Development of multinuclear MRI for image guided therapy of glioma patients

开发用于神经胶质瘤患者图像引导治疗的多核 MRI

• 批准号: 10655918
• 负责人: Ovidiu C Andronesi
• 金额: $ 61.68万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655918
• 关键词: 19q; Acceleration; Address; Adjuvant Therapy; Anatomy; Biological Assay; Biopsy; Brain; Central Nervous System Neoplasms; Classification; Clinical; Clinical Trials; Computer software; Consensus; Cystathionine; Data Analyses; Detection; Development; Diagnosis; Epigenetic Process; Excision; Gene Expression; Glioma; Glutamates; Glutamine; Glycine; Goals; Grant; Hybrids; Image; Image-Guided Surgery; Imaging Device; Immune system; Immunotherapy; Individual; Intervention; Isocitrate Dehydrogenase; Label; Life; Longitudinal Studies; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Maps; Metabolic; Metabolic Pathway; Metabolism; Methods; Mission; Modality; Molecular; Monitor; Multiparametric Analysis; Mutation; Neuronavigation; Neurosurgeon; Nicotinamide adenine dinucleotide; Nuclear; Operative Surgical Procedures; Outcome; Patients; Performance; Phosphorus; Phosphorylation; Positron-Emission Tomography; Primary Brain Neoplasms; Progression-Free Survivals; Protons; Public Health; Quality of life; Radiation; Relapse; Reporting; Research; Resistance; Resolution; Role; SKIL gene; Sampling Biases; Scanning; Sensitivity and Specificity; Specificity; Survival Rate; Techniques; Testing; Time; Tracer; Work; World Health Organization; anatomic imaging; brain tumor resection; cancer imaging; cancer therapy; chemoradiation; clinical translation; cost effective; data quality; deep learning; deep learning model; fluorescence-guided surgery; image guided therapy; imaging modality; improved; improved outcome; in vivo; in vivo imaging; individual patient; individualized medicine; innovation; magnetic resonance spectroscopic imaging; metabolic imaging; metabolomics; molecular imaging; molecular marker; molecular pathology; multiparametric imaging; mutant; neuro-oncology; new therapeutic target; novel; novel therapeutic intervention; novel therapeutics; optimal treatments; patient stratification; pharmacologic; precision oncology; prevent; reconstruction; response; targeted treatment; treatment planning; treatment response; tumor; tumor progression; ward

7. Project Summary/Abstract Gliomas have a low survival rate of 36% at five-years, half the average survival rate across all cancers according to the last SEER and CBTRUS reports. Malignant brain tumors cause on average 20 years of potential life lost (YPLL), exceeding most cancers. Survival and YPLL have not improved for gliomas as in other cancers and urgent progress is needed. Recent studies showed maximal surgical resection extends survival of glioma patients. However, glioma margins are ambiguous on conventional anatomical imaging, and neurosurgeons are in great need for more specific imaging to map tumor boundary. Gliomas have large metabolic alterations, most notably D-2-hydroxyglutarate (2HG), cystathionine and nicotinamide adenine dinucleotide in isocitrate dehydrogenase (IDH) mutations. Imaging metabolism using proton (1H) and phosphorus (31P) magnetic resonance spectroscopic imaging (MRSI) has high specificity for glioma. Mapping tumor margins requires high resolution, which is challenging for metabolic imaging. Our project addresses neurosurgeons’ need for high resolution metabolic imaging. Recent discoveries highlighted metabolism role in modulating epigenetic factors, gene expression and immune system responsible for tumor progression. Hence, new treatment strategies target metabolic pathways to increase the effect of chemoradiation and immunotherapy to prevent tumor resistance and relapse. Metabolic imaging can accelerate clinical trials of novel therapies, and its development has been mandated by the last neuro-oncology consensus (SNO, EANO). The long-term goal of our research is to create non-invasive metabolic cancer imaging tools for personalized precision oncology. The objective of this application is to develop fast high-resolution whole-brain quantitative metabolic multinuclear MR imaging for image guided therapy of glioma patients. The central hypothesis of our proposal is that multinuclear MR imaging will enable clinicians deliver precision oncology treatments with improved outcomes tailored to individual glioma patients. We will perform three specific aims: 1) develop 1H-MRSI for intra-operative image guided surgical removal of gliomas, 2) develop 31P-MRSI at ultra-high field to guide pharmacologic interventions in glioma, 3) clinical translation of multinuclear MRI for treatment of glioma patients. There are strong rationales for the proposed research: 1) there is no alternative in vivo imaging that is specific for IDH mutations, 2) MRSI is non-invasive and safe to scan without radiation and tracer, 3) fast, 4) cost effective, 5) probes entire tumor and healthy brain without sampling bias of biopsies, 6) can be performed pre-surgically and in inoperable patients. The approach is innovative because it employs the first available whole-brain 2HG imaging at high resolution accelerated by deep learning compressed sensing, novel receive-shim array hardware for 31P-MRSI to improve data quality, and automated high-throughput processing by deep learning. The contribution of the proposed research will be significant because it will provide clinicians a validated precision oncology imaging tool to select optimal treatment in glioma patients.

