Assessment of renal and hepatic dysfunction by co-exposure to toxic metals (Cd, Pb) and fluoride in people living nearby an industrial zone.

Togo's phosphate processing plant at Kpeme discharges waste, containing Cd, Pb, and fluoride, into the sea and on the soil. Heavy metals toxicity on kidneys and the liver has been studied. However, fluoride toxicity on these organs remains to be investigated. The present study deals with the variation in renal and hepatic functioning parameters due to fluoride, Cd and Pb. Totally, 350 volunteers were recruited from five different localities around this phosphate processing plant for sample collection. Cd and Pb contents in blood samples were determined by spectrophotometry and fluoride by the titanium chloride method. Biochemical parameters were measured using Biolab kits. The pollutant contents were elevated in polluted areas where ASAT, ALAT, creatinine, and urea increased, and total protein decreased. Correlation and multivariate tests showed that fluoride is related to the various pathologies mentioned. PCA revealed that phosphate processing in Togo is a source of renal and hepatic toxicity.

A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion.

No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = - 0.874, P < 0.001), AST (R = - 0.812, P = 0.004) and ALT (R = - 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.

Assessment of renal and hepato-protective potential of guava leaves in male Sprague dawley rats.

Present research project was an attempt to explore the functional/nutraceutical worth of guava leaves from two locally grown varieties (Ruby & Safeda). For the purpose, guava leaves extract was fed to experimental male Sprague Dawley rats to explore the nutraceutical potential of guava leaves against hepatotoxicity. Two studies were performed on two types of rats i.e. study I (normal rats), study II (hepatotoxic rats). In both studies, 250 mg/kg each of pink guava leaves extracts (T1) and white guava leaves extracts (T2) was added in the feed. Feed intake and body weights of the rats were recorded. At the end of the first and eighth week of study, the blood samples of the rats were analyzed to check the effect of guava leaves extracts on renal functioning (Alkaline Phosphatase, Alanine Transaminase and Aspartate Transaminase) as well as liver functioning parameters including urea and creatinine. In both studies, comparatively higher feed consumption was observed in the control group than the rest of the treatments. At the end of study I, the highest weight (207±9.21 g) was observed in T0 whereas, during study II, the maximum value (202±5.58 g) was found in T2 (rats consuming white guava leaves extract) that indicates its effectiveness against hepatotoxicity. Regarding renal functioning tests, pink guava leaves were more effective in decreasing urea and creatinine levels in rats as compared to the white guava leaves in both study plans. Likewise, in each of study trial, pink guava leaves were more effective in reducing AST, ALT and ALP than white guava leaves and control. From the present investigation, it is deduced that guava leaves were effective against hepatotoxicity.

Cost-utility analysis of selective internal radiation therapy with Y-90 resin microspheres in hepatocellular carcinoma.

Background: The study assessed the cost-utility of selective internal radiation therapy (SIRT) with Y-90 resin microspheres versus sorafenib in UK patients with unresectable hepatocellular carcinoma ineligible for transarterial chemoembolization. Materials & methods: A lifetime partitioned survival model was developed for patients with low tumor burden (≤25%) and good liver function (albumin-bilirubin grade 1). Efficacy, safety and quality of life data were from a European Phase III randomized controlled trial and published studies. Resource use was from registries and clinical surveys. Results: Discounted quality-adjusted life-years were 1.982 and 1.381, and discounted total costs were £29,143 and 30,927, for SIRT and sorafenib, respectively. Conclusion: SIRT has the potential to be a dominant (more efficacious/less costly) or cost-effective alternative to sorafenib in patients with unresectable hepatocellular carcinoma.

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment.

