Hepatic artery infusion pump (HAIP) therapy in combination with targeted delivery of IL-12 for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma: a phase II trial protocol.

Background: Treatment of advanced liver tumors remains challenging. Although immune checkpoint inhibition has revolutionized treatment for many cancers, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. Investigation into additional immunomodulatory therapies for these cancers is needed. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with robust anti-tumor activity, but systemic adverse effects largely terminated therapeutic development of recombinant human IL-12 (rhIL-12). PDS01ADC is a novel human monoclonal antibody (NHS76) conjugated to two IL-12 heterodimers with established safety in phase I trials. The NHS76 antibody specifically targets histone/DNA complexes which are accessible only in regions of cell death and this antibody has been shown to accumulate locally in tumors. Methods: Patients with unresectable metastatic colorectal cancer (mCRC) or unresectable intrahepatic cholangiocarcinoma (ICC) will receive synchronization of subcutaneous PDS01ADC with floxuridine delivered via a hepatic artery infusion pump (HAIP). The primary outcome measured in this study will be overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes measured in this study will include hepatic and non-hepatic progression-free survival (PFS), overall survival, and safety of PDS01ADC combination therapy with HAIP. Discussion: Poor clinical response of these liver tumors to immunotherapy is likely due to various factors, including poor immune infiltrate into the tumor and immunosuppression by the tumor microenvironment. By exploiting the tumor cell death induced by HAIP locoregional therapy in combination with systemic chemotherapy, PDS01ADC is poised to modulate the tumor immune microenvironment to improve outcomes for patients undergoing HAIP therapy. Trial Registration: ClinicalTrials.gov (ID NCT05286814 version 2023-10-18); https://clinicaltrials.gov/study/NCT05286814?term=NCT05286814&rank=1.

Comparison of efficacy and safety of conventional transarterial chemoembolization and drug-eluting bead transarterial chemoembolization in unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective cohort study.

PURPOSE: The efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional TACE (c-TACE) in the treatment of patients with unresectable intrahepatic cholangiocarcinoma (ICC) remained controversial. Therefore, we aimed to compare the efficacy and safety between c-TACE and DEB-TACE among patients with ICC. METHOD: Between June 10, 2016 and November 19, 2022, consecutive patients with pathological diagnoses of ICC were divided into the DEB-TACE group and the c-TACE group based on the type of TACE treatment they received. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) between the two groups. Propensity score matching (PSM) was used to balance the characteristics between the c-TACE group and the DEB-TACE group. RESULTS: A total of 132 patients were included in this study, with 64 patients in the c-TACE group and 68 patients in the DEB-TACE group. The median OS for c-TACE and DEB-TACE was 5 and 12 months, respectively. The objective response rate (ORR) for c-TACE and DEB-TACE was 0 % and 66.2 %, respectively; the disease control rate (DCR) was 37.5 % and 91.2 %. There were no significant differences between c-TACE and DEB-TACE among adverse effects at 3 months after treatment (P > 0.05). The results remained consistent after PSM. The Cox regression demonstrated that the DEB-TACE was an independent protective factor for OS. CONCLUSIONS: Patients in the DEB-TACE group had longer OS and higher ORR and DCR than those in the c-TACE group, but no significant difference was observed between the two groups regarding adverse effects.

Single-cell analysis defines LGALS1 + fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma.

