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

项目摘要 实体肿瘤造成的骨损害，如乳腺癌、前列腺癌或肾癌，即起源于骨骼的肿瘤 骨髓，如多发性骨髓瘤(MM)，或其他非恶性肌肉骨骼病变 在骨架上的任何地方。这些骨骼损伤会引起疼痛和脊髓压迫，导致病理改变。 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 这些骨骼损伤是通过全身X光或骨扫描来识别的，只能在晚期识别。而当 建议将全身磁共振成像(WBMRI)用于预处理评估(例如，在 在实践中，MRI通常局限于脊柱和骨盆区域，以最大限度地减少患者的不适，损害 由于几何失真而产生的图像质量，以及由于采集时间延长而导致的高成本。要解决这个问题 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，用于 增强肿瘤的显着性(检测)，通过同时分离改善病变可视化 脂肪和液体的混杂信号。与弥散加权成像(DWI)的WBMRI相比， 镜头检测增强了病变检测(&gt；40%)，扫描时间大大缩短(&lt；10分钟)，而且没有 图像失真。这种方法还提高了胸部和腹部区域对运动的健壮性， 然而，由于T2衰变，尤其是在脊柱和四肢，它的图像模糊，限制了 诊断性能。在目前的建议中，我们将通过制定下一个- 生成WBMRI-使用单次和多次采集的高效组合进行检测。检测 还可以为定量脂肪分数(FF)图生成脂肪信号，这些图可以用作 嗯，因为肿瘤细胞取代了脂肪，脂肪是骨髓的主要成分。这种方法还使我们开发了一种 基于检测的DWI技术，可准确测量表观扩散系数(ADC)。具体的 目标是：1)开发使用单激发和多激发检测的集成WBMRI，以及 定量的FF图；2)开发基于检测的DWI，具有准确的ADC测量；以及3) 评估集成的WBMRI，包括检测-弥散加权成像和对比剂增强灌注，以获得有效的骨 病变检测和治疗反应评估。我们将在多发性骨髓瘤中使用骨损伤作为概念验证 以实现这些项目目标。该项目的成功结果将是一个有效的WBMRI 以精确的FF和ADC测量作为成像生物标志物的协议，在检测和测量中得到验证 多发性骨髓瘤患者的治疗反应。这个WBMRI结合了包括灌注在内的增强MRI， 将是一种极具成本效益和实用的方法(45分钟的餐桌时间)，广泛用于 世界各地的临床实践。这将使多发性骨髓瘤患者和患有其他骨骼病变的患者受益， 包括儿科患者在内的长期随访，没有PET/CT的缺点。这将提供相关的 为治疗决策提供临床信息，积极影响患者的生活质量和总体生存。

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.