Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits.

AIMS: Cytoplasmic dynein heavy chain (DYNC1H1) is a multi-subunit protein complex that provides motor force for movement of cargo on microtubules and traffics them back to the soma. In humans, mutations along the DYNC1H1 gene result in intellectual disabilities, cognitive delays, and neurologic and motor deficits. The aim of the study was to generate a mouse model to a newly identified de novo heterozygous DYNC1H1 mutation, within a functional ATPase domain (c9052C > T(P3018S)), identified in a child with motor deficits, and intellectual disabilities. RESULTS: P3018S heterozygous (HET) knockin mice are viable; homozygotes are lethal. Metabolic and EchoMRI™ testing show that HET mice have a higher metabolic rate, are more active, and have less body fat compared to wildtype mice. Neurobehavioral studies show that HET mice perform worse when traversing elevated balance beams, and on the negative geotaxis test. Immunofluorescent staining shows neuronal migration abnormalities in the dorsal and lateral neocortex with heterotopia in layer I. Neuron-subtype specific transcription factors CUX1 and CTGF identified PI+ neurons from layers II/III and VI respectively in cortical layer I, and abnormal pyramidal neurons with MAP2+ dendrites projecting downward from the pial surface. CONCLUSION: The HET mice are a good model for the motor deficits seen in the child, and highlights the importance of cytoplasmic dynein in the maintenance of cortical function and dendritic orientation relative to the pial surface. Our results are discussed in the context of other dynein mutant mice and in relation to clinical presentation in humans with DYNC1H1 mutations.

The importance of speckle tracking echocardiography in the evaluation of cardiac functions in patients with rheumatoid arthritis.

Objectives: In this study, we aimed to analyze the layer-specific strain values obtained by speckle tracking echocardiography (STE) method in the determination of subclinical cardiac dysfunction in rheumatoid arthritis (RA) patients. Patients and methods: Between February 2019 and October 2019, a total of 63 female RA patients (mean age: 51.82±6.07 years; range, 40 and 65 years) who had a confirmed diagnosis were included. Thirty-one age-matched female healthy individuals (mean age: 50.71±5.37 years; range, 40 and 65 years) were selected as the control group. The patients were divided into three groups according to the duration of disease as <5 years, 5-10 years and >10 years. The Disease Activity Score in 28 joint - C-reactive protein (CRP) was used to determine disease activation. The standard assessment included complete serum CRP, anti-cyclic citrullinated peptide, rheumatoid factor, N-terminal pro B-type natriuretic peptide (NT-proBNP), and homocysteine. Global longitudinal strain (GLS) analysis was performed with STE. Results: The NT-proBNP values were found to be higher in RA patients compared to the control group (p=0.044). In terms of conventional echocardiographic parameters, a significant difference between E/A and E/E' ratios was observed (p<0.001 and p=0.015). Endocardium, transmural, and epicardium GLS values obtained by STE were found to be lower in RA patients (p<0.05). The left ventricular (LV) GLS values worsened, as the duration of disease increased (p<0.05). There was a significant correlation between RA disease activity and LV GLS values, showing that increasing levels of disease activity was associated with worse LV GLS (r=0.583, p<0.01 and r=0.681, p<0.01 and r=0.689, p<0.01 for endocardium, transmural and epicardium, respectively). Conclusion: Our study results suggest that the layer-specific GLS values obtained by STE decrease in RA patients.

Description of the Two-Dimensional Layer-Specific Strain Echocardiography Phenotype of Arrhythmogenic Left Ventricular Cardiomyopathy.

