Effects of Sex and Age on Fat Fraction, Diffusion-Weighted Image Signal Intensity and Apparent Diffusion Coefficient in the Bone Marrow of Asymptomatic Individuals: A Cross-Sectional Whole-Body MRI Study

Abstract

We aimed to describe the relationships between the relative fat fraction (%FF), muscle-normalized diffusion-weighted (DW) image signal intensity and water apparent diffusion coefficient (ADC), sex and age for normal bone marrow, in the normal population. Our retrospective cohort consisted of 100 asymptomatic individuals, equally divided by sex and 10-year age groups, who underwent whole-body MRI at 1.5 T for early cancer detection. Semi-automated segmentation of global bone marrow volume was performed using the DW images and the resulting segmentation masks were projected onto the ADC and %FF maps for extraction of parameter values. Differences in the parameter values between sexes at age ranges were assessed using the Mann-Whitney and Kruskal-Wallis tests. The Spearman correlation coefficient r was used to assess the relationship of each imaging parameter with age, and of %FF with ADC and normalized DW signal intensity values. The average %FF of normal bone marrow was 65.6 ± 7.2%, while nSI_b50, nSI_b900 and ADC were 1.7 ± 0.5, 3.2 ± 0.9 and 422 ± 67 μm²/s, respectively. The bone marrow %FF values increased with age in both sexes (r = 0.63 and r = 0.64, respectively, p < 0.001). Values of nSI_b50 and nSI_b900 were higher in younger women compared to men of the same age groups (p < 0.017), but this difference decreased with age. In our cohort of asymptomatic individuals, the values of bone marrow relative %FF, normalized DW image signal intensity and ADC indicate higher cellularity in premenopausal women, with increasing bone marrow fat with aging in both sexes.

Keywords: ADC; DWI; asymptomatic individuals; bone marrow; fat fraction; sex and age; whole-body MRI.

Figure A1

Scatterplots showing the correlation of apparent diffusion coefficient (ADC, left), muscle-normalized signal intensity of b50 and b900 images (nSI_b50, middle, and nSI_b900, right) and the fat fraction values (%FF). Linear regression lines and equations are reported.

Figure 1

Illustration of the process for apparent diffusion coefficient (ADC) and relative fat fractions (%FF) extraction in a 30-year-old man who performed WB-MRI for early cancer detection. Based on the acquired diffusion-weighted image (b900) seen in coronal MIP with inverted grayscale (A), the bone marrow mask (B) was obtained using a semi-automated software that combines calculation of a simulated diffusion-weighted image, signal intensity thresholding, and manual editing. Only the three lower body stations were considered for the analysis because the head/neck coil array yielded different signal-to-noise levels for the head/neck station that would have necessitated a separate threshold value for semi-automated segmentation. The bone marrow mask was projected onto the ADC map computed from the diffusion-weighted image (C), the ADC distribution in bone marrow obtained (yellow histogram) and the median value (red line) calculated (D). The %FF map computed from the Dixon images was slice matched and resampled to the resolution of the diffusion-weighted images and the bone marrow mask projected onto the resampled fat fraction map (E) to extract the distribution of bone marrow %FF values and to calculate the median value (red line) (F). Voxels with %FF values below 15% or ADC above 1000 µm²/s were excluded from the masks to limit measure biases produced by soft tissues included in the bone marrow segmentation due to subject motion between sequence acquisitions.

Figure 2

High b-value (b = 900 s/mm²) inverted gray-scale coronal maximum-intensity-projection images of 6 asymptomatic individuals. (A) In our cohort, the bone marrow signal intensity of women (♀) aged between 30 and 50 was higher compared to the bone marrow signal of older women (B) and adult men (♂) of all age groups (D,E). This difference may be attributable to the higher cellularity, water content and possibly higher perfusion of pre-menopausal women bone marrow. Images (C,F) show two examples of individuals for which the semi-automatic segmentation method used in this study was not applicable, due to hypointense bone marrow signal intensity on high b-value inverted gray-scale coronal maximum-intensity-projection images.

Figure 3

Comparison of the distributions of %FF, ADC, nSI_b50 and nSI_b900 values measured in bone marrow, by sex and age groups. It is clear that fat fraction (%FF) values increase with age for both men and women. The ADC, nSI_b50 and nSI_b900 values are higher in women between 30 and 49 years than in men of corresponding age groups (asterisks denote the significance level: * p < 0.05, ** p < 0.01, *** p < 0.001). ADC, nSI_b50 and nSI_b900 values in women were lower in the three subsequent age groups (50 years and older), probably due to menopause-induced changes in bone marrow composition, but a significant difference was observed in the ADC values of women and men of the 50–59 age group. On the contrary, the values of ADC, nSI_b50 and nSI_b900 measured in men were roughly constant across age groups.