The recently introduced microphysiological systems (MPS) cultivating human organoids are expected to perform better than animals in the preclinical tests phase of drug developing process because they are genetically human and recapitulate the interplay among tissues. In this study, the human intestinal barrier (emulated by a co-culture of Caco-2 and HT-29 cells) and the liver equivalent (emulated by spheroids made of differentiated HepaRG cells and human hepatic stellate cells) were integrated into a two-organ chip (2-OC) microfluidic device to assess some acetaminophen (APAP) pharmacokinetic (PK) and toxicological properties. The MPS had three assemblies: Intestine only 2-OC, Liver only 2-OC, and Intestine/Liver 2-OC with the same media perfusing both organoids. For PK assessments, we dosed the APAP in the media at preset timepoints after administering it either over the intestinal barrier (emulating the oral route) or in the media (emulating the intravenous route), at 12 µM and 2 µM respectively. The media samples were analyzed by reversed-phase high-pressure liquid chromatography (HPLC). Organoids were analyzed for gene expression, for TEER values, for protein expression and activity, and then collected, fixed, and submitted to a set of morphological evaluations. The MTT technique performed well in assessing the organoid viability, but the high content analyses (HCA) were able to detect very early toxic events in response to APAP treatment. We verified that the media flow does not significantly affect the APAP absorption whereas it significantly improves the liver equivalent functionality. The APAP human intestinal absorption and hepatic metabolism could be emulated in the MPS. The association between MPS data and in silico modeling has great potential to improve the predictability of the in vitro methods and provide better accuracy than animal models in pharmacokinetic and toxicological studies.

Assessment of liver and renal functions in human immunodeficiency virus-infected persons on highly active antiretroviral therapy: A mixed cohort study.

BACKGROUND: Indian data on potential hepatorenal toxic effects of highly active antiretroviral therapy (HAART) in HIV/AIDS-affected persons is lacking. OBJECTIVES: To assess hepatorenal abnormalities in HIV-infected persons on HAART in a hospital-based mixed cohort study using concurrent and nonconcurrent data analysis. METHODS: Hepatorenal function tests, urinalysis and ultrasonogaphy for liver/kidneys (when applicable) were assessed in 400 (men 185; women 215) persons aged 2-84 (mean 47.8) years on HAART. Acute liver toxicity, acute kidney injury and chronic kidney disease were defined depending upon abnormal serum alanine aminotransferase, urea and creatinine levels/clearance as per standard guidelines. RESULTS: The duration of HAART was 1 month to 9 years (mean 3.7 years) with 284 (71%) individuals being on treatment for ≤5years. The major HAART regimens included zidovudine + lamivudine + nevirapine in 175 (43.8%), tenofovir + lamivudine + efavirenz in 174 (43.5%) and zidovudine + lamivudine + efavirenz in 20 (5%) individuals and were associated with grade-1 hepatic dysfunction in 57 (14.3%) individuals, with men aged between 31 and 45 years on antiretroviral therapy for >5 years being mainly affected. Forty two (17.1%) of 246 individuals with anemia and 15 (9.7%) of 154 individuals without anemia showed hepatic dysfunction. None had acute kidney injury, chronic kidney disease or abnormal urinalysis or ultrasonography. In contrast, the pretreatment elevated serum alanine amiotranerase in 99 (22.3%) and blood urea and/or creatinine levels in 16 (4%) individuals decreased significantly post highly active antiretroviral therapy. CONCLUSIONS: The study reflects the low frequency of regimen based highly active antiretroviral therapy-associated hepatic or nephrotoxicity despite prolonged use, especially in the absence of other risk factors. Preexisting anemia appears an important risk factor for highly active antiretroviral therapy-induced hepatotoxicity (OR 1.90, Cl 95% CI 1.02-3.57, P = 0.04). Highly active antiretroviral therapy-associated nephrotoxicity was not a significant problem. Study of viral load or other risk factors and potential of each drug for hepatorenal toxicity/dysfunction in HIV affected were not part of the study. A small number of subjects and retrospective analysis of biochemical parameters were other important limitations.

Assessment of abdominal organ motion using cine magnetic resonance imaging in different gastric motilities: a comparison between fasting and postprandial states.

