A Multicenter Study on Preoperative Assessment of Lymphovascular Space Invasion in Early-Stage Cervical Cancer Based on Multimodal MR Radiomics.

BACKGROUND: As lymphovascular space invasion (LVSI) was closely related to lymph node metastasis and prognosis, the preoperative assessment of LVSI in early-stage cervical cancer is crucial for patients. PURPOSE: To develop and validate nomogram based on multimodal MR radiomics to assess LVSI status in cervical cancer patients. STUDY TYPE: Retrospective. POPULATION: The study included 168 cervical cancer patients, of whom 129 cases (age 51.36 ± 9.99 years) from institution 1 were included as the training cohort and 39 cases (age 52.59 ± 10.23 years) from institution 2 were included as the external test cohort. FIELD STRENGTH/SEQUENCE: There were 1.5 T and 3.0 T MRI scans (T1-weighted imaging [T1WI], fat-saturated T2-weighted imaging [FS-T2WI], and contrast-enhanced [CE]). ASSESSMENT: Six machine learning models were built and selected to construct the radiomics signature. The nomogram model was constructed by combining the radiomics signature with the clinical signature, which was then validated for discrimination, calibration, and clinical usefulness. STATISTICAL TESTS: The clinical characteristics were compared using t-tests, Mann-Whitney U tests, or chi-square tests. The Spearman and LASSO methods were used to select radiomics features. The receiver operating characteristic (ROC) analysis was performed, and the area under the curve (AUC), accuracy, sensitivity, and specificity were calculated. RESULTS: The logistic regression (LR) model performed best in each sequence. The AUC of CE-T1-T2WI-combined was the highest in the LR model, with an AUC of 0.775 (95% CI: 0.570-0.979) in external test cohort. The nomogram showed high predictive performance in the training (AUC: 0.883 [95% CI: 0.823-0.943]) and test cohort (AUC: 0.830 [95% CI: 0.657-1.000]) for predicting LVSI. Decision curve analysis demonstrated that the nomogram was clinically useful. DATA CONCLUSION: Our findings suggest that the proposed nomogram model based on multimodal MRI of CE T1WI-T2WI-combined could be used to assess LVSI status in early cervical cancer. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

A radiomics based approach using adrenal gland and periadrenal fat CT images to allocate COVID-19 health care resources fairly.

BACKGROUND: The value of radiomics features from the adrenal gland and periadrenal fat CT images for predicting disease progression in patients with COVID-19 has not been studied extensively. We assess the value of radiomics features from the adrenal gland and periadrenal fat CT images in predicting COVID-19 disease exacerbation. METHODS: A total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed a 3D V-net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted. RESULTS: The auto-segmentation framework yielded a dice value 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.717, 0.716, 0.736, 0.760, and 0.833 in the validation set. FM and RN had better predictive efficacy than CM (P < 0.0001) in the training set. RN showed that there was no significant difference in the validation set (mean absolute error [MAE] = 0.04) and test set (MAE = 0.075) between predictive and actual results. Decision curve analysis showed that if the threshold probability was between 0.4 and 0.8 in the validation set or between 0.3 and 0.7 in the test set, it could gain more net benefits using RN than FM and CM. CONCLUSIONS: Radiomics features extracted from the adrenal gland and periadrenal fat CT images are related to disease exacerbation in patients with COVID-19.

Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing.

Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.

Morphologic changes in the visual cortex of patients with anisometropic amblyopia: a surface-based morphometry study.

BACKGROUND: Amblyopia is generally considered a neurodevelopmental disorder that results from abnormal visual experiences in early childhood and may persist to adulthood. The neural basis of amblyopia has been a matter of interest for many decades, but the critical neural processing sites in amblyopia are not entirely understood. Although many functional neuroimaging studies have found abnormal neuronal responses both within and beyond V1, few studies have focused on the neurophysiologic abnormalities in the visual cortex from the viewpoint of potential structural reorganization. In this study, we used a well-validated and highly accurate surface-based method to examine cortical morphologic changes in the visual cortex using multiple parameters (including cortical thickness, surface area, volume and mean curvature). RESULTS: The cortical thicknesses of the bilateral V1, left V2, left ventral V3, left V4 and left V5/MT+ in patients were significantly thinner than that in controls. The mean curvature of the bilateral V1 was significantly increased in the patients compared with the controls. For the surface area and gray matter volume, no significant differences were found between patients and controls in all region of interests. The cortical thicknesses of the bilateral V1 were both negatively correlated with the amount of anisometropia. No significant correlations were found between any other surface parameters and clinical variables. CONCLUSION: In addition to cortical thickness, the altered mean curvature of the cortex may indicate neuroanatomic impairments of the visual cortex in patients with anisometropic amblyopia. Moreover, the structural changes were bilateral in the primary visual cortex but were unilateral in the secondary and more senior visual cortex.

