Enhancing microbial superoxide generation and conversion to hydroxyl radicals for enhanced bioremediation using iron-binding ligands.

Harnessing bacteria for superoxide production in bioremediation holds immense promise, yet its practical application is hindered by slow production rates and the relatively weak redox potential of superoxide. This study delves into a cost-effective approach to amplify superoxide production using an Arthrobacter strain, a prevalent soil bacterial genus. Our research reveals that introducing a carbon source along with specific iron-binding ligands, including deferoxamine (DFO), diethylenetriamine pentaacetate (DTPA), citrate, and oxalate, robustly augments microbial superoxide generation. Moreover, our findings suggest that these iron-binding ligands play a pivotal role in converting superoxide into hydroxyl radicals by modulating the electron transfer rate between Fe(III)/Fe(II) and superoxide. Remarkably, among the tested ligands, only DTPA emerges as a potent promoter of this conversion process when complexed with Fe(III). We identify an optimal Fe(III) to DTPA ratio of approximately 1:1 for enhancing hydroxyl radical production within the Arthrobacter culture. This research underscores the efficacy of simultaneously introducing carbon sources and DTPA in facilitating superoxide production and its subsequent conversion to hydroxyl radicals, significantly elevating bioremediation performance. Furthermore, our study reveals that DTPA augments superoxide production in cultures of diverse soils, with various soil microorganisms beyond Arthrobacter identified as contributors to superoxide generation. This emphasizes the universal applicability of DTPA across multiple bacterial genera. In conclusion, our study introduces a promising methodology for enhancing microbial superoxide production and its conversion into hydroxyl radicals. These findings hold substantial implications for the deployment of microbial reactive oxygen species in bioremediation, offering innovative solutions for addressing environmental contamination challenges.

Comparison of Different Equations with GFR Measured by Scintigraphy in Kidney Donors.

Background: Technetium-99m diethylene-triamine-pentaacetate (99mTc-DTPA)-based scintigraphy is a convenient way to assess measured glomerular filtration rate (mGFR) in kidney donors. Equations have been developed to calculate GFR in the general population. This study aims to identify the best among commonly employed equations to better predict GFR when compared with scintigraphy-based mGFR. Also, the trends in mGFR values were studied over 1 year post-donation. Materials and Methods: Thirty-four kidney donors were recruited for this study from November 2017 to November 2018 and followed-up for a year. Estimated GFR (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) Equation, Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation, and Nankivell formula; the values were compared to that obtained using 99mTc-DTPA both pre-and post-donation. Correlation and agreement between the eGFR and mGFR were studied using Statistical Package for the Social Sciences (SPSS) version 23.0 and Microsoft Excel. Results: mGFR was augmented by 32.3 ± 27.8% in the remnant kidney post-donation. The baseline mGFR, post-donation mGFR, and the quantum of its increase post-donation did not differ between overweight donors and donors with normal body mass index (BMI). mGFR correlated poorly with all the eGFR equations both pre- and post-donation. Bland-Altman analysis showed weak agreement with significant bias and variance between mGFR and all eGFR equations. Conclusion: In Indian kidney donors, mGFR by 99mTc-DTPA scintigraphy shows poor correlation and agreement with the commonly used eGFR equations. An individualized approach is needed to assess the kidney function of live donors to minimize harm to both the recipient and the donor.

Gd-EOB-DTPA-enhanced MR imaging features of hepatocellular carcinoma in non-cirrhotic liver.

