Baseline white matter function predicts short-term treatment response in first-episode schizophrenia.

BACKGROUND AND PURPOSE: The detection and characterization of functional activities in the gray matter of schizophrenia (SZ) have been widely explored. However, the relationship between resting-state functional signals in the white matter of first-episode SZ and short-term treatment response remains unclear. METHODS: Thirty-six patients with first-episode SZ and 44 matched healthy controls were recruited in this study. Patients were classified as nonresponders and responders based on response to antipsychotic medication during a single hospitalization. The fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) of white matter were calculated. The relationships between functional changes and clinical features were analyzed. In addition, voxel-based morphometry was performed to analyze the white matter volume. RESULTS: One-way analysis of variance showed significant differences of fALFF and ReHo in the left posterior thalamic radiation and left cingulum (hippocampus) in the patient group, and the areas were regarded as seeds. The FC was calculated between seeds and other white matter networks. Compared with responders, nonresponders showed significantly increased FC between the left cingulum (hippocampus) and left posterior thalamic radiation, splenium of corpus callosum, and left tapetum, and were associated with the changes of clinical assessment. However, there was no difference in white matter volume between groups. CONCLUSION: Our work provides a novel insight that psycho-neuroimaging-based white matter function holds promise for influencing the clinical diagnosis and treatment of SZ.

Differentiation of Neoplastic and Non-neoplastic Intracranial Enhancement Lesions Using Three-Dimensional Pseudo-Continuous Arterial Spin Labeling.

Background and Purpose: It is sometimes difficult to effectively distinguish non-neoplastic from neoplastic intracranial enhancement lesions using conventional magnetic resonance imaging (MRI). This study aimed to evaluate the diagnostic performance of three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) to differentiate non-neoplastic from neoplastic enhancement lesions intracranially. Materials and Methods: This prospective study included thirty-five patients with high-grade gliomas (HGG), twelve patients with brain metastasis, and fifteen non-neoplastic patients who underwent conventional, contrast enhancement and 3D-pCASL imaging at 3.0-T MR; all lesions were significantly enhanced. Quantitative parameters including cerebral blood flow (CBF) and relative cerebral blood flow (rCBF) were compared between neoplastic and non-neoplastic using Student's t-test. In addition, the area under the receiver operating characteristic (ROC) curve (AUC) was measured to assess the differentiation diagnostic performance of each parameter. Results: The non-neoplastic group demonstrated significantly lower rCBF values of lesions and perilesional edema compared with the neoplastic group. For the ROC analysis, both relative cerebral blood flow of lesion (rCBF-L) and relative cerebral blood flow of perilesional edema (rCBF-PE) had good diagnostic performance for discriminating non-neoplastic from neoplastic lesions, with an AUC of 0.994 and 0.846, respectively. Conclusion: 3D-pCASL may contribute to differentiation of non-neoplastic from neoplastic lesions.

Triple network hypothesis-related disrupted connections in schizophrenia: A spectral dynamic causal modeling analysis with functional magnetic resonance imaging.

OBJECTIVE: The symptom-related neurobiology characteristic of schizophrenia in the brain from a network perspective is still poorly understood, leading to a lack of potential biologically-based markers and difficulty identifying therapeutic targets. We aim to test the dysregulated cross-network interactions among the Salience Network (SN), Central Executive Network (CEN) and Default Mode Network (DMN) and how they contributed to different symptoms in schizophrenia patients. METHODS: We examined network interactions among the SN, CEN and DMN in 76 patients with schizophrenia vs. 80 well-matched controls using dynamic causal modeling (DCM). We further analyzed the relation between network dynamics and Positive and Negative Syndrome Scale (PANSS). RESULTS: We observed that the DMN, CEN and SN across healthy controls and schizophrenia patients showed several similarities within or between-network pattern in the resting state. Comparing schizophrenia to controls, SN-centered cross-network interactions were most significantly reduced. Crucially, the strength of connections from CEN subnetwork 1 to DMN subnetwork 1 was positively correlated with the Positive Score of PANSS. The connection from the DMN subnetwork 2 to CEN subnetwork 2 was negatively correlated with the Negative Score of PANSS. CONCLUSIONS: Our study provides strong evidence for the dysregulation among SN, CEN and DMN in a triple-network perspective in schizophrenia. The connection between DMN and CEN could be clinically-relevant neurobiological signature of schizophrenia symptoms. Our study indicated that the description of brain triple network hypothesis could be a novel and possible bio-marker for schizophrenia.

