desired point within the volume spanned by the control points. This method does not rely on specific chamber geometry, so the motion of any tagged structure can be tracked. Examples of displacement and strain analysis for both ventricles are also presented.
NOGA left ventricular (LV) electromechanical mapping (EMM) can be used to distinguish among infarcted, ischemic, and normal myocardium. We investigated the use of percutaneous LV EMM to assess the efficacy of myocardial gene transfer (GTx) of naked plasmid DNA encoding for vascular endothelial growth factor (phVEGF(165)), administered during surgery by direct myocardial injection in patients with chronic myocardial ischemia.
A total of 13 consecutive patients (8 men, mean age 60.1+/-2. 3 years) with chronic stable angina due to angiographically documented coronary artery disease, all of whom had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with direct myocardial injection of phVEGF(165) via a minithoracotomy. Foci of ischemic myocardium were identified on LV EMM by preserved viability associated with an impairment in linear local shortening. Myocardial viability, defined by mean unipolar and bipolar voltage recordings >/=5 and >/=2 mV, respectively, did not change significantly after GTx. Analysis of linear local shortening in areas of myocardial ischemia, however, disclosed significant improvement after (15.26+/-0.98%) versus before (9.94+/-1.53%, P:=0. 004) phVEGF(165) GTx. The area of ischemic myocardium was consequently reduced from 6.45+/-1.37 cm(2) before GTx to 0.95+/-0. 41 cm(2) after GTx (P:=0.001). These findings corresponded to improved perfusion scores calculated from single-photon emission CT-sestamibi myocardial perfusion scans recorded at rest (7.4+/-2.1 before GTx versus 4.5+/-1.4 after GTx, P:=0.009) and after pharmacological stress (12.8+/-2.7 before GTx versus 8.5+/-1.7 after GTx, P:=0.047).
The results of EMM constitute objective evidence that phVEGF(165) GTx augments perfusion of ischemic myocardium. These findings, together with reduction in the size of the defects documented at rest by serial single-photon emission CT-sestamibi imaging, suggest that phVEGF(165) GTx may successfully rescue foci of hibernating myocardium.
Recent studies indicate that magnetic resonance imaging (MRI) after the administration of contrast material can be used to distinguish between reversible and irreversible myocardial ischemic injury regardless of the extent of wall motion or the age of the infarct. We hypothesized that the results of contrast-enhanced MRI can be used to predict whether regions of abnormal ventricular contraction will improve after revascularization in patients with coronary artery disease.
Gadolinium-enhanced MRI was performed in 50 patients with ventricular dysfunction before they underwent surgical or percutaneous revascularization. The transmural extent of hyperenhanced regions was postulated to represent the transmural extent of nonviable myocardium. The extent of regional contractility at the same locations was determined by cine MRI before and after revascularization in 41 patients.
Contrast-enhanced MRI showed hyperenhancement of myocardial tissue in 40 of 50 patients before revascularization. In all patients with hyperenhancement the difference in image intensity between hyperenhanced regions and regions without hyperenhancement was more than 6 SD. Before revascularization, 804 of the 2093 myocardial segments analyzed (38 percent) had abnormal contractility, and 694 segments (33 percent) had some areas of hyperenhancement. In an analysis of all 804 dysfunctional segments, the likelihood of improvement in regional contractility after revascularization decreased progressively as the transmural extent of hyperenhancement before revascularization increased (P<0.001). For instance, contractility increased in 256 of 329 segments (78 percent) with no hyperenhancement before revascularization, but in only 1 of 58 segments with hyperenhancement of more than 75 percent of tissue. The percentage of the left ventricle that was both dysfunctional and not hyperenhanced before revascularization was strongly related to the degree of improvement in the global mean wall-motion score (P<0.001) and the ejection fraction (P<0.001) after revascularization.
Reversible myocardial dysfunction can be identified by contrast-enhanced MRI before coronary revascularization.
This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility.
Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage > or =6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (P=0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (P=0.003) and a reduction in end-systolic volume (P=0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (P<0.0005) at 4 months after treatment.
Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrow-derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function.
We describe a registration and tracking technique to integrate cardiac X-ray images and cardiac magnetic resonance (MR) images acquired from a combined X-ray and MR interventional suite (XMR). Optical tracking is used to determine the transformation matrices relating MR image coordinates and X-ray image coordinates. Calibration of X-ray projection geometry and tracking of the X-ray C-arm and table enable three-dimensional (3-D) reconstruction of vessel centerlines and catheters from bi-plane X-ray views. We can, therefore, combine single X-ray projection images with registered projection MR images from a volume acquisition, and we can also display 3-D reconstructions of catheters within a 3-D or multi-slice MR volume. Registration errors were assessed using phantom experiments. Errors in the combined projection images (two-dimensional target registration error--TRE) were found to be 2.4 to 4.2 mm, and the errors in the integrated volume representation (3-D TRE) were found to be 4.6 to 5.1 mm. These errors are clinically acceptable for alignment of images of the great vessels and the chambers of the heart. Results are shown for two patients. The first involves overlay of a catheter used for invasive pressure measurements on an MR volume that provides anatomical context. The second involves overlay of invasive electrode catheters (including a basket catheter) on a tagged MR volume in order to relate electrophysiology to myocardial motion in a patient with an arrhythmia. Visual assessment of these results suggests the errors were of a similar magnitude to those obtained in the phantom measurements.
The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype. MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately.
A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wall motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter navigation and multiple cell injections were performed entirely with MR fluoroscopy at 8 frames/s with 1.7x3.3x8-mm voxels. Infarct-enhanced MR fluoroscopy permitted excellent delineation of infarct borders. All injections were safely and successfully delivered to their preselected targets, including infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on delivery in vivo and post mortem.
Precise targeted delivery of potentially regenerative cellular treatments to recent myocardial infarction borders is feasible with an MR catheter delivery system. MR fluoroscopy permits visualization of catheter navigation, myocardial function, infarct borders, and labeled cells after injection.
