Search tips
Search criteria

Results 1-25 (765)

Clipboard (0)

Select a Filter Below

Year of Publication
more »
Document Types
1.  Design and performance of a small-animal imaging system using synthetic collimation 
Physics in medicine and biology  2013;58(10):3397-3412.
This work outlines the design and construction of a single-photon emission computed tomography (SPECT) imaging system based on the concept of synthetic collimation. A focused multi-pinhole collimator is constructed using rapid-prototyping and casting techniques. The collimator projects the centre of the field of view (FOV) through forty-six pinholes when the detector is adjacent to the collimator, with the number reducing towards the edge of the FOV. The detector is then moved further from the collimator to increase the magnification of the system. The object distance remains constant, and each new detector distance is a new system configuration. The level of overlap of the pinhole projections increases as the system magnification increases, but the number of projections subtended by the detector is reduced. There is no rotation in the system; a single tomographic angle is used in each system configuration. Image reconstruction is performed using maximum-likelihood expectation-maximization (MLEM), and an experimentally measured system matrix. The system matrix is measured for each configuration on a coarse grid, using a point source. The pinholes are individually identified and tracked, and a Gaussian fit is made to each projection. The coefficients of these fits are used to interpolate the system matrix. The system is validated experimentally with a hot-rod phantom. The Fourier crosstalk matrix is also measured to provide an estimate of the average spatial resolution along each axis over the entire FOV. The 3D synthetic-collimator image is formed by estimating the activity distribution within the FOV, and summing the activities in the voxels along the axis perpendicular to the collimator face.
PMCID: PMC4520437  PMID: 23618819
2.  Dual-Dictionary Learning-Based Iterative Image Reconstruction for Spectral Computed Tomography Application 
Physics in medicine and biology  2012;57(24):8217-8229.
In this study, we investigated the effectiveness of a novel Iterative Reconstruction (IR) method coupled with Dual-Dictionary Learning (DDL) for image reconstruction in a dedicated breast Computed Tomography (CT) system based on a Cadmium-Zinc-Telluride (CZT) photon-counting detector and compared it to the Filtered-Back-Projection (FBP) method with the ultimate goal of reducing the number of projections necessary for reconstruction without sacrificing image quality. Postmortem breast samples were scanned in a fan-beam CT system and were reconstructed from 100–600 projections with both IR and FBP methods. The Contrast-to-Noise Ratio (CNR) between the glandular and adipose tissues of the postmortem breast samples was calculated to compare the quality of images reconstructed from IR and FBP. The spatial resolution of the two reconstruction techniques was evaluated using Aluminum (Al) wires with diameters of 643, 813, 1020, 1290 and 1630 µm in a plastic epoxy resin phantom with diameter of 13 cm. Both the spatial resolution and the CNR were improved with IR compared to FBP for the images reconstructed from the same number of projections. In comparison with FBP reconstruction, the CNR was improved from 3.4 to 7.5 by using the IR method with 6-fold fewer projections while maintaining the same spatial resolution. The study demonstrated that the IR method coupled with DDL could significantly reduce the required number of projections for a CT reconstruction compared to FBP method while achieving a much better CNR and maintaining the same spatial resolution. From this, the radiation dose and scanning time can potentially be reduced by a factor of approximately 6 by using this IR method for image reconstruction in a CZT-based breast CT system.
PMCID: PMC4511115  PMID: 23192234
Iterative reconstruction; Dual-dictionary learning; Contrast-to-noise ratio; Spatial resolution; Spectral breast computed tomography
3.  Digital Anthropomorphic Phantoms of Non-Rigid Human Respiratory and Voluntary Body Motion for Investigating Motion Correction in Emission Imaging 
Physics in medicine and biology  2014;59(14):3669-3682.
The development of methods for correcting patient motion in emission tomography has been receiving increased attention. Often performance of these methods is evaluated through simulations using digital anthropomorphic phantoms, such as the commonly used XCAT phantom, which models both respiratory and cardiac motion based on human studies. However, non-rigid body motion, which is frequently seen in clinical studies, is not present in the standard XCAT phantom. In addition, respiratory motion in the standard phantom is limited to a single generic trend. In this work, to obtain more realistic representation of motion, we developed a series of individual-specific XCAT phantoms modeling non-rigid respiratory and non-rigid body motions derived from the MRI acquisitions of volunteers. Acquisitions were performed in the sagittal orientation using the Navigator methodology. Baseline (no motion) acquisitions at end-expiration were obtained at the beginning of each imaging session for each volunteer. For the body motion studies, MRI was again acquired only at end-expiration for five body motion poses (shoulder stretch, shoulder twist, lateral bend, side roll, and axial slide). For the respiratory motion studies, MRI was acquired during free/regular breathing. The MR slices were then retrospectively sorted into 14 amplitude-binned respiratory states, end-expiration, end-inspiration, six intermediary states during inspiration, and six during expiration using the recorded Navigator signal. XCAT phantoms were then generated based on these MRI data by interactive alignment of the organ contours of the XCAT with the MRI slices using a GUI. Thus far we have created 5 body motion and 5 respiratory motion XCAT phantoms from MRI acquisitions of 6 healthy volunteers (3 males and 3 females). Non-rigid motion exhibited by the volunteers was reflected in both respiratory and body motion phantoms with a varying extent and character for each individual. In addition to these phantoms, we recorded the position of markers placed on the chest of volunteers for the body motion studies, which could be used as external motion measurement. Using these phantoms and external motion data, investigators will be able to test their motion correction approaches for realistic motion obtained from different individuals. The NURBS data and the parameter files for these phantoms are freely available for downloading and can be used with the XCAT license.*
PMCID: PMC4082965  PMID: 24925891
Respiratory and body motion; motion correction; XCAT phantoms; PET; SPECT
4.  An investigation of a PRESAGE® in-vivo dosimeter for brachytherapy 
Physics in medicine and biology  2014;59(14):3893-3905.
