Enzyme Activity-Based Optical Probe: Imaging Aminopeptidases N in Vulnerable Plaque and Serum.

Cardiovascular disease, a chronic and progressive arterial wall disease, is increasingly recognized for its clinical significance. Aminopeptidases N (APN), crucial in the pathophysiological processes of vulnerable plaque, have been linked to endothelial dysfunction, oxidative stress, and plaque formation, thus highlighting their potential as biomarkers for disease progression. However, current detection methods for APN in body fluids and in vivo have limitations, including insufficient sensitivity and specificity, time delays, and the inability to directly reflect enzyme activity in plaques. To address these challenges, we developed an optical probe, HD-APN, for in vivo imaging of aminopeptidases, providing a potential implementation in cardiovascular disease. Our work demonstrated the applicability of HD-APN for specific monitoring of aminopeptidase levels in plaques and serum, shedding light on its potential for further research in cardiovascular disease.

Promoting In Vivo NIR-II Fluorescent Imaging for Lipid in Lipid Metabolism Diseases Diagnosis.

Lipid metabolism diseases have become a tremendous risk worldwide, along with the development of productivity and particular attention to public health. It has been an urgent necessity to exploit reliable imaging strategies for lipids and thus to monitor fatty liver diseases. Herein, by converting the NIR-I signal to the NIR-II signal with IR1061 for the monitoring of lipid, the in vivo imaging of fatty liver disease was promoted on the contrast and visual effect. The main advantages of the imaging promotion in this work included a long emission wavelength, rapid response, and high signal-background-ratio (SBR) value. After promoting the NIR-I signal to NIR-II signal, IR1061 achieved higher SBR value and exhibited a dose-dependent fluorescence intensity at 1100 nm along with the increase of the EtOH proportion as well as steady and selective optical responses toward liposomes. IR1061 was further applied in the in vivo imaging of lipid in fatty liver diseases. In spite of the differences in body weight gain and TC level between healthy mice and fatty liver diseases two models, IR1061 achieved high-resolution imaging in the liver region to monitor the fatty liver disease status. This work might be informatic for the clinical diagnosis and therapeutical treatments of fatty liver diseases.

Impaired glymphatic system revealed by DTI-ALPS in cerebral palsy due to periventricular leukomalacia: relation with brain lesion burden and hand dysfunction.

PURPOSE: Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL. METHODS: We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP. RESULTS: There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect. CONCLUSION: This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.

Value of multiparametric magnetic resonance imaging for evaluating chronic kidney disease and renal fibrosis.

OBJECTIVES: To identify optimized MRI markers for evaluating chronic kidney disease (CKD) and renal interstitial fibrosis (IF). MATERIALS AND METHODS: This prospective study included 43 patients with CKD and 20 controls. The CKD group was divided into mild and moderate-to-severe subgroups based on pathological results. Scanned sequences included T1 mapping, R2* mapping, intravoxel incoherent motion imaging, and diffusion-weighted imaging. One-way analyses of variance were used to compare MRI parameters among groups. Correlations of MRI parameters with estimated glomerular filtration rate (eGFR) and renal IF were analyzed using age as covariates. The support vector machine (SVM) model was used to evaluate the diagnostic efficacy of multiparametric MRI. RESULTS: Compared to control values, renal cortical apparent diffusion coefficient (cADC), medullary ADC (mADC), cortical pure diffusion coefficient (cDt), medullary Dt (mDt), cortical shifted apparent diffusion coefficient (csADC), and medullary sADC (msADC) values gradually decreased in the mild and moderate-to-severe groups, while cortical T1 (cT1) and medullary T1 (mT1) values gradually increased. Values of cADC, mADC, cDt, mDt, cT1, mT1, csADC, and msADC were significantly associated with eGFR and IF (p < 0.001). The SVM model indicated that multiparametric MRI combining cT1 and csADC can distinguish patients with CKD from controls with high accuracy (0.84), sensitivity (0.70), and specificity (0.92) (AUC: 0.96). Multiparametric MRI combining cT1 and cADC exhibited high accuracy (0.91), sensitivity (0.95), and specificity (0.81) for evaluating IF severity (AUC: 0.96). CONCLUSION: Multiparametric MRI combining T1 mapping and diffusion imaging may be of clinical utility in non-invasive assessment of CKD and IF. CLINICAL RELEVANCE STATEMENT: This study shows that multiparametric MRI combining T1 mapping and diffusion imaging may be clinically useful in the non-invasive assessment of chronic kidney disease (CKD) and interstitial fibrosis; this could provide information for risk stratification, diagnosis, treatment, and prognosis. KEY POINTS: • Optimized MRI markers for evaluating chronic kidney disease and renal interstitial fibrosis were investigated. • Renal cortex/medullary T1 values increased as interstitial fibrosis increased; cortical shifted apparent diffusion coefficient (csADC) correlated significantly with eGFR and interstitial fibrosis. • Support vector machine (SVM) combining cortical T1 (cT1) and csADC/cADC effectively identifies chronic kidney disease and accurately predicts renal interstitial fibrosis.

