Inverse treatment planning for an electronic brachytherapy system delivering anisotropic radiation therapy.

An inverse radiation treatment planning algorithm for Sensus Healthcare's SculpturaTM electronic brachytherapy system has been designed. The algorithm makes use of simulated annealing to optimize the conformation number (CN) of the treatment plan. The highly anisotropic dose distributions produced by the SculpturaTM x-ray source empower the inverse treatment planning algorithm to achieve highly conformal treatment plans for a wide range of prescribed planning target volumes. Over a set of 10 datasets the algorithm achieved an average CN of 0.79 ± 0.08 and an average gamma passing rate of 0.90 ± 0.10 at 5%/5 mm. A regularization term that encouraged short treatment plans was used, and it was found that the total treatment time could be reduced by 20% with only a nominal reduction in the CN and gamma passing rate. It was also found that downsampling the voxelized volume (from 3203 to 643 voxels) prior to optimization resulted in a 150× speedup in the optimization time (from 2 + minutes to < 1 s) without affecting the quality of the treatment plan.

Characterization of an x-ray source with a partitioned diamond-tungsten target for electronic brachytherapy with 3D beam directionality.

The Sculptura™ is a new high-dose-rate electronic brachytherapy system developed by Sensus Healthcare. By combining a steerable electron beam with a partitioned diamond-tungsten x-ray target, the x-ray source of the Sculptura™ is capable of producing highly anisotropic dose distributions, thus achieving true 3D beam directionality. This article reports the spectral and dosimetric characterization of the Sculptura™ x-ray source through a combination of measurements and Monte Carlo simulations for operating points between 50-100 kV. Excellent agreement (~5% discrepancy) between the simulations and measurements was obtained for in-air dose rate characterization. The validated simulations were then used to calculate the dose distribution in water. Dose rates of >2 cGy/min/µA can be produced at 100 kV, thus delivering 10 Gy in 1 min for typical operating conditions. The dose distributions are sharply peaked, with a full-width at half-maximum azimuth of about 100°.

Localization of cardiac volume and patient features in inverse geometry x-ray fluoroscopy.

The scanning-beam digital x-ray (SBDX) system is an inverse geometry x-ray fluoroscopy technology that performs real-time tomosynthesis at planes perpendicular to the source-detector axis. The live display is a composite image which portrays sharp features (e.g. coronary arteries) extracted from a 16 cm thick reconstruction volume. We present a method for automatically determining the position of the cardiac volume prior to acquisition of a coronary angiogram. In the algorithm, a single non-contrast frame is reconstructed over a 44 cm thickness using shift-and-add digital tomosynthesis. Gradient filtering is applied to each plane to emphasize features such as the cardiomediastinal contour, diaphragm, and lung texture, and then sharpness vs. plane position curves are generated. Three sharpness metrics were investigated: average gradient in the bright field, maximum gradient, and the number of normalized gradients exceeding 0.5. A model correlating the peak sharpness in a non-contrast frame and the midplane of the coronary arteries in a contrast-enhanced frame was established using 37 SBDX angiographic loops (64-136 kg human subjects, 0-30° cranial-caudal). The average gradient in the bright field (primarily lung) and the number of normalized gradients >0.5 each yielded peaks correlated to the coronary midplane. The rms deviation between the predicted and true midplane was 1.57 cm. For a 16 cm reconstruction volume and the 5.5-11.5 cm thick cardiac volumes in this study, midplane estimation errors of 2.25-5.25 cm were tolerable. Tomosynthesis-based localization of cardiac volume is feasible. This technique could be applied prior to coronary angiography, or to assist in isocentering the patient for rotational angiography.

Dynamic electronic collimation method for 3-D catheter tracking on a scanning-beam digital x-ray system.

