Efficacy of acupuncture and pharmacological therapies for vascular cognitive impairment with no dementia: a network meta-analysis.

Background and objective: Vascular cognitive impairment with no dementia (VCIND) is considered to be the prodromal stage of vascular dementia, characterized by insidious onset. Although acupuncture and drug therapies are effective, the optimal therapy for VCIND remains to be further determined. Therefore, we conducted a network meta-analysis to compare the effectiveness of acupuncture therapies and current common medicines for VCIND. Methods: We searched eight electronic databases to identify eligible randomized controlled trials of patients with VCIND treated by acupuncture or drug therapies. The primary outcome was Montreal Cognitive Assessment, and the secondary outcome was Mini-Mental State Examination. We conducted the network meta-analysis within a Bayesian framework. Weighted mean difference with 95% confidence intervals were applied as effect sizes to continuous data for all outcomes. Sensitivity analysis was done to assess the robustness of the findings, and we also carried out a subgroup analysis based on age. We assessed the risk of bias using the Risk of Bias 2.0 tool and applied the Grade of Recommendation Assessment, Development and Evaluation (GRADE) to assess the quality of the outcomes. This study was registered with PROSPERO, number CRD42022331718. Results: A total of 33 studies with 14 interventions were included, including 2603 participants. In terms of the primary outcome, manual acupuncture plus herbal decoction was considered to be the most effective intervention (P = 91.41%), followed by electroacupuncture (P = 60.77%) and manual acupuncture plus piracetam (P = 42.58%), whereas donepezil hydrochloride ranked the least efficacious intervention (P = 54.19%). For the secondary outcome, electroacupuncture plus nimodipine was considered to be the most effective intervention (P = 42.70%), followed by manual acupuncture plus nimodipine (P = 30.62%) and manual acupuncture (P = 28.89%), whereas nimodipine ranked the least efficacious intervention (P = 44.56%). Conclusion: Manual acupuncture plus herbal decoction might be the most effective intervention for VCIND. The combination of acupuncture and drug therapy had a tendency to perform better than monotherapy in terms of clinical outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=331718, identifier: CRD42022331718.

Multimodality neuroimaging in vascular mild cognitive impairment: A narrative review of current evidence.

The vascular mild cognitive impairment (VaMCI) is generally accepted as the premonition stage of vascular dementia (VaD). However, most studies are focused mainly on VaD as a diagnosis in patients, thus neglecting the VaMCI stage. VaMCI stage, though, is easily diagnosed by vascular injuries and represents a high-risk period for the future decline of patients' cognitive functions. The existing studies in China and abroad have found that magnetic resonance imaging technology can provide imaging markers related to the occurrence and development of VaMCI, which is an important tool for detecting the changes in microstructure and function of VaMCI patients. Nevertheless, most of the existing studies evaluate the information of a single modal image. Due to the different imaging principles, the data provided by a single modal image are limited. In contrast, multi-modal magnetic resonance imaging research can provide multiple comprehensive data such as tissue anatomy and function. Here, a narrative review of published articles on multimodality neuroimaging in VaMCI diagnosis was conducted，and the utilization of certain neuroimaging bio-markers in clinical applications was narrated. These markers include evaluation of vascular dysfunction before tissue damages and quantification of the extent of network connectivity disruption. We further provide recommendations for early detection, progress, prompt treatment response of VaMCI, as well as optimization of the personalized treatment plan.

Establishment of a sequential dual tracer 18 F-NaF/18 F-FDG PET protocol for imaging the equine foot.

The combination of 18 F-Sodium Fluoride (18 F-NaF) and 18 F-FluoroDeoxyGlucose (18 F-FDG) for positron emission tomography (PET) imaging of the equine foot is appealing for detection of both osseous and soft tissue lesions in a single scan. As the combination of tracers could lead to a loss of information, a sequential approach, consisting in imaging with one tracer prior to injecting the second tracer, might be valuable. The goals of this prospective, methods comparison, exploratory study were to establish the order of tracer injection and timing for imaging. Six research horses were imaged under general anesthesia with 18 F-NaF PET, 18 F-FDG PET, dual 18 F-NaF/18 F-FDG PET, and CT. Proper uptake could be identified in tendon lesions as early as 10 min after 18F-FDG injection. Bone uptake was limited when 18F-NaF was injected under general anesthesia, even at 1 h after injection, when compared with 18 F-NaF injection prior to anesthesia. The sensitivity and specificity of the dual tracer scans were 0.77 (0.63 to 0.86) and 0.98 (0.96 to 0.99) respectively, to assess 18 F-NaF uptake and 0.5 (0.28 to 0.72) and 0.98 (0.95 to 0.99), respectively, for 18F-FDG uptake. These results suggest that the sequential dual tracer approach is a pertinent technique to optimize the PET data gained from a single anesthetic episode. Based on dynamics of tracer uptake, the optimal protocol consists in injecting 18F-NaF prior to anesthesia, acquire 18F-NaF data then inject 18F-FDG and start acquisition of dual tracer PET data 10 min later. This protocol should be further validated in a larger clinical study.

