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Pulmonary perfusion imaging in the rodent lung using Dynamic Contrast Enhanced MRI
Magnetic Resonance in Medicine
Abstract
With the development of various models of pulmonary disease, there is tremendous interest in quantitative regional assessment of pulmonary function. While ventilation imaging has been addressed to a certain extent, perfusion imaging for small animals has not kept pace. In humans and large animals perfusion can be assessed using dynamic contrast-enhanced (DCE) MRI with a single bolus injection of a gadolinium (Gd)-based contrast agent. But the method developed for the clinic cannot be translated directly to image the rodent due to the combined requirements of higher spatial and temporal resolution. This work describes a novel image acquisition technique staggered over multiple, repeatable bolus injections of contrast agent using an automated microinjector, synchronized with image acquisition to achieve dynamic first-pass contrast enhancement in the rat lung. This allows dynamic first-pass imaging that can be used to quantify pulmonary perfusion. Further improvements are made in the spatial and temporal resolution by combining the multiple injection acquisition method with Interleaved Radial Imaging and "Sliding window-keyhole" reconstruction (IRIS). The results demonstrate a simultaneous increase in spatial resolution (<200 mum) and temporal resolution (<200 ms) over previous methods, with a limited loss in signal-to-noise-ratio.
... The gas exchange of the lung can be determined by functional MRI methods. It is important to have a match between the perfusion of blood and the ventilation of air in order to have an effective and properly working gas exchange (Mistry et al., 2008). There is often a mismatch between these parameters in many pulmonary diseases. ...
... However, quantitative perfusion MRI is not very common in clinical diagnostics and preclinical quantitative assessments are even more uncommon. Quantitative measurements of pulmonary perfusion with rodents have only been done in one study (Mistry et al., 2008). MRI of rodents involves difficulties such as requirements for better spatial resolution due to smaller vessels and organs. ...
... The body weight of rat is around 300 times less compared to man. Additionally, better temporal resolution is needed because of the cardiac rate in rats is about 5 times faster compared to man (Mistry et al., 2008). ...
... A number of well-established techniques are used for measuring cardiopulmonary blood flow including the Fick method, thermodilution, magnetic flowmetry, microspheres, Doppler ultrasound, magnetic resonance imaging ͑MRI͒, computed tomography ͑CT͒, and positron emission tomography ͑PET͒. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] Fick's method is the gold standard for measuring cardiac output ͑CO͒ in absolute units ͑ml/min͒; however, it is a global measurement of the entire body ͑nonregional͒. Regional measurements can be made using thermodilution, an advantage over Fick's method, but the reported values are relative measurements. ...
... Several different methods have been developed for perfusion MRI based on the flow or the use of injectable contrast agents. 10,19,20 These methods are also challenging when translating them to the spatial and temporal resolutions required for small animals, and calibration can be particularly problematic. ...
... Small animal DSA imaging has been described in previous work, which provides repeatable high-spatial and high-temporal resolution imaging in the living rodent. 10,[23][24][25][26] The anatomical imaging from DSA can be used to derive blood flow metrics using a nonparametric deconvolution technique. 27 This blood flow calculation is a relative measurement specific to each animal. ...
The use of preclinical rodent models of disease continues to grow because these models help elucidate pathogenic mechanisms and provide robust test beds for drug development. Among the major anatomic and physiologic indicators of disease progression and genetic or drug modification of responses are measurements of blood vessel caliber and flow. Moreover, cardiopulmonary blood flow is a critical indicator of gas exchange. Current methods of measuring cardiopulmonary blood flow suffer from some or all of the following limitations--they produce relative values, are limited to global measurements, do not provide vasculature visualization, are not able to measure acute changes, are invasive, or require euthanasia.
In this study, high-spatial and high-temporal resolution x-ray digital subtraction angiography (DSA) was used to obtain vasculature visualization, quantitative blood flow in absolute metrics (ml/min instead of arbitrary units or velocity), and relative blood volume dynamics from discrete regions of interest on a pixel-by-pixel basis (100 x 100 microm2).
A series of calibrations linked the DSA flow measurements to standard physiological measurement using thermodilution and Fick's method for cardiac output (CO), which in eight anesthetized Fischer-344 rats was found to be 37.0 +/- 5.1 ml/min. Phantom experiments were conducted to calibrate the radiographic density to vessel thickness, allowing a link of DSA cardiac output measurements to cardiopulmonary blood flow measurements in discrete regions of interest. The scaling factor linking relative DSA cardiac output measurements to the Fick's absolute measurements was found to be 18.90 x CODSA = COFick.
This calibrated DSA approach allows repeated simultaneous visualization of vasculature and measurement of blood flow dynamics on a regional level in the living rat.
... It is designed such that the time saved by reducing acquired data would lead to adequate temporal resolution for the study. Various methods have been proposed to reduce the number of sampling points by designing optimal sampling patterns that lead to increased quality of image reconstruction [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. Most of these sampling patterns, utilize prior knowledge of the signal of interest. ...
... Many variations and improvements have been made to both the keyhole and RIGR techniques, such as keyhole with elliptical and rhomboid windows, radial keyhole [3] and Two-reference RIGR (TRIGR) [4]. In several other methods, [5]- [9], categorized as data sharing methods, the missing data can be obtained from adjacent frames by assuming that the dynamics in an image sequence change only by a small amount from frame to frame. ...
The critical challenge in Dynamic Contrast Enhanced-Magnetic Resonance Imaging(DCE-MRI) is the trade-off between spatial and temporal resolution due to the limited availability of acquisition time. To address this, it is imperative to under-sample k-space and to develop specific reconstruction techniques. Our proposed method reconstructs high quality images from under-sampled dynamic k-space data by proposing 2 main improvements; i) design of an adaptive k-space sampling lattice and ii) Edge-Enhanced reconstruction technique. A high resolution dataset obtained before the start of the dynamic phase is utilized. The sampling pattern is designed to adapt to the nature of k-space energy distribution obtained from the static high resolution data. For image reconstruction, the well-known compressed sensing-based Total Variation (TV) minimization constrained reconstruction scheme is utilized by incorporating the gradient information obtained from the static high resolution data. The proposed method is tested on 7 real dynamic time-series consisting of 2 breast data sets and 5 abdomen data sets spanning 1196 images in all. For data availability of only 10%, performance improvement is seen across various quality metrics. Average improvements in Universal Image Quality Index and Structural Similarity Index Metric of up to 28% and 24% on breast data and about 17% and 9% on abdomen data, respectively, are obtained for the proposed method as against the baseline TV-reconstruction with variable density random sampling pattern.
... Using a combination of 1 HE und 3 HE, resolution of ventilated airways in mice up to 70 μm was possible (Chen et al 2005). Pulmonary perfusion imaging in a rat model using repeated injection of a gadolinium-based contrast agent represented lung structures with a spatial resolution up to 200 μm (Mistry et al 2008). ...
... Additional information from simulation data (Wall et al 2010, Wiechert et al 2009 is of special interest in the area of research of lung physiology and pathophysiology because of spatial and temporal limitations of most experimental methods. Other candidates for the development of computational lung models are advanced MRI techniques using contrast gas or aerosol coupled to a triggered respirator (Mistry et al 2008, Chen et al 2005, Mistry et al 2010. Advantages of these MRI techniques are in vivo imaging combined with a high temporal resolution. ...
Using conventional methods, three-dimensional imaging of the lung is challenging because of the low contrast between air and tissue and the large differences in dimensions between various pulmonary structures. The small distal airway structures and the high air-to-tissue ratio of lung tissue require an imaging technique which reliably discriminates between air and water. The objective of this study was to assess whether neutron computed tomography would satisfy such a requirement. This method utilizes the unique characteristic of neutrons of directly interacting with the atomic nucleus rather than being scattered by the atomic shell. Neutron computed tomography was tested in rats and allowed differentiation of larger lung structures (e.g., lobes) and distal airways. Airways could be identified reliably down to the sixth bronchial generation, in some cases even down to the tenth generation. The lung could be stabilized for sufficiently long exposure times to achieve an image resolution of 50-60 µm, which is the current physical resolution limit of the neutron computed tomography facility. Neutron computed tomography allowed excellent lung imaging without the need for additional tissue preparation or contrast media. The enhanced structural resolution obtained by applying this new research technique may improve understanding of lung physiology and respiratory therapy.
... Therefore, lung perfusion quantification in small rodents has only been reported in rats with ASL or DCE techniques. 11,47,52 In the current study, we combined the tyGA technique with a SENCEFUL approach for deriving qualitative and quantitative perfusion data as well as with single bolus Gd injection. Even although quantitative perfusion data in mice are rare, the resulting values compared well with the reported data of Tibiletti et al. 11 derived from ASL. ...
Imaging the lung parenchyma with MRI is particularly difficult in small animals due to the high respiratory and heart rates, and ultrashort T2* at high magnetic field strength caused by the high susceptibilities induced by the air-tissue interfaces. In this study, a 2D ultrashort echo-time (UTE) technique was combined with tiny golden angle (tyGA) ordering. Data were acquired continuously at 11.7 T and retrospective center-of-k-space gating was applied to reconstruct respiratory multistage images. Lung (proton) density (fP ), T2*, signal-to-noise ratio (SNR), fractional ventilation (FV) and perfusion (f) were quantified, and the application to dynamic contrast agent (CA)-enhanced (DCE) qualitative perfusion assessment tested. The interobserver and intraobserver and interstudy reproducibility of the quantitative parameters were investigated. High-quality images of the lung parenchyma could be acquired in all animals. Over all lung regions a mean T2* of 0.20 ± 0.05 ms was observed. FV resulted as 0.31 ± 0.13, and a trend towards lower SNR values during inspiration (EX: SNR = 12.48 ± 6.68, IN: SNR = 11.79 ± 5.86) and a significant (P < 0.001) decrease in lung density (EX: fP = 0.69 ± 0.13, IN: fP = 0.62 ± 0.13) were observed. Quantitative perfusion results as 34.63 ± 9.05 mL/cm3 /min (systole) and 32.77 ± 8.55 mL/cm3 /min (diastole) on average. The CA dynamics could be assessed and, because of the continuous nature of the data acquisition, reconstructed at different temporal resolutions. Where a good to excellent interobserver reproducibility and an excellent intraobserver reproducibility resulted, the interstudy reproducibility was only fair to good. In conclusion, the combination of tiny golden angles with UTE (2D tyGA UTE) resulted in a reliable imaging technique for lung morphology and function in mice, providing uniform k-space coverage and thus low-artefact images of the lung parenchyma after gating.
