Examining the role of dopamine in methylphenidate's effects on resting brain function.

The amplitude of low-frequency fluctuations (ALFF) and global functional connectivity density (gFCD) are fMRI (Functional MRI) metrics widely used to assess resting brain function. However, their differential sensitivity to stimulant-induced dopamine (DA) increases, including the rate of DA rise and the relationship between them, have not been investigated. Here we used, simultaneous PET-fMRI to examine the association between dynamic changes in striatal DA and brain activity as assessed by ALFF and gFCD, following placebo, intravenous (IV), or oral methylphenidate (MP) administration, using a within-subject double-blind placebo-controlled design. In putamen, MP significantly reduced D2/3 receptor availability and strongly reduced ALFF and increased gFCD in the brain for IV-MP (Cohen's d > 1.6) but less so for oral-MP (Cohen's d < 0.6). Enhanced gFCD was associated with both the level and the rate of striatal DA increases, whereas decreased ALFF was only associated with the level of DA increases. These findings suggest distinct representations of neurovascular activation with ALFF and gFCD by stimulant-induced DA increases with differential sensitivity to the rate and the level of DA increases. We also observed an inverse association between gFCD and ALFF that was markedly enhanced during IV-MP, which could reflect an increased contribution from MP's vasoactive properties.

Synaptic signaling modeled by functional connectivity predicts metabolic demands of the human brain.

PURPOSE: The human brain is characterized by interacting large-scale functional networks fueled by glucose metabolism. Since former studies could not sufficiently clarify how these functional connections shape glucose metabolism, we aimed to provide a neurophysiologically-based approach. METHODS: 51 healthy volunteers underwent simultaneous PET/MRI to obtain BOLD functional connectivity and [18F]FDG glucose metabolism. These multimodal imaging proxies of fMRI and PET were combined in a whole-brain extension of metabolic connectivity mapping. Specifically, functional connectivity of all brain regions were used as input to explain glucose metabolism of a given target region. This enabled the modeling of postsynaptic energy demands by incoming signals from distinct brain regions. RESULTS: Functional connectivity input explained a substantial part of metabolic demands but with pronounced regional variations (34 - 76%). During cognitive task performance this multimodal association revealed a shift to higher network integration compared to resting state. In healthy aging, a dedifferentiation (decreased segregated/modular structure of the brain) of brain networks during rest was observed. Furthermore, by including data from mRNA maps, [11C]UCB-J synaptic density and aerobic glycolysis (oxygen-to-glucose index from PET data), we show that whole-brain functional input reflects non-oxidative, on-demand metabolism of synaptic signaling. The metabolically-derived directionality of functional inputs further marked them as top-down predictions. In addition, the approach uncovered formerly hidden networks with superior efficiency through metabolically informed network partitioning. CONCLUSIONS: Applying multimodal imaging, we decipher a crucial part of the metabolic and neurophysiological basis of functional connections in the brain as interregional on-demand synaptic signaling fueled by anaerobic metabolism. The observed task- and age-related effects indicate promising future applications to characterize human brain function and clinical alterations.

High-temporal resolution functional PET/MRI reveals coupling between human metabolic and hemodynamic brain response.

PURPOSE: Positron emission tomography (PET) provides precise molecular information on physiological processes, but its low temporal resolution is a major obstacle. Consequently, we characterized the metabolic response of the human brain to working memory performance using an optimized functional PET (fPET) framework at a temporal resolution of 3 s. METHODS: Thirty-five healthy volunteers underwent fPET with [18F]FDG bolus plus constant infusion, 19 of those at a hybrid PET/MRI scanner. During the scan, an n-back working memory paradigm was completed. fPET data were reconstructed to 3 s temporal resolution and processed with a novel sliding window filter to increase signal to noise ratio. BOLD fMRI signals were acquired at 2 s. RESULTS: Consistent with simulated kinetic modeling, we observed a constant increase in the [18F]FDG signal during task execution, followed by a rapid return to baseline after stimulation ceased. These task-specific changes were robustly observed in brain regions involved in working memory processing. The simultaneous acquisition of BOLD fMRI revealed that the temporal coupling between hemodynamic and metabolic signals in the primary motor cortex was related to individual behavioral performance during working memory. Furthermore, task-induced BOLD deactivations in the posteromedial default mode network were accompanied by distinct temporal patterns in glucose metabolism, which were dependent on the metabolic demands of the corresponding task-positive networks. CONCLUSIONS: In sum, the proposed approach enables the advancement from parallel to truly synchronized investigation of metabolic and hemodynamic responses during cognitive processing. This allows to capture unique information in the temporal domain, which is not accessible to conventional PET imaging.