BACKGROUND: Arrhythmogenic left ventricular cardiomyopathy (ALVC) is characterized by fibrofatty myocardial replacement demonstrated on cardiac magnetic resonance by late gadolinium enhancement (LGE) mainly involving the subepicardium. The aims of this study were to describe the layer-specific strain (LSS) echocardiography phenotype of ALVC and to compare it with LGE features. METHODS: All consecutive ALVC pathogenic genetic variant carriers and noncarrier relatives were separated into four prespecified groups (overt ALVC [group 1], isolated LGE [group 2], pathogenic genetic variant carrier without ALVC phenotype [group 3], and no genetic variant carrier [group 4]) and studied accordingly using cardiac magnetic resonance and LSS echocardiography. RESULTS: Eighty-five individuals were included. Endocardial global longitudinal strain (GLS)-epicardial GLS (GLSepi) gradient was altered predominantly in group 1, illustrating transmural strain alteration in overt ALVC (3.8 ± 1.1 in group 1, 4.3 ± 2.2 in group 2, 5.2 ± 1.2 in group 3, and 5.4 ± 1.6 in group 4; P = .0017), whereas GLSepi was impaired predominantly in group 2 (endocardial GLS and GLSepi were 15.0 ± 4.1% and 11.2 ± 3.3%, respectively, in group 1; 20.5 ± 2.8% and 16.2 ± 5.5% in group 2; 23.4 ± 3.3% and 18.2 ± 2.7% in group 3; and 24.6 ± 2.8% and 19.2 ± 1.9% in group 4; P < .0001 for all). GLSepi was able to detect subepicardial LGE in genetic variant carriers without overt ALVC with an area under curve of 0.84 (95% CI, 0.73-0.95). However, segmental epicardial and endocardial strain behaved similarly and showed comparable diagnostic values for segmental LGE detection (areas under the curve, 0.72; [95% CI, 0.69-0.76] and 0.73 [95% CI, 0.70-0.76], respectively, P = .40). CONCLUSIONS: LSS alteration in ALVC progresses from the epicardium to the endocardium along with disease severity. Irrespective of LSS analysis, which did not provide incremental diagnostic value for the detection and localization of LGE, strain echocardiography was shown to be a potential surrogate marker of LGE, including in apparently healthy individuals with isolated LV fibrosis.

Incremental value of myocardial global longitudinal strain in predicting major adverse cardiac events among patients with hypertrophic cardiomyopathy.

OBJECTIVES: Endocardial global longitudinal strain (endo-GLS) measured with echocardiography (echo) has been demonstrated to be associated with myocardial fibrosis (MF) and is a prognostic predictor in patients with hypertrophic cardiomyopathy (HCM). Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging showed that MF is primarily located in the myocardial layer of the extremely hypertrophic septal or ventricular wall. We hypothesized that GLS of the myocardial layer (myo-GLS) is more strongly correlated with the extent of LGE (%LGE) and is a more powerful prognostic factor than endo-GLS. METHODS: A total of 177 inpatients (54.0 [IQR: 43.0, 64.0] years, female 37.3%) with HCM were retrospectively included from May 2019 to April 2021. Among them, 162 patients underwent echocardiographic examination and contrast-enhanced CMR within 7 days. Myo-GLS and %LGE were blindly assessed in a core laboratory. All the patients were followed after they were discharged. RESULTS: During a mean follow-up of 33.77 [IQR 30.05, 35.40] months, 14 participants (7.91%) experienced major adverse cardiac events (MACE). The MACE (+) group showed lower absolute endo-GLS and myo-GLS than the MACE (-) group. Myo-GLS was more associated with %LGE (r = -.68, P < .001) than endo-GLS (r = -.64, P < .001). Cox multivariable analysis indicated that absolute myo-GLS was independently associated with MACE (adjusted hazard ratio = .75, P < .05). Myo-GLS was better than endo-GLS at detecting MACE (+) patients (-8.64%, AUC .939 vs. - 16.375%, AUC .898, P < .05). CONCLUSIONS: Myo-GLS is a stronger predictor of MACE than endo-GLS in patients with HCM and is highly correlated with %LGE.

Evaluation of the Left Ventricular Myocardium Using Layer-Specific Strain Analysis in Adolescent Athletes Performing High-Intensity Interval Training.