... Perfusion sustains the normal pulmonary gas exchange and is one of the main functions of the lungs (1). Lung perfusion imaging measures the blood circulation within the lung and is commonly used in the clinic to present the regional functional information (2). ...
Functional lung avoidance radiation therapy aims to minimize dose delivery to the normal lung tissue while favoring dose deposition in the defective lung tissue based on the regional function information. However, the clinical acquisition of pulmonary functional images is resource-demanding, inconvenient, and technically challenging. This study aims to investigate the deep learning-based lung functional image synthesis from the CT domain. Forty-two pulmonary macro-aggregated albumin SPECT/CT perfusion scans were retrospectively collected from the hospital. A deep learning-based framework (including image preparation, image processing, and proposed convolutional neural network) was adopted to extract features from 3D CT images and synthesize perfusion as estimations of regional lung function. Ablation experiments were performed to assess the effects of each framework component by removing each element of the framework and analyzing the testing performances. Major results showed that the removal of the CT contrast enhancement component in the image processing resulted in the largest drop in framework performance, compared to the optimal performance (~12%). In the CNN part, all the three components (residual module, ROI attention, and skip attention) were approximately equally important to the framework performance; removing one of them resulted in a 3–5% decline in performance. The proposed CNN improved ~4% overall performance and ~350% computational efficiency, compared to the U-Net model. The deep convolutional neural network, in conjunction with image processing for feature enhancement, is capable of feature extraction from CT images for pulmonary perfusion synthesis. In the proposed framework, image processing, especially CT contrast enhancement, plays a crucial role in the perfusion synthesis. This CTPM framework provides insights for relevant research studies in the future and enables other researchers to leverage for the development of optimized CNN models for functional lung avoidance radiation therapy.
... There are a number of imaging modalities used for diagnosis and clinical management of ARDS (Mills, 2003;Mistry et al., 2008;Cereda et al., 2016;Thompson et al., 2017). Chest X-ray radiography and computed tomography (CT) are extensively used imaging techniques to assess lung inflammation, injury and progression, where edema and immune cell infiltrates appear as opacities (Figure 1). ...
Pulmonary inflammation is a hallmark of several pulmonary disorders including acute lung injury and acute respiratory distress syndrome. Moreover, it has been shown that patients with hyperinflammatory phenotype have a significantly higher mortality rate. Despite this, current therapeutic approaches focus on managing the injury rather than subsiding the inflammatory burden of the lung. This is because of the lack of appropriate non-invasive biomarkers that can be used clinically to assess pulmonary inflammation. In this review, we discuss two metabolic imaging tools that can be used to non-invasively assess lung inflammation. The first method, Positron Emission Tomography (PET), is widely used in clinical oncology and quantifies flux in metabolic pathways by measuring uptake of a radiolabeled molecule into the cells. The second method, hyperpolarized ¹³C MRI, is an emerging tool that interrogates the branching points of the metabolic pathways to quantify the fate of metabolites. We discuss the differences and similarities between these techniques and discuss their clinical applications.
... By evaluating the RV-peak and the LA-peak in Fig. 8a, there is a time shift of approx. 1 s resulting from the passage time through the pulmonary circuit. This value is in accordance with the TIC results in [32]. In Fig. 8a, furthermore, the TIC belonging to the lung VOI presents its signal peak between the signal peaks of the right heart and the signal peaks of the left heart. ...
Non-invasive quantification of functional parameters of the cardiovascular system, in particular the heart, remains very challenging with current imaging techniques. This aspect is mainly due to the fact, that the spatiotemporal resolution of current imaging methods, such as Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET), does not offer the desired data repetition rates in the context of real-time data acquisition and thus, can cause artifacts and misinterpretations in accelerated data acquisition approaches. We present a fast non-invasive and quantitative dual-modal in situ cardiovascular assessment using a hybrid imaging system which combines the new imaging modality Magnetic Particle Imaging (MPI) and MRI. This pre-clinical hybrid imaging system provides either a 0:5T homogeneous B0 field for MRI or a 2:2T=m gradient field featuring a Field- Free-Point for MPI. A comprehensive coil system allows in both imaging modes for spatial encoding, signal excitation and reception. In this work, 3-dimensional anatomical information acquired with MRI is combined with in situ sequentially acquired time-resolved 3D (i.e. 3D+t) MPI bolus tracking of superparamagnetic iron oxide nanoparticles. MPI data were acquired during a 21μl (40μmol(Fe)=kgBW) bolus tail vein injection under free-breathing with an ungated and non-triggered MPI scan with a repetition rate of 46 volumes per seconds. We successfully determined quantitative hemodynamics as 3D+t velocity vector estimations of a beating rat’s heart by analyzing 3 seconds of 3D+t MPI image data. The used hybrid system allows for MR-based MPI Field-of-View planning and cardiac crosssectional anatomy analysis, precise co-registration of dualmodal datasets, as well as for MPI-based hemodynamic functional analysis using an optical flow technique. We present the first in-vivo results of a new methodology, allowing for fast, non-invasive, quantitative and in situ hybrid cardiovascular assessment, showing its potential for future clinical applications.
... Imaging techniques have been developed over the years to study pulmonary perfusion, not only as a tool to investigate the sequelae of vascular obstruction, such as acute and chronic pulmonary embolism (PE), but lately also as a potential tool to characterise inflammation and the malignancy potential of lung lesions [1][2][3]. ...
Subtraction computed tomography (SCT) is a technique that uses software-based motion correction between an unenhanced and an enhanced CT scan for obtaining the iodine distribution in the pulmonary parenchyma. This technique has been implemented in clinical practice for the evaluation of lung perfusion in CT pulmonary angiography (CTPA) in patients with suspicion of acute and chronic pulmonary embolism, with acceptable radiation dose. This paper discusses the technical principles, clinical interpretation, benefits and limitations of arterial subtraction CTPA.
Key Points
• SCT uses motion correction and image subtraction between an unenhanced and an enhanced CT scan to obtain iodine distribution in the pulmonary parenchyma.
• SCT could have an added value in detection of pulmonary embolism.
• SCT requires only software implementation, making it potentially more widely available for patient care than dual-energy CT.
... Liposomal-iodinated contrast agent may facilitate the early detection and diagnosis of pulmonary lesions, and have implications on treatment response and monitoring (16). Additionally, although a number of reports have introduced various diagnoses of early-stage lung cancer by CEMRI using a contrast agent, nano-particle sized contrast agents present additional benefits than other contrast agents for the diagnosis of lung cancer, including high sensitivity and specificity (17)(18)(19). Therefore, in the present study the auxiliary role of chistosan/Fe 3 O 4 -encapsulated bispecific antibodies (BsAbCENS) in CEMRI-diagnosed lung cancer was investigated. ...
Recent studies have indicated that magnetic resonance imaging (MRI) efficiently diagnoses lung cancer. However, the efficacy of MRI in diagnosing lung cancer requires improving for patients in the early stage of the disease. In the present study, a novel nano-sized contrast agent of chistosan/Fe3O4-enclosed bispecific antibodies (BsAbCENS) was introduced, which targeted carcino-embryonic antigen (CEA) and neuron-specific enolase (NSE) in lung cancer cells. The diagnostic efficacy of contrast-enhanced MRI with BsAbCENS (CEMRI-BsAbCENS) was investigated in a total of 182 patients with suspected lung cancer who had high serum levels of CEA and NSE. BsAbCENS was administered by pulmonary inhalation prior to the MRI scan. The results revealed that CEA and NSE were overexpressed in human lung cancer cell lines. BsAbCENS bound with CEA and NSE on the surface of human lung cancer cells and produced a higher signal intensity than MRI alone for the diagnosis of patients with lung cancer. The diagnostic data revealed that CEMRI-BsAbCENS diagnosed 124/182 lung cancer cases, whereas CEMRI only diagnosed 98/182, which was significantly less (P<0.01). In addition, the survival rate of patients with lung cancer diagnosed by CEMRI-BsAbCENS was significantly higher than the mean 5-year survival rate (P<0.01). Furthermore, the pharmacodynamics demonstrated that BsAbCENS was metabolized within 24 h. The results of the present study indicate that the efficacy and accuracy of lung cancer diagnosis are improved by CEMRI-BsAbCENS. In conclusion, these results provide a potential novel protocol for the diagnosis of tumors in patients with suspected early stage lung cancer.
... A wide variety of other physical phenomena such as flow and diffusion can be detected, and many of these specialized techniques have important applications to the study of lung development and disease. For example, pulmonary perfusion can be measured noninvasively by performing high temporal resolution imaging in conjunction with an intravascular bolus injection of a gadolinium-based contrast agent (102). The contrast agent alters the relaxation properties of nearby water molecules, and with appropriate pharmacokinetic modeling one can derive the relevant perfusion features such as transit time. ...
In vivo imaging is an important tool for pre-clinical studies of lung function and disease. The widespread availability of multimodal animal imaging systems and the rapid rate of diagnostic contrast agent development has empowered researchers to non-invasively study lung function and pulmonary disorders. Investigators can identify, track, and quantify biological processes over time. In this review, we highlight the fundamental principles of bioluminescence, fluorescence, planar X-ray, X-ray computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging modalities (such as positron emission tomography and single photon emission computed tomography; PET and SPECT) that have been successfully employed for the study of lung function and pulmonary disorders in a pre-clinical setting. The major principles, benefits, and applications of each imaging modality and technology are reviewed. Limitations and the future prospective of multimodal imaging in pulmonary physiology are also discussed. In vivo imaging bridges molecular biological studies, drug design and discovery, and the imaging field with modern medical practice, and as such, will continue to be a mainstay in biomedical research.
... The Tomographic DSA (TDSA) approach was based on the paradigm that the same time-density curves can be reproduced in a number of consecutive injections of contrast agent at a series of different angles of rotation. A similar multiple injection paradigm was used by Mistry et al. with DCE MRI [6] . Since in TDSA we have used a limited angle acquisition and tomosynthesis as a reconstruction algorithm, isotropic resolution was not possible. ...
Quantitative in-vivo imaging of lung perfusion in rodents can provide
critical information for preclinical studies. However, the combined
challenges of high temporal and spatial resolution have made routine
quantitative perfusion imaging difficult in rodents. We have recently
developed a dual tube/detector micro-CT scanner that is well suited to
capture first-pass kinetics of a bolus of contrast agent used to compute
perfusion information. Our approach is based on the paradigm that the
same time density curves can be reproduced in a number of consecutive,
small (i.e. 50μL) injections of iodinated contrast agent at a series
of different angles. This reproducibility is ensured by the high-level
integration of the imaging components of our system, with a
micro-injector, a mechanical ventilator, and monitoring applications.
