Retest Reproducibility Research Articles

Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36: Test–retest reproducibility and head-to-head comparison with the antagonist [18F]altanserin

Introduction[11C]Cimbi-36 is a recently developed serotonin 2A (5-HT2A) receptor agonist positron emission tomography (PET) radioligand that has been successfully applied for human neuroimaging. Here, we investigate the test–retest variability of cerebral [11C]Cimbi-36 PET and compare [11C]Cimbi-36 and the 5-HT2A receptor antagonist [18F]altanserin. MethodsSixteen healthy volunteers (mean age 23.9±6.4years, 6 males) were scanned twice with a high resolution research tomography PET scanner. All subjects were scanned after a bolus of [11C]Cimbi-36; eight were scanned twice to determine test–retest variability in [11C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [18F]altanserin. Regional differences in the brain distribution of [11C]Cimbi-36 and [18F]altanserin were assessed with a correlation of regional binding measures and with voxel-based analysis. ResultsTest–retest variability of [11C]Cimbi-36 non-displaceable binding potential (BPND) was consistently <5% in high-binding regions and lower for reference tissue models as compared to a 2-tissue compartment model. We found a highly significant correlation between regional BPNDs measured with [11C]Cimbi-36 and [18F]altanserin (mean Pearson's r: 0.95±0.04) suggesting similar cortical binding of the radioligands. Relatively higher binding with [11C]Cimbi-36 as compared to [18F]altanserin was found in the choroid plexus and hippocampus in the human brain. ConclusionsExcellent test–retest reproducibility highlights the potential of [11C]Cimbi-36 for PET imaging of 5-HT2A receptor agonist binding in vivo. Our data suggest that Cimbi-36 and altanserin both bind to 5-HT2A receptors, but in regions with high 5-HT2C receptor density, choroid plexus and hippocampus, the [11C]Cimbi-36 binding likely represents binding to both 5-HT2A and 5-HT2C receptors.

Test–retest Reproducibility of the Assessment of Motor and Process Skills in Children with Unilateral Cerebral Palsy

ABSTRACTAims: To examine test–retest reproducibility of the Assessment of Motor and Process Skills (AMPS) in children aged 8–16 years with unilateral cerebral palsy (UCP). Methods: Thirty children with mild to moderate UCP (mean age = 11y 7m, SD 2y 4m; males = 18; Manual Ability Classification System level I = 10, II = 20; Gross Motor Function Classification System level I = 9, II = 21) enrolled in a large randomized controlled trial were recruited via consecutive series sampling. Children carried out two AMPS tasks over two consecutive days according to standardized AMPS administration procedures. The standard error of measurement (SEM), smallest detectable change (SDC), 95% limits of agreement using the Bland–Altman method, and intraclass correlation coefficients (ICC; 2,1) were calculated. Results: The SDC was 0.23 logits for the AMPS motor scale and 0.30 logits for the AMPS process scale. Test–retest reliability was excellent for both the AMPS motor scale (ICC = 0.93) and the AMPS process scale (ICC = 0.86). Intra-rater reliability (n = 10) was excellent for AMPS motor scale (ICC = 0.96) and AMPS process scale (ICC = 0.98). Conclusions: The AMPS can be used by therapists with 8- to 16-year-old children with UCP as an outcome measure with changes in scores reflecting real changes in performance or capacity.

Discriminant validity and test re-test reproducibility of a gait assessment in patients with vestibular dysfunction.

BackgroundGait function may be impaired in patients with vestibular disorders, making gait assessment in the clinical setting relevant for this patient population. The purpose of this study was to evaluate the discriminant validity of a gait assessment protocol between patients with vestibular disorders and healthy participants. Furthermore, test re-test reproducibility and the measurement error of gait performance measures in patients with vestibular lesions was performed under different walking conditions.MethodsGait parameters of thirty-five patients with vestibular disorders and twenty-seven healthy controls were assessed twice with the GAITRite® system. Discriminant validity, reproducibility (intra class correlation [ICC]) and the measurement error (standard error of measurement [SEM], smallest detectable change [SDC]) were determined for gait speed, cadence and step length. Bland-Altman plots were made to assess systematic bias between tests.ResultsA significant effect of grouping on gait performance indicates discriminant validity of gait assessment. All tests revealed differences between patients and healthy controls (p < 0.01). The ICCs for test re-test reproducibility were excellent (0.70-0.96) and measurement error showed acceptable SDC values for gait parameters derived from three walking conditions (9-19 %). Bland-Altman plots indicated no systematic bias.ConclusionsGood validity and reproducibility of GAITRite® system measurements suggest that this system could facilitate the study of gait in patients with vestibular disorders in clinical settings. The SDC values for gait are generally small enough to detect changes after a rehabilitation program for patients with vestibular disorders.

