Clinical trials for neurodegenerative diseases are hampered by the lack of quantitative and objective biomarkers that reflect treatment effects in the brain. Magnetic resonance spectroscopy (MRS) has potential to directly assess disease-modifying effects of therapeutic interventions in the brain. However, MRS has not made the transition to the clinical setting, largely due to lack of standardization of data acquisition and analysis methods and compromised data quality obtained with standard clinical packages, which result in poor reproducibility of neurochemical concentrations. The primary objective of this project is to facilitate translation of advanced MRS technology to the clinical setting in a strategic alliance between MR physicists, software engineers and physician scientists. This Partnership for MRS Biomarker Development is comprised of 3 phases and incorporates a gradual shift from MRI/MRS to clinical expertise at the sites involved: Phase I has established an MR- technologist ready advanced MRS protocol on two widely-used clinical 3T platforms (Siemens and Philips). Phase II is assessing the performance of the protocol under ideal conditions (efficacy), namely at sites where MRI/S and clinical trial expertise overlap. We focus on hereditary spinocerebellar ataxias (SCA) because the patient cohorts are well-characterized and they present the greatest need for multi-center investigations to sufficiently sample the patient population in trials. Finally, Phase III will assess the performance of the protocol under ordinary conditions (effectiveness), i.e. in a clinical setting with rotating MR technologists. This phase will focus on Alzheimer disease (AD), the most common cause of age associated cognitive decline and dementia, and take advantage of large ongoing neuroimaging investigations. We now have an unanticipated opportunity to implement and test the advanced MRS protocol on all 3 major MRI scanner platforms (Siemens, Philips and GE) by utilizing the GE platform instead of Philips at one of the Phase III sites, University of Michigan. The MRS pulse sequence has already been implemented on the GE platform in collaboration with the Global Spectroscopy Leader of GE Healthcare. This administrative supplement is requested to support the additional testing that will be required at U Michigan to implement the full protocol, including communication of the MRS sequence with additional technology we have developed in Phase I, to automate volume-of-interest selection.
The overall goal of this project is to build a multi-institute partnership to establish the feasibility of using advanced, quantitative imaging technology in the clinical setting for neurodegenerative diseases. The technology is intended for noninvasive monitoring of pathology and effects of treatments in the brain. In this supplement, we request funds to implement and evaluate the advanced imaging technology on all 3 major MRI platforms (Siemens, Philips and GE), instead of the original plan to utilize only two platforms. This is an unanticipated opportunity that will substantially increase the value of the project because harmonization of advanced imaging technology across all 3 platforms is a pressing need in our field.
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| Deelchand, Dinesh K; Kantarci, Kejal; Öz, Gülin (2018) Improved localization, spectral quality, and repeatability with advanced MRS methodology in the clinical setting. Magn Reson Med 79:1241-1250 |
| Joers, James M; Deelchand, Dinesh K; Lyu, Tianmeng et al. (2018) Neurochemical abnormalities in premanifest and early spinocerebellar ataxias. Ann Neurol 83:816-829 |
| Zeydan, Burcu; Deelchand, Dinesh K; Tosakulwong, Nirubol et al. (2017) Decreased Glutamate Levels in Patients with Amnestic Mild Cognitive Impairment: An sLASER Proton MR Spectroscopy and PiB-PET Study. J Neuroimaging 27:630-636 |
| Cheong, Ian; Marja?ska, Ma?gorzata; Deelchand, Dinesh K et al. (2017) Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis. Neurochem Res 42:1833-1844 |