Sampling is controlled through a biological pulse sequence implemented
in LabVIEW. Image reconstruction is based on a simultaneous algebraic
reconstruction technique implemented on a GPU. The capabilities of 4D
micro-CT imaging are demonstrated in studies on lung perfusion in rats.
We report 4D micro-CT imaging in the rat lung with a heartbeat temporal
resolution of 140 ms and reconstructed voxels of 88 μm. The approach
can be readily extended to a wide range of important preclinical models,
such as tumor perfusion and angiogenesis, and renal function.
... 23 The acquisition of radial trajectories leads to substantial oversampling at the center of k-space where most of the information related to pixel intensity is encoded. Hence, as shown for 2D sequences, 20,24 radial sampling lends itself naturally to kspace filtering strategies having a fundamental principle sim-ilar to keyhole imaging. In this work, we will refer to these techniques as "radial keyhole." ...
Purpose:
Dynamic contrast-enhanced (DCE) MRI has been widely used as a quantitative imaging method for monitoring tumor response to therapy. The simultaneous challenges of increasing temporal and spatial resolution in a setting where the signal from the much smaller voxel is weaker have made this MR technique difficult to implement in small-animal imaging. Existing protocols employed in preclinical DCE-MRI acquire a limited number of slices resulting in potentially lost information in the third dimension. This study describes and compares a family of four-dimensional (3D spatial + time), projection acquisition, radial keyhole-sampling strategies that support high spatial and temporal resolution.
Methods:
The 4D method is based on a RF-spoiled, steady-state, gradient-recalled sequence with minimal echo time. An interleaved 3D radial trajectory with a quasi-uniform distribution of points in k-space was used for sampling temporally resolved datasets. These volumes were reconstructed with three different k-space filters encompassing a range of possible radial keyhole strategies. The effect of k-space filtering on spatial and temporal resolution was studied in a 5 mM CuSO(4) phantom consisting of a meshgrid with 350-μm spacing and in 12 tumors from three cell lines (HT-29, LoVo, MX-1) and a primary mouse sarcoma model (three tumors∕group). The time-to-peak signal intensity was used to assess the effect of the reconstruction filters on temporal resolution. As a measure of heterogeneity in the third dimension, the authors analyzed the spatial distribution of the rate of transport (K(trans)) of the contrast agent across the endothelium barrier for several different types of tumors.
Results:
Four-dimensional radial keyhole imaging does not degrade the system spatial resolution. Phantom studies indicate there is a maximum 40% decrease in signal-to-noise ratio as compared to a fully sampled dataset. T1 measurements obtained with the interleaved radial technique do not differ significantly from those made with a conventional Cartesian spin-echo sequence. A bin-by-bin comparison of the distribution of the time-to-peak parameter shows that 4D radial keyhole reconstruction does not cause significant temporal blurring when a temporal resolution of 9.9 s is used for the subsamples of the keyhole data. In vivo studies reveal substantial tumor heterogeneity in the third spatial dimension that may be missed with lower resolution imaging protocols.
Conclusions:
Volumetric keyhole imaging with projection acquisition provides a means to increase spatiotemporal resolution and coverage over that provided by existing 2D Cartesian protocols. Furthermore, there is no difference in temporal resolution between the higher spatial resolution keyhole reconstruction and the undersampled projection data. The technique allows one to measure complex heterogeneity of kinetic parameters with isotropic, microscopic spatial resolution.
... The level of regional agreement as visualized in DW-MRI and DSC-MRI can be used to estimate a time-course estimate of infarct progression and functional impairment (30). MR-based perfusion studies in a small animal model have been carried out using novel MR pulse sequences that can meet the high spatial and temporal resolution demands observed in these small animals (31). ...
Imaging research and advances in systems engineering have enabled the transition of medical imaging from a means for accomplishing traditional anatomic visualization (i.e., orthopedic planar film X ray) to a means for noninvasively assessing a variety of functional measures. Perfusion imaging is one of the major highlights in functional imaging. In this work, various methods for measuring perfusion using widely-available commercial imaging modalities and contrast agents, specifically X ray and MR (magnetic resonance), will be described. The first section reviews general methods used for perfusion imaging, and the second section provides modality-specific information, focusing on the contrast mechanisms used to calculate perfusion-related parameters. The goal of these descriptions is to illustrate how perfusion imaging can be applied to radiation biology research.
... Such an approach has been used to analyze a rabbit model of pulmonary embolism (Keilholz et al., 2009) and a newborn piglet model of pulmonary hypertension (Ryhammer et al., 2007). Mistry et al. (2008) developed a cinematic (CINE) technique based on the acquisition of radial images during repeated contrast agent injection matched to the physiology of the animal using a microinjector, enabling perfusion imaging at high spatial and temporal resolution in artificially ventilated small rodents. The feasibility of lung perfusion with arterial spin labeling precluding the administration of contrast material has been demonstrated in rabbit models of pulmonary embolism and during repeated balloon occlusion of a segmental pulmonary artery as well as during pharmacological stimulation in pigs (Roberts et al., 2001). ...
With the incidence of respiratory diseases increasing throughout the world, new therapies are needed. This review provides a short overview of different imaging techniques of interest for drug discovery and development within the pulmonary disease area. The focus is on studies performed in both animals and humans, which are of importance for understanding pathophysiological aspects and evaluating new drugs. Rather than emphasizing particular lung diseases, the noninvasive diagnosis and quantification of a number of characteristics related to several pathological conditions of the lung are addressed: inflammation, mucus secretion and clearance, emphysema, ventilation, perfusion, fibrosis, airway remodeling, and pulmonary arterial hypertension. Techniques are discussed based on their present use or potential future utilization in the context of drug studies.
... The fourth and final step in the general image reconstruction procedure is to apply an inverse spatial Fourier transform to s psf (k, t) or ŝ(k, t) to produce an estimate of ρ(x, t). This result can be taken as the final reconstruction for ρ(x, t), or alternatively, ρ psf can be used to regularize the final reconstruction (27) such that [8] where λ 2 is the regularization parameter, and W is a weighting function. (ℱ is a Fourier transform from x to k.) ...
Dynamic contrast-enhanced MRI (or DCE-MRI) is a useful tool for measuring blood flow and perfusion, and it has found use in the study of pulmonary perfusion in animal models. However, DCE-MRI experiments are difficult in small animals such as rats. A recently developed method known as Interleaved Radial Imaging and Sliding window-keyhole (IRIS) addresses this problem by using a data acquisition scheme that covers (k,t)-space with data acquired from multiple bolus injections of a contrast agent. However, the temporal resolution of IRIS is limited by the effects of temporal averaging inherent in the sliding window and keyhole operations. This article describes a new method to cover (k,t)-space based on the theory of partially separable functions (PSF). Specifically, a sparse sampling of (k,t)-space is performed to acquire two data sets, one with high-temporal resolution and the other with extended k-space coverage. The high-temporal resolution training data are used to determine the temporal basis functions of the PSF model, whereas the other data set is used to determine the spatial variations of the model. The proposed method was validated by simulations and demonstrated by an experimental study. In this particular study, the proposed method achieved a temporal resolution of 32 msec.
... This opens the possibility of novel DSA methods to quantify real-time changes in blood flow. The injector has already been applied to a number of x-ray and MRI studies for vasculature imaging, perfusion, and flow measurements2324252627. ...
The availability of genetically altered animal models of human disease for basic research has generated great interest in new imaging methodologies. Digital subtraction angiography (DSA) offers an appealing approach to functional imaging in small animals because of the high spatial and temporal resolution, and the ability to visualize and measure blood flow. The micro-injector described here meets crucial performance parameters to ensure optimal vessel enhancement without significantly increasing the total blood volume or producing overlap of enhanced structures. The micro-injector can inject small, reproducible volumes of contrast agent at high flow rates with computer-controlled timing synchronized to cardiopulmonary activity. Iterative bench-top and live animal experiments with both rat and mouse have been conducted to evaluate the performance of this computer-controlled micro-injector, a first demonstration of a new device designed explicitly for the unique requirements of DSA in small animals. Injection protocols were optimized and screened for potential physiological impact. For the optimized protocols, we found that changes in the time-density curves for representative regions of interest in the thorax were due primarily to physiological changes, independent of micro-injector parameters.
Purpose
To develop a deep learning-based computed tomography (CT) perfusion mapping (DL-CTPM) method that synthesizes lung perfusion images from CT images.
Methods and Materials
This paper presents a retrospective analysis of the pulmonary technetium-99m-labeled macro-aggregated albumin (MAA) single-photon emission computed tomography (SPECT)/CT scans obtained from 73 patients at xx Hospital in Hong Kong in 2019. The left and right lung scans were separated to double the size of the dataset to 146. A three-dimensional attention residual neural network (ARNN) was constructed to extract textural features from the CT images and reconstruct corresponding functional images. Eighty-four samples were randomly selected for training and cross-validation, and the remaining 62 were used for model testing in terms of voxel-wise agreement and function-wise concordance. To assess the voxel-wise agreement, the Spearman’s correlation coefficient (R) and structural similarity index measure (SSIM) between the images predicted by the DL-CTPM and the corresponding SPECT perfusion images were computed to assess the statistical and perceptual image similarities, respectively. To assess the function-wise concordance, the Dice similarity coefficient (DSC) was computed to determine the similarity of the low/high functional lung volumes.
Results
The evaluation of the voxel-wise agreement showed a moderate-to-high voxel value correlation (0.6733 ± 0.1728) and high structural similarity (0.7635 ± 0.0697) between the SPECT and DL-CTPM predicted perfusions. The evaluation of the function-wise concordance obtained an average DSC value of 0.8183 ± 0.0752 for high-functional lungs, ranging from 0.5819 to 0.9255, and 0.6501 ± 0.1061 for low-functional lungs, ranging from 0.2405 to 0.8212. Ninety-four percent of the test cases demonstrated high concordance (DSC > 0.7) between the high functional volumes contoured from the predicted and ground-truth perfusions.
Conclusions
We developed a novel DL-CTPM method for estimating perfusion-based lung functional images from the CT domain using a 3D ARNN, which yielded moderate-to-high voxel-wise approximations of lung perfusion. To further contextualize these results toward future clinical application, a multi-institutional large-cohort study is warranted.
