Simultaneous Denoising of Dynamic PET Images Based on Deep Image Prior.

Parametric imaging obtained from kinetic modeling analysis of dynamic positron emission tomography (PET) data is a useful tool for quantifying tracer kinetics. However, pixel-wise time-activity curves have high noise levels which lead to poor quality of parametric images. To solve this limitation, we proposed a new image denoising method based on deep image prior (DIP). Like the original DIP method, the proposed DIP method is an unsupervised method, in which no training dataset is required. However, the difference is that our method can simultaneously denoise all dynamic PET images. Moreover, we propose a modified version of the DIP method called double DIP (DDIP), which has two DIP architectures. The additional DIP model is used to generate high-quality input data for the second DIP model. Computer simulations were performed to evaluate the performance of the proposed DIP-based methods. Our simulation results showed that the DDIP method outperformed the single DIP method. In addition, the DDIP method combined with data augmentation could generate PET parametric images with superior image quality compared to the spatiotemporal-based non-local means filtering and high constrained backprojection. Our preliminary results show that our proposed DDIP method is a novel and effective unsupervised method for simultaneously denoising dynamic PET images.

Generation of Brain Dual-Energy CT from Single-Energy CT Using Deep Learning.

Deep learning (DL) has shown great potential in conversions between various imaging modalities. Similarly, DL can be applied to synthesize a high-kV computed tomography (CT) image from its corresponding low-kV CT image. This indicates the feasibility of obtaining dual-energy CT (DECT) images without purchasing a DECT scanner. In this study, we investigated whether a low-to-high kV mapping was better than a high-to-low kV mapping. We used a U-Net model to perform conversions between different kV CT images. Moreover, we proposed a double U-Net model to improve the quality of original single-energy CT images. Ninety-eight patients who underwent brain DECT scans were used to train, validate, and test the proposed DL-based model. The results showed that the low-to-high kV conversion was better than the high-to-low kV conversion. In addition, the DL-based DECT images had better signal-to-noise ratios (SNRs) than the true (original) DECT images, but at the expense of a slight loss in spatial resolution. The mean CT number differences between the true and DL-based DECT images were within [Formula: see text] 1 HU. No statistically significant difference in CT number measurements was found between the true and DL-based DECT images (p > 0.05). The DL-based DECT images with improved SNR could produce low-noise virtual monoenergetic images. Our preliminary results indicate that DL has the potential to generate brain DECT images using single-energy brain CT images.

Anti-apoptotic effect of San Huang Shel Shin Tang cyclodextrin complex (SHSSTc) on CCl4 -induced hepatotoxicity in rats.

The metabolic loading is heavier in liver especially when injured or inflammation. San Huang Shel Shin Tang (SHSST) was an old traditional herbal decoction, which composed with Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (1:1:2 in weight), can provide a liver protection effects. We used a beta-cyclodextrin (ß-CD) drug modification method in reduce of the necessary dose of the SHSST. As the results, the FAS-FADD expressions leaded apoptosis in CCl4 intraperitoneal (IP) injection induced acute liver injury in rats. Silymarin, baicalein, SHSST, and SHSST ß-CD complex (SHSSTc) pretreatments protected liver through the decreasing of the expressions of FAS-FADD and downstream caspase-3 and caspase-8. Particularly, SHSSTc (30 mg/kg day) treatment enhanced cell survival pathway activation through the PI3K, Akt and Bad phosphorylation. Compared with SHSST as well as silymarin and baicalein, SHSSTc provided a magnificent liver protection effect, especially in survival pathway activation/TUNEL-apoptotic cell reduction/serum cholesterol level suppression. All these data suggested that ß-CD complex modified the SHSST and promoted the bioavailability and liver protection effects. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 663-670, 2016.

Anti-apoptosis effects on hearts of SHSST cyclodextrin complex in a carbon tetrachloride-induced cirrhotic cardiomyopathy rat model.

