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This paper summarizes the 2020 Diversity in Radiology and Molecular Imaging: What We Need to Know Conference, a three-day virtual conference held September 9–11, 2020. The World Molecular Imaging Society (WMIS) and Stanford University jointly organized this event to provide a forum for WMIS members and affiliates worldwide to openly discuss issues pertaining to diversity in science, technology, engineering, and mathematics (STEM). The participants discussed three main conference themes, “racial diversity in STEM,” “women in STEM,” and “global health,” which were discussed through seven plenary lectures, twelve scientific presentations, and nine roundtable discussions, respectively. Breakout sessions were designed to flip the classroom and seek input from attendees on important topics such as increasing the representation of underrepresented minority (URM) members and women in STEM, generating pipeline programs in the fields of molecular imaging, supporting existing URM and women members in their career pursuits, developing mechanisms to effectively address microaggressions, providing leadership opportunities for URM and women STEM members, improving global health research, and developing strategies to advance culturally competent healthcare. Supplementary Information The online version contains supplementary material available at 10.1007/s11307-021-01610-3.

A radiology research interest group of medical students, with the necessary infrastructure and resident leadership, may create a productive environment for research and career development for all p...

Compartmental modeling analysis of 11C-raclopride (RAC) PET data can be used to measure the dopaminergic response to intra-scan behavioral tasks. Bias in estimates of binding potential (BPND) and its dynamic changes (ΔBPND) can arise both when head motion is present and when the compartmental model used for parameter estimation deviates from the underlying biology. The purpose of this study was to characterize the effects of motion and model bias within the context of a behavioral task challenge, examining the impacts of different mitigation strategies. Seventy healthy adults were administered bolus plus constant infusion RAC during a simultaneous PET/magnetic resonance (MR) scan with a reward task experiment. BPND and ΔBPND were estimated using an extension of the Multilinear Reference Tissue Model (E-MRTM2) and a new method (DE-MRTM2) was proposed to selectively discount the contribution of the initial uptake period. Motion was effectively corrected with a standard frame-based approach, which performed equivalently to a more complex reconstruction-based approach. DE-MRTM2 produced estimates of ΔBPND in putamen and nucleus accumbens that were significantly different from those estimated from E-MRTM2, while also decoupling ΔBPND values from first-pass k2′ estimation and removing skew in the spatial bias distribution of parametric ΔBPND estimates within the striatum.

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance–positron emission tomography (MR–PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR–PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

11C-Raclopride (RAC) positron emission tomography (PET) is used to study dopamine response to pharmacological and behavioral challenges. Behavioral challenges produce smaller responses than pharmacological challenges and are more susceptible to sources of bias, including motion bias. The purpose of this study was to characterize the effect of motion bias within the context of a behavioral task challenge, examining the impact of different motion correction strategies, different task response magnitudes, and intra-versus interframe motion.MethodsSeventy healthy young adults were administered bolus plus constant infusion 11C-Raclopride (RAC) and imaged for 90 min on a 3-Tesla simultaneous PET/magnetic resonance (MR) scanner during which a functional MRI (fMRI) reward task experiment was conducted. Kinetic analysis was performed using an extension of the multilinear reference tissue model (MRTM), which encoded the task response as a unit step function at the start of the task (t = 40 min). The quantitative impacts of different approaches to motion correction (frame-based, reconstruction-based, none) were compared using voxel maps of change in binding potential (ΔBPND). Motion bias was compared to task effect by simulating different levels of ΔBPND (0%, 5%, 10%, 20%) in conjunction with simulating high and no motion. Intraframe motion was simulated using motion estimates derived from the simultaneously acquired MR data. The relative impact of intraframe motion was evaluated by comparing maps of bias in ΔBPND before and after applying frame-based motion correction.ResultsAmong the high-motion subjects, failure to perform motion correction resulted in large artifacts. Frame- and reconstruction-based approaches both corrected for motion effectively, with the former showing moderately more intense ΔBPND values (both positive and negative) in and around the striatum. At low task response magnitudes, simulations showed that motion bias can have a greater relative effect. At 5% ΔBPND, motion bias accounted for 60% of the total bias, while at 10% ΔBPND, it accounted for only 34%. Simulating high-temporal resolution motion, frame-based motion correction was shown to counteract the majority of the of the motion bias effect. The remaining bias attributable to intraframe motion accounted for only 8% of the total.ConclusionMotion bias can have a corrupting effect on RAC studies of behavioral task challenges, particularly as the magnitude of the response decreases. Applying motion correction mitigates most of the bias, and specifically correcting for interframe motion provides the bulk of the benefit.

