Brain ?-aminobutyric acid (GABA) detection in vivo with the J-editing (1) H MRS technique: a comprehensive methodological evaluation of sensitivity enhancement, macromolecule contamination and test-retest reliability.
Project description:We assessed the test-retest reliability of high spatial resolution diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Diffusion MRI was acquired using a Siemens 3 Tesla Prisma scanner with 80?mT/m gradients and a 32-channel head coil from each of 3 concussive traumatic brain injury (cTBI) patients and 4 controls twice 0 to 24 days apart. Coefficients of variation (CoV) for DTI parameters were calculated in each DTI Studio parcellated white matter tract at 1.25?mm and 1.75?mm isotropic voxel resolution, as well as DKI parameters at 1.75?mm isotropic. Overall, fractional anisotropy had the best reliability, with mean CoV at 5% for 1.25?mm and 3.5% for 1.75?mm isotropic voxels. Mean CoV for the other DTI metrics were <7.0% for both 1.25 and 1.75?mm isotropic voxels. The mean CoV was ?4.5% across the DKI metrics. In the commonly injured orbitofrontal and temporal pole regions CoV was <3.5% for all parameters. Thus, with appropriate processing, high spatial resolution advanced diffusion MRI has good to excellent test-retest reproducibility in both human cTBI patients and controls. However, further technical improvements will be needed to reliably discern the most subtle diffusion abnormalities, especially at high spatial resolution.
Project description:Coping with predeath grief (PDG) is an unmet need in caregivers of persons with dementia (PWD). The Marwit-Meuser Caregiver Grief Inventory (MM-CGI) and its abbreviated MM-CGI-Short-Form (MM-CGI-SF) are among the few empirically developed scales that detect PDG, yet they have not been substantially validated outside United States. We evaluated the reliability and validity of the PDG scales in a multiethnic Asian population distinct from that of United States.Family caregivers of community-dwelling PWD (n = 300) completed self-administered questionnaires containing MM-CGI and other scales of related construct. Sixty percent of the participants repeated the questionnaires 1 week later for test-retest reliability. Internal-consistency reliability was assessed by Cronbach's ?, test-retest reliability by intraclass-correlation-coefficient, construct validity by Spearman's correlation-coefficient, and factorial validity by confirmatory factor analysis (CFA). Cohen's ? was used to compare the agreement between MM-CGI and a commonly-used caregiver burden scale (Zarit Burden Interview).MM-CGI and MM-CGI-SF demonstrated internal-consistency reliability, test-retest reliability, construct validity, and known-group validity. In CFA, MM-CGI showed modest model-fit (comparative-fit-index, CFI = .80; Tucker-Lewis-index, TLI = .79), whereas MM-CGI-SF showed better model-fit (CFI = .91; TLI = .90). Eighty-six percent of the caregivers reported average or high levels of PDG, with 18% reporting high PDG. High scores in the caregiver burden scale only showed modest agreement with high scores in MM-CGI (? = .47).MM-CGI and MM-CGI-SF demonstrated adequate psychometric properties and utility, beyond that of a caregiver burden scale, in detecting high PDG in a multiethnic Asian population. They open the way for PDG intervention in clinical care, as well as further exploration in caregiver research.
Project description:<h4>Objective</h4>Since the inflammatory process has been implicated in the pathophysiology of psychiatric disorder, an important issue emerging is to assess the test-retest reliability of cytokine measurement in healthy individuals and patients with schizophrenia. The objective of the present study was to investigate the test-retest reliability of bead-based multiplex immunoassay technology (BMIT) for cytokine measurement by using a Bland-Altman plot (BAP).<h4>Methods</h4>Twenty healthy individuals and twenty patients with schizophrenia were enrolled, and a 17-plex cytokine assay was used to measure inflammatory biomarkers at baseline and two weeks later. The test-retest reliability was examined by BAP, 95% limits of agreement (LOA), intraclass correlation coefficient (ICC), and coefficient of repeatability (CoR).<h4>Results</h4>In the healthy controls, only interleukin (IL)-2, IL-13, IL-10, IL-17, and macrophage inflammatory protein-1? showed excellent ICC. The BAP with 95% LOA determined that 13 cytokines showed acceptable 95% LOA for a 2-week test-retest reliability, and only IL-1?, IL-12 and tumor necrosis factor (TNF)-? had significant test-retest bias. The CoR of cytokines varied significantly, ranging from 1.72 to 218.1. Compared with healthy controls, patients with schizophrenia showed significantly higher levels of IL-5, IL-13, and TNF-? and significantly lower levels of IL-4, IL-12, and interferon-gamma (IFN-?). Of these six cytokines, IL-12 and TNF-? were considered suboptimal reliability.<h4>Conclusion</h4>The findings from ICC and CoR implied that the test-retest reliability of BMIT for cytokine measurement were suboptimal. However, the BAP with 95% LOA confirmed that BMIT can reliably distinguish schizophrenia from healthy individuals in cytokine measurement, while significant within-subject variation and between-group overlapping were evident in cytokine expression.
