Frese Sabina, Strasser Bernhard, Hingerl Lukas, Montrazi Elton, Frydman Lucio, Motyka Stanislav, Bader Viola, Duguid Anna, Osburg Aaron, Krssak Martin, Lanzenberger Rupert, Scherer Thomas, Bogner Wolfgang, Niess Fabian
From the High Field MR Center, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (S.F., B.S., L.H., S.M., V.B., A.D., A.O., W.B., F.N.); Department of Chemical and Biological Physics, Weizmann Institute of Science, Rehovot, Israel (E.M., L.F.); Christian Doppler Laboratory for MR Imaging Biomarkers (BIOMAK), Vienna, Austria (S.M., W.B.); Department of Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria (M.K., T.S.); and Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria (R.L.).
Invest Radiol. 2025 Apr 25. doi: 10.1097/RLI.0000000000001196.
Deuterium (2H) metabolic imaging (DMI) is an emerging magnetic resonance technique to non-invasively map human brain glucose (Glc) uptake and downstream metabolism following oral or intravenous administration of 2H-labeled Glc. The achievable spatial resolution is limited due to inherently low sensitivity of DMI. This hinders potential clinical translation. The purpose of this study was to improve the signal-to-noise ratio (SNR) of 3D DMI via a balanced steady-state free precession (bSSFP) acquisition scheme combined with fast non-Cartesian spatial-spectral sampling to enable high-resolution dynamic imaging of neural Glc uptake and glutamate+glutamine (Glx) synthesis of the human brain at 7T.
Six healthy volunteers (2 f/4 m) were scanned after oral administration of 0.8 g/kg [6,6']-2H-Glc using a novel density-weighted bSSFP acquisition scheme combined with fast 3D concentric ring trajectory (CRT) k-space sampling at 7T. Time-resolved whole brain DMI datasets were acquired for approximately 80 minutes (7 minutes per dataset) after oral 2H-labeled Glc administration with 0.75 mL and 0.36 mL isotropic spatial resolution and results were compared to conventional spoiled Free Induction Decay (FID) 2H-MRSI with CRT readout at matched nominal spatial resolution. Dynamic DMI measurements of the brain were accompanied by simultaneous systemic Glc measurements of the interstitial fluid using a continuous Glc monitoring (CGM) sensor (on the upper arm). The correlation between brain and interstitial Glc levels was analyzed using linear mixed models.
The bSSFP-CRT approach achieved SNRs that were up to 3-fold higher than conventional spoiled FID-CRT 2H-MRSI. This enabled a 2-fold higher spatial resolution. Seventy minutes after oral tracer uptake comparable 2H-Glc, 2H-Glx, and 2H-water concentrations were detected using both acquisition schemes at both, regular and high spatial resolutions (0.75 ml and 0.36 mL isotropic). The mean Areas Under the Curve (AUC) for interstitial fluid Glc measurements obtained using a CGM sensor was 509 ± 65 mM·min. This is 3.4 times higher than the mean AUC of brain Glc measurements of 149 ± 43 mM·min obtained via DMI. The linear mixed models fitted to assess the relationship between CGM measures and brain 2H-Glc yielded statistically significant slope estimates in both GM (β1 = 0.47, P = 0.01) and WM (β1 = 0.36, P = 0.03).
In this study we successfully implemented a balanced steady-state free precession (bSSFP) acquisition scheme for dynamic whole-brain human DMI at 7T. A 3-fold SNR increase compared to conventional spoiled acquisition allowed us to double the spatial resolution achieved using conventional FID-CRT DMI. Systemic continuous glucose measurements, combined with dynamic DMI, demonstrate significant potential for clinical applications. This could help improve our understanding of brain glucose metabolism by linking it to time-resolved peripheral glucose levels. Importantly, these measurements are conducted in a minimally invasive and physiological manner.
氘（2H）代谢成像（DMI）是一种新兴的磁共振技术，可在口服或静脉注射2H标记的葡萄糖后，无创地绘制人类大脑葡萄糖（Glc）摄取及下游代谢情况。由于DMI本身灵敏度较低，其可实现的空间分辨率受限，这阻碍了其潜在的临床应用转化。本研究的目的是通过平衡稳态自由进动（bSSFP）采集方案结合快速非笛卡尔空间谱采样，提高3D DMI的信噪比（SNR），从而在7T条件下对人类大脑神经Glc摄取和谷氨酸+谷氨酰胺（Glx）合成进行高分辨率动态成像。
6名健康志愿者（2名女性/4名男性）在口服0.8 g/kg [6,6']-2H-Glc后，采用一种新型的密度加权bSSFP采集方案结合7T条件下的快速3D同心环轨迹（CRT）k空间采样进行扫描。口服2H标记的葡萄糖后，以0.75 mL和0.36 mL各向同性空间分辨率采集时间分辨的全脑DMI数据集约80分钟（每个数据集7分钟），并将结果与在匹配的标称空间分辨率下采用CRT读出的传统扰相自由感应衰减（FID）2H-MRSI进行比较。大脑的动态DMI测量同时使用连续葡萄糖监测（CGM）传感器（在上臂）对组织间液进行全身葡萄糖测量。使用线性混合模型分析大脑和组织间葡萄糖水平之间的相关性。
bSSFP-CRT方法实现的SNR比传统扰相FID-CRT 2H-MRSI高3倍。这使得空间分辨率提高了2倍。口服示踪剂摄取2H-Glc 70分钟后，在常规和高空间分辨率（0.75 ml和0.36 mL各向同性）下，两种采集方案均检测到了相当的2H-Glc、2H-Glx和2H-水浓度。使用CGM传感器获得的组织间液葡萄糖测量的平均曲线下面积（AUC）为509±65 mM·min。这比通过DMI获得的大脑葡萄糖测量的平均AUC（149±43 mM·min）高3.4倍。用于评估CGM测量值与大脑2H-Glc之间关系的线性混合模型在灰质（β1 = 0.47，P = 0.01）和白质（β1 = 0.36，P = 0.03）中均产生了具有统计学意义的斜率估计值。
在本研究中，我们成功地在7T条件下为动态全脑人类DMI实施了平衡稳态自由进动（bSSFP）采集方案。与传统扰相采集相比，SNR提高了3倍，使我们能够将使用传统FID-CRT DMI实现的空间分辨率提高一倍。全身连续葡萄糖测量与动态DMI相结合，显示出巨大的临床应用潜力。这有助于通过将大脑葡萄糖代谢与时间分辨的外周葡萄糖水平联系起来，增进我们对大脑葡萄糖代谢的理解。重要的是，这些测量是以微创和生理的方式进行的。
