Recovery of the spatially-variant deformations in dual-panel PET reconstructions using deep-learning.

Dual panel PET systems, such as Breast-PET (B-PET) scanner, exhibit strong asymmetric and anisotropic spatially-variant deformations in the reconstructed images due to the limited-angle data and strong depth of interaction effects for the oblique LORs inherent in such systems. In our previous work, we studied time-of-flight (TOF) effects and image-based spatially-variant PSF resolution models within dual-panel PET reconstruction to reduce these deformations. The application of PSF based models led to better and more uniform quantification of small lesions across the field of view (FOV). However, the ability of such a model to correct for PSF deformation is limited to small objects. On the other hand, large object deformations caused by the limited-angle reconstruction cannot be corrected with the PSF modeling alone. In this work, we investigate the ability of deep-learning (DL) networks to recover such strong spatially-variant image deformations using first simulated PSF deformations in image space of a generic dual panel PET system and then using simulated and acquired phantom reconstructions from dual panel B-PET system developed in our lab at University of Pennsylvania. For the studies using real B-PET data, the network was trained on the simulated synthetic data sets providing ground truth for objects resembling experimentally acquired phantoms on which the network deformation corrections were then tested. The synthetic and acquired limited-angle B-PET data were reconstructed using DIRECT-RAMLA reconstructions, which were then used as the network inputs. Our results demonstrate that DL approaches can significantly eliminate deformations of limited angle systems and improve their quantitative performance.

Advances in Breast PET Instrumentation.

Dedicated breast PET scanners currently have a spatial resolution in the 1.5 to 2 mm range, and the ability to provide tomographic images and quantitative data. They are also commercially available from a few vendors. A review of past and recent advances in the development and performance of dedicated breast PET scanners is summarized.

Novel Perlin-based Phantoms Using 3D Models of Compressed Breast Shape and Fractal Noise.

Virtual clinical trials (VCTs) have been used widely to evaluate digital breast tomosynthesis (DBT) systems. VCTs require realistic simulations of the breast anatomy (phantoms) to characterize lesions and to estimate risk of masking cancers. This study introduces the use of Perlin-based phantoms to optimize the acquisition geometry of a novel DBT prototype. These phantoms were developed using a GPU implementation of a novel library called Perlin-CuPy. The breast anatomy is simulated using 3D models under mammography cranio-caudal compression. In total, 240 phantoms were created using compressed breast thickness, chest-wall to nipple distance, and skin thickness that varied in a {[35, 75], [59, 130), [1.0, 2.0]} mm interval, respectively. DBT projections and reconstructions of the phantoms were simulated using two acquisition geometries of our DBT prototype. The performance of both acquisition geometries was compared using breast volume segmentations of the Perlin phantoms. Results show that breast volume estimates are improved with the introduction of posterior-anterior motion of the x-ray source in DBT acquisitions. The breast volume is overestimated in DBT, varying substantially with the acquisition geometry; segmentation errors are more evident for thicker and larger breasts. These results provide additional evidence and suggest that custom acquisition geometries can improve the performance and accuracy in DBT. Perlin phantoms help to identify limitations in acquisition geometries and to optimize the performance of the DBT prototypes.

Pre-clinical evaluation and optimization of image quality for a Next Generation Tomosynthesis prototype.

A next generation tomosynthesis (NGT) prototype has been developed to investigate alternative scanning geometries for digital breast tomosynthesis (DBT). The NGT system uses a 2D plane as an address space for the x-ray source to define an acquisition geometry. In previous work, tests of physics have been used as objective metrics to evaluate image quality for NGT. In this work, the performance of custom NGT acquisition geometries is evaluated for mastectomy specimens to validate previous phantom experiments. Two custom acquisition geometries - incorporating T- and K-shaped source motion paths in the posteroanterior direction - were compared with a conventional DBT acquisition geometry. Noise power spectra (NPS) are calculated using 3D image reconstructions of the three acquisition geometries to evaluate the degradation of image quality due to noise and to visualize NGT sampling properties in the Fourier domain. NPS are used to describe features of the specimen image reconstructions and compare acquisition geometries. NGT acquisition geometries were found to improve high-frequency performance with isotropic super resolution, reduce out-of-plane reconstruction artifacts, and improve overall image reconstruction quality. The T-geometry combines the benefits of narrow- and wide-angle tomosynthesis in a single scan improving high-frequency spatial resolution and out-of-plane blurring, respectively.

