Test-retest Reproducibility Research Articles

Validation, kinetic modeling, and test-retest reproducibility of [18F]SynVesT-1 for PET imaging of synaptic vesicle glycoprotein 2A in mice

Alterations in synaptic vesicle glycoprotein 2 A (SV2A) have been associated with several neuropsychiatric and neurodegenerative disorders. Therefore, SV2A positron emission tomography (PET) imaging may provide a unique tool to investigate synaptic density dynamics during disease progression and after therapeutic intervention. This study aims to extensively characterize the novel radioligand [18F]SynVesT-1 for preclinical applications. In C57Bl/6J mice (n = 39), we assessed the plasma profile of [18F]SynVesT-1, validated the use of a noninvasive image-derived input function (IDIF) compared to an arterial input function (AIF), performed a blocking study with levetiracetam (50 and 200 mg/kg, i.p.) to verify the specificity towards SV2A, examined kinetic models for volume of distribution (VT) quantification, and explored test-retest reproducibility of [18F]SynVesT-1 in the central nervous system (CNS). Plasma availability of [18F]SynVesT-1 decreased rapidly (13.4 ± 1.5% at 30 min post-injection). VT based on AIF and IDIF showed excellent agreement (r2 = 0.95, p < 0.0001) and could be reliably estimated with a 60-min acquisition. The blocking study resulted in a complete blockade with no suitable reference region. Test-retest analysis indicated good reproducibility (mean absolute variability <10%). In conclusion, [18F]SynVesT-1 is selective for SV2A with optimal kinetics representing a candidate tool to quantify CNS synaptic density non-invasively.

Recruiting "clean" chronic insomnia participants: the unicorn of sleep research.

Recruiting "clean" chronic insomnia participants: the unicorn of sleep research.

Reproducibility of Respiratory Chemoreflex Characterization by Modified Rebreathing

Modified hypoxic and hyperoxic rebreathing is used to characterize central and peripheral respiratory chemoreflexes in humans. This study examined within‐ and between‐day reproducibility of the key parameters that are identified by this method: ventilatory recruitment threshold (VRT) and chemoreflex sensitivity. Seven healthy males (mean ± SD; age: 27±5 years) visited the laboratory on 4 occasions to performrepetitions of modified rebreathing tests in isoxic‐hypoxic (end‐tidal PO2 (PETO2) =50 mmHg) and ‐hyperoxic conditions (PETO2=150 mmHg). Days 1 and 2 consisted of three repeatedhyperoxic and three hypoxic trials, respectively; Days 3 and 4 included both a hyperoxic and a hypoxic trial completed in a counterbalanced order. Ventilation, end‐tidal PCO2 (PETCO2) and PETO2 were measured breath‐by‐breath by pneumotach and dual gas analyser. For each rebreathing trial, the PETCO2 at which ventilation began to rise was identified as the VRT (mmHg) and the slope of the response above VRT provided respiratory chemoreflex sensitivity (L∙min‐1∙mmHg‐1). Within‐ and between‐day reproducibility was assessed by one‐way ANOVA and intraclass correlation (ICC) analyses. The VRT was not different between trials performed on a single day for bothhyperoxic (44±2, 45±3, vs 44±3 mmHg; for Trials 1, 2, vs 3, respectively; p=0.50; ICC=0.926) and hypoxic rebreathing (40±3, 40±4, vs 40±4 mmHg; p=0.66; ICC=0.994). Chemoreflex sensitivity also was not different between trials performed on the same day in hyperoxic (4.3±2.2, 5.0±3.1, vs4.8±2.3 L∙min‐1∙mmHg‐1; p=0.33; ICC=0.955) or hypoxic conditions (5.6±2.2, 6.2±2.7, 5.7±2.0 L∙min‐1∙mmHg‐1; p=0.33; ICC=0.953). Between days, the VRT was not different for hyperoxic rebreathing (44±3 vs 44±2 vs 45±2 mmHg for Days 1, 3, vs 4, respectively; p=0.10; ICC=0.813) but was different for hypoxic rebreathing (40±3 vs 40±2 vs 41±3 mmHg for Days 2‐4, respectively; p=0.01; ICC=0.931). Chemoreflex sensitivity was not different between days for either hyperoxic (4.8±2.5,4.4±2.7, vs 4.9±2.0 L∙min‐1∙mmHg‐1; p=0.01; ICC=0.906) or hypoxic rebreathing (5.8±2.2, 5.8±2.6, vs 7.8±2.8 L∙min‐1∙mmHg‐1; p=0.01; ICC=0.750). Collectively, these data indicate that model parameters derived from hyperoxic and hypoxic modified rebreathing have good‐to‐excellent test‐retest reproducibility when repeated on the same or different days.

