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BACKGROUND AND OBJECTIVES: Post-COVID condition (PCC) is common and often involves neuropsychiatric symptoms. This study aimed to use blood oxygenation level-dependent fMRI (BOLD-fMRI) to assess whether participants with PCC had abnormal brain activation during working memory (WM) and whether the abnormal brain activation could predict cognitive performance, motor function, or psychiatric symptoms. METHODS: The participants with PCC had documented coronavirus disease 2019 (COVID-19) at least 6 weeks before enrollment. Healthy control participants had no prior history of COVID-19 and negative tests for severe acute respiratory syndrome coronavirus 2. Participants were assessed using 3 NIH Toolbox (NIHTB) batteries for Cognition (NIHTB-CB), Emotion (NIHTB-EB), and Motor function (NIHTB-MB) and selected tests from the Patient-Reported Outcomes Measurement Information System (PROMIS). Each had BOLD-fMRI at 3T, during WM (N-back) tasks with increasing attentional/WM load. RESULTS: One hundred sixty-nine participants were screened; 50 fulfilled the study criteria and had complete and usable data sets for this cross-sectional cohort study. Twenty-nine participants with PCC were diagnosed with COVID-19 242 ± 156 days earlier; they had similar ages (42 ± 12 vs 41 ± 12 years), gender proportion (65% vs 57%), racial/ethnic distribution, handedness, education, and socioeconomic status, as the 21 uninfected healthy controls. Despite the high prevalence of memory (79%) and concentration (93%) complaints, the PCC group had similar performance on the NIHTB-CB as the controls. However, participants with PCC had greater brain activation than the controls across the network (false discovery rate-corrected p = 0.003, Tmax = 4.17), with greater activation in the right superior frontal gyrus (p = 0.009, Cohen d = 0.81, 95% CI 0.15-1.46) but lesser deactivation in the default mode regions (p = 0.001, d = 1.03, 95% CI 0.61-1.99). Compared with controls, participants with PCC also had poorer dexterity and endurance on the NIHTB-MB, higher T scores for negative affect and perceived stress, but lower T scores for psychological well-being on the NIHTB-EB, as well as more pain symptoms and poorer mental and physical health on measures from the PROMIS. Greater brain activation predicted poorer scores on measures that were abnormal on the NIHTB-EB. DISCUSSION: Participants with PCC and neuropsychiatric symptoms demonstrated compensatory neural processes with greater usage of alternate brain regions, and reorganized networks, to maintain normal performance during WM tasks. BOLD-fMRI was sensitive for detecting brain abnormalities that correlated with various quantitative neuropsychiatric symptoms.

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Objectives: We aimed to compare brain white matter integrity in participants with post-COVID-19 conditions (PCC) and healthy controls. Methods: We compared cognitive performance (NIH Toolbox®), psychiatric symptoms and diffusion tensor imaging (DTI) metrics between 23 PCC participants and 24 controls. Fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities were measured in 9 white matter tracts and 6 subcortical regions using MRICloud. Results: Compared to controls, PCC had similar cognitive performance, but greater psychiatric symptoms and perceived stress, as well as higher FA and lower diffusivities in multiple white matter tracts (ANCOVA-p-values≤0.001-0.048). Amongst women, PCC had higher left amygdala-MD than controls (sex-by-PCC p=0.006). Regardless of COVID-19 history, higher sagittal strata-FA predicted greater fatigue (r=0.48-0.52, p<0.001) in all participants, and higher left amygdala-MD predicted greater fatigue (r=0.61, p<0.001) and anxiety (r=0.69, p<0.001) in women, and higher perceived stress (r=0.45, p=0.002) for all participants. Conclusions: Microstructural abnormalities are evident in PCC participants averaged six months after COVID-19. The restricted diffusivity (with reduced MD) and higher FA suggest enhanced myelination or increased magnetic susceptibility from iron deposition, as seen in stress conditions. The higher amygdala-MD in female PCC suggests persistent neuroinflammation, which might contribute to their fatigue, anxiety, and perceived stress.

