Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood flow and oxygen extraction fraction in stroke mice

Abstract

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO2 and CBF. This study employed the recently developed in vivo 17O MR spectroscopic imaging to simultaneously assess CMRO2, CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of 17O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive 17O-MR approach for rapidly imaging CMRO2, CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO2 and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising 17O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This 17O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy.

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

“…Additionally, 13 C MRS studies (in animal and human) allows the correlation between neuronal glucose oxidation and neuronal activity, and revealed high oxidative metabolism demand during neuronal activation Chhina et al, 2001;Hyder et al, 1996Hyder et al, , 1997. In vivo 17 O NMR may also be used to directly and non-invasively determine CMR O2 (Mateescu, 2003;Zhu and Chen, 2011;Zhu et al, 2005) with high reliability and reproducibility (Zhu et al, 2007), as well as the simultaneous in vivo measurements of CBF (Zhu et al, 2013), which may help unraveling the role of oxidative metabolism during functional activity.…”

High‐resolution dynamic oxygen‐17 MR imaging of mouse brain with golden‐ratio–based radial sampling and k‐space–weighted image reconstruction

“…In the current study, we were able to achieve an effective temporal resolution of 7.56 s with a voxel size of 11.25 mL (5.625 mL nominal) at 9.4 T. The flexibility of choosing a k-space filter to achieve adequate temporal resolution allows application of this method to quantify CMRO 2 in 17 O 2 inhalation studies. For a typical 17 O 2 inhalation study, only a small amount of gas is delivered in $2 min to reduce the cost for 17 O 2 (8,9). Having a reduced amount of 17 O 2 available in vivo causes reduced signal increases, leading to lower SNR at peak and steady-state.…”

“…In addition, using a short echo time to minimize signal loss in 17 O-MRI is critical due to the short transverse relaxation time of 17 O (5). 17 O-MRI has been used extensively to evaluate cerebral metabolic activity in rats (6), healthy cats (7), and mice (8,9). Quantification of the cerebral metabolic rate of oxygen consumption (CMRO 2 (8,10,11).…”

“…17 O-MRI has been used extensively to evaluate cerebral metabolic activity in rats (6), healthy cats (7), and mice (8,9). Quantification of the cerebral metabolic rate of oxygen consumption (CMRO 2 (8,10,11). Most of these studies used spectroscopic imaging methods with Cartesian encoding (10), but alternative 17 O-MRI methods have used ultrashort echo time sequences with non-Cartesian encoding (12)(13)(14), including the density-adapted three-dimensional (3D) radial pulse sequence (12,13) and the flexible twisted projection imaging acquisition (14).…”

In Vivo Photoacoustic Imaging of Brain Injury and Rehabilitation by High‐Efficient Near‐Infrared Dye Labeled Mesenchymal Stem Cells with Enhanced Brain Barrier Permeability

“…It is a new emerging imaging technique that permits ample contrasts on account of the chromophore absorption 11. Recently, PAT has been widely used on both structural and functional imaging of tumor,12 microvessels,13 brain functions,14 vasculature related diseases,15 and other applications 16, 17. Due to these advantages, we employed fast PAT to monitor the damage region of the mouse brain and its recovery with both skull and scalp intact.…”