Altered hippocampal GABA and glutamate levels and uncoupling from functional connectivity in multiple sclerosis.

There is growing evidence for dysfunctional glutamatergic excitation and/or gamma-aminobutyric acid (GABA)ergic inhibition in patients with multiple sclerosis (MS). Cognitive impairment may occur during the early stages of MS and hippocampal abnormalities have been suggested as biomarkers. However, researchers have not clearly determined whether changes in hippocampal GABA and glutamate (Glu) levels are associated with cognitive impairment and aberrant neural activity in patients with MS. We used magnetic resonance spectroscopy to measure GABA+ and Glu levels in the left hippocampal region of 29 patients with relapsing-remitting MS and 29 healthy controls (HCs). Resting-state functional connectivity (FC) with the hippocampus was also examined. Compared to HCs, patients exhibited significantly lower GABA+ and Glu levels, which were associated with verbal and visuospatial memory deficits, respectively. Patients also showed decreased FC strengths between the hippocampus and several cortical regions, which are located within the default mode network. Moreover, hippocampal GABA+ levels and Glu/GABA+ ratios correlated with the FC strengths in HCs but not in patients with MS. This study describes a novel method for investigating the complex relationships among excitatory/inhibitory neurotransmitters, brain connectivity and cognition in health and disease. Strategies that modulate Glu and GABA neurotransmission may represent new therapeutic treatments for patients with MS.

Orbito-frontal cortex mechanism of inhibition of return in current and remitted depression.

Deficient inhibition of return (IOR) for emotional materials is an important cognitive biomarker of depression. However, its neural mechanism and role in depression remission remain largely unknown. Using functional magnetic resonance imaging (fMRI), this study observed the neural foundation of inhibition of return in individuals with current (n = 30) and remitted (n = 27) depression and in healthy controls (n = 33), by using a cue-target task. The results showed that individuals with remitted depression (RMD) possessed a nonavoidant attention model for sad faces, which indicated a cue validity and was correlated with enhanced task- and resting-state activation and function connectivity in orbitofrontal cortex (OFC). The patients with major depressive disorder (MDD), in contrast, displayed an IOR effect for all faces, which indicated a strategy of attention avoidance due to the high cognitive burden in the cue-target task, and was correlated with decreased resting-state activation and function connectivity in OFC. Moreover, the hippocampus, a less-known cortex in IOR, showed a contrary model, that is, lower activation in depression remission and higher task- and resting-state activation in depressive episodes. The results suggest the OFC mechanism of the IOR effect in remitted depression and the hippocampus mechanism of the IOR effect in depressive episodes, which offer potential biomarkers for the clinical treatment of depression.

Disrupted local neural activity and functional connectivity in subjective tinnitus patients: evidence from resting-state fMRI study.

PURPOSE: The study aimed to investigate the abnormal alterations of both the intra-regional brain activity and inter-regional functional connectivity (FC) in patients with subjective tinnitus (ST) using resting-state functional MRI (rs-fMRI) methods. METHODS: Twenty-five ST patients and 25 normal controls (NCs) were included and underwent resting-state functional magnetic resonance imaging scans. ReHo, fALFF, and seed-based FC were calculated and compared between ST patients and NCs. Meanwhile, correlation analyses were calculated between altered connectivity and clinical data in ST patients. RESULTS: Compared with NCs, ST patients exhibited increased ReHo and fALFF values in the right middle temporal gyrus (MTG), and the ReHo values were also increased in the right cuneus. In contrast, decreased ReHo values in ST patients were observed in the right middle frontal gyrus (MFG) and left cerebellar anterior lobe. Considering these brain areas with altered ReHo and fALFF clusters as seeds, the right MTG (ReHo) exhibited decreased connectivity with the right MFG, lingual gyrus, and left cerebellar posterior lobe, besides, the right cuneus showed decreased connectivity with the right MTG. In ST patients, the decreased FC between the right MTG (ReHo) and the right MFG was also positively correlated with the Tinnitus handicap inventory score (r = 0.675, P = 0.001). CONCLUSION: The present study revealed that ST patients had altered regional neural activity and inter-regional connectivity in partial auditory and non-auditory brain regions, mainly involving the default mode network and audio-visual network, which could further improve our understanding of the neuroimaging mechanism in ST.

