Dual-Emissive Detection of ATP and Hypochlorite Ions for Monitoring Inflammation-Driven Liver Injury In Vitro and In Vivo.

Reactive oxygen species play a pivotal role in liver disease, contributing to severe liver damage and chronic inflammation. In liver injury driven by inflammation, adenosine-5'-triphosphate (ATP) and hypochlorite ion (ClO-) emerge as novel biomarkers, reflecting mitochondrial dysfunction and amplified oxidative stress, respectively. However, the dynamic fluctuations of ATP and ClO- in hepatocytes and mouse livers remain unclear, and multidetection techniques for these biomarkers are yet to be developed. This study presents RATP-NClO, a dual-channel fluorescent bioprobe capable of synchronously detecting ATP and ClO- ions. RATP-NClO exhibits excellent selectivity and sensitivity for ATP and ClO- ions, demonstrating a dual-channel fluorescence response in a murine hepatocyte cell line. Upon intravenous administration, RATP-NClO reveals synchronized ATP depletion and ClO- amplification in the livers of mice with experimental metabolic dysfunction-associated steatohepatitis (MASH). Through a comprehensive analysis of the principal mechanism of the developed bioprobe and the verification of its reliable detection ability in both in vitro and in vivo settings, we propose it as a unique tool for monitoring changes in intracellular ATP and ClO- level. These findings underscore its potential for practical image-based monitoring and functional phenotyping of MASH pathogenesis.

Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

BACKGROUND: The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. METHODS: The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. RESULTS: A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55 months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. CONCLUSION: Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

Quantification of enlarged deep medullary vein volumes in Sturge-Weber syndrome.

Background: Enlarged deep medullary veins (EDMVs) in patients with Sturge-Weber syndrome (SWS) may channel venous blood from the surface to the deep vein system in brain regions affected by the leptomeningeal venous malformation. Thus, the quantification of EDMV volume may provide an objective imaging marker for this vascular compensatory process. The present study proposes a novel analytical method to quantify enlarged EDMV volumes in the affected hemisphere of patients with unilateral SWS. Methods: Twenty young subjects, including 10 patients with unilateral SWS and 10 healthy siblings (age 14.5±6.7 and 16.0±7.0 years, respectively) underwent 3T brain MRI scanning using susceptibility-weighted imaging (SWI) and volumetric T1-weighted sequences. The proposed image analytic steps segmented EDMVs in white matter regions, defined on the volumetric T1-weighted images, by statistically associating the likelihood of intensity, location, and tubular shape on SWI. The volumes of the segmented EDMVs, calculated in each hemisphere, were compared between affected and unaffected hemispheres. EDMV volumes were also correlated with visually assessed EDMV scores, hemispheric white matter volumes, and cortical surface areas. Parametric tests including Pearson's correlation, unpaired and paired t-tests, were used. A P value <0.05 was considered statistically significant. Results: It was found that EDMVs were identified well in SWS-affected hemispheres while calcified regions were excluded. Mean EDMV volumes in the SWS-affected hemispheres were 10-12-fold greater than in the unaffected or healthy control hemispheres; while white matter volumes and cortical surface areas were lower. EDMV volumes in the SWS-affected hemispheres showed a strong positive correlation with the visual EDMV scores (r=0.88, P=0.001) and an inverse correlation with cortical surface area ratios (r=-0.65, P=0.04) but no correlation with white matter volume ratios. Conclusions: EDMVs were detected in the SWS-affected atrophic hemispheres reliably while avoiding calcified regions. The approach can be used to quantify enlarged deep cerebral veins in the human brain, which may provide a potential marker of cerebral venous remodeling.

[Imaging Findings of Spinal Metastases with Differential Diagnosis: Focusing on Solitary Spinal Lesion in Older Patients]. / ì „ì´ì„± 척추 ì¢ ì–‘ì˜ 영상 소견: ê³ ë ¹ 환자의 단일병소를 중심으로 한 감별 질환.

If a solitary spinal lesion is found in an older patient, bone metastasis can be primarily considered as the diagnosis. Bone metastasis can occur anywhere, but it mostly occurs in the vertebral body and may sometimes show typical imaging findings, presenting as a single lesion. Therefore, differentiating it from other lesions that mimic bone metastases can be challenging, potentially leading to delayed diagnosis and initiation of primary cancer treatment. This review provides an overview of imaging findings and clinical guidelines for bone metastases and discusses its differences from other diseases that can occur as solitary spinal lesions in older patients.