Assessing the variability and correlation between SUV and ADC parameters of head and neck cancers derived from simultaneous PET/MRI: A single-center study.

OBJECTIVE: Intratumoral heterogeneity is associated with poor outcomes in head and neck cancer (HNC) patients owing to chemoradiotherapy resistance. [18 F]-FDG positron emission tomography (PET) / Magnetic Resonance Imaging (MRI) provides spatial information about tumor mass, allowing intratumor heterogeneity assessment through histogram analysis. However, variability in quantitative PET/MRI parameter measurements could influence their reliability in assessing patient prognosis. Therefore, to use standardized uptake value (SUV) and apparent diffusion coefficient (ADC) parameters for assessing tumor response, this study aimed to measure SUV and ADC's variability and assess their relationship in HNC. METHODS: First, ADC variability was measured in an in-house diffusion phantom and in five healthy volunteers. The SUV variability was only measured with the NEMA phantom using a clinical imaging protocol. Furthermore, simultaneous PET/MRI data of 11 HNC patients were retrospectively collected from the National Cyclotron and PET center in Chulabhorn Hospital. Tumor contours were manually drawn from PET images by an experienced nuclear medicine radiologist before tumor volume segmentation. Next, SUV and ADC's histogram were used to extract statistic variables of ADC and SUV: mean, median, min, max, skewness, kurtosis, and 5th , 10th , 25th , 50th , 75th , 90th , and 95th percentiles. Finally, the correlation between the statistic variables of ADC and SUV, as well as Metabolic Tumor volume and Total Lesion Glycolysis parameters was assessed using Pearson's correlation. RESULTS: This pilot study showed that both parameters' maximum coefficient of variation was 13.9% and 9.8% in the phantom and in vivo, respectively. Furthermore, we found a strong and negative correlation between SUVmax and ADVmed (r = -0.75, P = 0.01). CONCLUSION: The SUV and ADC obtained by simultaneous PET/MRI can be potentially used as an imaging biomarker for assessing intratumoral heterogeneity in patients with HNC. The low variability and relationship between SUV and ADC could allow multimodal prediction of tumor response in future studies.

Elucidating the complementarity of resting-state networks derived from dynamic [18F]FDG and hemodynamic fluctuations using simultaneous small-animal PET/MRI.

Functional connectivity (FC) and resting-state network (RSN) analyses using functional magnetic resonance imaging (fMRI) have evolved into a growing field of research and have provided useful biomarkers for the assessment of brain function in neurological disorders. However, the underlying mechanisms of the blood oxygen level-dependant (BOLD) signal are not fully resolved due to its inherent complexity. In contrast, [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) has been shown to provide a more direct measure of local synaptic activity and may have additional value for the readout and interpretation of brain connectivity. We performed an RSN analysis from simultaneously acquired PET/fMRI data on a single-subject level to directly compare fMRI and [18F]FDG-PET-derived networks during the resting state. Simultaneous [18F]FDG-PET/fMRI scans were performed in 30 rats. Pairwise correlation analysis, as well as independent component analysis (ICA), were used to compare the readouts of both methods. We identified three RSNs with a high degree of similarity between PET and fMRI-derived readouts: the default-mode-like network (DMN), the basal ganglia network and the cerebellar-midbrain network. Overall, [18F]FDG connectivity indicated increased integration between different, often distant, brain areas compared to the results indicated by the more segregated fMRI-derived FC. Additionally, several networks exclusive to either modality were observed using ICA. These networks included mainly bilateral cortical networks of a limited spatial extent for fMRI and more spatially widespread networks for [18F]FDG-PET, often involving several subcortical areas. This is the first study using simultaneous PET/fMRI to report RSNs subject-wise from dynamic [18F]FDG tracer delivery and BOLD fluctuations with both independent component analysis (ICA) and pairwise correlation analysis in small animals. Our findings support previous studies, which show a close link between local synaptic glucose consumption and BOLD-fMRI-derived FC. However, several brain regions were exclusively attributed to either [18F]FDG or BOLD-derived networks underlining the complementarity of this hybrid imaging approach, which may contribute to the understanding of brain functional organization and could be of interest for future clinical applications.

