Arthroscopic partial meniscectomy versus physical therapy for traumatic meniscal tears in a young study population: a randomised controlled trial.

OBJECTIVE: To compare outcomes from arthroscopic partial meniscectomy versus physical therapy in young patients with traumatic meniscal tears. METHODS: We conducted a multicentre, open-labelled, randomised controlled trial in patients aged 18-45 years, with a recent onset, traumatic, MRI-verified, isolated meniscal tear without knee osteoarthritis. Patients were randomised to arthroscopic partial meniscectomy or standardised physical therapy with an optional delayed arthroscopic partial meniscectomy after 3-month follow-up. The primary outcome was the International Knee Documentation Committee (IKDC) score (best 100, worst 0) at 24 months, which measures patients' perception of symptoms, knee function and ability to participate in sports activities. RESULTS: Between 2014 and 2018, 100 patients were included (mean age 35.1 (SD 8.1), 76% male, 34 competitive or elite athletes). Forty-nine were randomised to arthroscopic partial meniscectomy and 51 to physical therapy. In the physical therapy group, 21 patients (41%) received delayed arthroscopic partial meniscectomy during the follow-up period. In both groups, improvement in IKDC scores was clinically relevant during follow-up compared with baseline scores. At 24 months mean (95% CI) IKDC scores were 78 (71 to 84) out of 100 points in the arthroscopic partial meniscectomy group and 78 (71 to 84) in the physical therapy group with a between group difference of 0.1 (95% CI -7.6 to 7.7) points out of 100. CONCLUSIONS: In this trial involving young patients with isolated traumatic meniscal tears, early arthroscopic partial meniscectomy was not superior to a strategy of physical therapy with optional delayed arthroscopic partial meniscectomy at 24-month follow-up. TRIAL REGISTRATION: https://www.trialregister.nl/trials.

3D MRI in Osteoarthritis.

Osteoarthritis (OA) is among the top 10 burdensome diseases, with the knee the most affected joint. Magnetic resonance imaging (MRI) allows whole-knee assessment, making it ideally suited for imaging OA, considered a multitissue disease. Three-dimensional (3D) MRI enables the comprehensive assessment of OA, including quantitative morphometry of various joint tissues. Manual tissue segmentation on 3D MRI is challenging but may be overcome by advanced automated image analysis methods including artificial intelligence (AI). This review presents examples of the utility of 3D MRI for knee OA, focusing on the articular cartilage, bone, meniscus, synovium, and infrapatellar fat pad, and it highlights several applications of AI that facilitate segmentation, lesion detection, and disease classification.

Time-saving opportunities in knee osteoarthritis: T2 mapping and structural imaging of the knee using a single 5-min MRI scan.

OBJECTIVES: To assess the discriminative power of a 5-min quantitative double-echo steady-state (qDESS) sequence for simultaneous T2 measurements of cartilage and meniscus, and structural knee osteoarthritis (OA) assessment, in a clinical OA population, using radiographic knee OA as reference standard. METHODS: Fifty-three subjects were included and divided over three groups based on radiographic and clinical knee OA: 20 subjects with no OA (Kellgren-Lawrence grade (KLG) 0), 18 with mild OA (KLG2), and 15 with moderate OA (KLG3). All patients underwent a 5-min qDESS scan. We measured T2 relaxation times in four cartilage and four meniscus regions of interest (ROIs) and performed structural OA evaluation with the MRI Osteoarthritis Knee Score (MOAKS) using qDESS with multiplanar reformatting. Between-group differences in T2 values and MOAKS were calculated using ANOVA. Correlations of the reference standard (i.e., radiographic knee OA) with T2 and MOAKS were assessed with correlation analyses for ordinal variables. RESULTS: In cartilage, mean T2 values were 36.1 ± SD 4.3, 40.6 ± 5.9, and 47.1 ± 4.3 ms for no, mild, and moderate OA, respectively (p < 0.001). In menisci, mean T2 values were 15 ± 3.6, 17.5 ± 3.8, and 20.6 ± 4.7 ms for no, mild, and moderate OA, respectively (p < 0.001). Statistically significant correlations were found between radiographic OA and T2 and between radiographic OA and MOAKS in all ROIs (p < 0.05). CONCLUSION: Quantitative T2 and structural assessment of cartilage and meniscus, using a single 5-min qDESS scan, can distinguish between different grades of radiographic OA, demonstrating the potential of qDESS as an efficient tool for OA imaging. KEY POINTS: • Quantitative T2values of cartilage and meniscus as well as structural assessment of the knee with a single 5-min quantitative double-echo steady-state (qDESS) scan can distinguish between different grades of knee osteoarthritis (OA). • Quantitative and structural qDESS-based measurements correlate significantly with the reference standard, radiographic degree of OA, for all cartilage and meniscus regions. • By providing quantitative measurements and diagnostic image quality in one rapid MRI scan, qDESS has great potential for application in large-scale clinical trials in knee OA.

