Chronic brain tissue remodeling after stroke in rat: A 1-year multiparametric magnetic resonance imaging study

Rats subjected to 2 h of transient middle cerebral artery occlusion were studied temporally over 1 year by magnetic resonance imaging (MRI) and behavioral testing. Multiparameter MRI measures of T2, T1, T1 in the presence of off-resonance saturation of the bound proton signal (T1sat), apparent diffusion coefficient (ADC) and susceptibility-weighted imaging (SWI) were obtained at 1 day, 1, 2, 3 and 4 weeks, and 3, 6, 9 and 12 months post-ischemia. Regions of interest included: ischemic core (damaged both at 1 day and later); new lesion (normal at 1 day, but damaged later); and recovery (damaged at 1 day, but normal later) areas. Hematoxylin and eosin, Prussian blue and ED-1, a monoclonal antibody murine macrophage marker, stainings were performed for histological assessment. Core area T2 and ADC values increased until ~ 6 months, and T1 and T1sat until ~ 12 months. New lesion area MRI parameter values increased until ~ 6 months (T2, T1 and ADC), or ~ 1 year (T1sat). Lesion area was largest at 1 day (mean ± SD: 37.0 ± 13.7 mm2) and smallest at 1 year (18.1 ± 10.5 mm2). Recovery area was largest at 3 weeks (8.9 ± 3.8 mm2) and smallest at 1 year (6.4 ± 3.3 mm2). The ipsilateral/contralateral ventricle area ratio was 0.7 ± 0.2 at 1 day and increased significantly at 1 year (2.4 ± 0.7). Iron-laden macrophages, histologically confirmed at 1 year, were detected in the lesion borders by SWI at 3, 6, 9 and 12 months. Our data indicate that MRI detectable changes of ischemia-damaged brain tissue continue for at least 1 year post-ischemia.

Research Highlights
► T2, T1, T1sat, and ADC MRI parameters were studied to document the long-term temporal evolution of stroke-damaged tissues in the brains of aged animals.
► Multiparametric MRI detectable changes in stroke-damaged brain-tissues appeared to continue for at least 1 year.
► Volumetric measures indicated that the ipsilateral ventricle was compressed at 24 h and then gradually increased suggesting continuous tissue loss over the 1 year study period.
► Iron containing macrophages were found in the histological sections corresponding to hypointense regions found near the border of lesions on SWI suggesting an ongoing inflammatory response out to 1 year.