Combined [18F]FDG-PET with MRI structural patterns in predicting post-surgical seizure outcomes in temporal lobe epilepsy patients.

OBJECTIVES: To integrate the glucose metabolism measured using [18F]FDG PET/CT and anatomical features measured using MRI to forecast the post-surgical seizure outcomes of intractable temporal lobe epilepsy. METHODS: This retrospective study enrolled 63 patients with drug-resistant temporal lobe epilepsy. Z-transform of the patients' PET images based on comparison with a database of healthy controls, cortical thickness, and quantitative anisotropy (QA) of the diffusion spectrum imaging concordant/non-concordant with cortical resection was adopted to quantify their predictive values for the post-surgical seizure outcomes. RESULTS: The PET hypometabolism region was concordant with the surgical field in 47 of the 63 patients. Forty-two patients were seizure-free post-surgery. The sensitivity and specificity of PET in predicting seizure freedom were 89.4% and 68.8%, respectively. Complete resection of foci with overlapped PET, cortical thickness, and QA abnormalities resulted in Engel I in 27 patients, which was a good predictor of seizure freedom with an odds ratio (OR) of 19.57 (95% CI 2.38-161.25, p = 0.006). Hypometabolism involved in multiple lobes (OR = 7.18, 95% CI 1.02-50.75, p = 0.048) and foci of hypometabolism with QA/cortical thickness abnormalities outside surgical field (OR = 14.72, 95% CI 2.13-101.56, p = 0.006) were two major predictors of Engel III/IV outcomes. ORs of QA to predict Engel I and seizure recurrence were 14.64 (95% CI 2.90-73.80, p = 0.001) and 12.01 (95% CI 2.91-49.65, p = 0.001), respectively. CONCLUSION: Combined PET and structural pattern is helpful to predict the post-surgical seizure outcomes and worse outcomes of Engel III/IV. This might decrease unnecessary surgical injuries to patients who are potentially not amenable to surgery. KEY POINTS: • A combined metabolic and structural pattern is helpful to predict the post-surgical seizure outcomes. • Favorable post-surgical seizure outcome was most likely reached in patients whose hypometabolism overlapped with the structural changes. • Hypometabolism in multiple lobes and QA or cortical thickness abnormalities outside the surgical field were predictors of worse seizure outcomes of Engel III/IV.

Identifying and characterizing projections from the subthalamic nucleus to the cerebellum in humans.

A connection between the subthalamic nucleus (STN) and the cerebellum which has been shown to exist in non-human primates, was recently identified in humans. However, its anatomical features, network properties and function have yet to be elucidated in humans. In the present study, we quantified the STN-cerebellum pathway in humans and explored its function based on structural observations. Anatomical features and asymmetry index (AI) were explored using high definition fiber tractography data of 30 individuals from the Massachusetts General Hospital - Human Connectome Project adult diffusion database. Pearson's correlation analysis was performed to determine the interrelationship between the subdivisions of the STN-cerebellum and the global cortical-STN connections. The pathway was visualized bilaterally in all the subjects. Typically, after setting out from the STN, the STN-cerebellum projections incorporated into the nearby corticopontine tracts, passing through the cerebral peduncle, mediated by the pontine nucleus and then connecting in two opposite directions to join the bilateral middle cerebellar peduncle. On the group averaged level, 78.03% and 62.54% of fibers from the right and left STN respectively, distributed to Crus I in the cerebellum, part of the remaining fibers projected to Crus II, with most of the fibers crossing contralaterally. According to the AI evaluation, 60% of the participants were right STN dominant, 23% were left STN dominant, and 17% were relatively symmetric. Pearson's correlation analysis further indicated that the number of pathways from mesial Brodmann area 8 to the STN (hyperdirect pathway associated with decision making) was positively correlated with the number of fibers from the right STN to Crus I. The insertion and termination, the right-side dominance, and the positive correlation with the hyperdirect pathway all suggest that the STN-cerebellum pathway might be involved in decision-making processes.

Automatic labeling of the fanning and curving shape of Meyer's loop for epilepsy surgery: an atlas extracted from high-definition fiber tractography.

BACKGROUND: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time. METHODS: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients). RESULTS: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively. CONCLUSION: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

Diffusion spectrum imaging predicts hippocampal sclerosis in mesial temporal lobe epilepsy patients.

OBJECTIVES: Epileptic patients suffer from seizure recurrence after surgery due to the challenging localization. Improvement of the noninvasive imaging-based approach for a better definition of the abnormalities would be helpful for a better outcome. METHODS: The quantitative anisotropy (QA) of diffusion spectrum imaging (DSI) is a quantitative scalar of evaluating the water diffusivity. Herein, we investigated the association between neuronal diameters or density acquired in literature and QA of DSI as well as the seizure localization in temporal lobe epilepsy. Thirty healthy controls (HCs) and 30 patients with hippocampal sclerosis (HS) were retrospectively analyzed. QA values were calculated and interactively compared between the areas with different neuronal diameter/density acquired from literature in the HCP-1021 template. Diagnostic tests were performed on Z-transformed asymmetry indices (AIs) of QA (which exclude physical asymmetry) among HS patients to evaluate its clinical value. RESULTS: The QA values in HCs conformed with different pyramidal cell distributions ranged from giant to small; corresponding groups were the motor-sensory, associative, and limbic groups, respectively. Additionally, the QA value was correlated with the neuronal diameter/density in cortical layer IIIc (correlation coefficient with diameter: 0.529, p = 0.035; density: -0.678, p = 0.011). Decreases in cingulum hippocampal segments (Chs) were consistently observed on the sclerosed side in patients. The area under the curve of the Z-transformed AI in Chs to the lateralization of HS was 0.957 (sensitivity: 0.909, specificity: 0.895). INTERPRETATION: QA based on DSI is likely to be useful to provide information to reflect the neuronal diameter/density and further facilitate localization of epileptic tissues.

