Publications by Year: 2021

AD is the highly severe part of the dementia spectrum and impairs cognitive abilities of individuals, bringing economic, societal and psychological burdens beyond the diseased. A promising approach in AD research is the analysis of structural and functional brain connectomes, i.e., sNETs and fNETs, respectively. We propose to use tensor representation (B-tensor) of uni-modal and multi-modal brain connectomes to define a low-dimensional space via tensor factorization. We show on a cohort of 47 subjects, spanning the spectrum of dementia, that diagnosis with an accuracy of 77% to 100% is achievable in a 5D connectome space using different structural and functional connectome constructions in a uni-modal and multi-modal fashion. We further show that multi-modal tensor factorization improves the results suggesting complementary information in structure and function. A neurological assessment of the connectivity patterns identified largely agrees with prior knowledge, yet also suggests new associations that may play a role in the disease progress.

RATIONALE AND OBJECTIVES: Bronchiectasis (BE) is associated with chronic obstructive pulmonary disease (COPD), but emphysema and small airways disease, main pathologic features of COPD, have been sparsely studied in BE. We aimed to objectively assess those features in smokers with and without radiographic BE and examine its relationships to airflow obstruction and exercise capacity. MATERIAL AND METHODS: We measured emphysema and small airways disease on paired inspiratory-expiratory computed tomography (CT) scans with the parametric response map (PRM and PRM) method in 1184 smokers with and without radiographic BE. PRM and PRM are expressed as the percentage of lung area. Clinical, spirometry, and exercise capacity data were measured with standardized methods. The differences in PRM and PRM between subjects with and without radiographic BE were assessed using multivariable linear regression analysis, and their associations with FEV and six-minute walk test (6MWT) were assessed with generalized linear models. RESULTS: Out of 1184 subjects, 383 (32%) had radiographic BE. PRM but not PRM was higher in subjects with radiographic BE than those without radiographic BE in adjusted models. Subjects with radiographic BE and PRM (defined as >=5% on paired CTs) had lower FEV (least square mean, 1479 mL vs. 2350 mL p < 0.0001) and 6MWT (372 m vs. 426 m p = 0.0007) than those with radiographic BE alone in adjusted models. CONCLUSION: Smokers with radiographic BE have an increased burden of emphysema on paired CTs, and those with radiographic BE and emphysema have lower airflow and exercise capacity.

Compared to healthy controls (HCs), individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit more symptoms of sensory processing disorder (SPD), which is associated with difficulties in educational and social activities. Most studies examining comorbid SPD-ADHD have been conducted with children and have not explored relations to brain volumes. In this pilot study, we assessed a subtype of SPD, sensory modulation disorder (SMD), and its relation to select brain volumes in adults with ADHD. We administered part of the Sensory Processing 3-Dimensions Scale (SP3D) to assess subtypes of SMD and collected structural imaging scans from 25 adults with ADHD and 29 healthy controls (HCs). Relative to HCs, subjects with ADHD scored higher on sensory craving (SC) and sensory under-responsivity (SUR) subscales. Although sensory over-responsivity (SOR) was marginally higher, this was no longer true when accounting for co-occurring anxiety. In individuals with ADHD, both SC and SUR were positively associated with amygdalar volume, SUR was also positively associated with striatal volume, whereas SOR was negatively associated with posterior ventral diencephalon volume. These preliminary findings suggest that SC and SUR may be characteristic of ADHD while SOR may be driven by co-occurring anxiety. Because different modalities were associated with different brain volumes, our findings also suggest that the modalities may involve unique neural circuits, but with a partial overlap between SC and SUR. These pilot data provide support for conducting studies examining SMD in larger samples of adults with ADHD to determine reproducibility, applicability and implications of these findings.

OBJECTIVES: It is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP). METHODS: Twenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FA), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed. RESULTS: There were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP ( < 0.05). FA changes in CHR-P were associated with significantly lower FA and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP. CONCLUSIONS: Our study suggests that cellular (FA) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals.

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor.

