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Quantification of bone marrow edema in RA by using high-speed T2-corrected multiecho acquisition of 1H magnetic resonance spectroscopy
Wenzhao Yuan1, Yiwu Lei1, Cheng Tang1, Fang Qin1, Jing Wen1, Chenhui Li2, Min Ling1, Jiang Huang1, Huiting Zhang3, and Liling Long1
1The First Affiliated Hospital of Guangxi Medical University, Nanning, China, 2Siemens Healthcare Ltd., Guangzhou, China, 3Siemens Healthcare Ltd., Wuhan, China

Synopsis

The purpose of this study was to determine whether high-speed T2-corrected multiecho (HISTO) sequences can quantify bone marrow edema (BME) in the capitate bone in rheumatoid arthritis (RA), and whether the HISTO fat fraction (FF) reflects therapeutic effectiveness.

The results showed that the HISTO sequence can measure the bone marrow FF of the wrist joint in RA patients. We also found that the HISTO sequence may help quantify BME in RA and help monitor the effectiveness of RA treatment.

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the chronic inflammation of peripheral joints, which leads to progressive structural damage, long-term disability, and premature mortality[1]. Bone marrow edema (BME) of RA is a powerful independent predictor of progressive joint damage, and can be used to predict the course of the disease[2-8]. Histopathological studies have shown that BME or osteitis results in the replacement of the normal fat tissues of the bone marrow with inflammatory cells in RA, which is manifested as an increase in tissue water content[9,10,11]. Therefore, it is possible to determine the severity of BME in RA by monitoring the changes in the fat content of the bone marrow.The high-speed T2-corrected multiecho (HISTO) has proved useful for the quantitative assessment of fatty liver[12-14] and muscle fatty lesions[15].Therefore, the objectives of this study were to (a) determine the feasibility of using the HISTO sequence for the quantitative assessment of BME in the capitate bone in RA-affected wrists, and (b) identify whether the FF value on HISTO sequences can be used to monitor the effectiveness of RA treatment.

Methods and materials

This prospective study enrolled 25 patients (19 women; average age, 45.08 ± 13.48 years) with RA and 21 normal control subjects (15 women; age, 49.17 ± 6.56 years) from the local hospital between March and December 2019. Every subject was clearly told the whole experimental procedure and signed an informed consent form to participate in the current study, which was approved by the Medicine Ethics Committee of our hospital.
The RA patients underwent MRI with HISTO sequence at the baseline and after 4, 8, and 12 weeks of treatment. Rheumatoid factor (RF), erythrocyte-sedimentation rate (ESR), C-reactive protein (CRP), platelet count (PLT), and 28-joint Disease Activity Score using ESR (DAS28-ESR) were recorded on the day of each MRI examination by a rheumatologist blinded to the MRI findings. In all patients, RA was diagnosed according to the American College of Rheumatology/European League Against Rheumatism criteria[16]. The healthy subjects underwent only the HISTO sequence at a single time point. For all participants, a 3.0-T scanner with a 15-channel joint coil was used for scanning with the same parameters.
First, a three-dimensional (3D) T1 space sequence was performed, and followed by T2-weighted sequence with fat saturation which was acquired to confirm the absence of other diseases in all subjects. Reconstruction of the axial, coronal, and sagittal planes of the wrist joint was performed using the 3D-T1 space images, which were used to guide the localization of the capitate bone with the HISTO grid. Scan parameters are shown in Table 1.
Statistical analysis was performed using SPSS (version 22, Chicago, IL, USA). Differences in age, body mass index (BMI), and HISTO FF values between the control and patient groups at the baseline were tested using the independent-samples t-test. The gender difference between the control and patient groups at the baseline was examined using the chi-square test. Bland-Altman plots were used to assess the repeatability of measurements in the control group. In the RA patient group, correlations between the DAS28-ESR, RF, ESR, CRP, PLT, and HISTO FF values at the baseline, and the change in these values with each treatment course were assessed using Spearman correlation analysis. Repeated-measures analysis of variance (ANOVA) was used to analyze the trend of the correlation between the DAS28-ESR and HISTO FF values in RA patients. In all analyses, P values of <0.05 were taken to indicate a statistically significant difference.

