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2018 Fiscal Year Annual Research Report

パラ水素誘起核偏極によるピルビン酸の超偏極13C MRI代謝イメージング法の発展

Research Project

Project/Area Number 18F18114
Research InstitutionHokkaido University
Host Researcher 松元 慎吾  北海道大学, 情報科学研究院, 准教授 (90741041)
Foreign Research Fellow STEWART NEIL  北海道大学, 情報科学研究科, 外国人特別研究員
Project Period (FY) 2018-07-25 – 2020-03-31
KeywordsMRI / 核偏極 / 代謝 / 分子イメージング
Outline of Annual Research Achievements

Hyperpolarization is a means to obtain ~10000-fold signal enhancement in MRI, enabling visualization of otherwise undetectable biological compounds. Recently-developed side-arm (SA) para-hydrogen induced polarization (PHIP) presents a cost-effective method for producing hyperpolarized 13C for in vivo metabolic MRI. Our research goals are: (i) validate 13C-pyruvate polarized by SA-PHIP as an in vivo metabolic probe in small-animal disease models; (ii) expand the current suite of 13C probes that can be polarized by PHIP for metabolic MRI for cancer and other biological applications, and validate these in vivo; (iii) allow long-term monitoring of metabolism by development of HP 13C probes with extended hyperpolarization lifetime.
We have achieved ~80,000-fold signal enhancement of 13C-allypyruvate and 20,000-fold of pyruvate in MRI by improvement of the procedures of para-hydrogenation and following proton to carbon polarization transfer, which polarization level is high enough to conduct metabolic MRI. We also developed a partial-k space image acquisition for chemical shift imaging and deep learning image reconstruction technique to boost image data acquisition, shortening an image acquisition time to a fifth of default sequence.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Hyperpolarization is a means to obtain ~10000-fold signal enhancement in MRI, enabling visualization of otherwise undetectable biological compounds. Recently-developed side-arm (SA) para-hydrogen induced polarization (PHIP) presents a cost-effective method for producing hyperpolarized 13C for in vivo metabolic MRI. Our research goals are: (i) validate 13C-pyruvate polarized by SA-PHIP as an in vivo metabolic probe in small-animal disease models; (ii) expand the current suite of 13C probes that can be polarized by PHIP for metabolic MRI for cancer and other biological applications, and validate these in vivo; (iii) allow long-term monitoring of metabolism by development of HP 13C probes with extended hyperpolarization lifetime.
By improvement of the procedures of para-hydrogenation and following proton to carbon polarization transfer, we have successfully achieved ~80,000-fold signal enhancement of 13C-allypyruvate and 20,000-fold of pyruvate in MRI compared to the thermal signal at 1.5T using the cost effective PHIP technique, which polarization level is high enough to conduct hyperpolarized 13C metabolic MRI. We also developed a partial-k space image acquisition for chemical shift imaging and deep learning image reconstruction technique to boost image data acquisition, shortening an image acquisition time to a fifth of default sequence.

Strategy for Future Research Activity

The polarization of 13C-pyruvate by a PHIP technique is going to be further improved by optimizing the procedure of hydrolysis of alcohol side-arm, and plan to apply the SA PHIP polarized 13C-pyuvate for metabolic imaging of xenografts of hepatic cancer and squamous cell carcinoma. The image quality will be compared to the images obtained by the standard DNP based hyperpolarization technique. We also expand the developed SA PHIP technique to other useful metabolic probe such as 13C-fumarate for non-invasive necrosis imaging. In parallel, to maximize the information available from 13C-pyruvate metabolic imaging experiments, we will further optimize existing imaging strategies to maximize the temporal resolution of dynamic metabolic imaging, and to develop tailored image acquisition techniques for our desired applications.

Research Products

(1 results)

All 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Long-range heteronuclear J-coupling constants in esters: Implications for 13C metabolic MRI by side-arm parahydrogen-induced polarization.2018

    • Author(s)
      Stewart NJ, Kumeta H, Tomohiro M, Hashimoto T, Hatae N, Matsumoto S.
    • Journal Title

      J Magn Reson.

      Volume: 296 Pages: 85-92

    • DOI

      0.1016/j.jmr.2018.08.009

    • Peer Reviewed

URL: 

Published: 2019-12-27  

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