Deep learning-based automated lesion segmentation on pediatric focal cortical dysplasia II preoperative MRI: a reliable approach.

OBJECTIVES: Focal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II. METHODS: High-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance. RESULTS: The 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset. CONCLUSION: This pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection. CRITICAL RELEVANCE STATEMENT: Our fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes. KEY POINTS: • Simplified image processing promotes the DL model implemented in clinical practice. • The histopathological confirmed lesion masks enhance the clinical credibility of the AI model. • The voxel-level evaluation metrics benefit lesion detection and clinical decisions.

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.

Objectives: To 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. Methods: 25 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. Results: The 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. Conclusion: FCD 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.

Intracranial electrophysiological recordings on a swine model of mesial temporal lobe epilepsy.

Objective: To test the feasibility and reliability of intracranial electrophysiological recordings in an acute status epilepticus model on laboratory swine. Method: Intrahippocampal injection of kainic acid (KA) was performed on 17 male Bama pigs (Sus scrofa domestica) weighing between 25 and 35 kg. Two stereoelectroencephalography (SEEG) electrodes with a total of 16 channels were implanted bilaterally along the sensorimotor cortex to the hippocampus. Brain electrical activity was recorded 2 h daily for 9-28 days. Three KA dosages were tested to evaluate the quantities capable of evoking status epilepticus. Local field potentials (LFPs) were recorded and compared before and after the KA injection. We quantified the epileptic patterns, including the interictal spikes, seizures, and high-frequency oscillations (HFOs), up to 4 weeks after the KA injection. Test-retest reliability using intraclass correlation coefficients (ICCs) were performed on interictal HFO rates to evaluate the recording stability of this model. Results: The KA dosage test suggested that a 10 µl (1.0 µg/µl) intrahippocampal injection could successfully evoke status epilepticus lasting from 4 to 12 h. At this dosage, eight pigs (50% of total) had prolonged epileptic events (tonic-chronic seizures + interictal spikes n = 5, interictal spikes alone n = 3) in the later 4 weeks of the video-SEEG recording period. Four pigs (25% of total) had no epileptic activities, and another four (25%) had lost the cap or did not complete the experiments. Animals that showed epileptiform events were grouped as E + (n = 8) and the four animals showing no signs of epileptic events were grouped as E- (n = 4). A total of 46 electrophysiological seizures were captured in the 4-week post-KA period from 4 E + animals, with the earliest onset on day 9. The seizure durations ranged from 12 to 45 s. A significant increase of hippocampal HFOs rate (num/min) was observed in the E+ group during the post-KA period (weeks 1, 2,4, p < 0.05) compared to the baseline. But the E-showed no change or a decrease (in week 2, p = 0.43) compared to their baseline rate. The between-group comparison showed much higher HFO rates in E + vs. E - (F = 35, p < 0.01). The high ICC value [ICC (1, k) = 0.81, p < 0.05] quantified from the HFO rate suggested that this model had a stable measurement of HFOs during the four-week post-KA periods. Significance: This study measured intracranial electrophysiological activity in a swine model of KA-induced mesial temporal lobe epilepsy (mTLE). Using the clinical SEEG electrode, we distinguished abnormal EEG patterns in the swine brain. The high test-retest reliability of HFO rates in the post-KA period suggests the utility of this model for studying mechanisms of epileptogenesis. The use of swine may provide satisfactory translational value for clinical epilepsy research.

Prognostic analysis in children with focal cortical dysplasia II undergoing epilepsy surgery: Clinical and radiological factors.