Vertebral Venous Congestion That May Mimic Vertebral Metastasis on Contrast-Enhanced Chest Computed Tomography in Chemoport Inserted Patients.

OBJECTIVE: This study aimed to determine the prevalence of vertebral venous congestion (VVC) in patients with chemoport insertion, evaluate the imaging characteristics of nodular VVC, and identify the factors associated with VVC. MATERIALS AND METHODS: This retrospective single-center study was based on follow-up contrast-enhanced chest computed tomography (CT) of 1412 adult patients who underwent chemoport insertion between January 2016 and December 2016. The prevalence of venous stenosis, reflux, and VVC were evaluated. The imaging features of nodular VVC, including specific locations within the vertebral body, were analyzed. To identify the factors associated with VVC, patients with VVC were compared with a subset of patients without VVC who had been followed up for > 3 years without developing VVC after chemoport insertion. Toward this, a multivariable logistic regression analysis was performed. RESULTS: After excluding 333 patients, 1079 were analyzed (mean age ± standard deviation, 62.3 ± 11.6 years; 540 females). The prevalence of VVC was 5.8% (63/1079), with all patients (63/63) demonstrating vertebral venous reflux and 67% (42/63) with innominate vein stenosis. The median interval between chemoport insertion and VVC was 515 days (interquartile range, 204-881 days). The prevalence of nodular VVC was 1.5% (16/1079), with a mean size of 5.9 ± 3.1 mm and attenuation of 784 ± 162 HU. Nodular VVC tended to be located subcortically. Forty-four patients with VVC underwent CT examinations with contrast injections in both arms; the VVC disappeared in 70% (31/44) when the contrast was injected in the arm contralateral to the chemoport site. Bevacizumab use was independently associated with VVC (odds ratio, 3.45; P < 0.001). CONCLUSION: The prevalence of VVC and nodular VVC was low in patients who underwent chemoport insertion. Nodular VVC was always accompanied by vertebral venous reflux and tended to be located subcortically. To avoid VVC, contrast injection in the arm contralateral to the chemoport site is preferred.

Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases.

Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPRmt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPRmt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.

Differentiation of malignant from benign ampullary strictures: A prediction nomogram based on MR imaging and clinical findings.

PURPOSE: To construct a predictive nomogram based on contrast-enhanced magnetic resonance imaging (MRI) and clinical findings for differentiating malignant from benign ampullary strictures. METHOD: In this retrospective study, 76 patients with ampullary strictures (51 benign and 25 malignant) who underwent contrast-enhanced MRI were enrolled. Imaging findings were evaluated independently by two abdominal radiologists who reached consensus. Clinical findings were also collected. Significant findings for malignant ampullary strictures were assessed by univariable and multivariable logistic regression analyses. Based on the results of multivariable analysis, a nomogram to differentiate malignant from benign ampullary strictures was developed and internally validated. RESULTS: In multivariable analysis, presence of an ampullary mass (odds ratio [OR]: 8.42, p = 0.047), bulging ampulla (OR: 8.32, p = 0.033), diffusion restriction of the ampulla (OR: 42.76, p = 0.004) on MRI, and jaundice (OR: 12.41, p = 0.019) were significant predictors of malignant ampullary strictures. A predictive nomogram was constructed using these findings. Among them, diffusion restriction of the ampulla showed the highest OR and predictor score on the nomogram. The calibration plots for internal validation achieved strong agreement between the predicted probabilities and the actual rates of malignant ampullary strictures. CONCLUSION: A combination of significant contrast-enhanced MRI and clinical findings of ampullary mass, bulging ampulla, diffusion restriction of the ampulla, and jaundice may be useful in the prediction of malignant ampullary stricture.

Detecting residual soft tissue sarcoma after unplanned excision; model-free analysis of dynamic contrast-enhanced MRI at short-term follow-up.

