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NeuroImage Sep 2021Few studies have focused on the connection between glymphatic dysfunction and cerebral small vessel disease (CSVD), partially due to the lack of non-invasive methods to...
Few studies have focused on the connection between glymphatic dysfunction and cerebral small vessel disease (CSVD), partially due to the lack of non-invasive methods to measure glymphatic function. We established modified index for diffusion tensor image analysis along the perivascular space (mALPS-index), which was calculated on diffusion tensor image (DTI), compared it with the classical detection of glymphatic clearance function calculated on Glymphatic MRI after intrathecal administration of gadolinium (study 1), and analyzed the relationship between CSVD imaging markers and mALPS-index in CSVD patients from the CIRCLE study (ClinicalTrials.gov ID: NCT03542734) (study 2). Among 39 patients included in study 1, mALPS-index were significantly related to glymphatic clearance function calculated on Glymphatic MRI ( r = -0.772~-0.844, p < 0.001). A total of 330 CSVD patients were included in study 2. Severer periventricular and deep white matter hyperintensities (β = -0.332, p < 0.001; β = -0.293, p < 0.001), number of lacunas (β = -0.215, p < 0.001), number of microbleeds (β = -0.152, p = 0.005), and severer enlarged perivascular spaces in basal ganglia (β = -0.223, p < 0.001) were related to mALPS-index. Our results indicated that non-invasive mALPS-index might represent glymphatic clearance function, which could be applied in clinic in future. Glymphatic clearance function might play a role in the development of CSVD.
Topics: Adult; Aged; Brain; Cerebral Small Vessel Diseases; Female; Gadolinium DTPA; Glymphatic System; Humans; Magnetic Resonance Imaging; Male; Middle Aged; White Matter
PubMed: 34118396
DOI: 10.1016/j.neuroimage.2021.118257 -
European Radiology Jul 2021To develop radiomics-based nomograms for preoperative microvascular invasion (MVI) and recurrence-free survival (RFS) prediction in patients with solitary hepatocellular...
Multi-scale and multi-parametric radiomics of gadoxetate disodium-enhanced MRI predicts microvascular invasion and outcome in patients with solitary hepatocellular carcinoma ≤ 5 cm.
OBJECTIVES
To develop radiomics-based nomograms for preoperative microvascular invasion (MVI) and recurrence-free survival (RFS) prediction in patients with solitary hepatocellular carcinoma (HCC) ≤ 5 cm.
METHODS
Between March 2012 and September 2019, 356 patients with pathologically confirmed solitary HCC ≤ 5 cm who underwent preoperative gadoxetate disodium-enhanced MRI were retrospectively enrolled. MVI was graded as M0, M1, or M2 according to the number and distribution of invaded vessels. Radiomics features were extracted from DWI, arterial, portal venous, and hepatobiliary phase images in regions of the entire tumor, peritumoral area ≤ 10 mm, and randomly selected liver tissue. Multivariate analysis identified the independent predictors for MVI and RFS, with nomogram visualized the ultimately predictive models.
RESULTS
Elevated alpha-fetoprotein, total bilirubin and radiomics values, peritumoral enhancement, and incomplete or absent capsule enhancement were independent risk factors for MVI. The AUCs of MVI nomogram reached 0.920 (95% CI: 0.861-0.979) using random forest and 0.879 (95% CI: 0.820-0.938) using logistic regression analysis in validation cohort (n = 106). With the 5-year RFS rate of 68.4%, the median RFS of MVI-positive (M2 and M1) and MVI-negative (M0) patients were 30.5 (11.9 and 40.9) and > 96.9 months (p < 0.001), respectively. Age, histologic MVI, alkaline phosphatase, and alanine aminotransferase independently predicted recurrence, yielding AUC of 0.654 (95% CI: 0.538-0.769, n = 99) in RFS validation cohort. Instead of histologic MVI, the preoperatively predicted MVI by MVI nomogram using random forest achieved comparable accuracy in MVI stratification and RFS prediction.
CONCLUSIONS
Preoperative radiomics-based nomogram using random forest is a potential biomarker of MVI and RFS prediction for solitary HCC ≤ 5 cm.
KEY POINTS
• The radiomics score was the predominant independent predictor of MVI which was the primary independent risk factor for postoperative recurrence. • The radiomics-based nomogram using either random forest or logistic regression analysis has obtained the best preoperative prediction of MVI in HCC patients so far. • As an excellent substitute for the invasive histologic MVI, the preoperatively predicted MVI by MVI nomogram using random forest (MVI-RF) achieved comparable accuracy in MVI stratification and outcome, reinforcing the radiologic understanding of HCC angioinvasion and progression.
Topics: Carcinoma, Hepatocellular; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 33447861
DOI: 10.1007/s00330-020-07601-2 -
Cell Host & Microbe Jul 2022Acinetobacter baumannii is a leading cause of hospital-acquired infections, where outbreaks are driven by its ability to persist on surfaces in a desiccated state. Here,...