Lateralizing the affected side of hippocampal sclerosis with quantitative high angular resolution diffusion scalars: a preliminary approach validated by diffusion spectrum imaging.

BACKGROUND: Conflicts in regarding the lateralization of the seizure onset for mesial temporal lobe epilepsy (MTLE) are frequently encountered during presurgical evaluation. As a more elaborate, quantified protocol, indices of diffusion spectrum imaging (DSI) might be sensitive to evaluate the seizure involvement. However, the accuracy was less revealed. Herein, we determined the lateralizing value of the DSI indices among MTLE patients. METHODS: Eleven MTLE patients were enrolled together with 11 matched health contrasts. All the participants underwent a DSI scan and with reconstruction of the diffusion scalar, including quantitative anisotropy (QA), isotropic (ISO), and track density imaging (TDI) values. Statistics of these indices were applied to identify the differences between the healthy and ipsilateral sides, and those between the patients and the controls, with special attention to areas of the crura of fornix (FORX), the parahippocampal radiation of the cingulum (PHCR), the hippocampus (HP), parahippocampus (PHC), amygdala (AM) and entorhinal cortex (EC). RESULTS: Regarding lateralization, TDI of the FORX and the PHCR reached an AUC value of 0.95 and 0.93, respectively (P<0.05), and QA, ISO, TDI of the PHCR, as well as TDI of the FORX were statistically significant amongst the laterals of the patients (P<0.05). Also, the QA of the PHCR were statistically different in the patients' ipsilateral side relative to the contrasts (P<0.017). The diffusion level on different grey matter structures were significantly decreased including HP, AM and EC in GQI space (P<0.017). CONCLUSIONS: The quantitative diffusion scalars of the DSI, especially TDI of the FORX and the PHCR, are sensitive indices to define the ipsilateral side for MTLE patients. For preliminary exploration, the use of quantitative DSI scalars may help to improve the seizure outcome by increasing the accuracy of localization and lateralization for MTLE.

A highly conductive self-assembled multilayer graphene nanosheet film for electronic tattoos in the applications of human electrophysiology and strain sensing.

Highly conductive, conformable and gel-free electrodes are desirable in human electrophysiology. Besides, intimately coupling with human skin, wearable strain sensors can detect numerous physiological signals, such as wrist pulse and breath. In this study, a multilayer graphene nanosheet film (MGNF) with high conductivity was prepared by the Marangoni self-assembly for using in tattoo dry electrodes (TDEs) and in a graphene tattoo strain sensor (GTSS). Compared to commercial Ag/AgCl gel electrodes, TDEs have lower skin-electrode contact impedance and could detect human electrocardiogram for 24-hour wearing more accurately as well as electromyogram. Through designing a slim serpentine ribbon structure, a resistance-type GTSS, without deterioration even after 2000 cycles, is well demonstrated for human wrist pulse and breath sensing. With the advantages of high conductivity and conformability, MGNF provides support to fabricate low-cost, customizable, and high-performance electronic tattoos for human electrophysiology and strain sensing.

Projections of Brodmann Area 6 to the Pyramidal Tract in Humans: Quantifications Using High Angular Resolution Data.

Primate studies indicate that the pyramidal tract (PyT) could originate from Brodmann area (BA) 6. However, in humans, the accurate origin of PyT from BA 6 is still uncertain owing to difficulties in visualizing anatomical features such as the fanning shape at the corona radiata and multiple crossings at the semioval centrum. High angular-resolution diffusion imaging (HARDI) could reliably replicate these anatomical features. We explored the origin of the human PyT from BA 6 using HARDI. With HARDI data of 30 adults from the Massachusetts General Hospital-Human Connectome Project (MGH-HCP) database and the HCP 1021 template (average of 1021 HCP diffusion data), we visualized the PyT at the 30-averaged group level and the 1021 large-sample level and validated the observations in each of the individuals. Endpoints of the fibers within each subregion were quantified. PyT fibers originating from the BA 6 were consistently visualized in all images. Specifically, the bilateral supplementary motor area (SMA) and dorsal premotor area (dPMA) were consistently found to contribute to the PyT. PyT fibers from BA 6 and those from BA 4 exhibited a twisting topology. The PyT contains fibers originating from the SMA and dPMA in BA 6. Infarction of these regions or aging would result in incomplete provision of information to the PyT and concomitant decreases in motor planning and coordination abilities.

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

BACKGROUND: Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. MATERIALS AND METHODS: A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. RESULTS: The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. CONCLUSIONS: The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

Mussel-inspired adhesive and transferable free-standing films by self-assembling dexamethasone encapsulated BSA nanoparticles and vancomycin immobilized oxidized alginate.

This study developed an adhesive and transferable free-standing (FS) film with dual function of osteoinductivity and antibacterial activity, which was obtained by sequentially assembling vancomycin immobilized oxidized sodium alginate and dexamethasone encapsulated chitosan coated BSA nanoparticles on a poly-dopamine layer. The FS films enabled the dual release of vancomycin and dexamethasone. The FS films had excellent osteoinductivity and antibacterial activity by cell culture and antibacterial assay. The FS film was detached from substrates and transferred to non-fouling surfaces by a wet transfer method, which demonstrated that the adhesive FS film is potential to modify biopolymers with non-fouling surfaces in mild and biocompatible conditions for biomedical applications.

PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions.

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.