Determining accurate in-vivo dosimetry in brachytherapy treatment with high dose gradients is challenging. Here we introduce, investigate, and characterize a novel in-vivo dosimeter and readout technique with the potential to address this problem. A cylindrical (4 mm x 20 mm) tissue equivalent radiochromic dosimeter PRESAGE® In-Vivo (PRESAGE®-IV) is investigated. Two readout methods of the radiation induced change in optical density (OD) were investigated: (i) volume-averaged readout by spectrophotometer, and (ii) a line profile readout by 2D projection imaging utilizing a high-resolution (50 micron) telecentric optical system. Method (i) is considered the gold standard when applied to PRESAGE® in optical cuvettes. The feasibility of both methods was evaluated by comparison to standard measurements on PRESAGE® in optical cuvettes via spectrophotometer. An end-to-end feasibility study was performed by a side-by-side comparison with TLDs in an 192Ir HDR delivery. 7 and 8 Gy was delivered to PRESAGE®-IV and TLDs attached to the surface of a vaginal cylinder. Known geometry enabled direct comparison of measured dose with commissioned treatment planning system. A high-resolution readout study under a steep dose gradient region showed 98.9% (5%/1 mm) agreement between PRESAGE®-IV and Gafchromic® EBT2 Film. Spectrometer measurements exhibited a linear dose response between 0–15 Gy with sensitivity of 0.0133 ± 0.0007 ΔOD/(Gy·cm) at the 95% confidence interval. Method (ii) yielded a linear response with sensitivity of 0.0132 ± 0.0006 (ΔOD/Gy), within 2% of method (i). Method (i) has poor spatial resolution due to volume averaging. Method (ii) has higher resolution (~1mm) without loss of sensitivity or increased noise. Both readout methods are shown to be feasible. The end-to-end comparison revealed a 2.5% agreement between PRESAGE®-IV and treatment plan in regions of uniform high dose. PRESAGE®-IV shows promise for in-vivo dose verification, although improved sensitivity would be desirable. Advantages include high-resolution, convenience and fast, low-cost readout.
PMCID: PMC4136760  PMID: 24957850
5.  Deformable Image Registration with Local Rigidity Constraints for Cone-Beam CT Guided Spine Surgery 
Physics in medicine and biology  2014;59(14):3761-3787.
Image-guided spine surgery is associated with reduced co-morbidity and improved surgical outcome. However, precise localization of target anatomy and adjacent nerves and vessels relative to planning information (e.g., device trajectories) can be challenged by anatomical deformation. Rigid registration alone fails to account for deformation associated with changes in spine curvature, and conventional deformable registration fails to account for rigidity of the vertebrae, causing unrealistic distortions in the registered image that can confound high-precision surgery. We developed and evaluated a deformable registration method capable of preserving rigidity of bones while resolving the deformation of surrounding soft tissue. The method aligns preoperative CT to intraoperative CBCT using free-form deformation (FFD) with constraints on rigid body motion imposed according to a simple intensity threshold of bone intensities. The constraints enforced 3 properties of a rigid transformation – namely, constraints on affinity (AC), orthogonality (OC), and properness (PC). The method also incorporated an injectivity constraint (IC) to preserve topology. Physical experiments involving phantoms, an ovine spine, and a human cadaver as well as digital simulations were performed to evaluate the sensitivity to registration parameters, preservation of rigid body morphology, and overall registration accuracy of constrained FFD in comparison to conventional unconstrained FFD (denoted uFFD) and Demons registration. FFD with orthogonality and injectivity constraints (denoted FFD+OC+IC) demonstrated improved performance compared to uFFD and Demons. Affinity and properness constraints offered little or no additional improvement. The FFD+OC+IC method preserved rigid body morphology at near-ideal values of zero dilatation (𝒟 = 0.05, compared to 0.39 and 0.56 for uFFD and Demons, respectively) and shear (𝒮 = 0.08, compared to 0.36 and 0.44 for uFFD and Demons, respectively). Target registration error (TRE) was similarly improved for FFD+OC+IC (0.7 mm), compared to 1.4 and 1.8 mm for uFFD and Demons. Results were validated in human cadaver studies using CT and CBCT images, with FFD+OC+IC providing excellent preservation of rigid morphology and equivalent or improved TRE. The approach therefore overcomes distortions intrinsic to unconstrained FFD and could better facilitate high-precision image-guided spine surgery.
PMCID: PMC4118832  PMID: 24937093
deformable registration; Demons registration; free-form deformation; cone-beam CT; image-guided surgery
6.  Measuring Myofiber Orientations from High-frequency Ultrasound Images Using Multiscale Decompositions 
Physics in medicine and biology  2014;59(14):3907-3924.