Acinetobacter baumannii is a leading cause of hospital-acquired infections, where outbreaks are driven by its ability to persist on surfaces in a desiccated state. Here, we show that A. baumannii causes more virulent pneumonia following desiccation and profile the genetic requirements for desiccation. We find that desiccation tolerance is enhanced upon the disruption of Lon protease, which targets unfolded and aggregated proteins for degradation. Notably, two bacterial hydrophilins, DtpA and DtpB, are transcriptionally upregulated in Δlon via the two-component regulator, BfmR. These proteins, both hydrophilic and intrinsically disordered, promote desiccation tolerance in A. baumannii. Additionally, recombinant DtpA protects purified enzymes from inactivation and improves the desiccation tolerance of a probiotic bacterium when heterologously expressed. These results demonstrate a connection between environmental persistence and pathogenicity in A. baumannii, provide insight into the mechanisms of extreme desiccation tolerance, and reveal potential applications for bacterial hydrophilins in the preservation of protein- and live bacteria-based pharmaceuticals.
Topics: Acinetobacter baumannii; Bacterial Proteins; Desiccation; Pentetic Acid; Virulence
PubMed: 35413266
DOI: 10.1016/j.chom.2022.03.019 -
AJNR. American Journal of Neuroradiology Jul 2018
Topics: Animals; Crush Injuries; Gadolinium DTPA; Rats; Sciatic Nerve
PubMed: 29700050
DOI: 10.3174/ajnr.A5661 -
Proceedings of the National Academy of... Jul 2022Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3...
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3 (DLL3) on their cell surface. Taking advantage of DLL3 overexpression, we developed and evaluated lutetium-177 (Lu)-labeled DLL3-targeting antibody SC16 (Lu-DTPA-SC16) as a treatment for NEPC. SC16 was functionalized with DTPA-CHX-A" chelator and radiolabeled with Lu to produce Lu-DTPA-SC16. Specificity and selectivity of Lu-DTPA-SC16 were evaluated in vitro and in vivo using NCI-H660 (NEPC, DLL3-positive) and DU145 (adenocarcinoma, DLL3-negative) cells and xenografts. Dose-dependent treatment efficacy and specificity of Lu-DTPA-SC16 radionuclide therapy were evaluated in H660 and DU145 xenograft-bearing mice. Safety of the agent was assessed by monitoring hematologic parameters. Lu-DTPA-SC16 showed high tumor uptake and specificity in H660 xenografts, with minimal uptake in DU145 xenografts. At all three tested doses of Lu-DTPA-SC16 (4.63, 9.25, and 27.75 MBq/mouse), complete responses were observed in H660-bearing mice; 9.25 and 27.75 MBq/mouse doses were curative. Even the lowest tested dose proved curative in five (63%) of eight mice, and recurring tumors could be successfully re-treated at the same dose to achieve complete responses. In DU145 xenografts, Lu-DTPA-SC16 therapy did not inhibit tumor growth. Platelets and hematocrit transiently dropped, reaching nadir at 2 to 3 wk. This was out of range only in the highest-dose cohort and quickly recovered to normal range by week 4. Weight loss was observed only in the highest-dose cohort. Therefore, our data demonstrate that Lu-DTPA-SC16 is a potent and safe radioimmunotherapeutic agent for testing in humans with NEPC.
Topics: Animals; Antibodies, Monoclonal, Humanized; Carcinoma, Neuroendocrine; Chelating Agents; Humans; Intracellular Signaling Peptides and Proteins; Ligands; Lutetium; Male; Membrane Proteins; Mice; Pentetic Acid; Prostatic Neoplasms; Radioimmunotherapy; Radioisotopes; Xenograft Model Antitumor Assays
PubMed: 35759660
DOI: 10.1073/pnas.2203820119 -
Magnetic Resonance in Medical Sciences... Mar 2022Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an... (Review)
Review
Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an extracellular contrast agent in the early phase after intravenous injection, and then is taken up by hepatocytes later. Using this contrast agent, we can evaluate the hemodynamics of the liver and liver tumors, and can therefore improve the detection and characterization of hepatocellular carcinoma (HCC). Gd-EOB-DTPA helps in the more accurate detection of hypervascular HCC than by other agents. In addition, Gd-EOB-DTPA can detect hypovascular HCC, which is an early stage of the multi-stage carcinogenesis, with a low signal in the hepatobiliary phase. In addition to tumor detection and characterization, Gd-EOB-DTPA contrast-enhanced MR imaging can be applied for liver function evaluation and prognoses evaluation. Thus, Gd-EOB-DTPA plays an important role in the diagnosis of HCC. However, we have to employ optimal imaging techniques to improve the diagnostic ability. In this review, we aimed to discuss the characteristics of the contrast media, optimal imaging techniques, diagnosis, and applications.
