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1. Inhibition of bone erosion, determined by high-resolution peripheral quantitative computed tomography (HR-pQCT), in rheumatoid arthritis patients receiving a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab vs csDMARD therapy alone: an open-label, randomized, parallel-group study

Author

Naoki Iwamoto, Ko Chiba, Shuntaro Sato, Kazuteru Shiraishi, Kounosuke Watanabe, Nozomi Oki, Akitomo Okada, Tomohiro Koga, Shin-ya Kawashiri, Mami Tamai, Naoki Hosogaya, Masako Furuyama, Makiko Kobayashi, Kengo Saito, Naoki Okubo, Masataka Uetani, Makoto Osaki, and Atsushi Kawakami

Subjects
Bone erosion, csDMARDs, Denosumab, HR-pQCT, Rheumatoid arthritis, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background This exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods In this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety. Results In total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2–3 metacarpal heads at 6 months was − 0.57 mm (− 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs − 0.22 mm (− 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: − 0.35 mm [− 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2–3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%). Conclusions Although the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. Japan Registry for Clinical Trials, jRCTs071180018

Published
2022
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2. Analysis of bone erosions in rheumatoid arthritis using HR-pQCT: Development of a measurement algorithm and assessment of longitudinal changes

Author

Kazuteru Shiraishi, Ko Chiba, Kounosuke Watanabe, Nozomi Oki, Naoki Iwamoto, Shoken Amano, Akihiko Yonekura, Masato Tomita, Masataka Uetani, Atsushi Kawakami, and Makoto Osaki

Subjects
Medicine, Science
Abstract

Purpose The purpose of this study was to establish an algorithm for measuring bone erosions at metacarpophalangeal (MCP) joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), to investigate the precision of measurements, and to assess longitudinal changes in bone erosions among patients with rheumatoid arthritis (RA). Methods The 2nd and 3rd MCP joints were scanned at a voxel size of 60.7 μm using second-generation HR-pQCT. Bone erosions on MCP joints were identified using a semi-automated algorithm we developed, and each erosion parameter was measured. Measurement reproducibility was evaluated in 19 healthy subjects using intraclass correlation coefficients (ICCs) and root mean square percent coefficient of variance (RMS%CV). Finally, longitudinal changes in bone erosions over a period of 12 months were assessed in 26 patients with RA based on the calculated least significant change (LSC). Results Reproducibilities for measurement parameters regarding bone erosions with our algorithm were good (all ICCs ≥ 0.98; all RMS%CVs < 5%). No erosion parameters showed significant changes after 12 months of treatment in terms of median values in all erosions, while both progression and repair of erosions were observed individually (e.g., erosion volume: progression, 26% (+0.62 mm3); repair, 34% (-0.85 mm3); no change, 40%). Conclusions The measurement algorithm developed for bone erosions at MCP joints showed good reproducibility. Both progression and repair of bone erosions were observed in patients with RA even after 12 months of appropriate treatment. Our algorithm may be useful to investigate the etiology of RA and assess drug efficacy.

Published
2022

3. Dose-escalated Salvage Whole-pelvic Radiotherapy for Biochemical Recurrence After Radical Prostatectomy for High-risk Prostate Cancer.

Author

SHUHEI MIYAZAKI, YUTARO TASAKI, MIKA NAKATAKE, KOICHI HONDA, DAISUKE NAKAMURA, AKIKO EGAWA, NOZOMI OKI, KENSUKE MITSUNARI, YUICHIRO NAKAMURA, RYOICHI IMAMURA, and RYO TOYA

Subjects
RADICAL prostatectomy, PROSTATE cancer, INTENSITY modulated radiotherapy, RADIOTHERAPY, OVERALL survival
Abstract

