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All sourcesNASA NTRSDOE OSTI
DOE OSTI2011

Quantitative PET Imaging Using A Comprehensive Monte Carlo System Model

We present the complete image generation methodology developed for the RatCAP PET scanner, which can be extended to other PET systems for which a Monte Carlo-based system model is feasible. The miniature RatCAP presents a unique set of advantages as well as challenges for image processing, and a combination of conventional methods and novel ideas developed specifically for this tomograph have been implemented. The crux of our approach is a low-noise Monte Carlo-generated probability matrix with integrated corrections for all physical effects that impact PET image quality. The generation and optimization of this matrix are discussed in detail, along with the estimation of correction factors and their incorporation into the reconstruction framework. Phantom studies and Monte Carlo simulations are used to evaluate the reconstruction as well as individual corrections for random coincidences, photon scatter, attenuation, and detector efficiency variations in terms of bias and noise. Finally, a realistic rat brain phantom study reconstructed using this methodology is shown to recover >; 90% of the contrast for hot as well as cold regions. The goal has been to realize the potential of quantitative neuroreceptor imaging with the RatCAP.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2014

Field of view extension and truncation correction for MR-based human attenuation correction in simultaneous MR/PET imaging

Purpose: In quantitative PET imaging, it is critical to accurately measure and compensate for the attenuation of the photons absorbed in the tissue. While in PET/CT the linear attenuation coefficients can be easily determined from a low-dose CT-based transmission scan, in whole-body MR/PET the computation of the linear attenuation coefficients is based on the MR data. However, a constraint of the MR-based attenuation correction (AC) is the MR-inherent field-of-view (FoV) limitation due to static magnetic field (B{sub 0}) inhomogeneities and gradient nonlinearities. Therefore, the MR-based human AC map may be truncated or geometrically distorted toward the edges of the FoV and, consequently, the PET reconstruction with MR-based AC may be biased. This is especially of impact laterally where the patient arms rest beside the body and are not fully considered. Methods: A method is proposed to extend the MR FoV by determining an optimal readout gradient field which locally compensates B{sub 0} inhomogeneities and gradient nonlinearities. This technique was used to reduce truncation in AC maps of 12 patients, and the impact on the PET quantification was analyzed and compared to truncated data without applying the FoV extension and additionally to an established approach of PET-based FoV extension. Results: The truncation artifacts in the MR-based AC maps were successfully reduced in all patients, and the mean body volume was thereby increased by 5.4%. In some cases large patient-dependent changes in SUV of up to 30% were observed in individual lesions when compared to the standard truncated attenuation map. Conclusions: The proposed technique successfully extends the MR FoV in MR-based attenuation correction and shows an improvement of PET quantification in whole-body MR/PET hybrid imaging. In comparison to the PET-based completion of the truncated body contour, the proposed method is also applicable to specialized PET tracers with little uptake in the arms and might reduce the computation time by obviating the need for iterative calculations of the PET emission data beyond those required for reconstructing images.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

{sup 90}Y -PET imaging: Exploring limitations and accuracy under conditions of low counts and high random fraction