Topics: Carcinoma, Hepatocellular; Contrast Media; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging
PubMed: 34421091
DOI: 10.2463/mrms.rev.2021-0031 -
Abdominal Radiology (New York) Nov 2020The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, allowing not only a morphologic but also a functional... (Review)
Review
The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, allowing not only a morphologic but also a functional evaluation of the hepatobiliary system. The mechanism of uptake and excretion of gadoxetic acid via transporters, such as organic anion transporting polypeptides (OATP1,3), multidrug resistance-associated protein 2 (MRP2) and MRP3, has been elucidated in the literature. Furthermore, GA uptake can be estimated on either static images or on dynamic imaging, for example, the hepatic extraction fraction (HEF) and liver perfusion. GA-enhanced MRI has achieved an important role in evaluating morphology and function in chronic liver diseases (CLD), allowing to distinguish between the two subgroups of nonalcoholic fatty liver diseases (NAFLD), simple steatosis and nonalcoholic steatohepatitis (NASH), and help to stage fibrosis and cirrhosis, predict liver transplant graft survival, and preoperatively evaluate the risk of liver failure if major resection is planned. Finally, because of its noninvasive nature, GA-enhanced MRI can be used for long-term follow-up and post-treatment monitoring. This review article aims to describe the current role of GA-enhanced MRI in quantifying liver function in a variety of hepatobiliary disorders.
Topics: Contrast Media; Gadolinium DTPA; Humans; Liver; Liver Neoplasms; Magnetic Resonance Imaging
PubMed: 33034671
DOI: 10.1007/s00261-020-02779-x -
European Radiology Mar 2016Liver-specific MRI is a fast-growing field, with technological and protocol advancements providing more robust imaging and allowing a greater depth of information per...
OBJECTIVES
Liver-specific MRI is a fast-growing field, with technological and protocol advancements providing more robust imaging and allowing a greater depth of information per examination. This article reports the evidence for, and expert thinking on, current challenges in liver-specific MRI, as discussed at the 7th International Forum for Liver MRI, which was held in Shanghai, China, in October 2013.
METHODS
Topics discussed included the role of gadoxetic acid-enhanced MRI in the differentiation of focal nodular hyperplasia from hepatocellular adenoma and small hepatocellular carcinoma (HCC) from small intrahepatic cholangiocarcinoma (in patients with chronic liver disease), the differentiation of low-grade dysplastic nodule (DN) from pre-malignant high-grade DN and early HCC, and treatment planning and assessment of treatment response for patients with HCC and colorectal liver metastasis. Optimization of the gadoxetic acid-enhanced MRI protocol to gain robust arterial and hepatobiliary phase images was also discussed.
RESULTS AND CONCLUSIONS
Gadoxetic acid-enhanced MRI demonstrates added value for the detection and characterization of focal liver lesions and shows promise in a number of new indications, including regional liver functional assessment and patient monitoring after therapy; however, more data are needed in some areas, and further developments are needed to translate cutting-edge techniques into clinical practice.
KEY POINTS
Liver-specific MRI is a fast-growing field, with many technological and protocol advancements. Gadoxetic acid-enhanced MRI demonstrates value for detecting and characterizing focal liver lesions. Gadoxetic acid-enhanced MRI shows promise in regional functional assessment and patient monitoring. Further developments are needed to translate cutting-edge techniques into clinical practice.
Topics: Adenoma, Liver Cell; Carcinoma, Hepatocellular; Cholangiocarcinoma; Contrast Media; Diagnosis, Differential; Focal Nodular Hyperplasia; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Precancerous Conditions
PubMed: 26070500
DOI: 10.1007/s00330-015-3873-2 -
World Journal of Gastroenterology Aug 2020The use of liver magnetic resonance imaging is increasing thanks to its multiparametric sequences that allow a better tissue characterization, and the use of... (Review)
Review
The use of liver magnetic resonance imaging is increasing thanks to its multiparametric sequences that allow a better tissue characterization, and the use of hepatobiliary contrast agents. This review aims to evaluate gadoxetic acid enhanced magnetic resonance imaging in the diagnosis and staging of cholangiocarcinoma and its different clinical and radiological classifications proposed in the literature. We also analyze the epidemiology, risk factors in correlation with clinical findings and laboratory data.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Contrast Media; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Retrospective Studies; Sensitivity and Specificity
PubMed: 32848332
DOI: 10.3748/wjg.v26.i29.4261 -
Korean Journal of Radiology Jan 2019Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses.... (Review)
Review
Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses. However, since the report that nephrogenic systemic fibrosis is linked to the use of GBCAs in subjects with severe renal diseases, accumulating evidence has suggested that GBCAs are not cleared entirely from our bodies; some GBCAs are deposited in our tissues, including the brain. GBCA deposition in the brain is mostly linked to the specific chelate structure of the GBCA: linear GBCAs were responsible for brain deposition in almost all reported studies. This review aimed to summarize the current knowledge about GBCA brain deposition and discuss its clinical implications.
Topics: Brain; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Magnetic Resonance Imaging
PubMed: 30627029
DOI: 10.3348/kjr.2018.0356