Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

White matter microstructural alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis: A tract-based spatial statistics study.

BACKGROUND: Cognitive impairment is common in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis; however, neural mechanisms underlying this impairment remain unclear. Diffusion tensor imaging (DTI) is a potential method for studying the condition of white matter fibers in patients with anti-NMDAR encephalitis, allowing for an analysis of the neuroimaging mechanisms of cognitive impairment in conjunction with cognitive scales. This study aimed to explore white matter microstructural alterations and their correlation with cognitive function in patients with anti-NMDAR encephalitis. METHODS: DTI data were collected from 22 patients with anti-NMDAR encephalitis (aged 29.00(19.75, 39.50) years; 12 males, 10 females) and 20 healthy controls (HCs) (aged 24.50(21.25, 32.00); 12 males, 8 females) matched for age, sex, and educational level. Changes in the white matter microstructure were analyzed using tract-based spatial statistics. Pearson correlation analysis was used to explore the correlation between white matter integrity and neuropsychological scores. RESULTS: Compared with HCs, patients with anti-NMDAR encephalitis showed decreased fractional anisotropy and increased mean diffusivity values in extensive white matter regions, which were associated with disease severity, memory, and executive and visuospatial functions. CONCLUSION: Widespread impairment of the structural integrity of the white matter in the brain is significantly associated with cognitive dysfunction in patients with anti-NMDAR encephalitis, providing neuroimaging evidence for studying the underlying mechanisms.

Diagnostic identification of chronic insomnia using ALFF and FC features of resting-state functional MRI and logistic regression approach.

This study investigated whether the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) features could be used as potentially neurological markers to identify chronic insomnia (CI) using resting-state functional MRI and machine learning method logistic regression (LR). This study included 49 CI patients and 47 healthy controls (HC). Voxel-wise features, including the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC), were extracted from resting-state functional magnetic resonance brain images. Then, we divided the data into two independent cohorts for training (44 CI patients and 42 HC patients), and independent validation (5 CI patients and 5 HC patients) by using logistic regression. The model was evaluated using 20 rounds of fivefold cross­validation for training. In particular, a two-sample t-test (GRF corrected, p-voxel < 0.001, p-cluster < 0.05) was used for feature selection during the model training. Finally, single­shot testing of the final model was performed on the independent validation cohort. A correlation analysis (Bonferroni correction, p < 0.05/4) was also conducted to determine whether the features contributing to the prediction were correlated with clinical characteristics, including the Insomnia Severity Index (ISI), Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS). Results showed that resting-state features had a discrimination accuracy of 86.40%, with a sensitivity of 93.00% and specificity of 79.80%. The area under the curve (AUC) was 0.89 (all [Formula: see text]< 0.001). The ALFF and FC features showed significant differences between the CI patients and HC. The regions contributing to the prediction mainly included the anterior cingulate, prefrontal cortex, orbital part of the frontal lobe, angular gyrus, cingulate gyrus, praecuneus, parietal lobe, temporal gyrus, superior temporal gyrus, and middle temporal gyrus. Furthermore, some specific functional connectivity among related regions was positively correlated with the ISI, and also negatively related to the SDS in correlation analysis. Our current study suggested that ALFF and FC in the regions contributing to diagnostic identification might serve as potential neuromarkers for CI.

Differentiation of Thyroid Nodules (C-TIRADS 4) by Combining Contrast-Enhanced Ultrasound Diagnosis Model With Chinese Thyroid Imaging Reporting and Data System.