T2 mapping of the meniscus is a biomarker for early osteoarthritis.

PURPOSE: To evaluate in vivo T2 mapping as quantitative, imaging-based biomarker for meniscal degeneration in humans, by studying the correlation between T2 relaxation time and degree of histological degeneration as reference standard. METHODS: In this prospective validation study, 13 menisci from seven patients with radiographic knee osteoarthritis (median age 67 years, three males) were included. Menisci were obtained during total knee replacement surgery. All patients underwent pre-operative magnetic resonance imaging using a 3-T MR scanner which included a T2 mapping pulse sequence with multiple echoes. Histological analysis of the collected menisci was performed using the Pauli score, involving surface integrity, cellularity, matrix organization, and staining intensity. Mean T2 relaxation times were calculated in meniscal regions of interest corresponding with the areas scored histologically, using a multi-slice multi-echo postprocessing algorithm. Correlation between T2 mapping and histology was assessed using a generalized least squares model fit by maximum likelihood. RESULTS: The mean T2 relaxation time was 22.4 ± 2.7 ms (range 18.5-27). The median histological score was 10, IQR 7-11 (range 4-13). A strong correlation between T2 relaxation time and histological score was found (rs = 0.84, CI 95% 0.64-0.93). CONCLUSION: In vivo T2 mapping of the human meniscus correlates strongly with histological degeneration, suggesting that T2 mapping enables the detection and quantification of early compositional changes of the meniscus in knee OA. KEY POINTS: • Prospective histology-based study showed that in vivo T 2 mapping of the human meniscus correlates strongly with histological degeneration. • Meniscal T 2 mapping allows detection and quantifying of compositional changes, without need for contrast or special MRI hardware. • Meniscal T 2 mapping provides a biomarker for early OA, potentially allowing early treatment strategies and prevention of OA progression.

Five-minute knee MRI for simultaneous morphometry and T2 relaxometry of cartilage and meniscus and for semiquantitative radiological assessment using double-echo in steady-state at 3T.

BACKGROUND: Biomarkers for assessing osteoarthritis activity necessitate multiple MRI sequences with long acquisition times. PURPOSE: To perform 5-minute simultaneous morphometry (thickness/volume measurements) and T2 relaxometry of both cartilage and meniscus, and semiquantitative MRI Osteoarthritis Knee Scoring (MOAKS). STUDY TYPE: Prospective. SUBJECTS: Fifteen healthy volunteers for morphometry and T2 measurements, and 15 patients (five each Kellgren-Lawrence grades 0/2/3) for MOAKS assessment. FIELD STRENGTH/SEQUENCE: A 5-minute double-echo steady-state (DESS) sequence was evaluated for generating quantitative and semiquantitative osteoarthritis biomarkers at 3T. ASSESSMENT: Flip angle simulations evaluated tissue signals and sensitivity of T2 measurements. Morphometry and T2 reproducibility was compared against morphometry-optimized and relaxometry-optimized sequences. Repeatability was assessed by scanning five volunteers twice. MOAKS reproducibility was compared to MOAKS derived from a clinical knee MRI protocol by two readers. STATISTICAL TESTS: Coefficients of variation (CVs), concordance confidence intervals (CCI), and Wilcoxon signed-rank tests compared morphometry and relaxometry measurements with their reference standards. DESS MOAKS positive percent agreement (PPA), negative percentage agreement (NPA), and interreader agreement was calculated using the clinical protocol as a reference. Biomarker variations between Kellgren-Lawrence groups were evaluated using Wilcoxon rank-sum tests. RESULTS: Cartilage thickness (P = 0.65), cartilage T2 (P = 0.69), and meniscus T2 (P = 0.06) did not significantly differ from their reference standard (with a 20° DESS flip angle). DESS slightly overestimated meniscus volume (P < 0.001). Accuracy and repeatability CVs were <3.3%, except the meniscus T2 accuracy (7.6%). DESS MOAKS had substantial interreader agreement and high PPA/NPA values of 87%/90%. Bone marrow lesions and menisci had slightly lower PPAs. Cartilage and meniscus T2 , and MOAKS (cartilage surface area, osteophytes, cysts, and total score) was higher in Kellgren-Lawrence groups 2 and 3 than group 0 (P < 0.05). DATA CONCLUSION: The 5-minute DESS sequence permits MOAKS assessment for a majority of tissues, along with repeatable and reproducible simultaneous cartilage and meniscus T2 relaxometry and morphometry measurements. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1328-1341.