High-frequency ultrasound (HFU) has the ability to image both skeletal and cardiac muscles. The quantitative assessment of these myofiber orientations has a number of applications in both research and clinical examinations; however, difficulties arise due to the severe speckle noise contained in the HFU images. Thus, for the purpose of automatically measuring myofiber orientations from two-dimensional HFU images, we propose a two-step multiscale image decomposition method. It combines a nonlinear anisotropic diffusion filter (NLADF) and a coherence enhancing diffusion filter (CEDF) to extract myofibers. This method has been verified by ultrasound data from simulated phantoms, excised fiber phantoms, specimens of porcine hearts, and human skeletal muscles in vivo. The quantitative evaluations of both phantoms indicated that the myofiber measurements of our proposed method were more accurate than other methods. The myofiber orientations extracted from different layers of the porcine hearts matched the prediction of an established cardiac mode and demonstrated the feasibility of extracting cardiac myofiber orientations from HFU images ex vivo. Moreover, HFU also demonstrated the ability to measure myofiber orientations in vivo.
PMCID: PMC4137038  PMID: 24957945
ultrasound imaging; Myofiber orientation; Multiscale decomposition
7.  Performance evaluation of the Ingenuity TF PET/CT scanner with a focus on high count-rate conditions 
Physics in medicine and biology  2014;59(14):3843-3859.
This study evaluated the positron emission tomography (PET) imaging performance of the Ingenuity TF 128 PET/computed tomography (CT) scanner which has a PET component that was designed to support a wider radioactivity range than is possible with those of Gemini TF PET/CT and Ingenuity TF PET/MR. Spatial resolution, sensitivity, count rate characteristics and image quality were evaluated according to the NEMA NU 2–2007 standard and ACR phantom accreditation procedures; these were supplemented by additional measurements intended to characterize the system under conditions that would be encountered during quantitative cardiac imaging with 82Rb. Image quality was evaluated using a hot spheres phantom, and various contrast recovery and noise measurements were made from replicated images. Timing and energy resolution, dead time, and the linearity of the image activity concentration, were all measured over a wide range of count rates. Spatial resolution (4.8– 5.1 mm FWHM), sensitivity (7.3 cps kBq−1), peak noise-equivalent count rate (124 kcps), and peak trues rate (365 kcps)were similar to those of the Gemini TF PET/CT. Contrast recovery was higher with a 2 mm, body-detail reconstruction than with a 4 mm, body reconstruction, although the precision was reduced. The noise equivalent count rate peak was broad (within 10% of peak from 241–609 MBq). The activity measured in phantom images was within 10% of the true activity for count rates up to those observed in 82Rb cardiac PET studies.
PMCID: PMC4457340  PMID: 24955921
positron emission tomography; performance; high count rate
8.  Measurement of gastric meal and secretion volumes using magnetic resonance imaging 
Physics in medicine and biology  2015;60(3):1367-1383.
MRI can assess multiple gastric functions without ionizing radiation. However, time consuming image acquisition and analysis of gastric volume data, plus confounding of gastric emptying measurements by gastric secretions mixed with the test meal have limited its use to research centres. This study presents an MRI acquisition protocol and analysis algorithm suitable for the clinical measurement of gastric volume and secretion volume. Reproducibility of gastric volume measurements was assessed using data from 10 healthy volunteers following a liquid test meal with rapid MRI acquisition within one breath-hold and semi-automated analysis. Dilution of the ingested meal with gastric secretion was estimated using a respiratory-triggered T1 mapping protocol. Accuracy of the secretion volume measurements was assessed using data from 24 healthy volunteers following a mixed (liquid/solid) test meal with MRI meal volumes compared to data acquired using gamma scintigraphy (GS) on the same subjects studied on a separate study day. The mean (SD) coefficient of variance between 3 observers for both total gastric contents (including meal, secretions and air) and just the gastric contents (meal and secretion only) was 3 (2) % at large gastric volumes (> 200 ml). Mean (SD) secretion volumes post meal ingestion were 64 (51) ml and 110 (40) ml at 15 and 75 minutes respectively. Comparison with GS meal volumes, showed that MRI meal only volume (after correction for secretion volume) were similar to GS, with a linear regression gradient (std err) of 1.06 (0.10) and intercept −11 (24) ml. In conclusion, (i) rapid acquisition removed the requirement to image during prolonged breath-hold (ii) semi-automatic analysis greatly reduced time required to derive measurements and (iii) correction for secretion volumes provides accurate assessment of gastric meal volumes and emptying. Together these features provide the scientific basis of a protocol which would be suitable in clinical practice.
PMCID: PMC4502365  PMID: 25592405
Gastric Volume; MRI; secretion
9.  Fundamental Limits of Scintillation Detector Timing Precision 
Physics in medicine and biology  2014;59(13):3261-3286.
In this paper we review the primary factors that affect the timing precision of a scintillation detector. Monte Carlo calculations were performed to explore the dependence of the timing precision on the number of photoelectrons, the scintillator decay and rise times, the depth of interaction uncertainty, the time dispersion of the optical photons (modeled as an exponential decay), the photodetector rise time and transit time jitter, the leading-edge trigger level, and electronic noise.
The Monte Carlo code was used to estimate the practical limits on the timing precision for an energy deposition of 511 keV in 3 mm × 3 mm × 30 mm Lu2SiO5:Ce and LaBr3:Ce crystals. The calculated timing precisions are consistent with the best experimental literature values. We then calculated the timing precision for 820 cases that sampled scintillator rise times from 0 to 1.0 ns, photon dispersion times from 0 to 0.2 ns, photodetector time jitters from 0 to 0.5 ns fwhm, and A from 10 to 10,000 photoelectrons per ns decay time. Since the timing precision R was found to depend on A−1/2 more than any other factor, we tabulated the parameter B, where R = BA−1/2. An empirical analytical formula was found that fit the tabulated values of B with an rms deviation of 2.2% of the value of B.
