Feasibility of Concurrent 1H MRS & 31P MRSI at 7T: Brain Energy Metabolism Responses to Hyperglycemia

TL;DR

It is shown that 1H and 31P MRS(I) can be interleaved at 7 T to measure energy metabolism within a single session to track a glucose-related 1H signal alongside 31P measures of high-energy phosphate metabolism during a hyperglycemic clamp.

Abstract

How the human brain adjusts fuel handling and its bioenergetic state during changing glucose levels remains difficult to assess noninvasively. In this study, we established an interleaved multinuclear 7 T MR spectroscopy protocol to track a glucose-related 1H signal alongside 31P measures of high-energy phosphate metabolism during a hyperglycemic clamp. Five healthy adults completed a morning, fasted infusion experiment consisting of baseline, ramp-up, and hyperglycemic stages over approx. 120 min. Short-block, short-TE 1H single-voxel spectroscopy (STEAM, TE = 11 ms; mean block duration 5.71 (SD:0.62 min)) was acquired in frontal cortex and quantified using the composite Glucose+Taurine (Glc+Tau) measure. 31P was acquired with rapid 3D PETALUTE MRSI using an ultrashort echo time (UTE; TE = 65 micros; 381 s per block), and high-energy phosphate ratios were derived from a posterior cortical region of interest. Across participants, 1H Glc+Tau increased with blood glucose and showed significant elevations from baseline into hyperglycemia. In parallel, 31P ratios exhibited smaller but significant glycemia-linked responses: both PCr/Pi and gamma-ATP/Pi increased with blood glucose and differed across glucose clamp stages. These findings show that 1H and 31P MRS(I) can be interleaved at 7 T to measure energy metabolism within a single session

Figures (6)

• Figure 1: Interleaved $^{1}$H/$^{31}$P MRS protocol during hyperglycemic clamp at 7 T. (A) Timing diagram showing repeated blood-glucose sampling (gray), interleaved $^{31}$P PETALUTE MRSI blocks (orange) and $^{1}$H MRS blocks (blue) across baseline, ramp-up, and two hyperglycemic stages. The glucose infusion period is indicated in green; total measurement time $\approx$120 min. (B) Anatomical reference (MP2RAGE) overlaid and $^{31}$P PETALUTE first time point image with ROIs marked (Participant 3): frontal $^{1}$H SVS voxel (20$\times$20$\times$20 mm$^{3}$, blue) and the posterior $^{31}$P used for PETALUTE voxel averaging (60$\times$60$\times$40 mm$^{3}$, orange). (C) Representative time-resolved spectra (Participant 3) acquired throughout the session for $^{31}$P (left; Pi and PCr highlighted) and $^{1}$H (right; Glc+Tau region highlighted).
• Figure 2: Participant-specific clamp performance and metabolite time courses. Rows show individual participants. Left column: blood glucose (blue, left axis) and glucose infusion rate (orange, right axis) over time. Middle column: baseline-normalized $^{1}$H Glc+Tau measured from the frontal SVS voxel. Right column: baseline-normalized $^{31}$P PCr/Pi derived from PETALUTE ROI spectra. Shaded backgrounds indicate clamp-stages (baseline, ramp-up, Hyperglycemia I, Hyperglycemia II) using the same color scheme as Figure \ref{['fig:fig1']}. Dashed horizontal lines denote the baseline normalization reference (value = 1).
• Figure 3: Associations between blood glucose, $^{1}$H Glc+Tau, and $^{31}$P PCr/Pi. (A) $^{1}$H Glc+Tau versus blood glucose across all participants and time points. The solid line indicates the linear mixed-effects fit (random intercept per subject); the repeated-measures correlation coefficient ($r_m$) and $p$-values are reported in-panel. (B) $^{31}$P PCr/Pi versus $^{1}$H Glc+Tau with linear fit and repeated-measures correlation. (C) $^{31}$P PCr/Pi versus blood glucose with linear fit and repeated-measures correlation. Marker color encodes time relative to infusion start (minutes; color bar).
• Figure 4: Clamp-stage-dependent changes in $^{1}$H Glc+Tau and $^{31}$P PCr/Pi. (A) Baseline-normalized $^{1}$H Glc+Tau across clamp-stages (Baseline, Ramp-up, Hyperglycemia I, Hyperglycemia II, and pooled Hyperglycemia (I+II)). (B) Baseline-normalized $^{31}$P PCr/Pi across the same clamp-stages. Boxplots show median and interquartile range; whiskers indicate range and points represent individual measurements; Horizontal brackets denote significant post-hoc differences between clamp-stages ($^{*}p<0.05$, $^{**}p<0.01$, $^{***}p<0.001$).
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