This study assessed abdominal organ motion induced by gastroduodenal motilities in volunteers during fasting and postprandial states, using cine magnetic resonance imaging (cine-MRI). Thirty-five volunteers underwent cine-MRI while holding their breath in the fasting and postprandial states. Gastric motility was quantified by the amplitude and velocity of antral peristaltic waves. Duodenal motility was evaluated as the change of duodenal diameter. Abdominal organ motion was measured in the liver, pancreas and kidneys. Motion was quantified by calculating maximal organ displacement in the left-right, antero-posterior and caudal-cranial directions. Median antral amplitude and velocity in the fasting and postprandial states were 7.7 and 15.1 mm (P < 0.01), and 1.3 and 2.5 mm/s (P < 0.01), respectively. Duodenal motility did not change. Median displacement for all organs ranged from 0.9 to 2.9 mm in the fasting state and from 1.0 to 2.9 mm in the postprandial state. Significant increases in abdominal organ displacement in the postprandial state were observed in the right lobe of the liver, pancreatic head and both kidneys. Differences in the median displacement of these organs between the two states were all <1 mm. Although the motion of several abdominal organs increased in the postprandial state, the difference between the two states was quite small. Thus, our study suggests that treatment planning and irradiation need not include strict management of gastric conditions, nor the addition of excess margins to compensate for differences in the intra-fractional abdominal organ motion under different gastric motilities in the fasting and postprandial states.

Assessment of the structural reorganization of liver and biochemical parameters of blood serum after introduction of zinc nanoparticles and its oxides.

The demand for nanoparticles of metals and their oxides in medicine and biology is indisputable. To ensure the safe use of the unique capabilities of nanostructures, in particular, essential metals and their oxides, and to further search for ways leveling side effects of toxic effects in biomedical applications, a multifaceted approach to the study of their properties is needed, primarily affecting the effects on the organism level. In this connection, the purpose of the present research was to study the effect of zinc nanoparticles (ZnNPs) and zinc oxide nanoparticles (ZnONPs) on structural reorganization of the liver and morpho-biochemical parameters of rat blood. The test substances exhibit a hepatotoxic effect upon their single intraperitoneal administration to rats. In the experiment, increased activity of gamma glutamyltransferase (GGT) and lactate dehydrogenase (LDH), increased expression of caspase-3, the presence of signs of oxidative stress, inflammation, and capillary-trophic insufficiency, and induction of tumor necrosis factor (TNF-α), and colony stimulating factor 2 (granulocyte-macrophage) (GM-CSF) were registered in the experiment. The level of interferon-γ in the experimental groups tended to decrease in comparison with the control group. The observed effects progressed in time, most noticeably manifested in the case of ZnONPs. Comparing the dosages, ZnNPs are less toxic than ZnONPs.

Practical guidelines for the use of technetium-99m mebrofenin hepatobiliary scintigraphy in the quantitative assessment of liver function.

Surgical resection remains the most important curative treatment for liver tumors; however, it harbors the risk of developing posthepatectomy liver failure. The principal risk is associated with the quality and quantity of the future remnant liver. Therefore, preoperative assessment of the future remnant liver is essential in patients scheduled for major liver resection. Technetium-99m mebrofenin hepatobiliary scintigraphy (HBS) in combination with single-photon emission computed tomography/computed tomography is increasingly applied for the quantitative assessment of liver function before major liver surgery. This dynamic quantitative liver function test allows assessment of both total and regional liver function, represented by the hepatic mebrofenin uptake rate, thereby assisting in adequate patient selection. Since routine implementation, it has shown to reduce the risk of posthepatectomy liver failure and has proven to be more valuable than volumetric assessment. To ensure optimal and reproducible results that can be compared across different centers, it is crucial to standardize the methodology and ensure practical applicability of this technique, thereby facilitating external validation and multicenter trials. This article provides an overview of the HBS methodology used at some of the largest HBS centers and covers practical details in the application of HBS for the quantitative scintigraphic assessment of liver function.

Assessment of cardiac-driven liver movements with filtered harmonic phase image representation, optical flow quantification, and motion amplification.

