Frederic Mantlik

MRI-Based Attenuation Correction for Whole-Body PET/MRI: Quantitative Evaluation of Segmentation- and Atlas-Based Methods

PET/MRI is an emerging dual-modality imaging technology that requires new approaches to PET attenuation correction (AC). We assessed 2 algorithms for whole-body MRI-based AC (MRAC): a basic MR image segmentation algorithm and a method based on atlas registration and pattern recognition (AT&PR). Methods: Eleven patients each underwent a whole-body PET/CT study and a separate multibed whole-body MRI study. The MR image segmentation algorithm uses a combination of image thresholds, Dixon fat–water segmentation, and component analysis to detect the lungs. MR images are segmented into 5 tissue classes (not including bone), and each class is assigned a default linear attenuation value. The AT&PR algorithm uses a database of previously aligned pairs of MRI/CT image volumes. For each patient, these pairs are registered to the patient MRI volume, and machine-learning techniques are used to predict attenuation values on a continuous scale. MRAC methods are compared via the quantitative analysis of AC PET images using volumes of interest in normal organs and on lesions. We assume the PET/CT values after CT-based AC to be the reference standard. Results: In regions of normal physiologic uptake, the average error of the mean standardized uptake value was 14.1% ± 10.2% and 7.7% ± 8.4% for the segmentation and the AT&PR methods, respectively. Lesion-based errors were 7.5% ± 7.9% for the segmentation method and 5.7% ± 4.7% for the AT&PR method. Conclusion: The MRAC method using AT&PR provided better overall PET quantification accuracy than the basic MR image segmentation approach. This better quantification was due to the significantly reduced volume of errors made regarding volumes of interest within or near bones and the slightly reduced volume of errors made regarding areas outside the lungs.

MR-Based PET Attenuation Correction for PET/MR Imaging

Recent progress has allowed hybrid positron emission tomography/magnetic resonance (PET/MR) systems to make the transition from research prototypes to systems with full potential for clinical imaging. Options for directly measuring the attenuation maps, as is possible with PET/computed tomography or PET transmission scans, are not included in PET/MR scanners. New methods to compute attenuation maps from MR data have therefore been developed.

MR-Based Attenuation Correction Methods for Improved PET Quantification in Lesions Within Bone and Susceptibility Artifact Regions

Hybrid PET/MR systems have recently entered clinical practice. Thus, the accuracy of MR-based attenuation correction in simultaneously acquired data can now be investigated. We assessed the accuracy of 4 methods of MR-based attenuation correction in lesions within soft tissue, bone, and MR susceptibility artifacts: 2 segmentation-based methods (SEG1, provided by the manufacturer, and SEG2, a method with atlas-based susceptibility artifact correction); an atlas- and pattern recognition–based method (AT&PR), which also used artifact correction; and a new method combining AT&PR and SEG2 (SEG2wBONE). Methods: Attenuation maps were calculated for the PET/MR datasets of 10 patients acquired on a whole-body PET/MR system, allowing for simultaneous acquisition of PET and MR data. Eighty percent iso-contour volumes of interest were placed on lesions in soft tissue (n = 21), in bone (n = 20), near bone (n = 19), and within or near MR susceptibility artifacts (n = 9). Relative mean volume-of-interest differences were calculated with CT-based attenuation correction as a reference. Results: For soft-tissue lesions, none of the methods revealed a significant difference in PET standardized uptake value relative to CT-based attenuation correction (SEG1, −2.6% ± 5.8%; SEG2, −1.6% ± 4.9%; AT&PR, −4.7% ± 6.5%; SEG2wBONE, 0.2% ± 5.3%). For bone lesions, underestimation of PET standardized uptake values was found for all methods, with minimized error for the atlas-based approaches (SEG1, −16.1% ± 9.7%; SEG2, −11.0% ± 6.7%; AT&PR, −6.6% ± 5.0%; SEG2wBONE, −4.7% ± 4.4%). For lesions near bone, underestimations of lower magnitude were observed (SEG1, −12.0% ± 7.4%; SEG2, −9.2% ± 6.5%; AT&PR, −4.6% ± 7.8%; SEG2wBONE, −4.2% ± 6.2%). For lesions affected by MR susceptibility artifacts, quantification errors could be reduced using the atlas-based artifact correction (SEG1, −54.0% ± 38.4%; SEG2, −15.0% ± 12.2%; AT&PR, −4.1% ± 11.2%; SEG2wBONE, 0.6% ± 11.1%). Conclusion: For soft-tissue lesions, none of the evaluated methods showed statistically significant errors. For bone lesions, significant underestimations of −16% and −11% occurred for methods in which bone tissue was ignored (SEG1 and SEG2). In the present attenuation correction schemes, uncorrected MR susceptibility artifacts typically result in reduced attenuation values, potentially leading to highly reduced PET standardized uptake values, rendering lesions indistinguishable from background. While AT&PR and SEG2wBONE show accurate results in both soft tissue and bone, SEG2wBONE uses a two-step approach for tissue classification, which increases the robustness of prediction and can be applied retrospectively if more precision in bone areas is needed.

