Search

Abstract Background Excessive pericyte coverage promotes tumor growth, and a downregulation may solve this dilemma. Due to the double-edged sword role of vascular pericytes in tumor microenvironment (TME), indiscriminately decreasing pericyte coverage by imatinib causes poor treatment outcomes. Here, we optimized the use of imatinib in a colorectal cancer (CRC) model in high pericyte-coverage status, and revealed the value of multiparametric magnetic resonance imaging (mpMRI) at 9.4T in monitoring treatment-related changes in pericyte coverage and the TME. Methods CRC xenograft models were evaluated by histological vascular characterizations and mpMRI. Mice with the highest pericyte coverage were treated with imatinib or saline; then, vascular characterizations, tumor apoptosis and HIF-1α level were analyzed histologically, and alterations in the expression of Bcl-2/bax pathway were assessed through qPCR. The effects of imatinib were monitored by dynamic contrast-enhanced (DCE)-, diffusion-weighted imaging (DWI)- and amide proton transfer chemical exchange saturation transfer (APT CEST)-MRI at 9.4T. Results The DCE- parameters provided a good histologic match the tumor vascular characterizations. In the high pericyte coverage status, imatinib exhibited significant tumor growth inhibition, necrosis increase and pericyte coverage downregulation, and these changes were accompanied by increased vessel permeability, decreased microvessel density (MVD), increased tumor apoptosis and altered gene expression of apoptosis-related Bcl-2/bax pathway. Strategically, a 4-day imatinib effectively decreased pericyte coverage and HIF-1α level, and continuous treatment led to a less marked decrease in pericyte coverage and re-elevated HIF-1α level. Correlation analysis confirmed the feasibility of using mpMRI parameters to monitor imatinib treatment, with DCE-derived Ve and Ktrans being most correlated with pericyte coverage, Ve with vessel permeability, AUC with microvessel density (MVD), DWI-derived ADC with tumor apoptosis, and APT CEST-derived MTRasym at 1 µT with HIF-1α. Conclusions These results provided an optimized imatinib regimen to achieve decreasing pericyte coverage and HIF-1α level in the high pericyte-coverage CRC model, and offered an ultrahigh-field multiparametric MRI approach for monitoring pericyte coverage and dynamics response of the TME to treatment.

Abstract Background Magnetic resonance imaging (MRI) can diagnose meniscal lesions anatomically, while quantitative MRI can reflect the changes of meniscal histology and biochemical structure. Our study aims to explore the association between the measurement values obtained from synthetic magnetic resonance imaging (SyMRI) and Stoller grades. Additionally, we aim to assess the diagnostic accuracy of SyMRI in determining the extent of meniscus injury. This potential accuracy could contribute to minimizing unnecessary invasive examinations and providing guidance for clinical treatment. Methods Total of 60 (n=60) patients requiring knee arthroscopic surgery and 20 (n=20) healthy subjects were collected from July 2022 to November 2022. All subjects underwent conventional MRI and SyMRI. Manual measurements of the T1, T2 and proton density (PD) values were conducted for both normal menisci and the most severely affected position of injured menisci. These measurements corresponded to the Stoller grade of meniscus injuries observed in the conventional MRI. All patients and healthy subjects were divided into normal group, degeneration group and torn group according to the Stoller grade on conventional MRI. One-way analysis of variance (ANOVA) was employed to compare the T1, T2 and PD values of the meniscus among 3 groups. The accuracy of SyMRI in diagnosing meniscus injury was assessed by comparing the findings with arthroscopic observations. The diagnostic efficiency of meniscus degeneration and tear between conventional MRI and SyMRI were analyzed using McNemar test. Furthermore, a receiver operating characteristic curve (ROC curve) was constructed and the area under the curve (AUC) was utilized for evaluation. Results According to the measurements of SyMRI, there was no statistical difference of T1 value or PD value measured by SyMRI among the normal group, degeneration group and torn group, while the difference of T2 value was statistically significant among 3 groups (P=0.001). The arthroscopic findings showed that 11 patients were meniscal degeneration and 49 patients were meniscal tears. The arthroscopic findings were used as the gold standard, and the difference of T1 and PD values among the 3 groups was not statistically significant, while the difference of T2 values (32.81±2.51 of normal group, 44.85±3.98 of degeneration group and 54.42±3.82 of torn group) was statistically significant (P=0.001). When the threshold of T2 value was 51.67 (ms), the maximum Yoden index was 0.787 and the AUC value was 0.934. Conclusions The measurement values derived from SyMRI could reflect the Stoller grade, illustrating that SyMRI has good consistency with conventional MRI. Moreover, the notable consistency observed between SyMRI and arthroscopy suggests a potential role for SyMRI in guiding clinical diagnoses.