Purpose Coronavirus disease 2019 and the publicly documented deaths of countless Black individuals have highlighted the need to confront systemic racism, address racial/ethnic disparities, and improve diversity and inclusion in radiology. Several radiology departments have begun to create diversity, equity, and inclusion (DEI) committees to systematically address DEI issues in radiology. However, there are few articles that provide departments with guidance on how to create DEI committees to comprehensively address DEI issues in radiology. The purpose of this review is to provide readers with a framework and practical tips for creating a comprehensive, institutionally aligned radiology DEI committee. Methods The authors describe key components of the strategic planning process and lessons learned in the creation of a radiology DEI committee, on the basis of the experience of an integrated, academic northeastern radiology department. Results A hospital-based strategic planning process defining the DEI vision, mission, goals, and strategies was used to inform the formation of the radiology department DEI committee. The radiology department performed gap analyses by conducting internal and external research. Strengths, weaknesses, opportunities, and threats analyses were performed on the basis of consultations with institutional and other departmental DEI leaders as well as DEI leaders from other academic medical centers. This framework served as the basis for the creation of the radiology departmental DEI committee, including a steering committee and four task forces (education, research, patient experience, and workforce development), each charged with addressing specific institutional goals and strategies. Conclusions This review provides academic radiology departments with a blueprint to create a comprehensive, institutionally aligned radiology DEI committee.

BACKGROUND Disproportionally high rates of COVID-19 have been noted among communities with limited English proficiency (LEP), resulting in an unmet need for improved multilingual care and interpreter services. To enhance multilingual care, we created a freely available web app (RadTranslate™) that provides multilingual radiology exam instructions. The purpose of this study was to evaluate the implementation of this intervention in radiology. METHODS The device-agnostic web app leverages artificial-intelligence text-to-speech to provide standardized, human-like spoken exam instructions in the patient’s preferred language. Standardized phrases were collected from a consensus group consisting of technologists, radiologists, and ancillary staff. RadTranslate was piloted in Spanish for chest radiographs (CXR) performed at a COVID-19 triage outpatient center that served a predominantly Spanish-speaking Latine community. Implementation included a tablet displaying the app in the CXR room. Imaging appointment duration (IAD) was measured and compared between pre- and post-implementation groups. RESULTS In the 63-day test period following launch, there were 1267 app uses, with technologists voluntarily switching exclusively to RadTranslate for Spanish-speaking patients. The most used phrases were a general explanation of the exam (30% of total) followed by instructions to disrobe and remove any jewelry (12%). There was no significant difference in the IAD, 11±7 min (mean ± standard deviation) and 12±3 for standard-of-care versus RadTranslate, respectively; however, variability was significantly lower when RadTranslate was used (p=0.003). CONCLUSION AI-aided multilingual audio instructions were successfully integrated into imaging workflows, reducing strain on medical interpreters and variance in throughput resulting in more reliable average exam length., RadTranslate (www.radtranslate.com), a web-based tool, allows standardized audio imaging exam instructions to be given in a patient’s native language via a simple interface, and reduces variability in exam times among non-English patients receiving chest radiographs.

