Abstract Attention-deficit hyperactivity disorder (ADHD) is a neurological and neurodevelopmental childhood-onset disorder characterized by a persistent pattern of inattentiveness, impulsiveness, restlessness, and hyperactivity. These symptoms may continue in 55–66% of cases from childhood into adulthood. Even though the precise etiology of ADHD is not fully understood, it is considered as a multifactorial and heterogeneous disorder with several contributing factors such as heritability, auxiliary to neurodevelopmental issues, severe brain injuries, neuroinflammation, consanguineous marriages, premature birth, and exposure to environmental toxins. Neuroimaging and neurodevelopmental assessments may help to explore the possible role of genetic variations on ADHD neuropsychobiology. Multiple genetic studies have observed a strong genetic association with various aspects of neuropsychobiological functions, including neural abnormalities and delayed neurodevelopment in ADHD. The advancement in neuroimaging and molecular genomics offers the opportunity to analyze the impact of genetic variations alongside its dysregulated pathways on structural and functional derived brain imaging phenotypes in various neurological and psychiatric disorders, including ADHD. Recently, neuroimaging genomic studies observed a significant association of brain imaging phenotypes with genetic susceptibility in ADHD. Integrating the neuroimaging-derived phenotypes with genomics deciphers various neurobiological pathways that can be leveraged for the development of novel clinical biomarkers, new treatment modalities as well as therapeutic interventions for ADHD patients. In this review, we discuss the neurobiology of ADHD with particular emphasis on structural and functional changes in the ADHD brain and their interactions with complex genomic variations utilizing imaging genetics methodologies. We also highlight the genetic variants supposedly allied with the development of ADHD and how these, in turn, may affect the brain circuit function and related behaviors. In addition to reviewing imaging genetic studies, we also examine the need for complementary approaches at various levels of biological complexity and emphasize the importance of combining and integrating results to explore biological pathways involved in ADHD disorder. These approaches include animal models, computational biology, bioinformatics analyses, and multimodal imaging genetics studies.
Adults with obstructive sleep apnea (OSA) show significant autonomic and neuropsychologic deficits, which may derive from damage to insular regions that serve those functions. The aim was to assess glial and neuronal status from anterior insular metabolites in OSA versus controls, using proton magnetic resonance spectroscopy (PMRS), and thus to provide insights for neuroprotection against tissue changes, and to reduce injury consequences. Cross-sectional study. University-based medical center. Thirty-six patients with OSA, 53 controls. None. We performed PMRS in bilateral anterior insulae using a 3.0-Tesla magnetic resonance imaging scanner, calculated N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), myo-inositol/creatine (MI/Cr), and MI/NAA metabolite ratios, and examined daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and neuropsychologic status (Beck Depression Inventory II [BDI-II] and Beck Anxiety Inventory [BAI]). Body mass index, BAI, BDI-II, PSQI, and ESS significantly differed between groups. NAA/ Cr ratios were significantly reduced bilaterally, and left-sided MI/Cr and MI/NAA ratios were increased in OSA over controls. Significant positive correlations emerged between left insular MI/Cr ratios and apnea-hypopnea index values, right insular Cho/Cr ratios and BDI-II and BAI scores, and negative correlations appeared between left insular NAA/Cr ratios and PSQI scores and between right-side MI/Cr ratios and baseline and nadir change in O2 saturation. Adults with obstructive sleep apnea showed bilaterally reduced N-acetylaspartate and left-side increased myo-inositol anterior insular metabolites, indicating neuronal damage and increased glial activation, respectively, which may contribute to abnormal autonomic and neuropsychologic functions in the condition. The activated glial status likely indicates increased inflammatory action that may induce more neuronal injury, and suggests separate approaches for glial and neuronal protection.
MRI is useful in assessing inflammatory soft tissue and bone involvement, including synovitis, tenosynovitis, osteitis, and erosions, in patients with early inflammatory arthritis (EIA). Over 90% of patients with EIA show MRI evidence of synovitis, and 70-80% have tenosynovitis [1]. It serves as a diagnostic tool, identifies poor prognostic markers and provides a semi-quantitative approach to evaluate patient outcomes. With the evolving emphasis on early diagnosis and treat-to-target strategies in RA management, there is a growing need to better understand MRI findings in EIA patients. This understanding is crucial for discerning predictive patterns and enabling more precise diagnostic and prognostic applications.
