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

对比增强磁共振成像（MRI）是脑肿瘤诊断的基石， 治疗计划虽然其对转移灶的敏感性上级于CT或PET-CT，但小病灶（<5- mm）和软脑膜扩散仍然可能被遗漏，这可能对预后产生重大影响， 计划立体定向放射外科手术，以及使用靶向生物制剂，通过血脑 屏障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将是 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 弛豫增强稳态（T1 RESS），大大提高了肿瘤的可见性， 增强MRI。与现有的神经影像学技术相比，T1 RESS至少使肿瘤- 背景对比度，同时显著改善肿瘤-背景对比度-噪声比。一个 “不平衡”版本（uT 1 RESS）使血管变暗，是我们提案的重点。 在发表在《科学进展》上的一项针对54名成年患者的初步研究中，uT 1 RESS提供了 肿瘤-脑对比度显著提高两倍或更高， 与标准护理MPPT和其他脉冲序列相比， 通常被用来给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的软脑膜病变 技术可以明确识别。 这项为期五年的赠款提案的主要假设是，T1 RESS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，同时还减少了扫描 次第二个假设是，用放射性核素治疗获得的肿瘤-脑对比度的两倍改善， uT 1 RESS可用于使钆基造影剂（GBCA）的使用量大幅减少两倍 剂量.沿着Bloch方程研究脑肿瘤患者、健康志愿者和幻肢 建模将用于指导序列优化。这些优化工作之后，将有两个- 机构研究，以确定该技术的准确性。我们的具体目标如下： 1.在健康受试者和脑肿瘤患者中应用uT 1 RESS，系统评价 各种序列参数的图像外观，对比度，信噪比和病变清晰度，并优化 最大化肿瘤可见度同时最小化扫描时间和图像伪影的技术。 2.进行一项初步研究，以确定是否使用uT 1 RESS和双重 减少的GBCA造影剂剂量不劣于使用标准造影剂剂量的MPPT。 3.在3 T下进行一项双中心研究试验，以描述脑转移瘤的外观， uT 1 RESS，并确定其与标准治疗MPT 3相比对小脑转移瘤的准确性。

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.