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Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls), attenuates diet-induced obesity (DIO) in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO) in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes.

BACKGROUND & AIMS:Obesity is a leading healthcare issue contributing to metabolic diseases. There is a great interest in non-invasive approaches for quantitating abdominal fat in obese animals and humans. In this work, we propose an automated method to distinguish and quantify subcutaneous and visceral adipose tissues (SAT and VAT) in rodents during obesity and weight loss interventions. We have also investigated the influence of different magnetic resonance sequences and sources of variability in quantification of fat depots. MATERIALS AND METHODS:High-fat diet fed rodents were utilized for investigating the changes during obesity, exercise, and calorie restriction interventions (N = 7/cohort). Imaging was performed on a 7T Bruker ClinScan scanner using fast spin echo (FSE) and Dixon imaging methods to estimate the fat depots. Finally, we quantified the SAT and VAT volumes between the L1-L5 lumbar vertebrae using the proposed automatic hybrid geodesic region-based curve evolution algorithm. RESULTS:Significant changes in SAT and VAT volumes (p

This review article serves to highlight radiological services as a major cost driver for the healthcare sector, and the potential improvements in productivity and cost savings that can be generated by incorporating artificial intelligence (AI) into the radiology workflow, referencing Singapore healthcare as an example. More specifically, we will discuss the opportunities for AI in lowering healthcare costs and supporting transformational shifts in our care model in the following domains: predictive analytics for optimising throughput and appropriate referrals, computer vision for image enhancement (to increase scanner efficiency and decrease radiation exposure) and pattern recognition (to aid human interpretation and worklist prioritisation), natural language processing and large language models for optimising reports and text data-mining. In the context of preventive health, we will discuss how AI can support population level screening for major disease burdens through opportunistic screening and democratise expertise to increase access to radiological services in primary and community care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Sim, Bhanu Prakash, Huang and Tan.)

Background: Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis., Results: We found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10., Conclusions: The early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.

Background: Effective stem cell therapy is dependent on the stem cell quality that is determined by their differentiation potential, impairment of which leads to poor engraftment and survival into the target cells. However, limitations in our understanding and the lack of reliable markers that can predict their maturation efficacies have hindered the development of stem cells as an effective therapeutic strategy. Our previous study identified CD10, a pro-adipogenic, depot-specific prospective cell surface marker of human adipose-derived stem cells (ASCs). Here, we aim to determine if CD10 can be used as a prospective marker to predict mature adipocyte quality and play a direct role in adipocyte maturation., Methods: We first generated 14 primary human subject-derived ASCs and stable immortalized CD10 knockdown and overexpression lines for 4 subjects by the lentiviral transduction system. To evaluate the role of CD10 in adipogenesis, the adipogenic potential of the human subject samples were scored against their respective CD10 transcript levels. Assessment of UCP1 expression levels was performed to correlate CD10 levels to the browning potential of mature ASCs. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to determine CD10-dependent regulation of various targets. Seahorse analysis of oxidative metabolism and lipolysis assay were studied. Lastly, as a proof-of-concept study, we used CD10 as a prospective marker for screening nuclear receptor ligands library., Results: We identified intrinsic CD10 levels as a positive determinant of adipocyte maturation as well as browning potential of ASCs. Interestingly, CD10 regulates ASC's adipogenic maturation non-canonically by modulating endogenous lipolysis without affecting the classical peroxisome proliferator-activated receptor gamma (PPARγ)-dependent adipogenic pathways. Furthermore, our CD10-mediated screening analysis identified dexamethasone and retinoic acid as stimulator and inhibitor of adipogenesis, respectively, indicating CD10 as a useful biomarker for pro-adipogenic drug screening., Conclusion: Overall, we establish CD10 as a functionally relevant ASC biomarker, which may be a prerequisite to identify high-quality cell populations for improving metabolic diseases.