Objectives:
To describe the MRI findings in patients with EIA and to determine whether there is any difference between seropositive and seronegative EIA.
Methods:
All consecutive patients with EIA seen between June 2023 and December 2023 were assessed. EIA was defined as onset of symptoms in the past 6 months and lack of overt clinical synovitis but MRI evidence of inflammation. Demographic information, clinical features, serological parameters, rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP) levels, laboratory results (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP]), and MRI findings were collected for each patient. MRI scans were assessed by a radiologist who was blinded to the patient's clinical information and diagnosis. The radiologist evaluated the bone marrow edema, synovitis, erosions, triangular cartilage lesions, tenosynovitis, joint space narrowing, and ganglion cysts.
Results:
A total of 45 patients were evaluated, of which 36 were female, with a median age of 49 years(IQR: 40.5-59.5). The median symptom duration before diagnosis was 3 months(IQR:1.3-6). Oligoarticular joint pain was the most common pattern observed in 42%, followed by palindromic in 35% and additive in 22%. RF was positive in 13 patients (29%), and 18 (40%) tested positive for anti-CCP antibodies. Raised ESR was observed in 44%, and 37% had elevated CRP levels. The most prevalent MRI finding was synovitis in 34(75%), followed by tenosynovitis in 25(55%), flexor tenosynovitis in 22(48%) and extensor tenosynovitis in 17(37%) patients. Bone marrow edema was found in 15(33%), predominantly in the carpal bones (16%). Erosions were detected in 29% of the patients (Figure 1). Triangular cartilage lesions were observed in 7(15.5%), joint space narrowing in 2(4%), and ganglion cysts in 11 patients(4%). A comparison of MRI findings in the seropositive and seronegative groups showed that seropositive patients had significantly higher CRP levels and subclinical PIP synovitis. There were no significant differences in bone marrow edema, erosion, triangular cartilage lesions, or ganglion cysts (Figure 2).
Conclusion:
This study provides valuable insights into the diagnostic utility of MRI for detecting subclinical synovitis and erosions within the first six months of inflammatory arthritis. Additionally, it advances our understanding of the ability of MRI to distinguish inflammatory patterns across different forms of arthritis. Notably, seropositive patients exhibited elevated CRP levels and subclinical synovitis in the PIP joints compared with seronegative patients. Identifying the distribution patterns in MRI from this study can be utilized in future neural network analyses and deep machine learning, offering potential diagnostic and prognostic implications. We are recruiting more patients over the next 6 months and then intend to follow up this cohort for long term.
REFERENCES:
[1] McQueen FM, Stewart N, Crabbe J, Robinson E, Yeoman S, Tan PL, et al. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis. 1998 Jun; 57(6):350–6.
This study was designed to use the structural MRI data to characterize volumetric changes in gray matter and white matter, and to determine variations in cortical thickness, in a group of HIV-infected individuals to understand how their brain structural changes are associated with their neuropsychological state compared to a group of healthy individuals with similar social, behavioral backgrounds. Despite the demographic similarities and cART, we observed reduced gray and white matter volumes, as well as altered cortical thickness in HIV-infected participants compared with healthy controls. In addition, the neuroanatomic changes in HIV-infected patients showed statistically significant correlations with memory scores.