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AI has, to varying degrees, affected all aspects of molecular imaging, from image acquisition to diagnosis. During the last decade, the advent of deep learning in particular has transformed medical image analysis. Although the majority of recent advances have resulted from neural-network models applied to image segmentation, a broad range of techniques has shown promise for image reconstruction, image synthesis, differential-diagnosis generation, and treatment guidance. Applications of AI for drug design indicate the way forward for using AI to facilitate molecular-probe design, which is still in its early stages. Deep-learning models have demonstrated increased efficiency and image quality for PET reconstruction from sinogram data. Generative adversarial networks (GANs), which are paired neural networks that are jointly trained to generate and classify images, have found applications in modality transformation, artifact reduction, and synthetic-PET-image generation. Some AI applications, based either partly or completely on neural-network approaches, have demonstrated superior differential-diagnosis generation relative to radiologists. However, AI models have a history of brittleness, and physicians and patients may not trust AI applications that cannot explain their reasoning. To date, the majority of molecular-imaging applications of AI have been confined to research projects, and are only beginning to find their ways into routine clinical workflows via commercialization and, in some cases, integration into scanner hardware. Evaluation of actual clinical products will yield more realistic assessments of AI's utility in molecular imaging.

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Many brain disorders - such as Alzheimer's disease, Parkinson's disease, schizophrenia and autism - are heterogeneous, that is, they may have several subtypes. Traditionally, clinicians have identified subtypes, such as subtypes of psychosis, using clinical criteria. Neuroimaging has the potential to detect subtypes based on objective biomarker-based criteria; however, there are no studies that evaluate the application of combining unsupervised machine learning and anatomical connectivity analysis to accomplish this goal. We propose a computational framework to detect subtypes based on anatomical connectivity computed from diffusion tensor imaging data, in a data-driven and fully automated way. The proposed method exhibits excellent performance on simulated data. We also applied this approach to a real-world dataset: the Nathan Kline Institute data set. The Nathan Kline Institute study consists of 137 normal adult subjects (mean age 41 years (standard deviation 18), male/female 85/52). We examined the association between detected subtypes and the impulsive behavior scale. We found that a subtype characterized by lower connectivity scores was associated with a higher positive urgency score; positive urgency is a vulnerability marker for drug addiction. The top-ranked connections characterizing subtypes involve several brain regions, including the anterior cingulate gyrus, median cingulate gyrus, thalamus, superior frontal gyrus (medial), middle frontal gyrus (orbital part), inferior frontal gyrus (triangular part), superior frontal gyrus, precuneus and putamen. The proposed framework is extendable, and can be used to detect subtypes from other features, including clinical and genomic biomarkers.

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Inadequate imaging surveillance has been identified as the most significant contributor to abdominal aortic aneurysm (AAA) rupture. Radiologists can contribute value to patient care and reduce morbidity and mortality related to AAA by incorporating evidence-based management recommendations from the ACR and Society of Vascular Surgery into their report impression. The challenges lie in achieving 100% radiologist compliance to incorporate the recommendations and ensuring that the patient is notified by their provider, the follow-up examination is scheduled, and the patient returns for an imaging test that may be scheduled 3 to 5 years in the future. To address these barriers, radiology quality and informatics leads have harnessed IT solutions to facilitate integration of content, communication of results, and patient follow-up.

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RATIONALE AND OBJECTIVES: Here we review the current state of multicenter radiology research (MRR), and utilize a survey of experienced researchers to identify common advantages, barriers, and resources to guide future investigators. MATERIALS AND METHODS: The Association of University Radiologists established a Radiology Research Alliance task force, Multi-center Research Studies in Radiology, composed of 12 society members to review MRR. A REDCap survey was designed to gain more insight from experienced researchers. Recipients were authors identified from a PubMed database search, utilizing search terms "multicenter" or "multisite" and "radiology." The survey included investigator background information, reasons why, barriers to, and resources that investigators found helpful in conducting or participating in MRR. RESULTS: The survey was completed by 23 of 80 recipients (29%), the majority (76%) of whom served as a primary investigator on at least one MRR project. Respondents reported meeting collaborators at national or international (74%) and society (39%) meetings. The most common perceived advantages of MRR were increased sample size (100%) and improved generalizability (91%). External funding was considered the most significant barrier to MRR, reported by 26% of respondents. Institutional funding, setting up a central picture archiving and communication system, and setting up a central database were considered a significant barrier by 30%, 22%, and 22% of respondents, respectively. Resources for overcoming barriers included motivated staff (74%), strong leadership (70%), regular conference calls (57%), and at least one face-to-face meeting (57%). CONCLUSIONS: Barriers to MRR include funding and establishing a central database and a picture archiving and communication system. Upon embarking on an MRR project, forming a motivated team who meets and speaks regularly is essential.

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Longitudinal brain morphometry probes time-related brain morphometric patterns. We propose a method called dynamic network modeling with continuous valued nodes to generate a dynamic brain network from continuous valued longitudinal morphometric data. The mathematical framework of this method is based on state-space modeling. We use a bootstrap-enhanced least absolute shrinkage operator to solve the network-structure generation problem. In contrast to discrete dynamic Bayesian network modeling, the proposed method enables network generation directly from continuous valued high-dimensional short sequence data, being free from any discretization process. We applied the proposed method to a study of normal brain development.

