Metabolic MR Imaging for Studies of Human Brain Disease

Type of Award: Spark
Date Awarded: January 2009
Award End Date: December 2010
Amount Awarded: $ 400,000.00
PI(s): Keith Thulborn, PhD, UIC; Thomas Meade, PhD, NU; Y. Jeong, PhD, UIC;

Abstract: The treatment for human disease at the earliest stages requires sensitive, quantitative, and non-destructive diagnostic monitoring methods. Magnetic resonance imaging (MRI) is one of the few technologies capable of localized, nondestructive metabolic characterization without ionizing radiation. The high spatial and temporal resolution of MR imaging provides the means to investigate physiology at the systems level (i.e., whole organisms).

This project develops a new dimension of MR imaging to monitor metabolic changes expressed in the earliest stages of disease and during response to treatment. It will focus on obtaining insights into the interrelated problems of developmental and molecular biology and clinical diseases by i. generating MR probes that function as real-time in vivo physiological reporters (exogenous), ii. develop quantitative parameters of metabolic concentrations and rates that reflect tissue health (endogenous) and iii. correlate in vivo image analysis by pharmacokinetic methods. Although applicable to any location in the body, the human brain will be the initial target organ.

Bioscales will be created using MR signals. The signals will be derived from metabolites occurring naturally in the body, or from bioactivated probes that detect specific biochemical processes. New classes of probes will be synthesized and optimized and human and non-human primate MRI studies will be performed at the enhanced sensitivity of 9.4 Tesla to calibrate these bioscales for metabolic modeling of the healthy brain.

These metabolic models will be combined with enhanced MR imaging applicable to clinical field strengths of 3.0 Telsa. This translational approach will result in metabolic imaging for monitoring the earliest stages of diseases, thereby stimulating the development of earlier, and therefore less expensive, interventions. The strategic plan of the NIH emphasizes healthcare cost containment through earlier treatment of disease. Metabolic imaging using both exogenous and endogenous agents is an essential technology for developing such early intervention strategies for humans.