# Downfield MR spectroscopic imaging of the human brain

> **NIH NIH K99** · JOHNS HOPKINS UNIVERSITY · 2024 · $136,231

## Abstract

Project Summary
In proton magnetic resonance spectroscopy (MRS) of the human brain, signals arise both upfield (UF) and
downfield (DF) from the water resonance. While UF MRS and MR spectroscopic imaging (MRSI) have been
extensively studied in humans over the last 30 years, there have been very few downfield studies, and all of
them used single voxel spatial localization. Recently, our group developed the first single slice approach for in
vivo DF-MRSI at 3T5. Subsequently, I have further implemented the first three-dimensional (3D) DF-MRSI
methods in the human brain with whole brain coverage, on both clinical high-field (3T) and research ultra-high-
field (7T) MR systems.
 Currently, there are two significant technical challenges for DF-MRSI, namely (a) the lack of pulse sequences
to acquire 3D DF-MRSI with optimum sensitivity in the shortest possible scan time, and (b) specific software for
the accurate quantification and visualization of the broad and significantly overlapping DF signals. In addition,
the clinical and neuroscience applications of DF-MRSI have yet to be explored. To address these issues, I
propose to develop optimized 3D DF-MRSI pulse sequences for both 3T and 7T, and also to develop an open-
source software package for improved quantification, analysis, and visualization of DF resonances. DF spectra
contain signals from both exchangeable and non-exchangeable protons, and the information content of DF-
MRSI may therefore be complementary to chemical exchange saturation transfer (CEST) MRI. In particular,
amide-proton transfer (APT) CEST has proven quite successful for the evaluation of human brain tumors; in
the R00 phase of this proposal, after establishing normative values and reproducibility, a comparison of the
value of 3D DF-MRSI vs. APT-CEST in patients with glioma will be performed. In particular, I will focus on the
ability to distinguish recurrent tumor from radiation necrosis in patients treated for high grade glioma; this is an
important diagnostic question that directly effects choice of treatment, and which is often difficult to answer
using conventional MRI.
 Developing these novel techniques requires substantial expertise both in MRSI sequence development and
in data analysis. This proposal builds upon my unique record in biomedical imaging with new training from a
mentoring team of globally recognized experts in the fields of MRSI, clinical multimodal spectroscopic imaging,
and development of post-processing and analysis software at the Johns Hopkins University with outstanding
career development resources to successfully train me during this Pathway to Independence Award. This
project will generate novel tools to study metabolic processes in neurological and neuropathological processes
and leverage their potential to advance the understanding of brain tumors, potentially indicating new routes
toward improved diagnosis and efficient therapy strategies.

## Key facts

- **NIH application ID:** 10841623
- **Project number:** 5K99EB034768-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** İpek Özdemir
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $136,231
- **Award type:** 5
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841623

## Citation

> US National Institutes of Health, RePORTER application 10841623, Downfield MR spectroscopic imaging of the human brain (5K99EB034768-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10841623. Licensed CC0.

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