Purpose: {sup 90}Y -positron emission tomography (PET) imaging is becoming a recognized modality for postinfusion quantitative assessment following radioembolization therapy. However, the extremely low counts and high random fraction associated with {sup 90}Y -PET may significantly impair both qualitative and quantitative results. The aim of this work was to study image quality and noise level in relation to the quantification and bias performance of two types of Siemens PET scanners when imaging {sup 90}Y and to compare experimental results with clinical data from two types of commercially available {sup 90}Y microspheres. Methods: Data were acquired on both Siemens Biograph TruePoint [non-time-of-flight (TOF)] and Biograph microcomputed tomography (mCT) (TOF) PET/CT scanners. The study was conducted in three phases. The first aimed to assess quantification and bias for different reconstruction methods according to random fraction and number of true counts in the scan. The NEMA 1994 PET phantom was filled with water with one cylindrical insert left empty (air) and the other filled with a solution of {sup 90}Y . The phantom was scanned for 60 min in the PET/CT scanner every one or two days. The second phase used the NEMA 2001 PET phantom to derive noise and image quality metrics. The spheres and the background were filled with a {sup 90}Y solution in an 8:1 contrast ratio and four 30 min acquisitions were performed over a one week period. Finally, 32 patient data (8 treated with Therasphere{sup ®} and 24 with SIR-Spheres{sup ®}) were retrospectively reconstructed and activity in the whole field of view and the liver was compared to theoretical injected activity. Results: The contribution of both bremsstrahlung and LSO trues was found to be negligible, allowing data to be decay corrected to obtain correct quantification. In general, the recovered activity for all reconstruction methods was stable over the range studied, with a small bias appearing at extremely high random fraction and low counts for iterative algorithms. Point spread function (PSF) correction and TOF reconstruction in general reduce background variability and noise and increase recovered concentration. Results for patient data indicated a good correlation between the expected and PET reconstructed activities. A linear relationship between the expected and the measured activities in the organ of interest was observed for all reconstruction method used: a linearity coefficient of 0.89 ± 0.05 for the Biograph mCT and 0.81 ± 0.05 for the Biograph TruePoint. Conclusions: Due to the low counts and high random fraction, accurate image quantification of {sup 90}Y during selective internal radionuclide therapy is affected by random coincidence estimation, scatter correction, and any positivity constraint of the algorithm. Nevertheless, phantom and patient studies showed that the impact of number of true and random coincidences on quantitative results was found to be limited as long as ordinary Poisson ordered subsets expectation maximization reconstruction algorithms with random smoothing are used. Adding PSF correction and TOF information to the reconstruction greatly improves the image quality in terms of bias, variability, noise reduction, and detectability. On the patient studies, the total activity in the field of view is in general accurately measured by Biograph mCT and slightly overestimated by the Biograph TruePoint.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

A 3D MR-acquisition scheme for nonrigid bulk motion correction in simultaneous PET-MR

Purpose: Positron emission tomography (PET) is a highly sensitive medical imaging technique commonly used to detect and assess tumor lesions. Magnetic resonance imaging (MRI) provides high resolution anatomical images with different contrasts and a range of additional information important for cancer diagnosis. Recently, simultaneous PET-MR systems have been released with the promise to provide complementary information from both modalities in a single examination. Due to long scan times, subject nonrigid bulk motion, i.e., changes of the patient's position on the scanner table leading to nonrigid changes of the patient's anatomy, during data acquisition can negatively impair image quality and tracer uptake quantification. A 3D MR-acquisition scheme is proposed to detect and correct for nonrigid bulk motion in simultaneously acquired PET-MR data. Methods: A respiratory navigated three dimensional (3D) MR-acquisition with Radial Phase Encoding (RPE) is used to obtain T1- and T2-weighted data with an isotropic resolution of 1.5 mm. Healthy volunteers are asked to move the abdomen two to three times during data acquisition resulting in overall 19 movements at arbitrary time points. The acquisition scheme is used to retrospectively reconstruct dynamic 3D MR images with different temporal resolutions. Nonrigid bulk motion is detected and corrected in this image data. A simultaneous PET acquisition is simulated and the effect of motion correction is assessed on image quality and standardized uptake values (SUV) for lesions with different diameters. Results: Six respiratory gated 3D data sets with T1- and T2-weighted contrast have been obtained in healthy volunteers. All bulk motion shifts have successfully been detected and motion fields describing the transformation between the different motion states could be obtained with an accuracy of 1.71 ± 0.29 mm. The PET simulation showed errors of up to 67% in measured SUV due to bulk motion which could be reduced to less than 10% with the proposed motion compensation approach. Conclusions: A MR acquisition scheme which yields both high resolution 3D anatomical data and highly accurate nonrigid motion information without an increase in scan time is presented. The proposed method leads to a strong improvement in both MR and PET image quality and ensures an accurate assessment of tracer uptake.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Patient motion effects on the quantification of regional myocardial blood flow with dynamic PET imaging

