Improved Detection of Cerebral Metastases using a using a Novel T1 Relaxation-Enhanced Steady-State (T1RESS) MRI Technique

使用新型 T1 弛豫增强稳态 (T1RESS) MRI 技术改进脑转移瘤的检测

• 批准号: 10440636
• 负责人: Robert R. Edelman
• 金额: $ 53.11万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-12 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10440636
• 关键词: Adult; Anatomy; Appearance; Applications Grants; Biological Products; Blood; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Neoplasms; Cerebrum; Clinical; Contrast Media; Deposition; Detection; Disease; Dose; Enhancing Lesion; Equation; Fatty acid glycerol esters; Frequencies; Gadolinium; Goals; Image; Imaging Techniques; Institution; Lesion; Magnetic Resonance Imaging; Metastatic malignant neoplasm to brain; Methods; Modeling; Morphologic artifacts; Neck; Neoplasm Metastasis; Nephrogenic Systemic Fibrosis; Noise; Ocular orbit; Patients; Phase; Physiologic pulse; Pilot Projects; Positron-Emission Tomography; Prognosis; Publishing; Radiosurgery; Relaxation; Research; Resolution; Scanning; Science; Sensitivity and Specificity; Signal Transduction; Site; Specificity; Techniques; Time; Tissues; Variant; Water; base; brain magnetic resonance imaging; brain tumor imaging; cancer imaging; contrast enhanced; cost; diagnostic accuracy; dosage; healthy volunteer; improved; neuroimaging; novel; risk minimization; skull base; standard of care; treatment planning; tumor; tumor diagnosis

Contrast-enhanced magnetic resonance imaging (MRI) is the cornerstone for brain tumor diagnosis and treatment planning. While its sensitivity for metastases is superior to that of CT or PET-CT, small lesions (<5- mm) and leptomeningeal spread may still be missed, which can have a major impact on prognosis and planning for stereotactic radiosurgery, as well as on the use of targeted biologics that cross the blood-brain barrier. A method that could further improve the sensitivity and specificity of MRI for brain tumors would be of great clinical benefit. Towards this end, we have developed a new class of pulse sequences, called T1 Relaxation-Enhanced Steady-State (T1RESS), that greatly improves the visibility of tumors in contrast- enhanced MRI. Compared with existing neuroimaging techniques, T1RESS at least doubles the tumor-to- background contrast while significantly improving the tumor-to-background contrast-to-noise ratio. An “unbalanced” version (uT1RESS) renders blood vessel dark and is the focus of our proposal. In a preliminary study of 54 adult patients that was published in Science Advances, uT1RESS provided a remarkable twofold or greater improvement in tumor-to-brain contrast along with a marked improvement in lesion-to-brain contrast-to-noise in comparison to standard-of-care MPRAGE and other pulse sequences that are commonly used to image brain tumors. We found that even small metastatic tumor deposits and leptomeningeal lesions that were difficult to distinguish from small blood vessels with standard imaging techniques could be unambiguously identified. The primary hypothesis of this five-year grant proposal is that T1RESS will significantly improve the sensitivity for small brain metastases compared with existing MRI pulse sequences, while also reducing scan times. A secondary hypothesis is that the twofold improvement in tumor-to-brain contrast obtained with uT1RESS can be used to enable a substantial twofold reduction in gadolinium-based contrast agent (GBCA) dosage. Studies of phantoms, healthy volunteers, and patients with brain tumors along with Bloch equation modeling will be used to guide sequence optimization. These optimization efforts will be followed by a two- institution study to determine the accuracy of the technique. Our specific aims are as follows: 1. To apply uT1RESS in healthy subjects and patients with brain tumors to systematically evaluate the impact of various sequence parameters on image appearance, contrast, SNR, and lesion sharpness, and to optimize the technique to maximize tumor visibility while minimizing scan time and image artifacts. 2. To perform a pilot study to determine whether metrics of tumor visibility using uT1RESS and a twofold reduced GBCA contrast agent dosage are noninferior to MPRAGE with a standard contrast agent dosage. 3. To perform a two-site research trial at 3T to characterize the appearance of brain metastases with uT1RESS, and to determine its accuracy for small brain metastases compared to standard-of-care MPRAGE.

对比增强磁共振成像（MRI）是脑肿瘤诊断和治疗的基石 治疗计划。虽然其对转移的敏感性优于 CT 或 PET-CT，但对于小病灶（<5- mm）和软脑膜扩散仍可能被遗漏，这可能对预后和预后产生重大影响 规划立体定向放射外科手术，以及使用穿过血脑的靶向生物制剂 障碍。一种可以进一步提高 MRI 对脑肿瘤的敏感性和特异性的方法是 巨大的临床效益。为此，我们开发了一类新的脉冲序列，称为 T1 松弛增强稳态 (T1RESS)，大大提高了对比中肿瘤的可见度 增强磁共振成像。与现有的神经影像技术相比，T1RESS 至少将肿瘤与 背景对比度，同时显着提高肿瘤与背景对比度噪声比。一个 “不平衡”版本（uT1RESS）使血管变暗，是我们提案的重点。 在 Science Advances 上发表的一项针对 54 名成年患者的初步研究中，uT1RESS 提供了 肿瘤与大脑的对比度显着提高两倍或更大，同时 与标准护理 MPRAGE 和其他脉冲序列相比，病变与大脑的对比噪声 通常用于脑肿瘤成像。我们发现即使是小的转移性肿瘤沉积物 标准成像难以与小血管区分开的软脑膜病变 可以明确地识别技术。 这项五年拨款提案的主要假设是 T1RESS 将显着改善 与现有 MRI 脉冲序列相比，对小脑转移瘤的敏感性更高，同时还减少了扫描 次。第二个假设是，肿瘤与大脑的对比得到了两倍的改善 uT1RESS 可用于大幅减少钆基造影剂 (GBCA) 的两倍 剂量。根据布洛赫方程对体模、健康志愿者和脑肿瘤患者进行研究 建模将用于指导序列优化。这些优化工作之后将进行两步： 机构研究以确定该技术的准确性。我们的具体目标如下： 1. 将uT1RESS应用于健康受试者和脑肿瘤患者，系统评估其影响 各种序列参数对图像外观、对比度、SNR 和病变清晰度的影响，并进行优化 该技术可最大限度地提高肿瘤可见度，同时最大限度地减少扫描时间和图像伪影。 2. 进行一项试点研究，以确定是否可以使用 uT1RESS 和双重 减少的 GBCA 造影剂剂量并不逊色于标准造影剂剂量的 MPRAGE。 3. 在 3T 下进行两处研究试验，以表征脑转移瘤的外观 uT1RESS，并确定其与标准护理 MPRAGE 相比对小脑转移瘤的准确性。