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Optimized radiographic spectra for small animal digital subtraction angiography
Abstract
The increasing use of small animals in basic research has spurred interest in new imaging methodologies. Digital subtraction angiography (DSA) offers a particularly appealing approach to functional imaging in the small animal. This study examines the optimal x-ray, molybdenum (Mo) or tungsten (W) target sources, and technique to produce the highest quality small animal functional subtraction angiograms in terms of contrast and signal-difference-to-noise ratio squared (SdNR2). Two limiting conditions were considered-normalization with respect to dose and normalization against tube loading. Image contrast and SdNR2 were simulated using an established x-ray model. DSA images of live rats were taken at two representative tube potentials for the W and Mo sources. Results show that for small animal DSA, the Mo source provides better contrast. However, with digital detectors, SdNR2 is the more relevant figure of merit. The W source operated at kVps >60 achieved a higher SdNR2. The highest SdNR2 was obtained at voltages above 90 kVp. However, operation at the higher potential results in significantly greater dose and tube load and reduced contrast quantization. A reasonable tradeoff can be achieved at tube potentials at the beginning of the performance plateau, around 70 kVp, where the relative gain in SdNR2 is the greatest.
... CACT was acquired in the control animal using 120 kVp at 200 and 150 mA with variations of scan time and frames per second (fps) ( Table I) using commercially available protocols. A low voltage prototype protocol (P4) of 80 kVp, 85 mA, 5 ms with 60 fps and 5-second scan time (sc) was also used to acquire CACT images based on prior work in small animals (19). The total angular range covered in a 10 (5) sec acquisition was 208 (205 ) for each rotational run. ...
... R1 images with standard reconstruction revealed an ill-defined hypodense area in the left lobe of the liver, which could be assumed to be a tumor, however the image quality was not sufficient to characterize the lesion. . Motion compensated reconstruction with standard resolution With application of motion compensated reconstruction (17,19,20) to the standard reconstructions (Figure 2c and 2d) there was a slight Table I), and rabbit 2 (R2) images were acquired using the prototype x-ray technique (d in Figure 1, P4 in Table I). A number of 3D reconstruction and motion compensation combinations were applied: Standard resolution reconstruction (a and b), motion compensation applied in addition to standard reconstruction (c and d), high resolution reconstruction with motion compensation (e and f). ...
... Furthermore, the low kVp x-ray technique showed improved IQ compared to the standard 120 kVp technique. This is due to the improved x-ray contrast at lower photon energies (19,22). For the standard 32 cm computed tomography dose index (CTDI) phantom improved contrast to noise ratio (CNR) for iodine contrast studies has been shown with the low kVp protocol used in this study (23). ...
Introduction:
C-Arm CT (CACT) is a new imaging modality in liver oncology therapy that allows for the acquisition of 3D images intra-procedurally. CACT has been used to enhance intra-arterial therapies for the liver by improving lesion detection, avoiding non-target embolization, and allowing for more selective delivery of agents. However, one of the limitations of this technology is image artifacts created by respiratory motion.
Purpose:
To determine in this preliminary study improvements in image acquisition, motion compensation, and high resolution 3D reconstruction that can improve CACT image quality (IQ).
Material and methods:
Three adult male New Zealand white rabbits were used for this study. First, a control rabbit was used to select the best x-ray acquisition imaging protocol and then two rabbits were implanted with liver tumor to further develop 3D image reconstruction and motion compensation algorithms.
Results:
The best IQ was obtained using the low 80 kVp protocol with motion compensated reconstruction with high resolution and fast acquisition speed (60 fps, 5 s/scan, and 312 images).
Conclusion:
IQ improved by: (1) decreasing acquisition time, (2) applying motion-compensated reconstruction, and (3) high resolution 3D reconstruction. The findings of this study can be applied to future animal studies and eventually could be translated into the clinical environment.
... 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 radiographic system used for this work has been constructed for functional small animal imaging with both highspatial resolution ͑100ϫ 100 m 2 pixels͒ and high-temporal resolution ͑10 ms exposures at 10 frames/s͒. 2,[23][24][25][26][35][36][37] The system employs a unique LABVIEW ͑National Instruments, Austin, TX͒ sequencer that allows synchronization of breathing, contrast injection, radiographic exposure, and digital frame acquisition with cardiac cycle. Images were acquired with x-ray techniques ͑80 kVp, 160 mA, and 10 ms͒ optimized for small animal DSA and thus limited beam hardening effects. ...
... Images were acquired with x-ray techniques ͑80 kVp, 160 mA, and 10 ms͒ optimized for small animal DSA and thus limited beam hardening effects. 26 Thermodilution measurements were acquired simultaneously with DSA images by capturing the output from the thermocouples with the LABVIEW sequence, which provided time sequences where the radiographic density of the DSA image was indexed to a thermodilution measurement at the same time. Each run was composed of 30 x-ray images following one contrast injection. ...
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.
... In addition, one such study also reported the usage of a high concentration of ICA (� 623mg-I/ml) [8]. In many high-end systems, i.e., systems offering high resolution, X-ray cameras consist of an X-ray scintillator either optically coupled or directly coupled with optical fibers to a cooled CCD camera [19]. Most systems offering high frame rates for angiography study utilize pulsed clinical X-ray tubes with large focal spots. ...
... The light collection efficiency (g oc ) = 0.0145 based on Eq 3. Each optical photon is expected to create 24 (19) electrons corresponding to monochrome(RGB) CMOS sensor [15]. ...
We present the design and characterization of an X-ray imaging system consisting of an off-the-shelf CMOS sensor optically coupled to a CsI scintillator. The camera can perform both high-resolution and functional cardiac imaging. High-resolution 3D imaging requires microfocus X-ray tubes and expensive detectors, while pre-clinical functional cardiac imaging requires high flux pulsed (clinical) X-ray tubes and high-end cameras. Our work describes an X-ray camera, namely an “optically coupled X-ray(OCX) detector,” used for both the aforementioned applications with no change in the specifications. We constructed the imaging detector with two different CMOS optical imaging cameras called CMOS sensors, 1.A monochrome CMOS sensor coupled with an f1.4 lens and 2.an RGB CMOS sensor coupled with an f0.95 prime lens. The imaging system consisted of our X-ray camera, micro-focus X-ray source (50kVp and 1mA), and a rotary stage controlled from a personal computer (PC) and LabVIEW interface. The detective quantum efficiency (DQE) of the imaging system(monochrome) estimated using a cascaded linear model was 17% at 10 lp/mm. The system modulation transfer function (MTF) and the noise power spectrum (NPS) were inputs to the DQE estimation. Because of the RGB camera’s low quantum efficiency (QE), the OCX detector DQE was 19% at 5 lp/mm. The contrast to noise ratio (CNR) at different frame rates was studied using the capillary tubes filled with various dilutions of iodinated contrast agents. In-vivo cardiac angiography demonstrated that blood vessels of the order of 100 microns or above were visible at 40 frames per second despite the low X-ray flux. For high-resolution 3D imaging, the system was characterized by imaging a cylindrical micro-CT contrast phantom and comparing it against images from a commercial scanner.
... Por otro lado, en los sistemas digitales la adquisición de la imagen puede optimizarse independientemente del despliegue de la imagen. Además, se puede decidir sobre la mejor combinaciónánodo-filtro para obtener una imagen específica [6]. ...
... La CHR calculada se obtuvo usando la relación 2.8. Dada esta definición, es necesario convertir el espectro de 6 Se usó un tubo de rayos X con el mismoánodo (W), voltajes de operación iguales y un filtrado (Al) similar a lo usado en el NIST, se obtuvieron las CHR con la CI y varios grosores de Al como material de referencia. 7 Según la nomenclatura del NIST los haces menos filtrados inician con "L", los haces medianamente filtrados inician con "M", y los altamente filtrados con "H" energía a un espectro de exposición, con las relaciones 2.9-2.12. ...
... For example, some researchers have implemented x-ray-based DSA of the thoracic and liver vasculature in mice. [17][18][19][20][21] Focusing on neurovascular imaging, we found no publications describing x-ray-based DSA of the murine cerebrovasculature. ...
... So far, only 1 group presented useful results on the method of cerebrovascular DSA in mice. 8,13,14,19,20 These results were obtained using a third-generation synchrotron radiation facility (SPring 8). Advantages of using a synchrotron are that it produces a significantly higher photon flux than conventional x-ray sources and the monochromatized x-ray energies just above the iodine K-edge energy produce the highest contrast. ...
Investigation of the anatomy, patency, and blood flow of arterial and venous vessels in small animal models of cerebral ischemia, venous thrombosis, or vasospasm is of major interest. However, due to their small caliber, in vivo examination of these vessels is technically challenging. Using micro-CT, we compared the feasibility of in vivo DSA and CTA of the murine cerebrovasculature using an intra-arterial route of contrast administration.
The ECA was catheterized in 5 C57BL/6J mice. During intra-arterial injection of an iodized contrast agent (30 μL/1 sec), DSA of the intra- and extracranial vessels was performed in mice breathing room air and repeated in hypoxic/hypercapnic mice. Micro-CTA was performed within 20 seconds of intra-arterial contrast injection (220 μL/20 sec). Image quality of both methods was compared. Radiation dose measurements were performed with thermoluminescence dosimeters.
Both methods provided high-resolution images of the murine cerebrovasculature, with the smallest identifiable vessel calibers of ≤50 μm. Due to its high temporal resolution of 30 fps, DSA allowed identification of anastomoses between the ICA and ECA by detection of retrograde flow within the superficial temporal artery. Micro-CTA during intra-arterial contrast injection resulted in a reduced injection volume and a higher contrast-to-noise ratio (19.0 ± 1.0) compared with DSA (10.0 ± 1.8) or micro-CTA when using an intravenous injection route (1.3 ± 0.4).
DSA of the murine cerebrovasculature is feasible using micro-CT and allows precise and repeated measurements of the vessel caliber, and changes of the vessel caliber, while providing relevant information on blood flow in vivo.
... To decrease the brightness of the image, thereby improving the contrast visible in the stained nerve, the voltage should be decreased, followed by the current (Sharir et al., 2011). At the same time, higher spatial resolution and statistical considerations require higher exposures to maintain the SNR (Lin et al., 2006). The highest exposure (0.25 fps) of the microCT scanner was used in the optimal protocol. ...