The theoretical lower bound of the timing precision was calculated for the example of 0.5 ns rise time, 0.1 ns photon dispersion, and 0.2 ns fwhm photodetector time jitter. The lower bound was at most 15% lower than leading-edge timing discrimination for A from 10 to 10,000 photoelectrons/ns.
A timing precision of 8 ps fwhm should be possible for an energy deposition of 511 keV using currently available photodetectors if a theoretically possible scintillator were developed that could produce 10,000 photoelectrons/ns.
PMCID: PMC4071963  PMID: 24874216
10.  Modeling the Efficiency of a Magnetic Needle for Collecting Magnetic Cells 
Physics in medicine and biology  2014;59(13):3319-3335.
As new magnetic nanoparticle-based technologies are developed and new target cells are identified, there is a critical need to understand the features important for magnetic isolation of specific cells in fluids, an increasingly important tool in disease research and diagnosis. To investigate magnetic cell collection, cell-sized spherical microparticles, coated with superparamagnetic nanoparticles, were suspended in 1) glycerine-water solutions, chosen to approximate the range of viscosities of bone marrow, and 2) water in which 3, 5, 10 and 100 % of the total suspended microspheres are coated with magnetic nanoparticles, to model collection of rare magnetic nanoparticle-coated cells from a mixture of cells in a fluid. The magnetic microspheres were collected on a magnetic needle, and we demonstrate that the collection efficiency vs. time can be modeled using a simple, heuristically-derived function, with three physically-significant parameters. The function enables experimentally-obtained collection efficiencies to be scaled to extract the effective drag of the suspending medium. The results of this analysis demonstrate that the effective drag scales linearly with fluid viscosity, as expected. Surprisingly, increasing the number of non-magnetic microspheres in the suspending fluid results increases the collection of magnetic microspheres, corresponding to a decrease in the effective drag of the medium.
PMCID: PMC4084562  PMID: 24874577
magnetic separation; magnetic nanoparticles; magnetic needle; rare cell detection
11.  Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions 
Physics in medicine and biology  2014;59(13):3465-3481.
Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 seconds using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650-kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P<0.05) after PSNE injection and this was well correlated with enhanced HIFU-mediated heating in tumors. The peak temperature rise induced by sonication was significantly higher (P<0.05) after PSNE injection. For example, the mean percent change in temperature achieved at 5.2 W of acoustic power was 46 ± 22% with PSNE injection. The results indicate that PSNE nucleates cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could potentially be used to reduce the time and/or acoustic intensity required for HIFU-mediated heating, thereby increasing the feasibility and clinical efficacy of HIFU thermal ablation therapy.
PMCID: PMC4119424  PMID: 24899634
MR-guided high intensity focused ultrasound; Phase-shift nanoemulsions; Acoustic droplet vaporization; Microbubble cavitation; Tumor ablation
12.  Limited-angle tomography for analyzer-based phase-contrast X-ray imaging 
Physics in medicine and biology  2014;59(13):3483-3500.
Multiple-Image Radiography (MIR) is an analyzer-based phase-contrast X-ray imaging method (ABI), which is emerging as a potential alternative to conventional radiography. MIR simultaneously generates three planar parametric images containing information about scattering, refraction and attenuation properties of the object. The MIR planar images are linear tomographic projections of the corresponding object properties, which allows reconstruction of volumetric images using computed tomography (CT) methods. However, when acquiring a full range of linear projections around the tissue of interest is not feasible or the scanning time is limited, limited-angle tomography techniques can be used to reconstruct these volumetric images near the central plane, which is the plane that contains the pivot point of the tomographic movement. In this work, we use computer simulations to explore the applicability of limited-angle tomography to MIR. We also investigate the accuracy of reconstructions as a function of number of tomographic angles for a fixed total radiation exposure. We use this function to find an optimal range of angles over which data should be acquired for limited-angle tomography MIR (LAT-MIR). Next, we apply the LAT-MIR technique to experimentally acquired MIR projections obtained in a cadaveric human thumb study. We compare the reconstructed slices near the central plane to the same slices reconstructed by CT-MIR using the full angular view around the object. Finally, we perform a task-based evaluation of LAT-MIR performance for different numbers of angular views, and use template matching to detect cartilage in the refraction image near the central plane. We use the signal-to-noise ratio of this test as the detectability metric to investigate an optimum range of tomographic angles for detecting soft tissues in LAT-MIR. Both results show that there is an optimum range of angular view for data acquisition where LAT-MIR yields the best performance, comparable to CT-MIR only if one considers volumetric images near the central plane and not the whole volume.
PMCID: PMC4136387  PMID: 24898008
X-ray; phase contrast; tomosynthesis; limited angle tomography
13.  4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors 
Physics in medicine and biology  2014;59(13):3431-3452.
Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.
PMCID: PMC4139294  PMID: 24889215
4D optimization; ion therapy; carbon; proton therapy; motion; lung; beam tracking
14.  Limiting factors for the scintillation detector coincidence resolving time in positron emission tomography 
Physics in medicine and biology  2014;59(13):3615-3635.
