Using a multimodal near-infrared spectroscopy and MRI to quantify gray matter metabolic rate for oxygen: A hypothermia validation study

Mada Hashem,Qiong Zhang,Ying Wu,Thomas W Johnson,Jeff F Dunn

doi:10.1016/j.neuroimage.2019.116315

Mada Hashem, Qiong Zhang + Show 3 more

Open Access

https://doi.org/10.1016/j.neuroimage.2019.116315

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Journal: NeuroImage	Publication Date: Oct 25, 2019
Citations: 15	License type: cc-by

Affiliation: University of Calgary

Abstract

Non-invasive quantitative imaging of cerebral oxygen metabolism (CMRO2) in small animal models is crucial to understand the role of oxidative metabolism in healthy and diseased brains. In this study, we developed a multimodal method combining near-infrared spectroscopy (NIRS) and MRI to non-invasively study oxygen delivery and consumption in the cortex of mouse and rat models. The term CASNIRS is proposed to the technique that measures CMRO2 with ASL and NIRS. To determine the reliability of this method, CMRO2 values were compared with reported values measured with other techniques. Also, the sensitivity of the CASNIRS technique to detect changes in CMRO2 in the cortex of the animals was assessed by applying a reduction in core temperature, which is known to reduce CMRO2. Cerebral blood flow (CBF) and CMRO2 were measured in five mice and five rats at a core temperature of 37 °C followed by another measurement at 33 °C. CMRO2 was 7.8 ± 1.8 and 3.7 ± 0.9 (ml/100 g/min, mean ± SD) in mice and rats respectively. These values are in good agreement with reported values measured by 15O PET, 17O NMR, and BOLD fMRI. In hypothermia, we detected a significant decrease of 37% and 32% in CMRO2 in the cortex of mice and rats, respectively. Q10 was calculated to be 3.2 in mice and 2.7 in rats.In this study we showed that it is possible to assess absolute values of metabolic correlates such as CMRO2, CBF and oxygen extraction fraction (OEF) noninvasively in living brain of mice and rats by combining NIRS with MRI. This will open new possibilities for studying brain metabolism in patients as well as the many mouse/rat models of brain disorders.

Highlights

The brain is highly aerobic, using approximately 20% of the body’s total oxygen uptake
In this study we showed that it is possible to assess absolute values of metabolic correlates such as CMRO2, cerebral blood flow (CBF) and oxygen extraction fraction (OEF) noninvasively in living brain of mice and rats
We showed that with a custom-built broadband near-infrared spectroscopy (NIRS) system and an adapted processing pipeline based on the second differential method, it is possible to quantify the absolute concentration of dHb at any given time point in the cortex of rat models (Zhang et al, 2010)

Summary

Introduction

The brain is highly aerobic, using approximately 20% of the body’s total oxygen uptake. The gray matter (GM) consumes 3–4 times more oxygen than the white matter (Dunning and Wolff, 1937; Pantano et al, 1984) and has a higher mitochondrial density (Gerstl et al, 1969; Santuy et al, 2018) This requirement for oxygen means that changes in the rate of oxygen uptake, i.e., the cerebral metabolic rate of oxygen (CMRO2), should be a sensitive index of injury and disease. Both CMRO2 and CBF may be affected These physiological parameters can be detected currently by neuroimaging modalities such as positron emission tomography (PET) (Mintun et al, 1984; Ter-Pogossian et al, 1970), functional magnetic resonance imaging (fMRI) (Hyder et al, 2001; Sicard and Duong, 2005), and 17O-NMR (Zhu et al, 2005). We propose a novel method for quantification of CMRO2, that is tailored to rodent models, and has potential for use in patients

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