A novel approach to measure local cerebral haematocrit using MRI

The percentage blood volume occupied by red blood cells is known as haematocrit. While it is straightforward to measure haematocrit in large arteries, it is very challenging to do it in microvasculature (cerebral haematocrit). Currently, this can only be done using invasive methods (e.g. PET), but their use is very limited. Local variations in cerebral haematocrit have been reported in various brain abnormalities (e.g. stroke, tumours). We propose a new approach to image cerebral haematocrit using MRI, which relies on combining data from two measurements: one that provides haematocrit-weighted and other one haematocrit-independent values of the same parameter, thus providing an easily obtainable measurement of this important physiological parameter. Four different implementations are described, with one illustrated as proof-of-concept using data from healthy subjects. Cerebral haematocrit measurements were found to be in general agreement with literature values from invasive techniques (e.g. cerebral/arterial ratios of 0.88 and 0.86 for sub-cortical and cortical regions), and showed good test–retest reproducibility (e.g. coefficient-of-variation: 15% and 13% for those regions). The method was also able to detect statistically significant haematocrit gender differences in cortical regions (p < 0.01). The proposed MRI technique should have important applications in various neurological diseases, such as in stroke and brain tumours.

Multicenter Reproducibility of 18F-Fluciclatide PET Imaging in Subjects with Solid Tumors.

Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for αvβ3/αvβ5 integrin, which can be radiolabeled for PET imaging of angiogenesis. Thus, (18)F-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of (18)F-fluciclatide in multiple solid-tumor types. Thirty-nine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of (18)F-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. (18)F-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r = 0.92, P < 0.05, at 40 min; r = 0.94, P < 0.05, at 65 min; r = 0.94, P < 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 ± 0.18 at 40 min, 0.003 ± 0.19 at 65 min, and 0.025 ± 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter (18)F-FDG studies. The test-retest reproducibility of (18)F-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients.

Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study

To date, limited data are available regarding the inter-site consistency of test–retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test–retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test–retest reproducibility in the consortium was high (ICC=0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test–retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (≈4% test–retest error, ICC=0.85), the medial frontal cortex the least reliable (≈12%, ICC=0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response.

Quantification of [11C]PIB PET for Imaging Myelin in the Human Brain: A Test—Retest Reproducibility Study in High-Resolution Research Tomography

An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [(11)C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [(11)C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test-retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [(11)C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers <1%) and reproducibility (intraclass correlation coefficient (ICC) >0.95). [(11)C]PIB parametric maps were also found to be significantly correlated (R(2)>0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [(11)C]PIB imaging and nonmyelin-associated proteins.

Test-retest reproducibility of the metabotropic glutamate receptor 5 ligand [¹⁸F]FPEB with bolus plus constant infusion in humans.

[(18)F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test-retest reproducibility of [(18)F]FPEB in the human brain. Seven healthy male subjects were scanned twice, 3 - 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [(18)F]FPEB. Four methods were used to estimate volume of distribution (V T): equilibrium analysis (EQ) using arterial (EQA) or venous input data (EQV), MA1, and a two-tissue compartment model (2 T). Binding potential (BP ND) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test-retest variability (aTRV) of V T and BP ND were calculated for each method. Venous blood measurements (C V) were compared with arterial input (C A) to examine their usability in EQ analysis. Regional V T estimated by the four methods displayed a high degree of agreement (r (2) ranging from 0.83 to 0.99 among the methods), although EQA and EQV overestimated V T by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V T were 11 % by EQA, 12 % by EQV, 14 % by MA1 and 14 % by 2 T. Regional BP ND also agreed well among the methods and mean aTRV of BP ND was 8 - 12 % (CWM) and 7 - 9 % (CGM). Venous and arterial blood concentrations of [(18)F]FPEB were well matched during equilibrium (C V = 1.01 · C A, r (2) = 0.95). [(18)F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [(18)F]FPEB is an excellent PET imaging tracer for mGluR5 in humans.