Effect of Huangdisan grain on improving cognitive impairment in VD rats and its mechanism in immune inflammatory response.

BACKGROUND: Vascular dementia (VD) is the second most common type of dementia after Alzheimer's disease (AD). Although the incidence rate is very high, there is no definitive treatment for VD. And it has serious impact on the quality of life of VD patients. In recent years, more and more studies about the clinical efficacy and pharmacological effects of traditional Chinese medicine (TCM) in the treatment of VD have been conducted. And Huangdisan grain has been used to treat VD patients with a good curative effect in clinic. OBJECTIVE: This study was designed to investigate the effect of Huangdisan grain on the inflammatory response and cognitive function of VD rats modeled by bilateral common carotid artery occlusion (BCCAO), that aimed to improve the treatment methods for VD. METHODS: 8-week-old healthy SPF male Wistar rats (280 ± 20 g) were randomly divided into the normal group (Gn, n = 10), sham operated group (Gs, n = 10), and operated group (Go, n = 35). The VD rat models in Go group were established by BCCAO. 8 weeks after surgery, the operated rats were screened by the hidden platform trail of Morris Water Maze (MWM), and the rats with cognitive dysfunction were further randomly divided into the impaired group (Gi, n = 10) and TCM group (Gm, n = 10). The VD rats in Gm group were given the intragastric administration of Huangdisan grain decoction once a day for 8 weeks, and the other groups were given intragastric administration of normal saline. Then the cognitive ability of rats in each group was detected by the MWM Test. The lymphocyte subsets in peripheral blood and hippocampus of rats were measured by flow cytometry. The levels of cytokines (IL-1ß, IL-2, IL-4, IL-10, TNF-α, INF-γ, MIP-2, COX-2, iNOS) in peripheral blood and hippocampus were measured by ELISA (enzyme linked immunosorbent assay). The number of Iba-1+ CD68+ co-positive cells in the CA1 region of hippocampus was measured by immunofluorescence. RESULTS: Compared with the Gn group, the escape latencies of the Gi group were prolonged (P < 0.01), the time spent in the former platform quadrant was shortened (P < 0.01), and the number of times of crossing over the former platform location was reduced (P < 0.05). But compared with the Gi group, the escape latencies of Gm group were shortened (P < 0.01), the time spent in the former platform quadrant was prolonged (P < 0.05), and the number of times of crossing over the former platform location was increased (P < 0.05). The number of Iba-1+ CD68+ co-positive cells in the CA1 region of hippocampus of VD rats in Gi group was increased (P < 0.01) compared with the Gn group. And the proportions of T Cells, CD4+ T Cells, CD8+ T Cells in the hippocampus were increased (P < 0.01). The level of pro-inflammatory cytokines in the hippocampus was increased significantly, such as IL-1ß (P < 0.01), IL-2 (P < 0.01), TNF-α (P < 0.05), IFN-γ (P < 0.01), COX-2 (P < 0.01), MIP-2 (P < 0.01) and iNOS (P < 0.05). And the level of IL-10 (P < 0.01), a kind of anti-inflammatory cytokine, was decreased. The proportions of T Cells (P < 0.05), CD4+ T Cells (P < 0.01) and NK Cells (P < 0.05) in the peripheral blood of the VD rats in Gi group were decreased, and the level of IL-1ß, IL-2, TNF-α, IFN-γ, COX-2, MIP-2 and iNOS was increased significantly (P < 0.01) compared with the Gn group. Meanwhile, the level of IL-4 and IL-10 was decreased (P < 0.01). Huangdisan grain could reduce the number of Iba-1+ CD68+ co-positive cells in the CA1 region of hippocampus (P < 0.01), decrease the proportions of T Cells, CD4+ T Cells, CD8+ T Cells and the level of IL-1ß, MIP-2 in hippocampus (P < 0.01) of VD rats. Moreover, it could rise the proportion of NK Cells (P < 0.01) and the level of IL-4 (P < 0.05), IL-10 (P < 0.05), and decrease the level of IL-1ß (P < 0.01), IL-2 (P < 0.05), TNF-α (P < 0.01), IFN-γ (P < 0.01), COX-2 (P < 0.01) and MIP-2 (P < 0.01) in peripheral blood of VD rats. CONCLUSION: This study indicated that Huangdisan grain could decrease the activation of microglia/macrophages, regulate the proportions of lymphocyte subsets and the level of cytokines, which could adjust the immunologic abnormalities of VD rats, and ultimately improve cognitive function.