Heritability of the Effective Connectivity in the Resting-State Default Mode Network.

The default mode network (DMN) is thought to reflect endogenous neural activity, which is considered as one of the most intriguing phenomena in cognitive neuroscience. Previous studies have found that key regions within the DMN are highly interconnected. Here, we characterized the genetic influences on causal or directed information flow within the DMN during the resting state. In this study, we recruited 46 pairs of twins and collected fMRI imaging data using a 3.0 T scanner. Dynamic causal modeling was conducted for each participant, and a structural equation model was used to calculate the heritability of DMN in terms of its effective connectivity. Model comparison favored a full-connected model. Structural equal modeling was used to estimate the additive genetics (A), common environment (C) and unique environment (E) contributions to variance for the DMN effective connectivity. The ACE model was preferred in the comparison of structural equation models. Heritability of DMN effective connectivity was 0.54, suggesting that the genetic made a greater contribution to the effective connectivity within DMN. Establishing the heritability of default-mode effective connectivity endorses the use of resting-state networks as endophenotypes or intermediate phenotypes in the search for the genetic basis of psychiatric or neurological illnesses.

Altered interhemispheric functional connectivity in patients with anisometropic and strabismic amblyopia: a resting-state fMRI study.

PURPOSE: Altered brain functional connectivity has been reported in patients with amblyopia by recent neuroimaging studies. However, relatively little is known about the alterations in interhemispheric functional connectivity in amblyopia. The present study aimed to investigate the functional connectivity patterns between homotopic regions across hemispheres in patients with anisometropic and strabismic amblyopia under resting state. METHODS: Nineteen monocular anisometropic amblyopia (AA), 18 strabismic amblyopia (SA), and 20 normal-sight controls (NC) were enrolled in this study. After a comprehensive ophthalmologic examination, resting-state fMRI scanning was performed in all participants. The pattern of the interhemispheric functional connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach. VMHC values differences within and between three groups were compared, and correlations between VMHC values and each the clinical variable were also analyzed. RESULTS: Altered VMHC was observed in AA and SA patients in lingual gyrus and fusiform gyrus compared with NC subjects. The altered VMHC of lingual gyrus showed a pattern of AA > SA > NC, while the altered VMHC of fusiform gyrus showed a pattern of AA > NC > SA. Moreover, the VMHC values of lingual gyrus were positively correlated with the stereoacuity both in AA and SA patients, and the VMHC values of fusiform gyrus were positively correlated with the amount of anisometropia just in AA patients. CONCLUSION: These findings suggest that interhemispheric functional coordination between several homotopic visual-related brain regions is impaired both in AA and SA patients under resting state and revealed the similarities and differences in interhemispheric functional connectivity between the anisometropic and strabismic amblyopia.

Distinct patterns of spontaneous brain activity between children and adults with anisometropic amblyopia: a resting-state fMRI study.

PURPOSE: To detect the altered spontaneous brain activity patterns in children and adults with anisometropic amblyopia using resting-state functional magnetic resonance imaging (rs-fMRI) technique combined with the amplitude of low-frequency fluctuation (ALFF) method. METHODS: Thirty-two monocular anisometropic amblyopia and 34 normal-sight controls were divided into child group and adult group. Rs-fMRI was performed in all participants and analysis of ALFF value within the whole brain was conducted in each subject. ALFF value differences between the patients and controls in the two groups were compared via an independent two-sample t test. RESULTS: The amblyopic children mainly exhibited increased ALFF in part of the bilateral calcarine (BA17), the left middle occipital gyrus (BA18/19), and the left postcentral gyrus (BA2). By contrast, the amblyopic adults showed decreased ALFF in the bilateral precuneus cortex (part of BA7), and the standardized ALFF value of bilateral precuneus were correlated with the amount of anisometropia of the amblyopic adults. CONCLUSIONS: Rs-fMRI is an effective noninvasive technique for exploring brain activity of the anisometropic amblyopia. Our findings demonstrated that brain activity changed both in amblyopic children and adults under the resting state, and revealed the differences in spontaneous activity patterns between the amblyopic children and adults.