Clinical utility of simultaneous whole-body 18F-FDG PET/MRI as a single-step imaging modality in the staging of primary nasopharyngeal carcinoma.

PURPOSE: Both head and neck magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) play a crucial role in the staging of primary nasopharyngeal carcinoma (NPC). In this study, we sought to prospectively investigate the clinical utility of simultaneous whole-body 18F-FDG PET/MRI for primary staging of NPC patients. METHODS: We examined 113 patients with histologically confirmed NPC who underwent pretreatment, simultaneous whole-body PET/MRI and PET/CT for primary tumor staging. The images obtained with the different imaging modalities were interpreted independently and compared with each other. RESULTS: PET/MRI increased the accuracy of head and neck MRI for assessment of primary tumor extent in four patients via addition of FDG uptake information to increase the conspicuity of morphologically subtle lesions. PET/MR images were more discernible than PET/CT images for mapping tumor extension, especially intracranial invasion. Regarding the N staging assessment, the sensitivity of PET/MRI (99.5%) was higher than that of head and neck MRI (94.2%) and PET/CT (90.9%). PET/MRI was particularly useful for distinguishing retropharyngeal nodal metastasis from adjacent nasopharyngeal tumors. For distant metastasis evaluation, PET/MRI exhibited a similar sensitivity (90% vs. 86.7% vs. 83.3%), but higher positive predictive value (93.1% vs. 78.8% vs. 83.3%) than whole-body MRI and PET/CT, respectively. CONCLUSIONS: For tumor staging of NPC, simultaneous whole-body PET/MRI was more accurate than head and neck MRI and PET/CT, and may serve as a single-step staging modality.

PETcoil: first results from a second-generation RF-penetrable TOF-PET brain insert for simultaneous PET/MRI.

Simultaneous positron emission tomography (PET)/magnetic resonance imaging provides concurrent information about anatomic, functional, and molecular changes in disease. We are developing a second generation MR-compatible RF-penetrable TOF-PET insert. The insert has a smaller scintillation crystal size and ring diameter compared to clinical whole-body PET scanners, resulting in higher spatial resolution and sensitivity. This paper reports the initial system performance of this full-ring PET insert. The global photopeak energy resolution and global coincidence time resolution, 11.74 ± 0.03 % FWHM and 238.1 ± 0.5 ps FWHM, respectively, are preserved as we scaled up the system to a full ring comprising 12, 288 LYSO-SiPM channels (crystal size: 3.2 × 3.2 × 20 mm3). Throughout a ten-hour experiment, the system performance remained stable, exhibiting a less than 1% change in all measured parameters. In a resolution phantom study, the system successfully resolved all 2.8 mm diameter rods, achieving an average VPR of 0.28 ± 0.08 without TOF and 0.24 ± 0.07 with TOF applied. Moreover, the implementation of TOF in the Hoffman phantom study also enhanced image quality. Initial MR compatibility studies of the full PET ring were performed with it unpowered as a milestone to focus on looking for material and geometry-related artifacts. During all MR studies, the MR body coil functioned as both the transmit and receive coil, and no observable artifacts were detected. As expected, using the body coil also as the RF receiver, MR image signal-to-noise ratio exhibited degradation (∼30%), so we are developing a high quality receive-only coil that resides inside the PET ring.

Qualitative and Quantitative Evaluation of Morpho-Metabolic Changes in Bone Cartilage Complex of Knee Joint in Osteoarthritis Using Simultaneous 18F-NaF PET/MRI-A Pilot Study.

