Phenotyping of myocardial involvement by cardiac magnetic resonance in idiopathic inflammatory myopathies.

OBJECTIVES: Cardiac dysfunction is commonly noted in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the characteristics of cardiac dysfunction using cardiac magnetic resonance (CMR) in polymyositis (PM), dermatomyositis (DM) and necrotising myositis (NM). METHODS: Fifty-one patients with IIMs and 20 matched healthy controls (HCs) were assessed using CMR examination. The clinical data, cardiac serum markers and autoimmune antibodies were determined for all patients. Cardiac involvement was identified by myocardial native T1, extracellular volume (ECV), late gadolinium enhancement (LGE) and left ventricular ejection fraction (LVEF). RESULTS: Different subtypes of IIMs showed different patterns of LGE and varying degrees of myocardial damage. The PM subgroup showed higher native T1 (p = 0.010) and ECV (p = 0.000) than the HCs. The prevalence of LGE was comparable between the PM and DM subgroups (40.0% vs. 31.6%, p = 0.741); however, it was higher in the PM subgroup than in the NM subgroup (40% vs. 0.0%, p = 0.014). Patients with positive LGE in the PM subgroup showed a higher proportion of positive LGE (p = 0.018) and lower LVEF (p = 0.024) than those with positive LGE in the DM subgroup. In multivariate analysis, the presence of LGE could be predicted by increased NT-proBNP (p = 0.036, OR = 1.001) and anti-MDA-5 antibody positivity (p = 0.011, OR = 12.4). The risk factors associated with native T1 were NT-proBNP (p = 0.016, ß = 0.353) and body mass index (BMI) (p = 0.024, ß = - 0.331). CONCLUSIONS: Distinct cardiac involvements in different subtypes of IIMs were identified using CMR. Elevated NT-proBNP and a low BMI were the risk factors associated with LGE and elevated native T1. KEY POINTS: • The characteristics of cardiac involvement in different subtypes of IIMs could be identified with cardiac magnetic resonance. • The NT-proBNP levels could reflect focal and diffuse myocardial damage in patients with IIMs.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in myocardial and skeletal muscles in idiopathic inflammatory cardiomyopathy.

BACKGROUND: Idiopathic inflammatory myopathy (IIM) manifest as systematic muscle involvement. Multiparametric cardiovascular magnetic resonance (CMR) could be a useful technique to detect systemic involvement and disease progression in IIM patients. This study aimed to describe the tissue characteristics and dynamic changes in myocardial and skeletal muscles after treatment in IIM patients. METHODS: Forty-four consecutively recruited IIM patients (49.0 ± 12.0 years; 22 males) underwent 3 T CMR at first diagnosis, and 28 patients underwent follow-up scan after receiving standard treatment for more than 1 year. Thirty age- and sex-matched healthy subjects served as controls. The CMR protocol included: cines, T2-weighted (T2w), late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) evaluated for the myocardium, and T1 and T2 mapping and ECV evaluated for skeletal muscles. Correlations between laboratory biomarkers and myocardial and skeletal tissue characteristics were analyzed. Comparisons between baseline and follow-up scans were performed using paired t-tests. RESULTS: At baseline, IIM patients showed significantly decreased hematocrit, higher left ventricular (LV) mass index, right ventricular (RV) volume index, myocardial and skeletal native T1, T2 mapping, and ECV than healthy controls. Significant correlations were found among myocardial native T1, T2 mapping, and ECV values and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, and significant correlations between skeletal T2 mapping and inflammatory biomarkers in IIM patients. During the follow-up, 28 patients underwent repeated CMR scan (median interval, 14.5 months, interquartile range: 13.2-15.5 months). Significant relief from clinical symptoms and decreased inflammatory biomarkers levels were observed. Significant reduction in myocardial native T1, T2, ECV, and skeletal native T1, T2, and ECV were observed during the follow-up assessment. CONCLUSIONS: Both myocardial and skeletal muscles in newly diagnosed IIM patients show distinct characteristics on multiparametric CMR. In addition, significant changes were observed in patients showing clinical remission after effective treatment, which suggests that quantitative T1, T2, and ECV techniques may have potential clinical value in IIM patients.

Nifekalant: A New Option for Pre-Excited Atrial Fibrillation With a High-Risk Accessory Pathway.