Introduction Cirrhosis is an abnormal liver condition, mainly caused by viral hepatitis B or C, fatty liver diseases and alcoholism. Ascites is common complication of cirrhosis, associated with poor quality of life, abnormal cognitive functions, increased work disability and increased risk of infection, consequently development of hepatic encephalopathy1. Studies have suggested that inflammation caused by secondary infection with hyper ammonia act as synergistic factor responsible for hepatic encephalopathy in cirrhotic patients2. Magnetic resonance imaging (MRI) is the most commonly used method to observe brain abnormalities in in cirrhotic patients. These patients showed hyperintensities in basal ganglion on T1-weighted MRI and abnormal brain metabolites such as increased Glx, decreased myo-inositol and choline level on MR spectroscopy (MRS), decreased magnetization transfer ratio, and increased mean diffusivity on diffusion tensor imaging MRI 3,4,5,6,7,8. Though different neuroimaging studies investigated structural, diffusion, functional and metabolic brain changes in adult cirrhotic, the regional changes in gray matter and structural brain connectivity are not yet studied in pediatric cirrhotic patients. In this study, we evaluated the gray matter changes and global and regional topological properties of structural brain networks in pediatric cirrhotic compared to pediatric controls. Materials and methods Institutional regulatory board and ethics committee approved the current study protocol. 22 pediatric cirrhotic (mean age 11.6 ± 3.4 years, no prior HE), and 17 age and sex matched heathy controls were included in this study. Written informed consent was obtained from each individual prior study. Cirrhosis was diagnosed by the presence of a combination of high serum-ascites albumin gradient ascites, splenomegaly, large varices without EHPVO, irregular liver surface, portal vein ≥ 13 mm and collaterals. Magnetic resonance imaging (MRI) was performed at 3-T clinical MR Scanner (GE Healthcare Technologies, Milwaukee, WI, United States) using a standard quadrature head coil. Conventional T2-, T1-weighted imaging and high-resolution T1-weighted structural imaging using a fast spoiled gradient echo BRAVO pulse sequence (TR = 8.4 ms; TE = 3.32 ms; inversion time = 400 ms; FA = 13°; matrix size = 512′512; FOV = 240′240 mm 2 ; slice-thickness = 1.0 mm), were performed on each subject. T2-, T1-weighted images were examined for any gross brain pathology, such as cysts, tumors, or any other mass lesions, and presence of such anomaly was used as an exclusion criteria. We used high-resolution T1-weighted structural images for measuring regional gray matter changes and construction of structural network. Brain imaging data were processed using the statistical parametric mapping package (SPM8, http://www.fil.ion.ucl.ac.uk/spm/ ), MRIcroN, and MATLAB-based (The Math Works Inc, Natick, MA) custom software. High-resolution T1-weighted images from all subjects were visually examined for the presence of tumors and cysts. High-resolution T1-weighted images corrected for any bias and inhomogeneity-corrected images were partitioned into gray, white, and cerebrospinal fluid tissue types using a unified segmentation approach9,10. Gray matter tissues maps were normalized to the Montreal Neurological Institute (MNI) space and were modulated and smoothed using a Gaussian filter (FWHM, 10 mm). For the strctural networks construction we used graph theory based analysis using GAT software by using gray matter maps as described in details elsewhere11. In brief we generated 90 cortical and subcortical regions of interest (ROIs), excluding the cerebellum, from the Automated Anatomical Labeling (AAL) atlas using the WFU PickAtlas Toolbox. The extracted residual volumes of all 90 anatomical ROIs were used for construction of structural correlation networks. Statistical analysis All statistical computations were performed using the Statistical Package for Social Sciences (SPSS) version 16.0 (SPSS Inc., Chicago, USA). The normalized and smoothed gray matter tissue probability maps were compared between groups using analysis of covariance (ANCOVA; uncorrected threshold, p = 0.01; extended threshold, 100 voxels), with age and gender included as covariates. A p value of less than 0.05 was considered to be statistically significant. Results Glass brain images in Fig. 1 are showing significantly lower gray matter volumes (GMV) in multiple brain sites with few brain areas showing significantly higher GMV in pediatric cirrhotic compared to those of controls (Fig. 1). The correlation matrix of the cirrhotic group showed overall lower correlation strength than the control group (Fig. 2). In pediatric cirrhotic reduced brain network characteristic