Positron Emission Tomography And Magnetic Resonance Imaging Research Articles

Are central and systemic inflammation associated with fatigue in cerebral small vessel disease?

Fatigue is a common symptom in cerebral small vessel disease (SVD), but its pathogenesis is poorly understood. It has been suggested that inflammation may play a role. We determined whether central (neuro) inflammation and peripheral inflammation were associated with fatigue in SVD. Notably, 36 patients with moderate-to-severe SVD underwent neuropsychometric testing, combined positron emission tomography and magnetic resonance imaging (PET-MRI) scan, and blood draw for the analysis of inflammatory blood biomarkers. Microglial signal was taken as a proxy for neuroinflammation, assessed with radioligand 11C-PK11195. Of these, 30 subjects had full PET datasets for analysis. We assessed global 11C-PK11195 binding and hotspots of 11C-PK11195 binding in the normal-appearing white matter, lesioned tissue, and combined total white matter. Peripheral inflammation was assessed with serum C-reactive protein (CRP) and using the Olink cardiovascular III proteomic panel comprising 92 biomarkers of cardiovascular inflammation and endothelial activation. Fatigue was assessed using the fatigue severity scale (FSS), the visual analog fatigue scale, and a subscale of the Geriatric Depression Scale. Mean (SD) age was 68.7 (11.2) years, and 63.9% were male. Of these, 55.6% showed fatigue on the FSS. Fatigued participants had higher disability scores (p = 0.02), higher total GDS scores (p = 0.02), and more commonly reported a history of depression (p = 0.04). 11C-PK11195 ligand binding in the white matter was not associated with any measure of fatigue. Serum CRP was significantly associated with average fatigue score on FSS (ρ = 0.48, p = 0.004); this association persisted when controlling for age, sex, disability score, and depression (β = 0.49, 95% CI (0.17, 2.26), p = 0.03). Blood biomarkers from the Olink panel showed no association with fatigue. In symptomatic SVD patients, neuroinflammation, assessed with microglial marker 11C-PK11195, was not associated with fatigue. We found some evidence for a role of systematic inflammation, evidenced by an association between fatigue severity and raised CRP, but further studies are required to understand this relationship and inform whether it could be therapeutically modified to reduce fatigue severity. Data for this study are available from the corresponding author upon reasonable request.

Excretion of glucose analogue with SGLT2 affinity predicts response effectiveness to sodium glucose transporter 2 inhibitors in patients with type 2 diabetes mellitus

PurposeSodium-glucose cotransporter 2 inhibitor (SGLT2i) regulation, developed as treatment for patients with type 2 diabetes, can be imaged with the glucose analogue alpha-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me4FDG), a positron emission tomography (PET) tracer with a high affinity for SGLT1 and SGLT2 proteins. With regard to therapy effectiveness, we aimed to investigate whether clinical parameters or Me4FDG excretion could predict response to SGLT2i in patients with type 2 diabetes.MethodsIn a longitudinal, prospective study, 19 patients with type 2 diabetes underwent Me4FDG combined PET and magnetic resonance imaging (PET/MRI) scans at baseline and 2 weeks after initiation of therapy with SGLT2i, accompanied by the collection of blood and urine samples. Me4FDG-excretion was determined from the Me4FDG uptake in the bladder. Long-term response was determined by HbA1c level after 3 months; a strong response to the therapy was defined as a reduction of HbA1c by at least 10% from baseline.ResultsSGLT2i resulted in significantly increased Me4FDG excretion (4.8 vs. 45.0, P < 0.001) and urine glucose (56 vs. 2806 mg/dl, P < 0.001). Baseline urine glucose and baseline Me4FDG excretion correlated both with long-term decline in HbA1c with r = 0.55 (P < 0.05). However, only Me4FDG excretion was a predictor of a strong response to SGLT2i (P = 0.005, OR 1.9).ConclusionsUsing Me4FDG-PET, we demonstrated for the first time renal SGLT2-related excretion before and after short-term SGLT2i treatment. In contrary to other clinical parameters, SGLT2-related excretion before treatment was a robust predictor of long-term HbA1c response in patients with type 2 diabetes, suggesting that therapy effectiveness is only dependent of endogenous SGLT2 processes.

PET-MRI of Coronary Artery Disease.