The Plasticity of Brain Gray Matter and White Matter following Lower Limb Amputation.

Accumulating evidence has indicated that amputation induces functional reorganization in the sensory and motor cortices. However, the extent of structural changes after lower limb amputation in patients without phantom pain remains uncertain. We studied 17 adult patients with right lower limb amputation and 18 healthy control subjects using T1-weighted magnetic resonance imaging and diffusion tensor imaging. Cortical thickness and fractional anisotropy (FA) of white matter (WM) were investigated. In amputees, a thinning trend was seen in the left premotor cortex (PMC). Smaller clusters were also noted in the visual-to-motor regions. In addition, the amputees also exhibited a decreased FA in the right superior corona radiata and WM regions underlying the right temporal lobe and left PMC. Fiber tractography from these WM regions showed microstructural changes in the commissural fibers connecting the bilateral premotor cortices, compatible with the hypothesis that amputation can lead to a change in interhemispheric interactions. Finally, the lower limb amputees also displayed significant FA reduction in the right inferior frontooccipital fasciculus, which is negatively correlated with the time since amputation. In conclusion, our findings indicate that the amputation of lower limb could induce changes in the cortical representation of the missing limb and the underlying WM connections.

Differentiation of bland from neoplastic thrombus of the portal vein in patients with hepatocellular carcinoma: application of susceptibility-weighted MR imaging.

BACKGROUND: Neoplastic and bland portal vein thrombi (PVT) are both common in patients with hepatocellular carcinoma (HCC). The correct discrimination of them is essential for therapeutic strategies planning and survival predicting. The current study aims to investigate the value of susceptibility-weighted imaging (SWI) in differentiating bland from neoplastic PVT in HCC patients. METHODS: 20 HCC patients with bland PVT and 22 HCC patients with neoplastic PVT were imaged with non-contrast SWI at 3.0 Tesla MRI. The signal intensity (SI) of the PVT and HCC lesions in the same patients was compared on SW images. The phase values of the PVT were compared between neoplastic and bland thrombi cohorts. Receiver operator characteristics (ROC) analysis was conducted to evaluate the diagnostic ability of the phase values for neoplastic and bland thrombi discrimination. RESULTS: 20 of 22 neoplastic PVT were judged similar SI and 2 were judged lower SI than their HCC. For 20 bland PVT, 19 were judged lower SI and 1 was judged similar SI as their HCC (P<0.001). The average phase values (0.361 ± 0.224) of the bland PVT were significantly higher than those of the neoplastic PVT (-0.328 ± 0.127, P<0.001). The AUC for phase values in differentiating bland from neoplastic PVT was 0.989. The best cut-off value was -0.195, which gave a sensitivity of 95% and a specificity of 95.5%. CONCLUSIONS: SW imaging appears to be a promising new method for distinguishing neoplastic from bland PVT. The high sensitivity and specificity suggest its high value in clinical practice.

Radiomics models to predict bone marrow metastasis of neuroblastoma using CT.

Background: Bone marrow is the leading site for metastasis from neuroblastoma and affects the prognosis of patients with neuroblastoma. However, the accurate diagnosis of bone marrow metastasis is limited by the high spatial and temporal heterogeneity of neuroblastoma. Radiomics analysis has been applied in various cancers to build accurate diagnostic models but has not yet been applied to bone marrow metastasis of neuroblastoma. Methods: We retrospectively collected information from 187 patients pathologically diagnosed with neuroblastoma and divided them into training and validation sets in a ratio of 7:3. A total of 2632 radiomics features were retrieved from venous and arterial phases of contrast-enhanced computed tomography (CT), and nine machine learning approaches were used to build radiomics models, including multilayer perceptron (MLP), extreme gradient boosting, and random forest. We also constructed radiomics-clinical models that combined radiomics features with clinical predictors such as age, gender, ascites, and lymph gland metastasis. The performance of the models was evaluated with receiver operating characteristics (ROC) curves, calibration curves, and risk decile plots. Results: The MLP radiomics model yielded an area under the ROC curve (AUC) of 0.97 (95% confidence interval [CI]: 0.95-0.99) on the training set and 0.90 (95% CI: 0.82-0.95) on the validation set. The radiomics-clinical model using an MLP yielded an AUC of 0.93 (95% CI: 0.89-0.96) on the training set and 0.91 (95% CI: 0.85-0.97) on the validation set. Conclusions: MLP-based radiomics and radiomics-clinical models can precisely predict bone marrow metastasis in patients with neuroblastoma.

