Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia.

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

[Retracted] Application of a novel targeting nanoparticle contrast agent combined with magnetic resonance imaging in the diagnosis of intraductal papillary mucinous neoplasm.

[This retracts the article DOI: 10.3892/etm.2018.6349.].

The value of multiparameter MRI of early cervical cancer combined with SCC-Ag in predicting its pelvic lymph node metastasis.

Purpose: To investigate the value of multiparameter MRI of early cervical cancer (ECC) combined with pre-treatment serum squamous cell carcinoma antigen (SCC-Ag) in predicting its pelvic lymph node metastasis (PLNM). Material and methods: 115 patients with pathologically confirmed FIGO IB1~IIA2 cervical cancer were retrospectively included and divided into the PLNM group and the non-PLNM group according to pathological results. Quantitative parameters of the primary tumor include Ktrans, Kep, Ve from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), ADCmean, ADCmin, ADCmax, D, D* and f from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) were measured. Pre-treatment serum SCC-Ag was obtained. The difference of the above parameters between the two groups were compared using the student t-test or Mann-Whitney U test. Multivariate Logistic regression analysis was performed to determine independent risk factors. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy of individual parameters and their combination in predicting PLNM from ECC. Results: The PLNM group presented higher SCC-Ag [14.25 (6.74,36.75) ng/ml vs.2.13 (1.32,6.00) ng/ml, P<0.001] and lower Ktrans (0.51 ± 0.20 min-1 vs.0.80 ± 0.33 min-1, P < 0.001), ADCmean (0.85 ± 0.09 mm/s2 vs.1.06 ± 0.35 mm/s2, P<0.001), ADCmin [0.67 (0.61,0.75) mm/s2 vs. 0.75 (0.64,0.90) mm/s2, P = 0.012] and f (0.91 ± 0.09 vs. 0.27 ± 0.14, P = 0.001) than the non-LNM group. Multivariate analysis showed that SCC-Ag (OR = 1.154, P = 0.007), Ktrans (OR=0.003, P < 0.001) and f (OR = 0.001, P=0.036) were independent risk factors of PLNM. The combination of SCC-Ag, Ktrans and f possessed the best predicting efficacy for PLNM with an area under curve (AUC) of 0.896, which is higher than any individual parameter: SCC-Ag (0.824), Ktrans (0.797), and f (0.703). The sensitivity and specificity of the combination were 79.1% and 94.0%, respectively. Conclusions: Quantitative parameters Ktrans and f derived from DCE-MRI and IVIM-DWI of primary tumor and SCC-Ag have great value in predicting PLNM. The diagnostic efficacy of their combination has been further improved.

Decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance treatment significantly improves survival outcomes in relapsed/refractory B-ALL patients.

OBJECTIVE: We aimed to evaluate the efficacy of decitabine consolidation after treatment with CD19/CD22 chimeric antigen receptor T-cell (CAR-T) for patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL). METHODS: We retrospectively analysed 48 patients with r/r B-ALL who received CD19/CD22 CAR-T therapy between September 2017 and May 2021. Sixteen patients received decitabine consolidation (20 mg/m2/day for 5 days at 3-month intervals) after CAR-T therapy (DAC group), while 32 patients did not receive decitabine consolidation (CON group). Overall survival (OS), leukaemia-free survival (LFS), and cumulative incidence of relapse (CIR) were evaluated in both groups. Time-to-event analysis was performed using the Kaplan-Meier method. RESULTS: The median follow-up periods in the DAC and CON groups were 41.2 months and 28.6 months, respectively. The 4-year OS and 4-year LFS rates in both groups were 93.3 % and 64.3 % (P=0.029) and 87.5 % and 55.9 % (P=0.059), respectively. The 1-year CIR was 6.25 % and 28.6 %, respectively. Univariate and multivariate Cox regression analyses showed that decitabine consolidation after CAR-T therapy was significantly associated with superior OS (hazard ratio [HR]: 0.121, 95 % confidence interval [CI]: 0.015-0.947, P=0.044), and bridging to haematopoietic stem cell transplantation after CAR-T therapy was significantly associated with superior LFS (HR: 0.279, 95 %CI: 0.093-0.840, P=0.023). CONCLUSIONS: Our study recommends decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance strategy to improve the survival outcomes of patients with r/r B-ALL.