Association of TLR4 (896A/G and 1196C/T) Gene Polymorphisms with Asthma Risk: A Meta-Analysis.

BACKGROUND: Conflicting data have been reported on the association between Toll-like receptor 4 (TLR4) +896A/G and +1196C/T polymorphisms and the risk of asthma. Therefore, we conducted this meta-analysis to clarify the effect of TLR4 +896A/G and +1196C/T polymorphisms on the risk of asthma. MATERIAL AND METHODS: An electronic literature search was performed using PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data to find relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. All statistical analyses were conducted using STATA software version 12.0. RESULTS: A total of 14 studies with 2873 asthma cases and 3110 controls were included. The pooled results indicated a significant association between TLR4 +1196C/T polymorphism and the risk of asthma (T vs. C: OR=0.79, 95%CI=0.63-0.99, P=0.04; TT+CT vs. CC: OR=0.76, 95%CI=0.59-0.96, P=0.03; CT vs. CC: OR=0.74, 95%CI=0.58-0.95, P=0.02). In subgroup analysis by ethnicity, TLR4 +1196C/T polymorphism was significantly associated with asthma risk in Asians (T vs. C: OR=0.73, 95%CI=0.54-0.98, P=0.04; TT+CT vs. CC: OR=0.70, 95%CI=0.51-0.96, P=0.03; CT vs. CC: OR=0.69, 95%CI=0.50-0.96, P=0.03), but not in whites. For TLR4 +896A/G polymorphism, no significant association was found between TLR4 +896A/G polymorphism and asthma risk under any genetic models. CONCLUSIONS: The results of this meta-analysis suggest that T allele of the TLR4 +1196C/T might act as a protective factor against the development of asthma.

Diagnosis for autism spectrum disorder children using T1-based gray matter and arterial spin labeling-based cerebral blood flow network metrics.

Introduction: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in motor skills, communication, emotional expression, and social interaction. Accurate diagnosis of ASD remains challenging due to the reliance on subjective behavioral observations and assessment scales, lacking objective diagnostic indicators. Methods: In this study, we introduced a novel approach for diagnosing ASD, leveraging T1-based gray matter and ASL-based cerebral blood flow network metrics. Thirty preschool-aged patients with ASD and twenty-two typically developing (TD) individuals were enrolled. Brain network features, including gray matter and cerebral blood flow metrics, were extracted from both T1-weighted magnetic resonance imaging (MRI) and ASL images. Feature selection was performed using statistical t-tests and Minimum Redundancy Maximum Relevance (mRMR). A machine learning model based on random vector functional link network was constructed for diagnosis. Results: The proposed approach demonstrated a classification accuracy of 84.91% in distinguishing ASD from TD. Key discriminating network features were identified in the inferior frontal gyrus and superior occipital gyrus, regions critical for social and executive functions in ASD patients. Discussion: Our study presents an objective and effective approach to the clinical diagnosis of ASD, overcoming the limitations of subjective behavioral observations. The identified brain network features provide insights into the neurobiological mechanisms underlying ASD, potentially leading to more targeted interventions.