Molecular Mechanism of Electroacupuncture Regulating Cerebral Arterial Contractile Protein in Rats with Cerebral Infarction Based on MLCK Pathway.

OBJECTIVE: To explore the effect of electroacupuncture (EA) intervention on the vasoconstriction of cerebral artery smooth muscle cells after cerebral infarction. METHODS: Male Wistar rats were randomly divided into 3 groups by a random number table: the model group (n=24), the EA group (n=24), and the normal group (n=6). The model and the EA groups were divided into different time subgroups at 0.5, 1, 3, and 6 h after middle cerebral artery occlusion (MCAO), with 6 rats in each subgroup. MCAO model was established using intraluminal suture occlusion method. The EA group was given EA treatment at acupoint Shuigou (GV 26) instantly after MCAO for 20 min. The contents of cerebrovascular smooth muscle MLCK, the 3 subunits of myosin light chain phosphatase (MLCP) MYPT1, PP1c-δ and M20, as well as myosin-ATPase activity were detected using immunohistochemistry and Western blotting. RESULTS: The overall expression level of the MYPT1 and PP1c-δ in the model group was significantly higher (P<0.01). After EA intervention, the 0.5 h group expression level was close to that of the normal group (P>0.05), and the other subgroups were still significantly higher than the normal group (P<0.01). After EA intervention, the expression level of each subgroup was significantly lower than the corresponding model group. There was a significant difference between the 0.5 and 1 h subgroups (P<0.01), while a difference was also observed between the 3 and 6 h subgroups (P<0.05). The dynamic change rule gradually increased with the prolongation of infarction time within 6 h after infarction. CONCLUSION: EA intervention can inhibit contraction of cerebral vascular smooth muscle cells and regulate smooth muscle relaxation by regulating MLCK pathway.

Relating18F-FDG image signal-to-noise ratio to time-of-flight noise-equivalent count rate in total-body PET using the uEXPLORER scanner.

Objective.This work assessed the relationship between image signal-to-noise ratio (SNR) and total-body noise-equivalent count rate (NECR)-for both non-time-of-flight (TOF) NECR and TOF-NECR-in a long uniform water cylinder and 14 healthy human subjects using the uEXPLORER total-body PET/CT scanner.Approach.A TOF-NEC expression was modified for list-mode PET data, and both the non-TOF NECR and TOF-NECR were compared using datasets from a long uniform water cylinder and 14 human subjects scanned up to 12 h after radiotracer injection.Main results.The TOF-NECR for the uniform water cylinder was found to be linearly proportional to the TOF-reconstructed image SNR2in the range of radioactivity concentrations studied, but not for non-TOF NECR as indicated by the reducedR2value. The results suggest that the use of TOF-NECR to estimate the count rate performance of TOF-enabled PET systems may be more appropriate for predicting the SNR of TOF-reconstructed images.Significance.Image quality in PET is commonly characterized by image SNR and, correspondingly, the NECR. While the use of NECR for predicting image quality in conventional PET systems is well-studied, the relationship between SNR and NECR has not been examined in detail in long axial field-of-view total-body PET systems, especially for human subjects. Furthermore, the current NEMA NU 2-2018 standard does not account for count rate performance gains due to TOF in the NECR evaluation. The relationship between image SNR and total-body NECR in long axial FOV PET was assessed for the first time using the uEXPLORER total-body PET/CT scanner.

[Acupuncture for improving neuroinflammation in vascular dementia rats by regulating Th1/Th2 cells balance in peripheral blood].

OBJECTIVE: To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD. METHODS: A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus. RESULTS: There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01). CONCLUSION: Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.

Effect of Electro-acupuncture on Vasomotor Symptoms in Rats with Acute Cerebral Infarction Based on Phosphatidylinositol System.