The Modified Back Beliefs Questionnaire as a tool to screen for incorrect beliefs regarding back pain: Cross-cultural adaptation and measurement properties

BackgroundThe Modified Back Beliefs Questionnaire (MBBQ) evaluates and screens for incorrect beliefs about low back pain (LBP). Although the MBBQ has been used to assess, its measurement properties remain unknown therefore, a rigorous cross-cultural validation is necessary. ObjectiveTo translate and cross-culturally adapt the MBBQ into Brazilian Portuguese and investigate its measurement properties. MethodsThe MBBQ was translated and cross-culturally adapted into Brazilian Portuguese. In the final stage of the cross-cultural adaptation process, the translated version was tested with 30 physical therapists to check the understanding of each item. Then, we evaluated the measurement properties in a sample of 100 physical therapists. We calculated test-retest reliability, internal consistency, standard error of the measurement (SEM) and minimal detectable change (MDC). The Pain Attitudes and Beliefs Scale for Physiotherapists (PABS.PT) was used in the construct validity analysis. ResultsThe reliability analysis showed high internal consistency, good to excellent test-retest reproducibility. Cronbach alpha coefficient for the MBBQ inevitability score was 0.80 and for the composite score 0.89. Intraclass correlation coefficient (ICC) for the Inevitability score was 0.67 (95%CI: 0.55 to 0.77) and 0.79 (95%CI: 0.70 to 0.86) for the composite score. The MBBQ inevitability and composite scores showed SEM of 1.9 and 2.4 points and minimal detectable change (MDC) of 5.1 and 6.7 points, respectively. Construct validity analyses showed moderate to excellent correlation of the MBBQ scores and the biomedical subscale of the PABS.PT. ConclusionsMBBQ showed acceptable measurement properties and may be considered a reliable and valid tool to assess physical therapists' beliefs about low back pain.

Temporal contrast adaptation in the analysis of visual function in primary open-angle glaucoma

PurposeTo explore the utility of the recovery time (RT) after temporal contrast adaptation in primary open-angle glaucoma (POAG) visual function analysis, especially in severe and end-stage glaucoma, by the Erlanger Flicker Test (EFT).MethodsThis study included 80 POAG eyes (45 subjects) and 20 normal eyes (20 subjects). POAG eyes were divided into 5 groups. The diagnostic efficacy of the EFT was assessed, and the RT of POAG eyes at different stages was compared. The EFT results were compared with glaucomatous structure and function test results. A nomogram was developed to predict disease progression by the RT and structural indicators.ResultsIn the normal eyes, as the test contrast increased, the RT gradually decreased. The EFT test–retest reproducibility was good, with intraclass correlation coefficient values of 0.6 (P < 0.05) for each test contrast. At 12%, 25%, and 35% contrast, the RT in the severe and end-stage glaucoma eyes was significantly prolonged compared with the control group (P < 0.05). The RT at different contrasts was significantly correlated with visual acuity, mean defect, mean sensitivity, and general and individual quadrant optic nerve fiber layer thickness (P ≤ 0.001). The receiver operating curve indicated that RT12% showed the best overall area under the curve (0.863). We included RT25% and average optic nerve fiber layer thickness in constructing the nomogram. POAG eyes were further divided into 8 stages. According to the probability distribution, this model showed good performance for visual function analysis in advanced glaucoma.ConclusionsCombined with traditional glaucomatous structural and functional parameters, the EFT can be used in the diagnosis and visual function analysis of POAG, especially for severe and end-stage glaucoma. It could be a potential test for disease staging in severe and end-stage glaucoma.

