Comparison of Diffusion Tensor Imaging Metrics in Normal-Appearing White Matter to Cerebrovascular Lesions and Correlation with Cerebrovascular Disease Risk Factors and Severity

Seyyed M H Haddad; Christopher J M Scott; Miracle Ozzoude; Courtney Berezuk; Melissa Holmes; Sabrina Adamo; Joel Ramirez; Stephen R Arnott; Nuwan D Nanayakkara; Malcolm Binns; Derek Beaton; Wendy Lou; Kelly Sunderland; Sujeevini Sujanthan; Jane Lawrence; Donna Kwan; Brian Tan; Leanne Casaubon; Jennifer Mandzia; Demetrios Sahlas; Gustavo Saposnik; Ayman Hassan; Brian Levine; Paula McLaughlin; J B Orange; Angela Roberts; Angela Troyer; Sandra E Black; Dar Dowlatshahi; Stephen C Strother; Richard H Swartz; Sean Symons; Manuel Montero-Odasso; Ondri Investigators; Robert Bartha

doi:10.1155/2022/5860364

Comparison of Diffusion Tensor Imaging Metrics in Normal-Appearing White Matter to Cerebrovascular Lesions and Correlation with Cerebrovascular Disease Risk Factors and Severity

Int J Biomed Imaging. 2022 Oct 21:2022:5860364. doi: 10.1155/2022/5860364. eCollection 2022.

Authors

Seyyed M H Haddad¹, Christopher J M Scott^{2

3}, Miracle Ozzoude^{2

3}, Courtney Berezuk⁴, Melissa Holmes^{2

3}, Sabrina Adamo⁵, Joel Ramirez^{2

3}, Stephen R Arnott⁶, Nuwan D Nanayakkara¹, Malcolm Binns⁶, Derek Beaton⁶, Wendy Lou⁷, Kelly Sunderland⁶, Sujeevini Sujanthan⁶, Jane Lawrence⁸, Donna Kwan⁹, Brian Tan⁶, Leanne Casaubon¹⁰, Jennifer Mandzia¹¹, Demetrios Sahlas¹², Gustavo Saposnik¹³, Ayman Hassan¹⁴, Brian Levine⁶, Paula McLaughlin⁹, J B Orange¹⁵, Angela Roberts¹⁶, Angela Troyer⁶, Sandra E Black^{2

3

6

17}, Dar Dowlatshahi¹⁸, Stephen C Strother^{6

19}, Richard H Swartz¹⁷, Sean Symons²⁰, Manuel Montero-Odasso²¹, Ondri Investigators²², Robert Bartha^{1

23}

Affiliations

¹ Centre for Functional and Metabolic Mapping, Robarts Research Institute, University of Western Ontario, London, Canada.
² L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
³ Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Canada.
⁴ Clinical Psychology, University of Toronto, Toronto, Canada.
⁵ Clinical Neurosciences, University of Toronto, Toronto, Canada.
⁶ Rotman Research Institute, Baycrest Health Sciences, Toronto, Canada.
⁷ Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
⁸ Thunder Bay Regional Health Research Institute, Thunder Bay, Canada.
⁹ Queen's University, Kingston, Canada.
¹⁰ Department of Medicine, University of Toronto, Toronto, Canada.
¹¹ Department of Medicine, Division of Neurology, University of Western Ontario, London, Canada.
¹² Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Canada.
¹³ Li Ka Shing Knowledge Institute, Toronto, Canada.
¹⁴ Thunder Bay Regional Research Institute, Thunder Bay, Canada.
¹⁵ School of Communication Sciences and Disorders, Western University, London, Canada.
¹⁶ Roxelyn and Richard Pepper Department of Communication Sciences and Disorder, Northwestern University, Evanston, USA.
¹⁷ Sunnybrook Health Sciences Centre, University of Toronto, Stroke Research Program, Toronto, Canada.
¹⁸ Ottawa Hospital Research Institute, Ottawa, Canada.
¹⁹ Department of Medical Biophysics, University of Toronto, Toronto, Canada.
²⁰ Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Canada.
²¹ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, St. Joseph's Health Care London, London, Canada.
²² Ontario Neurodegenerative Disease Initiative, Ontario Brain Institute, Toronto, Canada.
²³ Department of Medical Biophysics, University of Western Ontario, London, Canada.

Abstract

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T₁-weighted, proton density-weighted, T₂-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.