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Several studies have compared phase contrast magnetic resonance imaging (PC‐MRI) with arterial spin labeling (ASL) in the same cohort of subjects. However, these earlier comparisons included subjects across a wide age range, which can contribute to increased intersubject variability. We compared the range and variability of CBF based on PC‐MRI and ASL in a group of young subjects. We also explored whether the comparison between PC‐MRI and ASL was dependent on sex. Thirty young subjects (17 females) were recruited in this study. The CBF from PC‐MRI (CBFPC) was calculated as the total blood flow normalized to brain parenchyma mass. The CBF from ASL (CBFASL) was quantified based on the perfusion kinetic model. The ratio between CBFASL and CBFPC was calculated. Females exhibited significantly higher CBF using both PC‐MRI (p < 0.05) and ASL (p < 0.005) compared with males. The disparity in CBF between sexes was more prominent in ASL measurements. A significant correlation was observed between CBFPC and CBFASL values (r = 0.47, p < 0.01), and CBFASL tended to be lower than CBFPC values (p < 0.001). This difference between CBFASL and CBFPC was more pronounced in males, as evidenced by the smaller CBFASL/CBFPC ratio in males (p < 0.05). The measurement of global CBF with PC‐MRI and ASL are correlated, but CBFASL exhibits lower values than CBFPC. As the underestimation of CBFASL is prominent in males, ASL amplifies the sexual dimorphism in CBF compared with PC‐MRI. [ABSTRACT FROM AUTHOR]

Intraoperative navigation systems have been widely applied in spinal fusion surgery to improve the implantation accuracy of spinal screws using orthogonal tomographic and surface-rendering imaging. However, these images contain limited anatomical information and no information on bone volume contact by the implanted screw, which has been proven to affect the stability of implanted screws. This study proposed a novel drilled surface imaging technique that displays anatomical integration properties to calculate the contact bone volume (CBV) of the screws implanted along an implantation trajectory. A cylinder was used to represent the area traversed by the screws, which was manually rotated and translated to a predetermined implantation trajectory according to a vertebra model obtained using computed tomography (CT) image volumes. The drilled surface image was reconstructed by interpolating the CT numbers at the predefined sampling points on the cylinder surface. The anatomical integration property and CBV of the screw implanted along the transpedicular trajectory (TT) and cortical bone trajectory (CBT) were evaluated and compared. The drilled surface image fully revealed the contact anatomical structure of the screw under the trajectories, improving the understanding of the anatomical integration of the screw and surrounding tissues. On average, the CBV of the CBT was 30% greater than that of the TT. The proposed drilled surface image may be applied in preoperative planning and integrated into intraoperative navigation systems to evaluate the anatomical integration and degree of bone contact of the screw implanted along a trajectory. [ABSTRACT FROM AUTHOR]

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a significant role in tumor stage as it can be used to measure tissue perfusion and permeability of tumors. Purpose: To investigate the relationships between both quantitative and semi-quantitative variables obtained from DCE-MRI and tongue cancer stages. Material and Methods: Mean values of Ktrans, enhancement ratio (ER), wash-in slope (slope), and the 95th percentile (95%) values of the distribution for Ktrans, ER, and slope values (Ktrans (95%), ER (95%), and slope (95%), respectively) were calculated for 53 patients with tongue cancers (American Joint Committee on Cancer 8th Edition stage group: 10 in stages I and II, 14 in stage III, 21 in stage IVa, and eight in stage IVb as determined by histopathologic assessment). The relationship between tumor staging and each of the six DCE-MRI parameters was assessed separately using ordinal logistic regression. Results: The logistic regression analysis revealed that both mean and 95th percentile values of Ktrans were significantly and positively correlated with tongue cancer stage (P < 0.01). More aggressive tumor stages had larger kinetic parameter. Moreover, the semi-quantitative parameters, such as ER (95%) and slope (95%), may be more significant predictors for evaluating tongue cancer stages than the mean ER and mean slope. Conclusion: Both quantitative and semi-quantitative imaging biomarkers are useful for evaluating the stages of tongue cancer, and the indices obtained from DCE-MRI were positively correlated with the tumor stages. These parameters have the potential to non-invasively evaluate the stages of tongue cancer in the clinical setting. [ABSTRACT FROM AUTHOR]