Objective To characterize [11 C]-PBR28 brain uptake using positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). We have previously shown increased [11 C]-PBR28 uptake in the precentral gyrus in a small group of ALS patients. Herein, we confirm our initial finding, study the longitudinal changes, and characterize the gray versus white matter distribution of [11 C]-PBR28 uptake in a larger cohort of patients with ALS and PLS. Methods Eighty-five participants including 53 with ALS, 11 with PLS, and 21 healthy controls underwent integrated [11 C]-PBR28 PET-magnetic resonance brain imaging. Patients were clinically assessed using the Upper Motor Neuron Burden (UMNB) and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). [11 C]-PBR28 uptake was quantified as standardized uptake value ratio (SUVR) and compared between groups. Cortical thickness and fractional anisotropy were compared between groups and correlated with SUVR and the clinical data. [11 C]-PBR28 uptake and ALSFRS-R were compared longitudinally over 6 months in 10 ALS individuals. Results Whole brain voxelwise, surface-based, and region of interest analyses revealed increased [11 C]-PBR28 uptake in the precentral and paracentral gyri in ALS, and in the subcortical white matter for the same regions in PLS, compared to controls. The increase in [11 C]-PBR28 uptake colocalized and correlated with cortical thinning, reduced fractional anisotropy, and increased mean diffusivity, and correlated with higher UMNB score. No significant changes were detected in [11 C]-PBR28 uptake over 6 months despite clinical progression. Interpretation Glial activation measured by in vivo [11 C]-PBR28 PET is increased in pathologically relevant regions in people with ALS and correlates with clinical measures. Ann Neurol 2018;83:1186-1197.

Background Subject motion in positron emission tomography (PET) studies leads to image blurring and artifacts; simultaneously acquired magnetic resonance imaging (MRI) data provides a means for motion correction (MC) in integrated PET/MRI scanners. Purpose To assess the effect of realistic head motion and MR-based MC on static [18 F]-fluorodeoxyglucose (FDG) PET images in dementia patients. Study type Observational study. Population Thirty dementia subjects were recruited. Field strength/sequence 3T hybrid PET/MR scanner where EPI-based and T1 -weighted sequences were acquired simultaneously with the PET data. Assessment Head motion parameters estimated from high temporal resolution MR volumes were used for PET MC. The MR-based MC method was compared to PET frame-based MC methods in which motion parameters were estimated by coregistering 5-minute frames before and after accounting for the attenuation-emission mismatch. The relative changes in standardized uptake value ratios (SUVRs) between the PET volumes processed with the various MC methods, without MC, and the PET volumes with simulated motion were compared in relevant brain regions. Statistical tests The absolute value of the regional SUVR relative change was assessed with pairwise paired t-tests testing at the P = 0.05 level, comparing the values obtained through different MR-based MC processing methods as well as across different motion groups. The intraregion voxelwise variability of regional SUVRs obtained through different MR-based MC processing methods was also assessed with pairwise paired t-tests testing at the P = 0.05 level. Results MC had a greater impact on PET data quantification in subjects with larger amplitude motion (higher than 18% in the medial orbitofrontal cortex) and greater changes were generally observed for the MR-based MC method compared to the frame-based methods. Furthermore, a mean relative change of ∼4% was observed after MC even at the group level, suggesting the importance of routinely applying this correction. The intraregion voxelwise variability of regional SUVRs was also decreased using MR-based MC. All comparisons were significant at the P = 0.05 level. Data conclusion Incorporating temporally correlated MR data to account for intraframe motion has a positive impact on the FDG PET image quality and data quantification in dementia patients. Level of evidence 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1288-1296.

Pain interventions with no active ingredient, placebo, are sometimes effective in treating chronic pain conditions. Prior studies on the neurobiological underpinnings of placebo analgesia indicate endogenous opioid release and changes in brain responses and functional connectivity during pain anticipation and pain experience in healthy subjects. Here, we investigated placebo analgesia in healthy subjects and in interictal migraine patients (n = 9) and matched healthy controls (n = 9) using 11C-diprenoprhine Positron Emission Tomography (PET) and simultaneous functional Magnetic Resonance Imaging (fMRI). Intravenous saline injections (the placebo) led to lower pain ratings, but we did not find evidence for an altered placebo response in interictal migraine subjects as compared to healthy subjects., Highlights • Simultaneous fMRI and 11C-Diprenoprhine PET of migraineurs and controls before and after placebo analgesia • Placebo led to an overall reduction in pain ratings, with no significant differences between patients and controls • Structural changes in migraine, but no effects of placebo or diagnosis on pain fMRI or on opioid receptor binding.