7. 项目总结/摘要 神经胶质瘤的五年生存率很低，仅为 36%，是所有癌症平均生存率的一半 根据最新的 SEER 和 CTRUS 报告。恶性脑肿瘤平均导致 20 年 潜在生命损失 (YPLL)，超过大多数癌症。神经胶质瘤的生存率和 YPLL 并未改善，如 其他癌症，亟待取得进展。最近的研究表明最大手术切除范围扩大 胶质瘤患者的生存率。然而，在传统的解剖成像中，神经胶质瘤的边缘是不明确的，并且 神经外科医生非常需要更具体的成像来绘制肿瘤边界。胶质瘤有大 代谢改变，最显着的是 D-2-羟基戊二酸 (2HG)、胱硫醚和烟酰胺腺嘌呤 异柠檬酸脱氢酶（IDH）突变中的二核苷酸。使用质子 (1H) 和 磷（31P）磁共振波谱成像（MRSI）对神经胶质瘤具有高度特异性。测绘 肿瘤边缘需要高分辨率，这对代谢成像具有挑战性。我们的项目地址 神经外科医生对高分辨率代谢成像的需求。最近的发现强调了新陈代谢的作用 调节与肿瘤进展有关的表观遗传因素、基因表达和免疫系统。因此， 新的治疗策略针对代谢途径以增强放化疗的效果 免疫疗法可预防肿瘤耐药和复发。代谢成像可以加速临床试验 最新的神经肿瘤学共识（SNO， 埃诺）。我们研究的长期目标是创建非侵入性代谢癌症成像工具 个性化精准肿瘤学。该应用程序的目标是开发快速高分辨率全脑 定量代谢多核磁共振成像用于神经胶质瘤患者的图像引导治疗。中央 我们提议的假设是，多核磁共振成像将使临床医生能够提供精准的肿瘤学治疗 针对个别神经胶质瘤患者量身定制的治疗效果有所改善。我们将实现三个具体目标： 1) 开发 1H-MRSI 用于术中图像引导的神经胶质瘤手术切除，2) 开发 31P-MRSI 超高场指导神经胶质瘤的药物干预，3）多核 MRI 的临床转化 神经胶质瘤患者的治疗。拟议的研究有充分的理由：1）没有其他选择 特异性针对 IDH 突变的体内成像，2) MRSI 是非侵入性的，无需辐射即可安全扫描， 示踪剂，3) 快速，4) 成本效益高，5) 探测整个肿瘤和健康大脑，没有活检取样偏差，6) 可以在术前和无法手术的患者中进行。该方法具有创新性，因为它采用了 第一个可用的高分辨率全脑 2HG 成像，通过深度学习压缩感知加速， 用于 31P-MRSI 的新型接收匀场阵列硬件，可提高数据质量和自动化高通量 通过深度学习进行处理。拟议研究的贡献将是重大的，因为它将 为临床医生提供经过验证的精准肿瘤成像工具，以选择神经胶质瘤患者的最佳治疗方法。

项目成果

In Vivo Absolute Metabolite Quantification Using a Multiplexed ERETIC-RX Array Coil for Whole-Brain MR Spectroscopic Imaging.

• DOI: 10.1002/jmri.28028
• 发表时间: 2022-07
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Thapa, Bijaya;Mareyam, Azma;Stockmann, Jason;Strasser, Bernhard;Keil, Boris;Hoecht, Philipp;Carp, Stefan;Li, Xianqi;Wang, Zhe;Chang, Yulin, V;Dietrich, Jorg;Uhlmann, Erik;Cahill, Daniel P.;Batchelor, Tracy;Wald, Lawrence;Andronesi, Ovidiu C.
• 通讯作者: Andronesi, Ovidiu C.

Whole-Slab 3D MR Spectroscopic Imaging of the Human Brain With Spiral-Out-In Sampling at 7T.

• DOI: 10.1002/jmri.27437
• 发表时间: 2021-04
• 期刊: Journal of magnetic resonance imaging : JMRI
• 作者: Esmaeili M;Strasser B;Bogner W;Moser P;Wang Z;Andronesi OC
• 通讯作者: Andronesi OC

Deep learning super-resolution magnetic resonance spectroscopic imaging of brain metabolism and mutant isocitrate dehydrogenase glioma.

• DOI: 10.1093/noajnl/vdac071
• 发表时间: 2022-01
• 期刊: NEURO-ONCOLOGY ADVANCES
• 作者: Li, Xianqi;Strasser, Bernhard;Neuberger, Ulf;Vollmuth, Philipp;Bendszus, Martin;Wick, Wolfgang;Dietrich, Jorg;Batchelor, Tracy T.;Cahill, Daniel P.;Andronesi, Ovidiu C.
• 通讯作者: Andronesi, Ovidiu C.

Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients.

成像神经化学和大脑结构跟踪患者ALS的临床下降和机制。

• DOI: 10.3389/fneur.2020.590573
• 发表时间: 2020
• 期刊: Frontiers in neurology
• 影响因子: 3.4
• 作者: Andronesi OC;Nicholson K;Jafari-Khouzani K;Bogner W;Wang J;Chan J;Macklin EA;Levine-Weinberg M;Breen C;Schwarzschild MA;Cudkowicz M;Rosen BR;Paganoni S;Ratai EM
• 通讯作者: Ratai EM