• Mean diffusivity (MD) was subject to anesthesia regimens. • The estimated MD was higher under isoflurane anesthesia than that under alpha-chloralose anesthesia. • Fractional anisotropy (FA) quantitation was also influenced by the anesthesia regimens. • Compared with the alpha-chloralose protocol, the isoflurane protocol resulted in the lower FA. Diffusion tensor imaging (DTI) in animal models are essential for translational neuroscience studies. A critical step in animal studies is the use of anesthetics. Understanding the influence of specific anesthesia regimes on DTI-derived parameters, such as fractional anisotropy (FA) and mean diffusivity (MD), is imperative when comparing results between animal studies using different anesthetics. Here, the quantification of FA and MD under different anesthetic regimes, alpha-chloralose and isoflurane, is discussed. We also used a range of b-values to determine whether the anesthetic effect was b-value dependent. The first group of rats (n = 6) was anesthetized with alpha-chloralose (80 mg/kg), whereas the second group of rats (n = 7) was anesthetized with isoflurane (1.5%). DTI was performed with b-values of 500, 1500, and 1500s/mm2, and the MD and FA were assessed individually. Anesthesia-specific differences in MD were apparent, as manifested by the higher estimated MD under isoflurane anesthesia than that under alpha-chloralose anesthesia (P < 0.001). MD values increased with decreasing b-value in all regions studied, and the degree of increase when rats were anesthetized with isoflurane was more pronounced than that associated with alpha-chloralose (P < 0.05). FA quantitation was also influenced by anesthesia regimens to varying extents, depending on the brain regions and b-values. In conclusion, both scanning parameters and the anesthesia regimens significantly impacted the quantification of DTI indices. [ABSTRACT FROM AUTHOR]

Rationale: Caffeine is a widely studied psychostimulant, even though its exact effect on brain activity remains to be elucidated. Positron emission tomography (PET) allows studying mechanisms underlying cerebral metabolic responses to caffeine in caffeine-naïve rats. Rodent studies are typically performed under anesthesia. However, the anesthesia may affect neurotransmitter systems targeted by tested drugs. Objectives: The scope of the present study was to address the impairing or enhancing effect of two common anesthetics, alpha-chloralose and isoflurane, on the kinetics of caffeine. Methods: The first group of rats (n = 15) were anesthetized under 1.5% isoflurane anesthesia. The second group of rats (n = 15) were anesthetized under alpha-chloralose (80 mg/kg). These rats received an intravenous injection of saline (n = 5) or of 2.5 mg/kg (n = 5) or 40 mg/kg (n = 5) caffeine for both groups. Results: With 2.5 mg/kg or 40 mg/kg caffeine, whole-brain cerebral metabolism was significantly reduced by 17.2% and 17% (both P < 0.01), respectively, under alpha-chloralose anesthesia. However, the lower dose of caffeine (2.5 mg/kg) had a limited effect on brain metabolism, whereas its higher dose (40 mg/kg) produced enhancements in brain metabolism in the striatum, hippocampus, and thalamus (all P < 0.05) under isoflurane anesthesia. Conclusion: These findings demonstrate significant differences in brain responses to caffeine on the basic of the anesthesia regimen used, which highlights the importance of attention to the anesthetic used when interpreting findings from animal pharmacological studies because of possible interactions between the anesthetic and the drug under study. [ABSTRACT FROM AUTHOR]

Although cerebrovascular factors are the second leading cause of cognitive impairment and dementia in elderly, the precise spatial and temporal trajectories of vascular decline in aging have not been fully characterized. With an advanced cerebrovascular reactivity (CVR) MRI technique that specifically informs vascular stiffness and dilatory ability of cerebral vessels, we present four-year longitudinal CVR data measured in 116 healthy individuals (20–88 years of age). Our data revealed a spatial heterogeneity in vascular decline in aging ( p  = 0.003), in that temporal lobe showed the fastest rate of longitudinal CVR decline, followed by parietal and frontal lobes. The rate of CVR decline was also age-dependent. Middle age, not older age, manifested the fastest rate of longitudinal CVR decline ( p  < 0.05). Longitudinal changes in CVR were associated with changes in processing speed ( p  = 0.031) and episodic memory ( p  = 0.022), but not with working memory or reasoning. The rate of longitudinal CVR change was not different between hypertensive and normotensive participants. However, cross-sectionally, individuals with hypertension revealed in a lower CVR compared to normotensive participants ( p  = 0.016). These findings help elucidate age-related decline in brain hemodynamics and support CVR as a non-invasive biomarker in evaluating cerebrovascular conditions in elderly individuals. [ABSTRACT FROM AUTHOR]