Scanning-beam digital x-ray (SBDX) is an inverse geometry x-ray fluoroscopy system capable of tomosynthesis-based 3-D catheter tracking. This work proposes a method of dose-reduced 3-D catheter tracking using dynamic electronic collimation (DEC) of the SBDX scanning x-ray tube. This is achieved through the selective deactivation of focal spot positions not needed for the catheter tracking task. The technique was retrospectively evaluated with SBDX detector data recorded during a phantom study. DEC imaging of a catheter tip at isocenter required 340 active focal spots per frame versus 4473 spots in full field-of-view (FOV) mode. The dose-area product (DAP) and peak skin dose (PSD) for DEC versus full FOV scanning were calculated using an SBDX Monte Carlo simulation code. The average DAP was reduced to 7.8% of the full FOV value, consistent with the relative number of active focal spots (7.6%). For image sequences with a moving catheter, PSD was 33.6% to 34.8% of the full FOV value. The root-mean-squared-deviation between DEC-based 3-D tracking coordinates and full FOV 3-D tracking coordinates was less than 0.1 mm. The 3-D distance between the tracked tip and the sheath centerline averaged 0.75 mm. DEC is a feasible method for dose reduction during SBDX 3-D catheter tracking.

Improved targeting accuracy of lung tumor biopsies with scanning-beam digital x-ray tomosynthesis image guidance.

PURPOSE: Electromagnetic navigation bronchoscopy (ENB) provides improved targeting accuracy during transbronchial biopsies of suspicious nodules. The greatest weakness of ENB-based guidance is the registration divergence that exists between the planning CT, acquired days or weeks before the intervention, and the patient on the table on the day of the intervention. Augmenting ENB guidance with real-time tomosynthesis imaging during the intervention could mitigate the divergence and further improve the yield of ENB-guided transbronchial biopsies. The real-time tomosynthesis prototype, the scanning-beam digital x-ray (SBDX) system, does not currently display images reconstructed by the iterative algorithm that was developed for this lung imaging application. A protocol using fiducial markers was therefore implemented to permit evaluation of potential improvements that would be provided by the SBDX system in a clinical setting. METHODS: Ten 7 mm lesions (5 per side) were injected into the periphery of each of four preserved pig lungs. The lungs were then placed in a vacuum chamber that permitted simulation of realistic motion and deformation due to breathing. Standard clinical CT scans of the pig lung phantoms were acquired and reconstructed with isotropic resolution of 0.625 mm. Standard ENB-guided biopsy procedures including target identification, path planning, CT-to-lung registration and navigation to the lesion were carried out, and a fiducial marker was placed at the location at which a biopsy would have been acquired. The channel-to-target distance provided by the ENB system prior to fiducial placement was noted. The lung phantoms were then imaged using the SBDX system, and using high-resolution conebeam CT. The distance between the fiducial marker tip and the lesion was measured in SBDX images and in the gold-standard conebeam-CT images. The channel-to-target divergence predicted by the ENB system and measured in the SBDX images was compared to the gold standard to determine if improved targeting accuracy could be achieved using SBDX image guidance. RESULTS: As expected, the ENB system showed poorer targeting accuracy for small peripheral nodules. Only 20 nodules of the 40 injected could be adequately reached using ENB guidance alone. The SBDX system was capable of visualizing these small lesions, and measured fiducial-to-target distances on SBDX agreed well with measurements in gold-standard conebeam-CT images (p = 0.0001). The correlation between gold-standard conebeam-CT distances and predicted fiducial-to-target distances provided by the ENB system was poor (p = 0.72), primarily due to inaccurate ENB CT-to-body registration and movement due to breathing. CONCLUSIONS: The SBDX system permits visualization of small lung nodules, as well as accurate measurement of channel-to-target distances. Combined use of ENB with SBDX real-time image guidance could improve accuracy and yield of biopsies, particularly of those lesions located in the periphery of the lung.

Method for dose-reduced 3D catheter tracking on a scanning-beam digital x-ray system using dynamic electronic collimation.