Dual-Activated Photoacoustic Probe for Reliably Detecting Hydroxyl Radical in Ischemic Cardiovascular Disease in Mouse and Human Samples.

Cardiovascular disease (CVD) is a chronic disease characterized by the accumulation of lipids and fibrous tissue within the arterial walls, potentially leading to vascular obstruction and an increased risk of heart disease and stroke. Hydroxyl radicals play a significant role in the formation and progression of CVD as they can instigate lipid peroxidation, resulting in cellular damage and inflammatory responses. However, precisely detecting hydroxyl radicals in CVD lesions presents significant challenges due to their high reactivity and short lifespan. Herein, we present the development and application of a novel activatable optical probe, Cy-OH-LP, designed to detect hydroxyl radicals in lipid-rich environments specifically. Built on the Cy7 molecular skeleton, Cy-OH-LP exhibits near-infrared absorption and fluorescence characteristics, and its specific response to hydroxyl radicals enables a turn-on signal in both photoacoustic and fluorescence spectra. The probe demonstrated excellent selectivity and stability in various tests. Furthermore, Cy-OH-LP was successfully applied in an in vivo model to detect hydroxyl radicals in mouse models, providing a potential tool for diagnosing and monitoring AS. The biosafety of Cy-OH-LP was also verified, showing low cytotoxicity and no significant organ damage in mice. The findings suggest that Cy-OH-LP is a promising tool for the specific detection of hydroxyl radicals in lipid-rich environments, providing new possibilities for research and clinical applications in the field of oxidative stress-related diseases.

Corrigendum: Diagnosis for autism spectrum disorder children using T1-based gray matter and arterial spin labeling-based cerebral blood flow network metrics.

[This corrects the article DOI: 10.3389/fnins.2024.1356241.].

In Vivo Imaging of γ-Glutamyl Transferase in Cardiovascular Diseases with a Photoacoustic Probe.

In this work, a photoacoustic (PA) probe, HDS-GGT, was developed for the in vivo imaging of cardiovascular diseases by monitoring the γ-glutamyl transferase (GGT) dynamics. HDS-GGT exhibited a stable PA signal with auxiliary absorbance and NIRF variation after the trigger by GGT. In all three modalities of absorbance, NIRF, and PA, HDS-GGT could quantitatively reflect the GGT level. In PA modality, HDS-GGT indicated the practical advantages including high sensitivity, high stability, and high specificity. In living oxidized low-density lipoprotein-induced RAW264.7 cells, HDS-GGT indicated proper capability for imaging the plaques by visualizing the GGT dynamics. Moreover, during imaging in living model mice, HDS-GGT was achieved to distinguish the plaques from healthy blood vessels via a multiview PA presentation. HDS-GGT could also suggest the severity of plaques in the extracted aorta from the model mice, which was consistent with the histological staining results. The information herein might be useful for future investigations on cardiovascular diseases.

Application of Multimodal MRI in the Early Diagnosis of Autism Spectrum Disorders: A Review.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in children. Early diagnosis and intervention can remodel the neural structure of the brain and improve quality of life but may be inaccurate if based solely on clinical symptoms and assessment scales. Therefore, we aimed to analyze multimodal magnetic resonance imaging (MRI) data from the existing literature and review the abnormal changes in brain structural-functional networks, perfusion, neuronal metabolism, and the glymphatic system in children with ASD, which could help in early diagnosis and precise intervention. Structural MRI revealed morphological differences, abnormal developmental trajectories, and network connectivity changes in the brain at different ages. Functional MRI revealed disruption of functional networks, abnormal perfusion, and neurovascular decoupling associated with core ASD symptoms. Proton magnetic resonance spectroscopy revealed abnormal changes in the neuronal metabolites during different periods. Decreased diffusion tensor imaging signals along the perivascular space index reflected impaired glymphatic system function in children with ASD. Differences in age, subtype, degree of brain damage, and remodeling in children with ASD led to heterogeneity in research results. Multimodal MRI is expected to further assist in early and accurate clinical diagnosis of ASD through deep learning combined with genomics and artificial intelligence.

