Improving the replicability of neuroimaging findings by thresholding effect sizes instead of p‐values

The classical approach for testing statistical images using spatial extent inference (SEI) thresholds the statistical image based on the p‐value. This approach has an unfortunate consequence on the replicability of neuroimaging findings because the targeted brain regions are affected by the sample size—larger studies have more power to detect smaller effects. Here, we use simulations based on the preprocessed Autism Brain Imaging Data Exchange (ABIDE) to show that thresholding statistical images by effect sizes has more consistent estimates of activated regions across studies than thresholding by p‐values. Using a constant effect size threshold means that the p‐value threshold naturally scales with the sample size to ensure that the target set is similar across repetitions of the study that use different sample sizes. As a consequence of thresholding by the effect size, the type 1 and type 2 error rates go to zero as the sample size gets larger. We use a newly proposed robust effect size index that is defined for an arbitrary statistical image so that effect size thresholding can be used regardless of the test statistic or model.     

Abnormalities of intrinsic brain activity in essential tremor: A meta‐analysis of resting‐state functional imaging

Neuroimaging studies using a variety of techniques have demonstrated abnormal patterns of spontaneous brain activity in patients with essential tremor (ET). However, the findings are variable and inconsistent, hindering understanding of underlying neuropathology. We conducted a meta‐analysis of whole‐brain resting‐state functional neuroimaging studies in ET compared to healthy controls (HC), using anisotropic effect‐size seed‐based d mapping, to identify the most consistent brain activity alterations and their relation to clinical features. After systematic literature search, we included 13 studies reporting 14 comparisons, describing 286 ET patients and 254 HC. Subgroup analyses were conducted considering medication status, head tremor status, and methodological factors. Brain activity in ET is altered not only in the cerebellum and cerebral motor cortex, but also in nonmotor cortical regions including prefrontal cortex and insula. Most of the results remained unchanged in subgroup analyses of patients with head tremor, medication‐naive patients, studies with statistical threshold correction, and the large subgroup of studies using functional magnetic resonance imaging. These findings not only show consistent and robust abnormalities in specific brain regions but also provide new information on the biology of patient heterogeneity, and thus help to elucidate the pathophysiology of ET.     

Direct Impact of Motor Cortical Stimulation on the Blood Oxygen-level Dependent Response in Rats

Purpose:Neuropathic pain is a complex and distressing chronic illness in modern medicine. Since 1990s, motor cortex stimulation (MCS) has emerged as a potential treatment for chronic neuropathic pain; however, the precise mechanisms underlying analgesia induced by MCS are not completely understood. The purpose of the present study was to investigate the blood oxygen-level dependent (BOLD) response in the brain during MCS.Methods:We inserted a bipolar tungsten electrode into the primary motor cortex (M1) of adult male Wistar rats. Functional magnetic resonance imaging (fMRI) scans were implemented simultaneously with the electrical stimulation of M1 and the BOLD signals taken from the fMRI were used as an index to reflect the response against MCS.Results:Our results demonstrated that the bilateral M1, ipsilateral caudate-putamen, and ipsilateral primary somatosensory cortex to the stimulation spot were activated after the onset of MCS. The BOLD signal time courses were analysed in these regions and similar temporal characteristics were found.Conclusion:By conducting direct cortical stimulation of the rodent brain to investigate its instant effect using fMRI, we identified encephalic regions directly involved in the instant motor cortical stimulation effects in healthy rat models. This result may be essential in establishing a foundation for further research on the underlying neuropathways associated with the MCS effects.     

Cell refractive index: Models,insights, applications and future perspectives

Cell refractive index (RI) is an intrinsic optical parameter that governs the propagation of light (i.e., scattering and absorption) in the cell matrix. The RI of cell is sensitively correlated with its mass distribution and thereby has the capability to provide important insights for diverse biological models. Herein, we review the cell refractive index and the fundamental models for measurement of cell RI, summarize the published RI data of cell and cell organelles and discuss the associated insights. Illustrative applications of cell RI in cell biology are also outlined. Finally, future research trends and applications of cell RI, including novel imaging techniques, reshaping flow cytometry and microfluidic platforms for single cell manipulation are discussed. The rapid technological advances in optical imaging integrated with microfluidic regime seems to enable deeper understanding of subcellular dynamics with high spatio-temporal resolution in real time.     

Is choroidal vascularity index a useful marker in different stages of idiopathic epiretinal membranes?

