On the Origin of the Brain Semi‐Heavy Water Deuterium MR Signal Following Administration of Deuterated Metabolic Substrate: A Cautionary Tale
Year: 2026
Type: article
Abstract: ABSTRACT Purpose To evaluate the extent to which the appearance of HOD in the brain following systemic administration of a deuterated substrate is due to local brain metabolism versus body metabolism. Methods [6,6‐ 2 H 2 ]glucose, which is transported across the blood‐brain barrier (BBB), and [6,6‐ 2 H 2 ]fructose (Fruc), which does not cross the BBB, were administered to four mouse cohorts. Cohorts included wild‐type mice, glucose transporter deficiency mice, which have decreased brain glucose uptake from the blood, and littermate control mice. A separate wild‐type cohort received a 15‐μL intramuscular (leg) injection of D 2 O. Brain‐localized DMRS experiments employed the ISIS single‐voxel protocol at 11.74 T. Results Following leg D 2 O injection, semi‐heavy water (HOD) appears within the brain in minutes, reaching steady state shortly thereafter. Body metabolism of [6,6‐ 2 H 2 ]fructose produces HOD that also appears in the brain within minutes following subcutaneous administration, with an initial rate (mM/min) substantially greater than following administration of [6,6‐ 2 H 2 ]glucose. Deuterated glucose from body metabolism of [6,6‐ 2 H 2 ]fructose also appears in the brain. The terminal rates for HOD appearance in the brain are indistinguishable for the four cohorts examined despite there being up to a five‐fold difference in brain concentration (mM) of deuterium‐labeled glucose. Conclusion Body production of HOD dominates the initial increase of HOD in brain following administration of [6,6‐ 2 H 2 ]fructose and likely contributes significantly to the increase of HOD in brain following administration of [6,6‐ 2 H 2 ]glucose. Interpretation of HOD concentrations as representative of organ‐specific metabolism requires careful consideration of control experiments and assessment of HOD contributions from body metabolism of the administered deuterated substrate.
Source: Magnetic Resonance in Medicine
DOI: 10.1002/mrm.70347
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,680
OpenAlex ID: W7140191651