Background: To date, most countries lifted the restriction requirement and coexisted with SARS-CoV-2. Thus, dietary behavior for preventing SARS-CoV-2 infection becomes an interesting issue on a daily basis. Coffee consumption is connected with reduced COVID-19 risk and correlated to COVID-19 severity. However, the mechanisms of coffee for the reduction of COVID-19 risk are still unclear. Results: Here, we identified that coffee can inhibit multiple variants of the SARS-CoV-2 infection by restraining the binding of the SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (ACE2), and reducing transmembrane serine protease 2 (TMPRSS2) and cathepsin L (CTSL) activity. Then, we used the method of "Here" (HRMS-exploring-recombination-examining) and found that isochlorogenic acid A, B, and C of coffee ingredients showed their potential to inhibit SARS-CoV-2 infection (inhibitory efficiency 43–54%). In addition, decaffeinated coffee still preserves inhibitory activity against SARS-CoV-2. Finally, in a human trial of 64 subjects, we identified that coffee consumption (approximately 1–2 cups/day) is sufficient to inhibit infection of multiple variants of SARS-CoV-2 entry, suggesting coffee could be a dietary strategy to prevent SARS-CoV2 infection. Conclusions: This study verified moderate coffee consumption, including decaffeination, can provide a new guideline for the prevention of SARS-CoV-2. Based on the results, we also suggest a coffee-drinking plan for people to prevent infection in the post-COVID-19 era. [ABSTRACT FROM AUTHOR]

Osteoporosis is a disease characterized by a degradation of bone structures. Various methods have been developed to diagnose osteoporosis by measuring bone mineral density (BMD) of patients. However, BMDs from these methods were not equivalent and were incomparable. In addition, partial volume effect introduces errors in estimating bone volume from computed tomography (CT) images using image segmentation. In this study, a two-compartment model (TCM) was proposed to calculate bone volume fraction (BV/TV) and BMD from CT images. The TCM considers bones to be composed of two sub-materials. Various equivalent BV/TV and BMD can be calculated by applying corresponding sub-material pairs in the TCM. In contrast to image segmentation, the TCM prevented the influence of the partial volume effect by calculating the volume percentage of sub-material in each image voxel. Validations of the TCM were performed using bone-equivalent uniform phantoms, a 3D-printed trabecular-structural phantom, a temporal bone flap, and abdominal CT images. By using the TCM, the calculated BV/TVs of the uniform phantoms were within percent errors of ±2%; the percent errors of the structural volumes with various CT slice thickness were below 9%; the volume of the temporal bone flap was close to that from micro-CT images with a percent error of 4.1%. No significant difference (p >0.01) was found between the areal BMD of lumbar vertebrae calculated using the TCM and measured using dual-energy X-ray absorptiometry. In conclusion, the proposed TCM could be applied to diagnose osteoporosis, while providing a basis for comparing various measurement methods. [ABSTRACT FROM PUBLISHER]

Purpose To measure wall shear stress (WSS) in the common carotid arteries (CCA) of a spontaneously hypertensive rat (SHR) model and a normotensive Wistar Kyoto rat (WKY) model by 2D phase-contrast magnetic resonance imaging (PC-MRI). Materials and methods PC-MRI was performed on 7 SHR and 7 WKY at ages of 4 and 7 months at a 7 T scanner. Images in the middle CCA (CCA mid ) and in the bifurcation of CCA (CCA bifur ) were acquired. The WSS values for differentiating characteristics between two models were calculated. Further, its location-specific change, regional distribution along the CCA circumference, and the reproducibility were evaluated. Results In the 4-month-old rats, SHR showed lower temporal averaged WSS (WSS avg ) and peak systolic WSS (WSS s ) in the CCA bifur in comparison with WKY (WSS avg : 0.95 ± 0.18 vs. 1.30 ± 0.36 N/m 2 ( P < 0.01); WSS s : 1.68 ± 0.70 vs. 3.22 ± 2.49 N/m 2 ( P < 0.05)). We observed the same trends in the 7-month-old rats. In the SHR model, the WSS avg was lower in the CCA bifur than in the CCA mid . The regional distribution of WSS avg along the circumference of CCA showed lower values in WKY, particularly in posterior segments of CCA bifur . The intra-observer, intra-scan and inter-scan reproducibility was acceptable and the disagreements were ranged from − 0.05 to 0.06 N/m 2 . Conclusion This study evaluated WSS in SHR and WKY models by 2D PC-MRI. High reproducibility analyses further indicated the reliability of measurements of WSS in the CCA of SHR and WKY models using PC-MRI at 7 T. [ABSTRACT FROM AUTHOR]

Acupuncture is an alternative treatment for primary dysmenorrhea (PDM). However, mechanisms by which acupuncture exerts its analgesic properties are still unclear. This study aimed to explore the cerebral blood flow (CBF) response to verum and sham acupuncture treatments, and further investigate whether pre-treatment CBF is capable of assessing symptom changes after interventions. A total of 11 PDM patients in the verum group and 12 patients in the sham group participated in this study. Pain rating index (PRI), CBF, and gonadal hormone levels were acquired before and after 8-week treatments. Both verum and sham acupuncture treatments exert its analgesic effect on PDM after intervention as PRI reduced (p < 0.05). Blood gonadal levels were not significantly different after acupuncture in both groups (all p > 0.05). In the verum group, intervention-related decreases in CBF were observed in the right dorsal anterior cingulate cortex. In the sham group, regions identified as showing reductions in CBF after acupuncture included the left ventromedial prefrontal cortex, left caudate, and left insula. Patients with higher baseline CBF in the left precuneus and right hippocampus were accompanied with worse treatment response to acupuncture intervention. Mechanisms of verum and sham acupuncture treatments are dissimilar as manifested by different brain responses. [ABSTRACT FROM AUTHOR]