OBJECTIVE: To investigate the effect of electro-acupuncture (EA) on vasomotor symptoms in rats with acute cerebral infarction, by observing the changes in the expression of factors related to the phosphatidylinositol (PI) system. METHODS: Forty-two Wistar rats were randomly divided into 3 groups by a random number table: the control group (n=6), the model group (n=18) and the EA group (n=18). The EA group was given EA treatment at Shuigou (GV 26) instantly after modeling with middle cerebral artery occlusion (MCAO) method, while the model and control groups were not given any treatment. The degrees of neurological deficiency were evaluated using neurological severity scores (NSS) and the brain blood flow was evaluated by a laser scanning confocal microscope. Western blot analysis was conducted to detect the expression levels of G-protein subtype (Gq) and calmodulin (CaM). Competition for protein binding was conducted to detect the expression level of inositol triphosphate (IP3). Thin layer quantitative analysis was conducted to detect the expression level of diacylglycerol (DAG). The expression level of intracellular concentration of free calcium ion ([Ca2+]i) was detected by flow cytometry. RESULTS: The NSS of the model group was significantly higher than the control group at 3 and 6 h after MCAO (P<0.01), while the EA group was significantly lower than the model group at 6 h (P<0.01). The cerebral blood flow in the model group was significantly lower than the control group at 1, 3 and 6 h after MCAO (P<0.01), while for the EA group it was remarkably higher than the model group at the same time points (P<0.01). The expressions of Gq, CaM, IP3, DAG and [Ca2+]i in the model group were significantly higher than the control group (P<0.05 or P<0.01), and those in the EA group were significantly lower than the model group at the same time points (P<0.05 or P<0.01). CONCLUSION: EA treatment at GV 26 can effectively decrease the over-expression of related factors of PI system in rats with acute cerebral infarction, improve cerebral autonomy movement, and alleviate cerebral vascular spasm.

Acupuncture Can Regulate the Distribution of Lymphocyte Subsets and the Levels of Inflammatory Cytokines in Patients With Mild to Moderate Vascular Dementia.

Background: Vascular dementia (VD) is the second most common type of dementia after Alzheimer's disease, but there is a lack of definitive treatment for VD. Acupuncture treatment is effective in improving the cognitive impairment and behavioral capacity of patients with VD. In recent years, more studies indicated that peripheral inflammation and abnormal peripheral immune function may aggravate neuroinflammation and cognitive dysfunction. However, there are few studies about the acupuncture and the abnormal peripheral immune function of VD. Also, few studies concern the regulating effect of acupuncture on peripheral immunity of patients with VD. Objective: The aim of this study was to explore the effect of the "sanjiao" acupuncture method on peripheral immunity of patients with mild to moderate VD. Methods: A total of 30 patients with VD were involved in the acupuncture group (AG), which was treated with the "sanjiao" acupuncture method once a day for six times a week and lasted for 12 weeks, and 30 healthy elderly people were assigned to the normal group (NG), which had no treatment. The distribution of lymphocyte subsets and the levels of some inflammatory cytokines in the peripheral blood of subjects were evaluated using the flow cytometry (FCM) and the enzyme-linked immunosorbent assay (ELISA). Results: A total of 60 subjects were involved in this study, while 58 subjects completed the entire trial. Before treatment, the levels of CD3+ T, CD4+ T cells, CD4+/CD8+, Tregs, B cells, IFN-γ, and IL-10 in patients with VD were significantly decreased compared with the normal group (all P < 0.05 or P < 0.01). The level of TNF-α in peripheral blood of patients with VD was significantly increased (P < 0.01). After acupuncture treatment, the levels of CD3+ T, CD4+ T cells, and IFN-γ were significantly increased (all P < 0.05 or P < 0.01). The level of TNF-α was significantly decreased (P < 0.01). The proportion of Tregs was increased (P < 0.01), but it was still lower than that of the normal group (P < 0.05). Conclusion: The acupuncture method can increase the proportion of CD3+, CD4+ T cells, and Tregs in peripheral blood of patients with VD. And, it reduces the levels of pro-inflammatory factor TNF-α, which achieves the anti-inflammatory effects and immunostimulation. It suggests that acupuncture can improve the peripheral immune dysfunction of patients with VD by regulating the distribution of lymphocyte subsets and the levels of inflammatory cytokines. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR-IOR-17012052].