A Prototype of a Stereoacuity Test Using a Head-Mounted Display

Purpose: To evaluate the test-retest reliability of a contour-based stereoacuity test using a head-mounted display (HMD) and compare it with other stereotests.Methods: Thirty-two healthy adults aged 23-47 years were recruited from a tertiary hospital between August 2017 and July 2018. Two separate contour-based circles (crossed disparity: 135-1,350 arcsecs) were generated on a high-resolution phone display (Galaxy S7; Samsung, Seoul, Korea) using an HMD (Galaxy Gear VR). Two images were independently projected to each eye as graded circles with a random dot background. The results of the new HMD stereotest were compared to those of the standard Randot and TNO stereotests. The test-retest reliability was assessed using the Bland-Altman plot and Cohen’s kappa statistics.Results: Among the 32 study participants, 17 (53%) were males and the mean age was 30.1 ± 4.8 years (range: 23-47). The mean stereoacuity was 160.3 ± 53.5 arcsecs in the first HMD stereotest (HMD1), 28.4 ± 12.5 arcsecs in the Randot stereotest, 96.1 ± 83.5 arcsecs in the TNO stereotest, and 143.3 ± 47.7 arcsecs in the second HMD stereotest (HMD2). The Bland-Altman plot showed a mean difference of 0.042 (-0.189 to +0.272, 95% limits of agreement) between HMD1 and HMD2. The reliability analysis showed an intraclass correlation coefficient of 0.499 (p = 0.022) and agreement of 81.25% in Cohen’s kappa statistics (Cohen’s kappa index = 0.119, p = 0.017).Conclusions: The HMD stereotest without monocular cues showed fair test-retest reliability and reproducibility. Further studies using a high resolution display are needed to confirm the validity of the HMD stereotest.

A Custom-Made Electronic Dynamometer for Evaluation of Peak Ankle Torque after COVID-19.

The negative effects of SARS-CoV-2 infection on the musculoskeletal system include symptoms of fatigue and sarcopenia. The aim of this study is to assess the impact of COVID-19 on foot muscle strength and evaluate the reproducibility of peak ankle torque measurements in time by using a custom-made electronic dynamometer. In this observational cohort study, we compare two groups of four participants, one exposed to COVID-19 throughout measurements and one unexposed. Peak ankle torque was measured using a portable custom-made electronic dynamometer. Ankle plantar flexor and dorsiflexor muscle strength was captured for both feet at different ankle angles prior and post COVID-19. Average peak torque demonstrated no significant statistical differences between initial and final moment for both groups (p = 0.945). An increase of 4.8%, p = 0.746 was obtained in the group with COVID-19 and a decrease of 1.3%, p = 0.953 was obtained in the group without COVID-19. Multivariate analysis demonstrated no significant differences between the two groups (p = 0.797). There was a very good test–retest reproducibility between the measurements in initial and final moments (ICC = 0.78, p < 0.001). In conclusion, peak torque variability is similar in both COVID-19 and non-COVID-19 groups and the custom-made electronic dynamometer is a reproducible method for repetitive ankle peak torque measurements.

Test-retest reliability of FreeSurfer-derived volume, area and cortical thickness from MPRAGE and MP2RAGE brain MRI images

Background and purposeLarge MRI studies often pool data gathered from widely varying imaging sequences. Pooled data creates a potential source of variation in structural analyses which may cause misinterpretation of findings. The purpose of this study is to determine if data acquired using different scan sequences, head coils and scanners offers consistent structural measurements. Materials and methodsParticipants (163 right-handed males: 82 typically developing controls, 81 participants with autism spectrum disorder) were scanned on the same day using an MPRAGE sequence with a 12-channel headcoil on a Siemens 3T Trio scanner and an MP2RAGE sequence with a 64-channel headcoil on a Siemens 3T Prisma scanner. Segmentation was performed using FreeSurfer to identify regions exhibiting variation between sequences on measures of volume, surface area, and cortical thickness. Intraclass correlation coefficient (ICC) and mean percent difference (MPD) were used as test-retest reproducibility measures. ResultsICC for total brain segmented volume yielded a 0.99 intraclass correlation, demonstrating high overall volumetric reproducibility. Comparison of individual regions of interest resulted in greater variation. Volumetric variability, although low overall, was greatest in the entorhinal cortex (ICC = 0.71), frontal (ICC = 0.60) and temporal (ICC = 0.60) poles. Surface area variability was greatest in the insula (ICC = 0.65), temporal (ICC = 0.64) and frontal (ICC = 0.68) poles. Cortical thickness was most variable in the frontal (ICC = 0.41) and temporal (ICC = 0.35) poles. ConclusionData collected on different scanners and head coils using MPRAGE and MP2RAGE are generally consistent for surface area and volume estimates. However, regional variability may constrain accuracy in some regions and cortical thickness measurements exhibit higher generalized variability.