PURPOSE: To characterize cardiac-driven liver movements using a harmonic phase image representation (HARP) with an optical flow quantification and motion amplification method. The method was applied to define the cardiac trigger delay providing minimal signal losses in liver DWI images. METHODS: The 16-s breath-hold balanced-SSFP time resolved 20 images/s were acquired at 3T in coronal and sagittal orientations. A peripheral pulse unit signal was recorded. Cardiac-triggered DWI images were acquired after different peripheral pulse unit delays. A steerable pyramid decomposition with multiple orientations and spatial frequencies was applied. The liver motion field-map was derived from temporal variations of the HARP representation filtered around the cardiac frequency. Liver displacements were quantified with an optical flow method; moreover the right liver motion was amplified. RESULTS: The largest displacements were observed in the left liver (feet-head:3.70 ± 1.06 mm; anterior-posterior: 2.35 ± 0.51 mm). Displacements were statistically significantly weaker in the middle right liver (0.47 ± 0.11 mm; P = 0.0156). The average error was 0.013 ± 0.022 mm (coronal plane) and 0.021 ± 0.041 mm (sagittal plane). The velocity field demonstrated opposing movements of the right liver extremities during the cardiac cycle. DWI signal loss was minimized in regions and instants of smallest amplitude of both velocity and velocity gradient. CONCLUSION: Cardiac-driven liver movements were quantified with combined cardiac frequency-filtered HARP and optical flow methods. A motion phase opposition between right liver extremities was demonstrated. Displacement amplitude and velocity were larger in the left liver especially along the vertical direction. Motion amplification visually emphasized cardiac-driven right liver displacements. The optimal cardiac timing minimizing signal loss in liver DWI images was derived.

Assessment of Liver Function Using Pharmacokinetic Parameters of Gd-EOB-DTPA: Experimental Study in Rat Hepatectomy Model.

Objectives: To determine whether the pharmacokinetic parameters of Gd-EOB-DTPA can identify the difference in liver function in a rat hepatectomy model. Methods: A total of 56 eight-week-old male Sprague-Dawley rats were divided into the following groups: control group without hepatectomy (n = 16), 70% hepatectomy group (n = 14), and 90% hepatectomy group (n = 26). On postoperative day 2, Gd-EOB-DTPA (0.1 mmol/kg) was injected intravenously and serial blood samples were obtained. Pharmacokinetic analysis was performed using a noncompartmental method. Statistical analysis was performed using one-way analysis of variance and post hoc pairwise group comparisons. Results: After excluding 6 rats that died unexpectedly, blood samples were obtained from 16, 14, and 20 rats in the control group, 70% hepatectomy group, and 90% hepatectomy group. There was a significant increase in area under the concentration-time curve from time zero to the time of the last measurable concentration between the 70% and 90% hepatectomy group (P < 0.001). The volume of distribution at steady state was significantly decreased between the control and 70% hepatectomy group (P < 0.001). The clearance was significantly different in all pairwise group comparisons (P < 0.001). Conclusions: The vascular clearance of Gd-EOB-DTPA can identify the difference in liver function in a rat hepatectomy model.

Application of hepatocyte-like cells to enhance hepatic safety risk assessment in drug discovery.

Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures. There are two areas within the drug discovery pipeline that the generation of a stable, metabolically functional hepatocyte-like cell with unlimited supply would have major impact. First, in routine, cell health risk-assessment assays where hepatic cell lines are typically deployed. Second, at later stages of the drug discovery pipeline approaching candidate nomination where bespoke/investigational studies refining and understanding the risk to patients use patient-derived induced pluripotent stem cell (iPSC) hepatocytes retaining characteristics from the patient, e.g. HLA susceptibility alleles, iPSC hepatocytes with defined disease phenotypes or genetic characteristics that have the potential to make the hepatocyte more sensitive to a particular stress mechanism. Functionality of patient-centric hepatocyte-like cells is likely to be enhanced when coupled with emerging culture systems, such as three-dimensional spheroids or microphysiological systems. Ultimately, the aspiration to confidently use human-relevant in vitro models to predict human-specific hepatic toxicity depends on the integration of promising emerging technologies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.