Recently, there have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by magnetic resonance imaging (MRI). The purpose of this study was to evaluate the efficiency and toxicity of labeling cells using 2 commercially available Food and Drug Administration (FDA)-approved agents, ferumoxides, a suspension of dextran-coated SPIO used as an MRI contrast agent, and protamine sulfate, conventionally used to reverse heparin anticoagulation but also used ex vivo as a cationic transfection agent. After labeling of human mesenchymal stem cells (MSCs) and hematopoietic (CD34+) stem cells and other mammalian cells with ferumoxides-protamine sulfate complexes (FE-Pro), cellular toxicity, functional capacity, and quantitative cellular iron incorporation were determined. FE-Pro-labeled cells demonstrated no short- or long-term toxicity, changes in differentiation capacity of the stem cells, or changes in phenotype when compared with unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 2.01 +/- 0.1 pg for CD34+ cells and 10.94 +/- 1.86 pg for MSCs with 100% of cells labeled. Cell labeling using these agents should facilitate the translation of this method to clinical trials for evaluation of trafficking of infused or transplanted cells by MRI.
The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue.
Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion.
Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001).
In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures.
Longitudinal and multi-site clinical studies create the imperative to characterize and correct technological sources of variance that limit image reproducibility in high-resolution structural MRI studies, thus facilitating precise, quantitative, platform-independent, multi-site evaluation. In this work, we investigated the effects that imaging gradient non-linearity have on reproducibility of multi-site human MRI. We applied an image distortion correction method based on spherical harmonics description of the gradients and verified the accuracy of the method using phantom data. The correction method was then applied to the brain image data from a group of subjects scanned twice at multiple sites having different 1.5 T platforms. Within-site and across-site variability of the image data was assessed by evaluating voxel-based image intensity reproducibility. The image intensity reproducibility of the human brain data was significantly improved with distortion correction, suggesting that this method may offer improved reproducibility in morphometry studies. We provide the source code for the gradient distortion algorithm together with the phantom data.
Guidance systems designed for neurosurgery, hip surgery, and spine surgery, and for approaches to other anatomy that is relatively rigid can use rigid-body transformations to accomplish image registration. These systems often rely on point-based registration to determine the transformation, and many such systems use attached fiducial markers to establish accurate fiducial points for the registration, the points being established by some fiducial localization process. Accuracy is important to these systems, as is knowledge of the level of that accuracy. An advantage of marker-based systems, particularly those in which the markers are bone-implanted, is that registration error depends only on the fiducial localization error (FLE) and is thus to a large extent independent of the particular object being registered. Thus, it should be possible to predict the clinical accuracy of marker-based systems on the basis of experimental measurements made with phantoms or previous patients. This paper presents two new expressions for estimating registration accuracy of such systems and points out a danger in using a traditional measure of registration accuracy. The new expressions represent fundamental theoretical results with regard to the relationship between localization error and registration error in rigid-body, point-based registration. Rigid-body, point-based registration is achieved by finding the rigid transformation that minimizes "fiducial registration error" (FRE), which is the root mean square distance between homologous fiducials after registration. Closed form solutions have been known since 1966. The expected value (FRE/sup 2/) depends on the number N of fiducials and expected squared value of FLE, (FLE/sup 2/), but in 1979 it was shown that (FRE/sup 2/) is approximately independent of the fiducial configuration C. The importance of this surprising result seems not yet to have been appreciated by the registration community: Poor registrations caused by poor fiducia-
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l configurations may appear to be good due to a small FRE value. A more critical and direct measure of registration error is the "target registration error" (TRE), which is the distance between homologous points other than the centroids of fiducials. Efforts to characterize its behavior have been made since 1989. Published numerical simulations have shown that (TRE/sup 2/) is roughly proportional to (FLE/sup 2/)/N and, unlike (FRE/sup 2/), does depend in some way on C. Thus, FRE, which is often used as feedback to the surgeon using a point-based guidance system, is in fact an unreliable indicator of registration-accuracy. In this work the authors derive approximate expressions for (TRE/sup 2/), and for the expected squared alignment error of an individual fiducial. They validate both approximations through numerical simulations. The former expression can be used to provide reliable feedback to the surgeon during surgery and to guide the placement of markers before surgery, or at least to warn the surgeon of potentially dangerous fiducial placements; the latter expression leads to a surprising conclusion: Expected registration accuracy (TRE) is worst near the fiducials that are most closely aligned! This revelation should be of particular concern to surgeons who may at present be relying on fiducial alignment as an indicator of the accuracy of their point-based guidance systems.
Background:
The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype. MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately.
Methods and results:
A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wall motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter navigation and multiple cell injections were performed entirely with MR fluoroscopy at 8 frames/s with 1.7x3.3x8-mm voxels. Infarct-enhanced MR fluoroscopy permitted excellent delineation of infarct borders. All injections were safely and successfully delivered to their preselected targets, including infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on delivery in vivo and post mortem.
Conclusions:
Precise targeted delivery of potentially regenerative cellular treatments to recent myocardial infarction borders is feasible with an MR catheter delivery system. MR fluoroscopy permits visualization of catheter navigation, myocardial function, infarct borders, and labeled cells after injection.
We present our co-registration results of two complementary imaging modalities, MRI and X-ray angiography (XA), using dual modality fiducial markers. Validation experiments were conducted using a vascular phantom with eight fiducial markers around its periphery. Gradient-distortion-corrected 3D MRI was used to image the phantom and determine the 3D locations of the markers. XA imaging was performed at various C-arm orientations. These images were corrected for geometric distortion, and projection parameters were optimized using a calibration phantom. Closed-form 3D-to-3D rigid-body registration was performed between the MR markers and a D reconstruction of the markers from multiple XA images. 3D-to-2D registration was performed using a single XA image by projecting the MR markers onto the XA image and iteratively minimizing the 2D errors between the projected markers and their observed locations in the image. The RMS registration error was 0.77 mm for the 3D-to-3D registration, and 1.53 pixels for the 3D-to-2D registration. We also showed that registration can be performed at a large IS where many markers are visible, then the image can be zoomed in maintaining the registration. This requires calibration of imperfections in the zoom operation of the image intensifier. When we applied the registration used for an IS of 330 mm to an image acquired with an IS of 130 mm, the error was 42.16 pixels before zoom correction and 3.37 pixels after. This method offers the possibility of new therapies where the soft-tissue contrast of MRI and the high-resolution imaging of XA are both needed.
Targets for radiofrequency (RF) ablation of atrial fibrillation, atrial flutter, and nonidiopathic ventricular tachycardia are increasingly being selected on the basis of anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures and is associated with radiation risk, other approaches to mapping may be beneficial.