Objectives: To establish a contrast-enhanced ultrasound (CEUS) diagnostic schedule by CEUS analysis of thyroid nodules of C-TIRADS 4. To establish a CEUS-TIRADS diagnostic model to differentiate thyroid nodules (C-TIRADS 4) by combining CEUS with Chinese thyroid imaging reporting and data system (C-TIRADS). Methods: A total of 228 thyroid nodules (C-TIRADS 4) were estimated by CEUS. The arrival time, enhancement degree, enhancement homogeneity, enhancement pattern, enhancement ring, and wash-out time were analyzed in CEUS for all of the nodules. Multivariate factors logistic analysis was performed and a CEUS diagnostic schedule was established. If the nodule had a regular hyper-enhancement ring or got a score of less than 2 in CEUS analysis, CEUS-TIRADS subtracted 1 category. If the nodule got a score of 2 in the CEUS schedule, the CEUS-TIRADS category remained the same as before. If the nodule got a score of more than 2 in the CEUS schedule, CEUS-TIRADS added 1 category. When it reflected an absent enhancement in CEUS, the nodule was judged as CEUS-TIRADS 3. All of the C-TIRADS 4 nodules were re-graded by CEUS-TIRADS. We then compare the diagnosis performance of C-TIRADS, CEUS, and CEUS-TIRADS by sensitivity, specificity, and accuracy. Results: Among the 228 C-TIRADS 4 nodules, 69 were determined as C-TIRADS 4a, 114 were C-TIRADS 4b, and 45 were C-TIRADS 4c. The sensitivity, specificity, and accuracy of C-TIRADS were 93.1%, 55.3%, and 74.6% respectively. The area under the curve was 0.753. Later arrival time, hypo-enhancement, heterogeneous enhancement, centripetal enhancement, and rapid washout were risk factors of malignancy in multivariate analysis. The sensitivity, specificity, and accuracy of CEUS were 78.7%, 87.5%, and 83.3% respectively. The area under the curve was 0.803. By CEUS-TIRADS diagnostic model combining CEUS with C-TIRADS, a total of 127 cases were determined as malignancy (111 were malignant and 16 were benign) and 101 were diagnosed as benign ones (5 were malignant and 96 were benign). The sensitivity, specificity, and accuracy of CEUS-TIRADS were 95.7%, 85.7%, and 92.1% respectively. The area under the curve was 0.916. The diagnostic performance of CEUS-TIRADS was significantly better than CEUS and C-TIRADS. The difference was statistically significant (P<0.05). Conclusions: The diagnostic schedule of CEUS could get better diagnostic performance than US in the differentiation of thyroid nodules. The CEUS-TIRADS combining CEUS analysis with C-TIRADS could make up for the deficient sensibility of C-TIRADS, showing a better diagnostic performance than US and CEUS.

Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression.

Rationale: Glucose oxidase (GOx)-based biocatalytic nanoreactors can cut off the energy supply of tumors for starvation therapy and deoxygenation-activated chemotherapy. However, these nanoreactors, including mesoporous silica, calcium phosphate, metal-organic framework, or polymer nanocarriers, cannot completely block the reaction of GOx with glucose in the blood, inducing systemic toxicity from hydrogen peroxide (H2O2) and anoxia. The low enzyme loading capacity can reduce systemic toxicity but limits its therapeutic effect. Here, we describe a real 'ON/OFF' intelligent nanoreactor with a core-shell structure (GOx + tirazapamine (TPZ))/ZIF-8@ZIF-8 modified with the red cell membrane (GTZ@Z-RBM) for cargo delivery. Methods: GTZ@Z-RBM nanoparticles (NPs) were prepared by the co-precipitation and epitaxial growth process under mild conditions. The core-shell structure loaded with GOx and TPZ was characterized for hydrate particle size and surface charge. The GTZ@Z-RBM NPs morphology, drug, and GOx loading/releasing abilities, system toxicity, multimodal synergistic therapy, and tumor metastasis suppression were investigated. The in vitro and in vivo outcomes of GTZ@Z-RBM NPs were assessed in 4T1 breast cancer cells. Results: GTZ@Z-RBM NPs could spatially isolate the enzyme from glucose in a physiological environment, reducing systemic toxicity. The fabricated nanoreactor with high enzyme loading capacity and good biocompatibility could deliver GOx and TPZ to the tumors, thereby exhausting glucose, generating H2O2, and aggravating hypoxic microenvironment for starvation therapy, DNA damage, and deoxygenation-activated chemotherapy. Significantly, the synergistic therapy effectively suppressed the breast cancer metastasis in mice and prolonged life without systemic toxicity. The in vitro and in vivo results provided evidence that our biomimetic nanoreactor had a powerful synergistic cascade effect in treating breast cancer. Conclusion: GTZ@Z-RBM NPs can be used as an 'ON/OFF' intelligent nanoreactor to deliver GOx and TPZ for multimodal synergistic therapy and tumor metastasis suppression.

