Fentanyl overdose: Temporal effects and prognostic factors in SKH1 mice.

Fentanyl exposure and overdose are growing concerns in public health and occupational safety. This study aimed to establish parameters of fentanyl lethality in SKH1 mice for future overdose research. Lethality was determined using the up-down procedure, with subjects monitored post-administration using pulse oximetry (5 min) and then whole-body plethysmography (40 min). Following the determination of subcutaneous dose-response, [18F]Fluorodeoxyglucose positron emission tomography (18 F-FDG PET) was performed after LD10 fentanyl at 40 min, 6 h, 24 h or 7 days post-dose. LD10 and LD50 were observed to be 110 and 135 mg/kg, respectively, and consistent with four-parameter logistic fit values of 111.2 and 134.6 mg/kg (r2  = 0.9996). Overdose (LD10 or greater) yielded three distinct cardiovascular groups: survival, non-survival with blood oxygen saturation (SpO2) minimum ≥37% and non-survival with SpO2 <37%. Breaths per minute, minute volume and inspiratory quotient were significantly different between surviving and non-surviving animals for up to 40 min post-injection. 18 F-FDG PET revealed decreased glucose uptake in the heart, lungs and brain for up to 24 h. These findings provide critical insights into fentanyl lethality in SKH1 mice, including non-invasive respiratory effects and organ-specific impacts that are invaluable for future translational studies investigating the temporal effects of fentanyl overdose.

Quantitative single photon emission computed tomography derived standardized uptake values on 99mTc-PYP scan in patients with suspected ATTR cardiac amyloidosis.

Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR.

A dedicated breast-PET/CT scanner: Numerical observer study of lesion detection.

BACKGROUND: Dedicated, breast-specific positron emission tomography (BPET)-cone-beam computed tomography (BPET/CT) systems have been developed to improve detection and diagnosis of cancer in women with indeterminate mammograms caused by radiodense breasts. The absorption of X-rays that often vexes mammography in this subset of women does not affect the detection of the high energy annihilation photons used in PET. PET imaging of the breast, however, is subject to limitations caused by their comparatively low spatial resolution (∼2 mm) and often moderate radiotracer uptake in lesions. PURPOSE: The purpose of this investigation is to explore the PET-based lesion detection capabilities of a BPET/CT scanner developed by the Department of Radiology Instrumentation group at West Virginia University. METHODS: The PET component of the system consists of a rotating pair of 96 × 72 arrays of 2 × 2 × 15 mm3 LYSO scintillator elements. The cone-beam-CT component utilized a pulsed X-ray source and flat panel detector operated in portrait orientation. The density maps created by the CT scanner were used to correct the BPET data for photon attenuation and Compton scattering. The nonuniform uptake of 18 F-fluorodeoxyglucose (FDG) in normal breast tissue was emulated in a specially designed phantom consisting of an acrylic cylinder filled with a mixture of acrylic beads and liquid containing FDG. FDG-avid lesions were simulated with agar spheres (3, 4, 6, 8, and 10 mm diameters) containing vary amounts of FDG to produce target-to-background ratios (TBR) of 6:1, 8:1, and 10:1. The spheres also contained X-ray contrast agent to make even the smallest ones readily visible in CT images. Positions of all the lesions were identified in the CT images. These positions were used to extract signal present and signal absent sub-images from the PET images. The sub-images were then input to software that calculated areas-under-the-curve for two numerical model observers (Laguerre-Gauss channelized Hotelling observer and non-prewhitening matched filter). RESULTS: The results showed that the smallest detectable lesion with this system is no smaller than ∼3 mm in diameter with a TBR of 6:1. Simulated lesions with diameters of 4 mm and greater were calculated to have good to excellent likelihood of detection for all TBRs tested. CONCLUSION: The results from this investigation identified the detectability capabilities and limitations for a dedicated breast-PET/CT scanner. Its ability to detect relatively small simulated FDG-avid breast lesions for a range of TBRs indicates its potential for clinical application. Finally, the study used methodologies that could be applied to a detectability assessment of other PET/CT scanners.