Background/Aim: To investigate the institutional experience of dose-escalated salvage whole-pelvic radiotherapy (WPRT) with the simultaneous integrated boost (SIB) technique in patients with biochemical recurrence (BCR) after radical prostatectomy for high-risk prostate cancer. Patients and Methods: This retrospective study included 21 patients with BCR who received radical prostatectomy for high-risk prostate cancer and underwent salvage RT. Clinical target volume (CTV) of the whole pelvis (CTV56) included the prostate bed, common iliac, external iliac, internal iliac, and obturator lymph node regions. The boost CTV (CTV66) included the prostate bed. Planning target volumes (PTV) were generated by adding a margin of 6-8 mm to CTV (PTV56 and PTV66). Doses of 56.1 and 66 Gy in 33 fractions were delivered to PTV56 and PTV66, respectively. Results: The 5-year biochemical progressionfree survival, overall survival, and cause-specific survival rates were 72%, 94%, and 94%, respectively. A grade 3 late genitourinary toxicity event of gross hematuria was observed in one patient (4%). Acute and late toxicities of grade ≥3, other than gross hematuria, were not observed in any patient. Conclusion: Dose-escalated salvage WPRT using the SIB technique provides appropriate tumor control without increasing the incident of significant toxicities. [ABSTRACT FROM AUTHOR]

Published
2024
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5. FDG-PET vs. chemical shift MR imaging in differentiating intertrabecular metastasis from hematopoietic bone marrow hyperplasia

Author

Daisuke Niino, Nozomi Oki, Reiko Ideguchi, Masataka Uetani, Hirofumi Koike, and Yohei Ikebe

Subjects
medicine.medical_treatment, Intertrabecular metastasis, Standardized uptake value, Metastasis, Bone Marrow, Fluorodeoxyglucose F18, medicine, Humans, Cutoff, Radiology, Nuclear Medicine and imaging, FDG-PET CT, Retrospective Studies, Hyperplasia, business.industry, medicine.disease, Magnetic Resonance Imaging, Radiation therapy, Haematopoiesis, medicine.anatomical_structure, Hematopoietic bone marrow hyperplasia, Positron-Emission Tomography, Original Article, Bone marrow, Radiopharmaceuticals, Chemical shift imaging, business, Nuclear medicine, Bone marrow hyperplasia, MRI
Abstract

Purpose To evaluate the utility of SUVmax on FDG-PET and chemical shift imaging (CSI) on MRI in the differentiation of intertrabecular metastasis (ITM) from hematopoietic bone marrow hyperplasia (HBMH). Patients and methods We retrospectively evaluated 54 indeterminate focal bone marrow lesions in 44 patients detected on FDG-PET. The lesions were assigned to the metastasis group (M group, 29 lesions of 24 patients) and the non-metastasis group (non-M group, 25 lesions of 20 patients) based on the follow-up or the histopathological studies. The lesions were assessed with the maximum standardized uptake value (SUVmax) on FDG-PET CT images and signal change ratio (SCR) on CSI. Results The median SUVmax were 5.62 and 2.91; the median SCR were − 0.08 and − 34.8 in M and non-M groups respectively, with significant difference (p max was 4.48 with a sensitivity of 72.4%, a specificity of 100%, and AUC of 0.905. The cutoff value of SCR was − 6.15 with a sensitivity of 82.8%, a specificity of 80%, and AUC of 0.818. Conclusion FDG-PET and CSI on MRI are useful in distinguishing ITM from HBMH. Though their sensitivities are similar, the specificity of FDG-PET was higher than that of MRI.

Published
2021

6. Computed diffusion-weighted imaging for differentiating synovial proliferation from joint effusion in hand arthritis

Author

Koichi Murakami, Yuki Tanaka, Hiroyuki Sugimori, Motoshi Fujimori, Tamotsu Kamishima, Nozomi Oki, and Takatoshi Aoki

