Spencer L. Bowen

Initial Characterization of a Dedicated Breast PET/CT Scanner During Human Imaging

We have constructed a dedicated breast PET/CT scanner capable of high-resolution functional and anatomic imaging. Here, we present an initial characterization of scanner performance during patient imaging. Methods: The system consisted of a lutetium oxyorthosilicate–based dual–planar head PET camera (crystal size, 3 × 3 × 20 mm) and 768-slice cone-beam CT. The position of the PET heads (separation and height) could be adjusted for varying breast dimensions. For scanning, the patient lay prone on a specialized bed and inserted a single pendent breast through an aperture in the table top. Compression of the breast as used in mammography is not required. PET and CT systems rotate in the coronal plane underneath the patient sequentially to collect fully tomographic datasets. PET images were reconstructed with the fully 3-dimensional maximum a posteriori method, and CT images were reconstructed with the Feldkamp algorithm, then spatially registered and fused for display. Phantom scans were obtained to assess the registration accuracy between PET and CT images and the influence of PET electronics and activity on CT image quality. We imaged 4 women with mammographic findings highly suggestive of breast cancer (breast imaging reporting and data system, category 5) in an ongoing clinical trial. Patients were injected with 18F-FDG and imaged for 12.5 min per breast. From patient data, noise-equivalent counting rates and the singles-to-trues ratio (a surrogate for the randoms fraction) were calculated. Results: The average registration error between PET and CT images was 0.18 mm. PET electronics and activity did not significantly affect CT image quality. For the patient trial, biopsy-confirmed cancers were visualized on dedicated breast PET/CT on all patient scans, including the detection of ductal carcinoma in situ in 1 case. The singles-to-trues ratio was found to be inversely correlated with breast volume in the field of view, suggesting that larger breasts trend toward increased noise-equivalent counting rates for all other things equal. Conclusion: Scanning of the uncompressed breast with dedicated breast PET/CT can accurately visualize suspected lesions in 3 dimensions.

PET characteristics of a dedicated breast PET/CT scanner prototype

A dedicated breast PET/CT system has been constructed at our institution, with the goal of having increased spatial resolution and sensitivity compared to whole-body systems. The purpose of this work is to describe the design and the performance characteristics of the PET component of this device. Average spatial resolution of a line source in warm background using maximum a posteriori (MAP) reconstruction was 2.5 mm, while the average spatial resolution of a phantom containing point sources using filtered back projection (FBP) was 3.27 mm. A sensitivity profile was computed with a point source translated across the axial field of view (FOV) and a peak sensitivity of 1.64% was measured at the center of the FOV. The average energy resolution determined on a per-crystal basis was 25%. The characteristic dead time for the front-end electronics and data acquisition (DAQ) was determined to be 145 ns and 3.6 micros, respectively. With no activity outside the FOV, a peak noise-equivalent count rate of 18.6 kcps was achieved at 318 microCi (11.766 MBq) in a cylindrical phantom of diameter 75 mm. After the effects of exposing PET detectors to x-ray flux were evaluated and ameliorated, a combined PET/CT scan was performed. The percentage standard deviations of uniformity along axial and transaxial directions were 3.7% and 2.8%, respectively. The impact of the increased reconstructed spatial resolution compared to typical whole-body PET scanners is currently being assessed in a clinical trial.

High-resolution 18F-FDG PET with MRI for monitoring response to treatment in rheumatoid arthritis

