Publications

2020

Hegde RR, Kelly S, Lutz O, Guimond S, Karayumak SC, Mike L, Mesholam-Gately RI, Pasternak O, Kubicki M, Eack SM, et al. Association of white matter microstructure and extracellular free-water with cognitive performance in the early course of schizophrenia. Psychiatry Res Neuroimaging. 2020;305:111159. doi:10.1016/j.pscychresns.2020.111159
Schizophrenia (SZ) is proposed as a disorder of dysconnectivity underlying cognitive impairments and clinical manifestations. Although previous studies have shown extracellular changes in white matter of first-episode SZ, little is known about the transition period towards chronicity and its association with cognition. Free-water (FW) imaging was applied to 79 early course SZ participants and 29 controls to detect white matter axonal and extracellular differences during this phase of illness. Diffusion-weighted images were collected from two sites, harmonized, and processed using a pipeline separately modeling water diffusion in tissue (FAt) and extracellular space (FW). Tract-Based Spatial Statistics was performed using the ENIGMA-DTI protocols. SZ showed FAt reductions in the posterior thalamic radiation (PTR) and FW elevations in the cingulum compared to controls, suggesting FAt and FW changes in the early course of SZ. In SZ, greater FAt of the fornix & stria terminalis (FXST) was positively associated with Theory of Mind performance; average whole-brain FAt, FAt of the FXST and the PTR were positively associated with greater working memory performance; average whole-brain FAt was positively associated with visual learning. Further studies are necessary to better understand the neurobiological mechanisms of SZ for developing intervention strategies to preserve brain structure and function.
Washko GR, Nardelli P, Ash SY, Rahaghi FN, Sanchez-Ferrero GV, Come CE, Dransfield MT, Kalhan R, Han MK, Bhatt SP, et al. Smaller Left Ventricle Size at Noncontrast CT Is Associated with Lower Mortality in COPDGene Participants. Radiology. 2020;296(1):208–215. doi:10.1148/radiol.2020191793
Background Smokers with chronic obstructive pulmonary disease (COPD) have smaller left ventricles (LVs) due to reduced preload. Skeletal muscle wasting is also common in COPD, but less is known about its contribution to LV size. Purpose To explore the relationships between CT metrics of emphysema, venous vascular volume, and sarcopenia with the LV epicardial volume (LV) (myocardium and chamber) estimated from chest CT images in participants with COPD and then to determine the clinical relevance of the LV in multivariable models, including sex and anthropomorphic metrics. Materials and Methods The COPDGene study (ClinicalTrials.gov identifier: NCT00608764) is an ongoing prospective longitudinal observational investigation that began in 2006. LV, distal pulmonary venous blood volume for vessels smaller than 5 mm in cross section (BV5), CT emphysema, and pectoralis muscle area were retrospectively extracted from 3318 nongated, unenhanced COPDGene CT scans. Multivariable linear and Cox regression models were used to explore the association between emphysema, venous BV5, pectoralis muscle area, and LV as well as the association of LV with health status using the St George’s Respiratory Questionnaire, 6-minute walk distance, and all-cause mortality. Results The median age of the cohort was 64 years (interquartile range, 57-70 years). Of the 2423 participants, 1806 were men and 617 were African American. The median LV between Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 and GOLD 4 COPD was reduced by 13.9% in women and 17.7% in men ( .001 for both). In fully adjusted models, higher emphysema percentage (β = -4.2; 95% confidence interval [CI]: -5.0, -3.4; .001), venous BV5 (β = 7.0; 95% CI: 5.7, 8.2; .001), and pectoralis muscle area (β = 2.7; 95% CI: 1.2, 4.1; .001) were independently associated with reduced LV. Reductions in LV were associated with improved health status (β = 0.3; 95% CI: 0.1, 0.4) and 6-minute walk distance (β = -12.2; 95% CI: -15.2, -9.3). These effects were greater in women than in men. The effect of reduced LV on mortality (hazard ratio: 1.07; 95% CI: 1.05, 1.09) did not vary by sex. Conclusion In women more than men with chronic obstructive pulmonary disease, a reduction in the estimated left ventricle epicardial volume correlated with a loss of pulmonary venous vasculature, greater pectoralis muscle sarcopenia, and lower all-cause mortality. © RSNA, 2020
