MRI based quantification of global cerebral metabolism

The human brain predominantly relies on oxidative metabolism of glucose to meet its enormous energy requirements. The total amount of energy consumed by the brain can be indirectly measured by quantifying global cerebral metabolic rate of oxygen consumption (CMRO2). CMRO2 is known to be closely related to neuronal functioning and hence can serve as an important marker of brain vitality and health. Accurate absolute CMRO2 quantification would enable detailed investigation of the neuro-metabolic-hemodynamic relationships underlying cerebral activation and pathology. Despite the considerable utility and importance of determining absolute CMRO2, a robust and reliable method adaptable to clinical and functional applications is lacking. We propose a method for simultaneous measurement of cerebral blood flow (CBF) and venous oxygen saturation (SvO2) with a high temporal resolution (&sim30s at 3T). The former is quantified by using phase contrast MRI and the latter by MR susceptometry based oximetry. Fick's first law is used to determine CMRO2 from the above two parameters. This thesis first explored the feasibility of using the proposed methodology for in-vivo CMRO2 quantification and tested the validity of the underlying model assumptions. The hemodynamic and metabolic measurements obtained in-vivo agreed well with previous literature results. Next, the accuracy of the proposed MR susceptometry based oximetry was evaluated against the clinically established gold standard (co-oximetry measurements) and the two methods showed excellent agreement. Further the sensitivity of the proposed method to detect physiologically expected changes in response to a stimulus (hypercapnia) was examined. In line with the known vasodilatory effect of hypercapnia, an increase in CBF and SvO2 was observed. However, no statistically significant change in CMRO2 was noted. The method was then translated clinically in small pilot studies to investigate neonates with congenital heart disease (CHD) and adolescents with sickle cell disease (SCD). In the CHD study, the MR measured hemodynamic parameters were cross validated with optical measurements and a significant association between post-operative CMRO2 and brain injury was observed. In the SCD study, chronic transfusions were associated with lower cerebral blood flows and oxygen extraction fractions. Both of these populations are at significant risk for cerebral ischemia, thus making quantification of cerebral hemodynamic and metabolic parameters valuable. Additional insights gained would provide greater understanding of the pathophysiology of these illnesses with implications for clinical management paradigms. Lastly, we explored a quick T2 based method for determining oxygen saturation of blood. The method relies on complex difference subtraction of velocity encoded projections and unlike susceptometry based oximetry is not restricted by the vessel orientation with respect to main magnetic field or the need for surrounding reference tissue. The method demonstrated sensitivity to oxygenation differences between different cerebral territories (cortex vs. deep brain) as well as in response to a hypercapnic stimulus. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) This dissertation is available at ScholarlyCommons: http://repository.upenn. edu/edissertations/523 Graduate Group Bioengineering First Advisor Felix W. Wehrli Subject Categories Biomedical | Radiology This dissertation is available at ScholarlyCommons: http://repository.upenn. edu/edissertations/523 MRI BASED QUANTIFICATION OF GLOBAL CEREBRAL METABOLISM Varsha Jain A DISSERTATION in Bioengineering Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2012 Supervisor of Dissertation ____________________ Felix W.Wehrli, Ph.D Professor of Radiology Graduate Group Chair ____________________ Beth Winkelstein, Ph.D Professor of Bioengineering Dissertation Committee Beth Winkelstein, Ph.D, Professor of Bioengineering (Chair) John Detre, M.D, Professor of Neurology and Radiology Hee Kwon Song, Ph.D, Associate Professor of Radiologic Science in Radiology