Simultaneous positron emission tomography and magnetic resonance imaging (PET-MRI) combines the anatomical detail and tissue characterization of MRI with the functional information from PET. Within the coronary arteries, this hybrid technique can be used to identify biological activity combined with anatomically high-risk plaque features to better understand the processes underlying coronary atherosclerosis. Furthermore, the downstream effects of coronary artery disease on the myocardium can be characterized by providing information on myocardial perfusion, viability, and function. This review will describe the current capabilities of PET-MRI in coronary artery disease and discuss the limitations and future directions of this emerging technique. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

68Ga-DOTATOC-PET/MRI-A Secure One-Stop Shop Imaging Tool for Robotic Radiosurgery Treatment Planning in Patients with Optic Nerve Sheath Meningioma.

Simple SummaryThrough combined information about spatial spread in magnetic resonance imaging (MRI) and positron emission tomography (PET), gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) PET/MRI before radiosurgery allows safe treatment planning for optic nerve sheath meningiomas (ONSM). Moreover, because of specific receptor stocking, diagnostic accuracy is improved without the need for biopsy. Thus, Ga68-DOTATOC-PET/MRI can be considered a safe “one-stop shop” image tool prior to radiosurgery for ONSM.Optic nerve sheath meningiomas (ONSM) are rare but can lead to irreversible blindness. Hybrid imaging may enhance tumor delineation and diagnostic accuracy via receptor binding. However, relevant clinical data for ONSM are lacking. We evaluated the feasibility of receptor-based hybrid imaging prior to robotic radiosurgery (RRS). We retrospectively analyzed all of our institution’s patients with suspected ONSM who underwent combined positron emission tomography and magnetic resonance imaging (PET/MRI) with gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) before RRS between 2018 and 2019. Eight patients with ten suspected ONSM (female = 7; median age, 51.2 years; IQR, 43.0–66.0) were included. Nine out of ten ONSM were deemed PET-positive with a median standard uptake value (SUV) max of 5.6 (IQR, 2.6–7.8). For all nine ONSM that presented 68Ga-DOTATOC uptake, hybrid PET/MRI was used for target volume contouring prior to RSS. At a median follow-up of 11.7 months (IQR, 9.4–16.4), tumor control was achieved in all patients. Radiosurgery resulted in the improvement of visual acuity in two of eight patients, whereas six showed stable vision. Ga68-DOTATOC-PET/MRI can be used for target volume contouring prior to RRS for ONSM as it enables safe treatment planning and improves diagnostic accuracy.

SimPET: a Preclinical PET Insert for Simultaneous PET/MR Imaging.

SimPET/M7 system is a small-animal dedicated simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI) scanner. The SimPET insert has been upgraded from its prototype with a focus on count rate performance and sensitivity. The M7 scanner is a 1-T permanent magnet-based compact MRI system without any cryogens. Here, we present performance evaluation results of SimPET along with the results of mutual interference evaluation and simultaneously acquired PET/MR imaging. Following NEMA NU 4-2008 standard, we evaluated the performance of the SimPET system. The M7 MRI compatibility of SimPET was also assessed by analyzing MRI images of a uniform phantom under different PET conditions and PET count rates with different MRI pulse sequences. Mouse imaging was performed including a whole-body 18F-NaF PET scan and a simultaneous PET/MRI scan with 64Cu-NOTA-ironoxide. The spatial resolution at center based on 3D OSEM without and with warm background was 0.7mm and 1.45mm, respectively. Peak sensitivity was 4.21% (energy window = 250-750keV). The peak noise equivalent count rate with the same energy window was 151kcps at 38.4MBq. The uniformity was 4.42%, and the spillover ratios in water- and air-filled chambers were 14.6% and 12.7%, respectively. In the hot rod phantom image, 0.75-mm-diameter rods were distinguishable. There were no remarkable differences in the SNR and uniformity of MRI images and PET count rates with different PET conditions and MRI pulse sequences. In the whole-body 18F-NaF PET images, fine skeletal structures were well resolved. In the simultaneous PET/MRI study with 64Cu-NOTA-ironoxide, both PET and MRI signals changed before and after injection of the dual-modal imaging probe, which was evident with the exact spatiotemporal correlation. We demonstrated that the SimPET scanner has a high count rate performance and excellent spatial resolution. The combined SimPET/M7 enabled simultaneous PET/MR imaging studies with no remarkable mutual interference between the two imaging modalities.

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.