CD19 chimeric antigen receptor-T cells as bridging therapy to allogeneic hematopoietic cell transplantation improves outcome in patients with refractory/relapsed B-cell acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR)-T cell therapy has been confirmed improving remission rates in refractory patients or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). However, the added benefits of undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T therapy remain a subject of debate. In this research we investigated the efficiency and long-term outcomes of CD19 CAR-T bridging with allo-HSCT in R/R B-ALL patients. A total of 42 patients were brought into the cohort studies. Our findings revealed that patients who appected CAR-T followed by HSCT had a 1-year overall survival (OS) rate of 70 % and a 1-year leukemia-free survival (LFS) rate of 95 %. Moreover, patients who underwent this combined treatment had higher OS and LFS rates compared to those who received CAR-T therapy alone. In conclusion, the results of this clinical trial provide compelling evidence for the safety and efficacy of using CAR-T therapy as a bridging strategy to allo-HSCT in patients with R/R B-ALL.

Evaluation of left ventricular blood flow kinetic energy in patients with acute myocardial infarction by 4D Flow MRI: a preliminary study.

PURPOSE: To evaluate the intracavity left ventricular (LV) blood flow kinetic energy (KE) parameters using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). METHODS: Thirty AMI patients and twenty controls were examined via CMR, which included cine imaging, late gadolinium enhancement (LGE) and global heart 4D flow imaging. The KE parameters were indexed to LV end-diastolic volume (EDV) to obtain average, systolic and diastolic KE as well as the proportion of LV in-plane KE (%). These parameters were compared between the AMI patients and controls and between the two subgroups. RESULTS: Analysis of the LV blood flow KE parameters at different levels of the LV cavity and in different segments of the same level showed that the basal level had the highest blood flow KE while the apical level had the lowest in the control group. There were no significant differences in diastolic KE, systolic in-plane KE and diastolic in-plane KE between the anterior wall and posterior wall (p > 0.05), only the systolic KE had a significant difference between them (p < 0.05). Compared with those in the control group, the average (10.7 ± 3.3 µJ/mL vs. 14.7 ± 3.6 µJ/mL, p < 0.001), systolic (14.6 ± 5.1 µJ/mL vs. 18.9 ± 3.9 µJ/mL, p = 0.003) and diastolic KE (7.9 ± 2.5 µJ/mL vs. 10.6 ± 3.8 µJ/mL, p = 0.018) were significantly lower in the AMI group. The average KE in the infarct segment was lower than that in the noninfarct segment in the AMI group (49.5 ± 18.7 µJ/mL vs. 126.3 ± 50.7 µJ/mL, p < 0.001), while the proportion of systolic in-plane KE increased significantly (61.8%±11.5 vs. 42.9%±14.4, p = 0.001). CONCLUSION: The 4D Flow MRI technique can be used to quantitatively evaluate LV regional hemodynamic parameters. There were differences in the KE parameters of LV blood flow at different levels and in different segments of the same level in healthy people. In AMI patients, the average KE of the infarct segment decreased, while the proportion of systolic in-plane KE significantly increased.

MRI findings in 1 case of primary gallbladder lymphoma.

We describe a case of gallbladder extra-nodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-ML). MALT-ML is rare, and its clinical manifestations are lack of specificity. A few cases have been reported, and no characteristic imaging features have been described. We discussed the challenges of MRI in diagnosing MALT-ML of gallbladder, especially in differentiating it from gallbladder cancer. We found a "comb-like" sign in the inner wall of gallbladder on T2WI, which may be helpful in diagnosing gallbladder MALT-ML.

Rituximab potentially improves clinical outcomes of CAR-T therapy for r/r B-ALL via sensitizing leukemia cells to CAR-T-mediated cytotoxicity and reducing CAR-T exhaustion.