Can we predict the clinical outcome of arthroscopic partial meniscectomy? A systematic review.

NHS-PROSPERO REGISTRATION NUMBER: 42016048592 OBJECTIVE: In order to make a more evidence-based selection of patients who would benefit the most from arthroscopic partial meniscectomy (APM), knowledge of prognostic factors is essential. We conducted a systematic review of predictors for the clinical outcome following APM. DESIGN: Systematic review DATA SOURCES: Medline, Embase, Cochrane Central Register, Web of Science, SPORTDiscus, PubMed Publisher, Google Scholar INCLUSION CRITERIA: Report an association between factor(s) and clinical outcome; validated questionnaire; follow-up >1 year. EXCLUSION CRITERIA: <20 subjects; anterior cruciate ligament-deficient patients; discoid menisci; meniscus repair, transplantation or implants; total or open meniscectomy. METHODS: One reviewer extracted the data, two reviewers assessed the risk of bias and performed a best-evidence synthesis. RESULTS: Finally, 32 studies met the inclusion criteria. Moderate evidence was found, that the presence of radiological knee osteoarthritis at baseline and longer duration of symptoms (>1 year) are associated with worse clinical outcome following APM. In addition, resecting >50% of meniscal tissue and leaving a non-intact meniscal rim after meniscectomy are intra-articular predictive factors for worse clinical outcome. Moderate evidence was found that sex, onset of symptoms (acute or chronic), tear type or preoperative sport level are not predictors for clinical outcome. Conflicting evidence was found for the prognostic value of age, perioperative chondral damage, body mass index and leg alignment. SUMMARY/CONCLUSION: Long duration of symptoms (>1 year), radiological knee osteoarthritis and resecting >50% of meniscus are associated with a worse clinical outcome following APM. These prognostic factors should be considered in clinical decision making for patients with meniscal tears.

Cost-effectiveness of arthroscopic partial meniscectomy versus physical therapy for traumatic meniscal tears in patients aged under 45 years.

Aims: The aim of this study was to evaluate the cost-effectiveness of arthroscopic partial meniscectomy versus physical therapy plus optional delayed arthroscopic partial meniscectomy in young patients aged under 45 years with traumatic meniscal tears. Methods: We conducted a multicentre, open-labelled, randomized controlled trial in patients aged 18 to 45 years, with a recent onset, traumatic, MRI-verified, isolated meniscal tear without knee osteoarthritis. Patients were randomized to arthroscopic partial meniscectomy or standardized physical therapy with an optional delayed arthroscopic partial meniscectomy after three months of follow-up. We performed a cost-utility analysis on the randomization groups to compare both treatments over a 24-month follow-up period. Cost utility was calculated as incremental costs per quality-adjusted life year (QALY) gained of arthroscopic partial meniscectomy compared to physical therapy. Calculations were performed from a healthcare system perspective and a societal perspective. Results: A total of 100 patients were included: 49 were randomized to arthroscopic partial meniscectomy and 51 to physical therapy. In the physical therapy group, 21 patients (41%) received delayed arthroscopic partial meniscectomy during follow-up. Over 24 months, patients in the arthroscopic partial meniscectomy group had a mean 0.005 QALYs lower quality of life (95% confidence interval -0.13 to 0.14). The cost-utility ratio was €-160,000/QALY from the healthcare perspective and €-223,372/QALY from the societal perspective, indicating that arthroscopic partial meniscectomy incurs additional costs without any added health benefit. Conclusion: Arthroscopic partial meniscectomy is arthroscopic partial meniscectomy is unlikely to be cost-effective in treating young patients with isolated traumatic meniscal tears compared to physical therapy as a primary health intervention. Arthroscopic partial meniscectomy leads to a similar quality of life, but higher costs, compared to physical therapy plus optional delayed arthroscopic partial meniscectomy.