Gender Differences in Cerebral Metabolism Induced by Polarized Light in Mice Brain: A Quantum Coherence Model

We present direct evidence of the polarized light effect of coherence in computational neuronal dynamics in female, but not male mice brain. We measured the accumulation of [18F] fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) during light stimulation with yellow and polarized filters compared to dark condition. Fourier analysis was performed using mean standardized uptake values (SUV) of [18F]FDG for each stimulus condition to derive the spectral density coefficients for analysis and spectral plots of cross-correlation function, cross amplitude, phase spectrum, gain, coherency and multiple regression analysis. PET images show gender differences during polarized light stimulation, with greater tracer accumulation in the visual cortex in female than in male mice. In male mice, there was classical superposition of waves of polarized and yellow lights, shown by significantly attenuated long-term depression at cortical C-peak in the ventral stream of the left visual cortex. Conversely, in female mice, polarized light particle evoked accentuated long-term potentiation at subcortical S-peak in the dorsal stream in the right visual cortex. Coherence may occur in the visual system in female mice within the cortical ‘cytochrome oxidase (CO) blobs’, which are spatially and functionally connected through nested hierarchical neural networks of structures implicated as environment for non-trivial features such as coherence.

Semi-automatic segmentation from intrinsically-registered 18F-FDG\u2013PET/MRI for treatment response assessment in a breast cancer cohort: comparison to manual DCE\u2013MRI

ObjectivesTo investigate the reliability of simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI)-derived biomarkers using semi-automated Gaussian mixture model (GMM) segmentation on PET images, against conventional manual tumor segmentation on dynamic contrast-enhanced (DCE) images.Materials and methodsTwenty-four breast cancer patients underwent PET/MRI (following 18F-fluorodeoxyglucose (18F-FDG) injection) at baseline and during neoadjuvant treatment, yielding 53 data sets (24 untreated, 29 treated). Two-dimensional tumor segmentation was performed manually on DCE–MRI images (manual DCE) and using GMM with corresponding PET images (GMM–PET). Tumor area and mean apparent diffusion coefficient (ADC) derived from both segmentation methods were compared, and spatial overlap between the segmentations was assessed with Dice similarity coefficient and center-of-gravity displacement.ResultsNo significant differences were observed between mean ADC and tumor area derived from manual DCE segmentation and GMM–PET. There were strong positive correlations for tumor area and ADC derived from manual DCE and GMM–PET for untreated and treated lesions. The mean Dice score for GMM–PET was 0.770 and 0.649 for untreated and treated lesions, respectively.DiscussionUsing PET/MRI, tumor area and mean ADC value estimated with a GMM–PET can replicate manual DCE tumor definition from MRI for monitoring neoadjuvant treatment response in breast cancer.

18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression

Background and aimsThe advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18F-fluorodeoxyglucose (18F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis. MethodsGöttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression. ResultsAt study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBRMax (95% confidence interval) CITBRMax: 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CITBRMax: -5.94;-0.07). No difference was observed between DNO and Control (CITBRMax: −2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρs = 0.58; MMP9, ρs = 0.46; SPP1, ρs = 0.44 and CTSK, ρs = 0.49; (p ≤ 0.01 for all). ConclusionsIn a model of atherosclerosis, 18F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation.

Rigid-body motion correction in hybrid PET/MRI using spherical navigator echoes

Integrated positron emission tomography and magnetic resonance imaging (PET/MRI) is an imaging technology that provides complementary anatomical and functional information for medical diagnostics. Both PET and MRI are highly susceptible to motion artifacts due, in part, to long acquisition times. The simultaneous acquisition of the two modalities presents the opportunity to use MRI navigator techniques for motion correction of both PET and MRI data. For this task, we propose spherical navigator echoes (SNAVs)—3D k-space navigators that can accurately and rapidly measure rigid body motion in all six degrees of freedom.SNAVs were incorporated into turbo FLASH (tfl)—a product fast gradient echo sequence—to create the tfl-SNAV pulse sequence. Acquiring in vivo brain images from a healthy volunteer with both sequences first compared the tfl-SNAV and product tfl sequences. It was observed that incorporation of the SNAVs into the image sequence did not have any detrimental impact on the image quality.The SNAV motion correction technique was evaluated using an anthropomorphic brain phantom. Following a stationary reference image where the tfl-SNAV sequence was acquired along with simultaneous list-mode PET, three identical PET/MRI scans were performed where the phantom was moved several times throughout each acquisition. This motion—up to 11° and 14 mm—resulted in motion artifacts in both PET and MR images. Following SNAV motion correction of the MRI and PET list-mode data, artifact reduction was achieved for both the PET and MR images in all three motion trials. The corrected images have improved image quality and are quantitatively more similar to the ground truth reference images.