An electromagnetic catheter positioning system was superimposed on 3D MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MR images in real time. In vitro accuracy and precision during catheter navigation were assessed in a phantom model and were 1.11+/-0.06 and 0.30+/-0.07 mm (mean+/-SEM), respectively. Left and right heart catheterization was performed in 7 swine without the use of fluoroscopy, yielding an in vivo accuracy and precision of 2.74+/-0.52 and 1.97+/-0.44 mm, respectively. To assess the reproducibility of RF ablation, RF lesions were created repeatedly at the identical anatomic site in the right atrium (n=8 swine). Average distance of the repeated right atrial ablations was 3.92+/-0.5 mm. Straight 3-point lines were created in the right and left ventricles to determine the ability to facilitate complex ablation procedures (n=6 swine). The ventricular lesions deviated 1.70+/-0.24 mm from a straight line, and the point distance differed by 2.25+/-0.63 mm from the pathological specimen.
Real-time display of the catheter position on 3D MRI allows accurate and precise RF ablation guided by the true anatomy. This may facilitate anatomically based ablation procedures in, for instance, atrial fibrillation or nonidiopathic ventricular tachycardia and decrease radiation times.
Gross histochemical delineation of myocardium which has lost dehydrogenase enzyme activity has been shown to facilitate macroscopic recognition of necrotic myocardium. The present study was undertaken to assess the accuracy of the triphenyl tetrazolium chloride (TTC) technique for quantitating myocardial infarct size very early after coronary occlusion. In 16 closed-chest dogs the left anterior descending coronary artery was occluded with an intra-arterial balloon. Twelve dogs were killed 6 hours after occlusion, their hearts excised, cut from apex to base into 1 cm thick slices, and incubated in TTC. Whole-mount histologic sections of each slice were prepared. Myocardial infarct size was measured by planimetry of photographs of each gross slice and histologic section using classical criteria of necrosis. Myocardial infarct size determined in 54 slices by the TTC technique and histologically was similar (25 +/- 16% vs 27 +/- 16% of the left ventricular mass, mean +/- SD) with close correlation between the two methods (r = 0.91). Four dogs were killed 3 hours after occlusion and TTC stained and unstained myocardium was studied by electron microscopy. When the TTC technique identified necrosis so did electron microscopy. Areas identified by the TTC technique as non-necrotic were either normal or only ischemic by electron microscopy. Thus, using TTC, necrosis can be quantitated reliably 6, and even 3 hours after coronary occlusion, before histologic changes are clearly diagnostic. This technique represents a reliable, practical means for quantitation of recent infarction and for studying the evolution of ischemic injury in its early phase.
Methods for the noninvasive measurement of three-dimensional myocardial motion with MRI have recently been developed using presaturation tagging and velocity-encoded phase maps. The quality of clinical cardiac MRI studies has also recently improved with the advent of breath-hold scanning. The combination of breath-hold imaging with tagging and velocity-encoding sequences has made the measurement of myocardial wall motion in patients a simple and reproducible exam. These methods make it possible to quantify the severity and extent of regional heart wall motion abnormalities both at rest and during stress. This article reviews the MRI techniques developed for these applications.
Background —Catheter-based myocardial gene transfer (GTx) has not been previously tested in human subjects. Accordingly, we performed a pilot study to investigate the feasibility and safety of catheter-based myocardial GTx of naked plasmid DNA encoding vascular endothelial growth factor-2 (phVEGF-2) in patients with chronic myocardial ischemia.
Methods and Results —A steerable, deflectable 8F catheter incorporating a 27-guage needle was advanced percutaneously to the left ventricular myocardium of 6 patients with chronic myocardial ischemia. Patients were randomized (1:1) to receive phVEGF-2 (total dose, 200 μg), which was administered as 6 injections into ischemic myocardium (total, 6.0 mL), or placebo (mock procedure). Injections were guided by NOGA left ventricular electromechanical mapping. Patients initially randomized to placebo became eligible for phVEGF-2 GTx if they had no clinical improvement 90 days after their initial procedure. Catheter injections (n=36) caused no changes in heart rate or blood pressure. No sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforations were observed. phVEGF-2–transfected patients experienced reduced angina (before versus after GTx, 36.2±2.3 versus 3.5±1.2 episodes/week) and reduced nitroglycerin consumption (33.8±2.3 versus 4.1±1.5 tablets/week) for up to 360 days after GTx; reduced ischemia by electromechanical mapping (mean area of ischemia, 10.2±3.5 versus 2.8±1.6 cm ² , P =0.04); and improved myocardial perfusion by SPECT-sestamibi scanning for up to 90 days after GTx when compared with images obtained after control procedure.
Conclusions —This randomized trial of catheter-based phVEGF-2 myocardial GTx provides preliminary indications regarding the feasibility, safety, and potential efficacy of percutaneous myocardial GTx to human left ventricular myocardium.
In an effort to develop a guiding and monitoring tool for transmyocardial gene transfer, we have evaluated the feasibility of intracardiac echocardiography (ICE) to guide percutaneous endomyocardial gene transfer (PEGT), and monitor complications, in a pig model. ICE (5.5-10 MHz), complemented by fluoroscopy, was utilized to guide a needle injection into the heart in 19 normal pigs. Using this system, we injected Evans blue dye into eight pigs (group I), a mixture of pCK-CAT plasmid and India ink into seven pigs (group II), and pCK-LacZ plasmid into four pigs (group III). In all pigs, ICE contributed to the injection procedure by guiding the catheter to anatomically distinct sites, and by assisting stabilization of the catheter-endocardial contact. ICE predicted the injection sites correctly in 56 of 64 sites (87.5%) in group I, and in 42 of 42 sites (100%) in group II. Leakage of injectate into the left ventricular cavity could be detected by the microbubbles generated. The sites of injections appeared as foci of bright myocardial echodensity, which persisted until the end of the procedure. The procedures were not associated with significant morbidity or mortality. The expression of the chloramphenicol acetyltransferase (CAT) gene was identified in 40 sites from 42 injections (95.2%) in group II. In group III, histology showed positive beta-galactosidase staining of myocytes limited around the needle track with low transfection efficiency (<1%). These results suggest that real-time ICE monitoring proves safe and useful during PEGT for guiding needle injection, monitoring leakage, ensuring delivery of injectate into the myocardium, and instantly diagnosing cardiac complications, resulting in successful gene transfer.