We present Monte Carlo computational methods for estimating the coincidence resolving time (CRT) of scintillator detector pairs in positron emission tomography (PET) and present results for Lu2SiO5:Ce (LSO), LaBr3:Ce, and a hypothetical ultra-fast scintillator with a 1 ns decay time. The calculations were applied to both single-ended and double-ended photodetector readout with leading-edge triggering. They explicitly include (1) the intrinsic scintillator properties (luminosity, rise time, decay time, and index of refraction), (2) the exponentially distributed depths of interaction, (3) the optical photon transport efficiency, delay, and time dispersion, (4) the photodetector properties (fill factor, quantum efficiency, transit time jitter, and single electron response), and (5) the determination of the trigger level that optimizes the CRT. The calculations for single-ended readout include the delayed photons from the opposite reflective surface. The calculations for double-ended readout include the simple average of the two photodetector trigger times, as well as more accurate estimators of the annihilation photon entrance time using the pulse height ratio to estimate the depth of interaction and correct for annihilation photon, optical photon, and trigger delays. For time-of-flight (TOF) PET we combine stopping power and TOF information in a figure of merit equal to the sensitivity gain relative to whole-body non-TOF PET using LSO.
For LSO, a decay time of 37 ns, a total photoelectron count of 4,000, and a photodetector with 0.2 ns full-width at half-maximum (fwhm) timing jitter, single-ended readout has a CRT of 0.16 ns fwhm and double-ended readout has a CRT of 0.111 ns fwhm. For LaBr3:Ce, a rise time of 0.2 ns, a decay time of 18 ns, and a total of 7,600 photoelectrons the CRT numbers are 0.14 and 0.072 ns fwhm, respectively. For a the ultra-fast scintillator with a decay time of 1 ns and a total of 4,000 photoelectrons, the CRT numbers are 0.070 and 0.020 ns fwhm, respectively.
PMCID: PMC4397582  PMID: 24922188
15.  Statistical LOR estimation for a high-resolution dMiCE PET detector 
Physics in medicine and biology  2009;54(20):6369-6382.
We develop a statistical line of response (LOR) estimator of the three-dimensional interaction positions of a pair of annihilation photons in a PET detector module with depth of interaction capability. The three-dimensional points of interaction of a coincidence pair of photons within the detector module are estimated by calculation of an expectation of the points of interaction conditioned on the signals measured by the photosensors. This conditional expectation is computed from estimates of the probability density function of the light collection process and a model of the kinetics of photon interactions in the detector module. Our algorithm is capable of handling coincidences where each annihilation photon interacts any number of times within the detector module before being completely absorbed or escaping. In the case of multiple interactions, our algorithm estimates the position of the first interaction for each of the coincidence photons. This LOR estimation algorithm is developed for a high-resolution PET detector capable of providing depth-of-interaction information. Depth of interaction is measured by tailoring the light shared between two adjacent detector elements. These light-sharing crystal pairs are referred to as dMiCE and are being developed in our lab. Each detector element in the prototype system has a 2 × 2 mm2 cross section and is directly coupled to a micro-pixel avalanche photodiode (MAPD). In this set-up, the distribution of the ratio of light shared between two adjacent detector elements can be expressed as a function of the depth of interaction. Monte Carlo experiments are performed using our LOR estimation algorithm and compared with Anger logic. We show that our LOR estimation algorithm provides a significant improvement over Anger logic under a variety of parameters.
PMCID: PMC4491195  PMID: 19809102
16.  Experimental realization of fluence field modulated CT using digital beam attenuation 
Physics in medicine and biology  2014;59(5):1305-1326.
Tailoring CT scan acquisition parameters to individual patients is a topic of much research in the CT imaging community. It is now common place to find automatically adjusted tube current options for modern CT scanners. In addition, the use of beam shaping filters, commonly called bowtie filters, is available on most CT systems and allows for different body regions to receive different incident x-ray fluence distributions. However, no method currently exists which allows for the form of the incident x-ray fluence distribution to change as a function of view angle. This study represents the first experimental realization of fluence field modulated CT (FFMCT) for a c-arm geometry CT scan. Methods: X-ray fluence modulation is accomplished using a digital beam attenuator (DBA). The device is composed of 10 iron wedge pairs that modulate the thickness of iron x-rays must traverse before reaching a patient. Using this device, experimental data was taken using a Siemens Zeego c-arm scanner. Scans were performed on a cylindrical polyethylene phantom and on two different sections of an anthropomorphic phantom. The DBA was used to equalize the x-ray fluence striking the detector for each scan. Non DBA, or “flat field” scans were also acquired of the same phantom objects for comparison. In addition, a scan was performed in which the DBA was used to enable volume of interest (VOI) imaging. In VOI, only a small sub-volume within a patient receives full dose and the rest of the patient receives a much lower dose. Data corrections unique to using a piece-wise constant modulator were also developed.
The feasibility of FFMCT implemented using a DBA device has been demonstrated. Initial results suggest dose reductions of up to 3.6 times relative to “flat field” CT. In addition to dose reduction, the DBA enables a large improvement in image noise uniformity and the ability to provide regionally enhanced signal to noise using VOI imaging techniques.
The results presented in this paper take the field of FFMCT from the theoretical stage to that of possible clinical implementation. FFMCT, as shown in this paper, can reduce patient dose while maintaining or improving image quality. In addition, the DBA has been experimentally shown to be well suited to implement entirely new imaging methods like photon counting and VOI imaging.