Expanded ROS Generation and Hypoxia Reversal: Excipient-free Self-assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy.

The efficacy of photodynamic therapy (PDT)-related cancer therapies is significantly restricted by two irreconcilable obstacles, i.e., low reactive oxygen species (ROS) generation capability and hypoxia which constrains the immune response. Herein, this work develops a self-assembled clinical photosensitizer indocyanine green (ICG) and the HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) nanoparticles (ISDN) without any excipient. This work discovers that the hydrophobic interaction forces between ICG and 17-DMAG promote the photostability of ICG and its intersystem crossing (ISC) process, thereby improving the ROS quantum yield from 0.112 to 0.46. Augmented ROS generation enhances PDT efficacy and further enhances immunogenic cell death (ICD) effects. 17-DMAG inhibits the HSP90/hypoxia-inducible factor 1α (HIF-1α) axis to dramatically reverse the immunosuppressive tumor microenvironment caused by PDT-aggravated hypoxia. In a mouse model of pancreatic cancer, ISDN markedly improve cytotoxic T lymphocyte infiltration and MHC I and MHC II activation, demonstrating the superior ICD effects in situ tumor and the powerful systematic antitumor immunity generation, eventually achieving vigorous antitumor and recurrence resistance. This study proposes an unsophisticated and versatile strategy to significantly improve PDT efficacy for enhancing systemic antitumor immunity and potentially extending it to multiple cancers.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Inferior frontal white matter asymmetry correlates with executive control of attention.

White matter (WM) asymmetries of the human brain have been well documented using diffusion tensor imaging (DTI). However, the relationship between WM asymmetry pattern and cognitive performance is poorly understood. By means of tract-based spatial statistics (TBSS) and voxel-based analyses of whole brain, this study examined the WM asymmetries and the correlations between WM integrity/asymmetries and three distinct components of attention, namely alerting, orienting, and executive control (EC), which were assessed by attention network test (ANT). We revealed a number of WM anisotropy asymmetries, including leftward asymmetry of cingulum, corticospinal tract and cerebral peduncle, rightward asymmetry of internal capsule, superior longitudinal fasciculus and posterior corona radiata, as well as heterogeneous asymmetries in anterior corpus callosum and anterior corona radiata (ACR). Moreover, specific correlation was found between asymmetric pattern of inferior frontal ACR and EC performance. Additionally, this study also proposed that there were no significant relationships of WM anisotropy asymmetries to alerting and orienting functions. Further clusters of interest analyses and probabilistic fiber tracking validated our findings. In conclusion, there are a number of differences in WM integrity between human brain hemispheres. Specially, the anisotropy asymmetry in inferior frontal ACR plays a crucial role in EC function. Our finding is supportive of the functional studies of inferior frontal regions and in keeping with the theory of the brain lateralization on human ventral attention system.

[Effects of functional connectivity between anterior cingulate cortex and dorsolateral prefrontal cortex on executive control of attention in healthy individuals].

OBJECTIVE: To explore the presence of functional connectivity between anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) during the manipulation of attentional network test (ANT) and its relationship with behavioral performance. METHODS: Functional magnetic resonance imaging was performed on 25 healthy subjects aged 17 - 20 years. And ANT was used as a paradigm. Functional connectivity between ACC-DLPFC was tested and correlation analysis conducted between functional connectivity coefficients and behavioral scores of ANT. RESULTS: Significant functional connectivity between the dorsal ACC (dACC) with bilateral DLPFC was found. Furthermore, event-related functional connectivity coefficients between left dACC and left DLPFC were negatively associated with the behavioral scores of executive control (r = -0.63; P < 0.01). CONCLUSION: Our findings provide new evidence that ACC and DLPFC are functionally connected and such functional connectivity has advantageous influence on executive control function of attention so as to contribute to our understanding of the integrated role of these brain regions in attentional network.