PURPOSE: Despite chimeric antigen receptor (CAR) T-cell therapy has achieved great advances in recent year, approximately 50% of relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL) patients treated with CAR-T experience relapse 6 months post CAR-T treatment. CD20 express on 30 to 50% of B-ALL, which makes CD20 Monoclonal Antibody as one of the potential therapy strategies to decrease the tumor burden and improve the efficacy of CAR-T therapy. Adding Rituximab to chemotherapy protocol had been demonstrated to improve the outcome for CD20-positive ALL. However, rare study explored the influence of Rituximab combined with CAR-T therapy. METHODS: We retrospectively analyzed 20 r/r B-ALL patients who received CAR-T therapy, all of whom had failed multiple lines of therapy. Before CAR-T infusion, we administered Rituximab to 10 patients with high CD20 expression at a dose of 375 mg/m2 for 1 day. Meanwhile, we selected 10 patients with the comparable features who underwent CAR-T treatment without Rituximab in the same period as the control group. In vitro, the surface molecule expression and killing of CAR-T post Rituximab-treated B-ALL cells co-incubated with CAR-T cells were detected by flow cytometry. RESULTS: The median follow-up of Rituximab and Control groups were 29.27 and 9.83 months. We found that adding Rituximab may confer a favorable prognosis compared with Control group. The 2-year overall survival (OS) and leukemia-free survival (LFS) rates both were longer in the Rituximab group (90% vs. 26.7%, p = 0.0342; 41.7% vs. 25%, p = 0.308). In vitro, we observed that Rituximab-treated tumour cells are more sensitive to CAR-T killing and a broad range of cytokines and chemokines were produced when Rituximab-treated Nalm-6 cells co-cultured with 19-22CAR-T cells, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). To investigate whether Rituximab has an effect on CAR-T persistence, we stimulated CAR-T cells repeatedly in vitro with Rituximab-treated Nalm-6 to evaluate the changes in CAR-T surface exhaustion molecules at different times. We found that the expression of exhaustion molecules (LAG-3, PD-1, TIM-3) on CAR-T cells were significantly lower in the Rituximab group than in the Control group. CONCLUSION: Rituximab combined with CAR-T therapy is effective for improving the long-term prognosis of B-ALL patients who have failed multiple lines of therapy. In vitro, we observed that rituximab potentially improves CAR-T efficacy by sensitizing ALL to CART-mediated cytotoxicity and reducing CAR-T exhaustion.

PD-1 downregulation enhances CAR-T cell antitumor efficiency by preserving a cell memory phenotype and reducing exhaustion.

BACKGROUND: Despite the encouraging outcome of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) in managing relapsed or refractory multiple myeloma (RRMM) patients, the therapeutic side effects and dysfunctions of CAR-T cells have limited the efficacy and clinical application of this promising approach. METHODS: In this study, we incorporated a short hairpin RNA cassette targeting PD-1 into a BCMA-CAR with an OX-40 costimulatory domain. The transduced PD-1KD BCMA CAR-T cells were evaluated for surface CAR expression, T-cell proliferation, cytotoxicity, cytokine production, and subsets when they were exposed to a single or repetitive antigen stimulation. Safety and efficacy were initially observed in a phase I clinical trial for RRMM patients. RESULTS: Compared with parental BCMA CAR-T cells, PD-1KD BCMA CAR-T cell therapy showed reduced T-cell exhaustion and increased percentage of memory T cells in vitro. Better antitumor activity in vivo was also observed in PD-1KD BCMA CAR-T group. In the phase I clinical trial of the CAR-T cell therapy for seven RRMM patients, safety and efficacy were initially observed in all seven patients, including four patients (4/7, 57.1%) with at least one extramedullary site and four patients (4/7, 57.1%) with high-risk cytogenetics. The overall response rate was 85.7% (6/7). Four patients had a stringent complete response (sCR), one patient had a CR, one patient had a partial response, and one patient had stable disease. Safety profile was also observed in these patients, with an incidence of manageable mild to moderate cytokine release syndrome and without the occurrence of neurological toxicity. CONCLUSIONS: Our study demonstrates a design concept of CAR-T cells independent of antigen specificity and provides an alternative approach for improving the efficacy of CAR-T cell therapy.

Corrigendum: Prediction of severe CRS and determination of biomarkers in B cell-acute lymphoblastic leukemia treated with CAR-T cells.

[This corrects the article DOI: 10.3389/fimmu.2023.1273507.].

Identification and Expression Analysis of the Nucleotidyl Transferase Protein (NTP) Family in Soybean (Glycine max) under Various Abiotic Stresses.

Nucleotidyl transferases (NTPs) are common transferases in eukaryotes and play a crucial role in nucleotide modifications at the 3' end of RNA. In plants, NTPs can regulate RNA stability by influencing 3' end modifications, which in turn affect plant growth, development, stress responses, and disease resistance. Although the functions of NTP family members have been extensively studied in Arabidopsis, rice, and maize, there is limited knowledge about NTP genes in soybeans. In this study, we identified 16 members of the NTP family in soybeans, including two subfamilies (G1 and G2) with distinct secondary structures, conserved motifs, and domain distributions at the protein level. Evolutionary analysis of genes in the NTP family across multiple species and gene collinearity analysis revealed a relatively conserved evolutionary pattern. Analysis of the tertiary structure of the proteins showed that NTPs have three conserved aspartic acids that bind together to form a possible active site. Tissue-specific expression analysis indicated that some NTP genes exhibit tissue-specific expression, likely due to their specific functions. Stress expression analysis showed significant differences in the expression levels of NTP genes under high salt, drought, and cold stress. Additionally, RNA-seq analysis of soybean plants subjected to salt and drought stress further confirmed the association of soybean NTP genes with abiotic stress responses. Subcellular localization experiments revealed that GmNTP2 and GmNTP14, which likely have similar functions to HESO1 and URT1, are located in the nucleus. These research findings provide a foundation for further investigations into the functions of NTP family genes in soybeans.