To propose an MR-based method for generating continuous-valued head attenuation maps and to assess its accuracy and reproducibility. Demonstrating that novel MR-based photon attenuation correction methods are both accurate and reproducible is essential prior to using them routinely in research and clinical studies on integrated PET/MR scanners. Continuous-valued linear attenuation coefficient maps (“μ-maps”) were generated by combining atlases that provided the prior probability of voxel positions belonging to a certain tissue class (air, soft tissue, or bone) and an MR intensity-based likelihood classifier to produce posterior probability maps of tissue classes. These probabilities were used as weights to generate the μ-maps. The accuracy of this probabilistic atlas-based continuous-valued μ-map (“PAC-map”) generation method was assessed by calculating the voxel-wise absolute relative change (RC) between the MR-based and scaled CT-based attenuation-corrected PET images. To assess reproducibility, we performed pair-wise comparisons of the RC values obtained from the PET images reconstructed using the μ-maps generated from the data acquired at three time points. The proposed method produced continuous-valued μ-maps that qualitatively reflected the variable anatomy in patients with brain tumor and agreed well with the scaled CT-based μ-maps. The absolute RC comparing the resulting PET volumes was 1.76 ± 2.33 %, quantitatively demonstrating that the method is accurate. Additionally, we also showed that the method is highly reproducible, the mean RC value for the PET images reconstructed using the μ-maps obtained at the three visits being 0.65 ± 0.95 %. Accurate and highly reproducible continuous-valued head μ-maps can be generated from MR data using a probabilistic atlas-based approach.

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.

Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand 11C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for 11C-PBR28, nine patient–control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29–63 for patients and 28–65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. * Abbreviations : LBP : low back pain SUV : standardized uptake value

Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [11C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38–68 years) and ten age- and [11C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33–65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (pFWE, Highlights • We used PET to image in vivo glial activation in the brain of patients with ALS. • Increased [11C]PBR28 binding was observed in motor cortices in patients with ALS. • Glial activation in the motor cortex correlated with ALS disease severity. • Findings suggest clinical relevance of brain inflammation measured in vivo in ALS. • [11C]-PBR28 could be used as an in vivo marker of upper motor neuron injury in ALS.

OBJECTIVE: To characterize [(11)C]-PBR28 brain uptake using positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS), and primary lateral sclerosis (PLS). We have previously shown increased [(11)C]-PBR28 uptake in the precentral gyrus in a small group of ALS patients. Herein, we confirm our initial finding, study the longitudinal changes, and characterize the gray vs. white matter distribution of [(11)C]-PBR28 uptake in a larger cohort of patients with ALS and PLS. METHODS: Eighty-five participants including 53 ALS, 11 PLS and 21 healthy controls underwent integrated [(11)C]-PBR28 PET-MR brain imaging. Patients were clinically assessed using the upper motor neuron burden (UMNB), and the revised ALS functional rating scale (ALSFRS-R). [(11)C]-PBR28 uptake was quantified as standardized uptake value ratio (SUVR), and compared between groups. Cortical thickness, and fractional anisotropy were compared between groups and correlated with SUVR and the clinical data. [(11)C]-PBR28 uptake and ALSFRS-R were compared longitudinally over six-month in ten ALS individuals. RESULTS: Whole brain voxel-wise, surface-based and region of interest analyses revealed increased [(11)C]-PBR28 uptake in the precentral and paracentral gyri in ALS, and in the sub-cortical white matter for the same regions in PLS, compared to controls. The increase in [(11)C]-PBR28 uptake co-localized and correlated with cortical thinning, reduced fractional anisotropy, increased mean diffusivity, and correlated with higher UMNB score. No significant changes were detected in [(11)C]-PBR28 uptake over six-month despite clinical progression. INTERPRETATION: Glial activation measured by in vivo [(11)C]-PBR28 PET is increased in pathologically relevant regions in people with ALS and correlates with clinical measures.