Transcultural validation of the SIGAM mobility grades in French: The SIGAM-Fr

BackgroundThe main French language scales evaluating functioning after lower-limb amputation have not undergone exhaustive psychometric validation. ObjectiveA transcultural validation of the Special Interest Group in Amputee Medicine (SIGAM) mobility grades questionnaire, with 21 closed questions, as an administered questionnaire. MethodsThe questionnaire translation, back-translation and original-author validation was followed by a pretest with 5 patients to check comprehension. The psychometric properties of the scale were validated with 49 patients at the definitive prosthesis stage by an investigator via telephone. Criterion validity was evaluated by comparison with the Houghton Scale score and construct validity by correlation between the questionnaire scores and convergent dimensions (performing everyday activities and performing transfers on a numerical rating scale [NRS], 2-min walk test) and divergent dimensions (managing medication and stump skin care on an NRS). Internal consistency was assessed by the Kuder–Richardson Formula 20 (KR-20) coefficient and test–retest reproducibility by the Cohen kappa coefficient. ResultsThe resulting questionnaire was validated by the original author after the back-translation. It showed good psychometric properties when administered by an investigator as a self-reporting questionnaire, excellent criterion validity (r=0.89, P<0.01), excellent reproducibility (kappa coefficient 0.87) and satisfactory construct validity. The KR-20 coefficient was 0.67. ConclusionThe French version of the SIGAM mobility grades questionnaire (SIGAM-Fr) has satisfactory psychometric properties and can be administered in clinical practice.

Test-retest reproducibility of binding parameters in humans with 11C-LY2795050, an antagonist PET radiotracer for the κ opioid receptor.

(11)C-LY2795050 is a new antagonist PET radioligand for the κ opioid receptor (KOR). In this study, we assessed the reproducibility of the binding parameters of (11)C-LY2795050 in healthy human subjects. Sixteen healthy subjects (11 men and 5 women) underwent 2 separate 90-min PET scans with arterial input function and plasma free fraction (fP) measurements. The 2-tissue-compartment model and multilinear analysis-1 were applied to calculate 5 outcome measures in 14 brain regions: distribution volume (VT), VT normalized by fP (VT/fP), and 3 binding potentials (nondisplaceable binding potential, binding potential relative to total plasma concentration, and binding potential relative to free plasma concentration: BPND, BPP, BPF, respectively). Since KOR is distributed ubiquitously throughout the brain, there are no suitable reference regions. We used a fixed fraction of individual cerebellar VT value (VT,CER) as the nondisplaceable VT (VND) (VND = VT,CER/1.17). The relative and absolute test-retest variability and intraclass correlation coefficient were evaluated for the outcome measures of (11)C-LY2795050. The test-retest variability of (11)C-LY2795050 for VT was no more than 10% in any region and was 12% in the amygdala. For binding potential (BPND and BPP), the test-retest variability was good in regions of moderate and high KOR density (BPND > 0.4) and poor in regions of low density. Correction by fP (VT/fP or BPF) did not improve the test-retest performance. Our results suggest that quantification of (11)C-LY2795050 imaging is reproducible and reliable in regions with moderate and high KOR density. Therefore, we conclude that this first antagonist radiotracer is highly useful for PET studies of KOR.

Reproducibility of self-reported melanoma risk factors in melanoma patients.