Purpose: Patient motion is a common problem during dynamic positron emission tomography (PET) scans for quantification of myocardial blood flow (MBF). The purpose of this study was to quantify the prevalence of body motion in a clinical setting and evaluate with realistic phantoms the effects of motion on blood flow quantification, including CT attenuation correction (CTAC) artifacts that result from PET–CT misalignment. Methods: A cohort of 236 sequential patients was analyzed for patient motion under resting and peak stress conditions by two independent observers. The presence of motion, affected time-frames, and direction of motion was recorded; discrepancy between observers was resolved by consensus review. Based on these results, patient body motion effects on MBF quantification were characterized using the digital NURBS-based cardiac-torso phantom, with characteristic time activity curves (TACs) assigned to the heart wall (myocardium) and blood regions. Simulated projection data were corrected for attenuation and reconstructed using filtered back-projection. All simulations were performed without noise added, and a single CT image was used for attenuation correction and aligned to the early- or late-frame PET images. Results: In the patient cohort, mild motion of 0.5 ± 0.1 cm occurred in 24% and moderate motion of 1.0 ± 0.3 cm occurred in 38% of patients. Motion in the superior/inferior direction accounted for 45% of all detected motion, with 30% in the superior direction. Anterior/posterior motion was predominant (29%) in the posterior direction. Left/right motion occurred in 24% of cases, with similar proportions in the left and right directions. Computer simulation studies indicated that errors in MBF can approach 500% for scans with severe patient motion (up to 2 cm). The largest errors occurred when the heart wall was shifted left toward the adjacent lung region, resulting in a severe undercorrection for attenuation of the heart wall. Simulations also indicated that the magnitude of MBF errors resulting from motion in the superior/inferior and anterior/posterior directions was similar (up to 250%). Body motion effects were more detrimental for higher resolution PET imaging (2 vs 10 mm full-width at half-maximum), and for motion occurring during the mid-to-late time-frames. Motion correction of the reconstructed dynamic image series resulted in significant reduction in MBF errors, but did not account for the residual PET–CTAC misalignment artifacts. MBF bias was reduced further using global partial-volume correction, and using dynamic alignment of the PET projection data to the CT scan for accurate attenuation correction during image reconstruction. Conclusions: Patient body motion can produce MBF estimation errors up to 500%. To reduce these errors, new motion correction algorithms must be effective in identifying motion in the left/right direction, and in the mid-to-late time-frames, since these conditions produce the largest errors in MBF, particularly for high resolution PET imaging. Ideally, motion correction should be done before or during image reconstruction to eliminate PET-CTAC misalignment artifacts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

MR/PET quantification tools: Registration, segmentation, classification, and MR-based attenuation correction

Purpose: Combined MR/PET is a relatively new, hybrid imaging modality. A human MR/PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR/PET for brain imaging. Methods: The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR/PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with [{sup 11}C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. Results: For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. Conclusions: MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR/PET.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

TU-A-18A-01: Basic Principles of PET/CT, Calibration Methods and Contrast Recovery Across Multiple Cameras

This continuing education session will discuss the physical principles of PET/CT imaging and characterization of contrast recovery using accreditation phantoms. A detailed overview will be given on the physical principles of PET including positron decay physics, 2D and 3D data acquisition, time-of-flight, scatter correction, CT attenuation correction, and image reconstruction. Instrument quality control and calibration procedures will be discussed. Technical challenges, common image artifacts and strategies to mitigate these issues will also be discussed. Data will be presented on acquisition techniques and reconstruction parameters affecting contrast recovery. The discussion will emphasize the minimization of reconstruction differences in quantification metrics such as SUV and contrast recovery coefficients for the NEMA and ACR clinical trial phantoms. Data from new and older generation scanners will be shown including comparison of contrast recovery measurements to their analytical solutions. The goal of this session is to update attendees on the quality control and calibration of PET/CT scanners, on methods to establish a common calibration for PET/CT scanners to control for instrument variance across multiple sites. Learning Objectives: Review the physical principles of PET/CT, quality control and calibration Gain further understanding on how to apply techniques for improving quantitative agreement across multiple cameras Describe the differences between measured and expected contrast recovery for the NEMA and ACR PET phantoms.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Metal artifact reduction strategies for improved attenuation correction in hybrid PET/CT imaging

