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 1. Develop and Optimize QUTE-CE protocol for 3D clinical imaging at 3T. This project will primarily use the Siemens 3T TrioTim MRI scanner with 20-channel head coil. 3 tasks will be pursued to develop the optimizing protocol. Task 1: Develop a UTE imaging protocol. Task 2: Develop a robust trajectory for improved image reconstruction and signal quantification. Task 3: Implement a robust methodology for accounting for B1+ inhomogeneity. Specific Aim 2. 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. 15 healthy volunteers will be imaged in the Siemens Trio 3T scanner with Ferumoxytol contrast agent and using the protocol optimized in Aim 1. Blood draws will be taken before and after administration for validation of the quantitative estimation of the blood CA. Specific Aim 3. 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 (1) whole brain angiography, (2) full brain voxel based cerebral blood volume (CBV) maps, (3) 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: 1) Positive contrast imaging with a safe contrast agent providing an alternative to Gd based contrast agents that have been shown to be toxic. 2) Non-invasive live whole brain vascular imaging with exceptional clarity and definition. 3) 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.
Public Health Relevance Statement: 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 doesn't currently exist, and which could lead to many exciting discoveries and clinical applications in neurology.
Project Terms: Accounting; Address; Angiography; Atlases; base; Biological Assay; Blood; Blood Circulation; Blood Vessels; Brain; Brain imaging; Brain region; cerebral blood volume; cerebrovascular; Clinical; clinical application; clinical imaging; Clinical Research; Clinical Trials; Computer software; contrast enhanced; contrast imaging; Contrast Media; Custom; Data; Diagnosis; Disease; Equation; Extravasation; FDA approved; Ferumoxytol; Gadolinium; General Hospitals; Head; Health; healthy volunteer; Human; human subject; Image; image reconstruction; Imaging Techniques; improved; Institution; Institutional Review Boards; interest; iron oxide; Lead; Legal patent; Magnetic nanoparticles; Magnetic Resonance Imaging; Maps; Massachusetts; Measurement; Methodology; Methods; Morphologic artifacts; mouse model; nanomedicine; nanoparticle; neuroimaging; Neurologic; Neurology; Neuropathy; novel strategies; nuclear imaging; Participant; Patients; Phase; Physiologic pulse; Physiological; Predisposition; Protocols documentation; Publications; Radiation; Radiation Toxicity; radiologist; Rattus; Scanning; Signal Transduction; Small Business Technology Transfer Research; Techniques; Technology; Testing; Time; Tissues; tool; Toxic effect; Translations; Universities; Validation; Venous system