Acupuncture Can Regulate the Peripheral Immune Cell Spectrum and Inflammatory Environment of the Vascular Dementia Rat, and Improve the Cognitive Dysfunction of the Rats.

OBJECTIVE: The aim of this study is to analyze the effects of acupuncture on peripheral immune function, inflammation, and cognitive impairment in vascular dementia (VD) rats. METHODS: In this study, 2-month-old healthy male Wistar rats (260-280 g) were assigned to the groups as follows: normal group (Gn, n = 10), sham-operated group (Gs, n = 10), and operated group (Go, n = 45). The Go group was established by permanent, bilateral common carotid artery occlusion (BCCAO). Two months after operation, the operated rats were screened by hidden platform trial and the rats with cognitive dysfunction were further randomly divided into impaired group (Gi), acupoint group (Ga), and non-acupoint group (Gna) with 10 rats in each group. The Ga group was given acupuncture treatment for 14 days with a rest for every 7 days. After treatment, the Morris water maze (MWM) test was performed to evaluate the spatial learning and memory abilities of rats. The lymphocyte subsets in peripheral blood and spleen of rats were measured by flow cytometry. The levels of cytokines [i.e., interleukin (IL)-1ß, IL-2, IL-4, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ)], chemokines (i.e., macrophage inflammatory protein-2 (MIP-2)), and other inflammatory mediators (i.e., cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS)) in peripheral blood and hippocampus were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the Gn group, the Gi rats presented long escape latencies to find the platform. After acupuncture treatment, the escape latencies of the Ga group were rescued markedly when compared with the Gi group (P < 0.05). The proportion of CD4 + T lymphocytes in both spleen and peripheral blood in the Ga group increased (P < 0.05) in comparison with the Gi group. There is an obvious reduction in IL-1ß (P < 0.05), IL-2 (P < 0.05), TNF-α (P < 0.01), INF-γ (P < 0.01), MIP-2 (P < 0.05), and iNOS (P < 0.01), coming along with the increased levels of IL-4 and IL-10 (P < 0.01) in the Ga group when compared with the Gi group. In addition, the hippocampus proinflammatory factors IL-1ß (P < 0.01), IL-2 (P < 0.01), TNF-α (P < 0.05), INF-γ (P < 0.05), MIP-2 (P < 0.05), iNOS (P < 0.01), and COX-2 decreased in the Ga group, whereas the anti-inflammatory factors IL-4 and IL-10 (P < 0.01) increased. CONCLUSION: There are abnormal immune function and peripheral inflammation in VD rats. Acupuncture can regulate the peripheral immune function and inflammation of the VD rats and can improve the cognitive dysfunction of the rats.

Anatomically aided PET image reconstruction using deep neural networks.

PURPOSE: The developments of PET/CT and PET/MR scanners provide opportunities for improving PET image quality by using anatomical information. In this paper, we propose a novel co-learning three-dimensional (3D) convolutional neural network (CNN) to extract modality-specific features from PET/CT image pairs and integrate complementary features into an iterative reconstruction framework to improve PET image reconstruction. METHODS: We used a pretrained deep neural network to represent PET images. The network was trained using low-count PET and CT image pairs as inputs and high-count PET images as labels. This network was then incorporated into a constrained maximum likelihood framework to regularize PET image reconstruction. Two different network structures were investigated for the integration of anatomical information from CT images. One was a multichannel CNN, which treated PET and CT volumes as separate channels of the input. The other one was multibranch CNN, which implemented separate encoders for PET and CT images to extract latent features and fed the combined latent features into a decoder. Using computer-based Monte Carlo simulations and two real patient datasets, the proposed method has been compared with existing methods, including the maximum likelihood expectation maximization (MLEM) reconstruction, a kernel-based reconstruction and a CNN-based deep penalty method with and without anatomical guidance. RESULTS: Reconstructed images showed that the proposed constrained ML reconstruction approach produced higher quality images than the competing methods. The tumors in the lung region have higher contrast in the proposed constrained ML reconstruction than in the CNN-based deep penalty reconstruction. The image quality was further improved by incorporating the anatomical information. Moreover, the liver standard deviation was lower in the proposed approach than all the competing methods at a matched lesion contrast. CONCLUSIONS: The supervised co-learning strategy can improve the performance of constrained maximum likelihood reconstruction. Compared with existing techniques, the proposed method produced a better lesion contrast versus background standard deviation trade-off curve, which can potentially improve lesion detection.