Image-guided selection of Gd@C-dots as sensitizers to improve radiotherapy of non-small cell lung cancer.

BACKGROUND: Recently, gadolinium-intercalated carbon dots (Gd@C-dots) have demonstrated potential advantages over traditional high-Z nanoparticles (HZNPs) as radiosensitizers due to their high stability, minimal metal leakage, and remarkable efficacy. RESULTS: In this work, two Gd@C-dots formulations were fabricated which bore carboxylic acid (CA-Gd@C-dots) or amino group (pPD-Gd@C-dots), respectively, on the carbon shell. While it is critical to develop innovative nanomateirals for cancer therapy, determining their tumor accumulation and retention is equally important. Therefore, in vivo positron emission tomography (PET) was performed, which found that 64Cu-labeled pPD-Gd@C-dots demonstrated significantly improved tumor retention (up to 48 h post injection) compared with CA-Gd@C-dots. Indeed, cell uptake of 64Cu-pPD-Gd@C-dots reached close to 60% of total dose compared with ~ 5% of 64Cu-CA-Gd@C-dots. pPD-Gd@C-dots was therefore further evaluated as a new radiosensitizer for non-small cell lung cancer treatment. While single dose radiation plus intratumorally injected pPD-Gd@C-dots did lead to improved tumor suppression, the inhibition effect was further improved with two doses of radiation. The persistent retention of pPD-Gd@C-dots in tumor region eliminates the need of reinjecting radiosensitizer for the second radiation. CONCLUSIONS: PET offers a simple and straightforward way to study nanoparticle retention in vivo, and the selected pPD-Gd@C-dots hold great potential as an effective radiosensitizer.

Development of Bispecific NT-PSMA Heterodimer for Prostate Cancer Imaging: A Potential Approach to Address Tumor Heterogeneity.

Prostate cancer is a heterogeneous disease with a poor survival rate at late stage. In this report, a dual targeting PET agent was developed to partially address the tumor heterogeneity issue. The heterodimer F-BCN-PSMA-NT was designed to target PSMA and neurotensin receptor1 (NTR1), both of which have demonstrated great potential in prostate cancer management. The heterodimer was synthesized through the conjugation of Glu-urea-lys(Ahx) (PSMA targeting motif) and NT20.3 (NTR1 targeting motif) to a symmetric trifunctional linker, bearing an azide group for further modification. Radio-labeling was performed using strain promoted azide-alkyne click reaction with high yield. Cell based assays suggested that F-BCN-PSMA-NT has comparable or only slightly reduced binding affinity with the corresponding monomers. Small animal PET clearly demonstrated that the heterodimer probe has prominent uptake not only in NTR1 positive/PSMA negative PC-3 tumors (1.4 ± 0.3%ID/g), but also in the PSMA positive/NTR1 negative LnCap tumors (1.3 ± 0.2%ID/g). The tracer showed comparable tumor to background ratio with each monomer. In summary, prostate cancer is a heterogeneous disease in need of improved diagnostics and treatments. The PSMA-NT heterodimer represents a new class of molecules that can be used to target two distinct antigens related to prostate cancer. In addition to the imaging applications demonstrated in this study, the agent also holds great potential on the treatment of heterogeneous prostate cancer.

Hydrophilic 18F-labeled trans-5-oxocene (oxoTCO) for efficient construction of PET agents with improved tumor-to-background ratios in neurotensin receptor (NTR) imaging.