A proof-of-concept study of an in-situ partial-ring time-of-flight PET scanner for proton beam verification.

Development of a PET system capable of in-situ imaging requires a design that can accommodate the proton treatment beam nozzle. Among the several PET instrumentation approaches developed thus far, the dual-panel PET scanner is often used as it is simpler to develop and integrate within the proton therapy gantry. Partial-angle coverage of these systems can however lead to limited-angle artefacts in the reconstructed PET image. We have previously demonstrated via simulations that time-of-flight (TOF) reconstruction reduces the artifacts accompanying limited-angle data, and permits proton range measurement with 1-2 mm accuracy and precision. In this work we show measured results from a small proof-of-concept dual-panel PET system that uses TOF information to reconstruct PET data acquired after proton irradiation. The PET scanner comprises of two detector modules, each comprised of an array of 4×4×30 mm3 lanthanum bromide scintillator. Measurements are performed with an oxygen-rich gel-water, an adipose tissue equivalent material, and in vitro tissue phantoms. For each phantom measurement, 2 Gy dose was deposited using 54 - 100 MeV proton beams. For each phantom, a Monte Carlo simulation generating the expected distribution of PET isotope from the corresponding proton irradiation was also performed. Proton range was calculated by drawing multiple depth-profiles over a central region encompassing the proton dose deposition. For each profile, proton range was calculated using two techniques (a) 50% pick-off from the distal edge of the profile, and (b) comparing the measured and Monte Carlo profile to minimize the absolute sum of differences over the entire profile. A 10 min PET acquisition acquired with minimal delay post proton-irradiation is compared with a 10 min PET scan acquired after a 20 min delay. Measurements show that PET acquisition with minimal delay is necessary to collect 15O signal, and maximize 11C signal collection with a short PET acquisition. In comparison with the 50% pick-off technique, the shift technique is more robust and offers better precision in measuring the proton range for the different phantoms. Range measurements from PET images acquired with minimal delay, and the shift technique demonstrate the ability to achieve <1.5 mm accuracy and precision in estimating proton range.

Evaluating attenuation correction strategies in a dedicated, single-gantry breast PET-tomosynthesis scanner.

We are developing a dedicated, combined breast positron emission tomography (PET)-tomosynthesis scanner. Both the PET and digital breast tomosynthesis (DBT) scanners are integrated in a single gantry to provide spatially co-registered 3D PET-tomosynthesis images. The DBT image will be used to identify the breast boundary and breast density to improve the quantitative accuracy of the PET image. This paper explores PET attenuation correction (AC) strategies that can be performed with the combined breast PET-DBT scanner to obtain more accurate, quantitative high-resolution 3D PET images. The PET detector is comprised of a 32 × 32 array of 1.5 × 1.5 × 15 mm3 LYSO crystals. The PET scanner utilizes two detector heads separated by either 9 or 11 cm, with each detector head having a 4 × 2 arrangement of PET detectors. GEANT4 Application for Tomographic Emission simulations were performed using an anthropomorphic breast phantom with heterogeneous attenuation under clinical DBT-compression. FDG-avid lesions, each 5 mm in diameter with 8:1 uptake, were simulated at four locations within the breast. Simulations were performed with a scan time of 2 min. PET AC was performed using the actual breast simulation model as well as DBT reconstructed volumetric images to derive the breast outline. In addition to using the known breast density as defined by the breast model, we also modeled it as uniform patient-independent soft-tissue, and as a uniform patient-specific material derived from breast tissue composition. Measured absolute lesion uptake was used to evaluate the quantitative accuracy of performing AC using the various strategies. This study demonstrates that AC is necessary to obtain a closer estimate of the true lesion uptake and background activity in the breast. The DBT image dataset assists in measuring lesion uptake with low bias by facilitating accurate breast delineation as well as providing accurate information related to the breast tissue composition. While both the uniform soft-tissue and patient-specific material approaches provides a close estimate to the ground truth, <5% bias can be achieved by using a uniform patient-specific material to define the attenuation map.