Background Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post-mortem studies, but its role in primary lateral sclerosis (PLS) is unknown. Objectives To localize and measure glia activation in people with PLS compared to healthy controls (HC). Methods Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET). The radiotracer [11C]-PBR28 was used to obtain PET-based measures of 18 kDa translocator protein (TSPO) expression, a marker of activated glial cells. MR techniques included a structural sequence to measure cortical thickness and diffusion tensor imaging (DTI) to assess white matter integrity. Results PET data showed increased [11C]-PBR28 uptake in anatomically-relevant motor regions which co-localized with areas of regional gray matter atrophy and decreased subcortical fractional anisotropy. Conclusions This study supports a link between glia activation and neuronal degeneration in PLS, and suggests that these disease mechanisms can be measured in vivo in PLS. Future studies are needed to determine the longitudinal changes of these imaging measures and to clarify if MR-PET with [11C]-PBR28 can be used as a biomarker for drug development in the context of clinical trials for PLS., Highlights • Is there a relationship between glia activation, cortical atrophy, and subcortical white matter abnormalities in people with primary lateral sclerosis (PLS)? • In this cross-sectional in vivo multi-modal (MR-PET) neuroimaging study, we show evidence of glia activation in the motor regions in PLS patients compared to healthy controls. The increased glia activation co-localizes with areas of structural abnormalities including cortical atrophy and subcortical white matter changes. • MR-PET neuroimaging is a powerful technique to localize and quantify glia activation and structural abnormalities, and may represent a novel in vivo biomarker of disease mechanisms in PLS.

Purpose Simultaneous acquisition of MR and positron emission tomography (PET) images requires the placement of the MR detection coil inside the PET detector ring where it absorbs and scatters photons. This constraint is the principal barrier to achieving optimum sensitivity on each modality. Here, we present a 31-channel PET-compatible brain array coil with reduced attenuation but improved MR sensitivity. Methods A series of component tests were performed to identify tradeoffs between PET and MR performance. Aspects studied include the remote positioning of preamplifiers, coax size, coil trace size/material, and plastic housing. We then maximized PET performance at minimal cost to MR sensitivity. The coil was evaluated for MR performance (signal to noise ratio [SNR], g-factor) and PET attenuation. Results The coil design showed an improvement in attenuation by 190% (average) compared with conventional 32-channel arrays, and no loss in MR SNR. Moreover, the 31-channel coil displayed an SNR improvement of 230% (cortical region of interest) compared with a PET-optimized 8-channel array with similar attenuation properties. Implementing attenuation correction of the 31-channel array successfully removed PET artifacts, which were comparable to those of the 8-channel array. Conclusion The design of the 31-channel PET-compatible coil enables higher sensitivity for PET/MR imaging, paving the way for novel applications in this hybrid-imaging domain. Magn Reson Med 73:2363–2375, 2015. © 2014 Wiley Periodicals, Inc.

The purpose of this work--the first of its kind--was to evaluate the impact of chronic selective histone deacetylase (HDAC) inhibitor treatment on brain activity using uptake of the radioligand (18)F-fluorodeoxyglucose and positron emission tomography ((18)FDG-PET). HDAC dysfunction and other epigenetic mechanisms are implicated in diverse CNS disorders and animal research suggests HDAC inhibition may provide a lead toward developing improved treatment. To begin to better understand the role of the class I HDAC subtypes HDAC 1, 2 and 3 in modulating brain activity, we utilized two benzamide inhibitors from the literature, compound 60 (Cpd-60) and CI-994 which selectively inhibit HDAC 1 and 2 or HDACs 1, 2 and 3, respectively. One day after the seventh treatment with Cpd-60 (22.5 mg/kg) or CI-994 (5 mg/kg), (18)FDG-PET experiments (n=11-12 rats per treatment group) revealed significant, local changes in brain glucose utilization. These 2-17% changes were represented by increases and decreases in glucose uptake. The pattern of changes was similar but distinct between Cpd-60 and CI-994, supporting that (18)FDG-PET is a useful tool to examine the relationship between HDAC subtype activity and brain activity. Further work using additional selective HDAC inhibitors will be needed to clarify these effects as well as to understand how brain activity changes influence behavioral response.

Integrated scanners capable of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) data acquisition are now available for human use. Although the scanners' manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the 2 modalities, the potential physiological inference has not been evaluated. In this study, we have studied the influence of the acoustic noise produced by the magnetic resonance (MR) gradients on brain fludeoxyglucose (FDG) uptake in the Siemens MR-BrainPET prototype. Although particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed.The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, 10 healthy volunteers underwent 2 simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a "quiet" (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a "noisy" (test) environment in which MR sequences were run for the entire time. Cortical and subcortical regions of interest were derived from the high-resolution morphological MR data using FreeSurfer. The changes in the FDG uptake in the FreeSurfer-derived regions of interest between the 2 conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer.Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The region of interest-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13% [4.73%]) and static (4.18% [2.87%]) images. The SPM8 analysis showed no statistically significant clusters in any images when a P0.05 (corrected) was used; however, a P0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left, 8.37% [1.55%]; right, 8.20% [1.17%]) but only unilateral increase in the static image (left, 8.68% [3.89%]).Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in the FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation-related) changes in the FDG uptake in this region if the expected effects are of comparable amplitude.