Subjects
Adult, Male, Computed diffusion-weighted imaging, Contrast enhancement, Hand Joints, media_common.quotation_subject, Immunology, Sensitivity and Specificity, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Synovial proliferation, Rheumatology, Region of interest, Image Interpretation, Computer-Assisted, Humans, Immunology and Allergy, Effective diffusion coefficient, Contrast (vision), Medicine, 030212 general & internal medicine, Aged, media_common, 030203 arthritis & rheumatology, Synovitis, business.industry, Arthritis, Synovial Membrane, Area under the curve, Middle Aged, Joint effusion, Magnetic Resonance Imaging, Diffusion Magnetic Resonance Imaging, Hand arthritis, Female, medicine.symptom, Nuclear medicine, business, MRI, Diffusion MRI
Abstract

The objective of this study is to investigate computed DWI (cDWI) as an alternative method to contrast-enhanced MRI in comparison with directory measured DWI (mDWI) and apparent diffusion coefficient (ADC) for differentiating synovial proliferation from joint effusion. Nine patients suspected with RA (5 women) were included in this study. A radiologist identified region of interest (ROI) based on STIR, and evaluated using a 5-point grading scale of 0 (fluid) to 4 (synovial proliferation) according to the degree of contrast enhancement within the ROI. cDWI was synthesized for b values from 1000 to 2000 at 200 s/mm(2) intervals using the combination of b values at mDWI. In addition to ADC values, contrast ratios were calculated using signal intensity for each ROI on the mDWI and cDWI. Visual assessment by a radiologist was conducted between pairs of STIR image and mDWI or cDWI. ROI grades were most significantly correlated with cDWI(2000) based on b values of 400-1000 s/mm(2) (r(s) = 0.405, p < 0.01). The area under the curve of cDWI(2000) based on b values of 400-1000 s/mm(2) (0.762) was larger than that of ADC values (0.570-0.608) when comparing low versus high contrast enhancement grades. Both cDWI(1800) (200-1000) and cDWI(2000) (400-1000) demonstrated high sensitivity and specificity in visual assessment (84.6% and 66.7%, respectively). The cDWI(2000) based on b values of 400-1000 s/mm(2) may be useful for noninvasive differentiation of synovial proliferation from joint effusion in hand arthritis.

Published
2019

7. Quantification of Joint Space Width Difference on Radiography Via Phase-Only Correlation (POC) Analysis: a Phantom Study Comparing with Various Tomographical Modalities Using Conventional Margin-Contouring

Author

Wanxuan Fang, Kenichi Tamura, Toshikazu Ueda, Nobutoshi Yasojima, Tianyu Zeng, Masataka Uetani, Yafei Ou, Koichi Murakami, Shun Shishido, Ko Chiba, Nozomi Oki, Keitaro Sato, Kenneth Sutherland, Kazuyuki Minowa, Masayuki Ikebe, Tamotsu Kamishima, and Aimi Taguchi

Subjects
Computer science, Radiography, Imaging phantom, Article, 030218 nuclear medicine & medical imaging, Metacarpophalangeal Joint, 03 medical and health sciences, 0302 clinical medicine, Margin (machine learning), Finger Joint, medicine, Humans, Radiology, Nuclear Medicine and imaging, Joint (geology), Contouring, Radiological and Ultrasound Technology, business.industry, Phantoms, Imaging, Metacarpophalangeal joint, Tomosynthesis, Computer Science Applications, medicine.anatomical_structure, Finger joint, Female, business, Nuclear medicine, Tomography, X-Ray Computed, 030217 neurology & neurosurgery
Abstract