Neuroimaging-based brain-age prediction of first-episode schizophrenia and the alteration of brain age after early medication.

BACKGROUND: Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear. AIMS: To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age. METHOD: The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed. RESULTS: The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = -0.326, P = 0.014). CONCLUSIONS: The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.

Grading of Glioma: combined diagnostic value of amide proton transfer weighted, arterial spin labeling and diffusion weighted magnetic resonance imaging.

BACKGROUND: To investigate the ability of amide proton transfer (APT) weighted magnetic resonance imaging (MRI), arterial spin labeling (ASL), diffusion weighted imaging (DWI) and the combination for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). METHODS: Twenty-seven patients including nine LGGs and eighteen HGGs underwent conventional, APT, ASL and DWI MRI with a 3.0-T MR scanner. Histogram analyses was performed and quantitative parameters including mean apparent diffusion coefficient (ADC mean), 20th-percentile ADC (ADC 20th), mean APT (APT mean), 90th-percentile APT (APT 90th), relative mean cerebral blood flow (rCBF mean) and relative 90th-percentile CBF (rCBF 90th) were compared between HGGs and LGGs. The diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis of each parameter and their combination. Correlations were analyzed among the MRI parameters and Ki-67. RESULTS: The APT values were significantly higher in the HGGs compared to the LGGs (p <  0.005), whereas ADC values were significantly lower in HGGs than LGGs (P <  0.0001). The ADC 20th and APT mean had higher discrimination abilities compared with other single parameters, with the area under the ROC curve (AUC) of 0.877 and 0.840. Adding ADC parameter, the discrimination ability of APT and rCBF significantly improved. The ADC was negatively correlated with the APT and rCBF value, respectively, while APT value was positively correlated with rCBF value. Significant correlations between ADC values and Ki-67 were also observed. CONCLUSIONS: APT and DWI are valuable in differentiating HGGs from LGGs. The combination of APT, DWI and ASL imaging could improve the ability for discriminating HGGs from LGGs.

PlGF signaling and macrophage repolarization contribute to the anti-neoplastic effect of metformin.

Placental growth factor (PlGF) related signaling pathway has been shown to have close relationship with the progression of cancers. Metformin has been reported to have an inhibitory effect on PlGF expression in a breast cancer model. However, little is known about whether the anti-neoplastic activity of metformin is contributed by its inhibitory effect on PlGF expression. Protein, mRNA and secretion levels of PlGF were tested and the proliferation of cancer cells was determined. After treatment of metformin, BALB/c mice bearing 4T1 tumors were sacrificed and immunohistochemistry staining of the tumor sections was obtained. Baseline expression of autocrine PlGF varied between different breast cancer cell lines, while the expression of vascular endothelial growth factor receptor-1 (VEGFR-1) was comparable between cell lines. Other clinical data showed that the expression of PlGF other than VEGFR-1 had a prognostic value for patients with breast cancers. Metformin significantly decreased the secretion and mRNA levels of PlGF, which greatly contributed to its inhibitory effect on the proliferation of breast cancer cells with high P1GF expression. The unresponsiveness of tumor cells with low PlGF expression to genetic silencing was reversed by the supplementation of exogenous PlGF. Systemic metformin administration apparently inhibited the in vivo growth of 4T1 carcinoma, which was accompanied by the repolarization of macrophages from M2 to M1. These findings indicated that both autocrine and paracrine PlGF signaling and macrophage repolarization are involved in the progression of breast cancer, which could be targeted by metformin.

Gray matter volume changes following antipsychotic therapy in first-episode schizophrenia patients: A longitudinal voxel-based morphometric study.

