Next-Generation Whole-Body MRI for Detection and Assessment of Therapy Response in Bone Lesions

项目摘要 来自实体瘤的骨病变，如乳腺癌、前列腺癌或肾癌，肿瘤起源于骨 可能发生骨髓炎，如多发性骨髓瘤（MM）或其他非恶性肌肉骨骼病变 在骨架的任何地方。这些骨病变引起疼痛和脊髓压迫，导致病理性 骨折和瘫痪，从而降低患者的生活质量。目前的治疗方法依赖于诊断 这些骨病变通过全身X光或骨扫描，这只会发现他们在先进的阶段。而 推荐全身磁共振成像（WBMRI）用于治疗前评估（例如，在 MM），MRI在实践中通常仅限于脊柱和骨盆区域，以最大限度地减少患者不适， 几何失真造成的图像质量问题，以及由于采集时间延长造成的高成本问题。为了解决这个 为了满足临床需求，我们开发了一种新的WBMRI技术：“双回波T2加权采集， 增强型肿瘤清晰度（DETECT），通过同时分离 脂肪和液体的混杂信号与WBMRI和弥散加权成像（DWI）相比，单次- shot DETECT在相当短的扫描时间（<10分钟）内增加了病变检测（>40%）， 图像失真该方法还提高了对胸部和腹部区域中的运动的鲁棒性， 然而，由于特别是在脊柱和四肢中的T2衰减，其遭受图像模糊，限制了 诊断性能。在目前的提案中，我们将通过开发下一个解决这些限制- 使用单激发和多激发采集的有效组合生成WBMRI-DETECT。检测 还生成定量脂肪分数（FF）图的脂肪信号，可用作预后生物标志物， MM，因为肿瘤细胞取代了骨髓的主要成分脂肪。这种方法也使我们开发了一种 基于DETECT的DWI技术，用于精确测量表观扩散系数（ADC）。具体 目的是：1）开发一个集成的WBMRI使用单次激发和多次激发检测，沿着 定量FF图; 2）开发具有准确ADC测量值的基于DETECT的DWI;以及3） 评价集成WBMRI，包括DETECT-DWI和对比增强灌注，以获得有效骨 病变检测和治疗反应评估。我们将使用多发性骨髓瘤的骨病变作为概念验证 为实现这些目标，该项目的成功结果将是一个有效的WBMRI 使用准确的FF和ADC测量作为成像生物标志物的方案，在检测和测量中得到验证 MM患者的治疗反应。该WBMRI与对比增强MRI（包括灌注）相结合， 将是一种非常具有成本效益和实用的方法（<45分钟的餐桌时间），可广泛用于 世界各地的临床实践。这将使MM患者和患有其他骨病变的患者受益， 包括长期随访期间的儿科患者，而没有PET/CT的缺点。这将提供相关 为治疗决策提供临床信息，以积极影响患者的生活质量和总生存期。

Project Summary Bone lesions from solid tumors such as breast, prostate, or kidney cancers, tumors originating in the bone marrow such as multiple myeloma (MM), or other non-malignant musculoskeletal pathologies can occur anywhere in the skeleton. These bone lesions cause pain and spinal cord compressions, leading to pathologic fractures and paralysis, thereby diminishing the patient's quality of life. Current therapies rely on diagnosing these bone lesions by whole-body X-ray or bone scans, which only identify them at advanced stages. While whole-body magnetic resonance imaging (WBMRI) is recommended for pretreatment assessment (e.g., in MM), MRI is often limited to spine and pelvic regions in practice to minimize patient discomfort, compromised image quality from geometric distortion, and high costs due to prolonged acquisition times. To address this unmet clinical need, we developed a novel WBMRI technique: `Dual-Echo T2-weighted acquisition for Enhanced Conspicuity of Tumors' (DETECT), for improved lesion visualization by simultaneously separating the confounding signals of fat and fluid. Compared to WBMRI with diffusion-weighted imaging (DWI), single- shot DETECT increased lesion detection (>40%) in considerably shorter scan times (<10 min) and without image distortions. This method also improved robustness to motion in the thoracic and abdomen regions, however, it suffers from image blurring due to T2-decay particularly in spine and extremities, limiting the diagnostic performance. In the current proposal, we will address these limitations by developing the next- generation WBMRI-DETECT using an efficient combination of single-shot and multi-shot acquisitions. DETECT also generates fat signal for quantitative fat fraction (FF) maps that can be used as a prognostic biomarker in MM, since tumor cells replace fat, a major constituent of bone marrow. This method also led us to develop a DETECT-based DWI technique for accurate measurement of apparent diffusion coefficient (ADC). The specific aims are: 1) To develop an integrated WBMRI using single-shot and multi-shot DETECT, along with quantitative FF maps; 2) To develop a DETECT-based DWI with accurate ADC measurements; and 3) To evaluate the integrated WBMRI, including DETECT-DWI and contrast-enhanced perfusion, for efficient bone lesion detection and therapy response assessment. We will use bone lesions in MM as the proof-of-concept disease to achieve these project goals. The successful outcome of this project will be an efficient WBMRI protocol with accurate FF and ADC measures as imaging biomarkers, validated in detection and measuring therapy response in MM patients. This WBMRI in combination with contrast-enhanced MRI including perfusion, will be an excellent cost-effective and practical approach (<45 minutes of table time) for widespread use in clinical practices across the world. This will benefit MM patients and patients suffering from other bone lesions, including pediatric patients during long follow-ups, without the drawbacks of PET/CT. This will provide relevant clinical information for treatment decisions to positively impact patients' quality of life and overall survival.