Metallic implants are known to generate bright and dark streaking artifacts in x-ray computed tomography (CT) images, which in turn propagate to corresponding functional positron emission tomography (PET) images during the CT-based attenuation correction procedure commonly used on hybrid clinical PET/CT scanners. Therefore, visual artifacts and overestimation and/or underestimation of the tracer uptake in regions adjacent to metallic implants are likely to occur and as such, inaccurate quantification of the tracer uptake and potential erroneous clinical interpretation of PET images is expected. Accurate quantification of PET data requires metal artifact reduction (MAR) of the CT images prior to the application of the CT-based attenuation correction procedure. In this review, the origins of metallic artifacts and their impact on clinical PET/CT imaging are discussed. Moreover, a brief overview of proposed MAR methods and their advantages and drawbacks is presented. Although most of the presented MAR methods are mainly developed for diagnostic CT imaging, their potential application in PET/CT imaging is highlighted. The challenges associated with comparative evaluation of these methods in a clinical environment in the absence of a gold standard are also discussed.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2024

Evaluation of partial volume correction and analysis of longitudinal [ 18 F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models

Purpose: We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [ 18 F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM). Methods: We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates. Results: The VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability. Conclusion: The results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [ 18 F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability. Clinical trial registration: NCT02640092 and NCT03289143.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Correction of quantification errors in pelvic and spinal lesions caused by ignoring higher photon attenuation of bone in [{sup 18}F]NaF PET/MR

Purpose: MR-based attenuation correction (MRAC) in routine clinical whole-body positron emission tomography and magnetic resonance imaging (PET/MRI) is based on tissue type segmentation. Due to lack of MR signal in cortical bone and the varying signal of spongeous bone, standard whole-body segmentation-based MRAC ignores the higher attenuation of bone compared to the one of soft tissue (MRAC{sub nobone}). The authors aim to quantify and reduce the bias introduced by MRAC{sub nobone} in the standard uptake value (SUV) of spinal and pelvic lesions in 20 PET/MRI examinations with [{sup 18}F]NaF. Methods: The authors reconstructed 20 PET/MR [{sup 18}F]NaF patient data sets acquired with a Philips Ingenuity TF PET/MRI. The PET raw data were reconstructed with two different attenuation images. First, the authors used the vendor-provided MRAC algorithm that ignores the higher attenuation of bone to reconstruct PET{sub nobone}. Second, the authors used a threshold-based algorithm developed in their group to automatically segment bone structures in the [{sup 18}F]NaF PET images. Subsequently, an attenuation coefficient of 0.11 cm{sup −1} was assigned to the segmented bone regions in the MRI-based attenuation image (MRAC{sub bone}) which was used to reconstruct PET{sub bone}. The automatic bone segmentation algorithm was validated in six PET/CT [{sup 18}F]NaF examinations. Relative SUV{sub mean} and SUV{sub max} differences between PET{sub bone} and PET{sub nobone} of 8 pelvic and 41 spinal lesions, and of other regions such as lung, liver, and bladder, were calculated. By varying the assigned bone attenuation coefficient from 0.11 to 0.13 cm{sup −1}, the authors investigated its influence on the reconstructed SUVs of the lesions. Results: The comparison of [{sup 18}F]NaF-based and CT-based bone segmentation in the six PET/CT patients showed a Dice similarity of 0.7 with a true positive rate of 0.72 and a false discovery rate of 0.33. The [{sup 18}F]NaF-based bone segmentation worked well in the pelvis and spine. However, it showed artifacts in the skull and in the extremities. The analysis of the 20 [{sup 18}F]NaF PET/MRI examinations revealed relative SUV{sub max} differences between PET{sub nobone} and PET{sub bone} of (−8.8% ± 2.7%, p = 0.01) and (−8.1% ± 1.9%, p = 2.4 × 10{sup −8}) in pelvic and spinal lesions, respectively. A maximum SUV{sub max} underestimation of −13.7% was found in lesion in the third cervical spine. The averaged SUV{sub mean} differences in volumes of interests in lung, liver, and bladder were below 3%. The average SUV{sub max} differences in pelvic and spinal lesions increased from −9% to −18% and −8% to −17%, respectively, when increasing the assigned bone attenuation coefficient from 0.11 to 0.13 cm{sup −1}. Conclusions: The developed automatic [{sup 18}F]NaF PET-based bone segmentation allows to include higher bone attenuation in whole-body MRAC and thus improves quantification accuracy for pelvic and spinal lesions in [{sup 18}F]NaF PET/MRI examinations. In nonbone structures (e.g., lung, liver, and bladder), MRAC{sub nobone} yields clinically acceptable accuracy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Evaluation of in vivo quantification accuracy of the Ingenuity-TF PET/MR