After administration of gadolinium, infarcted myocardium exhibits delayed hyperenhancement and can be imaged using an inversion recovery (IR) sequence. The performance of such a method when using magnitude-reconstructed images is highly sensitive to the inversion recovery time (TI) selected. Using phase-sensitive reconstruction, it is possible to use a nominal value of TI, eliminate several breath-holds otherwise needed to find the precise null time for normal myocardium, and achieve a consistent contrast. Phase-sensitive detection is used to remove the background phase while preserving the sign of the desired magnetization during IR. Experimental results are presented which demonstrate the benefits of both phase-sensitive IR image reconstruction and surface coil intensity normalization for detecting myocardial infarction (MI). The phase-sensitive reconstruction method reduces the variation in apparent infarct size that is observed in the magnitude images as TI is changed. Phase-sensitive detection also has the advantage of decreasing the sensitivity to changes in tissue T(1) with increasing delay from contrast agent injection.
Direct intramyocardial injection may permit local delivery of protein and gene therapy agents for myocardial and coronary artery disease. Little is known about the immediate fate of materials administered via percutaneous endomyocardial catheters or via surgical epicardial injection. In this study, we use a novel method to evaluate the acute retention of agents injected directly into the myocardium, compare epicardial with the percutaneous endocardial and postmortem delivery, and evaluate the influence of injectate volume on myocardial retention. Fifteen 40-50 kg pigs underwent overlapping myocardial injections using a percutaneous endomyocardial catheter, an epicardial needle via an open chest, and epicardial needle postmortem. Multiple distinct 15 micro neutron-activated microsphere species were used as tracers. Two or three myocardial walls were injected in each animal using 3.5 mm, 27-28 gauge needles at varying injectate volumes. Animals were sacrificed immediately. Myocardial walls were divided and multiple microsphere species were quantified. In an additional study, nine 70 kg pigs underwent percutaneous endomyocardial injections with replication-deficient adenovirus encoding for the production of lac-Z. The injectate volume was varied, while the viral particle number remained constant. The animals were sacrificed 5 days after the percutaneous injections; the heart, liver, and spleen were collected for beta-galactosidase activity. Endomyocardial injection was associated with 43% +/- 15% microsphere retention, compared with 15% +/- 21% (P < 0.01) retention of open chest epicardial injection and 89% +/- 60% (P < 0.01) for postmortem injection. Reducing the injectate volume from 100 to 10 microL improved microsphere retention (P = 0.01). There was a trend toward improved viral transfection associated with smaller injection volumes. Despite direct intramyocardial administration, a significant fraction of injectate is not retained locally. Catheter-based needle endomyocardial injection is associated with equivalent or superior injectate retention compared with open chest epicardial injection. Proportionately, more injectate may be retained at lower volumes. Loss may involve a combination of channel leakage, venous, and lymphatic return.
This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective, randomized, double-blind, placebo-controlled, dose-escalating study of inoperable patients with class III or IV angina.
A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients (age, 61+/-2 years) with chronic myocardial ischemia who were not candidates for conventional revascularization. Patients were randomized in a double-blind fashion to receive 6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 microg (n=9), 800 microg (n=9), or 2000 microg (n=1) guided by LV electromechanical (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections were delivered and caused no hemodynamic alterations, sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus placebo-treated patients (-1.3 versus -0.1, P=0.04). Remaining efficacy end points--including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by > or =2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data--all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment.
This phase 1/2, double-blind, randomized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer. The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted.
This study was performed to evaluate the angiogenic effect of implantation of peripheral blood mononuclear cells (PB-MNCs) compared with bone marrow mononuclear cells (BM-MNCs) into ischemic hibernating myocardium.
A NOGA electromechanical system was used to map the hibernating region and to inject cells. PB-MNCs and BM-MNCs contained similar levels of vascular endothelial growth factor and basic fibroblast growth factor, whereas contents of angiogenic cytokines (interleukin-1beta and tumor necrosis factor-alpha) were larger in PB-MNCs. Numbers of endothelial progenitors were approximately 500-fold higher in BM-MNCs. In BM-MNC-implanted myocardia of pigs, an increase in systolic function (ejection fraction from 33% to 52%) and regional blood flow (2.1-fold) and a reduction of the ischemic area (from 29% to 8%) were observed. PB-MNC implantation reduced the ischemic area (from 31% to 17%), the extent of which was less than that seen with BM-MNCs. In saline-implanted myocardium, the ischemic area expanded (from 28% to 38%), and systolic function deteriorated. Angiography revealed an increase in collateral vessel formation by PB-MNC or BM-MNC implantation. Capillary numbers were increased 2.6- and 1.7-fold by BM-MNC and PB-MNC implantation, respectively. BM-MNCs but not PB-MNCs were incorporated into neocapillaries.
Catheter-based implantation of PB-MNCs can effectively improve collateral perfusion and regional function in hibernating ischemic myocardium by its ability to mainly supply angiogenic factors and cytokines.
Results of experimental studies have shown that intramyocardial implantation of bone marrow cells induces neovascularisation and improves heart function after myocardial infarction. Our aim was to test this notion in people. We implanted autologous mononuclear bone marrow cells into the ischaemic myocardium of eight patients with severe ischaemic heart disease as guided by electromechanical mapping with a percutaneous catheter procedure. After 3 months of follow-up, there was improvement in symptoms, myocardial perfusion, and function at the ischaemic region on MRI. Future randomised, controlled studies are required to validate this initial encouraging result.
To implement a successful acute pain service the following factors are the most important for success: anaesthesiologist-supervised pain nurses and an ongoing educational programme for patients and all health personnel involved in the care of surgical patients. The benefits in increased patient satisfaction and improved outcome after surgery will far outweigh the costs of running an acute pain service that raises standards of pain management throughout the hospital. Optimal use of basic pharmacological analgesia will improve relief of post-operative pain for most surgical patients. More advanced approaches, such as well-tailored epidural analgesia, are needed to relieve severe dynamic pain (e.g. when coughing). This may reduce markedly risks of complications in patients at high risk of developing post-operative respiratory infections and cardiac ischaemic events. More aggressive methods for post-operative pain management need robust routines that will discover the early symptoms and signs of potentially serious complications. High preparedness must be present for swift and correct handling of the rare but potentially catastrophic complications of bleeding and infection in the spinal canal. Chronic pain is common after surgery. Better acute pain relief may reduce this distressing long-term complication of surgery. Research into the long-term effects of optimal neuraxial analgesia and drugs that dampen glutamatergic hyperphenomena (hyperalgesia/allodynia) are urgently needed to verify whether these approaches can reduce the problem of intractable chronic post-operative pain.
We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia.