Results

Age, gender, and BMI did not significantly differ between the patient and control groups at the baseline .
From the baseline to 12 weeks, the mean DAS28-ESR and CRP values in RA patients decreased, while the mean HISTO FF increased. The average RF, ESR, and PLT decreased from the baseline to 8 weeks, but increased again at 12 weeks (Table 2).
Bland-Altman plots showed good interobserver agreement of HISTO FF measurements between two repeated positioning scans (Figure 1). Patients with RA had lower HISTO FF of the capitate bone at the baseline than the control subjects (P < 0.05).
There was no correlation between DAS28-ESR, serological indicators, and HISTO FF in RA patients at the baseline (P > 0.05). After the treatment, the changes in HISTO FF and DAS28-ESR at 4, 8, and 12 weeks showed moderate negative correlations with each other (P < 0.05). The change in HISTO FF was significantly positively correlated with the change in RF at 4 weeks and significantly negatively correlated with the change in PLT at 12 weeks (P < 0.05) (Table 3).
Repeated-measures ANOVA showed an interaction between the DAS28-ESR and HISTO FF from the baseline to 12 weeks as HISTO FF increased, DAS28-ESR decreased (Figure 2).

Discussion and Conclusion

The change in FF at each time point and the overall trend of the changes in FF were negatively correlated with DAS28-ESR. However, the FF could not accurately reflect the changes in RF, ESR, CRP, and PLT.The HISTO sequence can measure the bone marrow FF of the wrist joint in RA patients. The HISTO sequence may help quantify BME in RA and help monitor the effectiveness of RA treatment.

Acknowledgements

Acknowledgments: This research study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.We would like to thank Medjaden Bioscience Limited for scientific editing of this manuscript.

References

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Figures

Table 1 Scan parameters of MRI with all participants HISTO, high-speed T2-corrected multiecho; TE, echo time; TR, repetition time; T2WI-FS, T2-weighted sequence with fat saturation; 3D-T1 space, three-dimensional T1 space

Table 2 Clinical data and HISTO FF values of RA patients at each follow-up time point (mean ± SD) CRP, C-reactive protein; DAS28-ESR, 28-joint disease activity score using erythrocyte-sedimentation rate; ESR, erythrocyte-sedimentation rate; FF, fat fraction; HISTO, high-speed T2-corrected multiecho sequence; PLT, platelet count; RA, rheumatoid arthritis; RF, rheumatoid factor Change 1, the baseline value minus the value at 4 weeks Change 2, the value at 4 weeks minus the value at 8 weeks Change 3, the value at 8 weeks minus the value at 12 weeks

Table 3 Correlation analysis of HISTO FF and clinical characteristics CRP, C-reactive protein; DAS28-ESR, 28-joint disease activity score using erythrocyte-sedimentation rate; ESR, erythrocyte-sedimentation rate; FF, fat fraction; HISTO, high-speed T2-corrected multiecho sequence; PLT, platelet count; RA, rheumatoid arthritis; RF, rheumatoid factor Change 1, the baseline value minus the value at 4 weeks Change 2, the value at 4 weeks minus the value at 8 weeks Change 3, the value at 8 weeks minus the value at 12 weeks

Fig. 1 Bland-Altman plots of the differences in high-speed T2-corrected multiecho (HISTO) fat fraction (FF) measurements generated by two repeated positioning scans. The dotted red lines demarcate 1.96 standard deviations (SDs), and the blue lines depict their 95% prediction limits. The plot shows good interobserver agreement

Fig. 2 Trend of the correlation between DAS28-ESR and HISTO values in RA patients during treatment. DAS28-ESR, 28-joint Disease Activity Score using erythrocyte-sedimentation rate; HISTO, high-speed T2-corrected multiecho sequence; FF, fat fraction; RA, rheumatoid arthritis

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)
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