Malloy, Craig R.

Abstract Hyperpolarized [1-¹³C]pyruvate MRI provides real-time, radiation-free insight into myocardial pyruvate metabolism and mitochondrial oxidative capacity, yet its utility in patients with severe multivessel coronary artery disease before and after surgical revascularization remains unknown. Here we show, in the first prospective study applying this technique to three-vessel disease, that serial imaging is feasible and safe with no serious adverse events in 22 injections. Healthy myocardium displayed a bicarbonate-to-total hyperpolarized carbon product ratio of 0.66 ± 0.13, indicating that the majority of pyruvate undergoes oxidation. Patients exhibited significantly lower ratios in the inferolateral segment (P = 0.03) with reciprocal increases in lactate, and global ratios correlated with left ventricular ejection fraction (r = 0.695, P = 0.006). Post-revascularization changes were heterogeneous across individuals. These findings establish hyperpolarized 13C MRI as a powerful tool for noninvasive assessment of myocardial metabolism in multivessel coronary artery disease and support its potential for longitudinal therapeutic monitoring.

Introduction: Hyperpolarized [1- 13 C] pyruvate magnetic resonance imaging (HP- 13 C MRI) enables real-time, noninvasive assessment of myocardial metabolism. While the technique is increasingly applied in cardiac research, dedicated tools for standardized analysis remain limited. We developed HP- 13 CMRAnalyst , a MATLAB-based application that supports dynamic 13 C data processing through semi-automated segmentation, time-course extraction, and metabolic ratio mapping (Figure 1A). Hypothesis: An integrated platform combining multi-frame 13 C data import, cine co-registration, multi-segment analysis, and voxel-level ratio mapping facilitates reproducible quantification of myocardial metabolism. Methods: HP- 13 CMRAnalyst was implemented in MATLAB App Designer and distributed as an .mlappinstall package. It accepts DICOM or NIfTI dynamic pyruvate, lactate, and bicarbonate images (∼3 s resolution; ≤ 60 s)(Figure 1B). Cine-registered T 1 -weighted images guide AHA 17-segment LV segmentation on short axis (SAX) and long axis (LAX) views (Figure 1C). A time slider displays metabolite overlays. Peak intensities are extracted per segment to compute bicarbonate/lactate and bicarbonate/pyruvate ratios. Pixel-wise ratio maps are exported as CSV, MATLAB struct, and PDF summaries. Results: Eight subjects (n = 4 healthy; n = 4 coronary artery disease [CAD]), each imaged pre- and post-CABG (total n = 12 datasets; age 55 ± 12 years), were processed in < 5 min per dataset on a standard desktop (MATLAB R2024b). Semi-automated versus manual segmentation agreement was high (Dice 0.89–0.93). Inter-observer variability for segmental bicarbonate/(bicarbonate + lactate) ratios were minimal biases < 0.005 and limits of agreement within ± 0.083 across all observer pairs (Figure 1D). Ratio maps qualitatively revealed regional metabolic heterogeneity. Automated reports accurately reflected metadata and segmental summaries. The GUI, logs, and summary files streamline standardized processing. Conclusions: HP- 13 CMRAnalyst delivers a rapid (< 5 min), reproducible framework for dynamic HP- 13 C MRI analysis. By combining semi-automated segmentation and pixel-level ratio mapping with low inter-observer variability, this platform may accelerate adoption of 13 C metabolic imaging in human cardiac research.

ABSTRACTSurgical biopsy of brainstem tumors carries a risk of neurological injury. We performed magnetic resonance spectroscopy (MRS) of 2‐hydroxyglutarate (2HG) and glycine in patients with brainstem tumors to assess the feasibility of detecting and quantifying 2HG in the brainstem to obviate the need for a diagnostic biopsy and to establish the clinical significance of glycine MRS in brainstem tumors in vivo. Twenty adult patients with radiographically identified presumed brainstem gliomas were prospectively enrolled in the study. Proton MRS was obtained at 3T with a protocol tailored for detection of 2HG and glycine (TE 97‐ms PRESS). Spectra were fit using LCModel software and in‐house basis signals of metabolites and lipids. The metabolite concentrations were quantified with reference to water and examined with respect to clinical outcomes, including postgadolinium MRI and overall survival time. MRS data from 19 patients were included in subsequent analysis, excluding suboptimal data from one patient. Tumors with elevated 2HG (> 1.9 mM, N = 8) and undetectable 2HG (< 0.3 mM, N = 11) were clearly distinguishable. Tumors with elevated glycine (> 1.5 mM, N = 4) showed rapid progression. Kaplan–Meier survival analyses with metabolite measures demonstrated that tumors with 2HG higher than 1.0 mM were significantly associated with a favorable prognosis (p = 0.01). In contrast, tumors with glycine higher than 2.5 mM showed a strong association with poor survival (p = 0.0005). The data confirm detection of 2HG in brainstem tumors at a concentration that is consistent with an IDH mutation and expected good prognosis, whereas elevated glycine in brainstem tumors portends rapid tumor progression and a worse prognosis.