Myocardial ischemia was induced by placement of an ameroid constrictor around swine left circumflex artery. Four weeks after constrictor placement, CD31+ mononuclear cells (MNCs) were freshly isolated from the peripheral blood of each animal. After overnight incubation of CD31+ MNCs in noncoated plates, nonadhesive cells (NA/CD31+ MNCs) were harvested as the endothelial progenitor cell-enriched fraction. Nonadhesive CD31- cells (NA/CD31- MNCs) were also prepared. Autologous transplantation of 10(7) NA/CD31+ MNCs, 10(7) NA/CD31- MNCs, or PBS was performed with a NOGA mapping injection catheter to target ischemic myocardium. In a parallel study, 10(5) human CD34+ MNCs, 10(5) human CD34- MNCs, or PBS was transplanted into ischemic myocardium of nude rats 10 minutes after ligation of the left anterior descending coronary artery. In the swine study, ischemic area by NOGA mapping, Rentrop grade angiographic collateral development, and echocardiographic left ventricular ejection fraction improved significantly 4 weeks after transplantation of NA/CD31+ MNCs but not after injection of NA/CD31- MNCs or PBS. Capillary density in ischemic myocardium 4 weeks after transplantation was significantly greater in the NA/CD31+ MNC group than the control groups. In the rat study, echocardiographic left ventricular systolic function and capillary density were significantly better preserved in the CD34+ MNC group than in the control groups 4 weeks after myocardial ischemia.
These favorable outcomes encourage future clinical trials of catheter-based, intramyocardial transplantation of autologous CD34+ MNCs in the setting of chronic myocardial ischemia.
We compared catheter-based electromechanical mapping (NOGA system, Biosense-Webster, Haifa, Israel) with positron emission tomography (PET) and single photon emission computed tomography (SPECT) for prediction of reversibly dysfunctional myocardium (RDM) and irreversibly dysfunctional myocardium (IDM) in patients with severe left ventricular dysfunction. Furthermore, we established the optimal discriminatory value of NOGA measurements for distinction between RDM and IDM.
The NOGA system can detect viable myocardium but has not been used for prediction of post-revascularization contractile function in patients with ischemic cardiomyopathy.
Twenty patients (19 males, age [mean +/- SD] 60 +/- 16 years, ejection fraction [EF] 29 +/- 6%) underwent viability testing with NOGA and PET or SPECT before revascularization. Left ventricular function was studied at baseline and six months after revascularization.
The EF increased to 34 +/- 13% at six months (p < 0.05 vs. baseline). The 58 RDM and 57 IDM regions differed with regard to unipolar voltage amplitude (UVA) (9.2 +/- 3.9 mV vs. 7.6 +/- 4.0 mV, p < 0.05), normalized UVA (106 +/- 54% vs. 75 +/- 39%, p < 0.05), and tracer uptake (76 +/- 17% vs. 60 +/- 20%, p < 0.05). The NOGA local shortening did not distinguish between RDM and IDM (6.4 +/- 5.8% vs. 5.4 +/- 6.6%). By receiver operating characteristic curve analysis, myocardial tracer uptake had better diagnostic performance than UVA (area under curve [AUC] +/- SE: 0.82 +/- 0.04 vs. 0.63 +/- 0.05, p < 0.05) and normalized UVA (AUC +/- SE: 0.70 +/- 0.05, p < 0.05). Optimal threshold was defined as the value yielding sensitivity = specificity for prediction of RDM. Sensitivity and specificity were 59% at a UVA of 8.4 mV, 65% at a normalized UVA of 83%, and 78% at a tracer uptake of 69%.
The NOGA system may discriminate RDM from IDM with optimal discriminatory values for UVA and normalized UVA of 8.4 mV and 83%, respectively. However, the diagnostic performance does not reach the level obtained by PET and SPECT in patients with severe heart failure.
Transplantation of skeletal myogenic precursor cells (mpc) into the myocardium using a non-surgical procedure.
Closed-chest mpc transplantation was assessed in pigs using the NOGA-Biosense device allowing both electromechanical mapping of the left ventricle (LV), and guided mpc injections through endocardium.
We successively established that: (1) adequate preimplantation handling of mpc can be achieved when mpc are kept in 0.1% serum albumin-containing medium until implantation; (2) mpc are neither retained nor destroyed in the catheter or the needle and their passage does not affect their survival, growth and differentiation; (3) large numbers of autologous mpc can be actually transplanted in the LV myocardium by transendocardial route, as assessed by post-mortem examination of pigs injected with iron-loaded mpc; (4) cell injection into the myocardium does not induce conspicuous cell mortality since more than 80% of mpc recovered from LV tissue are alive 15 min after injection; (5) mpc injections can be guided into circumscribed LV targets such as infarcted areas, as assessed by comparison of map injection sites with location of iron-loaded mpc at post-mortem examination of LV myocardium.
This new approach may pave the way for a large spectrum of cell therapies targeting myocardial diseases.
Percutaneous transendomyocardial injection with an injection catheter is a new drug delivery method for e.g. therapeutic angiogenesis. Little is known about the efficacy of this drug delivery technique. We studied efficiency and retention of transendomyocardial injections with a NOGA guided injection catheter system by using scintigraphy with radio-labeled model drugs.
Ten non-ischemic landrace pigs were used. In each animal 2-3 transendomyocardial injections were performed using a 3-D mapping based catheter system called NOGA. As a model for proteins like angiogenic growth factors we used (99m)Tc labeled albumin and as a model for small particles like microspheres or adenovirus we used (99m)Tc labeled colloid albumin. Efficiency of the injections and retention of the transendomyocardial deposited substance were evaluated by a gamma camera during and after injection of 0.1 or 0.2 ml.
All 29 injections showed scintigraphic proof of intramyocardial deposition. The average injection efficiency of all 29 injections was 26 +/- 23%. The average injection efficiency of 0.1 and 0.2 ml injections were 33 +/- 30% (n = 8) and 24 +/- 20% (n = 21), respectively (p = 0.33). Intramyocardial retention curves of albumin showed a rapid wash-out within the first 2 hours of the injection, whereas the retention of colloid albumin showed no decrease. In conclusion, transendomyocardial delivery of proteins or particles with an injection catheter show favorable efficiency rates, however the retention time of intramyocardial deposited small proteins like albumin is short. This may indicate the need for sustained release systems of angiogenic growth factors for intramyocardal injection in therapeutic angiogenesis.
