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

用于检测和评估骨病变治疗反应的新一代全身 MRI

• 批准号: 10716642
• 负责人: Ananth Jayaseelan Madhuranthakam
• 金额: $ 54.82万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716642
• 关键词: Abdomen; Address; Anatomy; Bone Marrow; Bone Marrow Transplantation; Bone marrow biopsy; Chest; Clinical; Clinical Trials; Detection; Development; Diagnosis; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Fatty acid glycerol esters; Generations; Goals; Image; Image Enhancement; Imaging Techniques; Imaging technology; Industry Standard; Lesion; Limb structure; Liquid substance; Localized Lesion; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Maps; Marrow; Measurement; Measures; Metastatic Neoplasm to the Bone; Methods; Morphologic artifacts; Motion; Multiple Myeloma; Musculoskeletal; Neoadjuvant Therapy; Non-Malignant; Outcome; PET/CT scan; Pain; Paralysed; Pathological fracture; Pathology; Patient Care; Patients; Pelvis; Performance; Perfusion; Prognosis; Prognostic Marker; Progression-Free Survivals; Protocols documentation; Quality of life; Recommendation; Reference Standards; Renal carcinoma; Resolution; Roentgen Rays; Scanning; Signal Transduction; Skeleton; Solid Neoplasm; Testing; Time; Vertebral column; Visualization; bone; bone imaging; bone loss; clinical practice; clinical translation; clinically relevant; contrast enhanced; cost; cost effective; experience; fluorodeoxyglucose positron emission tomography; imaging biomarker; imaging detection; imaging modality; improved; in vivo; innovation; malignant breast neoplasm; neoplastic cell; next generation; novel; pediatric patients; spinal cord compression; standard of care; treatment response; tumor

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.

项目摘要 来自乳房，前列腺或肾脏癌等实体瘤的骨骼病变，肿瘤起源于骨骼 可能发生多发性骨髓瘤（MM）或其他非恶性肌肉骨骼病理 骨骼中的任何地方。这些骨骼病变会引起疼痛和脊髓压缩，导致病理 骨折和瘫痪，从而降低了患者的生活质量。当前的疗法依靠诊断 这些通过全身X射线或骨扫描进行的骨骼病变，仅在晚期识别它们。尽管 建议对全身磁共振成像（WBMRI）进行预处理评估（例如，在 mm），MRI通常仅限于脊柱和骨盆区域，以最大程度地减少患者的不适感 几何扭曲的图像质量以及由于收购时间延长而产生的高成本。解决这个问题 未满足的临床需求，我们开发了一种新颖的WBMRI技术：`双回声T2加权采集 增强肿瘤（检测）的显着性，以通过分离来改善病变可视化 脂肪和液体的混杂信号。与具有扩散加权成像（DWI）的WBMRI相比 射击检测在较短的扫描时间（<10分钟）中，射击发现增加了病变检测（> 40％），没有 图像扭曲。此方法还提高了胸腔和腹部区域运动的鲁棒性， 然而，由于T2-Decay，特别是在脊柱和四肢，它的图像遭受了模糊的痛苦，限制了 诊断性能。在当前的提案中，我们将通过开发下一步来解决这些局限 使用单枪和多弹药采集的有效组合，生成WBMRI检测。探测 还生成用于定量脂肪分数（FF）图的脂肪信号，可以用作预后生物标志物 MM，由于肿瘤细胞取代了脂肪，这是骨髓的主要成分。这种方法还使我们开发了 基于检测的DWI技术，用于准确测量表观扩散系数（ADC）。具体 目的是：1）使用单杆和多摄像检测来开发集成的WBMRI， 定量FF图； 2）使用准确的ADC测量开发基于检测的DWI；和3）到 评估综合WBMRI，包括检测-DWI和对比增强灌注，以进行有效的骨头 病变检测和治疗反应评估。我们将在MM中使用骨骼病变作为概念证明 疾病以实现这些项目目标。该项目的成功结果将是有效的WBMRI 具有准确的FF和ADC度量作为成像生物标志物的协议，在检测和测量中验证 MM患者的治疗反应。该WBMRI与对比增强的MRI结合使用，包括灌注， 将是一种出色的成本效益和实用方法（<45分钟的餐桌时间），以广泛使用 世界各地的临床实践。这将使MM患者和患有其他骨骼病变的患者受益， 在长期随访中包括小儿患者，而没有PET/CT的缺点。这将提供相关的 治疗决策的临床信息，以积极影响患者的生活质量和整体生存。