Background: Dental cone beam computed tomography (CBCT) is commonly used to evaluate cancellous bone density before dental implant surgery. However, to our knowledge, no measurement approach has been standardized yet. This study aimed to evaluate the relationship between three different regions of interest (ROI) methods on cancellous bone density at the dental implant site using dental CBCT images. Methods: Patients' dental CBCT images (n = 300) obtained before dental implant surgery were processed using Mimics (Materialise, Leuven, Belgium). At the potential implant sites, the rectangle, cylinder, and surrounding cylinder ROI methods were used to measure bone density. Repeated measures one-way analysis of variance was performed to compare the three ROI methods in terms of measurement results. Pearson correlation analysis was performed to identify the likely pair-wise correlations between the three ROI methods. Results: The density value obtained using the surrounding cylinder approach (grayscale value [GV],523.56 ± 228.03) was significantly higher than the values obtained using the rectangle (GV, 497.04 ± 236.69) and cylinder (GV,493 ± 231.19) ROI methods in terms of results. Furthermore, significant correlations were noted between the ROI methods (r > 0.965; p < 0.001). Conclusions: The density measured using the surrounding cylinder method was the highest. The choice of method may not influence the trends of measurement results. Trial registration: This study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH111-REC3-205. Informed consent was waived by the Institutional Review Board of China Medical University Hospital, CMUH111-REC3-205, owing to the retrospective nature of the study. [ABSTRACT FROM AUTHOR]

Background and Purpose: Multimodality magnetic resonance imaging (MRI) can provide complementary information in the assessment of brain tumors. We aimed to segment tumor in amide proton transfer-weighted (APTw) images and to investigate multiparametric MRI biomarkers for the assessment of glioma response to radiotherapy. For tumor extraction, we evaluated a semiautomated segmentation method based on region of interest (ROI) results by comparing it with the manual segmentation method.Methods: Thirteen nude rats injected with U87 tumor cells were irradiated by an 8-Gy radiation dose. All MRI scans were performed on a 4.7-T animal scanner preradiation, and at day 1, day 4, and day 8 postradiation. Two experts performed manual and semiautomated methods to extract tumor ROIs on APTw images. Multimodality MRI signals of the tumors, including structural (T2 and T1 ), functional (apparent diffusion coefficient and blood flow), and molecular (APTw and magnetization transfer ratio or MTR), were calculated and compared quantitatively.Results: The semiautomated method provided more reliable tumor extraction results on APTw images than the manual segmentation, in less time. A considerable increase in the ADC intensities of the tumor was observed during the postradiation. A steady decrease in the blood flow values and in the APTw signal intensities were found after radiotherapy.Conclusions: The semiautomated method of tumor extraction showed greater efficiency and stability than the manual method. Apparent diffusion coefficient, blood flow, and APTw are all useful biomarkers in assessing glioma response to radiotherapy. [ABSTRACT FROM AUTHOR]

By reducing the cerebral blood flow and thereby increasing the resting deoxyhaemoglobin concentration, many human studies have shown that caffeine has a beneficial effect on enhancing the magnitude of blood‐oxygenation‐level‐dependent (BOLD) responses. However, the effect of caffeine on BOLD responses in animals under anaesthesia has not been demonstrated. In this study, we aimed to determine the effect of systemic caffeine administration on BOLD responses in rats under alpha‐chloralose. By applying electric whisker pad stimulation to male Sprague‐Dawley rats, we performed fMRI measurements before and after the caffeine injection (40 mg/kg, n = 7) or an equivalent volume of saline (n = 6) at 7T. To understand the potential perturbation of animal physiology during stimulation, arterial blood pressure was measured in a separate group of animals (n = 3) outside the scanner. Caffeine significantly decreased baseline BOLD signals (p =.05) due to the increased deoxyhaemoglobin level. Both BOLD responses and t‐values in the primary somatosensory cortex were significantly increased (both p <.05). The blood pressure changed insignificantly (p >.05). No significant differences in BOLD responses and t‐values were observed in the control condition of saline injection (both p >.05). These findings suggested that, although the cerebral activity was lower under alpha‐chloralose anaesthesia, the higher level of deoxygemoglobin at the baseline under the caffeinated condition can benefit the magnitude of BOLD responses in rats. These findings suggest that animal models might serve as potential platforms for further caffeine‐related fMRI research studies. [ABSTRACT FROM AUTHOR]

