Abstract Despite intensive research, brain tumors are amongst the malignancies with the worst prognosis; therefore, a prompt diagnosis and thoughtful assessment of the disease is required. The resistance of brain tumors to most forms of conventional therapy has led researchers to explore the underlying biology in search of new vulnerabilities and biomarkers. The unique metabolism of brain tumors represents one potential vulnerability and the basis for a system of classification. Profiling this aberrant metabolism requires a method to accurately measure and report differences in metabolite concentrations. Magnetic resonance-based techniques provide a framework for examining tumor tissue and the evolution of disease. NMR analysis of biofluids collected from patients suffering from brain cancer can provide biological information about disease status. In particular, urine and plasma can serve to monitor the evolution of disease through the changes observed in the metabolic profiles. Moreover, cerebrospinal fluid can be utilized as a direct reporter of cerebral activity since it carries the chemicals exchanged with the brain tissue and the tumor mass. Metabolic reprogramming has recently been included as one of the hallmarks of cancer. Accordingly, the metabolic rewiring experienced by these tumors to sustain rapid growth and proliferation can also serve as a potential therapeutic target. The combination of 13C tracing approaches with the utilization of different NMR spectral modalities has allowed investigations of the upregulation of glycolysis in the aggressive forms of brain tumors, including glioblastomas, and the discovery of the utilization of acetate as an alternative cellular fuel in brain metastasis and gliomas. One of the major contributions of magnetic resonance to the assessment of brain tumors has been the non-invasive determination of 2-hydroxyglutarate in tumors harboring a mutation in isocitrate dehydrogenase 1. The mutational status of this enzyme already serves as a key feature in the clinical classification of brain neoplasia in routine clinical practice and pilot studies have established the use of in vivo magnetic resonance spectroscopy (MRS) for monitoring disease progression and treatment response in IDH mutant gliomas. However, the development of bespoke methods for 2HG detection by MRS has been required, and this has prevented the wider implementation of MRS methodology into the clinic. One of the main challenges for improving the management of the disease is to obtain an accurate insight into the response to treatment, so that the patient can be promptly diverted into a new therapy if resistant or maintained on the original therapy if responsive. The implementation of 13C hyperpolarized magnetic resonance spectroscopic imaging (MRSI) has allowed detection of changes in tumor metabolism associated with a treatment, and as such has been revealed as a remarkable tool for monitoring response to therapeutic strategies. In summary, the application of magnetic resonance-based methodologies to the diagnosis and management of brain tumor patients, in addition to its utilization in the investigation of its tumor-associated metabolic rewiring, is helping to unravel the biological basis of malignancies of the central nervous system.

中文翻译：

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用于研究中枢神经系统恶性肿瘤的磁共振波谱

摘要 尽管进行了深入研究，脑肿瘤仍是预后最差的恶性肿瘤之一。因此，需要对疾病进行及时的诊断和周到的评估。脑肿瘤对大多数常规疗法的抵抗力促使研究人员探索潜在的生物学以寻找新的弱点和生物标志物。脑肿瘤的独特代谢代表了一种潜在的脆弱性，也是分类系统的基础。分析这种异常代谢需要一种方法来准确测量和报告代谢物浓度的差异。基于磁共振的技术为检查肿瘤组织和疾病的演变提供了一个框架。从患有脑癌的患者身上收集的生物流体的 NMR 分析可以提供有关疾病状态的生物学信息。特别是，尿液和血浆可以通过在代谢谱中观察到的变化来监测疾病的演变。此外，脑脊液可用作大脑活动的直接报告者，因为它携带与脑组织和肿瘤块交换的化学物质。代谢重编程最近被列为癌症的标志之一。因此，这些肿瘤为维持快速生长和增殖而经历的代谢重组也可以作为潜在的治疗靶点。13C 追踪方法与不同 NMR 光谱模式的使用相结合，可以研究侵袭性脑肿瘤（包括胶质母细胞瘤）中糖酵解的上调，以及发现利用醋酸盐作为脑转移和神经胶质瘤的替代细胞燃料。磁共振对脑肿瘤评估的主要贡献之一是无创测定异柠檬酸脱氢酶 1 突变的肿瘤中的 2-羟基戊二酸。这种酶的突变状态已经成为临床研究的一个关键特征在常规临床实践和初步研究中，脑瘤形成的分类已经确立了使用体内磁共振波谱 (MRS) 来监测 IDH 突变胶质瘤的疾病进展和治疗反应。然而，需要开发通过 MRS 检测 2HG 的定制方法，这阻碍了 MRS 方法在临床中的更广泛实施。改善疾病管理的主要挑战之一是准确了解对治疗的反应，以便患者在耐药时可以迅速转向新疗法，或者如果有反应则维持原疗法。13C 超极化磁共振光谱成像 (MRSI) 的实施允许检测与治疗相关的肿瘤代谢变化，因此已被揭示为监测对治疗策略的反应的非凡工具。总之，基于磁共振的方法在脑肿瘤患者的诊断和管理中的应用，除了在其肿瘤相关代谢重组研究中的应用外，还有助于揭示中枢神经系统恶性肿瘤的生物学基础。系统。