The incidence rate of intrahepatic cholangiocarcinoma (ICC), which has a poor prognosis, is rapidly increasing. To investigate the intratumor heterogeneity of ICC, we analyzed single-cell RNA sequencing data from the primary tumor and adjacent normal tissues of 14 treatment-naïve patients. We identified ten major cell types, along with 45 subclusters of cells. Notably, we identified a fibroblast cluster, Fibroblast_LUM+, which was preferably enriched in tumor tissues and actively interacted with cholangiocytes. LGALS1 was verified as a marker gene of Fibroblast_LUM+, contributing to the malignant phenotype of ICC. The higher amount of LGALS1 + fibroblasts were associated with poorer overall survival in ICC patients. LGALS1 + fibroblasts activated the proliferation and migration of tumor cells by upregulating the expression levels of CCR2, ADAM15, and ß-integrin. Silencing LGALS1 in cancer-associated fibroblasts (CAFs) suppressed CAF-augmented tumor cell migration and invasion in vitro as well as tumor formation in vivo, suggesting that blockade of LGALS1 serves as a potential therapeutic approach for ICC. Taken together, our single-cell analysis provides insight into the interaction between malignant cells and specific subtypes of fibroblasts. Our work will further the understanding of the intratumor heterogeneity of ICC and provide novel strategies for the treatment of ICC by targeting fibroblasts in the tumor microenvironment.

Digitoxin inhibits ICC cell properties via the NF­κB/ST6GAL1 signaling pathway.

Intrahepatic cholangiocarcinoma (ICC) is a type of liver cancer associated with poor prognosis and increased mortality; the limited treatment strategy highlights the urgent need for investigation. Traditional Chinese Medicine (TCM), used alone or in combination with other treatments, can enhance therapeutic efficacy, improve life quality of patients and extend overall survival. In total, two rounds of screening of a TCM library of 2,538 active compounds were conducted using a Cell Counting Kit­8 assay and ICC cell lines. Cell proliferation and migration abilities were assessed through colony formation, 5­ethynyl­2'­deoxyuridine, would healing and Transwell assays. The impact of digitoxin (DT) on signaling pathways was initially investigated using RNA sequencing and further validated using reverse transcription­quantitative PCR, western blotting, lectin blotting and flow cytometry. ICC cells stably overexpressing ST6 ß­galactoside α­2,6­sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. It was shown that DT emerged as a highly effective anti­ICC candidate from two rounds high­throughput library screening. DT could inhibit the proliferation and migration of ICC cells by suppressing NF­κB activation and reducing nuclear phosphorylated­NF­κB levels, along with diminishing ST6GAL1 mRNA and protein expression. The aforementioned biological effects and signal pathways of DT could be counteracted by overexpressing ST6GAL1 in ICC cells. In conclusion, DT suppressed ICC cell proliferation and migration by targeting the NF­κB/ST6GAL1 signaling axis. The findings of the present study indicated the promising therapeutic effects of DT in managing ICC, offering new avenues for treatment strategies.

Radiomics as a measure superior to common similarity metrics for tumor segmentation performance evaluation.

PURPOSE: To propose radiomics features as a superior measure for evaluating the segmentation ability of physicians and auto-segmentation tools and to compare its performance with the most commonly used metrics: Dice similarity coefficient (DSC), surface Dice similarity coefficient (sDSC), and Hausdorff distance (HD). MATERIALS/METHODS: The data of 10 lung cancer patients' CT images with nine tumor segmentations per tumor were downloaded from the RIDER (Reference Database to Evaluate Response) database. Radiomics features of 90 segmented tumors were extracted using the PyRadiomics program. The intraclass correlation coefficient (ICC) of radiomics features were used to evaluate the segmentation similarity and compare their performance with DSC, sDSC, and HD. We calculated one ICC per radiomics feature and per tumor for nine segmentations and 36 ICCs per radiomics feature for 36 pairs of nine segmentations. Meanwhile, there were 360 DSC, sDSC, and HD values calculated for 36 pairs for 10 tumors. RESULTS: The ICC of radiomics features exhibited greater sensitivity to segmentation changes than DSC and sDSC. The ICCs of the wavelet-LLL first order Maximum, wavelet-LLL glcm MCC, wavelet-LLL glcm Cluster Shade features ranged from 0.130 to 0.997, 0.033 to 0.978, and 0.160 to 0.998, respectively. On the other hand, all DSC and sDSC were larger than 0.778 and 0.700, respectively, while HD varied from 0 to 1.9 mm. The results indicated that the radiomics features could capture subtle variations in tumor segmentation characteristics, which could not be easily detected by DSC and sDSC. CONCLUSIONS: This study demonstrates the superiority of radiomics features with ICC as a measure for evaluating a physician's tumor segmentation ability and the performance of auto-segmentation tools. Radiomics features offer a more sensitive and comprehensive evaluation, providing valuable insights into tumor characteristics. Therefore, the new metrics can be used to evaluate new auto-segmentation methods and enhance trainees' segmentation skills in medical training and education.