Objectives Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes.Methods Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM.Results On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p

Abstract Background Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. Methods The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. Results The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P

Abstract Background The goal of this study was to create a nomogram using routine parameters to predict leptomeningeal metastases (LMs) in advanced lung adenocarcinoma (LAC) patients to prevent needless exams or lumbar punctures and to assist in accurately diagnosing LMs. Methods Two hundred and seventy‐three patients with LMs and brain metastases were retrospectively reviewed and divided into derivation (n = 191) and validation (n = 82) cohorts using a 3:7 random allocation. All LAC patients with LMs had positive cerebrospinal fluid cytology results and brain metastases confirmed by magnetic resonance imaging. Binary logistic regression with backward stepwise selection was used to identify significant characteristics. A predictive nomogram based on the logistic model was assessed through receiver operating characteristic curves. The validation cohort and Hosmer–Lemeshow test were used for internal validation of the nomogram. Results Five clinicopathological parameters, namely, gene mutations, surgery at the primary lung cancer site, clinical symptoms of the head, N stage, and therapeutic strategy, were used as predictors of LMs. The area under the curve was 0.946 (95% CI 0.912–0.979) for the training cohort and 0.861 (95% CI 0.761–0.961) for the internal validation cohort. There was no significant difference in performance between the two cohorts (p = 0.116). In the internal validation, calibration plots revealed that the nomogram predictions were well suited to the actual outcomes. Conclusions We created a user‐friendly nomogram to predict LMs in advanced lung cancer patients, which could help guide treatment decisions and reduce unnecessary lumbar punctures.

Intracranial atherosclerotic ischemic stroke dramatically impacts the quality of life among the elderly. Statins therapy has been proven to be effective in plaque stabilization and alleviation in patients with intracranial atherosclerotic ischemic stroke. According to recent studies, these effects may be directly related to lipid levels rather than specific lipid-lowering drugs. Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK-9 inhibitor) are newer effective lipid-lowering drugs increasingly prescribed to patients at high cardiovascular risk to lower LDL cholesterol. Studies have provided evidence that PCSK9 inhibitor combined with statin therapy can lead to a decrease in the plaque volume measured by intravascular ultrasound in coronary heart disease patients. But the efficacy of combination of the two drugs in symptomatic intracranial artery stenosis has been unknown. Here we provide a case which was reported to suggest that a combination of Evolocumab and intensive statin therapy might reverse or alleviate symptomatic intracranial artery stenosis.

Abstract Background Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion. Methods A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation. Results The near-infrared responsive on-demand oxygen releasing nanoplatform O2-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O2-PPSiI. Conclusions Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC. Graphical Abstract

Abstract Introduction The bilateral common carotid artery occlusion (BCCAO) rat model is an ideal animal model for simulating the pathology of chronic brain hypoperfusion in humans. However, dynamic changes in neuronal activity, cellular edema, and neuronal structural integrity in vivo after BCCAO have rarely been reported. The purpose of this study is to use a 9.4 T MRI to explore the pathophysiological mechanisms of vascular dementia. Materials and Methods Twelve Sprague–Dawley (SD) rats were randomly divided into two groups: the sham group and the model group (n = 6 for each group). Rats were subjected to MRI using T2*WI, diffusion tensor imaging (DTI), and DWI sequences by MRI at the following six time points: presurgery and 6 h, 3 days, 7 days, 21 days, and 28 days postsurgery. Then, the T2*, fractional anisotropy (FA), and average apparent diffusion coefficient (ADC) values were measured in the bilateral cortices and hippocampi. After MRI scanning, all rats in both groups were subjected to the Y‐maze test, novel object recognition test, and open‐field test to assess their learning, memory, cognition, and locomotor activity. Results The T2*, FA, and ADC values in the cerebral cortex and hippocampus decreased sharply at 6 h after BCCAO in the model group compared with those of the sham group. By Day 28, the T2* and ADC values gradually increased to close to those in the sham group, but the FA values changed little, and the rats in the model group had worse learning, memory, and cognition and less locomotor activity than the rats in the sham group. Conclusions The BCCAO is an ideal rat model for studying the pathophysiological mechanisms of vascular dementia.

Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0–4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8–5.0 ppm from water while exchange rates varied from ~680 to 2340 s−1 at pH 7.2, which allows strong CEST contrast on scanners down to B0 = 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.

Sonodynamics has emerged as a new potential therapy for breast cancer in recent years. However, GSH-mediated redox systems in cancer cells make them tolerable to oxidative stress-related therapy. Herein, in this study, with G6PD, the gatekeeper enzyme of the pentose phosphate pathway, as the regulative target, a self-assembled thermosensitive chitosan-pluronic hydrogel coloaded with ICG (sono-sensitive agent) and RRx-001 (IR@CPGel) was successfully prepared to enhance SDT through interference with redox homeostasis. Both in vitro and in vivo antitumor investigations verified that when integrated with sonodynamic therapy applied in breast cancer treatment, local administration of IR@CPgel could enhance ROS generation under LIFU irradiation and trigger the intrinsic apoptotic pathway of cancer cells, thus effectively inhibiting tumor growth in a safe manner. Moreover, RRx-001 may interfere with redox homeostasis in cancer cells by downregulating G6PD expression. Due to this redox imbalance, proapoptotic signals, such as P21 and P53, were enhanced, and metastasis-related signals, including MMP-2, ZEB1 and HIF-1α, were effectively reduced. Taken together, this work aimed to enhance the efficacy of sonodynamic therapy through local administration of self-assembled IR@CPGel to interfere with redox homeostasis and thus amplify the oxidative stress microenvironment in tumor tissues. In a word, this work provides a new strategy for the SDT enhancement in breast cancer therapy.

Angiomyofibroblastoma (AMF) is a rare benign myofibroblastic tumor that mainly occurs in the genital tract of middle-aged female patients. However, it can also arise in the scrotum, spermatic cord, and bladder. We described, herein, a case of a 42-year-old patient who was admitted to our hospital with a left scrotal mass. Imaging examinations showed that the mass had abundant vessels and displayed obvious progressive intensification on enhanced MRI. The following histopathological and immunohistochemical studies led to the diagnosis of AMF. Here, we describe the magnetic resonance imaging findings of a case of scrotal AMF. We hope that the information can help radiologists to identify AMF.

