Subtle Structural Abnormalities Research Articles

Potential applications of 7 Tesla magnetic resonance imaging in paediatric neuroimaging: Feasibility and challenges

Potential applications of 7 Tesla magnetic resonance imaging in paediatric neuroimaging: Feasibility and challenges

To explore the potential mechanisms of cognitive impairment in children with MRI-negative pharmacoresistant epilepsy due to focal cortical dysplasia: A pilot study from gray matter structure view

ObjectivesTo investigate the characteristics of brain structure in children with focal cortical dysplasia (FCD)-induced pharmacoresistant epilepsy, and explore the potential mechanisms of cognitive impairment from the view of gray matter alteration. Methods25 pharmacoresistant pediatric patients with pathologically confirmed focal cortical dysplasia (FCD), and 25 gender-matched healthy controls were included in this study. 3.0T MRI data and intelligence tests using the Wechsler Intelligence Scale for Children-Forth Edition (WISC-IV) were generated for all subjects. Voxel-based morphometry (VBM)-diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) and surface-based morphometry (SBM) analyses were performed to analyze gray matter volume and cortical structure. Two-sample t-tests were used to compare the differences in gray matter volume (P＜0.05, FWE) and cortical thickness (P＜0.001, FWE) between the two groups. Also, the Spearman rank correlation analyses were employed to determine the relationship between structural alterations and neuropsychological results. ResultsThe WISC-IV scores of the FCD group were significantly lower than those of the HC group in terms of full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) (all P＜0.01). Compared with the HC group, in the FCD group, the gray matter volume (GMV) reduced significantly in the left cerebellum_8, cerebellum_Crus2, and bilateral thalamus (P＜0.05, FWE); the GMV increased in the bilateral medial frontal gyrus, right precuneus, and left inferior temporal gyrus (P＜0.05, FWE), and the cortical thickness increased in the bilateral frontal, parietal, and temporal areas (P＜0.001, FWE). Correlation analyses showed that the age of seizure onset had positive correlations with the WISC-IV scores significantly. Meanwhile, the cortex thicknesses of the left pars opercularis gyrus, left middle temporal gyrus, and right inferior temporal gyrus had negative correlations with the WISC-IV scores significantly. ConclusionFCD patients showed subtle structural abnormalities in multiple brain regions, with significant involvement of the primary visual cortex and language function cortex. And we also demonstrated a crucial correlation between gray matter structural alteration and cognitive impairment.

Reduced right ventricular outflow tract strain at cardiac magnetic resonance correlates with low-voltage areas at unipolar electroanatomic mapping in patients with brugada syndrome

Abstract Background Brugada Syndrome (BrS) was initially described as a channelopathy without underlying structural substrate, but pathological and electroanatomic abnormalities of the right ventricular outflow tract (RVOT), are increasingly recognized, suggesting a possible role of electroanatomic mapping (EAM) in risk stratification of these patients. New echocardiographic and cardiac magnetic resonance (CMR) tools are able to identify subtle structural and functional myocardial abnormalities associated with an increased arrhythmic risk. Purpose We aimed to assess the presence of structural and functional abnormalities of RVOT by CMR-derived RV and RVOT feature tracking in BrS patients. We also sought to evaluate the relationship between RVOT functional abnormalities and the presence and extension of RVOT abnormal voltage areas at EAM. Methods we retrospectively enrolled BrS patients submitted to CMR comprehensive of RVOT sequences and bipolar and unipolar endocardial EAM. Abnormal voltage areas were defined by the presence of signal amplitude <4mV at unipolar mapping and signal amplitude <1.5mV at bipolar mapping. We included a control group of 15 healthy volunteers submitted to CMR including RVOT sequences. Results We studied 16 patients, 12/16 males, mean age 42±9 years. In all cases CMR showed normal left and right ventricular ejection fraction (LVEF 57±4%, RVEF 56±6%). RVOT peak strain values were significantly impaired in BrS patients compared to controls (-17.9±8.6% vs -26.4±9.5%, p=0.011), while RV-GLS did not differ between the two groups (-22.2±4.0% vs 24.6±2.5%, p=0.061). EAM showed the presence of pathological voltages at both unipolar and bipolar mapping in 12 patients, abnormal unipolar and normal bipolar maps in 1 case and both unipolar and bipolar normal maps in 3 patients. Median extent of abnormal voltage areas was 5.3 cm2 [IQ 1-4 = 0.6-9.3 cm2] at unipolar and 4.1 cm2 [IQ 1-4 = 0.7-7.5 cm2] at bipolar map. RVOT peak strain showed a significant correlation with abnormal voltage areas at unipolar EAM (r=0.546, r2=0.525, p=0.029). Patients with both unipolar and bipolar normal maps (n=3) had normal RVOT strain values compared to controls (-25.7±3.9 vs -26.4±9.5%, p=0.90). Conclusions In patients with BrS, RVOT peak strain is significantly reduced compared to controls and is associated with abnormal voltage areas at endocardial unipolar EAM. Noninvasive evaluation of BrS patients with CMR-derived RVOT feature tracking may help to identify patients requiring invasive evaluation with EAM. Prospective studies evaluating the prognostic role of RVOT strain and EAM in BrS patients are needed.