OBJECTIVE: To evaluate clinical, pathological and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) findings of hepatocellular carcinoma (HCC) in non-cirrhotic livers and compare with HCC in cirrhotic livers. METHODS: This retrospective study included patients with pathologically confirmed HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI between January 2015 and October 2021. Propensity scores were utilized to match non-cirrhotic HCCs (NCHCCs) patients with cirrhotic HCCs (CHCCs) patients. The clinical, pathological and MR imaging features of NCHCCs were compared with CHCCs. Correlation between these features and the presence of NCHCCs were analyzed by logistic regression analysis. The predictive efficacy was evaluated using receiver operating characteristic (ROC) analysis. The area under the receiver operating characteristic curve (AUC) was used to compare performance, and the Delong test was used to compare AUCs. RESULTS: After propensity score matching (1:3), a total of 144 patients with HCCs (36 NCHCCs and 108 CHCCs) were included. NCHCCs were larger in tumor size than CHCCs (P < 0.001, Cohen's d = 0.737). NCHCCs were more common in patients who have hepatitis C (5.6 % vs 1.9 %, P > 0.05) or have no known liver disease (11.1 % vs 0.9 %, P = 0.004), while hepatitis B was more common in CHCC patients (83.3 % vs 97.2 %, P = 0.003). Compared with CHCCs, NCHCCs more frequently demonstrated non-smooth tumor margin (P = 0.001, Cramer's V = 0.273), peri-tumoral hyperintensity (P < 0.05, Cramer's V = 0.185), hyperintense and heterogeneous signals in hepatobiliary phase (HBP) (P < 0.05). CHCCs were more likely to have satellite nodules compared to NCHCCs (33.3 % vs 57.4 %, P < 0.05, Cramer's V = 0.209). Based on the univariate and multivariate logistic regression analysis, the tumor size, non-smooth tumor margin, heterogeneous intensity in HBP and satellite nodule were significantly correlated to NCHCCs (P all <0.05). ROC curve analysis demonstrated that tumor size and non-smooth tumor margin were potential imaging predictors for the diagnosis of NCHCC, with AUC values of 0.715 and 0.639, respectively. The combination of the two imaging features for identifying NCHCC achieved an AUC value of 0.761, with a sensitivity of 0.889 and a specificity of 0.630. CONCLUSION: NCHCCs were more likely to show larger tumor size, non-smooth tumor margin, peri-tumoral hyperintensity, as well as hyperintense and heterogeneous signals in HBP at Gd-EOB-DTPA-enhanced MR imaging compared with NCHCCs. Tumor size and non-smooth tumor margin in HBP may help to discriminate NCHCCs.

Multi-echo three-dimensional (3D) Dixon sequence combined with disodium gadolinium for risk stratification of advanced fibrosis in metabolic dysfunction-associated steatotic liver disease.

Background: The hepatic steatosis and fibrosis related to metabolic dysfunction-associated steatotic liver disease (MASLD) are important factors in the progression. The Multi echo three-dimensional (3D) Dixon sequence can obtain a single breath hold scan for a fat fraction map and an R2* map. The R2* value is usually used to evaluate iron deposition. Whether the change in R2* value is related to liver fibrosis after injection of gadolinium disulfide (Gd) should be noted. This study evaluates the value of enhanced magnetic relaxation time in the risk stratification of liver fibrosis by analyzing the changes in R2* before and after Gd enhancement, and explores the potential application of Multi echo 3D Dixon sequence in one-stop evaluation of MASLD. Methods: This retrospective study included 138 MASLD patients who underwent Gadolinum ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI) examination in The First Affiliated Hospital of Chongqing Medical University from June 2020 to December 2021. Finally, 90 subjects were divided into moderate and high-risk fibrosis group and low-risk fibrosis group by two-step assessment of liver fibrosis. Multi-echo 3D chemical shift imaging sequence (Q-Dixon) sequences and gradient-echo T1WI (Vibe-Dixon) sequence were performed during the non-enhanced phase and hepatobiliary phase, respectively, and then the signal-intensity enhancement (SE) and magnetic relaxation-time enhancement (RE) values were calculated. The interobserver correlation coefficient was used to evaluate the consistency between observers. Univariate t-test was used to analyze the differences in RE and SE of liver fibrosis among different risk levels. Delong analysis was performed on receiver operating characteristic (ROC) curve to evaluate the difference in diagnostic efficacy between RE and SE in differentiating the risk level of liver fibrosis. Results: Among the 90 patients, 55 (61.1%) belonged to the low-risk group and 35 (38.9%) belonged to the medium-to-high-risk group. The average RE and SE values were 1.23±0.15 and 1.57±0.23 in the low-risk group and 0.99±0.09 and 1.38±0.21 in both the medium-to-high-risk group (P<0.01). The ROC curve showed that the area under the curve (AUC) value of RE was 0.922, with a corresponding optimal threshold of 0.713, sensitivity of 0.852, and specificity of 0.861. The AUC value of SE was 0.724, with a corresponding optimal threshold of 0.352, sensitivity of 0.519, and specificity of 0.833. The AUC difference between RE and SE for the predictive value of different risk assessments was 0.198, and the 95% confidence interval of the difference was 0.084-0.312. The Delong test showed that the difference was significant (P<0.01). Conclusions: Magnetic RE had high effectiveness for distinguishing between liver-fibrosis risk levels. The combination of the Q-Dixon sequence and Gd-EOB-DTPA has the potential of one-stop evaluation of MASLD.