Purpose: The quantitative accuracy of standardized uptake values (SUVs) and tracer kinetic uptake parameters in patient investigations strongly depends on accurate determination of regional activity concentrations in positron emission tomography (PET) data. This determination rests on the assumption that the given scanner calibration is valid in vivo. In a previous study, we introduced a method to test this assumption. This method allows to identify discrepancies in quantitative accuracy in vivo by comparison of activity concentrations of urine samples measured in a well-counter with activity concentrations extracted from PET images of the bladder. In the present study, we have applied this method to the Philips Ingenuity-TF PET/MR since at the present stage, absolute quantitative accuracy of combined PET/MR systems is still under investigation. Methods: Twenty one clinical whole-body F18-FDG scans were included in this study. The bladder region was imaged as the last bed position and urine samples were collected afterward. PET images were reconstructed including MR-based attenuation correction with and without truncation compensation and 3D regions-of-interest (ROIs) of the bladder were delineated by three observers. To exclude partial volume effects, ROIs were concentrically shrunk by 8–10 mm. Then, activity concentrations were determined in the PET images for the bladder and for the urine by measuring the samples in a calibrated well-counter. In addition, linearity measurements of SUV vs singles rate and measurements of the stability of the coincidence rate of “true” events of the PET/MR system were performed over a period of 4 months. Results: The measured in vivo activity concentrations were significantly lower in PET/MR than in the well-counter with a ratio of the former to the latter of 0.756 ± 0.060 (mean ± std. dev.), a range of 0.604–0.858, and a P value of 3.9 ⋅ 10{sup −14}. While the stability measurements of the coincidence rate of “true” events showed no relevant deviation over time, the linearity scans revealed a systematic error of 8%–11% (avg. 9%) for the range of singles rates present in the bladder scans. After correcting for this systematic bias caused by shortcomings of the manufacturers calibration procedure, the PET to well-counter ratio increased to 0.832 ± 0.064 (0.668 –0.941), P = 1.1 ⋅ 10{sup −10}. After compensating for truncation of the upper extremities in the MR-based attenuation maps, the ratio further improved to 0.871 ± 0.069 (0.693–0.992), P = 3.9 ⋅ 10{sup −8}. Conclusions: Our results show that the Philips PET/MR underestimates activity concentrations in the bladder by 17%, which is 7 percentage points (pp.) larger than in the previously investigated PET and PET/CT systems. We attribute this increased underestimation to remaining limitations of the MR-based attenuation correction. Our results suggest that only a 2 pp. larger underestimation of activity concentrations compared to PET/CT can be observed if compensation of attenuation truncation of the upper extremities is applied. Thus, quantification accuracy of the Philips Ingenuity-TF PET/MR can be considered acceptable for clinical purposes given the ±10% error margin in the EANM guidelines. The comparison of PET images from the bladder region with urine samples has proven a useful method. It might be interesting for evaluation and comparison of the in vivo quantitative accuracy of PET, PET/CT, and especially PET/MR systems from different manufacturers or in multicenter trials.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Sensitivity estimation in time-of-flight list-mode positron emission tomography

Purpose: An accurate quantification of the images in positron emission tomography (PET) requires knowing the actual sensitivity at each voxel, which represents the probability that a positron emitted in that voxel is finally detected as a coincidence of two gamma rays in a pair of detectors in the PET scanner. This sensitivity depends on the characteristics of the acquisition, as it is affected by the attenuation of the annihilation gamma rays in the body, and possible variations of the sensitivity of the scanner detectors. In this work, the authors propose a new approach to handle time-of-flight (TOF) list-mode PET data, which allows performing either or both, a self-attenuation correction, and self-normalization correction based on emission data only. Methods: The authors derive the theory using a fully Bayesian statistical model of complete data. The authors perform an initial evaluation of algorithms derived from that theory and proposed in this work using numerical 2D list-mode simulations with different TOF resolutions and total number of detected coincidences. Effects of randoms and scatter are not simulated. Results: The authors found that proposed algorithms successfully correct for unknown attenuation and scanner normalization for simulated 2D list-mode TOF-PET data. Conclusions: A new method is presented that can be used for corrections for attenuation and normalization (sensitivity) using TOF list-mode data.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