OBJECTIVES: To evaluate diagnostic utility of additional DCE-MRI for detecting residual soft tissue sarcomas (STS) after unplanned excision (UPE). METHODS: We retrospectively evaluated 32 patients with UPE of STS, followed by conventional MRI with DCE-MRI and wide excision (WE), between November 2019 and January 2022. Residual tumors on conventional MRI were categorized into three groups: Lesion-type-0, no abnormal enhancement, Lesion-type-1, an indeterminate lesion, and Lesion-type-2, a definite enhancing nodule. On DCE-MRI, ROIs were manually placed on enhancing areas of suspected residual tumor. The mean and 95th percentile values of AUC of time-intensity curve were calculated at 60, 90, and 120 s of Enhancement-cycle-1 and -2. Optimal DCE parameters were identified by ROC analysis. Diagnostic performance of conventional MRI and DCE-MRI was compared using McNemar's test. RESULTS: On WE, residual tumor was present in 23 (71.9%) of 32 patients. On MRI, Lesion-type-1 was found in 16/32 (50%) patients and Lesion-type-2 in 16/32 (50%). The optimal DCE parameter was the 95th percentile value of AUC at 120s of Enhancement-cycle-2. The sensitivity, specificity, and AUC were as follows: 65.2% (95% CI, 45.8-85.7%), 88.9% (CI, 68.4-100%), and 0.77 (CI, 0.62-0.92) for conventional MRI, and 100%, 55.6% (CI, 23.1-88.0%), and 0.78 (CI, 0.61-0.95) for combined conventional and DCE-MRI. CONCLUSIONS: Additional DCE-MRI aided in detecting residual STS after UPE, particularly in cases without definite soft tissue nodular enhancement. ADVANCES IN KNOWLEDGE: Close follow up may be suggested for patients showing abnormality in DCE-MRI, with more suspicion of residual tumor.

Extremely Rare CT and MRI Findings of Peritoneal Leiomyoma Mimicking Hepatic Mass: A Case Report.

Leiomyoma is a common benign tumor from smooth muscle cells, mostly in the uterus. Peritoneal leiomyomas (PLs) are extremely rare and mostly reported as disseminated peritoneal leiomyomatosis. However, to the best of out knowledge, radiologic findings of isolated PL are not reported in English literature. Herein, we introduce the radiologic findings of PL mimicking hepatic mass in a 34-year-old female. CT showed a mass with curvilinear heterogeneous enhancement at the liver's peripheral area. On MRI, the mass showed gradual and heterogeneous enhancement on gadoxetic acid-enhanced MRI and diffusion restriction. The radiologic diagnosis was a benign hepatic tumor, such as degenerated hemangioma, adenoma, and inflammatory myofibroblastic tumor; however, the mass was diagnosed as PL pathologically.

All-cause and major-cause mortality associated with sleep latency in the Korean Genome and Epidemiology Study (KoGES): a population-based prospective cohort study.

BACKGROUND: The all-cause and cause-specific mortality risk associated with sleep latencies in the general adult population is unknown. We aimed to investigate the association of habitual prolonged sleep latency with long-term all-cause and cause-specific mortality in adults. METHODS: The Korean Genome and Epidemiology Study (KoGES) is a population-based prospective cohort study comprising community-dwelling men and women aged 40-69 years from Ansan, South Korea. The cohort was studied bi-annually from April 17, 2003, to Dec 15, 2020, and the current analysis included all individuals who completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire between April 17, 2003, and Feb 23, 2005. The final study population comprised 3757 participants. Data were analysed from Aug 1, 2021, to May 31, 2022. The main exposure was sleep latency groups based on the PSQI questionnaire: fell asleep in 15 min or less, fell asleep in 16-30 min, occasional prolonged sleep latency (fell asleep in >30 min once or twice a week in the past month) and habitual prolonged sleep latency (fell asleep in >60 min more than once a week or fell asleep in >30 min ≥3 times a week, or both) in the past month at baseline. Outcomes were all-cause and cause-specific (cancer, cardiovascular disease, and other causes) mortality reported during the 18-year study period. Cox proportional hazards regression models were used to examine the prospective relationship between sleep latency and all-cause mortality, and competing risk analyses were done to investigate the association of sleep latency with cause-specific mortality. FINDINGS: During a median follow-up of 16·7 years (IQR 16·3-17·4), 226 deaths were reported. After adjusting for demographic characteristics, physical characteristics, lifestyle factors, chronic conditions, and sleep variables, self-reported habitual prolonged sleep latency was associated with an increased risk of all-cause mortality (hazard ratio [HR] 2·22, 95% CI 1·38-3·57) compared to the reference group (those who fell asleep in 16-30 min). In the fully adjusted model, habitual prolonged sleep latency was associated with a more than doubled risk of dying from cancer compared to the reference group (HR 2·74, 95% CI 1·29-5·82). No significant association was observed between habitual prolonged sleep latency and deaths from cardiovascular disease and other causes. INTERPRETATION: In this population-based prospective cohort study, habitual prolonged sleep latency was independently associated with an increased risk of all-cause and cancer-specific mortality in adults (independently of demographic characteristics, lifestyle factors, chronic morbidities, and other sleep variables). Although further studies are warranted to investigate the causality of the relationship, strategies or interventions to prevent habitual prolonged sleep latencies might enhance longevity in the general adult population. FUNDING: Korea Centers for Disease Control and Prevention.