Background
Due to the lack of understanding of the fascicular organisation, vagus nerve stimulation (VNS) leads to unwanted off-target effects. Micro-computed tomography (microCT) can be used to trace fascicles from periphery and image fascicular anatomy.
New method
In this study, we present a simple and reproducible method for imaging fascicles in peripheral nerves with iodine staining and microCT for the determination of fascicular anatomy and organisation.
Results
At the determined optimal pre-processing steps and scanning parameters, the microCT protocol allowed for segmentation and tracking of fascicles within the nerves. This was achieved after 24 hours and 120 hours of staining with Lugol’s solution (1% total iodine) for rat sciatic and pig vagus nerves, respectively, and the following scanning parameters: 4 µm voxel size, 35 kVp energy, 114 µA current, 4 W power, 0.25 fps in 4 s exposure time, 3176 projections and a molybdenum target.
Comparison with existing method(s)
This optimised method for imaging fascicles provides high-resolution, three-dimensional images and full imaging penetration depth not obtainable with methods typically used such as histology, magnetic resonance imaging and optical coherence tomography whilst obviating time-consuming pre-processing methods, the amount of memory required, destruction of the samples and the cost associated with current microCT methods.
Conclusion
The optimised microCT protocol facilitates segmentation and tracking of the fascicles within the nerve. The resulting segmentation map of the functional anatomical organisation of the vagus nerve will enable selective VNS ultimately allowing for the avoidance of the off-target effects and improving its therapeutic efficacy.
... To decrease the brightness of the image, thereby improving the contrast visible in the stained nerve, the voltage should be decreased, followed by the current (Sharir et al., 2011). At the same time, higher spatial resolution and statistical considerations require higher exposures to maintain the SNR (Lin et al., 2006). The highest exposure (0.25 fps) of the microCT scanner was used in the optimal protocol. ...
Vagus nerve stimulation (VNS) is a promising therapy for treatment of various conditions resistant to standard therapeutics. However, due to the lack of understanding of the fascicular organisation of the vagus nerve, VNS leads to unwanted off-target effects. Micro-computed tomography (microCT) can be used to trace fascicles from periphery and image fascicular anatomy. In this work we optimised the microCT protocol of the rat sciatic and subsequent pig vagus nerves.
After differential staining, the optimal staining time was selected and scanning parameters were altered in subsequent scans. Scans were reconstructed, visualised in ImageJ and fascicles segmented with a custom algorithm in Matlab to determine ultimate parameters for tracking of the nerve. Successful segmentation for tracking of individual fascicles was achieved after 24 hours and 120 hours of staining with Lugol’s solution (1% total iodine) for rat sciatic and pig vagus nerves, respectively, and the following scanning parameters: 4 µm voxel size, 35 kVp energy, 114 µA current, 4 W power, 0.25 fps in 4 s exposure time, 3176 projections and a molybdenum target.
The optimised microCT protocol allows for segmentation and tracking of the fascicles within the nerve. This will be used to scan the full length of the pig, and possibly, the human vagus nerves. The resulting segmentation map of the functional anatomical organisation of the vagus nerve will enable selective VNS ultimately allowing for the avoidance of the off-target effects and improving its therapeutic efficacy.
... In this case, functional perfusion imaging, and angiographic imaging in general, can be addressed particularly well in small animal models using digital subtraction angiography (DSA). We have used DSA for both lung and tumor perfusion in the rodents [3,4] . To overcome the projection nature of DSA, tomosynthesis has been used to recover the depth information [5] . ...
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.
... Microcomputed tomography (microCT) systems generate 3D X-ray images of small animals enabling non-invasive studies to help creating models of human disease and evaluating pharmaceutical approaches [1,2]. MicroCTs require special features from the X-ray beam, due to the tradeoff between image quality and absorbed dose for small live subjects [3,4]. In general, X-ray tubes operate between 40 and 90 kV, focal spot sizes are of the order of tens of microns [2] and absorbed doses are between 0.1 and 0.3 Gy for a complete tomographic study [5]. ...
Non-filtered X-ray spectra from three tubes (Oxford Instruments Ultrabright microfocus W anode, Apogee Series 5000 with W and Mo anodes) appropriate for microCT scanners have been measured using a CdTe solid-state detector. The normalized and efficiency-corrected spectra have been parameterized using Boone et al. [10] third-order polynomial expression, obtaining good agreement with the data (typical mean ratio between parameterization and measurement equals 1.02, with standard deviation 0.10). Attenuation of the computed spectra by external filters was analytically simulated, obtaining results that agree well with direct measurements. The air kerma angular distribution of the X-ray beams was measured and the magnitude of the heel effect was evaluated. Tungsten collimators provided by the detector manufacturer had to be used to reduce dead time and it was found that their apertures do not necessarily agree with the nominal values.
... The scan parameters were 70 kVp, 400 mA and 45 kVp, 400 mA. The typical DSA technique used for our small animal imaging consisted of a series of 30 exposures (3,11). ...
Digital subtraction angiography (DSA) X-ray imaging for small animals can be used for functional phenotyping given its ability to capture rapid physiological changes at high spatial and temporal resolution. The higher temporal and spatial requirements for small-animal imaging drive the need for short, high-flux X-ray pulses. However, high doses of ionizing radiation can affect the physiology. The purpose of this study was to verify and apply metal oxide semiconductor field effect transistor (MOSFET) technology to dosimetry for small-animal diagnostic imaging. A tungsten anode X-ray source was used to expose a tissue-equivalent mouse phantom. Dose measurements were made on the phantom surface and interior. The MOSFETs were verified with thermoluminescence dosim-eters (TLDs). Bland-Altman analysis showed that the MOS-FET results agreed with the TLD results (bias, 0.0625). Using typical small animal DSA scan parameters, the dose ranged from 0.7 to 2.2 cGy. Application of the MOSFETs in the small animal environment provided two main benefits: (1) the availability of results in near real-time instead of the hours needed for TLD processes and (2) the ability to support multiple exposures with different X-ray techniques (various of kVp, mA and ms) using the same MOSFET. This MOSFET technology has proven to be a fast, reliable small animal dosimetry method for DSA imaging and is a good system for dose monitoring for serial and gene expression studies.
... Whilst DSa of the murine cerebrovasculature has hitherto only been reported by a group of researchers using a synchrotron for generation of monochromatic radiation [22,23], this study demonstrated that a similar approach can be undertaken using micro-ct. Others, however, used a microct setup for DSa of the rat and murine thoracic and liver vessels [24][25][26]. ...
Mice are often used as small animal models of brain ischemia, venous thrombosis, or vasospasm. This article aimed at providing an overview of the currently available methodologies for in vivo imaging of the murine cerebrovasculature and comparing the capabilities and limitations of the different methods.
Micro-computed tomography angiography (CTA) was performed during intra-arterial and intravenous administration of a contrast agent bolus. Digital subtraction angiography (DSA) was performed during intra-arterial administration of contrast agent using the micro-CT scanner. Time-of-flight (ToF) magnetic resonance (MR) angiography was performed using a small animal scanner (9.4 T) equipped with a cryogenic transceive quadrature coil. Datasets were compared for scan time, contrast-to-noise ratio (CNR), temporal and spatial resolution, radiation dose, contrast agent dose and detailed recognition of cerebrovascular structures.
Highest spatial resolution was achieved using micro-CTA (16 x 16 x 16 µm) and DSA (14 x 14 µm). Compared to micro-CTA (20-40 s) and ToF-MRA (57 min), DSA provided highest temporal resolutions (30 fps) allowing analyses of the cerebrovascular blood flow. Highest mean CNR was reached using ToF-MRA (50.7 ± 15.0), while CNR of micro-CTA depended on the intra-arterial (19.0 ± 1.0) and intravenous (1.3 ± 0.4) use of agents. The CNR of DSA was 10.0 ± 1.8.
The use of dedicated small animal scanners allows cerebrovascular imaging in live animals as small as mice. As each of the methods analyzed has its advantages and limitations, choosing the best suited imaging modality for a defined question is of great importance. By this means the aforementioned methods offer a great potential for future projects in preclinical cerebrovascular research including ischemic stroke or vasospasm.
... To meet this need, the technology for in vivo, small animal imaging has advanced rapidly in recent years to include magnetic resonance microscopy(Johnson, Hedlund et al. 1992), micro-CT(Holdsworth and Thornton 2002), micro-ultrasound(Hoit 2001), micro-PET/SPECT(Herschman 2003), and optical methods based on fluorescence and bioluminescence(Ntziachristos, Ripoll et al. 2005). We and others have recently added x-ray-based digital subtraction angiography (DSA) (Buhalog, Yasuda et al. ; Lin, Samei et al. 2006; Badea, Hedlund et al. 2007; Badea, Drangova et al. 2008) to this imaging armamentarium. ...
X-ray based digital subtraction angiography (DSA) is a common clinical imaging method for vascular morphology and function. Coronary artery characterization is one of its most important applications. We show that bi-plane DSA of rat coronary arteries can provide a powerful imaging tool for translational safety assessment in drug discovery.
A novel, dual tube/detector system, constructed explicitly for preclinical imaging, supports image acquisition at 10 frames/s with 88-micron spatial resolution. Ventilation, x-ray exposure, and contrast injection are all precisely synchronized using a biological sequence controller implemented as a LabVIEW application. A set of experiments were performed to test and optimize the sampling and image quality. We applied the DSA imaging protocol to record changes in the visualization of coronaries and myocardial perfusion induced by a vasodilator drug, nitroprusside. The drug was infused into a tail vein catheter using a peristaltic infusion pump at a rate of 0.07 mL/h for 3 min (dose: 0.0875 mg). Multiple DSA sequences were acquired before, during, and up to 25 min after drug infusion. Perfusion maps of the heart were generated in MATLAB to compare the drug effects over time.
The best trade-off between the injection time, pressure, and image quality was achieved at 60 PSI, with the injection of 150 ms occurring early in diastole (60 ms delay) and resulting in the delivery of 113 μL of contrast agent. DSA images clearly show the main branches of the coronary arteries in an intact, beating heart. The drug test demonstrated that DSA can detect relative changes in coronary circulation via perfusion maps.