Eur J Nucl Med Mol Imaging (2010) 37:1047 DOI 10.1007/s00259-009-1364-x IMAGE OF THE MONTH High-resolution 18 F-FDG PET with MRI for monitoring response to treatment in rheumatoid arthritis Abhijit J. Chaudhari & Spencer L. Bowen & George W. Burkett & Nathan J. Packard & Felipe Godinez & Anand A. Joshi & Stanley M. Naguwa & David K. Shelton & John C. Hunter & John M. Boone & Michael H. Buonocore & Ramsey D. Badawi Received: 20 November 2009 / Accepted: 10 December 2009 / Published online: 30 January 2010 # The Author(s) 2010. This article is published with open access at Springerlink.com Molecular imaging can potentially provide means for mon- itoring response to therapy in rheumatoid arthritis (RA) early in the course of disease [1].Quantitative measurements of RA disease activity made in the wrist by whole-body PET scanners, however, have inadequate accuracy because of limited spatial resolution [2]. A high-resolution PET/CT scanner for imaging extremities has been built at our insti- tution [3]. In conjunction with a clinical MRI scanner, high- resolution PET/MR images can be obtained for the wrist. The CT image is used for PET/MR image coregistration. A 57-year-old female with established RA was stable until a recent clinical flare-up in the right wrist. Clinical exami- nation revealed synovitis, swelling, and diminished range of motion. The patient also had a history of osteoarthritis (OA). An extremity 18 F-FDG PET/CT scan immediately following MRI at baseline was performed on this patient. Tumor necrosis factor alpha (TNF-α) inhibitor (etanercept) therapy was then initiated as a part of the patient’s standard of care. The patient was re-scanned 5 weeks after starting treatment. The figure shows high-resolution 18 F-FDG PET images (pseudocolor) overlaid on pre-contrast MRI images (gray This work was funded by the NIH grants UL1-RR024146, R01CA129561, R01EB002138 and the UC Davis Imaging Research Center. A. J. Chaudhari (*) : S. L. Bowen : G. W. Burkett : N. J. Packard : F. Godinez : D. K. Shelton : J. C. Hunter : J. M. Boone : M. H. Buonocore : R. D. Badawi Department of Radiology, UC Davis Medical Center, Sacramento, CA, USA e-mail: ajchaudhari@ucdavis.edu A. A. Joshi Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA S. M. Naguwa Department of Internal Medicine, UC Davis Medical Center, Sacramento, CA, USA scale) at baseline (left column) and 5 weeks (right column). Significant reduction in PET signal (suggesting reduced inflammation) in the synovium and at sites of erosions (white arrows) is visible. The green arrow shows inflammation due to OA. Physician examination at 3 months confirmed that this patient responded positively to etanercept. This case illustrates the potential of high-resolution PET with MRI for quantitative visualization of early response to therapy in RA. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Brenner W. 18F-FDG PET in rheumatoid arthritis: there still is a long way to go. J Nucl Med. 2004;45(6):927–9. 2. Beckers C, Ribbens C, Andre B, Marcelis S, Kaye O, Mathy L, et al. Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET. J Nucl Med. 2004;45(6):956–64. 3. Bowen SL, Wu Y, Chaudhari AJ, Fu L, Packard NJ, Burkett GW, et al. Initial characterization of a dedicated breast PET/CT scanner during human imaging. J Nucl Med. 2009;50(9):1401–8.

Different partial volume correction methods lead to different conclusions: An (18)F-FDG-PET study of aging.

A cross-sectional group study of the effects of aging on brain metabolism as measured with (18)F-FDG-PET was performed using several different partial volume correction (PVC) methods: no correction (NoPVC), Meltzer (MZ), Müller-Gärtner (MG), and the symmetric geometric transfer matrix (SGTM) using 99 subjects aged 65-87years from the Harvard Aging Brain study. Sensitivity to parameter selection was tested for MZ and MG. The various methods and parameter settings resulted in an extremely wide range of conclusions as to the effects of age on metabolism, from almost no changes to virtually all of cortical regions showing a decrease with age. Simulations showed that NoPVC had significant bias that made the age effect on metabolism appear to be much larger and more significant than it is. MZ was found to be the same as NoPVC for liberal brain masks; for conservative brain masks, MZ showed few areas correlated with age. MG and SGTM were found to be similar; however, MG was sensitive to a thresholding parameter that can result in data loss. CSF uptake was surprisingly high at about 15% of that in gray matter. The exclusion of CSF from SGTM and MG models, which is almost universally done, caused a substantial loss in the power to detect age-related changes. This diversity of results reflects the literature on the metabolism of aging and suggests that extreme care should be taken when applying PVC or interpreting results that have been corrected for partial volume effects. Using the SGTM, significant age-related changes of about 7% per decade were found in frontal and cingulate cortices as well as primary visual and insular cortices.

