Near‐infrared diffuse reflectance signals for monitoring spreading depolarizations and progression of the lesion in a male rat focal cerebral ischemia model

Abstract

In ischemic stroke research, a better understanding of the pathophysiology and development of neuroprotection methods are crucial, for which in vivo imaging to monitor spreading depolarizations (SDs) and evolution of tissue damage is desired. Since these events are accompanied by cellular morphological changes, light-scattering signals, which are sensitive to cellular and subcellular morphology, can be used for monitoring them. In this study, we performed transcranial imaging of near-infrared (NIR) diffuse reflectance at ∼800 nm, which sensitively reflects light-scattering change, and examined how NIR reflectance is correlated with simultaneously measured cerebral blood flow (CBF) for a rat middle cerebral artery occlusion (MCAO) model. After MCAO, wavelike NIR reflectance changes indicating occurrence of SDs were generated and propagated around the ischemic core for ∼90 min, during which time NIR reflectance increased not only within the ischemic core but also in the peripheral region. The area with increased reflectance expanded with increase in the number of SD occurrences, the correlation coefficient being 0.7686 (n = 5). The area with increased reflectance had become infarcted at 24 hr after MCAO. The infarct region was found to be associated with hypoperfusion or no-flow response to SD, but hyperemia or hypoperfusion followed by hyperemia response to SD was also observed, and the regional heterogeneity seemed to be connected with the rat cerebrovasculature and hence existence/absence of collateral flow. The results suggest that NIR reflectance signals depicted early evolution of tissue damage, which was not seen by CBF changes, and enabled lesion progression monitoring in the present stroke model.

Hemodynamics and Tissue Optical Properties in Bimodal Infarctions Induced by Middle Cerebral Artery Occlusion

“…Therefore, the author supposed that their observation of decreased scattering during MCAO may be due to the change in cellular structure in response to acute injury [ 43 ]. Others investigated changes of NIR light scattering imaging in the model of permanent MCAO to monitor spatiotemporal distribution of spreading depolarization (SD) and development of the infarction [ 58 ]. In the core area of infarction, a sudden drop in scattering intensity induced by MCAO was detected and followed by a gradual increase and repetitive wavelike changes induced by SDs.…”

“…In the peripheral region of the infarction, instead of a sudden drop immediately after the MCAO, a gradually increase followed by repetitive SDs were observed through the whole time. The authors speculate that the gradual increased scattering after MCAO may be associated with morphological alteration due to neuronal injury, although the discussion on the sudden drop of the scattering in the beginning of the MCAO was lacking [ 58 ]. We propose that our finding of decreased μs’ was consistent with previous reports in MCAO [ 43 , 58 ].…”

“…The authors speculate that the gradual increased scattering after MCAO may be associated with morphological alteration due to neuronal injury, although the discussion on the sudden drop of the scattering in the beginning of the MCAO was lacking [ 58 ]. We propose that our finding of decreased μs’ was consistent with previous reports in MCAO [ 43 , 58 ].…”

Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

“…28 More recently, several groups have used optical imaging to measure and characterize SD in animal models of cerebral ischemia. [29][30][31][32] Optical methods can also quantify ischemia-induced mismatches between cerebral blood flow (CBF) and brain metabolism that are indicative of impaired autoregulation. [33][34][35][36][37][38][39] Additionally, via measurement of tissue scattering, optical techniques can also interrogate neuronal damage caused by cytotoxic edema and dendritic beading.…”