Quantitative MRI Assessment of Bone Marrow Disease in Myelofibrosis: A Prospective Study

Abstract

Purpose To evaluate quantitative MRI parameters for assessing bone marrow composition and fibrosis in individuals with myelofibrosis (MF), as a noninvasive alternative to biopsy. Materials and Methods This prospective, single-site study (ClinicalTrials.gov identifier no. NCT01973881) included participants with MF and with non-MF myeloproliferative neoplasms (MPNs) and healthy controls who underwent MRI scans from November 2016 to January 2024. Different MRI sequences assessed fat content (proton density fat fraction), cellularity (apparent diffusion coefficient, ADC), and cellularity/macromolecular structure (magnetization transfer ratio, MTR) across lumbar vertebrae, ilium, and femoral heads. The authors used linear discriminant analysis to classify the extent of bone marrow fibrosis for each participant based on ADC values. Results This study included 66 participants (45 with MF and 15 with other MPNs [34 female] and six healthy controls (four male)]. The median age was 63 years among participants with MF and other MPNs and 62 years among healthy controls. Participants in the MF subgroup showed elevated ADCs and MTRs with lower bone marrow fat than healthy controls. Individual bone marrow MRI metrics generally correlated across anatomic sites (Pearson r = 0.57-0.89). ADC in the ilium showed the highest correlation with pathologic grade of bone marrow fibrosis (Kendall τ_B = 0.44, P = .01). ADC values near the linear discriminant analysis threshold in two to three anatomic sites correlated with increased risk of overt bone marrow fibrosis (odds ratio = 5.81, P = .01). Conclusion Quantitative bone marrow MRI parameters, particularly ADC, correlated with bone marrow fibrosis and disease severity in MF. Keywords: MR Imaging, Hematologic Supplemental material is available for this article. © RSNA, 2025.

Keywords: Hematologic; MR Imaging.

Graphical abstract

Figure 1:

MRI helps assess bone marrow in multiple anatomic locations. (A) The imaging study captured data from bone marrow in three anatomic locations: lumbar vertebral bodies, ilium, and femoral heads. We reconstructed apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) maps in all three anatomic locations and magnetization transfer ratio (MTR) maps in the ilium, resulting in seven total MRI-anatomy metrics to evaluate bone marrow. Bone marrow in each anatomic location (yellow arrowheads) is identified on representative PDFF maps from a healthy 62-year-old male individual (created with BioRender [2025]; https://BioRender.com/w35xmi7). (B) We quantify bone marrow volumes from each region. Each dot represents the volume of quantified bone marrow from individual participants in each anatomic region. Numbers in each bar denote the mean quantified volume of bone marrow per region. ADC = apparent diffusion coefficient, FH = femoral head, IL = ilium, MTR = magnetization transfer ratio, PDFF = proton density fat fraction, VB = lumbar vertebral bodies.

Figure 2:

MRI reveals differences in bone marrow in healthy participants and those with non-MF MPN and MF. Panels display representative coronal ADC and PDFF reformatted images and axial MTR images for (A) healthy (62-year-old male) participant and participants with (B) MPN–polycythemia vera (57-year-old male) and (C) MF (67-year-old male). Red arrows identify bone marrow sites of interest in the lumbar spine, ilium, and femoral heads. ADC = apparent diffusion coefficient, MF = myelofibrosis, MPN = myeloproliferative neoplasm, MTR = magnetization transfer ratio, PDFFF = proton density fat fraction.

Figure 3:

ADC and PDFF correlate among anatomic regions. Panels illustrate relationships among lumbar vertebral bodies, ilium, and femoral head bone marrow for (A) PDFF and (B) ADC. X- and y-axes show mean values for percentage of fat measured with (A) PDFF and (B) ADC (10⁻⁶ mm²/sec) in vertebral bodies and ilium, respectively, while the pseudocolor scale for symbols for each participant reflects mean (A) PDFF (% fat) and (B) ADC (10⁻⁶ mm²/sec) values in femoral heads. Pearson correlation coefficients, r, for each MRI metric across anatomic regions are PDFF: r_VB:IL = 0.86, r_VB:FH = 0.72, r_IL:FH = 0.89; ADC: r_VB:IL = 0.86, r_VB:FH = 0.57, r_IL:FH = 0.66; P < .01 for all correlations. Analyses include all participants with non-MF MPN and MF, with ADC and PDFF data from all three anatomic regions. PDFF is given as percentage of fat. ADC is in units of × 10⁻⁶ mm²/sec. ADC = apparent diffusion coefficient, FH = femoral head, IL = ilium, MF = myelofibrosis, MPN = myeloproliferative neoplasm, PDFF = proton density fat fraction, VB = vertebral bodies.

Figure 4:

MRI helps detect differences in bone marrow among participants with non-MF MPN and MF and healthy participants. Graphs show quantification of (A) PDFF, (B) ADC, and (C) MTR from bone marrow of healthy participants and participants with non-MF MPN and MF. PDFF decreases, ADC increases, and MTR increases compared with healthy bone marrow. Individual data points represent mean bone marrow values for each participant, with the bars denoting the mean and error bars denoting the 95% CI of the sample mean. P values calculated using multiple comparisons test (Tukey method). * P < .05, ** P < .01, *** P < .001. ADC = apparent diffusion coefficient, MF = myelofibrosis, MPN = myeloproliferative neoplasm, MTR = magnetization transfer ratio, PDFF = proton density fat fraction.

Figure 5:

Quantification of each MRI metric is illustrated for (A) vertebral body, (B) ilium, and (C) femoral head bone marrow in participants with an increasing number of abnormal MRI metrics. Each data point is the median value for each group of abnormal MRI metrics. Gray bands indicate the healthy 95% CI of the mean for each metric. PDFF is given as percentage of fat. ADC is in units of × 10⁻⁶ mm²/sec. MTR is a normalized ratio on a scale of 0–1. ADC = apparent diffusion coefficient, MTR = magnetized transfer ratio, PDFF = proton density fat fraction.

Figure 6:

Bone marrow MRI correlates with MF fibrosis grade. (A) ADC, (B) PDFF (% fat), and (C) MTR (normalized ratio from 0 to 1) values from the ilium increase with bone marrow MF grade assessed with biopsy (Tukey multiple comparisons test, *P < .05, **P < .01, ***P < .001). (D) Bone marrow cellularity is greater in participants with MF in this cohort compared with participants with non-MF MPN (P = .03, unpaired t test). (E) Cellularity does not trend with MF fibrotic grade. (F) Using Fisher exact test, we demonstrate significant association between early fibrosis (MF grades 0–1) and overt fibrosis (MF grades 2–3) and abnormal ADC MRI (P < .01 odds ratio = 5.81). (G) We evaluated Kendall rank correlation between each MRI metric and the MF grade and bone marrow cellularity. All listed correlations were significant (P < .05); we do not list nonsignificant. PDFF is given as percentage of fat. ADC is in units of × 10⁻⁶ mm²/sec. MTR is a normalized ratio on a scale of 0–1. ADC = apparent diffusion coefficient, MF = myelofibrosis, MPN = myeloproliferative neoplasm, MTR = magnetization transfer ratio, PDFF = proton density fat fraction.