As melanoma researchers continue to investigate environmental and lifestyle-related risk factors, questionnaire data remain important. The reproducibility of a questionnaire on melanoma risk factors was investigated using a test-retest approach in 389 Dutch melanoma patients. In 2011, 389 melanoma patients filled out a questionnaire on melanoma risk factors twice. Test-retest reproducibility was assessed by calculating kappas (κ), weighted kappas (κw), and intraclass correlation coefficients (ICCs) for categorical, ordinal, and continuous variables, respectively. Stratified analyses were carried out by sex, age group, education level, and time since diagnosis. The median time between the questionnaires was 31 days. The reproducibility was substantial for questions on phenotypic characteristics (κ/κw/ICC=0.62-0.77), fair-to-substantial for sun exposure and sun protection behavior (κ/κw/ICC=0.38-0.79), and moderate for sunburn history (κ/κw=0.42-0.51). No clear differences were observed between men and women. Younger patients showed a better reproducibility in nine of the 29 questions compared with older patients and higher educated patients showed a better reproducibility in four of the 29 questions. Patients with a diagnosis shorter than 1.5 years ago had a better reproducibility in four out of 29 items compared with patients with a diagnosis 1.5-3.0 years ago. Our study showed that self-reported information on melanoma risk factors is fairly well reproducible. Although this does not guarantee validity, this type of questionnaire seems to be useful in research settings. The reproducibility is slightly better in young patients and patients with a higher education level, which can be taken into account when interpreting results from epidemiological studies.

Mapping the end-tidal CO2 response function in the resting-state BOLD fMRI signal: Spatial specificity, test–retest reliability and effect of fMRI sampling rate

The blood oxygenation level dependent (BOLD) signal measures brain function indirectly through physiological processes and hence is susceptible to global physiological changes. Specifically, fluctuations in end-tidal CO2 (PETCO2), in addition to cardiac rate variation (CRV), and respiratory volume per time (RVT) variations, have been known to confound the resting-state fMRI (rs-fMRI) signal. Previous studies addressed the resting-state fMRI response function to CRV and RVT, but no attempt has been made to directly estimate the voxel-wise response function to PETCO2. Moreover, the potential interactions among PETCO2, CRV, and RVT necessitate their simultaneous inclusion in a multi-regression model to estimate the PETCO2 response. In this study, we use such a model to estimate the voxel-wise PETCO2 response functions directly from rs-fMRI data of nine healthy subjects. We also characterized the effect of sampling rate (TR=2seconds vs. 323ms) on the temporal and spatial variability of the PETCO2 response function in addition to that of CRV and RVT. In addition, we assess the test–retest reproducibility of the response functions to PETCO2, CRV and RVT. We found that despite overlaps across their spatial patterns, PETCO2 explains a unique portion of the rs-fMRI signal variance compared to RVT and CRV. We also found the shapes of the estimated responses are very similar between long- and short-TR data, although responses estimated from short-TR data have higher reproducibility.

Reproducibility of spatio-temporal and dynamic parameters in various, daily occurring, turning conditions

ObjectiveThis study aims to assess the test–retest reproducibility of specific spatio-temporal (foot placement, foot contact time) and dynamic (resultant horizontal and vertical ground reaction force) gait parameters of three different, everyday occurring, turning conditions. The subjects were tested at two subsequent days. Out of this setting the purpose of this study is to clarify, if turning locomotion is stable when performed at different test occurrences. MethodsEight subjects completed three different daily occurring turning conditions along turns with a given walking velocity of 5km/h (±10%). Subjects had to complete the turns three times clockwise and counter clockwise. The measurements were recorded with a 3D motion analysis system (Vicon®) and two force sensitive platforms (AMTI®), connected to the motion analysis system. ResultsThe analysis yields for most of the parameters and turning conditions ICCs from good (r=0.72; p=.06) to high (r=0.96; p<.01) magnitude for the measured spatio-temporal and dynamic parameters. ConclusionsBased on our findings it can be assumed that locomotion strategies, related to the measured gait parameters of common daily turning tasks, are stable and reproducible.