Within-subject reliability of brain networks during advanced meditation: An intensively sampled 7 Tesla MRI case study.

Advanced meditation such as jhana meditation can produce various altered states of consciousness (jhanas) and cultivate rewarding psychological qualities including joy, peace, compassion, and attentional stability. Mapping the neurobiological substrates of jhana meditation can inform the development and application of advanced meditation to enhance well-being. Only two prior studies have attempted to investigate the neural correlates of jhana meditation, and the rarity of adept practitioners has largely restricted the size and extent of these studies. Therefore, examining the consistency and reliability of observed brain responses associated with jhana meditation can be valuable. In this study, we aimed to characterize functional magnetic resonance imaging (fMRI) reliability within a single subject over repeated runs in canonical brain networks during jhana meditation performed by an adept practitioner over 5 days (27 fMRI runs) inside an ultra-high field 7 Tesla MRI scanner. We found that thalamus and several cortical networks, that is, the somatomotor, limbic, default-mode, control, and temporo-parietal, demonstrated good within-subject reliability across all jhanas. Additionally, we found that several other relevant brain networks (e.g., attention, salience) showed noticeable increases in reliability when fMRI measurements were adjusted for variability in self-reported phenomenology related to jhana meditation. Overall, we present a preliminary template of reliable brain areas likely underpinning core neurocognitive elements of jhana meditation, and highlight the utility of neurophenomenological experimental designs for better characterizing neuronal variability associated with advanced meditative states.

Separating individual and group-level cooperation in the Public Goods Game.

Cooperation in the Public Goods Game (PGG) is determined by a mixture of individual differences (e.g. personality, social preferences) and group dynamics (e.g. reciprocation, social norms). However, to our knowledge, no thorough attempt has been made to separate individual and group levels of cooperation and to quantify the variance in cooperation that can be attributed to the group level. In an analysis of 10 open datasets (total N = 4,556, 1,003 groups, 7-50 rounds), we chart the trajectory of individual and group-level variance across rounds of repeated PGGs. We find that the portion of group-level variance increases initially and plateaus around the fifth round, typically at a level between 20 and 50%. In addition, we identify four factors that increase the portion of group-level variance: (i) punishment opportunities; (ii) detailed feedback including all group members' decisions; (iii) small groups (≤4 players); and (iv) groups with homogenous social preferences.

Ultrasound accuracy in evaluating renal calculi in Maysan province.

Renal calculi are a common clinical presentation. While ultrasound (US) is a widely used imaging modality for kidney stone diagnosis due to its accessibility and lower cost, its accuracy compared to computerized tomography (CT), the gold standard, remains understudied. This cross-sectional study evaluated the diagnostic accuracy of ultrasound for detecting and characterizing kidney stones compared to computed tomography (CT). Fifty-six patients with suspected kidney stones based on flank pain underwent abdominal ultrasound to assess stone presence, size, location, and the severity of any hydronephrosis (kidney swelling). These findings were then confirmed with a subsequent non-contrast CT scan. There was a fair agreement between US and CT (Kappa = 0.368) for detecting the stone location. The US could not detect 7 (12.5%) stones, being less sensitive in the middle and upper calyx compared to CT. There was a fair agreement between the US and CT (Kappa = 0.394) for detecting the severity of hydronephrosis. The US was less sensitive to moderate and severe hydronephrosis compared to CT. The abdominal ultrasound demonstrated excellent reliability for stone size measurement (intraclass correlation = 0.924), with CT measurements only slightly larger on average (mean difference 0.9 mm). Although abdominal ultrasound provides reliable stone size assessment, its capacity to accurately localize stones and assess hydronephrosis severity is limited.

