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Characterization of regional left ventricular function in nonhuman primates using magnetic resonance imaging biomarkers: a test-retest repeatability and inter-subject variability study.

ABSTRACT: Pre-clinical animal models are important to study the fundamental biological and functional mechanisms involved in the longitudinal evolution of heart failure (HF). Particularly, large animal models, like nonhuman primates (NHPs), that possess greater physiological, biochemical, and phylogenetic similarity to humans are gaining interest. To assess the translatability of these models into human diseases, imaging biomarkers play a significant role in non-invasive phenotyping, prediction of downstream remodeling, and evaluation of novel experimental therapeutics. This paper sheds insight into NHP cardiac function through the quantification of magnetic resonance (MR) imaging biomarkers that comprehensively characterize the spatiotemporal dynamics of left ventricular (LV) systolic pumping and LV diastolic relaxation. MR tagging and phase contrast (PC) imaging were used to quantify NHP cardiac strain and flow. Temporal inter-relationships between rotational mechanics, myocardial strain and LV chamber flow are presented, and functional biomarkers are evaluated through test-retest repeatability and inter subject variability analyses. The temporal trends observed in strain and flow was similar to published data in humans. Our results indicate a dominant dimension based pumping during early systole, followed by a torsion dominant pumping action during late systole. Early diastole is characterized by close to 65% of untwist, the remainder of which likely contributes to efficient filling during atrial kick. Our data reveal that moderate to good intra-subject repeatability was observed for peak strain, strain-rates, E/circumferential strain-rate (CSR) ratio, E/longitudinal strain-rate (LSR) ratio, and deceleration time. The inter-subject variability was high for strain dyssynchrony, diastolic strain-rates, peak torsion and peak untwist rate. We have successfully characterized cardiac function in NHPs using MR imaging. Peak strain, average systolic strain-rate, diastolic E/CSR and E/LSR ratios, and deceleration time were identified as robust biomarkers that could potentially be applied to future pre-clinical drug studies.

SUBMITTER: Sampath S

PROVIDER: S-EPMC4444127 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Project description:BackgroundQuantification and visualisation of left ventricular (LV) blood flow is afforded by three-dimensional, time resolved phase contrast cardiovascular magnetic resonance (CMR 4D flow). However, few data exist upon the repeatability and variability of these parameters in a healthy population. We aimed to assess the repeatability and variability over time of LV 4D CMR flow measurements.MethodsForty five controls underwent CMR 4D flow data acquisition. Of these, 10 underwent a second scan within the same visit (scan-rescan), 25 returned for a second visit (interval scan; median interval 52 days, IQR 28-57 days). The LV-end diastolic volume (EDV) was divided into four flow components: 1) Direct flow: inflow that passes directly to ejection; 2) Retained inflow: inflow that enters and resides within the LV; 3) Delayed ejection flow: starts within the LV and is ejected and 4) Residual volume: blood that resides within the LV for > 2 cardiac cycles. Each flow components' volume was related to the EDV (volume-ratio). The kinetic energy at end-diastole (ED) was measured and divided by the components' volume.ResultsThe dominant flow component in all 45 controls was the direct flow (volume ratio 38 ± 4%) followed by the residual volume (30 ± 4%), then delayed ejection flow (16 ± 3%) and retained inflow (16 ± 4%). The kinetic energy at ED for each component was direct flow (7.8 ± 3.0 microJ/ml), retained inflow (4.1 ± 2.0 microJ/ml), delayed ejection flow (6.3 ± 2.3 microJ/ml) and the residual volume (1.2 ± 0.5 microJ/ml). The coefficients of variation for the scan-rescan ranged from 2.5%-9.2% for the flow components' volume ratio and between 13.5%-17.7% for the kinetic energy. The interval scan results showed higher coefficients of variation with values from 6.2-16.1% for the flow components' volume ratio and 16.9-29.0% for the kinetic energy of the flow components.ConclusionLV flow components' volume and their associated kinetic energy values are repeatable and stable within a population over time. However, the variability of these measurements in individuals over time is greater than can be attributed to sources of error in the data acquisition and analysis, suggesting that additional physiological factors may influence LV flow measurements.