Assessment of neurohepatic DNA damage in male Sprague-Dawley rats exposed to organophosphates and pyrethroid insecticides.

The current work was undertaken to test the genotoxic potential of chlorpyrifos (CPF), dimethoate, and lambda cyhalothrin (LCT) insecticides in rat brain and liver using the single cell gel electrophoresis (comet assay). Three groups of adult male Sprague-Dawley rats were exposed orally to one third LD50of CPF, dimethoate, or LCT for 24 and 48 h while the control group received corn oil. Serum samples were collected for estimation of malondialdehyde (MDA) and glutathione peroxidase (GPx); the brain and liver samples were used for comet assay and for histopathological examination. Results showed that signs of neurotoxicity appeared clinically as backward stretching of hind limb and splayed gait in dimethoate and LCT groups, respectively. CPF, LCT, and dimethoate induced oxidative stress indicated by increased MDA and decreased GPx levels. CPF and LCT caused severe DNA damage in the brain and liver at 24 and 48 h indicated by increased percentage of DNA in tail, tail length, tail moment, and olive tail moment. Dimethoate induced mild DNA damage in the brain and liver at 48 h. Histopathological changes were observed in the cerebrum, cerebellum, and liver of exposed rats. The results concluded that CPF, LCT, and dimethoate insecticides induced oxidative stress and DNA damage associated with histological changes in the brain and liver of exposed rats.

Contribution of structural brain phenotypes to the variance in resting energy expenditure in healthy Caucasian subjects.

Brain gray (GM) and white matter (WM) volumes are related to weight changes. The impact of structural variations in GM and WM on the variance in resting energy expenditure (REE) and the REE-on-fat-free mass (FFM) association is unknown. The aim of this study was to address this in healthy Caucasian subjects. Cross-sectional data analysis of 493 healthy Caucasian subjects (age range 6-80 years; 3 age groups) was conducted with comprehensive information on FFM, organ and tissue masses, and detailed brain composition as assessed by whole body magnetic resonance imaging and REE (assessed by indirect calorimetry). REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. FFM was the major determinant of REE (70.6%); individual masses of liver, total brain, and heart explained a further 2.1% of the variance in REE. Replacing total brain with GM and WM did not change the total R2. Nevertheless, GM added more to the variance in REE (5.6%) and corresponding residuals (12.5%) than did total brain. Additionally, up to 12% was explained by age and sex (<2%). There was a systematic bias between REE and REEc with positive values in younger subjects but negative values in older ones. This bias remained after substituting the specific metabolic rate of brain with the specific metabolic rates of GM and WM. In healthy Caucasian subjects, GM and WM contributed to the variance in REE. Detailed brain structures do not explain the bias between REE and REEc. NEW & NOTEWORTHY Detailed brain composition (gray and white matter) contributed to the variances of resting energy expenditure (REE) and REE-on-fat-free mass residuals. Gray matter explained most of the variances, and for future studies on energy expenditure, brain compartments should be analyzed separately with regard to their different energy needs.

Taste receptors in the gut - A new target for health promoting properties in diet.

In this review we describe a new target for food functionality, the taste receptors in the gastrointestinal tract. These receptors are involved in an intricate signalling network for monitoring of taste and nutrient intake, homeostasis and energy metabolism, and they are also an early warning system for toxic substances in our diet. Especially the receptors for bitter taste provide a new possibility to activate a number of health related signalling pathways, already at low concentrations of the active substance, without requiring uptake into the body and transport via the circulation. When ligands bind to these receptors, signalling is induced either via peptide hormones into the circulation to other organs in the body, or via nerve fibers directly to the brain.

Assessment of functional liver reserve: old and new in 99mTc-sulfur colloid scintigraphy.