Head-to-head comparison of contrast-enhanced CT, dual-layer spectral-detector CT, and Gd-EOB-DTPA-enhanced MR in detecting neuroendocrine tumor liver metastases.

PURPOSE: To explore the optimal of kiloelectron voltage (keV) of virtual monoenergetic imaging (VMI) of dual-layer spectral-detector CT (DLCT) in detecting neuroendocrine tumor liver metastases (NETLM) and to investigate diagnostic performance of polyenergetic images (PEI), DLCT, and Gd-EOB-DTPA-enhanced MR. METHODS: Seventy-two patients with suspected NETLM who underwent DLCT and Gd-EOB-DTPA-enhanced MR were retrospectively enrolled. Tumor signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between PEI and VMI at 40-140 keV. Two radiologists read the CT examinations with and without VMI separately in consensus. Two other radiologists read the Gd-EOB-DTPA-enhanced MR in consensus. The diagnostic performance was evaluated. Reference standard was histopathology, follow-up, and interpretation of all available imaging. RESULTS: The highest SNR and CNR were observed at VMI40keV, significantly higher than PEI in the arterial and venous phases (all P<0.01). A total of 477 lesions were identified (396 metastases, 81 benign lesions). Per-lesion AUC was 0.86, 0.91, and 0.97 (PEI, DLCT, and Gd-EOB-DTPA-enhanced MR, respectively). Sensitivity of PEI, DLCT, and Gd-EOB-DTPA-enhanced MRI were 0.76, 0.86, and 0.95, respectively. DLCT significantly improved sensitivity compared to PEI. MR had significantly higher sensitivity than DLCT and PEI. Subgroup analysis demonstrated that the difference in diagnostic performance was concentrated on lesions < 10 mm. CONCLUSION: The image quality of VMI40keV is higher than that of PEI. DLCT with VMI40keV provides better diagnostic sensitivity for NETLM detection than PEI. Gd-EOB-DTPA-enhanced MR yielded the best diagnostic performance for NETLM detection.

MR elastography vs a combination of common non-invasive tests for estimation of severe liver fibrosis in patients with hepatobiliary tumors.