Scanning-beam digital x-ray (SBDX) is an inverse geometry x-ray fluoroscopy system capable of tomosynthesis-based 3D catheter tracking. This work proposes a method of dose-reduced 3D tracking using dynamic electronic collimation (DEC) of the SBDX scanning x-ray tube. Positions in the 2D focal spot array are selectively activated to create a region-of-interest (ROI) x-ray field around the tracked catheter. The ROI position is updated for each frame based on a motion vector calculated from the two most recent 3D tracking results. The technique was evaluated with SBDX data acquired as a catheter tip inside a chest phantom was pulled along a 3D trajectory. DEC scans were retrospectively generated from the detector images stored for each focal spot position. DEC imaging of a catheter tip in a volume measuring 11.4 cm across at isocenter required 340 active focal spots per frame, versus 4473 spots in full-FOV mode. The dose-area-product (DAP) and peak skin dose (PSD) for DEC versus full field-of-view (FOV) scanning were calculated using an SBDX Monte Carlo simulation code. DAP was reduced to 7.4% to 8.4% of the full-FOV value, consistent with the relative number of active focal spots (7.6%). For image sequences with a moving catheter, PSD was 33.6% to 34.8% of the full-FOV value. The root-mean-squared-deviation between DEC-based 3D tracking coordinates and full-FOV 3D tracking coordinates was less than 0.1 mm. The 3D distance between the tracked tip and the sheath centerline averaged 0.75 mm. Dynamic electronic collimation can reduce dose with minimal change in tracking performance.

Depth-resolved registration of transesophageal echo to x-ray fluoroscopy using an inverse geometry fluoroscopy system.

PURPOSE: Image registration between standard x-ray fluoroscopy and transesophageal echocardiography (TEE) has recently been proposed. Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system designed for cardiac procedures. This study presents a method for 3D registration of SBDX and TEE images based on the tomosynthesis and 3D tracking capabilities of SBDX. METHODS: The registration algorithm utilizes the stack of tomosynthetic planes produced by the SBDX system to estimate the physical 3D coordinates of salient key-points on the TEE probe. The key-points are used to arrive at an initial estimate of the probe pose, which is then refined using a 2D/3D registration method adapted for inverse geometry fluoroscopy. A phantom study was conducted to evaluate probe pose estimation accuracy relative to the ground truth, as defined by a set of coregistered fiducial markers. This experiment was conducted with varying probe poses and levels of signal difference-to-noise ratio (SDNR). Additional phantom and in vivo studies were performed to evaluate the correspondence of catheter tip positions in TEE and x-ray images following registration of the two modalities. RESULTS: Target registration error (TRE) was used to characterize both pose estimation and registration accuracy. In the study of pose estimation accuracy, successful pose estimates (3D TRE < 5.0 mm) were obtained in 97% of cases when the SDNR was 5.9 or higher in seven out of eight poses. Under these conditions, 3D TRE was 2.32 ± 1.88 mm, and 2D (projection) TRE was 1.61 ± 1.36 mm. Probe localization error along the source-detector axis was 0.87 ± 1.31 mm. For the in vivo experiments, mean 3D TRE ranged from 2.6 to 4.6 mm and mean 2D TRE ranged from 1.1 to 1.6 mm. Anatomy extracted from the echo images appeared well aligned when projected onto the SBDX images. CONCLUSIONS: Full 6 DOF image registration between SBDX and TEE is feasible and accurate to within 5 mm. Future studies will focus on real-time implementation and application-specific analysis.

Detector, collimator and real-time reconstructor for a new scanning-beam digital x-ray (SBDX) prototype.

Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system for low dose cardiac imaging. The use of a narrow scanned x-ray beam in SBDX reduces detected x-ray scatter and improves dose efficiency, however the tight beam collimation also limits the maximum achievable x-ray fluence. To increase the fluence available for imaging, we have constructed a new SBDX prototype with a wider x-ray beam, larger-area detector, and new real-time image reconstructor. Imaging is performed with a scanning source that generates 40,328 narrow overlapping projections from 71 × 71 focal spot positions for every 1/15 s scan period. A high speed 2-mm thick CdTe photon counting detector was constructed with 320×160 elements and 10.6 cm × 5.3 cm area (full readout every 1.28 µs), providing an 86% increase in area over the previous SBDX prototype. A matching multihole collimator was fabricated from layers of tungsten, brass, and lead, and a multi-GPU reconstructor was assembled to reconstruct the stream of captured detector images into full field-of-view images in real time. Thirty-two tomosynthetic planes spaced by 5 mm plus a multiplane composite image are produced for each scan frame. Noise equivalent quanta on the new SBDX prototype measured 63%-71% higher than the previous prototype. X-ray scatter fraction was 3.9-7.8% when imaging 23.3-32.6 cm acrylic phantoms, versus 2.3-4.2% with the previous prototype. Coronary angiographic imaging at 15 frame/s was successfully performed on the new SBDX prototype, with live display of either a multiplane composite or single plane image.