Hansson B, Bloch KM, Owman T, Nilsson M, Lätt J, Olsrud J, Björkman-Burtscher IM. Subjectively Reported Effects Experienced in an Actively Shielded 7T MRI: A Large-Scale Study. J Magn Reson Imaging. 2020;52(4):1265–1276. doi:10.1002/jmri.27139
BACKGROUND: Ultrahigh-field (UHF) MRI advances towards clinical use. Patient compliance is generally high, but few large-scale studies have investigated the effects experienced in 7T MRI systems, especially considering peripheral nerve stimulation (PNS) and caregiving. PURPOSE: To evaluate the quantity, the intensity, and subjective experiences from short-term effects, focusing on the levels of comfort and compliance of subjects. STUDY TYPE: Prospective. POPULATION: In all, 954 consecutive MRIs in 801 subjects for 3 years. FIELD STRENGTH: 7T. ASSESSMENT: After the 7T examination, a questionnaire was used to collect data. STATISTICAL TESTS: Descriptive statistics, Spearman’s rank correlation, Mann-Whitney U-test, and t-test.
Lampinen B, Zampeli A, Björkman-Burtscher IM, Szczepankiewicz F, en KK, Strandberg MC, Nilsson M. Tensor-valued diffusion MRI differentiates cortex and white matter in malformations of cortical development associated with epilepsy. Epilepsia. 2020;61(8):1701–1713. doi:10.1111/epi.16605
OBJECTIVE: Delineation of malformations of cortical development (MCD) is central in presurgical evaluation of drug-resistant epilepsy. Delineation using magnetic resonance imaging (MRI) can be ambiguous, however, because the conventional T - and T -weighted contrasts depend strongly on myelin for differentiation of cortical tissue and white matter. Variations in myelin content within both cortex and white matter may cause MCD findings on MRI to change size, become undetectable, or disagree with histopathology. The novel tensor-valued diffusion MRI (dMRI) technique maps microscopic diffusion anisotropy, which is sensitive to axons rather than myelin. This work investigated whether tensor-valued dMRI may improve differentiation of cortex and white matter in the delineation of MCD.
Zhang F, Noh T, Juvekar P, Frisken SF, Rigolo L, Norton I, Kapur T, Pujol S, Wells W, Yarmarkovich A, et al. SlicerDMRI: Diffusion MRI and Tractography Research Software for Brain Cancer Surgery Planning and Visualization. JCO Clin Cancer Inform. 2020;4:299–309. doi:10.1200/CCI.19.00141
PURPOSE: We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health-supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors. PATIENTS AND METHODS: In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI. RESULTS: We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each. CONCLUSION: SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.
Finsterwalder S, Vlegels N, Gesierich B, Caballero M \ AA, Weaver NA, Franzmeier N, Georgakis MK, Konieczny MJ, Koek HL, Karch CM, et al. Small vessel disease more than Alzheimer’s disease determines diffusion MRI alterations in memory clinic patients. Alzheimers Dement. 2020;16(11):1504–1514. doi:10.1002/alz.12150
INTRODUCTION: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer’s disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations.
Baxi M, Di Biase MA, Lyall AE, Cetin-Karayumak S, Seitz J, Ning L, Makris N, Rosene D, Kubicki M, Rathi Y. Quantifying Genetic and Environmental Influence on Gray Matter Microstructure Using Diffusion MRI. Cereb Cortex. 2020;30(12):6191–6205. doi:10.1093/cercor/bhaa174
Early neuroimaging work in twin studies focused on studying genetic and environmental influence on gray matter macrostructure. However, it is also important to understand how gray matter microstructure is influenced by genes and environment to facilitate future investigations of their influence in mental disorders. Advanced diffusion MRI (dMRI) measures allow more accurate assessment of gray matter microstructure compared with conventional diffusion tensor measures. To understand genetic and environmental influence on gray matter, we used diffusion and structural MRI data from a large twin and sibling study (N = 840) and computed advanced dMRI measures including return to origin probability (RTOP), which is heavily weighted toward intracellular and intra-axonal restricted spaces, and mean squared displacement (MSD), more heavily weighted to diffusion in extracellular space and large cell bodies in gray matter. We show that while macrostructural features like brain volume are mainly genetically influenced, RTOP and MSD can together tap into both genetic and environmental influence on microstructure.