T2 mapping of healthy knee cartilage: multicenter multivendor reproducibility.

BACKGROUND: T2 mapping is increasingly used to quantify cartilage degeneration in knee osteoarthritis (OA), yet reproducibility studies in a multicenter setting are limited. The purpose of this study was to determine the longitudinal reproducibility and multicenter variation of cartilage T2 mapping, using various MRI equipment and acquisition protocols. METHODS: In this prospective multicenter study, four traveling, healthy human subjects underwent T2 mapping twice at five different centers with a 6-month-interval. Centers had various MRI scanners, field strengths, and T2 mapping acquisition protocols. Mean T2 values were calculated in six cartilage regions of interest (ROIs) as well as an average value per patient. A phantom was scanned once at each center. To evaluate longitudinal reproducibility, intraclass correlation coefficients (ICC), root-mean-square coefficient of variation (RMS-CV), and a Bland-Altman plot were used. To assess the variation of in vivo and phantom T2 values across centers, ANOVA was performed. RESULTS: ICCs of the T2 mapping measurements per ROI and the ROI's combined ranged from 0.73 to 0.91, indicating good to excellent longitudinal reproducibility. RMS-CVs ranged from 1.1% to 1.5% (per ROI) and 0.6% to 1.6% (ROIs combined) across the centers. A Bland-Altman plot did not reveal a systematic error. Evident, but consistent, discrepancies in T2 values were observed across centers, both in vivo and in the phantom. CONCLUSIONS: The results of this study suggest that T2 mapping can be used to longitudinal assess cartilage degeneration in multicenter studies. Given the differences in absolute cartilage T2 values across centers, absolute T2 values derived from various centers in multicenter multivendor trials should not be pooled.

Traumatic Meniscal Tears Are Associated With Meniscal Degeneration.

BACKGROUND: Meniscal tears are traditionally classified into traumatic versus degenerative tears. Although this classification plays a major role in clinical decision making, no consensus exists on the exact definition of a traumatic or degenerative tear, and the histopathological basis for this classification is unclear. PURPOSE: To assess the histological degree of meniscal degeneration in patients with a traumatic meniscal tear, as compared with intact meniscal tissue and osteoarthritic meniscal tissue. STUDY DESIGN: Descriptive laboratory study. METHODS: Traumatically torn meniscal tissue was collected during arthroscopic partial meniscectomy. As a control group, intact meniscal tissue was used from transfemoral amputations or direct postmortem dissections. Meniscal tissue from osteoarthritic knees was obtained during total knee replacement surgery. Meniscal tissue was processed, stained, and histologically analyzed with the Pauli scoring system (range, 0-18), comprising the subdomains surface integrity, cellularity, collagen organization, and matrix staining. Scoring was performed by 2 independent observers, blinded to condition, region, and patient data of the meniscus. RESULTS: The traumatic meniscal tear group contained 43 patients (34 men; median age, 29 years; median body mass index [BMI], 24 kg/m2); the intact meniscal tissue group, 8 patients (3 men; median age, 58 years; median BMI, 30 kg/m2); and the osteoarthritic group, 14 patients (4 men; median age, 66 years; median BMI, 28 kg/m2). After adjustment for sex, age, and BMI, patients with a traumatic meniscal tear had a significantly higher histological score than patients with intact meniscal tissue (2.7-point difference; P = .035). Histological score between the traumatic and osteoarthritic groups was not different. CONCLUSION: Traumatically torn menisci possess a higher degree of degeneration than intact menisci. Our results suggest that patients with a traumatic meniscal tear may already have had a certain degree of meniscal degeneration. These findings potentially challenge the classic view of traumatic versus degenerative meniscal tears. CLINICAL RELEVANCE: Our findings provide a better understanding of the tissue condition of a torn meniscus. This knowledge may help clinicians decide on choice of treatment and may lead to new perspectives to prevent knee osteoarthritis in patients with a torn meniscus.