WE-AB-204-01: Performance Characterization of Regularized-Reconstruction Algorithm for 90Y PET/CT Images

Purpose: {sup 90}Y PET/CT imaging and quantification have recently been suggested as an approach of treatment verification. However, due to low positron yield (32ppm), the {sup 90}Y-PET/CT images are very noisy. Iterative reconstruction techniques that employ regularization, e.g. block sequential regularized expectation maximization (BSREM) algorithm (recently implemented on GE scanners – QClear™), has the potential to increase quantitative accuracy with lower noise penalty compared to OSEM. Our aim is to investigate the performance of RR algorithms in {sup 90}Y PET/CT studies. Methods: A NEMA IEC phantom filled with 3GBq {sup 90}YCl{sub 2} (to simulate patient treatment) was imaged on GE-D690 for 1800s/bed. The sphere-to-background ratio of 7. The data were reconstructed using OSEM and BSREM with PSF modeling and TOF correction while varying the iterations (IT) from 1–6 with fixed 24subsets. For BSREM, the edge-preservation parameter (γ ) was 2 and the penalty-parameters (β) was varied 350–950. In all cases a post-reconstruction filter of 5.2mm (2pixel) transaxial and standard z-axis were used. Sphere average activity concentration (AC) and background standard deviation (SD) were then calculated from VOIs drawn in the spheres and background. Results: Increasing IT from 1to6, the %SD in OSEM increased from 30% to 80%, whereas %SD in BSREM images increased by <5% for all βs. BSREM with β=350 didn’t offer any improvement over OSEM (convergence of mean achieved at 2 IT, in this study). Increasing β from 350 to 950 reduced the AC accuracy of small spheres (<20mm) by 10% and noise from 40% to 20%, which resulted in CNR increase from 11 to 17. Conclusion: In count-limited studies such as {sup 90}Y PET/CT, BSREM can be used to suppress image noise and increase CNR at the expense of a relatively small decrease of quantitative accuracy. The BSREM parameters need to be optimized for each study depending on the radionuclides and count densities. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA13898 and was also partly supported by General Electric.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Vision 20/20: Magnetic resonance imaging-guided attenuation correction in PET/MRI: Challenges, solutions, and opportunities

Attenuation correction is an essential component of the long chain of data correction techniques required to achieve the full potential of quantitative positron emission tomography (PET) imaging. The development of combined PET/magnetic resonance imaging (MRI) systems mandated the widespread interest in developing novel strategies for deriving accurate attenuation maps with the aim to improve the quantitative accuracy of these emerging hybrid imaging systems. The attenuation map in PET/MRI should ideally be derived from anatomical MR images; however, MRI intensities reflect proton density and relaxation time properties of biological tissues rather than their electron density and photon attenuation properties. Therefore, in contrast to PET/computed tomography, there is a lack of standardized global mapping between the intensities of MRI signal and linear attenuation coefficients at 511 keV. Moreover, in standard MRI sequences, bones and lung tissues do not produce measurable signals owing to their low proton density and short transverse relaxation times. MR images are also inevitably subject to artifacts that degrade their quality, thus compromising their applicability for the task of attenuation correction in PET/MRI. MRI-guided attenuation correction strategies can be classified in three broad categories: (i) segmentation-based approaches, (ii) atlas-registration and machine learning methods, and (iii) emission/transmission-based approaches. This paper summarizes past and current state-of-the-art developments and latest advances in PET/MRI attenuation correction. The advantages and drawbacks of each approach for addressing the challenges of MR-based attenuation correction are comprehensively described. The opportunities brought by both MRI and PET imaging modalities for deriving accurate attenuation maps and improving PET quantification will be elaborated. Future prospects and potential clinical applications of these techniques and their integration in commercial systems will also be discussed.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2014