Evaluation of advanced methods and materials for construction of scintillation detector light guides.

New techniques for fabrication of optically clear structures (3D printing and casting) can be applied to fabrication of light guides, especially complex -shaped ones, for scintillation detectors. In this investigation, we explored the spectral transmissivity of sample light guides created with different fabrication methods and materials. A spectrophotometer was used to measure the transmissivity of the samples to determine their compatibility with a number of commonly used inorganic scintillators (NaI(Tl), BGO, LaBr3, LaCr3, CSI(Tl) and LYSO). These measurements showed that stereolithography with a Stratasys 3D printer using Somos WaterClear Ultra 10122® produced the most compatible light guide with common organic scintillators, especially LYSO (peak emission λ=420 nm) (a scintillator commonly used in positron emission tomography (PET) imaging). Additionally, Polytek Poly-Optic® 1730 clear urethane produced a cast light guide that was the most optically compatible with these scintillators. To demonstrate the ability to create a unique shaped scintillation detector using 3D-printing and casting methods, a small arc-shaped piece of LYSO was coupled to a 4 × 4 array of 4 mm2 silicon photomultipliers (SiPM) using light guides made from these materials. For comparative purposes, a light guide was also fabricated using standard acrylic, a material often used in current light guides. All detectors produced similar event position maps. The energy resolution for 18F (511 keV photopeak) was 13% for the acrylic light-guide-based detector, while it was 18% for the printed light-guide-based detector and 20% for the cast light-guide-based detector. Results from this study demonstrate that advanced fabrication methods have the potential to facilitate creation of light guides for scintillation detectors. Continued advancements in materials and methods will likely result in improved optical performance for 3D-printed structures.

Deep residual-convolutional neural networks for event positioning in a monolithic annular PET scanner.

PET scanners based on monolithic pieces of scintillator can potentially produce superior performance characteristics (high spatial resolution and detection sensitivity, for example) compared to conventional PET scanners. Consequently, we initiated development of a preclinical PET system based on a single 7.2 cm long annulus of LYSO, called AnnPET. While this system could facilitate creation of high-quality images, its unique geometry results in optics that can complicate estimation of event positioning in the detector. To address this challenge, we evaluated deep-residual convolutional neural networks (DR-CNN) to estimate the three-dimensional position of annihilation photon interactions. Monte Carlo simulations of the AnnPET scanner were used to replicate the physics, including optics, of the scanner. It was determined that a ten-layer-DR-CNN was most suited to application with AnnPET. The errors between known event positions, and those estimated by this network and those calculated with the commonly used center-of-mass algorithm (COM) were used to assess performance. The mean absolute errors (MAE) for the ten-layer-DR-CNN-based event positions were 0.54 mm, 0.42 mm and 0.45 mm along thex(axial)-,y(transaxial)- andz- (depth-of-interaction) axes, respectively. For COM estimates, the MAEs were 1.22 mm, 1.04 mm and 2.79 mm in thex-,y- andz-directions, respectively. Reconstruction of the network-estimated data with the 3D-FBP algorithm (5 mm source offset) yielded spatial resolutions (full-width-at-half-maximum (FWHM)) of 0.8 mm (radial), 0.7 mm (tangential) and 0.71 mm (axial). Reconstruction of the COM-derived data yielded spatial resolutions (FWHM) of 1.15 mm (radial), 0.96 mm (tangential) and 1.14 mm (axial). These findings demonstrated that use of a ten-layer-DR-CNN with a PET scanner based on a monolithic annulus of scintillator has the potential to produce excellent performance compared to standard analytical methods.

A combined positron emission tomography (PET)-electron paramagnetic resonance imaging (EPRI) system: initial evaluation of a prototype scanner.

