Three-dimensional ultrasound to investigate synovitis in first carpometacarpal osteoarthritis: A feasibility study.

BACKGROUND: Synovitis is one of the defining characteristics of osteoarthritis (OA) in the carpometacarpal (CMC1) joint of the thumb. Quantitative characterization of synovial volume is important for furthering our understanding of CMC1 OA disease progression, treatment response, and monitoring strategies. In previous studies, three-dimensional ultrasound (3-D US) has demonstrated the feasibility of being a point-of-care system for monitoring knee OA. However, 3-D US has not been tested on the smaller joints of the hand, which presents unique physiological and imaging challenges. PURPOSE: To develop and validate a novel application of 3-D US to monitor soft-tissue characteristics of OA in a CMC1 OA patient population compared to the current gold standard, magnetic resonance imaging (MRI). METHODS: A motorized submerged transducer moving assembly was designed for this device specifically for imaging the joints of the hands and wrist. The device used a linear 3-D scanning approach, where a 14L5 2-D transducer was translated over the region of interest. Two imaging phantoms were used to test the linear and volumetric measurement accuracy of the 3-D US device. To evaluate the accuracy of the reconstructed 3-D US geometry, a multilayer monofilament string-grid phantom (10 mm square grid) was scanned. To validate the volumetric measurement capabilities of the system, a simulated synovial tissue phantom with an embedded synovial effusion was fabricated and imaged. Ten CMC1 OA patients were imaged by our 3-D US and a 3.0 T MRI system to compare synovial volumes. The synovial volumes were manually segmented by two raters on the 2D slices of the 3D US reconstruction and MR images, to assess the accuracy and precision of the device for determining synovial tissue volumes. The Standard Error of Measurement and Minimal Detectable Change was used to assess the precision and sensitivity of the volume measurements. Paired sample t-tests were used to assess statistical significance. Additionally, rater reliability was assessed using Intra-Class Correlation (ICC) coefficients. RESULTS: The largest percent difference observed between the known physical volume of synovial extrusion in the phantom and the volume measured by our 3D US was 1.1% (p-value = 0.03). The mean volume difference between the 3-D US and the gold standard MRI was 1.78% (p-value = 0.48). The 3-D US synovial tissue volume measurements had a Standard Error Measurement (SEm ) of 11.21 mm3 and a Minimal Detectible Change (MDC) of 31.06 mm3 , while the MRI synovial tissue volume measurements had an SEM of 16.82 mm3 and an MDC of 46.63 mm3 . Excellent inter- and intra-rater reliability (ICCs = 0.94-0.99) observed across all imaging modalities and raters. CONCLUSION: Our results indicate the feasibility of applying 3-D US technology to provide accurate and precise CMC1 synovial tissue volume measurements, similar to MRI volume measurements. Lower MDC and SEm values for 3-D US volume measurements indicate that it is a precise measurement tool to assess synovial volume and that it is sensitive to variation between volume segmentations. The application of this imaging technique to monitor OA pathogenesis and treatment response over time at the patient's bedside should be thoroughly investigated in future studies.

Cross-sectional reliability and concurrent validity of a quantitative 2-dimensional ultrasound image analysis of effusion and synovial hypertrophy in knee osteoarthritis.

Objective: Effusion-synovitis is related to pain and progression in knee osteoarthritis (OA), but current gold standard ultrasound (US) measures are limited to semi-quantitative grading of joint distension or 1-dimensional thickness measures. A novel quantitative 2-dimensional image analysis methodology is applied to US images of effusion-synovitis; reliability and concurrent validity was assessed in patients with knee OA. Methods: Cross sectional analysis of US images collected from 51 patients with symptomatic knee OA were processed in ImageJ and segmented in 3DSlicer to produce a binary mask of the supra-patellar synovitis region of interest (ROI). Area measures (mm2) of total synovitis, effusion and hypertrophy components were exported. Intra-rater reliability and test-retest reliability (1-14 days washout) were estimated with intra-class correlation coefficients (ICCs). Concurrent validity was measured by Spearman correlations between quantitative measures and gold standard OMERACT and caliper measurements of synovitis. Results: Intra-rater reliability for hypertrophy area was estimated at 0.98, 0.99 for effusion area, and 0.99 for total synovitis area. The test-retest reliability for total synovitis area was 0.63 (SEM 87.8 â€‹mm2), 0.59 for hypertrophy area (SEM 21.0 â€‹mm2), and 0.64 for effusion area (SEM 73.8 â€‹mm2). Correlation between total synovitis area and OMERACT grade was 0.84, 0.81 between total synovitis area and effusion-synovitis calipers, and 0.81 between total effusion area and effusion calipers. Conclusion: This new research tool for image analysis demonstrated excellent intra-rater reliability, good concurrent validity, and moderate test-retest reliability. Quantitative 2D US measures of effusion-synovitis and its individual components may enhance the study and management of knee OA.