Background Articular cartilage (AC) loss and deterioration, as well as bone remodeling, are all symptoms of osteoarthritis (OA). As a result, an ideal imaging technique for researching OA is required, which must be sensitive to both soft tissue and bone health. Objective The aim of this study was to assess the potential of simultaneous 18F sodium fluoride (18F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI) to identify as well as classify osseous metabolic abnormalities in knee OA and to see if degenerative changes in the cartilage and bone on MRI might be correlated with subchondral 18F-NaF uptake on PET. Methods Sixteen (32 knees) volunteers with no past history of knee injury, with or without pain, were enrolled for the research from January to July 2021. The images of both knees were taken utilizing an molecular magnetic resonance (mMR) body matrix coil on a simultaneous PET/MRI biograph mMR. The acquisition was conducted after 45 minutes of intravenous infusion of 18F-NaF 185-370 MBq (5-10 mCi) over one PET bed for 40 minutes, while MRI sequences were performed simultaneously. Results All pathologies showed significantly higher maximum standardized uptake value (SUV max ) than the background. Thirty-four subchondral magic spots were identified on 18F-NaF PET without any structural alteration on MRI. Bone marrow lesions (BMLs) and osteophytes with higher MRI osteoarthritis knee score (MOAKS) score showed higher 18F-NaF uptake (grade1˂grade2˂grade3). BMLs had corresponding AC degeneration. There was discordance between grade 1 osteophytes (86.6%), sclerosis (53.7%) and grade 1 BML in cruciate ligament insertion site (91.66%); they did not have high uptake of 18F-NaF. In case of cartilage, there was significant difference between AC grades and average subchondral SUV max and T2* relaxometry (grade0˂grade1˂grade2˂grade3˂grade4). BMLs are much more metabolically active than other pathologies, while sclerosis is the least. We also found that the subchondral uptake was statistically increased in the areas of pathology: Conclusion 18F-NaF PET/MRI was able to detect knee abnormalities unseen on MRI alone and simultaneously assessed metabolic and structural markers of knee OA across multiple tissues in the joint. Thus, it is a promising tool for detection of early metabolic changes in OA.

The PETcoil project: PET performance evaluation of two detector modules for a second generation RF-penetrable TOF-PET brain dedicated insert for simultaneous PET/MRI.

Objective. We are developing a portable, 'RF-penetrable', brain-dedicated time of flight (TOF)-PET insert (PETcoil) for simultaneous PET/MRI.Approach. In this paper, we evaluate the PET performance of two fully assembled detector modules for this insert design outside the MR room.Main results. The global coincidence time resolution, global 511 keV energy resolution, coincidence count rate, and detector temperature achieved over 2 h data collection were 242.2 ± 0.4 ps full width at half maximum (FWHM), 11.19% ± 0.02% FWHM, 22.0 ± 0.1 kcps, and 23.5 °C ± 0.3 °C, respectively. The intrinsic spatial resolutions in the axial and transaxial directions were 2.74 ± 0.01 mm FWHM and 2.88 ± 0.03 mm FWHM, respectively.Significance. These results demonstrate excellent TOF capability and the performance and stability necessary for scaling up to a full ring comprising 16 detector modules.

Performance evaluation of a PET insert for preclinical MRI in stand-alone PET and simultaneous PET-MRI modes.

BACKGROUND: This study aimed to evaluate the performance of a preclinical PET insert in three configurations: as a stand-alone unit outside the MRI bore, inside the bore of a cryogen-free 3T MRI and, finally, while performing simultaneous PET/MRI studies. METHODS: The PET insert consists of two rings of six detectors, each detector comprising 8 × 12 SiPMs reading out dual offset layers of pixelated LYSO crystals with a 1.4-mm pitch. The inner diameter is 60 mm, transaxial field of view (FoV) 40 mm and axial FoV 98 mm. Evaluation was based on NEMA NU 4-2008 guidelines with appropriate modifications. Spatial resolution and sensitivity were measured inside and outside the MR bore. Image quality, count rate and quantitative performance were measured in all three configurations. The effect of temperature stability on PET sensitivity during fast spin echo sequences was also evaluated. B0 field homogeneity and T1 and T2 relaxation times were measured using a water-filled phantom, with and without simultaneous PET operation. Finally, PET and MRI scans of a mouse injected with 10 MBq [18F]NaF and a mouse injected with 16 MBq [18F]FDG were performed in sequential and simultaneous modes. RESULTS: Peak absolute sensitivity was 10.15% with an energy window of 250-750 keV. Absolute sensitivity values outside and inside the MR bore with MR idle agreed to within 0.1%. Outside the MR bore, spatial resolution was 1.21/1.59 mm FWHM (radial/tangential) 5 mm from the centre of the FoV which compared well with 1.19/1.26 mm FWHM inside the MR bore. There were no substantial differences between all three scan configurations in terms of peak NEC rate (175 kcps at 17 MBq), scatter or random fractions. Uniformity and recovery coefficients were also consistent between scanning modes. B0 field homogeneity and T1 and T2 relaxation times were unaltered by the presence of the PET insert. No significant differences were observed between sequential and simultaneous scans of the animals. CONCLUSIONS: We conclude that the performance of the PET insert and MRI system is not significantly affected by the scanning mode.