The advent of hybrid scanners, combining complementary modalities, has revolutionized the application of advanced imaging technology to clinical practice and biomedical research. In this project, we investigated the melding of two complementary, functional imaging methods: positron emission tomography (PET) and electron paramagnetic resonance imaging (EPRI). PET radiotracers can provide important information about cellular parameters, such as glucose metabolism. While EPR probes can provide assessment of tissue microenvironment, measuring oxygenation and pH, for example. Therefore, a combined PET/EPRI scanner promises to provide new insights not attainable with current imagers by simultaneous acquisition of multiple components of tissue microenvironments. To explore the simultaneous acquisition of PET and EPR images, a prototype system was created by combining two existing scanners. Specifically, a silicon photomultiplier (SiPM)-based PET scanner ring designed as a portable scanner was combined with an EPRI scanner designed for the imaging of small animals. The ability of the system to obtain simultaneous images was assessed with a small phantom consisting of four cylinders containing both a PET tracer and EPR spin probe. The resulting images demonstrated the ability to obtain contemporaneous PET and EPR images without cross-modality interference. Given the promising results from this initial investigation, the next step in this project is the construction of the next generation pre-clinical PET/EPRI scanner for multi-parametric assessment of physiologically-important parameters of tissue microenvironments.

A dedicated breast-PET/CT scanner: Evaluation of basic performance characteristics.

PURPOSE: Application of advanced imaging techniques, such as PET and x ray CT, can potentially improve detection of breast cancer. Unfortunately, both modalities have challenges in the detection of some lesions. The combination of the two techniques, however, could potentially lead to an overall improvement in diagnostic breast imaging. The purpose of this investigation is to test the basic performance of a new dedicated breast-PET/CT. METHODS: The PET component consists of a rotating pair of detectors. Its performance was evaluated using the NEMA NU4-2008 protocols. The CT component utilizes a pulsed x ray source and flat panel detector mounted on the same gantry as the PET scanner. Its performance was assessed using specialized phantoms. The radiation dose to a breast during CT imaging was explored by the measurement of free-in-air kerma and air kerma measured at the center of a 16 cm-diameter PMMA cylinder. Finally, the combined capabilities of the system were demonstrated by imaging of a micro-hot-rod phantom. RESULTS: Overall, performance of the PET component is comparable to many pre-clinical and other dedicated breast-PET scanners. Its spatial resolution is 2.2 mm, 5 mm from the center of the scanner using images created with the single-sliced-filtered-backprojection algorithm. Peak NECR is 24.6 kcps; peak sensitivity is 1.36%; the scatter fraction is 27%. Spatial resolution of the CT scanner is 1.1 lp/mm at 10% MTF. The free-in-air kerma is 2.33 mGy, while the PMMA-air kerma is 1.24 mGy. Finally, combined imaging of a micro-hot-rod phantom illustrated the potential utility of the dual-modality images produced by the system. CONCLUSION: The basic performance characteristics of a new dedicated breast-PET/CT scanner are good, demonstrating that its performance is similar to current dedicated PET and CT scanners. The potential value of this system is the capability to produce combined duality-modality images that could improve detection of breast disease. The next stage in development of this system is testing with more advanced phantoms and human subjects.

Small animal, positron emission tomography-magnetic resonance imaging system based on a clinical magnetic resonance imaging scanner: evaluation of basic imaging performance.

Development of advanced preclinical imaging techniques has had an important impact on the field of biomedical research, with positron emission tomography (PET) imaging the most mature of these efforts. Developers of preclinical PET scanners have joined the recent multimodality imaging trend by combining PET imaging with other modalities, such as magnetic resonance imaging (MRI). Our group has developed a combined PET-MRI insert for the imaging of animals up to the size of rats in a clinical 3T MRI scanner. The system utilizes a sequential scanner configuration instead of the more common coplanar geometry. The PET component of the system consists of a ring of 12 liquid-cooled, SiPM-based detector modules ( diameter = 15.2 cm ). System performance was evaluated with the NEMA NU 4-2008 protocol. Spatial resolution is ∼ 1.71 mm 5 cm from the center of the field-of-view measured from single-slice rebinned filtered backprojection-reconstructed images. Peak noise equivalent count rate is 17.7 kcps at 8.5 MBq; peak sensitivity is 2.9%. The MRI component of the system is composed of a 12-cm-diameter birdcage transmit/receive coil with a dual-preamplifier interface possessing very low noise preamplifiers. System performance was evaluated using American College of Radiology-based methods. Image homogeneity is 99%; the ghosting ratio is 0.0054. The signal-to-noise ratio is 95 and spatial resolution is ∼ 0.25 mm . There was no discernable cross-modality interference.