Monte Carlo simulation of inverse geometry x-ray fluoroscopy using a modified MC-GPU framework.

Scanning-Beam Digital X-ray (SBDX) is a technology for low-dose fluoroscopy that employs inverse geometry x-ray beam scanning. To assist with rapid modeling of inverse geometry x-ray systems, we have developed a Monte Carlo (MC) simulation tool based on the MC-GPU framework. MC-GPU version 1.3 was modified to implement a 2D array of focal spot positions on a plane, with individually adjustable x-ray outputs, each producing a narrow x-ray beam directed toward a stationary photon-counting detector array. Geometric accuracy and blurring behavior in tomosynthesis reconstructions were evaluated from simulated images of a 3D arrangement of spheres. The artifact spread function from simulation agreed with experiment to within 1.6% (rRMSD). Detected x-ray scatter fraction was simulated for two SBDX detector geometries and compared to experiments. For the current SBDX prototype (10.6 cm wide by 5.3 cm tall detector), x-ray scatter fraction measured 2.8-6.4% (18.6-31.5 cm acrylic, 100 kV), versus 2.1-4.5% in MC simulation. Experimental trends in scatter versus detector size and phantom thickness were observed in simulation. For dose evaluation, an anthropomorphic phantom was imaged using regular and regional adaptive exposure (RAE) scanning. The reduction in kerma-area-product resulting from RAE scanning was 45% in radiochromic film measurements, versus 46% in simulation. The integral kerma calculated from TLD measurement points within the phantom was 57% lower when using RAE, versus 61% lower in simulation. This MC tool may be used to estimate tomographic blur, detected scatter, and dose distributions when developing inverse geometry x-ray systems.

Calibration-free coronary artery measurements for interventional device sizing using inverse geometry x-ray fluoroscopy: in vivo validation.

Proper sizing of interventional devices to match coronary vessel dimensions improves procedural efficiency and therapeutic outcomes. We have developed a method that uses an inverse geometry x-ray fluoroscopy system [scanning beam digital x-ray (SBDX)] to automatically determine vessel dimensions from angiograms without the need for magnification calibration or optimal views. For each frame period (1/15th of a second), SBDX acquires a sequence of narrow beam projections and performs digital tomosynthesis at multiple plane positions. A three-dimensional model of the vessel is reconstructed by localizing the depth of the vessel edges from the tomosynthesis images, and the model is used to calculate the length and diameter in units of millimeters. The in vivo algorithm performance was evaluated in a healthy porcine model by comparing end-diastolic length and diameter measurements from SBDX to coronary computed tomography angiography (CCTA) and intravascular ultrasound (IVUS), respectively. The length error was -0.49 ± 1.76 mm(SBDX- CCTA, mean ± 1 SD). The diameter error was 0.07 ± 0.27 mm (SBDX - minimum IVUS diameter, mean ± 1 SD). The in vivo agreement between SBDX-based vessel sizing and gold standard techniques supports the feasibility of calibration-free coronary vessel sizing using inverse geometry x-ray fluoroscopy.

Calibration-Free Coronary Artery Measurements for Interventional Device Sizing using Inverse Geometry X-ray Fluoroscopy: In Vivo Validation.

Proper sizing of interventional devices to match coronary vessel dimensions improves procedural efficiency and therapeutic outcomes. We have developed a novel method using inverse geometry x-ray fluoroscopy to automatically determine vessel dimensions without the need for magnification calibration or optimal views. To validate this method in vivo, we compared results to intravascular ultrasound (IVUS) and coronary computed tomography angiography (CCTA) in a healthy porcine model. Coronary angiography was performed using Scanning-Beam Digital X-ray (SBDX), an inverse geometry fluoroscopy system that performs multiplane digital x-ray tomosynthesis in real time. From a single frame, 3D reconstruction of the arteries was performed by localizing the depth of vessel lumen edges. The 3D model was used to directly calculate length and to determine the best imaging plane to use for diameter measurements, where out-of-plane blur was minimized and the known pixel spacing was used to obtain absolute vessel diameter. End-diastolic length and diameter measurements were compared to measurements from CCTA and IVUS, respectively. For vessel segment lengths measuring 6 mm to 73 mm by CCTA, the SBDX length error was -0.49 ± 1.76 mm (SBDX - CCTA, mean ± 1 SD). For vessel diameters measuring 2.1 mm to 3.6 mm by IVUS, the SBDX diameter error was 0.07 ± 0.27 mm (SBDX - minimum IVUS diameter, mean ± 1 SD). The in vivo agreement between SBDX-based vessel sizing and gold standard techniques supports the feasibility of calibration-free coronary vessel sizing using inverse geometry x-ray fluoroscopy.