Spatially-variant image-based modeling of PSF deformations with application to a limited angle geometry from a dual-panel breast-PET imager.

Dual-panel PET system configuration can lead to spatially variable point-spread functions (PSF) of considerable deformations due to depth-of-interaction effects and limited angular coverage. If not modelled properly, these effects result in decreased and inconsistent recovery of lesion activity across the field-of-view (FOV), as well as mispositioning of lesions in the reconstructed image caused by strong PSF asymmetries. We implemented and evaluated models of such PSF deformations with spatially-variant image-based resolution modeling (IRM) within reconstruction (varRM) using the Direct Image REConstruction for Time-of-flight (DIRECT) method and within post-reconstruction deconvolution methods. In addition, DIRECT reconstruction was performed with a spatially-invariant IRM (invRM) and without resolution modeling (noRM) for comparison. The methods were evaluated using simulated data for a realistic breast model with a set of 5 mm lesions located throughout the FOV of a dual-panel Breast-PET scanner. We simulated high-count data to focus on the ability of each method to correctly recover the PSF deformations, and a clinically realistic count level to assess the impact of low count data on the quantitative performance of the evaluated techniques. Performance of the methods evaluated herein was assessed by comparing lesion activity recovery (%BIAS), consistency (%SD) across the FOV, overall error (%RMSE), and recovery of each lesion location. As expected, all techniques using IRM provide considerable improvement over the noRM reconstruction. For the high-count cases, the overall quantitative performance of all IRM techniques, whether within reconstruction or within post-reconstruction, is similar if the lesion location misplacements are ignored. However, invRM provides less consistent performance on activity across lesions and is not able to recover accurate lesion locations. For a clinically realistic count level, varRM reconstruction consistently outperforms all compared approaches, while the post-reconstruction IRM approaches exhibit higher %SD and %RMSE values due to being more affected by the data noise than the within-reconstruction IRM approaches.

Performance evaluation of the MOLECUBES ß-CUBE-a high spatial resolution and high sensitivity small animal PET scanner utilizing monolithic LYSO scintillation detectors.

The MOLECUBES ß-CUBE scanner is the newest amongst commercially available preclinical PET scanners for dedicated small animal imaging. The scanner is compact, lightweight and utilizes a small footprint to facilitate bench-top imaging. It can be used individually, or in combination with the X-CUBE CT scanner, which provides the ability to perform all necessary PET data corrections and provide fully quantitative PET images. The PET detector comprises of an 8 mm thick monolithic LYSO scintillator read-out by an array of 3 mm × 3 mm Hamamatsu silicon photomultipliers. The monolithic scintillator provides the ability to measure depth-of-interaction which aids in the development of such a compact scanner. With a scanner diameter of 7.6 cm and axial length of 13 cm it is suitable for imaging both whole-body mice and rats. This paper presents the design and imaging performance of the ß-CUBE scanner. NEMA NU4-2008 characterization and a variety of phantom and animal imaging studies to demonstrate the quantitative imaging performance of the PET scanner are presented. Spatial resolution of 1 mm is measured with a filtered-back projection reconstruction algorithm at the center of the scanner and DOI measurement helps maintain the excellent spatial resolution over the entire imaging FOV. An absolute peak sensitivity of 12.4% is measured with a 255-765 keV energy window. The scanner demonstrates good count-rate performance, with a peak NEC of 300 kcps and 160 kcps measured with ~900 µCi in the NEMA mouse and rat phantoms, respectively. Imaging data with the NEMA image quality phantom and Micro Derenzo phantoms demonstrate the ability to achieve good image quality and accurate quantitative data. Image uniformity of 7.4% and spill-over ratio of 8% were measured. The superior spatial resolution, excellent energy resolution and sensitivity also provide superior contrast recovery, with ~70% recovery for the 2 mm rods. While current commercial preclinical PET scanners have spatial resolution in the 1-2 mm range, the 1 mm3 volumetric resolution presents significant improvement over current commercially available preclinical PET scanners. In combination with the X-CUBE scanner it provides the ability to perform fully quantitative imaging with spatially co-registered high-resolution 3D PET-CT images.