Total-Body Quantitative Parametric Imaging of Early Kinetics of 18F-FDG.

Parametric imaging has been shown to provide better quantitation physiologically than SUV imaging in PET. With the increased sensitivity from a recently developed total-body PET scanner, whole-body scans with higher temporal resolution become possible for dynamic analysis and parametric imaging. In this paper, we focus on deriving the parameter k1 using compartmental modeling and on developing a method to acquire whole-body 18F-FDG PET parametric images using only the first 90 s of the postinjection scan data with the total-body PET system. Methods: Dynamic projections were acquired with a time interval of 1 s for the first 30 s and a time interval of 2 s for the following minute. Image-derived input functions were acquired from the reconstructed dynamic sequences in the ascending aorta. A 1-tissue-compartment model with 4 parameters (k1, k2, blood fraction, and delay time) was used. A maximum-likelihood-based estimation method was developed with the 1-tissue-compartment model solution. The accuracy of the acquired parameters was compared with the ones estimated using a 2-tissue-compartment irreversible model with 1-h-long data. Results: All 4 parametric images were successfully calculated using data from 2 volunteers. By comparing the time-activity curves acquired from the volumes of interest, we showed that the parameters estimated using our method were able to predict the time-activity curves of the early dynamics of 18F-FDG in different organs. The delay-time effects for different organs were also clearly visible in the reconstructed delay-time image with delay variations of as large as 40 s. The estimated parameters using both 90-s data and 1-h data agreed well for k1 and blood fraction, whereas a large difference in k2 was found between the 90-s and 1-h data, suggesting k2 cannot be reliably estimated from the 90-s scan. Conclusion: We have shown that with total-body PET and the increased sensitivity, it is possible to estimate parametric images based on the very early dynamics after 18F-FDG injection. The estimated k1 might potentially be used clinically as an indicator for identifying abnormalities.

3D/4D Reconstruction and Quantitative Total Body Imaging.

Total-body PET image reconstruction follows a similar procedure to the image reconstruction process for standard whole-body PET scanners. One unique aspect of total-body imaging is simultaneous coverage of the entire human body, which makes it convenient to perform total-body dynamic PET scans. Therefore, four-dimensional dynamic PET reconstruction and parametric imaging are of great interest in total-body imaging. This article covers some basics of PET image reconstruction and then focuses on three- and four-dimensional PET reconstruction for total-body imaging. Methods for image formation from raw measurements in total-body PET are described. Challenges and opportunities in total-body PET image reconstruction are discussed.

Canine immunoglobulin F(ab')2 fragments protect cats against feline parvovirus virus infection.

Feline parvovirus virus (FPV) causes severe diarrhea and leukopenia in felines, and threatening the health of wild and domestic felines. Currently, specific drugs to treat FPV have not yet been developed. In this study, IgG was extracted from inactivated FPV-immunized dog sera. Canine F(ab')2 fragments were obtained from pepsin-digested IgG and then purified by protein-G column chromatography. The results showed that canine immunoglobulin F(ab')2 fragments showed efficient neutralizing activity in vitro against FPV and had therapeutic and prophylactic effects in FPV infected cats. The anti-FPV-specific F(ab')2 fragment can significantly alleviate the clinical symptoms of FPV infected cats and reduce the viral loads of the intestinal tract. These results indicated that the F(ab')2 fragment prepared from inactivated FPV-immunized felines may be used as a prophylactic and therapeutic agent for diseases caused by FPV.

Generative adversarial network based regularized image reconstruction for PET.

Positron emission tomography (PET) is an ill-posed inverse problem and suffers high noise due to limited number of detected events. Prior information can be used to improve the quality of reconstructed PET images. Deep neural networks have also been applied to regularized image reconstruction. One method is to use a pretrained denoising neural network to represent the PET image and to perform a constrained maximum likelihood estimation. In this work, we propose to use a generative adversarial network (GAN) to further improve the network performance. We also modify the objective function to include a data-matching term on the network input. Experimental studies using computer-based Monte Carlo simulations and real patient datasets demonstrate that the proposed method leads to noticeable improvements over the kernel-based and U-net-based regularization methods in terms of lesion contrast recovery versus background noise trade-offs.

Oroxylin A Reduces Vasoconstriction in Rat Aortic Rings through Promoting NO Production and NOS Protein Expression via Estrogen Receptor Signal Pathway.