An 18F-labeled trans-5-oxocene (oxoTCO) that is used to construct a PET probe for neurotensin receptor (NTR) imaging through tetrazine ligation is described here. PET probe construction proceeds with 70% RCY based on 18F-oxoTCO and is completed within seconds. The in vivo behaviour of the oxoTCO based PET probe was compared with those of analogous probes that were prepared from 18F-labeled s-TCO and d-TCO tracers. The hydrophilic 18F-oxoTCO probe showed a significantly higher tumor-to-background ratio while displaying comparable tumor uptake relative to the 18F-dTCO and 18F-sTCO derived probes.

The efficiency of 18F labelling of a prostate specific membrane antigen ligand via strain-promoted azide-alkyne reaction: reaction speed versus hydrophilicity.

Here we report the 18F labeling of a prostate specific membrane antigen (PSMA) ligand via a strain promoted oxa-dibenzocyclooctyne (ODIBO)- or bicyclo[6.1.0]nonyne (BCN)-azide reaction. Although ODIBO reacts with azide 20 fold faster than BCN, in vivo PET imaging suggests that 18F-BCN-azide-PSMA demonstrated much higher tumor uptake and a much higher tumor to background contrast.

Nicorandil for the prevention of contrast-induced nephropathy: A meta-analysis of randomized controlled trials.

INTRODUCTION: Nicorandil has been suggested as a preventative strategy against the incidence of contrast-induced nephropathy (CIN). However, results of relevant randomized controlled trials (RCTs) were inconsistent. AIMS: We performed a meta-analysis of RCTs to evaluate the preventive efficacy of periprocedural treatment of nicorandil against the incidence of CIN. METHODS: Relevant RCTs were identified via search of PubMed, Embase, and Cochrane's Library databases. Results were pooled using a random-effect model. Subgroup analyses were performed to evaluate the potential influence of administering routes on the efficacy of nicorandil against CIN incidence. RESULTS: Four RCTs with 709 patients were included. Treatment of nicorandil significantly reduced the incidence of CIN as compared with controls (risk ration [RR]: 0.38, 95% confidence interval [CI]: 0.19 ~ 0.74, P = .005) with moderate heterogeneity (I2  = 33%). Results of subsequent subgroup analysis showed that nicorandil significantly reduced the risk of CIN if orally administered (RR: 0.32, P < .001), but did not if intravenously administered (RR: 0.47, I2  = 68%). Moreover, treatment with nicorandil was associated with significantly less increment of SCr (weight mean difference [WMD]: -3.98%, P < .001) and a tendency of less increment of cystatin C (WMD: -3.86%, P = .08) after 48-hour contrast exposure as compared with controls. CONCLUSIONS: Periprocedural treatment with nicorandil may be preventative against the incidence of CIN in patients undergoing contrast exposure. The influence of periprocedural nicorandil on clinical outcome in these patients deserves further investigation.

Imaging Neurotensin Receptor in Prostate Cancer With 64Cu-Labeled Neurotensin Analogs.

INTRODUCTION: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. MATERIALS AND METHODS: Three 64Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N',N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR+ HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts. RESULTS: All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, 64Cu-NOTA-NT and 64Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with 64Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity. CONCLUSIONS: Our results demonstrated that 64Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1.

Aberrant interhemispheric functional and structural connectivity in heroin-dependent individuals.

Models of heroin addiction emphasize the role of disrupted frontostriatal circuitry supporting cognitive control processes. However, heroin addiction-related alterations in functional and structural interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. The corpus callosum (CC), which connects homologous regions of the cortex, is the major conduit for information transfer between the cerebral hemispheres and represents a structural connectivity index between hemispheres. We compared interhemispheric voxel-mirrored homotopic connectivity (VMHC) and CC volume between 45 heroin dependent-individuals (HDIs) and 35 non-addict individuals. We observed significant reduction of VMHC in a number of regions, particularly the striatum/limbic system regions, and significant decrease in splenium and genu sub-regions of CC in HDI. Importantly, within HDI, VMHC in the dorsal lateral prefrontal cortex (DLPFC) correlated with genu CC volume, VMHC in the putamen, VMHC in the DLPFC and genu CC volume and splenium CC volume were negatively correlated with heroin duration and impulsivity traits. Further analyses demonstrated that impairment of VMHC of bilateral DLPFC partially mediated the association between genu CC volumes decreased and increased impulsivity in HDI. Our results reveal a substantial impairment of interhemispheric coordination in the HDI. Further, interhemispheric connectivity correlated with the duration of heroin abuse and higher impulsivity behavior in HDI. Our findings provide insight into a heroin addicts' related pathophysiology and reinforce an integrative view of the interhemispheric cerebral functional and structural organization.