68Ga-PSMA-11 PET/CT in a Case of Isolated Parietal Peritoneal Metastasis From Prostate Adenocarcinoma.

Isolated peritoneal metastasis of prostate cancer is extremely rare. We present 68Ga-PSMA-11 PET/CT findings in a case of isolated parietal peritoneal metastasis from prostate adenocarcinoma 35 months after radical prostatectomy. The peritoneal metastases showed multifocal intense PSMA uptake, but subtle structural abnormalities on 68Ga-PSMA-11 PET/CT. The patient was subsequently treated with androgen deprivation therapy. The peritoneal metastases progressed 25 months after the initiation of androgen deprivation therapy and were removed surgically. Histologic and immunohistochemical evaluation revealed metastatic prostate adenocarcinoma with treatment-related neuroendocrine differentiation. This case demonstrates the usefulness of 68Ga-PSMA-11 PET/CT in identifying atypical metastasis from prostate adenocarcinoma.

Maternal Hypertensive Disorders of Pregnancy and Cardiac Structure and Function in the Newborn

BackgroundMaternal hypertensive disorders of pregnancy (HDPs) are strongly associated with offspring congenital heart defects. ObjectivesThis study assessed whether infants exposed to maternal HDPs were also more likely to have subtle cardiac structural and functional abnormalities than unexposed infants. MethodsWe used regression analyses to compare: 1) left ventricular parameters from conventional echocardiography performed in infants from the Copenhagen Baby Heart Study born to mothers with preeclampsia, gestational hypertension (GH), or no HDP; and 2) advanced echocardiographic parameters for 545 term infants born to mothers with preeclampsia and 545 matched infants not exposed to HDPs. ResultsCompared with infants unexposed to HDPs (n = 17,384), infants exposed to preeclampsia (n = 754) had a thicker interventricular septum in end-diastole (adjusted mean difference [± SD] 0.05 [±0.02] mm; P = 0.004), thicker left ventricular posterior wall (0.04 [±0.02] mm; P = 0.009), larger left ventricular internal diameter (0.12 [±0.06] mm; P = 0.04), and larger left ventricular volume (0.21 [±0.10] mL; P = 0.03). Systolic function changes included increased fractional shortening (0.36% [±0.14%]; P = 0.01) and stroke volume (0.18 [±0.07] mL; P = 0.006), whereas diastolic function changes included lower transmitral early peak inflow velocity (−1.76 [±0.49] mL; P = 0.0003), lower mitral annulus lateral wall a' (−0.21 [±0.09] cm/s; P = 0.02), and smaller lateral E/e’ (−1.06 [±0.38] cm/s; P = 0.005). Conversely, there was little evidence of any association between maternal GH (n = 469) and offspring left ventricular parameters. ConclusionsMaternal preeclampsia, but not GH, was associated with subtle newborn cardiac morphological and functional alterations, including thickening of the left ventricular myocardium and altered systolic and diastolic function.

