Development of a Frontier Magnetic Resonance (MR) Imaging Technology As a Tool for Visualization and Quantified Vascular-Feature Measurement for Use in Brain and Behavioral Research on Small Animals
The burden of mental illness continues to be a growing challenge in the United States. At the same time, thescientific community continues to study the brain and behavior, revealing relationships between brain structureand function and physiology and illness. The outer scope of brain and behavior research is governed by theimaging and analytical tools available to scientists. Magnetic resonance imaging (MRI) has greatly improved thestudy of the brain. However, even advanced forms of the technology have significant limitations. Specifically, allMRI techniques rely on a qualitative signal for semi-quantitative measurements. Moreover, standard MRIacquisition exhibit as much as 70% signal amplitude bias change with the orientation of the cerebral cortical (andhence the large pial vessels) relative to magnetic field. Quantitative Ultra-short Time-to-Echo Contrast-Enhanced(QUTE-CE, pronounced "cute-see") MRI is a novel imaging modality that generates a quantitative signal directlyrepresentative of physiological information that can broaden the outer limit of what current technology makespossible. QUTE-CE advantages, thus far, include production of the highest quantitative measurement of CAconcentration in mice; development of unprecedent non-invasive in vivo maps of brain vascular structure (CBV);mapping of neurofunctional response; biomarkers for cancer treatment efficacy; and, measurement of blood-brain barrier (BBB) leakage. This project strives to create a robust software suite to overcome current limitationsunlocking the potential of phMRI and fMRI measurement with higher sampling time, increasing signal-to-noiseby 1.67 compared to radial sampling and enabling sliding-window reconstruction for simultaneous high-spatialand temporal image reconstruction using the same data set. To achieve this, the project aims to develop andoptimize a software prototype for use with industry-standard 7T small animal research scanners, implementingImaginostics' proprietary 3D UTE Radial Cones Pulse Sequence. Next, the project strives to test softwareprototypes and analytically characterize biomarkers. The goal of the project is to ultimately improve andstandardize measurements to complement or replace existing options for a more precise approach that isuniquely quantitative at both the individual and group levels. This means potentially fewer animals would beneeded to arrive at meaningful results. Moreover, structural, functional and BBB leakage metrics can be capturedwithin one imaging session, greatly enriching the study of healthy and disordered brains. Overall, these effortscan help advance pre-clinical and related brain research efforts on small animals, by incorporating a novel MRIimaging technology into the repertoire of researchers.
Public Health Relevance Statement: PROJECT NARRATIVE
The growing burden of mental illness in the United States has reinforced the need for continued research and
study of the brain using all imaging tools available to scientists. Thus far, Magnetic Resonance Imaging (MRI)
technology has proven to be instrumental in advancing our understanding of the brain, but has limitations in its
current form. This project strives to develop a new MRI technology -- Quantitative Ultra-short Time-to-Echo
Contrast-Enhanced (QUTE-CE, pronounced "cute-see") -- for use in brain research in small animals, expanding
the analytical tool box of researchers and galvanizing improved understanding of the brain.
