The brain’s reserve of blood supply provides important information regarding brain health, and can be a sensitive biomarker in vascular cognitive impairment (VCI). This project will develop a novel technique for measuring vascular reserve that does not need an explicit vascular challenge. (Current technologies require the injection of pharmacological agents or the inhalation of CO2-enriched gases, which increase patient burden and may not be widely applicable.) VCI is the second leading cause of dementia after Alzheimer’s disease (AD). However, while AD biomarkers are relatively well developed, biomarkers for VCI pathology in the brain are more limited. Cerebrovascular reactivity (CVR), an index of cerebral vessel’s capacity to dilate in response to stimulation, is a promising marker of the brain’s vascular function. Our overarching hypothesis is that CVR is a plausible biomarker for the diagnosis of VCI, for which no other biomarkers are currently available. The central goal of this project is to develop a gas-free CVR MRI technique that can provide comparable sensitivity to CO2-inhalation CVR but with a higher level of comfort for patients. This new technique is largely based on resting-state scans and exploits spontaneous fluctuations in the subject’s breathing pattern, but also introduces intermittent modulations of their breathing rhythm to enhance fluctuations in their end-tidal CO2. 

The neonatal brain’s use of oxygen can be an important biomarker of neural development and brain tissue viability. Birth asphyxia causes hypoxic brain injury and is one of the leading causes of neonatal death and long-term disability. The goal of this project is to develop and evaluate the clinical utility of novel biomarkers related to the neonatal brain’s oxygen utilization, including cerebral metabolic rate of oxygen (CMRO2) and its key component, oxygen extraction rate (OEF). Cerebral oxygen consumption is a central piece in the pathological process underlying birth asphyxia. However, at present, no practical techniques to assess cerebral oxygen metabolism in human neonates exist. Positron emission tomography (PET) methods that have been used for adult CMRO2 imaging cannot be easily used in the neonatal population due to the complexity of the procedures and radiation concerns. We will develop an MR based technique to measure OEF and CMRO2 without using any exogenous contrast agent. A critical component in OEF and CMRO2 quantification is venous oxygen saturation. In this project, we will devise a novel pulse sequence, accelerated T2-Relaxation-Under-Phase-Contrast (aTRU-PC), to measure venous oxygenation in a region-specific manner, from which OEF and CMRO2 will be quantified. Upon the completion of this project, we will be able to provide the neonatal neuroimaging community with a new MRI technique for quantitative assessment of brain oxygen utilization and will have demonstrated its clinical utility in hypoxic ischemic encephalopathy.

fMRI is an important tool used to study neural activity associated with emotional aging, but its findings may be confounded by vascular declines. This project aims to measure vascular function in the aging brain and examine how fMRI results in emotional aging are modified by age-related changes in vascular function. This represents the first study in the field to characterize age-related differences in the emotional neural circuit using advanced, vascular-corrected fMRI techniques. Dr. Liu previously developed a novel technique to measure cerebrovascular reactivity (CVR) and cerebral blood volume (CBV) using gas-inhalation (e.g., CO2, O2) MRI, which can be used to calibrate the fMRI signal to improve its inference of neural activity. Dr. Liu and her team have previously applied this technique in a memory- encoding aging study, and found that much of the previously reported decrease in visual activation in aging is due to vascular decline and that prefrontal hyperactivation in memory encoding is more pervasive than previously thought. The proposed work seeks to apply this exciting novel technique to the study of emotional aging. The central aim is to characterize the age effect in emotional neural function after correcting for vascular differences.