Protein PDZ and LIM domain 3 (PDLIM3) is a cytoskeletal protein, colocalizing with α-actinin on the Z line of mature muscle fibers. It plays a key role in dilated cardiomyopathy (DCM), muscular dystrophy, and tumor progression. However, correlations between PDLIM3 expression, prognosis, and tumor-infiltrating immune cells in gastric cancer are unknown. Therefore, we leveraged the Oncomine, GEPIA, GEO, and HPA databases to evaluate PDLIM3 expression in tumors. We also quantified PDLIM3 expression in 15 matched pairs of gastric tumor and nontumor tissues by immunohistochemistry. The Kaplan-Meier method was employed to determine the relationship between PDLIM3 expression and clinical outcomes. GO and KEGG analyses were performed to illuminate the molecular mechanisms of action of PDLIM3. TIMER2.0 and GEPIA were applied to investigate correlations between PDLIM3 expression and gene marker subsets signifying immune infiltration, with TIMER2.0 exploring the correlations between PDLIM3 and related signaling pathways. Gastric cancer tissues were found to express more PDLIM3 than nontumor tissues. PDLIM3 overexpression was associated with shorter OS and PFS of gastric cancer patients (OS HR=2.02, P=9.8e−10; PFS HR=1.77, P=7.5e−06). PDLIM3 was also positively correlated with worse OS and PFS according to gastric cancer staging, Her-2 overexpression, differentiation grade, and Lauren classification. PDLIM3 was shown to be associated with immunological responses by GO, while it was related to PI3K/Akt signal pathways by KEGG analysis. Furthermore, increased PDLIM3 expression was significantly correlated with greater infiltration of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. PDLIM3 expression had significant positive correlations with a variety of immune marker subsets. Finally, correlations were found between PDLIM3 and crucial markers of signaling pathways involving PI3K/Akt and p38 MAPK. Thus, upregulation of PDLIM3 was significantly associated with poor prognosis, immune cell infiltration, and activation of two key signal pathways in gastric cancer. We propose that PDLIM3 could be used as a biomarker to predict prognosis and immune cell infiltration in gastric cancer.

Selenium nanoparticle (SeNP)-based nanotherapeutics have become an emerging cancer therapy, while effective drug delivery remains a technical hurdle. A theranostic approach, through which imaging companions are integrated with SeNPs, will allow image-guided drug delivery and, therefore, is highly desirable. Traditional methods require the chemical conjugation of imaging agents to the surface of nanoparticles, which may impede the later clinical translation. In this study, we developed a label-free strategy in which lentinan-functionalized SeNPs (LNT-SeNPs) are detected using MRI by the hydroxyl protons carried on LNT molecules. The in vitro phantom study showed that LNT and LNT-SeNPs have a strong CEST signal at 1.0 ppm apart from the water resonance, suggesting an in vivo detectability in the µM concentration range. Demonstrated on CT26 colon tumor cells, LNT-SeNPs exert a strong anticancer effect (IC50 = 4.8 μM), prominently attributed to the ability to generate intracellular reactive oxygen species. However, when testing in a mouse model of CT26 tumors, administration of LNT-SeNPs alone was found unable to deliver sufficient drugs to the tumor, leading to poor treatment responses. To improve the drug delivery, we co-injected LNT-SeNPs and TNF-α, a previously reported drug that could effectively damage the endothelial cells in the tumor vasculature, thereby increasing drug delivery to the tumor. Our results revealed a 75% increase in the intratumoral CEST MRI signal, indicating a markedly increased delivery efficiency of LNT-SeNPs when combined with TNF-α. The combination therapy also resulted in a significantly enhanced treatment outcome, as revealed by the tumor growth study. Taken together, our study demonstrates the first label-free, SeNP-based theranostic system, in which LNT was used for both functional surface coating and CEST MRI signal generating. Such a theranostic LNT-SeNP system is advantageous because it requires chemical labeling and, therefore, has high biocompatibility and low translatable barriers.

With the aging population, stroke has gradually become the leading cause of death and disability among adults. It is necessary to verify whether multi-delay pseudo-continuous arterial spin labeling (pCASL) MRI can be used as a standard neuroimaging protocol in the patients with ischemic stroke. We aimed to investigate the clinical utility of multi-delay pCASL for evaluating cerebral perfusion in ischemic stroke disease. Twenty-one ischemic stroke patients [18 men and 3 women; median age, 62 years (age range, 37–84 years)] were enrolled in this study. All patients underwent examinations, including the multi-delay pCASL protocol (using 6 PLDs between 1,000 and 3,500 ms) and computed tomography perfusion (CTP). The cerebral blood flow (CBF) and arterial transit time (ATT) maps were obtained by the multi-delay pCASL protocol, while CBF and mean transit time (MTT) maps were derived by CTP measurements. Based on the voxel level analysis, Pearson correlation coefficients were used to estimate the associations between the two modalities in the gray matter, white matter, and whole brain of each subject. Moderate to high positive associations between ASL-CBF and CTP-CBF were acquired by voxel-level-wise analysis in the gray matter, white matter, and whole brain of the enrolled patients (all P < 0.005), and the average Pearson correlation coefficients were 0.647, 0.585, and 0.646, respectively. Highly significant positive correlations between ASL-ATT and CTP-MTT were obtained by voxel-level-wise associations in the gray matter, white matter, and whole brain (all P < 0.005), and the average Pearson correlation coefficients were 0.787, 0.707, and 0.799, respectively. In addition, significant associations between ASL and CT perfusion were obtained in the gray, white matter and whole brain, according to the subgroup analyses of patient’s age and disease stage. There is a correlation between perfusion parameters from multi-delay pCASL and CT perfusion imaging in patients with ischemic stroke. Multi-delay pCASL is radiation-free and non-invasive, and could be an alternative method to CT scans for assessing perfusion in ischemic stroke disease.