Correlations Between Structural Brain Abnormalities, Cognition and Electroclinical Characteristics in Patients With Juvenile Myoclonic Epilepsy.

ObjectiveTo explore the structural brain abnormality and its relationship with neuropsychological disorders and electroclinical characteristics in juvenile myoclonic epilepsy (JME) patients.MethodsSixty-seven patients diagnosed with JME and 56 healthy controls were enrolled. All subjects underwent MRI using T1-weighted 3D brain structural images with 1 mm thickness. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were performed. They also underwent a series of neuropsychological tests to assess cognitive function. The correlation analyses were conducted between structural changes, neuropsychological outcomes, and electroclinical features.ResultsThe gray matter concentration (GMC) was decreased in the bilateral pre-central and post-central gyrus, right anterior cingulate gyrus, left posterior orbital region, bilateral occipital regions, bilateral hippocampus and bilateral caudate nucleus in the JME groups (corrected P < 0.05). The evaluation of gray matter volume (GMV) showed significant decrease respectively in bilateral pre-central and post-central gyrus, left paracentral lobule, left orbital gyrus, left amygdala, left basal ganglia and left thalamus of JME patients (P < 0.05). The cortex thicknesses of the right inferior temporal gyrus, right insular gyrus, and right cingulate gyrus had negative correlations with the disease duration significantly. At the same time, the whole-brain white matter volume was positively associated with the course of the disease (P < 0.05). Patients with persistent abnormal EEG discharges had significantly less whole-brain gray matter volume than JME patients with normal EEG (P = 0.03). Correlation analyses and linear regression analyses showed that, in addition to the gray matter volumes of frontal and parietal lobe, the temporal lobe, as well as the basal ganglia and thalamus, were also significantly correlated with neuropsychological tests' results (P < 0.05).ConclusionThe JME patients showed subtle structural abnormalities in multiple brain regions that were not only limited to the frontal lobe but also included the thalamus, basal ganglia, parietal lobe, temporal lobe and some occipital cortex, with significant involvement of the primary somatosensory cortex and primary motor cortex. And we significantly demonstrated a correlation between structural abnormalities and cognitive impairment. In addition, the course of disease and abnormal discharges had a specific negative correlation with the structural changes.

Biventricular Myocardial Fibrosis and Sudden Death in Patients With Brugada Syndrome

BackgroundElectrophysiological, imaging, and pathological studies have reported the presence of subtle structural abnormalities in hearts from patients with Brugada syndrome (BrS). However, data concerning disease involvement outside of the right ventricular outflow tract are limited. ObjectivesThis study sought to characterize the presence and distribution of ventricular myocardial fibrosis in a cohort of decedents experiencing sudden cardiac death caused by BrS. MethodsThe authors evaluated 28 whole hearts from consecutive sudden cardiac death cases attributed to BrS and 29 hearts from a comparator group comprised of noncardiac deaths (control subjects). Cardiac tissue from 6 regions across the right and left ventricle were stained with Picrosirius red for collagen and tissue composition was determined using image analysis software. Postmortem genetic testing was performed in cases with DNA retained for analysis. ResultsOf 28 BrS decedents (75% men; median age of death 25 years), death occurred in sleep or at rest in 24 of 28 (86%). The highest proportion of collagen was observed in the epicardial right ventricular outflow tract of the BrS group (23.7%; 95% CI: 20.8%-26.9%). Ventricular myocardium from BrS decedents demonstrated a higher proportion of collagen compared with control subjects (ratio 1.45; 95% CI: 1.22-1.71; P < 0.001), with no significant interactions with respect to sampling location or tissue layer. There was insufficient evidence to support differences in collagen proportion in SCN5A-positive cases (n = 5) when compared with control subjects (ratio 1.23; 95% CI: 0.75-1.43; P = 0.27). ConclusionsBrugada syndrome is associated with increased collagen content throughout right and left ventricular myocardium, irrespective of sampling location or myocardial layer.