Intravoxel incoherent motion diffusion imaging of the liver: Optimal b-value subsampling and impact on parameter precision and reproducibility

PurposeTo increase diffusion sampling efficiency in intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) of the liver by reducing the number of diffusion weightings (b-values). Materials and methodsIn this IRB approved HIPAA compliant prospective study, 53 subjects (M/F 38/15, mean age 52±13 y) underwent IVIM DWI at 1.5T using 16 b-values (0–800s/mm2), with 14 subjects having repeat exams to assess IVIM parameter reproducibility. A biexponential diffusion model was used to quantify IVIM hepatic parameters (PF: perfusion fraction, D: true diffusion and D*: pseudo diffusion). All possible subsets of the 16 b-values were probed, with number of b values ranging from 4 to 15, and corresponding parameters were quantified for each subset. For each b-value subset, global parameter estimation error was computed against the parameters obtained with all 16 b-values and the subsets providing the lowest error were selected. Interscan estimation error was also evaluated between repeat exams to assess reproducibility of the IVIM technique in the liver. The optimal b-values distribution was selected such that the number of b-values was minimal while keeping parameter estimation error below interscan reproducibility error. ResultsAs the number of b-values decreased, the estimation error increased for all parameters, reflecting decreased precision of IVIM metrics. Using an optimal set of 4 b-values (0, 15, 150 and 800s/mm2), the errors were 6.5, 22.8 and 66.1% for D, PF and D* respectively. These values lie within the range of test–retest reproducibility for the corresponding parameters, with errors of 12.0, 32.3 and 193.8% for D, PF and D* respectively. ConclusionA set of 4 optimized b-values can be used to estimate IVIM parameters in the liver with significantly shorter acquisition time (up to 75%), without substantial degradation of IVIM parameter precision and reproducibility compared to the 16 b-value acquisition used as the reference.

Investigation of a matrix sentence test in noise: Reproducibility and discrimination function in cochlear implant patients

Objective: The aim of this study was to describe common properties (reproducibility, discrimination function, and its steepness) of matrix tests used for cochlear implant (CI) users and to obtain data for the German-language version matrix test, the Oldenburg sentence test (OLSA), presented in noise. Design: The speech reception thresholds (SRT) in noise were measured by means of an adaptive test procedure, and by measurement at various signal-to-noise ratios to determine the course of the entire discrimination function per subject. Study sample: The measurements were performed on 38 CI users fitted with a Cochlear™ Freedom® or a Cochlear™ Nucleus® 5 CI system. Results: The test–retest reproducibility showed a significant dependence on the SRT in noise. For the better performers, the test-retest difference was found to be smaller, while for the poorer performers the difference increased. For the better performers, the slope of the discrimination function at SRT (s50) was comparable to that for individuals with normal hearing, while for the poorer performers the s50 tended to be significantly reduced. Conclusions: As the CI users differed significantly in their SRT and their s50, a unified discrimination function for CI users must not be used. Further tailoring of the procedure may be required, especially for poorer CI performers.

Cardiac strain during upright cycle ergometry in adolescent males.

Little evidence exists with regard to changes in cardiac strain that occur during submaximal exercise in young males. The aims of the study were to evaluate the changes that occur in longitudinal (L), radial (R), and endocardial circumferential (EC) strain during submaximal upright cycle ergometry and to examine the test-retest reproducibility of these measurements. Fourteen recreationally active, adolescent (age: 17.9 ± 0.7 years) males volunteered for the study. All subjects underwent an incremental (40 W) submaximal cycle ergometer test. L, R, and EC strain values were obtained using speckle tracking, from two-dimensional B-mode images of the left ventricle (LV) during rest and the initial stages of submaximal exercise (40 and 80 W). The average of 6 LV segments was used to determine both peak wall deformation (%) and the time to peak deformation (ms). There was a statistically (P < 0.05) significant increase from rest to submaximal exercise for peak deformation for L, R, and EC strain. There was a statistically significant (P < 0.05) decrease from rest to submaximal exercise for time to peak for L and R and EC strain and between submaximal workloads for time to peak for L strain and EC strain. Coefficients of variation demonstrated reproducibility for upright strain and strain rate measurements similar to published supine measurements. This study has demonstrated that changes in left ventricular wall deformation (L, R and EC strain) that occur during the transition from rest to submaximal exercise can be reliably measured and confirm that a healthy LV has a hyperdynamic response to exercise.

Variability in color-choice Stroop performance within and across EEG and MRI laboratory contexts.