Abstract Background To report the first case of a cerebral arteriovenous malformation (AVM) with ocular symptoms and review the characteristics of this case and the main point of confusion for the diagnosis of such a case. Case presentation A 58-year-old woman presented to the ophthalmology clinic with 1 and a half years of right eye redness, ocular hypertension and recurrent headache. One and a half years ago she was diagnosed with right eye dry eye and glaucoma and had received treatment according to this diagnosis. However, none of the treatments led to any improvement in redness and headache. Physical examination revealed dry eye and severe corkscrew hyperaemia with dilated vessels in the right eye. The results of fundoscopic examination of both eyes were normal. After we considered that the symptoms may be related to abnormal intracranial vessels, computed tomography angiography and venography (CTA + CTV) were performed, and the results showed an arteriovenous malformation in the right parietal-occipital area in the brain. The AVM was definitively located by further examination with digital subtraction angiography (DSA). After AVM endovascular embolism treatment, the conjunctival congestion of the right eye was significantly relieved, and the intraocular pressure decreased to normal. Conclusion In clinical practice, when corkscrew hyperaemia accompanied by neurological symptoms is found, cerebral vascular diseases might be considered. In this case, the ophthalmologist’s diagnosis should combine disease history and imaging examination.

Background Gamma-delta (γδ) T lymphocytes are primed to potently respond to pathogens and transformed cells by recognizing a broad range of antigens. However, adoptive immunotherapy with γδT cells has exhibited mixed treatment responses. Better understanding of γδT cell biology and stratifying healthy donors for allogeneic adoptive therapy is clinically needed to fully realize the therapeutic potential of γδT cells.Methods We examine 98 blood samples from healthy donors and measure their expansion capacity after zoledronate stimulation, and test the migration and cytotoxic effector function of expanded γδT cells in 2D culture, 3D tumor spheroid and patient-derived melanoma organoid assays.Results We find that γδT cell expansion capacity is independent of expansion methods, gender, age and HLA type. Basal γδT cell levels in Peripheral blood mononuclear cell (PBMC) correlate well with their expansion, migration and cytotoxic effector capacity in vitro. Circulating γδT cells with lower expression of PD-1, CTLA-4, Eomes, T-bet and CD69, or higher IFN-γ production expand better. γδT cells with central memory and effector memory phenotypes are significantly more abundant in good expanders. A cut-off level of 0.82% γδT cells in PBMC stratifies good versus poor γδT cell expansion with a sensitivity of 97.78%, specificity of 90.48% and area under the curve of 0.968 in a healthy individual. Donors with higher Vδ2 Index Score in PBMC have greater anti-tumor functions including migratory function and cytotoxicity.Conclusions Our results demonstrate that the interindividual γδT cell functions correlate with their circulating levels in healthy donors. Examination of circulating γδT cell level may be used to select healthy donors to participate in γδT-based immunotherapies.

Abstract Antiangiogenic tyrosine kinase inhibitors (AA‐TKIs) have become a promising therapeutic strategy for colorectal cancer (CRC). In clinical practice, a significant proportion of cancer patients temporarily discontinue AA‐TKI treatment due to recurrent toxicities, economic burden or acquired resistance. However, AA‐TKI therapy withdrawal‐induced tumour revascularization frequently occurs, hampering the clinical application of AA‐TKIs. Here, this study demonstrates that tumour perivascular cells mediate tumour revascularization after withdrawal of AA‐TKI therapy. Pharmacological inhibition and genetic ablation of perivascular cells largely attenuate the rebound effect of CRC vascularization in the AA‐TKI cessation experimental settings. Mechanistically, tumour perivascular cell‐derived extracellular vehicles (TPC‐EVs) contain Gas6 that instigates the recruitment of endothelial progenitor cells (EPCs) for tumour revascularization via activating the Axl pathway. Gas6 silence and an Axl inhibitor markedly inhibit tumour revascularization by impairing EPC recruitment. Consequently, combination therapy of regorafenib with the Axl inhibitor improves overall survival in mice metastatic CRC model by inhibiting tumour growth. Together, these data shed new mechanistic insights into perivascular cells in off‐AA‐TKI‐induced tumour revascularization and indicate that blocking the Axl signalling may provide an attractive anticancer approach for sustaining long‐lasting angiostatic effects to improve the therapeutic outcomes of antiangiogenic drugs in CRC.