Project description:Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited ?-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.
Project description:Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established. We examined 4-hour test-retest reliability and 10 month test-retest stability of individual differences in gene expression in 10 12-year-old children. Blood was collected on four occasions: 10am and 2pm on day one and 10 months later at 10am and 2pm. Total RNA was hybridised to Affymetrix-U133 plus 2.0 arrays.
Project description:Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established. We examined 4-hour test-retest reliability and 10 month test-retest stability of individual differences in gene expression in 10 12-year-old children. Overall design: Blood was collected on four occasions: 10am and 2pm on day one and 10 months later at 10am and 2pm. Total RNA was hybridised to Affymetrix-U133 plus 2.0 arrays.
Project description:BACKGROUND:The experience of grief in family caregivers as they provide care for persons with dementia is often overlooked. The Marwit-Meuser Caregiver Grief Inventory (MM-CGI) is one among the few scales that capture such experiences. In a recent study, MM-CGI was found to contain three subscales identifying dimensions of loss in caregivers-Personal-Sacrifice Burden (PSB), Heartfelt Sadness, Longing, and Worry (HSLW), and Felt Isolation (FI). We aimed to evaluate the validity and utility of these dimensions in a multiethnic Asian population. METHODS:Family caregivers (n = 394) completed MM-CGI and scales assessing caregiver burden, depression, and gains. Internal consistency reliability was examined using Cronbach ?; test-retest reliability using intraclass correlation coefficient; and construct validity using Pearson correlation coefficient. The utility of the MM-CGI dimensions was evaluated by comparing caregivers with high subscale scores across dementia stages and caregiving relationship. RESULTS:The three dimensions of MM-CGI exhibited adequate internal consistency, test-retest reliability, construct validity, and known-group validity. PSB correlated most strongly with caregiver burden (r = 0.78); HSLW with caregiver depression (r = 0.75); and FI with caregiver burden and caregiver depression (r = 0.60, respectively). Caregivers with high total grief scores tended to experience most difficulty with HSLW (90.8%), followed by PSB (75.4%) and FI (46.2%). The three dimensions also increased across the dementia stages, with FI higher in mild dementia, PSB higher in moderate dementia, and HSLW higher in severe dementia. Spousal caregivers experienced most difficulty in HSLW, whereas children caregivers experienced similar levels of difficulty across the dimensions. CONCLUSIONS:The three dimensions of MM-CGI captured distinct aspects of caregiver grief in a multiethnic Asian population and would enable more individualized assessments and interventions for caregiver grief.
Project description:The purpose of this study was to assess the concurrent validity and test-retest reliability of a linear position transducer (LPT) for the squat jump (SJ) and counter-movement jump (CMJ) height. Twenty-eight subjects (25.18 ± 7.1 years) performed three SJs followed by three CMJs using a force plate concurrently with the LPT to test validity. Subjects returned on a separate day, at least 48 h apart, to measure test-retest reliability. A t-test showed a significant difference between the two devices for both SJ (p < 0.001) and CMJ (p < 0.001) while Bland?Altman analysis for validity revealed that the LPT overestimated jump height for both SJ (mean difference (MD) = 8.01 ± 2.93 cm) and CMJ (MD = 8.68 ± 2.99 cm). With regards to reliability of the LPT, mean intraclass correlation (ICC) for both SJ (ICC = 0.84) and CMJ (ICC = 0.95) were high, and Bland?Altman analysis showed mean differences lower than minimal detectable change (MDC) between the days for both SJ (MD = 1.89 ± 4.16 cm vs. MDC = 2.72 cm) and CMJ (MD = 0.47 ± 3.23 cm vs. MDC = 2.11 cm). Additionally, there was a low coefficient of variation (CV) between days for both SJ (CV = 3.25%) and CMJ (CV = 0.74%). Therefore, while the LPT overestimates jump height, it is a reliable tool for tracking changes in jump height to measure performance improvement and monitor fatigue.