A novel graphical evaluation of agreement

BackgroundThe Bland-Altman plot with the limits of agreement has been widely used as an absolute index for assessing test-retest reliability or reproducibility between two measurements. We have observed that in the settings where the relative index such as concordance correlation coefficient (CCC) or intraclass correlation coefficient is employed, the limits of agreement approach may be inconsistent with the scaled index. Particularly, the broad width of the limits of agreement may indicate a lack of agreement when the two measurements are highly concordant but an acceptable difference is not known and the common variance of the data is large. This research aims to create a novel, CCC-based guidance for graphical evaluation of reproducibility or reliability.MethodsThe concordance correlation coefficient is used to create a 100(1-α)% reference band from two measurements. Simulation studies and real examples, including the peak expiratory flow rate data in Bland and Altman’s paper and the test-retest reproducibility data of the Radiomics study, are implemented to assess the use of the reference band.ResultsIn the absence of an acceptable difference between measurements, we found that the limits of agreement may not be consistent with the concordance correlation coefficient. Our simulation study results and real data application show that the proposed method can provide practitioners with a novel graphical evaluation that is consistent with results from the concordance correlation coefficient.ConclusionsOur proposed novel scaled index-based guidance can be used for the graphical evaluation of reproducibility or reliability and may have advantages over the limits of agreement in settings where the concordance correlation coefficient is employed.

γ-aminobutyric acid measurement in the human brain at 7T: Short echo-time or Mescher-Garwood editing.

The purposes of the current study were to introduce a Mescher–Garwood (MEGA) semi‐adiabatic spin‐echo full‐intensity localization (MEGA‐sSPECIAL) sequence with macromolecule (MM) subtraction and to compare the test–retest reproducibility of γ‐aminobutyric acid (GABA) measurements at 7 T using the sSPECIAL and MEGA‐sSPECIAL sequences. The MEGA‐sSPECIAL editing scheme using asymmetric adiabatic and highly selective Gaussian pulses was used to compare its GABA measurement reproducibility with that of short echo‐time (TE) sSPECIAL. Proton magnetic resonance spectra were acquired in the motor cortex (M1) and medial prefrontal cortex (mPFC) using the sSPECIAL (TR/TE = 4000/16 ms) and MEGA‐sSPECIAL sequences (TR/TE = 4000/80 ms). The metabolites were quantified using LCModel with unsuppressed water spectra. The concentrations are reported in institutional units. The test–retest reproducibility was evaluated by scanning each subject twice. Between‐session reproducibility was assessed using coefficients of variation (CVs), Pearson's r correlation coefficients, and intraclass correlation coefficients (ICCs). Intersequence agreement was evaluated using Pearson's r correlation coefficients and Bland–Altman plots. Regarding GABA measurements by sSPECIAL, the GABA concentrations were 0.92 ± 0.31 (IU) in the M1 and 1.56 ± 0.49 (IU) in the mPFC. This demonstrated strong between‐session correlation across both regions (r = 0.81, p < 0.01; ICC = 0.82). The CVs between the two scans were 21.8% in the M1 and 10.2% in the mPFC. On the other hand, the GABA measurements by MEGA‐sSPECIAL were 0.52 ± 0.04 (IU) in the M1 and 1.04 ± 0.24 (IU) in the mPFC. MEGA‐sSPECIAL demonstrated strong between‐session correlation across the two regions (r = 0.98, p < 0.001; ICC = 0.98) and lower CVs than sSPECIAL, providing 4.1% in the M1 and 5.8% in the mPFC. The MEGA‐editing method showed better reproducibility of GABA measurements in both brain regions compared with the short‐TE sSPECIAL method. Thus it is a more sensitive method with which to detect small changes in areas with low GABA concentrations. In GABA‐rich brain regions, GABA measurements can be achieved reproducibly using both methods.

Test–Retest Reproducibility of In Vivo Magnetization Transfer Ratio and Saturation Index in Mice at 9.4 Tesla

