University of Michigan Quantitative Co-Clinical Imaging Research Resource

密歇根大学定量联合临床成像研究资源

• 批准号: 10002208
• 负责人: THOMAS L CHENEVERT
• 金额: $ 62.84万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002208
• 关键词: Abdomen; Address; Anatomy; Animals; Architecture; Autopsy; Biopsy; Bone Marrow; Bone Marrow Cells; Bone Marrow Diseases; Bone marrow biopsy; Cells; Cellularity; Chronic; Clinical; Clinical Medicine; Clinical Trials; Code; Communities; Computer software; Confidence Intervals; DNA Sequence Alteration; Data; Data Set; Deposition; Development; Diffusion; Disease; Ensure; Environment; FDA approved; Fatty acid glycerol esters; Fibrosis; Genetic; Genomics; Goals; Hematologic Neoplasms; Hematopoietic Neoplasms; Hematopoietic stem cells; Heterogeneity; Histology; Human; Image; Image Analysis; Imaging Phantoms; Imaging Techniques; Inflammation; Institution; Internet; Investigation; Investigational Therapies; JAK1 gene; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Methods; Michigan; Multi-Institutional Clinical Trial; Mus; Myelofibrosis; Myeloproliferative disease; Oncologist; Oncology; Output; Pain; Patient Care; Patients; Pharmaceutical Preparations; Physicians; Pre-Clinical Model; Preclinical Drug Development; Procedures; Protocols documentation; Protons; Publications; Reproducibility; Research; Research Personnel; Resources; Sampling Errors; Scanning; Severities; Severity of illness; Site; Skeleton; Spleen; Standardization; Techniques; Testing; The Cancer Imaging Archive; Three-Dimensional Imaging; Time; Tissues; Translations; Universities; Validation; Vendor; Water; Work; base; bone; cancer therapy; clinical imaging; density; disease heterogeneity; driver mutation; drug development; drug testing; experience; human imaging; human subject; image processing; imaging biomarker; imaging modality; imaging study; improved; inhibitor/antagonist; millimeter; mouse model; novel therapeutics; patient population; pre-clinical; preclinical imaging; preclinical trial; predicting response; quantitative imaging; response; response biomarker; standard of care; success; treatment response; user-friendly; water diffusion; web site

PROJECT SUMMARY/ABSTRACT Quantitative imaging methods to detect cancer and assess response to therapy are cornerstones of pre-clinical drug development, clinical trials, and patient care. Success of quantitative imaging in oncology relies on standardization of protocols for image acquisition and analysis to ensure reproducibility within a single site over time and across institutions for multi-site clinical trials. Work by our group and others in the Quantitative Imaging Network and Quantitative Imaging Biomarkers Alliance continues to advance standardization procedures for clinical imaging. However, similar rigor has not been applied to pre-clinical imaging studies of cancer therapy in mice. The disconnect between standardization and validation methods incorporated into imaging studies for humans versus mice contributes to ongoing challenges with reproducibility in drug development and successful translation of new drugs to clinical medicine. To ensure direct, quantitative comparisons between pre-clinical and clinical imaging, we will establish a resource for quantitative MRI of bone marrow composition and architecture in myelofibrosis (MF), a chronic hematologic cancer marked by progressive fibrosis and destruction of bone marrow. This resource will extend quantitative imaging into hematologic cancers, a group of malignancies understudied and underserved by imaging because current methods generate largely qualitative data that cannot be used reliably as biomarkers for response to therapy. We will analyze key metrics of bone marrow disease using FDA-approved MRI sequences included in standard software packages for pre-clinical 7T and clinical 3T scanners: 1) bone marrow composition and cellularity (quantitative Dixon technique for fat/water); 2) replacement of normal bone marrow cells and bone trabecula (mobility of water (diffusion, DWI)); and 3) extent and severity of fibrosis (magnetization transfer (MT)). As part of standardization procedures for both mouse and human imaging, we will measure repeatability of imaging data using phantoms for each MRI sequence and test/retest imaging procedures for mouse and human subjects to establish confidence intervals. We also will standardize workflow for quantifying bone marrow MRI data with parametric response mapping (PRM), a voxel-wise image processing method we devised to capture spatial and temporal heterogeneity of imaging data during treatment. After establishing standard operating procedures for quantitative bone marrow MRI (Aim 1), we will apply these methods to co-clinical trials with standard-of-care and investigational therapies for MF, matching driver mutations for MF present in our patient population with our mouse model (Aim 2). To disseminate these methods to the imaging community, we will post standard operating procedures for MRI protocols, mouse models of MF, and PRM of bone marrow MRI data (Aim 3). We also will deposit curated imaging data in the TCIA, enabling other investigators to mine these data and test new hypotheses. Overall, this resource will reduce variability in quantitative bone marrow MRI in both mice and humans, improving the ability to reliably implement these imaging biomarkers to advance co-clinical trials and drug development MF and likely other hematologic malignancies.

项目总结/摘要 检测癌症和评估对治疗的反应的定量成像方法是临床前诊断的基石。 药物开发、临床试验和患者护理。定量成像在肿瘤学中的成功依赖于 图像采集和分析协议的标准化，以确保在单个部位内的再现性， 时间和跨机构进行多中心临床试验。我们小组和其他人在定量成像领域的工作 网络和定量成像生物标志物联盟继续推进标准化程序， 临床影像学然而，类似的严格性尚未应用于癌症治疗的临床前成像研究， 小鼠标准化和验证方法之间的脱节纳入成像研究， 人类与小鼠的对比有助于药物开发和成功的可重复性的持续挑战 将新药转化为临床药物。为了确保临床前和 临床成像，我们将建立一个资源，定量磁共振成像的骨髓组成和结构 在骨髓纤维化（MF）中，一种以进行性纤维化和骨质破坏为特征的慢性血液学癌症 骨髓这一资源将扩大定量成像到血液癌症，一组恶性肿瘤 由于目前的方法产生的主要是定性数据， 可靠地用作治疗反应的生物标志物。我们将分析骨髓疾病的关键指标 使用标准软件包中包含的FDA批准的MRI序列，用于临床前7 T和临床3 T 扫描仪：1）骨髓成分和细胞结构（脂肪/水的定量狄克逊技术）; 2）置换 正常骨髓细胞和骨小梁（水的流动性（扩散，DWI））;和3）范围和严重程度 纤维化（磁化转移（MT））。作为小鼠和人类标准化程序的一部分 成像，我们将使用体模测量每个MRI序列的成像数据的可重复性，并进行测试/重新测试 用于小鼠和人类受试者的成像程序以建立置信区间。我们还将标准化 使用参数响应映射（PRM）量化骨髓MRI数据的工作流程， 我们设计了一种处理方法来捕获治疗期间成像数据的空间和时间异质性。 在建立定量骨髓MRI的标准操作程序（目标1）后，我们将应用这些标准操作程序。 MF标准治疗和研究性治疗的联合临床试验方法，匹配驱动突变 对于我们的小鼠模型中存在于我们的患者群体中的MF（目的2）。将这些方法传播给 成像社区，我们将张贴标准操作程序的MRI协议，小鼠模型的MF， 骨髓MRI数据的PRM（目的3）。我们还将存款策展成像数据在TCIA，使其他 调查人员挖掘这些数据并测试新的假设。总的来说，这一资源将减少 在小鼠和人类中进行定量骨髓MRI，提高可靠实施这些成像的能力 生物标志物，以推进共同临床试验和药物开发MF和可能的其他血液恶性肿瘤。