across a range of network densities was observed compared to control (Fig. 3). Pediatric cirrhotic also showed altered structural connectivity networks and hubs (Fig. 4). Discussion Cirrhotic patients showed altered gray matter volumes suggesting the brain tissue injury and decreased regional connectivity (clustering coefficient), while reduced global network organization (small worldness) and integration (hubs) suggesting decreased robustness and efficiency of the brain network. These results contribute to novel insights regarding the neurobiological mechanisms underlying cognitive deficits in these patients. The pathophysiological mechanism of brain tissue injury may include hyper ammonia secondary to inflammation resulting neuronal tissue injury2. This structural analysis using voxel based and graph theory might provide a more appropriate paradigm for understanding complicated neurobiological mechanism of cirrhotic patients, and may help to improve the clinical managements of these patients 12. References 1. Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy: definition, nomenclature, diagnosis, and quantification-final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998.Hepatology 2002;35:716–21. 2. Butterworth RF. Pathogenesis of hepatic encephalopathy in cirrhosis: the concept of synergism revisited. Metab Brain Dis. 2015. 3. Lai PH, Chen C, Liang HL, et al. Hyperintense basal ganglia on T1-weighted MR imaging. AJR Am J Roentgenol 1999;172:1109–15. 4. Geissler A, Lock G, Fründ R, et al. Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging. Hepatology 1997;25:48–54. 5. Rovira A, Grivé E, Pedraza S, et al. Magnetization transfer ratio values and proton MR spectroscopy of normal-appearing cerebral white matter in patients with liver cirrhosis. AJNR Am J Neuroradiol 2001;22:1137–42. 6. Laubenberger J, Häussinger D, Bayer S, et al. Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis. Gastroenterology 1997;112:1610–16. 7. Miese F, Kircheis G, Wittsack HJ, et al. 1H-MR spectroscopy, magnetization transfer, and diffusion-weighted imaging in alcoholic and nonalcoholic patients with cirrhosis with hepatic encephalopathy. AJNR Am J Neuroradiol 2006;27:1019–26. 8. Kale RA, Gupta RK, Saraswat VA, et al. Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology 2006;43:698–706. 9. Ashburner J., Friston K. Multimodal image coregistration and partitioning—a unified framework. Neuroimage. 1997;6:209–217 10. Friston K.J., Holmes A., Worsley K.J., Poline J.B., Frith C.D., Frackowiak R.S. Statistical parametric maps in functional imaging: a general linear approach. Hum. Brain Mapp.1995;2:189–210. 11. Hosseini SM, Hoeft F, Kesler SR GAT: a graph-theoretical analysis toolbox for analyzing between-group differences in large-scale structural and functional brain networks. PLoS One. 2012;7:e40709. 12. Petrella JR: Use of graph theory to evaluate brain networks: a clinical tool for a small world? Radiology 2011, 259:317–320.
Background Even with radical surgery, a significant percentage of patients of esophageal cancer experience recurrent disease. Aims The aim of the current study is to define the impact of different histopathological factors on the recurrence and survival in carcinoma esophagus following surgery. Materials and Methods A retrospective review of 182 patients of esophageal carcinoma, operated between January 2011 and December 2016, was done. In our study, 92 patients underwent upfront surgery and 90 took neo-adjuvant/perioperative treatment before planned surgery. To compare the proportion between two groups, chi-square test was used and to compare the median between the two groups, Mann—Whitney U test was used. Factors affecting the survival were analyzed using the Kaplan–Meier survival curve to compare the median survival time across groups log rank (Mantel–Cox) test was used. Results Out of 182 patients, 55 patients developed recurrences, in which 19 were loco-regional and 36 were systemic. Patients with lymph node-positive disease on final histopathology had more recurrence than lymph node-negative (39.74%, 31/78) versus (23%, 24/104), p = 0.01 (significant). Patients with features such as PNI-positive, poor differentiation, lymph node-positive, ENE, and higher stage disease had statistically significant, lower DFS and OS with p -value < 0.05. Patients with adenocarcinoma histology had more systemic recurrences and statistically significant lower DFS than SCC with p -value < 0.05. Conclusions Systemic recurrences are more common. PNI, ENE, grade, lymph node-positive disease, and higher pathologic stage had statistically significant negative impact on both DFS and OS. On multivariate analysis, whereas ENE had an impact on DFS alone.
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