Magnetization transfer saturation (MTsat) imaging was developed to reduce T1 dependence and improve specificity to myelin, compared to the widely used MT ratio (MTR) approach, while maintaining a feasible scan time. As MTsat imaging is an emerging technique, the reproducibility of MTsat compared to MTR must be evaluated. To assess the test-retest reproducibility of MTR and MTsat in the mouse brain at 9.4T and calculate sample sizes potentially required to detect effect sizes ranging from 6% to 14%. Prospective. Twelve healthy C57Bl/6 mice. 9.4 T; magnetization transfer imaging using FLASH-3D Gradient Echo; T2-weighted TurboRARE spin echo. All mice were scanned at two timepoints (5 days apart). MTR and MTsat maps were analyzed using mean region-of-interest (ROIs: corpus callosum [CC], internal capsule [IC], hippocampus [HC], cortex [CX], and thalamus [TH]), and whole brain voxel-wise analysis. Bland-Altman plots were used to assess biases between test-retest measurements. Test-retest reproducibility was evaluated via between and within-subject coefficients of variation (bsCV and wsCV, respectively). Sample sizes required were calculated (significance level: 95%; power: 80%), given effect sizes ranging from 6% to 14%, using both between and within-subject approaches. Results were considered statistically significant at P ≤ 0.05. Bland-Altman plots showed negligible biases between test-retest sessions (MTR: 0.0009; MTsat: 0). ROI-based and voxel-wise CVs revealed high reproducibility for both MTR (ROI-bsCV/wsCV: CC-4.5/2.8%; IC-6.1/5.2%; HC-5.7/4.6%; CX-5.1/2.3%; TH-7.4/4.9%) and MTsat (ROI-bsCV/wsCV: CC-6.3/4.8%; IC-7.3/5.1%; HC-9.5/6.4%; CX-6.7/6.5%; TH-7.2/5.3%). With a sample size of 6, changes on the order of 15% could be detected in MTR and MTsat, both between and within subjects, while smaller changes (6%-8%) required sample sizes of 10-15 for MTR, and 15-20 for MTsat. MTsat exhibited comparable reproducibility to MTR, while providing sensitivity to myelin with less T1 dependence than MTR. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

The Moroccan dialect version of the Insomnia Severity Index

BackgroundThe objective of the present study was to translate and linguistically validate in Moroccan dialect the original English version of the Insomnia Severity Index (ISI). The translation and adaptation of this scale are obtained by using the process forward translations and backward translations. The participants filled out the final questionnaire two times with an interval of 10 days. Cronbach’s alpha coefficient assesses the acceptability and internal reliability. As for the test-retest reproducibility, we used the inter-class correlation coefficient (ICC) (95% confidence interval (CI)) and the kappa coefficient, as well as the convergent validity for each scale.ResultsThe sample included 120 subjects, 49 men (40.8%) and 71 women (59.2%). The mean age of participants was 29.23 ± 6.69 years. The translated version was quite acceptable. The Cronbach’s alpha coefficient was 0.83. The CCI (95% CI) was 0.99 (0.989, 0.995), while the kappa coefficient was 0.76. The correlations between the items of each questionnaire and its score showed good to strong positive correlations.ConclusionsThese results concluded that psychometric properties are adequate compared to the original version. Thus, this translated version had to be used for the sleep assessment in the Moroccan population.

Test-retest reproducibility of echocardiography and CMR in the same patients for assessing left atrial function

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia Background Cardiovascular magnetic resonance (CMR) has been shown to give higher left atrial (LA) volumes than trans-thoracic echocardiography (TTE) but the agreement and test-retest reproducibility of LA functional measure have not been directly compared in the same patient cohort. Methods People with type 2 diabetes mellitus (T2D) without cardiovascular disease underwent TTE and CMR on the same day on two separate occasions with a mean period of 11± 4 days. TTE images were analysed using TomTec-ARENA (v2.4, 2D-CPA), where Medis Suite (v3.1, medical imaging system) was used for CMR images. The analysis included LA strain, corresponding to LA reservoir, conduit, and booster pump (contraction function), LA volumes, and LA emptying fraction (LAEF), which was calculated using area length method. Strain and volume were assessed on 4- and 2-chamber long-axis and average values were calculated for both modalities. Results 10 participants with T2D (mean age 65.6 ± 7.3 years, 50% male) were studied. CMR LA volumes were significantly higher and LAEF significantly lower compared to TTE (P &amp;lt; 0.01 for all), whilst reservoir strain on CMR was lower compared to TTE (29.2 ± 6.5 vs 33.8 ± 3.7, p = 0.04). The inter-modality agreement was moderate for LA volumes and contraction strain (ICC ≥0.55) and poor for LAEF, strain at reservoir and conduit. Overall, the test-retest reproducibility of CMR was higher than for TTE, but the overall limits of agreement were not too dissimilar on Bland-Altman analysis (Table &amp; Figure). TTE reproducibility was good for LA volumes and strain at conduit (CoV 18-24%, ICC ∼0.80) and moderate for LAEF, strain at reservoir and contraction. CMR showed excellent test-retest reproducibility for LA volumes, EF and strain at reservoir (CoV 7-20%, ICC ≥0.83). Conclusion The test-retest reproducibility of CMR is slightly better than TTE for LA assessment using volumes and strain. LA volumes have superior reproducibility compared to functional LA parameters. Abstract Table: Test-retest reproducibility Abstract Figure: Bland-Altman plot

First-in-human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with 18F-T-401.