Minimizing the need for coil attenuation correction in integrated PET/MRI at 1.5 T using low-density MR-linac receive arrays.

The simultaneous use of positron emission tomography (PET) and magnetic resonance imaging (MRI) requires attenuation correction (AC) of photon-attenuating objects, such as MRI receive arrays. However, AC of flexible, on-body arrays is complex and therefore often omitted. This can lead to significant, spatially varying PET signal losses when conventional MRI receive arrays are used. Only few dedicated, photon transparent PET/MRI arrays exist, none of which are compatible with our new, wide-bore 1.5 T PET/MRI system dedicated to radiotherapy planning. In this work, we investigated the use of 1.5 T MR-linac (MRL) receive arrays for PET/MRI, as these were designed to have a low photon attenuation for accurate dose delivery and can be connected to the new 1.5 T PET/MRI scanner. Three arrays were assessed: an 8-channel clinically-used MRL array, a 32-channel prototype MRL array, and a conventional MRI receive array. We experimentally determined, simulated, and compared the impact of these arrays on the PET sensitivity and image reconstructions. Furthermore, MRI performance was compared. Overall coil-induced PET sensitivity losses were reduced from 8.5% (conventional) to 1.7% (clinical MRL) and 0.7% (prototype MRL). Phantom measurements showed local signal errors of up to 32.7% (conventional) versus 3.6% (clinical MRL) and 3.5% (prototype MRL). Simulations with data of eight cancer patients showed average signal losses were reduced from 14.3% (conventional) to 1.2% (clinical MRL) and 1.0% (prototype MRL). MRI data showed that the signal-to-noise ratio of the MRL arrays was slightly lower at depth (110 versus 135). The parallel imaging performance of the conventional and prototype MRL arrays was similar, while the clinical MRL array's performance was lower. In conclusion, MRL arrays reducein-vivoPET signal losses >10×, which decreases, or eliminates, the need for coil AC on a new 1.5 T PET/MRI system. The prototype MRL array allows flexible coil positioning without compromising PET or MRI performance. One limitation of MRL arrays is their limited radiolucent PET window (field of view) in the craniocaudal direction.

Locoregional Extension Patterns of Nasopharyngeal Carcinoma Detected by FDG PET/MR.

PURPOSE: We sought to define the locoregional extension patterns of nasopharyngeal carcinomas (NPCs) by positron emission tomography (PET)/magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation. METHODS: Between May 2017 and March 2021, 331 consecutive patients with nonmetastatic NPCs who underwent pretreatment, simultaneous whole-body PET/MRI for staging were included in this study. RESULTS: The high-risk regions included the base of the sphenoid bone, the prestyloid compartment, prevertebral muscle, foramen lacerum, medial pterygoid plate, sphenoidal sinus, clivus, petrous apex, and foramen ovale. When the high-risk regions were invaded, the incidence rates of tumor invasion into the medium-risk regions increased. In contrast, when the high-risk regions were not involved, the incidence rates of tumor invasion into the medium-risk regions were mostly less than 10%, excluding the post-styloid compartment and oropharynx. According to the updated consensus guidelines of the neck node levels for head and neck tumors from 2013, level IIa (77.3%, 256/331), level IIb (75.8%, 251/331), and level VIIa (71.3%, 236/331) were the most frequently involved levels, followed by levels III (42.6%), Va (13.9%), IVa (8.8%), IVb (3.6%), Ib (3.6%), Vb (2.4%), VIIb (2.4%), VIII (1.8%), Vc (0.9%), and Xa (0.3%). Skip lymph node metastasis occurred in only 1.9% of patients. CONCLUSIONS: For NPCs, primary disease and regional lymph node spread follow an orderly pattern, and a skip pattern of lymph node metastasis was unusual. Involved level radiotherapy might be feasible for cervical lymph node levels below the caudal border of cricoid cartilage and level VIIb.