A real-time regional adaptive exposure method for saving dose-area product in x-ray fluoroscopy.

PURPOSE: Reduction of radiation dose in x-ray imaging has been recognized as a high priority in the medical community. Here the authors show that a regional adaptive exposure method can reduce dose-area product (DAP) in x-ray fluoroscopy. The authors' method is particularly geared toward providing dose savings for the pediatric population. METHODS: The scanning beam digital x-ray system uses a large-area x-ray source with 8000 focal spots in combination with a small photon-counting detector. An imaging frame is obtained by acquiring and reconstructing up to 8000 detector images, each viewing only a small portion of the patient. Regional adaptive exposure was implemented by varying the exposure of the detector images depending on the local opacity of the object. A family of phantoms ranging in size from infant to obese adult was imaged in anteroposterior view with and without adaptive exposure. The DAP delivered to each phantom was measured in each case, and noise performance was compared by generating noise arrays to represent regional noise in the images. These noise arrays were generated by dividing the image into regions of about 6 mm(2), calculating the relative noise in each region, and placing the relative noise value of each region in a one-dimensional array (noise array) sorted from highest to lowest. Dose-area product savings were calculated as the difference between the ratio of DAP with adaptive exposure to DAP without adaptive exposure. The authors modified this value by a correction factor that matches the noise arrays where relative noise is the highest to report a final dose-area product savings. RESULTS: The average dose-area product saving across the phantom family was (42 ± 8)% with the highest dose-area product saving in the child-sized phantom (50%) and the lowest in the phantom mimicking an obese adult (23%). CONCLUSIONS: Phantom measurements indicate that a regional adaptive exposure method can produce large DAP savings without compromising the noise performance in the image regions with highest noise.

The feasibility of an inverse geometry CT system with stationary source arrays.

PURPOSE: Inverse geometry computed tomography (IGCT) has been proposed as a new system architecture that combines a small detector with a large, distributed source. This geometry can suppress cone-beam artifacts, reduce scatter, and increase dose efficiency. However, the temporal resolution of IGCT is still limited by the gantry rotation time. Large reductions in rotation time are in turn difficult due to the large source array and associated power electronics. We examine the feasibility of using stationary source arrays for IGCT in order to achieve better temporal resolution. We anticipate that multiple source arrays are necessary, with each source array physically separated from adjacent ones. METHODS: Key feasibility issues include spatial resolution, artifacts, flux, noise, collimation, and system timing clashes. The separation between the different source arrays leads to missing views, complicating reconstruction. For the special case of three source arrays, a two-stage reconstruction algorithm is used to estimate the missing views. Collimation is achieved using a rotating collimator with a small number of holes. A set of equally spaced source spots are designated on the source arrays, and a source spot is energized when a collimator hole is aligned with it. System timing clashes occur when multiple source spots are scheduled to be energized simultaneously. We examine flux considerations to evaluate whether sufficient flux is available for clinical applications. RESULTS: The two-stage reconstruction algorithm suppresses cone-beam artifacts while maintaining resolution and noise characteristics comparable to standard third generation systems. The residual artifacts are much smaller in magnitude than the cone-beam artifacts eliminated. A mathematical condition is given relating collimator hole locations and the number of virtual source spots for which system timing clashes are avoided. With optimization, sufficient flux may be achieved for many clinical applications. CONCLUSIONS: IGCT with stationary source arrays could be an imaging platform potentially capable of imaging a complete 16-cm thick volume within a tenth of a second.

X-ray dose reduction through adaptive exposure in fluoroscopic imaging.