The methodology for DSA imaging of rat coronary arteries can serve as a template for future translational studies to assist in safety evaluation of new pharmaceuticals. Although x-ray imaging involves radiation, the associated dose (0.4 Gy) is not a major limitation.
... Because selective arterial catheterization combined with DSA is the only method that provides a means for real-time high spatial and temporal resolution imaging of the delivery and distribution of drugs, devices, or cells, it was our intent to develop a method that would allow investigators to repeatedly perform, during an extended period of time, arterial catheterizations and angiography in a rodent. [1][2][3][4][5][6][7] To our knowledge, there has been no work describing techniques that would allow minimally invasive endovascular interventions and DSA examinations to be performed on rodents in such a manner that the animals could survive and then be studied subsequently with angiography at Ն2 followup intervals. By using the transfemoral techniques described below, we have optimized a vascular access protocol for rats so that it is possible to perform organ-specific selective angiogra-phy (eg, renal, subclavian, aortic, hepatic, mesenteric, iliac, and cerebral arteries) in such a way that at least 3 separate DSA studies can be performed on the same vessels in the same animal during an extended period of time. ...
Imaging is a key element in the study of many rodent models of human diseases. The application of DSA has been limited in these studies in part because of a lack of a method that allows serial intra-arterial examinations to be performed during an extended period of time. It was our intent to develop and test a method for performing sequential arterial catheterizations and DSA in rats.
Using a transfemoral approach, we subjected 12 adult male Harvey rats to 3 sequential DSA examinations during a 6- to 8-week period. At each examination, 2 selective arterial catheterizations and a DSA were performed. Animals were monitored for ill effects, and images from the 3 examinations were compared for quality and the presence of any arterial injury.
Ten of the 12 rats survived all 3 examinations. There were no adverse effects noted and no evidence of arterial injury from the examinations.
With the technique described, it is possible to perform serial arterial catheterizations and DSA in rats. This technique will be useful as an adjunct in the use of rodents for the study of human diseases.
... X-ray exposure was determined using an ionization chamber (Electrometer Model 9015, Probe 10×5-6, MDH Radcal, Monrovia, CA). Exposure (Roentgens) was converted to dose (Gray) using an f-factor of 0.9312 (Lin and Samei, 2006). The appropriate x-ray techniques (mAs at 70 kVp) were empirically tuned to produce 0-12 Gy of x-ray dose (Rossler et al., 2006). ...
Osteoarthritis (OA) is associated with increased levels of reactive oxygen species. This study investigated if increased oxidative DNA damage accumulates in OA articular cartilage compared with non-OA articular cartilage from pigs with spontaneous OA. Additionally, the ability of nitric oxide (NO) or peroxynitrite (ONOO(-)) induced DNA damage in non-OA chondrocytes to undergo endogenous repair was investigated. Porcine femoral condyles were graded for the stage of OA, macroscopically by the Collins Scale, and histologically by the modified Mankin Grade. Levels of DNA damage were determined in non-OA and OA cartilage, using the comet assay. For calibration, DNA damage was measured by exposing non-OA chondrocytes to 0-12 Gray (Gy) of X-ray irradiation. Non-OA articular chondrocytes were treated with 0-500 microM of NO donors (NOC-18 or SIN-1), and DNA damage assessed after treatment and 5 days recovery. A significant increase (P < 0.01) in oxidative DNA damage occurred in OA chondrocytes in joints with Mankin Grades 3 or greater, compared to non-OA chondrocytes. The percentage of nuclei containing DNA damage increased significantly (P < 0.001) from early to late grades of OA. An increase of approximately 0.65-1.7 breaks/1,000 kb of DNA occurred in OA, compared to non-OA nuclei. NOC-18 or SIN-1 caused significant DNA damage (P < 0.001) in non-OA chondrocytes that did not undergo full endogenous repair after 5 days (P < 0.05). Our data suggest significant levels of oxidative DNA damage occur in OA chondrocytes that accumulates with OA progression. Additionally, DNA damage induced by NO and ONOO(-) in non-OA chondrocytes does not undergo full endogenous repair.
... First suggested by Mistretta et al 7 , DSA is now a routine clinical exam. To date, there have been only limited studies using DSA in small animals [8][9][10] . Yet, potential exists for this modality given its ease of use, potential speed, and relatively low cost. ...
In vivo measurements of perfusion present a challenge to existing small animal imaging techniques such as magnetic resonance microscopy, micro computed tomography, micro positron emission tomography, and microSPECT, due to combined requirements for high spatial and temporal resolution. We demonstrate the use of tomographic digital subtraction angiography (TDSA) for estimation of perfusion in small animals. TDSA augments conventional digital subtraction angiography (DSA) by providing three-dimensional spatial information using tomosynthesis algorithms. TDSA is based on the novel paradigm that the same time density curves can be reproduced in a number of consecutive injections of microL volumes of contrast at a series of different angles of rotation. The capabilities of TDSA are established in studies on lung perfusion in rats. Using an imaging system developed in-house, we acquired data for four-dimensional (4D) imaging with temporal resolution of 140 ms, in-plane spatial resolution of 100 microm, and slice thickness on the order of millimeters. Based on a structured experimental approach, we optimized TDSA imaging providing a good trade-off between slice thickness, the number of injections, contrast to noise, and immunity to artifacts. Both DSA and TDSA images were used to create parametric maps of perfusion. TDSA imaging has potential application in a number of areas where functional perfusion measurements in 4D can provide valuable insight into animal models of disease and response to therapeutics.
... 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.
The contrast of iodine to soft tissue (water) decreases with higher tube voltage in reconstructed 3D X-ray images. Improved acquisition protocols with a tube voltage of about 80 kV for imaging iodine have been proposed earlier for diagnostic CT imaging. We investigate the contrast-to-noise ratio (CNR) and the CNR-to-dose ratio (CDR) for different concentrations of iodinated contrast agent inserts in water background. The tube voltage of the protocol is lowered from 123 kV to 83 kV in 10 kV steps. A series of measurements with 16 different settings of tube voltage, current and filter settings are investigated. The weighted computed tomography dose index CTDIW for the new protocol settings is measured.
Four protocols with tube voltages between 83 kV and 103 kV and similar X-ray dose are compared to the original protocol. A low contrast phantom, containing a water filled cylinder with 5 tubes of different mixtures of iodine contrast inside a 32 cm PMMA ring, is imaged with each protocol. Increased contrast of the iodine filled tubes to the water background is clearly visible in the reconstructed volumes for lower tube voltage and less copper filtering. The best results are obtained with the (83 kV, 561 mA, 0.4 Cu) – protocol. This protocol may improve iodine contrast agent visibility in various D imaging applications. For large patients a higher tube voltage, e.g. the (103 kV, 325 mA, 0.4 Cu) – protocol, may be used to avoid tube power limitations at 83 kV. This protocol still has improved iodine imaging compared to the 123 kV protocol and a larger tube power reserve.
Small animal microcomputed tomography (microCT) studies with iodine-based contrast media are commonly used in preclinical research. While the use of contrast media improves the quality of the images, it can also result in an increase in the absorbed dose to organs with high concentration of the contrast agent, which might cause radiation damage to the animal. In this work we present the results of a Monte Carlo investigation of a microCT dosimetry study using mouse-sized cylindrical water phantoms with iodine contrast insets for different X-ray spectra (Mo and W targets, 30−80kVp), iodine concentrations (0, 5, 10 and 15mgmL−1) and contrast object sizes (3 and 10mm diameter). Our results indicate an absorbed dose increase in the contrast-inset regions with respect to the absorbed dose distribution within a reference uniform water phantom. The calculated spatial absorbed dose distributions show large gradients due to beam hardening effects, and large absorbed dose enhancement as the mean energy of the beam and iodine concentration increase. We have found that absorbed doses in iodine contrast objects can increase by a factor of up to 12 for a realistic 80kVp X-ray spectra and an iodine concentration of 15mgmL−1.
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.
Small-animal imaging has a critical role in phenotyping, drug discovery and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to review in vivo x-ray based small-animal imaging, with a focus on in vivo micro-computed tomography (micro-CT) and digital subtraction angiography (DSA). We present the principles, technologies, image quality parameters and types of applications. We show that both methods can be used not only to provide morphological, but also functional information, such as cardiac function estimation or perfusion. Compared to other modalities, x-ray based imaging is usually regarded as being able to provide higher throughput at lower cost and adequate resolution. The limitations are usually associated with the relatively poor contrast mechanisms and potential radiation damage due to ionizing radiation, although the use of contrast agents and careful design of studies can address these limitations. We hope that the information will effectively address how x-ray based imaging can be exploited for successful in vivo preclinical imaging.
Digital subtraction angiography (DSA) X-ray imaging for small animals can be used for functional phenotyping given its ability to capture rapid physiological changes at high spatial and temporal resolution. The higher temporal and spatial requirements for small-animal imaging drive the need for short, high-flux X-ray pulses. However, high doses of ionizing radiation can affect the physiology. The purpose of this study was to verify and apply metal oxide semiconductor field effect transistor (MOSFET) technology to dosimetry for small-animal diagnostic imaging. A tungsten anode X-ray source was used to expose a tissue-equivalent mouse phantom. Dose measurements were made on the phantom surface and interior. The MOSFETs were verified with thermoluminescence dosimeters (TLDs). Bland-Altman analysis showed that the MOSFET results agreed with the TLD results (bias, 0.0625). Using typical small animal DSA scan parameters, the dose ranged from 0.7 to 2.2 cGy. Application of the MOSFETs in the small animal environment provided two main benefits: (1) the availability of results in near real-time instead of the hours needed for TLD processes and (2) the ability to support multiple exposures with different X-ray techniques (various of kVp, mA and ms) using the same MOSFET. This MOSFET technology has proven to be a fast, reliable small animal dosimetry method for DSA imaging and is a good system for dose monitoring for serial and gene expression studies.