PMCID: PMC4487678  PMID: 24556823
fluence field modulated CT; volume of interest imaging; dynamic collimator
17.  Extension of the NCAT phantom for the investigation of intra-fraction respiratory motion in IMRT using 4D Monte Carlo 
Physics in medicine and biology  2010;55(5):1475-1490.
The purpose of this work was to create a computational platform for studying motion in intensity modulated radiotherapy (IMRT). Specifically, the non-uniform rational B-spline (NURB) cardiac and torso (NCAT) phantom was modified for use in a four-dimensional Monte Carlo (4D-MC) simulation system to investigate the effect of respiratory-induced intra-fraction organ motion on IMRT dose distributions as a function of diaphragm motion, lesion size and lung density. Treatment plans for four clinical scenarios were designed: diaphragm peak-to-peak amplitude of 1 cm and 3 cm, and two lesion sizes—2 cm and 4 cm diameter placed in the lower lobe of the right lung. Lung density was changed for each phase using a conservation of mass calculation. Further, a new heterogeneous lung model was implemented and tested. Each lesion had an internal target volume (ITV) subsequently expanded by 15 mm isotropically to give the planning target volume (PTV). The PTV was prescribed to receive 72 Gy in 40 fractions. The MLC leaf sequence defined by the planning system for each patient was exported and used as input into the MC system. MC simulations using the dose planning method (DPM) code together with deformable image registration based on the NCAT deformation field were used to find a composite dose distribution for each phantom. These composite distributions were subsequently analyzed using information from the dose volume histograms (DVH). Lesion motion amplitude has the largest effect on the dose distribution. Tumor size was found to have a smaller effect and can be mitigated by ensuring the planning constraints are optimized for the tumor size. The use of a dynamic or heterogeneous lung density model over a respiratory cycle does not appear to be an important factor with a ≤ 0.6% change in the mean dose received by the ITV, PTV and right lung. The heterogeneous model increases the realism of the NCAT phantom and may provide more accurate simulations in radiation therapy investigations that use the phantom. This work further evaluates the NCAT phantom for use as a tool in radiation therapy research in addition to its extensive use in diagnostic imaging and nuclear medicine research. Our results indicate that the NCAT phantom, combined with 4D-MC simulations, is a useful tool in radiation therapy investigations and may allow the study of relative effects in many clinically relevant situations.
PMCID: PMC4482131  PMID: 20157230
18.  A modular method to handle multiple time-dependent quantities in Monte Carlo simulations 
Physics in medicine and biology  2012;57(11):3295-3308.
A general method for handling time-dependent quantities in Monte Carlo simulations was developed to make such simulations more accessible to the medical community for a wide range of applications in radiotherapy, including fluence and dose calculation. To describe time-dependent changes in the most general way, we developed a grammar of functions that we call “Time Features”. When a simulation quantity, such as the position of a geometrical object, an angle, a magnetic field, a current, etc., takes its value from a Time Feature, that quantity varies over time. The operation of time-dependent simulation was separated into distinct parts: the Sequence samples time values either sequentially at equal increments or randomly from a uniform distribution (allowing quantities to vary continuously in time), then each time-dependent quantity is calculated according to its Time Feature. Due to this modular structure, time-dependent simulations, even in the presence of multiple time-dependent quantities, can be efficiently performed in a single simulation with any given time resolution. This approach has been implemented in TOPAS (TOol for PArticle Simulation), designed to make Monte Carlo simulations with Geant4 more accessible to both clinical and research physicists. To demonstrate the method, three clinical situations were simulated: a variable water column used to verify constancy of the Bragg peak of the Crocker Lab eye treatment facility of the University of California, the double-scattering treatment mode of the passive beam scattering system at Massachusetts General Hospital (MGH), where a spinning range modulator wheel (RMW) accompanied by beam current modulation produces a spread-out Bragg Peak, and the scanning mode at MGH, where time-dependent pulse shape, energy distribution and magnetic fields control Bragg peak positions. Results confirm the clinical applicability of the method.
PMCID: PMC4477630  PMID: 22572201
19.  Image Artefact Propagation in Motion Estimation and Reconstruction in Interventional Cardiac C-arm CT 
Physics in medicine and biology  2014;59(12):3121-3138.
The acquisition of data for cardiac imaging using a C-arm CT system requires several seconds and multiple heartbeats. Hence, incorporation of motion correction in the reconstruction step may improve the resulting image quality. Cardiac motion can be estimated by deformable 3-D/3-D registration performed on initial 3-D images of different heart phases. This motion information can be used for a motion-compensated reconstruction allowing the use of all acquired data for image reconstruction. However, the result of the registration procedure and hence the estimated deformations are influenced by the quality of the initial 3-D images. In this paper, the sensitivity of the 3-D/3-D registration step to the image quality of the initial images is studied. Different reconstruction algorithms are evaluated for a recently proposed cardiac C-arm CT acquisition protocol. The initial 3-D images are all based on retrospective electrocardiogram (ECG)-gated data. ECG-gating of data from a single C-arm rotation provides only a few projections per heart phase for image reconstruction. This view sparsity leads to prominent streak artefacts and a poor signal to noise ratio. Five different initial image reconstructions are evaluated: (1) cone beam filtered-backprojection (FDK), (2) cone beam filtered-backprojection and an additional bilateral filter (FFDK), (3) removal of the shadow of dense objects (catheter, pacing electrode, etc.) before reconstruction with a cone beam filtered-backprojection (cathFDK), (4) removal of the shadow of dense objects before reconstruction with a cone beam filtered-backprojection and a bilateral filter (cathFFDK). The last method (5) is an iterative few-view reconstruction (FV), the prior image constrained compressed sensing (PICCS) combined with the improved total variation (iTV) algorithm. All reconstructions are investigated with respect to the final motion-compensated reconstruction quality. The algorithms were tested on a mathematical phantom data set with and without a catheter and on two porcine models using qualitative and quantitative measures. The quantitative results of the phantom experiments show that if no dense object is present within the scan field of view, the quality of the FDK initial images is sufficient for motion estimation via 3-D/3-D registration. When a catheter or pacing electrode is present, the shadow of these objects needs to be removed before the initial image reconstruction. An additional bilateral filter shows no major improvement with respect to the final motion-compensated reconstruction quality. The results with respect to image quality of the cathFDK, cathFFDK and FV images are comparable. As conclusion, in terms of computational complexity, the algorithm of choice is the cathFDK algorithm.
