Interleaved imaging of cerebral hemodynamics and blood flow index to monitor ischemic stroke and treatment in rat by volumetric diffuse optical tomography

Abstract

Diffuse optical tomography (DOT) has been used by several groups to assess cerebral hemodynamics of cerebral ischemia in humans and animals. In this study, we combined DOT with an indocyanine green (ICG)-tracking method to achieve interleaved images of cerebral hemodynamics and blood flow index (BFI) using two middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images with high-spatial resolution, we first integrated a depth compensation algorithm (DCA) with a volumetric mesh-based rat head model to generate three-dimensional (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat models were collected using interleaved strategy for cerebral hemodynamics and BFI during and after ischemic stroke, with and without a thrombolytic therapy for the embolic MCAO model. The acquired animal data were further analyzed using the integrated rat-atlas-guided DOT method to form time-evolving 3D images of both cerebral hemodynamics and BFI. In particular, we were able to show and identify therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced ischemic model. This paper demonstrates that volumetric DOT is capable of providing high-quality, interleaved images of cerebral hemodynamics and blood perfusion in small animals during and after ischemic stroke, with excellent 3D visualization and quantifications.

Keywords: 3D; BFI; CBF; CCA; CT; DCA; DOT; DYNOT; Depth compensation algorithm; Diffuse optical tomography; ECA; Embolism-induced ischemic model; FEM; G(I); G(II); Group I to represent the suture-induced MCAO rat model; Group II to represent the embolism-induced MCAO rat model; HbO(2); HbR; HbT; Hemodynamic concentration contrast; ICA; ICG; Indocyanine green; MCA; MCAO; MRI; Middle cerebra artery occlusion; NIR; NIRFAST; NIRS; OD; ROI; RW; Ratio(BFI); Stroke; Three-dimensional reconstruction; a FEM-based MATLAB package; blood flow index; cerebral blood flow; common carotid artery; computed tomography; deoxygenated hemoglobin concentration; depth compensation algorithm; diffuse optical tomography; dynamic near-infrared optical tomographic instrument; external carotid artery; finite element model; internal carotid artery; magnetic resonance imaging; middle cerebral artery; middle cerebral artery occlusion; near-infrared; near-infrared spectroscopy; optical density; oxygenated hemoglobin concentration; rCBF; ratio between two spatially-averaged BFI values within ROI-2 and ROI-1; real world; recombinant tissue plasminogen activator; region of interest; regional CBF; rtPA; three-dimensional; total hemoglobin concentration.