CdTe Strip Detector Characterization for High Resolution Small Animal PET

Excellent spatial resolution is a requirement for preclinical PET imaging. In order to achieve spatial resolution of significantly better than one millimeter, an appealing possibility is to employ direct detector materials, such as cadmium telluride (CdTe). Prototype thin orthogonal strip detectors have been developed for testing. They have dimensions of 20 mm by 20 mm and are 0.5 mm thick, and have strips of 0.5 mm pitch on one side and 2.5 mm pitch on the other. Results are presented for the energy resolution (3% at 511 keV), intrinsic position resolution (equal to the 0.5 mm strip pitch), and timing resolution (3 ns FWHM in coincidence with an LSO detector, 8 ns FWHM for coincidence of two CdTe detectors) of the detectors. A PET scanner design is proposed using blocks made of the CdTe strip detectors, oriented in the blocks with their thin edges toward the center of the scanner. Simulation results suggest that this scanner, using a threshold of 250 keV, would have a sensitivity of 3.4% for a point source at its center.

Crystal identification in positron emission tomography using nonrigid registration to a Fourier-based template

Modern positron emission tomography (PET) detectors are typically made from 2D modular arrays of scintillation crystals. Their characteristic flood field response (or flood histogram) must be segmented in order to correctly determine the crystal of annihilation photon interaction in the system. Crystal identification information thus generated is also needed for accurate system modeling as well as for detailed detector characterization and performance studies. In this paper, we present a semi-automatic general purpose template-guided scheme for the segmentation of flood histograms. We first generate a template image that exploits the spatial frequency information in the given flood histogram using Fourier-space analysis. This template image is a lower order approximation of the flood histogram, and can be segmented with horizontal and vertical lines drawn midway between adjacent peaks in the histogram. The template is then registered to the given flood histogram by a diffeomorphic polynomial-based warping scheme that is capable of iteratively minimizing intensity differences. The displacement field thus calculated is applied to the segmentation of the template resulting in a segmentation of the given flood histogram. We evaluate our segmentation scheme for a photomultiplier tube based PET detector, a detector with readout by a position-sensitive avalanche photodiode (PSAPD) and a detector consisting of a stack of photomultiplier tubes and scintillator arrays. Further, we quantitatively compare the performance of the proposed method to that of a manual segmentation scheme using reconstructed images of a line-source phantom. We also present an adaptive method for distortion reduction in flood histograms obtained for PET detectors that use PSAPDs.

Simulation study of spatial resolution and sensitivity for the tapered depth of interaction PET detectors for small animal imaging

Improvements to current small animal PET scanners can be made by improving the sensitivity and the spatial resolution of the scanner. In the past, efforts have been made to minimize the crystal dimensions in the axial and transaxial directions to improve the spatial resolution and to increase the crystal length to improve the sensitivity of the scanner. We have designed tapered PET detectors with the purpose of reducing the gaps between detector modules and optimizing the sensitivity of a future-generation small animal PET scanner. In this work, we investigate spatial resolution and sensitivity of a scanner based on tapered detector elements using Monte Carlo simulations. For tapered detector elements more scintillation material is used per detector resulting in a higher sensitivity of the scanner. However, since the detector elements are not uniform in size, degradation in spatial resolution is also expected. To investigate characteristics of tapered PET detectors, the spatial resolution and sensitivity of a one-ring scanner were simulated for a system based on traditional cuboid detectors and a scanner based on tapered detectors. Additionally, the effect of depth of interaction (DOI) resolution on the spatial resolution for the traditional and tapered detectors was evaluated. All simulations were performed using the Monte Carlo simulation package GATE. Using the tapered arrays, a 64% improvement in the sensitivity across the field of view was found compared with traditional detectors for the same ring diameter. The level of DOI encoding was found to be the dominating factor in determining the radial spatial resolution and not the detector shape. For all levels of DOI encoding, no significant difference was found for the spatial resolution when comparing the tapered and the cuboid detectors. Detectors employing the tapered crystal design along with excellent DOI resolution will lead to PET scanners with higher sensitivity and uniform spatial resolution across the field of view.