This project’s main objective was to develop and implement a molecular imaging tool based on hyperpolarized 13C magnetic resonance imaging (MRI) to quantitatively interrogate lung metabolism. The pulmonary system plays a major role in performing a variety of biochemical functions that maintain body homeostasis, but that undergo significant detrimental alteration in the setting of lung injury and/or inflammation. Such changes cause lactic acid to be released from the lungs and are associated with increased patient mortality. The ability to directly measure both changes in lung metabolism and its spatial heterogeneity can provide insight into the relationship between abnormal mechanics and cellularity in diseased lung tissue. This work primarily focuses on small and large mammalian species as a stepping stone toward translation to human subjects. The key deliverables of this project are acquisition and quantification tools for the regional assessment of hyperpolarized pyruvate’s conversion to lactate in lung tissue. To demonstrate the utility of our method, we used a two-hit animal model of acid aspiration and ventilator-induced lung injury that mimics a variety of inflammatory pulmonary diseases including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We measure the conversion of pyruvate to lactate using hyperpolarized lactate-to-pyruvate ratio, and show that this ratio is significantly correlated with inflammatory activity in the lung tissue as well as the degree of systemic hypoxemia. To further investigate hypoxia’s contribution to increased pulmonary lactate production, we assessed overall lung metabolism in non-injured hypoxic animals: while pulmonary pyruvate metabolism is resilient to moderate levels of hypoxemia, it changes significantly as a result of severe hypoxemia. Our data suggest that the increased lactate-to-pyruvate ratio in injured lungs is predominantly caused by inflammation. Next, we used our techniques to image both healthy and injured pigs on a clinical scanner in order to demonstrate the potential clinical translatability of hyperpolarized 13C imaging. Finally, we explored the possibility of using other imaging pulse sequences to achieve higher spatial and temporal resolution in both small and large animals, concluding that our method can serve as a future basis for rapid, high-resolution metabolic imaging of the lungs.
With the incidence of respiratory diseases increasing throughout the world, new therapies are needed. This chapter provides a short overview of different MRI techniques of interest for drug discovery and development within the pulmonary disease area. The focus is on studies performed both in animals and humans, which are of importance to understand pathophysiological aspects and to evaluate new drugs. Rather than emphasizing particular lung diseases, the noninvasive diagnosis and quantification of a number of characteristics related to several pathological conditions of the lung are addressed: inflammation, mucus secretion and clearance, emphysema, ventilation, perfusion, fibrosis, airway remodeling, and pulmonary arterial hypertension. Techniques are discussed based on their present use or potential future utilization in the context of drug studies.
Purpose:
To investigate pulmonary metabolic alterations during progression of acute lung injury.
Methods:
Using hyperpolarized [1-(13) C] pyruvate imaging, we measured pulmonary lactate and pyruvate in 15 ventilated rats 1, 2, and 4 h after initiation of mechanical ventilation. Lung compliance was used as a marker for injury progression. 5 untreated rats were used as controls; 5 rats (injured-1) received 1 ml/kg and another 5 rats (injured-2) received 2 ml/kg hydrochloric acid (pH 1.25) in the trachea at 70 min.
Results:
The mean lactate-to-pyruvate ratio of the injured-1 cohort was 0.15 ± 0.02 and 0.15 ± 0.03 at baseline and 1 h after the injury, and significantly increased from the baseline value 3 h after the injury to 0.23 ± 0.02 (P = 0.002). The mean lactate-to-pyruvate ratio of the injured-2 cohort decreased from 0.14 ± 0.03 at baseline to 0.08 ± 0.02 1 h after the injury and further decreased to 0.07 ± 0.02 (P = 0.08) 3 h after injury. No significant change was observed in the control group. Compliance in both injured groups decreased significantly after the injury (P < 0.01).
Conclusions:
Our findings suggest that in severe cases of lung injury, edema and hyperperfusion in the injured lung tissue may complicate interpretation of the pulmonary lactate-to-pyruvate ratio as a marker of inflammation. However, combining the lactate-to-pyruvate ratio with pulmonary compliance provides more insight into the progression of the injury and its severity. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Blood perfusion in lung parenchyma is an important property for assessing lung function. In small animals, its quantitation is limited even with radioactive isotopes or dynamic contrast-enhanced MRI techniques. In this study, the feasibility flow-sensitive alternating inversion recovery (FAIR) for the quantification of blood flow in lung parenchyma in free breathing rats at 7 T has been investigated. In order to obtain sufficient signal from the short T2 * lung parenchyma, a 2D ultra-short echo time (UTE) Look-Locker read-out has been implemented. Acquisitions were segmented to maintain acquisition time within an acceptable range. A method to perform retrospective respiratory gating (DC-SG) has been applied to investigate the impact of respiratory movement. Reproducibilities within and between sessions were estimated, and the ability of FAIR-UTE to identify the decrease of lung perfusion under hyperoxic conditions was tested. The implemented technique allowed for the visualization of lung parenchyma with excellent SNR and no respiratory artifact even in ungated acquisitions. Lung parenchyma perfusion was obtained as 32.54 ± 2.26 mL/g/min in the left lung, and 34.09 ± 2.75 mL/g/min in the right lung. Application of retrospective gating significantly but minimally changes the perfusion values, implying that respiratory gating may not be necessary with this center-our acquisition method. A decrease of 10% in lung perfusion was found between normoxic and hyperoxic conditions, proving the feasibility of the FAIR-UTE approach to quantify lung perfusion changes.
Magnetic resonance imaging (MRI) has emerged as the imaging modality of choice in a wide variety experimental and clinical applications. In this dissertation, I will describe novel MRI techniques for the characterization of neural and pulmonary vascular function in preclinical models of disease.
In the first part of this dissertation, experimental results will be presented comparing the identification of ischemic lesions in experimental stroke using dynamic susceptibility contrast (DSC) and a well validated arterial spin labeling (ASL). We show that DSC measurements of an index of cerebral blood flow are sensitive to ischemia, treatment, and stroke subregions. Further, we derived a threshold of cerebral blood flow for ischemia as measured by DSC. Finally, we show that ischemic lesion volumes as defined by DSC are comparable to those defined by ASL.
In the second part of this dissertation, a methodology of visualizing clots in experimental animal models of stroke is presented. Clots were rendered visible by MRI through the addition of a gadolinium based contrast agent during formation. Modified clots were used to induce an experimental embolic middle cerebral artery occlusion. Clots in the cerebral vasculature were visualized in vivo using MRI. Further, the efficacy of recombinant tissue plasminogen activator (r-tPA) and the combination of r-tPA and recombinant annexin-2 (rA2) was characterized by clot visualization during lysis.
In the third part of this dissertation, we present results of the application of hyperpolarized helium (HP-He) in the characterization of new model of experimental pulmonary ischemia. The longitudinal relaxation time of HP-He is sensitive to the presence of paramagnetic oxygen. During ischemia, oxygen exchange from the airspaces of the lungs to the capillaries is hindered resulting in increased alveolar oxygen content which resulted in the shortening of the HP-He longitudinal relaxation time. Results of measurements of the HP-He relaxation time in both normal and ischemic animals are presented.
In the final part of this dissertation, I will present results of a new method to measure pulmonary blood volume (PBV) using proton based MRI. A T1 weighted, inversion recovery spin echo sequence with cardiac and respiratory gating was developed to measure the changes in signal intensity of lung parenchyma before and after the injection of a long acting intravascular contrast agent. PBV is related to the signal change in the lung parenchyma and blood before and after contrast agent. We validate our method using a model of hypoxic pulmonary vasoconstriction in rats.
Magnetic resonance imaging (MRI) can be used in pre-clinical studies as a non-invasive imaging tool for assessing the morphological and functional impact of lung diseases and for evaluating the efficacy of potential treatments for airways diseases. Hyperpolarized gases ((3)He or (129)Xe) MRI provides insight into the lung ventilation function. Lung proton MRI provides information on lung diseases associated with inflammatory activity or with changes in lung tissue density. These imaging techniques can be implemented with non-invasive protocols appropriate for longitudinal investigations in small animal models of lung diseases. This chapter will detail two (3)He and proton lung MR imaging protocols applied on two models of lung pathology in rodents.
Introduction:
Cardiopulmonary blood flow is an important indicator of organ function. Limitations in measuring blood flow in live rodents suggest that rapid physiological changes may be overlooked. For instance, relative measurements limit imaging to whole organs or large sections without adequately visualizing vasculature. Additionally, current methods use small samples and invasive techniques that often require killing animals, limiting sampling speed, or both. A recently developed high spatial- and temporal-resolution X-ray digital subtraction angiography (DSA) system visualizes vasculature and measures blood flow in rodents. This study was the first to use this system to measure changes in cardiopulmonary blood flow in rats after administering the vasoconstrictor phenylephrine.
Methods:
Cardiopulmonary blood flow and vascular anatomy were assessed in 11 rats before, during, and after recovery from phenylephrine. After acquiring DSA images at 12 time points, a calibrated non-parametric deconvolution technique using singular value decomposition (SVD) was applied to calculate quantitative aortic blood flow in absolute metrics (mL/min). Trans-pulmonary transit time was calculated as the time interval between maximum signal enhancement in the pulmonary trunk and aorta. Pulmonary blood volume was calculated based on the central volume principle. Statistical analysis compared differences in trans-pulmonary blood volume and pressure, and aortic diameter using paired t-tests on baseline, peak, and late-recovery time points.
Results:
Phenylephrine had dramatic qualitative and quantitative effects on vascular anatomy and blood flow. Major vessels distended significantly (aorta, ~1.2-times baseline) and mean arterial blood pressure increased ~2 times. Pulmonary blood volume, flow, pressure, and aortic diameter were not significantly different between baseline and late recovery, but differences were significant between baseline and peak, as well as peak and recovery time points.
Discussion:
The DSA system with calibrated SVD technique acquired blood flow measurements every 30s with a high level of regional specificity, thus providing a new option for in vivo functional assessment in small animals.
Quantitative in vivo imaging of lung perfusion in rodents can provide critical information for preclinical studies. However, the combined challenges of high temporal and spatial resolution have made routine quantitative perfusion imaging difficult in small animals. The purpose of this work is to demonstrate 4D micro-CT for perfusion imaging in rodents at heartbeat temporal resolution and isotropic spatial resolution.
We have recently developed a dual tube/detector micro-CT scanner that is well suited to capture first pass kinetics of a bolus of contrast agent used to compute perfusion information. Our approach is based on the paradigm that similar time density curves can be reproduced in a number of consecutive, small volume injections of iodinated contrast agent at a series of different angles. This reproducibility is ensured by the high-level integration of the imaging components of our system with a microinjector, a mechanical ventilator, and monitoring applications. Sampling is controlled through a biological pulse sequence implemented in LABVIEW. Image reconstruction is based on a simultaneous algebraic reconstruction technique implemented on a graphic processor unit. The capabilities of 4D micro-CT imaging are demonstrated in studies on lung perfusion in rats.