A peptide of PilZ domain-containing protein controls wastewater-treatment-membrane biofouling by inducing bacterial attachment.

Membrane-based wastewater reclamation is used to mitigate water scarcity; however, irreversible biofouling is an elusive problem that hinders the efficiency of a forward-osmosis (FO) membrane-based process, and the protein responsible for fouling is unknown. Herein, we identified fouling proteins by analyzing the microbiome and proteome of wastewater extracellular polymeric substances responsible for strong irreversible FO-membrane fouling. The IGLSSLPR peptide of a PilZ domain-containing protein was found to recruit bacterial attachment when immobilized on the membrane surface while suppressing it when dissolved, in a similar manner to the Arg-Gly-Asp (RGD) peptide in mammalian cell cultures. Bacteria adhere to IGLSSLPR and poly-l-lysine-coated membranes with similar energies and exhibit water fluxes that decline similarly, which is ascribable to interaction as strong as electrostatic interactions in the peptide-coated membranes. We conclude that IGLSSLPR is the key domain responsible for membrane fouling and can be used to develop antifouling technology against bacteria, which is similar to the current usage of RGD peptide in mammalian cell cultures.

Ulnar neuropathy at the elbow: associations of pre-operative DTI parameters with clinical outcomes after cubital tunnel decompression.

OBJECTIVES: To evaluate whether DTI parameters of the ulnar nerve at the elbow are associated with clinical outcomes in patients receiving cubital tunnel decompression (CTD) surgery for ulnar neuropathy. METHODS: This retrospective study included 21 patients with cubital tunnel syndrome who received CTD surgery between January 2019 and November 2020. All patients underwent pre-operative elbow MRI, including DTI. Region-of-interest analysis was performed on the ulnar nerve at three levels around the elbow: above (level 1), cubital tunnel (level 2), and below (level 3). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated on three sections at each level. Clinical data on symptom improvement in respect to pain and tingling sensation after CTD were recorded. Logistic regression analysis was used to compare DTI parameters of the nerve at three levels and the entire nerve course between patients with and without symptom improvement after CTD. RESULTS: After CTD, 16 patients showed improvement in symptoms, but five did not. ROC analysis of DTI parameters showed that AUCs of FA, AD, and MD were higher at level 1 than at levels 2 and 3, with FA showing the highest AUC (level 1: FA, 0.7104 [95% CI, 0.5206-0.9002] vs AD, 0.6521 [95% CI, 0.4900-0.8142] vs MD, 0.6153 [95% CI, 0.4187-0.8119]). CONCLUSION: In patients who underwent CTD surgery for ulnar neuropathy at the elbow, the DTI parameters of FA, AD, and MD above the cubital tunnel level were associated with clinical outcomes, with FA showing the strongest associations. KEY POINTS: • After CTD surgery for ulnar neuropathy at the elbow, persistent symptoms may be observed, depending on symptom severity. • DTI parameters of the ulnar nerve at the elbow showed differences in their capacity for discriminating between patients with and without symptom improvement following CTD surgery, with this capacity depending on the nerve level at the elbow. • FA, AD, and MD measured above the cubital tunnel on pre-operative DTI may be associated with surgical outcomes, with FA showing the strongest association (AUC at level 1, 0.7104 [95% CI, 0.5206-0.9002]).

Biocompatible 7-nitro-2,1,3-benzoxadiazole-embedded naphthalimide for exploring endogenous H2S in living cells.

Hydrogen sulfide (H2S) is a central signaling and antioxidant biomolecule involved in various biological processes. As inappropriate levels of H2S in the human body are closely related to various diseases, including cancer, a tool capable of detecting H2S with high selectivity and sensitivity in living systems is urgently required. In this work, we intended to develop a biocompatible and activatable fluorescent molecular probe for detecting H2S generation in living cells. The 7-nitro-2,1,3-benzoxadiazole-imbedded naphthalimide (1) probe presented here responds specifically to H2S and produces readily detectable fluorescence at 530 nm. Interestingly, probe 1 exhibited significant fluorescence responses to changes in endogenous H2S levels as well as high biocompatibility and permeability in living HeLa cells. This allowed for the real-time monitoring of endogenous H2S generation as an antioxidant defense response in the oxidatively stressed cells.

