Test-retest Error Research Articles

The Test-Retest Reliability of Pain Outcome Measures in People With Phantom Limb Pain.

To quantify the test-retest reliability of 3 patient-reported outcome measures of pain for people living with phantom limb pain (PLP) and assess the impact of test-retest errors on future research and clinical decisions. Thirty-nine participants (30 males), mean (SD) age: 55 (16), mean (SD) years postamputation: 6.8 (8.3), reported their PLP levels on a visual analogue scale (VAS) for pain intensity, the revised short-form McGill Pain Questionnaire (SF-MPQ-2), and a pain diary, on 2 occasions 7 to 14 days apart. Mean systematic change, within-subjects SD, limits of agreement (LOA), coefficient of variation, and the intraclass correlation coefficient (ICC) were quantified alongside their respective 95% confidence intervals (95% CIs). Systematic learning effects (mean changes) were not clinically relevant across the VAS, SF-MPQ-2, and pain diary. Within-subject SDs (95% CI) were 11.8 (9.6-15.3), 0.9 (0.7-1.2), and 8.6 (6.9-11.5), respectively. LOA (95% CI) were 32.6 (26.5-42.4), 2.5 (2-3.3), and 23.9 (19.2-31.8), respectively. ICCs (95% CI) were 0.8 (0.6-0.9), 0.8 (0.7-0.9), and 0.9 (0.8-0.9), respectively, but may have been inflated by sample heterogeneity. The test-retest errors allowed detection of clinically relevant effect sizes with feasible sample sizes in future studies, but individual errors were large. For people with PLP, a pain intensity VAS, the SF-MPQ-2, and a pain diary show an acceptable level of intersession reliability for use in future clinical trials with feasible sample sizes. Nevertheless, the random error observed for all 3 of the pain outcome measures suggests they should be interpreted with caution in case studies and when monitoring individuals' clinical status and progress.

Non-rigid-registration-based positioning and labelling of triaxial OPMs on a flexible cap for wearable magnetoencephalography

BackgroundRecent advances in highly sensitive miniaturized optically pumped magnetometers (OPMs) have enabled the development of wearable magnetoencephalography (MEG) offering great flexibility in experimental setting. The OPM array for wearable MEG is typically attached to a flexible cap and exhibits a variable spatial layout across different subjects, which imposes challenges concerning the efficient positioning and labelling of OPMs. New methodA pair of reflective markers are affixed to each triaxial OPM sensor above its cable to determine its location and sensitive axes. A non-rigid registration of optically digitized marker locations with a pre-labelled template of marker locations is performed to map newly digitized markers to OPMs. ResultsThe positioning and labelling of 66 OPM sensors could be completed within 35 s. Across ten experiments, all OPMs were accurately labelled, and the mean test-retest errors were 0.48 mm for sensor locations and 0.20 degree for sensitive axes. By combining six OPMs’ positions with their respective recordings, magnetic dipoles inside a phantom were located with a mean error of 5.5 mm, and the best fitted dipole for MEG with auditory stimuli presented was located on a subject’s primary auditory cortex. Comparison with existing methodsThe proposed method reduces the reliance on error-prone and laborious manual operations inherent in existing methods, therefore significantly improving the efficiency of OPM positioning and labelling on a flexible cap. ConclusionWe developed a method for the precise and rapid positioning and labelling triaxial OPMs on a flexible cap, thereby facilitating the practical implementation of wearable OPM-MEG.

Validity and Reliability of Thoracic-Mounted Inertial Measurement Units to Derive Gait Characteristics During Running.