Advances in simultaneous PET/MR for imaging neuroreceptor function.

Hybrid imaging using PET/MRI has emerged as a platform for elucidating novel neurobiology, molecular and functional changes in disease, and responses to physiological or pharmacological interventions. For the central nervous system, PET/MRI has provided insights into biochemical processes, linking selective molecular targets and distributed brain function. This review highlights several examples that leverage the strengths of simultaneous PET/MRI, which includes measuring the perturbation of multi-modal imaging signals on dynamic timescales during pharmacological challenges, physiological interventions or behavioral tasks. We discuss important considerations for the experimental design of dynamic PET/MRI studies and data analysis approaches for comparing and quantifying simultaneous PET/MRI data. The primary focus of this review is on functional PET/MRI studies of neurotransmitter and receptor systems, with an emphasis on the dopamine, opioid, serotonin and glutamate systems as molecular neuromodulators. In this context, we provide an overview of studies that employ interventions to alter the activity of neuroreceptors or the release of neurotransmitters. Overall, we emphasize how the synergistic use of simultaneous PET/MRI with appropriate study design and interventions has the potential to expand our knowledge about the molecular and functional dynamics of the living human brain. Finally, we give an outlook on the future opportunities for simultaneous PET/MRI.

PET/MRI Versus PET/CT for Whole-Body Staging: Results from a Single-Center Observational Study on 1,003 Sequential Examinations.

Our purpose was to investigate differences between PET/MRI and PET/CT in lesion detection and classification in oncologic whole-body examinations and to investigate radiation exposure differences between the 2 modalities. Methods: In this observational single-center study, 1,003 oncologic examinations (918 patients; mean age, 57.8 ± 14.4 y) were included. Patients underwent PET/CT and subsequent PET/MRI (149.8 ± 49.7 min after tracer administration). Examinations were reviewed by radiologists and nuclear medicine physicians in consensus. Additional findings, characterization of indeterminate findings on PET/CT, and missed findings on PET/MRI, including their clinical relevance and effective dose of both modalities, were investigated. The McNemar test was used to compare lesion detection between the 2 hybrid imaging modalities (P < 0.001, indicating statistical significance). Results: Additional information on PET/MRI was reported for 26.3% (264/1,003) of examinations, compared with PET/CT (P < 0.001). Of these, additional malignant findings were detected in 5.3% (53/1,003), leading to a change in TNM staging in 2.9% (29/1,003) due to PET/MRI. Definite lesion classification of indeterminate PET/CT findings was possible in 11.1% (111/1,003) with PET/MRI. In 2.9% (29/1,003), lesions detected on PET/CT were not visible on PET/MRI. Malignant lesions were missed in 1.2% (12/1,003) on PET/MRI, leading to a change in TNM staging in 0.5% (5/1,003). The estimated mean effective dose for whole-body PET/CT amounted to 17.6 ± 8.7 mSv, in comparison to 3.6 ± 1.4 mSv for PET/MRI, resulting in a potential dose reduction of 79.6% (P < 0.001). Conclusion: PET/MRI facilitates staging comparable to that of PET/CT and improves lesion detectability in selected cancers, potentially helping to promote fast, efficient local and whole-body staging in 1 step, when additional MRI is recommended. Furthermore, younger patients may benefit from the reduced radiation exposure of PET/MRI.

Reconfiguration of functional brain networks and metabolic cost converge during task performance.

The ability to solve cognitive tasks depends upon adaptive changes in the organization of whole-brain functional networks. However, the link between task-induced network reconfigurations and their underlying energy demands is poorly understood. We address this by multimodal network analyses integrating functional and molecular neuroimaging acquired concurrently during a complex cognitive task. Task engagement elicited a marked increase in the association between glucose consumption and functional brain network reorganization. This convergence between metabolic and neural processes was specific to feedforward connections linking the visual and dorsal attention networks, in accordance with task requirements of visuo-spatial reasoning. Further increases in cognitive load above initial task engagement did not affect the relationship between metabolism and network reorganization but only modulated existing interactions. Our findings show how the upregulation of key computational mechanisms to support cognitive performance unveils the complex, interdependent changes in neural metabolism and neuro-vascular responses.

Joint PET-MRI image reconstruction using a patch-based joint-dictionary prior.