Promoting the application of pediatric radiomics via an integrated medical engineering approach.

Radiomics is widely used in adult tumors but has been rarely applied to the field of pediatrics. Promoting the application of radiomics in pediatric diseases, especially in the early diagnosis and stratified treatment of tumors, is of great value to the realization of the WHO 2030 "Global Initiative for Childhood Cancer." This paper discusses the general characteristics of radiomics, the particularity of its application to pediatric diseases, and the current status and prospects of pediatric radiomics. Radiomics is a data-driven science, and the combination of medicine and engineering plays a decisive role in improving data quality, data diversity, and sample size. Compared with adult radiomics, pediatric radiomics is significantly different in data type, disease spectrum, disease staging, and progression. Some progress has been made in the identification, classification, stratification, survival prediction, and prognosis of tumor diseases. In the future, big data applications from multiple centers and cross-talent training should be strengthened to improve the benefits for clinical workers and children.

Machine-learning radiomics to predict bone marrow metastasis of neuroblastoma using magnetic resonance imaging.

Background: Neuroblastoma is one common pediatric malignancy notorious for high temporal and spatial heterogeneities. More than half of its patients develop distant metastases involving vascularized organs, especially the bone marrow. It is thus necessary to have an economical, noninvasive method without much radiation for follow-ups. Radiomics has been used in many cancers to assist accurate diagnosis but not yet in bone marrow metastasis in neuroblastoma. Methods: A total of 182 patients with neuroblastoma were retrospectively collected and randomly divided into the training and validation sets. Five-hundred and seventy-two radiomics features were extracted from magnetic resonance imaging, among which 41 significant ones were selected via T-test for model development. We attempted 13 machine-learning algorithms and eventually chose three best-performed models. The integrative performance evaluations are based on the area under the curves (AUCs), calibration curves, risk deciles plots, and other indexes. Results: Extreme gradient boosting, random forest (RF), and adaptive boosting were the top three to predict bone marrow metastases in neuroblastoma while RF was the most accurate one. Its AUC was 0.90 (0.86-0.93), F1 score was 0.82, sensitivity was 0.76, and negative predictive value was 0.79 in the training set. The values were 0.82 (0.71-0.93), 0.80, 0.75, and 0.92 in the validation set, respectively. Conclusions: Radiomics models are likely to contribute more to metastatic diagnoses and the formulation of personalized healthcare strategies in clinics. It has great potential of being a revolutionary method to replace traditional interventions in the future.

Repolarizing tumor-associated macrophages by layered double hydroxide-based deacidification agent for tumor chemodynamic therapy and immunotherapy.

Tumor-associated macrophages (TAMs)-mediated immunotherapy has attracted extensive attention in tumor elimination. However, the acidic tumor microenvironment (TME) severely limits the phenotype of TAMs to pro-tumoral M2 state, suppressing immune response efficacy against tumors. Herein, novel poly(acrylic acid) (PAA)-coated, doxorubicin (DOX)-loaded layered double hydroxide (LDH) nanosheets (NSs) were developed as deacidification agent to repolarize TAMs from pro-tumoral M2 to anti-tumoral M1 phenotype for tumor elimination through combined chemodynamic therapy and immunotherapy. When located in tumor regions, LDH-PAA@DOX NSs display good deacidification capacity to neutralize acidic TME, achieving the repolarization of TAMs to M1 phenotype and further activating CD8+ T cells. During the deacidification process, these NSs are acid-responsive and degrade to release Fe3+ and DOX. The former can be reduced to Fe2+ by intracellular glutathione, meanwhile disrupting the antioxidant defense system of tumor cells. The latter can damage tumor cells directly and further stimulate the production of hydrogen peroxide, providing abundant substrate for the Fenton reaction. Toxic hydroxyl radical is excessively produced through Fe2+-mediated Fenton reaction to cause intratumoral oxidative stress. In vivo data revealed that significant tumor elimination can be achieved under LDH-PAA@DOX treatment. This work not only provides a promising paradigm for neutralizing acidic TME using deacidification agent but also highlights the effectiveness of combined chemodynamic therapy and immunotherapy in tumor treatment.