PMCID: PMC4110354  PMID: 24840084
20.  Design of a digital phantom population for myocardial perfusion SPECT imaging research 
Physics in medicine and biology  2014;59(12):2935-2953.
Digital phantoms and Monte Carlo (MC) simulations have become important tools for optimizing and evaluating instrumentation, acquisition and processing methods for myocardial perfusion SPECT (MPS). In this work, we designed a new adult digital phantom population and generated corresponding Tc-99m and Tl-201 projections for use in MPS research. The population is based on the 3D XCAT phantom with organ parameters sampled from the Emory PET Torso Model Database. Phantoms included 3 variations each in body size, heart size, and subcutaneous adipose tissue level, for a total of 27 phantoms of each gender. The SimSET Monte Carlo code and angular response functions were used to model interactions in the body and the collimator-detector system, respectively. We divided each phantom into seven organs, each simulated separately, allowing use of post-simulation summing to efficiently model uptake variations. Also, we adapted and used a criterion based on the relative Poisson effective count level to determine the required number of simulated photons for each simulated organ. This technique provided a quantitative estimate of the true noise in the simulated projection data, including residual MC simulation noise. Projections were generated in 1 keV wide energy windows from 48-184 keV assuming perfect energy resolution to permit study of the effects of window width, energy resolution, and crosstalk in the context of dual isotope MPS. We have developed a comprehensive method for efficiently simulating realistic projections for a realistic population of phantoms in the context of MPS imaging. The new phantom population and realistic database of simulated projections will be useful in performing mathematical and human observer studies to evaluate various acquisition and processing methods such as optimizing the energy window width, investigating the effect of energy resolution on image quality and evaluating compensation methods for degrading factors such as crosstalk in the context of single and dual isotope MPS.
PMCID: PMC4180510  PMID: 24841729
Digital phantom population; Myocardial Perfusion SPECT and Monte Carlo simulation
21.  Sparse-view X-ray CT Reconstruction via Total Generalized Variation Regularization 
Physics in medicine and biology  2014;59(12):2997-3017.
Sparse-view CT reconstruction algorithms via total variation (TV) optimize the data iteratively on the basis of a noise- and artifact-reducing model, resulting in significant radiation dose reduction while maintaining image quality. However, the piecewise constant assumption of TV minimization often leads to the appearance of noticeable patchy artifacts in reconstructed images. To obviate this drawback, we present a penalized weighted least-squares (PWLS) scheme to retain the image quality by incorporating the new concept of total generalized variation (TGV) regularization. We refer to the proposed scheme as “PWLS-TGV” for simplicity. Specifically, TGV regularization utilizes higher order derivatives of the objective image, and the weighted least-squares term considers data-dependent variance estimation, which fully contribute to improving the image quality with sparse-view projection measurement. Subsequently, an alternating optimization algorithm was adopted to minimize the associative objective function. To evaluate the PWLS-TGV method, both qualitative and quantitative studies were conducted by using digital and physical phantoms. Experimental results show that the present PWLS-TGV method can achieve images with several noticeable gains over the original TV-based method in terms of accuracy and resolution properties.
PMCID: PMC4219274  PMID: 24842150
x-ray; sparse-view; total variation; total generalized variation; regularization
22.  GPU-based fast Monte Carlo dose calculation for proton therapy 
Physics in medicine and biology  2012;57(23):7783-7797.
Accurate radiation dose calculation is essential for successful proton radiotherapy. Monte Carlo (MC) simulation is considered to be the most accurate method. However, the long computation time limits it from routine clinical applications. Recently, graphics processing units (GPUs) have been widely used to accelerate computationally intensive tasks in radiotherapy. We have developed a fast MC dose calculation package, gPMC, for proton dose calculation on a GPU. In gPMC, proton transport is modeled by the class II condensed history simulation scheme with a continuous slowing down approximation. Ionization, elastic and inelastic proton nucleus interactions are considered. Energy straggling and multiple scattering are modeled. Secondary electrons are not transported and their energies are locally deposited. After an inelastic nuclear interaction event, a variety of products are generated using an empirical model. Among them, charged nuclear fragments are terminated with energy locally deposited. Secondary protons are stored in a stack and transported after finishing transport of the primary protons, while secondary neutral particles are neglected. gPMC is implemented on the GPU under the CUDA platform. We have validated gPMC using the TOPAS/Geant4 MC code as the gold standard. For various cases including homogeneous and inhomogeneous phantoms as well as a patient case, good agreements between gPMC and TOPAS/Geant4 are observed. The gamma passing rate for the 2%/2 mm criterion is over 98.7% in the region with dose greater than 10% maximum dose in all cases, excluding low-density air regions. With gPMC it takes only 6–22 s to simulate 10 million source protons to achieve ~1% relative statistical uncertainty, depending on the phantoms and energy. This is an extremely high efficiency compared to the computational time of tens of CPU hours for TOPAS/Geant4. Our fast GPU-based code can thus facilitate the routine use of MC dose calculation in proton therapy.