Adipogenesis is essential in in vitro experimentation to assess differentiation capability of stem cells, and therefore, its accurate measurement is important. Quantitative analysis of adipogenic levels, however, is challenging and often susceptible to errors due to non-specific reading or manual estimation by observers. To this end, we developed a novel adipocyte quantification algorithm, named Fast Adipogenesis Tracking System (FATS), based on computer vision libraries. The FATS algorithm is versatile and capable of accurately detecting and quantifying percentage of cells undergoing adipogenic and browning differentiation even under difficult conditions such as the presence of large cell clumps or high cell densities. The algorithm was tested on various cell lines including 3T3-L1 cells, adipose-derived mesenchymal stem cells (ASCs), and induced pluripotent stem cell (iPSC)-derived cells. The FATS algorithm is particularly useful for adipogenic measurement of embryoid bodies derived from pluripotent stem cells and was capable of accurately distinguishing adipogenic cells from false-positive stains. We then demonstrate the effectiveness of the FATS algorithm for screening of nuclear receptor ligands that affect adipogenesis in the high-throughput manner. Together, the FATS offer a universal and automated image-based method to quantify adipocyte differentiation of different cell lines in both standard and high-throughput workflows.

Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/deletion of serine palmitoyltransferase (Sptlc), the first enzyme in the sphingolipid biosynthesis cascade, in mice markedly altered adipose morphology and metabolism, particularly in subcutaneous adipose tissue. The reduction in adipose sphingolipids increased brown and beige/brite adipocyte numbers, mitochondrial activity, and insulin sensitivity. The manipulation also increased numbers of anti-inflammatory M2 macrophages in the adipose bed and induced secretion of insulin-sensitizing adipokines. By comparison, deletion of serine palmitoyltransferase from macrophages had no discernible effects on metabolic homeostasis or adipose function. These data indicate that newly synthesized adipocyte sphingolipids are nutrient signals that drive changes in the adipose phenotype to influence whole-body energy expenditure and nutrient metabolism., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity.

Objective: Brown adipose tissue (BAT) plays a key role for thermogenesis in mammals and infants. Recent confirmation of BAT presence in adult humans has aroused great interest for its potential to initiate weight-loss and normalize metabolic disorders in diabetes and obesity. Reliable detection and differentiation of BAT from the surrounding white adipose tissue (WAT) and muscle is critical for assessment/quantification of BAT volume. This study evaluates magnetic resonance (MR) acquisition for BAT and the efficacy of different automated methods for MR features-based BAT segmentation to identify the best suitable method., Materials and Methods: Multi-point Dixon and multi-echo T2 spin-echo images were acquired from 12 mice using an Agilent 9.4T scanner. Four segmentation methods: multidimensional thresholding (MTh); region-growing (RG); fuzzy c-means (FCM) and neural-network (NNet) were evaluated for the interscapular region and validated against manually defined BAT, WAT and muscle., Results: Statistical analysis of BAT segmentation yielded a median Dice-Statistical-Index, and sensitivity of 89.92% for NNet, 82.86% for FCM, 72.74% for RG, and 72.70%, for MTh, respectively., Conclusion: This study demonstrates that NNet improves the specificity to BAT from surrounding tissue based on 3-point Dixon and T2 MRI. This method facilitates quantification and longitudinal measurement of BAT in preclinical-models and human subjects.

Objective: The aim was to auto-segment and characterize brown adipose, white adipose and muscle tissues in rats by multi-parametric magnetic resonance imaging with validation by histology and UCP1., Materials and Methods: Male Wistar rats were randomized into two groups for thermoneutral (n = 8) and cold exposure (n = 8) interventions, and quantitative MRI was performed longitudinally at 7 and 11 weeks. Prior to imaging, rats were maintained at either thermoneutral body temperature (36 ± 0.5 °C), or short term cold exposure (26 ± 0.5 °C). Neural network based automatic segmentation was performed on multi-parametric images including fat fraction, T2 and T2* maps. Isolated tissues were subjected to histology and UCP1 analysis., Results: Multi-parametric approach showed precise delineation of the interscapular brown adipose tissue (iBAT), white adipose tissue (WAT) and muscle regions. Neural network based segmentation results were compared with manually drawn regions of interest, and showed 96.6 and 97.1% accuracy for WAT and BAT respectively. Longitudinal assessment of the iBAT volumes showed a reduction at 11 weeks of age compared to 7 weeks. The cold exposed group showed increased iBAT volume compared to thermoneutral group at both 7 and 11 weeks. Histology and UCP1 expression analysis supported our imaging results., Conclusion: Multi-parametric MR based neural network auto-segmentation provides accurate separation of BAT, WAT and muscle tissues in the interscapular region. The cold exposure improves the classification and quantification of heterogeneous BAT.

