Measurement of Cerebral Metabolism and Vascular Function with Magnetic Resonance Imaging

The brain relies on oxidative metabolism to function properly. Cerebral metabolic rate of oxygen (CMRO2) is thus an important marker for brain health. Existing techniques for quantification of CMRO2 with positron emission tomography (PET) or magnetic resonance imaging (MRI) involve special equipment and/or exogenous agents, and may not be suitable for routine clinical studies. To fill this gap, I developed a noninvasive method for quantifying whole brain CMRO2. This method uses the Fick principle of arterio-venous difference for the calculation of CMRO2.and employs phase-contrast MRI for quantitative blood flow measurement and T2-relaxation-under-spin-tagging (TRUST) MRI for venous oxygenation estimation. During this thesis, I conducted several technical development studies. I first optimized TRUST and phase-contrast MR imaging parameters and demonstrated the ability to measure CMRO2 using completely non-invasive procedures. I further performed calibration and validations studies to show that blood oxygenation measured with TRUST reveals an excellent agreement with the gold standard Pulse Oximetry method. A final technical study was to improve the speed and reliability of TRUST MRI by shortening the scan duration by 60% while reducing the measuring error by half.

I have also applied this novel CMRO2 method in better understanding brain physiology in younger and older adults. I studied the effect of CO2 inhalation (also known as hypercapnia) on brain metabolism. A reduced CMRO2 was observed and this effect was further supported by findings using functional connectivity MRI and electroencephalography techniques. I also investigated the effect of O2 modulation (hypoxia and hyperoxia) on brain metabolism and showed a dose dependent effect of O2 concentration on brain activity. Finally, I used this method to assess aged-related differences in brain metabolism and blood supply, and demonstrated a paradoxically higher metabolic rate in older adults, which may be associated with lower neural efficiency in elderly individuals.