Deep Learning Network with Spatial Attention Module for Detecting Acute Bilirubin Encephalopathy in Newborns Based on Multimodal MRI.

BACKGROUND: Acute bilirubin encephalopathy (ABE) is a significant cause of neonatal mortality and disability. Early detection and treatment of ABE can prevent the further development of ABE and its long-term complications. Due to the limited classification ability of single-modal magnetic resonance imaging (MRI), this study aimed to validate the classification performance of a new deep learning model based on multimodal MRI images. Additionally, the study evaluated the effect of a spatial attention module (SAM) on improving the model's diagnostic performance in distinguishing ABE. METHODS: This study enrolled a total of 97 neonates diagnosed with ABE and 80 neonates diagnosed with hyperbilirubinemia (HB, non-ABE). Each patient underwent three types of multimodal imaging, which included T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and an apparent diffusion coefficient (ADC) map. A multimodal MRI classification model based on the ResNet18 network with spatial attention modules was built to distinguish ABE from non-ABE. All combinations of the three types of images were used as inputs to test the model's classification performance, and we also analyzed the prediction performance of models with SAMs through comparative experiments. RESULTS: The results indicated that the diagnostic performance of the multimodal image combination was better than any single-modal image, and the combination of T1WI and T2WI achieved the best classification performance (accuracy = 0.808 ± 0.069, area under the curve = 0.808 ± 0.057). The ADC images performed the worst among the three modalities' images. Adding spatial attention modules significantly improved the model's classification performance. CONCLUSION: Our experiment showed that a multimodal image classification network with spatial attention modules significantly improved the accuracy of ABE classification.

Effect of auricular acupuncture on neuroplasticity of stroke patients with motor dysfunction: A fNIRS study.

Cerebral Stroke is an acute cerebrovascular disease, a disease of brain tissue damage caused by the sudden rupture or blockage of blood vessels in the brain that prevents blood flow to the brain. Acupuncture has become a popular treatment for stroke, with auricular acupuncture providing a new idea for stroke treatment. However, the neuromodulatory mechanism of auricular acupuncture in the brain is still unclear. The aim of this study was to investigate the effect of auricular acupuncture in the treatment of upper limb dysfunction and the activation of specific brain regions in stroke patients. Forty patients with stroke hemiplegia who met the nerf criteria were included in the experiment and randomly assigned into two groups (20 patients in each group): the auricular acupuncture group and the control group. Fugl-Meyer score (FMA) assessment of upper limb motor function, motor evoked potential (MEP) measurement, and functional near-infrared brain function imaging (fNIRS) data acquisition in the primary motor M1 area of the brain at rest were performed before and after treatment, respectively. It was found that: 1) after auricular acupuncture treatment, the patients in the auricular acupuncture group showed significantly greater peak MEP and significantly higher oxyhemoglobin content in the M1 region of the brain compared with the control group, with a significant activation effect (MEP: P-value = 0.032, t = -2.22; HbO2; f = 4.225, p = 0.046); 2) in the clinical efficacy assessment, the FMA score in the auricular acupuncture group after treatment (p = 0.0122, t = 2.769). The results suggest that auricular acupuncture has an ameliorative effect on upper limb motor deficits after stroke and that activation of the M1 region of the brain may be a key node in auricular acupuncture for treating upper limb dysfunction in stroke patients, a finding that emphasizes the potential for clinical application of auricular acupuncture therapy for stroke patients with potential mechanisms influencing the outcome.

Clinical progression, pathological characteristics, and radiological findings in children with diffuse leptomeningeal glioneuronal tumors: A systematic review.