Purpose: An automatic, accurate and fast segmentation of hemorrhage in brain Computed Tomography (CT) images is necessary for quantification and treatment planning when assessing a large number of data sets. Though manual segmentation is accurate, it is time consuming and tedious. Semi-automatic methods need user interactions and might introduce variability in results. Our study proposes a modified distance regularized level set evolution (MDRLSE) algorithm for hemorrhage segmentation., Methods: Study data set (from the ongoing CLEAR-IVH phase III clinical trial) is comprised of 200 sequential CT scans of 40 patients collected at 10 different hospitals using different machines/vendors. Data set contained both constant and variable slice thickness scans. Our study included pre-processing (filtering and skull removal), segmentation (MDRLSE which is a two-stage method with shrinking and expansion) with modified parameters for faster convergence and higher accuracy and post-processing (reduction in false positives and false negatives)., Results: Results are validated against the gold standard marked manually by a trained CT reader and neurologist. Data sets are grouped as small, medium and large based on the volume of blood. Statistical analysis is performed for both training and test data sets in each group. The median Dice statistical indices (DSI) for the 3 groups are 0.8971, 0.8580 and 0.9173 respectively. Pre- and post-processing enhanced the DSI by 8 and 4% respectively., Conclusions: The MDRLSE improved the accuracy and speed for segmentation and calculation of the hemorrhage volume compared to the original DRLSE method. The method generates quantitative information, which is useful for specific decision making and reduces the time needed for the clinicians to localize and segment the hemorrhagic regions.

Accurate quantification of haemorrhage volume in a computed tomography (CT) scan is critical in the management and treatment planning of intraventricular (IVH) and intracerebral haemorrhage (ICH). Manual and semi-automatic methods are laborious and time-consuming limiting their applicability to small data sets. In clinical trials measurements are done at different locations and on a large number of data; an accurate, consistent and automatic method is preferred. A fast and efficient method based on texture energy for identification and segmentation of hemorrhagic regions in the CT scans is proposed. The data set for the study was obtained from CLEAR-IVH clinical trial phase III (41 patients' 201 sequential CT scans from ten different hospitals, slice thickness 2.5-10 mm and from different scanners). The DICOM data were windowed, skull stripped, convolved with textural energy masks and segmented using a hybrid method (a combination of thresholding and fuzzy c-means). Artifacts were removed by statistical analysis and morphological processing. Segmentation results were compared with the ground truth. Descriptive statistics, Dice statistical index (DSI), Bland-Altman and mean difference analysis were carried out. The median sensitivity, specificity and DSI for slice identification and haemorrhage segmentation were 86.25%, 100%, 0.9254 and 84.90%, 99.94%, 0.8710, respectively. The algorithm takes about one minute to process a scan in MATLAB(®). A hybrid method-based volumetry of haemorrhage in CT is reliable, observer independent, efficient, reduces the time and labour. It also generates quantitative data that is important for precise therapeutic decision-making.

Existing methods of neuroimage registration typically require high quality scans and are time-consuming. We propose a simple and fast method which allows intra-patient multi-modal and time-series neuroimage registration as well as landmark identification (including commissures and superior/inferior brain landmarks) for sparse data. The method is based on elliptical approximation of the brain cortical surface in the vicinity of the midsagittal plane (MSP). Scan registration is performed by a 3D affine transformation based on parameters of the cortex elliptical fit and by aligning the MSPs. The landmarks are computed using a statistical localization method based on analysis of 53 structural scans without detectable pathology. The method is illustrated for multi-modal registration, analysis of hemorrhagic stroke time series, and ischemic stroke follow ups, as well as for localization of hardly visible or not discernible landmarks in sparse neuroimages. The method also enables a statistical localization of landmarks in sparse morphological/non-morphological images, where landmark points may be invisible.