Small rodents such as mice and rats are frequently used in animal experiments for several reasons. In the past, animal experiments were frequently associated with invasive methods and groups of animals had to be killed to perform longitudinal studies. Today's modern imaging techniques such as magnetic resonance imaging (MRI) allow non-invasive longitudinal monitoring of multiple parameters. Although only a few institutions have access to dedicated small animal MR scanners, most institutions carrying out animal experiments have access to clinical MR scanners. Technological advances and the increasing field strength of clinical scanners make MRI a broadly available and viable technique in preclinical in vivo research. This review provides an overview of current concepts, limitations, and recent studies dealing with small animal imaging using clinical MR scanners.
Mask mode intravenous digital subtraction angiography (IV-DSA) image quality is directly dependent on the arterial time-concentration curve peak and width produced by contrast media. Curves with high peak iodine concentration produce excellent difference images. Curves that are narrow appear and disappear quickly and minimize movement artifacts. Using a noninvasive x-ray technique for quantitative measurement of contrast media time-concentration curve parameters and cardiac output, three experimental data bases were analyzed. From the analyses, equations defining curve peak and width were derived and validated. Width is proportional to central blood volume and inversely proportional to cardiac output. Peak is proportional to the quantity of contrast media injected and inversely proportional to central blood volume. Hypertonic contrast media increases central blood volume and lowers curve peak. Optimal contrast media for IV-DSA is low in concentration and high in volume. In addition, low concentration contrast media may be more comfortable for the patient causing fewer motion artifacts.
At a given radiation dosage and field of view, five variables are under meaningful control for intravenous digital subtraction angiography (IV-DSA): concentration and quantity of contrast media injected, volume of injectate, rate of injection, and site of injection. Some controversy exists regarding the selection of a central vs. a peripheral injection site for IV-DSA. This study determined the influence of the site of injection on the peak and width of the arterial time-concentration curve produced by contrast media. Using a noninvasive, in vivo, quantitative x-ray measurement method, 36 separate injections (10 ml of ioxaglate at 8 ml/sec) were administered into the cephalic vein, subclavian vein, and main pulmonary artery in dogs. Injection sites were varied using a Latin-square experimental design. Cardiac output, central blood volume and the peak and width of the contrast media time-concentration curves were measured. The average peak enhancement was greatest for the pulmonary artery injection site. Normalizing peak and width values to make the pulmonary artery values 100%, the average peak values for injections into the subclavian vein and cephalic vein were 93% and 56%, and the average widths were 141% and 163%, respectively. These data support the use of a more central injection site for optimizing IV-DSA examinations.
Computerized fluoroscopy is a system comprising on-line digital time and energy subtraction algorithms designed to isolate and enhance the iodine signal from image intensified fluoroscopy. The apparatus is described and its use for time subtraction intravenous arteriography of the carotid, abdominal, extremely arteries, as well as the heart, is illustrated. Vascular diseases such as stenoses, obstruction, emboli, ulcerative plaques, and aneurysms are readily demonstrated. The technique has a potential for evaluating cardiac motion and the patency of coronary artery bypass grafts. The method appears to be a safe and less expensive alternative to catheter arteriography and angiocardiography in certain instances.
A Monte Carlo program has been developed that incorporates a voxel phantom of an adult patient in a model of the complete X-ray imaging system, including the anti-scatter grid and screen-film receptor. This allows the realistic estimation of patient dose and the corresponding image (optical density map) for a wide range of equipment configurations. This paper focuses on the application of the program to lumbar spine anteroposterior and lateral screen-film examinations. The program has been applied to study the variation of physical image quality measures and effective dose for changing system parameters such as tube voltage, grid design and screen-film system speed. These variations form the basis for optimization of these system parameters. In our approach to optimization, the best systems are those that can match (or come close to) the calculated image quality measure of systems preferred in a recent European clinical trial, but with lower patient dose. The largest dose savings found were 21% for a 400 speed class system with a grid having a strip density of 40 cm(-1) and a grid ratio of 16. A further dose saving of 13% was possible when a 600 speed class system was employed. The best systems found from the optimization correspond to those recommended by the European Commission guidelines on image quality criteria for diagnostic radiographic images.
Cardiopulmonary imaging in rodents using micro‐computed tomography (CT) is a challenging task due to both cardiac and pulmonary motion and the limited fluence rate available from micro‐focus x‐ray tubes of most commercial systems. Successful imaging in the mouse requires recognition of both the spatial and temporal scales and their impact on the required fluence rate. Smaller voxels require an increase in the total number of photons (integrated fluence) used in the reconstructed image for constant signal‐to‐noise ratio. The faster heart rates require shorter exposures to minimize cardiac motion blur imposing even higher demands on the fluence rate. We describe a system with fixed tube/detector and with a rotating specimen. A large focal spot x‐ray tube capable of producing high fluence rates with short exposure times was used. The geometry is optimized to match focal spot blur with detector pitch and the resolution limits imposed by the reproducibility of gating. Thus, it is possible to achieve isotropic spatial resolution of 100μm with a fluence rate at the detector 250 times that of a conventional cone beam micro‐CT system with rotating detector and microfocal x‐ray tube. Motion is minimized for any single projection with 10ms exposures that are synchronized to both cardiac and breathing motion. System performance was validated in vivo by studies of the cardiopulmonary structures in C57BL/6 mice, demonstrating the value of motion integration with a bright x‐ray source.
Attenuation correction is one of the important corrections required for quantitative positron emission tomography (PET). This work will compare the quantitative accuracy of attenuation correction using a simple global scale factor with traditional transmission-based methods acquired either with a small animal PET or a small animal x-ray computed tomography (CT) scanner. Two phantoms (one mouse-sized and one rat-sized) and two animal subjects (one mouse and one rat) were scanned in CTI Concorde Microsystem's microPET Focus for emission and transmission data and in ImTek's MicroCAT II for transmission data. PET emission image values were calibrated against a scintillation well counter. Results indicate that the scale factor method of attenuation correction places the average measured activity concentration about the expected value, without correcting for the cupping artefact from attenuation. Noise analysis in the phantom studies with the PET-based method shows that noise in the transmission data increases the noise in the corrected emission data. The CT-based method was accurate and delivered low-noise images suitable for both PET data correction and PET tracer localization.
Demonstrate noninvasive imaging methods for in vivo characterization of cardiac structure and function in mice using a micro-CT system that provides high photon fluence rate and integrated motion control.
Simultaneous cardiac- and respiratory-gated micro-CT was performed in C57BL/6 mice during constant intravenous infusion of a conventional iodinated contrast agent (Isovue-370), and after a single intravenous injection of a blood pool contrast agent (Fenestra VC). Multiple phases of the cardiac cycle were reconstructed with contrast to noise and spatial resolution sufficient for quantitative assessment of cardiac function.
Contrast enhancement with Isovue-370 increased over time with a maximum of approximately 500 HU (aorta) and 900 HU (kidney cortex). Fenestra VC provided more constant enhancement over 3 hr, with maximum enhancement of approximately 620 HU (aorta) and approximately 90 HU (kidney cortex). The maximum enhancement difference between blood and myocardium in the heart was approximately 250 HU for Isovue-370 and approximately 500 HU for Fenestra VC. In mice with Fenestra VC, volumetric measurements of the left ventricle were performed and cardiac function was estimated by ejection fraction, stroke volume, and cardiac output.
Image quality with Fenestra VC was sufficient for morphological and functional studies required for a standardized method of cardiac phenotyping of the mouse.
A Monte Carlo program has been developed that incorporates a voxel phantom of an adult patient in a model of the complete X-ray imaging system, including the anti-scatter grid and screen–film receptor. This allows the realistic estimation of patient dose and the corresponding image (optical density map) for a wide range of equipment configurations. This paper focuses on the application of the program to lumbar spine anteroposterior and lateral screen–film examinations. The program has been applied to study the variation of physical image quality measures and effective dose for changing system parameters such as tube voltage, grid design and screen–film system speed. These variations form the basis for optimization of these system parameters. In our approach to optimization, the best systems are those that can match (or come close to) the calculated image quality measure of systems preferred in a recent European clinical trial, but with lower patient dose. The largest dose savings found were 21% for a 400 speed class system with a grid having a strip density of 40 cm⁻¹ and a grid ratio of 16. A further dose saving of 13% was possible when a 600 speed class system was employed. The best systems found from the optimization correspond to those recommended by the European Commission guidelines on image quality criteria for diagnostic radiographic images.
The handbook is a compendium of experimentally acquired and corrected x-ray spectra obtained from three conventional mammographic x-ray tubes (tungsten, molybdenum-tungsten, and molybdenum targets) and from a special purpose tube often used for mammography (RSI tungsten anode). The experimental data are divided into five parts. The first section presents graphical displays of exposure data (mR/mAs at 1 meter) that correspond to experimental spectra. The second section describes and compares parameters of 30 kVp x-ray beams produced by the anode material types used in mammographic tubes. The third section describes the data format used for displaying the graphical overlays and for the numerical tabulation of x-ray spectra. In the fourth section specifically selected spectral overlays are used to (1) compare the energy content of x-ray beams produced by different anode materials and x-ray systems, (2) illustrate x-ray beam shaping by using K-edge filters, and (3) demonstrate x-ray beam hardening with phantom materials. The last section contains numerical tabulations of x-ray spectra produced by mammographic tubes. While these spectra may not be inclusive they should be representative of a range of mammographic techniques of each tube and system tested. The additional information contained with each tabulation should make it possible for the experimenter to simulate each spectrum by measuring the kVp, filtration, and HVL of the x-ray beam.
The bremsstrahlung energy distribution from a thick tungsten target is calculated from the Sommerfeld and Born-approximation thin-target formulas, taking into account electron energy losses, electron backscatter losses, and photon attenuation in the target. Over-all agreement with measurement is 20% in the 12-100-keV energy range, increasing to 50% at 300 keV. Semiempirical expressions are developed that give 20% over-all agreement with measurement in the 12-300-keV energy range.
An abstract is not available.