For simultaneous positron-emission-tomography and magnetic-resonance-imaging (PET-MRI) systems, while early methods relied on independently reconstructing PET and MRI images, recent works have demonstrated improvement in image reconstructions of both PET and MRI using joint reconstruction methods. The current state-of-the-art joint reconstruction priors rely on fine-scale PET-MRI dependencies through the image gradients at corresponding spatial locations in the PET and MRI images. In the general context of image restoration, compared to gradient-based models, patch-based models (e.g., sparse dictionaries) have demonstrated better performance by modeling image texture better. Thus, we propose a novel joint PET-MRI patch-based dictionary prior that learns inter-modality higher-order dependencies together with intra-modality textural patterns in the images. We model the joint-dictionary prior as a Markov random field and propose a novel Bayesian framework for joint reconstruction of PET and accelerated-MRI images, using expectation maximization for inference. We evaluate all methods on simulated brain datasets as well as on in vivo datasets. We compare our joint dictionary prior with the recently proposed joint priors based on image gradients, as well as independently applied patch-based priors. Our method demonstrates qualitative and quantitative improvement over the state of the art in both PET and MRI reconstructions.

PET performance evaluation of the small-animal Hyperion IID PET/MRI insert based on the NEMA NU-4 standard.

The Hyperion IID PET insert is the first scanner using fully digital silicon photomultipliers for simultaneous PET/MR imaging of small animals up to rabbit size. In this work, we evaluate the PET performance based on the National Eletrical Manufacturers Association (NEMA) NU 4-2008 standard, whose standardized measurement protocols allow comparison of different small-animal PET scanners. The Hyperion IID small-animal PET/MR insert comprises three rings of 20 detector stacks with pixelated scintillator arrays with a crystal pitch of 1 mm, read out with digital silicon photomultipliers. The scanner has a large ring diameter of 209.6 mm and an axial field of view of 96.7 mm. We evaluated the spatial resolution, energy resolution, time resolution and sensitivity by scanning a 22Na point source. The count rates and scatter fractions were measured for a wide range of 18F activity inside a mouse-sized scatter phantom. We evaluated the image quality using the mouse-sized image quality phantom specified in the NEMA NU4 standard, filled with 18F. Additionally, we verified the in-vivo imaging capabilities by performing a simultaneous PET/MRI scan of a mouse injected with 18F-FDG. We processed all measurement data with an energy window of 250 keV to 625 keV and a coincidence time window of 2 ns. The filtered-backprojection reconstruction of the point source has a full width at half maximum (FWHM) of 1.7 mm near the isocenter and degrades to 2.5 mm at a radial distance of 50 mm. The scanner's average energy resolution is 12.7% (ΔE/E FWHM) and the coincidence resolution time is 609 ps. The peak absolute sensitivity is 4.0% and the true and noise-equivalent count rates reach their peak at an activity of 46 MBq with 483 kcps and 407 kcps, respectively, with a scatter fraction of 13%. The iterative reconstruction of the image quality phantom has a uniformity of 3.7%, and recovery coefficients from 0.29, 0.91 and 0.94 for rod diameters of 1 mm, 3 mm and 5 mm, respectively. After application of scatter and attenuation corrections, the air- and water-filled cold regions have spill-over ratios of 6.3% and 5.4%, respectively. The Hyperion IID PET/MR insert provides state-of-the-art PET performance while enabling simultaneous PET/MRI acquisition of small animals up to rabbit size.

Simultaneous PET/MRI in assessing the response to chemo/radiotherapy in head and neck carcinoma: initial experience.

The purpose of the study was to assess by simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) the response to chemotherapy (CHT) and/or radiotherapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). Five patients with HNSCC underwent simultaneous PET/MRI examination before and after CHT and/or RT. Standard uptake volume (SUV), apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, and iAUC pre- and post-treatment values were extracted and compared. The response to treatment was assessed according to RECIST criteria and classified as complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD). In patient 1, PR was observed with increased ADC, Ktrans, and Ve values and reduction of SUV, iAUC, and Kep values; during clinical and instrumental follow-up, the patient experienced disease progression. Patient 2, classified as PR, showed increased ADC values and reduction of SUV and all perfusion parameters; follow-up demonstrated disease stability. Patient 3, considered as SD, showed increase of ADC and all perfusion values with a mild decrease of SUV; PD was observed during clinical and instrumental follow-up. Patients 4 and 5 showed a CR with no detectable tumor lesions at post-treatment PET/MRI examination, confirmed by 1-year follow-up. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess and predict the response to CHT and/or RT in patients with HNSCC.

