Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Sci Rep. 2019 Mar 4;9(1):3410. doi: 10.1038/s41598-019-38981-1.
Metabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only.C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements unless dissolution dynamic nuclear polarization (dDNP) is used to increase the signal, which brings additional complications for clinical use. We show here a new method of imaging glucose metabolism in vivo by MRI chemical shift imaging (CSI) experiments that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12s and an overall spatial resolution that compares favorably to F-FDG PET.
代谢重编程是癌症的一个特征,异常代谢与许多其他病理有关。能够检测到这些变化的分子成像技术已经成为癌症诊断、治疗计划和监测的必要手段。特别是,FDG-PET 由于其通过测量葡萄糖摄取来检测异常分子途径的独特能力,已成为癌症的一种重要成像方式。然而,FDG-PET 有其局限性,限制了它在某些情况下的用途,而且所获得的信息仅限于葡萄糖摄取。C 磁共振波谱在理论上比 FDG-PET 具有某些优势,但由于其固有低灵敏度,除了使用溶解动态核极化 (dDNP) 来增加信号外,其主要用途限于单像素测量,这给临床应用带来了额外的复杂性。我们在这里展示了一种通过 MRI 化学位移成像 (CSI) 实验在体内成像葡萄糖代谢的新方法,该方法依赖于一种简单但稳健高效的后处理过程,即通过更高维奇异值分解的模拟,张量分解。使用这种方法,我们在 dDNP 和非超极化非局部化实验中实现了信噪比的数量级提高,而不会牺牲准确性。在 CSI 实验中,观察到大约 30 倍的信号增强,足以在不进行超极化的情况下对指示沃伯格效应的葡萄糖到乳酸的转化进行成像,时间分辨率为 12 秒,整体空间分辨率与 F-FDG PET 相当。