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.

项目总结 这份R21提案寻求开发一种基于细胞大小的MRI技术，使用过滤器进行选择性大小的MR成像 经扩散时间(SSIFT)是诊断高血压性脑转移瘤的一种新方法 特异性，并评价其鉴别复发性骨髓瘤和放射性坏死(RN)的可能性。 立体定向放射外科(SRS)。大约10%-30%的癌症患者最终将发展为BM 而SRS是BM患者提高局部控制率的常用治疗方法。然而， 大约10%-20%的治疗后的骨髓最终会发展成新的造影剂增强病变，要么是RN，要么是 复发性骨髓瘤。这两种类型的损害通常发生在相似的时间范围内，但需要治疗 不同的是：RN可以保守治疗以缓解症状；相比之下，肿瘤复发通常 通过手术或进一步放射治疗来控制肿瘤的进展。不幸的是，RN无法区分 使用基于Gd的造影剂的标准护理MRI上肿瘤复发的原因是 在两种类型的病变中血脑屏障(BBB)的破坏。因此，有必要在临床上 放射肿瘤学开发一种可靠的非侵入性成像方法来区分肿瘤复发和 RN。尽管许多人试图开发各种先进的成像方法来解决这个临床问题 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 生物标志物。我们在此提出了一种新的想法，即利用细胞大小的内源性信息来区分BM 来自RN。与我们以前的定量细胞大小MRI扫描时间长不同，我们在这里提出了一种快速的 SSIFT方法，用作基于细胞大小的过滤器，选择性地强调来自大型癌症的信号 同时抑制其他大脑异常信号的细胞，如RN。我们已经验证了 SSIFT在临床前动物模型中显示其区分BM和RN的能力，但仍不清楚 SSIFT对BM患者是否有效。我们在此假设SSIFT是一种实用、可靠和特定的 对有能力区分复发骨髓和肾小球肾炎患者进行骨髓成像的方法。为了测试这一点 假设，我们已经组建了一个多学科团队，并提出[目标1]来提炼一个可靠和高效的 SSIFT方案在BM影像诊断中的应用[目的2]评价SSIFT对BM的临床鉴别诊断能力 SRS诱导的RN复发BM。完成后，拟议的研究将开辟新的领域，以 建立一种新型的基于细胞大小的MRI技术，旨在解决一个重要的、常见的 BM患者接受SRS治疗的两难境地。此外，区分BM的能力 肿瘤周围的水肿使这一新方法成为BM患者的另一种可能的成像方法 有肾功能障碍的患者，他们不是基于格拉试剂的磁共振成像的候选对象。