We report 4D micro-CT imaging in the rat lung with a heartbeat temporal resolution (approximately 150 ms) and isotropic 3D reconstruction with a voxel size of 88 microm based on sampling using 16 injections of 50 microL each. The total volume of contrast agent injected during the experiments (0.8 mL) was less than 10% of the total blood volume in a rat. This volume was not injected in a single bolus, but in multiple injections separated by at least 2 min interval to allow for clearance and adaptation. We assessed the reproducibility of the time density curves with multiple injections and found that these are very similar. The average time density curves for the first eight and last eight injections are slightly different, i.e., for the last eight injections, both the maximum of the average time density curves and its area under the curve are decreased by 3.8% and 7.2%, respectively, relative to the average time density curves based on the first eight injections. The radiation dose associated with our 4D micro-CT imaging is 0.16 Gy and is therefore in the range of a typical micro-CT dose.
4D micro-CT-based perfusion imaging demonstrated here has immediate application in a wide range of preclinical studies such as tumor perfusion, angiogenesis, and renal function. Although our imaging system is in many ways unique, we believe that our approach based on the multiple injection paradigm can be used with the newly developed flat-panel slip-ring-based micro-CT to increase their temporal resolution in dynamic perfusion studies.
The global increase in asthma, chronic obstructive pulmonary disease, and other pulmonary diseases has stimulated interest in preclinical rat models of pulmonary disease. Imaging methods for study of these models is particularly appealing since the results can be readily translated to the clinical setting. Comprehensive understanding of lung function can be achieved by performing registered pulmonary ventilation and perfusion imaging studies in the same animal. While ventilation imaging has been addressed for small animals, quantitative pulmonary perfusion imaging has not been feasible until recently, with our proposed technique for quantitative perfusion imaging using multiple contrast-agent injections and a view-sharing radial imaging technique. Here, we combine the method with registered ventilation imaging using hyperpolarized (3)He in an airway obstruction rodent model. To our knowledge, this is the first comprehensive quantitative assessment of lung function in small animals at high spatial resolution. Standard deviation of the log (V/Q) is used as a quantitative biomarker to differentiate heterogeneity between the control and treatment group. The estimated value of the biomarker lies within the normal range of values reported in the literature. The biomarker that was extracted using the imaging technique described in this work showed statistically significant differences between the control rats and those with airway obstruction.
A review is presented of Veterinary Nuclear Medicine focusing on scintigraphical examinations. Most frequently applied clinical examination protocols are described, i.e. bone, thyroid, hepatic, renal, brain, cardiac and pulmonary scintigraphy, as well as oncological and inflammation scintigraphy, and miscellaneous scintigraphical examinations. Emphasis is placed on the types of procedures and the clinical information gained therefrom. No attempt is made to present or justify procedural details concerning instrumentation, radiopharmaceutical preparations, kinetic or radiation safety aspects. Detailed examinations are described following a schematic framework as: radiopharmaceuticals, examination protocol, indications and data evaluation, and illustrations. All the illustrations were taken between 1995 and 1999 from the data archive of the authors.
Balogh L., G. Andócs, J. Thuróczy, T. Németh, J. Láng, K. Bodó, G. A. Jánoki: Veterinary Nuclear Medicine. Scintigraphical examinations - a review. Acta Vet. Brno 68, 1999: 231-239. A review is presented of Veterinary Nuclear Medicine focusing on scintigraphical examinations. Most frequently applied clinical examination protocols are described, i.e. bone, thyroid, hepatic, renal, brain, cardiac and pulmonary scintigraphy, as well as oncological and inflammation scintigraphy, and miscellaneous scintigraphical examinations. Emphasis is placed on the types of procedures and the clinical information gained therefrom. No attempt is made to present or justify procedural details concerning instrumentation, radiopharmaceutical preparations, kinetic or radiation safety aspects. Detailed examinations are described following a schematic framework as: radiopharmaceuticals, examination protocol, indications and data evaluation, and illustrations. All the illustrations were taken between 1995 and 1999 from the data archive of the authors.
A method of magnetic resonance image acquisition and reconstruction is described in which high imaging rates and fast reconstruction times are allowed. The acquisition is a modification of the basic FLASH sequence but with a restricted number N of phase encodings. The encodings are applied sequentially, periodically, and continuously. Images are formed by sliding a window of width N encodings along the acquired data and reconstructing an image for each position of the window. In general the acquisition time per image exceeds the time between successive images, and the method thus has a temporal lag. Experimental studies were performed with a dynamic phantom using 48 phase encodings and a TR of 20 ms, for an image acquisition time of about 1 s. The image display rate in the reconstructed sequence was 12.5 images/s, and the image sequence portrayed the motion of the phantom. Additional studies were done with 24 encodings. It is shown how the sliding window technique lends itself to high-speed reconstruction, with each newly acquired echo used to quickly update the image on display. The combination of the acquisition technique described and a hardware implementation of the reconstruction algorithm can result in realtime MR image acquisition and reconstruction.
We previously reported that the levels of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are depressed in microsomes prepared from lungs of rats with acute Pseudomonas pneumonia. We also showed a potential role for cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) in contractile responses of both normal pulmonary arteries and pulmonary arteries from rats with pneumonia. The CYP2J subfamily enzymes (endogenous source of EETs and HETEs) are constitutively expressed in human and rat lungs where they are localized in vascular smooth muscle and endothelium. The purpose of this study was to determine if CYP2J proteins are modified in pneumonia. Pseudomonas organisms were injected via a tracheostomy in the lungs of rats. Later (44 h), lungs were frozen, and microsomes were prepared from pneumonia and control rat lung homogenates. Lung microsomal proteins were then immunoblotted with anti-CYP2B1/2B2, anti-CYP4A, anti-CYP2J9pep2 (which reacts with rat CYP2J3), anti-CYP2J6pep1 (which reacts with rat CYP2J4), anti-CYP2J2pep4, or anti-CYP2J2pep3 (both of which react with all known CYP2J isozymes). Western blotting revealed a prominent 55-kDa band with anti-CYP2J2pep3, anti-CYP2J2pep4, and anti-CYP2J6pep1 (but not anti-CYP2J9pep2) that was reduced in pneumonia compared with control lung microsomes. The CYP2B bands (51-52 kDa) were less prominent and not different between pneumonia and control lungs. CYP4A proteins (20-HETE sources) were not detected in rat lung microsomes. Therefore, rat lung contains a protein with immunological characteristics similar to CYP2J4, and this CYP is reduced after pneumonia. We speculate that CYP2J (but not CYP2B) enzymes and their AA metabolic products (EETs) are involved in the modulation of pulmonary vascular tone in pneumonia in rats.
Interventional magnetic resonance imaging (IMRI) is a rapidly emerging application for MRI in which diagnostic and therapeutic procedures are performed with MR image guidance. Real‐time or near‐real‐time image acquisition and relative insensitivity to motion are essential for most intraoperative, therapeutic, and diagnostic procedures performed under MR guidance. The purpose of this work was to demonstrate the development and utility of two alternative rapid acquisition strategies during IMRI that are analogous to computed tomography fluoroscopy or keyhole MRI in a radial rather than rectilinear coordinate frame. The two strategies discussed here, interleaved projection reconstruction and continuous projection reconstruction, are compared and the feasibility of their application in experimental interventional applications is studied. J. Magn. Reson. Imaging 2001;13:142–151. © 2001 Wiley‐Liss, Inc.
A novel technique for manipulating contrast in projection reconstruction MRI is described. The method takes advantage of the fact that the central region of k-space is oversampled, allowing one to choose different filters to enhance or reduce the amount that each view contributes to the central region, which dominates image contrast. The technique is implemented into a fast spin-echo (FSE) sequence, and it is shown that multiple T-2-weighted images can be reconstructed from a single image data set. These images are shown to be nearly identical to those acquired with the Cartesian-sampled FSE sequence at different effective echo times. Further, it is demonstrated that T-2 maps can be generated from a single image data set. This technique also has the potential to be useful in dynamic contrast enhancement studies, capable of yielding a series of images at a significantly higher effective temporal resolution than what is currently possible with other methods, without sacrificing spatial resolution. (C) 2000 Wiley-Liss, Inc.
Using in vivo magnetic resonance microscopy, registered 1H and hyperpolarized 3He images of the rat lung were obtained with a resolution of 0.098 × 0.098 × 0.469 mm (4.5 × 10–3 mm3). The requisite stability and SNR was achieved through an integration of scan-synchronous ventilation, dual-frequency RF coils, anisotropic projection encoding, and variable RF excitation. The total acquisition time was 21 min for the 3He images and 64 min for the 1H image. Airways down to the 6th and 7th orders are clearly visible. Magn Reson Med 45:365–370, 2001. © 2001 Wiley-Liss, Inc.
A comparison of dynamic results of a multi-echo contrast-enhanced perfusion study obtained from a keyhole imaging experiment and the results from low-resolution updates is presented. If, for each dynamic state, a separate reference image exists, high spatial resolution in the dynamic results can be preserved through keyhole imaging. If only one reference image can be used, the dynamic keyhole results still offer high spatial frequency content due to spatial phase discontinuities in the images. These often exist at the outline of organs and result from the fat in connective tissues. If the basic assumption of keyhole imaging, namely, that the relevant information is centered in k-space, is violated, as in T *2-weighted gradient-echo images, keyhole imaging can lead to erroneous results even though the update images themselves seem to be free of any artifacts. J. Magn. Reson. Imaging 2000;11:312–323. © 2000 Wiley-Liss, Inc.
An imaging technique is described that allows the reconstruction of a series of images at high temporal rates, while simultaneously providing images at high spatial resolution. The method allows one to arbitrarily choose from among several combinations of temporal/spatial resolutions during postprocessing. This flexibility is accomplished by strategically interleaving multiple undersampled projection reconstruction datasets (or subapertures), in which each set can be used to reconstruct a high temporal resolution image. Images with increasingly higher spatial resolutions can subsequently be formed by combining two or more subaperture datasets. The technique is demonstrated in vivo to assess the kinetics of contrast enhancement and to visualize the architectural features of suspicious breast lesions. Magn Reson Med 46:503–509, 2001. © 2001 Wiley-Liss, Inc.