Horsley, BJ, Tofari, PJ, Halson, SL, Kemp, JG, Chalkley, D, Cole, MH, Johnston, RD, and Cormack, SJ. Validity and reliability of thoracic-mounted inertial measurement units to derive gait characteristics during running. J Strength Cond Res 38(2): 274-282, 2024-Inertial measurement units (IMUs) attached to the tibia or lumbar spine can be used to analyze running gait but, with team-sports, are often contained in global navigation satellite system (GNSS) units worn on the thoracic spine. We assessed the validity and reliability of thoracic-mounted IMUs to derive gait characteristics, including peak vertical ground reaction force (vGRF peak ) and vertical stiffness (K vert ). Sixteen recreationally active subjects performed 40 m run throughs at 3-4, 5-6, and 7-8 m·s -1 . Inertial measurement units were attached to the tibia, lumbar, and thoracic spine, whereas 2 GNSS units were also worn on the thoracic spine. Initial contact (IC) from a validated algorithm was evaluated with F1 score and agreement (mean difference ± SD ) of gait data with the tibia and lumbar spine using nonparametric limits of agreement (LoA). Test-retest error {coefficient of variation, CV (95% confidence interval [CI])} established reliability. Thoracic IMUs detected a nearly perfect proportion (F1 ≥ 0.95) of IC events compared with tibia and lumbar sites. Step length had the strongest agreement (0 ± 0.04 m) at 3-4 m·s -1 , whereas contact time improved from 3 to 4 (-0.028 ± 0.018 second) to 7-8 m·s -1 (-0.004 ± 0.013 second). All values for K vert fell within the LoA at 7-8 m·s -1 . Test-retest error was ≤12.8% for all gait characteristics obtained from GNSS units, where K vert was most reliable at 3-4 m·s -1 (6.8% [5.2, 9.6]) and vGRF peak at 7-8 m·s -1 (3.7% [2.5, 5.2]). The thoracic-spine site is suitable to derive gait characteristics, including K vert , from IMUs within GNSS units, eliminating the need for additional sensors to analyze running gait.

Validity and reliability of an opto-electric training system in elite and national level ISSF air rifle shooters

The validity of a commonly used optoelectronic training system was examined by identifying the variables that predicted shot score, investigating their ability to discriminate standard, and assessing the predictive variables’ test–retest error. A repeated-measures approach assessed test–retest error, a cross-sectional approach compared standards of shooters and an observational approach examined predictors of shot score. 21 elite and 8 national-standard athletes participated. Multiple linear regression, independent t tests, typical error and coefficient of variation assessed predictors of shot score, discrimination between standards and test–retest error respectively. Stability of aiming predicted 84.2% of the variance in shot score. Six Scatt Expert variables, 10a0, 10a5, 10.0, 10.5, Speed in the last 250 mm, and stability of aiming, discriminated standard (P < 0.05). Test–retest error ranged from a coefficient of variance of 0.72% for 10a0 to 30.69% for Accuracy of Aiming. Stability of aiming had a typical error of 0.55 mm and a coefficient of variance of 13.93%. Results suggest that this optoelectronic training system possesses construct validity if stability of aiming is used as the outcome measure.

The 2-Point Method: A Quick, Accurate, and Repeatable Approach to Estimate Ultrasound-Derived Quadriceps Femoris Cross-Sectional Area.

To analyze the feasibility of the 2-point method for estimating ultrasound-derived quadriceps femoris cross-sectional area (QUADACSA). First, (1)the agreement between QUADACSA measured by panoramic ultrasound and magnetic resonance imaging (MRI) was studied, and thereafter, we examined 2 approaches of the 2-point method in terms of (2)estimation errors and (3)test-retest repeatability. Both thighs of 16 young men were analyzed. Ultrasound-QUADACSA versus MRI-QUADACSA comparison was conducted at 6 thigh lengths (20%-70% of the thigh length). Thereafter, ultrasound-QUADACSA corresponding to 30% and 60% (2-point30%-60%) or 20% and 70% (2-point20%-70%) were used to estimate QUADACSA of the remaining regions. Estimated QUADACSA resulting from both 2-point approaches was compared with the measured one. Finally, the test-retest repeatability was examined by comparing the errors generated on 2 separate estimations. Statistics included the standard error of measurement (SEM) expressed in absolute (in square centimeters) and relative terms (in percentage) as a coefficient of variation (CV), as well as the intraclass correlation cofficient (ICC) and bias. An excellent agreement (ICC ≥ 0.980) and reduced errors (SEM ≤ 2.43cm2) resulted from the ultrasound-QUADACSA versus MRI-QUADACSA comparison. Although estimation errors found were reduced (CV ≤ 7.50%), they proved to be lower and less biased for the 2-point30%-60%, especially at the central regions (SEM ≤ 2.01cm2; bias ≤ 0.89cm2). Similarly, repeatability analysis revealed lower test-retest errors for the 2-point30%-60% (CV ≤ 1.9%) than for the 2-point20%-70% (CV ≤ 4.6%). The 2-point method, especially that implemented using the 30% and 60% regions, represents an accurate and repeatable strategy to evaluate QUADACSA.

