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

项目总结

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.