The extrapolated or practical range Rex of monoenergetic electrons in the energy region 0.3 keV–30 MeV for the absorbers of atomic number 6–92 has been found to be expressed by a single simiempirical equation of the form Rex=a_1[(1/a_2)ln(1+a_2τ)−a_3τ/(1+a_4τ^a_5)], where τ is the incident kinetic energy in units of the rest energy of the electron, and the parameters ai (i=1, 2, …, 5) are given by simple functions of atomic number Z. Values of nine constants to express ai have been determined by least-squares fit to a total of 232 experimental points reported in 18 references; the data used have been confined to those obtained from number- transmission measurement. The rms deviation of the equation from the experimental data is 4.5% for energies above 1 MeV and 8.4% for the entire energy region. Although the latter value is rather large, it is mainly due to large fluctuation of the experimental data for energies below 1 MeV. An approximate inverse relation which expresses τ as a function of Rex is also given.
A method is proposed for calculating L and K photon emission from thick tungsten targets bombarded by electrons accelerated by potentials of 12–300 kV. Electron energy losses, electron backscatter losses, and photon attenuation in the target are included. Agreement with measured K emission is obtained using the Arthurs-Moiseiwitsch ionization cross sections and an expression of the form CZ (E<sub>0</sub>-k) 1- exp (-3k/E<sub>K</sub>) (k/E<sub>0</sub>)<sup>1/3</sup> 1- exp (-E<sub>0</sub>/E<sub>K</sub>) to describe the bremsstrahlung energy distribution. Satisfactory agreement with L-emission measurements is obtained using the Mott-Massey cross-section formula with constants B<sub>L<sub>i</sub></sub>=4 E<sub>L<sub>i</sub></sub>, b<sub>L<sub>I</sub></sub>=0.25×1.6, b<sub>L<sub>II</sub></sub>=0.25×2.75, and b<sub>L<sub>III</sub></sub>=0.25×4.2. Indirect radiation contributes 54–82% of the total K emission and 5–8% of the total L emission. The Webster-Clark empirical relation I<sub>i</sub>=C<sub>i</sub>(U<sub>0</sub>-1)<sup>n</sup>i agrees with calculation for U<sub>0</sub>≪3, with C<sub>K</sub>=5.1×10<sup>11</sup> photon/sec mA sr, n<sub>K</sub>=1.67, C<sub>L</sub>=2.6×10<sup>11</sup> photon/sec mA sr, and n<sub>L</sub>=1.5.
X-ray source filtration as a means to reduce patient dose while maintaining image quality was investigated for CT scanners. The CT values, their variances for various materials, and the surface dose to a cylindrical phantom were calculated for different filter thicknesses and composition as well as for different tube potentials. Thermoluminescent dosimetry indicated that the maximum dose could be predicted by calculation with an accuracy of 10% (+/- 2 s.d.). The product of the variance of the CT values times surface dose was used to establish the appropriate thickness and composition of the filter, a figure of merit that was independent of dose and noise when the sole source of noise was Poisson statistics. This analysis indicated that source filter materials with an atomic number from 29 to 40 are optimum, and if aluminum is used, the minimum thickness, at 120 kVp, should be 4 mm.
Possible mammographic advantages of "trans-molybdenum" anodes (atomic number greater than ZMo) are decreased dose because the fluorescent radiation is more penetrating, and increased useful output; contrast degradation is known to be tolerable. The output per mAs, the HVT in Al, and the penetration in Lucite were measured spectroscopically for an experimental Rh-anode tube and also for Mo- and W-anode mammographic tubes. The trans-molybdenum tube was shown to have output and dose advantages over Mo anodes, and output and contrast advantages over normal and selectively filtered W anodes. Possible applications in areas other than mammography are briefly discussed.
The digital subtraction angiography has revealed the great potential of the angiographic diagnostics of children lung diseases with its intravenous introduction of contrast material, greatly reduced amount of the contrast agent used and the irradiation dose applied. Angiopulmography is one of the basic methods for proving the presence of malformations, their characteristic and degree of development. We did 29 digital subtraction angiographies in 13 children aged 2 months to 7 years. We found the following malformations: hypoplasia of one of the branches of a. pulmonalis with the other branch aneurysmally dilated, hypoplasia and agenesis of a lobar branch, confirmed also by digital bronchoradiography, lobar emphysema, mediastinal and pulmonary hemangiomatosis. In addition to the advantages given above the digital subtraction angiography reduces the trauma rate due to the possibility of avoiding catheterization by using peripheral venous pathways. It also allows both qualitative and quantitative processing of the image.
A silicon target storage tube has been used in a new technique for enhancing time-dependent mass differences. The storage tube's unique ability far positive and negative video integrations is used. The method relies upon summing the differences of a series of consecutive positive and negative images taken in synchrony with the instants of maximum deviation of a time-dependent mass. Possible applications include the production of arterial maps by exploiting the small pulsatile distention of the pulmonary arteries or the motion of the vessels in the region of the aortic arch. The details of this technique and our preliminary results using phantems are discussed.
A comparative study of radionuclide scanning (perfusion studies in all 18 patients and ventilation studies in 9) and digital subtraction angiography (DSA) was performed in 18 patients with suspected pulmonary thromboembolism. In 17 patients good visualization of the arteries was obtained with DSA; 10 of these patients had no pre-existing lung disease, and 7 had chronic obstructive pulmonary disease (COPD). The information provided by DSA in this small group was equal to or better than that of scintigraphy, especially in patients with COPD, and the reliability of DSA was superior to that of radionuclide scintigraphy. Methods for preventing motion artifacts with DSA are also described.
Detectability of low-contrast objects (vessels) in subtraction imaging depends on the noise properties of the image. There is a structure imposed upon the quantum noise that is due to the attenuation of the subtracted background object; this structure is referred to as a "noise print." It is shown to be a function of the manner of presubtraction processing (linear or logarithmic) and the local thickness of the attenuator in the x-ray beam path. The influence of the noise print on the visibility of vessels in subtraction images is demonstrated.
The conversion of fluoroscopic x-ray data into a digital form has an added advantage for the study of the central cardiovascular system: it permits the contrast enhancement of the images and also facilitates quantitative and functional analysis of the x-ray data. Several applications are described in this article.
Initial clinical application of a system for digital subtraction angiography (DSA) to the human cardiovascular system in 88 patients is reported. The equipment consisted of a specially designed computer system integrated with a fluoroscopic and radiographic apparatus for digitization, manipulation, and display of data. After intravenous injection of contrast material, adequate visualization of the heart and carotid, thoracic, abdominal, and femoral arteries was obtained with sufficient quality to obviate conventional angiography in many clinical settings. In this mode, nonselective opacification is obtained. However, DSA was also used to extend the capability of selective angiography. The availability of quantitative information permitted the determination of rates of transit of contrast material in various organs which may give insights of their physiologic performance.
Digital video subtraction angiography (DVSA) after central intravenous administration of contrast media was used in experimental animals and in patients with suspected coronary artery disease to quantitate left ventricular dimensions and regional and global contractile function. In animals, measurements of left ventricular (LV) volumes, wall thickness, ejection fraction, segmental contraction, and cardiac output correlated closely with sonocardiometry or thermodilution measurements. In patients, volumes and ejection fractions calculated from mask mode digital images correlated closely with direct left ventriculography. Global and segmental contractile function was displayed in patients by ejection shell images, stroke volume images, and time interval difference images. Central cardiovascular function was also quantitated by measurement of pulmonary transit time and calculation of pulmonary blood volume from digital fluoroscopic images. DVSA was shown to be useful and accurate in the quantitation of central cardiovascular physiology.
Attempts to simulate Mo-anode spectra for film mammography by using Mo filters with W-anode tubes have been reported by several workers, and others have generated W-like continua for xeromammographic purposes by heavy Al filtration of Mo-anode tubes. In the present work the success of these simulations was tested by Si(Li) spectrometric methods that measured the spectral shapes and the exposure levels. Comparisons of Mo-anode/Al-filter with W-anode/Al-filter combinations were made, and also of W-anode/M-filter with Mo-anode/Mo-folter combinations. In certain circumstance the spectral shape is moderately well simulated but in all cases the useful output is less in the simulations than in the original spectra. The general conclusion is that simulation is always less attractive than direct use of the desired anode.
The present study reports the development and characterization of a murine model of right ventricular dysfunction following graded constriction in the pulmonary artery via microsurgical approaches. To analyze in vivo ventricular function, a technique of x-ray contrast microangiography was developed to allow the quantitative analysis of ventricular volumes and of ejection fraction in normal and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial banding for 14 days resulted in right ventricular dilatation and dysfunction, associated with right atrial enlargement, and angiographic evidence of tricuspid regurgitation. These effects were dependent on the extent of hemodynamic overload, since more moderate pulmonary arterial constriction resulted in hypertrophy with maintenance of right ventricular function. With severe pulmonary artery constriction, the murine right ventricle displays a failing heart phenotype including chamber dilation with reduced function that resembles right ventricular dysfunction in man during chronic pulmonary arterial hypertension. Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca(2+)-ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction. By coupling mouse genetics with this murine model and the ability to assess cardiac function in vivo, one should be able to test the role of the down-regulation of phospholamban and other defined alterations in the cardiac muscle gene program in the onset of the failing heart phenotype.
The aim was to develop a digital video contrast angiographic method for assessing global left ventricular function and volume in vivo in the rat and then to apply it to a study of ventricular remodelling after coronary occlusion, with and without reperfusion.
Digital contrast angiography was performed on 29 rats, including the following groups: sham operated (n = 11), non-transmural myocardial infarction produced by reperfusion (n = 8), and transmural infarction produced by permanent occlusion (n = 10). Under anaesthesia three weeks later, biplane fluoroscopic images were acquired following venous contrast injection. Levophase images were digitised, and left ventricular end diastolic and end systolic volumes and ejection fractions were obtained using an area-length method. Left ventricular ejection fraction data also were calculated by videodensitometry from video density curves.
Compared to the sham operated group, the reperfused group showed a significant decrease in left ventricular ejection fraction, at 53(SD 7) v 70(5)% (p < 0.01), and an increase in end diastolic volume. The permanent occlusion group showed a further decrease in the ejection fraction [40(8)%] and a further significant increase in end diastolic volume compared to the reperfused group (p < 0.01). Left ventricular ejection fraction correlated inversely with percent infarct size (r = 0.882) and showed a positive correlation with the spared epicardial area (r = 0.721). Most haemodynamic variables, including maximum left ventricular dP/dt, failed to discriminate between the groups. The methods showed reasonable accuracy when tested in vitro using contrast filled balloons. In vivo, the left ventricular ejection fraction calculated by densitometry showed adequate interobserver variability (2 SD +/- 8.5 percentage points), but the area-length method showed somewhat more scatter.