Assessment of localization accuracy and postsurgical prediction of simultaneous 18F-FDG PET/MRI in refractory epilepsy patients.

To evaluate the accuracies of simultaneous 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) in preoperative localization and the postsurgical prediction. This retrospective study was performed on ninety-eight patients diagnosed with refractory epilepsy whose presurgical evaluation included [18F]-FDG PET/MRI, with 1-year post-surgery follow-up between August 2016 and December 2018. PET/MRI images were interpreted by two radiologists and a nuclear medicine physician to localize the EOZ using standard visual analysis and asymmetry index based on standard uptake value (SUV). The localization accuracy and predictive performance of simultaneous 18F-FDG PET/MRI based on the surgial pathology and postsurgical outcome were evaluated. A total of 41.8% (41/98) patients were found to have a definitely structural abnormality on the MR portion of PET/MRI; 93.9% (92/98) were shown hypometabolism on the PET portion of the hybrid PET/MRI. PET/MRI identified 18 cases with subtle structural abnormalities on MRI re-read. Six percent (6/98) of patients PET/MRI were negative. A total of 65.3% (64/98) patients showed seizure-free at 1-year follow-up after epilepsy surgery. The sensitivity, specificity, and accuracy of [18F]-FDG PET/MRI was 95.3%, 8.8%, and 65.3% for seizure onset localization based on surgical pathology and postsurgical outcome, respectively. Multivariate regression analysis indicated that concordant of EOZ localization between PET/MRI and surgical resection range, which was a good positive predictor of seizure freedom (Engel I) (OR = 14.741, 95% CI 3.934-55.033, p < 0.001). [18F]-FDG PET/MRI used as two combined modalities providing additional sensitivity when detecting possible epileptic foci and will probably improve the surgical outcome. • Sensitivity, specificity, and accuracy of [18F]-FDG PET/MRI were 95.3%, 8.8%, and 65.3% for seizure onset localization based on surgical pathology and postsurgical outcome, respectively. • Concordance of EOZ localization between PET/MRI and surgical resection range was a good positive predictor of seizure freedom; presurgical [18F]-FDG PET/MRI will probably improve the surgical outcome.

Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome.

Brugada syndrome and early repolarization syndrome are both classified as J-wave syndromes, with a similar mechanism of arrhythmogenesis and with the same basis for genesis of the characteristic electrocardiographic features. The Brugada syndrome is now considered a conduction disorder based on subtle structural abnormalities in the right ventricular outflow tract. Recent evidence suggests structural substrate in patients with the early repolarization syndrome as well. We propose a unifying mechanism based on these structural abnormalities explaining both arrhythmogenesis and the electrocardiographic changes. In addition, we speculate that, with increasing technical advances in imaging techniques and their spatial resolution, these syndromes will be reclassified as structural heart diseases or cardiomyopathies.

Arm-Leg Blood Pressure Gradient in Clinic to Predict Arch Hemodynamics and Ventricular Size after Coarctation Repair

Objective: Patients with successfully repaired coarctation of the aorta (CoA) need continued follow-up due to risks of restenosis and abnormal arterial compliance, causing early onset hypertension/coronary artery disease. We hypothesize that subtle hemodynamic and structural abnormalities can be predicted in the clinic by an abnormal arm-leg blood pressure (BP) gradient (i.e. arm &gt; leg systolic BP). Design: Uncomplicated CoA patients repaired between 1990 and 2007 with follow-up clinic visits documenting right arm and leg systolic BPs, along with a recent echocardiogram, were studied. Data included the Doppler peak instantaneous (PeakV) and mean velocities (MeanV) in the descending aorta along with measures of the proximal transverse arch (TA) diameter and left ventricular wall (LVPWd) thickness. Measurements were indexed by Z-scores. Patients were grouped by higher systolic BP in the leg (Group 1) or arm (Group 2). Results: Eighty-one patients met the criteria with 52 in Group 1 (median 12.5 years follow-up) and 29 in Group 2 (median 12 years follow-up). Group 2 group had significantly increased arm systolic BP Z-scores (p &lt;0.01), PeakV (p &lt;10-4 ), MeanV (p &lt;10-6 ), and LVPWd (p &lt;0.01) compared to Group 1. There was no difference, however, in arm diastolic BP (p =0.7) or TA diameter (p =0.5). These relationships held true even in otherwise “silent” patients without clinical hypertension. Conclusion: Abnormal arm-leg blood pressure gradients accurately identified CoA patients with elevated arch velocities and increased ventricular wall thickness years after repair. The arm-leg pressure measurements could more accurately select patients in need of further imaging studies and therapeutic interventions.

