There is a fundamental limit in the ability to diagnose early signs of mild Traumatic Brain Injury (mTBI), as its structural changes are indiscernible with current neuroimaging techniques. Continued existence of this gap in detection ability is an important problem because it limits our predictive ability of mTBI symptom presentation, as well as our understanding of its pathology and therapy options. The phase of the MRI signal is emerging as a new rapidly developing imaging framework, showing increased sensitivity to Electro-Magnetic Tissue Property (EMTP) of mTBI biomarkers compared to the widely utilized magnitude signal. Our long term goal is to extract EMTP measurements from MR phase in order to (a) detect mTBI earlier and (b) accurately estimate the level of mTBI biomarkers. The objective of this particular application is two-fold: Training objective - to provide the PI with te mentored training in order to develop the clinical skills needed for an independent career in bioimaging. Technical objective - to improve the detection and estimation of mTBI biomarkers using high- resolution quantification of one specific EMTP feature, magnetic susceptibility. Our central hypothesis is that maximizing the contrast available from high-resolution MR phase would enable better detection of cerebral micro- bleeds (CMBs) and improved estimation of iron concentration with magnetic susceptibility imaging methods, such Susceptibility-Weighted Imaging (SWI) and Quantitative Susceptibility Mapping (QSM). This hypothesis has been formulated based on preliminary data which showed that our novel MR phase imaging framework substantially reduces the fundamental limits of phase measurements and yields an order of magnitude gain in the Contrast to Noise Ratio (CNR) of phase. The rationale here is that attainment of this objective would enable early detection of mTBI, as well as improved prediction of mTBI symptom presentation. To test the hypothesis, and attain the training objective, we will pursue the following aims:
Aim 1 : Maximize the CNR attainable from high resolution MR phase measurements.
Aim 2 : Improve the micro-bleed detection performance of SWI and QSM.
Aim 3 : Increase the iron concentration estimation performance of SWI and QSM. The proposed research is signifi- cant because it will advance the development of methods capable of detecting and estimating mTBI biomarkers at earlier stages. The proposed approach is innovative because it represents a fundamental departure from established approaches used to both, acquire and compute phase information in MRI. The training component of this project is significant because it is specifically targeted towards enhancing the biomedical aspects in the PI's background. The proposed mentored research will prepare the PI to become an independent investigator via didactic and progressive exposure to: (a) lectures in biomedical imaging and brain physiology, focusing on mTBI, (b) training in programming MR pulse sequences, focusing on imaging in brain trauma settings, (c) exposure to clinical research environment, focusing on inter-disciplinary collaborations, and (d) preparation of competitive grant applications.
The proposed research is relevant to public health because it enables the development of a novel technology which will allow the clinicians to (a) identify mTBI patients at an earlier stage in the disease process, and (b) accurately and quantitatively assess diagnosed mTBI patients. Thus, the project is relevant to NIH's mission because it will contribute towards the advancement of knowledge of mTBI disease process which will enable the development of methods that reduce the burdens of illness and disability associated with this injury.
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