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PURPOSE: For children with sickle cell disease (SCD) and at low risk category of stroke, we aim to build a predictive model to differentiate those with decline of intelligence-quotient (IQ) from counterparts without decline, based on structural magnetic-resonance (MR) imaging volumetric analysis. MATERIALS AND METHODS: This preliminary prospective cohort study included 25 children with SCD, homozygous for hemoglobin S, with no history of stroke and transcranial Doppler mean velocities below 170cm/s at baseline. We administered the Kaufman Brief Intelligence Test (K-BIT) to each child at yearly intervals for 2-4 years. Each child underwent MR examination within 30 days of the baseline K-BIT evaluation date. We calculated K-BIT change rates, and used rate of change in K-BIT to classify children into two groups: a decline group and a non-decline group. We then generated predictive models to predict K-BIT decline/non-decline based on regional gray-matter (GM) volumes computed from structural MR images. RESULTS: We identified six structures (the left median cingulate gyrus, the right middle occipital gyrus, the left inferior occipital gyrus, the right fusiform gyrus, the right middle temporal gyrus, the right inferior temporal gyrus) that, when assessed for volume at baseline, are jointly predictive of whether a child would suffer subsequent K-BIT decline. Based on these six regional GM volumes and the baseline K-BIT, we built a prognostic model using the K* algorithm. The accuracy, sensitivity and specificity were 0.84, 0.78 and 0.86, respectively. CONCLUSIONS: GM volumetric analysis predicts subsequent IQ decline for children with SCD.

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OBJECTIVE: Manually segmented traumatic pelvic hematoma volumes are strongly predictive of active bleeding at conventional angiography, but the method is time intensive, limiting its clinical applicability. We compared volumetric analysis using semi-automated region growing segmentation to manual segmentation and diameter-based size estimates in patients with pelvic hematomas after blunt pelvic trauma. MATERIALS AND METHODS: A 14-patient cohort was selected in an anonymous randomized fashion from a dataset of patients with pelvic binders at MDCT, collected retrospectively as part of a HIPAA-compliant IRB-approved study from January 2008 to December 2013. To evaluate intermethod differences, one reader (R1) performed three volume measurements using the manual technique and three volume measurements using the semi-automated technique. To evaluate interobserver differences for semi-automated segmentation, a second reader (R2) performed three semi-automated measurements. One-way analysis of variance was used to compare differences in mean volumes. Time effort was also compared. Correlation between the two methods as well as two shorthand appraisals (greatest diameter, and the ABC/2 method for estimating ellipsoid volumes) was assessed with Spearman's rho (r). RESULTS: Intraobserver variability was lower for semi-automated compared to manual segmentation, with standard deviations ranging between ±5-32 mL and ±17-84 mL, respectively (p = 0.0003). There was no significant difference in mean volumes between the two readers' semi-automated measurements (p = 0.83); however, means were lower for the semi-automated compared with the manual technique (manual: mean and SD 309.6 ± 139 mL; R1 semi-auto: 229.6 ± 88.2 mL, p = 0.004; R2 semi-auto: 243.79 ± 99.7 mL, p = 0.021). Despite differences in means, the correlation between the two methods was very strong and highly significant (r = 0.91, p < 0.001). Correlations with diameter-based methods were only moderate and nonsignificant. Mean semi-automated segmentation time effort was 2 min and 6 s and 2 min and 35 s for R1 and R2, respectively, vs. 22 min and 8 s for manual segmentation. CONCLUSION: Semi-automated pelvic hematoma volumes correlate strongly with manually segmented volumes. Since semi-automated segmentation can be performed reliably and efficiently, volumetric analysis of traumatic pelvic hematomas is potentially valuable at the point-of-care.

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PURPOSE: Electroconvulsive therapy (ECT) is generally contraindicated in patients with intracranial mass lesions or in the presence of increased intracranial pressure. The purpose of this study was to determine the prevalence of incidental abnormalities on routine cross-sectional head imaging, including CT and MRI, that would preclude subsequent ECT. METHODS: This retrospective study involved a review of the electronic medical records of 105 patients (totaling 108 imaging studies) between April 27, 2007, and March 20, 2015, referred for cranial CT or MRI with the primary indication of pre-ECT evaluation. The probability of occurrence of imaging findings that would preclude ECT was computed. A cost analysis was also performed on the practice of routine pre-ECT imaging. RESULTS: Of the 105 patients who presented with the primary indication of ECT clearance (totaling 108 scans), 1 scan (0.93%) revealed findings that precluded ECT. None of the studies demonstrated findings that indicated increased intracranial pressure. A cost analysis revealed that at least $18,662.70 and 521.97 relative value units must be expended to identify one patient with intracranial pathology precluding ECT. CONCLUSIONS: The findings of this study demonstrate an extremely low prevalence of findings that preclude ECT on routine cross-sectional head imaging. The costs incurred in identifying a potential contraindication are high. The authors suggest that the performance of pre-ECT neuroimaging be driven by the clinical examination.