A multifractal approach to space-filling recovery for PET quantification

Purpose: A new image-based methodology is developed for estimating the apparent space-filling properties of an object of interest in PET imaging without need for a robust segmentation step and used to recover accurate estimates of total lesion activity (TLA). Methods: A multifractal approach and the fractal dimension are proposed to recover the apparent space-filling index of a lesion (tumor volume, TV) embedded in nonzero background. A practical implementation is proposed, and the index is subsequently used with mean standardized uptake value (SUV {sub mean}) to correct TLA estimates obtained from approximate lesion contours. The methodology is illustrated on fractal and synthetic objects contaminated by partial volume effects (PVEs), validated on realistic {sup 18}F-fluorodeoxyglucose PET simulations and tested for its robustness using a clinical {sup 18}F-fluorothymidine PET test–retest dataset. Results: TLA estimates were stable for a range of resolutions typical in PET oncology (4–6 mm). By contrast, the space-filling index and intensity estimates were resolution dependent. TLA was generally recovered within 15% of ground truth on postfiltered PET images affected by PVEs. Volumes were recovered within 15% variability in the repeatability study. Results indicated that TLA is a more robust index than other traditional metrics such as SUV {sub mean} or TV measurements across imaging protocols. Conclusions: The fractal procedure reported here is proposed as a simple and effective computational alternative to existing methodologies which require the incorporation of image preprocessing steps (i.e., partial volume correction and automatic segmentation) prior to quantification.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

MO-G-17A-01: Innovative High-Performance PET Imaging System for Preclinical Imaging and Translational Researches

Purpose: To develop a practical and compact preclinical PET with innovative technologies for substantially improved imaging performance required for the advanced imaging applications. Methods: Several key components of detector, readout electronics and data acquisition have been developed and evaluated for achieving leapfrogged imaging performance over a prototype animal PET we had developed. The new detector module consists of an 8×8 array of 1.5×1.5×30 mm{sup 3} LYSO scintillators with each end coupled to a latest 4×4 array of 3×3 mm{sup 2} Silicon Photomultipliers (with ∼0.2 mm insensitive gap between pixels) through a 2.0 mm thick transparent light spreader. Scintillator surface and reflector/coupling were designed and fabricated to reserve air-gap to achieve higher depth-of-interaction (DOI) resolution and other detector performance. Front-end readout electronics with upgraded 16-ch ASIC was newly developed and tested, so as the compact and high density FPGA based data acquisition and transfer system targeting 10M/s coincidence counting rate with low power consumption. The new detector module performance of energy, timing and DOI resolutions with the data acquisition system were evaluated. Initial Na-22 point source image was acquired with 2 rotating detectors to assess the system imaging capability. Results: No insensitive gaps at the detector edge and thus it is capable for tiling to a large-scale detector panel. All 64 crystals inside the detector were clearly separated from a flood-source image. Measured energy, timing, and DOI resolutions are around 17%, 2.7 ns and 1.96 mm (mean value). Point source image is acquired successfully without detector/electronics calibration and data correction. Conclusion: Newly developed advanced detector and readout electronics will be enable achieving targeted scalable and compact PET system in stationary configuration with >15% sensitivity, ∼1.3 mm uniform imaging resolution, and fast acquisition counting rate capability for substantially improved imaging and quantification performance for small animal imaging and image-guided radiotherapy applications. This work was supported by a research award RP120326 from Cancer Prevention and Research Institute of Texas.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2022