ObjectiveThis study aimed to investigate the effectiveness of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in monitoring tumor responses to antiangiogenic therapy combined with hypoxia-activated prodrugs (HAPs).Materials and methodsEstablishing colon cancer xenograft model by subcutaneously injecting the HCT116 cell line into BALB/C nude mice. Twenty-four tumor-bearing mice were randomly divided into four groups and injected with bevacizumab combined with TH-302 (A), bevacizumab (B), TH-302 (C), or saline (D) on days 1, 4, 7, 10 and 13. Functional MRI was performed before and at 3, 6, 9, 12 and 15 days after treatment. Pathologic examinations, including HE staining, HIF-1α and CD31 immunohistochemical staining, and TUNEL and Ki-67 immunofluorescent staining, were performed after the last scan.ResultsAt the end of the study, Group A showed the lowest tumor volume, followed by Groups B, C, and D (F=120.652, P

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) now has been used to diagnose prostate cancer (PCa). Equivocal lesions are defined as PIRADS category 3 or a Likert scale of 1 to 5 category 3 lesions. Currently, there are no clear recommendations for the management of these lesions. This study aimed to estimate the diagnostic capacity of DCE-MRI for PCa and clinically significant prostate cancer (csPCa) in equivocal lesions.Materials and methodsTwo researchers searched PubMed, Embase and Web of Science to identify studies that met our subject. We searched for articles that mention the accuracy of the diagnosis of DCE-MRI for PCa or csPCa in equivocal lesions and used histopathological results as the reference standard. We used a tool (the Quality Assessment of Diagnostic Accuracy Studies-2 tool) to evaluate the quality of the studies that we screened out. Meta-regression was used to explore the reasons for heterogeneity in results.ResultsTen articles were eventually included in our study. The sensitivity, specificity and 95% confidence intervals (CI) for DCE-MRI in diagnosing csPCa were 0.67 (95% CI, 0.56–0.76), 0.58 (95% CI, 0.46–0.68). The sensitivity and specificity and 95% CI for DCE-MRI in diagnosing PCa were 0.57 (95% CI, 0.46–0.68), 0.58 (95% CI, 0.45–0.70). The areas under the curve (AUC) of DCE-MRI were 0.67 (95% CI, 0.63–0.71) and 0.60 (95% CI, 0.55–0.64) while diagnosing csPCa and PCa. Through meta-regression, we found that study design, magnetic field strength, the definition of csPCa, and the scoring system were the sources of heterogeneity.ConclusionThe results of our study indicate that the role of DCE-MRI in equivocal lesions may be limited.

Massive reinforced concrete (MRC) structures are utilized in a variety of applications where both mechanical and thermal properties are of concern. A 1:2 large-scale test model of the steel-lined reinforced concrete penstock (a kind of MRC) and a coupled thermomechanical numerical analysis are both implemented to investigate the thermomechanical effects on structural behavior. Three different temperature fields and eight temperature gradients are selected to explore how the temperature affects the crack width, steel stress, and deformation. The results show that the numerical simulation results are consistent with the experimental results and that this method can be applied to other similar MRC structure analysis. The thermal effect can cause 10−3~10−2 mm thermal crack width and ±45 MPa thermal stress and this may lead the total crack width to exceed the limited value and the reinforcement stress beyond the yield strength. Consequently, the influence of the thermomechanical loads cannot be ignored and the corresponding temperature control measures must be taken to ensure structural safety and durability.

ObjectivesNano-drug delivery system is an interesting field in precise cancer treatment, but few study has reported the microenvironmental changes after such treatment. This study aimed to detect the hemodynamic and microenvironmental changes in a lung cancer xenograft model after treated with doxorubicin (DOX) encapsulated by a cyclic arginine-glycine-aspartic acid polypeptide modified poly-(lactic-co-glycolic acid) nanosystem (cRGD-PLGA@DOX) using functional magnetic resonance imaging.Materials and MethodsThirty-two tumor-bearing mice were randomly divided into four groups. Group A was treated with 0.9% saline, Group B with 4 mg/kg of doxorubicin, Group C with 2 mg/kg of cRGD-PLGA@DOX, and Group D with 4 mg/kg of cRGD-PLGA@DOX. Intravoxel incoherent motion diffusion-weighed imaging (IVIM-DWI) and R2∗ mapping were performed, and D∗, f, D, and R2∗ values were obtained before and1, 2, and 3 weeks after treatment. They were sacrificed for pathological examination after examinations.ResultsThe reconstructed cRGD-PLGA@DOX was homogeneous, well-dispersed, and spherical in shape, with an average size of 180 nm. Group D demonstrated the smallest tumor volume and highest tumor inhibition rate in 3 weeks. D value of Group B, C, and D manifested an upward trend in 3 weeks with the highest increase in Group D. D∗ values shared a similar increased trends with f values in Group A, B, and C in 3 weeks, except Group D. R2∗ value of Group A gradually increased in 3 weeks, but the trends were reversed in the treatment groups. D value was significantly negative with Ki-67 expression (r = −0.757, P < 0.001) but positive with TUNEL (r = 0.621, P < 0.001), and phosphate and tension homology deleted on chromosome ten (PTEN) staining (r = 0.57, P = 0.004). R2∗ value was closely correlated with HIF-1a (r = 0.721, P < 0.001).ConclusionThe nano-drug demonstrated an enhanced anti-tumor effect without the need of increased chemotherapeutic dosage. The tumor microenvironment such as cellular and perfusion changes during treatment can be non-invasively detected by two functional MRI including IVIM-DWI and R2∗ mapping.