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Using resting-state functional magnetic resonance imaging (rs-fMRI) to study functional connectivity is of great importance to understand normal development and function as well as a host of neurological and psychiatric disorders. Seed-based analysis is one of the most widely used rs-fMRI analysis methods. Here we describe a freely available large scale functional connectivity data mining software package called Advanced Connectivity Analysis (ACA). ACA enables large-scale seed-based analysis and brain-behavior analysis. It can seamlessly examine a large number of seed regions with minimal user input. ACA has a brain-behavior analysis component to delineate associations among imaging biomarkers and one or more behavioral variables. We demonstrate applications of ACA to rs-fMRI data sets from a study of autism.

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Defining brain structures of interest is an important preliminary step in brain-connectivity analysis. Researchers interested in connectivity patterns among brain structures typically employ manually delineated volumes of interest, or regions in a readily available atlas, to limit the scope of connectivity analysis to relevant regions. However, most structural brain atlases, and manually delineated volumes of interest, do not take voxel-wise connectivity patterns into consideration, and therefore may not be ideal for anatomic connectivity analysis. We herein propose a method to parcellate the brain into regions of interest based on connectivity. We formulate connectivity-based parcellation as a graph-cut problem, which we solve approximately using a novel multi-class Hopfield network algorithm. We demonstrate the application of this approach using diffusion tensor imaging data from an ongoing study of schizophrenia. Compared to a standard anatomic atlas, the connectivity-based atlas supports better classification performance when distinguishing schizophrenic from normal subjects. Comparing connectivity patterns averaged across the normal and schizophrenic subjects, we note significant systematic differences between the two atlases.

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Diffusion tensor imaging (DTI) provides connectivity information that helps illuminate the processes underlying normal development as well as brain disorders such as autism and schizophrenia. Researchers have widely adopted graph representations to model DTI connectivity among brain structures; however, most measures of connectivity have been centered on nodes, rather than edges, in these graphs. We present an edge-based algorithm for assessing anatomic connectivity; this approach provides information about connections among brain structures, rather than information about structures themselves. This perspective allows us to formulate multivariate graph-based models of altered connectivity that distinguish among experimental groups. We demonstrate the utility of this approach by analyzing data from an ongoing study of schizophrenia.

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Motor impairment after stroke is related to the integrity of the corticospinal tract (CST). However, considerable variability in motor impairment remains unexplained. To increase the accuracy in evaluating long-term motor function after ischemic stroke, we tested the hypothesis that combining diffusion tensor imaging (DTI) and gray matter (GM) volumetry can better characterize long-term motor deficit than either method alone in patients with chronic stroke. We recruited 31 patients whose Medical Research Council strength grade was ≤ 3/5 in the extensor muscles of the affected upper extremity in the acute phase. We used the Upper Extremity Fugl-Meyer (UE-FM) assessment to evaluate motor impairment, and as the primary outcome variable. We computed the fractional anisotropy ratio of the entire CST (CSTratio) and the volume of interest ratio (VOIratio), between ipsilesional and contralesional hemispheres, to explain long-term motor impairment. The results showed that CSTratio, VOIratio of motor-related brain regions, and VOIratio in the temporal lobe were correlated with UE-FM. A multiple regression model including CSTratio and VOIratio of the caudate nucleus explained 40.7% of the variability in UE-FM. The adjusted R2 of the regression model with CSTratio as an independent variable was 29.4%, and that of using VOIratio of the caudate nucleus as an independent variable was 23.1%. These results suggest that combining DTI and GM volumetry may achieve better explanation of long-term motor deficit in stroke patients, than using either measure individually. This finding may provide guidance in determining optimal neurorehabilitative interventions.

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Dysfunction of brain structural and functional connectivity is increasingly being recognized as playing an important role in many brain disorders. Diffusion tensor imaging (DTI) and functional magnetic resonance (fMR) imaging are widely used to infer structural and functional connectivity, respectively. How to combine structural and functional connectivity patterns for predictive modeling is an important, yet open, problem. We propose a new method, called Bayesian prediction based on multidimensional connectivity profiling (BMCP), to distinguish subjects at the individual level based on structural and functional connectivity patterns. BMCP combines finite mixture modeling and Bayesian network classification. We demonstrate its use in distinguishing young and elderly adults based on DTI and resting-state fMR data.

