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Research Objective: Post-coronavirus disease 2019 condition (PCC) is prevalent, with high socioeconomic and healthcare burden internationally. Many common PCC symptoms suggest brain injury, but the underlying biological mechanisms remain poorly understood. Towards filling this knowledge gap and developing targeted brain treatments, the NeuroCOVID19 study commenced in spring 2020 involving detailed magnetic resonance imaging (MRI) of the brain; electroencephalography; and assessment of symptoms and behaviors[1]. Notably, dynamic susceptibility contrast (DSC) MRI is included to assess cerebral microvessel pathophysiology [2], and test whether DSC cerebral blood flow (CBF) and vascular leakage parameter K2 are altered in PCC individuals compared to controls. Methods: To date, DSC data have been collected for 14 healthy controls (9 female (F), mean (standard deviation) age = 44(13)), and 63 PCC participants (55 self-isolated while infected, 37 F, age = 42(12); 8 hospitalized while infected, 5 F, age=54(11)). DSC MRI was performed at 3 T (1.74 mm in-plane resolution, 8 mm slices, 140 time points, 1.25 s temporal resolution) using Gadovist contrast agent. Data were analyzed with a custom pipeline to generate CBF and K2 maps (see representative healthy control data, Fig. 1) followed by voxel-wise two-tailed t-tests with correction for multiple comparisons. Results/Conclusions: No statistically significant group differences were observed, but there were notable trends between self-isolated PCC individuals and controls for CBF and K2 when a region of interest analysis was conducted for the thalamus - consistent with previous NeuroCOVID19 CBF results obtained using arterial spin labeling[3], and with reports that leaky brain vasculature elevates risk of acute COVID19[1]. These results help confirm that there are observable changes in cerebrovascular physiological parameters due to PCC, either as a direct or indirect consequence of SARS-CoV2 infection. 1. Macintosh BJ et al., CMAJ Open 2021.2. Boxerman JL et al., AJNR 2006.3. Kim WSH et al., JMRI 2022.
Sunday, November 12, 2023 at 1:00 PM-5:00 PM
The coronavirus disease 2019 (COVID-19) represents an unprecedented public health crisis. These is also growing evidence that the disease affects the central nervous system, via both direct and indirect pathways. These effects may be long-lasting, with growing case numbers of post-acute COVID-19 syndrome (PACS), in which symptoms and neurological issues persist more than 12 weeks post-infection. Among the symptoms associated with PACS, fatigue is a major concern, given its high prevalence and impact on daily functioning. In other disorders with high rates of fatigue, subcortical structures are frequently implicated, such as the brainstem, basal ganglia and thalamus. These areas are also vulnerable to COVID-related injury, identified via clinical imaging and neuropathology. Hence, imaging biomarkers of microstructural injury that correlate with post-COVID fatigue are of significant interest. A promising approach to this challenge is texture-based analysis (TBA) of structural brain scans. This approach can provide information about subtle changes in tissue microstructure that cannot be discerned by eye. In the present study, we apply TBA to subcortical structures of T1-weighted anatomical scans collected as part of the Toronto-based NeuroCOVID-19 study. We compared Haralick texture features for self-isolating individuals who tested positive for SARS-CoV-2 and had persistent symptoms, along with controls who had cold or flulike symptoms but tested negative for SARS-CoV-2, with both groups imaged an average of 4-5 months after COVID testing. Significant differences were seen in grey matter texture for COVID-19 patients with persistent fatigue, relative to both COVID-19 patients without fatigue and controls. This included decreased Energy (-15.0% ± 2.1%) and increased Entropy (7.9% ± 1.0%) in the brain stem and thalamus, along with decreased Correlation (-25.3% ± 4.1%) in the putamen, all at p<0.001. These findings provide encouraging evidence for abnormal tissue texture as a biomarker of post-COVID fatigue, providing new insights into this highly prevalent disorder.
