Global Cost-Effectiveness of Transcatheter vs. Surgical Aortic Valve Replacement in Severe Aortic Stenosis: A Systematic Review and Meta-Analysis.

BACKGROUD: Transcatheter aortic valve replacement (TAVR) is a less invasive treatment option for patients with severe aortic stenosis (AS); however, its economic benefits in patients with low to intermediate surgical risk remain controversial and vary by country. We conducted a systematic review to compare the economic benefits of TAVR versus surgical aortic valve replacement (SAVR). METHODS: We searched six databases, including PubMed, Medline, Scopus, Web of Science, Embase, and Clinical Trials for randomized controlled trials on the economic benefits of TAVR with different valve types and SAVR in symptomatic AS patients with low to intermediate surgical risk, from inception to October 2023. We extracted data on quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), with ICER converted to 2023 United States dollars (USD) exchange rates. RESULTS: Fifteen studies met the inclusion criteria, with the overall quality ranging from intermediate to high. Among these, TAVR was found to be cost-effective in 14 studies, while in one study conducted in a developing country, TAVR was not cost-effective. When adjusted to 2023 USD, the ICER values ranged from $3,669 to $340,038 per QALY gained. CONCLUSION: TAVR appears to be a cost-effective alternative to SAVR in patients with low to intermediate AS. In all studies, TAVR was associated with a significant increase in QALYs compared to SAVR. As it is an expensive procedure, the cost-effectiveness of TAVR depends on each country's ICER and willingness-to-pay threshold.

Tumor perfusion enhancement by focus ultrasound-induced blood-brain barrier opening to potentiate anti-PD-1 immunotherapy of glioma.

OBJECTIVE: To demonstrate the feasibility of using focused ultrasound to enhance delivery of PD-1 inhibitors in glioma rats and determine if such an approach increases treatment efficacy. METHODS: C6 glioma in situ rat model was used in this study. Transcranial irradiation with FUS combined with microbubbles was administered to open the blood-brain barrier (BBB). The efficacy of BBB opening was evaluated in normal rats. The rats with glioma were grouped to evaluate the role of PD-1 inhibitors combined with FUS-induced immune responses in suppressing glioma when the BBB opens. Flow cytometry was used to examine the changes of immune cell populations of lymphocytes in peripheral blood, tumor tissue and spleen tissue of the rats. A section of rat brain tissue was also used for histological and immunohistochemical analysis. The survival of the rats was then monitored; the tumor progression and changes in blood perfusion of tumor were dynamically observed in vivo using multimodal MRI. RESULTS: FUS combined with microbubbles could enhance the blood perfusion of tumors by increasing the permeability of BBB (p < 0.0001), thus promoting the infiltration of CD4+ T lymphocytes (p < 0.01). Compared with the control group, the combination treatment group had increased in the infiltration number of CD4+(p < 0.05) and CD8+ T (p < 0.05); the tumor volume of the combined treatment group was smaller than that of the control group (p < 0.01) and the survival rate of the rats was prolonged (p < 0.05). CONCLUSIONS: In this study, we demonstrated that the transient opening of the BBB induced by FUS enhanced tumor vascular perfusion and facilitated the delivery of PD-1 inhibitors, ultimately improving the therapeutic efficacy for glioblastoma.

Causality between migraine and cardiovascular disease: a bidirectional Mendelian randomization study.