Objective: The aim of this study was to investigate the value of clinical profiles and radiological findings in assessing postsurgical outcomes in children with focal cortical dysplasia (FCD) II while exploring prognostic predictors of this disease. Methods: We retrospectively reviewed 50 patients with postoperative pathologically confirmed FCD II from January 2016 to June 2021. The clinical profiles and preoperative radiological findings were measured and analyzed. The patients were classified into four classes based on the Engel Class Outcome System at the last follow-up. For the analysis, the patients were divided into two categories based on Engel I and Engel II-IV, namely, seizure-free and non-seizure-free groups. Qualitative and quantitative factors were subsequently compared by groups using comparative statistics. Receiver operating characteristic (ROC) curves were used to identify the predictors of prognosis in children with FCD II. Results: Thirty-seven patients (74%) had Engel class I outcomes. The minimum postsurgical follow-up was 1 year. At the epilepsy onset, patients who attained seizure freedom were older and less likely to have no apparent lesions on the preoperative MRI ("MRI-negative"). The non-seizure-free group exhibited a higher gray matter signal intensity ratio (GR) on 3D T1-MPRAGE images (p = 0.006), with a lower GR on T2WI images (p = 0.003) and FLAIR images (p = 0.032). The ROC curve indicated that the model that combined the GR value of all MRI sequences (AUC, 0.87; 95% CI, 0.77-0.97; p < 0.001; 86% sensitivity, 85% specificity) was able to predict prognosis accurately. Conclusion: A lower age at the onset or the MRI-negative finding of FCD lesions suggests a poor prognosis for children with FCD II. The model consisting of GR values from three MRI sequences facilitates the prognostic assessment of FCD II patients with subtle MRI abnormalities to prevent worse outcomes.

Resective epilepsy surgery for West syndrome: The Hypsarrhythmic Asymmetric Scoring Scheme is a determining predictor of seizure outcome.

OBJECTIVE: It has been suggested that asymmetric hypsarrhythmia is associated with structural etiology. We devised the Hypsarrhythmic Asymmetric Scoring Scheme (HASS) to quantify the degree of hypsarrhythmic asymmetry in a retrospective series of patients who underwent surgical treatment at our center. The present study aimed to investigate the role of HASS in predicting the postsurgical seizure outcomes. METHODS: We retrospectively analyzed the records of 46 children with hypsarrhythmia who underwent resective epilepsy surgery between 2018 and 2020 and were followed up for at least 1 year after surgery. Hypsarrhythmia severity in each hemisphere was quantified and scored. The HASS score was calculated as the difference between the two hemispheres. Univariate results were submitted to logistic regression models to identify independent predictors for favorable surgical outcomes. RESULTS: Of the 46 patients who underwent resective surgery, Engel's class I-Ⅱ outcomes were achieved in 34 (73.9%). The Engel I-Ⅱ group had a significantly higher HASS score than the Engel Ⅲ-Ⅳ group (p<0.001). Multivariate analysis showed that the HASS score was the only significant predictor of good outcomes (p = 0.011). Further receiver operating characteristic analysis showed that a threshold of 7 yielded a better seizure outcome with a sensitivity of 97.06% and specificity of 83.33%. SIGNIFICANCE: As the first hypsarrhythmia scoring system specially designed for presurgical evaluation, the HASS score may contribute to predicting the postsurgical seizure outcome from the electroencephalography perspective.

Investigation of novel de novo KCNC2 variants causing severe developmental and early-onset epileptic encephalopathy.

Purpose The voltage-gated potassium channel Kv3.2, encoded by KCNC2, facilitates fast-spiking GABAergic interneurons to fire action potentials at high frequencies. It is pivotal to maintaining excitation/inhibition balance in mammalian brains. This study identified two novel de novo KCNC2 variants, p.Pro470Ser (P470S) and p.Phe382Leu (F382L), in patients with early onset developmental and epileptic encephalopathy (DEE). Methods To examine the molecular basis of DEE, we studied the functional characteristics of variant channels using patch-clamp techniques and computational modeling. Results Whole-cell patch clamp recordings from infected HEK293 cells revealed that channel activation and deactivation kinetics strongly decreased in both Kv3.2 P470S and F382L variant channels. This decrease also occurred in Kv3.2 p.Val471Leu (V471L) channels, known to be associated with DEE. In addition, Kv3.2 F382L and V471L variants exhibited a significant increase in channel conductance and a ∼20 mV negative shift in the threshold for voltage-dependent activation. Simulations of model GABAergic interneurons revealed that all variants decreased neuronal firing frequency. Thus, the variants' net loss-of-function effects disinhibited neural networks. Conclusion Our findings provide compelling evidence supporting the role of KCNC2 as a disease-causing gene in human neurodevelopmental delay and epilepsy.

PDD-guided tumor excision combined with photodynamic therapy in patients with extramammary Paget's disease.