Dopamine orchestrates changes in cortical network synchrony that underlie working memory, as revealed with simultaneous PET-MRI., Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory–emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli. In contrast, striatal D1 predicted opposing effects within these two networks but no between-network effects. These findings specifically link cortical dopamine signaling to network crosstalk that redirects cognitive resources to working memory, echoing neuromodulatory effects of D1 signaling on the level of cortical microcircuits.

Here we report a generalizable solid/solution phase strategy for the synthesis of discrete bimodal fibrin-targeted imaging probes. A fibrin-specific peptide was conjugated with two distinct imaging reporters at the C- and N-terminus. In vitro studies demonstrated retention of fibrin affinity and specificity. Imaging studies showed that these probes could detect fibrin over a wide range of probe concentrations by optical, magnetic resonance, and positron emission tomography imaging.

Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired MRI data can be used for motion tracking. In this work, a novel algorithm for data processing and rigid-body motion correction (MC) for the MRI-compatible BrainPET prototype scanner is described, and proof-of-principle phantom and human studies are presented. Methods: To account for motion, the PET prompt and random coincidences and sensitivity data for postnormalization were processed in the line-of-response (LOR) space according to the MRI-derived motion estimates. The processing time on the standard BrainPET workstation is approximately 16 s for each motion estimate. After rebinning in the sinogram space, the motion corrected data were summed, and the PET volume was reconstructed using the attenuation and scatter sinograms in the reference position. The accuracy of the MC algorithm was first tested using a Hoffman phantom. Next, human volunteer studies were performed, and motion estimates were obtained using 2 high-temporal-resolution MRI-based motion-tracking techniques. Results: After accounting for the misalignment between the 2 scanners, perfectly coregistered MRI and PET volumes were reproducibly obtained. The MRI output gates inserted into the PET list-mode allow the temporal correlation of the 2 datasets within 0.2 ms. The Hoffman phantom volume reconstructed by processing the PET data in the LOR space was similar to the one obtained by processing the data using the standard methods and applying the MC in the image space, demonstrating the quantitative accuracy of the procedure. In human volunteer studies, motion estimates were obtained from echo planar imaging and cloverleaf navigator sequences every 3 s and 20 ms, respectively. Motion-deblurred PET images, with excellent delineation of specific brain structures, were obtained using these 2 MRI-based estimates. Conclusion: An MRI-based MC algorithm was implemented for an integrated MR-PET scanner. High-temporal-resolution MRI-derived motion estimates (obtained while simultaneously acquiring anatomic or functional MRI data) can be used for PET MC. An MRI-based MC method has the potential to improve PET image quality, increasing its reliability, reproducibility, and quantitative accuracy, and to benefit many neurologic applications.

Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α[subscript 2]-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness., National Institutes of Health (U.S.) (DP1-OD003646), National Institutes of Health (U.S.) (TR01-GM104948), National Institutes of Health (U.S.) (DP2-OD006454)