Outcomes of allogeneic hematopoietic stem cell transplantation in R/R DLBCL patients with failure of CAR-T therapy.

From October 2017 to June 2022, we retrospectively report outcomes of R/R DLBCL patients with failure of CAR-T therapy, then receiving allo-HSCT. Among 10 patients, 5 were males and 5 females, with a median age of 43.5 (27-52) years. All patients were diagnosed refractory/relapsed diffuse large B cell lymphoma. The median time from CAR-T treatment to transplantation was 84.5 (31-370) days. The median follow-up was 21 (3-69) months. 5/10 patients attained CR and 1/10 patient attained PR during the follow up. The objective response rate (ORR) was 60%. The 1-year overall survival (OS) and progression-free survival (PFS) were 70% and 40%, respectively. At the time of the analysis, 6 patients were still living. During the follow up, four patients have died and the causes were disease relapses and progressions (2 patients), acute renal failure (1 patient), severe pulmonary infection (1 patient). Non-relapse was 20.0%.

Circulating tumor DNA determining hyperprogressive disease after CAR-T therapy alarms in DLBCL: a case report and literature review.

Chimeric antigen receptor T-cell therapy (CAR-T) has been widely applied in the clinical practice of relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) due to its promising effects. Hyperprogressive disease (HPD) has gained attention for rapid tumor progression and has become a therapeutic and prognostic challenge. Here, we present a patient who had suffered from several recurrences previously and controlled well with a very small tumor lesion left was infused with CD19/CD22 bispecific CAR-T, with no immune effector cell-associated neurotoxicity syndrome, or cytokine release syndrome observed. However, rapid deterioration, subsequent imaging examination, circulating tumor DNA, and serum biomarkers detection identified HPD. The patient did not respond to salvage treatment and died 40 days after infusion. To our knowledge, only one case of HPD in DLBCL after CAR-T therapy has been reported. This fatal case alarmed the risk of HPD and the ctDNA profile monitoring we used was performed as a non-invasive method to diagnose HPD, providing far-reaching practical instruction for CAR-T therapy.

Prediction of severe CRS and determination of biomarkers in B cell-acute lymphoblastic leukemia treated with CAR-T cells.

Introduction: CAR-T cell therapy is a novel approach in the treatment of hematological tumors. However, it is associated with life-threatening side effects, such as the severe cytokine release syndrome (sCRS). Therefore, predicting the occurrence and development of sCRS is of great significance for clinical CAR-T therapy. The study of existing clinical data by artificial intelligence may bring useful information. Methods: By analyzing the heat map of clinical factors and comparing them between severe and non-severe CRS, we can identify significant differences among these factors and understand their interrelationships. Ultimately, a decision tree approach was employed to predict the timing of severe CRS in both children and adults, considering variables such as the same day, the day before, and initial values. Results: We measured cytokines and clinical biomarkers in 202 patients who received CAR-T therapy. Peak levels of 25 clinical factors, including IFN-γ, IL6, IL10, ferritin, and D-dimer, were highly associated with severe CRS after CAR T cell infusion. Using the decision tree model, we were able to accurately predict which patients would develop severe CRS consisting of three clinical factors, classified as same-day, day-ahead, and initial value prediction. Changes in serum biomarkers, including C-reactive protein and ferritin, were associated with CRS, but did not alone predict the development of severe CRS. Conclusion: Our research will provide significant information for the timely prevention and treatment of sCRS, during CAR-T immunotherapy for tumors, which is essential to reduce the mortality rate of patients.

Effects of Transcranial Direct Current Stimulation on Graph Naming Function and Brain Connectivity in Post-Infarction Aphasia Patients: An fMRI Study.