Electromyographic Activity of Sternocleidomastoid Muscle in Individuals With Neck Pain and Healthy Volunteers: A Reliability and Between-Group Differences Examination

ObjectivesThe purpose of this study was to evaluate the electromyographic activity of the sternocleidomastoid muscle during the performance of the craniocervical flexion test (CCFT) in individuals with neck pain and healthy volunteers, assess the reliability of this method, and examine possible between-population differences. MethodsElectromyographic activity of the sternocleidomastoid muscles of 22 individuals with neck pain and 22 healthy participants was recorded during the 55 stages of the CCFT. Pain (visual analog scale) and disability (Neck Disability Index) levels and pain duration were recorded for the participants with neck pain. Reliability of electromyography was evaluated with the intraclass correlation coefficient, standard error of measurement, and minimum detectable change. ResultsWithin-day reliability indices of electromyographic activity were very good to excellent (intraclass correlation coefficients, 0.86-0.98; standard error of measurement, 1.8%-7.6%; minimum detectable change, 5.0%-21.1%). For the head-lift normalization method, 2-way analysis of variance revealed significant between-group differences (P < .02); however, these were not clinically significant when reliability test-retest error was considered. Differences between contraction levels were significant (P < .001); however, the group by contraction level interaction factor was nonsignificant. Therefore, the between-groups electromyographic increases noted with increasing contraction levels were similar. No correlation was identified between participants’ electromyography data and pain or disability. ConclusionIn participants with moderate pain, disability, and pain duration, no clear alterations in electromyographic activity of the sternocleidomastoid could be detected with the CCFT. Reliability of the test used was very good.

Absolute and relative reliability of SCRuM test battery components assembled for schoolboy rugby players playing competitive rugby in low-resource settings: A pragmatic in-season test-retest approach.

Schoolboy rugby is a popular sport which forms the bedrock of rugby development in many African countries, including Zimbabwe. With burgeoning talent identification programmes, the development of multi-dimensional, logically-validated, and reliable test batteries is essential to inform the objective selection of potentially talented young rugby athletes. This study sought evidence on the absolute and relative test-retest reliability of the component test items in the newly-assembled SCRuM test battery. Utilising a pragmatic test-retest experimental design, a sample of 41 Under-19 schoolboy players playing competitive rugby in the elite Super Eight Schools Rugby League in Harare, Zimbabwe, participated in the study. Physiological and game-specific skills tests which showed good to excellent relative reliability and acceptable absolute reliability, included: 20 m and 40 m speed, L-run, Vertical Jump (VJ), 60 s Push-Up, 2 kg Medicine Ball Chest Throw test (2 kg MBCT), Wall Sit Leg Strength test (WSLS), Repeated High Intensity Exercise test (RHIE), One Repetition Maximum Back Squat (1-RM BS) and Bench Press tests (1-RM BP), Yo-Yo Intermittent Recovery Level 1 test (Yo-Yo IRT L1), Tackling Proficiency test, Passing Ability Skill test and Running and Catching Ability skill test. All these tests are reliable and warrant inclusion in the SCRuM test battery for possible profiling of U19 schoolboy rugby players during the 'in-season' phase provided there is adequate participant familiarisation and test standardisation. The test-retest ICCs and measurement errors are generalisable to other young athletes in this population, making the tests useful for the evaluation of training and developmental effects of the measured constructs.

Paraspinal strength and electromyographic fatigue in patients with sub-acute back pain and controls: Reliability, clinical applicability and between-group differences.