Cirrhotic cardiomyopathy (CCM) is a common cardiac dysfunction in patients waiting for orthotopic liver transplantation (OLT). Carbon tetrachloride (CCl4) intraperitoneal (IP) injection has been reported as successful in a cirrhosis-induced CCM model. In this work, we used the same assay for CCM induction using CCl4 (0.2 mg/kg) IP injection twice per day for 14 days during the cardiac protection drugs treatment process. The cardiac protection drugs were silymarin (100 mg/kg/day), baicalein (30 mg/kg/day), San Huang Shel Shin Tang (SHSST, 30 mg/kg/day) and ß-cyclodextrin modified SHSST (SHSSTc, 30 mg/kg/day and 300 mg/kg/day). After 4 weeks of treatment, the SHSSTc cardiac protection effects were determined through activation of the IGF1R cell survival pathway and inhibition of Fas-FADD death domain induced-apoptosis. SHSSTc cardiac protection was enhanced through ß-cyclodextrin modification, which increased bio-availability, and displayed stronger protective effects than silymarin and baicalein, both of which are well-known liver protection drugs. Thus, SHSSTc might provide the best therapeutic benefit in CCM treatment.

SHSST cyclodextrin complex prevents the fibrosis effect on CCl4-induced cirrhotic cardiomyopathy in rats through TGF-ß pathway inhibition effects.

Patients with liver cirrhosis also have subtle cardiac structure or function abnormalities. This cardiac dysfunction commonly occurs in 56% of waiting orthotopic liver transplantation (OLT) patients and is defined as cirrhotic cardiomyopathy (CCM). Up to now, there is no standard treatment because CCM does not have a solidly established diagnosis and is based on high clinical suspicion. The liver function of CCM is particularly limited, making patients vulnerable to more drug treatments. Here, we use silymarin (100 mg/kg/day), baicalein (30 mg/kg/day), San Huang Shel Shin Tang (SHSST, 30 mg/kg/day) and ß-cyclodextrin modified SHSST (SHSSTc, 30 and 300 mg/kg/day) treatments for a CCl4-induced CCM rat model. The results show that silymarin, baicalein and SHSST treatments can only slightly reduce the collagen accumulation in CCM rat hearts. However, SHSSTc treatment protects the heart in CCM and significantly inhibits collagen acumination and the fibrosis regulating transforming growth factor-ß (TGF-ß) pathway expression. SHSSTc treatments further reduced the heart weight and the ratio between left ventricular weight (LVW) and tibia length (TL). This experimental data show that water solubility improved ß-cyclodextrin modified Chinese herbal medicine formula (SHSSTc) can provide an excellent heart protection effect through TGF-ß pathway inhibition.

In-hospital mortality predictors among hospitalized adults and those with chronic kidney disease with dengue.

BACKGROUND: Accurately identifying risk factors that predict fatality in dengue is crucial for patient triage and clinical management. Our objective was to identify predictors of death associated with dengue and investigate the clinical characteristics and risk factors among patients with chronic kidney disease (CKD) who died from dengue. METHODS: A multicenter longitudinal observation study conducted from 2008 to 2019. RESULTS: A total of 1272 patients (113 who died and 1186 who recovered) diagnosed with dengue were included. Old age, CKD, and an elevated white blood cell count at hospital presentation were identified as independent predictors of in-hospital mortality among individuals infected with the dengue virus. In a subgroup analysis of 138 patients with CKD infected with dengue virus, 64 (46.3%) patients died, with 46 (33.3%) patients dying within 7 days after symptom onset. Among 64 fatal dengue patients with CKD, 34.4% were in stages 2 and 3 of kidney disease, 51.5% were in stages 4 and 5, and 14.1% had end stage renal disease as per the classification by Kidney Disease Improving Global Outcomes. Multivariate analysis revealed that initial altered consciousness, pulmonary edema, and leukocytosis during hospitalization were independently associated with in-hospital mortality in CKD patients infected with the dengue virus. Leukocytosis during hospitalization and severe hepatitis were independent risk factors for death within 7 days after dengue illness onset in CKD patients. CONCLUSIONS: This study offers valuable insights into predictors linked to fatality in dengue and reinforces the importance of optimizing patient triage to improve the quality of care.

Pathological humerus fracture due to anti-interferon-gamma autoantibodies: A case report.

