Obtaining absolute quantitative information is a formidable task given the complex nature of the MR signal. We have developed a new technique Quantitative Ultra-short Time-to-Echo Contrast-Enhanced (QUTE- CE) MRI utilizing UTE sequences with SuperParamagnetic Iron Oxide Nanoparticles (SPION) that leads to quantifiable vascular images with unprecedented clarity and definition. The ultra-short time scale limits susceptibility dependent signal dephasing by giving T2 effects negligible time to propagate, and also limits the influence of physiological effects, resulting in snapshots of the vasculature that are independent of flow velocity, arterial or venous systems, or vessel orientation. We have shown in mice models at 7T that with optimized pulse sequences (TE, TR, FA), we can acquire UTE images with signal predicted by the Spoiled Gradient Echo (SPGR) equation as a function of concentration, thus defining a new approach to Quantitative MRI. We have found that QUTE-CE is particularly optimal with SPIONs, specifically ferumoxytol an FDA approved iron-oxide nanopharmaceutical. The nanoparticles lead to long blood circulation with minimal leakage from vasculature, resulting in very high vascular delineation and highest vascular/tissue contrast. Here we propose to optimize QUTE-CE at 7T in rat models, and validate our hypothesis that QUTE-CE can be implemented for quantitative functional MRI (qfMRI) in rat brains by establishing a vascular brain atlas, and then studying changes under drug insults.
The specific aims of this project are summarized below.
Specific Aim 1. Establish and optimize QUTE-CE MRI for quantitative functional neuroimaging (qfMRI). We hypothesize that the unique ability of QUTE-CE to provide an absolute quantitative signal can be extended to measuring the CBV per voxel in the brain by using a partial-voluming model, in which each voxel consists of a linear combination of signal from both tissue and blood within it. Task 1 will optimize the QUTE-CE protocol for neuroimaging, by developing a robust trajectory for improved image reconstruction and signal quantification. Task 2 will measure tissue intensity, IT, and blood intensity, IB, per image. The CBV will be calculated using a two-volume partial-voluming model for tissue and blood. Task 3 will construct a vascular atlas using a custom 174 region anatomical atlas to segment specific regions within the brain.
Specific Aim 2. Evaluate the change in neuropathies due to drug insults. We hypothesize a compensatory increase in capillary density as measured by QUTE-CE in brain areas such as hypothalamus and basal ganglia e.g. accumbens and striatum, when animals are continuously exposed to oxycodone. Task 1 will test the technique by exposing animals to oxycodone administration, analyzing resulting vascular abnormalities, and quantifying CBV and associating changes in them with the 174 regions of the Vascular Brain Atlas. Task 2 will compare measured vascularity to histological studies using staining of histological slices. Task 3 will compare QUTE-CE with other methods including DTI, ?R2, steady-state susceptibility contrast mapping (SSGRE), and steady state CBV (SS_CBV).

Public Health Relevance

TITLE: Quantitative Neurovascular Imaging for Drug Abuse Research This project seeks to develop a new method of quantitative magnetic resonance imaging using ultra-short time-to-echo pulses and magnetic nanoparticles as contrast agent. The new approach yields positive contrast images of the brain vasculature with unparalleled clarity and definition, and provides quantitative data on cerebral blood volume, leading to new information on brain function and neurological health related to drug addiction and abuse.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZDA1-SXM-M (13)S)
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Pariyadath, Vani
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Northeastern University
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United States
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