High-intensity interval training (HIIT) has been demonstrated to be an efficient way of improving physical performance in adolescent athletes compared to conventional training modalities. The objective of this study was to evaluate the impact of HIIT on the myocardial function of adolescent athletes, specifically focusing on left ventricular (LV) function, using conventional echocardiography and layer-specific strain (LSS) analysis. A total of 19 male adolescent athletes (with mean age of 16.83 ± 1.29 years) participating in various football clubs were recruited for this study. During the course of 8 weeks, these adolescent male athletes engaged in HIIT program centered around running. Upon completion of HIIT program, a treadmill exercise test was conducted. Subsequently, conventional and LSS echocardiography were conducted to acquire the evaluation of LV myocardial function. Interventricular septum thickness and ventricular mass index were significantly increased post high-intensity interval training (p < 0.005). After the HIIT, the treadmill exercise test demonstrated a significant increase in test duration and metabolic equivalent compared to the pre-training values (p < 0.005). Post high-intensity interval training, LSS analysis revealed significantly improved LV circumferential strain values in the basal and mid-segments of the left ventricle when compared to the pre-training measurements (p < 0.005). The implementation of high-intensity interval training led to an enhancement of circumferential LSS in the LV, indicating a favorable physiological adaptation and improved efficiency of the myocardium.

Submillimeter fMRI Acquisition Techniques for Detection of Laminar and Columnar Level Brain Activation.

Since the first demonstration in the early 1990s, functional MRI (fMRI) has emerged as one of the most powerful, noninvasive neuroimaging tools to probe brain functions. Subsequently, fMRI techniques have advanced remarkably, enabling the acquisition of functional signals with a submillimeter voxel size. This innovation has opened the possibility of investigating subcortical neural activities with respect to the cortical depths or cortical columns. For this purpose, numerous previous works have endeavored to design suitable functional contrast mechanisms and dedicated imaging techniques. Depending on the choice of the functional contrast, functional signals can be detected with high sensitivity or with improved spatial specificity to the actual activation site, and the pertaining issues have been discussed in a number of earlier works. This review paper primarily aims to provide an overview of the subcortical fMRI techniques that allow the acquisition of functional signals with a submillimeter resolution. Here, the advantages and disadvantages of the imaging techniques will be described and compared. We also summarize supplementary imaging techniques that assist in the analysis of the subcortical brain activation for more accurate mapping with reduced geometric deformation. This review suggests that there is no single universally accepted method as the gold standard for subcortical fMRI. Instead, the functional contrast and the corresponding readout imaging technique should be carefully determined depending on the purpose of the study. Due to the technical limitations of current fMRI techniques, most subcortical fMRI studies have only targeted partial brain regions. As a future prospect, the spatiotemporal resolution of fMRI will be pushed to satisfy the community's need for a deeper understanding of whole-brain functions and the underlying connectivity in order to achieve the ultimate goal of a time-resolved and layer-specific spatial scale. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Layer-specific strain in patients with cardiac amyloidosis using tissue tracking MR.

Background: Cardiac infiltration is the major predictor of poor prognosis in patients with systemic amyloidosis, thus it becomes of great importance to evaluate cardiac involvement. Purpose: We aimed to evaluate left ventricular myocardial deformation alteration in patients with cardiac amyloidosis (CA) using layer-specific tissue tracking MR. Material and Methods: Thirty-nine patients with CA were enrolled. Thirty-nine normal controls were also recruited. Layer-specific tissue tracking analysis was done based on cine MR images. Results: Compared with the control group, a significant reduction in LV whole layer strain values (GLS, GCS, and GRS) and layer-specific strain values was found in patients with CA (all P < 0.01). In addition, GRS and GLS, as well as subendocardial and subepicardial GLS, GRS, and GCS, were all diminished in patients with CA and reduced LVEF, when compared to those with preserved or mid-range LVEF (all P < 0.05). GCS showed the largest AUC (0.9952, P = 0.0001) with a sensitivity of 93.1% and specificity of 90% to predict reduced LVEF (<40%). Moreover, GCS was the only independent predictor of LV systolic dysfunction (Odds Ratio: 3.30, 95% CI:1.341-8.12, and P = 0.009). Conclusion: Layer-specific tissue tracking MR could be a useful method to assess left ventricular myocardial deformation in patients with CA.

Quantitative evaluation of myocardial layer-specific strain using two-dimensional speckle tracking echocardiography in septic patients.

