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Backgroud: Tumor radiotherapy combined with immunotherapy for solid tumors has been proposed, but tumor vascular structure abnormalities and immune microenvironment often affect the therapeutic effect of tumor, and there are few reports on multimodal imaging markers in the study of tumor therapeutic response. The purpose of this study was to evaluate the dynamic monitoring of tumor blood vessels and microenvironment induced by radiotherapy by magnetic resonance imaging /photoacoustic imaging (MR/PA) imaging, and to explore the therapeutic effect of tumor radiotherapy combined with PD-L1 immunocheckpoint inhibitor. Methods The tumor-bearing mice (TBM) were randomly allocated to six groups: the low-dose group, high-dose group, low-dose + PD-L1 group, high-dose + PD-L1 group, anti-PD-L1 group and control group. Animals received 2 Gy/14 Fx (low-dose group) or 8 Gy/3 Fx (high-dose group) radiation and the combination treatment groups were given an anti-PD-L1 antibody for two consecutive weeks. MR/PA imaging was used to noninvasively evaluate the response of breast cancer model to different doses of radiotherapy, combined with histopathological techniques to observe the changes of tumor vessels and microenvironment. Results The inhibitory effect of high-dose radiotherapy on tumors was significantly greater than that of low-dose radiotherapy, with the MR images revealing that the signal intensity (SI) decreased significantly (p༜0.05). Compared with those in the other groups, the tumor vascular density decreased significantly, and the vascular maturity index (VMI) increased significantly in the low-dose group (p༜0.05). The PA images showed that the deoxyhemoglobin (HbR) and total hemoglobin (HbT) levels decreased and the SO2 level increased after radiation treatment. In addition, the high-dose group had an increased number of tumor-infiltrating lymphocytes (CD4+ T and CD8+ T cells) and natural killer (NK) cells and increased PD-L1 expression in the tumors (p༜0.05). The combination of radiotherapy and immunotherapy increased the survival rate of the mice, and a regimen of an 8 Gy dose of radiation combined with immunotherapy inhibited tumor growth and increased the survival rate of the mice to a greater degree than the 2 Gy radiation dose with immunotherapy combination (p = 0. 002). Conclusion Differential fractionation radiotherapy doses exert different effects on tumor vascular remodeling and the immune microenvironment, and MR/PA can be used to evaluate tumor vascular remodeling after radiotherapy, which is of great significance for the clinical applications of radiotherapy combined with immunotherapy.

ObjectiveBrain tissue changes dynamically during aging. The purpose of this study was to use synthetic magnetic resonance imaging (syMRI) to evaluate the changes in relaxation values in different brain regions during brain aging and to construct a brain age prediction model.Materials and methodsQuantitative MRI was performed on 1,000 healthy people (≥ 18 years old) from September 2020 to October 2021. T1, T2 and proton density (PD) values were simultaneously measured in 17 regions of interest (the cerebellar hemispheric cortex, pons, amygdala, hippocampal head, hippocampal tail, temporal lobe, occipital lobe, frontal lobe, caudate nucleus, lentiform nucleus, dorsal thalamus, centrum semiovale, parietal lobe, precentral gyrus, postcentral gyrus, substantia nigra, and red nucleus). The relationship between the relaxation values and age was investigated. In addition, we analyzed the relationship between brain tissue values and sex. Finally, the participants were divided into two age groups: < 60 years old and ≥ 60 years old. Logistic regression analysis was carried out on the two groups of data. According to the weight of related factors, a brain age prediction model was established and verified.ResultsWe obtained the specific reference value range of different brain regions of individuals in different age groups and found that there were differences in relaxation values in brain tissue between different sexes in the same age group. Moreover, the relaxation values of most brain regions in males were slightly higher than those in females. In the study of age and brain relaxation, it was found that brain relaxation values were correlated with age. The T1 values of the centrum semiovale increased with age, the PD values of the centrum semiovale increased with age, while the T2 values of the caudate nucleus and lentiform nucleus decreased with age. Seven brain age prediction models were constructed with high sensitivity and specificity, among which the combined T1, T2 and PD values showed the best prediction efficiency. In the training set, the area under the curve (AUC), specificity and sensitivity were 0.959 [95% confidence interval (CI): 0.945–0.974], 91.51% and 89.36%, respectively. In the test cohort, the above indicators were 0.916 (95% CI: 0.882–0.951), 89.24% and 80.33%, respectively.ConclusionOur study provides specific reference ranges of T1, T2, and PD values in different brain regions from healthy adults of different ages. In addition, there are differences in brain relaxation values in some brain regions between different sexes, which help to provide new ideas for brain diseases that differ according to sex. The brain age model based on synthetic MRI is helpful to determine brain age.

Purpose Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport in different stages after heroin addiction.Methods Rodent models of heroin addiction (HA) and heroin relapse (HR) were established by injection of different doses of heroin solution at different times. Heroin-induced learning and memory deficits were evaluated by the Morris water maze (MWM). MEMRI was used to dynamically evaluate axonal transport through the olfactory pathway. The expression of proteins related to axonal structure and function were assessed by western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes. Neurofilament heavy chain (NF-H) protein levels were analyzed by immunofluorescence staining.Result HA model rats and especially HR model rats showed worse spatial learning and memory abilities than control rats. Compared with HA model rats and control rats, HR model rats exhibited a significant increase in escape latency and significant decreases in the number of platform location crossings and time spent in the target quadrant. Mn2+ transport was accelerated in HA model rats. HR model rats exhibited a severely insufficient capacity for Mn2+ transport, and the axonal transport rate (ATR) was significantly reduced in these rats compared to control rats (P<0.001). The levels of cytoplasmic dynein and KIF5 in rats in the HR group were significantly decreased (P<0.001), and the levels of energy-related proteins, including COX IV and ATPB, were lower in the HR group than the control group (P<0.001). The brains of heroin-exposed rats showed an abnormal ultrastructure, exhibiting neuronal apoptosis and mitochondrial dysfunction. Heroin decreased the expression of NF-H, with the staining intensity being significantly reduced in tissues from HA and HR model rats (P<0.05).Conclusion MEMRI can detect axonal transport dysfunction caused by long-term repeated exposure to heroin, and decreases in the levels of motor proteins and mitochondrial dysfunction may be the main causes of this axonal transport impairment. Thus, the study shows that MEMRI is a potential tool for visualizing axonal transport in individuals experiencing drug addiction, providing a new direction for the evaluation of addictive drug withdrawal.

We aimed to differentiate between T1 stage nasopharyngeal carcinoma (NPC) and nasopharyngeal lymphoid hyperplasia using multiple b-values Turbo-spin-echo DWI acquisition. Turbo-spin-echo DWI were adopted to minimize susceptibility artifacts in nasopharynx. Mono-exponential and bi-exponential models were both used to generate ADC, D, D* and f maps. We found that T1 stage NPC had significant lower ADC and D, higher D* than nasopharyngeal lymphoid hyperplasia. Furthermore, D has best diagnostic efficacy with highest area under curve in ROC analysis, indicating that it's a potential imaging biomarker for accurate early diagnosis of T1 stage NPC.