Phenotyping of lumbosacral stenosis in Labrador retrievers using computed tomography.

Deep phenotyping tools for characterizing preclinical morphological conditions are important for supporting genetic research studies. Objectives of this retrospective, cross-sectional, methods comparison study were to describe and compare qualitative and quantitative deep phenotypic characteristics of lumbosacral stenosis in Labrador retrievers using computed tomography (CT). Lumbosacral CT scans and medical records were retrieved from data archives at three veterinary hospitals. Using previously published qualitative CT diagnostic criteria, a board-certified veterinary radiologist assigned dogs as either lumbosacral stenosis positive or lumbosacral stenosis negative at six vertebral locations. A second observer independently measured vertebral canal area, vertebral fat area, and vertebral body area; and calculated ratios of vertebral canal area/vertebral body area and vertebral fat area/vertebral body area (fat area ratio) at all six locations. Twenty-five dogs were sampled (lumbosacral stenosis negative, 11 dogs; lumbosacral stenosis positive, 14 dogs). Of the six locations, cranial L6 was the most affected by lumbosacral stenosis (33%). Five of six dogs (83%) with clinical signs of lumbosacral pain were lumbosacral stenosis positive at two or more levels. All four quantitative variables were significantly smaller at the cranial aspects of the L6 and L7 vertebral foramina than at the caudal aspects (P < 0.0001). Fat area ratio was a significant predictor of lumbosacral stenosis positive status at all six locations with cranial L6 having the greatest predictive value (R2 = 0.43) and range of predictive probability (25-90%). Findings from the current study supported the use of CT as a deep phenotyping tool for future research studies of lumbosacral stenosis in Labrador retrievers.

Preclinical positron emission tomography scanner based on a monolithic annulus of scintillator: initial design study.

Positron emission tomography (PET) scanners designed for imaging of small animals have transformed translational research by reducing the necessity to invasively monitor physiology and disease progression. Virtually all of these scanners are based on the use of pixelated detector modules arranged in rings. This design, while generally successful, has some limitations. Specifically, use of discrete detector modules to construct PET scanners reduces detection sensitivity and can introduce artifacts in reconstructed images, requiring the use of correction methods. To address these challenges, and facilitate measurement of photon depth-of-interaction in the detector, we investigated a small animal PET scanner (called AnnPET) based on a monolithic annulus of scintillator. The scanner was created by placing 12 flat facets around the outer surface of the scintillator to accommodate placement of silicon photomultiplier arrays. Its performance characteristics were explored using Monte Carlo simulations and sections of the NEMA NU4-2008 protocol. Results from this study revealed that AnnPET's reconstructed spatial resolution is predicted to be [Formula: see text] full width at half maximum in the radial, tangential, and axial directions. Peak detection sensitivity is predicted to be 10.1%. Images of simulated phantoms (mini-hot rod and mouse whole body) yielded promising results, indicating the potential of this system for enhancing PET imaging of small animals.

Concept of an upright wearable positron emission tomography imager in humans.