BACKGROUNDParaspinal muscle strength and fatigue are considered important in low back pain (LBP) prevention and rehabilitation. High reliability of paraspinal strength and electromyographic (EMG)-fatigue parameters has not been universally reported. Moreover, the discriminative validity of these parameters requires further exploration, under the threat of potentially poor reliability of the methods examined.AIMTo investigate the reliability and discriminative validity of paraspinal strength and EMG-related fatigue in subjects with recurrent LBP and healthy participants.METHODSTest-retest measurements were performed in 26 healthy and 66 LBP volunteers, for reliability. Paraspinal isometric maximal and mean strength were determined with a maximum voluntary isometric contraction (MVIC) protocol, performed in a custom-made device. For the fatigue test, participants performed a 60% MIVC level continuous isometric contraction of the paraspinals, in conjunction with EMG analysis from 4 muscle sites of the lumbar spine. Initial median frequency (IMF), the median frequency slope (MFslope), as well as the root mean square (RMS) slope EMG parameters were used as fatigue measures. Data were analysed with repeated measures ANOVA for test-retest differences. For reliability, the intraclass correlation coefficient (ICC3,1), standard error of the measurement (SEM) and the smallest detectable difference (SDD) were reported. Group-related differences for fatigue measures were analysed with a Multivariate Analysis of Covariance, with age, weight and strength as covariates.RESULTSIsometric strength presented statistically significant between-day differences (P < 0.01), however these did not exceed 10% (healthy: 7.2%/LBP-patients: 9.7%) and ICC reliability values were excellent, yet test-retest error was increased for the patient group (healthy: ICC3,1: 0.92-0.96, SEM: 5.72-5.94 Hz, SDD: 18.51%-18.57%/LBP-patients: ICC3,1: 0.91-0.96, SEM: 6.49-6.96, SDD: 30.75%-31.61%). For the frequency data, IMF reliability was excellent (healthy: ICC3,1: 0.91-0.94, SEM: 3.45-7.27 Hz, SDD: 9.56%-20.14%/patients: ICC3,1: 0.90-0.94, SEM: 6.41-7.59 Hz, SDD: 17.75%-21.02%) and of MF raw and normalised slopes was good (healthy: ICC3,1: 0.78-0.82, SEM: 4.93-6.02 Hz, SDD: 13.66-16.67%/LBP-patients: ICC3,1: 0.83-0.85, SEM: 6.75-7.47 Hz, SDD: 18.69%-20.69%). However, the reliability for RMS data presented unacceptably high SDD values and were not considered further. For discriminative validity, less MVIC and less steep MFslopes were registered for the patient group (P < 0.01).CONCLUSIONReliability and discriminative ability of paraspinal strength and EMG-related frequency parameters were demonstrated in healthy participants and patients with LBP.

Test-retest reliability and smallest detectable change (SDC) of MRI-based cartilage thickness analysis in a large multicenter randomized controlled clinical trial of knee osteoarthritis

Test-retest reliability and smallest detectable change (SDC) of MRI-based cartilage thickness analysis in a large multicenter randomized controlled clinical trial of knee osteoarthritis

Assessment methods of vastus lateralis muscle architecture using panoramic ultrasound: a new approach, test-retest reliability and measurement error

Abstract Extended-field-of-view ultrasonography is a valid alternative to determine the dimensions of the skeletal striated muscle; however, some factors may influence the final measurement. The aim of this study was to determine the test-retest reliability and measurement error of vastus lateralis muscle architecture variables through internal anatomical landmarks and to compare three fixed determined points using extended-field-of-view ultrasonography. Twelve young (24 ± 6 years) adult university male students participated in the study. Images were obtained through extended-field-of-view ultrasonography of the vastus lateralis muscle. Measurements were made for muscle thickness (MT), fascicle length (FL), and fascicle pennation angle (FA) using a method that identifies internal anatomical landmarks. MT was also measured at predetermined distances of 2 cm proximal, 6 cm proximal, and 2 cm distal. One-way ANOVA with repeated measures did not identify any test-retest significant differences for all variables measured. Typical measurement error in centimeters (cm) or degrees (º), coefficient of variation in percentage (%) and intraclass correlation coefficient were MT = 0.07 cm, 2.93%, 0.964; FL = 0.31 cm, 2.89%, 0.947; FA = 0.92°, 4.08%, 0.942; MT 2 cm proximal = 0.10 cm, 3.77%, 0.910; MT 6 cm proximal = 0.27 cm, 9.66%, 0.576; MT 2 cm distal = 0.35 cm, 19.76%, 0.564. MT, FL and FA showed high reliability and low measurement error. Internal anatomical landmarks proved to be more reliable and presented smaller measurement errors when compared to the predetermined distances method.

Heart Rate Variability and Direct Current Measurement Characteristics in Professional Mixed Martial Arts Athletes.

This study’s purpose was to examine heart rate variability (HRV) and direct current potential (DC) measures’ sensitivity and correlations between changes in the acute recovery and stress scale (ARSS) and the previous day’s training load. Training load, HRV, DC and ARSS data were collected from fourteen professional mixed martial arts athletes (32.6 ± 5.3 years, 174.8 ± 8.8 cm, 79.2 ± 17.5 kg) the following morning after hard, easy and rest days. Sensitivity was expressed as a signal-to-noise ratio (SNR, inter-day typical error (TE) or coefficient of variation (%CV) divided by intra-day TE or %CV). Correlations between HRV, DC and ARSS with training load were also examined. The SNRs for the various HRV and DC measures were acceptable to good (1.02–2.85). There was a 23.1% CV average increase between measures taken between different locations versus the same location. Training load changes were not correlated with HRV/DC but were correlated with ARSS stress variables. Practitioners should be aware of HRV/DC variability; however the daily training signal was greater than the test-retest error in this investigation. Upon awakening, HRV/DC measures appear superior for standardization and planning. HRV and DC measures were less sensitive to the previous day’s training load than ARSS measures.

