A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms

Accurate lesion segmentation is critical in stroke rehabilitation research for the quantifcation of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in stroke research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-consuming, subjective, and requires neuroanatomical expertise. We previously released an open-source dataset of stroke T1w MRIs and manually-segmented lesion masks (ATLAS v1.2, N=304) to encourage the development of better algorithms. However, many methods developed with ATLAS v1.2 report low accuracy, are not publicly accessible or are improperly validated, limiting their utility to the feld. Here we present ATLAS v2.0 (N=1271), a larger dataset of T1w MRIs and manually segmented lesion masks that includes training (n=655), test (hidden masks, n=300), and generalizability (hidden MRIs and masks, n=316) datasets. Algorithm development using this larger sample should lead to more robust solutions; the hidden datasets allow for unbiased performance evaluation via segmentation challenges. We anticipate that ATLAS v2.0 will lead to improved algorithms, facilitating large-scale stroke research.Sook-Lei Liew ... Brenton G. Hordacre ... et al

Abnormally reduced primary motor cortex output is related to impaired hand function in chronic stroke

Item does not contain fulltextBackground: Stroke often involves primary motor cortex (M1) and its corticospinal projections (CST). As hand function is critically dependent on these structures, its recovery is often incomplete. The neuronal substrate supporting affected hand function is not well understood but likely involves reorganized M1 and CST of the lesioned hemisphere (M1IL and CSTIL). Objective: We hypothesized that affected hand function in chronic stroke is related to structural and functional reorganization of M1IL and CSTIL. Methods: We tested 18 patients with chronic ischemic stroke involving M1 or CST. Their hand function was compared to 18 age matched healthy subjects. M1IL thickness and CSTIL fractional anisotropy (FA) were determined with MRI and compared to measures of the other hemisphere. Transcranial magnetic stimulation (TMS) was applied to M1IL to determine its input output function (stimulus response curve, SRC). The plateau of the SRC (MEPmax), inflection point and slope parameters of the curve were extracted. Results were compared to measures in 12 age matched healthy controls. Results: MEPmax of M1IL was significantly smaller (p=0.02) in the patients, indicating reduced CSTIL motor output, and was correlated with impaired hand function (p=0.02). M1IL thickness (p>0.01) and CSTIL-FA (p>0.01) were reduced but did not correlate with hand function. Conclusions: The results indicate that employed M1IL or CSTIL structural measures do not explain the extent of impairment in hand function once M1 and CST are sufficiently functional for TMS to evoke a motor potential. Instead, impairment of hand function is best explained by the abnormally low output from M1IL.15 p

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis

BACKGROUND: Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. METHODS AND RESULTS: Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=−0.26) and contralesional (P=0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=−0.21) and extent of sensorimotor damage (P=0.003; β=−0.15). CONCLUSIONS: The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.Artemis Zavaliangos-Petropulu, PhD, Bethany Lo, BSc, Miranda R. Donnelly, MS, Nicolas Schweighofer, PhD, Keith Lohse, PhD, PStat, Neda Jahanshad, PhD, Giuseppe Barisano, MD, Nerisa Banaj, PhD, Michael R. Borich, PhD, Lara A. Boyd, PhD, Cathrin M. Buetefisch, MD, PhD, Winston D. Byblow, PhD, Jessica M. Cassidy, PhD, Charalambos C. Charalambous, PhD, Adriana B. Conforto, PhD, Julie A. DiCarlo, MSc, Adrienne N. Dula, PhD, Natalia Egorova-Brumley, PhD, Mark R. Etherton, MD, PhD, Wuwei Feng, MD, Kelene A. Fercho, PhD, Fatemeh Geranmayeh, PhD, Colleen A. Hanlon, PhD, Kathryn S. Hayward, PhD, Brenton Hordacre, PhD, Steven A. Kautz, PhD, Mohamed Salah Khlif, PhD, Hosung Kim, PhD, Amy Kuceyeski, PhD, David J. Lin, MD, Jingchun Liu, MD, Martin Lotze, MD, Bradley J. MacIntosh, PhD, John L. Margetis, OTD, Feroze B. Mohamed, PhD, Fabrizio Piras, PhD, Ander Ramos-Murguialday, PhD, Kate P. Revill, PhD, Pamela S. Roberts, PhD, Andrew D. Robertson, PhD, Heidi M. Schambra, MD, Na Jin Seo, PhD, Mark S. Shiroishi, MD, Cathy M. Stinear, PhD, Surjo R. Soekadar, MD, Gianfranco Spalletta, MD, PhD, Myriam Taga, PhD, Wai Kwong Tang, MD, Gregory T. Thielman, EdD, Daniela Vecchio, PhD, Nick S. Ward, MD, Lars T. Westlye, PhD, Emilio Werden, PhD, Carolee Winstein, PhD, PT, George F. Wittenberg, MD, PhD, Steven L. Wolf, PhD, Kristin A. Wong, MD, Chunshui Yu, MD, Amy Brodtmann, MD, PhD, Steven C. Cramer, MD, Paul M. Thompson, PhD, Sook-Lei Liew, PhD, OTR,

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. Here, we examined the impact of brain age, a measure of neurobiological aging derived from whole brain structural neuroimaging, on post-stroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good versus poor outcomes. METHODS: We conducted a cross-sectional observational study using a multi-site dataset of 3D brain structural MRIs and clinical measures from ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a three-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good versus poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β=0.21; 95% CI 0.04,0.38, P=0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (β=-0.28; 95% CI: -0.41,-0.15, P<0.001) and across multiple domains of function (β=-0.14; 95% CI: -0.22,-0.06, P<0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI: 3%,58%, P=0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (OR=1.04, 95% CI: 1.01,1.08, P=0.004). CONCLUSIONS: We provide evidence that younger brain age is associated with superior post-stroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of post-stroke outcomes compared to focal injury measures alone, opening new possibilities for potential therapeutic targets.Sook-Lei Liew ... Brenton Hordacre ... et al