To examine the reproducibility of the Stroop effect, behavioral data from 22 healthy female individuals were repeatedly (three-month interval between two separate measurement sessions) obtained while performing a color-choice Stroop task under realistic magnetic resonance imaging (MRI) and electroencephalography (EEG) laboratory conditions. At the group statistical level, the Stroop effect, indicated by longer response times for incongruent than for congruent stimulus conditions, was consistently present for almost all examined measurement levels. However, differential effects of laboratory contexts on retest reproducibility were observed across repeated measurement levels, both within and between sessions. These results challenge existing theories about the underlying nature of Stroop interference processing. It appears necessary to apply a multitheoretical approach, because intraindividual variability within and across measurement sessions suggests potential fluctuations in the individual mental strategies applied, recruitment of varying memory resources, the influence of mediator variables such as working memory capacity and/or attention, and many more possible variations. Single-observation studies run the risk of favoring a single theoretical concept and therefore underestimating the individual factor. We further conclude that dependent analysis-of-variance statistics are a more fit test for reproducibility than are correlative reliability estimations.

Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects

Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2×2×2mm3, b=700s/mm2, 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test–retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test–retest reproducibility. White matter b0 SNR reproducibility was on average 7±1% with no significant MRI site effects. Whole brain analysis resulted in no significant test–retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2–4% range for FA and AD and 2–6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios.

41 Correlation and Reproducibility of Invasive and Non-invasive Haemodynamic Parameters for Identifying Optimal AV Delay in Cardiac Resynchronisation Therapy

BackgroundAcute haemodynamic measurements can be used for AV delay (AVD) optimisation of cardiac resynchronisation therapy (CRT). It is uncertain whether non-invasive measurements are as reliable as those measured invasively.Methods37 patients...

Evaluation of the agonist PET radioligand [11C]GR103545 to image kappa opioid receptor in humans: Kinetic model selection, test–retest reproducibility and receptor occupancy by the antagonist PF-04455242

IntroductionKappa opioid receptors (KOR) are implicated in several brain disorders. In this report, a first-in-human positron emission tomography (PET) study was conducted with the potent and selective KOR agonist tracer, [11C]GR103545, to determine an appropriate kinetic model for analysis of PET imaging data and assess the test–retest reproducibility of model-derived binding parameters. The non-displaceable distribution volume (VND) was estimated from a blocking study with naltrexone. In addition, KOR occupancy of PF-04455242, a selective KOR antagonist that is active in preclinical models of depression, was also investigated. MethodsFor determination of a kinetic model and evaluation of test–retest reproducibility, 11 subjects were scanned twice with [11C]GR103545. Seven subjects were scanned before and 75min after oral administration of naltrexone (150mg). For the KOR occupancy study, six subjects were scanned at baseline and 1.5h and 8h after an oral dose of PF-04455242 (15mg, n=1 and 30mg, n=5). Metabolite-corrected arterial input functions were measured and all scans were 150min in duration. Regional time-activity curves (TACs) were analyzed with 1- and 2-tissue compartment models (1TC and 2TC) and the multilinear analysis (MA1) method to derive regional volume of distribution (VT). Relative test–retest variability (TRV), absolute test–retest variability (aTRV) and intra-class coefficient (ICC) were calculated to assess test–retest reproducibility of regional VT. Occupancy plots were computed for blocking studies to estimate occupancy and VND. The half maximal inhibitory concentration (IC50) of PF-04455242 was determined from occupancies and drug concentrations in plasma. [11C]GR103545 in vivo KD was also estimated. ResultsRegional TACs were well described by the 2TC model and MA1. However, 2TC VT was sometimes estimated with high standard error. Thus MA1 was the model of choice. Test–retest variability was ~15%, depending on the outcome measure. The blocking studies with naltrexone and PF-04455242 showed that VT was reduced in all regions; thus no suitable reference region is available for the radiotracer. VND was estimated reliably from the occupancy plot of naltrexone blocking (VND=3.4±0.9mL/cm3). The IC50 of PF-04455242 was calculated as 55ng/mL. [11C]GR103545 in vivo KD value was estimated as 0.069nmol/L. Conclusions[11C]GR103545 PET can be used to image and quantify KOR in humans, although it has slow kinetics and variability of model-derived kinetic parameters is higher than desirable. This tracer should be suitable for use in receptor occupancy studies, particularly those that target high occupancy.