Since image acquisition times in MRI have been reduced considerably over recent years, several new important application areas of MRI have appeared. In addition to pure static anatomic information, the evolution of a dynamic process may be visualized by a sequence of temporal snapshots of the process acquired within a short time period. This makes applications like interactive or interventional MRI as well as the acquisition of additional functional information feasible. For high temporal resolution, all these applications require a quasi real-time image acquisition during the time the interaction or dynamic process evolves. We present an approach to realtime imaging using a continuous radial acquisition scheme. The intrinsic advantages of radial or projection reconstruction (PR) techniques are used to minimize motion-related image distortions. Modifications of the acquisition scheme as well as dedicated reconstruction techniques are used to further reduce the temporal blurring due to the finite acquisition time of one entire data set in our approach. So far we have used this technique for the visualization of active joint motion.
Although dynamic imaging is presently used for various applications, it is still limited by the temporal resolution. In this paper, we present a new technique that uses a random phase-encoding strategy to facilitate faster and smoother update of images and to improve the temporal resolution in dynamic studies. The technique was implemented on a conventional clinical scanner and demonstrated with various in vivo studies. Technical details, simulations, and experimental results are described. Images from experimental studies indicate that the new technique is robust in generating dynamic images and can be potentially utilized for clinical applications.
Interventional magnetic resonance imaging (IMRI) is a rapidly emerging application for MRI in which diagnostic and therapeutic procedures are performed with MR image guidance. Real-time or near-real-time image acquisition and relative insensitivity to motion are essential for most intraoperative, therapeutic, and diagnostic procedures performed under MR guidance. The purpose of this work was to demonstrate the development and utility of two alternative rapid acquisition strategies during IMRI that are analogous to computed tomography fluoroscopy or keyhole MRI in a radial rather than rectilinear coordinate frame. The two strategies discussed here, interleaved projection reconstruction and continuous projection reconstruction, are compared and the feasibility of their application in experimental interventional applications is studied. J. Magn. Reson. Imaging 2001;13:142–151. © 2001 Wiley-Liss, Inc.
The use of aerosolized gadopentetate dimeglumine to define regional lung ventilation and of intravenously administered polylysine-(gadopentetate dimeglumine)40 to assess regional lung perfusion was investigated. In 10 healthy rats who breathed aerosolized gadopentetate dimeglumine (0.25 mol/L) for 5 minutes, pulmonary signal intensity increased diffusely in both lungs by more than 70%. When the same animals received intravenously administered polylysine-(gadopentetate dimeglumine)40 (0.1 mmol of gadolinium per kilogram), there was an additional 300% enhancement of the pulmonary parenchyma. In a rat model of acute unilateral pulmonary embolism (n = 5), perfusion defects were identified after administration of polylysine-(gadopentetate dimeglumine)40, but no ventilation abnormality was seen after inhalation of gadopentetate dimeglumine. In a rat model of acute unilateral airway obstruction (n = 5), only the ventilated right lung enhanced after inhalation of gadopentetate dimeglumine. In four of these animals, the focal ventilation defect was accompanied by a matched decrease in perfusion, seen after enhancement of the blood pool with polylysine-(gadopentetate dimeglumine)40.
The organ distribution of radiopharmaceuticals in the rat is usually estimated using 7% of body weight (BW) for blood volume (BV). In spite of its important impact on the evaluation of new agents, this value has not been validated adequately. We therefore studied blood volume in 70 awake Wistar rats (100 to 400 g BW) in which red blood cell volume (RBCV) and plasma volume (PV) were measured simultaneously. Red blood cell volume was measured by in vitro RBC-tagging with Tc-99m in Sn-pyrophosphate, 0.05 microgram per ml of blood; plasma volume was measured with I-125 human serum albumin (HSA). Ten minutes after injection of the dose, 0.5 ml of blood was withdrawn from the carotid or femoral artery and duplicate samples of 0.025 ml of blood were counted after separating RBCs from plasma. Total blood volume was calculated by adding RBC volume and plasma volume. The relationship for the entire group was: BV (ml) = 0.06 X BW + 0.77 (r = 0.99, n = 70, p less than 0.001). The difference between male and female rats was not statistically significant. The use of an arbitrary value of 7% for estimation of blood volume can lead to significant errors in calculating radiopharmaceutical distribution. The use of the general formula for the blood-volume calculation described here should improve the accuracy and reliability of estimates of radiopharmaceutical distribution.
Tracer dilution curves are useful for describing blood flow through vessels and organs. Empirically determined curves for flow through nonbranching vessels have been shown to correspond to a mathematical function called the gamma variate. This paper presents a derivation of the gamma-variate relationship, discusses some of the properties of the gamma variate and its use in problems involving organ blood flow and recirculation.
Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeroes for the missing data is followed, blurring results. Substituting instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be usefully accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradient- and spin-echo images are shown. The method is believed to be compatible with other acceleration methods such as half-Fourier reconstruction and reading of more than one line of k space per excitation.
A rapid dynamic imaging sequence has been developed in which only the 32 phase encoding steps that encode low spatial frequencies are collected for each dynamic image. These are substituted into a previously acquired, 128 x 128 raw data set prior to image reconstruction. In this way the dynamic information is retained while the overall appearance is improved in comparison with images obtained by zero filling to 128 x 128, leading to better qualitative evaluation. The limited k-space sampling means that the technique is most effective for large homogeneous areas of signal change since fine changes in contrast are imperfectly recorded.
Since image acquisition times in MRI have been reduced considerably over recent years, several new important application areas of MRI have appeared. In addition to pure static anatomic information, the evolution of a dynamic process may be visualized by a sequence of temporal snapshots of the process acquired within a short time period. This makes applications like interactive or interventional MRI as well as the acquisition of additional functional information feasible. For high temporal resolution, all these applications require a quasi real-time image acquisition during the time the interaction or dynamic process evolves. We present an approach to real-time imaging using a continuous radial acquisition scheme. The intrinsic advantages of radial or projection reconstruction (PR) techniques are used to minimize motion-related image distortions. Modifications of the acquisition scheme as well as dedicated reconstruction techniques are used to further reduce the temporal blurring due to the finite acquisition time of one entire data set in our approach. So far we have used this technique for the visualization of active joint motion.
Magnetic resonance imaging (MRI) relies on magnetisation of hydrogen nuclei (protons) of water molecules in tissue as source of the signal. This technique has been valuable for studying tissues that contain significant amounts of water, but biological settings with low proton content, notably the lungs, are difficult to image. We report use of spin-polarised helium-3 for lung MRI.
A volunteer inhaled hyperpolarised 3He to fill the lungs, which were imaged with a conventional MRI detector assembly. The nuclear spin polarisation of helium, and other noble gases, can be greatly enhanced by laser optical pumping and is about 10(5) times larger than the polarisation of water protons. This enormous gain in polarisation easily overcomes the loss in signal due to the lower density of the gas.
The in-vivo experiment was done in a whole-body MRI scanner. The 3He image showed clear demarcation of the lung against diaphragm, heart, chest wall, and blood vessels (which gave no signal). The signal intensity within the air spaces was greatest in lung regions that are preferentially ventilated in the supine position; less well ventilated areas, such as the apices, showed a weaker signal.
MRI with hyperpolarised 3He gas could be an alternative to established nuclear medicine methods. The ability to image air spaces offers the possibility of investigating physiological and pathophysiological processes in pulmonary ventilation and differences in its regional distribution.
The authors imaged the lungs of live guinea pigs with hyperpolarized (HP) helium-3 as a magnetic resonance (MR) signal source. HP He-3 gas produced through spin exchange with rubidium metal vapor was delivered through an MR-compatible, small-animal ventilator. Two- and three-dimensional lung images acquired with ventilation-gated, radial k-space sampling showed complete ventilation of both lungs. All images were of high quality, demonstrating that HP He-3 allows high-signal-intensity MR imaging in living systems.
Two healthy volunteers who had inhaled approximately 0.75 L of laser-polarized helium-3 gas underwent magnetic resonance imaging at 1.5 T with fast gradient-echo pulse sequences and small flip angles ( < 10 degrees). Thick-section (20 mm) coronal images, time-course data (30 images collected every 1.8 seconds), and thin-section (6 mm) images were acquired. Subjects were able to breathe the gas (12% polarization) without difficulty. Thick-section images were of good quality and had a signal-to-noise ratio (S/N) of 32:1 near the surface coil and 16:1 farther away. The time images showed regional differences, which indicated potential value for quantitation. High-resolution images showed greater detail and a S/N of approximately 6:1.
The nuclear spin polarization of noble gases can be enhanced strongly by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization on the order of 0.4-0.6. This is about 10(5) times larger than the polarization of water protons at thermal equilibrium used in conventional MRI. We demonstrate that hyperpolarized 3He gas can be applied to nuclear magnetic resonance imaging of organs with air-filled spaces in humans. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T. Anatomical details of the upper respiratory tract and of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.
An MR angiographic technique, referred to as 3D TRICKS (3D time-resolved imaging of contrast kinetics) has been developed. This technique combines and extends to 3D imaging several previously published elements. These elements include an increased sampling rate for lower spatial frequencies, temporal interpolation of k-space views, and zero-filling in the slice-encoding dimension. When appropriately combined, these elements permit reconstruction of a series of 3D image sets having an effective temporal frame rate of one volume every 2-6 s. Acquiring a temporal series of images offers advantages over the current contrast-enhanced 3D MRA techniques in that it I) increases the likelihood that an arterial-only 3D image set will be obtained. II) permits the passage of the contrast agent to be observed, and III) allows temporal-processing techniques to be applied to yield additional information, or improve image quality.
Increasing pulmonary blood flow and the associated rise in capillary perfusion pressure cause capillary recruitment. The resulting increase in capillary volume limits the decrease in capillary transit time. We hypothesize that small species with relatively high resting metabolic rates are more likely to utilize a larger fraction of gas-exchange reserve at rest. Without reserve, we anticipate that capillary transit time will decrease rapidly as pulmonary blood flow rises. To test this hypothesis, we measured capillary recruitment and transit time in isolated rat lungs. As flow increased, transit time decreased, and capillaries were recruited. The decrease in transit time was limited by an increase in the homogeneity of the transit time distribution and an increased capillary volume due, in part, to recruitment. The recruitable capillaries, however, were nearly completely perfused at flow rates and pressures that were less than basal for the intact animal. This suggests that a limited reserve of recruitable capillaries in the lungs of species with high resting metabolic rates may contribute to their inability to raise O2 consumption manyfold above basal values.
Data collection of MRI which is sampled nonuniformly in k-space is often interpolated onto a Cartesian grid for fast reconstruction. The collected data must be properly weighted before interpolation, for accurate reconstruction. We propose a criterion for choosing the weighting function necessary to compensate for nonuniform sampling density. A numerical iterative method to find a weighting function that meets that criterion is also given. This method uses only the coordinates of the sampled data; unlike previous methods, it does not require knowledge of the trajectories and can easily handle trajectories that "cross" in k-space. Moreover, the method can handle sampling patterns that are undersampled in some regions of k-space and does not require a post-gridding density correction. Weighting functions for various data collection strategies are shown. Synthesized and collected in vivo data also illustrate aspects of this method.