We present an approach for head MR-based attenuation correction (AC) based on the Statistical Parametric Mapping 8 (SPM8) software, which combines segmentation- and atlas-based features to provide a robust technique to generate attenuation maps (μ maps) from MR data in integrated PET/MR scanners. Methods: Coregistered anatomic MR and CT images of 15 glioblastoma subjects were used to generate the templates. The MR images from these subjects were first segmented into 6 tissue classes (gray matter, white matter, cerebrospinal fluid, bone, soft tissue, and air), which were then nonrigidly coregistered using a diffeomorphic approach. A similar procedure was used to coregister the anatomic MR data for a new subject to the template. Finally, the CT-like images obtained by applying the inverse transformations were converted to linear attenuation coefficients to be used for AC of PET data. The method was validated on 16 new subjects with brain tumors (n = 12) or mild cognitive impairment (n = 4) who underwent CT and PET/MR scans. The μ maps and corresponding reconstructed PET images were compared with those obtained using the gold standard CT-based approach and the Dixon-based method available on the Biograph mMR scanner. Relative change (RC) images were generated in each case, and voxel- and region-of-interest–based analyses were performed. Results: The leave-one-out cross-validation analysis of the data from the 15 atlas-generation subjects showed small errors in brain linear attenuation coefficients (RC, 1.38% ± 4.52%) compared with the gold standard. Similar results (RC, 1.86% ± 4.06%) were obtained from the analysis of the atlas-validation datasets. The voxel- and region-of-interest–based analysis of the corresponding reconstructed PET images revealed quantification errors of 3.87% ± 5.0% and 2.74% ± 2.28%, respectively. The Dixon-based method performed substantially worse (the mean RC values were 13.0% ± 10.25% and 9.38% ± 4.97%, respectively). Areas closer to the skull showed the largest improvement. Conclusion: We have presented an SPM8-based approach for deriving the head μ map from MR data to be used for PET AC in integrated PET/MR scanners. Its implementation is straightforward and requires only the morphologic data acquired with a single MR sequence. The method is accurate and robust, combining the strengths of both segmentation- and atlas-based approaches while minimizing their drawbacks.

We describe a novel semi-automated pipeline which integrates advanced data analysis tools for MR and PET with advanced PET reconstruction correction methods (partial volume effect correction [PVC], motion correction [MC], attenuation correction [AC]) in a user-friendly Matlab graphical user interface (GUI). The reconstruction and analysis GUI is written in Matlab. Computationally intensive tasks in the pipeline are automatically transferred to a high-performance computing cluster and retrieved. Descriptions of the commercial packages used can be found in their corresponding references. SPM8 [1] is used in MC and AC processing. Comkat [2] and PMOD [3] are used for kinetic modeling. FSL [4] and SPM8 are used for group analysis. Freesurfer [5] is used for regions-of-interest (ROI) definition and smoothing. Data preprocessing: Head-motion is derived from a number of sources: echo-planar MR images, MR-based motion navigators, and directly from the PET data when MR data is unavailable (e.g. during shimming). Subsequently, the ME-MPRAGE is reoriented to the reference position. Cortical and subcortical ROIs are labeled using FreeSurfer; similarly, the MPRAGE is registered to MNI-space for generating subject-specific atlases. Image reconstruction: An OP-OSEM algorithm is used for PET reconstruction [6]. MC [7] and PVC [8] can be performed using the results from data preprocessing. AC can be imported directly from CT, using MR-images [9], or through atlas-based methods. Automated Bolus Arrival Time (BAT) & Image-Derived Input Function: The singles count rate is recorded during PET acquisition. The BAT is determined by fitting a trilinear piecewise function and used as the reference time. Time-of-Flight MR can then be used to segment the arteries of the head and an image-derived input function can be determined using short frames. We presented a novel pipeline which interfaces with a number of different commercial software to provide improved PET data quantification.

We describe a new MR-based attenuation correction (MRAC) method for neurological studies performed using integrated PET/MR scanners. The method, combining the advantages of image segmentation and atlas-based approaches to generate a high-resolution template, is based on the widely available SPM8 software and provides robust and accurate linear attenuation coefficients (LACs) for head while requiring minimal user interaction. Atlas generation: 3T MR and CT images from 15 glioblastoma subjects were used to generate the high-resolution atlas. MR images were segmented into 6 tissue classes: GM, WM, CSF, soft tissue, bone and air)[1]. Tissue classes were then coregistered using an iterative diffeomorphic image registration algorithm [2] to form the template. Atlas validation: The template was validated on 16 subjects. SyN [3] and IRTK [4], considered state-of-the-art for non-rigid image registration[5], were used for comparison. Final attenuation maps were created from the warped CT atlas following [6]. PET images were then reconstructed using the proposed methods as well as the manufacturer’s built-in method (dual-echo Dixon-VIBE sequence) [7] and compared to the gold standard CT-based attenuation correction (CTAC). The qualitative and quantitative analysis of the attenuation maps revealed that the SPM8-based method produces very robust results (Figure ​(Figure1).1). In terms of the PET data quantification, we observed improvements of > 70% compared to the VIBE-based method (Table ​(Table11 and Figure ​Figure2).2). When compared to SyN-based image registration, the SPM8 approach showed improved global results on the brain area (Figures ​(Figures11 and ​and22). Figure 1 Comparison of LACs from a validation subject for our proposed method (A), the SyN method (B) and the manufacturer’s built-in Dixon method (C) to the gold standard CTAC (D). Image differences with respect to the gold standard CTAC of our method ... Table 1 Summary of voxel- and ROI-based results between our method (atlas) and the current manufacturer’s method (Dixon) Figure 2 PET images from a validation subject reconstructed with our proposed method (A), with the SyN method (B) and with the manufacturer’s built-in Dixon method (C), compared with the gold standard CTAC (D). Relative changes (in % with respect to gold ... We presented a new MRAC technique for brain images acquired on simultaneous PET/MR scanners. The new approach relies on segmentation- and atlas-based features to provide robust and more accurate LACs than using state-of-art non-rigid image registration while avoiding sophisticated user input or interaction.