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

OBJECTIVES: To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. METHODS: We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. RESULTS: We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. CONCLUSIONS: These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. KEY POINTS: • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.

Abnormal white matter structural networks characterize heroin-dependent individuals: a network analysis.

Neuroimaging studies suggested that drug addiction is linked to abnormal brain functional connectivity. However, little is known about the alteration of brain white matter (WM) connectivity in addictive drug users and nearly no study has been performed to examine the alterations of brain WM connectivity in heroin-dependent individuals (HDIs). Diffusion tensor imaging (DTI) offers a comprehensive technique to map the whole brain WM connectivity in vivo. In this study, we acquired DTI datasets from 20 HDIs and 18 healthy controls and constructed their brain WM structural networks using a deterministic fibre tracking approach. Using graph theoretical analysis, we explored the global and nodal topological parameters of brain network for both groups and adopted a network-based statistic (NBS) approach to assess between-group differences in inter-regional WM connections. Statistical analysis indicated the global efficiency and network strength were significantly increased, but the characteristic path length was significantly decreased in the HDIs compared with the controls. We also found that in the HDIs, the nodal efficiency was significantly increased in the left prefrontal cortex, bilateral orbital frontal cortices and left anterior cingulate gyrus. Moreover, the NBS analysis revealed that in the HDIs, the significant increased connections were located in the paralimbic, orbitofrontal, prefrontal and temporal regions. Our results may reflect the disruption of whole brain WM structural networks in the HDIs. Our findings suggest that mapping brain WM structural network may be helpful for better understanding the neuromechanism of heroin addiction.

Role of P311 in interleukin-1α-induced epithelial to myofibroblast transition in kidney tubular epithelial cells.

Tubular epithelial-myofibroblast transition (TEMT) is an important process in renal tubulointerstitial fibrosis. Interleukin-1α (IL-1α) and transforming growth factor-ß1 (TGF-ß1) have been demonstrated to be key inducers of TEMT. In mouse embryonic fibroblast cells (NIH3T3), P311 protein induces phenotypic changes that are consistent to myofibroblast transformation. In the present study, we investigated the role of P311 gene and protein as well as potential mechanisms underlying TEMT in normal rat kidney tubular epithelial cells (NRK52E). Morphological and molecular changes were determined in NRK52E cells that were treated with IL-1α and/or P311 antibodies. The results showed that the NRK52E cells triggered by IL-1α became fibroblast-like cells, exhibiting hypertrophy of elongated and fusiform-shaped cells. IL-1α induced a time-dependent increase in P311 gene expression in NRK52E cells, with a peak time at 4 days. The expression levels of P311 gene were positively correlated with α-SMA and TGF-ß1 gene expression levels. Anti-P311 antibody inhibited P311 and α-SMA expression in the presence of IL-1α. In contrast, anti-P311 antibody increased the expression of TGF-ß1 gene in cells cultured with IL-1α. Therefore, P311 gene, together with α-SMA and TGF-ß1 genes, was induced in the process of TEMT. P311 protein triggered by interleukin-1α may promote TEMT through a TGF-ß1-independent pathway.

Aberrant default-mode functional and structural connectivity in heroin-dependent individuals.