OBJECTIVE: The study aimed to investigate the mechanisms of impairment and recovery in graph naming functions among patients with aphasia due to cerebral infarction. Specifically, the study compared immediate effects of transcranial Direct Current Stimulation (tDCS) treatment in patients at different stages post-infarction: the acute phase and the recovery period. METHODS: Twenty-eight patients were selected, consisting of 16 in the acute phase (AP) and 12 in the recovery period (RP), along with 18 healthy controls. Both patient groups underwent two weeks of tDCS treatment. Post-treatment changes in functional connectivity (FC) within language-related brain regions, as well as in graph naming abilities, were assessed in both patient groups. RESULTS: Both AP and RP groups exhibited significant improvements in graph naming ability following tDCS treatment. Compared to healthy controls, patients showed decreased functional connectivity in multiple brain regions of both hemispheres, particularly in the dominant hemisphere. Post-treatment assessments revealed significant increases in functional connectivity within the bilateral frontotemporal lobes for both AP and RP groups, and within the bilateral temporo-occipital regions for the AP group. Moreover, the RP group demonstrated decreased functional connectivity in the left temporal lobe post-treatment, which had shown increased functional connectivity pre-treatment. CONCLUSIONS: This study suggests that tDCS can effectively enhance graph naming functions in patients with post-infarction aphasia. The therapeutic effects appear to be mediated by enhancing functional connectivity within bilateral frontotemporal lobes.

Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia-reperfusion in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate advanced MRI findings in the bilateral hippocampus CA1 region of rats with hemorrhagic shock reperfusion (HSR) and their correlation with histopathological results. Additionally, this study aimed to identify effective MRI examination methods and detection indexes for assessing HSR. METHODS: Rats were randomized into the HSR and the Sham groups with 24 rats in each group. MRI examination included diffusion kurtosis imaging (DKI) and 3-dimensional arterial spin labeling (3D-ASL). Apoptosis and pyroptosis were evaluated directly from tissue. RESULTS: In the HSR group, cerebral blood flow (CBF) was significantly lower than that of the Sham group, while radial kurtosis (Kr), axial kurtosis (Ka), and mean kurtosis (MK) were all higher. In the HSR group, fractional anisotropy (FA) at 12 and 24 hours and radial diffusivity, axial diffusivity (Da), and mean diffusivity (MD) at 3 and 6 hours were lower than in the Sham group. MD and Da at 24 hours in the HSR group were significantly higher. The apoptosis rate and pyroptosis rate were also enhanced in the HSR group. CBF, FA, MK, Ka, and Kr values in the early stage were strongly correlated with apoptosis rate and pyroptosis rate. The metrics were obtained from DKI and 3D-ASL. CONCLUSIONS: Advanced MRI metrics from DKI and 3D-ASL, including CBF, FA, Ka, Kr, and MK values, are useful to evaluate abnormal blood perfusion and microstructural changes in the hippocampus CA1 area in the setting of incomplete cerebral ischemia-reperfusion in rats induced by HSR.

Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin's lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton's tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

Assessment of nucleus accumbens impairment in a rat model of postoperative cognitive dysfunction using diffusion tensor imaging.

BACKGROUND: Postoperative cognitive dysfunction (POCD) often occurs in elderly patients, causing depression and other symptoms. Nucleus accumbens (NAc) is involved in depression. We investigate the diffusion tensor imaging (DTI) parameters of NAc in a POCD model of depression. METHODS: Twenty-month-old male Sprague-Dawley (SD) rats were randomly divided into the POCD and Sham groups. The POCD group underwent exploratory laparotomy to establish a POCD depression model, while the Sham group underwent a sham operation. The fractional anisotropy (FA) and mean diffusivity (MD) values of the bilateral NAc, behavioural changes of forced swimming test and sucrose preference rate, and pathological changes of glial fibrillary acidic protein (GFAP) fluorescent intensity were observed at 15 days (D15 ) and 30 days (D30 ) after the operation. RESULTS: The FA value of the bilateral NAc area in the POCD group was lower than that in the Sham group at the two time periods after the operation (P < 0.05). However, the MD value at D30 was higher in the POCD group than in the Sham group (P < 0.05). The FA value in the POCD group was lower at D30 than at D15 (P < 0.05). The floating time was prolonged while the sucrose preference rate was decreased in the POCD group compared with the Sham group (P < 0.05). The floating time in the POCD group was longer at D30 than at D15 . However, the sucrose preference rate in the POCD was lower at D30 than at D15 . The GFAP fluorescent intensity in the bilateral NAc region in the POCD group was higher than in the Sham group (P < 0.05). CONCLUSION: Microstructural changes of the NAc area are associated with POCD related depression. In addition, FA and MD were demonstrated to be effective in diagnosing and monitoring postoperative depression and its severity.