Sevoflurane-induced high-frequency oscillations, effective connectivity and intraoperative classification of epileptic brain areas.

OBJECTIVE: To determine how sevoflurane anesthesia modulates intraoperative epilepsy biomarkers on electrocorticography, including high-frequency oscillation (HFO) effective connectivity (EC), and to investigate their relation to epileptogenicity and anatomical white matter. METHODS: We studied eight pediatric drug-resistant focal epilepsy patients who achieved seizure control after invasive monitoring and resective surgery. We visualized spatial distributions of the electrocorticography biomarkers at an oxygen baseline, three time-points while sevoflurane was increasing, and at a plateau of 2 minimum alveolar concentration (MAC) sevoflurane. HFO EC was combined with diffusion-weighted imaging, in dynamic tractography. RESULTS: Intraoperative HFO EC diffusely increased as a function of sevoflurane concentration, although most in epileptogenic sites (defined as those included in the resection); their ability to classify epileptogenicity was optimized at sevoflurane 2 MAC. HFO EC could be visualized on major white matter tracts, as a function of sevoflurane level. CONCLUSIONS: The results strengthened the hypothesis that sevoflurane-activated HFO biomarkers may help intraoperatively localize the epileptogenic zone. SIGNIFICANCE: Our results help characterize how HFOs at non-epileptogenic and epileptogenic networks respond to sevoflurane. It may be warranted to establish a normative HFO atlas incorporating the modifying effects of sevoflurane and major white matter pathways, as critical reference in epilepsy presurgical evaluation.

A bio-friendly biotin-coupled and azide-functionalized naphthalimide for real-time endogenous hydrogen sulfide analysis in living cells.

Hydrogen sulfide (H2S) is involved in various biological processes. Thereby, abnormal levels of H2S are reported to be related to various human diseases including cancer. Currently, many fluorescent probes are pioneered to detect H2S by taking advantages of naphthalimides' unique internal charge transfer (ICT) property. However, most probes often require a high content of organic solvents or surfactants, and are limited to the analysis of exogenous H2S treated externally in live cell studies, and have difficulties in analyzing endogenous H2S, thus limiting their practical use. In this study, we developed a bio-friendly biotin-coupled and azide-functionalized naphthalimide (1) as a fluorescent probe enabling real-time analysis of H2S in living system. Probe was able to provide a fluorescence at 545 nm via H2S-mediated azide reduction selectively without interference by biologically abundant constituents and pH effects. In a biological study using A549 cells, probe readily penetrated living cells without cytotoxicity, and unreacted probes showed almost no fluorescence, enabling real-time detection of H2S in living cells without requiring separate washing process. More importantly, under stimulation with various H2S inducers and inhibitors, probe was able to provide an effective fluorescence response against fluctuations in endogenous H2S, a key requirement for H2S studies. Probe 1 can be applied as a useful chemical tool and enables the analysis of H2S and the study of H2S-related cell functions in a variety of environments.

Stereotactic body radiotherapy using helical tomotherapy for hepatocellular carcinoma: clinical outcome and dosimetric comparison of Hi-ART vs. Radixact.