Background: Neoadjuvant chemotherapy (NAC) is commonly utilized in preoperative treatment for local breast cancer, and it gives high clinical response rates and can result in pathologic complete response (pCR) in 6–25% of patients. In recent years, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been increasingly used to assess the pathological response of breast cancer to NAC. In present analysis, we assess the diagnostic performance of DCE-MRI in evaluating the pathological response of breast cancer to NAC.Materials and Methods: A systematic search in PubMed, the Cochrane Library, and Web of Science for original studies was performed. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the methodological quality of the included studies. Patient, study, and imaging characteristics were extracted, and sufficient data to reconstruct 2 × 2 tables were obtained. Data pooling, heterogeneity testing, forest plot construction, meta-regression analysis and sensitivity analysis were performed using Stata version 12.0 (StataCorp LP, College Station, TX).Results: Eighteen studies (969 patients with breast cancer) were included in the present meta-analysis. The pooled sensitivity and specificity of DCE-MRI were 0.80 (95% confidence interval [CI]: 0.70, 0.88) and 0.84 (95% [CI]: 0.79, 0.88), respectively. Meta-regression analysis found no significant factors affecting heterogeneity. Sensitivity analysis showed that studies that set pathological complete response (pCR) (n = 14) as a responder showed a tendency for higher sensitivity compared with those that set pCR and near pCR together (n = 5) as a responder (0.83 vs. 0.72), and studies (n = 14) that used DCE-MRI to early predict the pathological response of breast cancer had a higher sensitivity (0.83 vs. 0.71) and equivalent specificity (0.80 vs. 0.86) compared to studies (n = 5) that assessed the response after NAC completion.Conclusion: Our results indicated that DCE-MRI could be considered an important auxiliary method for evaluating the pathological response of breast cancer to NAC and used as an effective method for dynamically monitoring the efficacy during NAC. DCE-MRI also performed well in predicting the pCR of breast cancer to NAC. However, due to the heterogeneity of the included studies, caution should be exercised in applying our results.

For the reinforced concrete frame-shear wall (RCF-SW) structures in hydropower plants (HPs), the tensile cracking and compressive crushing of the reinforced concrete (RC) members are considered as the main potential damage. This paper presents a methodology to assess the seismic performance of RCF-SW structures. In this methodology, a concrete damage plasticity model is employed to simulate the reinforced concrete, and the structural seismic responses are investigated through nonlinear incremental dynamic analysis (IDA). Several engineering demand parameters (EDPs) based on the material damage are proposed to identify the structural engineering limit states and damage states at the member level. The case of x HP is provided as an example to illustrate the methodology and discuss the probable nonlinear response and structural damage state. The concrete damage evolution, reinforcement stresses, and drift ratios of the RCF-SW structure are presented, and the engineering limit states and structural damage states are identified. In comparison with the drift ratio index, the EDPs based on material damage are more suitable for identifying the damage state of the RCF-SW structure, whose damage is controlled by the damage of the RC members.

Abstract Background Cerebrovascular events are frequently associated with hemodynamic disturbance caused by internal carotid artery (ICA) stenosis. It is challenging to determine the ischemia-related carotid stenosis during the intervention only using digital subtracted angiography (DSA). Inspired by the performance of well-established FFRct technique in hemodynamic assessment of significant coronary stenosis, we introduced a pressure-based carotid arterial functional assessment (CAFA) index generated from computational fluid dynamic (CFD) simulation in DSA data, and investigated its feasibility in the assessment of hemodynamic disturbance preliminarily using pressure-wired measurement and arterial spin labeling (ASL) MRI as references. Methods The cerebral multi-delay multi-parametric ASL-MRI and carotid DSA including trans-stenotic pressure-wired measurement were implemented on a 65-year-old man with asymptomatic unilateral (left) ICA stenosis. A CFD simulation using simplified boundary condition was performed in DSA data to calculate the CAFA index. The cerebral blood flow (CBF) and arterial transit time (ATT) of ICA territories were acquired. Results CFD simulation showed good correlation (r = 0.839, P = 0.001) with slight systematic overestimation (mean difference − 0.007, standard deviation 0.017) compared with pressure-wired measurement. No significant difference was observed between them (P = 0.09). Though the narrowing degree of in the involved ICA was about 70%, the simulated and measured CAFA (0.942/0.937) revealed a functionally nonsignificant stenosis which was also verified by a compensatory final CBF (fronto-temporal/fronto-parietal region: 51.58/45.62 ml/100 g/min) and slightly prolonged ATT (1.23/1.4 s) in the involved territories, together with a normal left–right percentage difference (2.1–8.85%). Conclusions The DSA based CFD simulation showed good consistence with invasive approach and could be used as a cost-saving and efficient way to study the relationship between hemodynamic disorder caused by ICA stenosis and subsequent perfusion variations in brain. Further research should focus on the role of noninvasive pressure-based CAFA in screening asymptomatic ischemia-causing carotid stenosis.

The integration of diagnosis and therapy is an effective way to improve therapeutic effects for cancer patients, which has acquired widely attentions from researchers. Herein, a multifunctional drug-loaded nanosystem (F/A-PLGA@DOX/SPIO) has been designed and synthesized to reduce the side effects of traditional chemotherapy drugs and realize simultaneous tumor diagnosis and treatment. The surface modification of folic acid (FA) and activatable cell-penetrating peptide (ACPP) endows the nanosystem with excellent cancer targeting capabilities, thus reducing toxicity to normal organs. Besides, the F/A-PLGA@DOX/SPIO nanosystem can serve as an excellent magnetic resonance imaging (MRI) T2-negative contrast agent. More importantly, according to in vitro experiments, the F/A-PLGA@DOX/SPIO nanosystem can promote the overproduction of reactive oxygen species (ROS) within A549 lung cancer cells, inducing cell apoptosis, greatly enhancing the antineoplastic effect. Furthermore, with the help of MRI technology, the targeting imaging of the F/A-PLGA@DOX/SPIO nanosystem within tumors and the dynamic monitoring of medicine efficacy can be realized. Therefore, this study provided a multifunctional drug-loaded F/A-PLGA@DOX/SPIO targeted nanosystem for magnetic resonance molecular imaging-guided theranostics, which has excellent potential for the application in tumor diagnosis and therapy.