Oroxylin A, a flavonoid, is naturally produced in many medicinal plants. Our previous study identified it as a phytoestrogen. Based on this, the present study investigated its vasoconstriction reducing effects and whether the action was mediated by the estrogen receptor (ER) signal pathway. Long-term in vitro treatment with oroxylin A reduced Ach-induced vasorelaxation and NE-mediated or KCl-mediated contractile responses in rat aortic rings. These effects were interfered by an ER inhibitor ICI 182,780. Rat cardiac microvascular endothelial cells (CMECs) and aortic vascular smooth muscle cells (VSMCs) were used to study the possible underlying mechanisms. Oroxylin A activated the ER signal pathway. In CMECs, it increased NO production and eNOS protein expression. In VSMCs, it promoted NO production and iNOS protein expression. These effects were also inhibited by ICI 182,780. Besides, oroxylin A stimulated ERα and ERß protein expression in CMECs and VSMCs. All these findings suggest that the ER signal pathway takes part in the vasoconstriction reducing effects of oroxylin A.

Subsecond total-body imaging using ultrasensitive positron emission tomography.

A 194-cm-long total-body positron emission tomography/computed tomography (PET/CT) scanner (uEXPLORER), has been constructed to offer a transformative platform for human radiotracer imaging in clinical research and healthcare. Its total-body coverage and exceptional sensitivity provide opportunities for innovative studies of physiology, biochemistry, and pharmacology. The objective of this study is to develop a method to perform ultrahigh (100 ms) temporal resolution dynamic PET imaging by combining advanced dynamic image reconstruction paradigms with the uEXPLORER scanner. We aim to capture the fast dynamics of initial radiotracer distribution, as well as cardiac motion, in the human body. The results show that we can visualize radiotracer transport in the body on timescales of 100 ms and obtain motion-frozen images with superior image quality compared to conventional methods. The proposed method has applications in studying fast tracer dynamics, such as blood flow and the dynamic response to neural modulation, as well as performing real-time motion tracking (e.g., cardiac and respiratory motion, and gross body motion) without any external monitoring device (e.g., electrocardiogram, breathing belt, or optical trackers).

Maximum likelihood activity and attenuation estimation using both emission and transmission data with application to utilization of Lu-176 background radiation in TOF PET.

PURPOSE: We present a new method for joint reconstruction of activity and attenuation images using both emission and transmission data and demonstrate its advantage over the standard maximum likelihood activity and attenuation (MLAA) reconstruction using emission data alone. METHODS: We define a joint likelihood function including both time-of-flight (TOF) emission data and transmission data. The latter can be obtained from an external source or from Lu-176 background radiation. Activity and attenuation images are estimated jointly by maximizing the likelihood function. The proposed method solves the undetermined scale problem in the conventional MLAA. A monotonically convergent algorithm was derived to optimize the objective function. Furthermore, we present a theoretical analysis of the noise propagation in the joint reconstruction. Simulations and phantom experiments were conducted to validate the feasibility of the proposed method. RESULTS: Quantitatively correct and less noisy images were reconstructed with the proposed method. Artifacts in the attenuation map reconstructed from the standard MLAA were removed by incorporating transmission data. Noise analysis was validated with different transmission sources and transmission count levels. The theoretical prediction indicated that noise of activity map would not change in a large range of transmission count level and a very low transmission count level could result in good estimation. CONCLUSIONS: The results demonstrate the feasibility of obtaining quantitatively correct images in TOF PET by using both emission and (weak) transmission data. The noise analysis also provides guidance for choosing a proper transmission source configuration to reduce noise propagation.

Total-Body Dynamic Reconstruction and Parametric Imaging on the uEXPLORER.