BACKGROUND: Photodynamic diagnosis (PDD) is a technique that plays a role in visualizing tumor size during the assessment of surgery. Photodynamic therapy (PDT) is a treatment apart from surgery, chemotherapy, radiotherapy, and immunotherapy that is approved for several types of tumors and nonmalignant diseases. The purpose of this study was to illustrate the efficiency and safety of PDD-guided tumor excision combined with ALA-PDT in patients with extramammary Paget's disease (EMPD). METHODS: In our study, 7 cases of EMPD were treated with PDD-guided tumor excision combined with ALA-PDT. After removal of the tumor detected by PDD, each tumor region was irradiated with 177 J/cm2 using a 635 nm laser for 15 min. Two to four ALA-PDT cycles were applied during and after surgery. EMPD was confirmed by biopsy. RESULTS: PDD may forecast tumor margins in EMPD to guide surgery, and PDT has an inhibitory effect on tumor growth. There was no local recurrence in the follow-up of 2.9 years (range, 0.8-5 years). Only one patient experienced distant recurrence under the armpit. The patients with EMPD were able to complete the treatment protocol, with good results and no significant side effects. CONCLUSIONS: The present study demonstrated an effective protocol using PDD for diagnosis and PDT for multiple therapies, showing potential as a clinical treatment for EMPD.

Efficacy and safety of ALA-PDT in treatment of diabetic foot ulcer with infection.

BACKGROUND: Diabetic foot ulcers (DFUs) with infection is a major clinical issue, as the infection not only potentially devastate the wound healing, but also is the factor that most often leads to amputation. Nevertheless, traditional antibiotic treatment is often insufficient to clear the infection, which could lead to side effects. Photodynamic therapy (PDT) has broad-spectral antibacterial activity. Meanwhile, it is difficult to induce antibiotic resistance. Here, we aim to evaluate the safety and efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of DFUs with infection. METHODS: In our study, 5 diabetic patients with infectious DFUs were diagnosed by pathological examination and the depth of wound was examined by X-Ray. All patients' wounds were firstly irradiated with 20% ALA-PDT (635 nm, 100 J/cm2, 80 mW/cm2) using the red LED to control the infection. Treatment will be combined with debridement if there is granulation necrosis or secretion on the wound surface. PDT sessions were performed weekly in all patients until healing was achieved. All patients were followed up for 0.6-1.2 years after treatment. RESULTS: In 5 patients, the DFUs with infection was completely controlled by ALA-PDT. There was no recurrence of DFUs in the follow-up of 0.9 years (range, 0.6-1.2 years) after the treatment. CONCLUSIONS: ALA-PDT treatment for DFUs with infection show successful outcomes and might ultimately avoid amputation.

Automatic Electrophysiological Noise Reduction and Epileptic Seizure Detection for Stereoelectroencephalography.

The objective of this study was to develop a computational algorithm capable of locating artifacts and identifying epileptic seizures, which specifically implementing in clinical stereoelectroencephalography (SEEG) recordings. Based on the nonstationary nature and broadband features of SEEG signals, a comprehensive strategy combined with the complex wavelet transform (CWT) and multi-layer thresholding method was implemented for both noise reduction and seizure detection. The artifacts removal pipeline integrated edge artifact removal, discrete spectrum analysis, and peak density evaluation. For automatic seizure detection, integrated power analysis and multi-dynamic thresholding were applied. The F1score was applied to evaluate overall performance of the algorithm. The algorithm was tested using expert-marked, double-blinded, clinical SEEG data from seven patients undergoing presurgical evaluation. This approach achieved the F1 score of 0.86 for noise reduction and 0.88 for seizure detection. This offline-approach method with minimum parameter tuning procedures and no prior information required, proved to be a feasible and solid solution for clinical SEEG data evaluation. Moreover, the algorithm can be improved with additional tuning and implemented with machine learning postprocessing pipelines.

A combination of preoperative or intraoperative MB-PDT and surgery in the treatment of giant cutaneous squamous cell carcinoma with infection.