Background: Helical tomotherapy (HT), a unique rotational dose delivery machine, has been updated from Hi-ART to Radixact. We retrospectively evaluated the treatment outcomes of stereotactic body radiotherapy (SBRT) using HT for hepatocellular carcinoma (HCC) and compared the dosimetric details of Hi-ART and Radixact. Methods: Between April 2014 and November 2020, 28 patients with HCC were treated with SBRT using HT for a cure at Soonchunhyang University College of Medicine, Bucheon. According to the Barcelona Clinic Liver Cancer classification, 9 patients had stage 0 disease, 12 had stage A, 4 had stage B, and 3 had stage C. The tumor size ranged from 1 cm to 8 cm (median, 2 cm). The SBRT dose ranged from 40 to 60 Gy (median, 48 Gy) with 4 fractions. Twenty-three patients were treated with Hi-ART and 5 patients were treated with Radixact. To compare the dosimetric parameters between Hi-ART and Radixact, we created treatment plans with the same constraints, pitch, modulation factor, and field width for the same patient in pairs. Results: The median follow-up time from the date of SBRT administration was 24 months (range, 3-67 months). The local failure-free survival and intrahepatic failure-free survival rates were 96% and 58% at 1 year, 84% and 36% at 2 years, and 76% and 18% at 3 years, respectively. The overall survival rate was 93% at 1 year, 93% at 2 years, and 53% at 3 years, respectively. When the paired treatment plans were reviewed, the beam-on time and intermediate dose-spillage were found to be significantly reduced in Radixact than Hi-ART (P<0.001). With regard to normal organ sparing, the irradiated dose to the total liver, normal liver, heart, and kidney was significantly lower with Radixact (P<0.001). Conclusions: SBRT using HT for HCC showed favorable treatment outcomes. Radixact, the latest version, physically improved treatment efficiency by reducing treatment time and provided better organ sparing than Hi-ART.

Multi-Scale Deep Learning of Clinically Acquired Multi-Modal MRI Improves the Localization of Seizure Onset Zone in Children With Drug-Resistant Epilepsy.

The present study investigates the effectiveness of a deep learning neural network for non-invasively localizing the seizure onset zone (SOZ) using multi-modal MRI data that are clinically acquired from children with drug-resistant epilepsy. A cortical parcellation was applied to localize the SOZ in cortical nodes of the epileptogenic hemisphere. At each node, the laminar surface analysis was followed to sample 1) the relative intensity of gray matter and white matter in multi-modal MRI and 2) the neighboring white matter connectivity using diffusion tractography edge strengths. A cross-validation was employed to train and test all layers of a multi-scale residual neural network (msResNet) that can classify SOZ node in an end-to-end fashion. A prediction probability of a given node belonging to the SOZ class was proposed as a non-invasive MRI marker of seizure onset likelihood. In an independent validation cohort, the proposed MRI marker provided a very large effect size of Cohen's d = 1.21 between SOZ and non-SOZ, and classified SOZ with a balanced accuracy of 0.75 in lesional and 0.67 in non-lesional MRI groups. The subsequent multi-variate logistic regression found the incorporation of the proposed MRI marker into interictal intracranial EEG (iEEG) markers further improves the differentiation between the epileptogenic focus (defined as SOZ resected during surgery) and non-epileptogenic sites (i.e., non-SOZ sites preserved during surgery) up to 15 % in non-lesional MRI group, suggesting that the proposed MRI marker could improve the localization of epileptogenic foci for successful pediatric epilepsy surgery.

Developmental organization of neural dynamics supporting auditory perception.

PURPOSE: A prominent view of language acquisition involves learning to ignore irrelevant auditory signals through functional reorganization, enabling more efficient processing of relevant information. Yet, few studies have characterized the neural spatiotemporal dynamics supporting rapid detection and subsequent disregard of irrelevant auditory information, in the developing brain. To address this unknown, the present study modeled the developmental acquisition of cost-efficient neural dynamics for auditory processing, using intracranial electrocorticographic responses measured in individuals receiving standard-of-care treatment for drug-resistant, focal epilepsy. We also provided evidence demonstrating the maturation of an anterior-to-posterior functional division within the superior-temporal gyrus (STG), which is known to exist in the adult STG. METHODS: We studied 32 patients undergoing extraoperative electrocorticography (age range: eight months to 28 years) and analyzed 2,039 intracranial electrode sites outside the seizure onset zone, interictal spike-generating areas, and MRI lesions. Patients were given forward (normal) speech sounds, backward-played speech sounds, and signal-correlated noises during a task-free condition. We then quantified sound processing-related neural costs at given time windows using high-gamma amplitude at 70-110 Hz and animated the group-level high-gamma dynamics on a spatially normalized three-dimensional brain surface. Finally, we determined if age independently contributed to high-gamma dynamics across brain regions and time windows. RESULTS: Group-level analysis of noise-related neural costs in the STG revealed developmental enhancement of early high-gamma augmentation and diminution of delayed augmentation. Analysis of speech-related high-gamma activity demonstrated an anterior-to-posterior functional parcellation in the STG. The left anterior STG showed sustained augmentation throughout stimulus presentation, whereas the left posterior STG showed transient augmentation after stimulus onset. We found a double dissociation between the locations and developmental changes in speech sound-related high-gamma dynamics. Early left anterior STG high-gamma augmentation (i.e., within 200 ms post-stimulus onset) showed developmental enhancement, whereas delayed left posterior STG high-gamma augmentation declined with development. CONCLUSIONS: Our observations support the model that, with age, the human STG refines neural dynamics to rapidly detect and subsequently disregard uninformative acoustic noises. Our study also supports the notion that the anterior-to-posterior functional division within the left STG is gradually strengthened for efficient speech-sound perception after birth.