Project description:<h4>Purpose</h4>This study compared subcutaneous adipose tissue (SAT) measurements using a skinfold caliper and Renco Lean-Meater Series 12 A-mode portable ultrasound scanner (A-US). It aimed to assess their inter- and intra-rater reliability and measure the agreement between both methods.<h4>Methods</h4>Eighty-four volunteers of different fitness levels were divided into three groups by ?6 skinfolds: G1 ? 55 mm (n = 33 males); G2 > 55 mm (n = 32 males); G3 = 98.0 ± 52.3 mm (n = 19 females). Triceps, subscapular, biceps, iliac crest, supraspinal, abdominal, front thigh and medial calf were assessed by ultrasound and skinfolds. Two technicians for both tools performed triplicate measures. Intraclass correlation (ICC), technical error of measurement (TEM) and coefficients of variation (CVs) were applied for test-retest and inter-rater reliability. Non-Parametric statistics were used in order to establish possible statistical differences and correlation between skinfolds thickness and uncompressed subcutaneous adipose tissue thickness from ultrasound. The amount of agreement between both methods was assessed with Lin's coefficient and a scatterplot of all site locations. A Bland-Altman plot was constructed to establish limits of agreement between groups and regression analysis was employed to assess the ability of skinfolds to explain the variance of ultrasound.<h4>Results</h4>Test-retest ICC for skinfolds and ultrasound were higher than 0.989 and 0.793, respectively. Inter-rater ICC for skinfolds was 0.999 with a 95% CI of 0.995 to 0.999 and for ultrasound was 0.755 with a much larger 95% CI of 0.622 to 0.841. TEMs (> 8.50%) and CVs (> 6.72%) compromised ultrasound reliability. Statistical differences were found in most of the analysed anatomical sites (p < 0.001) except in biceps G2 (Z = -1.150, p = 0.25) and G3 (Z = -1.309, p = 0.19). Good correlations (r > 0.7, p ? 0.05) were reported at almost all anatomical sites and groups except for biceps (G1: Rho = 0.26, p = 0.140) and abdominal (G2: Rho = -0.16, p = 0.38; G3: Rho = 0.43, p = 0.068). Lin's concordance correlation coefficient registered low values of agreement between skinfolds and A-mode ultrasound (ranged from-0.009-0.646). The scatterplot and the estimated regression line drawn through the midst of all anatomical sites of the whole sample had a slope of 0.51 and R2 adjusted = 0.62 was obtained. The combined analysis between the Bland-Altman plot and the linear regression showed that specifically in the G2 and G3 groups, as the SAT increases the differences between skinfolds and ultrasounds measurements also increases.<h4>Conclusions</h4>The Renco Lean-Meater ultrasound is not interchangeable with skinfold measures. Its utility is questionable, particularly for assessing SAT in active adult populations. Its poor test-retest and inter-rater reliability as well as the lack of agreement when compared to the skinfolds would exclude the free use of the A-mode ultrasound scanner in its hypothetical replacing of the classical calipers.
Project description:The reproducibility of gamma-aminobutyric acid (GABA) quantification results, obtained with MRSI, was determined on a 3 T MR scanner in healthy adults. In this study, a spiral-encoded, GABA-edited, MEGA-LASER MRSI sequence with real-time motion-scanner-instability corrections was applied for robust 3D mapping of neurotransmitters in the brain. In particular, the GABA+ (i.e. GABA plus macromolecule contamination) and Glx (i.e. glutamate plus glutamine contamination) signal was measured. This sequence enables 3D-MRSI with about 3 cm3 nominal resolution in about 20 min. Since reliable quantification of GABA is challenging, the spatial distribution of the inter-subject and intra-subject variability of GABA+ and Glx levels was studied via test-retest assessment in 14 healthy volunteers (seven men-seven women). For both inter-subject and intra-subject repeated measurement sessions a low coefficient of variation (CV) and a high intraclass correlation coefficient (ICC) were found for GABA+ and Glx ratios across all evaluated voxels (intra-/inter-subject: GABA+ ratios, CV ~ 8%-ICC > 0.75; Glx ratios, CV ~ 6%-ICC > 0.70). The same was found in selected brain regions for Glx ratios versus GABA+ ratios (CV varied from about 5% versus about 8% in occipital and parietal regions, to about 8% versus about 10% in the frontal area, thalamus, and basal ganglia). These results provide evidence that 3D mapping of GABA+ and Glx using the described methodology provides high reproducibility for application in clinical and neuroscientific studies.