X-ray fluoroscopy is widely used for image guidance during cardiac intervention. However, radiation dose in these procedures can be high, and this is a significant concern, particularly in pediatric applications. Pediatrics procedures are in general much more complex than those performed on adults and thus are on average four to eight times longer. Furthermore, children can undergo up to 10 fluoroscopic procedures by the age of 10, and have been shown to have a three-fold higher risk of developing fatal cancer throughout their life than the general population. We have shown that radiation dose can be significantly reduced in adult cardiac procedures by using our scanning beam digital x-ray (SBDX) system-- a fluoroscopic imaging system that employs an inverse imaging geometry (Figure 1, Movie 1 and Figure 2). Instead of a single focal spot and an extended detector as used in conventional systems, our approach utilizes an extended X-ray source with multiple focal spots focused on a small detector. Our X-ray source consists of a scanning electron beam sequentially illuminating up to 9,000 focal spot positions. Each focal spot projects a small portion of the imaging volume onto the detector. In contrast to a conventional system where the final image is directly projected onto the detector, the SBDX uses a dedicated algorithm to reconstruct the final image from the 9,000 detector images. For pediatric applications, dose savings with the SBDX system are expected to be smaller than in adult procedures. However, the SBDX system allows for additional dose savings by implementing an electronic adaptive exposure technique. Key to this method is the multi-beam scanning technique of the SBDX system: rather than exposing every part of the image with the same radiation dose, we can dynamically vary the exposure depending on the opacity of the region exposed. Therefore, we can significantly reduce exposure in radiolucent areas and maintain exposure in more opaque regions. In our current implementation, the adaptive exposure requires user interaction (Figure 3). However, in the future, the adaptive exposure will be real time and fully automatic. We have performed experiments with an anthropomorphic phantom and compared measured radiation dose with and without adaptive exposure using a dose area product (DAP) meter. In the experiment presented here, we find a dose reduction of 30%.

Computed tomographic metal artifact reduction for the detection and quantitation of small features near large metallic implants: a comparison of published methods.

Computed tomographic imaging of tissue surrounding metallic implants is often limited by metal artifacts. This paper compares 3 existing metal artifact reduction techniques that are based on segmentation of metal-affected regions in native images, followed by reprojection of segmented areas into original Radon space, removal of metal trace(s), and renewed reconstruction: Detector row-wise linear interpolation, 2-dimensional interpolation, and combination of row-wise linear interpolation and adaptive filtering. For each method, improvements of CT number accuracy and signal-noise as well as contrast-noise ratios near the prosthesis and in the image periphery over the values found for native images were evaluated in a phantom experiment simulating osteolytic bone lesions of different size and density around a Chrome-Cobalt hip prosthesis stem. Improvement in diagnostic usability was evaluated as lesion detectability by size. Quantitative and qualitative results showed that the linear interpolation and the combination method removed the artifacts most effectively. The mean accuracy error over different regions of interest placed in the direct vicinity of the metal and in the periphery of the object decreased 10-fold with linear interpolation. These methods increased contrast-noise ratio up to 68% of that measured on artifact-free images for the least dense lesion. Qualitatively, the linear interpolation and the combination method improved the lesion detectability and enabled differentiation of different lesion densities. However, in proximity to the stem, some artifacts remained for all methods. We conclude that published algorithms for metal artifact reduction substantially improve image quality for CT imaging of a metallic object and may be adequate for quantitative measurements except for the direct vicinity of the metallic object.

Monte Carlo simulations of compact gamma cameras based on avalanche photodiodes.

Avalanche photodiodes (APDs), and in particular position-sensitive avalanche photodiodes (PSAPDs), are an attractive alternative to photomultiplier tubes (PMTs) for reading out scintillators for PET and SPECT. These solid-state devices offer high gain and quantum efficiency, and can potentially lead to more compact and robust imaging systems with improved spatial and energy resolution. In order to evaluate this performance improvement, we have conducted Monte Carlo simulations of gamma cameras based on avalanche photodiodes. Specifically, we investigated the relative merit of discrete and PSAPDs in a simple continuous crystal gamma camera. The simulated camera was composed of either a 4 x 4 array of four channels 8 x 8 mm2 PSAPDs or an 8 x 8 array of 4 x 4 mm2 discrete APDs. These configurations, requiring 64 channels readout each, were used to read the scintillation light from a 6 mm thick continuous CsI:Tl crystal covering the entire 3.6 x 3.6 cm2 photodiode array. The simulations, conducted with GEANT4, accounted for the optical properties of the materials, the noise characteristics of the photodiodes and the nonlinear charge division in PSAPDs. The performance of the simulated camera was evaluated in terms of spatial resolution, energy resolution and spatial uniformity at 99mTc (140 keV) and 125I ( approximately 30 keV) energies. Intrinsic spatial resolutions of 1.0 and 0.9 mm were obtained for the APD- and PSAPD-based cameras respectively for 99mTc, and corresponding values of 1.2 and 1.3 mm FWHM for 125I. The simulations yielded maximal energy resolutions of 7% and 23% for 99mTc and 125I, respectively. PSAPDs also provided better spatial uniformity than APDs in the simple system studied. These results suggest that APDs constitute an attractive technology especially suitable to build compact, small field of view gamma cameras dedicated, for example, to small animal or organ imaging.