OBJECTIVES: To evaluate the accuracy of combined imaging and blood test indices related to liver fibrosis (LF) compared to magnetic resonance elastography (MRE) for estimating severe LF (F3-4) in preoperative patients. METHODS: This retrospective study included patients who underwent MRE, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, and dynamic CT before liver resection. Liver stiffness measurement (LSM) using MRE, liver-to-spleen signal intensity ratio (LSR) using Gd-EOB-DTPA-enhanced MRI, and spleen volume normalized to body surface area (SV/BSA) using CT volumetry were measured. Laboratory parameters, including levels of type IV collagen 7S and hyaluronic acid, were also measured. Logistic regression and receiver operating characteristic analyses were performed to identify parameters that could estimate severe LF more accurately than LSM alone. RESULTS: A total of 81 patients (mean age, 67 years ± 9.9 [SD]; 58 men) were enrolled. Multivariable logistic regression analysis indicated that LSR (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.05-0.37, p < 0.001), SV/BSA (OR: 1.25, 95% CI: 1.02-1.52, p = 0.03) and type IV collagen 7S (OR: 1.84, 95% CI: 1.12-3.00, p = 0.02) were associated with severe LF. Receiver operating characteristic analysis showed that for estimating severe LF, the area under the curve was significantly larger for the combination of LSR, SV/BSA, and type IV collagen 7S than for LSM alone (0.95 vs 0.85, p = 0.04). CONCLUSION: The combined evaluation of LSR, SV/BSA, and type IV collagen 7S obtained by clinically common preoperative examinations was more accurate than MRE alone for estimating severe LF in preoperative patients. KEY POINTS: Question What indicators among the imaging and blood tests commonly performed preoperatively can provide a more accurate estimate of severe LF compared to MRE? Findings The combination of LSR, SV/BSA, and type IV collagen 7S was more accurate than an LSM alone for estimating severe LF. Clinical relevance A combination of commonly performed non-invasive preoperative tests provides a more accurate estimation of severe LF than MR elastography, an examination with relatively limited.

Non-invasive imaging biomarkers in chronic liver disease.

Chronic liver disease (CLD) is a global and worldwide clinical challenge, considering that different underlying liver entities can lead to hepatic dysfunction. In the past, blood tests and clinical evaluation were the main noninvasive tools used to detect, diagnose and follow-up patients with CLD; in case of clinical suspicion of CLD or unclear diagnosis, liver biopsy has been considered as the reference standard to rule out different chronic liver conditions. Nowadays, noninvasive tests have gained a central role in the clinical pathway. Particularly, liver stiffness measurement (LSM) and cross-sectional imaging techniques can provide transversal information to clinicians, helping them to correctly manage, treat and follow patients during time. Cross-sectional imaging techniques, namely computed tomography (CT) and magnetic resonance imaging (MRI), have plenty of potential. Both techniques allow to compute the liver surface nodularity (LSN), associated with CLDs and risk of decompensation. MRI can also help quantify fatty liver infiltration, mainly with the proton density fat fraction (PDFF) sequences, and detect and quantify fibrosis, especially thanks to elastography (MRE). Advanced techniques, such as intravoxel incoherent motion (IVIM), T1- and T2- mapping are promising tools for detecting fibrosis deposition. Furthermore, the injection of hepatobiliary contrast agents has gained an important role not only in liver lesion characterization but also in assessing liver function, especially in CLDs. Finally, the broad development of radiomics signatures, applied to CT and MR, can be considered the next future approach to CLDs. The aim of this review is to provide a comprehensive overview of the current advancements and applications of both invasive and noninvasive imaging techniques in the evaluation and management of CLD.

Beyond Averages: Unpacking Disparities in School-Based Vaccination Coverage in Eastern Sydney: An Ecological Analysis.