Accuracy and repeatability of automated femorotibial cartilage segmentation using convolutional neural networks - data from the osteoarthritis initiative healthy reference cohort

Purpose: Convolutional neural networks (CNNs), such as the U-net, have been reported to show excellent performance for automated segmentation of medical images. When applied to articular cartilage from knee MRI scans, automated cartilage segmentations using CNNs displayed moderate to good agreement with manual segmentation, with Dice similarity coefficients (DSC) from approximately 0.70 to 0.90 in past work. The objective of the current study was to evaluate the performance of a 2D U-net architecture for different MRI orientations and contrasts, and to compare the long-term test-retest error of cartilage thickness measurements between automated and manual segmentations.

Effects of signal averaging, gradient encoding scheme, and spatial resolution on diffusion kurtosis imaging: An empirical study using 7T MRI.

Although diffusion gradient directions and b-values have been optimized for diffusion kurtosis imaging (DKI), little is known about the effect of signal averaging on DKI reliability. To evaluate how signal averaging influences the reliability of DKI indices using two gradient encoding schemes with three spatial resolutions. Prospective. Fifteen naïve Sprague-Dawley rats. DKI was performed at 7T using two schemes (30 directions with three b-values [30d-3b] and six directions with 15 b-values [6d-15b]), three resolutions, and eight repetitions. DKI reliability was assessed using voxelwise relative error (σ) and test-retest error of fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) within gray matter (GM) and white matter (WM). The number of excitations (NEX) was optimized by considering DKI reliability. The influence of the partial volume effect (PVE) was also assessed. One-way analysis of variance. The 30d-3b scheme, compared with the 6d-15b scheme, exhibited apparently smaller σFA and σMK (eg, at NEX 1, in GM, for three resolutions, σFA : 19.9-38.2% vs. 34.2-61.4%, σMK : 6.9-11.4% vs. 14.1-15.4%) and similar σMD (all differences between two schemes <1.6%). The optimal NEX was determined as 2 for enabling a reliable measurement of DKI-derived indices. The PVE at the lowest resolution apparently increased σFA for both schemes (19.9% for 30d-3b and 34.2% for 6d-15b) and σMK for the 6d-15b scheme (14.7%) in GM, and exerted lower effects on MK values for the 30d-3b scheme (P > 0.05). A higher number of diffusion directions would benefit FA and MK estimation. A higher spatial resolution helps to reduce PVE. By using the 30d-3b scheme, MK is considered a robust index to reflect microstructural changes in GM and WM. We propose a systematic approach to determine the optimal DKI protocols for appropriate preclinical settings. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1593-1603.

Layer-Specific Segmental Longitudinal Strain Measurements: Capability of Detecting Myocardial Scar and Differences in Feasibility, Accuracy, and Reproducibility, Among Four Vendors A Report From the EACVI-ASE Strain Standardization Task Force

Segmental longitudinal strain (SLS) is reported to be vendor specific. Despite standardization efforts, vendors still use different myocardial layers for strain measurements. It is unclear, however, which layer is the most favorable for clinical purposes. Therefore, in this study we evaluated the reproducibility, accuracy, and scar detection ability of SLS measurements from different myocardial layers. In data sets of 58 patients with prior myocardial infarction and five healthy volunteers, we measured the intervendor bias, the relative test-retest variability, and scar discrimination ability of endocardial and midwall SLS, using software packages from four different companies (GE, Siemens, Toshiba, and TomTec). Cardiac magnetic resonance delayed enhancement images were used as the reference standard of scar definition. Variability of SLS measurements was significant among the vendors for both midwall and endocardium. In addition, relative errors of SLS measurements varied considerably among vendors (P<.001 for both layers). Comparisons of test-retest errors from different layers for individual vendors did not show any significant differences. Regardless of the vendor, both endocardial and midwall strain values were decreased in scarred segments. Endocardial to midwall ratio of strain measurements showed no difference between scar-free and scarred segments. Endocardial and midwall strain parameters showed no significant difference in scar detection capability. Layer-specific SLS measurements vary significantly among vendors. Endocardial and midwall SLS measurements have a high yet comparable test-retest variability. Combining layer-specific SLS measurements does not provide additional information for detection of regional functional abnormalities. Our results donot provide evidence to favor the use of one myocardial layer over another.

