title: Measurement of distinctive features of cortical spreading depolarizations with different MRI contrasts.
abstract: Growing clinical evidence suggests critical involvement of spreading depolarizations (SDs) in the pathophysiology of neurological disorders such as migraine and stroke. MRI provides powerful tools to detect and assess co-occurring cerebral hemodynamic and cellular changes during SDs. This study reports the feasibility and advantages of two MRI scans, based on balanced steady-state free precession (b-SSFP) and diffusion-weighted multi-spin-echo (DT2), heretofore unexplored for monitoring SDs. These were compared with gradient-echo MRI. SDs were induced by KCl application in rat brain. Known for high SNR, the T2- and T1-based b-SSFP contrast was hypothesized to provide higher spatiotemporal specificity than T2*-based gradient-echo scanning. DT2 scanning was designed to provide simultaneous T2 and apparent diffusion coefficient (ADC) measurements, thus enabling combined quantitative assessment of hemodynamic and cellular changes during SDs. Procedures were developed to automate identification of SD-induced responses in all the scans. These responses were analyzed to determine detection sensitivity and temporal characteristics of signals from each scanning method. Cluster analysis was performed to elucidate unique temporal patterns for each contrast. All scans allowed detection of SD-induced responses. b-SSFP scans showed significantly larger relative intensity changes, narrower peak widths and greater spatial specificity compared with gradient-echo MRI. SD-induced effects on ADC, calculated from DT2 scans, showed the most pronounced signal changes, displaying about 20% decrease, as against 10-15% signal increases observed with b-SSFP and gradient-echo scanning. Cluster analysis revealed additional temporal sub-patterns, such as an initial dip on gradient-echo scans and temporally shifted T2 and proton density changes in DT2 data. To summarize, b-SSFP and DT2 scanning provide distinct information on SDs compared with gradient-echo MRI. DT2 scanning, with its potential to simultaneously provide cellular and hemodynamic information, can offer unique information on the inter-relationship between these processes in pathologic brain, which may improve monitoring of spreading depolarizations in (pre)clinical settings.
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Umesh Rudrapatna
authors.forename: Arend M
authors.initials: AM
authors.lastname: Hamming
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Wermer
authors.forename: Annette
authors.initials: A
authors.lastname: van der Toorn
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
mesh_terms: D000465:Algorithms; D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D005071:Evoked Potentials / Q000502:physiology*; D005240:Feasibility Studies; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D062211:Spatio-Temporal Analysis
keywords: Applications, Spreading Depolarization, SSFP, Combined ADC and T2; Functional MRI (fMRI) Methods; Methods and Engineering, Neurological; Methods and Engineering, fMRI signal characteristics; Other functional MRI methods