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TOMOGRAPHY, March 2016, Volume 2, Issue 1: 67-78
DOI: 10.18383/j.tom.2016.00115

Pilot Study of Quantitative MRI Parametric Response Mapping of Bone Marrow Fat for Treatment Assessment in Myelofibrosis

Gary D. Luker1,2,3, Huong (Marie) Nguyen4, Benjamin A. Hoff1, Craig J. Galbán1, Diego Hernando5, Thomas L. Chenevert1, Moshe Talpaz4, and Brian D. Ross1,6

1Center for Molecular Imaging, Department of Radiology, and 2Departments of Biomedical Engineering and 3Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan; 4Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan; 5Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin; and 6Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan

Abstract

Myelofibrosis (MF) is a hematologic neoplasm arising as a primary disease or secondary to other blood malignancies. Both primary and secondary MF develop progressive fibrosis of bone marrow, displacing normal hematopoietic cells to other organs and disrupting normal production of mature blood cells. Activation of JAK2 signaling in hematopoietic stem cells commonly causes MF, and ruxolitinib, a drug targeting this pathway, is the preferred treatment for many patients. However, current measures of disease status in MF do not necessarily predict response to treatment with ruxolitinib or other drugs. Bone marrow biopsies are invasive and prone to sampling error, while measurements of spleen volume only indirectly reflect status of bone marrow. Toward the goal of developing an imaging biomarker for treatment response in MF, we present preliminary results from a prospective clinical study evaluating parametric response mapping (PRM) of quantitative Dixon MRI bone marrow fat fraction maps in four MF patients treated with ruxolitinib. PRM allows voxel-wise identification of temporal changes in quantitative imaging readouts, in this case bone marrow fat. We identified heterogeneous responses of bone marrow fat among patients and within different bone marrow sites in the same patient. Changes in bone marrow fat fraction also were discordant with reductions in spleen volume, the standard imaging metric for treatment response. This study provides initial support for PRM analysis of quantitative MRI of bone marrow fat to monitor therapy in MF, setting the stage for larger studies to further develop and validate this method as a complementary imaging biomarker.

Supplemental Media

  • Video 1

    A 4-dimensional (4D) display of the anatomic PRM display over the course of therapy for patient 1.

  • Video 2

    A 4-dimensional (4D) display of the anatomic PRM display over the course of therapy for patient 2.

  • Video 3

    A 4-dimensional (4D) display of the anatomic PRM display over the course of therapy for patient 3.

  • Video 4

    A 4-dimensional (4D) display of the anatomic PRM display over the course of therapy for patient 4.

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