In children with sickle cell disease, there is a clinical need for non-invasive quantification of the degree of hemometabolic stress in these patients to mitigate risk of stroke. Frequency-domain near-infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) measures of regional oxygen extraction fraction, cerebral blood flow, and cerebral metabolic rate of oxygen have potential to provide markers of cerebral metabolic stress. In this study, we characterize the intra-subject and inter-operator repeatability of these measures, and we correlate DCS measures of cerebral blood flow index against both arterial spin-labeled MRI and transcranial Doppler ultrasound in a cohort of pediatric SCD patients.
We assess a novel means of measuring cerebrovascular reactivity (CVR) in awake mice using intraperitoneal injection of acetazolamide combined with continuous monitoring of cerebral blood flow with a minimally invasive diffuse correlation spectroscopy (DCS).
Significance: Cerebrovascular reactivity (CVR), defined as the ability of the cerebral vasculature to dilate or constrict in response to a vasoactive stimulus, is an important indicator of the brain’s vascular health. However, mechanisms of cerebrovascular dysregulation are poorly understood, and no effective treatment strategies for impaired CVR exist. Preclinical murine models provide an excellent platform for interrogating mechanisms underlying CVR dysregulation and determining novel therapeutics that restore impaired CVR. However, quantification of CVR in mice is challenging.
Aim: We present means of assessing CVR in awake mice using intraperitoneal injection of acetazolamide (ACZ) combined with continuous monitoring of cerebral blood flow.
Approach: Measurements of cerebral blood flow were made with a minimally invasive diffuse correlation spectroscopy sensor that was secured to an optical window glued to the intact skull. Two source–detector separations (3 and 4.5 mm) per hemisphere were used to probe different depths. CVR was quantified as the relative increase in blood flow due to ACZ. CVR was assessed once daily for 5 days in 5 mice.
Results: We found that CVR and the response half-time were remarkably similar across hemispheres and across 3- versus 4.5-mm separations, suggesting a homogenous, whole brain response to ACZ. Mean(std) intra- and intermouse coefficients of variations were 15(9)% and 19(10)%, respectively, for global CVR and 24(15)% and 27(11)%, respectively, for global response half-time.
Conclusion: In sum, we report a repeatable method of measuring CVR in free-behaving mice which can be used to screen for impairments with disease and to track changes in CVR with therapeutic interventions.
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