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OBJECTIVES: We aimed to evaluate the prognostic value of dynamic susceptibility contrast (DSC) MR perfusion in elderly patients with glioblastomas (GBM). METHODS: Thirty five patients aged ≥65 and 35 aged <65 years old, (referred to as elderly and younger, respectively) were included in this retrospective study. The median relative cerebral volume (rCBV) from the enhancing region (rCBVER-Med) and immediate peritumoral region (rCBVIPR-Med) and maximum rCBV from the enhancing region of the tumor (rCBVER-Max) were compared and correlated with survival data. Analysis was repeated after rCBVs were dichotomized into high and low values and after excluding elderly patients who did not receive postoperative chemoradiation (34.3%). Kaplan-Meyer survival curves and parametric and semi-parametric regression tests were used for analysis. RESULTS: All rCBV parameters were higher in elderly compared to younger patients (p < 0.05). After adjustment for age, none were independently associated with shorter survival (p > 0.05). After rCBV dichotomization into high and low values, high rCBV in elderly was independently associated with shorter survival compared to low rCBV in elderly, or any rCBV in younger patients (p < 0.05). CONCLUSION: rCBV can be an imaging biomarker to identify a subgroup of GBM patients in the elderly with worse prognosis compared to others. KEY POINTS: • GBM perfusion parameters are higher in elderly compared to younger patients. • rCBV can identify a subgroup of elderly patients with worse prognosis. • rCBV can be an imaging biomarker for prognostication in GBM. • The identified elderly patients may benefit from anti-angiogenic treatment.

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BACKGROUND: Classifying individuals based on magnetic resonance data is an important task in neuroscience. Existing brain network-based methods to classify subjects analyze data from a cross-sectional study and these methods cannot classify subjects based on longitudinal data. We propose a network-based predictive modeling method to classify subjects based on longitudinal magnetic resonance data. NEW METHOD: Our method generates a dynamic Bayesian network model for each group which represents complex spatiotemporal interactions among brain regions, and then calculates a score representing that subject's deviation from expected network patterns. This network-derived score, along with other candidate predictors, are used to construct predictive models. RESULTS: We validated the proposed method based on simulated data and the Alzheimer's Disease Neuroimaging Initiative study. For the Alzheimer's Disease Neuroimaging Initiative study, we built a predictive model based on the baseline biomarker characterizing the baseline state and the network-based score which was constructed based on the state transition probability matrix. We found that this combined model achieved 0.86 accuracy, 0.85 sensitivity, and 0.87 specificity. COMPARISON WITH EXISTING METHODS: For the Alzheimer's Disease Neuroimaging Initiative study, the model based on the baseline biomarkers achieved 0.77 accuracy. The accuracy of our model is significantly better than the model based on the baseline biomarkers (p-value=0.002). CONCLUSIONS: We have presented a method to classify subjects based on structural dynamic network model based scores. This method is of great importance to distinguish subjects based on structural network dynamics and the understanding of the network architecture of brain processes and disorders.

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Automated brain tumor image segmentation with high accuracy and reproducibility holds a big potential to enhance the current clinical practice. Dictionary learning (DL) techniques have been applied successfully to various image processing tasks recently. In this work, kernel extensions of the DL approach are adopted. Both reconstructive and discriminative versions of the kernel DL technique are considered, which can efficiently incorporate multi-modal nonlinear feature mappings based on the kernel trick. Our novel discriminative kernel DL formulation allows joint learning of a task-driven kernel-based dictionary and a linear classifier using a K-SVD-type algorithm. The proposed approaches were tested using real brain magnetic resonance (MR) images of patients with high-grade glioma. The obtained preliminary performances are competitive with the state of the art. The discriminative kernel DL approach is seen to reduce computational burden without much sacrifice in performance.

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Establishing relationships among brain structures and cognitive functions is a central task in cognitive neuroscience. Existing methods to establish associations among a set of function variables and a set of brain regions, such as dissociation logic and conjunction analysis, are hypothesis-driven. We propose a new data-driven approach to structure-function association analysis. We validated it by analyzing a simulated atrophy study. We applied the proposed method to a study of aging and dementia. We found that the most significant age-related and dementia-related volume reductions were in the hippocampal formation and the supramarginal gyrus, respectively. These findings suggest a multi-component brain-aging model.

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