Quantitative evaluation using image biomarkers calculated from threshold-segmented low-attenuation areas on chest computed tomography (CT) images for diagnosing chronic obstructive pulmonary diseases (COPD) has been widely investigated. However, the segmentation results depend on the applied threshold and slice thickness of the CT images because of the partial volume effect (PVE). In this study, the air volume fraction (AV/TV) of lungs was calculated from CT images using a two-compartment model (TCM) for COPD diagnosis. A relative air volume histogram (RAVH) was constructed using the AV/TV values to describe the air content characteristics of lungs. In phantom studies, the TCM accurately calculated total cavity volumes and foam masses with percent errors of less than 8% and ±4%, respectively. In patient studies, the relative volumes of normal and damaged lung tissues and the damaged-to-normal RV ratio were defined and calculated from the RAVHs as image biomarkers, which correctly differentiated COPD patients from controls in 2.5- and 5-mm-thick images with areas under receiver operating characteristic curves of >0.94. The AV/TV calculated using the TCM can prevent the effect of slice thickness, and the image biomarkers calculated from the RAVH are reliable for diagnosing COPD [ABSTRACT FROM AUTHOR]

Developing sensitive diagnostic methods for a longitudinal evaluation of the status of liver fibrosis is a priority. This study is aimed at assessing the significance of longitudinal positron emission tomography (PET) imaging with 18F-labeling tracers for assessing liver fibrosis in a rat model with bile duct ligation (BDL). Twenty-one 6-week-old Sprague-Dawley male rats were used in this study. Longitudinal PET images using [18F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) (n = 3), [18F]fluoroacetate ([18F]FAc) (n = 3), and 18F-fluoro-2-deoxy-D-glucose ([18F]FDG) (n = 3) were obtained at 0, 1, and 2 weeks after BDL. Biochemical assays, histological assays, immunohistochemical staining assays, and next generation sequencing analyses were also performed at 0 (n = 3), 1 (n = 3), 2 (n = 3), and 3 (n = 3) weeks after BDL, which demonstrated the severe damage in rat livers after BDL. Regarding [18F]FEPPA and [18F]FDG, there was a significantly higher uptake in the liver after BDL (both P < 0.05), which lasted until week 2. However, the uptake of [18F]FAc in the liver was not significantly different before and after BDL (P = 0.28). Collectively, both [18F]FEPPA and [18F]FDG can serve as sensitive probes for detecting the liver fibrosis. However, [18F]FAc is not recommended to diagnose liver fibrosis. [ABSTRACT FROM AUTHOR]

Gastric cancer contributes to cancer-related fatalities. Conventional chemotherapy faces challenges due to severe adverse effects, prompting recent research to focus on postbiotics, which are safer biomolecules derived from nonviable probiotics. Despite promising in vitro results, efficient in vivo delivery systems remain a challenge. This study aimed to design a potential nanoparticle (NP) formulation encapsulating the Lacticaseibacillus paracasei GMNL-133 (SGMNL-133) isolate to enhance its therapeutic efficacy in treating gastric cancer. We successfully isolated GMNL-133 (SGMNL-133) by optimizing the lysate extraction and column elution processes for L. paracasei GMNL-133, resulting in substantial enhancement of its capacity to inhibit the proliferation of gastric cancer cells. Additionally, we developed a potential NP utilizing arginine-chitosan and fucoidan encapsulating SGMNL-133. This innovative approach protected the SGMNL-133 from degradation by gastric acid, facilitated its penetration through the mucus layer, and enabled interaction with gastric cancer cells. Furthermore, in vivo experiments demonstrated that the encapsulation of SGMNL-133 in NPs significantly enhanced its efficacy in the treatment of orthotopic gastric tumors while simultaneously reducing tissue inflammation levels. Recent research highlights postbiotics as a safe alternative, but in vivo delivery remains a challenge. Our study optimized the extraction of the lysate and column elution of GMNL-133, yielding SGMNL-133. We also developed NPs to protect SGMNL-133 from gastric acid, enhance mucus penetration, and improve the interaction with gastric cancer cells. This combination significantly enhanced drug delivery and anti-gastric tumor activity. Recent research highlights postbiotics as a safer alternative, yet in vivo delivery remains a challenge. Our study optimizes lysate extraction and column elution for Lacticaseibacillus paracasei GMNL-133, yielding GMNL-133 (SGMNL-133). We've also developed nanoparticles to protect SGMNL-133 from gastric acid, enhance mucus penetration, and improve interaction with gastric cancer cells. This combination significantly enhances drug delivery and anti-gastric tumor activity. [Display omitted] [ABSTRACT FROM AUTHOR]