Statistical measures are described that are used in diagnostic imaging for expressing observer agreement in regard to categorical data. The measures are used to characterize the reliability of imaging methods and the reproducibility of disease classifications and, occasionally with great care, as the surrogate for accuracy. The review concentrates on the chance-corrected indices, kappa and weighted kappa. Examples from the imaging literature illustrate the method of calculation and the effects of both disease prevalence and the number of rating categories. Other measures of agreement that are used less frequently, including multiple-rater kappa, are referenced and described briefly.
We report on the procedural and six-month results of the first percutaneous and stand-alone study on myocardial repair with autologous skeletal myoblasts.
Preclinical studies have shown that skeletal myoblast transplantation to injured myocardium can partially restore left ventricular (LV) function.
In a pilot safety and feasibility study of five patients with symptomatic heart failure (HF) after an anterior wall infarction, autologous skeletal myoblasts were obtained from the quadriceps muscle and cultured in vitro for cell expansion. After a culturing process, 296 +/- 199 million cells were harvested (positive desmin staining 55 +/- 30%). With a NOGA-guided catheter system (Biosense-Webster, Waterloo, Belgium), 196 +/- 105 million cells were transendocardially injected into the infarcted area. Electrocardiographic and LV function assessment was done by Holter monitoring, LV angiography, nuclear radiography, dobutamine stress echocardiography, and magnetic resonance imaging (MRI).
All cell transplantation procedures were uneventful, and no serious adverse events occurred during follow-up. One patient received an implantable cardioverter-defibrillator after transplantation because of asymptomatic runs of nonsustained ventricular tachycardia. Compared with baseline, the LV ejection fraction increased from 36 +/- 11% to 41 +/- 9% (3 months, p = 0.009) and 45 +/- 8% (6 months, p = 0.23). Regional wall analysis by MRI showed significantly increased wall thickening at the target areas and less wall thickening in remote areas (wall thickening at target areas vs. 3 months follow-up: 0.9 +/- 2.3 mm vs. 1.8 +/- 2.4 mm, p = 0.008).
This pilot study is the first to demonstrate the potential and feasibility of percutaneous skeletal myoblast delivery as a stand-alone procedure for myocardial repair in patients with post-infarction HF. More data are needed to confirm its safety.
Although electromechanical mapping has been used to assess cardiac physiology, interpretation is dependent upon the spatial variability of endocardial voltage and local shortening in normal and viable dysfunctional myocardium, which is currently unknown.
NOGA mapping was performed in 13 pigs with an established model of viable dysfunctional myocardium produced by a chronic LAD stenosis, and five uninstrumented controls. Voltage maps (122 +/- 7 points each) were obtained in the closed-chest anesthetized state, and (18)F-2-deoxyglucose uptake and TTC staining confirmed viability.
There were systematic regional variations in voltage amplitude in both chronically-instrumented and control animals. Unipolar voltage was ~15% higher in LAD-supplied versus remote myocardium (10.8 +/- 0.3 vs. 8.9 +/- 0.4 mV, p < 0.001), with a similar relative difference in controls (14.0 +/- 0.5 vs. 12.0 +/- 0.4 mV, p < 0.02). In contrast, bipolar voltage was ~35% lower in the LAD territory of both groups (2.2 +/- 0.2 vs. 3.5 +/- 0.2 mV, p < 0.01 and 3.1 +/- 0.3 vs. 5.1 +/- 0.3 mV in controls, p < 0.01). The relative dispersion (SD/mean) of voltage was large, but significantly lower for unipolar versus bipolar measurements (39 +/- 1% vs. 70 +/- 2%, p < 0.001). Variability between hearts was partially related to end-systolic volume (r = 0.58, p < 0.05). Linear local shortening measurements were insensitive to detect anterior hypokinesis.
Our data demonstrates significant regional and spatial heterogeneity of endocardial voltage and NOGA-derived linear shortening in normal and viable dysfunctional myocardium, with large confidence intervals for individual measurements. Even though the absence of necrosis in this model precludes assessment of the sensitivity and specificity of NOGA mapping to identify infarction, our findings highlight important methodological limitations in using electromechanical mapping to determine viability.
In a series of in vitro and in vivo experiments, we evaluated the feasibility of integrating three-dimensional (3D) magnetic resonance imaging (MRI) and electroanatomic mapping (EAM) data to guide real-time left ventricular (LV) catheter manipulation.
Substrate-based catheter ablation of post-myocardial infarction ventricular tachycardia requires delineation of the scarred myocardium, typically using an EAM system. Cardiac MRI might facilitate this procedure by localizing this myocardial scar.
A custom program was employed to integrate 3D MRI datasets with real-time EAM. Initially, a plastic model of the LV was used to determine the optimal alignment/registration strategy. To determine the in vivo accuracy of the registration process, ablation lesions were directed at iatrogenic MRI-visible "targets" (iron oxide injections) within normal porcine LVs (n = 5). Finally, this image integration strategy was assessed in a porcine infarction model (n = 6) by targeting ablation lesions to the scar border.
The in vitro experiments revealed that registration of the LV alone results in inaccurate alignment due primarily to rotation along the chamber's long axis. Inclusion of the aorta in the registration process rectified this error. In the iron oxide injection experiments, the ablation lesions were 1.8 +/- 0.5 mm from the targets. In the porcine infarct model, the catheter could be reliably navigated to the mitral valve annulus, and the ablation lesions were uniformly situated at the scar borders.
These data suggest that registration of pre-acquired magnetic resonance images with real-time mapping is sufficiently accurate to guide LV catheter manipulation in a reliable and clinically relevant manner.
Objectives:
In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A(165)) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed.
Background:
Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials.
Methods:
Eighty "no-option" patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A(165) (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography.
Results:
No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 +/- 3% and 44 +/- 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A(165)-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients.
Conclusions:
The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe.
Local delivery of therapeutic agents into the myocardium is limited by suboptimal imaging. We evaluated the feasibility and accuracy of live 3D echo to guide left ventricular endomyocardial injection. An intramyocardial injection catheter was positioned in the left ventricle in five healthy Yorkshire pigs using fluoroscopy. All other catheter manipulations were performed with live biplane and 3D echo guidance. In each animal, a total of 12 endomyocardial injections (volume, 50-100 microl) of echo contrast mixed with blue tissue dye were performed. Four injections, 10 mm apart, were directed to three myocardial target zones: the anterior septum at the mitral valve level (zone 1); the posterolateral wall between the heads of the papillary muscles (zone 2); and the apex (zone 3). The injections were aimed to form a transverse line in zones 1 and 2 and an inverted triangular pyramid in zone 3. The animals were sacrificed, the hearts were inspected and the left ventricular endocardium was examined to create a map of injection marks. Success, defined as a visible injection of tissue dye, was 95%, and accuracy, defined as an injection into the target zone, was 83%. There was no significant difference in accuracy between the zones. Live 3D echo can successfully guide endomyocardial injections by accurately targeting specific myocardial zones, verifying catheter apposition and, when combined with echo contrast, providing real-time visualization of injectate deposition.