BackgroundThis study aims to evaluate the choroidal vascularity index in patients with idiopathic epiretinal membrane at different stages.MethodsThis prospective study included 125 eyes of 125 patients with idiopathic epiretinal membrane and 62 eyes of 62 healthy control subjects. In this study, epiretinal membrane stages were defined based on the spectral-domain optical coherence tomography staging system. The choroidal vascularity index was measured as the ratio of the luminal area to the stromal area in the central 1500 μm after binarization on enhanced depth imaging optical coherence tomography images. Data on epiretinal membrane stages, choroidal vascularity index, and best-corrected visual acuity were noted.ResultsOf 125 eyes with epiretinal membrane, 38 (30.4 %) had stage 1, 32 (25.6 %) had stage 2, and 55 (44 %) had stage 3 disease. Visual acuity was better in eyes with stage 1 or 2 epiretinal membrane than those with stage 3 epiretinal membrane (p < 0.001). The mean choroidal vascularity index was 2.29 ± 1.02 in the control, 2.23 ± 0.98 in the stage 1 epiretinal membrane, 2.22 ± 0.91 in the stage 2 epiretinal membrane, and 2.23 ± 1.11 in the stage 3 epiretinal membrane group. There was no significant difference between epiretinal membrane subgroups and the control group regarding the choroidal vascularity index (p = 0.81).ConclusionFrom the results obtained in the present study, the choroidal vascularity index was not effected by either the development or the progression of idiopathic epiretinal membrane.     

Combined stress myocardial CT perfusion and coronary CT angiography as a feasible strategy among patients presenting with acute chest pain to the emergency department

BackgroundA combined approach of myocardial CT perfusion (CTP) with coronary CT angiography (CTA) was shown to have better diagnostic accuracy than coronary CTA alone. However, data on cost benefits and length of stay when compared to other perfusion imaging modalities has not been evaluated. Therefore, we aim to perform a feasibility study to assess direct costs and length of stay of a combined stress CTP/CTA and use SPECT myocardial perfusion imaging (SPECT-MPI) as a benchmark, among chest pain patients at intermediate-risk for acute coronary syndrome (ACS) presenting to the emergency department (ED).MethodsThis is a prospective two-arm clinical trial (NCT02538861) with 43 patients enrolled in stress CTP/CTA arm (General Electric Revolution CT) and 102 in SPECT-MPI arm. Mean age of the study population was 65 ?± ?12 years; 56% were men. We used multivariable linear regression analysis to compare length of stay and direct costs between the two modalities.ResultsOverall, 9 out of the 43 patients (21%) with CTP/CTA testing had an abnormal test. Of these 9 patients, 7 patients underwent invasive coronary angiography and 6 patients were found to have obstructive coronary artery disease. Normal CTP/CTA test was found in 34 patients (79%), who were discharged home and all patients were free of major adverse cardiac events at 30 days. The mean length of stay was significantly shorter by 28% (mean difference: 14.7 ?h; 95% CI: 0.7, 21) among stress CTP/CTA (20 ?h [IQR: 16, 37]) compared to SPECT-MPI (30 ?h [IQR: 19, 44.5]). Mean direct costs were significantly lower by 44% (mean difference: $1535; 95% CI: 987, 2082) among stress CTA/CTP ($1750 [IQR: 1474, 2114] compared to SPECT-MPI ($2837 [IQR: 2491, 3554]).ConclusionCombined stress CTP/CTA is a feasible strategy for evaluation of chest pain patients presenting to ED at intermediate-risk for ACS and has the potential to lead to shorter length of stay and lower direct costs.     

Altered coupling of cerebral blood flow and functional connectivity strength in visual and higher order cognitive cortices in primary open angle glaucoma

Primary open-angle glaucoma (POAG) has been suggested to be a neurodegenerative disease associated with altered cerebral vascular hemodynamics and widespread disruption of neuronal activity within the visual, working memory, attention and executive networks. We hypothesized that disturbed neurovascular coupling in visual and higher order cognitive cortices exists in POAG patients and correlates with glaucoma stage and visual field defects. Through multimodal magnetic resonance imaging, we evaluated the cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations of the whole gray matter and CBF/FCS ratio per voxel for all subjects. Compared with normal controls, POAG patients showed reduced global CBF-FCS coupling and altered CBF/FCS ratios, predominantly in regions in the visual cortex, salience network, default mode network, and dorsal attentional network. The CBF/FCS ratio was negatively correlated with glaucoma stage, and positively correlated with visual field defects in the lingual gyrus in POAG patients. Moreover, early brain changes were detected in early POAG. These findings indicate neurovascular coupling dysfunction might exist in the visual and higher order cognitive cortices in POAG patients and its clinical relevance. The results may contribute to the monitoring of POAG progression and provide insight into the pathophysiology of the neurodegenerative process in POAG.     

