MAGNETIC RESONANCE STUDIES OF BONE MARROW HEMATOPOIESIS

提出的工作目标是开发一种非侵入性的测定方法来表征人骨髓中的造血活性，并测试其在监测和分期血液恶性肿瘤患者中的效用。目前，针吸和活检用于明确诊断和治疗监测。除了引起患者不适外，活检和抽吸仅限于骨的浅表区域，如髂后嵴。拟议的检测将通过提供疾病的空间范围的测量来补充针活检获得的信息，特别是在针活检无法到达的部位。该项目的技术目标与最近引进的磁共振骨髓扫描技术的发展有关。研究表明，使用高速磁共振成像方案，在一定程度上基于细胞内与细胞外水的自扩散系数，几乎完全分割白血病骨髓是可能的。此外，分割的质量足够高，可以促进投影扫描方法，从而可以快速评估疾病的程度。早期的骨髓磁共振研究不能明确地检测白血病浸润，而是测量与骨髓细胞相关的变化。目前的效果似乎特别筛选异常细胞在急性淋巴细胞白血病。该研究计划包括以下研究：1)提高该方法的灵敏度；2)确定该方法适用的血液学病理范围；3)评估其对患者管理的效用。患者群体将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。这些方法的效用将在以下方面进行评估：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；2)慢性白血病、淋巴瘤和骨髓增生异常综合征的分期。

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.