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PET/MRI scanners cannot be qualified in the manner adopted for hybrid PET/CT devices. The main hurdle with qualification in PET/MRI is that attenuation correction (AC) cannot be adequately measured in conventional PET phantoms because of the difficulty in converting the MR images of the physical structures (e.g., plastic) into electron density maps. Over the last decade, a plethora of novel MRI-based algorithms has been developed to more accurately derive the attenuation properties of the human head, including the skull. Although promising, none of these techniques has yet emerged as an optimal and universally adopted strategy for AC in PET/MRI. In this work, we propose a path for PET/MRI qualification for multicenter brain imaging studies. Specifically, our solution is to separate the head AC from the other factors that affect PET data quantification and use a patient as a phantom to assess the former. The emission data collected on the integrated PET/MRI scanner to be qualified should be reconstructed using both MRI- and CT-based AC methods, and whole-brain qualitative and quantitative (both voxelwise and regional) analyses should be performed. The MRI-based approach will be considered satisfactory if the PET quantification bias is within the acceptance criteria specified here. We have implemented this approach successfully across 2 PET/MRI scanner manufacturers at 2 sites.

Direct reconstruction methods have been developed to estimate parametric images directly from the measured PET sinograms by combining the PET imaging model and tracer kinetics in an integrated framework. Due to limited counts received, signal-to-noise-ratio (SNR) and resolution of parametric images produced by direct reconstruction frameworks are still limited. Recently supervised deep learning methods have been successfully applied to medical imaging denoising/reconstruction when large number of high-quality training labels are available. For static PET imaging, high-quality training labels can be acquired by extending the scanning time. However, this is not feasible for dynamic PET imaging, where the scanning time is already long enough. In this work, we proposed an unsupervised deep learning framework for direct parametric reconstruction from dynamic PET, which was tested on the Patlak model and the relative equilibrium Logan model. The training objective function was based on the PET statistical model. The patient's anatomical prior image, which is readily available from PET/CT or PET/MR scans, was supplied as the network input to provide a manifold constraint, and also utilized to construct a kernel layer to perform non-local feature denoising. The linear kinetic model was embedded in the network structure as a 1 ×1 ×1 convolution layer. Evaluations based on dynamic datasets of 18F-FDG and 11C-PiB tracers show that the proposed framework can outperform the traditional and the kernel method-based direct reconstruction methods.

Since the introduction of simultaneous PET/MRI in 2011, there have been significant advancements. In this review, we highlight several technical advancements that have been made primarily in attenuation and motion correction and discuss the status of multiple clinical applications using PET/MRI. This review is based on the experience at the first PET/MRI conference cosponsored by the International Society for Magnetic Resonance in Medicine and the Society of Nuclear Medicine and Molecular Imaging.

Recently, deep neural networks have been widely and successfully applied in computer vision tasks and have attracted growing interest in medical imaging. One barrier for the application of deep neural networks to medical imaging is the need for large amounts of prior training pairs, which is not always feasible in clinical practice. This is especially true for medical image reconstruction problems, where raw data are needed. Inspired by the deep image prior framework, in this paper, we proposed a personalized network training method where no prior training pairs are needed, but only the patient's own prior information. The network is updated during the iterative reconstruction process using the patient-specific prior information and measured data. We formulated the maximum-likelihood estimation as a constrained optimization problem and solved it using the alternating direction method of multipliers algorithm. Magnetic resonance imaging guided positron emission tomography reconstruction was employed as an example to demonstrate the effectiveness of the proposed framework. Quantification results based on simulation and real data show that the proposed reconstruction framework can outperform Gaussian post-smoothing and anatomically guided reconstructions using the kernel method or the neural-network penalty.

A main advantage of PET is that it provides quantitative measures of the radiotracer concentration, but its accuracy is confounded by several factors, including attenuation, subject motion, and limited spatial resolution. Using the information from one simultaneously acquired morphological MR sequence with embedded navigators, we propose an efficient method called MR-assisted PET data optimization (MaPET) to perform attenuation correction (AC), motion correction, and anatomy-aided reconstruction. Methods: For attenuation correction, voxel-wise linear attenuation coefficient maps were generated using an SPM8-based approach method on the MR volume. The embedded navigators were used to derive head motion estimates for event-based PET motion correction. The anatomy provided by the MR volume was incorporated into the PET image reconstruction using a kernel-based method. Region-based analyses were carried out to assess the quality of images generated through various stages of PET data optimization. Results: The optimized PET images reconstructed with MaPET was superior in image quality compared to images reconstructed using only attenuation correction, with high SNR and low coefficient of variation (5.08 and 0.229 in a composite cortical region compared to 3.12 and 0.570). The optimized images were also shown using the Cohen's d metric to achieve a greater effect size in distinguishing cortical regions with hypometabolism from regions of preserved metabolism in each individual for different diagnosis groups. Conclusion: We have shown the spatiotemporally correlated data acquired using a single MR sequence can be used for PET attenuation, motion and partial volume effects corrections and the MaPET method may enable more accurate assessment of pathological changes in dementia and other brain disorders.

