Quantitative Non Invasive Brain Imaging using Magnetic Nanoparticles

This Phase I STTR project is based upon 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 QUTE CE is particularly optimal using Ferumoxytol an FDA approved iron oxide nanopharmaceutical The technique was developed by PI Sridhar and his team at Northeastern University Northeastern University has licensed the QUTE CE MRI method to Theranano LLC for commercial translation The TheraNano QUTE CE MRI product is an imaging suite comprised of methods and software for quantitative non invasive brain imaging customized for use by clinical radiologists This Phase I STTR project will develop the QUTE CE MRI suite and validate with first in human studies The specific aims of this project are summarized here Specific Aim Develop and Optimize QUTE CE protocol for D clinical imaging at T This project will primarily use the Siemens T TrioTim MRI scanner with channel head coil tasks will be pursued to develop the optimizing protocol Task Develop a UTE imaging protocol Task Develop a robust trajectory for improved image reconstruction and signal quantification Task Implement a robust methodology for accounting for B inhomogeneity Specific Aim Validate the QUTE CE neuroimaging suite with studies in healthy human subjects These studies will be carried out at Massachusetts General Hospital MGH under the direction of Dr Mukesh Harisinghani a world renowned expert in clinical nanoparticle imaging and Dr John Chen an expert neuro radiologist The studies will have full approval of the MGH IRB healthy volunteers will be imaged in the Siemens Trio T scanner with Ferumoxytol contrast agent and using the protocol optimized in Aim Blood draws will be taken before and after administration for validation of the quantitative estimation of the blood CA Specific Aim Develop the QUTE CE MRI suite for non invasive quantitative brain imaging A radiologist friendly software suite will be developed for presentation and analysis of the subject scans The suite will present results for whole brain angiography full brain voxel based cerebral blood volume CBV maps the first CBV map of the human brain by registering the voxular data on a human brain map The analysis will also provide time dependent data for the blood pool concentration of contrast agent which will be cross checked with elemental analysis of the blood draw assay QUTE CE MRI addresses three critical unmet needs Positive contrast imaging with a safe contrast agent providing an alternative to Gd based contrast agents that have been shown to be toxic Non invasive live whole brain vascular imaging with exceptional clarity and definition Quantitative MRI where an absolute measurement of CA concentration is assayed competitive with nuclear imaging but without radiation toxicity The proposed studies should lead to groundbreaking results on brain function and neurological health PROJECT NARRATIVE TITLE Quantitative Non Invasive Brain Imaging Using Magnetic Nanoparticles This Phase I STTR project will develop a non invasive brain imaging technique QUTE CE MRI and validate the method with first in human studies The project will establish a human vascular atlas and will enable quantitative diagnosis of cerebrovascular abnormalities by revealing abnormal regions of the brain that characterize disease a tool which doesnandapos t currently exist and which could lead to many exciting discoveries and clinical applications in neurology