Several visual scoring methods are currently used to assess progression of rheumatoid arthritis (RA) on radiography. However, they are limited by its subjectivity and insufficient sensitivity. We have developed an original measurement system which uses a technique called phase-only correlation (POC). The purpose of this study is to validate the system by using a phantom simulating the joint of RA patients. A micrometer measurement apparatus that can adjust arbitrary joint space width (JSW) in a phantom joint was developed to define true JSW. The phantom was scanned with radiography, 320 multi detector CT (MDCT), high-resolution peripheral quantitative CT (HR-pQCT), cone beam CT (CBCT), and tomosynthesis. The width was adjusted to the average size of a women’s metacarpophalangeal joint, from 1.2 to 2.2 mm with increments of 0.1 mm and 0.01 mm. Radiographical images were analyzed by the POC-based system and manual method, and images from various tomographical modalities were measured via the automatic margin detection method. Correlation coefficients between true JSW difference and measured JSW difference were all strong at 0.1 mm intervals with radiography (POC-based system and manual method), CBCT, 320MDCT, HR-pQCT, and tomosynthesis. At 0.01 mm intervals, radiography (POC-based system), 320MDCT, and HR-pQCT had strong correlations, while radiography (manual method) and CBCT had low correlations, and tomosynthesis had no statistically significant correlation. The smallest detectable changes for radiography (POC-based system), radiography (manual method), 320MDCT, HR-pQCT, CBCT, and tomosynthesis were 0.020 mm, 0.041 mm, 0.076 mm, 0.077 mm, 0.057 mm, and 0.087 mm, respectively. We conclude that radiography analyzed with the POC-based system might sensitively detect minute joint space changes of the finger joint.

Published
2020

8. Intravoxel incoherent motion MRI for discrimination of synovial proliferation in the hand arthritis: A prospective proof-of-concept study

Author

Takatoshi Aoki, Koichi Murakami, Hiroyuki Sugimori, Motoshi Fujimori, Yutong Lu, Tamotsu Kamishima, Kenneth Sutherland, and Nozomi Oki

Subjects
Adult, Male, Hand Joints, Severity of Illness Index, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Region of interest, Image Interpretation, Computer-Assisted, Medicine, Effective diffusion coefficient, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Stage (cooking), Intravoxel incoherent motion, Rank correlation, Aged, Cell Proliferation, Receiver operating characteristic, business.industry, Arthritis, Synovial Membrane, Reproducibility of Results, Joint effusion, Middle Aged, Magnetic Resonance Imaging, Female, medicine.symptom, business, Nuclear medicine, Perfusion
Abstract

BACKGROUND Postcontrast-enhanced MRI is currently the reference standard for synovial proliferation in rheumatoid arthritis (RA). However, the technique is somewhat invasive due to the use of gadolinium contrast agents, which may cause severe adverse/side effects. Intravoxel incoherent motion (IVIM) simultaneously permits quantification of perfusion as well as diffusion using a single imaging scan. PURPOSE/HYPOTHESIS To test the capability of IVIM MRI for noninvasive discrimination of synovial proliferation in hand arthritis. STUDY TYPE Prospective. SUBJECTS Seven suspected RA patients (three women and four men; mean age, 61 years; range, 26-74 years). FIELD STRENGTH/SEQUENCE 3 T/short tau inversion recovery (STIR), IVIM, postcontrast-enhanced MRI. ASSESSMENT Region of interest (ROI) was identified based on STIR. Contrast-enhanced MRI was evaluated using a 5-point grading scale of 0 (water) to 4 (synovial proliferation) according to the degree of contrast enhancement within the ROI. For each ROI, we calculated the apparent diffusion coefficient (ADC) and IVIM parameters (molecular diffusion coefficient [D], perfusion fraction [f], and perfusion-related diffusion coefficient [D*]). These parameters were subsequently compared with ROI contrast enhancement grades. STATISTICAL TESTS Spearman's rank correlation test and a receiver operating characteristic (ROC) curve. RESULTS A total of 90 ROIs of suspected synovial proliferation and/or joint effusion were identified. ROI grades were correlated with ADC and D values (r S = -0.385, P < 0.001, r S = -0.458, P < 0.0001, respectively), but not with the f and D* values (r S = -0.010, P = 0.936, r S = -0.084, P = 0.505, respectively). The area under the curves (AUCs) of D values (0.708-0.888, P = 0.002-0.0002) were slightly larger than those of ADC values (0.692-0.791, P = 0.013-0.001) when comparing low- vs. high-contrast enhancement grades. DATA CONCLUSION The IVIM parameter D and ADC may be useful for the noninvasive identification of synovial proliferation in hand arthritis. LEVEL OF EVIDENCE 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1199-1206.

Published
2018

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