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

增强磁共振成像(MRI)是脑肿瘤诊断和治疗的基石 治疗计划。虽然它对转移的敏感性优于CT或PET-CT，但小病变(&lt；5- Mm)和软脑膜扩散仍有可能被错过，这可能对预后和 规划立体定向放射外科，以及跨血脑的靶向生物制剂的使用 障碍。可以进一步提高MRI对脑肿瘤的敏感性和特异性的方法是 极大的临床益处。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)，与之相比，它大大提高了肿瘤的可见度- 增强的核磁共振成像。与现有的神经成像技术相比，T1RESS至少使肿瘤与肿瘤的比率翻了一番 背景对比度，同时显著提高了肿瘤与背景的对比度噪声比。一个 “不平衡”版本(UT1RESS)使血管变暗，这是我们建议的重点。 在发表在《科学进展》上的一项对54名成年患者的初步研究中，uT1RESS提供了 肿瘤对脑的对比度显著提高两倍或更多，同时 与标准护理MPRAGE和其他脉冲序列进行比较的病变-脑对比噪声比 通常用于对脑瘤进行成像。我们发现，即使是微小的转移性肿瘤沉积和 标准影像难以与小血管区分的软脑膜病变 技术可以毫不含糊地识别出来。 这项为期五年的拨款提案的主要假设是，T1RESS将显著改善 与现有MRI脉冲序列相比，对小型脑转移瘤的敏感性，同时也减少了扫描 泰晤士报。第二个假设是，在肿瘤与大脑的对比中， UT1RESS可用于将基于Gd的造影剂(GBCA)的使用量大幅减少两倍 剂量。用Bloch方程对幻影、健康志愿者和脑瘤患者的研究 将使用建模来指导序列优化。在这些优化努力之后，将有两项- 机构研究，以确定技术的准确性。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，系统评价其影响 各种序列参数对图像外观、对比度、信噪比和病变清晰度的影响，并进行优化 这项技术可以最大限度地提高肿瘤的可见性，同时最大限度地减少扫描时间和图像伪影。 2.进行一项先导性研究，以确定使用uT1RESS和双重 减少的GBCA造影剂剂量不亚于标准造影剂剂量的MPRAGE。 3.在3T进行两个部位的研究试验，以表征脑转移瘤的外观 UT1RESS，并与标准护理MPRAGE相比，确定其对小型脑转移瘤的准确性。

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.