A multipinhole small animal SPECT system with submillimeter spatial resolution.

Single photon emission computed tomography (SPECT) is an important technology for molecular imaging studies of small animals. In this arena, there is an increasing demand for high performance imaging systems that offer improved spatial resolution and detection efficiency. We have designed a multipinhole small animal imaging system based on position sensitive avalanche photodiode (PSAPD) detectors with the goal of submillimeter spatial resolution and high detection efficiency, which will allow us to minimize the radiation dose to the animal and to shorten the time needed for the imaging study. Our design will use 8 x 24 mm2 PSAPD detector modules coupled to thallium-doped cesium iodide [CsI(Tl)] scintillators, which can achieve an intrinsic spatial resolution of 0.5 mm at 140 keV. These detectors will be arranged in rings of 24 modules each; the animal is positioned in the center of the 9 stationary detector rings which capture projection data from the animal with a cylindrical tungsten multipinhole collimator. The animal is supported on a bed which can be rocked about the central axis to increase angular sampling of the object. In contrast to conventional SPECT pinhole systems, in our design each pinhole views only a portion of the object. However, the ensemble of projection data from all of the multipinhole detectors provide angular sampling that is sufficient to reconstruct tomographic data from the object. The performance of this multipinhole PSAPD imaging system was simulated using a ray tracing program that models the appropriate point spread functions and then was compared against the performance of a dual-headed pinhole SPECT system. The detection efficiency of both systems was simulated and projection data of a hot rod phantom were generated and reconstructed to assess spatial resolution. Appropriate Poisson noise was added to the data to simulate an acquisition time of 15 min and an activity of 18.5 MBq distributed in the phantom. Both sets of data were reconstructed with an ML-EM reconstruction algorithm. In addition, the imaging performance of both systems was evaluated with a uniformity phantom and a realistic digital mouse phantom. Simulations show that our proposed system produces a spatial resolution of 0.8 mm and an average detection efficiency of 630 cps/MBq. In contrast, simulations of the dual-headed pinhole SPECT system produce a spatial resolution of 1.1 mm and an average detection efficiency of 53 cps/MBq. These results suggest that our novel design will achieve high spatial resolution and will improve the detection efficiency by more than an order of magnitude compared to a dual-headed pinhole SPECT system. We expect that this system can perform SPECT with submillimeter spatial resolution, high throughput, and low radiation dose suitable for in vivo imaging of small animals.

A novel approach to multipinhole SPECT for myocardial perfusion imaging.