BACKGROUND: Although global longitudinal strain (GLS) is proven to be reduced and associated with adverse outcomes in septic patients, it has not been elucidated whether or not layer-specific strains are reduced. We aimed to explore the layer-specific strains of left ventricular (LV) for assessing myocardial dysfunction in septic patients. METHODS: A prospective observational study of patients with sepsis was conducted in a tertiary hospital in China. Routine two-dimensional speckle tracking echocardiography was performed within 24 h of enrollment. Demographic data, laboratory values, and clinical outcomes were collected. RESULTS: We recruited 79 septic patients finally. The mean age of septic patients was 59.4 years old and 45 (57.0%) were male. The median Acute Physiology Age and Chronic Health Evaluation (APACHE II) score, and mean sequential organ failure assessment (SOFA) score of all patients were 19.0 and 7.7, respectively. According to the left ventricular ejection fraction (LVEF) value of 50%, the patients were categorized into two groups: SICM (sepsis-induced cardiomyopathy, LVEF < 50%, n = 22) and non-SICM group ( LVEF ≥ 50%, n = 57). The median LVEF of SICM and non-SICM patients were 41.9% and 58.7%, and SICM patients had less negative layer-specific strain and global strain than that of non-SICM patients. The echocardiographic comparison of non-SICM and healthy controls was conducted to explore the myocardial injuries of non-SICM patients and the non-SICM had worse LS-epi than that of controls (-18.5% vs. -21.4%, p = 0.024). CONCLUSION: There were 72.2% (57) septic patients presented with non-SICM (LVEF ≥ 50%), and the strain value of epicardium of them was less negative than healthy controls.

Evaluation of left ventricular function of pregnant women with autoimmune diseases using speckle tracking echocardiography.

Pregnancy can cause fluctuations in autoimmune diseases (AD) women, which may aggravate the cardiac damage. Maternal heart function is very important for maternal and fetal health. Therefore, early and accurate evaluation of the heart function of AD pregnant women is necessary. This study was aimed to evaluate the left ventricular (LV) function of AD pregnant women using two-dimensional speckle tracking echocardiography (2DSTE). A total of 96 subjects, including 26 non-pregnant AD patients (AD group), 33 AD pregnant women (AD-P group), and 37 healthy pregnant women (H-P group) were conducted. Baseline clinical and conventional echocardiography characteristics of all the subjects were collected. The 2DSTE was performed to acquire layer-specific strain parameters of LV. Compared with H-P group, AD-P group showed no significant differences in GLSmid and GLSepi. However, the GLSendo (24.10 [22.30 to 25.40] vs. 21.70 [19.05 to 25.15], P = 0.023) and ΔGLS (5.50 [4.80 to 6.00] vs. 4.90 [4.20 to 5.80], P = 0.017) were decreased, while the PSD (27 [23 to 32] vs. 32 [24 to 44], P = 0.014) was increased. At the segmental level, there was no significant difference in apex LSmid and LSepi between the two groups, while the AD-P group showed transmural dysfunction in basal and middle segments, and the LSendo in apex segments (32.84 [28.34 to 34.25] vs. 27.97 [21.87 to 33.61], P = 0.021) were significantly decreased. Compared with AD group, AD-P group showed no significant difference in ΔGLS, PSD, and GLS parameters of three layers. For the segmental level, there were no significant differences in the LSepi of the apex segment and the LS in three layers of the basal and middle segments between the two groups, while LSendo (32.69 [29.13 to 35.53] vs. 27.97 [21.87 to 33.60], P = 0.017) and LSmid (24.70 [22.24 to 27.78] vs. 21.32 [16.91 to 26.11], P = 0.023) in apex segments were significantly lower in AD-P group. The anti-SSA/Ro antibody were positive independently correlated with PSD. In conclusion, layer-specific strain parameters and PSD by 2DSTE provide an accurate and reproducible measurement of myocardial function. There are subclinical LV myocardial dysfunction in AD pregnant women. Besides, the positive of anti-SSA/Ro antibody maybe associated with LV myocardial dysfunction.

The clinical application of longitudinal layer specific strain as a diagnostic and prognostic instrument in ischemic heart diseases: A systematic review and meta-analysis.

