High-speed quantitative optical imaging of absolute metabolism in the rat cortex

Abstract

Quantitative measures of blood flow and metabolism are essential for improved assessment of brain health and response to ischemic injury. In this report, we demonstrate a multimodal technique for measuring the cerebral metabolic rate of oxygen (CMRO 2 ) in the rodent brain on an absolute scale (M O 2 / min). We use laser speckle imaging (LSI) at 809 nm and spatial frequency domain imaging (SFDI) at 655 nm, 730 nm, and 850 nm to obtain spatiotemporal maps of cerebral blood flow (CBF), tissue absorption ( a ), and tissue scattering ( s '). Knowledge of these three values enables calculation of a characteristic blood flow speed, which in turn is input to a mathematical model with a "zero-flow" boundary condition to calculate absolute CMRO 2 . We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation. With this model, the zero-flow condition occurs during entry into CA. The CMRO 2 values calculated with our method are in good agreement with those measured with magnetic resonance (MR) and positron emission tomography (PET) by other groups. Our technique provides a quantitative metric of cerebral metabolism that can potentially be used for comparison between animals and longitudinal monitoring of a single animal over multiple days, to assess differences in baseline metabolism and track recovery of metabolism in survival studies following ischemia and reperfusion.

Resuscitating the Globally Ischemic Brain: TTM and Beyond

“…Furthermore, we show that the flow-metabolism ratio (CBF/CMRO 2 ) in the brain at ultra-early time points (1-2 min after ROSC) may be diagnostic of CA severity (duration) and predict bursting, and this metric appears robust across different ischemia durations [190]. Additionally, we recently demonstrated that combining CBF and tissue oxygenation data shows promise for continuously measuring CMRO 2 on an absolute scale (e.g., μM O 2 /min), which has traditionally been more challenging to measure but potentially very important [191]. Absolute CMRO 2 measurement enables direct quantitative comparison between cerebral metabolism of multiple subjects or a single subject on multiple days, without the need for baseline measurements or perturbations such as hypercapnia.…”

Multimodal Optical Imaging to Investigate Spatiotemporal Changes in Cerebrovascular Function in AUDA Treatment of Acute Ischemic Stroke

“…from the vessels by the tissue, and HbO 2 i, j a is the molar concentration in the arterioles. According to previous studies, (OEF i, j )( HbO 2 i, j a ) is equivalent to the deoxygenated hemoglobin extracted by the tissue, as follows (Ghijsen et al, 2018;Wilson et al, 2019):…”

“…However, the reconstructed images of DOT are negatively impacted from poor spatial resolution owing to the diffuse nature of light in biological tissues (Dehghani et al, 2009). To solve spatial resolution, the LSCI technique with high spatial and temporal resolution (Takuwa et al, 2014;Chong et al, 2015;Ghijsen et al, 2018;Wilson et al, 2019) was adopted in combination with the OISI technique. Jones et al first implemented a dual camera and dual light source LSCI and OISI system using a dichroic beam splitter (Jones et al, 2008).…”