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry. Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60–90 min normalized standardized uptake value ratios sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors. Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis. Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is a functional imaging modality widely used in oncology, cardiology, and neuroscience. It is highly sensitive, but suffers from relatively poor spatial resolution, as compared with anatomical imaging modalities, such as magnetic resonance imaging (MRI). With the recent development of combined PET/MR systems, we can improve the PET image quality by incorporating MR information into image reconstruction. Previously, kernel learning has been successfully embedded into static and dynamic PET image reconstruction using either PET temporal or MRI information. Here, we combine both PET temporal and MRI information adaptively to improve the quality of direct Patlak reconstruction. We examined different approaches to combine the PET and MRI information in kernel learning to address the issue of potential mismatches between MRI and PET signals. Computer simulations and hybrid real-patient data acquired on a simultaneous PET/MR scanner were used to evaluate the proposed methods. Results show that the method that combines PET temporal information and MRI spatial information adaptively based on the structure similarity index has the best performance in terms of noise reduction and resolution improvement.

OBJECTIVE: In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. METHODS: Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. 11 C-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios. RESULTS: Relative to controls, MS subjects exhibited abnormally high 11 C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, 11 C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels. INTERPRETATION: In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790.

This paper extends the kernel method that was proposed previously for dynamic PET reconstruction, to incorporate anatomical side information into the PET reconstruction model. In contrast to existing methods that incorporate anatomical information using a penalized likelihood framework, the proposed method incorporates this information in the simpler maximum likelihood (ML) formulation and is amenable to ordered subsets. The new method also does not require any segmentation of the anatomical image to obtain edge information. We compare the kernel method with the Bowsher method for anatomically-aided PET image reconstruction through a simulated data set. Computer simulations demonstrate that the kernel method offers advantages over the Bowsher method in region of interest quantification. Additionally the kernel method is applied to a 3D patient data set. The kernel method results in reduced noise at a matched contrast level compared with the conventional ML expectation maximization algorithm.

Background: Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners and inserts are valuable tools for accurate diagnosis, treatment planning, and monitoring due to their complementary information. However, the integration of a PET system into an MRI scanner presents technical challenges for a distortion‐free operation. Purpose: We aim to develop a PET insert dedicated to breast imaging in combination with the 3T PET/MRI scanner Biograph mMR (Siemens Healthineers) as well as a brain PET insert for the 7T MRI scanner MAGNETOM Terra (Siemens Healthineers). For this development, we selected as a basis the C13500 series PET modules (Hamamatsu Photonics K.K.) as they offer an all‐in‐one solution with a scalable, modular design for compact integration with state‐of‐the‐art performance. The original PET modules were not designed to be operated with an MRI scanner, therefore we implemented several modifications such as signal transmission via plastic optical fiber, radio frequency (RF) shielding of the front‐end electronics, and filter for the power supply lines. In this work, we evaluated the mutual MRI compatibility between the modified PET modules and the 3T and 7T MRI scanner. Methods: We used a proof‐of‐concept setup with two detectors to comprehensively evaluate a potential distortion of the performance of the modified PET modules whilst exposing them to a variety of MR sequences up to the peak operation conditions of the Biograph mMR. A method using the periodicity of the sequences to identify distortions of the PET events in the phase of RF pulse transmission was introduced. Vice versa, the potential distortion of the Biograph mMR was evaluated by vendor proprietary MRI compatibility test sequences. Afterwards, these studies were extended to the MAGNETOM Terra. Results: No distortions were introduced by gradient field switching (field strength up to 20 mT/m at a slew rate of 66.0 T/ms−1). However, RF pulse transmission induced a reduction of the single event rate from 33.0 kcounts/s to 32.0 kcounts/s and a degradation of the coincidence resolution time from 251 to 299 ps. Further, the proposed method revealed artifacts in the energy and timing histograms. Finally, by using the front‐end filters it was possible to prevent any RF pulse induced distortion of event rate, energy, or time stamps even for a 700° flip angle (45.5 μT) sequence. The evaluations to assess potential distortions of the MRI scanner showed that carefully designed RF shielding boxes for the PET modules were required to prevent distortion of the RF spectra. The increase in B0 field inhomogeneity of 0.254 ppm and local changes of the B1 field of 12.5% introduced by the PET modules did not qualitatively affect the MR imaging with a spin echo and MPRAGE sequence for the Biograph mMR and the MAGNETOM Terra, respectively. Conclusion: Our study demonstrates the feasibility of using a modified version of the PET modules in combination with 3T and 7T MRI scanners. Building upon the encouraging MRI compatibility results from our proof‐of‐concept detectors, we will proceed to develop PET inserts for breast and brain imaging using these modules. [ABSTRACT FROM AUTHOR]

MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET data were acquired with an opioid radioligand, [(11)C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting that pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo.

The neurobiology of social bonding, despite its relevance to human mental health, has been studied primarily in rodents. In this study we used position emission tomography (PET), registered with structural magnetic resonance imaging (MRI) to investigate central glucose uptake in 17 males of a monogamous primate species, the titi monkey (Callicebus cupreus). Twelve pair-bonded males (including six with a lesion of the prefrontal cortex) and five lone males were scanned. The five lone males were re-scanned 48 h after pairing with a female. Significant differences in glucose uptake were found between males in long-term pair-bonds and lone males in areas including the nucleus accumbens, ventral pallidum, medial preoptic area, medial amygdala, and the supraoptic nucleus of the hypothalamus. In paired before and after comparisons, males showed significant changes following pairing in the right nucleus accumbens and ventral pallidum but not in other areas. Lesioned males showed significantly higher uptake in the posterior cingulate cortex than all other males. These results indicate some basic similarities between rodents and primates in the formation and maintenance of selective social bonds, but emphasize the importance of studying long-term maintenance in addition to short-term formation of social bonds.