Background: 2-dimensional Speckle-Tracking Echocardiography, to obtain longitudinal layer specific strain (LSS), has recently emerged as a novel and accurate non-invasive imaging technique for diagnosis as well as for prediction of adverse cardiac events. This systematic review and meta-analysis aimed to give an overview of the possible clinical implication and significance of longitudinal LSS. Methods: We conducted a systematic review and meta-analysis with all the studies involving layer specific strain in patients with ischemic heart disease (IHD). Of 40 eligible studies, 9 met our inclusion criteria. Studies that were included either investigated the prognostic value (n = 3) or the diagnostic value (n = 6) of longitudinal LSS. Results: The pooled meta-analysis showed that longitudinal LSS is a significant diagnostic marker for coronary artery disease (CAD) in patients with IHD. Endocardial LSS was found to be a good diagnostic marker for CAD in IHD patients (OR: 1.28, CI95% [1.11-1.48], p < 0.001, per 1% decrease). Epicardial (OR: 1.34, CI95% [1.14-1.56], p < 0.001, per 1% decrease), Mid-Myocardial (OR: 1.24, CI95% [1.12-1.38], p < 0.001, per 1% decrease) and endocardial (OR: 1.21, CI95% [1.09-1.35], p < 0.001, per 1% decrease) LSS all entailed diagnostic information regarding CAD, with epicardial LSS emerging as the superior diagnostic marker for CAD in patients with SAP. Endocardial LSS proved to be the better diagnostic marker of CAD in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). LSS was shown to be a good prognostic maker of adverse cardiac events in IHD patients. Two studies found endocardial circumferential strain to be the good predictor of outcome in CAD patients and when added to baseline characteristics. Epicardial LSS emerged as best predictor in acute coronary syndrome (ACS) patients. Conclusion: In patients with SAP, epicardial LSS was the stronger diagnostic marker while in NSTE-ACS patients, endocardial LSS was the stronger diagnostic marker. In addition, endocardial circumferential strain is the better predictor of adverse outcome in CAD patients whilst in ACS patients, epicardial LSS was found to be a better predictor of outcome.

Evaluation of Left Ventricular Systolic Function Using Layer-Specific Strain in Rats Performing Endurance Exercise: A Pilot Study.

OBJECTIVE: The functional characteristics of exercise-induced myocardial hypertrophy were studied in a rat model in conjunction with ultrasound layered strain technique to investigate the hidden changes in the heart brought about by exercise. METHODS: Forty specific pathogen free (SPF) adult Sprague-Dawley rats were selected and randomly divided into two groups of 20 exercise and 20 control rats. The longitudinal and circumferential strain parameters were measured using the ultrasonic stratified strain technique. The differences between the two groups and the predictive effect of stratified strain parameters on left ventricular systolic function were analyzed. RESULTS: The exercise group had significantly higher global endocardial myocardial longitudinal strain (GLSendo), global mid-myocardial global longitudinal strain (GLSmid) and global endocardial myocardial global longitudinal strain (GCSendo) values than the control group (p < 0.05). Even though global mid-myocardial circumferential strain (GCSmid) and global epicardial myocardial circumferential strain (GCSepi) were higher in the exercise group than in the control group, statistical significance was not reached (p > 0.05). Conventional echocardiography parameters were well correlated with GLSendo, GLSmid, and GCSendo (p < 0.05). GLSendo was the best predictor of left ventricular myocardial contractile performance in athletes determined using the receiver operating characteristic curve, with an area under the curve of 0.97, sensitivity of 95% and specificity of 90%. CONCLUSION: Rats performing endurance exercise exhibited subclinical changes in the heart after prolonged high-intensity exercise. A stratified strain parameter, GLSendo, played an important role in the evaluation of LV systolic performance in exercising rats.