Atrial fibrillation along with accessory pathway-induced ventricular pre-excitation may be life-threatening due to the high risk of developing severe hypotension, ventricular fibrillation, and sudden death. We demonstrate nifekalant as an effective agent in the pharmacological cardioversion of atrial fibrillation with high-risk accessory pathways. (Level of Difficulty: Intermediate.).

Early detection of myocardial involvement by T1 mapping of cardiac MRI in idiopathic inflammatory myopathy.

BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are common types of idiopathic inflammatory myopathy (IIM), wherein patients are prone to adverse cardiovascular events. PURPOSE: To explore the value of cardiac magnetic resonance imaging (MRI) for detecting cardiac involvement in PM/DM patients using a T1 mapping technique. STUDY TYPE: Prospective observational study. POPULATION: In all, 25 PM/DM patients free of cardiovascular symptoms and preserved ventricular systolic function and 25 healthy volunteers matched for age and sex served as controls. FIELD STRENGTH/SEQUENCE: Cardiac MRI at 3T, including steady-state free precession (SSFP) cine imaging, late gadolinium enhancement (LGE), and T1 mapping with modified Look-Locker inversion recovery (MOLLI). ASSESSMENT: Myocardial native T1 and extracellular volume (ECV) of the left ventricle as well as the correlations with disease activity were analyzed. STATISTICAL TESTS: Independent sample's t-test, Fisher's exact test, or chi-square test, Pearson's correlation (r) were applied. P ≤ 0.05 was considered significant. RESULTS: Left ventricular end-diastolic/end-systolic volume index (P = 0.643, P = 0.325, respectively), mass index (P = 0.719), and ejection fraction (P = 0.144) were not significantly different between PM/DM patients and controls. LGE was found in 19% of PM/DM patients and none of the control subjects. PM/DM patients showed significantly higher native T1 values (1263.7 ± 84.0 msec vs. 1200.6 ± 43.0 msec, P = 0.002) and expanded extracellular volume (ECV) (32.6 ± 3.7% vs. 26.7 ± 2.3%, P < 0.001) compared with control subjects. ECV values in PM/DM patients had a high proportion (60%) over the 95% percentile of normal controls. Meanwhile, there was a significant correlation between native T1 (r = 0.710, P = 0.0001) or ECV (r = 0.508, P = 0.01) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). DATA CONCLUSION: T1 mapping of cardiac MRI is valuable to detect subclinical myocardial involvement in PM/DM patients, and both myocardial native T1 and ECV could serve as early imaging markers for myocardial impairment in PM/DM. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:415-422.

Improved segmental myocardial strain reproducibility using deformable registration algorithms compared with feature tracking cardiac MRI and speckle tracking echocardiography.

BACKGROUND: Segmental myocardial strain using feature tracking (FT) cardiac MRI is not acceptable due to poor reproducibility. PURPOSE: To assess the reproducibility of left ventricle (LV) segmental myocardial strain measured by deformation registration algorithm (DRA). STUDY TYPE: Prospective clinical trial. SUBJECTS: Sixteen healthy volunteers and 28 hypertrophic cardiomyopathy (HCM) patients. FIELD STRENGTH/SEQUENCE: Retrospective ECG gating cardiac MRI imaging was performed at 3.0T with a steady-state free precession (SSFP) sequence. ASSESSMENT: LV global and segmental myocardial strains were analyzed by DRA, FT, and speckle tracking echocardiography (STE) by two experienced observers and the reproducibility of global and segmental strains were compared. STATISTICAL TESTS: Reproducibility was tested by coefficient of variation (COV) and intraclass correlation coefficient (ICC). Receiver operator curves as well as comparison of areas under the curve (AUC) were analyzed. RESULTS: DRA showed the best observer agreement on segmental strain evaluated by ICC, LS (longitudinal strain): intraobserver variability range (0.98,1.00), interobserver variability range (0.83,0.92), CS (circumferential strain): intraobserver variability range (0.90,0.99), interobserver variability range (0.80,0.97), RS (radial strain): intraobserver variability range (0.84,0.99), interobserver variability range (0.85,0.99). Segmental LS, CS, and RS agreements evaluated by COV for FT and STE were poor. LV global myocardial strain of HCM was significantly lower than controls for all applied techniques, but global CS by DRA had better accuracy compared to FT or STE for distinguishing HCM from healthy subjects: AUC 0.880 (DRA) vs. 0.577 (FT) or 0.736 (STE), P < 0.05. DATA CONCLUSIONS: DRA is a reliable and robust analysis tool for segmental myocardial strain. Global CS by DRA allows discrimination between HCM and normal controls with better accuracy compared with FT and STE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:404-414.