Background: Diffuse leptomeningeal glioneuronal tumors are rare leptomeningeal neoplasms composed of oligodendrocyte-like cells characterized by neuronal differentiation and a lack of isocitrate dehydrogenase gene mutation. Purpose: We aimed to analyze the clinical progression, pathological characteristics, and radiological findings of diffuse leptomeningeal glioneuronal tumors in children, as well as the relevance of clinico-radiological data. Data Sources: We searched MEDLINE, PubMed, and Web of Science to identify case reports, original articles, and review articles discussing diffuse leptomeningeal glioneuronal tumors published between 2000 and 2021. Study Selection: The analysis included 145 pediatric patients from 43 previous studies. Data Analysis: Data regarding patient pathology, MRI manifestations, clinical symptoms, and progression were collected. The relationship between imaging classification and pathological findings was using chi-square tests. Overall survival was analyzed using Kaplan-Meier curves. Data Synthesis: Parenchymal tumors were mainly located in the intramedullary areas of the cervical and thoracic spine, and patients which such tumors were prone to 1p-deletion (χ2 = 4.77, p=0.03) and KIAA1549-BRAF fusion (χ2 = 12.17, p<0.001). The median survival time was 173 months, and the survival curve fell significantly before 72 months. Parenchymal tumor location was associated with overall survival (p=0.03), patients with KIAA 1549-BRAF (+) and treated with chemotherapy exhibited a better clinical course (p<0.001). Limitations: The analysis included case reports rather than consecutively treated patients due to the rarity of diffuse leptomeningeal glioneuronal tumors, which may have introduced a bias. Conclusions: Early integration of clinical, pathological, and radiological findings is necessary for appropriate management of this tumor, as this may enable early treatment and improve prognosis.

Effects of auricular acupuncture stimulation on healthy adults' upper limb motor-evoked potentials: A randomized, crossover, double-blind study.

Objective: The aim of this study was to determine whether auricular acupuncture has neuromodulatory effects on the motor cortex of healthy adults. Methods: Fourteen healthy subjects received a real auricular acupuncture stimulation (SF1) session and a sham acupuncture stimulation session. The interval between the two types of stimulation was more than 24 h. A finger dexterity test (taping score and taping speed by using ipad) was assessed, and motor-evoked potentials (MEP) were assessed before and after each stimulation. Results: Before the treatment, there were no significant differences in MEP amplitude, tapping score, or tapping speed (P > 0.05) between the real and sham stimulation conditions. After the treatment, the MEP amplitude, tapping score, and tapping speed in the real stimulation condition increased significantly compared to the pre-stimulation measurements and were significantly higher than those in the sham stimulation condition (P < 0.01). In the sham stimulation condition, the MEP amplitude, tapping score, and tapping speed decreased significantly compared to the pre-stimulation measurements (P < 0.05). Conclusion: Acupuncture of auricular points can modulate the excitability of the motor cortex area of controlling the upper limbs. Clinical trial registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2100051608].

Lifetime distribution of spontaneous emission from emitter(s) in three-dimensional woodpile photonic crystals.

Spontaneous emission lifetime distribution in the basic unit cell or on a plane of the excited emitters embedded in woodpile photonics crystals with low refractive index contrast are investigated. It is found that the spontaneous emission lifetime distribution strongly depends on the position and transition frequency of the emitters, and has the same symmetry as that of the unit cell. The lifetimes of emitters near the upper gap edge are longer than that in the center of the pseudo-gap, which is quite a contrast to the conventional concept. Furthermore, it is revealed that the polarization orientation of the emitters has significant influence on the lifetime distribution, and may result in a high anisotropy factor (defined as the difference between the maximum and minimum values of the lifetime) up to 4.2. These results may be supplied in probing the lifetime distribution or orientation-dependent local density of states in future experiments.

Novel Compound Heterozygous Pathogenic Variants in SUOX Cause Isolated Sulfite Oxidase Deficiency in a Chinese Han Family.