There is an ongoing effort to develop better methods for noninvasive detection and characterization of thrombi. Here we describe the synthesis and evaluation of three new fibrin-targeted positron emission tomography (PET) probes (FBP1, FBP2, FBP3). Three fibrin-specific peptides were conjugated as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-monoamides at the C- and N-termini and chelated with (64)CuCl2. Probes were prepared with a specific activity ranging from 10 to 130 μCi/nmol. Both the peptides and the probes exhibited nanomolar dissociation constants (Kd) for the soluble fibrin fragment DD(E), although the Cu-DOTA derivatization resulted in a 2-3 fold loss in affinity relative to the parent peptide. Biodistribution and imaging studies were performed in a rat model of carotid artery thrombosis. For FBP1 and FBP2 at 120 min post injection, the vessel containing the thrombus showed the highest concentration of radioactivity after the excretory organs, that is, the liver and kidneys. This was confirmed ex vivo by autoradiography, which showed >4-fold activity in the thrombus-containing artery compared to the contralateral artery. FBP3 showed much lower thrombus uptake, and the difference was traced to greater metabolism of this probe. Hybrid MR-PET imaging with FBP1 or FBP2 confirmed that these probes were effective for the detection of an arterial thrombus in this rat model. A thrombus was visible on PET images as a region of high activity that corresponded to a region of arterial occlusion identified by simultaneous MR angiography. FBP1 and FBP2 represent promising new probes for the molecular imaging of thrombi.

Our goal in this study was to characterize the combined effect of MR-assisted motion correction (MC) and partial volume effects correction (PVEC) on the estimation of [11C]NNC112 binding potential (BP) in healthy volunteers. 29 subjects were scanned on the Siemens 3T MR-BrainPET scanner prototype. Emission data were acquired in list mode format for 90-minutes following the i.v. administration of ~8 mCi of [11C]NNC112. The head attenuation map was obtained from the MPRAGE data using an atlas-based method. Head motion estimates were derived from the MR data and used to correct the PET data in LOR space before image reconstruction [1]. PVEC was applied to the motion corrected data using the region-based voxel-wise (RBV) method [2] and regions of interest (ROIs) defined from the MPRAGE images using FreeSurfer and the measured point-spread function [3]. BPnd for each of the ROIs was estimated in PMOD using the simplified reference tissue kinetic (SRTM) model and the cerebellum as a reference tissue. Maximum translations of up to 9 mm and rotations of up to 12 degrees have been observed in this group of subjects (Figure ​(Figure1).1). Less variability in the tissue time activity curves (TACs) was noted after MC (the curves before and after MC for a representative subject are shown in Figure ​Figure2).2). The percentage changes in BPnd after MC and PVEC revealed both under- and overestimation in the ROIs analyzed (Figure ​(Figure3).3). The cumulative effect exceeded 100% for some of the structures analyzed. Figure 1 Maximum translations (left) and rotations (right) measured in 29 healthy volunteers scanned for 90 minutes Figure 2 TACs in the left and right caudate and cerebellar cortices before (left) and after (right) MR-assisted motion correction Figure 3 Percent change in NNC112 BPnd after motion and partial volume effects corrections Significant motion and PVE were observed in all the subjects, biasing the PET estimates. The combined effect is difficult to predict, depending on the size and location of the structure of interest and patient compliance. Without addressing these issues, the value of the BPnd’s derived from these data is questionable.