BACKGROUND: Various etiologies contribute to pathological fractures, including bone infections. Recently, non-tuberculosis Mycobacterium-related bone infections among patients with anti-interferon-gamma autoantibody-induced adult-onset immunodeficiency has raised concerns in Southeast Asia, with the common presentations including osteomyelitis. However, it also rarely manifests as traumatic fractures, as reported in this case. CASE SUMMARY: A diabetic female fractured her humerus after a traumatic accident and received fixation surgery. Abnormal necrotic bone tissue and abscess formation were noted, and she was diagnosed with a pathological fracture due to non-tuberculosis Mycobacterium infection. Multiple bone involvement was also revealed in a bone scan. Anti-interferon-gamma autoantibodies were then checked due to an unexplained immunocompromised status and found to be positive. Her humerus fracture and multiple bone infections healed after steroid and anti-non-tuberculosis Mycobacterium medication treatment following fixation surgery. CONCLUSION: Comprehensive preoperative evaluations may help identify pathological fractures and guide the treatment course.

Predicting admission to post-acute inpatient rehabilitation in patients with acute stroke.

OBJECTIVE: To identify predictors of admission to post-acute inpatient rehabilitation settings follow-ing acute care for stroke survivors in Taiwan. DESIGN: Prospective observation study. PARTICIPANTS: Stroke survivors (n = 558) admitted to acute care wards for inpatient rehabilitation (62% male; mean age 60.0 ± 12.2 years). METHODS: The primary outcome was whether survivors were admitted to post-acute inpatient rehabilitation settings after discharge from acute care wards. Logistic regression model was adopted to examine the predictors of admission to post-acute inpatient rehabilitation. A receiver operating characteristic curve was drawn to compute the ability of the predictors to discriminate the outcome. RESULTS: Multivariate analysis results indicated Activity Measure Post-Acute Care "6-Clicks" Basic Mobility score to be the only significant predictor of admission to post-acute inpatient rehabilitation (odds ratio = 0.44, 95% confidence interval: 0.34-0.56). Receiver operating characteristic curve analysis results indicated that the cut-off point for Basic Mobility was 13 (standardized score: 33.99). This yielded a sensitivity value of 0.98 and a specificity value of 0.96 for determining the admission to post-acute inpatient rehabilitation. CONCLUSION: Activity Measure Post-Acute Care "6-Clicks" Basic Mobility subscale scores at admission for acute care can predict admission to post-acute inpatient rehabilitation for stroke survivors in Taiwan. This tool can aid clinicians in formulating adequate discharge plans at an early stage, and thus improve the quality of care.

SHSST-cyclodextrin complex inhibits TGF-ß/Smad3/CTGF to a greater extent than silymarin in a rat model of carbon tetrachloride-induced liver injury.

At present, cirrhosis is an incurable liver disease. Transforming growth factor ß (TGF­ß) is important in myofibroblast induction during the cirrhosis initiation process. The current approach in the development of hepatoprotective drugs depends on TGF­ß inhibition. San Huang Shel Shin Tang (SHSST) is a traditional herbal decoction able to exert a protective effect on the liver, however, similar to silymarin, it is limited by its hydrophobicity. In the present study, SHSST was modified with ß­cyclodextrin to form a hydrophilic complex, which improved its bioavailability. In the carbon tetrachloride­induced acute injury animal model, the effects of pretreatment with silymarin, baicalein, SHSST and the SHSST­ß­CD­complex (SHSSTc) at a low and high dose were assessed. The biopsy results revealed marked liver protection following treatment with silymarin, baicalein and SHSST and these effects were improved further following pretreatment with SHSSTc. Protein analysis demonstrated that the hepatoprotective effects of silymarin occurred through inhibition of the TGF­ß/Smad­3/connective tissue growth factor (CTGF) signaling pathway. SHSSTc exerted the same protective mechanism, however, SHSSTc suppressed CTGF level to a greater extent compared with the groups treated with SHSST or silymarin. Only pretreatment with SHSST and SHSSTc exhibited partial enhancement in the expression of proteins involved in the regulation of liver regeneration, including extracellular­signal­regulated kinase 5, phospho­nuclear factor of activated T cells 3 and phospho­GATA4.