Diabetic patients often experience chronic inflammation and fibrosis in their cardiac tissues, highlighting the pressing need for the development of sensitive diagnostic methods for longitudinal assessment of diabetic cardiomyopathy. This study aims to evaluate the significance of an inflammatory marker known as translocator protein (TSPO) in a positron emission tomography (PET) protocol for longitudinally monitoring cardiac dysfunction in a diabetic animal model. Additionally, we compared the commonly used radiotracer, 18F-fluoro-2-deoxy- d -glucose (18F-FDG). Fourteen 7-week-old female Sprague-Dawley rats were used in this study. Longitudinal PET experiments were conducted using 18F- N -2-(2-fluoroethoxy)benzyl)- N -(4-phenoxypyridin-3-yl)acetamide (18F-FEPPA) (n = 3), the TSPO radiotracer, and 18F-FDG (n = 3), both before and after the onset of diabetes. Histological and immunohistochemical staining assays were also conducted in both the control (n = 4) and diabetes (n = 4) groups. Results indicated a significant increase in cardiac tissue uptake of 18F-FEPPA after the onset of diabetes (P < 0.05), aligning with elevated TSPO levels observed in diabetic animals according to histological data. Conversely, the uptake of 18F-FDG in cardiac tissue significantly decreased after the onset of diabetes (P < 0.05). These findings suggest that 18F-FEPPA can function as a sensitive probe for detecting chronic inflammation and fibrosis in the cardiac tissues of diabetic animals. [Display omitted] [ABSTRACT FROM AUTHOR]

Developing sensitive diagnostic methods for a longitudinal evaluation of the status of liver fibrosis is a priority. This study is aimed at assessing the significance of longitudinal positron emission tomography (PET) imaging with 18F-labeling tracers for assessing liver fibrosis in a rat model with bile duct ligation (BDL). Twenty-one 6-week-old Sprague-Dawley male rats were used in this study. Longitudinal PET images using [18F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) (n = 3), [18F]fluoroacetate ([18F]FAc) (n = 3), and 18F-fluoro-2-deoxy-D-glucose ([18F]FDG) (n = 3) were obtained at 0, 1, and 2 weeks after BDL. Biochemical assays, histological assays, immunohistochemical staining assays, and next generation sequencing analyses were also performed at 0 (n = 3), 1 (n = 3), 2 (n = 3), and 3 (n = 3) weeks after BDL, which demonstrated the severe damage in rat livers after BDL. Regarding [18F]FEPPA and [18F]FDG, there was a significantly higher uptake in the liver after BDL (both P < 0.05), which lasted until week 2. However, the uptake of [18F]FAc in the liver was not significantly different before and after BDL (P = 0.28). Collectively, both [18F]FEPPA and [18F]FDG can serve as sensitive probes for detecting the liver fibrosis. However, [18F]FAc is not recommended to diagnose liver fibrosis. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a fatal malignant tumor, and effective therapies to attenuate its progression are lacking. Nanoparticle (NP)-based solutions may enable the design of novel treatments to eliminate GC. Refined, receptor-targetable NPs can selectively target cancer cells and improve the cellular uptake of drugs. To overcome the current limitations and enhance the therapeutic effects, epigallocatechin-3-gallate (EGCG) and low-concentration doxorubicin (DX) were encapsulated in fucoidan and d-alpha-tocopherylpoly (ethylene glycol) succinate-conjugated hyaluronic acid-based NPs for targeting P-selectin-and cluster of differentiation (CD)44-expressing gastric tumors. The EGCG/DX-loaded NPs bound to GC cells and released bioactive combination drugs, demonstrating better anti-cancer effects than the EGCG/DX combination solution. In vivo assays in an orthotopic gastric tumor mouse model showed that the EGCG/DX-loaded NPs significantly increased the activity of gastric tumors without inducing organ injury. Overall, our EGCG/DX-NP system exerted a beneficial effect on GC treatment and may facilitate the development of nanomedicine-based combination chemotherapy against GC in the future. [ABSTRACT FROM AUTHOR]