School vaccination programs are crucial for achieving high immunisation coverage among adolescents, but substantial disparities exist across schools and regions. This ecological study aimed to determine associations between school characteristics and vaccination coverage for diphtheria-tetanus-acellular pertussis (dTpa) and human papillomavirus (HPV) vaccines among year 7 students in southeastern Sydney. An analysis of data from 70 mainstream schools participating in the 2019 South Eastern Sydney Local Health District School Vaccination Program utilised quasi-Poisson regression models to assess associations between vaccination coverage and school attendance, socio-educational status, Aboriginal enrolments, language background other than English (LBOTE), school sector (government, Catholic, or independent), and coeducation status. Median school coverage was 88% for dTpa, 88% for HPV-girls, and 86% for HPV-boys, with interquartile ranges of 82-93%, 84-92%, and 78-91%, respectively. Higher school attendance was associated with increased dTpa vaccination coverage (PR 1.14, 95% CI 1.02-1.27). Single-sex schools showed higher HPV vaccination coverage compared to coeducational schools for both girls (PR 2.24, 95% CI 2.04-2.46) and boys (PR 1.89, 95% CI 1.72-2.08). No significant associations were found for ICSEA, Aboriginal enrolments, LBOTE, or school sector. School attendance and coeducational status significantly influenced vaccination coverage, with differential impacts on dTpa and HPV vaccines. These findings highlight the need for targeted strategies to address disparities in school-based vaccination programs. Research using qualitative methods could be useful to understand the beliefs and attitudes contributing to these disparities in vaccine uptake so that programs can be tailored to maximise participation.

Functional liver imaging score (FLIS) can predict adverse events in HCC patients.

PURPOSE: To assess the performance of FLIS in predicting adverse outcomes, namely post-hepatectomy liver failure (PHLF) and death, in patients who underwent liver surgery for malignancies. METHODS: All consecutive patients who underwent liver resection and 1.5 T gadoxetic acid MR were enrolled. PHLF and overall survival (OS) were collected. Two radiologists with 18 and 8 years of experience in abdominal imaging, blinded to clinical data, evaluated all images. Radiologists evaluated liver parenchymal enhancement (EnQS), biliary contrast excretion (ExQS), and signal intensity of the portal vein relative to the liver parenchyma (PVsQs). Reliability analysis was computed with Cohen's Kappa. Cox regression analysis was calculated to determine which factors are associated with PHLF and OS. Area Under the Receiver Operating Characteristic curve (AUROC) was computed. RESULTS: 150 patients were enrolled, 58 (38.7 %) in the HCC group and 92 (61.3 %) in the non-HCC group. The reliability analysis between the two readers was almost perfect (κ = 0.998). The multivariate Cox analysis showed that only post-surgical blood transfusions and major resection were associated with adverse events [HR=8.96 (7.98-9.88), p = 0.034, and HR=0.99 (0.781-1.121), p = 0.032, respectively] in the whole population. In the HCC group, the multivariable Cox analysis showed that blood transfusions, major resection and FLIS were associated with adverse outcomes [HR=13.133 (2.988-55.142), p = 0.009, HR=0.987 (0.244-1.987), p = 0.021, and HR=1.891 (1.772-3.471), p = 0.039]. The FLIS AUROC to predict adverse outcomes was 0.660 (95 %CIs = 0.484-0.836), with 87 % sensitivity and 33.3 % specificity (81.1-94.4 and 22.1-42.1). CONCLUSIONS: FLIS can be considered a promising tool to preoperative depict patients at risk of PHLF and death.

Brain Death Scintigraphy: Do Not Blow the Flow.

Brain death denotes the loss of function in both the cerebrum and the brain stem, leading to coma, absence of spontaneous respiration in the setting of adequate stimulus, and the cessation of all brain stem reflexes. Although spinal reflexes such as deep tendon, plantar flexion, and withdrawal reflexes may persist, recovery is not possible. The cessation of brain function qualifies as death because of its central role in coordinating vital bodily functions. Although brain death is largely determined by a clinical and neurologic examination, confounding variables may necessitate ancillary testing such as cerebral brain perfusion imaging.

99mTc-DMSA and 99mTc-DTPA identified renal dysfunction due to microplastic polyethylene in murine model.

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1 mg/mL)/100 µL of PE for 12 weeks (n = 10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study.