PURPOSE: A semiquantitative assessment of hepatic reticuloendothelial system function using colloidal particles scintigraphy has been proposed previously as a surrogate for liver function evaluation. In this article, we present an updated method for the overall assessment of technetium-99m (Tc)-sulfur colloid (SC) biodistribution that combines information from planar and attenuation-corrected Tc-SC single-photon emission computed tomography (SPECT) images. The imaging protocol described here was developed as an easy-to-implement method to assess overall and regional liver function changes associated with chronic liver disease. PATIENTS AND METHODS: Thirty patients with chronic liver disease and primary liver cancers underwent Tc-SC whole-body planar imaging and upper-abdomen SPECT/computed tomography (CT) imaging before external beam radiation therapy. Liver plus spleen and bone marrow counts as a fraction of whole-body total counts were calculated from SC planar imaging. Attenuation correction Tc-SC images were rigidly coregistered with treatment planning CT images that contained liver and spleen regions-of-interest. Ratios of total liver counts to total spleen counts were obtained from the aligned Tc-SC SPECT and CT images, and were subsequently used to separate liver plus spleen counts obtained on the planar images. This hybrid SPECT/CT and planar scintigraphy approach yielded an updated estimation of whole-body SC distribution. These biodistribution estimates were compared with historical data for reference. Statistical associations of Tc-SC biodistribution to liver function parameters and liver disease scoring systems (Child-Pugh) were evaluated by Spearman rank correlation. RESULTS: Percentages of Tc-SC uptake ranged from 19.3 to 77.3% for the liver; 3.4 to 40.7% for the spleen; and 19.0 to 56.7% for the bone marrow. Spearman's correlation coefficient showed a significant statistical association between Child-Pugh score and bone marrow uptake at 0.55 (P≤0.05), liver uptake at 0.71 (P≤0.001), spleen uptake at 0.56 (P≤0.05), and spleen plus bone marrow uptake at 0.71 (P≤0.001). There was also a good correlation of SC uptake percentages with individual quantitative liver function components such as albumin and total bilirubin, and qualitative liver function components (varices, portal hypertension, ascites). For albumin: r=0.64 (P<0.001) compared with liver uptake percentage from the whole-body counts, r=0.49 (P<0.001) compared with splenic uptake percentage, and r=0.45 (P≤0.05) compared with bone marrow uptake percentage. CONCLUSION: We describe a novel liver function quantitative assessment method that combines whole-body planar images and SPECT/CT attenuation-corrected images of Tc-SC distribution. Attenuation-corrected SC images provide valuable regional liver function information, which is a unique feature compared with other imaging methods available. The results of our study indicate that the Tc-SC uptake by the liver, spleen, and bone marrow correlates with liver function parameters in patients with diffuse liver disease and the correlation with liver disease severity is slightly better for liver uptake percentages than for individual values of bone marrow and spleen uptake percentages.

Vasopressin: physiology, assessment and osmosensation.

Vasopressin (AVP) plays a major role in the regulation of water and sodium homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. AVP secretion is stimulated by a rise in plasma osmolality, a decline in blood volume or stress. V1a receptors are expressed in vascular smooth muscle cells, but the role of vasopressin in blood pressure regulation is still a matter of debate. AVP may also play a role in some metabolic pathways, including gluconeogenesis, through its action on V1a receptors expressed in the liver. It is now understood that thirst and arginine vasopressin (AVP) release are regulated not only by the classical homeostatic, intero-sensory plasma osmolality negative feedback, but also by novel, extero-sensory, anticipatory signals. AVP measurement is time-consuming, and AVP level in the blood in the physiological range is often below the detection limit of the assays. Recently, an immunoassay has been developed for the measurement of copeptin, a fragment of the pre-provasopressin molecule that is easier to measure. It has been shown to be a good surrogate marker of AVP.

Accuracy of real-time shear wave elastography in the assessment of normal liver tissue in the guinea pig (cavia porcellus).

