Differentiation of tumor progression from radiation necrosis using MR cell size imaging

使用 MR 细胞大小成像区分肿瘤进展与放射性坏死

• 批准号: 10651495
• 负责人: Junzhong Xu
• 金额: $ 24.54万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10651495
• 关键词: Address; Animal Model; Biopsy; Blood - brain barrier anatomy; Brain; Brain Neoplasms; Brain imaging; Cancer Patient; Cell Size; Clinic; Clinical; Computer Assisted; Contrast Media; Cranial Irradiation; Development; Diagnosis; Diffusion; Dimensions; Early Diagnosis; Edema; Enhancing Lesion; Foundations; Gadolinium; Image; Lesion; Liquid substance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Metastatic malignant neoplasm to brain; Metastatic/Recurrent; Methods; Monitor; Morbidity - disease rate; Necrosis Induction; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Patients; Process; Protocols documentation; Radiation; Radiation Oncology; Radiation necrosis; Radiosurgery; Recurrence; Recurrent tumor; Scanning; Signal Transduction; Source; Specificity; Spectrum Analysis; Structure; Techniques; Testing; Time; Validation; Variant; Work; accurate diagnosis; brain abnormalities; brain cell; brain tissue; cancer cell; cell type; clinical imaging; common treatment; diagnostic accuracy; diffusion anisotropy; effective therapy; imaging approach; imaging biomarker; imaging modality; improved; kidney dysfunction; multidisciplinary; non-invasive imaging; novel strategies; perfusion imaging; pre-clinical; reduce symptoms; standard of care; tumor; tumor progression; vasogenic edema

PROJECT SUMMARY This R21 proposal seeks to develop a cell-size-based MRI technique, Selective Size MR Imaging using Filters via diffusion Times (SSIFT), as a novel approach for imaging brain metastases (BM) in patients with high specificity, and to evaluate its potential to differentiate recurrent BM from radiation necrosis (RN) induced by stereotactic radiosurgery (SRS). Approximately 10–30% of all cancer patients will eventually develop BM in their lifetime, and SRS is a common treatment for patients with BM to improve the local control. However, about 10-20% of treated BM will eventually develop new contrast-enhancing lesions that are either RN or recurrent BM. These two types of lesions usually occur within a similar time frame but need to be treated differently: RN can be managed conservatively to alleviate symptoms; by contrast, tumor recurrence is often managed with surgery or further radiation to control tumor progression. Unfortunately, RN is indistinguishable from tumor recurrence on standard-of-care MRI with gadolinium (Gd)-based contrast agents due to the breakdown of the blood-brain barrier (BBB) in both types of lesions. Therefore, there is a need for clinical radiation oncology to develop a reliable non-invasive imaging method to differentiate tumor recurrence from RN. Despite numerous attempts to develop a variety of advanced imaging methods to tackle this clinical challenge, there is still no single imaging method that has been widely accepted as a reliable imaging biomarker. We hereby propose a new idea, i.e., to use endogenous information on cell size to differentiate BM from RN. Different from our previous quantitative cell size MRI with a long scan time, we propose here a fast SSIFT method that serves as a cell-size-based filter to selectively emphasize signals arising from large cancer cells with simultaneous suppression of signals from other brain abnormalities, such as RN. We have validated SSIFT in preclinical animal models to demonstrate its ability to differentiate BM from RN, but it remains unclear if SSIFT will work in patients with BM. We hereby hypothesize that SSIFT is a practical, reliable, and specific approach for imaging BM in patients with the capability to differentiate recurrent BM from RN. To test this hypothesis, we have assembled a multidisciplinary team and propose [Aim 1] to refine a reliable and efficient SSIFT protocol in imaging BM patients and [Aim 2] to evaluate the clinical ability of SSIFT in differentiating recurrent BM from RN induced by SRS. Upon completion, the proposed study will break new ground to establish a new type of cell-size-based MRI technique geared towards addressing an important, common dilemma in the management of BM patients with SRS treatments. In addition, the ability to differentiate BM from peri-tumor edema makes this new method another possible alternative imaging approach for BM patients with kidney dysfunction who are not candidates for gadolinium-agent-based MRI.

项目摘要 本R21提案旨在开发一种基于细胞大小的MRI技术，即使用滤波器的选择性大小MR成像 通过扩散时间（SSIFT），作为一种新的方法，成像脑转移瘤（BM）的患者高 特异性，并评估其区分复发性BM与放射性坏死（RN）的潜力， 立体定向放射外科（SRS）。大约10-30%的所有癌症患者最终将在24小时内发生BM。 SRS是BM患者改善局部控制的常用治疗方法。然而，在这方面， 约10-20%的治疗BM最终将发展为RN或RN的新的对比增强病变， 复发性BM。这两种类型的病变通常发生在相似的时间范围内，但需要治疗 不同的是：RN可以保守治疗以减轻症状;相比之下，肿瘤复发通常是 通过手术或进一步放射治疗来控制肿瘤进展。不幸的是，RN无法区分 使用基于钆（Gd）的造影剂进行标准护理MRI时，由于 在两种类型的病变中，血脑屏障（BBB）的破坏。因此，需要临床 放射肿瘤学开发一种可靠的非侵入性成像方法，以区分肿瘤复发和 注册护士尽管许多人尝试开发各种先进的成像方法来解决这种临床问题， 然而，尽管存在挑战，仍然没有一种单一的成像方法被广泛接受为可靠的成像方法， 生物标记物。我们在此提出一个新的想法，即，使用细胞大小的内源性信息来区分BM 从RN。不同于我们以前的定量细胞大小的MRI扫描时间长，我们在这里提出了一个快速 SSIFT方法，用作基于细胞大小的滤波器，以选择性地强调来自大癌症的信号 同时抑制来自其他大脑异常的信号的细胞，如RN。我们已经验证 在临床前动物模型中进行SSFT，以证明其区分BM和RN的能力，但目前尚不清楚 SSIFT是否对BM患者有效。因此，我们假设SSIFT是一种实用、可靠和特异的 在具有区分复发性BM和RN能力的患者中成像BM的方法。为了验证这一 假设，我们已经组建了一个多学科团队，并提出[目标1]，以完善一个可靠和有效的 目的2评价SSIFT在BM患者中的临床鉴别诊断能力 SRS诱导RN复发BM。这项研究完成后，将开创新局面， 建立一种新型的基于细胞大小的MRI技术， SRS治疗BM患者的管理困境。此外，区分BM的能力 使这种新方法成为BM患者的另一种可能的替代成像方法 患有肾功能不全的患者，不适合进行基于钆剂的MRI。