Increased Cerebellar Functional Connectivity With the Default-Mode Network in Unaffected Siblings of Schizophrenia Patients at Rest.

The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and the cerebellum participates in the high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities remains unclear in unaffected siblings of schizophrenia patients. Forty-six unaffected siblings of schizophrenia patients and 46 healthy controls were recruited for a resting-state scan. The images were analyzed using the functional connectivity (FC) method. The siblings showed significantly increased FCs between the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as between the lobule IX and the bilateral MPFC (orbital part) and right superior MPFC compared with the controls. No significantly decreased FC was observed in the siblings relative to the controls. The analyses were replicated in 49 first-episode, drug-naive patients with schizophrenia, and the results showed that the siblings and the patients shared increased FCs between the left Crus I and the left superior MPFC, as well as between the lobule IX and the left MPFC (orbital part) compared with the controls. These findings suggest that increased cerebellar-DMN connectivities emerge earlier than illness onset, which highlight the contribution of the cerebellum to the DMN alterations in unaffected siblings. The shared increased cerebellar-DMN connectivities between the patients and the siblings may be used as candidate endophenotypes for schizophrenia.

Abnormal causal connectivity by structural deficits in first-episode, drug-naive schizophrenia at rest.

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.

Decreased default-mode network homogeneity in unaffected siblings of schizophrenia patients at rest.

The dysconnectivity hypothesis proposes that abnormal resting state connectivity within the default-mode network (DMN) plays a key role in schizophrenia. Little is known, however, about alterations of the network homogeneity (NH) of the DMN in unaffected siblings of patients with schizophrenia. Unaffected siblings have unique advantages as subjects of neuroimaging studies independent of the clinical and treatment issues that complicate studies of the patients themselves. In the present study, we investigated NH of the DMN in unaffected siblings of schizophrenia. Participants comprised 46 unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls who underwent resting state functional magnetic resonance imaging (fMRI). Automated NH and group independent component analysis (ICA) approaches were used to analyze the data. Compared with healthy controls, the unaffected siblings of schizophrenia patients showed decreased DMN homogeneity in the left precuneus. No significantly increased DMN homogeneity was found in the sibling group relative to the control group. Our results suggest that there is decreased NH of the DMN in unaffected siblings of schizophrenia patients and indicate that the alternative perspective of examining the DMN NH in patients׳ siblings may improve understanding of the nature of schizophrenia.

Abnormal default-mode network homogeneity in first-episode, drug-naive major depressive disorder.

BACKGROUND: Default mode network (DMN) is one of the most commonly recognized resting-state networks in major depressive disorder (MDD). However, the homogeneity of this network in MDD is poorly understood. As such, this study was conducted to determine whether or not an abnormal network homogeneity (NH) of DMN is observed in patients with first-episode and drug-naive MDD. METHODS: Twenty-four first-episode drug-naive patients with MDD and twenty-four healthy control subjects participated in the study. NH and independent component analysis (ICA) methods were used to analyze data. RESULTS: Depressed patients exhibited a significantly increased NH in the left dorsal medial prefrontal cortex (MPFC) and decreased NH in the right inferior temporal gyrus (ITG) compared with the healthy control subjects. Receiver operating characteristic curves (ROC) were analyzed and results revealed that the NH values of MPFC and ITG could be applied as candidate markers with relatively high sensitivity and specificity to distinguish patients from healthy control subjects. No correlation was observed between the NH values of the two regions and clinical variables. CONCLUSIONS: Our findings suggested that an abnormal DMN homogeneity could be observed in MDD, which highlight the importance of the DMN in the pathophysiology of MDD.

Decreased regional activity of default-mode network in unaffected siblings of schizophrenia patients at rest.