Cerebrovascular reactivity (CVR) is a specific indicator of autoregulatory efficiency. Studies have demonstrated that CVR depends on the baseline vascular dilation status between groups. Within the brain, there also exist spatial variations in both the resting cerebral blood flow (CBF) and CVR across different cerebral regions. However, the relationship between the regional CBF and CVR remains unclear. Hence, the primary goal of this study was to investigate the relationship between the resting CBF using pseudocontinuous arterial spin labeling (pCASL) technique and CVR using blood oxygenation level‐dependent (BOLD) technique across different cerebral regions. Eleven male and 14 female young volunteers were recruited in this study. Each subject was asked to perform the breath‐holding challenge to evaluate CVR at 3 T. The resting CBF was measured using pCASL in each subject. The relationships between CBF and CVR across the lobes were evaluated using the Spearman's rank test. The results showed that, for both sexes, the frontal lobe had the maximal resting perfusion but minimal vascular response to hypercapnia, whereas the occipital lobe had the lowest baseline CBF but maximal reactivity to hypercapnia, suggesting low and high autoregulatory efficiencies at high and low resting CBF in the brain, respectively. Sex‐related differences were observed in CBF but not in CVR. These findings may be of clinical interest in the assessment of cerebrovascular reserve and regional‐dependent vascular diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a macrophage-targeted nanoparticle composed of hyaluronan/fucoidan complexes with polyethylene glycol-gelatin to encapsulate and deliver epigallocatechin-3-gallate (EGCG), a compound that can regulate macrophage activation and pro-inflammatory mediator production. We show that our nanoparticles can successfully bond to macrophages and deliver more EGCG than an EGCG solution treatment, confirming the anti-inflammatory effects of these nanoparticles in lipopolysaccharide-stimulated macrophages. The prepared nanoparticles were established with a small mean particle size (217.00 ± 14.00 nm), an acceptable polydispersity index (0.28 ± 0.07), an acceptable zeta potential value (−33.60 ± 1.30 mV), and a high EGCG loading efficiency (52.08% ± 5.37%). The targeting abilities of CD44 binding were increased as the hyaluronan concentration increased and decreased by adding a competitor CD44 antibody. Moreover, we found that fucoidan treatment significantly reduced macrophage migration after lipopolysaccharide treatment in a dose-responsive manner. In summary, we successfully created macrophage-targeted nanoparticles for effective targeted delivery of EGCG, which should aid in the development of future anti-inflammatory drugs against macrophage-related diseases. [ABSTRACT FROM AUTHOR]

The quantitative evaluation of computed tomography (CT) images is widely investigated and applied in clinical diagnosis. However, the CT number of tissue can vary with scanners or applied tube voltages because of the x-ray spectrum dependence of measured linear attenuation coefficients that degrades evaluation accuracy and limits multicenter or multimodality research. This study proposed a novel CT image synthesis method to correct the spectrum dependence of CT numbers by normalizing them to the same spectrum condition. Stoichiometric calibration was performed to derive the spectrum characteristic parameters (SCPs) of six spectra from two CT scanners with different applied tube voltages. Subsequently, conversion relationships between CT numbers and tissue parameters (TPs) were determined using the SCPs and standard tissue data. The CT number of a tissue measured from a spectrum condition was converted to TPs using these relationships, and the results were used to estimate the CT number of the tissue in another spectrum condition using the corresponding SCPs. Phantom, cadaver, and patient studies were performed to evaluate the proposed method. In the phantom study, image synthesis reduced the mean difference between the CT numbers of tissue-equivalent phantoms measured using different spectra from 57.96 to 33.94 HU. In the cadaveric study, the mean difference between the CT numbers of a temporal bone flap measured using different spectra was lowered by over 57%. In the patient image study, a significant difference of 81.5 HU was observed between the mean CT numbers of femoral shafts obtained from the two scanners; this difference was reduced to less than 17 HU, which was nonsignificant, when the proposed method was used. The proposed image synthesis method could reduce the spectrum dependence of CT numbers measured with different spectra and could be applied clinically to improve the accuracy of multicenter and multimodality evaluation and research. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the performance of histogram analysis in the time course of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for differentiating cancerous tissues from benign tissues in the prostate. Methods: We retrospectively analyzed the histograms of DCE-MRI of 30 patients. Histograms within regions of interest(ROI) in the peripheral zone (PZ) and transitional zone (TZ) were separately analyzed. The maximum difference wash-in slope (MWS) and delay phase slope (DPS) were defined for each voxel. Differences in histogram parameters, namely the mean, standard deviation (SD), the coefficient of variation (CV), kurtosis, skewness, interquartile range (IQR), percentile (P10, P25, P75, P90, and P90P10), Range, and modified full width at half-maximum (mFWHM) between cancerous and benign tissues were assessed. Results: In the TZ, CV for ROIs of 7.5 and 10mm was the only significantly different parameter of the MWS (P = 0.034 and P = 0.004, respectively), whereas many parameters of the DPS (mean, skewness, P10, P25, P50, P75 and P90) differed significantly (P = <0.001–0.016 and area under the curve [AUC] = 0.73–0.822). In the PZ, all parameters of the MWS exhibited significant differences, except kurtosis and skewness in the ROI of 7.5mm(P = <0.001–0.017 and AUC = 0.865–0.898). SD, IQR, mFWHM, P90P10 and Range were also significant differences in the DPS (P = 0.001–0.035). Conclusion: The histogram analysis of DCE-MRI is a potentially useful approach for differentiating prostate cancer from normal tissues. Different histogram parameters of the MWS and DPS should be applied in the TZ and PZ. [ABSTRACT FROM AUTHOR]