Monoacylglycerol lipase (MAGL) regulates cannabinoid neurotransmission and the pro-inflammatory arachidonic acid pathway by degrading endocannabinoids. MAGL inhibitors may accordingly act as cannabinoid-potentiating and anti-inflammatory agents. Although MAGL dysfunction has been implicated in neuropsychiatric disorders, it has never been visualized in vivo in human brain. The primary objective of the current study was to visualize MAGL in the human brain using the novel PET ligand 18F-T-401. Seven healthy males underwent 120-min dynamic 18F-T-401-PET scans with arterial blood sampling. Six subjects also underwent a second PET scan with 18F-T-401 within 2weeks of the first scan. For quantification of MAGL in the human brain, kinetic analyses using one- and two-tissue compartment models (1TCM and 2TCM, respectively), along with multilinear analysis (MA1) and Logan graphical analysis, were performed. Time-stability and test-retest reproducibility of 18F-T-401-PET were also evaluated. 18F-T-401 showed rapid uptake and gradual washout from the brain. Logan graphical analysis showed linearity in all subjects, indicating reversible radioligand kinetics. Using a metabolite-corrected arterial input function, MA1 estimated regional total distribution volume (VT) values by best identifiability. VT values were highest in the cerebral cortex, moderate in the thalamus and putamen, and lowest in white matter and the brainstem, which was in agreement with regional MAGL expression in the human brain. Time-stability analysis showed that MA1 estimated VT values with a minimal bias even using truncated 60-min scan data. Test-retest reliability was also excellent with the use of MA1. Here, we provide the first demonstration of in vivo visualization of MAGL in the human brain. 18F-T-401 showed excellent test-retest reliability, reversible kinetics, and stable estimation of VT values consistent with known regional MAGL expressions. PET with 18F-T-401-PET is promising tool for measurement of central MAGL.

Test-retest reproducibility comparison in resting and the mental task states: A sensor and source-level EEG spectral analysis

Previous test-retest analysis of EEG mostly focused on eyes open and eyes closed resting-state. However, less attention was paid to the EEG during the subject-driven mental imaginary task state. In the current study, we compared the test-retest reproducibility of EEG spectrum in three mental imaginary task states (i.e. performed mental arithmetic, recalled the events of their day, and silently sang lyrics) and two resting states (i.e. eyes open and closed) during three EEG sessions. The resting state with eyes closed has the highest reproducibility, while the resting state with eyes opened has the lowest reproducibility for the spectral features of EEG signals at the sensor level. However, the reproducibility during eyes-open ranked higher among the five states at the source level. Moreover, the mental arithmetic state has the highest reproducibility among all the three task states. And its reproducibility in certain rhythms (theta, gamma, etc) was higher than the resting states. The reproducibility of the EEG spectrum was also investigated from the perspective of large-scale brain networks. The dorsal attention network showed the highest reproducibility in a wide frequency range of the alpha and beta rhythms. Our study suggests the importance of task selection based on the target brain region and the target frequency band. This may provide some suggestions for future researchers to choose appropriate experimental paradigms and provide a guideline on EEG study for the basic and clinical applications.

Adaptation and Validation of a Sinhala version of the Radbound Oral Motor Inventory (ROMP) for Parkinson's disease.