BACKGROUND: Giant cutaneous squamous cell carcinoma (cSCC) with infection is a major clinical issue, as the infection not only promotes the progress of tumor, but also effects the success of surgery. Traditional antibiotic treatment is not always sufficient to clear the infection, especially for cSCC infected with multidrug-resistant bacteria. Photodynamic therapy (PDT) has broad-spectral antibacterial activity and non-selective pressure, which makes it difficult to induce antibiotic resistance. Here, we aim to evaluate the safety and efficacy of PDT, along with photosensitizers MB (Methylene blue) - in the treatment of cSCC infected with multidrug-resistant bacteria. METHODS: In our study, 6 patients with giant csCC accompanied infection were diagnosed by pathological examination and the depth of tumor tissues was examined by X-Ray or MRI. All patients' tumor wounds were firstly irradiated with MB-PDT (635 nm, 120 J/cm2, 100 mW/cm2) using the red LED to control the infection. After the control of infection was confirmed by the culture of secretion, tumor underwent expanded resection. Multi-point pathological monitoring was performed during the operation to assure that there was no residual tumor tissue on the wound, and the primary or secondary repair was performed according to the condition of the wound. If the wound requires the tissue flaps transplation in secondary stage, the wound was irradiated again with intraoperative MB-PDT to remove the possible residual tumor cells, as well as to prevent wound infection. All patients were followed up for 0.8-3 years after flap transplation. RESULTS: In 6 patients, the cSCC infection was completely controlled by MB-PDT, and the flap survival was 100%. There was no recurrence of cSCC in the follow-up of 1.6 years (range, 0.8-3 years) after the comminated treatment with MB-PDT and surgery. CONCLUSIONS: Multi-drug resistant bacteria could efficiently be killed by MB-PDT, and the combination of surgery with MB-PDT is a safe and effective approach for treating giant cSCC with infection.

Children With Intracranial Arachnoid Cysts: Classification and Treatment.

We performed a dynamic study of arachnoid cysts (ACs) using magnetic resonance cisternography (MRC) and proposed a classification of ACs.Twenty-three suitable patients in our hospital entered into this study according to our inclusion criteria. MRC images were collected in all the subjects at 1 and 24 hours after the administration of intrathecal gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA). We allocate the enrolled patients into 2 groups, MRC group and surgery group. The MRC results were considered before treatment in 1 group (MRC group, 13 patients), whereas another group was surgically treated without considering the MRC results (surgery group, 10 patients). We calculated the enhanced area of cyst using modified MacDonald Criteria from the images and measured the surrounding subarachnoid area as the reference.We found that it was practically useful to quantify 3 types of ACs, complete communicating, incomplete communicating, and noncommunicating, according to MRC results in this study. All the subjects in both groups are closely observed before the treatment and the follow-up using the MRI examination. In the surgery group, 5 patients were found that the area of cysts shrank in the follow-up stage. However, there was no significant difference in the percentage shrinkage area between the 2 groups.We concluded that MRC with Gd-DTPA as a contrast agent is of significant clinical value for the diagnosis and treatment of children with intracranial ACs. This classification based on dynamic MRC is useful for making surgical recommendations.

Studies of gas-phase reactions of cationic iron complexes of 2-pyrimidinyloxy-N-arylbenzylamines by electrospray ionization tandem mass spectrometry.

Electrospray ionization triple quadrupole mass spectrometry (ESI-TSQ-MS) and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) were used to investigate the interesting gas-phase reactions of the cationic iron (Fe) complexes of 2-pyrimidinyloxy-N-arylbenzylamines (1-6), which are generated by ESI when mixing their methanolic solutions. Further studies of these Fe complexes by collision-induced dissociation (CID) show that Fe(III) complexes undergo an interesting gas-phase single electron transfer (SET) reaction to give 1(•+) -6(•+) ,with loss of neutral FeCl(2) , whereas Fe(II) can catalyze gas-phase Smiles rearrangement reactions of compounds 1-6. By using different Fe(II)X(2) salts (X = Cl or Br) with a set of reactants, the role of the counterion (X(-) ) and the structure effect of the reactants on Fe(II)-catalyzed gas-phase Smiles rearrangement reactions are studied. Evidence obtained from by TSQ-MS and FTICR-MS experiments, hydrogen/deuterium (H/D) exchange experiments and theoretical computations supported some unique gas-phase chemistries initiated by introduction of Fe(II) into 1. Importantly, by comparing the distinct gas-phase reaction results of the cationic Fe(III) complexes with those of Fe(II) complexes, the charge state effects of iron on the gas-phase chemistries of Fe complexes are revealed.