Sunday, November 12, 2023 at 1:00 PM-5:00 PM
There is evidence that traumatic brain injury (TBI) has long-term consequences for brain health, including an increased risk for dementia and progressive brain atrophy. To date, however, there has been little direct examination of how TBI affects the rate of neurodegeneration for individuals with Alzheimer’s disease (AD). The present study examined this issue using a mixed design approach, applied to a cohort of 1124 participants from the National Alzheimer’s Coordinating Center (NACC) including 343 with AD, 127 with AD with TBI, 266 cognitively normal adults with TBI, and 388 cognitively normal adults without TBI. For these groups, cortical thickness measures were obtained from T1-weighted magnetic resonance imaging (MRI) data using FreeSurfer and in-house software. An initial cross-sectional analysis of this group at baseline used multiple linear regression to determine the interaction effects of AD and TBI on measures of cortical thickness. Among those with AD, TBI was associated with an earlier age of AD onset but, counter-intuitively, less cortical thinning in fronto-temporal regions, relative to non-AD controls. The results suggest that AD with TBI represents a physiologically distinct group from AD at baseline assessment. A second longitudinal analysis of this group used a partial least squares approach to measure group differences in the longitudinal change of cortical thickness values, for a subset of 154 participants with follow-up scans, assessed over an average time span of 33 months. The AD groups with and without TBI history more strongly expressed patterns of longitudinal frontal and temporal atrophy, while the cognitively normal control group displayed an intermediate pattern of atrophy, and the cognitively normal TBI group expressed the least atrophy. Further, comparison of AD and AD+TBI to their respective control groups showed a more pronounced effect of AD for the TBI groups. These results provide preliminary evidence of a relationship between TBI history and risk of accelerated cortical thinning in frontal and temporal regions. An improved understanding of the long-term outcomes of TBI has the potential to aid in the diagnosis and treatment of individuals with AD combined with history of TBI.
*G. M. D'SOUZA1,2, , N.W. CHURCHILL2,3, D. X. GUAN4, M. A. KHOURY1,2, S. J. GRAHAM1,5, S. KUMAR1,6, C. E. FISCHER1,2, T. A. SCHWEIZER1,2 1Univ. of Toronto, Toronto, ON, Canada; 2St. Michael's Hosp., Toronto, ON, Canada; 3Toronto Metropolitan Univ., Toronto, ON, Canada; 4Univ. of Calgary, Calgary, AB, Canada; 5Sunnybrook Res. Inst., Toronto, ON, Canada; 6Ctr. for Addiction and Mental Hlth., Toronto, ON, Canada
Wednesday, November 15, 2023 at 8:00 AM-12:00 PM
Concussion is a major health concern, with an estimated 4 million cases occurring annually in sport and recreation in North America alone. Recent neuroimaging studies have raised concerns about persistent post-concussion brain changes, suggesting that recovery of brain function is incomplete at medical clearance, potentially the increasing risk of subsequent injury. However, these studies are cross-sectional in design, comparing brain networks of concussed individuals to uninjured controls. It is essential that we measure how brain function is altered relative to its "pre-injury" state, in order to determine whether it has truly recovered at medical clearance or shows persistent changes. In this study, a large sample of 167 varsity athletes had resting-state functional magnetic resonance imaging (fMRI) collected at pre-season baseline. Of this cohort, 25 were later concussed, with imaging at acute injury, medical clearance, and up to one year later. An additional 27 athletes without concussion were re-imaged as controls. Concussed athletes showed significant post-concussion declines in anterior brain connectivity lasting beyond medical clearance. This study provides the first characterization of brain function after concussion, relative to the pre-injury brain. The results of this study indicate that disturbances in connectivity are present at and beyond medical clearance, highlighting the complex, long-term nature of recovery after injury.
N. CHURCHILL1, M. HUTCHISON2, S. J. GRAHAM3, *T. SCHWEIZER2; 1St. Michael's Hosp., Toronto, ON, Canada; 2Univ. of Toronto, Toronto, ON, Canada; 3Research, Physical Sci., Sunnybrook Hlth. Sci. Ctr., Toronto, ON, Canada
Wednesday, November 15, 2023 at 8:00AM-12:00 PM
Sunday, November 12, 2023 at 1:00 PM-5:00 PM