Background:The Radboud Oral Motor Inventory for Parkinson's disease (ROMP) is a patient-rated assessment measuring patients' perceptions of speech, swallowing, and saliva control among patients with idiopathic Parkinson's disease (IPD).Objective:The present study was carried out to adapt and validate the Sinhala version of the ROMP questionnaire in a Sinhala-speaking patient cohort diagnosed with IPD.Materials and Methods:The study population consisted of patients diagnosed with IPD attending a tertiary care neurology clinic at the National Hospital of Sri Lanka. ROMP was translated from English to Sinhala, and an expert committee verified its content. Construct validity was assessed by correlating the Sinhala ROMP scores with the subscales in speech, salivation, and swallowing of the Unified Parkinson's Disease Rating Scale and with five-point Likert-type scale to assess dysarthria, dysphagia, and drooling by a speech and language therapist. Test–retest reproducibility was assessed by repeating the questionnaire in 2 weeks.Results:A cohort of 21 patients was evaluated (male to female ratio = 2.5:1, mean age was 58.8 [±8.3] years). The Spearman's correlations between ROMP and the Likert-type scale assessment, that is, speech r = 0.85 (P < 0.01), swallowing r = 0.86 (P < 0.01), and drooling r = 0.88 (P < 0.01), and subscales of the UPDRS were statistically significant, that is, speech r = 0.75 (P < 0.01), swallowing r = 0.96 (P < 0.01), and salivation r = 0.94 (P < 0.01). Reproducibility of the three domains and total intraclass correlation coefficients indicated a high level of agreement in test–retest reproducibility (range: 0.98–0.99). The three subdomains of the instrument also had excellent internal consistency (total Cronbach's α = 0.99).Conclusion:The Sinhala version of ROMP has proved to be a good assessment tool for dysphagia, dysarthria, and drooling in the early stage of IPD patients.

Quality Control for 4D Flow MR Imaging.

In recent years, 4D flow MRI has become increasingly important in clinical applications for the blood vessels in the whole body, heart, and cerebrospinal fluid. 4D flow MRI has advantages over 2D cine phase-contrast (PC) MRI in that any targeted area of interest can be analyzed post-hoc, but there are some factors to be considered, such as ensuring measurement accuracy, a long imaging time and post-processing complexity, and interobserver variability.Due to the partial volume phenomenon caused by low spatial and temporal resolutions, the accuracy of flow measurement in 4D flow MRI is reduced. For spatial resolution, it is recommended to include at least four voxels in the vessel of interest, and if possible, six voxels. In large vessels such as the aorta, large voxels can be secured and SNR can be maintained, but in small cerebral vessels, SNR is reduced, resulting in reduced accuracy. A temporal resolution of less than 40 ms is recommended. The velocity-to-noise ratio (VNR) of low-velocity blood flow is low, resulting in poor measurement accuracy. The use of dual velocity encoding (VENC) or multi-VENC is recommended to avoid velocity wrap around and to increase VNR. In order to maintain sufficient spatio-temporal resolution, a longer imaging time is required, leading to potential patient movement during examination and a corresponding decrease in measurement accuracy.For the clinical application of new technologies, including various acceleration techniques, in vitro and in vivo accuracy verification based on existing accuracy-validated 2D cine PC MRI and 4D flow MRI, as well as accuracy verification on the conservation of mass' principle, should be performed, and intraobserver repeatability, interobserver reproducibility, and test-retest reproducibility should be checked.

Quantifying the excitatory-inhibitory balance: A comparison of SemiLASER and MEGA-SemiLASER for simultaneously measuring GABA and glutamate at 7T

The importance of the excitatory-inhibitory (E/I) balance in a wide range of cognitive and behavioral processes has prompted a commensurate interest in methods for reliably quantifying it. Proton Magnetic Resonance Spectroscopy (1H-MRS) remains the only method capable of safely and non-invasively measuring the concentrations of the brain's major excitatory (glutamate) and inhibitory (γ-aminobutyric-acid, GABA) neurotransmitters in-vivo. MRS relies on spectral Mescher-Garwood (MEGA) editing techniques at 3T to distinguish GABA from its overlapping resonances. However, with the increased spectral resolution at ultrahigh field strengths of 7T and above, non-edited spectroscopic techniques become potential viable alternatives to MEGA based approaches, and also address some of their shortcomings, such as signal loss, sensitivity to transmitter inhomogeneities and temporal resolution. We present a comprehensive comparison of both edited and non-edited strategies at 7T for simultaneously quantifying glutamate and GABA from the dorsal anterior cingulate cortex (dACC), and evaluate their reproducibility and relative bias. The combined root-mean-square test-retest reproducibility of Glu and GABA (CVE/I) was as low as 13.3% for unedited MRS at TE=80 ms using SemiLASER localization, while edited MRS at TE=80 ms yielded CVE/I=20% and 21% for asymmetric and symmetric MEGA editing, respectively. An unedited SemiLASER acquisition using a shorter echo time of TE=42 ms yielded CVE/I as low as 24.9%. Our results show that non-edited sequences at an echo time of 80 ms provide better reproducibility than either edited sequences at the same TE, or non-edited sequences at a shorter TE of 42 ms. This is supported by numerical simulations and is driven in part by a pseudo-singlet appearance of the GABA multiplets at TE=80 ms, and the excellent spectral resolution at 7T. Our results uphold a transition to non-edited MRS for monitoring the E/I balance at ultrahigh fields, and stress the importance of using a properly-optimized echo time.