Differentiating between benign and malignant ampullary strictures: a prediction model using a nomogram based on CT imaging and clinical findings.

OBJECTIVES: To construct a predictive nomogram for differentiating malignant from benign ampullary strictures using contrast-enhanced computed tomography (CT) findings combined with clinical findings. METHODS: In this retrospective study, 152 patients with ampullary stricture (98 benign and 54 malignant) who underwent contrast-enhanced CT were included. Various imaging findings of the ampulla, bile duct, main pancreatic duct, and periampullary area were evaluated and clinical findings including the presence of jaundice, carbohydrate antigen 19-9 level, and history of cholecystectomy were collected. Among them, statistically significant findings were identified using univariable and multivariable logistic regression analyses. A nomogram was constructed to differentiate benign and malignant ampullary strictures and was internally validated. RESULTS: Multivariable analysis revealed that jaundice (odds ratio [OR]: 17.33, p < 0.001), presence of an ampullary mass (OR: 24.40, p < 0.001), non-similar enhancement of the ampulla to the duodenum (OR: 31.96, p = 0.003), and proportional dilatation of the bile duct (OR: 7.98, p = 0.001) were independent significant factors for predicting the malignant ampullary stricture, and were used to construct a nomogram. Among them, non-similar enhancement of the ampulla to the duodenum showed the highest OR and predictor point on the nomogram. The calibration plots showed excellent agreement between the predicted probabilities and the actual rates of malignant ampullary strictures, on internal validation. CONCLUSIONS: Combination of clinical and imaging findings could aid in predicting malignant ampullary strictures using significant findings of jaundice, presence of ampullary mass, non-similar enhancement of the ampulla to the duodenum, and proportional dilatation of the bile duct. KEY POINTS: • The presence of jaundice, ampullary mass, non-similar enhancement of the ampulla, and proportional bile duct dilatation were significant findings for predicting malignant ampullary strictures. • Non-similar enhancement of the ampulla to the duodenum was a significant feature with the highest odds ratio for differentiating benign and malignant ampullary strictures. • The nomogram constructed using contrast-enhanced computed tomography imaging and clinical findings could aid in predicting malignant ampullary strictures.

Diffusion tractography predicts propagated high-frequency activity during epileptic spasms.

OBJECTIVE: To determine the structural networks that constrain propagation of ictal oscillations during epileptic spasm events, and compare the observed propagation patterns across patients with successful or unsuccessful surgical outcomes. METHODS: Subdural electrode recordings of 18 young patients (age 1-11 years) were analyzed during epileptic spasm events to determine ictal networks and quantify the amplitude and onset time of ictal oscillations across the cortical surface. Corresponding structural networks were generated with diffusion magnetic resonance imaging (MRI) tractography by seeding the cortical region associated with the earliest average oscillation onset time, and white matter pathways connecting active electrode regions within the ictal network were isolated. Properties of this structural network were used to predict oscillation onset times and amplitudes, and this relationship was compared across patients who did and did not achieve seizure freedom following resective surgery. RESULTS: Onset propagation patterns were relatively consistent across each patient's spasm events. An electrode's average ictal oscillation onset latency was most significantly associated with the length of direct corticocortical tracts connecting to the area with the earliest average oscillation onset (p < .001, model R2  = .54). Moreover, patients demonstrating a faster propagation of ictal oscillation signals within the corticocortical network were more likely to have seizure recurrence following resective surgery (p = .039). In addition, ictal oscillation amplitude was associated with connecting tractography length and weighted fractional anisotropy (FA) measures along these pathways (p = .002/.030, model R2  = .31/.25). Characteristics of analogous corticothalamic pathways did not show significant associations with ictal oscillation onset latency or amplitude. SIGNIFICANCE: Spatiotemporal propagation patterns of high-frequency activity in epileptic spasms align with length and FA measures from onset-originating corticocortical pathways. Considering the data in this individualized framework may help inform surgical decision-making and expectations of surgical outcomes.