BACKGROUND: Positron Emission Tomography (PET) is traditionally used to image patients in restrictive positions, with few devices allowing for upright, brain-dedicated imaging. Our team has explored the concept of wearable PET imagers which could provide functional brain imaging of freely moving subjects. To test feasibility and determine future considerations for development, we built a rudimentary proof-of-concept prototype (Helmet_PET) and conducted tests in phantoms and four human volunteers. METHODS: Twelve Silicon Photomultiplier-based detectors were assembled in a ring with exterior weight support and an interior mechanism that could be adjustably fitted to the head. We conducted brain phantom tests as well as scanned four patients scheduled for diagnostic F(18-) FDG PET/CT imaging. For human subjects the imager was angled such that field of view included basal ganglia and visual cortex to test for typical resting-state pattern. Imaging in two subjects was performed ~4 hr after PET/CT imaging to simulate lower injected F(18-) FDG dose by taking advantage of the natural radioactive decay of the tracer (F(18) half-life of 110 min), with an estimated imaging dosage of 25% of the standard. RESULTS: We found that imaging with a simple lightweight ring of detectors was feasible using a fraction of the standard radioligand dose. Activity levels in the human participants were quantitatively similar to standard PET in a set of anatomical ROIs. Typical resting-state brain pattern activation was demonstrated even in a 1 min scan of active head rotation. CONCLUSION: To our knowledge, this is the first demonstration of imaging a human subject with a novel wearable PET imager that moves with robust head movements. We discuss potential research and clinical applications that will drive the design of a fully functional device. Designs will need to consider trade-offs between a low weight device with high mobility and a heavier device with greater sensitivity and larger field of view.

TandemPET- A High Resolution, Small Animal, Virtual Pinhole-Based PET Scanner: Initial Design Study.

Mice are the perhaps the most common species of rodents used in biomedical research, but many of the current generation of small animal PET scanners are non-optimal for imaging these small rodents due to their relatively low resolution. Consequently, a number of researchers have investigated the development of high-resolution scanners to address this need. In this investigation, the design of a novel, high-resolution system based on the dual-detector, virtual-pinhole PET concept was explored via Monte Carlo simulations. Specifically, this system, called TandemPET, consists of a 5 cm × 5 cm high-resolution detector made-up of a 90 × 90 array of 0.5 mm × 0.5 mm × 10 mm (pitch= 0.55 mm) LYSO detector elements in coincidence with a lower resolution detector consisting of a 68 × 68 array of 1.5 mm × 1.5 mm × 10 mm LYSO detector elements (total size= 10.5 cm × 10.5 cm). Analyses indicated that TandemPET's optimal geometry is to position the high-resolution detector 3 cm from the center-of-rotation, with the lower resolution detector positioned 9 cm from center. Measurements using modified NEMA NU4-2008-based protocols revealed that the spatial resolution of the system is ~0.5 mm FWHM, after correction of positron range effects. Peak sensitivity is 2.1%, which is comparable to current small animal PET scanners. Images from a digital mouse brain phantom demonstrated the potential of the system for identifying important neurological structures.

Arrays of Segmented, Tapered Light Guides for Use with Large, Planar Scintillation Detectors.

Metabolic imaging techniques can potentially improve detection and diagnosis of cancer in women with radiodense and/or fibrocystic breasts. Our group has previously developed a high-resolution positron emission tomography imaging and biopsy device (PEM-PET) to detect and guide the biopsy of suspicious breast lesions. Initial testing revealed that the imaging field-of-view (FOV) of the scanner was smaller than the physical size of the detector's active area, which could hinder sampling of breast areas close to the chest wall. The purpose of this work was to utilize segmented, tapered light guides for optically coupling the scintillator arrays to arrays of position-sensitive photomultipliers to increase both the active FOV and identification of individual scintillator elements. Testing of the new system revealed that the optics of these structures made it possible to discern detector elements from the complete active area of the detector face. In the previous system the top and bottom rows and left and right columns were not identifiable. Additionally, use of the new light guides increased the contrast of individual detector elements by up to 129%. Improved element identification led to a spatial resolution increase by approximately 12%. Due to attenuation of light in the light guides the detector energy resolution decreased from 18.5% to 19.1%. Overall, these improvements should increase the field-of-view and spatial resolution of the dedicated breast-PET system.

