Fat Fraction MRI for Longitudinal Assessment of Bone Marrow Heterogeneity in a Mouse Model of Myelofibrosis

Lauren Brenner; Tanner H Robison; Timothy D Johnson; Kristen Pettit; Moshe Talpaz; Thomas L Chenevert; Brian D Ross; Gary D Luker

doi:10.3390/tomography11080082

Fat Fraction MRI for Longitudinal Assessment of Bone Marrow Heterogeneity in a Mouse Model of Myelofibrosis

Tomography. 2025 Jul 28;11(8):82. doi: 10.3390/tomography11080082.

Authors

Lauren Brenner^{1

2}, Tanner H Robison^{1

2}, Timothy D Johnson³, Kristen Pettit⁴, Moshe Talpaz⁴, Thomas L Chenevert¹, Brian D Ross^{1

5}, Gary D Luker^{1

2

6}

Affiliations

¹ Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
² Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
³ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
⁴ Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
⁵ Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
⁶ Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

Background/objectives: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the replacement of healthy bone marrow (BM) with malignant and fibrotic tissue. In a healthy state, bone marrow is composed of approximately 60-70% fat cells, which are replaced as disease progresses. Proton density fat fraction (PDFF), a non-invasive and quantitative MRI metric, enables analysis of BM architecture by measuring the percentage of fat versus cells in the environment. Our objective is to investigate variance in quantitative PDFF-MRI values over time as a marker of disease progression and response to treatment.

Methods: We analyzed existing data from three cohorts of mice: two groups with MF that failed to respond to therapy with approved drugs for MF (ruxolitinib, fedratinib), investigational compounds (navitoclax, balixafortide), or vehicle and monitored over time by MRI; the third group consisted of healthy controls imaged at a single time point. Using in-house MATLAB programs, we performed a voxel-wise analysis of PDFF values in lower extremity bone marrow, specifically comparing the variance of each voxel within and among mice.

Results: Our findings revealed a significant difference in PDFF values between healthy and diseased BM. With progressive disease non-responsive to therapy, the expansion of hematopoietic cells in BM nearly completely replaced normal fat, as determined by a markedly reduced PDFF and notable reduction in the variance in PDFF values in bone marrow over time.

Conclusions: This study validated our hypothesis that the variance in PDFF in BM decreases with disease progression, indicating pathologic expansion of hematopoietic cells. We can conclude that disease progression can be tracked by a decrease in PDFF values. Analyzing variance in PDFF may improve the assessment of disease progression in pre-clinical models and ultimately patients with MF.

Keywords: bone marrow; hematopoietic stem and progenitor cells; myelofibrosis; myeloproliferative neoplasms; proton density fat fraction; quantitative MRI.

MeSH terms

Animals
Bone Marrow* / diagnostic imaging
Bone Marrow* / pathology
Disease Models, Animal
Disease Progression
Longitudinal Studies
Magnetic Resonance Imaging* / methods
Mice
Primary Myelofibrosis* / diagnostic imaging
Primary Myelofibrosis* / drug therapy
Primary Myelofibrosis* / pathology

Abstract

MeSH terms

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