Diffusion-weighted magnetic resonance imaging using a preclinical 1\xa0T PET/MRI in healthy and tumor-bearing rats

BackgroundHybrid positron emission tomography and magnetic resonance imaging (PET/MRI) scanners are increasingly used for both clinical and preclinical imaging. Especially functional MRI sequences such as diffusion-weighted imaging (DWI) are of great interest as they provide information on a molecular level, thus, can be used as surrogate biomarkers. Due to technical restrictions, MR sequences need to be adapted for each system to perform reliable imaging. There is, to our knowledge, no suitable DWI protocol for 1 Tesla PET/MRI scanners. We aimed to establish such DWI protocol with focus on the choice of b values, suitable for longitudinal monitoring of tumor characteristics in a rat liver tumor model.Material and methodsDWI was first performed in 18 healthy rat livers using the scanner-dependent maximum of 4 b values (0, 100, 200, 300 s/mm2). Apparent diffusion coefficients (ADC) were calculated from different b value combinations and compared to the reference measurement with four b values. T2-weighted MRI and optimized DWI with best agreement between accuracy, scanning time, and system performance stability were used to monitor orthotopic hepatocellular carcinomas (HCC) in five rats of which three underwent additional 2-deoxy-2-(18F)fluoro-d-glucose(FDG)-PET imaging. ADCs were calculated for the tumor and the surrounding liver parenchyma and verified by histopathological analysis.ResultsCompared to the reference measurements, the combination b = 0, 200, 300 s/mm2 showed the highest correlation coefficient (rs = 0.92) and agreement while reducing the acquisition time. However, measurements with less than four b values yielded significantly higher ADCs (p < 0.001). When monitoring the HCC, an expected drop of the ADC was observed over time. These findings were paralleled by FDG-PET showing both an increase in tumor size and uptake heterogeneity. Interestingly, surrounding liver parenchyma also showed a change in ADC values revealing varying levels of inflammation by immunohistochemistry.ConclusionWe established a respiratory-gated DWI protocol for a preclinical 1 T PET/MRI scanner allowing to monitor growth-related changes in ADC values of orthotopic HCC liver tumors. By monitoring the changes in tumor ADCs over time, different cellular stages were described. However, each study needs to adapt the protocol further according to their question to generate best possible results.

Fourier Analysis of Cerebral Metabolism of Glucose: Gender Differences in Mechanisms of Color Processing in the Ventral and Dorsal Streams in Mice

Conventional imaging methods could not distinguish processes within the ventral and dorsal streams. The application of Fourier time series analysis was helpful to segregate changes in the ventral and dorsal streams of the visual system in male and female mice. The present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in the mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) during light stimulation with blue and yellow filters, compared to during conditions of darkness. Fourier analysis was performed using mean standardized uptake values (SUV) of [18F]FDG for each stimulus condition to derive spectral density estimates for each condition. In male mice, luminance opponency occurred by S-peak changes in the sub-cortical retino-geniculate pathways in the dorsal stream supplied by ganglionic arteries in the left visual cortex, while chromatic opponency involved C-peak changes in the cortico-subcortical pathways in the ventral stream perfused by cortical arteries in the left visual cortex. In female mice, there was resonance phenomenon at C-peak in the ventral stream perfused by the cortical arteries in the right visual cortex during luminance processing. Conversely, chromatic opponency caused by S-peak changes in the subcortical retino-geniculate pathways in the dorsal stream supplied by the ganglionic arteries in the right visual cortex. In conclusion, Fourier time series analysis uncovered distinct mechanisms of color processing in the ventral stream in males, while in female mice color processing was in the dorsal stream. It demonstrated that computation of colour processing as a conscious experience could have a wide range of applications in neuroscience, artificial intelligence and quantum mechanics.

Role of PET/MRI in oral cavity and oropharyngeal cancers based on the 8th edition of the AJCC cancer staging system: a pictorial essay.

The American Joint Committee on Cancer (AJCC) released the 8th edition of the AJCC cancer staging manual in 2017 that includes significant modifications from the 7th edition in the sections on oral cavity cancer (OCC) and oropharyngeal cancer (OPC). These highlights comprise the incorporation of the depth of invasion and exclusion of extrinsic tongue muscle involvement in the T staging of OCC, the separation of OPC staging based on the high-risk human papilloma virus status, and the inclusion of extranodal extension in N staging. The recent introduction of integrated positron emission tomography and magnetic resonance imaging (PET/MRI) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) has demonstrated the advantages of simultaneous PET and MR imaging with higher soft-tissue contrast, multiplanar image acquisition, and functional imaging capability. This pictorial essay discusses the role of 18F-FDG PET/MRI in the diagnosis of OCC and OPC based on the new cancer staging system.