Construction and Evaluation of a Prototype High Resolution, Silicon Photomultiplier-Based, Tandem Positron Emission Tomography System.

While the performance of most current commercially available PET scanners is sufficient for many standard clinical applications, some specific tasks likely require specialized imaging systems. The goal of this project is to explore the capabilities and limitations of a small, high-resolution prototype system for obtaining PET images. The scanner consists of a tandem of detectors. One is a small detector consisting of a 20 × 20 array of 0.7 × 0.7 × 3 mm3 (pitch 0.8 mm) LYSO elements. The scintillator array is coupled to an array of silicon photomultipliers. The second detector is a 96 × 72 array of 2 × 2 × 15 mm3 (pitch = 2.1 mm) LYSO elements coupled to PSPMTs. Separation between the two devices is 180 mm. The detectors are operated in coincidence with each other. Image reconstruction is performed using a limited angle, Maximum Likelihood Expectation Maximization (MLEM) algorithm. Evaluation of the device included measurements of spatial resolution and detection sensitivity as a function of distance. The transaxial radial and tangential spatial resolution of the system ranged from 0.6 mm to 0.9 mm FWHM; axial resolution ranged from 2.7 mm to 4.6 mm FWHM. Detection sensitivity ranged from 0.05 to 0.28%. Spatial resolution and field-of-view vary as a function of distance from the small detector. The tandem detector insert permitted differentiation of the smallest (1 mm diameter) rods in a mini-hot rod phantom. The results indicate that a tandem PET imaging scheme can be potentially employed in applications where high-resolution images over a small region are required.

Initial clinical test of a breast-PET scanner.

INTRODUCTION: The goal of this initial clinical study was to test a new positron emission/tomography imager and biopsy system (PEM/PET) in a small group of selected subjects to assess its clinical imaging capabilities. Specifically, the main task of this study is to determine whether the new system can successfully be used to produce images of known breast cancer and compare them to those acquired by standard techniques. METHODS: The PEM/PET system consists of two pairs of rotating radiation detectors located beneath a patient table. The scanner has a spatial resolution of ∼2 mm in all three dimensions. The subjects consisted of five patients diagnosed with locally advanced breast cancer ranging in age from 40 to 55 years old scheduled for pre-treatment, conventional whole body PET imaging with F-18 Fluorodeoxyglucose (FDG). The primary lesions were at least 2 cm in diameter. RESULTS: The images from the PEM/PET system demonstrated that this system is capable of identifying some lesions not visible in standard mammograms. Furthermore, while the relatively large lesions imaged in this study where all visualised by a standard whole body PET/CT scanner, some of the morphology of the tumours (ductal infiltration, for example) was better defined with the PEM/PET system. Significantly, these images were obtained immediately following a standard whole body PET scan. CONCLUSIONS: The initial testing of the new PEM/PET system demonstrated that the new system is capable of producing good quality breast-PET images compared standard methods.

Advancements to the planogram frequency-distance rebinning algorithm.