Dysconnectivity hypothesis posits that abnormal resting-state connectivity within the default-mode network (DMN) acts as a key role in schizophrenia. However, little is known about the regional alterations of the DMN in unaffected siblings of schizophrenia patients. Unaffected siblings have a unique advantage in neuroimaging studies independent of clinical and treatment issues that complicate studies on patients themselves. In the present study, we used fractional amplitude of low-frequency fluctuation (fALFF) to investigate regional alterations of the DMN in unaffected siblings of schizophrenia patients at rest. Forty-six unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). The fALFF and independent component analysis (ICA) approaches were used to analyze the data. The unaffected siblings of schizophrenia patients had lower fALFF than the controls in the left inferior temporal gyrus (ITG). No significantly increased fALFF was found in any brain regions in the siblings compared to that in the controls. Further receiver operating characteristic (ROC) curve and support vector machine (SVM) analyses showed that the fALFF values of the left ITG could be utilized to separate the siblings from the controls. Our results first suggest that there is decreased regional activity of the DMN in unaffected siblings of schizophrenia patients, and provide a clue that decreased regional activity of the left ITG could be applied as a candidate biomarker to identify the siblings from the controls.

Decreased resting-state interhemispheric functional connectivity in unaffected siblings of schizophrenia patients.

BACKGROUND: Neuroimaging studies in unaffected siblings of schizophrenia patients can provide clues to the pathophysiology for the development of schizophrenia. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in siblings, although the dysconnectivity hypothesis is prevailing in schizophrenia for years. In the present study, we used a newly validated voxel-mirrored homotopic connectivity (VMHC) method to identify whether aberrant interhemispheric FC was present in unaffected siblings at increased risk of developing schizophrenia at rest. METHODS: Forty-six unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). Automated VMHC was used to analyze the data. RESULTS: The sibling group had lower VMHC than the control group in the angular gyrus (AG) and the lingual gyrus/cerebellum lobule VI. No region exhibited higher VMHC in the sibling group than in the control group. There was no significant sex difference of the VMHC values between male siblings and female siblings or between male controls and female controls, although evidence has been accumulated that size and shape of the corpus callosum, and functional homotopy differ between men and women. CONCLUSIONS: Our results first suggest that interhemispheric resting-state FC of VMHC is disrupted in unaffected siblings of schizophrenia patients, and add a new clue of abnormal interhemispheric resting-state FC to the pathophysiology for the development of schizophrenia.

Abnormal default-mode network homogeneity in first-episode, drug-naive schizophrenia at rest.

BACKGROUND: Dysconnectivity hypothesis posits that schizophrenia relates to abnormal resting-state connectivity within the default-mode network (DMN) and this aberrant connectivity is considered as contribution of difficulties in self-referential and introspective processing. However, little is known about the alterations of the network homogeneity (NH) of the DMN in schizophrenia. In the present study, we used an automatic NH method to investigate the NH of the DMN in schizophrenia patients at rest. METHODS: Forty-nine first-episode, drug-naive schizophrenia patients and 50 age-, gender-, and education-matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI). An automated NH approach was used to analyze the data. RESULTS: Patients exhibited lower NH than controls in the left medial prefrontal cortex (MPFC) and the right middle temporal gyrus (MTG). Significantly higher NH values in the left posterior cingulate cortex (PCC) and the right cerebellum Crus I were found in the patient group than in the control group. No significant correlation was found between abnormal NH values and Positive and Negative Symptom Scale (PANSS) scores, duration of untreated psychosis (DUP), age or years of education in the patient group. CONCLUSIONS: Our findings suggest that abnormal NH of the DMN exists in first-episode, drug-naive schizophrenia and further highlight the importance of the DMN in the pathophysiology of schizophrenia.

Decreased resting-state interhemispheric coordination in first-episode, drug-naive paranoid schizophrenia.

BACKGROUND: Dysconnectivity hypothesis posits that schizophrenia relates to abnormalities in neuronal connectivity. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in patients with paranoid schizophrenia. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in patients with paranoid schizophrenia at rest. METHODS: Forty-nine first-episode, drug-naive patients with paranoid schizophrenia and 50 age-, gender-, and education-matched healthy subjects underwent a resting-state functional magnetic resonance imaging (fMRI) scans. An automated VMHC approach was used to analyze the data. RESULTS: Patients exhibited lower VMHC than healthy subjects in the precuneus (PCu), the precentral gyrus, the superior temporal gyrus (STG), the middle occipital gyrus (MOG), and the fusiform gyrus/cerebellum lobule VI. No region showed greater VMHC in the patient group than in the control group. Significantly negative correlation was observed between VMHC in the precentral gyrus and the PANSS positive/total scores, and between VMHC in the STG and the PANSS positive/negative/total scores. CONCLUSIONS: Our results suggest that interhemispheric resting-state FC of VMHC is reduced in paranoid schizophrenia with clinical implications for psychiatric symptomatology thus further contribute to the dysconnectivity hypothesis of schizophrenia.