Despite evidence of structural brain abnormalities in schizophrenia, the current study aimed to explore the effects of antipsychotic treatment on gray matter (GM) volume using structural magnetic resonance imaging (MRI) and investigate the relationship between brain structure and treatment response. The GM volumes of 33 patients with first-episode schizophrenia were calculated with voxel-based morphometry (VBM), with 33 matched healthy controls. Longitudinal volume changes within subjects after 4-month antipsychotic treatment were also evaluated. Correlation between volumetric changes and clinical symptoms derived from the Positive and Negative Syndrome Scale (PANSS) were further investigated. Compared with healthy controls, decreased GM volumes in the frontal gyrus were observed in schizophrenia patients. After 4-month treatment, patients showed significantly decreased GM volume primarily in the bilateral frontal, temporal and left parietal brain regions. In addition, the GM volume changes of the left postcentral gyrus was positively correlated with negative symptoms improvement, and the correlation analysis revealed the total PANSS scores changes were associated with GM volume changes in the right inferior frontal gyrus and the right superior temporal gyrus. Besides, non-responders had reduced GM volume in the bilateral middle frontal gyrus and the right superior frontal gyrus compared with responders and healthy controls. Our results suggest that the abnormality in the right frontal gyrus exists in the early stage of schizophrenia. Moreover, the relationship between antipsychotics and structural changes was identified. The GM volume might have the potential to reflect the symptom improvement in schizophrenia patients. And MRI may assist in predicting the antipsychotic treatment response in first-episode schizophrenia patients.

Differentiation of primary central nervous system lymphoma from high-grade glioma and brain metastasis using arterial spin labeling and dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND AND PURPOSE: Conventional magnetic resonance imaging (MRI) is sometimes difficult to distinguish primary central nervous system lymphoma (PCNSL) from other malignant brain tumors effectively. The study aimed to evaluate the diagnostic performance of arterial spin labeling (ASL) and dynamic contrast-enhanced (DCE)-derived permeability parameters to differentiate PCNSL from high-grade glioma (HGG) and brain metastasis. MATERIALS AND METHODS: Eight patients with PCNSL, twenty one patients with HGG and six brain metastasis underwent preoperative 3.0-T MR imaging including conventional, ASL and DCE. Quantitative parameters including relative cerebral blood flow (rCBF), extravascular extracellular volume fraction (Ve) and the volume transfer constant (Ktrans) among PCNSL, HGG and metastasis were compared with a one-way analysis of variance. In addition, the area under the receiver-operating characteristic (ROC) curve (AUC) was constructed to evaluate the differentiation diagnostic performance of each parameter and the combination. RESULTS: The PCNSL demonstrated significantly lower rCBF, higher Ktrans and Ve compared with HGG and metastasis. For the ROC analyses, both Ktrans and rCBF had good diagnostic performance for discriminating PCNSL from HGG and metastasis, with the AUC of 0.880 and 0.889. With the combination of rCBF and Ktrans, the diagnostic ability for PCNSL was improved with AUC of 0.986. CONCLUSION: rCBF and Ktrans are useful parameters for differentiating PCNSL from HGG and brain metastasis. The combination of rCBF and Ktrans further helps to improve the diagnostic performance of PCNSL.

[Nursing cooperation on circulation restore during microvascular submandibular gland transfer].

OBJECTIVE: To summarize the cooperative measures on circulation restore during the operation of microvascular submandibular gland transfer. METHODS: Fifty-six cases of microvascular submandibular gland transfer were performed in Peking University School & Hospital of Stomatology from January 2005 to March 2009. The related data was collected retrospectively and the cooperative measures on circulation restore during the operation were summarized. RESULTS: The circulation restore of transferred glands were satisfied in all 56 cases when the submandibular gland transfer operation finished. Thrombosis happened in 7 cases within the postoperative 48 hours and the secondary emergency operations were done. At last 6 glands were salvaged and the final successful rate was 98.21%. CONCLUSION: Successful circulation restore was one of the key points on microvascular submandibular gland transfer. The most important mission of the nursing during the operation was the prevention of vascular crisis. The main measures include persistent wet packing using narceine, fomentation using warm saline and special nursing on postoperative complications. Our experience proves that it is beneficial to the success of operation.