Shear wave elastography is a novel technique enabling real-time measurement of the elasticity of liver tissue. The color map is superimposed on the classic ultrasound image of the assessed tissue, which enables a precise evaluation of the stiffness of the liver tissue. The aim of the study was to assess the stiffness of normal liver tissue in the guinea pig using shear wave elastography. The study was carried out on 36 guinea pigs using the SuperSonic Imagine Aixplorer scanner, and a 1 to 6 MH convex SC6-1 transducer. An ultrasound guided Try-Cut liver core needle biopsy was carried out in all the studied animals and the collected samples were examined to exclude pathological lesions. The mean liver tissue stiffness ranged from 0.89 to 5.40 kPa. We found that shear wave elastography is an easy, non-invasive technique that can be used to assess the stiffness of liver tissue. The obtained results can be used in future studies to assess the types and changes of liver tissue in the course of various types of liver disease.

T1ρ mapping improvement using stretched-type adiabatic locking pulses for assessment of human liver function at 3T.

PURPOSE: The purpose of this study is to investigate the performance of stretched-type adiabatic spin lock pulses for homogeneous spin locking with a flexible spin lock time (TSL) setting. METHODS: T1ρ values were obtained from 61 patients and five normal volunteers who were categorized using the Child-Pugh classification and scanned using each spin lock pulse type. The pulses used were the block and two kinds of hyperbolic secant (HS); HS8_10, and HS8_5. Visual scoring was categorized using a four point scale (1:Severe, 2:Moderate, 3:Mild and 4:None) to evaluate the homogeneity of the T1ρ map and the source images obtained by each spin lock pulse. Mean T1ρ values among the patient groups with different Child-Pugh classification were compared. RESULTS: The visual assessment scores were 1.98 ± 1.05 for block pulse locking, 3.87 ± 0.39 for HS8_10 pulse locking, and 3.83 ± 0.45 for HS8_5 pulse locking, respectively. The scores between block pulse and HS8_10 were significantly different (p < 0.001), as were those between block pulse and HS8_5 (p < 0.001). The median T1ρ values of normal liver function, Child-Pugh A, and Child-Pugh B or C were 37.00 ms, 40.77 ms, and 42.20 ms for block pulse, 46.75 ms, 50.78 ms, and 55.60 ms for HS8_10, and 48.80 ms, 55.42 ms, and 57.80 ms for HS8_5, respectively. CONCLUSION: The spin locking sequence using stretched-type adiabatic pulses provides homogeneous liver T1ρ maps with reduced artifact and is necessary for a robust evaluation of liver function using T1ρ.

In vivo assessment of intracellular redox state in rat liver using hyperpolarized [1-13 C]Alanine.

PURPOSE: The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD+ ]. In this study, we assessed the use of hyperpolarized [1-13 C]alanine and the subsequent detection of the intracellular products of [1-13 C]pyruvate and [1-13 C]lactate as a useful substrate for assessing redox levels in the liver in vivo. METHODS: Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion. A solution of 80-mM hyperpolarized [1-13 C]alanine was injected intravenously at baseline (n = 8) and 45 min after ethanol infusion (n = 4), immediately followed by the dynamic acquisition of 13 C MRS spectra. RESULTS: In vivo rat liver spectra showed peaks from [1-13 C] alanine and the products of [1-13 C]lactate, [1-13 C]pyruvate, and 13 C-bicarbonate. A significantly increased 13 C-lactate/13 C-pyruvate ratio was observed after ethanol infusion (8.46 ± 0.58 at baseline versus 13.58 ± 0.69 after ethanol infusion; P < 0.001) consistent with the increased NADH produced by liver metabolism of ethanol to acetaldehyde and then acetate. A decrease in 13 C-bicarbonate production was also noted, potentially reflecting ethanol-induced mitochondrial redox changes. CONCLUSION: A method to measure in vivo tissue redox using hyperpolarized [1-13 C]alanine is presented, with the validity of the proposed 13 C-pyruvate/13 C-lactate metric tested using an ethanol challenge to alter liver redox state. Magn Reson Med 77:1741-1748, 2017. © 2017 International Society for Magnetic Resonance in Medicine.