Molecular imaging of T cell co-regulator factor B7-H3 with 89Zr-DS-5573a.

B7-H3 is a transmembrane protein widely expressed in a variety of cancers and has been shown to play a role in anti-tumor immunity. This study aims to develop a molecular imaging probe to identify B7-H3 expression in tumors and to develop 89Zr-DS-5573a as a theranostic that could aid patient selection in clinical Phase I studies.Methods: The anti-B7-H3 humanised monoclonal antibody DS-5573a was labeled with zirconium-89 (89Zr-), and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen binding affinity (Scatchard analysis), and serum stability in vitro. In vivo biodistribution and imaging studies were performed with positron emission tomography and magnetic resonance imaging (PET/MRI) studies to identify and quantitate 89Zr-DS-5573a tumor uptake in a B7-H3-positive breast cancer model (MDA-MB-231) and a B7-H3-negative murine colon cancer model (CT26). Imaging and biodistribution studies were also performed in MDA-MB-231 tumor-bearing SCID mice in the absence and presence of therapeutic DS-5573a antibody dose (3 mg/kg DS-5573a).Results: 89Zr-DS-5573a showed high and specific binding to B7-H3-expressing MDA-MB-231 cells (immunoreactivity on day 0, 75.0 ± 2.9%), and low binding to B7-H3-negative CT26 cells (immunoreactivity on day 0, 10.85 ± 0.11%) in vitro. 89Zr-DS-5573a demonstrated good serum stability in vitro with 57.2 ± 2.0% of immunoreactivity remaining on day 7. In vivo biodistribution studies showed high uptake of 89Zr-DS-5573a in B7-H3-expressing MDA-MB-231 tumor-bearing mice, achieving 32.32 ± 6.55 %ID/g on day 7 post injection in BALB/c nu/nu mice and 25.76 ± 1.79 %ID/g in SCID mice, with minimal evidence of non-specific uptake in normal tissues, and excellent tumor localization on PET/MRI. In a combined imaging/therapy study, receptor saturation was demonstrated in tumors responding to therapy.Conclusion: 89Zr-DS-5573a demonstrates specific and prolonged targeting of B7-H3-expressing tumors in vivo. Saturation of binding sites was demonstrated in tumors responding to DS-5573a therapy. These results indicate that 89Zr-DS-5573a has potential to target B7-H3-expressing tumors in cancer patients. Furthermore 89Zr-DS-5573a has the potential to provide important insights into T cell biology through its specific binding to B7-H3.

18F-cholin PET MRI (fusion of positron emission tomography and magnetic resonance imaging (PET/MRI) and extensive pelvic lymph node dissection (LND) in high-risk prostate cancer. Role of prostate health index in indication of PET MRI and LND

18F-cholin PET MRI (fusion of positron emission tomography and magnetic resonance imaging (PET/MRI) and extensive pelvic lymph node dissection (LND) in high-risk prostate cancer. Role of prostate health index in indication of PET MRI and LND

Gender differences in cerebral metabolism for color processing in mice: A PET/MRI Study.

IntroductionColor processing is a central component of mammalian vision. Gender-related differences of color processing revealed by non-invasive functional transcranial Doppler ultrasound suggested right hemisphere pattern for blue/yellow chromatic opponency by men, and a left hemisphere pattern by women.Materials and MethodsThe present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) with statistical parametric mapping (SPM) during light stimulation with blue and yellow filters compared to darkness condition.ResultsPET revealed a reverse pattern relative to dark condition compared to previous human studies: Male mice presented with left visual cortex dominance for blue through the right eye, while female mice presented with right visual cortex dominance for blue through the left eye. We applied statistical parametric mapping (SPM) to examine gender differences in activated architectonic areas within the orbital and medial prefrontal cortex and related cortical and sub-cortical areas that lead to the striatum, medial thalamus and other brain areas. The metabolic connectivity of the orbital and medial prefrontal cortex evoked by blue stimulation spread through a wide range of brain structures implicated in viscerosensory and visceromotor systems in the left intra-hemispheric regions in male, but in the right-to-left inter-hemispheric regions in female mice. Color functional ocular dominance plasticity was noted in the right eye in male mice but in the left eye in female mice.ConclusionsThis study of color processing in an animal model could be applied in the study of the role of gender differences in brain disease.

