Bilateral substantia nigra and pyramidal tract changes following experimental intracerebral hemorrhage: an MR diffusion tensor imaging study

Abstract

The amelioration of secondary neurological damage is among the most important therapeutic goals for patients with intracerebral hemorrhage (ICH). Secondary injury of the ipsilateral substantia nigra (SN) and pyramidal tract (PY) is common after cerebral stroke. Such injury has been characterized previously by anatomical or diffusion MRI, but not in a comprehensive manner, and the knowledge regarding the contralateral changes is relatively poor. This study examined longitudinally both contralateral and ipsilateral SN and PY changes following experimental ICH with diffusion tensor imaging (DTI) and histology. ICH was induced in 14 Sprague-Dawley rats by the infusion of collagenase into the right striatum. Four-shot, spin-echo, echo-planar DTI was performed at 7 T with a b value of 1000 s/mm(2) and 30 diffusion gradient directions at 3.5 h and days 1, 3, 7, 14, 42 and 120 after ICH. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ// ) and radial diffusivity (λ┴ ) were measured in SN and PY accordingly. Two to three rats were sacrificed at days 3, 7, 42 and 120 for histology. The contralateral SN showed an increase in λ// with perivascular enlargement during the first 3 days after ICH. The ipsilateral SN showed increases in FA, λ// , λ┴ and MD at day 1, dramatic decreases at day 3 with neuronal degeneration and neuropil vacuolation, and subsequent gradual normalization. The contralateral PY showed diffusivity decreases at day 1. The ipsilateral PY showed early decreases and then late increases in MD and λ┴, and continuously decreasing FA and λ// with progressive axonal loss and demyelination. In summary, DTI revealed early bilateral changes in SN and PY following ICH. The evolution of the ipsilateral parameters correlated with the histological findings. In the ipsilateral PY, λ// and λ┴ changes indicated evolving and complex pathological processes underlying the monotonic FA decrease. These results support the use of quantitative multiparametric DTI for the evaluation of SN and PY injuries in clinical and preclinical investigations of ICH.

Multimodality MRI assessment of grey and white matter injury and blood-brain barrier disruption after intracerebral haemorrhage in mice

“…DTI/MRI has been investigated as a promising technique to evaluate functional outcome and compare treatment effects in patients with ICH37. Only a few preclinical ICH studies have used FA to estimate white matter injury and repair181938. The first study showed decreased FA value at day 3 together with histologically determined neuronal degeneration, which continued to 120 days after collagenase-induced ICH in rats18.…”

“…Only a few preclinical ICH studies have used FA to estimate white matter injury and repair181938. The first study showed decreased FA value at day 3 together with histologically determined neuronal degeneration, which continued to 120 days after collagenase-induced ICH in rats18. The second study, which used the blood-injection ICH model in rats, also showed a decrease in FA in the tissue near the haemorrhagic region on days 1 and 3 but did not present longer-term data38.…”

“…In recent studies, investigators have reported MRI-assessed lesion volume and brain tissue loss by T2wt MRI141516, brain oedema volume by ADC17, white matter injury by DTI1819, and BBB disruption by T1-Gd MRI20, mostly in rats. None of the studies has used multimodality MRI to assess the grey and white matter injury and repair, perihaematomal oedema, or BBB disruption over time in a mouse ICH model.…”

Translational MR Neuroimaging of Stroke and Recovery

“…In densely packed white matter bundles, axonal membranes and myelination both contribute to FA, with the former arguably producing a greater contribution [49]. Focal ischemia models have correlated FA reductions with both axonal loss and demyelination [50, 51]. More generally following tissue damage, and particularly in gray matter, several studies have cautioned against interpreting FA as a simple combination of axonal density and white matter myelination.…”

Diffusion tensor imaging in hemorrhagic stroke

“…Shu-Jan Fan et al suggest that our poor understanding of the contralateral PY and substantia nigra (SN) changes following ICH as demonstrated in several other ICH animal model studies can be secondary to use of different ICH sites and different imaging time points in those studies (23, 43, 46, 49). In their study they employ a robust rodent ICH model utilizing intra-striatal collagenase infusion to create the hematoma (50). They then longitudinally quantitatively assessed the changes on DTI in both contralateral and ipsilateral SN and PY tracts following ICH which were compared with histological examination.…”