Role of Ancillary Techniques in Reporting Serous Fluid Cytology - "Redefining Categories, Refining Diagnosis".

Background: The "International System of Reporting Serous Fluid Cytology (TIS)" together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in reporting serous fluid cytology. Objective: To classify serous effusion fluid samples received at our department in line with "TIS", indicating the risk of malignancy (ROM), and directing appropriate usage of ancillary testing. Materials and Methods: Prospective study carried out from October 2021 to September 2022. The study included all pleural, ascitic, and pericardial fluid samples, reported according to 'TIS'. Flow cytometry and immunocytochemistry were ancillary methods utilized to assist in reporting. Cases with available history and convincing correlations didn't require further assessment. Results: A total of 1200 serous effusion samples were evaluated including 604 pleural, 591 ascitic, and 5 pericardial fluid samples. After categorization, there were 23 samples in non-diagnostic (ND, 1.9%), 575 in negative for malignancy (NFM, 47.91%), 44 in atypia of undetermined significance (AUS, 3.66%), 64 in suspicious for malignancy (SFM, 5.33%), and 494 in malignant category (MAL, 41.16%). Ancillary studies were beneficial in the recategorization of 26% (11/44) AUS cases, 29.6% (19/64) SFM cases, and it helped refine tumor characteristics in 35.42% (175/494) cases categorized as malignant. Final ROM calculated for each category: ND 25%, NFM 18.6%, AUS 66.6%, SFM 88%, and MAL 100%. Conclusion: Serous fluid is an easily obtainable sample that can provide opportunities for ancillary testing with clinical implications. In AUS and suspicious category although, diagnostic yield is increased however, a larger number of cases are required to obtain definite results.

Test-retest reliability and time-of-day variations of perfusion imaging at rest and during a vigilance task.

Arterial spin-labeled perfusion and blood oxygenation level-dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test-retest reliability of brain function across different times of the day remains poorly understood. This study examined the test-retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test-retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.

The Doppler Perfusion Index of the Liver and the Underlying Duplex Sonography of Visceral Vessels-A Systematic and Comprehensive Evaluation of Reproducibility.

Prior to the curative resection of colorectal carcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC), the exclusion of hepatic metastasis using cross-sectional imaging is mandatory. The Doppler perfusion index (DPI) of the liver is a promising method for detecting occult liver metastases, but the underlying visceral duplex sonography is critically viewed in terms of its reproducibility. The aim of this study was to investigate systematically the reproducibility of the measured variables, the calculated blood flow, and the DPI. Between February and September 2023, two examinations were performed on 80 subjects within a period of 0-30 days and at two previously defined quality levels, aligned to the German standards of the DEGUM. Correlation analyses were carried out using Pearson's correlation coefficient (PCC) and the intraclass correlation coefficient (ICC). The diameters, blood flow, and DPI showed a high degree of agreement (PCC of 0.9 and ICC of 0.9 for AHP). Provided that a precise standard of procedure is adhered to, the Doppler examination of AHC, AHP, and PV yields very reproducible blood flows and DPI, which is a prerequisite for a comprehensive investigation of its prognostic value for the prediction of metachronous hepatic metastasis in the context of curatively treated CRC or PDAC.

Connectome caricatures: removing large-amplitude co-activation patterns in resting-state fMRI emphasizes individual differences.

High-amplitude co-activation patterns are sparsely present during resting-state fMRI but drive functional connectivity1-5. Further, they resemble task activation patterns and are well-studied3,5-10. However, little research has characterized the remaining majority of the resting-state signal. In this work, we introduced caricaturing-a method to project resting-state data to a subspace orthogonal to a manifold of co-activation patterns estimated from the task fMRI data. Projecting to this subspace removes linear combinations of these co-activation patterns from the resting-state data to create Caricatured connectomes. We used rich task data from the Human Connectome Project (HCP)11 and the UCLA Consortium for Neuropsychiatric Phenomics12 to construct a manifold of task co-activation patterns. Caricatured connectomes were created by projecting resting-state data from the HCP and the Yale Test-Retest13 datasets away from this manifold. Like caricatures, these connectomes emphasized individual differences by reducing between-individual similarity and increasing individual identification14. They also improved predictive modeling of brain-phenotype associations. As caricaturing removes group-relevant task variance, it is an initial attempt to remove task-like co-activations from rest. Therefore, our results suggest that there is a useful signal beyond the dominating co-activations that drive resting-state functional connectivity, which may better characterize the brain's intrinsic functional architecture.