AIM: To explore the clinical imaging, laboratory and genetic characteristics of a newborn boy with isolated sulfite oxidase deficiency (ISOD) in a Chinese mainland cohort. METHODS: Homocysteine and uric acid in plasma and cysteine and total homocysteine in the blood spot were assessed in a Chinese newborn patient with progressive encephalopathy, tonic seizures, abnormal muscle tone, and feeding difficulties. Whole exome sequencing and Sanger sequencing facilitated an accurate diagnosis. The pathogenicity predictions and conservation analysis of the identified mutations were conducted by bioinformatics tools. RESULTS: Low total homocysteine was detected in the blood spot, while homocysteine and uric acid levels were normal in the plasma. S-sulfocysteine was abnormally elevated in urine. A follow-up examination revealed several progressive neuropathological findings. Also, intermittent convulsions and axial dystonia were observed. However, the coordination of sucking and swallowing was slightly improved. A novel paternal nonsense variant c.475G > T (p.Glu159∗) and a novel maternal missense variant c.1201A > G (p.Lys401Glu) in SUOX were identified in this case by co-segregation verification. CONCLUSION: This is the second report of early-onset ISOD case in a non-consanguineous Chinese mainland family. Combined with the clinical characteristics and biochemical indexes, we speculated that these two novel pathogenic variants of the SUOX gene underlie the cause of the disease in this patient. Next-generation sequencing (NGS) and Sanger sequencing provided reliable basis for clinical and prenatal diagnoses of this family, it also enriched the mutation spectrum of the SUOX gene.

Structural network performance for early diagnosis of spastic cerebral palsy in periventricular white matter injury.

Periventricular white matter injury (PWMI) is a common cause of spastic cerebral palsy (SCP). Diffusion tensor imaging (DTI) shows high sensitivity but moderate specificity for predicting SCP. The limited specificity may be due to the diverse and extensive brain injuries seen in infants with PWMI. We enrolled 72 infants with corrected age from 6 to 18 months in 3 groups: PWMI with SCP (n = 20), non-CP PWMI (n = 19), and control (n = 33) groups. We compared DTI-based brain network properties among the three groups and evaluated the diagnostic performance of brain network properties for SCP in PWMI infants. Our results show abnormal global parameters (reduced global and local efficiency, and increased shortest path length), and local parameters (reduced node efficiency) in the PWMI with SCP group. On logistic regression, the combined node efficiency of the bilateral precentral gyrus and right middle frontal gyrus had a high sensitivity (90%) and specificity (95%) for differentiating PWMI with SCP from non-CP PWMI, and significantly correlated with the Gross Motor Function Classification System scores. This study confirms that DTI-based brain network has great diagnostic performance for SCP in PWMI infants, and the combined node efficiency improves the diagnostic accuracy.

Specific White Matter Lesions Related to Motor Dysfunction in Spastic Cerebral Palsy: A Meta-analysis of Diffusion Tensor Imaging Studies.

BACKGROUND: Assessing motor impairment in spastic cerebral palsy is a key factor in the treatment and rehabilitation of patients. We intend to investigate the correlation between diffusion tensor imaging properties of sensorimotor pathways and motor function in spastic cerebral palsy using meta-analysis, and to determine specific white matter lesions that are closely related to motor dysfunction in spastic cerebral palsy. METHODS: We conducted a literature search of PubMed, Embase, Scopus, and Web of Science databases to identify trials published from January 1999 to January 2019 that had evaluated the correlation between fractional anisotropy and motor function scores in spastic cerebral palsy. Correlation coefficient (r) values were extracted for each study, and the extent of r was quantitatively explored. The r values between fractional anisotropy within different sensorimotor pathways and motor function scores were pooled respectively. RESULTS: Nineteen studies involving 504 children with spastic cerebral palsy, were included. Fractional anisotropy in both sensory and motor pathways significantly correlated with motor function scores. However, compared with the corticospinal tract and thalamic radiation, fractional anisotropy in the posterior limb of the internal capsule correlated more strongly with gross motor function classification system and upper limb motor function (r = -0.71, 95% confidence interval [CI] -0.80 to -0.60; r = 0.73, 95% CI 0.60-0.82, respectively; P < .05). CONCLUSIONS: Fractional anisotropy within the posterior limb of the internal capsule is more closely related to motor dysfunction and can potentially be a biomarker for evaluating the degree of motor impairment in spastic cerebral palsy.