Abstract Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54 ± 0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N = 39) revealed a similar correlation of 0.57 ± 0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase. Highlights • Hypercapnia BOLD data can be used to compute functional connectivity metrics. • ICA, region based, and graph-theory based results were all feasible. • Hypercapnia FC metrics were compatible with those obtained with resting-state data. • Hypercapnia FC metrics showed age-dependence similar to those in resting-state data. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the leading cause of degenerative dementia in the aging population. Patients with AD have alterations in cerebral hemodynamic function including reduced cerebral blood flow (CBF) and cerebral metabolic rate. Therefore, improved cerebrovascular function may be an attractive goal for pharmaceutical intervention in AD.Objective: We wished to observe the acute effects of sildenafil on cerebrovascular function and brain metabolism in patients with AD.Methods: We used several novel non-invasive MRI techniques to investigate the alterations of CBF, cerebral metabolic rate of oxygen (CMRO2), and cerebrovascular reactivity (CVR) after a single dose of sildenafil administration in order to assess its physiological effects in patients with AD. CBF, CMRO2, and CVR measurements using MRI were performed before and one hour after the oral administration of 50 mg sildenafil. Baseline Montreal Cognitive Assessment score was also obtained.Results: Complete CBF and CMRO2 data were obtained in twelve patients. Complete CVR data were obtained in eight patients. Global CBF and CMRO2 significantly increased (p = 0.03, p = 0.05, respectively) following sildenafil administration. Voxel-wise analyses of CBF maps showed that increased CBF was most pronounced in the bilateral medial temporal lobes. CVR significantly decreased after administration of sildenafil.Conclusion: Our data suggest that a single dose of sildenafil improves cerebral hemodynamic function and increases cerebral oxygen metabolism in patients with AD. [ABSTRACT FROM AUTHOR]

This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R2 = 0.74, p < 0.005). The hyperintensity of either 250 ± 50 mm3 (larger) or 100 ± 50 mm3 (smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study. [ABSTRACT FROM AUTHOR]

Knowing the patterns of brain differences with age in the young population could lead to a better understanding of the causes of certain psychiatric disorders; however, relevant information is insufficient. Here, a pattern of regional gray matter (GM) that changed with age in a young cohort aged 20–30 years was provided. Extending from previous age studies, all participants were imaged at both 1.5 T and 3 T to address the question of how far the field strength influences results. Fifty-nine young participants aged 20–30 years were scanned at both 1.5 T and 3 T. Voxel-based morphometry (VBM) was used to estimate the GM volume. Some brain regions showed a significant field strength-dependent difference in GM volume. VBM uncovered a significantly age-related increase in the GM volume in the left visual-associated area at 3 T, which was not detected at 1.5 T. In addition, voxels at 1.5 T that revealed a significant age-related reduction in the GM volume were found in the right cerebellum. In conclusion, age-related differences in human brain morphology could even be detected in a young cohort aged 20–30 years; however, the results varied across field strengths. Thus, field strength should be considered an important factor when comparing age-specific brain differences across studies. [ABSTRACT FROM AUTHOR]

Dental implant surgery is a common treatment for missing teeth. Its survival rate is considerably affected by host bone quality and quantity, which is often assessed prior to surgery through dental cone-beam computed tomography (CBCT). Dental CBCT was used in this study to evaluate dental implant sites for (1) differences in and (2) correlations between cancellous bone density and cortical bone thickness among four regions of the jawbone. In total, 315 dental implant sites (39 in the anterior mandible, 42 in the anterior maxilla, 107 in the posterior mandible, and 127 in the posterior maxilla) were identified in dental CBCT images from 128 patients. All CBCT images were loaded into Mimics 15.0 to measure cancellous bone density (unit: grayscale value (GV) and cortical bone thickness (unit: mm)). Differences among the four regions of the jawbone were evaluated using one-way analysis of variance and Scheffe's posttest. Pearson coefficients for correlations between cancellous bone density and cortical bone thickness were also calculated for the four jawbone regions. The results revealed that the mean cancellous bone density was highest in the anterior mandible (722 ± 227 GV), followed by the anterior maxilla (542 ± 208 GV), posterior mandible (535 ± 206 GV), and posterior maxilla (388 ± 206 GV). Cortical bone thickness was highest in the posterior mandible (1.15 ± 0.42 mm), followed by the anterior mandible (1.01 ± 0.32 mm), anterior maxilla (0.89 ± 0.26 mm), and posterior maxilla (0.72 ± 0.19 mm). In the whole jawbone, a weak correlation (r = 0.133, p = 0.041) was detected between cancellous bone density and cortical bone thickness. Furthermore, except for the anterior maxilla (r = 0.306, p = 0.048), no correlation between the two bone parameters was observed (all p > 0.05). Cancellous bone density and cortical bone thickness varies by implant site in the four regions of the jawbone. The cortical and cancellous bone of a jawbone dental implant site should be evaluated individually before surgery. [ABSTRACT FROM AUTHOR]