The world's first 194-cm-long total-body PET/CT scanner (uEXPLORER) has been built by the EXPLORER Consortium to offer a transformative platform for human molecular imaging in clinical research and health care. Its total-body coverage and ultra-high sensitivity provide opportunities for more accurate tracer kinetic analysis in studies of physiology, biochemistry, and pharmacology. The objective of this study was to demonstrate the capability of total-body parametric imaging and to quantify the improvement in image quality and kinetic parameter estimation by direct and kernel reconstruction of the uEXPLORER data. Methods: We developed quantitative parametric image reconstruction methods for kinetic analysis and used them to analyze the first human dynamic total-body PET study. A healthy female subject was recruited, and a 1-h dynamic scan was acquired during and after an intravenous injection of 256 MBq of 18F-FDG. Dynamic data were reconstructed using a 3-dimensional time-of-flight list-mode ordered-subsets expectation maximization (OSEM) algorithm and a kernel-based algorithm with all quantitative corrections implemented in the forward model. The Patlak graphical model was used to analyze the 18F-FDG kinetics in the whole body. The input function was extracted from a region over the descending aorta. For comparison, indirect Patlak analysis from reconstructed frames and direct reconstruction of parametric images from the list-mode data were obtained for the last 30 min of data. Results: Images reconstructed by OSEM showed good quality with low noise, even for the 1-s frames. The image quality was further improved using the kernel method. Total-body Patlak parametric images were obtained using either indirect estimation or direct reconstruction. The direct reconstruction method improved the parametric image quality, having a better contrast-versus-noise tradeoff than the indirect method, with a 2- to 3-fold variance reduction. The kernel-based indirect Patlak method offered image quality similar to the direct Patlak method, with less computation time and faster convergence. Conclusion: This study demonstrated the capability of total-body parametric imaging using the uEXPLORER. Furthermore, the results showed the benefits of kernel-regularized reconstruction and direct parametric reconstruction. Both can achieve superior image quality for tracer kinetic studies compared with the conventional indirect OSEM for total-body imaging.

[Using bioinformatics tools to explore cellular biological mechanisms of "Triple Energizer Acupuncture Method" in treating senile dementia].

OBJECTIVE: To observe the effect of needling "Danzhong" (CV17), "Zhongwan"(CV12), "Qihai" (CV6), "Xuehai"(SP10)and "Zusanli"(ST36) (Triple Energizer Acupuncture Method) on the learning-memory ability and profile of hippocampal differentially-expressed genes and proteins of SAMP8 mice (rapid aging mice), so as to explore its underlying mechanisms in improving Alzheimer's disease (AD)．. METHODS: A total of 60 SAMP8 were used as the dementia model and randomly divided into blank control, acupoint and non-acupoint groups (n＝20 per group). The 5 acupuncture points and non-acupoints (subcostal region) on the bilateral sides were needled with filiform needles and manipulated manually for 30 s at each one，once daily, 6 times a week for 4 weeks. The Morris water maze tests (location navigation tests and space probing trials) were used to evaluate the mouse's learning-memory ability. The hippocampal tissue was extracted to detect differentially expressed genes and proteins related to acupuncture intervention by gene chip and isobaric tags for relative and absolute quantitation (iTRAQ) techniques as well as bioinformatic analysis, separately. The information is analyzed through bioinformatics database tools. Finally, immunofluorescence staining was used to verify theresults of microarray analysis. RESULTS: Compared with mice of the control and non-acupoint groups, the escape latency of location navigation task of Morris water maze tests on 4th and 5th day of training was significantly shortened in mice of the acupoint group, and the duration of stay in the original safe-platform quadrant was significantly increased in the acupoint group (P<0.05). Gene microarray displayed that in comparison with the control group, 898 differentially expressed genes were up-regulated, 418 genes were down-regulated in the hippocampus of acupoint group. The iTRAQ analysis indicated that in the acupoint and non-acupoint groups, 286 and 299 differentially expressed proteins were up-regulated, 319 and 179 proteins down-regulated, respectively. Of the 34 terms containing 47 proteins up-regulated by acupoint needling, including intermediate filament, keratin filament, myelin sheath, postsynaptic density, neuron projection were related with neurite and cytoskele-ton. While in the non-acupoint group, of the 24 terms were listed by the system, only the myelin sheath involving 11 differentially expressed proteins functions in activities of neurite and cytoskeleton. Immunofluorescence staining of the hippocampal tissue showed that the high-density distribution areas of neurons and neurite fibers were characterized by decentralization and disordering, with the highlighted areas being mainly near the cell body parts in control mice, but in mice of the acupoint group, the highlighted areas at the neurite were relatively dense, the morphology of hippocampal cells was complete, the fiber structure was clear, dense and orderly, and the neurites were closely arranged and in order, indicating an improvement of the distribution and arrangement of nerve fibers after acupuncture. The height of neurite highlight area of the acupoint group was significantly higher than that of the non-acupoint group (P<0.05)．. CONCLUSION: The "Triple Energizer Acupuncture" of acupoints is able to improve the learning-memory ability in SAMP8, which may be related to its effects in regulating the expression and function of hippocampal genes and proteins related to neurite and cytoskeleton.