Whole-body bone marrow DWI correlates with age, anemia, and hematopoietic activity

doi:10.1016/j.ejrad.2019.07.022

European Journal of Radiology

Volume 118, September 2019, Pages 223-230

https://doi.org/10.1016/j.ejrad.2019.07.022 Get rights and content

Highlights

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Age, Hb, and RDW are the predominant predictors of bone marrow signals on DWI.
•
Low ADC and high visibility are relevant to young age, anemia and hematopoiesis.
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Bone marrow ADCs were positively correlated with age and PDFF.
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Fat-suppression methods and middle-age physiology may have affected the results.

Abstract

Purpose

To identify the predictors of bone-marrow DWI signals from anthropometric, complete blood count (CBC), and C-reactive protein (CRP), and to evaluate the association with fat-content in patients.

Method

This retrospective study was approved by the institutional review board. A total of 113 consecutive tumor patients underwent whole-body PET/MRI. Apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) were measured and averaged in lumbar vertebrae (L3-5) and bilateral ilia. Due to respiratory motion, ribs were evaluated by 3-point visual scoring on DWI with b = 800 (1: invisible, 2: partially visible, 3: fully visible). The relationships between ADC/visual scores and anthropometric, CBC, CRP, and PDFF were examined. In females, the age-dependency was evaluated.

Results

Multi-regression analyses identified age as the strongest predictor of lumbar ADC (standardized coefficient: β = 0.45), followed by red cell distribution width (RDW) (β = −0.24), while age was the strongest predictor of iliac ADC (β = 0.43), followed by hemoglobin (Hb) (β = 0.22). RDW was the strongest predictor (β = 0.47) for rib visual score and age was the second (β = -0.39). ADC showed significant positive correlations with PDFF at L3-5 and ilium. Lumbar ADC showed a decreasing trend during middle age in females.

Conclusions

Age, anemia (lower Hb), and increased hematopoietic activity (higher RDW) are the predominant predictors of ADC and the visibility of red marrow on DWI. Fat-suppression methods and bone-marrow physiology in middle-aged females may have affected the measured correlations between ADC and PDFF inconsistent with previous studies.

Introduction

Diffusion-weighted imaging (DWI) is a quantitative functional magnetic resonance imaging (MRI) technique complementary to positron emission tomography (PET) with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) [1]. Whole-body DWI with apparent diffusion coefficient (ADC) quantification is currently used for cancer staging and assessing treatment responses to diseases involving bone marrow [[2], [3], [4]]. Proton density fat fraction (PDFF) measurements have been used to assess hepatic steatosis [5,6], and whole-body PDFF imaging is being applied to evaluate the fat content of bone marrow in patients with benign and malignant diseases [7,8].

Bone marrow ¹⁸F-FDG uptake (reflecting glucose metabolism) is reported to be associated with age, white blood cell (WBC), serum C-reactive protein (CRP), and treatment with granulocyte colony-stimulating factor (GCSF) or erythropoietin [[9], [10], [11], [12], [13]]. However, the predictive factors for bone marrow signals on DWI are mostly unknown and may have an impact on image interpretation of bone marrow when using whole-body DWI to assess disease burden and treatment response. Moreover, it has been reported that fat content in bone marrow may be a major contributing factor to restricted diffusion in patients with myeloma [14].

The objectives of this study were twofold: first, to identify the predominant predictors for bone marrow signals on DWI from anthropometric and blood-related data including complete blood count (CBC) and CRP in patients; and second, to evaluate the association of bone marrow DWI with fat content in patients, and with age in females.

Section snippets

Patient population

We retrospectively reviewed the medical records of all tumor patients at diagnosis who underwent whole-body PET/MRI in our institute between February 2017 and October 2017. Patients were eligible for the study if they fulfilled the following criteria: (1) whole-body DWI and ADC maps were obtained, (2) CBC and CRP data measured within one week of the scan were available, and (3) normal renal function was established. Normal renal function is defined as an estimated glomerular filtration rate

Predictor of bone marrow ADC and visual scores

Bone marrow ADCs and the ranges for each region are presented with PDFF in Table 3. The results of multiple regression analyses to identify the predictors for bone marrow DWI are shown in Table 4. Age was the strongest predictor of lumbar ADC (standardized coefficient: β = 0.45, p < 0.0001), followed by red cell distribution width (RDW) (β = -0.24, p < 0.05). Age was the strongest predictor of iliac ADC (β = 0.43, p < 0.0001), followed by hemoglobin (Hb) (β = 0.22, p < 0.05). Fig. 2 shows the

Discussion

To the best of our knowledge, this is the first study based on a multiple regression analysis that has clearly identified the predictive factors for bone marrow signals on whole-body DWI in anthropometric and blood-related data including CBC and CRP. Younger age, lower Hb (anemia), and higher RDW (increased hematopoietic activity) were the predominant predictors of higher visibility and lower ADC of bone marrow in DWI. Though some of these results are consistent with the findings of previous

Author statement

All authors have approved the final article.