Quantitative Evaluation of Segmentation- and Atlas-Based Attenuation Correction for PET/MR on Pediatric Patients

Pediatric imaging is regarded as a key application for combined PET/MR imaging systems. Because existing MR-based attenuation-correction methods were not designed specifically for pediatric patients, we assessed the impact of 2 potentially influential factors: inter- and intrapatient variability of attenuation coefficients and anatomic variability. Furthermore, we evaluated the quantification accuracy of 3 methods for MR-based attenuation correction without (SEGbase) and with bone prediction using an adult and a pediatric atlas (SEGwBONEad and SEGwBONEpe, respectively) on PET data of pediatric patients. Methods: The variability of attenuation coefficients between and within pediatric (5–17 y, n = 17) and adult (27–66 y, n = 16) patient collectives was assessed on volumes of interest (VOIs) in CT datasets for different tissue types. Anatomic variability was assessed on SEGwBONEad/pe attenuation maps by computing mean differences to CT-based attenuation maps for regions of bone tissue, lungs, and soft tissue. PET quantification was evaluated on VOIs with physiologic uptake and on 80% isocontour VOIs with elevated uptake in the thorax and abdomen/pelvis. Inter- and intrapatient variability of the bias was assessed for each VOI group and method. Results: Statistically significant differences in mean VOI Hounsfield unit values and linear attenuation coefficients between adult and pediatric collectives were found in the lungs and femur. The prediction of attenuation maps using the pediatric atlas showed a reduced error in bone tissue and better delineation of bone structure. Evaluation of PET quantification accuracy showed statistically significant mean errors in mean standardized uptake values of −14% ± 5% and −23% ± 6% in bone marrow and femur-adjacent VOIs with physiologic uptake for SEGbase, which could be reduced to 0% ± 4% and −1% ± 5% using SEGwBONEpe attenuation maps. Bias in soft-tissue VOIs was less than 5% for all methods. Lung VOIs showed high SDs in the range of 15% for all methods. For VOIs with elevated uptake, mean and SD were less than 5% except in the thorax. Conclusion: The use of a dedicated atlas for the pediatric patient collective resulted in improved attenuation map prediction in osseous regions and reduced interpatient bias variation in femur-adjacent VOIs. For the lungs, in which intrapatient variation was higher for the pediatric collective, a patient- or group-specific attenuation coefficient might improve attenuation map accuracy. Mean errors of −14% and −23% in bone marrow and femur-adjacent VOIs can affect PET quantification in these regions when bone tissue is ignored.

Attenuation correction in MR-BrainPET with segmented T1-weighted MR images of the patient's head — A comparative study with CT

Our method for attenuation correction (AC) in MR-BrainPET with segmented T1-weighted MR images of the pa-tients head was applied to data from different MR-BrainPET scanners (Jülich, Tübingen) and compared to CT-based results.

Development of a novel depth of interaction PET detector using highly multiplexed G-APD cross-strip encoding

