This TRD, Magnetic Resonance Spectroscopy (MRS) and Multinuclear Imaging, has been actively involved in the development and evaluation of in vivo MRS and spectroscopic imaging (MRSI) technology for both protons (1H) and other nuclei from the founding of the CAMRTS P41 Research Resource Center in 1995 to the present. While some of our recent metabolic imaging studies involved a variety of organs including kidney, heart, and liver, our primary effort during the prior funding cycle was on the development of novel methods for measuring brain neurotransmitter levels and neurometabolic processes. Under this competitive renewal, we propose to build upon our successes in brain imaging technology with important refinements needed to translate hyperpolarized 13C MRSI techniques from animal to human applications, improve 1H MRS measures of steady-state neurotransmitter levels, and provide previously unavailable regional measures of neuroenergetic and neurotransmitter cycling rates throughout the human brain. These choices are based on meeting the current and future needs of collaborative projects ?Metabolic Therapy of GBM guided by MRS of hyperpolarized 13C-pyruvate? (PI: Lawrence Recht, Stanford University), ?1H MRS of GABA, Glu, and Gln? [PI: Brian Wandell, Stanford University), and Neuroimaging of Alcoholism (PI: Adolf Pfefferbaum, SRI International). Specifically, in vivo MRSI offers non-invasive identification, visualization, and quantification of brain biochemical markers and neurotransmitters, the assessment of abnormalities in injured or diseased brain tissue, the longitudinal monitoring of degenerative diseases, and the early evaluation of therapeutic interventions. 1H MRS is able to measure steady-state levels of GABA, glutamate (Glu), and glutamine (Glu), and infusion of 13C labeled substrates permits the measurement of tricarboxylic acid (TCA) cycle and neurotransmitter cycling rates. Furthermore, the ongoing development of hyperpolarized agents, i.e., MRIvisible compounds whose magnetization is four orders of magnitude higher than that normally achieved at in vivo temperatures, presents unprecedented opportunities to noninvasively monitor critical dynamic metabolic processes under both normal and pathologic conditions. New MRS technology will be developed in accordance with the following Specific Aims: 1) to develop optimized pulse sequences and hardware for clinical hyperpolarized 13C studies of the human brain and glioma treatment response, 2) to develop improved 1H MRS GABA, Glu, and Gln editing methods to robustly measure steady-state neurotransmitter levels throughout the human brain free from overlapping macromolecular resonances that limit current methods, and 3) to develop indirect-detection 1H-13C techniques to measure TCA and Glu/Gln cycling rates throughout the human brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB015891-25
Application #
9689550
Study Section
Special Emphasis Panel (ZEB1)
Project Start
Project End
2021-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
25
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Weber, Hans; Hargreaves, Brian A; Daniel, Bruce L (2018) Artifact-reduced imaging of biopsy needles with 2D multispectral imaging. Magn Reson Med 80:655-661
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Tian, Qiyuan; Wintermark, Max; Jeffrey Elias, W et al. (2018) Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor. Neuroimage Clin 19:572-580
Weber, Hans; Ghanouni, Pejman; Pascal-Tenorio, Aurea et al. (2018) MRI monitoring of focused ultrasound sonications near metallic hardware. Magn Reson Med 80:259-271
Hegarty 2nd, John P; Gu, Meng; Spielman, Daniel M et al. (2018) A proton MR spectroscopy study of the thalamus in twins with autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry 81:153-160
Srinivasan, Subashini; Hargreaves, Brian A; Daniel, Bruce L (2018) Fat-based registration of breast dynamic contrast enhanced water images. Magn Reson Med 79:2408-2414
Yoruk, Umit; Hargreaves, Brian A; Vasanawala, Shreyas S (2018) Automatic renal segmentation for MR urography using 3D-GrabCut and random forests. Magn Reson Med 79:1696-1707
Terem, Itamar; Ni, Wendy W; Goubran, Maged et al. (2018) Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI). Magn Reson Med 80:2549-2559
Levine, Evan; Hargreaves, Brian (2018) On-the-Fly Adaptive ${k}$ -Space Sampling for Linear MRI Reconstruction Using Moment-Based Spectral Analysis. IEEE Trans Med Imaging 37:557-567
Hargreaves, Brian A; Taviani, Valentina; Litwiller, Daniel V et al. (2018) 2D multi-spectral imaging for fast MRI near metal. Magn Reson Med 79:968-973

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