Twofold Reduction in Gadolinium Dose for Brain MRI Exams using a Novel Unbalanced T1 Relaxation-Enhanced Steady-State (uT1RESS) 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。 这个为期两年的赠款提案的主要假设是，R21赠款提案是双重或 由uT 1 RESS提供的对钆增强的灵敏度的更大改善将使得能够 GBCA剂量相应降低两倍，诊断准确性不劣于全剂量 使用标准神经成像技术的MRI。对幻影、健康志愿者和患有 脑肿瘤沿着与Bloch方程建模将用于指导序列优化。我们的具体 目标如下： 1.最大化uT 1 RESS对钆增强的灵敏度，同时优化图像质量 并且最小化扫描时间。 2.在3特斯拉下进行单中心研究试验，以确定半剂量对比增强MRI是否 使用uT 1 RESS不劣于使用标准神经成像技术的全剂量对比增强MRI， 脑肿瘤患者。

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 two-year grant proposal is that R21 grant proposal is that the twofold or greater improvement in sensitivity to gadolinium enhancement provided by uT1RESS will enable a corresponding twofold reduction in GBCA dose, with non-inferior diagnostic accuracy compared to full dose MRI using standard neuroimaging techniques. Studies of phantoms, healthy volunteers, and patients with brain tumors along with Bloch equation modeling will be used to guide sequence optimization. Our specific aims are as follows: 1. To maximize the sensitivity of uT1RESS to gadolinium enhancement while optimizing image quality and minimizing scan time. 2. To perform a single site research trial at 3 Tesla to determine whether half dose contrast-enhanced MRI using uT1RESS is non-inferior to full dose contrast-enhanced MRI using a standard neuroimaging technique in patients with brain tumors.