Simultaneous PET/MRI assessment of response to cytotoxic and hormone neo-adjuvant chemotherapy in breast cancer: a preliminary report.

The aim of this study was to assess the response to cytotoxic and hormone neo-adjuvant chemotherapy in four patients with locally advanced breast cancer by simultaneous PET/MRI. Four patients with locally advanced breast cancer underwent simultaneous PET/MRI of the breast using a 3 T Biograph mMR before and after neo-adjuvant chemotherapy (two patients were treated with hormone-therapy and two patients were treated with cytotoxic chemotherapy). Morpho-structural tumoral features and tumor size were assessed; area value, metabolic (SUV and MTV) and functional (ADC, K trans, V e, k ep and iAUC) data were obtained by positioning regions of interest. A comparison of all parameters between the pre- and post-treatment PET/MRI examinations and between the two different therapeutic schedules was assessed. In patients treated with cytotoxic chemotherapy and classified as PR, there was a significant reduction of post-treatment morphological, metabolic and functional parameters. In a patient treated with hormone therapy, classified as SD, there was an increase of all post-treatment perfusion parameters, a substantially stable ADC value and a poor reduction of lesion size and of maximum SUV (SUVmax) values; the last patient, treated with hormone therapy and classified as PR, showed a significant reduction of lesion size and SUVmax values with a reduction of perfusion parameters and substantially stable ADC values. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess the response to cytotoxic and hormone neo-adjuvant chemotherapy in patients with breast cancer. Future studies in a larger cohort of patients are warranted to confirm the results of this preliminary study.

Simultaneous 68Ga DOTATATE Positron Emission Tomography/Magnetic Resonance Imaging in Meningioma Target Contouring: Feasibility and Impact Upon Interobserver Variability Versus Positron Emission Tomography/Computed Tomography and Computed Tomography/Magnetic Resonance Imaging.

AIMS: The increasing use of highly conformal radiation techniques to treat meningioma confers a greater need for accurate targeting. Several groups have shown that positron emission tomography/computed tomography (PET/CT) information alters meningioma targets contoured by single observers, but whether this translates into improved accuracy has not been defined. As magnetic resonance imaging (MRI) is the cornerstone of meningioma target contouring, simultaneous PET/MRI may be superior to PET/CT. We assessed whether 68Ga DOTATATE PET imaging (from PET/CT and PET/MRI) reduced interobserver variability (IOV) in meningioma target volume contouring. MATERIALS AND METHODS: Ten patients with meningioma underwent simultaneous 68Ga DOTATATE PET/MRI followed by PET/CT. They were selected as it was anticipated that target volume definition in their cases would be particularly challenging. Three radiation oncologists contoured target volumes according to an agreed protocol: gross tumour volume (GTV) and clinical target volume (CTV) on CT/MRI alone, CT/MRI+PET(CT) and CT/MRI+PET(MRI). GTV/CTV Kouwenhoven conformity levels (KCL), regions of contour variation and qualitative differences between PET(CT) and PET(MRI) were evaluated. RESULTS: There was substantial IOV in contouring. GTV mean KCL: CT/MRI 0.34, CT/MRI+PET(CT) 0.38, CT/MRI+PET(MRI) 0.39 (P = 0.06). CTV mean KCL: CT/MRI 0.31, CT/MRI+PET(CT) 0.35, CT/MRI+PET(MRI) 0.35 (P = 0.04 for all groups; P > 0.05 for individual pairs). One observer consistently contoured largest and one smallest. Observers rarely decreased volumes in relation to PET. Most IOV occurred in bone followed by dural tail, postoperative bed and venous sinuses. Tumour edges were qualitatively clearer on PET(MRI) versus PET(CT), but this did not affect contouring. CONCLUSION: IOV in contouring challenging meningioma cases was large and only slightly improved with the addition of 68Ga DOTATATE PET. Simultaneous PET/MRI for meningioma contouring is feasible, but did not improve IOV versus PET/CT. Whether volumes can be safely reduced according to PET requires evaluation.