BACKGROUND: While growing evidence suggests a relationship between migraine and cardiovascular disease, the genetic evidence for a causal relationship between migraine and cardiovascular disease is still scarce. Investigating the causal association between migraine and cardiovascular disease is vital. METHODS: We carried out a bidirectional Mendelian randomization (MR) study including discovery samples and replication samples using publicly available genome-wide association study (GWAS) summary datasets and stringent screening instrumental variables. Four different MR techniques-Inverse variance weighted (IVW), MR ‒Egger, weighted median, and weighted mode-as well as various sensitivity analyses-Cochran's Q, IVW radial, leave-one-out (LOO), and MR-PRESSO-were utilized to investigate the causal relationship between cardiovascular disease and migraine. RESULTS: The protective causal effects of genetically predicted migraine on coronary artery disease (OR, 0.881; 95% CI 0.790-0.982; p = 0.023) and ischemic stroke (OR, 0.912; 95% CI 0.854-0.974; p = 0.006) were detected in forward MR analysis but not in any other cardiovascular disease. Consistently, we also discovered protective causal effects of coronary atherosclerosis (OR, 0.865; 95% CI 0.797-0.940; p = 0.001) and myocardial infarction (OR, 0.798; 95% CI 0.668-0.952; p = 0.012) on migraine in reverse MR analysis. CONCLUSION: We found a potential protective effect of migraine on coronary artery disease and ischemic stroke and a potential protective effect of coronary atherosclerosis and myocardial infarction on migraine. We emphasised epidemiological and genetic differences and the need for long-term safety monitoring of migraine medications and future research to improve cardiovascular outcomes in migraine patients.

Case report: Pulmonary artery sarcoma diagnosed through rare brain metastases.

We present the case of a 33-year-old male referred across several hospitals because of suspected chronic thromboembolic pulmonary hypertension (CTEPH). Initially admitted in October 2022 for a recurrent, severe cough and diagnosed with CTEPH, he received anticoagulant therapy. However, his symptoms worsened, necessitating a transfer to another facility for thrombolysis treatment. Following an episode of syncope, an MRI scan revealed a metastatic brain tumor. Subsequently, he experienced a third transfer to our hospital, emergency surgery was performed to alleviate cerebral edema and excise a lesion in the left frontal lobe. Postoperative pathology was inconclusive, but a multidisciplinary team meeting, aided by experienced radiologists, eventually confirmed a diagnosis of pulmonary artery sarcoma (PAS) with systemic metastases. This case underscores the necessity of promptly ruling out PAS in patients presenting with significant emboli in the central pulmonary arteries and suggests early referral to specialized centers for suspected cases.

Multiparametric MRI-based radiomics combined with pathomics features for prediction of the efficacy of neoadjuvant chemotherapy in breast cancer.

Purpose: The aim of this study is to investigate a new method that combines radiological and pathological breast cancer information to predict discrepancies in pathological responses for individualized treatment planning. We used baseline multiparametric magnetic resonance imaging and hematoxylin and eosin-stained biopsy slides to extract quantitative feature information and predict the pathological response to neoadjuvant chemotherapy in breast cancer patients. Methods: We retrospectively collected data from breast cancer patients who received neoadjuvant chemotherapy in our hospital from August 2016 to January 2018; multiparametric magnetic resonance imaging (contrast-enhanced T1-weighted imaging and diffusion-weighted imaging) and whole slide image of hematoxylin and eosin-stained biopsy sections were collected. Quantitative imaging features were extracted from the multiparametric magnetic resonance imaging and the whole slide image were used to construct a radiopathomics signature model powered by machine learning methods. Models based on multiparametric magnetic resonance imaging or whole slide image alone were also constructed for comparison and referred to as the radiomics signature and pathomics signature models, respectively. Four modeling methods were used to establish prediction models. Model performances were evaluated using receiver operating characteristic curve analysis and the area under the curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results: The radiopathomics signature model had favourable performance for the prediction of pathological complete response in the training set (the best value: area under the curve 0.83, accuracy 0.84, and sensitivity 0.87), and in the test set (the best value: area under the curve 0.91, accuracy 0.90, and sensitivity 0.88). In the test set, the radiopathomics signature model also significantly outperformed the radiomics signature (the best value: area under the curve 0.83, accuracy 0.64, and sensitivity 0.62), pathomics signature (the best value: area under the curve 0.60, accuracy 0.74, and sensitivity 0.62) (p > 0.05). Decision curve analysis and calibration curves confirmed the excellent performance of these prediction models in discrimination, calibration, and clinical usefulness. Conclusions: The results of this study suggest that radiopathomics, the combination of both radiological information regarding the whole tumor and pathological information at the cellular level, could potentially predict discrepancies in pathological response and provide evidence for rational treatment plans.