OBJECTIVE: Previous studies have revealed a substantial between-centre variability in DCE-MRI biomarkers of hepatocellular function in rats. This study aims to identify the main sources of variability by comparing data measured at different centres and field strengths, at different days in the same subjects, and over the course of several months in the same centre. MATERIALS AND METHODS: 13 substudies were conducted across three facilities on two 4.7 T and two 7 T scanners using a 3D spoiled gradient echo acquisition. All substudies included 3-6 male Wistar-Han rats each, either scanned once with vehicle (n = 76) or twice with either vehicle (n = 19) or 10 mg/kg of rifampicin (n = 13) at follow-up. Absolute values, between-centre reproducibility, within-subject repeatability, detection limits, and effect sizes were derived for hepatocellular uptake rate (Ktrans) and biliary excretion rate (kbh). Sources of variability were identified using analysis of variance and stratification by centre, field strength, and time period. RESULTS: Data showed significant differences between substudies of 31% for Ktrans (p = 0.013) and 43% for kbh (p < 0.001). Within-subject differences were substantially smaller for kbh (8%) but less so for Ktrans (25%). Rifampicin-induced inhibition was safely above the detection limits, with an effect size of 75 ± 3% in Ktrans and 67 ± 8% in kbh. Most of the variability in individual data was accounted for by between-subject (Ktrans = 23.5%; kbh = 42.5%) and between-centre (Ktrans = 44.9%; kbh = 50.9%) variability, substantially more than the between-day variation (Ktrans = 0.1%; kbh = 5.6%). Significant differences in kbh were found between field strengths at the same centre, between centres at the same field strength, and between repeat experiments over 2 months apart in the same centre. DISCUSSION: Between-centre bias caused by factors such as hardware differences, subject preparations, and operator dependence is the main source of variability in DCE-MRI of liver function in rats, closely followed by biological between-subject differences. Future method development should focus on reducing these sources of error to minimise the sample sizes needed to detect more subtle levels of inhibition.

Relationship between 1,5-anhydroglucitol and renal function assessed by dynamic renal scintigraphy in type 2 diabetes.

CONTEXT: The reliability of serum 1,5-anhydroglucitol (1,5-AG) in type 2 diabetic patients with renal insufficiency remains controversial. OBJECTIVE: To evaluate the relationship between renal function and serum 1,5-AG, and to assess the extent to which renal function influences 1,5-AG. METHODS: A total of 5337 participants with type 2 diabetes were enrolled. The measured glomerular filtration rate (mGFR) was assayed using 99mTc-DTPA dynamic renal scintigraphy. All subjects were stratified into five groups based on mGFR (≥ 120 [n = 507], 90-120 [n = 2015], 60-90 [n = 2178], 30-60 [n = 604], and < 30 mL/min/1.73 m2 [n = 33]). RESULTS: Overall, the serum 1,5-AG and mGFR levels were 3.3 (1.7-7.0) µg/mL and 88.6 ± 24.1 mL/min/1.73 m2, respectively. mGFR was found to be negatively correlated with 1,5-AG levels (r = -0.189, P < 0.001). Multiple linear regression revealed that mGFR was independently and negatively related to serum 1,5-AG after adjusting for covariates including HbA1c (P < 0.001). In subgroups with mGFR ≥ 30 mL/min/1.73 m2, the correlation coefficients between 1,5-AG and HbA1c, fasting plasma glucose, postprandial plasma glucose, and the differences between postprandial and fasting plasma glucose remained significant (range from -0.126 to -0.743, all P < 0.01). However, the link between 1,5-AG and traditional glycemic markers was attenuated in individuals with mGFR < 30 mL/min/1.73 m2. Sensitivity analysis after excluding anemic patients showed similar results regarding the relationship between serum 1,5-AG and HbA1c across the mGFR subgroups. CONCLUSIONS: Although we observed a weak inverse correlation (r = -0.189) between mGFR and serum 1,5-AG in type 2 diabetes, 1,5-AG remains a valid marker for assessing glucose control in subjects with mild or moderate renal dysfunction.

Differentiating Well-Differentiated from Poorly-Differentiated HCC: The Potential and the Limitation of Gd-EOB-DTPA in the Presence of Liver Cirrhosis.