Dissociation of regional activity in the default mode network in first-episode, drug-naive major depressive disorder at rest.

BACKGROUND: Major depressive disorder (MDD) is associated with altered neural activity in the default mode network (DMN). In the present study, we used a fractional amplitude of low-frequency fluctuations (fALFF) approach to directly investigate the features of spontaneous brain activity of the DMN in patients with the first-episode, drug-naive MDD at rest. METHODS: Twenty-four first-episode, drug-naive patients with MDD and 24 age-, gender-, and education-matched healthy subjects participated in the study. The fALFF and independent component analysis (ICA) approaches were utilized to analyze the data. RESULTS: Patients with MDD exhibited a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the left dorsal medial prefrontal cortex (MPFC) and decreased fALFF in the left parahippocampal gyrus (PHG). The increased fALFF values of the left dorsal MPFC were positively correlated to the Hamilton Rating Scale for Depression (HRSD) scores. CONCLUSIONS: Our results first suggested that there was a dissociation pattern of resting-state fALFF in the DMN in patient with MDD, which highlighted the importance of the DMN in the pathogenesis of MDD.

Is there a cerebellar compensatory effort in first-episode, treatment-naive major depressive disorder at rest?

BACKGROUND: This study was undertaken to explore whether there is a cerebellar compensatory response in patients with first-episode, treatment-naive major depressive disorder (MDD). The cerebellar compensatory response is defined as a cerebellar hyperactivity which would be inversely correlated with both the activation of the functionally connected cerebral regions and the depression severity. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data of 24 patients with MDD and 24 healthy subjects were analyzed with the fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity (FC) methods. The structural images were processed with the voxel-based morphometry (VBM) method. RESULTS: Compared to healthy controls, depressed patients had significantly increased fALFF in the left Crus I and the left cerebellar lobule VI. FC analysis of these two seeded regions found that depressed patients had increased FC between the left Crus I and the right hippocampus, but had decreased FC between the left Crus I and the left inferior parietal lobule (IPL), and between the left cerebellar lobule VI and bilateral inferior temporal gyrus. No correlation was observed between the abnormal fALFF of the seeds and their connected regions and the depression severity or the executive function. The VBM results did not show significant reduction in gray or white matter volume in any above-mentioned region. CONCLUSIONS: Our findings suggest that increased cerebellar activity at resting state may be a disease state phenomenon but not a compensatory response to the dysfunction of the default mode network (DMN) in MDD.

Decreased interhemispheric resting-state functional connectivity in first-episode, drug-naive major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is shown to have structural and functional abnormalities in specific brain areas and connections by recent neuroimaging studies. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (FC) in patients with MDD. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric FC of the whole brain in patients with MDD at rest. METHODS: Twenty-four first-episode, drug-naive patients with MDD and 24 age-, gender-, and education-matched healthy subjects underwent a resting-state functional magnetic resonance imaging (fMRI). An automated VMHC approach was used to analyze the data. RESULTS: Patients with MDD showed lower VMHC than healthy subjects in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex/precuneus (PCC/PCu), two core regions within default mode network (DMN). Both left and right MPFC showed reduced FC with the other frontal areas and with right anterior cingulate gyrus (ACC), while PCC/PCu exhibited abnormal FC with the frontal areas and thalamus in patient group. Significant positive correlation was observed between VMHC in MPFC and persistent error response of Wisconsin Card Sorting Test (WCST-Pre) in patients. Further ROC analysis revealed that VMHC in the MPFC and PCC/PCu could be used to differentiate the patients from healthy subjects with relatively high sensitivity and specificity. CONCLUSIONS: Our results suggest that decreased VMHC in brain regions within DMN may underlie the pathogenesis of MDD.