Factors associated with overdiagnosis of benign pulmonary nodules as malignancy: a retrospective cohort study.

OBJECTIVE: To establish a preoperative model for the differential diagnosis of benign and malignant pulmonary nodules (PNs), and to evaluate the related factors of overdiagnosis of benign PNs at the time of imaging assessments. MATERIALS AND METHODS: In this retrospective study, 357 patients (median age, 52 years; interquartile range, 46-59 years) with 407 PNs were included, who underwent surgical histopathologic evaluation between January 2020 and December 2020. Patients were divided into a training set (n = 285) and a validation set (n = 122) to develop a preoperative model to identify benign PNs. CT scan features were reviewed by two chest radiologists, and imaging findings were categorized. The overdiagnosis rate of benign PNs was calculated, and bivariate and multivariable logistic regression analyses were used to evaluate factors associated with benign PNs that were over-diagnosed as malignant PNs. RESULTS: The preoperative model identified features such as the absence of part-solid and non-solid nodules, absence of spiculation, absence of vascular convergence, larger lesion size, and CYFRA21-1 positivity as features for identifying benign PNs on imaging, with a high area under the receiver operating characteristic curve of 0.88 in the validation set. The overdiagnosis rate of benign PNs was found to be 50%. Independent risk factors for overdiagnosis included diagnosis as non-solid nodules, pleural retraction, vascular convergence, and larger lesion size at imaging. CONCLUSION: We developed a preoperative model for identifying benign and malignant PNs and evaluating factors that led to the overdiagnosis of benign PNs. This preoperative model and result may help clinicians and imaging physicians reduce unnecessary surgery.

Transcriptome profile analysis revealed the potential mechanism of LIPUS treatment for Adriamycin-induced chronic kidney disease rat.

Background: Developing effective therapeutic strategies to delay the progression of chronic kidney disease (CKD) remains a significant challenge. Low-intensity pulsed ultrasound (LIPUS) has demonstrated potential for treating CKD, but the underlying molecular mechanisms are still elusive. This study aimed to evaluate the therapeutic efficacy of LIPUS and to elucidate the involved genes and signaling pathways. Methods: The CKD model was established in rats using Adriamycin (ADR). The bilateral kidneys of CKD rats were continuously stimulated with LIPUS for a period of four weeks. The therapeutic efficacy was defined by renal function and histopathological evaluation. RNA sequencing was employed to profile the transcriptome of rat kidneys in each group. Cluster analysis was utilized to identify differentially expressed genes (DEGs), followed by enrichment analysis of their associated pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Results: LIPUS treatment improved ADR-induced renal dysfunction in the CKD group. Renal fibrosis and pathological damages were also alleviated in the ADR + LIPUS group compared to the ADR group. Cluster analysis identified 844 DEGs. GO enrichment analysis revealed enrichment in inflammatory response terms, while KEGG enrichment analysis highlighted the nuclear factor kappa B (NF-κB) signaling and ferroptosis-related pathways. Conclusion: Continuous LIPUS treatment improved ADR-induced renal fibrosis and dysfunction. The therapeutic effect of LIPUS was primarily due to its ability to suppress the CKD-related inflammation, which was associated with the modulation of the NF-κB and ferroptosis signaling pathways. These findings provide a new insight into the potential molecular mechanisms of LIPUS in treating CKD. Further research is necessary to confirm these findings and to identify potential therapeutic targets within these pathways.

Case Report: Myocardial dissection caused by ruptured sinus of Valsalva aneurysm in association with a bicuspid aortic valve.