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease.

Breakthrough of Hypoxia Limitation by Tumor-Targeting Photothermal Therapy-Enhanced Radiation Therapy.

Purpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers. Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity. Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors. Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.

Enhanced thorium decorporation and mitigation of toxicity through combined use of Liv52® and diethylenetriamine pentaacetate.

Thorium-232 (Th-232) is a promising fuel for advanced nuclear reactors. However, in case of internal human exposure to Th, there is currently no effective modality for its removal from liver and skeleton or for mitigating its effect. The FDA-approved agent, diethylenetriaminepentaacetate (DTPA), can remove Th and other actinides from blood circulation only. For the first time, a rationally-selected polyherbal hepatoprotective i.e. Liv52® (L52S), was evaluated in-combination with DTPA for its Th decorporation ability in Swiss mice. Inductively-coupled plasma mass spectroscopic analysis showed that oral administration of L52S in conjunction with DTPA significantly decreased Th burden from liver (20 %) and skeleton (33 %) as well as enhanced Th excretion (∼2.5 folds) through urine in comparison to DTPA or L52S alone. The combinatorial therapy was found to be complementary in-action, ameliorating Th-induced tissue damage in liver, spleen, and bone more effectively than monotherapy. Furthermore, markers of liver function (alanine transaminase) and liver inflammation and fibrosis (NF-κB & keratin) further validated the beneficial effect of L52S. The human consumption of L52S for various liver disorders further supports its clinical application for Th decorporation and mitigation of its health effects.

Synthesis of Gd-DTPA Carborane-Containing Compound and Its Immobilization on Iron Oxide Nanoparticles for Potential Application in Neutron Capture Therapy.

Cancer is one of the leading causes of global mortality, and its incidence is increasing annually. Neutron capture therapy (NCT) is a unique anticancer modality capable of selectively eliminating tumor cells within normal tissues. The development of accelerator-based, clinically mountable neutron sources has stimulated a worldwide search for new, more effective compounds for NCT. We synthesized magnetic iron oxide nanoparticles (NPs) that concurrently incorporate boron and gadolinium, potentially enhancing the effectiveness of NCT. These magnetic nanoparticles underwent sequential modifications through silane polycondensation and allylamine graft polymerization, enabling the creation of functional amino groups on their surface. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray (EDX), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and transmission electron microscopy (TEM). ICP-AES measurements indicated that boron (B) content in the NPs reached 3.56 ppm/mg, while gadolinium (Gd) averaged 0.26 ppm/mg. Gadolinium desorption was observed within 4 h, with a peak rate of 61.74%. The biocompatibility of the NPs was confirmed through their relatively low cytotoxicity and sufficient cellular tolerability. Using NPs at non-toxic concentrations, we obtained B accumulation of up to 5.724 × 1010 atoms per cell, sufficient for successful NCT. Although limited by its content in the NP composition, the Gd amount may also contribute to NCT along with its diagnostic properties. Further development of the NPs is ongoing, focusing on increasing the boron and gadolinium content and creating active tumor targeting.

Preoperative and postoperative MRI-based models versus clinical staging systems for predicting early recurrence in hepatocellular carcinoma.