Diffusion tensor imaging of articular cartilage using a navigated radial imaging spin-echo diffusion (RAISED) sequence

To validate a radial imaging spin-echo diffusion tensor (RAISED) sequence for high-resolution diffusion tensor imaging (DTI) of articular cartilage at 3T. The RAISED sequence implementation is described, including the used non-linear motion correction algorithm. The robustness to eddy currents was tested on phantoms, and accuracy of measurement was assessed with measurements of temperature-dependent diffusion of free water. Motion correction was validated by comparing RAISED with single-shot diffusion-weighted echo-planar imaging (EPI) measures. DTI was acquired in asymptomatic subjects (n = 6) and subjects with doubtful (Kellgren-Lawrence [KL] grade 1, n = 9) and mild (KL = 2, n = 9) symptomatic knee osteoarthritis (OA). MD and FA values without correction, and after all corrections, were calculated. A test-retest evaluation of the DTI acquisition on three asymptomatic and three OA subjects was also performed. The root mean squared coefficient of variationof the global test-restest reproducibility was 3.54% for MD and 5.34% for FA. MD was significantly increased in both femoral condyles (7-9%) of KL 1 and in the medial (11-17%) and lateral (10-12%) compartments of KL 2 subjects. Averaged FA presented a trend of lower values with increasing KL grade, which was significant for the medial femoral condyle (-11%) of KL 1 and all three compartments in KL 2 subjects (-18 to -11%). Group differences in MD and FA were only significant after motion correction. The RAISED sequence with the proposed reconstruction framework provides reproducible assessment of DTI parameters in vivo at 3T and potentially the early stages of the disease in large regions of interest. • DTI of articular cartilage is feasible at 3T with a multi-shot RAISED sequence with non-linear motion correction. • RAISED sequence allows estimation of the diffusion indices MD and FA with test-retest errors below 4% (MD) and 6% (FA). • RAISED-based measurement of DTI of articular cartilage with non-linear motion correction holds potential to differentiate healthy from OA subjects.

Assessing Biological and Methodological Aspects of Brain Volume Loss in Multiple Sclerosis

Before using brain volume loss (BVL) as a marker of therapeutic response in multiple sclerosis (MS), certain biological and methodological issues must be clarified. To assess the dynamics of BVL as MS progresses and to evaluate the repeatability and exchangeability of BVL estimates with Jacobian Integration (JI) and Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) (specifically, the Structural Image Evaluation, Using Normalisation, of Atrophy-Cross-Sectional [SIENA-X] tool or FMRIB's Integrated Registration and Segmentation Tool [FIRST]). A cohort of patients who had either clinically isolated syndrome or MS was enrolled from February 2011 through October 2015. All underwent a series of annual magnetic resonance imaging (MRI) scans. Images from 2 cohorts of healthy volunteers were used to evaluate short-term repeatability of the MRI measurements (n = 34) and annual BVL (n = 20). Data analysis occurred from January to May 2017. The goodness of fit of different models to the dynamics of BVL throughout the MS disease course was assessed. The short-term test-retest error was used as a measure of JI and FSL repeatability. The correlations (R2) of the changes quantified in the brain using JI and FSL, together with the accuracy of the annual BVL cutoffs to discriminate patients with MS from healthy volunteers, were used to measure compatibility of imaging methods. A total of 140 patients with clinically isolated syndrome or MS were enrolled, including 95 women (67.9%); the group had a median (interquartile range) age of 40.7 (33.6-48.1) years. Patients underwent 4 MRI scans with a median (interquartile range) interscan period of 364 (351-379) days. The 34 healthy volunteers (of whom 18 [53%] were women; median [IQR] age, 33.5 [26.2-42.5] years) and 20 healthy volunteers (of whom 10 [50%] were women; median [IQR] age, 33.0 [28.7-39.2] years) underwent 2 MRI scans within a median (IQR) of 24.5 (0.0-74.5) days and 384.5 (366.3-407.8) days for the short-term and long-term MRI follow-up, respectively. The BVL rates were higher in the first 5 years after MS onset (R2 = 0.65 for whole-brain volume change and R2 = 0.52 for gray matter volume change) with a direct association with steroids (β = 0.280; P = .02) and an inverse association with age at MS onset, particularly in the first 5 years (β = 0.015; P = .047). The reproducibility of FSL (SIENA) and JI was similar for whole-brain volume loss, while JI gave more precise, less biased estimates for specific brain regions than FSL (SIENA-X and FIRST). The correlation between whole-brain volume loss using JI and FSL was high (R2 = 0.92), but the same correlations were poor for specific brain regions. The area under curve of the whole-brain volume change to discriminate between patients with MS and healthy volunteers was similar, although the thresholds and accuracy index were distinct for JI and FSL. The proposed BVL threshold of less than 0.4% per year as a marker of therapeutic efficiency should be reconsidered because of the different dynamics of BVL as MS progresses and because of the limited reproducibility and variability of estimates using different imaging methods.