Early Clinical Experiences with Positron Emission Tomography–Magnetic Resonance Imaging in Epilepsy: Implications for Modeling the Neurovascular Unit

AbstractCortical function in normal and pathologic neurologic states is largely influenced by the activity of the neurovascular unit. Hybrid technologies that combine positron emission tomography and magnetic resonance imaging (PET/MRI) offer a chance for simultaneous noninvasive evaluation of cortical glucose consumption, blood flow, and cerebrovascular reactivity. We present differing PET/MRI results for two pediatric patients undergoing evaluation for medically refractory seizures, interpreted in the context of neurovascular unit behavior, suggesting the presence of ultrastructural changes at the level of the blood brain barrier in various epilepsy disorders.

Recent Developments in Combined PET/MRI

Combined positron emission tomography and magnetic resonance imaging (PET/MRI) is emerging as a powerful technique in clinical applications including oncology, neurology, and cardiology. In this review, we outline recent advances in the field, with particular focus on the study of neurodegenerative diseases, epilepsy, cardiac disorders, and oncology. We also highlight recent technical improvements in PET/MRI, with particular attention to attenuation correction and the integration with advanced MRI modalities including arterial spin labeling, fMRI, and hyperpolarized 13C magnetic resonance spectroscopy.

Simultaneous whole body (18)F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging for evaluation of pediatric cancer: Preliminary experience and comparison with (18)F-fluorodeoxyglucose positron emission tomography computed tomography.

To describe our preliminary experience with simultaneous whole body (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and magnetic resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients. This prospective, observational, single-center study was Health Insurance Portability and Accountability Act-compliant, and institutional review board approved. To be eligible, a patient was required to: (1) have a known or suspected cancer diagnosis; (2) be under the care of a pediatric hematologist/oncologist; and (3) be scheduled for clinically indicated (18)F-FDG positron emission tomography-computed tomography (PET-CT) examination at our institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET-CT examinations were performed using standard department protocols. PET-MRI studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET-MRI examinations were reviewed by consensus by two study personnel. Test performance characteristics of PET-MRI, for the detection of malignant lesions, including FDG maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET-CT as a reference standard. A total of 10 whole body PET-MRI exams were performed in 7 pediatric oncology patients. The mean patient age was 16.1 years (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and 21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93). PET-MRI SUVmax > 2.5 had 100% accuracy for discriminating benign from malignant lesions using PET-CT reference. Whole body DWI was also evaluated: the mean ADCmin of malignant lesions (780.2 + 326.6) was significantly lower than that of benign lesions (1246.2 + 417.3; P = 0.0003; Student's t test). A range of ADCmin thresholds for malignancy were evaluated, from 0.5-1.5 × 10(-3) mm(2)/s. The 1.0 × 10(-3) ADCmin threshold performed best compared with PET-CT reference (68.3% accuracy). However, the accuracy of PET-MRI SUVmax was significantly better than ADCmin for detecting malignant lesions compared with PET-CT reference (P < 0.0001; two-tailed McNemar's test). These results suggest a clinical role for simultaneous whole body PET-MRI in evaluating pediatric cancer patients.

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

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 (MRACnobone). The authors aim to quantify and reduce the bias introduced by MRACnobone in the standard uptake value (SUV) of spinal and pelvic lesions in 20 PET/MRI examinations with [18F]NaF. The authors reconstructed 20 PET/MR [18F]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 PETnobone. Second, the authors used a threshold-based algorithm developed in their group to automatically segment bone structures in the [18F]NaF PET images. Subsequently, an attenuation coefficient of 0.11 cm(-1) was assigned to the segmented bone regions in the MRI-based attenuation image (MRACbone) which was used to reconstruct PETbone. The automatic bone segmentation algorithm was validated in six PET/CT [18F]NaF examinations. Relative SUVmean and SUVmax differences between PETbone and PETnobone 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(-1), the authors investigated its influence on the reconstructed SUVs of the lesions. The comparison of [18F]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 [18F]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 [18F]NaF PET/MRI examinations revealed relative SUVmax differences between PETnobone and PETbone of (-8.8%±2.7%, p=0.01) and (-8.1%±1.9%, p=2.4×10(-8)) in pelvic and spinal lesions, respectively. A maximum SUVmax underestimation of -13.7% was found in lesion in the third cervical spine. The averaged SUVmean differences in volumes of interests in lung, liver, and bladder were below 3%. The average SUVmax 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(-1). The developed automatic [18F]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 [18F]NaF PET/MRI examinations. In nonbone structures (e.g., lung, liver, and bladder), MRACnobone yields clinically acceptable accuracy.