Monitoring multistage healthcare processes using state space models and a machine learning based framework.

Monitoring healthcare processes, such as surgical outcomes, with a keen focus on detecting changes and unnatural conditions at an early stage is crucial for healthcare professionals and administrators. In line with this goal, control charts, which are the most popular tool in the field of Statistical Process Monitoring, are widely employed to monitor therapeutic processes. Healthcare processes are often characterized by a multistage structure in which several components, states or stages form the final products or outcomes. In such complex scenarios, Multistage Process Monitoring (MPM) techniques become invaluable for monitoring distinct states of the process over time. However, the healthcare sector has seen limited studies employing MPM. This study aims to fill this gap by developing an MPM control chart tailored for healthcare data to promote early detection, confirmation, and patient safety. As it is important to detect unnatural conditions in healthcare processes at an early stage, the statistical control charts are combined with machine learning techniques (i.e., we deal with Intelligent Control Charting, ICC) to enhance detection ability. Through Monte Carlo simulations, our method demonstrates better performance compared to its statistical counterparts. To underline the practical application of the proposed ICC framework, real data from a two-stage thyroid cancer surgery is utilized. This real-world case serves as a compelling illustration of the effectiveness of the developed MPM control chart in a healthcare setting.

The sphingolipids change in exosomes from cancer patients and association between exosome release and sphingolipids level based on a pseudotargeted lipidomics method.

The lipid based ESCRT-independent mechanism, which contributes to MVB formation, is one of the crucial procedures in exosome biogenesis. n-SMase is a key lipid metabolism enzyme in this mechanism and can induce the hydrolysis of sphingomyelins (SMs) to ceramides (Cers), thereby promoting the formation of ILVs inside MVBs. Therefore, the regulation of n-SMase can realize the alteration in exosome release. According to the fact that cancer-associated cells have a tendency to release more exosomes than healthy cells, lipid extracts in exosomes from healthy volunteers, HCC and ICC patients were analyzed by a novel pseudotargeted lipidomics method focused on sphingolipids (SLs) to explore whether cancer-related features regulate the release of exosomes through the above pathway. Multivariate analysis based on the SLs expression could distinguish three groups well indicated that the SLs expression among the three groups were different. In cancer groups, two species of critical Cers were up-regulated, denoted as Cer (d18:1_16:0) and Cer (d18:1_18:0), while 55 kinds of SLs were down-regulated, including 40 species of SMs, such as SM (d18:1_16:0), SM (d18:1_18:1) and SM (d18:1_24:0). Meanwhile, several species of SM/Cer exhibited significant down-regulation. This substantial enhancement of the SMs hydrolysis to Cers process during exosome biogenesis suggested that cancer-related features may potentially promote an increase in exosome release through ESCRT-independent mechanism. Moreover, differential SLs have a capability of becoming potential biomarkers for disease diagnosis and classification with an AUC value of 0.9884 or 0.9806 for the comparison between healthy group and HCC or ICC groups, respectively. In addition, an association analysis conducted on the cell lines showed that changes in the SM/Cer contents in cells and their exosomes were negatively correlated with the levels of released exosomes, implied the regulation of exosome release levels can be achieved by modulating n-SMase and subsequent SL expression.

Discrepancies in Perceived Indulgent Parenting, Relationship Satisfaction, and Psychological Well-Being of Adolescents and Parents.