In this paper we consider the task of image reconstruction in positron emission tomography (PET) with the planogram frequency-distance rebinning (PFDR) algorithm. The PFDR algorithm is a rebinning algorithm for PET systems with panel detectors. The algorithm is derived in the planogram coordinate system which is a native data format for PET systems with panel detectors. A rebinning algorithm averages over the redundant four-dimensional set of PET data to produce a three-dimensional set of data. Images can be reconstructed from this rebinned three-dimensional set of data. This process enables one to reconstruct PET images more quickly than reconstructing directly from the four-dimensional PET data. The PFDR algorithm is an approximate rebinning algorithm. We show that implementing the PFDR algorithm followed by the (ramp) filtered backprojection (FBP) algorithm in linogram coordinates from multiple views reconstructs a filtered version of our image. We develop an explicit formula for this filter which can be used to achieve exact reconstruction by means of a modified FBP algorithm applied to the stack of rebinned linograms and can also be used to quantify the errors introduced by the PFDR algorithm. This filter is similar to the filter in the planogram filtered backprojection algorithm derived by Brasse et al. The planogram filtered backprojection and exact reconstruction with the PFDR algorithm require complete projections which can be completed with a reprojection algorithm. The PFDR algorithm is similar to the rebinning algorithm developed by Kao et al. By expressing the PFDR algorithm in detector coordinates, we provide a comparative analysis between the two algorithms. Numerical experiments using both simulated data and measured data from a positron emission mammography/tomography (PEM/PET) system are performed. Images are reconstructed by PFDR+FBP (PFDR followed by 2D FBP reconstruction), PFDRX (PFDR followed by the modified FBP algorithm for exact reconstruction) and planogram filtered backprojection image reconstruction algorithms. We show that the PFDRX algorithm produces images that are nearly as accurate as images reconstructed with the planogram filtered backprojection algorithm and more accurate than images reconstructed with the PFDR+FBP algorithm. Both the PFDR+FBP and PFDRX algorithms provide a dramatic improvement in computation time over the planogram filtered backprojection algorithm.

Investigation of breast cancer using two-dimensional MRS.

Proton (1H) MRS enables non-invasive biochemical assay with the potential to characterize malignant, benign and healthy breast tissues. In vitro studies using perchloric acid extracts and ex vivo magic angle spinning spectroscopy of intact biopsy tissues have been used to identify detectable metabolic alterations in breast cancer. The challenges of 1H MRS in vivo include low sensitivity and significant overlap of resonances due to limited chemical shift dispersion and significant inhomogeneous broadening at most clinical magnetic field strengths. Improvement in spectral resolution can be achieved in vivo and in vitro by recording the MR spectra spread over more than one dimension, thus facilitating unambiguous assignment of metabolite and lipid resonances in breast cancer. This article reviews the recent progress with two-dimensional MRS of breast cancer in vitro, ex vivo and in vivo. The discussion includes unambiguous detection of saturated and unsaturated fatty acids, as well as choline-containing groups such as free choline, phosphocholine, glycerophosphocholine and ethanolamines using two-dimensional MRS. In addition, characterization of invasive ductal carcinomas and healthy fatty/glandular breast tissues non-invasively using the classification and regression tree (CART) analysis of two-dimensional MRS data is reviewed.

Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans.

The link between body weight, lipid metabolism, and health risks is poorly understood and difficult to study. Magnetic resonance spectroscopy (MRS) permits noninvasive investigation of lipid metabolism. We extended existing two-dimensional MRS techniques to permit quantification of intra- and extramyocellular lipid (IMCL and EMCL, respectively) compartments and their degree of unsaturation in human subjects and correlated these results with body mass index (BMI). Using muscle creatine for normalization, we observed a statistically significant (P < 0.01) increase in the IMCL-to-creatine ratio with BMI (n = 8 subjects per group): 5.9 +/- 1.7 at BMI < 25, 10.9 +/- 1.82 at 25 < BMI < 30, and 13.1 +/- 0.87 at BMI > 30. Similarly, the degree of IMCL unsaturation decreased significantly (P < 0.01) with BMI: 1.51 +/- 0.08 at BMI < 25, 1.30 +/- 0.11 at 25 < BMI < 30, and 0.90 +/- 0.14 at BMI > 30. We conclude that important aspects of lipid metabolism can be evaluated by two-dimensional MRS and propose that degree of unsaturation measured noninvasively may serve as a biomarker for lipid metabolic defects associated with obesity.

Planogram rebinning with the frequency-distance relationship.

We present an efficient rebinning algorithm for positron emission tomography (PET) systems with panel detectors. The rebinning algorithm is derived in the planogram coordinate system which is the native data format for PET systems with panel detectors and is the 3-D extension of the 2-D linogram transform developed by Edholm. Theoretical error bounds and numerical results are included.