Abstract Background The invasive fractional flow reserve has been considered the gold standard for identifying ischaemia-related stenosis in patients with suspected coronary artery disease. Determining non-invasive FFR based on coronary computed tomographic angiography datasets using computational fluid dynamics tends to be a demanding process. Therefore, the diagnostic performance of a simplified method for the calculation of FFRCTA requires further evaluation. Objectives The aim of this study was to investigate the diagnostic performance of FFRCTA calculated based on a simplified method by referring to the invasive FFR in patient-specific coronary arteries and clinical decision-making. Methods Twenty-nine subjects included in this study underwent CCTA before undergoing clinically indicated invasive coronary angiography for suspected coronary artery disease. Pulsatile flow simulation and a novel boundary condition were used to obtain FFRCTA based on the CCTA datasets. The Pearson correlation, Bland–Altman plots and the diagnostic performance of FFRCTA and CCTA stenosis were analyzed by comparison to the invasive FFR reference standard. Ischaemia was defined as an FFR or FFRCTA ≤0.80, and anatomically obstructive CAD was defined as a CCTA stenosis >50%. Results FFRCTA and invasive FFR were well correlated (r = 0.742, P = 0.001). Slight systematic underestimation was found in FFRCTA (mean difference 0.03, standard deviation 0.05, P = 0.001). The area under the receiver-operating characteristic curve was 0.93 for FFRCTA and 0.75 for CCTA on a per-vessel basis. Per-patient accuracy, sensitivity and specificity were 79.3, 93.7 and 61.5%, respectively, for FFRCTA and 62.1, 87.5 and 30.7%, respectively, for CCTA. Per-vessel accuracy, sensitivity and specificity were 80.6, 94.1 and 68.4%, respectively, for FFRCTA and 61.6, 88.2 and 36.8%, respectively, for CCTA. Conclusions FFRCTA derived from pulsatile simulation with a simplified novel boundary condition was in good agreement with invasive FFR and showed better diagnostic performance compared to CCTA, suggesting that the simplified method has the potential to be an alternative and accurate way to assess the haemodynamic characteristics for coronary stenosis.

Under the circumstances of rapid expansion of diverse forms of volatile and intermittent renewable energy sources, hydropower stations have become increasingly indispensable for improving the quality of energy conversion processes. As a consequence, Francis turbines, one of the most popular options, need to operate under off-design conditions, particularly for partial load operation. In this paper, a prototype Francis turbine was used to investigate the pressure fluctuations and hydraulic axial thrust pulsation under four partial load conditions. The analyses of pressure fluctuations in the vaneless space, runner, and draft tube are discussed in detail. The observed precession frequency of the vortex rope is 0.24 times that of the runner rotational frequency, which is able to travel upstream (from the draft tube to the vaneless space). Frequencies of both 24.0 and 15.0 times that of the runner rotational frequency are detected in the recording points of the runner surface, while the main dominant frequency recorded in the vaneless zone is 15.0 times that of the runner rotational frequency. Apart from unsteady pressure fluctuations, the pulsating property of hydraulic axial thrust is discussed in depth. In conclusion, the pulsation of hydraulic axial thrust is derived from the pressure fluctuations of the runner surface and is more complicated than the pressure fluctuations.

Tumor vascular normalization has been proposed as a new concept in anti-tumor angiogenesis, and the normalization window is considered as an opportunity to increase the effect of chemoradiotherapy. However, there is still a lack of a non-invasive method for monitoring the process of tumor vascular normalization. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM DW-MRI) is an emerging approach which can effectively assess microperfusion in tumors, without the need for exogenous contrast agents. However, its role in monitoring tumor vascular normalization still needs further study. In this study, we established a tumor vascular normalization model of CT26 colon-carcinoma-bearing mice by means of Endostar treatment. We then employed IVIM DW-MRI and immunofluorescence to detect the process of tumor vascular normalization at different times after treatment. We found that the D* values of the Endostar group were significantly higher than those of the control group on days 4, 6, 8, and 10 after treatment, and the f values of the Endostar group were significantly higher than those of the control group on days 6 and 8. Furthermore, we confirmed through analysis of histologic parameters that Endostar treatment induced the CT26 tumor vascular normalization window starting from day 4 after treatment, and this window lasted for 6 days. Moreover, we found that D* and f values were well correlated with pericyte coverage (r = 0.469 and 0.504, respectively; P < 0.001, both) and relative perfusion (r = 0.424 and 0.457, respectively; P < 0.001, both). Taken together, our findings suggest that IVIM DW-MRI has the potential to serve as a non-invasive approach for monitoring Endostar-induced tumor vascular normalization.

Exploring and expanding the indications of common clinical drugs, such as statins, is important to improve the prognosis of patients with permanent cerebral infarction. It has been suggested that reversing the defects in cellular autophagy and ER stress with statin therapy may be a potential treatment option for reducing ischemic damage. Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (PMCAO) by electrocoagulation surgery. Atorvastatin (ATV, 10 mg/kg/day) or vehicle was administered intraperitoneally. Rats were divided into the vehicle-treated (SHAM), ATV pretreatment for MCAO (AMCAO), and 3-methyladenine (3MA) combined with ATV pretreatment (3MAMCAO) groups. Magnetic resonance imaging, as well as immunohistochemical and Western blot assessments, were performed 24 h after MCAO. Each ATV-treated group demonstrated significant reductions in infarct volume compared with that in the vehicle-treated group at 24 h after MCAO, which was associated with autophagy reduction and ER stress attenuation in neurons and neovascularization. Next, Western blotting was used to detect the levels of the autophagy-related proteins LC3B and P62 and of ER stress pathway proteins. However, 3MA significantly partially inhibited the ER stress pathway via limiting the autophagic flux in the AMCAO group. In conclusion, our results imply that the neuroprotective function of ATV depends on autophagic activity to diminish ER stress-related cell apoptosis in rats with PMCAO and suggest that compounds that inhibit autophagic activity might reduce the neuroprotective effect of ATV after brain ischemia.