Indulgent parenting has been associated with adolescents' psychological well-being problems; however, prior research has primarily relied on adolescents' report of such parenting behavior and its association with their own well-being, often overlooking parents' perceptions of indulgence and their own well-being. In this study, we address this gap in the literature by examining the agreement and disagreement between parents' and adolescents' perceptions of indulgent parenting and the implications for the psychological well-being of both adolescents and their parents. Further, we explore the role of adolescent-parent relationship satisfaction as a potential factor affecting these associations. Our investigation was based on data from 128 parent-adolescent dyads. Utilizing structural equation modeling with double-entry intraclass correlations (ICC_DE), our analyses revealed several main findings: (1) adolescents perceived higher levels of indulgent parenting than their parents did; (2) disagreement in perceived indulgent parenting between parents and adolescents was linked to psychological well-being problems for both adolescents and their parents; and (3) disagreement in perceptions in indulgent parenting had a stronger association with adolescents' well-being problems when adolescents reported greater relationship satisfaction with their parents. These findings provide insights into perceptions of indulgent parenting within parent-adolescent relationships and bring psychological implications for both adolescents and their parents.

Functional connectivity-hemodynamic (un)coupling changes in chronic mild brain injury are associated with mental health and neurocognitive indices: a resting state fMRI study.

PURPOSE: To examine hemodynamic and functional connectivity alterations and their association with neurocognitive and mental health indices in patients with chronic mild traumatic brain injury (mTBI). METHODS: Resting-state functional MRI (rs-fMRI) and neuropsychological assessment of 37 patients with chronic mTBI were performed. Intrinsic connectivity contrast (ICC) and time-shift analysis (TSA) of the rs-fMRI data allowed the assessment of regional hemodynamic and functional connectivity disturbances and their coupling (or uncoupling). Thirty-nine healthy age- and gender-matched participants were also examined. RESULTS: Patients with chronic mTBI displayed hypoconnectivity in bilateral hippocampi and parahippocampal gyri and increased connectivity in parietal areas (right angular gyrus and left superior parietal lobule (SPL)). Slower perfusion (hemodynamic lag) in the left anterior hippocampus was associated with higher self-reported symptoms of depression (r = - 0.53, p = .0006) and anxiety (r = - 0.484, p = .002), while faster perfusion (hemodynamic lead) in the left SPL was associated with lower semantic fluency (r = - 0.474, p = .002). Finally, functional coupling (high connectivity and hemodynamic lead) in the right anterior cingulate cortex (ACC)) was associated with lower performance on attention and visuomotor coordination (r = - 0.50, p = .001), while dysfunctional coupling (low connectivity and hemodynamic lag) in the left ventral posterior cingulate cortex (PCC) and right SPL was associated with lower scores on immediate passage memory (r = - 0.52, p = .001; r = - 0.53, p = .0006, respectively). Uncoupling in the right extrastriate visual cortex and posterior middle temporal gyrus was negatively associated with cognitive flexibility (r = - 0.50, p = .001). CONCLUSION: Hemodynamic and functional connectivity differences, indicating neurovascular (un)coupling, may be linked to mental health and neurocognitive indices in patients with chronic mTBI.

Three-Dimensional Fractal Analysis of the Interstitial Cells of Cajal Networks of Gastrointestinal Tissue Specimens.

Introduction: Several functional gastrointestinal disorders (FGIDs) have been associated with the degradation or remodeling of the network of interstitial cells of Cajal (ICC). Introducing fractal analysis to the field of gastroenterology as a promising data analytics approach to extract key structural characteristics that may provide insightful features for machine learning applications in disease diagnostics. Fractal geometry has advantages over several physically based parameters (or classical metrics) for analysis of intricate and complex microstructures that could be applied to ICC networks. Methods: In this study, three fractal structural parameters: Fractal Dimension, Lacunarity, and Succolarity were employed to characterize scale-invariant complexity, heterogeneity, and anisotropy; respectively of three types of gastric ICC network structures from a flat-mount transgenic mouse stomach. Results: The Fractal Dimension of ICC in the longitudinal muscle layer was found to be significantly lower than ICC in the myenteric plexus and circumferential muscle in the proximal, and distal antrum, respectively (both p < 0.0001). Conversely, the Lacunarity parameters for ICC-LM and ICC-CM were found to be significantly higher than ICC-MP in the proximal and in the distal antrum, respectively (both p < 0.0001). The Succolarity measures of ICC-LM network in the aboral direction were found to be consistently higher in the proximal than in the distal antrum (p < 0.05). Conclusions: The fractal parameters presented here could go beyond the limitation of classical metrics to provide better understanding of the structural-functional relationship between ICC networks and the conduction of gastric bioelectrical slow waves.