Project description:The stop signal task has been used to quantify the human inhibitory control. The inter-subject and intra-subject variability was investigated under the inhibition of human response with a realistic environmental scenario. In present study, we used a battleground scenario where a sniper-scope picture was the background, a target picture was a go signal, and a nontarget picture was a stop signal. The task instructions were to respond on the target image and inhibit the response if a nontarget image appeared. This scenario produced a threatening situation and endorsed the evaluation of how subject's response inhibition manifests in a real situation. In this study, 32 channels of electroencephalography (EEG) signals were collected from 20 participants during successful stop (response inhibition) and failed stop (response) trials. These EEG signals were used to predict two possible outcomes: successful stop or failed stop. The inter-subject variability (between-subjects) and intra-subject variability (within-subjects) affect the performance of participants in the classification system. The EEG signals of successful stop versus failed stop trials were classified using quadratic discriminant analysis (QDA) and linear discriminant analysis (LDA) (i.e., parametric) and K-nearest neighbor classifier (KNNC) and Parzen density-based (PARZEN) (i.e., nonparametric) under inter- and intra-subject variability. The EEG activities were found to increase during response inhibition in the frontal cortex (F3 and F4), presupplementary motor area (C3 and C4), parietal lobe (P3 and P4), and occipital (O1 and O2) lobe. Therefore, power spectral density (PSD) of EEG signals (1-50Hz) in F3, F4, C3, C4, P3, P4, O1, and O2 electrodes were measured in successful stop and failed stop trials. The PSD of the EEG signals was used as the feature input for the classifiers. Our proposed method shows an intra-subject classification accuracy of 97.61% for subject 15 with QDA classifier in C3 (left motor cortex) and an overall inter-subject classification accuracy of 71.66% ± 9.81% with the KNNC classifier in F3 (left frontal lobe). These results display how inter-subject and intra-subject variability affects the performance of the classification system. These findings can be used effectively to improve the psychopathology of attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), schizophrenia, and suicidality.

Project description:SignificanceThe Ohio Contrast Cards are a repeatable test of contrast sensitivity, and they reveal higher contrast sensitivity for low-vision patients than is shown by the Pelli-Robson chart.PurposeThis study aimed to compare the contrast sensitivity results and test/retest ±limits of agreement for the Ohio Contrast Cards and the Pelli-Robson letter contrast sensitivity chart on two challenging groups of participants, and to compare the Ohio Contrast Card results with grating acuity and the Pelli-Robson results with letter acuity.MethodsThe Ohio Contrast Card and Pelli-Robson tests were each performed twice by two different examiners within one visit on 40 elder patients in Primary Vision Care (>65 years old) and 23 to 27 low-vision school-aged students. Grating acuity was measured using the Teller Acuity Cards (all participants), and letter acuity was measured using ClearChart (elders) or the Bailey-Lovie chart (students).ResultsThe ±95% limits of agreement were similar for the Ohio Contrast Cards and the Pelli-Robson chart. The elders' limits of agreement were ±0.27 (Ohio Contrast Cards) and ±0.28 (Pelli-Robson); the students' limits of agreement were ±0.42 (Ohio Contrast Cards) and ±0.51 (Pelli-Robson). However, Ohio Contrast Card results were 0.41 log10 Michelson units more sensitive than the Pelli-Robson chart (over one line on the Pelli-Robson chart) for the elders and 0.90 log10 Michelson units (three lines on the Pelli-Robson chart) more sensitive for the elders (0.11 and 0.6 log10 Weber units, respectively). The Pelli-Robson results were correlated with letter acuities and Ohio Contrast Card results for both groups, and the Ohio Contrast Card results were correlated with Teller Acuity Card acuities for the elders.ConclusionsThe Ohio Contrast Cards and Pelli-Robson chart are similarly repeatable. Both contrast sensitivity tests can provide additional clinical information that is not available through visual acuity testing, and Ohio Contrast Card may provide additional information not available from the Pelli-Robson chart.

Project description:BackgroundRenal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease.PurposeTo determine intrasubject test-retest repeatability of renal MRI measurements.Study typeProspective.PopulationNineteen healthy subjects aged over 40 years.Field strength/sequencesT1 and T2 mapping, R2 * mapping or blood oxygenation level-dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T.AssessmentSubjects were scanned twice with ~1 week between visits. Total scan time was ~1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model.Statistical testTo assess the repeatability, a Bland-Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated.ResultsCoVs for relaxometry (T1 , T2 , R2 */BOLD) were below 6.1%, with the lowest CoVs for T2 maps and highest for R2 */BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP ), with CoVs ranging from 18-24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7-87% (lowest/highest values for medullary mean diffusivity and cortical FP , respectively) and intraclass correlation coefficients (ICCs) ranged from -0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively).Data conclusionCoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology.Level of evidence2 TECHNICAL EFFICACY: Stage 1.

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Characterization of regional left ventricular function in nonhuman primates using magnetic resonance imaging biomarkers: a test-retest repeatability and inter-subject variability study.

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