Test-Retest Reliability and Sensitivity to Change of Ultrasound-Based Methods of Measuring Synovial Inflammation in Knee Osteoarthritis.

OBJECTIVES: To assess test-retest reliability of musculoskeletal ultrasound (US) measures of inflammation in patients with knee osteoarthritis (OA) and to assess the sensitivity to change of US measures of inflammation in patients with knee OA. METHODS: To mimic a common clinical scenario, 36 patients (n = 70 knees) with symptomatic knee OA who were in stable condition underwent 2 assessments within 14 days by different operators and different US machines, graded by a single rater. Test-retest reliability was measured using Cohen's kappa coefficient, intraclass correlation coefficient (ICC), and absolute agreement parameters. A total of 51 patients (n = 72 knees) were tested immediately before and 21-28 days after intraarticular glucocorticoid injection to investigate sensitivity to change and longitudinal construct validity. Paired t-tests and standardized response mean (SRM) were used to assess sensitivity to change. Multivariate linear regression was used to investigate longitudinal construct validity of US with Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scores, while adjusting for covariates. RESULTS: US measures of inflammation demonstrated moderate (κ = 0.41, 0.60) to substantial (κ = 0.61, 0.80) agreement. Quantitative measures of synovitis and effusion demonstrated good test-retest reliability (ICC2,1 0.71, 0.92). US measures of synovitis and effusion demonstrated low-to-moderate sensitivity to change (SRM -0.29, -0.50). The associations between changes in US measures and KOOS pain scores over time were low, and 95% confidence intervals included zero. CONCLUSION: In a clinical setting, US measures of inflammatory features of knee OA have substantial reliability and low-to-moderate sensitivity to change, whereas measures of structural OA features are less reliable. Longitudinal construct validity of US measures of synovitis and effusion to KOOS pain scores is not strongly supported.

Automatic femoral articular cartilage segmentation using deep learning in three-dimensional ultrasound images of the knee.

Objective: This study aimed to develop a deep learning-based approach to automatically segment the femoral articular cartilage (FAC) in 3D ultrasound (US) images of the knee to increase time efficiency and decrease rater variability. Design: Our method involved deep learning predictions on 2DUS slices sampled in the transverse plane to view the cartilage of the femoral trochlea, followed by reconstruction into a 3D surface. A 2D U-Net was modified and trained using a dataset of 200 2DUS images resliced from 20 3DUS images. Segmentation accuracy was evaluated using a holdout dataset of 50 2DUS images resliced from 5 3DUS images. Absolute and signed error metrics were computed and FAC segmentation performance was compared between rater 1 and 2 manual segmentations. Results: Our U-Net-based algorithm performed with mean 3D DSC, recall, precision, VPD, MSD, and HD of 73.1 â€‹± â€‹3.9%, 74.8 â€‹± â€‹6.1%, 72.0 â€‹± â€‹6.3%, 10.4 â€‹± â€‹6.0%, 0.3 â€‹± â€‹0.1 â€‹mm, and 1.6 â€‹± â€‹0.7 â€‹mm, respectively. Compared to the individual 2D predictions, our algorithm demonstrated a decrease in performance after 3D reconstruction, but these differences were not found to be statistically significant. The percent difference between the manually segmented volumes of the 2 raters was 3.4%, and rater 2 demonstrated the largest VPD with 14.2 â€‹± â€‹11.4 â€‹mm3 compared to 10.4 â€‹± â€‹6.0 â€‹mm3 for rater 1. Conclusion: This study investigated the use of a modified U-Net algorithm to automatically segment the FAC in 3DUS knee images of healthy volunteers, demonstrating that this segmentation method would increase the efficiency of anterior femoral cartilage volume estimation and expedite the post-acquisition processing for 3D US images of the knee.