Digital video contrast angiography is a feasible method for the assessing global left ventricular function in the rat and should be useful in other small animal models. Significant differences in left ventricular volumes and ejection fractions were detected between reperfused and permanent occlusion groups, whereas haemodynamic variables showed non-significant trends. Reperfusion after 45 min of occlusion caused sparing of the epicardium, prevented unfavourable remodelling, and improved the ejection fraction compared to permanent occlusion.
The introduction of a dual-track anode X-ray unit for mammography (IGE Senographe DMR) prompts some consideration of the optimization of X-ray spectra used for this examination on existing units. A considerable number of the X-ray units used for screening and symptomatic mammography in the UK and elsewhere employ a molybdenum anode tube with molybdenum filtration, usually 0.03 mm thick, using a tube potential of around 30 kVp.
To compare the diagnostic performance of digital subtraction angiography (DSA) to that of film-screen angiography (FSA) for detecting acute pulmonary embolism (PE) in a porcine model.
DSA and FSA were performed in 13 pigs before and after central venous administration of autologous emboli. Results were compared to findings at necropsy with use of ex vivo pulmonary angiography to guide pathologic sectioning. The sensitivity and predictive value of a positive case for detecting each embolus were computed for each pulmonary artery branch order and compared with use of 95% confidence intervals. Interobserver variability among three readers for individual PE detection was calculated.
Pathologic examination of the lungs revealed 100 total PEs (location by vessel order: 1st = 1, 2nd = 0, 3rd = 15, 4th = 32, > 5th = 52). On average, FSA review identified 72 (72%) emboli and DSA review, 65 (65%). There was no significant difference in sensitivity or predictive value of a positive case between DSA and FSA for detecting emboli (P > .05). There was similar agreement among readers for individual PE detection with DSA (mean, 84%) and FSA (mean, 80%).
The diagnostic performance of DSA is equivalent to that of FSA for detecting emboli in porcine PA branches. Interobserver agreement for individual PE detection is similar for both imaging techniques.
Real time and high resolution functional imaging of cerebral perfusion was developed, which displays the color coded image of the cerebral perfusion index (PI) from the serial images of digital subtraction angiography (DSA). The small (3 x 3 pixels) regions of interest (ROI) were set on the images, and the time density curves of the contrast media for each ROI were obtained. The perfusion indices, corresponding to the mean transit time (MTT), were calculated for all the ROIs on the image in real time (5 sec) by the area over height method and then, converted to the PI image. A large ROI (64 x 64 pixels) was also used to estimate the parenchymal perfusion. In the normal subjects, consistent PI values at the various parts of the cerebral arteries were obtained, which reasonably agreed with the published values when converted to the blood flow. Then the study on the pathological subjects were made. Firstly, the alteration in the PI images agreed well with the CBF SPECT study in the case of moyamoya disease with the synangiosis operation. Secondly, even a 5% change of the parenchymal perfusion could be detected with the PI imaging, which was obscure when inspecting the series of DSA images, in the case of intra-arterial papaverine infusion for delayed vasospasm. Thirdly, the vortex inside a large aneurysm could be estimated with the same resolution as DSA. Our method offers real time, high resolution, projection angle independent and semiquantitative imaging of the cerebral perfusion from the conventional DSA images without introducing any new expensive devices. This method could be used to evaluate the therapeutic change and especially to monitor the rapidly changing cerebral perfusion in interventional angiography.
Calcitonin gene-related peptide (CGRP) is believed to play an important role in maintaining low pulmonary vascular resistance (PVR) and in modulating pulmonary vascular responses to chronic hypoxia; however, the effects of adenovirally mediated gene transfer of CGRP on the response to hypoxia are unknown.
In the present study, an adenoviral vector encoding prepro-CGRP (AdRSVCGRP) was used to examine the effects of in vivo gene transfer of CGRP on increases in PVR, right ventricular mass (RVM), and pulmonary vascular remodeling that occur in chronic hypoxia in the mouse. Intratracheal administration of AdRSVCGRP, followed by 16 days of chronic hypoxia (FIO(2) 0.10), increased lung CGRP and cAMP levels. The increase in pulmonary arterial pressure (PAP), PVR, RVM, and pulmonary vascular remodeling in response to chronic hypoxia was attenuated in animals overexpressing prepro-CGRP, whereas systemic pressure was not altered while in chronically hypoxic mice, angiotensin II and endothelin-1-induced increases in PAP were reduced, whereas decreases in PAP in response to CGRP and adrenomedullin were not changed and decreases in PAP in response to a cAMP phosphodiesterase inhibitor were enhanced by AdRSVCGRP.
In vivo CGRP lung gene transfer attenuates the increase in PVR and RVM, pulmonary vascular remodeling, and pressor responses in chronically hypoxic mice, suggesting that CGRP gene transfer alone and with a cAMP phosphodiesterase inhibitor may be useful for the treatment of pulmonary hypertensive disorders.
A computer program has been developed to model chest radiography. It incorporates a voxel phantom of an adult and includes antiscatter grid, radiographic screen, and film. Image quality is quantified by calculating the contrast (deltaOD) and the ideal observer signal-to-noise ratio (SNR(I)) for a number of relevant anatomical details at various positions in the anatomy. Detector noise and system unsharpness are modeled and their influence on image quality is considered. A measure of useful dynamic range is computed and defined as the fraction of the image that is reproduced at an optical density such that the film gradient exceeds a preset value. The effective dose is used as a measure of the radiation risk for the patient. A novel approach to patient dose and image quality optimization has been developed and implemented. It is based on a reference system acknowledged to yield acceptable image quality in a clinical trial. Two optimizations schemes have been studied, the first including the contrast of vessels as measure of image quality and the second scheme using also the signal-to-noise ratio of calcifications. Both schemes make use of our measure of useful dynamic range as a key quantity. A large variety of imaging conditions was simulated by varying the tube voltage, antiscatter device, screen-film system, and maximum optical density in the computed image. It was found that the optical density is crucial in screen-film chest radiography. Significant dose savings (30%-50%) can be accomplished without sacrificing image quality by using low-atomic-number grids with a low grid ratio or an air gap and more sensitive screen-film system. Dose-efficient configurations proposed by the model agree well with the example of good radiographic technique suggested by the European Commission.
Justification of radiological requests, standardization of procedures and optimization of protection measures are key principles in the protection of individuals exposed to ionizing radiation for diagnostic purposes. Nowhere is this more pertinent than in the imaging of children and, following the recent introduction of the Ionising Radiation (Medical Exposure) Regulations, there is now a regulatory requirement for diagnostic radiology departments to demonstrate compliance with these principles. A study was undertaken to compare all aspects of paediatric radiological practice at two specialist and two non-specialist centres. An initial study involved analysis of nearly 3000 patient doses. The second phase of the project involved assessment of referral criteria, radiographic technique and approximately 100 radiographs at each centre by two consultant paediatric radiologists. While all radiographs were found to be diagnostically acceptable, major differences in technique were evident, reflecting the disparity in experience between staff at the specialist and non-specialist centres. The large number of sub-optimum films encountered at the latter suggests that there is a need for specific training of less experienced radiographic and clinical staff.
To evaluate prospectively diagnostic accuracy of 1 mol/L gadobutrol as a contrast agent for intraarterial x-ray digital subtraction angiography (DSA) in comparison to iodinated, nonionic contrast media and 0.5 mol/L gadolinium-DTPA.
Flush arteriograms (ascending, descending, abdominal aorta, iliac, and femoral arteries) and selective angiograms (carotid, renal, and visceral arteries) were obtained from bilateral femoral arterial access (5 F sheaths) in 10 domestic pigs (70 kg body weight). Digital subtracted angiograms were obtained during injection of undiluted 1 mol/L gadobutrol, 300 mg I/mL iopromide, or 0.5 mol/L gadopentetate. Injection parameters (volume and velocity) were similar for all three contrast agents. In paired arteries, two different contrast media were used during the same angiographic run. Diagnostic quality and accuracy of the angiograms were evaluated on a three-step scale by three independent blinded investigators.
Sufficient nonselective angiographic images were obtained in 90% of cases using iodinated contrast material. Gadobutrol achieved sufficient nonselective angiograms in 64%. Selective angiograms were sufficient in 98% using iodinated contrast material, 90% using 1 mol/L Gadobutrol and 48% using 0.5 mol/L Gd-DTPA. Adverse reactions to any of the used contrast agents were not noted.
One mol/L Gadobutrol solution allows x-ray digital subtraction angiography with a diagnostic accuracy equivalent to 300 mg/mL iodinated contrast media, if selective injections are performed. Flush aortograms are of inferior image quality to iodinated contrast material.
The intrinsic resolution, noise, and signal-to-noise transfer characteristics of five commercial digital computed radiography (CR) systems were compared using identical experimental methods. The reader/screen combinations evaluated were Agfa ADC-Compact/MD-10, Agfa ADC-Compact/MD-30, Agfa ADC-Solo/MD-10, Agfa ADC-Solo/MD-30, Lumisys CR-2000/MD-10, Fuji FCR-9501 (HQ)/ST-Va, Kodak CR-400/GP-25, and Kodak CR-400/HR. Measurements were made at 70 and 115 kVp with 19 mm added aluminum filtration. The presampled modulation transfer functions (MTFs) of the systems were measured using an edge method. The noise power spectra (NPS) were determined by 2D Fourier analysis of uniformly exposed radiographs. The frequency-dependent detective quantum efficiencies (DQEs) were computed from the MTF, NPS, exposure measurements, and computational estimates of the ideal signal-to-noise ratios. Using 70 kVp and 0.1-0.12 mm pixel sizes, spatial frequencies of 2.1, 2.0, 2.2, 1.9, 2.0, 2.0, 2.3, 2.3, and 3.5 cycles/mm were measured at 0.2 MTF for the eight reader/screen combinations, respectively. Using 70 kVp, 7.74 x 10(-8) C/kg (0.3 mR), and 0.1-0.12 mm pixel sizes, DQE(0.15) values of 20.3%, 22.9%, 24.6%, 28.6%, 22.2%, 30.0%, 29.5%, and 17.3% were obtained for the eight combinations, respectively. The corresponding values at 115 kVp were 15.9%, 18.5%, 21.5%, 21.8%, 15.3%, 23.1%, 22.3%, and 13.8%, respectively. The findings of the study demonstrate the pixel size, orientation, beam quality, screen, and reader dependencies of image quality in CR systems. The physical performance of the systems having standard-resolution screens demonstrated similar resolution performance but more notable variations in DQE. The one high-resolution screen tested had reduced DQE and increased MTF at high frequencies.