Cell-based therapies for treatment of ischemic heart disease are currently under investigation. We previously reported the results of a phase I trial of transendocardial injection of autologous bone marrow mononuclear (ABMM) cells in patients with end-stage ischemic heart disease. The current report focuses on postmortem cardiac findings from one of the treated patients, who died 11 months after cell therapy.
Anatomicopathologic, morphometric, and immunocytochemical findings from the anterolateral ventricular wall (with cell therapy) were compared with findings from the interventricular septum (normal perfusion and no cell therapy) and from the inferoposterior ventricular wall (extensive scar tissue and no cell therapy). No signs of adverse events were found in the cell-injected areas. Capillary density was significantly higher (P<0.001) in the anterolateral wall than in the previously infarcted tissue in the posterior wall. The prominent vasculature of the anterolateral wall was associated with hyperplasia of pericytes, mural cells, and adventitia. Some of these cells had acquired cytoskeletal elements and contractile proteins (troponin, sarcomeric alpha-actinin, actinin), as well as the morphology of cardiomyocytes, and appeared to have migrated toward adjacent bundles of cardiomyocytes.
Eleven months after treatment, morphological and immunocytochemical analysis of the sites of ABMM cell injection showed no abnormal cell growth or tissue lesions and suggested that an active process of angiogenesis was present in both the fibrotic cicatricial tissue and the adjacent cardiac muscle. Some of the pericytes had acquired the morphology of cardiomyocytes, suggesting long-term sequential regeneration of the cardiac vascular tree and muscle.
The outcome of catheter ablation procedures of cardiac arrhythmias depends on the ability to evaluate the underlying mechanism and to depict target sites for ablation. Fusion of different imaging modalities within one system may improve electroanatomic modeling and facilitate ablation procedures.
The purpose of this study was to study the feasibility of fusion of multislice computed tomography (MSCT) with electroanatomic mapping to guide radiofrequency catheter ablation of atrial arrhythmias.
Sixteen patients (15 men, age 54 +/- 7 years) with drug-refractory atrial fibrillation (AF) underwent 64-slice MSCT within 2 days before radiofrequency catheter ablation. MSCT data were imported to the Carto electroanatomic mapping system. Using the new CartoMerge Image Integration Module, the MSCT images and the electroanatomic map were aligned. A statistical algorithm provided information about the accuracy of the fusion process.
In all patients, MSCT images could be fused with the electroanatomic map. Mean distance between the mapping points and the MSCT surface ranged from 1.7 +/- 1.2 mm to 2.8 +/- 1.8 mm. This resulted in an average of 2.1 +/- 0.2 mm for the patient group as a whole.
MSCT images can be fused with the three-dimensional electroanatomic mapping system in an accurate manner. Anatomy-based catheter ablation procedures for atrial arrhythmias may be facilitated by integration of different imaging modalities.
Image-guided intervention using pre-acquired CT/MR 3-dimensional images is an emerging strategy for atrial fibrillation (AF) ablation but may be limited by its use of static images to depict dynamic physiology. The effect of biologic factors such as respiration on the left atrial-pulmonary venous (LA-PV) anatomy is not well understood but is likely to have important implications. Conventional CT/MR imaging is performed during an inspiratory breath-hold, while electroanatomical mapping (EAM) during "quiet" breathing approximates an expiratory breath-hold. This study examined the effects of respiration on LA-PV anatomy and the error introduced by respiration on the integration of EAM with 3D MR imaging.
Pre-procedural MRI angiography was performed at both end-expiration (EXP) and end-inspiration (INSP) in 20 patients undergoing AF catheter ablation. 3D INSP and EXP surface reconstructions of the LA-PVs were compared. In selected pts, EAM data acquired during the ablation procedure (n=7) were integrated with the 3D MRI datasets.
Qualitative assessment of the INSP and EXP 3D images revealed splaying of the PVs and reduction in PV caliber of the right-sided PVs during held inspiration. After aligning these two datasets, the average surface-to-surface distance calculated by region ranged from 1.99mm (right middle PV) to 3.79mm (left superior PV). Registration of the EAM to the MRI models was better for the EXP dataset (2.30+/-0.73mm) than the INSP dataset (3.03+/-0.57mm; p=0.004).
There are significant changes in LA-PV anatomy with respiration. MR images acquired during standard held inspiration may introduce unnecessary errors in registration during image-guided intervention.
Modern nonfluoroscopic mapping systems construct 3D electroanatomic maps by tracking intracardiac catheters. They require specialized catheters and/or dedicated hardware. We developed a new method for electroanatomic mapping by merging detailed 3D models of the endocardial cavities with fluoroscopic images without the need for specialized hardware. This developmental work focused on the right atrium because of the difficulties in visualizing its anatomic landmarks in 3D with current approaches.
Cardiac MRI images were acquired in 39 patients referred for radiofrequency catheter ablation using balanced steady state free-precession sequences. We optimized acquisition and developed software for construction of detailed 3D models, after contouring of endocardial cavities with cross-checking of different imaging planes. 3D models were then merged with biplane fluoroscopic images by methods for image calibration and registration implemented in a custom software application. The feasibility and accuracy of this merging process were determined in heart-cast experiments and electroanatomic mapping in patients. Right atrial dimensions and relevant anatomic landmarks could be identified and measured in all 3D models. Cephalocaudal, posteroanterior, and lateroseptal diameters were, respectively, 65+/-11, 54+/-11, and 57+/-9 mm; posterior isthmus length was 26+/-6 mm; Eustachian valve height was 5+/-5 mm; and coronary sinus ostium height and width were 16+/-3 and 12+/-3 mm, respectively (n=39). The average alignment error was 0.2+/-0.3 mm in heart casts (n=40) and 1.9 to 2.5 mm in patient experiments (n=9), ie, acceptable for clinical use. In 11 patients, reliable catheter positioning and projection of activation times resulted in 3D electroanatomic maps with an unprecedented level of anatomic detail, which assisted ablation.
This new approach allows activation visualization in a highly detailed 3D anatomic environment without the need for a specialized nonfluoroscopic mapping system.