A theoretically simple and computationally efficient method to extract the midsagittal plane (MSP) from volumetric neuroimages is presented. The method works in two stages (coarse and fine) and is based on calculation of the Kullback and Leibler's (KL) measure, which characterizes the difference between two distributions. Slices along the sagittal direction are analyzed with respect to a reference slice to determine the coarse MSP. To calculate the final MSP, a local search algorithm is applied. The proposed method does not need any preprocessing, like reformatting, skull stripping, etc. The algorithm was validated quantitatively on 75 MRI datasets of different pulse sequences (T1WI, T2WI, FLAIR and SPGR) and MRA. The angular and distance errors between the calculated MSP and the ground truth lines marked by the expert were calculated. The average distance and angular deviation were 1.25 pixels and 0.63 degrees , respectively. In addition, the algorithm was tested qualitatively on PD, FLAIR, MRA, and CT datasets. To analyze the robustness of the method against rotation, inhomogeneity and noise, the phantom data were used.

We introduce and validate the Fast Talairach Transformation (FTT). FTT is a rapid version of the Talairach transformation (TT) with the modified Talairach landmarks. Landmark identification is fully automatic and done in 3 steps: calculation of midsagittal plane, computing of anterior commissure (AC) and posterior commissure (PC) landmarks, and calculation of cortical landmarks. To perform these steps, we use fast and anatomy-based algorithms employing simple operations. FTT was validated for 215 diversified T1-weighted and spoiled gradient recalled (SPGR) MRI data sets. It calculates the landmarks and warps the Talairach-Tournoux atlas fully automatically in about 5 sec on a standard computer. The average distance errors in landmark localization are (in mm): 1.16 (AC), 1.49 (PC), 0.08 (left), 0.13 (right), 0.48 (anterior), 0.16 (posterior), 0.35 (superior), and 0.52 (inferior). Extensions to FTT by introducing additional landmarks and applying nonlinear warping against the ventricular system are addressed. Application of FTT to other brain atlases of anatomy, function, tracts, cerebrovasculature, and blood supply territories is discussed. FTT may be useful in a clinical setting and research environment: (1) when the TT is used traditionally, (2) when a global brain structure positioning with quick searching and labeling is required, (3) in urgent cases for quick image interpretation (eg, acute stroke), (4) when the difference between nonlinear and piecewise linear warping is negligible, (5) when automatic processing of a large number of cases is required, (6) as an initial atlas-scan alignment before performing nonlinear warping, and (7) as an initial atlas-guided segmentation of brain structures before further local processing.

Rationale and Objectives: This study explores morphological relationships and structural variability of the corpus callosum (CC), fornix (Fo), anterior (AC), and posterior commissures (PC)., Materials and Methods: These structures are extracted automatically on the midsagittal plane. The CC and Fo are modeled using best-fit ellipses. The parameters characterizing these structures and relationships among them are points, distances, angles, and eccentricities. The minimum, maximum and mean values, standard deviations, and coefficients of variation for all parameters are calculated for 62 diversified MRI datasets. Subsequently, the regression analysis and parameter distribution study are performed., Results: The parameters have at least 10% variations. The major axis of CC and eccentricities of CC and Fo vary much less than the other parameters The major axis of CC is approximately parallel to the AC-PC line. The mean eccentricity of each of CC and Fo is greater than 0.95. The most significant correlation (P < .05) is observed between various angles and the angle between the major axes of CC and Fo. The correlation is also significant between other angles and distances. The Weibull distribution characterizes the major axis of CC, and distance between the AC and the most superior point of CC. Distribution of angle between the major axes of CC and Fo is log (logistic), and normal for the AC-PC distance., Conclusions: The AC-PC distance, used prevalently for brain normalization, is not correlated with any parameters except with the distance between the AC and the most superior point on the body of the CC with P < .05.