PURPOSE The aim of this study was to develop a prototype PET detector module for a combined small animal positron emission tomography and magnetic resonance imaging (PET/MRI) system. The most important factor for small animal imaging applications is the detection sensitivity of the PET camera, which can be optimized by utilizing longer scintillation crystals. At the same time, small animal PET systems must yield a high spatial resolution. The measured object is very close to the PET detector because the bore diameter of a high field animal MR scanner is limited. When used in combination with long scintillation crystals, these small-bore PET systems generate parallax errors that ultimately lead to a decreased spatial resolution. Thus, we developed a depth of interaction (DoI) encoding PET detector module that has a uniform spatial resolution across the whole field of view (FOV), high detection sensitivity, compactness, and insensitivity to magnetic fields. METHODS The approach was based on Geiger mode avalanche photodiode (G-APD) detectors with cross-strip encoding. The number of readout channels was reduced by a factor of 36 for the chosen block elements. Two 12 × 2 G-APD strip arrays (25 μm cells) were placed perpendicular on each face of a 12 × 12 lutetium oxyorthosilicate crystal block with a crystal size of 1.55 × 1.55 × 20 mm. The strip arrays were multiplexed into two channels and used to calculate the x, y coordinates for each array and the deposited energy. The DoI was measured in step sizes of 1.8 mm by a collimated (18)F source. The coincident resolved time (CRT) was analyzed at all DoI positions by acquiring the waveform for each event and applying a digital leading edge discriminator. RESULTS All 144 crystals were well resolved in the crystal flood map. The average full width half maximum (FWHM) energy resolution of the detector was 12.8% ± 1.5% with a FWHM CRT of 1.14 ± 0.02 ns. The average FWHM DoI resolution over 12 crystals was 2.90 ± 0.15 mm. CONCLUSIONS The novel DoI PET detector, which is based on strip G-APD arrays, yielded a DoI resolution of 2.9 mm and excellent timing and energy resolution. Its high multiplexing factor reduces the number of electronic channels. Thus, this cross-strip approach enables low-cost, high-performance PET detectors for dedicated small animal PET and PET/MRI and potentially clinical PET/MRI systems.

On the Quantification Accuracy, Homogeneity, and Stability of Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging Systems

ObjectiveA potential major application of simultaneous avalanche photodiode–based positron emission tomography (PET)/magnetic resonance imaging (MRI) systems are quantitative brain studies for cerebral blood flow measurements in combination with blood-oxygen-level–dependent or perfusion MRI, requiring a high performance for both modalities. Thus, we evaluated PET quantification accuracy and homogeneity for 2 different simultaneous PET/MRI systems (whole–body and brain scanner) compared with those of a state-of-the-art PET detector (PET/computed tomography) using phantom studies. In addition, we investigated the long-term stability of PET and quality of functional MRI measurements of a clinical whole-body PET/MRI scanner. Materials and MethodsPhantom measurements were conducted using spheres filled with [18F]-fluoride distributed in a homogeneous cylinder phantom at different positions inside the PET field of view. Recovery values and standard deviations were extracted from resulting PET images. The influence of magnetic resonance–based attenuation correction and that of activity outside the PET field of view on the recovery values of these spheres was evaluated. Furthermore, long-term PET stability of the whole-body PET/MRI system was assessed by evaluating position profiles, energy spectra, count rates, and recovery values from [68Ge]-phantom scans. Functional MRI applicability was tested in accordance with the functional Biomedical Information Research Network procedure. ResultsThe BrainPET system showed high recovery values (up to 99%) but also increased variability (up to 7.4%). Significant underestimations in PET quantification near activity outside the PET field of view were found (up to 80%). Using magnetic resonance–based attenuation correction led to an underestimation in PET activity of approximately 7%. In distinction, the whole-body PET/MRI system revealed performance similar to the PET/computed tomographic scanner (recovery values up to approximately 60% with a variability of approximately 4%). Long-term stability and fMRI performance of the whole-body PET/MRI scanner showed no degradation compared with stand-alone systems. ConclusionsHomogeneity and accuracy of avalanche photodiode-based PET detectors is comparable with those of the state-of-the-art detectors based on photomultiplier tubes. However, attenuation correction on PET/MRI systems has to be adapted carefully for quantitative PET measurements. The BrainPET system needs improved scatter correction to perform quantitative brain studies. The whole-body PET/MRI scanner, however, is applicable for quantitative brain studies.

Imaging Findings and Therapy Response Monitoring in Chronic Sclerodermatous Graft-Versus-Host Disease: Preliminary Data of a Simultaneous PET/MRI Approach

Purpose Our objective was a multifunctional imaging approach of chronic sclerodermatous graft-versus-host disease (ScGVHD) and its course during therapy using PET/MRI. Methods We performed partial-body PET/CT and PET/MRI of the calf in 6 consecutively recruited patients presenting with severe ScGVHD. The patients were treated with different immunosuppressive regimens and supportive therapies. PET/CT scanning started 60.5 ± 3.3 minutes, PET/MRI imaging 139.5 ± 16.7 minutes after 18F-FDG application. MRI acquisition included T1- (precontrast and postcontrast) and T2-weighted sequences. SUVmean, T1 contrast enhancement, and T2 signal intensity from region-of-interest analysis were calculated for different fascial and muscular compartments. In addition, musculoskeletal MRI findings and the modified Rodnan skin score were assessed. All patients underwent imaging follow-up. Results At baseline PET/MRI, ScGVHD-related musculoskeletal abnormalities consisted of increased signal and/or thickening of involved anatomical structures on T2-weighted and T1 postcontrast images as well as an increased FDG uptake. At follow-up, ScGVHD-related imaging findings decreased (SUVmean n = 4, mean T1 contrast enhancement n = 5, mean T2 signal intensity n = 3) or progressed (SUVmean n = 3, mean T1 contrast enhancement n = 2, mean T2 signal intensity n = 4). Clinically modified Rodnan skin score improved for 5 follow-ups and progressed for 2. SUVmean values correlated between PET/CT and PET/MRI acquisition (r = 0.660, P = 0.014), T1 contrast enhancement, and T2 signal (r = 0.668, P = 0.012), but not between the SUVmean values and the MRI parameters. Conclusions PET/MRI as a combined morphological and functional technique seems to assess the inflammatory processes from different points of view and provides therefore in part complementary information.