Structural Brain Network Reproducibility: Influence of Different Diffusion Acquisition and Tractography Reconstruction Schemes on Graph Metrics.

Background: Graph metrics of structural brain networks demonstrate to be a powerful tool for investigating brain topology at a large scale. However, the variability of the results related to applying different magnetic resonance acquisition schemes and tractography reconstruction techniques is not fully characterized. Materials and Methods: The present work aims to evaluate the influence of different combinations of diffusion acquisition schemes (single and multishell), diffusion models (tensor and spherical deconvolution), and tractography reconstruction approaches (deterministic and probabilistic) on the reproducibility of graph metrics derived from structural connectome on test/retest (TRT) data released by the Human Connectome Project. From each implemented experimental setup, both global and local graph metrics were evaluated and their reproducibility was estimated by the intraclass correlation coefficient (ICC). Moreover, the percentage relative standard deviation (pRSD) from the ICC values of local graph metrics was calculated to quantify how much the reproducibility varied across nodes within each experimental setup. Results: The presented results show that different combinations of diffusion acquisition schemes, diffusion models, and tractography algorithms can strongly affect the reproducibility of global and local graph metrics. The combination of constrained spherical deconvolution (CSD) and deterministic tractography gave generally high reproducibility (ICCs >0.75) and lowest pRSD for the considered graph metrics, meanwhile probabilistic CSD with a high b-value returned the highest reproducibility. Notably, the introduction of streamline selection filters on CSD can substantially affect the reproducibility. Discussion: This work demonstrates that the TRT reproducibility of graph metrics is generally high but can vary substantially with different combinations of acquisition and reconstruction schemes. Impact statement This work demonstrates the influence of different diffusion acquisition schemes, diffusion models, and tractography reconstruction approaches on the reproducibility of graph metrics derived from structural connectome. The presented findings impact on the choice of both acquisition protocol and processing pipeline for topological analyses to produce reproducible measurements for brain network studies.

Test-retest reproducibility of in vivo oscillating gradient and microscopic anisotropy diffusion MRI in mice at 9.4 Tesla.

Microstructure imaging with advanced diffusion MRI (dMRI) techniques have shown increased sensitivity and specificity to microstructural changes in various disease and injury models. Oscillating gradient spin echo (OGSE) dMRI, implemented by varying the oscillating gradient frequency, and microscopic anisotropy (μA) dMRI, implemented via tensor valued diffusion encoding, may provide additional insight by increasing sensitivity to smaller spatial scales and disentangling fiber orientation dispersion from true microstructural changes, respectively. The aims of this study were to characterize the test-retest reproducibility of in vivo OGSE and μA dMRI metrics in the mouse brain at 9.4 Tesla and provide estimates of required sample sizes for future investigations. Twelve adult C57Bl/6 mice were scanned twice (5 days apart). Each imaging session consisted of multifrequency OGSE and μA dMRI protocols. Metrics investigated included μA, linear diffusion kurtosis, isotropic diffusion kurtosis, and the diffusion dispersion rate (Λ), which explores the power-law frequency dependence of mean diffusivity. The dMRI metric maps were analyzed with mean region-of-interest (ROI) and whole brain voxel-wise analysis. Bland-Altman plots and coefficients of variation (CV) were used to assess the reproducibility of OGSE and μA metrics. Furthermore, we estimated sample sizes required to detect a variety of effect sizes. Bland-Altman plots showed negligible biases between test and retest sessions. ROI-based CVs revealed high reproducibility for most metrics (CVs < 15%). Voxel-wise CV maps revealed high reproducibility for μA (CVs ~ 10%), but low reproducibility for OGSE metrics (CVs ~ 50%). Most of the μA dMRI metrics are reproducible in both ROI-based and voxel-wise analysis, while the OGSE dMRI metrics are only reproducible in ROI-based analysis. Given feasible sample sizes (10-15), μA metrics and OGSE metrics may provide sensitivity to subtle microstructural changes (4-8%) and moderate changes (> 6%), respectively.