Our previous study has revealed that chronic cerebral hypoperfusion (CCH) activates a compensatory vascular mechanism attempting to maintain an optimal cerebral blood flow (CBF). However, this compensation fails to prevent neuronal death and cognitive impairment because neurons die prior to the restoration of normal CBF. Therefore, pharmacological invention may be critical to enhance the CBF for reducing neurodegeneration and memory deficit. Dl-3-n-butylphthalide (NBP) is a compound isolated from the seeds of Chinese celery and has been proven to be able to prevent neuronal loss, reduce inflammation and ameliorate memory deficits in acute ischemic animal models and stroke patients. In the present study, we used magnetic resonance imaging (MRI) techniques, immunohistochemistry and Morris water maze (MWM) to investigate whether NBP can accelerate CBF recovery, reduce neuronal death and improve cognitive deficits in CCH rats after permanent bilateral common carotid artery occlusion (BCCAO). Rats were intravenously injected with NBP (5 mg/kg) daily for 14 days beginning the first day after BCCAO. The results showed that NBP shortened recovery time of CBF to pre-occlusion levels at 2 weeks following BCCAO, compared to 4 weeks in the vehicle group, and enhanced hemodynamic compensation through dilation of the vertebral arteries (VAs) and increase in angiogenesis. NBP treatment also markedly reduced reactive astrogliosis and cell apoptosis and protected hippocampal neurons against ischemic injury. The escape latency of CCH rats in the MWM was also reduced in response to NBP treatment. These findings demonstrate that NBP can accelerate the recovery of CBF and improve cognitive function in a rat model of CCH, suggesting that NBP is a promising therapy for CCH patients or vascular dementia.

Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs.

PURPOSE:The aim of this study was to design a method of radionuclide for imaging and therapy of nasopharyngeal carcinoma (NPC) using the transferred human sodium/iodide symporter (hNIS) gene. METHODS:A stable NPC cell line expressing hNIS was established (CNE-2-hNIS). After 131I treatment, we detected proliferation and apoptosis of NPC cells, both in vitro and vivo. In vivo, the radioactivity of different organs of nude mice was counted and (99m)Tc imaging using SPECT was performed. The apparent diffusion coefficient (ADC) value changes of tumor xenografts were observed by diffusion-weighted magnetic resonance imaging (DW-MRI) within 6-24 days of 131I treatment. The correlation of ADC changes with apoptosis and proliferation was investigated. Post-treatment expression levels of P53, Bax, Bcl-2, Caspase-3, and Survivin proteins were detected by western blotting. RESULTS:131I uptake was higher in CNE-2-hNIS than in CNE-2 cells. The proliferation and apoptosis rate decreased and increased respectively both in vitro and vivo in the experimental group after 131I treatment. The experimental group tumors accumulated (99m)Tc in vivo, leading to a good visualization by SPECT. DW-MRI showed that ADC values increased in the experimental group 6 days after treatment, while ADC values were positively and negatively correlated with the apoptotic and Ki-67 proliferation indices, respectively. After treatment, CNE-2-hNIS cells up-regulated the expression of P53 and Survivin proteins and activated Caspase-3, and down-regulated the expression of Bcl-2 proteins. CONCLUSIONS:The radionuclide imaging and therapy technique for NPC hNIS-transfected cell lines can provide a new therapy strategy for monitoring and treatment of NPC.

Disrupted white matter integrity and abnormal cortical thickness are widely reported in the pathophysiology of obsessive-compulsive disorder (OCD). However, the relationship between alterations in white matter connectivity and cortical thickness in OCD is unclear. In addition, the heritability of this relationship is poorly understood. To investigate the relationship of white matter microstructure with cortical thickness, we measure fractional anisotropy (FA) of white matter in 30 OCD patients, 19 unaffected siblings and 30 matched healthy controls. Then, we take those regions of significantly altered FA in OCD patients compared with healthy controls to perform fiber tracking. Next, we calculate the fiber quantity in the same tracts. Lastly, we compare cortical thickness in the target regions of those tracts. Patients with OCD exhibited decreased FA in cingulum, arcuate fibers near the superior parietal lobule, inferior longitudinal fasciculus near the right superior temporal gyrus and uncinate fasciculus. Siblings showed reduced FA in arcuate fibers near the superior parietal lobule and anterior limb of internal capsule. Significant reductions in both fiber quantities and cortical thickness in OCD patients and their unaffected siblings were also observed in the projected brain areas when using the arcuate fibers near the left superior parietal lobule as the starting points. Reduced FA in the left superior parietal lobule was observed not only in patients with OCD but also in their unaffected siblings. Originated from the superior parietal lobule, the number of fibers was also found to be decreased and the corresponding cortical regions were thinner relative to controls. The linkage between disrupted white matter integrity and the abnormal cortical thickness may be a vulnerability marker for OCD.