In this report, we present a case of left-right sinus fusion in a Ruptured sinus of Valsalva aneurysm (RSVA) that perforated into the myocardium, giving rise to myocardial dissection. The existence of an anomalous bicuspid aortic valve (BAV) is contemplated as a potential etiological element in this context. Employing multimodal imaging modalities, encompassing transthoracic echocardiography and computed tomography (CT), facilitated the visualization of a dissecting hematoma situated within the myocardium subsequent to the RSVA. Following this, our patient underwent an Cabrol surgical intervention, received patch repair, and underwent mitral valve annuloplasty, during which a three-year period transpired without the occurrence of any deleterious cardiac events. In summary, this report establishes the cornerstone for the surgical intervention of RSVA, shedding light on the efficacious handling of RSVA-associated myocardial dissection. It posits that the presence of a BAV may serve as a predisposing factor to RSVA rupture, potentially elevating the susceptibility to myocardial dissection. The utilization of diverse multimodal imaging methodologies played an indispensable role in the detection of a hematoma within the myocardial tissue subsequent to the RSVA rupture. The uneventful three-year postoperative follow-up of the patient underscores the efficacy of the undertaken interventions.

The effect of tumor vascular remodeling and immune microenvironment activation induced by radiotherapy: quantitative evaluation with magnetic resonance/photoacoustic dual-modality imaging.

Background: 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 multimodal imaging technology can provide more accurate and comprehensive information in tumor research. The purpose of this study was to evaluate the dynamic monitoring of tumor blood vessels and microenvironment induced by radiotherapy by magnetic resonance/photoacoustic (MR/PA) imaging, and to explore its application value in radiotherapy combined with immunotherapy. Methods: The tumor-bearing mice were randomly allocated into six groups, which received different doses of radiation therapy (2 Gy ×14 or 8 Gy ×3) and anti-programmed death ligand-1 (PD-L1) antibody for two consecutive weeks. MR/PA imaging was used to noninvasively evaluate the response of tumor to different doses of radiotherapy, combined with histopathological techniques to observe the 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 decreased significantly (P<0.05). Compared with those in the other groups, the tumor vascular density decreased significantly (P<0.01), and the vascular maturity index increased significantly in the low-dose group (P<0.05). The PA images showed that the deoxyhemoglobin and total hemoglobin levels decreased and the SO2 level increased after radiation treatment (P<0.05). In addition, the high-dose group had an increased number of tumor-infiltrating lymphocytes (CD4+ T and CD8+ T cells) (P<0.01, P<0.05) and natural killer cells (P<0.001) and increased PD-L1 expression in the tumors (P<0.05). The combination of radiotherapy and immunotherapy increased the survival rate of the mice (P<0.05), 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). Conclusions: Differential fractionation radiotherapy doses exert biological effects on tumor vascular and the immune microenvironment, and MR/PA can be used to evaluate tumor vascular remodeling after radiotherapy, which has certain value for the clinical applications of radiotherapy combined with immunotherapy.

Diagnostic accuracy of glioma pseudoprogression identification with positron emission tomography imaging: a systematic review and meta-analysis.

Background: Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However, there is some controversy concerning the diagnostic accuracy of PET using different radiotracers to differentiate between glioma pseudoprogression (PsP) and true progression (TPR). The purpose of this meta-analysis was to systematically evaluate the methodological quality and clinical value of original studies for distinguishing PsP from TPR in glioma. Methods: The Medline, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception until September 1, 2022. Retrieved clinical studies only investigated the PsP cases but did not include the cases of radiation necrosis or other treatment-related changes. Eligible studies were screened for data extraction and evaluated by 2 independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A random effects model was used to describe summary receiver operating characteristics. Meta-regression and subgroup analyses were applied to identify any sources of heterogeneity. Results: The meta-analysis included 20 studies, comprising 317 (30.9%) patients with PsP and 708 (69.1%) with TPR. The summary sensitivity and specificity of general PET for identifying PsP were 0.86 [95% confidence interval (CI): 0.77-0.91] and 0.84 (95% CI: 0.79-0.88), respectively. The statistical heterogeneity was explained by sample size, study design, World Health Organization (WHO) grade, gold standard, and radiotracer type. The summary sensitivity and specificity of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET PET) were 0.80 (95% CI: 0.68-0.88) and 0.81 (95% CI: 0.75-0.85), respectively. The maximum tumor-to-brain ratio (TBRmax) and the mean tumor-to-brain ratio (TBRmean) both showed excellent diagnostic performance in 18F-FET studies, the summary sensitivity was 0.83 (95% CI: 0.72-0.91) and 0.79 (95% CI: 0.65-0.98), respectively, and the specificity was 0.76 (95% CI: 0.68-0.84) and 0.78 (95% CI: 0.64-0.88), respectively. Conclusions: PET imaging is generally accurate in identifying glioma PsP. Considering the credibility of meta-evidence and the practicability of using radiotracer, 18F-FET PET holds the highest clinical value, while TBRmax and TBRmean should be regarded as reliable parameters. PET used with the radiotracers and multiple-parameter combinations of PET with magnetic resonance imaging (MRI) and radiomics analysis have broad research and application prospects, whose diagnostic values for identifying glioma PsP warrant further investigation.