Anatomic structures such as the left atrium and the pulmonary veins (PVs) are not delineated by fluoroscopy because there is no contrast differentiation between them and the surrounding anatomy. Representation of an anatomic structure via a 3D model obtained from computed tomography (CT) imaging and subsequent projection of these images over the fluoroscopy system may help in navigation of the mapping and ablation catheter to the appropriate sites during electrophysiology procedures.
In this feasibility study, in vitro experiments were performed with a plastic heart model (phantom) with 2 catheters or radiopaque platinum beads placed in the phantom at the time of CT imaging and fluoroscopy. Subsequently, 20 consecutive patients underwent contrast-enhanced, ECG-gated CT scanning. Left atrial volumes were generated from the reconstructed data at &75% of the R-R interval during the cardiac cycle. Similarly, the superior vena cava and the coronary sinus were also reconstructed from these images. During the electrophysiology procedure, digital records (cine sequences) were obtained. Using predetermined algorithms, both the phantom model and the patients' 3D left atrial models derived from the CT were registered with projection images of fluoroscopy. Registration was performed with a transformation that linked the superior vena cava and the coronary sinus from the CT model with a catheter placed inside the coronary sinus via the superior vena cava. Registration was successfully accomplished with the plastic phantom and in all 20 patients. Registration accuracy was assessed in the phantom by assessing the overlapping beads seen both in the CT and the fluoroscopy images. The mean registration error was 1.4 mm (range 0.9 to 2.3 mm). Accuracy of the registered images was assessed in patients with recordings from a basket catheter placed sequentially in the superior PVs and by injecting contrast into the PVs to assess overlapping of contrast-filled PVs with the corresponding vessels on the registered images. The images could be calibrated quite accurately. Any rotational error, which was usually minor, could be corrected by rotating the images as needed.
Registration of 3D models of the left atrium and PVs with fluoroscopic images of the same is feasible and could enable appropriate navigation and localization of the mapping and ablation catheter during procedures such as atrial fibrillation ablation.
New ablation strategies for atrial fibrillation or nonidiopathic ventricular tachycardia are increasingly based on anatomic consideration and require the placement of ablation lesions at the correct anatomic locations. This study sought to evaluate the accuracy of the first clinically available image integration system for catheter ablation on 3-dimensional (3D) computed tomography (CT) images in real time.
After midline sternotomy, 2.3-mm CT fiducial markers were attached to the epicardial surface of each cardiac chamber in 9 mongrel dogs. Detailed 3D cardiac anatomy was reconstructed from contrast-enhanced, high-resolution CT images and registered to the electroanatomic maps of each cardiac chamber. To assess accuracy, targeted ablations were performed at each of the fiducial markers guided only by the reconstructed 3D images. At autopsy, the position error was 1.9+/-0.9 mm for the right atrium, 2.7+/-1.2 mm for the right ventricle, 1.8+/-1.0 mm for the left atrium, and 2.3+/-1.1 mm for the left ventricle. To evaluate the system's guidance of more complex clinical ablation strategies, ablations of the cavotricuspid isthmus (n=4), fossa ovalis (n=4), and pulmonary veins (n=6) were performed, which resulted in position errors of 1.8+/-1.5, 2.2+/-1.3, and 2.1+/-1.2 mm, respectively. Retrospective analysis revealed that a combination of landmark registration and the target chamber surface registration resulted in <3 mm accuracy in all 4 cardiac chambers.
Image integration with high-resolution 3D CT allows accurate placement of anatomically guided ablation lesions and can facilitate complex ablation strategies. This may provide significant advantages for anatomically based procedures such as ablation of atrial fibrillation and nonidiopathic ventricular tachycardia.
It is unclear what is the most efficient vector and growth factor for induction of therapeutic vascular growth in the heart. Furthermore, the histological nature of angiogenesis and potential side effects caused by different vascular endothelial growth factors (VEGFs) in myocardium have not been documented.
Adenoviruses (Ad) at 2 doses (2x10(11) and 2x10(12) viral particles) or naked plasmids (1 mg) encoding LacZ control, VEGF-A165, or the mature, soluble form of VEGF-D (VEGF-D(DeltaNDeltaC)) were injected intramyocardially with the NOGA catheter system into domestic pigs. AdVEGF-D(DeltaNDeltaC) gene transfer (GT) induced a dose-dependent myocardial protein production, as measured by ELISA, resulting in an efficient angiogenic effect 6 days after the injections. Also, AdVEGF-A165 produced high gene transfer efficacy, as demonstrated with immunohistochemistry, leading to prominent angiogenesis effects. Despite the catheter-mediated approach, angiogenesis induced by both AdVEGFs was transmural, with maximal effects in the epicardium. Histologically, strongly enlarged alpha-smooth muscle actin-positive microvessels involving abundant cell proliferation were found in the transduced regions, whereas microvessel density did not change. Myocardial contrast echocardiography and microspheres showed marked increases in perfusion in the transduced areas. VEGF-D(DeltaNDeltaC) but not matrix-bound VEGF-A165 was detected in plasma after adenoviral GT. A modified Miles assay demonstrated myocardial edema resulting in pericardial effusion with the higher AdVEGF doses. All effects returned to baseline by 3 weeks. Naked plasmid-mediated GT did not induce detectable protein production or vascular effects.
Like AdVEGF-A165, AdVEGF-D(DeltaNDeltaC) GT using the NOGA system produces efficient transmural angiogenesis and increases myocardial perfusion. AdVEGF-D(DeltaNDeltaC) could be useful for the induction of therapeutic vascular growth in the heart.
Author manuscript; available in PMC 2007 October 15 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript 18 Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI
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de Silva et al. Page 9 Circulation. Author manuscript; available in PMC 2007 October 15. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript 18. Arbab AS, Yocum GT, Kalish H, Jordan EK, Anderson SA, Khakoo AY, Read EJ, Frank JA. Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 2004;104:1217–1223. [PubMed: 15100158]
Intramyocardial de Silva et al. Page 8 Circulation Author manuscript; available in PMC 2007 October 15. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript transplantation of autologous endothelial progenitor cells for therapeutic neo-vascularization of myocardial ischemia
- A Kawamoto
- T Tkebuchava
- J Yamaguchi
- H Nishimura
- Ys Yoon
- C Milliken
- S Uchida
- O Masuo
- H Iwaguro
- H Ma
- A Hanley
- M Silver
- M Kearney
- Dw Losordo
- Jm Isner
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