Koelsch Bertram L, Sriram Renuka, Keshari Kayvan R, Leon Swisher Christine, Van Criekinge Mark, Sukumar Subramaniam, Vigneron Daniel B, Wang Zhen J, Larson Peder E Z, Kurhanewicz John
Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, CA, USA.
Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
J Magn Reson. 2016 Sep;270:115-123. doi: 10.1016/j.jmr.2016.07.002. Epub 2016 Jul 9.
This work demonstrates the separation of extra- and intracellular components of glycolytic metabolites with diffusion weighted hyperpolarized (13)C magnetic resonance spectroscopy. Using b-values of up to 15,000smm(-2), a multi-exponential signal response was measured for hyperpolarized [1-(13)C] pyruvate and lactate. By fitting the fast and slow asymptotes of these curves, their extra- and intracellular weighted diffusion coefficients were determined in cells perfused in a MR compatible bioreactor. In addition to measuring intracellular weighted diffusion, extra- and intracellular weighted hyperpolarized (13)C metabolites pools are assessed in real-time, including their modulation with inhibition of monocarboxylate transporters. These studies demonstrate the ability to simultaneously assess membrane transport in addition to enzymatic activity with the use of diffusion weighted hyperpolarized (13)C MR. This technique could be an indispensible tool to evaluate the impact of microenvironment on the presence, aggressiveness and metastatic potential of a variety of cancers.
这项工作展示了利用扩散加权超极化（13）C磁共振波谱法分离糖酵解代谢物的细胞外和细胞内成分。使用高达15,000smm（-2）的b值，测量了超极化[1-（13）C]丙酮酸和乳酸的多指数信号响应。通过拟合这些曲线的快速和慢速渐近线，在磁共振兼容生物反应器中灌注的细胞中确定了它们的细胞外和细胞内加权扩散系数。除了测量细胞内加权扩散外，还实时评估细胞外和细胞内加权超极化（13）C代谢物池，包括它们通过抑制单羧酸转运体的调节。这些研究证明了使用扩散加权超极化（13）C磁共振同时评估膜转运和酶活性的能力。这项技术可能是评估微环境对多种癌症的存在、侵袭性和转移潜力影响的不可或缺的工具。