Comparative Evaluation of Conventional and Advanced Magnetic Resonance Imaging (MRI) Sequences in Mesial Temporal Lobe Sclerosis Patients with Seizure

Background: Diffusion Tensor Imaging (DTI) is a new noninvasive dimension of magnetic resonance imaging (MRI) that provides insight into the white matter microstructure. In epilepsy, widespread DTI abnormalities have been reported in multiple studies in medical literature. In mesial temporal lobe sclerosis (MTLS) patients, conventional MRI may show enlargement of ipsilateral temporal horn &amp; reduction in volume of hippocampus in later stages of disease. However, DTI has been found to be useful in demonstrating the focus of epileptiform activity in brain especially in white matter very early in disease. Since DTI is a sensitive technique to detect subtle structural abnormalities causing epilepsy, hence it can be used to plan more successful epilepsy surgery. Therefore, we conducted a pilot study on twenty patients with seizure disorder using DTI where focal organic brain lesions were ruled-out. Aim: To assess the role of DTI in patients of MLTS with seizures.Subjects and Methods:Twenty patients with seizure disorder secondary to MLTS were evaluated using conventional MRI and DTI. We compared the final diagnosis achieved by clinical parameters correlated with EEG localization.Results:Ten out of twenty patients revealed abnormality on DTI that correlated with EEG correlation without obvious abnormality on conventional MRI representing a significant impact of DTI.Conclusion: DTI can sensitively detect structural changes in MLTS with epilepsy often undetectable on conventional MRI. Hence, DTI can serve as an important radiological tool guiding in management and presurgical evaluation of epilepsy patients considered as idiopathic or and refractory medication.

Advanced neuroimaging techniques for evaluating pediatric epilepsy.

Accurate localization of the seizure onset zone is important for better seizure outcomes and preventing deficits following epilepsy surgery. Recent advances in neuroimaging techniques have increased our understanding of the underlying etiology and improved our ability to noninvasively identify the seizure onset zone. Using epilepsy-specific magnetic resonance imaging (MRI) protocols, structural MRI allows better detection of the seizure onset zone, particularly when it is interpreted by experienced neuroradiologists. Ultra-high-field imaging and postprocessing analysis with automated machine learning algorithms can detect subtle structural abnormalities in MRI-negative patients. Tractography derived from diffusion tensor imaging can delineate white matter connections associated with epilepsy or eloquent function, thus, preventing deficits after epilepsy surgery. Arterial spin-labeling perfusion MRI, simultaneous electroencephalography (EEG)-functional MRI (fMRI), and magnetoencephalography (MEG) are noinvasive imaging modalities that can be used to localize the epileptogenic foci and assist in planning epilepsy surgery with positron emission tomography, ictal single-photon emission computed tomography, and intracranial EEG monitoring. MEG and fMRI can localize and lateralize the area of the cortex that is essential for language, motor, and memory function and identify its relationship with planned surgical resection sites to reduce the risk of neurological impairments. These advanced structural and functional imaging modalities can be combined with postprocessing methods to better understand the epileptic network and obtain valuable clinical information for predicting long-term outcomes in pediatric epilepsy.