Evaluation of Positron Emission Tomographic Tracers for Imaging of Papillomavirus-Induced Tumors in Rabbits

In this study, simultaneous positron emission tomography (PET)/magnetic resonance (MR) imaging was employed to evaluate the feasibility of the PET tracers 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG), 11C-choline, and 18F-fluorothymidine (18F-FLT) to detect papillomavirus-induced tumors in an established rabbit model system. The combined PET/MR allowed the analysis of tracer uptake of the tumors using the morphologic information acquired by MR. New Zealand White rabbits were infected with cottontail rabbit papillomavirus genomes and were imaged for up to 10 months with a simultaneous PET/MR system during the course of infection. The uptake characteristics of the PET tracers 11C-choline and 18F-FLT of tumors and reference tissues were examined relative to the clinical standard, 18F-FDG. Tracer biodistribution of various organs was measured by gamma-counting after the last PET scan and compared to the in vivo PET/MR 18F-FDG uptake. Increased tracer uptake was found 2 months postinfection in primary tumors with 18F-FDG and 11C-choline, whereas 18F-FLT failed to detect the tumors at all measured time points. Our data show that the PET tracer 18F-FDG is superior for imaging papillomavirus-induced tumors in rabbits compared to 11C-choline and 18F-FLT. However, 11C-choline imaging, which has previously been applied to detect various tumor entities in patients, appears to be an alternative to 18F-FDG.In this study, simultaneous positron emission tomography (PET)/magnetic resonance (MR) imaging was employed to evaluate the feasibility of the PET tracers 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG), 11C-choline, and 18F-fluorothymidine (18F-FLT) to detect papillomavirus-induced tumors in an established rabbit model system. The combined PET/MR allowed the analysis of tracer uptake of the tumors using the morphologic information acquired by MR. New Zealand White rabbits were infected with cottontail rabbit papillomavirus genomes and were imaged for up to 10 months with a simultaneous PET/MR system during the course of infection. The uptake characteristics of the PET tracers 11C-choline and 18F-FLT of tumors and reference tissues were examined relative to the clinical standard, 18F-FDG. Tracer biodistribution of various organs was measured by gamma-counting after the last PET scan and compared to the in vivo PET/MR 18F-FDG uptake. Increased tracer uptake was found 2 months postinfection in primary tumors with 18F-FDG and 11C-choline, whereas 18F-FLT failed to detect the tumors at all measured time points. Our data show that the PET tracer 18F-FDG is superior for imaging papillomavirus-induced tumors in rabbits compared to 11C-choline and 18F-FLT. However, 11C-choline imaging, which has previously been applied to detect various tumor entities in patients, appears to be an alternative to 18F-FDG.

A blind deconvolution approach for pseudo CT prediction from MR image pairs

Predicting a CT image or a map of the linear attenuation coefficients from the information provided by magnetic resonance imaging (MRI) is a challenging task. This problem is of significant importance for combined positron emission tomography (PET)/MRI scanners, as quantitative PET image reconstruction requires an attenuation map. In PET/CT this attenuation map is derived from the CT scan or from a rotating source, however, current PET/MR systems can not directly measure attenuation images - and indeed it is desirable to save the patient from the additional radiation exposure. Recent approaches tackle this problem by using MR sequences with ultra-short echo times (UTE). At the price of lower effective image resolution, the UTE image yields signal from bone and therefore provides valuable information for calculating the attenuation map. We propose a novel approach to this problem based on nonnegative blind deconvolution and present the first method that explicitly models the image degradation of the UTE image. Incorporating prior knowledge such as smoothness and a novel orthogonality constraint alleviates the deconvolution process. Due to its probabilistic formulation our approach allows hyperparameter estimation and is therefore parameter-free.