Application of dynamic contrast enhanced ultrasound analysis in predicting early response to systemic therapy of intrahepatic cholangiocarcinoma.

OBJECTIVE: To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) analysis in early prediction of tumor response to systemic treatment in patients with intrahepatic cholangiocarcinoma (ICC). PATIENTS & METHODS: In this retrospective study, patients diagnosed with ICC by core needle biopsy and histopathological results were included. All patients were diagnosed as advanced stages (stage III/IV) by the 8th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM staging system. Liver contrast-enhanced ultrasound (CEUS) examination, DCE-US analysis, CT/MRI, and blood tests were performed in all patients before and 2 months after systemic treatment. CEUS procedure was performed using an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, Germany) equipped with a 5C1 MHz convex array transducer. Time-intensity curves (TIC) and quantitative parameters were created with VueBox software. According to one-year results of the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) based on CT/MRI, patients were divided into the responder group (RG) and the non-responder group (NRG). Before and 2 months after systemic therapy, the DCE-US perfusion parameters was compared using the paired-sample t test and the Wilcoxon test. RESULTS: From September 2020 to December 2021, a total of 24 patients diagnosed with advanced ICC were included (11 males, 13 females, mean age 59.4 ± 1.8 years). According to the one year of m-RECIST results, 17 cases (70.8 %) were classified as non-responders by the final m-RECIST criteria, while 7 cases (19.2 %) were responders. Comparing before and 2 months after therapy, the RG took longer time to reach peak intensity, and the peak intensity of TIC was lower. While the TICs of NRG revealed faster enhancement after therapy. Among all DCE-US quantitative parameters, PE (peak enhancement), WiR (wash-in rate), WiPI (wash-in perfusion index) and WoR (wash-out rate) reduced significantly following 2 months of systemic therapy in RG (P < 0.05). Comparing to RG, PE and WiPI decreased slightly 2 months after therapy in NRG (P < 0.05). CONCLUSIONS: The DCE-US analysis with quantitative parameters has the potential value to make early and quantitative evaluation of treatment response to systemic therapy in ICC patients.

Feasibility of assessing non-invasive intracranial compliance using FSI simulation-based and MR elastography-based brain stiffness.

Intracranial compliance (ICC) refers to the change in intracranial volume per unit change in intracranial pressure (ICP). Magnetic resonance elastography (MRE) quantifies brain stiffness by measuring the shear modulus. Our objective is to investigate the relationship between ICC and brain stiffness through fluid-structure interaction (FSI) simulation, and to explore the feasibility of using MRE to assess ICC based on brain stiffness. This is invaluable due to the clinical importance of ICC, as well as the fast and non-invasive nature of the MRE procedure. We employed FSI simulation in hydrocephalus patients with aqueductal stenosis to non-invasively calculate ICP which is the basis of the calculation of ICC and FSI-based brain stiffness. The FSI simulated parameters used have been validated with experimental data. Our results showed that there is no relationship between FSI simulated-based brain stiffness and ICC in hydrocephalus patients. However, MRE-based brain stiffness may be sensitive to changes in intracranial fluid dynamic parameters such as cerebral perfusion pressure (CPP), cerebral blood flow (CBF), and ICP, as well as to mechano-vascular changes in the brain, which are determining parameters in ICC assessment. Although optimism has been found regarding the assessment of ICC using MRE-based brain stiffness, especially for acute-onset brain disorders, further studies are necessary to clarify their direct relationship.