Low intensity pulsed ultrasound ameliorates Adriamycin-induced chronic renal injury by inhibiting ferroptosis.

OBJECTIVE: It is very important to develop a new therapeutic strategy to cope with the increasing morbidity and mortality of chronic kidney disease (CKD). As a kind of physical therapy, low intensity pulsed ultrasound (LIPUS) has remarkable anti-inflammatory and repair-promoting effects and is expected to become a new therapeutic method for CKD. This study aims to clarify the treatment effect of LIPUS on CKD-related renal inflammation and fibrosis, and to further explore the potential signal network of LIPUS treatment for ameliorating chronic renal injury. METHODS: A rat model simulating the progress of CKD was established by twice tail-vein injection of Adriamycin (ADR). Under anesthesia, bilateral kidneys of CKD rats were continuously stimulated by LIPUS for four weeks. The parameters of LIPUS were 1.0 MHz, 60 mW/cm2, 50% duty cycle and 20 min/d. RESULTS: LIPUS treatment effectively inhibited ADR-induced renal inflammation and fibrosis, and improved CKD-related to oxidative stress and ferroptosis. In addition, the therapeutic effect of LIPUS is closely related to the regulation of TGF-ß1/Smad and Nrf2/keap1/HO-1 signalling pathways. DISCUSSION: This study provides a new direction for further mechanism research and lays an important foundation for clinical trials.

Persistent fifth aortic arch: a comprehensive literature review.

Persistent fifth aortic arch (PFAA) is an extremely rare congenital cardiovascular anomaly resulting from the failure of the fifth aortic arch to degenerate during embryonic development; it is often associated with various other cardiovascular anomalies. Despite being first reported by Van Praagh in 1969, there have been only a few individual case reports. Owing to its rarity and lack of comprehensive understanding, PFAA is often misdiagnosed or missed diagnosed during clinical. Thus, this review aimed to summarise the embryonic development, pathological classification, imaging diagnosis, and clinical treatment of PFAA to improve its overall understanding, ultimately helping in accurate diagnosis and treatment.

Prediction of brain age using quantitative parameters of synthetic magnetic resonance imaging.

Objective: Brain 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 methods: Quantitative 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. Results: We 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. Conclusion: Our 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.

Case report: A novel reciprocal ROS1-CD74 fusion in a NSCLC patient partially benefited from sequential tyrosine kinase inhibitors treatment.

Background: The clinical significance of majority oncogenic novel fusions is still unknown due to scarcity. Reciprocal ROS1 translocation is a rare form of ROS1 fusion and has not yet been clearly analyzed. Case presentation: A 44-year-old Chinese woman with a large dimension in the left lobe of the lung was admitted to the hospital with IVB lung adenocarcinoma. It was discovered that intron 28 of ROS1 and intron 6 of CD74 produced a unique reciprocal ROS1 rearrangement. In addition, the dual CD74-ROS1 fusions were discovered using the RNA next-generation sequencing (NGS) findings. Although benefiting from crizotinib and lorlatinib sequential treatment, the overall prognosis of the patient was relatively poor, whose progression-free survival was 4 and 5 months for crizotinib treatment and lorlatinib treatment, respectively. Conclusion: In summary, a novel ROS1-CD74 fusion identified by DNA NGS was translated into dual CD74-ROS1 transcripts. Furthermore, this patient with non-small cell lung cancer benefited from consecutive tyrosine kinase inhibitor therapy. Our discovery broadened the range of targetable ROS1 fusions and underlined the importance of sequential DNA and RNA sequencing in identifying uncommon but beneficial fusions, which eventually bring benefits to the patients.