The prediction of body fatness by BMI and skinfold thicknesses among children and adolescents

Background: Although the body mass index (BMI, kg?m^?2) is widely used as a measure of adiposity, it is a measure of excess weight, rather than excess body fat. It has been suggested that skinfold thicknesses be measured among overweight children to confirm the presence of excess adiposity.

Objective: The present study examined the additional information provided by skinfold thicknesses on body fatness, beyond that conveyed by BMI-for-age, among healthy 5- to 18-years old (n?=?1196).

Methods and procedures: Total body dual-energy X-ray absorptiometry (DXA) provided estimates of % body fat, and the sum of two skinfolds (triceps and subscapular) was used as an indicator of the overall skinfold thickness.

Results: As assessed by the multiple R²s and the residuals of various regression models, information on the skinfold sum significantly (?p?<?0.001) improved the prediction of body fatness beyond that obtained with BMI-for-age. For example, the use of the skinfold sum, in addition to BMI-for-age, increased the multiple R²s for predicting % body fat from 0.81 to 0.90 (boys), and from 0.82 to 0.89 (girls). The use of the skinfold sum also reduced the overall prediction errors (absolute value of the residuals) for % body fat by 20–30%, but these reductions varied substantially by BMI-for-age. Among overweight children, defined by a BMI-for-age ≥95th percentile, the skinfold sum reduced the predication errors for % body fat by only 7–9%.

Conclusions: Although skinfold thicknesses, when used in addition to BMI-for-age, can substantially improve the estimation of body fatness, the improvement among overweight children is small.     

Disrupted Intersubject Variability Architecture in Functional Connectomes in Schizophrenia

Schizophrenia (SCZ) is a highly heterogeneous disorder with remarkable intersubject variability in clinical presentations. Previous neuroimaging studies in SCZ have primarily focused on identifying group-averaged differences in the brain connectome between patients and healthy controls (HCs), largely neglecting the intersubject differences among patients. We acquired whole-brain resting-state functional MRI data from 121 SCZ patients and 183 HCs and examined the intersubject variability of the functional connectome (IVFC) in SCZ patients and HCs. Between-group differences were determined using permutation analysis. Then, we evaluated the relationship between IVFC and clinical variables in SCZ. Finally, we used datasets of patients with bipolar disorder (BD) and major depressive disorder (MDD) to assess the specificity of IVFC alteration in SCZ. The whole-brain IVFC pattern in the SCZ group was generally similar to that in HCs. Compared with the HC group, the SCZ group exhibited higher IVFC in the bilateral sensorimotor, visual, auditory, and subcortical regions. Moreover, altered IVFC was negatively correlated with age of onset, illness duration, and Brief Psychiatric Rating Scale scores and positively correlated with clinical heterogeneity. Although the SCZ shared altered IVFC in the visual cortex with BD and MDD, the alterations of IVFC in the sensorimotor, auditory, and subcortical cortices were specific to SCZ. The alterations of whole-brain IVFC in SCZ have potential implications for the understanding of the high clinical heterogeneity of SCZ and the future individualized clinical diagnosis and treatment of this disease.     

Liver steatosis assessment: Correlations among pathology,radiology, clinical data and automated image analysis software

Quantitating hepatic steatosis is important in many liver diseases and liver transplantation. Since steatosis estimation by pathologists has inherent intra- and inter-observer variability, we compared and contrasted computerized techniques with magnetic resonance imaging measurements, pathologist visual scoring, and clinical parameters. Computerized methods applied to whole slide images included a commercial positive pixel count algorithm and a custom algorithm programmed at our institution. For all liver samples (n = 59), including pediatric, adult, frozen section, and permanent specimens, statistically significant correlations were observed between pathology, radiology, and each image analysis modality (r = 0.75–0.97, p < 0.0001), with the strongest correlations in the pediatric cohort. Statistically significant relationships were observed between each method and with body mass index (r = 0.37–0.56, p from <0.0001 to <0.05) and with albumin (r = 0.55–0.64, p < 0.05) but not with alanine aminotransferase or aspartate aminotransferase. Although pathologist assessments correlated (r = 0.64–0.86, 0.92–0.97, and 0.78–0.91 for microvesicular, macrovesicular, and overall steatosis, respectively), the absolute values of hepatic steatosis visual assessment were susceptible to intra- and inter-observer variability, particularly for microvesicular steatosis. Image analysis, pathologist assessments, radiology measurements, and several clinical parameters all showed correlations in this study, providing evidence for the utility of each method in different clinical and research settings.