UNLABELLED: Myocardial perfusion imaging with SPECT remains critically important for diagnosing, assessing, and evaluating treatment of coronary artery disease. However, conventional rotational SPECT suffers from prolonged study times because of relatively low detection efficiency. We therefore have investigated a multipinhole collimator that could improve the detection efficiency in cardiac SPECT by a factor 5, while providing image quality comparable to standard rotational SPECT techniques using parallel-hole collimation. METHODS: We have measured the spatial resolution and efficiency of a 9-pinhole and a parallel-hole collimator mounted to a standard nuclear medicine gamma-camera as a function of distance from the collimator with a point source array. The efficiency was derived by integrating the detected counts, and the spatial resolution was determined from the full width at half maximum of the detected point spread function. In addition, we generated and reconstructed projection data of a 9-pinhole collimator from a digital heart phantom with a basal lesion. We simulated 3 scenarios: single view from left anterior, 2 views from left anterior and left lateral; and 4 views that include the 2 previous views and left lateral and anterior views. RESULTS: We found that the spatial resolution of the 9-pinhole collimator with 8-mm diameter pinholes was 30% poorer than that for the parallel-hole collimator, whereas the detection efficiency was increased by >10-fold. This predicts that a 9-pinhole collimator having the same spatial resolution as a parallel-hole collimator will have 5 times greater efficiency. Reconstructed data from 1 angular view of the 9-pinhole collimator showed the expected loss of spatial resolution in the longitudinal direction with reduced resolution of the basal lesion. In addition, the tomograms showed distortions in the apical region. In contrast, the reconstructed data from 2 and 4 views of the 9-pinhole collimator demonstrated good lesion definition and also produced images describing the shape and size of the heart more accurately. CONCLUSION: Our results indicate that myocardial multipinhole tomography with 2 or more views offers an image quality and spatial resolution comparable with current rotational SPECT techniques, but with the advantage of a 5-fold increase in efficiency.

Radiation dose estimate in small animal SPECT and PET.

Calculations of radiation dose are important in assessing the medical and biological implications of ionizing radiation in medical imaging techniques such as SPECT and PET. In contrast, radiation dose estimates of SPECT and PET imaging of small animals are not very well established. For that reason we have estimated the whole-body radiation dose to mice and rats for isotopes such as 18F, 99mTc, 201Tl, (111)In, 123I, and 125I that are used commonly for small animal imaging. We have approximated mouse and rat bodies with uniform soft tissue equivalent ellipsoids. The mouse and rat sized ellipsoids had a mass of 30 g and 300 g, respectively, and a ratio of the principal axes of 1:1:4 and 0.7:1:4. The absorbed fractions for various photon energies have been calculated using the Monte Carlo software package MCNP. Using these values, we then calculated MIRD S-values for two geometries that model the distribution of activity in the animal body: (a) a central point source and (b) a homogeneously distributed source, and compared these values against S-value calculations for small ellipsoids tabulated in MIRD Pamphlet 8 to validate our results. Finally we calculated the radiation dose taking into account the biological half-life of the radiopharmaceuticals and the amount of activity administered. Our calculations produced S-values between 1.06 x 10(-13) Gy/Bq s and 2.77 x 10(-13) Gy/Bq s for SPECT agents, and 15.0 x 10(-13) Gy/Bq s for the PET agent 18F, assuming mouse sized ellipsoids with uniform source distribution. The S-values for a central point source in an ellipsoid are about 10% higher than the values obtained for the uniform source distribution. Furthermore, the S-values for mouse sized ellipsoids are approximately 10 times higher than for the rat sized ellipsoids reflecting the difference in mass. We reviewed published data to obtain administered radioactivity and residence times for small animal imaging. From these values and our computed S-values we estimated that the whole body dose in small animals ranges between 6 cGy and 90 cGy for mice and between about 1 cGy and 27 cGy for rats. The whole body dose in small animal imaging can be very high in comparison to the lethal dose to mice (LD50/30 approximately 7 Gy). For this reason the dose in small animal imaging should be monitored carefully and the administered activity should be kept to a minimum. These results also underscore the need of further development of instrumentation that improves detection efficiency and reduces radiation dose in small animal imaging.

X-ray magnetic circular dichroism of Pseudomonas aeruginosa nickel(II) azurin.

We show that X-ray magnetic circular dichroism (XMCD) can be employed to probe the oxidation states and other electronic structural features of nickel active sites in proteins. As a calibration standard, we have measured XMCD and X-ray absorption (XAS) spectra for the nickel(II) derivative of Pseudomonas aeruginosa azurin (NiAz). Our analysis of these spectra confirms that the electronic ground state of NiAz is high-spin (S = 1); we also find that the L(3)-centroid energy is 853.1(1) eV, the branching ratio is 0.722(4), and the magnetic moment is 1.9(4) mu(B). Density functional theory (DFT) calculations on model NiAz structures establish that orbitals 3d(x2-y2) and 3d(z2) are the two valence holes in the high-spin Ni(II) ground state, and in accord with the experimentally determined orbital magnetic moment, the DFT results also demonstrate that both holes are highly delocalized, with 3d(x2-y2) having much greater ligand character.