Rationale and Objective: Accurate identification of the anterior commissure (AC) and posterior commissure (PC) is critical in neuroradiology, functional neurosurgery, human brain mapping, and neuroscience research. Moreover, major stereotactic brain atlases are based on the AC and PC. Our goal is to provide an algorithm for a rapid, robust, accurate and automatic identification of AC and PC., Materials and Method: The method exploits anatomical and radiological properties of AC, PC and surrounding structures, including morphological variability. The localization is done in two stages: coarse and fine. The coarse stage locates the AC and PC on the midsagittal plane by analyzing their relationships with the corpus callosum, fornix, and brainstem. The fine stage refines the AC and PC in a well-defined volume of interest, analyzing locations of lateral and third ventricles, interhemispheric fissure, and massa intermedia., Results: The algorithm was developed using simple operations, like histogramming, thresholding, region growing, 1D projections. It was tested on 94 diversified T1W and SPGR datasets. After the fine stage, 71 (76%) volumes had an error between 0-1 mm for the AC and 55 (59%) for the PC. The mean errors were 1.0 mm (AC) and 1.0 mm (PC). The accuracy has improved twice due to fine stage processing. The algorithm took about 1 second for coarse and 4 seconds for fine processing on P4, 2.5 GHz., Conclusion: The use of anatomical and radiological knowledge including variability in algorithm formulation aids in localization of structures more accurately and robustly. This fully automatic algorithm is potentially useful in clinical setting and for research.

The Talairach transformation (TT), the most prevalent method for brain normalization and atlas-to-data warping, is conceptually simple, fast and can be automated. Two problems with the TT in the clinical setting that are addressed in this article are reduced accuracy at the orbitofrontal cortex and upper corpus callosum (CC) and unsuitability for functional neurosurgery because of incomplete scanning. To increase dorsoventral accuracy, we introduce 2 additional landmarks: the top of the CC (SM) and the most ventral point of the orbitofrontal cortex on the midsagittal slab (IM). A method for their automatic calculation is proposed and validated against 55 diversified magnetic resonance (MR) imaging cases. The SM and IM landmarks are identified accurately and robustly in an automatic way. The average error of SM localization is 0.69 mm, and 91% of all cases have an error not greater than 1 mm. The average error of IM localization is 0.98 mm, approximately three quarters of cases have an error not greater than 1 mm, and 95% of all cases have an error not larger than 2 mm. The SM is correlated (R(2) = 0.72) with the most superior cortical landmark, whereas the IM is only loosely correlated (R(2) = 0.22) with the most inferior cortical landmark. On average, the original TT overlays the atlas axial plate at -24 on the orbitofrontal cortex as opposed to the correct plate at -28. Therefore, 1-dimensional ventral scaling in the original TT is insufficient to cope with variability in the orbitofrontal cortex. The key advantages of our approach are the preserved conceptual simplicity of the TT, fully automatic identification of the new landmarks, improved accuracy of the atlas-to-data match without compromising performance, and enabled TT use in functional neurosurgery when a dorsal part of the brain is not available in the scan.

This pilot study was carried out to find the feasibility of analyzing the maturity of the fetal lung using ultrasound images. Data were collected from normal pregnant women at intervals of two weeks from the gestation age of 24 to 38 weeks. Images were acquired at two centers located at different geographical locations. The total data acquired consisted of 750 images of immature and 250 images of mature class. A region of interest of 64 x 64 pixels was used for extracting the features. Various textural features were computed from the fetal lung and liver images. The ratios of fetal lung to liver feature values were investigated as possible indexes for classifying the images into those from mature (reduced pulmonary risk) and immature (possible pulmonary risk) lung. The features used are fractal dimension, lacunarity, and features derived from the histogram of the images. The following classifiers were used to classify the fetal lung images as belonging to mature or immature lung: nearest neighbor, k-nearest neighbor, modified k-nearest neighbor, multilayer perceptron, radial basis function network, and support vector machines. The classification accuracy obtained for the testing set ranges from 73% to 96%.

Fetal lung and liver tissues were examined by ultrasound in 240 subjects during 24 to 38 weeks of gestational age in order to investigate the feasibility of predicting the maturity of the lung from the textural features of sonograms. A region of interest of 64 x 64 pixels is used for extracting textural features. Since the histological properties of the liver are claimed to remain constant with respect to gestational age, features obtained from the lung region are compared with those from liver. Though the mean values of some of the features show a specific trend with respect to gestation age, the variance is too high to guarantee definite prediction of the gestational age. Thus, we restricted our purview to an investigation into the feasibility of fetal lung maturity prediction using statistical textural features. Out of 64 features extracted, those features that are correlated with gestation age and less computationally intensive are selected. The results of our study show that the sonographic features hold some promise in determining whether the fetal lung is mature or immature.