Repeatability and discrimination validity of cartilage imaging biomarkers for experimental medicine studies of knee osteoarthritis

PURPOSE The utility of magnetic resonance imaging (MRI) quantitative imaging biomarkers (QIBs) of cartilage in experimental medicine studies of potential disease modifying osteoarthritis treatments (DMOATs) is uncertain due to the small sample sizes and short follow-up involved. To be relevant to such studies, candidate QIBs must demonstrate acceptable repeatability, discriminative ability and responsiveness. The purpose of this study was to evaluate test-retest repeatability and discriminative ability of 4 cartilage QIBs at the knee (thickness, T1rho, T2 and delayed gadolinium enhanced MRI of cartilage [dGEMRIC]) to assess their utility in experimental medicine studies. METHODS We imaged 9 participants with mild-moderate knee osteoarthritis (OA), characterised by radiographs with medial tibiofemoral predominant disease and Kellgren-Lawrence grades 2-3, and 4 healthy volunteers (HVs) matched for age, sex and body mass index. Participants were imaged at baseline and 1 month. MR studies were performed on a 3T system (MR 750, GE Healthcare) and were split into 2 sessions. The first MR session included a 3-dimensional spoiled gradient echo (3D SPGR) sequence and T1rho and T2 mapping sequences. At the end of this session, we administered an intravenous gadolinium based contrast agent (Dotarem, Guerbet LLC) at double dose (0.2 mmol/kg). Participants then performed 10 minutes of exercise on a stationary cycle to facilitate contrast penetration into the joint for dGEMRIC. The second MR session began 90 minutes following injection of contrast agent and consisted of T1 mapping using a variable flip angle technique. MR pulse sequence details are provided in table 1. We performed surface based analysis of cartilage parameters using Stradwin software (http://mi.eng.cam.ac.uk/~rwp/stradwin). In brief, this consists of semi-automated thickness measurement on 3D SPGR images, with generation of accurate inner and outer cartilage surfaces. Following rigid registration of the compositional (T1rho, T2, dGEMRIC) data to the 3D SPGR images, the same surfaces were used to sample the compositional data. This analysis pipeline allows each parameter to be measured at ~5,000 surface vertices per participant. We assessed overall (pooled OA and HV data) test-retest repeatability by calculating the root-mean-square coefficient of variation (RMS-CV) and the smallest detectable change (SDC) for each parameter. We assessed overall discriminative validity by estimating effect sizes for the difference in the mean value of each parameter in OA participants and HVs. We also mapped the test-retest errors and mean difference in each parameter between groups onto a representative surface for each cartilage region. RESULTS Participant characteristics are provided in table 2. RMS-CVs, SDCs and effect size estimates are provided in table 3. Overall test-retest RMS-CV values ranged from 2.5% (T1rho) to 10.3% (dGEMRIC). The largest overall effect size was demonstrated for dGEMRIC (-1.3, 90% confidence interval [CI] -2.3 to -0.2), followed by thickness (-0.67, 90% CI -1.5 to 0.3), T1rho and T2 (both 0.61, 90% CI -0.4 to 1.5). Mapping of test-retest errors and between-group differences to a representative surface revealed substantial spatial heterogeneity in these metrics for all parameters (figure 1). This suggests that surface based approaches may offer improved sensitivity over traditional region of interest based measurements. CONCLUSION This study demonstrates that cartilage QIBs may be useful in experimental medicine studies of knee osteoarthritis. Statistical approaches reflecting the spatial heterogeneity of changes in cartilage should be used to provide an indication of where significant results are located, not just whether an average value is significantly different. Future work will evaluate responsiveness of these cartilage QIBs.

Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations.

PurposeTo implement a statistical framework for assessing the precision of several quantitative MRI metrics sensitive to myelin in the human spinal cord: T1, Magnetization Transfer Ratio (MTR), saturation imposed by an off-resonance pulse (MTsat) and Macromolecular Tissue Volume (MTV).MethodsThirty-three healthy subjects within two age groups (young, elderly) were scanned at 3T. Among them, 16 underwent the protocol twice to assess repeatability. Statistical reliability indexes such as the Minimal Detectable Change (MDC) were compared across metrics quantified within different cervical levels and white matter (WM) sub-regions. The differences between pathways and age groups were quantified and interpreted in context of the test-retest repeatability of the measurements.ResultsThe MDC was respectively 105.7ms, 2.77%, 0.37% and 4.08% for T1, MTR, MTsat and MTV when quantified over all WM, while the standard-deviation across subjects was 70.5ms, 1.34%, 0.20% and 2.44%. Even though particular WM regions did exhibit significant differences, these differences were on the same order as test-retest errors. No significant difference was found between age groups for all metrics.ConclusionWhile T1-based metrics (T1 and MTV) exhibited better reliability than MT-based measurements (MTR and MTsat), the observed differences between subjects or WM regions were comparable to (and often smaller than) the MDC. This makes it difficult to determine if observed changes are due to variations in myelin content, or simply due to measurement error. Measurement error remains a challenge in spinal cord myelin imaging, but this study provides statistical guidelines to standardize the field and make it possible to conduct large-scale multi-center studies.

Comparison of Feasibility, Accuracy, and Reproducibility of Layer-Specific Global Longitudinal Strain Measurements Among Five Different Vendors: A Report from the EACVI-ASE Strain Standardization Task Force

Despite standardization efforts, vendors still use information from different myocardial layers to calculate global longitudinal strain (GLS). Little is known about potential advantages or disadvantages of using these different layers in clinical practice. The authors therefore investigated the reproducibility and accuracy of GLS measurements from different myocardial layers. Sixty-three subjects were prospectively enrolled, in whom the intervendor bias and test-retest variability of endocardial GLS (E-GLS) and midwall GLS (M-GLS) were calculated, using software packages from five vendors that allow layer-specific GLS calculation (GE, Hitachi, Siemens, Toshiba, and TomTec). The impact of tracking quality and the interdependence of strain values from different layers were assessed by comparing test-retest errors between layers. For both E-GLS and M-GLS, significant bias was found among vendors. Relative test-retest variability of E-GLS values differed significantly among vendors, whereas M-GLS showed no significant difference (range, 5.4%-9.5% [P=.032] and 7.0%-11.2% [P=.200], respectively). Within-vendor test-retest variability was similar between E-GLS and M-GLS for all but one vendor. Absolute test-retest errors were highly correlated between E-GLS and M-GLS for all vendors. E-GLS and M-GLS measurements showed no relevant differences in robustness among vendors, although intervendor bias was higher for M-GLS compared with E-GLS. These data provide no technical argument in favor of a certain myocardial layer for global left ventricular functional assessment. Currently, the choice of which layer to use should therefore be based on the available clinical evidence in the literature.

Reliable measurements of brain atrophy in individual patients with multiple sclerosis.

IntroductionAs neurodegeneration is recognized as a major contributor to disability in multiple sclerosis (MS), brain atrophy quantification could have a high added value in clinical practice to assess treatment efficacy and disease progression, provided that it has a sufficiently low measurement error to draw meaningful conclusions for an individual patient.MethodIn this paper, we present an automated longitudinal method based on Jacobian integration for measuring whole‐brain and gray matter atrophy based on anatomical magnetic resonance images (MRI), named MSmetrix. MSmetrix is specifically designed to measure atrophy in patients with MS, by including iterative lesion segmentation and lesion filling based on FLAIR and T1‐weighted MRI scans.Results MS metrix is compared with SIENA with respect to test–retest error and consistency, resulting in an average test–retest error on an MS data set of 0.13% (MS metrix) and 0.17% (SIENA) and a consistency error of 0.07% (MS metrix) and 0.05% (SIENA). On a healthy subject data set including physiological variability the test–retest is 0.19% (MS metrix) and 0.31% (SIENA).ConclusionTherefore, we can conclude that MSmetrix could be of added value in clinical practice for the follow‐up of treatment and disease progression in MS patients.