Deuterium imaging of the Warburg effect at sub‐millimolar concentrations by joint processing of the kinetic and spectral dimensions

Author:

Montrazi Elton T.1,Bao Qingjia2,Martinho Ricardo P.13,Peters Dana C.4,Harris Talia5,Sasson Keren6,Agemy Lilach6,Scherz Avigdor6,Frydman Lucio1ORCID

Affiliation:

1. Department of Chemical and Biological Physics Weizmann Institute of Science Rehovot Israel

2. Innovation Academy for Precision Measurement Science and Technology Chinese Academy of Sciences Wuhan China

3. University of Twente Enschede The Netherlands

4. Department of Radiology and Biomedical Imaging Yale School of Medicine New Haven Connecticut USA

5. Department of Chemical Research Support Weizmann Institute of Science Rehovot Israel

6. Department of Plant and Environmental Science Weizmann Institute of Science Rehovot Israel

Abstract

Deuterium metabolic imaging (DMI) is a promising molecular MRI approach, which follows the administration of deuterated substrates and their metabolization. [6,6’‐2H2]‐glucose for instance is preferentially converted in tumors to [3,3’‐2H2]‐lactate as a result of the Warburg effect, providing a distinct resonance whose mapping using time‐resolved spectroscopic imaging can diagnose cancer. The MR detection of low‐concentration metabolites such as lactate, however, is challenging. It has been recently shown that multi‐echo balanced steady‐state free precession (ME‐bSSFP) increases the signal‐to‐noise ratio (SNR) of these experiments approximately threefold over regular chemical shift imaging; the present study examines how DMI's sensitivity can be increased further by advanced processing methods. Some of these, such as compressed sensing multiplicative denoising and block‐matching/3D filtering, can be applied to any spectroscopic/imaging methods. Sensitivity‐enhancing approaches were also specifically tailored to ME‐bSSFP DMI, by relying on priors related to the resonances' positions and to features of the metabolic kinetics. Two new methods are thus proposed that use these constraints for enhancing the sensitivity of both the spectral images and the metabolic kinetics. The ability of these methods to improve DMI is evidenced in pancreatic cancer studies carried at 15.2 T, where suitable implementations of the proposals imparted eightfold or more SNR improvement over the original ME‐bSSFP data, at no informational cost. Comparisons with other propositions in the literature are briefly discussed.

Funder

Weizmann Institute of Science

Perlman Family Foundation

Israel Science Foundation

Publisher

Wiley

Subject

Spectroscopy,Radiology, Nuclear Medicine and imaging,Molecular Medicine

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