BACKGROUND: To predict the early recurrence of HCC patients who received radical resection using preoperative variables based on Gd-EOB-DTPA enhanced MRI, followed by the comparison with the postoperative model and clinical staging systems. METHODS: One hundred and twenty-nine HCC patients who received radical resection were categorized into the early recurrence group (n = 48) and the early recurrence-free group (n = 81). Through COX regression analysis, statistically significant variables of laboratory, pathologic, and Gd-EOB-DTPA enhanced MRI results were identified. The preoperative and postoperative models were established to predict early recurrence, and the prognostic performances and differences were compared between the two models and clinical staging systems. RESULTS: Six variables were incorporated into the preoperative model, including alpha-fetoprotein (AFP) level, aspartate aminotransferase/platelet ratio index (APRI), rim arterial phase hyperenhancement (rim APHE), peritumoral hypointensity on hepatobiliary phase (HBP), CERHBP (tumor-to-liver SI ratio on hepatobiliary phase imaging), and ADC value. Moreover, the postoperative model was developed by adding microvascular invasion (MVI) and histological grade. The C-index of the preoperative model and postoperative model were 0.889 and 0.901 (p = 0.211) respectively. Using receiver operating characteristic curve analysis (ROC) and decision curve analysis (DCA), it was determined that the innovative models we developed had superior predictive capabilities for early recurrence in comparison to current clinical staging systems. HCC patients who received radical resection were stratified into low-, medium-, and high-risk groups on the basis of the preoperative and postoperative models. CONCLUSION: The preoperative and postoperative MRI-based models built in this study were more competent compared with clinical staging systems to predict the early recurrence in hepatocellular carcinoma.

The Combination of Gd-EOB-DTPA Enhanced T1 Mapping with Apparent Diffusion Coefficient could Improve the Diagnostic Efficacy of Hepatocellular Carcinoma Grading.

BACKGROUND: Accurately predicting the hepatocellular carcinoma (HCC) grade may facilitate the rational selection of treatment strategies. The diagnostic efficacy of the combination of Gadolinium ethoxybenzy diethylenetriamine pentaacetic (Gd-EOB-DTPA) enhancement T1 mapping and apparent diffusion coefficient (ADC) values in predicting HCC grade needs further validation. OBJECTIVES: This study aimed to assess the capacity of Gd-EOB-DTPA-enhanced T1 mapping and ADC values, both individually and in combination, to discriminate between different grades of HCC. MATERIALS AND METHODS: From July 2017 to February 2020, 96 patients (male, 83; mean age, 53.67 years; age range, 29-71 years) clinically diagnosed with HCC were included in the present study. All patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI, including T1 mapping sequence) before surgery or biopsy. All the patients were categorized into 3 groups according to the pathological results (including 24 cases of well-differentiated HCCs, 59 cases of moderately differentiated HCCs, 13 cases of and poorly differentiated HCCs). The mean Gd-EOB-DTPA enhanced T1 values (ΔT1=[(T1pre-T1post)/T1pre]×100%) and ADC values between different grading groups of HCC were calculated and compared. The area under the characteristics curve (AUC), the diagnostic threshold, sensitivity, and specificity of ΔT1 and ADC for differential diagnosis were analyzed. RESULTS: Mean ΔT1 was 58% for well-differentiated HCCs, 50% for moderately-differentiated HCCs, and 43% for poorly-differentiated HCCs. ΔT1 showed statistical differences between the groups (P<0.001). The mean ADC values of the 3 groups were 1.11×10-3 mm2/s, 0.91×10-3 mm2/s, and 0.80×10-3mm2/s, respectively. ADC showed statistical differences between the groups (P<0.001). In discriminating well- differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.751 (95% CI: 0.642, 0.859), the AUC of ADC was 0.782 (95% CI: 0.671, 0.894), the AUC of combined model was 0.811 (95% CI: 0.709, 0.914). In discriminating the poorly differentiated group from the moderately differentiated group, the AUC of ΔT1 was 0.768 (95% CI: 0.634, 0.902), the AUC of ADC was 0.754 (95% CI: 0.603, 0.904), and the AUC of the combined model was 0.841 (95% CI: 0.729, 0.953). CONCLUSION: Gd-EOB-DTPA enhanced T1 mapping, and ADC values have complementary effects on the sensitivity and specificity for identifying different HCC grades. A combined model of Gd-EOB-DTPA-enhanced MRI T1 mapping and ADC values could improve diagnostic performance for predicting HCC grades.

Comparative analysis of the performance of hepatobiliary agents in depicting MRI features of microvascular infiltration in hepatocellular carcinoma.

OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.