Relationship between Sinonasal Anatomical Variations and Symptom Severity in Patients with Chronic Rhinosinusitis

Background:Anatomical variations are subtle structural abnormalities around the osteomeatal complex that might obstruct paranasal sinus drainage and ventilation. The role of these anatomical variants in chronic rhinosinusitis is still controversial and unclear. The aim of this study was to determine the prevalence of anatomical variations and their relationship with the severity of symptoms in patients with chronic rhinosinusitis.Materials and Methods:This was a cross-sectional study conducted among randomly selected patients with chronic rhinosinusitis. Sinonasal Outcome Test-20 (SNOT-20) was used to assess the patient’s severity of symptoms. Computed tomographic scan was used to determine the presence of anatomical variations. The relationship between anatomical variations and symptom severity was determined using the Statistical Products and Service Solution (SPSS) version 20.0.Results:There were 70(58.3%) males and 50(41.7%) females within the age range of 17–60 years. SNOT-20 scoring showed 6(5.0%) of the patients with mild symptoms, 69(57.5%) with moderate, 37(30.8%) with severe, and 8(6.7%) with profound symptoms. The prevalence of sinonasal anatomical variants was 26.7%, which comprised of septal deviation (10.8%), agger nasi (6.7%), concha bullosa (4.2%), Haller cells (3.3%), and Onodi cells (1.7%). There was a statistically significant relationship between the anatomical variations and symptom severity (P = 0.000).Conclusion:This study found a significant relationship between anatomical variations and severity of chronic rhinosinusitis. The prevalence of anatomical variants was found to be 26.7%.

Systematic echo-doppler screening identifies subtle structural and functional cardiac abnormalities in type 2 diabetes mellitus without documented cardio vascular disease: DIACAR a prospective study

Type 2 diabetes mellitus (DM2) is associated with a high prevalence of cardio vascular (CV) disorders including heart failure. The prevalence of asymptomatic cardiac dysfunction in DM2 remains poorly documented in patients without a history of cardio vascular disease. The purpose of DIACAR is to characterize cardiac function by doppler-echocardiography in a population of DM2 without documented CV disease. One hundred and sixteen consecutive outpatients (63 males, 53 females) with DM2 were evaluated prospectively in a single center: 2D (Simpson biplane) & 3D (Heart Model Philips) left ventricular (LV) ejection fraction (EF), LV and left atrial (LA) volumes, 2D global longitudinal strain, diastolic function and LV mass index were measured. All patients with a documented history of CV disease or presenting with symptoms suggestive of any cardiac disorder were excluded. Patients were 57.8 ± 10.9 years old and had a history of DM2 of 12.7 ± 8.7 years. Fifty-two patients (45%) were treated with insulin. Body mass index was 29 ± 4.9 kg/m 2 . Mean values of the echo Doppler parameters were in the normal range ( Table 1 ). 2D Simpson EF and E/e’ were normal in all except one and two patients respectively. However, LV mass index was increased in 8/63 men and 10/53 women and LA volume index was increased in 14/116 patients whereas 2D Simpson LV volumes were all in the normal range. Finally, 2D global longitudinal strain was reduced in 44/105 patients. In a selected population of DM2 without documented CV disease, cardiac function assessed by EF and E/e’ was in the normal range in nearly all patients. By contrast, subtle abnormalities of LV and LA morphology as well as 2D global longitudinal strain were found in a significant proportion of these asymptomatic patients. These results suggest that a systematic screening of DM2 patients by doppler- echocardiography with 2D global longitudinal strain is useful for the early detection of cardiac abnormalities.

Detection of concealed structural heart disease by imaging in patients with apparently idiopathic premature ventricular complexes: A review of current literature