Novel Findings of Early Cardiac Dysfunction in Patients With Childhood-Onset Inflammatory Bowel Disease Using Layer-Specific Strain Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at a higher risk of developing cardiovascular diseases than healthy individuals, owing to persistent chronic inflammation and treatment effects. This study aimed to assess left ventricular function in patients with childhood-onset IBD using layer-specific strain analysis and to identify early indicators of cardiac dysfunction in them. METHODS: A total of 47 patients with childhood-onset ulcerative colitis (UC), 20 patients with Crohn's disease (CD), and 75 age- and sex-matched healthy control subjects were included in this study. Conventional echocardiographic measurements of layer-specific (ie, endocardium, midmyocardium, and epicardium) global longitudinal strain and global circumferential strain (GCS) were evaluated in these participants. RESULTS: Layer-specific strain analysis showed that global longitudinal strain was lower in all layers for the UC (P < .001) and CD (P < .001) groups, regardless of the age at onset, but that GCS was only lower in the midmyocardial (P = .032) and epicardial (P = .018) layers in the CD group than in the control group. Although the mean left ventricular wall thickness was not significantly different among the groups, it was significantly correlated with the GCS of the endocardial layer in the CD group (ρ= -0.615; P = .004), suggesting that thickening of the left ventricular wall occurred as a compensatory mechanism to maintain the endocardial strain in the CD group layer. CONCLUSIONS: Children and young adults with childhood-onset IBD displayed decreased midmyocardial deformation. Layer-specific strain could also be useful to identify indicators of cardiac dysfunction in patients with IBD.

Patients with inflammatory bowel disease are at a higher risk of developing cardiovascular disease than healthy individuals. Our study revealed that children and young adults with childhood-onset inflammatory bowel disease already have reduced myocardial deformability.

Tri-layered constitutive modelling unveils functional differences between the pig ascending and lower thoracic aorta.

The arterial wall's tri-layered macroscopic and layer-specific microscopic structure determine its mechanical properties, which vary at different arterial locations. Combining layer-specific mechanical data and tri-layered modelling, this study aimed to characterise functional differences between the pig ascending (AA) and lower thoracic aorta (LTA). AA and LTA segments were obtained for n=9 pigs. For each location, circumferentially and axially oriented intact wall and isolated layer strips were tested uniaxially and the layer-specific mechanical response modelled using a hyperelastic strain energy function. Then, layer-specific constitutive relations and intact wall mechanical data were combined to develop a tri-layered model of an AA and LTA cylindrical vessel, accounting for the layer-specific residual stresses. AA and LTA behaviours were then characterised for in vivo pressure ranges while stretched axially to in vivo length. The media dominated the AA response, bearing>2/3 of the circumferential load both at physiological (100 mmHg) and hypertensive pressures (160 mmHg). The LTA media bore most of the circumferential load at physiological pressure only (57±7% at 100 mmHg), while adventitia and media load bearings were comparable at 160 mmHg. Furthermore, increased axial elongation affected the media/adventitia load-bearing only at the LTA. The pig AA and LTA presented strong functional differences, likely reflecting their different roles in the circulation. The media-dominated compliant and anisotropic AA stores large amounts of elastic energy in response to both circumferential and axial deformations, which maximises diastolic recoiling function. This function is reduced at the LTA, where the adventitia shields the artery against supra-physiological circumferential and axial loads.

Evaluation of subclinical left ventricular systolic dysfunction in patients with acute-phase Kawasaki disease by hematological indices, layer-specific left ventricular longitudinal strain and global myocardial work.

PURPOSE: To evaluate subclinical LV systolic dysfunction in aKD patients by hematological indices, global layer-specific LV longitudinal strain and myocardial work (MW). METHODS: Forty-three normal controls and 42 aKD patients were enrolled in the present study. The peak systolic epimyocardial (GLSEpi), middle layer (GLSMid) and endomyocardial (GLSEndo) longitudinal strain, global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial work efficiency (GWE) were measured by two-dimensional speckle-tracking echocardiography in apical three-chamber, four-chamber, and two-chamber views. RESULTS: The absolute values of GLSEpi, GLSMid, and GLSEndo in aKD patients were significantly lower than those in normal controls (p < .01). The values of GCW and GWE were significantly lower than those of normal controls (p < .05). There were no significant differences among the AUCs of layer-specific LV GLS and global MW (p > .05). The correlation test showed that layer-specific LV GLS showed a good correlation with GCW. Multivariable analysis showed that Hb and LVEF were independent factors for GCW. CONCLUSION: In this research, we found that subclinical LV systolic dysfunction was detected by layer-specific GLS and MW in aKD patients. GCW has the same diagnostic value as layer-specific LV GLS. Hb and LVEF are independent factors of LV myocardial function.

Layer-specific correlates of detected and undetected auditory targets during attention.