BACKGROUND: In the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission. STUDY DESIGN AND METHODS: We conducted a retrospective multicenter study from two CTLS cohorts: Lahey Hospital and Medical Center (LHMC) CTLS program, Burlington, MA and Mount Auburn Hospital (MAH) CTLS program, Cambridge, MA. CTLS exams were qualitatively scored by radiologists at time of screening for presence of emphysema. Multivariable Cox regression models were used to evaluate the association between CT qualitative emphysema and all-cause, COPD-related, and pneumonia-related hospital admission. RESULTS: We included 4673 participants from the LHMC cohort and 915 from the MAH cohort. 57% and 51.9% of the LHMC and MAH cohorts had presence of CT emphysema, respectively. In the LHMC cohort, the presence of emphysema was associated with all-cause hospital admission (HR 1.15, CI 1.07-1.23; p < 0.001) and COPD-related admission (HR 1.64; 95% CI 1.14-2.36; p = 0.007), but not with pneumonia-related admission (HR 1.52; 95% CI 1.27-1.83; p < 0.001). In the MAH cohort, the presence of emphysema was only associated with COPD-related admission (HR 2.05; 95% CI 1.07-3.95; p = 0.031). CONCLUSION: Qualitative CT assessment of emphysema is associated with COPD-related hospital admission in a CTLS population. Identification of emphysema on CLTS exams may provide an opportunity for prevention and early intervention to reduce admission risk.

BACKGROUND: Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration. METHODS: A diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons. RESULTS: Compared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients. CONCLUSIONS: In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.

In this work, we present an unsupervised domain adaptation (UDA) method, named Panoptic Domain Adaptive Mask R-CNN (PDAM), for unsupervised instance segmentation in microscopy images. Since there currently lack methods particularly for UDA instance segmentation, we first design a Domain Adaptive Mask R-CNN (DAM) as the baseline, with cross-domain feature alignment at the image and instance levels. In addition to the image- and instance-level domain discrepancy, there also exists domain bias at the semantic level in the contextual information. Next, we, therefore, design a semantic segmentation branch with a domain discriminator to bridge the domain gap at the contextual level. By integrating the semantic- and instance-level feature adaptation, our method aligns the cross-domain features at the panoptic level. Third, we propose a task re-weighting mechanism to assign trade-off weights for the detection and segmentation loss functions. The task re-weighting mechanism solves the domain bias issue by alleviating the task learning for some iterations when the features contain source-specific factors. Furthermore, we design a feature similarity maximization mechanism to facilitate instance-level feature adaptation from the perspective of representational learning. Different from the typical feature alignment methods, our feature similarity maximization mechanism separates the domain-invariant and domain-specific features by enlarging their feature distribution dependency. Experimental results on three UDA instance segmentation scenarios with five datasets demonstrate the effectiveness of our proposed PDAM method, which outperforms state-of-the-art UDA methods by a large margin.

BACKGROUND AND PURPOSE: Lower reward responsiveness has been associated with fatigue in multiple sclerosis (MS). However, association of MS-related fatigue with damage to the mesocorticolimbic reward pathway (superolateral medial forebrain bundle [slMFB]) has not been assessed. We investigated the association of fatigue and depression with slMFB damage in MS patients stratified based on longitudinal fatigue patterns. METHODS: Patient stratification: 1. Sustained Fatigue (SF): latest two Modified Fatigue Impact Scale (MFIS) >= 38 (n = 26); 2. Reversible Fatigue (RF): latest MFIS < 38, and at least one previous MFIS >= 38 (n = 25); 3. Never Fatigued (NF): >= 5 consecutive MFIS < 38 (n = 42); 4. Healthy Controls (n = 6). Diffusion MRI-derived measures of fractional anisotropy (FA), axial (AD), mean (MD), and radial diffusivity (RD) of the slMFB were compared between the groups. Depression was assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: Depressed (CES-D >= 16) SF patients showed significantly higher MD and RD than nondepressed SF and RF, and depressed RF patients, and significantly lower FA than nondepressed SF and depressed RF patients in their left slMFB. Depressed SF patients showed significantly higher left slMFB MD and AD than healthy controls. CONCLUSION: Microstructural changes to the left slMFB may play a role in the comorbid development of fatigue and depression in MS.