BackgroundPremature ventricular complexes (PVCs) are the most common form of ventricular arrhythmia in the general population. While in most cases PVCs represent a primitive phenomenon with benign behavior, in a non‐negligible proportion of subjects frequent PVCs may be epiphenomenon of underlying occult heart diseases, requiring special medical attention since they have been resulted linked to increased total and cardiac mortality. Nevertheless, PVCs themselves, when incessantly frequent, may be responsible for left ventricular dysfunction in otherwise normal heart. Aim of this narrative review is to update current knowledge on the general approach to patients with frequent PVCs on the basis of available data, with a special focus on the value of imaging.HypothesisRoutine diagnostic work‐up not infrequently miss subtle concealed arrhythmic substrate, leading to erroneously refer to such arrhythmias as to “idiopathic”.MethodsLiterature search of PVCs articles was conducted in PubMed and Scopus electronic database.ResultsConflicting data arise from literature about the true clinical significance of idiopathic PVCs. There is growing body of data providing evidence that more advanced non‐invasive imaging modalities, such as cardiac magnetic resonance, have an incremental diagnostic and prognostic value. On the other hand, in some cases the prognostic significance of isolated subtle myocardial structural abnormalities in patients with PVCs, still remains area of uncertainty.ConclusionIn selected subjects with PVCs and high‐risk features for concealed arrhythmic substrate, traditional assessment to rule out the presence of heart disease, including surface ECG and transthoracic echocardiography, should be implemented with more advanced cardiovascular imaging modalities.

Structural and Functional Brain Alterations in Post-traumatic Headache Attributed to Mild Traumatic Brain Injury: A Narrative Review.

Introduction: By definition, post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) is not associated with brain structural abnormalities that are seen on routine clinical inspection of brain images. However, subtle brain structural abnormalities, as well as functional abnormalities, detected via research imaging techniques yield insights into the pathophysiology of PTH. The objective of this manuscript is to summarize published findings regarding research imaging of the brain in PTH attributed to mTBI.Methods:For this narrative review, PubMed was searched using the terms “post-traumatic headache” or “post-concussion headache” and “imaging” or “magnetic resonance imaging” or “research imaging” or “positron emission tomography”. Articles were chosen for inclusion based on their relevance to the topic.Results: Ten articles were ultimately included within this review. The studies investigated white matter tract integrity and functional connectivity in acute PTH, structural measures, white matter tract integrity, cerebral blood flow, and functional connectivity in persistent PTH (PPTH), and proton spectroscopy in both acute and persistent PTH. The articles demonstrate that acute and persistent PTH are associated with abnormalities in brain structure, that acute and persistent PTH are also associated with abnormalities in brain function, that it might be possible to predict the persistence of PTH using brain imaging findings, and that there are differences in imaging findings when comparing PTH to healthy controls and when comparing PTH to migraine. Although it is not entirely clear if the imaging findings are directly attributable to PTH as opposed to the underlying TBI or other post-TBI symptoms, correlations between the imaging findings with headache frequency and headache resolution suggest a true relationship between the imaging findings and PTH.Conclusions: PTH attributed to mTBI is associated with abnormalities in brain structure and function that can be detected via research imaging. Additional studies are needed to determine the specificity of the findings for PTH, to differentiate findings attributed to PTH from those attributed to the underlying TBI and coexistent post-TBI symptoms, and to determine the accuracy of imaging findings for predicting the development of PPTH.

Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders

Schizophrenia (SZ) is a debilitating mental illness with a multigenic aetiology and significant heritability. Despite extensive genetic studies, the molecular aetiology has remained enigmatic. A recent systems biology study suggested a protein-protein interaction network for SZ with 504 novel interactions. The onset of psychiatric disorders is predominant during adolescence, often accompanied by subtle structural abnormalities in multiple regions of the brain. The availability of BrainSpan Atlas data allowed us to re-examine the genes present in the SZ interactome as a function of space and time. The availability of genomes of healthy centenarians and nonpsychiatric Exome Aggregation Consortium database allowed us to identify the variants of criticality. The expression of the SZ candidate genes responsible for cognition and disease onset was studied in different brain regions during particular developmental stages. A subset of novel interactors detected in the network was further validated using gene expression data of post-mortem brains of patients with psychiatric illness. We have narrowed down the list of drug targets proposed by theprevious interactome study to 10 proteins. These proteins belonging to 81 biological pathways are targeted by 34 known Food and Drug Administration-approved drugs that have distinct potential for the treatment of neuropsychiatric disorders. We also report the possibility of targeting key genes belonging to celecoxib pharmacodynamics, Gα signalling and cGMP-PKG signalling pathwaysthat are not known to be specific to SZ aetiology.