Meniscal extrusion and degeneration during the course of osteoarthritis in the Murine collagenase-induced osteoarthritis model.

Meniscal damage is, despite its major role in knee osteoarthritis (OA), often neglected in OA animal models. We evaluated structural meniscal degeneration during the course of OA in the murine collagenase-induced OA (CIOA) model. To investigate this, OA was induced in the knee joints of 33 male C57BL/6 mice by an intra-articular injection of 10U collagenase. The mice were sacrificed after 1, 3, 7, 14, 28, and 56 days, and the knees were harvested and processed for histological analysis. As control, six knees were obtained from 16-week-old mice in which no OA was induced. Meniscal damage, meniscal extrusion, and articular cartilage damage were evaluated on thionin-stained sections. Associations between parameters of interest were evaluated with Spearman rho correlation tests. When compared to non-OA knees, meniscal extrusion was visible from day 1 onwards and meniscal degeneration had a tendency to increase over time. The meniscus damage appeared around the same time as articular cartilage damage (day 14-28) and was statistically significantly more pronounced anterior than posterior, and no differences were seen between medial and lateral menisci. Meniscus and articular cartilage damage were moderately associated in the CIOA knees (ρ = 0.57; 95%CI [0.23-0.78]). Our findings suggest that the CIOA model is a valuable model to study the role of meniscal damage during OA progression and can support the development of future preventative treatment strategies. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2416-2420, 2018.

Development and assessment of a digital X-ray software tool to determine vertebral rotation in adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: The amount of vertebral rotation in the axial plane is of key importance in the prognosis and treatment of adolescent idiopathic scoliosis (AIS). Current methods to determine vertebral rotation are either designed for use in analogue plain radiographs and not useful in digital images, or lack measurement precision and are therefore less suitable for the follow-up of rotation in AIS patients. PURPOSE: This study aimed to develop a digital X-ray software tool with high measurement precision to determine vertebral rotation in AIS, and to assess its (concurrent) validity and reliability. STUDY DESIGN/SETTING: In this study a combination of basic science and reliability methodology applied in both laboratory and clinical settings was used. METHODS: Software was developed using the algorithm of the Perdriolle torsion meter for analogue AP plain radiographs of the spine. Software was then assessed for (1) concurrent validity and (2) intra- and interobserver reliability. Plain radiographs of both human cadaver vertebrae and outpatient AIS patients were used. Concurrent validity was measured by two independent observers, both experienced in the assessment of plain radiographs. Reliability-measurements were performed by three independent spine surgeons. RESULTS: Pearson correlation of the software compared with the analogue Perdriolle torsion meter for mid-thoracic vertebrae was 0.98, for low-thoracic vertebrae 0.97 and for lumbar vertebrae 0.97. Measurement exactness of the software was within 5° in 62% of cases and within 10° in 97% of cases. Intraclass correlation coefficient (ICC) for inter-observer reliability was 0.92 (0.91-0.95), ICC for intra-observer reliability was 0.96 (0.94-0.97). CONCLUSIONS: We developed a digital X-ray software tool to determine vertebral rotation in AIS with a substantial concurrent validity and reliability, which may be useful for the follow-up of vertebral rotation in AIS patients.

Automated analysis of neuronal morphology, synapse number and synaptic recruitment.

The shape, structure and connectivity of nerve cells are important aspects of neuronal function. Genetic and epigenetic factors that alter neuronal morphology or synaptic localization of pre- and post-synaptic proteins contribute significantly to neuronal output and may underlie clinical states. To assess the impact of individual genes and disease-causing mutations on neuronal morphology, reliable methods are needed. Unfortunately, manual analysis of immuno-fluorescence images of neurons to quantify neuronal shape and synapse number, size and distribution is labor-intensive, time-consuming and subject to human bias and error. We have developed an automated image analysis routine using steerable filters and deconvolutions to automatically analyze dendrite and synapse characteristics in immuno-fluorescence images. Our approach reports dendrite morphology, synapse size and number but also synaptic vesicle density and synaptic accumulation of proteins as a function of distance from the soma as consistent as expert observers while reducing analysis time considerably. In addition, the routine can be used to detect and quantify a wide range of neuronal organelles and is capable of batch analysis of a large number of images enabling high-throughput analysis.