A digital x-ray imaging system was designed for small-animal studies. This system is a fiber-optics taper-coupled imaging system with two CCD arrays uniquely jointed. The x-ray source of the system has a small focal spot of 20 microm. This digital imaging system contains specially designed shelves to provide magnification levels, ranging from 1.5x to 5x. The system is characterized in terms of its properties of spatial resolution. An observer-based spatial resolution measurement was conducted with a line-pair target and a sector test pattern. The modulation transfer function of the system, with different magnifications, was studied by use of a 10-microm lead slit. The average resolutions at 50% and 5% modulations at 1x magnification were measured as 3.9 and 8.4 lp/mm, respectively, where lp indicates line pairs. With 5x magnification, the 50% and the 5% modulations provided 13.2- and 29.9-lp/mm, respectively, average spatial resolutions. The measurements showed consistency between the two individual CCD arrays; the difference in resolution between the two CCDs is less than 1%, even at high magnifications.
We report quantification of vasospasm following subarachnoid haemorrhage (SAH) and the effect of a new antivasospastic free radical scavenger (AVS) in rats, using an angiographic technique developed in our laboratory. We acquired single-exposure angiograms with mammographic equipment, using a 0.1 mm diameter focal spot and single-emulsion mammographic films. Contrast medium was injected through a PE50 catheter in the common carotid artery, after the external carotid artery had been ligated to divert flow towards the internal carotid artery territory. Measurements of the M1 and A1 segments and of the middle third of the basilar artery were made by projecting the angiograms directly as slides and using the endovascular catheter as an internal reference. We tested the technique on 40 male albino Sprague-Dawley rats divided into four groups: sham-operated+saline, SAH+saline, sham-operated+AVS and SAH+AVS. We were able to measure the diameter of the principal intracranial arteries in all the animals. With our technique, which is cost-effective when compared to many of those reported recently, we could detect intracranial vasospasm in all untreated rats with SAH, and confirm antivasospastic effects of AVS.
The P2 receptors that mediate contraction of the rat isolated small (SPA, 200–500 μm i.d.) and large (LPA, 1–1.5 mM i.d.) intrapulmonary arteries were characterized.
In endothelium-denuded vessels the contractile order of potency was α,β-methyleneATP (α,β-meATP)>>UDP=UTP=ATP=2-methylthioATP>ADP in the SPA and α,β-meATP=UTPUDP>2-methylthioATP, ATP>>ADP in the LPA. α,β-meATP, 2-methylthioATP and ATP had significantly greater effects in the SPA than the LPA (P<0.001), but there was no difference in the potency of UTP or UDP between the vessels.
In the SPA, P2X1 receptor desensitisation by α,β-meATP (100 μM) inhibited contractions to α,β-meATP (10 nM–300 μM), but not those to UTP or UDP (100 nM–300 μM). In the LPA, prolonged exposure to α,β-meATP (100 μM) did not desensitize P2X receptors.
Pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), suramin and reactive blue 2 (RB2) (30–300 μM) inhibited contractions evoked by α,β-meATP. UTP and UDP were potentiated by PPADS, unaffected by RB2 and inhibited, but not abolished by suramin. 1 and 3 mM suramin produced no further inhibition, indicating suramin-resistant components in the responses to UTP and UDP.
Thus, both P2X and P2Y receptors mediate contraction of rat large and small intrapulmonary arteries. P2Y agonist potency and sensitivity to antagonists were similar in small and large vessels, but P2X agonists were more potent in small arteries. This indicates differential expression of P2X, but not P2Y receptors along the pulmonary arterial tree.
British Journal of Pharmacology (2002) 137, 637–646. doi:10.1038/sj.bjp.0704915
Dynamic regional lung function was investigated in rats using a radial acquisition cine (RA-CINE) pulse sequence together with hyperpolarized (HP) (3)He gas delivered by a constant flow ventilator. Based on regional differences in the behavior of inspired air, the lung was conceptually divided into two regions (the major airways and the peripheral airspace) for purposes of functional analysis. To measure regional function in the major airways, a large RF flip angle (24 degrees) was applied to reduce (3)He magnetization in the peripheral airspace, and signal intensity (SI) was normalized with the projected airway diameter to estimate local airflow. Higher normalized signal intensity was observed in the left branch airway as compared to the right branch airway. To determine regional function in the peripheral airspace, a small RF flip angle (6 degrees) was used. Incremental increases of peripheral SI in successive lung images were consistent with the increase in lung volume. A new "skipping" scanning strategy using dummy frames allows a trade-off between the number of frames acquired for dynamic information, the RF flip angle, and the penetration depth of (3)He magnetization into the lung. This work provides a novel approach to simultaneously assess dynamic regional function and morphology.
To ascertain the optimum x-ray spectrum for chest radiography with a cesium iodide-amorphous silicon flat-panel detector.
End points for optimization included the ratio of tissue contrast to bone contrast and a figure of merit (FOM) equal to the square of the signal-to-noise ratio of tissue divided by incident exposure to the patient. Studies were conducted with both computer spectrum modeling and experimental measurement in narrow-beam and full-field exposure conditions for four tissue thicknesses (8-32 cm). Three parameters that affect spectra were considered: the atomic number (Z) of filter material (Z = 13, 26, 29, 42, 50, 56, 64, 74, and 82), kilovoltage (from 50 to 150 kVp), and filter thickness (from 0.25 to 2.00 half-value layer [HVL]).
Computer modeling and narrow-beam experimental data showed similar trends for the full range of parameters evaluated. Spectrum model results showed that copper filtration at 120 kVp or more was optimum for FOM. The ratio of contrasts showed a trend to be higher with higher kilovoltage and only a minor variation with filter material. Full-field experimental results, which reflect the added contribution of x-ray scatter, differed in magnitude but not trends from the narrow-beam data in all cases except the ratio of contrasts in the mediastinum.
The best performance overall, including both FOM and ratio of contrasts, was at 120 kVp with 1-HVL copper filtration (0.2 mm). With this beam spectrum and an increase in tube output (ie, milliampere seconds) of about 50%, a chest radiograph can be obtained with image quality approximately equal to that with a conventional spectrum but with about 25% less patient exposure.
Small-animal imaging has become increasingly more important as transgenic and knockout mice are produced to model human diseases. One imaging technique that has emerged is microcomputed tomography (micro-CT). For live-animal imaging, the precision in the images will be determined by the x-ray dose given to the animal. As a result, we propose a simple method to predict the noise performance of an x-ray micro-CT system as a function of dose and image resolution. An ideal, quantum-noise limited micro-CT scanner, assumed to have perfect resolution and ideal efficiency, was modeled. Using a simplified model, the coefficient of variation (COV) of the linear attenuation coefficient was calculated for a range of entrance doses and isotropic voxel sizes. COV calculations were performed for the ideal case and with simulated imperfections in efficiency and resolution. Our model was validated in phantom studies and mouse images were acquired with a specimen scanner to illustrate the results. A simplified model of noise propagation in the case of isotropic resolution indicates that the COV in the linear attenuation coefficient is proportional to (dose)(-1/2) and to the (isotropic voxel size)(-2) in the reconstructed volume. Therefore an improvement in the precision can be achieved only by increasing the isotropic voxel size (thereby decreasing the resolution of the image) or by increasing the x-ray dose. For the ideal scanner, a COV of 1% in the linear attenuation coefficient for an image of a mouse exposed to 0.25 Gy is obtained with a minimum isotropic voxel size of 135 microm. However, the same COV is achieved at a dose of 5.0 Gy with a 65 microm isotropic voxel size. Conversely, for a 68 mm diameter rat, a COV of 1% obtained from an image at 5.0 Gy would require an isotropic voxel size of 100 microm. These results indicate that short-term, potentially lethal, effects of ionizing radiation will limit high-resolution live animal imaging. As improvements in detector technology allow the resolution to improve, by decreasing the detector element size to tens of microns or less, high quality images will be limited by the x-ray dose administered. For the highest quality images, these doses will approach the lethal dose or LD50 for the animals. Approaching the lethal dose will affect the way experiments are planned, and may reduce opportunities for experiments involving imaging the same animal over time. Dose considerations will become much more important for live small-animal imaging as the limits of resolution are tested.
The aim of this study was to visualize hepatic microvessels (less than 100 microm in diameter) in vivo, which could not be visualized by conventional X-ray angiography, by using synchrotron radiation (ultra-bright and monochromatic X-ray).
Five female Balb/c nu/nu mice were used. To investigate the hepatic microvessels under nearly physiologic conditions, we performed in vivo aortography under anesthesia with 370 mgI/ml nonionic iodine contrast medium using monochromatic 17-keV X-rays generated by a synchrotron. Images were captured with a pixel matrix size of 1024 x 1024 at a rate of 30 pictures/s. The field of view was 7 mm x 7 mm and thus the pixel size was approximately 7 microm. Captured images were evaluated both qualitatively and quantitatively.
Small hepatic arterial and portal venous branches of the liver were visualized separately during one sequential aortogram. The minimum diameter of the vessels observed was approximately 20 microm, and the vessels which ran parallel to the hepatic artery were observed and it seemed to be intrahepatic peribiliary arterial plexus.
Our new experimental model would be useful for visualization of changes in the hepatic microcirculation under nearly physiologic conditions.
