Diffusion MRI of Treatment Response for De-escalation of Radiation Therapy

弥散 MRI 评估放射治疗降级的治疗反应

• 批准号: 9917739
• 负责人: Sungheon Gene Kim
• 金额: $ 7.35万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9917739
• 关键词: Acute; Animals; Biological Markers; Blood Volume; Caliber; Cancer Center; Cell Membrane Permeability; Cell Size; Cell Survival; Chronic; Clinical; Clinical Assessment Tool; Clinical Data; Clinical Research; Clinical Trials; Complex; Contrast Media; Data; Data Analyses; Dependence; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Progression; Dose; Early treatment; Enrollment; Enteral Feeding; Evaluation; Goals; Head and Neck Squamous Cell Carcinoma; Human Papillomavirus; Imaging Techniques; Inflammatory Response; Intercellular Fluid; Ion Channel; Lead; Length; Lesion; Leukopenia; Link; Lymph Node of Head, Face and Neck; MRI Scans; Magnetic Resonance Imaging; Measurable Disease; Measurement; Measures; Metabolism; Methods; Modeling; Monitor; Motion; Mucositis; Nodal; Oropharyngeal; Patient Selection; Patients; Perfusion; Phase II Clinical Trials; Population; Property; Radiation therapy; Risk; Scanning; Software Tools; Subgroup; Testing; Therapeutic; Time; Tissues; Toxic effect; Treatment Protocols; Tumor Biology; Tumor Volume; Uncertainty; Validation; Water; Weight; base; biophysical properties; cancer cell; cancer therapy; cancer type; chemoradiation; contrast enhanced; data acquisition; disorder control; experience; fluorodeoxyglucose positron emission tomography; imaging biomarker; improved; in vivo; in vivo imaging; individual patient; innovation; insight; novel; outcome forecast; personalized approach; pressure; recruit; response; simulation; standard care; success; tool; treatment response; tumor; tumor progression; water diffusion

PROJECT SUMMARY Chemo-radiation therapy is a standard treatment regimen for locally advanced head and neck squamous cell carcinoma (HNSCC). The treatment regimen, however, is difficult for patients as they experience high rates of grade 3 or higher toxicities including leukopenia (42%) and the need for feeding tube (52%). Recent studies showed that a subgroup of HNSCC patients with human-papilloma virus (HPV)-positive oropharyngeal (OP) SCC have significantly better prognosis. These clinical data lead to important considerations to de-intensify treatment for this low-risk, younger population in order to reduce acute and chronic toxicity without compromising disease control. It has been suggested that the adaptive de-escalation of treatment can be tailored for individual patients based on the early tumor volume change. However, volumetric assessment is often inadequate because the treatment response of a tumor can be heterogeneous in terms of (i) cell viability, (ii) cellular metabolism, and (iii) perfusion that are relevant to the success of any chemoradiation therapy. These complex changes may not be adequately represented by tumor volume change at the early stage. The proposed study is based on a combination of the quantitative diffusion MRI (dMRI) methods with their own technical innovations that can also be applied to other clinical studies. dMRI is a unique in vivo imaging technique sensitive to cellular microstructures at the scale of water diffusion length on the order of a few microns. However, quantitative dMRI remains challenging as dMRI data represent different biophysical properties of tissue depending on diffusion weighting strength (q) and diffusion time (t) used for the measurement. The scientific premise of the proposal is that this study will establish a quantitative way to utilize both q- and t-dependent dMRI data as a tailored approach to quantify cell viability, cellular metabolism and perfusion from this non-contrast MRI method. We demonstrated that both diffusion coefficient D and diffusional kurtosis coefficient K are promising imaging markers for cell viability. Cellular metabolism can be evaluated in terms of the water exchange τex, measured by the diffusion time-dependent K, that is regulated by the ATP- dependent trans-membrane ion channels co-transporting water molecules. Intravoxel incoherent motion MRI metrics (pseudo diffusivity, Dp; perfusion fraction, fp) can provide information about perfusion flow. Ultimately, these dMRI measures will better identify patients who have the potential to benefit from adaptive de-escalation or escalation of therapy. In this proposal, we will further optimize and establish a set of quantitative non-contrast imaging markers of cell viability (D and K), cellular metabolism (τex), and perfusion (fp⋅Dp) as a clinical tool for assessment of treatment response and validate it in a clinical trial. The data acquisition and analysis software tools to be developed in this study will enable comprehensive and quantitative assessment of cancer treatment response to tailor chemoradiation therapies for individual patients.

项目概要 放化疗是局部晚期头颈部鳞状细胞癌的标准治疗方案 癌（HNSCC）。然而，治疗方案对患者来说很困难，因为他们的复发率很高。 3 级或更高毒性，包括白细胞减少症 (42%) 和需要饲管 (52%)。最近的研究 研究表明，人类乳头状瘤病毒 (HPV) 阳性口咽 (OP) 的 HNSCC 患者亚组 SCC 的预后明显更好。这些临床数据导致了去强化的重要考虑 对这种低风险、年轻的人群进行治疗，以减少急性和慢性毒性，而无需 损害疾病控制。有人建议，可以采取适应性降级治疗 根据早期肿瘤体积变化为个体患者量身定制。然而，体积评估是 通常是不够的，因为肿瘤的治疗反应在（i）细胞活力方面可能存在异质性， (ii) 细胞代谢，以及 (iii) 与任何放化疗成功相关的灌注。 这些复杂的变化可能无法通过早期肿瘤体积的变化来充分代表。 拟议的研究基于定量扩散 MRI (dMRI) 方法与其自身方法的结合 技术创新也可以应用于其他临床研究。 dMRI 是一种独特的体内成像 对水扩散长度尺度上的细胞微观结构敏感的技术 微米。然而，定量 dMRI 仍然具有挑战性，因为 dMRI 数据代表不同的生物物理 组织的特性取决于用于扩散加权强度 (q) 和扩散时间 (t) 测量。该提案的科学前提是本研究将建立一种定量的方法来利用 q 和 t 依赖性 dMRI 数据作为量化细胞活力、细胞代谢和 这种非对比 MRI 方法的灌注。我们证明了扩散系数 D 和扩散系数 峰度系数 K 是有前景的细胞活力成像标记。细胞代谢可以通过以下方式进行评估： 水交换项 τex，由扩散时间相关的 K 测量，由 ATP- 调节 依赖跨膜离子通道共同运输水分子。体素内不相干运动 MRI 指标（伪扩散率，Dp；灌注分数，fp）可以提供有关灌注流量的信息。最终， 这些 dMRI 措施将更好地识别有可能从适应性降级中受益的患者 或升级治疗。 在本提案中，我们将进一步优化并建立一套细胞的定量非对比成像标记物。 活力（D 和 K）、细胞代谢（τex）和灌注（fp⋅Dp）作为评估治疗的临床工具 反应并在临床试验中对其进行验证。即将开发的数据采集和分析软件工具 这项研究将能够对癌症治疗反应进行全面和定量的评估，以定制 针对个别患者的放化疗。