Kinzel P, Marx CE, Sollmann N, Hartl E, Guenette JP, Kaufmann D, Bouix S, Pasternak O, Rathi Y, Coleman MJ, et al. Serum Neurosteroid Levels Are Associated With Cortical Thickness in Individuals Diagnosed With Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury. Clin EEG Neurosci. 2020;51(4):285–299. doi:10.1177/1550059420909676
Posttraumatic stress disorder (PTSD) co-occurring with mild traumatic brain injury (mTBI) is common in veterans. Worse clinical outcome in those with PTSD has been associated with decreased serum neurosteroid levels. Furthermore, decreased cortical thickness has been associated with both PTSD and mTBI. However, it is not known whether decreased neurosteroids are associated with decreased cortical thickness in PTSD co-occurring with mTBI. This study included 141 individuals divided into the following groups: () mTBI group (n = 32 [10 female, 22 male] veterans with a history of mTBI); () PTSD + mTBI group (n = 41 [6 female, 35 male] veterans with current PTSD with a history of mTBI); and () control group (n = 68 [35 female, 33 male] control participants), which were acquired through the Injury and Traumatic Stress (INTRuST) Clinical Consortium. Subjects underwent clinical assessment, magnetic resonance imaging at 3 T, and serum neurosteroid quantifications of allopregnanolone (ALLO) and pregnenolone (PREGN). Group differences in cortical thickness and associations between serum neurosteroid levels and cortical thickness were investigated. Cortical thickness was decreased in the PTSD + mTBI group compared with the other groups. In the PTSD + mTBI group, decreased cortical thickness was also associated with lower serum ALLO (right superior frontal cortex) and lower serum PREGN (left middle temporal and right orbitofrontal cortex). Cortical thickness in the middle temporal and orbitofrontal cortex was associated with PTSD symptom severity. There were no significant associations between neurosteroids and cortical thickness in the mTBI or control groups. Decreased cortical thickness in individuals with PTSD + mTBI is associated with decreased serum neurosteroid levels and greater PTSD symptom severity. Causality is unclear. However, future studies might investigate whether treatment with neurosteroids could counteract stress-induced neural atrophy in PTSD + mTBI by potentially preserving cortical thickness.
Pallanti S, Grassi E, Makris N, Gasic GP, Hollander E. Neurocovid-19: A clinical neuroscience-based approach to reduce SARS-CoV-2 related mental health sequelae. J Psychiatr Res. 2020;130:215–217. doi:10.1016/j.jpsychires.2020.08.008
Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, is a disaster due to not only its psychosocial impact but it also to its direct effects on the brain. The latest evidence suggests it has neuroinvasive mechanisms, in addition to neurological manifestations, and as seen in past pandemics, long-term sequelae are expected. Specific and well-structured interventions are necessary, and that’s why it’s important to ensure a continuity between primary care, emergency medicine, and psychiatry. Evidence shows that 2003 SARS (Severe Acute Respiratory Syndrome) survivors developed persistent psychiatric comorbidities after the infection, in addition to Chronic Fatigue Syndrome. A proper stratification of patients according not only to psychosocial factors but also an inflammatory panel and SARS-Cov-2’s direct effects on the central nervous system (CNS) and the immune system, may improve outcomes. The complexity of COVID-19’s pathology and the impact on the brain requires appropriate screening that has to go beyond the psychosocial impact, taking into account how stress and neuroinflammation affects the brain. This is a call for a clinical multidisciplinary approach to treat and prevent Sars-Cov-2 mental health sequelae.