The Most Cited Original Articles in Brain Imaging of Children With Cerebral Palsy: A Bibliometric Analysis Between 1984 and 2019.

Objective: Brain imaging is important in diagnosing children with cerebral palsy (CP) and in identifying its etiology. To provide study navigation in this field, a bibliometric analysis was conducted by analyzing the most highly cited articles. Methods: The Web of Science All Databases were used for literature search in this study. All original articles on imaging in children with CP were searched. Two reviewers screened the search results independently and eliminated articles based on exclusion criteria such as participants over 20 years old, topics referring to images outside of the brain, or trauma. According to descending order of yearly citation counts, the top 25% of all included articles were considered as highly cited articles. Information such as yearly citations, research purposes, imaging modalities, CP types, and study designs were recorded and analyzed. Results: A total of 50 highly cited articles ranked by yearly citations (from 23.85 to 3.33, 1991-2018) were included in this study. Considering different research purposes, these studies were classified into three categories: diagnosis studies (n = 25; 1991-2017, median: 2011), mechanism studies (n = 15; 1999-2018; median: 2014), and prognosis and therapeutic effect studies (n = 10; 2008-2017; median: 2014.5). First, for diagnosis studies, 22 studies used single modality and three used multi-modalities; the majority of these studies focused on diagnostic value evaluation (n = 10) and image performance (n = 12) of a single type of CP (n = 15) by using descriptive (n = 14) or cross-sectional approaches (n = 10). Second, for mechanism studies, the ratio between single and multi-modality was 8:7; most of these studies concentrated on a single subtype of spastic CP (hemiplegia = 10, quadriplegia = 2) with a cross-sectional study design (n = 10). Third, regarding the prognosis and therapeutic effect studies, the single vs. multi-modality ratio was 5:5, and these studies were dedicated to the efficiency of constraint-induced movement therapy in children with hemiplegia; paired design trials (n = 6) and randomized controlled trials (n = 2) were used more frequently. Conclusion: Studies using multi-modality and high-level evidence-based design to provide information regarding mechanism, prognosis, and therapeutic efficacy may be the potential future research direction in the field of CP research.

Treatment response prediction of rehabilitation program in children with cerebral palsy using radiomics strategy: protocol for a multicenter prospective cohort study in west China.

BACKGROUND: Cerebral palsy (CP) is a major cause of chronic childhood disability worldwide, causing activity limitation as well as impairments in sensation, cognition, and communication. Leveraging biomarkers to establish individualized predictions of future treatment responses will be of great value. We aim to develop and validate a model that can be used to predict the individualized treatment response in Children with CP. METHODS: A multicenter prospective cohort study will be conducted in 4 hospitals in west China. One hundred and thirty children with CP will be recruited and undergo clinical assessment using the Peabody Developmental Motor Scales, Manual Ability Classification System (MACS), Hand Assessment for Infants (HAI), Assisting Hand Assessment (AHA), and Gross Motor Function Classification System (GMFCS). The data collected will include MRI image, clinical status, and socioeconomic status. The clinical information and MRI features extracted using radiomics strategy will be combined for exploratory analysis. The accuracy, sensitivity, and specificity of the model will be assessed using multiple modeling methodologies. Internal and external validation will be used to evaluate the performance of the radiomics model. DISCUSSION: We hypothesized that the findings from this study could provide a critical step towards the prediction of treatment response in children with CP, which could also complement other biomarkers in the development of precision medicine approaches for this severe disorder. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT02979743).