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Magnetic resonance spectroscopy for the study of cns malignancies
Progress in Nuclear Magnetic Resonance Spectroscopy ( IF 7.3 ) Pub Date : 2021-02-01 , DOI: 10.1016/j.pnmrs.2020.11.001 Victor Ruiz-Rodado 1 , Jeffery R Brender 2 , Murali K Cherukuri 2 , Mark R Gilbert 1 , Mioara Larion 1
Progress in Nuclear Magnetic Resonance Spectroscopy ( IF 7.3 ) Pub Date : 2021-02-01 , DOI: 10.1016/j.pnmrs.2020.11.001 Victor Ruiz-Rodado 1 , Jeffery R Brender 2 , Murali K Cherukuri 2 , Mark R Gilbert 1 , Mioara Larion 1
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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：
磁共振波谱学用于中枢神经系统恶性肿瘤研究
摘要：尽管经过深入研究，脑肿瘤仍然是预后最差的恶性肿瘤之一。因此，需要对疾病进行及时诊断和深思熟虑的评估。脑肿瘤对大多数形式的常规治疗的耐药性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。脑肿瘤独特的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准确测量和报告代谢物浓度差异的方法。基于磁共振的技术提供了检查肿瘤组织和疾病演变的框架。对从脑癌患者身上采集的生物体液进行核磁共振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观察代谢谱的变化来监测疾病的演变。此外，脑脊液可以用作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，这些肿瘤维持快速生长和增殖所经历的代谢重连也可以作为潜在的治疗靶点。将 13C 示踪方法与不同 NMR 光谱模式的利用相结合，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，并发现利用乙酸作为脑转移和治疗中的替代细胞燃料。神经胶质瘤。 磁共振对脑肿瘤评估的主要贡献之一是非侵入性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成为临床中的一个关键特征。常规临床实践中脑肿瘤的分类和试点研究已经建立了使用体内磁共振波谱 (MRS) 来监测 IDH 突变神经胶质瘤的疾病进展和治疗反应。然而，需要开发 MRS 检测 2HG 的定制方法，这阻碍了 MRS 方法在临床中更广泛的实施。改善疾病管理的主要挑战之一是准确了解治疗反应，以便患者在出现耐药性时能够立即转向新疗法，或者在有反应时维持原始疗法。 13C超极化磁共振波谱成像（MRSI）的实施可以检测与治疗相关的肿瘤代谢变化，因此已被证明是监测治疗策略反应的出色工具。总之，基于磁共振的方法在脑肿瘤患者的诊断和治疗中的应用，除了用于研究肿瘤相关的代谢重连之外，还有助于揭示中枢神经系统恶性肿瘤的生物学基础。系统。
更新日期：2021-02-01
中文翻译：
磁共振波谱学用于中枢神经系统恶性肿瘤研究
摘要：尽管经过深入研究，脑肿瘤仍然是预后最差的恶性肿瘤之一。因此，需要对疾病进行及时诊断和深思熟虑的评估。脑肿瘤对大多数形式的常规治疗的耐药性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。脑肿瘤独特的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准确测量和报告代谢物浓度差异的方法。基于磁共振的技术提供了检查肿瘤组织和疾病演变的框架。对从脑癌患者身上采集的生物体液进行核磁共振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观察代谢谱的变化来监测疾病的演变。此外，脑脊液可以用作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，这些肿瘤维持快速生长和增殖所经历的代谢重连也可以作为潜在的治疗靶点。将 13C 示踪方法与不同 NMR 光谱模式的利用相结合，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，并发现利用乙酸作为脑转移和治疗中的替代细胞燃料。神经胶质瘤。 磁共振对脑肿瘤评估的主要贡献之一是非侵入性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成为临床中的一个关键特征。常规临床实践中脑肿瘤的分类和试点研究已经建立了使用体内磁共振波谱 (MRS) 来监测 IDH 突变神经胶质瘤的疾病进展和治疗反应。然而，需要开发 MRS 检测 2HG 的定制方法，这阻碍了 MRS 方法在临床中更广泛的实施。改善疾病管理的主要挑战之一是准确了解治疗反应，以便患者在出现耐药性时能够立即转向新疗法，或者在有反应时维持原始疗法。 13C超极化磁共振波谱成像（MRSI）的实施可以检测与治疗相关的肿瘤代谢变化，因此已被证明是监测治疗策略反应的出色工具。总之，基于磁共振的方法在脑肿瘤患者的诊断和治疗中的应用，除了用于研究肿瘤相关的代谢重连之外，还有助于揭示中枢神经系统恶性肿瘤的生物学基础。系统。
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