CT and MRI findings of intracranial extraskeletal mesenchymal chondrosarcoma-a case report and literature review.

Background: Intracranial extraskeletal mesenchymal chondrosarcoma (EMCS) is a rare neoplasm and often misdiagnosed before histopathological examination due to its rarity. There were few reports previously on the radiological features of intracranial EMCS. We described a 20-year-old male patient with intracranial EMCS focusing on the imaging characteristics. Case Description: The patient was admitted to our hospital due to headache and dizziness for two months, without nausea, vomiting, limb convulsions and loss of consciousness during the illness. Pre-contrast computed tomography (CT) revealed a large slightly hyperdense mass with irregularly lobulated margins in the right parietal and occipital region and multiple patchy calcifications in peripheral of the lesion. The inner table of right parietal bone adjacent to the mass was compressed, thickened, and eroded. Magnetic resonance imaging (MRI) exhibited intermediate and hypo-intensity on T1-weighted images (T1WI) and slight hyper-intensity on T2-weighted images (T2WI) with extremely high intensity rim of cerebral spinal fluid (CSF) and low intensity flow-void vessel. The mass demonstrated heterogeneous remarkable enhancement and "dural tail" sign also was noted. The important imaging signs of this case are irregular calcifications of soft tissue on CT and "dural tail" sign on MRI. The patient underwent tumor resection and was followed up postoperatively with serial MRI every three months. He was alive without obvious clinical symptoms and evidence of recurrence for 9 months. EMCS is a highly invasive tumor and it is difficult to differentiate EMCS from the other intracranial malignant tumors only by clinical characteristics or findings of CT and conventional MR imaging. Radiotherapy and chemotherapy after radical resection are the best treatment choice. Therefore, postoperative patients should be reviewed routinely. Conclusions: A knowledge of the imaging features could facilitate differentiation of intracranial EMCS, but the final diagnosis depends on pathological examinations. This paper focuses on the imaging characteristics of EMCS and fully describes the details of lesions in order to provide clinicians with effective differential diagnosis information and improve clinical decision-making.

Heroin Addiction Induces Axonal Transport Dysfunction in the Brain Detected by In Vivo MRI.

Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport at different stages of heroin addiction. Rat models of heroin addiction (HA) and prolonged heroin addiction (PHA) were established by injecting rats with heroin at different stages. Heroin-induced learning and memory deficits were evaluated in the Morris water maze (MWM), and MEMRI was used to dynamically evaluate axonal transport in the olfactory pathway. The expression of proteins related to axonal structure and function was also assessed by Western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes, and protein levels of neurofilament heavy chain (NF-H) were analyzed by immunofluorescence staining. HA rats, especially PHA rats, exhibited worse spatial learning and memory than control rats. Compared with HA rats and control rats, PHA rats exhibited significantly longer escape latencies, significantly fewer platform-location crossings, and significantly more time in the target quadrant during the MWM test. Mn2+ transport was accelerated in HA rats. PHA rats exhibited severely reduced Mn2+ transport, and the axonal transport rate (ATR) was significantly lower in these rats than in control rats (P < 0.001). The levels of cytoplasmic dynein and kinesin-1 were significantly decreased in the PHA group than in the control group (P < 0.001); additionally, the levels of energy-related proteins, including cytochrome c oxidase (COX) IV and ATP synthase subunit beta (ATPB), were lower in the PHA group (P < 0.001). The brains of heroin-exposed rats displayed an abnormal ultrastructure, with neuronal apoptosis and mitochondrial dysfunction. Heroin exposure decreased the expression of NF-H, as indicated by significantly reduced staining intensities in tissues from HA and PHA rats (P < 0.05). MEMRI detected axonal transport dysfunction caused by long-term repeated exposure to heroin. The main causes of axonal transport impairment may be decreases in the levels of motor proteins and mitochondrial dysfunction. This study shows that MEMRI is a potential tool for visualizing axonal transport in individuals with drug addictions, providing a new way to evaluate addictive encephalopathy.