Funding

This study was partly funded by Takeda Science Foundation.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Citation Excerpt :
With aging, red marrow converts to yellow marrow, fat content increases, explaining why fat needs to get considered. Mean ADC values do not differ significantly among premenopausal, perimenopausal and postmenopausal women; however, our results (r = −0.244, p = 0.042) and some other studies have found that ADC is weakly negatively correlated with age [19–23], likely due to red marrow converting to yellow marrow. With aging, water diffusion increases due to an increase in trabecular space, leading to an increase in ADC values.
Diffuse hyperintensities of the bone marrow in whole-body diffusion-weighted (DW) imaging (DWI) have been encountered more frequently in females aged 21–50 compared to elder females or men. Therefore, we aimed to visually evaluate DWI among pre-, peri- and postmenopausal women and to verify whether it correlates also quantitatively with hormonal status.
The prospective study was approved by our institutional review board and informed consent was obtained in a total of 70 healthy premenopausal, perimenopausal, and postmenopausal women aged 40–58 years from February 2017 to October 2017. The bone marrow DW imaging signal characteristics were visually evaluated in comparison to the erector spinae muscle. Imaging data were acquired using a 1.5 T MRI yielding signal intensity values from a DWI-pulse sequence (b-value of 800 s/mm²; apparent diffusion coefficient (ADC) maps from b-values of 0–800 s/mm²), and a T2 mapping sequence covering the L2-L4 lumbar vertebrae. Serous estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured through venous blood assay. The relationship of the mean DW signal intensity (SI_DWI) with T2 values, female hormone level, and mean ADC were analyzed using Spearman’s rho test.
The proportion of diffuse DWI hyperintensities of the bone marrow was significantly higher in premenopausal (91% (21/23)) women compared to peri- (75% (18/24)) and postmenopausal (8% (2/23)) women. A positive correlation was observed for the mean SI_DWI (median [interquartile range], 47.33 [30.14]) and mean T2 (mean ± SD, 121.01 ± 13.54) (r = 0.438, p < 0.001) as well as for the mean SI_DWI and E2 (median [interquartile range], 52.45 [92.78]) (r = 0.407, p < 0.001). A negative correlation was observed for the mean SI_DWI and serous FSH (median [interquartile range], 15.55 [42.08]) as well as for the mean SI_DWI and serous LH (median [interquartile range], 6.96 [31.06]) (r = −0.557, p < 0.001; r = −0.535, p < 0.001; respectively), but no significant correlation was found for mean SI_DWI and mean ADC (mean ± SD, 599.36 ± 82.70) (r = 0.099, p = 0.415). A negative correlation was also encountered for the mean T2 values and serous FSH (r = −0.339, p = 0.004) as well as for the mean T2 values and serous LH (r = −0.281, p = 0.018).
The mean SI_DWI correlates positively with mean T2 and serous E2 values, while there's no significant correlation with mean ADC, indicating that T2 shine-through effects might interfere with bone marrow signaling on DW images. Knowledge of the bone marrow signal characteristics changing in DW images in close relationship with menstrual status is essential to correctly interpret DWI in clinical practice.
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However, the sinusoids were increased around the bone marrow endosteum niches where a lot of uncontrollable hyperplasia of LSC was gathered in AL [20,21]. Anemia was the most common benign marrow hyperplasia, which were known to be marrow reconversion controllably, the cell proliferation and the vascularization was lower than AL [22]. We hypothesized that there are probably higher f value and lower D values of bone marrow in AL than in anemia.
To investigate the relationship between intravoxel incoherent motion (IVIM) parameters and histological parameters of vascularity and cellularity in marrow of hyperplasia disease and compare the difference between benign and malignant marrow disorders.
From August 2016 to March 2017, 43 newly diagnosed patients were recruited, which included 15 anemia patients (benign hemopathy) and 28 patients with acute leukemia (AL) (malignant hemopathy). All patients underwent IVIM in the lumbar marrow and the D, D*, f values were measured. The microvessel density (MVD) and cellularity of marrow were calculated from the sample of iliac crest biopsy. Pearson correlation analysis was used to study the relationship between IVIM-derived and histology-derived parameters. We performed unpaired t test to analyze the differences of all parameters between AL and anemia.
The MVD was positively correlated with f in patients with AL, anemia and both of them (r = 0.692, P < 0.001; r = 0.595, P = 0.019; r = 0.673, P < 0.001, respectively). But there was no correlation between D* and MVD in three groups. D was not related to bone marrow cellularity (BMC) in all groups. In addition, the f and MVD were higher in AL than anemia (t = 3.546, P = 0.001; t = 6.695, P < 0.001, respectively). The BMC was significantly higher in AL than in anemia (t = 3.330, P = 0.004), but D and D* value had no significant difference between the two groups.
The blood volume fraction f was positively correlated with the histological features of marrow in hematological disorders, while f can show the difference of vascularity between benign and malignant marrow disease.
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3.0-tesla magnetic resonance imaging in the assessment of postmenopausal osteoporosis: are technological advances capable of replacing bone densitometry?
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Research articleWhole-body bone marrow DWI correlates with age, anemia, and hematopoietic activity

Highlights

Abstract

Purpose

Method

Results

Conclusions

Introduction

Section snippets

Patient population

Predictor of bone marrow ADC and visual scores

Discussion

Author statement

Funding

Declaration of Competing Interest

Nucl. Med. Biol.

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Radiology

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Whole-body diffusion-weighted MR imaging for assessment of treatment response in myeloma

Radiology

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Radiology

Proton density fat fraction measurements at 1.5-and 3-T hepatic MR imaging: same-day agreement among readers and across two imager manufacturers

Radiology

Proton-density fat fraction and simultaneous R2*estimation as an MRI tool for assessment of osteoporosis

Eur. Radiol.

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Eur. Radiol.

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Research article
Whole-body bone marrow DWI correlates with age, anemia, and hematopoietic activity

Complementary roles of whole-body diffusion-weighted MRI and ¹⁸F-FDG PET: the state of the art and potential applications