PMCID: PMC4474737  PMID: 23128424
23.  Gauging the likelihood of stable cavitation from ultrasound contrast agents 
Physics in medicine and biology  2012;58(1):127-144.
The mechanical index (MI) was formulated to gauge the likelihood of adverse bioeffects from inertial cavitation. However, the MI formulation did not consider bubble activity from stable cavitation. This type of bubble activity can be readily nucleated from ultrasound contrast agents (UCAs) and has the potential to promote beneficial bioeffects. Here, the presence of stable cavitation is determined numerically by tracking the onset of subharmonic oscillations within a population of bubbles for frequencies up to 7 MHz and peak rarefactional pressures up to 3 MPa. In addition, the acoustic pressure rupture threshold of an UCA population was determined using the Marmottant model. The threshold for subharmonic emissions of optimally sized bubbles was found to be lower than the inertial cavitation threshold for all frequencies studied. The rupture thresholds of optimally sized UCAs were found to be lower than the threshold for subharmonic emissions for either single cycle or steady state acoustic excitations. Because the thresholds of both subharmonic emissions and UCA rupture are linearly dependent on frequency, an index of the form ICAV = Pr/f (where Pr is the peak rarefactional pressure in MPa and f is the frequency in MHz) was derived to gauge the likelihood of subharmonic emissions due to stable cavitation activity nucleated from UCAs.
PMCID: PMC4467591  PMID: 23221109
24.  A method for determination of the absorption and scattering properties interstitially in turbid media 
Physics in medicine and biology  2005;50(10):2291-2311.
We have developed a method to quickly determine tissue optical properties (absorption coefficient μa and transport scattering coefficient μs′) by measuring the ratio of light fluence rate to source power along a linear channel at a fixed distance (5 mm) from an isotropic point source. Diffuse light is collected by an isotropic detector whose position is determined by a computer-controlled step motor, with a positioning accuracy of better than 0.1 mm. The system automatically records and plots the light fluence rate per unit source power as a function of position. The result is fitted with a diffusion equation to determine μa and μs′. We use an integrating sphere to calibrate each source–detector pair, thus reducing uncertainty of individual calibrations. To test the ability of this algorithm to accurately recover the optical properties of the tissue, we made measurements in tissue simulating phantoms consisting of Liposyn at concentrations of 0.23, 0.53 and 1.14% μs′=1.7–9.1cm−1) in the presence of Higgins black India ink at concentrations of 0.002, 0.012 and 0.023% (μa = 0.1–1 cm−1). For comparison, the optical properties of each phantom are determined independently using broad-beam illumination. We find that μa and μs′ can be determined by this method with a standard (maximum) deviation of 8% (15%) and 18% (32%) for μa and μs′, respectively. The current method is effective for samples whose optical properties satisfy the requirement of the diffusion approximation. The error caused by the air cavity introduced by the catheter is small, except when μa is large (μa > 1 cm−1). We presented in vivo data measured in human prostate using this method.
PMCID: PMC4467592  PMID: 15876668
25.  Study of electrode pattern design for a CZT-based PET detector 
Physics in medicine and biology  2014;59(11):2599-2621.
We are developing a 1 mm resolution small animal positron emission tomography (PET) system using 3-D positioning Cadmium Zinc Telluride (CZT) photon detectors comprising 40 mm × 40 mm × 5 mm crystals metalized with a cross-strip electrode pattern with a 1 mm anode strip pitch. We optimized the electrode pattern design for intrinsic sensitivity and spatial, energy and time resolution performance using a test detector comprising cathode and steering electrode strips of varying dimensions. The study found 3 mm and 5 mm width cathode strips locate charge-shared photon interactions near cathode strip boundaries with equal precision. 3 mm width cathode strips exhibited large time resolution variability as a function of photon interaction location between the anode and cathode planes (~26 ns to ~127.5 ns FWHM for 0.5 mm and 4.2 mm depths, respectively). 5 mm width cathode strips by contrast exhibited more stable time resolution for the same interaction locations (~34 ns to ~83 ns FWHM), provided more linear spatial positioning in the direction orthogonal to the electrode planes, and as much as 68.4% improvement in photon sensitivity over the 3 mm wide cathode strips. The results were understood by analyzing the cathode strips’ weighting functions, which indicated a stronger “small pixel” effect in the 3 mm wide cathode strips. Photon sensitivity and anode energy resolution were seen to improve with decreasing steering electrode bias from 0 V to −80 V w.r.t the anode potential. A slight improvement in energy resolution was seen for wider steering electrode strips (400 μm vs. 100 μm) for charge-shared photon interactions. Although this study successfully focused on electrode pattern features for PET performance, the results are generally applicable to semiconductor photon detectors employing cross-trip electrode patterns.
PMCID: PMC4065862  PMID: 24786208
CZT; semiconductor detector; cross-strip electrode; charge collection; high resolution; PET; small animal

Results 1-25 (765)