BACKGROUND: Little is known about connectivity within the default mode network (DMN) in heroin-dependent individuals (HDIs). In the current study, diffusion-tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were combined to investigate both structural and functional connectivity within the DMN in HDIs. METHODS: Fourteen HDIs and 14 controls participated in the study. Structural (path length, tracts count, (fractional anisotropy) FA and (mean diffusivity) MD derived from DTI tractography)and functional (temporal correlation coefficient derived from rs-fMRI) DMN connectivity changes were examined in HDIs. Pearson correlation analysis was performed to compare the structural/functional indices and duration of heroin use/Iowa gambling task(IGT) performance in HDIs. RESULTS: HDIs had lower FA and higher MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to right parahippocampal gyrus (PHG), compared to the controls. HDIs also had decreased FA and track count in the tract connecting the PCC/PCUN and medial prefrontal cortex (MPFC), as well as decreased functional connectivity between the PCC/PCUN and bilateral PHG and MPFC, compared to controls. FA values for the tract connecting PCC/PCUN to the right PHG and connecting PCC/PCUN to the MPFC were negatively correlated to the duration of heroin use. The temporal correlation coefficients between the PCC/PCUN and the MPFC, and the FA values for the tract connecting the PCC/PCUN to the MPFC were positively correlated to IGT performance in HDIs. CONCLUSIONS: Structural and functional connectivity within the DMN are both disturbed in HDIs. This disturbance progresses as duration of heroin use increases and is related to deficits in decision making in HDIs.

Abnormal cortical thickness in heroin-dependent individuals.

Accumulating evidence from brain structural imaging studies on heroin dependence has supported links between brain morphological alterations and heroin exposure, particularly in gray matter volume or gray matter density. However, the effects of heroin exposure on cortical thickness and the relationship between cortical thickness and heroin addiction are not yet known. In this study, we acquired 3D high-resolution brain structural magnetic resonance imaging (MRI) data from 18 heroin-dependent individuals (HDIs) and 15 healthy controls (HCs). Using FreeSurfer, we detected abnormalities in cortical thickness in the HDIs. Based on a vertex-wise analysis, the HDIs showed significantly decreased cortical thickness in the bilateral superior frontal, left caudal middle frontal, right superior temporal, and right insular regions compared to the HCs but significantly increased cortical thickness in the left superior parietal, bilateral lingual, left temporal pole, right inferior parietal, right lateral occipital, and right cuneus regions. To supplement these results, a subsequent ROI-wise analysis was performed and showed decreased cortical thickness in the left superior frontal sulcus, left precuneus gyrus, left calcarine sulcus, left anterior transverse collateral sulcus, and the right medial occipital-temporal and lingual sulcus. These regions partially overlapped with the areas identified using the vertex-wise analysis. In addition, we found that the thickness in the right superior frontal and right insular regions was negatively correlated with the duration of heroin use. These results provide compelling evidence for cortical abnormality in HDIs and also suggest that the duration of heroin use may be a critical factor associated with the brain alteration.

Disrupted topological organization in whole-brain functional networks of heroin-dependent individuals: a resting-state FMRI study.

Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.

[Alterations in orbitofrontal cortex functional connectivity and decision making deficits in heroin-dependent individuals].

OBJECTIVE: To investigate the changes in orbitofrontal cortex (OFC) functional connectivity and its association with decision-making deficits in chronic heroin-dependent individuals (HDIs) and explore the neural mechanisms of heroin addiction and relapse. METHODS: Fourteen male chronic HDIs and 14 healthy subjects matched for age, education, and nicotine consumption participated in this study. Resting state functional magnetic resonance imaging (fMRI) was performed using a 1.5 T MR scanner. Functional connectivity of the OFC and the rest of the brain were calculated using REST software. Voxel-based analysis of the functional connectivity maps between the control and HDI groups was performed with two-sample t test. The Iowa gambling task (IGT) was used to assess the participants' decision making during uncertainty. RESULTS: Compared with the control group, the HDIs showed significantly decreased functional connectivity of the OFC and the right inferior parietal lobule (rIPL) (t=3.5, P<0.05). A significant negative correlation was noted between the functional connectivity of the OFC-rIPL and performance level at the IGT. CONCLUSION: The OFC-rIPL functional connectivity is significantly disrupted in HDIs, which may be the neural basis for decision-making deficits.