Management of Frailty: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To analyze and determine the comparative effectiveness of interventions targeting frailty prevention or treatment on frailty as a primary outcome and quality of life, cognition, depression, and adverse events as secondary outcomes. DESIGN: Systematic review and network meta-analysis (NMA). METHODS: Data sources-Relevant randomized controlled trials (RCTs) were identified by a systematic search of several electronic databases including MEDLINE, EMBASE, CINAHL, and AMED. Duplicate title and abstract and full-text screening, data extraction, and risk of bias assessment were performed. Data extraction-All RCTs examining frailty interventions aimed to decrease frailty were included. Comparators were standard care, placebo, or another intervention. Data synthesis-We performed both standard pairwise meta-analysis and Bayesian NMA. Dichotomous outcome data were pooled using the odds ratio effect size, whereas continuous outcome data were pooled using the standardized mean difference (SMD) effect size. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome. The quality of evidence was evaluated using the GRADE approach. RESULTS: A total of 66 RCTs were included after screening of 7090 citations and 749 full-text articles. NMA of frailty outcome (including 21 RCTs, 5262 participants, and 8 interventions) suggested that the physical activity intervention, when compared to placebo and standard care, was associated with reductions in frailty (SMD -0.92, 95% confidence interval -1.55, -0.29). According to SUCRA, physical activity intervention and physical activity plus nutritional supplementation were probably the most effective intervention (100% and 71% likelihood, respectively) to reduce frailty. Physical activity was probably the most effective or the second most effective interventions for all included outcomes. CONCLUSION AND IMPLICATIONS: Physical activity is one of the most effective frailty interventions. The quality of evidence of the current review is low and very low. More robust RCTs are needed to increase the confidence of our NMA results and the quality of evidence.

Review of Literature on Low-level Laser Therapy Benefits for Nonpharmacological Pain Control in Chronic Pain and Osteoarthritis.

Introduction: Low-level laser therapy (LLLT) is a form of light therapy that triggers biochemical changes within cells. Photons are absorbed by cellular photoreceptors, triggering chemical alterations and potential biochemical benefits to the human body. LLLT has been used in pain management for years and is also known as cold laser therapy, which uses low-frequency continuous laser of typically 600 to 1000 nm wavelength for pain reduction and healing stimulation. Many studies have demonstrated analgesic and anti-inflammatory effects provided by photobiomodulation in both experimental and clinical trials. Objective: The purpose of this research article was to present a summary of the possible pain management benefits of LLLT. Results: In cold laser therapy, coherent light of wavelength 600 to 1000 nm is applied to an area of concern with hope for photo-stimulating the tissues in a way that promotes and accelerates healing. This is evidenced by the similarity in absorption spectra between oxidized cytochrome c oxidase and action spectra from biological responses to light. LLLT, using the properties of coherent light, has been seen to produce pain relief and fibroblastic regeneration in clinical trials and laboratory experiments. LLLT has also been seen to significantly reduce pain in the acute setting; it is proposed that LLLT is able to reduce pain by lowering the level of biochemical markers and oxidative stress, and the formation of edema and hemorrhage. Many studies have demonstrated analgesic and anti-inflammatory effects provided by photobiomodulation in both experimental and clinical trials. Conclusion: Based on current research, the utilization of LLLT for pain management and osteoarthritic conditions may be a complementary strategy used in clinical practice to provide symptom management for patients suffering from osteoarthritis and chronic pain.

Prolotherapy and Low Level Laser Therapy: A Synergistic Approach to Pain Management in Chronic Osteoarthritis.

Regenerative injection therapy and low level laser therapy are alternative remedies known for their success in the treatment and symptomatic management of chronic musculoskeletal conditions. In response to the growing demand for alternative therapies in the face of the opioid epidemic, the authors conduct a literature review to investigate the potential for prolotherapy and LLLT to be used adjunctively to manage chronic osteoarthritis (OA). OA is a degenerative chronic musculoskeletal condition on the rise in North America, and is frequently treated with opioid medications. The regenerative action of prolotherapy and pain-modulating effects of LLLT may make these two therapies well-suited to synergistically provide improved outcomes for osteoarthritis patients without the side effects associated with opioid use. A narrative descriptive review through multiple medical databases (Google Scholar, PubMed, and MedLine) is conducted, restricted by the use of medical subject headings. 71 articles were selected for reading in full, and 40 articles were selected for use in the study after reading in full. A review of the literature revealed good clinical results in the use of prolotherapy and LLLT separately to manage chronic musculoskeletal pain due to osteoarthritis and other chronic conditions. It is also recognized in the literature that prolotherapy works most effectively when used adjunctively with other treatments. Downsides to the use of prolotherapy include mild side effects of pain, stiffness and bruising and potential adverse events as a result of injection. This study is limited by the lack of clinical trials available involving both LLLT and prolotherapy injections used adjunctively, and by the low number of high impact literature concerning the treatment of (specifically) osteoarthritis by alternative methods. The authors suggest that practicing health care providers consider utilizing LLLT and prolotherapy together as a supplementary method in the management of chronic pain due to osteoarthritis, to minimize the long-term prescription of opioids and emphasize a less invasive treatment for this debilitating condition.