The assessment of both pulmonary perfusion and ventilation is of crucial importance for a proper diagnosis of some lung diseases such as pulmonary embolism. In this study, we demonstrate the feasibility of combined magnetic resonance imaging lung ventilation and perfusion performed serially in rat lungs. Lung ventilation function was assessed using hyperpolarized 3He, and lung perfusion proton imaging was demonstrated using contrast agent injection. Both imaging techniques have been implemented using projection-reconstruction sequences with free induction decay signal acquisitions. The study focused on fast three-dimensional (3D) data acquisition. The projection-reconstruction sequences used in this study allowed 3D data set acquisition in several minutes without high-performance gradients. 3D proton perfusion/helium ventilation imaging has been demonstrated on an experimental rat model of pulmonary embolism showing normal lung ventilation associated with lung perfusion defect. Assuming the possibility, still under investigation, of showing lung obstruction pathologies using 3He imaging, these combined perfusion/ventilation methods could play a significant clinical role in the future for diagnosis of several pulmonary diseases.
Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway leading to prostacyclin (PGI2) production. Patients with severe pulmonary hypertension have a PGIS deficiency of their precapillary vessels, but the importance of this deficiency for lung vascular remodeling remains unclear. We hypothesized that selective pulmonary overexpression of PGIS may prevent the development of pulmonary hypertension. To study this hypothesis, transgenic mice were created with selective pulmonary PGIS overexpression using a construct of the 3.7-kb human surfactant protein-C (SP-C) promoter and the rat PGIS cDNA. Transgenic mice (Tg+) and nontransgenic littermates (Tg-) were subjected to a simulated altitude of 17,000 ft for 5 weeks, and right ventricular systolic pressure (RVSP) was measured. Histology was performed on the lungs. The Tg+ mice produced 2-fold more pulmonary 6-keto prostaglandin F1alpha (PGF1alpha) levels than did Tg- mice. After exposure to chronic hypobaric hypoxia, Tg+ mice have lower RVSP than do Tg- mice. Histologic examination of the lungs revealed nearly normal arteriolar vessels in the Tg+ mice in comparison with vessel wall hypertrophy in the Tg- mice. These studies demonstrate that Tg+ mice were protected from the development of pulmonary hypertension after exposure to chronic hypobaric hypoxia. We conclude that PGIS plays a major role in modifying the pulmonary vascular response to chronic hypoxia. This has important implications for the pathogenesis and treatment of severe pulmonary hypertension.
The feasibility of qualitative assessment of pulmonary perfusion using dynamic contrast enhanced MRI with ultra-short TE has recently been demonstrated. In the current study, quantitative analysis was attempted based on the indicator dilution principle using a pig model of pulmonary embolism. The results were compared with the absolute pulmonary perfusion obtained with colored microspheres. The inverse of apparent mean transit time (1/tau(app)), distribution volume (V), and V/tau(app) were correlated well with the absolute lung perfusion. This study demonstrates that MR has the potential to evaluate pulmonary perfusion quantitatively. Magn Reson Med 42:1033-1038, 1999.
Undersampled projection reconstruction (PR) is investigated as an alternative method for MRA (MR angiography). In conventional 3D Fourier transform (FT) MRA, resolution in the phase-encoding direction is proportional to acquisition time. Since the PR resolution in all directions is determined by the readout resolution, independent of the number of projections (Np), high resolution can be generated rapidly. However, artifacts increase for reduced Np. In X-ray CT, undersampling artifacts from bright objects like bone can dominate other tissue. In MRA, where bright, contrast-filled vessels dominate, artifacts are often acceptable and the greater resolution per unit time provided by undersampled PR can be realized. The resolution increase is limited by SNR reduction associated with reduced voxel size. The hybrid 3D sequence acquires fractional echo projections in the k(x)-k(y) plane and phase encodings in k(z). PR resolution and artifact characteristics are demonstrated in a phantom and in contrast-enhanced volunteer studies.
In time-resolved contrast-enhanced 3D MR angiography, spatial resolution is traded for high temporal resolution. A hybrid method is presented that attempts to reduce this tradeoff in two of the spatial dimensions. It combines an undersampled projection acquisition in two dimensions with variable rate k-space sampling in the third. Spatial resolution in the projection plane is determined by readout resolution and is limited primarily by signal-to-noise ratio. Oversampling the center of k-space combined with temporal k-space interpolation provides time frames with minimal venous contamination. Results demonstrating improved resolution in phantoms and volunteers are presented using angular undersampling factors up to eight with acceptable projection reconstruction artifacts.
A novel technique for manipulating contrast in projection reconstruction MRI is described. The method takes advantage of the fact that the central region of k-space is oversampled, allowing one to choose different filters to enhance or reduce the amount that each view contributes to the central region, which dominates image contrast. The technique is implemented into a fast spin-echo (FSE) sequence, and it is shown that multiple T(2)-weighted images can be reconstructed from a single image data set. These images are shown to be nearly identical to those acquired with the Cartesian-sampled FSE sequence at different effective echo times. Further, it is demonstrated that T(2) maps can be generated from a single image data set. This technique also has the potential to be useful in dynamic contrast enhancement studies, capable of yielding a series of images at a significantly higher effective temporal resolution than what is currently possible with other methods, without sacrificing spatial resolution.
Interventional magnetic resonance imaging (IMRI) is a rapidly emerging application for MRI in which diagnostic and therapeutic procedures are performed with MR image guidance. Real-time or near-real-time image acquisition and relative insensitivity to motion are essential for most intraoperative, therapeutic, and diagnostic procedures performed under MR guidance. The purpose of this work was to demonstrate the development and utility of two alternative rapid acquisition strategies during IMRI that are analogous to computed tomography fluoroscopy or keyhole MRI in a radial rather than rectilinear coordinate frame. The two strategies discussed here, interleaved projection reconstruction and continuous projection reconstruction, are compared and the feasibility of their application in experimental interventional applications is studied. J. Magn. Reson. Imaging 2001;13:142-151.
An imaging technique is described that allows the reconstruction of a series of images at high temporal rates, while simultaneously providing images at high spatial resolution. The method allows one to arbitrarily choose from among several combinations of temporal/spatial resolutions during postprocessing. This flexibility is accomplished by strategically interleaving multiple undersampled projection reconstruction datasets (or subapertures), in which each set can be used to reconstruct a high temporal resolution image. Images with increasingly higher spatial resolutions can subsequently be formed by combining two or more subaperture datasets. The technique is demonstrated in vivo to assess the kinetics of contrast enhancement and to visualize the architectural features of suspicious breast lesions.
Amiodarone (AM) is an antidysrhythmic agent with a propensity to cause pulmonary toxicity, including potentially fatal fibrosis. In the present study, the potential roles of c-Jun and transforming growth factor (TGF)-beta 1 in AM-induced inflammation and fibrogenesis were examined after intratracheal administration of AM (1.83 micromol/day on days 0 and 2) or an equivalent volume (0.4 ml) of distilled water to male Fischer 344 rats. Northern and immunoblot analyses demonstrated that lung TGF-beta 1 (mRNA and protein) expression was increased 1.5- to 1.8-fold relative to control during the early inflammation period and 1 day, 1 wk, and 2 wk post-AM treatment. Lung c-Jun protein expression was increased concomitantly with evidence of AM-induced fibrosis; at 5 wk post-AM treatment, c-Jun protein was increased 3.3-fold relative to control. The results indicate a role for induction of c-jun and TGF-beta 1 expression in the development of AM-induced pulmonary fibrosis in the Fischer 344 rat and provide potential targets for therapeutic intervention.
Three-dimensional (3D) perfusion imaging allows the assessment of pulmonary blood flow in parenchyma and main pulmonary arteries simultaneously. MRI using laser-polarized (3)He gas clearly shows the ventilation distribution with high signal-to-noise ratio (SNR). In this report, the feasibility of combined lung MR angiography, perfusion, and ventilation imaging is demonstrated in a porcine model. Ultrafast gradient-echo sequences have been used for 3D perfusion and angiographic imaging, in conjunction with the use of contrast agent injections. 2D multiple-section (3)He imaging was performed subsequently by inhalation of 450 ml of hyperpolarized (3)He gas. The MR techniques were examined in a series of porcine models with externally delivered pulmonary emboli and/or airway occlusions. With emboli, perfusion deficits without ventilation defects were observed; airway occlusion resulted in matched deficits in perfusion and ventilation. High-resolution MR angiography can unambiguously reveal the location and size of the blood emboli. The combination of the three imaging methods may provide complementary information on abnormal lung anatomy and function.
A contrast-enhanced dynamic magnetic resonance (MR) study was performed experimentally and clinically to describe perfusion characteristics of radiation-injured lung according to pathologic phases.
The MR study was performed before and at 0.5, 1, 2, 3, 4, and 7 months after 40 Gy-dose irradiation to the right hemithorax in 8 dogs, and clinically in 12 lung lesions of 9 patients with acute or fibrotic radiation pneumonitis. Altered Gd-DTPA kinetics in the affected lungs was assessed by time-signal intensity curves. MR findings were correlated with lung histology and CT images.
Within 1 month after irradiation, the irradiated animal lungs showed focal and persistent contrast enhancement relative to nonirradiated lungs. This abnormality was pronounced during the next 2 months. After 4 months, irradiated lungs conversely showed lower enhancement during the Gd-DTPA first-pass but were followed by persistently greater enhancement during Gd-DTPA redistribution phase. Similar differences in enhancement abnormalities between acute and fibrotic radiation pneumonitis were clinically observed.
These findings indicate that Gd-DTPA kinetics can be altered according to the histopathologic change in early/acute radiation pneumonitis and radiation fibrosis and that the contrast-enhanced perfusion MRI may help differentiate the phases of radiation pneumonitis.