The purpose of this simulation study was to evaluate the feasibility, benefits, and potential operating parameters of a quasi-monochromatic beam from a tungsten-target x-ray source yielding projection images. The application is intended for newly developed cone beam computed mammotomography (CmT) of an uncompressed breast. The value of a near monochromatic x-ray source for a fully 3D CmT application is the expected improved ability to separate tissues with very small differences in attenuation coefficients. The quasi-monochromatic beam is expected to yield enhanced tomographic image quality along with a low dose, equal to or less than that of dual view x-ray mammography. X-ray spectra were generated with a validated projection x-ray simulation tool (XSpect) for a range of tungsten tube potentials (40-100 kVp), filter materials (Z=51-65), and filter thicknesses (10th to 1000th value layer determined at 60 kVp). The breast was modeled from ICRU-44 breast tissue specifications, and a breast lesion was modeled as a 0.5 cm thick mass. The detector was modeled as a digital flat-panel detector with a 0.06 cm thick CsI x-ray absorption layer. Computed figures of merit (FOMs) included the ratio of mean beam energy post-breast to pre-breast and the ratio of lesion contrasts for edge-located and center-located lesions as indices of breast beam hardening, and SNR2/exposure and SNR2/dose as indices of exposure and dose efficiencies. The impact of optimization of these FOMs on lesion contrast is also examined. For all simulated filter materials at each given attenuation thickness [10th, 100th, 500th, 1000th value layers (VLs)], the mean and standard deviation of the pre-breast spectral full-width at tenth-maximum (FWTM) were 16.1 +/- 2.4, 10.3 +/- 2.2, 7.3 +/- 1.4, and 6.5 +/- 1.5 keV, respectively. The change in beam width at the tenth maximum from pre-breast to post-breast spectra ranged from 4.7 to 1.1 keV, for the thinnest and thickest filters, respectively. The higher Z filters (Z=57-63) produced a quasi-monochromatic beam that allowed the widest tube potential operating range (50-70 kVp) while maintaining minimal beam hardening and maximal SNR2/exposure and SNR2/dose, and providing a contrast greater than that obtained in the unfiltered case. Figures of merit improved with increasing filter thickness, with diminishing returns beyond the 500th value layer attenuation level. Operating parameters required to produce optimal spectra, while keeping exposures equal to that of dual view mammography, are within the capability of the commercial x-ray tube proposed for our experimental study, indicating that use of these highly attenuating filters is viable. Additional simulations comparing Mo/Mo, Mo/Rh, and W/Rh target/filter combinations indicate that they exhibit significantly lower SNR2/exposure than the present approach, precluding them from being used for computed mammotomography, while maintaining dose limitations and obtaining sufficient SNR. Beam hardening was also much higher in the existing techniques (17%-42%) than for our technique (2%). Simulations demonstrate that this quasi-monochromatic x-ray technique may enhance tissue separation for a newly developed cone beam computed mammotomography application for an uncompressed breast.
The purpose of this study evaluating a cesium iodide-amorphous silicon-based flat-panel detector was to optimize the x-ray spectrum for chest radiography combining excellent contrast-detail visibility with reduced patient exposure.
A Lucite plate with 36 drilled holes of varying diameter and depth was used as contrast-detail phantom. For 3 scatter body thicknesses (7.5 cm, 12.5 cm, 21.5 cm Lucite) images were obtained at 113 kVp, 117 kVp, and 125 kVp with additional copper filter of 0.2 and 0.3 mm, respectively. For each setting, radiographs acquired with 125 kVp and no copper filter were taken as standard of reference. On soft-copy displays, 3 observers blinded to the exposure technique evaluated the detectability of each aperture in each image according to a 5-point scale. The number of points given to all 36 holes per image was added. The scores of images acquired with filtration were compared with the standard images by means of a multivariate analysis of variance. Radiation burden was approximated by referring to the entrance dose and calculated using Monte Carlo method.
All 6 evaluated x-ray spectra resulted in a statistically equivalent contrast-detail performance when compared with the standard of reference. The combination 125 kVp with 0.3 mm copper was most favorable in terms of dose reduction (approximately 33%).
Within the constraints of the presented contrast-detail phantom study simulating chest radiography, the CsI/a-Si system enables an addition of up to 0.3 mm copper filtration without the need for compensatory reduction of the tube voltage for providing constant image quality. Beam filtration reduces radiation burden by about 33%.
Increasing use of transgenic animal models for pulmonary disease has raised the need for methods to assess pulmonary structure and function in a physiologically stable mouse. We report here an integrated protocol using magnetic resonance microscopy with gadolinium (Gd)-labeled starburst dendrimer (G6-1B4M-Gd, MW = 192 +/- 1 kDa, R(h) = 5.50 +/- 0.04 nm) and hyperpolarized (3)helium ((3)He) gas to acquire images that demonstrate pulmonary vasculature and ventilated airways in live mice (n = 9). Registered three-dimensional images of (1)H and (3)He were acquired during breath-hold at 2.0 T using radial acquisition (total acquisition time of 38 and 25 min, respectively). The macromolecular Gd-labeled dendrimer (a half-life of approximately 80 min) increased the signal-to-noise by 81 +/- 30% in the left ventricle, 43 +/- 22% in the lung periphery, and -4 +/- 5% in the chest wall, thus increasing the contrast of these structures relative to the less vascular surrounding tissues. A constant-flow ventilator was developed for the mouse to deliver varied gas mixtures of O(2) and N(2) (or (3)He) during imaging. To avoid hypoxemia, instrumental dead space was minimized and corrections were made to tidal volume lost due to gas compression. The stability of the physiologic support was assessed by the lack of spontaneous breathing and maintenance of a constant heart rate. We were able to stabilize the mouse for >8 hr using ventilation of 105 breath/min and approximately 0.2 mL/breath. The feasibility of acquiring both pulmonary vasculature and ventilated airways was demonstrated in the mouse lung with in-plane spatial resolution of 70 x 70 microm(2) and slice thickness of 800 microm.
One can acquire high-resolution pulmonary and cardiac images in live rodents with MR microscopy by synchronizing the image acquisition to the breathing cycle across multiple breaths, and gating to the cardiac cycle. The precision with which one can synchronize image acquisition to the motion defines the ultimate resolution limit that can be attained in such studies. The present work was performed to evaluate how reliably the pulmonary and cardiac structures return to the same position from breath to breath and beat to beat across the prolonged period required for MR microscopy. Radiopaque beads were surgically glued to the abdominal surface of the diaphragm and on the cardiac ventricles of anesthetized, mechanically ventilated rats. We evaluated the range of motion for the beads (relative to a reference vertebral bead) using digital microradiography with two specific biological gating methods: 1) ventilation synchronous acquisition, and 2) both ventilation synchronous and cardiac-gated acquisitions. The standard deviation (SD) of the displacement was < or =100 microm, which is comparable to the resolution limit for in vivo MRI imposed by signal-to-noise ratio (SNR) constraints. With careful control of motion, its impact on resolution can be limited. This work provides the first quantitative measure of the motion-imposed resolution limits for in vivo imaging.
We present the automated segmentation of magnetic resonance microscopy (MRM) images of the C57BL/6J mouse brain into 21 neuroanatomical structures, including the ventricular system, corpus callosum, hippocampus, caudate putamen, inferior colliculus, internal capsule, globus pallidus, and substantia nigra. The segmentation algorithm operates on multispectral, three-dimensional (3D) MR data acquired at 90-microm isotropic resolution. Probabilistic information used in the segmentation is extracted from training datasets of T2-weighted, proton density-weighted, and diffusion-weighted acquisitions. Spatial information is employed in the form of prior probabilities of occurrence of a structure at a location (location priors) and the pairwise probabilities between structures (contextual priors). Validation using standard morphometry indices shows good consistency between automatically segmented and manually traced data. Results achieved in the mouse brain are comparable with those achieved in human brain studies using similar techniques. The segmentation algorithm shows excellent potential for routine morphological phenotyping of mouse models.
The transition to digital radiology has provided new opportunities for improved image quality, made possible by the superior detective quantum efficiency and post-processing capabilities of new imaging systems, and advanced imaging applications, made possible by rapid digital image acquisition. However, this transition has taken place largely without optimising the radiographic technique used to acquire the images. This paper proposes a framework for optimising the acquisition of digital X-ray images. The proposed approach is based on the signal and noise characteristics of the digital images and the applied exposure. Signal is defined, based on the clinical task involved in an imaging application, as the difference between the detector signal with and without a target present against a representative background. Noise is determined from the noise properties of uniformly acquired images of the background, taking into consideration the absorption properties of the detector. Incident exposure is estimated or otherwise measured free in air, and converted to dose. The main figure of merit (FOM) for optimisation is defined as the signal-difference-to-noise ratio (SdNR) squared per unit exposure or (more preferably) dose. This paper highlights three specific technique optimisation studies that used this approach to optimise the radiographic technique for digital chest and breast applications. In the first study, which was focused on chest radiography with a CsI flat-panel detector, a range of kV(p) (50-150) and filtration (Z = 13-82) were examined in terms of their associated FOM as well as soft tissue to bone contrast, a factor of importance in digital chest radiography. The results indicated that additive Cu filtration can improve image quality. A second study in digital mammography using a selenium direct flat-panel detector indicated improved SdNR per unit exposure with the use of a tungsten target and a rhodium filter than conventional molybdenum target/molybdenum filter techniques. Finally, a third study focusing on cone-beam computed tomography of the breast using a CsI flat-panel detector indicated that high Z filtration of a tungsten target X-ray beam can notably improve the signal and noise characteristics of the image. The general findings highlight the fact that the techniques that are conventionally assumed to be optimum may need to be revisited for digital radiography.
To assess left ventricular (LV) and right ventricular (RV)
systolic and diastolic function in rats and mice, the authors developed
a field-by-field angiographic analysis program. Interlaced video images
were acquired on a videotape recorder under a constant fluoroscopic
technique, and digitized at 512×512, 8-b, 30-frames/s resolution.
Fields were separated to improve the temporal resolution. Field-by-field
video-density curves for LV and RV were derived. Beat averaging was
performed after correcting for varying contrast between beats. The
following parameters were measured: (1) heart rate, (2) ejection
fraction, (3) end diastolic volumes, (4) stroke volume, (5) cardiac
output, (6) mean systolic ejection rate, (7) peak ejection rate, (8)
peak filling rate, (9) time to peak filling, and (10) time to peak
ejection rate