Combining white matter diffusion and geometry for tract-specific alignment and variability analysis

We present a framework for along-tract analysis of white matter (WM) fiber bundles based on diffusion tensor imaging (DTI) and tractography. We introduce the novel concept of fiber-flux density for modeling fiber tracts’ geometry, and combine it with diffusion-based measures to define vector descriptors called Fiber-Flux Diffusion Density (FFDD). The proposed model captures informative features of WM tracts at both the microscopic (diffusion-related) and macroscopic (geometry-related) scales, thus enabling improved sensitivity to subtle structural abnormalities that are not reflected by either diffusion or geometrical properties alone. A key step in this framework is the construction of an FFDD dissimilarity measure for sub-voxel alignment of fiber bundles, based on the fast marching method (FMM). The obtained aligned WM tracts enable meaningful inter-subject comparisons and group-wise statistical analysis. Moreover, we show that the FMM alignment can be generalized in a straight forward manner to a single-shot co-alignment of multiple fiber bundles. The proposed alignment technique is shown to outperform a well-established, commonly used DTI registration algorithm. We demonstrate the FFDD framework on the Human Connectome Project (HCP) diffusion MRI dataset, as well as on two different datasets of contact sports players. We test our method using longitudinal scans of a basketball player diagnosed with a traumatic brain injury, showing compatibility with structural MRI findings. We further perform a group study comparing mid- and post-season scans of 13 active football players exposed to repetitive head trauma, to 17 non-player control (NPC) subjects. Results reveal statistically significant FFDD differences (p-values<0.05) between the groups, as well as increased abnormalities over time at spatially-consistent locations within several major fiber tracts of football players.

Neuroimaging in Hereditary Spastic Paraplegias: Current Use and Future Perspectives.

Hereditary spastic paraplegias (HSP) are a large group of genetic diseases characterized by progressive degeneration of the long tracts of the spinal cord, namely the corticospinal tracts and dorsal columns. Genotypic and phenotypic heterogeneity is a hallmark of this group of diseases, which makes proper diagnosis and management often challenging. In this scenario, magnetic resonance imaging (MRI) emerges as a valuable tool to assist in the exclusion of mimicking disorders and in the detailed phenotypic characterization. Some neuroradiological signs have been reported in specific subtypes of HSP and are therefore helpful to guide genetic testing/interpretation. In addition, advanced MRI techniques enable detection of subtle structural abnormalities not visible on routine scans in the spinal cord and brain of subjects with HSP. In particular, quantitative spinal cord morphometry and diffusion tensor imaging look promising tools to uncover the pathophysiology and to track progression of these diseases. In the current review article, we discuss the current use and future perspectives of MRI in the context of HSP.

Morphometric analysis program combined with magnetoencephalogram in the localization of epileptogenic foci in MRI-negative pharmacoresistant focal epilepsy patients

Objective: To investigate the value of morphometric analysis program (MAP) combined with magnetoencephalogram (MEG) in the localization of epileptogenic foci in MRI-negative pharmacoresistant focal epilepsy (MNPFE) patients. Methods: A total of 42 consecutive MNPFE patients from Epilepsy center, Xuanwu Hospital, Capital Medical University from January 2015 to December 2016 were enrolled. The analysis process of MAP and magnetoencephalography (MEG) were performed independently. When the MAP+ region and the MEG+ region was in the same lobe, the MAP+ region was defined as the MAP+MEG+ region. The analysis results of MAP and MEG were used to do correlation analysis with surgical outcomes separately or simultaneously. Results: The positive rate of MAP was 69% (29/42), and the complete resection of MAP+ region was significantly associated with seizure-free outcome (P=0.027). The positive detection rate of MEG was 100% (42/42), and there was no significant association between the complete resection of MEG+ region and seizure-free outcome (P=0.517). The positive rate of MAP+MEG+ was 43% (18/42), and the complete resection of MAP+MEG+ region was significantly associated with seizure-free outcome (P=0.009). Conclusion: The combination of MAP which indicates subtle structural abnormalities and MEG which pictures electrophysiological features could probably achieve better epileptogenic foci localization in MNPFE patients.