Optimizing quantification of MK6240 tau PET in unimpaired older adults

Accurate measurement of Alzheimer's disease (AD) pathology in older adults without significant clinical impairment is critical to assessing intervention strategies aimed at slowing AD-related cognitive decline. The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (POINTER) is a 2-year randomized controlled trial to evaluate the effect of multicomponent risk reduction strategies in older adults (60-79 years) who are cognitively unimpaired but at increased risk for cognitive decline/dementia due to factors such as cardiovascular disease and family history. The POINTER Imaging ancillary study is collecting tau-PET ([ 18 F]MK6240), beta-amyloid (Aβ)-PET ([ 18 F]florbetaben [FBB]) and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at-risk sample. Here 481 participants (70.0±5.0; 66% F) with baseline MK6240, FBB and structural MRI scans were included. PET scans were coregistered to the structural MRI which was used to create FreeSurfer-defined reference regions and target regions of interest (ROIs). We also created off-target signal (OTS) ROIs to examine the magnitude and distribution of MK6240 OTS across the brain as well as relationships between OTS and age, sex, and race. OTS was unimodally distributed, highly correlated across OTS ROIs and related to younger age and sex but not race. Aiming to identify an optimal processing approach for MK6240 that would reduce the influence of OTS, we compared our previously validated MRI-guided standard PET processing and 6 alternative approaches. The alternate approaches included combinations of reference region erosion and meningeal OTS masking before spatial smoothing as well as partial volume correction. To compare processing approaches we examined relationships between target ROIs (entorhinal cortex (ERC), hippocampus or a temporal meta-ROI (MetaROI)) SUVR and age, sex, race, Aβ and a general cognitive status measure, the Modified Telephone Interview for Cognitive Status (TICSm). Overall, the processing approaches performed similarly, and none showed a meaningful improvement over standard processing. Across processing approaches we observed previously reported relationships with MK6240 target ROIs including positive associations with age, an Aβ+> Aβ- effect and negative associations with cognition. In sum, we demonstrated that different methods for minimizing effects of OTS, which is highly correlated across the brain within subject, produced no substantive change in our performance metrics. This is likely because OTS contaminates both reference and target regions and this contamination largely cancels out in SUVR data. Caution should be used when efforts to reduce OTS focus on target or reference regions in isolation as this may exacerbate OTS contamination in SUVR data.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Integrated PET/MR breast cancer imaging: Attenuation correction and implementation of a 16-channel RF coil

Purpose: This study aims to develop, implement, and evaluate a 16-channel radiofrequency (RF) coil for integrated positron emission tomography/magnetic resonance (PET/MR) imaging of breast cancer. The RF coil is designed for optimized MR imaging performance and PET transparency and attenuation correction (AC) is applied for accurate PET quantification. Methods: A 16-channel breast array RF coil was designed for integrated PET/MR hybrid imaging of breast cancer lesions. The RF coil features a lightweight rigid design and is positioned with a spacer at a defined position on the patient table of an integrated PET/MR system. Attenuation correction is performed by generating and applying a dedicated 3D CT-based template attenuation map. Reposition accuracy of the RF coil on the system patient table while using the positioning frame was tested in repeated measurements using MR-visible markers. The MR, PET, and PET/MR imaging performances were systematically evaluated using modular breast phantoms. Attenuation correction of the RF coil was evaluated with difference measurements of the active breast phantoms filled with radiotracer in the PET detector with and without the RF coil in place, serving as a standard of reference measurement. The overall PET/MR imaging performance and PET quantification accuracy of the new 16-channel RF coil and its AC were then evaluated in first clinical examinations on ten patients with local breast cancer. Results: The RF breast array coil provides excellent signal-to-noise ratio and signal homogeneity across the volume of the breast phantoms in MR imaging and visualizes small structures in the phantoms down to 0.4 mm in plane. Difference measurements with PET revealed a global loss and thus attenuation of counts by 13% (mean value across the whole phantom volume) when the RF coil is placed in the PET detector. Local attenuation ranging from 0% in the middle of the phantoms up to 24% was detected in the peripheral regions of the phantoms at positions closer to attenuating hardware structures of the RF coil. The position accuracy of the RF coil on the patient table when using the positioning frame was determined well below 1 mm for all three spatial dimensions. This ensures perfect position match between the RF coil and its three-dimensional attenuation template during the PET data reconstruction process. When applying the CT-based AC of the RF coil, the global attenuation bias was mostly compensated to ±0.5% across the entire breast imaging volume. The patient study revealed high quality MR, PET, and combined PET/MR imaging of breast cancer. Quantitative activity measurements in all 11 breast cancer lesions of the ten patients resulted in increased mean difference values of SUV{sub max} 11.8% (minimum 3.2%; maximum 23.2%) between nonAC images and images when AC of the RF breast coil was applied. This supports the quantitative results of the phantom study as well as successful attenuation correction of the RF coil. Conclusions: A 16-channel breast RF coil was designed for optimized MR imaging performance and PET transparency and was successfully integrated with its dedicated attenuation correction template into a whole-body PET/MR system. Systematic PET/MR imaging evaluation with phantoms and an initial study on patients with breast cancer provided excellent MR and PET image quality and accurate PET quantification.

60 APPLIED LIFE SCIENCES↗