Design simulation of a rotating dual-headed PET/CT scanner for breast imaging

A PET system based on a pair of opposing LSO detectors for breast imaging has previously been described by Doshi et al (IEEE Trans. Nucl. Sci. 48: 811-815, 2001). This system has undergone some modifications in geometry and electronics and is being integrated into a dedicated breast CT system. In this work we perform a design simulation of the new system with a view to determining areas for future improvements. Simulations were performed using the public domain GATE software, based on the GEANT 4 particle simulation engine. The NURBS-based NCAT phantom was used to create an anthropomorphic activity and attenuation distribution. We show that activity outside of the field of view has a major impact on singles-to-trues ratios and is an important design constraint. The coincidence time window width and system dead-time both have a significant effect on noise equivalent count-rates, and efforts to reduce them on a future prototype are likely to be worthwhile.

Influence of the partial volume correction method on 18F-fluorodeoxyglucose brain kinetic modelling from dynamic PET images reconstructed with resolution model based OSEM

Kinetic parameters estimated from dynamic (18)F-fluorodeoxyglucose ((18)F-FDG) PET acquisitions have been used frequently to assess brain function in humans. Neglecting partial volume correction (PVC) for a dynamic series has been shown to produce significant bias in model estimates. Accurate PVC requires a space-variant model describing the reconstructed image spatial point spread function (PSF) that accounts for resolution limitations, including non-uniformities across the field of view due to the parallax effect. For ordered subsets expectation maximization (OSEM), image resolution convergence is local and influenced significantly by the number of iterations, the count density, and background-to-target ratio. As both count density and background-to-target values for a brain structure can change during a dynamic scan, the local image resolution may also concurrently vary. When PVC is applied post-reconstruction the kinetic parameter estimates may be biased when neglecting the frame-dependent resolution. We explored the influence of the PVC method and implementation on kinetic parameters estimated by fitting (18)F-FDG dynamic data acquired on a dedicated brain PET scanner and reconstructed with and without PSF modelling in the OSEM algorithm. The performance of several PVC algorithms was quantified with a phantom experiment, an anthropomorphic Monte Carlo simulation, and a patient scan. Using the last frame reconstructed image only for regional spread function (RSF) generation, as opposed to computing RSFs for each frame independently, and applying perturbation geometric transfer matrix PVC with PSF based OSEM produced the lowest magnitude bias kinetic parameter estimates in most instances, although at the cost of increased noise compared to the PVC methods utilizing conventional OSEM. Use of the last frame RSFs for PVC with no PSF modelling in the OSEM algorithm produced the lowest bias in cerebral metabolic rate of glucose estimates, although by less than 5% in most cases compared to the other PVC methods. The results indicate that the PVC implementation and choice of PSF modelling in the reconstruction can significantly impact model parameters.

An X-ray Computed Tomography/Positron Emission Tomography System Designed Specifically for Breast Imaging

Mammography has served the population of women who are at-risk for breast cancer well over the past 30 years. While mammography has undergone a number of changes as digital detector technology has advanced, other modalities such as computed tomography have experienced technological sophistication over this same time frame as well. The advent of large field of view flat panel detector systems enable the development of breast CT and several other niche CT applications, which rely on cone beam geometry. The breast, it turns out, is well suited to cone beam CT imaging because the lack of bones reduces artifacts, and the natural tapering of the breast anteriorly reduces the x-ray path lengths through the breast at large cone angle, reducing cone beam artifacts as well. We are in the process of designing a third prototype system which will enable the use of breast CT for image guided interventional procedures. This system will have several copies fabricated so that several breast CT scanners can be used in a multi-institutional clinical trial to better understand the role that this technology can bring to breast imaging.