Focused Ultrasound Promotes the Delivery of Gastrodin and Enhances the Protective Effect on Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common chronic neurodegenerative disease globally; however, it lacks effective treatment at present. Focused ultrasound (FUS) combined with microbubbles could increase the efficacy of drug delivery to specific brain regions and is becoming a promising technology for the treatment of central nervous system diseases. In this study, we explored the therapeutic potential of FUS-mediated blood-brain barrier (BBB) opening of the left striatum to deliver gastrodin (GAS) in a subacute PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration of GAS in the left hemisphere was detected by ultra-high performance liquid chromatography electrospray Q-Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap) and the distribution of tyrosine hydroxylase (TH) neurons was detected by immunohistochemical staining. The expression of TH, Dopamine transporter (DAT), cleaved-caspase-3, B-cell lymphoma 2 (Bcl-2), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYN) protein were detected by western blotting. Analysis showed that the concentration of GAS in the left hemisphere of PD mice increased by approximately 1.8-fold after the BBB was opened. FUS-mediated GAS delivery provided optimal neuroprotective effects and was superior to the GAS or FUS control group. In addition, FUS enhanced GAS delivery significantly increased the expression of Bcl-2, BDNF, PSD-95, and SYN protein in the left striatum (P < 0.05) and reduced the levels of cleaved-caspase-3 remarkably (P = 0.001). In conclusion, the enhanced delivery by FUS effectively strengthened the protective effect of GAS on dopaminergic neurons which may be related to the reinforcement of the anti-apoptotic activity and the expression of synaptic-related proteins in the striatum. Data suggests that FUS-enhanced GAS delivery may represent a new strategy for PD treatment.

Cranial irradiation-induced impairment of axonal transport and sexual function in male rats and imaging of the olfactory pathway by MRI.

PURPOSE: The aim of this study was to evaluate the effect of radiation-induced brain injury (RIBI) on axonal transport (AT) and sexual function. METHODS AND MATERIALS: Adult male rats received whole-brain radiation with a total dose of 30 Gy (15 Gy with 2 fractions) to build a RIBI model. Foraging behavior and sexual function were assessed, and MRI was performed 8 weeks after brain irradiation. MRI was performed in the early and delayed phases after perfusion of MnCl2 into the rat nostril. The levels of motor proteins and proteins involved in energy metabolism and AT were determined by Western blotting. The levels of sex hormones in the blood were measured by ELISA. Ultrastructural analysis was performed with a transmission electron microscope. RESULTS: The foraging ability of rats was reduced after brain irradiation, and the foraging time of the radiation group was longer than that of the control group (P < 0.05). The sexual function of rats in the radiation group was markedly decreased. Compared with control rats, radiation-treated rats showed significant decreases in serum testosterone, FSH, LH, and GnRH levels (P < 0.001). Mn2+ uptake in the olfactory bulb (OB) in the early phase and delayed phase was lower in the radiation group than in the control group (P < 0.05). The AT rate in the lateral olfactory tracts (LOT) and the transsynaptic AT rate were significantly lower in the irradiated rats than in the control rats (P < 0.05). The levels of the motor proteins kinesin-1 and cytoplasmic dynein were significantly decreased in the irradiation group (P < 0.05). The expression of the energy metabolism-related proteins ATPB and COX IV was significantly lower in the irradiated rats than in the control rats (P < 0.05). Apoptosis and synaptic damage were observed after irradiation. CONCLUSION: MRI of the olfactory pathway can be used to assess AT impairment in RIBI models. AT deficits secondary to radiation damage are the result of multiple factors, including declines in motor protein levels, neuronal apoptosis, synaptic damage and energy metabolism dysfunction. Cranial irradiation-induced sexual dysfunction was associated with decreased sex hormone levels secondary to hypothalamic-pituitary-gonadal axis injury.

Correction: MR imaging biomarkers evaluating vascular normalization window after anti-vessel treatment.

[This corrects the article DOI: 10.18632/oncotarget.22600.].