This study investigates the distribution of ventilation-perfusion (V/Q) signal intensity (SI) ratios using oxygen-enhanced and arterial spin labeling (ASL) techniques in the lungs of 10 healthy volunteers. Ventilation and perfusion images were simultaneously acquired using the flow-sensitive alternating inversion recovery (FAIR) method as volunteers alternately inhaled room air and 100% oxygen. Images of the T(1) distribution were calculated for five volunteers for both selective (T(1f)) and nonselective (T(1)) inversion. The average T(1) was 1360 ms +/- 116 ms, and the average T(1f) was 1012 ms +/- 112 ms, yielding a difference that is statistically significant (P < 0.002). Excluding large pulmonary vessels, the average V/Q SI ratios were 0.355 +/- 0.073 for the left lung and 0.371 +/- 0.093 for the right lung, which are in agreement with the theoretical V/Q SI ratio. Plots of the V/Q SI ratio are similar to the logarithmic normal distribution obtained by multiple inert gas elimination techniques, with a range of ratios matching ventilation and perfusion. This MRI V/Q technique is completely noninvasive and does not involve ionized radiation. A limitation of this method is the nonsimultaneous acquisition of perfusion and ventilation data, with oxygen administered only for the ventilation data.
A method - PA-keyhole - for 2D/3D dynamic magnetic resonance imaging with radial scanning is proposed. PA-keyhole exploits the inherent strong oversampling in the center of k-space, which contains crucial temporal information regarding contrast evolution. The method is based on: (1). a rearrangement of the temporal order of 2D/3D isotropic distributions of trajectories during the scan into subdistributions according to the desired time resolution, (2). a new post-acquisition keyhole approach based on the replacement of the central disk/sphere in k-space using data solely from a subdistribution, and (3). reconstruction of 2D/3D dynamic (time-resolved) images using 2D/3D-gridding with Pipe's approach to the sampling density compensation and 2D/3D-IFFT. The scan time is not increased with respect to a conventional 2D/3D radial scan of the same spatial resolution; in addition, one benefits from the dynamic information. The abilities of PA-keyhole and the sliding window techniques to restore simulated dynamic contrast changes are compared. Results are shown both for 2D and 3D dynamic imaging using experimental data. An application to in-vivo ventilation of rat lungs using hyperpolarized helium is demonstrated.
Quantitative determination of in-vivo gadolinium diethylenetriamine-pentaacid (Gd-DTPA) concentration is attractive in various studies involving perfusion, tracer kinetics and permeability constants. Using a 1.5 T clinical system and a 7 T small-bore system, we evaluated a method for absolute determination of Gd-DTPA concentrations in plasma solutions. Different solutions of Gd-DTPA and (99m)Tc-DTPA were mixed in human plasma and concentrations in the range of 0-5.0 mmol/l (1.5 T system) or 0-3.0 mmol/l (7 T system) of Gd-DTPA were divided into thirteen tubes. All MRI measurements were carried out using conventional sequences (SE, FLASH and GRASS). The MR measured intensity was converted to Gd-DTPA concentration by mathematical interpretation of the sequences. All MRI sequences showed, that the measured concentrations of Gd-DTPA revealed a slight non-linear difference compared with the calculated Gd-DTPA concentrations determined by the plasma (99m)Tc-DTPA using gamma counting. This non-linearity was most pronounced at high Gd-DTPA concentrations, suggesting that the discrepancy could be a result of an increased plasma relaxivity at higher concentrations. Adjustment of measured Gd-DTPA concentration was therefore performed using a selected power function, A[Gd-DTPA](a), which yielded the best linear relationship. Regression analysis showed that the scaling constant (A) varied from 0.11 to 97.45 and the power constant (a) varied from 0.83 to 1.6. Based on these constants, the MRI measured concentrations of Gd-DTPA did not differ from the calculated concentrations of Gd-DTPA obtained from reference measurements of (99m)Tc-DTPA. In the 1.5 T system, a linear relationship (r(2) > or = 0.95) was demonstrated in the range of 0-5.0 mmol/l Gd-DTPA, and in the 7 T system, a linear relationship (r(2) > or = 0.92) was demonstrated in the range of 0-3.0 mmol/l Gd-DTPA. Additionally, the effect of signal-to-noise on measured concentrations of Gd-DTPA was simulated using MR data of the mixed solutions of Gd-DTPA in plasma and the analytical expression of the pulse sequences. The simulations showed that the concentrations were most sensitive to noise in the GRASS sequence. In conclusion, this study demonstrates a novel approach to quantify accurately the Gd-DTPA concentration directly from MRI signal data using different routine sequences.
A new generation of imaging devices now make it possible to generate both structural and functional images for the study of lung biology in small animals, including common laboratory mouse and rat models. "Micro" X-ray computed tomography and positron emission tomography scanners, highly sensitive cooled charge coupled device cameras for bioluminescence and fluorescence imaging, high magnetic field magnetic resonance imaging scanners, and recent advances in ultrasound system technology can be used to study such diverse processes as ventilation, perfusion, pulmonary hypertension, lung inflammation, and gene transfer, among others. Images from more than one modality can also be fused, allowing structure-function and function-function relationships to be studied on a regional basis. These new instruments, part of an emerging suite of techniques collectively known as "molecular imaging," provide an enormous potential for elucidating lung biology in intact animal models and systems.
A method for dynamic imaging in MRI is presented that enables the acquisition of a series of images with both high temporal and high spatial resolution. The technique, which is based on the projection reconstruction (PR) imaging scheme, utilizes distinct data acquisition and reconstruction strategies to achieve this simultaneous capability. First, during acquisition, data are collected in multiple undersampled passes, with the view angles interleaved in such a way that those of subsequent passes bisect the views of earlier ones. During reconstruction, these views are weighted according to a previously described k-space weighted image contrast (KWIC) technique that enables the manipulation of image contrast by selective filtering. Unlike conventional undersampled PR methods, the proposed dynamic KWIC technique does not suffer from low image SNR or image degradation due to streaking artifacts. The effectiveness of dynamic KWIC is demonstrated in both simulations and in vivo, high-resolution, contrast-enhanced imaging of breast lesions.
Emphysema is one component of chronic obstructive pulmonary disease (COPD), a respiratory disease currently increasing in prevalence worldwide. The mainstay therapy adopted to treat patients with COPD is glucocorticoids; unfortunately, this treatment has limited impact on disease symptoms or underlying airway inflammation.
There is an urgent need to develop therapies that modify both the underlying inflammation, thought to be involved in disease progression, and the structural changes in the emphysematous lung.
We have characterized an elastase-driven model of experimental emphysema in the rat that demonstrates COPD-like airway inflammation and determined the impact of a clinically relevant glucocorticoid.
We observed an increase in lung neutrophils, lymphomononuclear cells, mucus production, and inflammatory cytokines. Also present were increases in average air space area, which are associated with emphysema-like changes in lung function, such as increased residual volume and decreased flow; these increases in area were maintained for up to 10 weeks. In addition, we observed that elastase-induced airway neutrophilia is steroid resistant. Interestingly, the inflammation observed after elastase administration was found to be temporally associated with a lack of nuclear factor-kappaB pathway activation. This apparent nuclear factor-kappaB-independent inflammation may explain why treatment with a glucocorticoid was ineffective in this preclinical model and could suggest parallels in the steroid-resistant human disease.
We believe that this model, in addition to its suitability for testing therapies that may modify existing emphysema, could be useful in the search for new therapies to reduce the steroid-resistant airway inflammation evident in COPD.
Allergic asthma is a complex chronic inflammatory disease of the airways and its etiology is multifactorial. It involves the recruitment and activation of many inflammatory and structural cells, all of which release inflammatory mediators that result in typical pathological changes of asthma. The features of asthma addressed in this Brown Norway (BN) rat animal model include an analysis of cellular infiltrations in the lung, inflammatory factors in bronchoalveolar lavage (BAL), total immunoglobulin E (IgE) production in serum, and changes in delayed-onset respiratory reactions upon four inhalation challenges (every 2 wk) with polymeric diphenylmethane diisocyanate (MDI) aerosol in two groups of topically sensitized rats. The dependence on the induction-related variables was analyzed by using almost identical surface area doses but different total doses per animal. This regimen caused acute exacerbations of delayed-onset respiratory reactions, for which intensity increased with each challenge. After the fourth challenge BAL neutrophils, lymphocytes, eosinophils, cell counts, protein, and lactate dehydrogenase (LDH) as well as lung weights were significantly increased in sensitized rats relative to naive but challenged controls. Histopathology revealed activated bronchial lymphatic tissue, increased recruitment of inflammatory cells, the beginning of peribronchial/peribronchiolar fibrosis, thickening of alveolar septae, and vascular hypertrophy. Total IgE in serum was significantly increased in sensitized rats. Thus, high-dose topical induction to, and repeated inhalation challenges with, MDI was associated with a marked neutrophilic and a less consistent eosinophilic inflammatory response. With regard to the relative sensitivity of endpoints, those that integrate independently a series of complex physiological events appeared to be most practical to probe positive responses in this animal model. These include postchallenge changes in Penh to identify respiratory responses delayed in onset as well as inflammatory changes in BAL. In summary, this extension of a previous study that used 16 mg MDI/m(3) instead of 39 mg MDI/m(3) that was used in the current study for challenge exposures demonstrates that protocol variables are most critical for the outcome of test. Moreover, the sensitivity of this bioassay to define the typical asthma phenotype can be markedly improved by measurements of respiratory responses delayed in onset rather than immediate in onset. Accordingly, to increase the efficacy of this asthma model moderately irritant concentrations of the hapten have to be used for challenge and at least three to four adequately spaced challenge exposures are required to elicit a typical asthma phenotype.
The Fourier inversion method for reconstruction of images in computerized tomography has not been widely used owing to the perceived difficulty of interpolating from polar or other measurement grids to the Cartesian grid required for fast numerical Fourier inversion. Although the Fourier inversion method is recognized as being computationally faster than the back-projection method for parallel ray projection data, the artifacts resulting from inaccurate interpolation have generally limited application of the method. This paper presents a computationally efficient gridding algorithm which can be used with direct Fourier transformation to achieve arbitrarily small artifact levels. The method has potential for application to other measurement geometries such as fan-beam projections and diffraction tomography and NMR imaging.
Undersampled projection-reconstruction imaging for time resolved contrast-enhanced imaging
- Vigen KK
- Peters DC
- Grist TM
- Block WF
- Mistretta CA
Respiratory physiology-the essentials
- Jb West
West, JB. Respiratory physiology-the essentials-. In: Coryell, PA., editor. Vol. 5th ed. Baltimore:
Williams & Wilkins; 1995. p. 193
15 O, Superscript (15) Uppercase " Oh " T 2 *, Uppercase " Tee
- Superscript He
He, Superscript (3) Uppercase " H ", lowercase " ee "
15 O, Superscript (15) Uppercase " Oh "
T 2 *, Uppercase " Tee ", subscript (2), superscript (Star)
N 2, Uppercase " N ", subscript (2)
ºC, degrees, Uppercase C
Δϕ, Greek upper case delta of " phi "