In everyday life, the processing of acoustic information allows us to react to subtle changes in the auditory scene. Yet even when closely attending to sounds in the context of a task, we occasionally miss task-relevant features. The neural computations that underlie our ability to detect behavioral relevant sound changes are thought to be grounded in both feedforward and feedback processes within the auditory hierarchy. Here, we assessed the role of feedforward and feedback contributions in primary and non-primary auditory areas during behavioral detection of target sounds using submillimeter spatial resolution functional magnetic resonance imaging (fMRI) at high-fields (7 T) in humans. We demonstrate that the successful detection of subtle temporal shifts in target sounds leads to a selective increase of activation in superficial layers of primary auditory cortex (PAC). These results indicate that feedback signals reaching as far back as PAC may be relevant to the detection of targets in the auditory scene.

MicroRNA-218 regulates neuronal radial migration and morphogenesis by targeting Satb2 in developing neocortex.

Neuronal migration and morphogenesis are fundamental processes for cortical development. Their defects may cause abnormities in neural circuit formation and even neuropsychiatric disorders. Many proteins, especially layer-specific transcription factors and adhesion molecules, have been reported to regulate the processes. However, the involvement of non-coding RNAs in cortical development has not been extensively studied. Here, we identified microRNA-218 (miR-218) as a layer V-specific microRNA in mouse brains. Expression of miR-218 was elevated in patients with autism spectrum disorder (ASD) and schizophrenia. We found in this study that miR-218 overexpression in developing mouse cortex led to severe defects in radial migration, morphogenesis, and spatial distribution of the cortical neurons. Moreover, we identified Satb2, an upper-layer marker, as a molecular target repressed by miR-218. These results suggest an underlying mechanism of miR-218 involvement in neuropsychiatric disorders, and the interactions of layer-specific non-coding RNAs and proteins in regulating cortical development.

Measurement of Layer-Specific Mechanical Properties of Intact Blood Vessels Based on Intravascular Optical Coherence Tomography.

PURPOSE: The biomechanical analysis of stress and strain state of multilayered blood vessels has shown great importance in vascular pathology and physiology. However, there is a lack of method in measuring the mechanical property of each layer of a vascular sample without splitting up the wall. METHODS: Here we develop a vascular inflation test method based on intravascular optical coherence tomography (IVOCT) imaging and inverse parametric estimation. We propose a three-step inverse parametric estimation method to solve the six constitutive parameters of the GOH models for the intima-media and adventitia of the coronaries simultaneously. A bilayer silicone vascular phantom inflation test and a virtual deformation test using finite element simulated data are conducted to evaluate the accuracy of the proposed method. RESULTS: The virtual deformation test demonstrates that the errors of the constitutive constants are less than 2.56% determined by the proposed inverse parametric estimation method. The stress-strain curves of a bilayer silicone vascular phantom obtained based on the parameters determined by the proposed method match well with those obtained by the uniaxial test. CONCLUSION: The proposed layer-specific vascular mechanical property measurement method provides a new experimental method for mechanical properties characterization of blood vessels. It also has the potential to be used for patient-specific mechanical properties estimation with IVOCT imaging in vivo.

Evaluation of left ventricular function in ischemia with non-obstructive coronary arteries: a research based on adenosine stress myocardial contrast echocardiography.

Patients with ischemia with non-obstructive coronary arteries (INOCA) have an increased risk of adverse cardiovascular events in the future, which is widespread but underdiagnosed. The purpose of this study is to explore the application value of adenosine stress myocardial contrast echocardiography (ASMCE) in INOCA disease, so that clinicians can early identify and intervene patients with left ventricular function subclinical impairment in INOCA. We enrolled 118 patients with INOCA by ASMCE and invasive coronary angiography (ICA), 97 of whom had complete data. The study population was divided into two subgroups depending on coronary flow velocity reserve (CFVR): impaired CFVR group (n = 34) and normal CFVR group (n = 63). Global longitudinal strain endocardial myocardial (GLSendo), mid-myocardial (GLSmid) and epicardial myocardial (GLSepi) increased after stress in both groups; transmural strain, wall motion scored index (WMSI) and myocardial perfusion scored index (MPSI) increased and FORCE decreased in impaired CFVR group after stress, but there was no difference in normal group before and after stress. There was no significant difference in left ventricular myocardial mechanical parameters, including ΔGLSendo, ΔGLSmid, ΔGLSepi, GLSendo-epi Reserve, Δpeak strain dispersion (PSD), PSD Reserve between the two groups, but ΔEF, strain reserve and left ventricular contractile reserve (LVCR) in the impaired CFVR group were lower than those in the normal CFVR group, while ΔWMSI and ΔMPSI were increased. CFVR can be a clinically valuable indicator in the ASMCE diagnosis of patients with microvascular angina pectoris in INOCA. In the evaluation of left ventricular function in INOCA patients, attention should be paid not only to myocardial deformation, but also to the dynamic changes of LVCR and myocardial perfusion during peak hyperemia.