Design and performance of a high spatial resolution, time-of-flight PET detector.

This paper describes the design and performance of a high spatial resolution PET detector with time-of-flight capabilities. With an emphasis on high spatial resolution and sensitivity, we initially evaluated the performance of several 1.5 × 1.5 and 2.0 × 2.0 mm2 and 12-15 mm long LYSO crystals read out by several appropriately sized PMTs. Experiments to evaluate the impact of reflector on detector performance were performed and the final detector consisted of a 32 × 32 array of 1.5 × 1.5 × 15 mm3 LYSO crystals packed with a diffuse reflector and read out by a single Hamamatsu 64 channel multi-anode PMT. Such a design made it compact, modular and offered a cost-effective solution to obtaining excellent energy and timing resolution. To minimize the number of readout signals, a compact front-end readout electronics that summed anode signals along each of the orthogonal directions was also developed. Experimental evaluation of detector performance demonstrates clear discrimination of the crystals within the detector. An average energy resolution (FWHM) of 12.7 ± 2.6% and average coincidence timing resolution (FWHM) of 348 ps was measured, demonstrating suitability for use in the development of a high spatial resolution time-of-flight scanner for dedicated breast PET imaging.

Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph.

Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have until now required general anesthesia to immobilize the subject, which precludes behavioral studies. We present a method for imaging awake, behaving rats with PET that allows the simultaneous study of behavior. Key components include the 'rat conscious animal PET' or RatCAP, a miniature portable PET scanner that is mounted on the rat's head, a mobility system that allows considerable freedom of movement, radiotracer administration techniques and methods for quantifying behavior and correlating the two data sets. The simultaneity of the PET and behavioral data provides a multidimensional tool for studying the functions of different brain regions and their molecular constituents.

PET imaging of thin objects: measuring the effects of positron range and partial-volume averaging in the leaf of Nicotiana tabacum.

INTRODUCTION: PET imaging in plants is receiving increased interest as a new strategy to measure plant responses to environmental stimuli and as a tool for phenotyping genetically engineered plants. PET imaging in plants, however, poses new challenges. In particular, the leaves of most plants are so thin that a large fraction of positrons emitted from PET isotopes ((18)F, (11)C, (13)N) escape while even state-of-the-art PET cameras have significant partial-volume errors for such thin objects. Although these limitations are acknowledged by researchers, little data have been published on them. METHODS: Here we measured the magnitude and distribution of escaping positrons from the leaf of Nicotiana tabacum for the radionuclides (18)F, (11)C and (13)N using a commercial small-animal PET scanner. Imaging results were compared to radionuclide concentrations measured from dissection and counting and to a Monte Carlo simulation using GATE (Geant4 Application for Tomographic Emission). RESULTS: Simulated and experimentally determined escape fractions were consistent. The fractions of positrons (mean±S.D.) escaping the leaf parenchyma were measured to be 59±1.1%, 64±4.4% and 67±1.9% for (18)F, (11)C and (13)N, respectively. Escape fractions were lower in thicker leaf areas like the midrib. Partial-volume averaging underestimated activity concentrations in the leaf blade by a factor of 10 to 15. CONCLUSIONS: The foregoing effects combine to yield PET images whose contrast does not reflect the actual activity concentrations. These errors can be largely corrected by integrating activity along the PET axis perpendicular to the leaf surface, including detection of escaped positrons, and calculating concentration using a measured leaf thickness.