MAGNETIC RESONANCE STUDIES OF BONE MARROW HEMATOPOIESIS

这项拟议工作的目标是开发一种非侵入性的方法来表征人骨髓的造血活性，并测试其在监测和分期恶性血液病患者中的有效性。目前，针吸和活检用于明确诊断和治疗监测。除了引起病人不适外，活组织检查和抽吸仅限于骨骼的浅表区域，如后髂骨。拟议的化验将通过提供疾病空间范围的测量，特别是在针吸活检无法到达的部位，来补充从针吸活检获得的信息。该项目的技术目标与最近引进的磁共振骨髓扫描技术的开发有关。已经证明，使用高速磁共振成像方案与对比度部分基于细胞内和细胞外水的自扩散系数，可以几乎完全地分割白血病骨髓。此外，分割的质量足够高，可以促进投影扫描方法，从而快速评估疾病的程度。早期对骨髓的磁共振研究不能明确地发现白血病的渗透，而是测量到与骨髓细胞密度有关的变化。目前的效果似乎是特异性地筛查急性淋巴细胞白血病中的异常细胞。研究计划包括1)提高该方法的灵敏度，2)确定适用的血液病理学范围，以及3)评估其对患者管理的有效性。患者群体包括急性和慢性白血病、淋巴瘤、多发性骨髓瘤和骨髓增生异常综合征。这些方法的实用性将在1)监测急性和慢性白血病、淋巴瘤和多发性骨髓瘤的治疗效果，以及2)慢性白血病、淋巴瘤和骨髓增生异常综合征的分期方面进行评估。

The goals of the proposed work are to develop a non-invasive assay for characterizing hematopoieitic activity in human bone marrow, and to test its utility in monitoring and staging patients with hematologic malignancies. Presently, the needle aspirate and biopsy are used for definitive diagnosis and therapeutic monitoring. In addition to causing patient discomfort, biopsies and aspirates are limited to superficial areas of bone, such as the posterior iliac crest. The proposed assay will be designed to complement information obtained from the needle biopsy by providing a measure of the spatial extent of disease, particularly at sites inaccessible to the needle biopsy. The technical goals of the project are concerned with the development of recently introduced magnetic resonance bone marrow scanning technology. It was demonstrated that nearly complete segmentation of leukemic bone marrow was possible using a high speed magnetic resonance imaging protocol with contrast based in part upon the self-diffusion coefficient of intracellular versus extracellular water. Furthermore, the quality of the segmentation was high enough to facilitate a projection scan approach which allows a rapid assessment of extent of disease. Earlier studies of the bone marrow by magnetic resonance could not definitively detect leukemic infiltration, but rather measured changes related to bone marrow cellularity. The present effect appears to specifically screen for abnormal cells in acute lymphocytic leukemia. The research plan includes studies to 1) improve the sensitivity of the method, 2) determine the range of hematologic pathologies where it is applicable, and 3) assess its utility for patient management. Patient populations will include acute and chronic leukemia, lymphoma, multiple myeloma, and myelodysplastic syndrome. The utility of the methods will be assessed in 1) monitoring therapeutic efficacy in acute and chronic leukemia, lymphoma, and multiple myeloma, and 2) staging in chronic leukemia, lymphoma, and myelodysplastic syndrome.