The evaluation of coronary microvascular obstruction in patients with STEMI by cardiac magnetic resonance T2-STIR image and layer-specific analysis of 2-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography.

This study was designed to assess coronary microvascular obstruction (MVO) in patients with acute ST-segment elevation myocardial infarction (STEMI) by cardiac magnetic resonance T2-weighted short tau inversion recovery (T2-STIR) image and layer-specific analysis of 2-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography (LDDSE-LS2D-STE). 32 patients were enrolled to perform cardiac magnetic resonance and echocardiography 5-7 days after primary percutaneous coronary intervention. Infarcted myocardium was categorized into MVO+ group and MVO- group by late gadolinium enhancement as gold standard. At T2-weighted image, the area of hyper-intense region and hypo-intense core inside were marked as A1, A2 and A2/A1 > 0 represented MVO. Strain parameters were composed of longitudinal strain (LS), circumferential strain and radial strain at rest and dobutamine stress. There were 94 MVO+ segments, 136 MVO- segments according to gold standard. 96 segments had hypo-intense core at T2-STIR image. The sensitivity and specificity of T2-STIR in detecting MVO were 91.49 and 92.65%. Endocardial LS was superior to other parameters, and stress endocardial LS was higher than that of resting endocardial LS (sensitivity: 77.11% vs 72.29%, specificity: 93.28% vs 83.19%, AUC: 0.87 vs 0.82, P < 0.05). The combination of T2-STIR and stress endocardial LS in parallel test could improve sensitivity significantly (98.05% vs 91.49%). T2-STIR has higher diagnostic value in detecting MVO with some limitations. However, LDDSE-LS2D-STE with cost-effective and handling may be a good alternative to T2-STIR. It provides additional and reliable diagnostic tools to identify MVO in STEMI patients after reperfusion.

Usefulness of layer-specific strain for evaluating and predicting recovery of left ventricular myocardial function in patients undergoing hybrid coronary revascularization.

PURPOSE: This study aimed to determine if layer-specific strain (LSS) can be used to evaluate and predict left ventricular (LV) recovery in patients with multi-vessel coronary artery disease (CAD) undergoing hybrid coronary revascularization (HCR) using speckle tracking echocardiography (STE). METHODS: A total of 187 consecutive CAD patients who received HCR in our hospital were prospectively enrolled. 30 healthy individuals with matched age and gender were enrolled as a control group. Echocardiography was performed for CAD patients before and 1, 2, and 6 months after HCR. Comprehensive conventional and LSS echocardiography parameters were collected. LV recovery was defined as improvement in LV ejection fraction (LVEF) > 5% at 6-months follow-up compared with baseline. Logistic regression analysis was used to test the correlates of LV recovery. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of correlates for predicting LV recovery. RESULTS: LVEF and LV strain in CAD patients were significantly decreased compared with control subjects. Endocardial global longitudinal strain (Endo-GLS) improved significantly at 1-month follow-up (14.2 ± 1.6% vs. 13.8 ± 1.5%, P < 0.05), and LVGLS and global circumferential strain (GCS) improved significantly at 2-months follow-up. Multivariate regression revealed that Endo-GLS, GLS, and SYNTAX score before HCR were independently correlated to LV recovery. Endo-GLS had an optimal cutoff value of 13.2% for predicting LV recovery with sensitivity of 91% and specificity of 78%. CONCLUSION: LV myocardial systolic function in CAD patients was impaired before HCR and significantly improved after HCR. Endo-GLS was independently correlated to and has optimal predictive value for LV recovery.