A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol.

BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients. METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations. DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes. TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .

Enhancing students' understanding of cardiac physiology by using 4D visualization.

Difficulties in achieving knowledge about physiology and anatomy of the beating heart highlight the challenges with more traditional pedagogical methods. Recent research regarding anatomy education has mainly focused on digital three-dimensional models. However, these pedagogical improvements may not be entirely applicable to cardiac anatomy and physiology due to the multidimensional complexity with moving anatomy and complex blood flow. The aim of this study was therefore to evaluate whether high quality time-resolved anatomical images combined with realistic blood flow simulations improve the understanding of cardiac structures and function. Three time-resolved datasets were acquired using time-resolved computed tomography and blood flow was computed using Computational Fluid Dynamics. The anatomical and blood flow information was combined and interactively visualized using volume rendering on an advanced stereo projection system. The setup was tested in interactive lectures for medical students. Ninety-seven students participated. Summative assessment of examinations showed significantly improved mean score (18.1 ± 4.5 vs 20.3 ± 4.9, p = 0.002). This improvement was driven by knowledge regarding myocardial hypertrophy and pressure-velocity differences over a stenotic valve. Additionally, a supplementary formative assessment showed significantly more agreeing answers than disagreeing answers (p < 0.001) when the participants subjectively evaluated the contribution of the visualizations to their education and knowledge. In conclusion, the use of simultaneous visualization of time-resolved anatomy data and simulated blood flow improved medical students' results, with a particular effect on understanding of cardiac physiology and these simulations may be useful educational tools for teaching complex anatomical and physiological concepts.

Evaluating the prevalence and severity of NAFLD in primary care: the EPSONIP study protocol.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 20-30% of the general adult population. NAFLD patients with type 2 diabetes mellitus (T2DM) are at an increased risk of advanced fibrosis, which puts them at risk of cardiovascular complications, hepatocellular carcinoma, or liver failure. Liver biopsy is the gold standard for assessing hepatic fibrosis. However, its utility is inherently limited. Consequently, the prevalence and characteristics of T2DM patients with advanced fibrosis are unknown. Therefore, the purpose of the current study is to evaluate the prevalence and severity of NAFLD in patients with T2DM by recruiting participants from primary care, using the latest imaging modalities, to collect a cohort of well phenotyped patients. METHODS: We will prospectively recruit 400 patients with T2DM using biomarkers to assess their status. Specifically, we will evaluate liver fat content using magnetic resonance imaging (MRI); hepatic fibrosis using MR elastography and vibration-controlled transient elastography; muscle composition and body fat distribution using water-fat separated whole body MRI; and cardiac function, structure, and tissue characteristics, using cardiovascular MRI. DISCUSSION: We expect that the study will uncover potential mechanisms of advanced hepatic fibrosis in NAFLD and T2DM and equip the clinician with better diagnostic tools for the care of T2DM patients with NAFLD. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03864510. Registered 6 March 2019, https://clinicaltrials.gov/ct2/show/NCT03864510 .

Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort.

Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images.

Biomarkers of liver fibrosis: prospective comparison of multimodal magnetic resonance, serum algorithms and transient elastography.

BACKGROUND AND AIMS: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available. METHODS: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King's Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score). RESULTS: The diagnostic performance (AUROC) for identification of significant fibrosis (F2-4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3-4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively. CONCLUSION: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summaryExcessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.

Liver R2* is affected by both iron and fat: A dual biopsy-validated study of chronic liver disease.

BACKGROUND: Liver iron content (LIC) in chronic liver disease (CLD) is currently determined by performing an invasive liver biopsy. MRI using R2* relaxometry is a noninvasive alternative for estimating LIC. Fat accumulation in the liver, or proton density fat fraction (PDFF), may be a possible confounder of R2* measurements. Previous studies of the effect of PDFF on R2* have not used quantitative LIC measurement. PURPOSE: To assess the associations between R2*, LIC, PDFF, and liver histology in patients with suspected CLD. STUDY TYPE: Prospective. POPULATION: Eighty-one patients with suspected CLD. FIELD STRENGTH/SEQUENCE: 1.5 T. Multiecho turbo field echo to quantify R2*. PRESS MRS to quantify PDFF. ASSESSMENT: Each patient underwent an MR examination, followed by two needle biopsies immediately following the MR examination. The first biopsy was used for conventional histological assessment of LIC, whereas the second biopsy was used to quantitatively measure LIC using mass spectrometry. R2* was correlated with both LIC and PDFF. A correction for the influence of fat on R2* was calculated. STATISTICAL TESTS: Pearson correlation, linear regression, and area under the receiver operating curve. RESULTS: There was a positive linear correlation between R2* and PDFF (R = 0.69), after removing data from patients with elevated iron levels, as defined by LIC. R2*, corrected for PDFF, was the best method for identifying patients with elevated iron levels, with a correlation of R = 0.87 and a sensitivity and specificity of 87.5% and 98.6%, respectively. DATA CONCLUSION: PDFF increases R2*. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:325-333.

Using a 3% Proton Density Fat Fraction as a Cut-Off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results From Histopathology Analysis.

It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (1H-MRS), instead of collecting and analyzing liver biopsy specimens to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of 1H-MRS PDFF in the measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, 1H-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (≥6 mo) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereologic point counts (SPCs). We correlated the 1H-MRS PDFF findings with SPCs (r = 0.92; P < .001). 1H-MRS PDFF results correlated with histopathology results (ρ = 0.87; P < .001), and SPCs correlated with histopathology results (ρ = 0.88; P < .001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values less than 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve noninvasive detection of steatosis.

Is there a superior simulator for human anatomy education? How virtual dissection can overcome the anatomic and pedagogic limitations of cadaveric dissection.

Educators must select the best tools to teach anatomy to future physicians and traditionally, cadavers have always been considered the "gold standard" simulator for living anatomy. However, new advances in technology and radiology have created new teaching tools, such as virtual dissection, which provide students with new learning opportunities. Virtual dissection is a novel way of studying human anatomy through patient computed tomography (CT) scans. Through touchscreen technology, students can work together in groups to "virtually dissect" the CT scans to better understand complex anatomic relationships. This article presents the anatomic and pedagogic limitations of cadaveric dissection and explains what virtual dissection is and how this new technology may be used to overcome these limitations.

Robust water fat separated dual-echo MRI by phase-sensitive reconstruction.

PURPOSE: The purpose of this work was to develop and evaluate a robust water-fat separation method for T1-weighted symmetric two-point Dixon data. THEORY AND METHODS: A method for water-fat separation by phase unwrapping of the opposite-phase images by phase-sensitive reconstruction (PSR) is introduced. PSR consists of three steps; (1), identification of clusters of tissue voxels; (2), unwrapping of the phase in each cluster by solving Poisson's equation; and (3), finding the correct sign of each unwrapped opposite-phase cluster, so that the water-fat images are assigned the correct identities. Robustness was evaluated by counting the number of water-fat swap artifacts in a total of 733 image volumes. The method was also compared to commercial software. RESULTS: In the water-fat separated image volumes, the PSR method failed to unwrap the phase of one cluster and misclassified 10. One swap was observed in areas affected by motion and was constricted to the affected area. Twenty swaps were observed surrounding susceptibility artifacts, none of which spread outside the artifact affected regions. The PSR method had fewer swaps when compared to commercial software. CONCLUSION: The PSR method can robustly produce water-fat separated whole-body images based on symmetric two-echo spoiled gradient echo images, under both ideal conditions and in the presence of common artifacts. Magn Reson Med 78:1208-1216, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA.

OBJECTIVES: To apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage. METHODS: A total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (K (Hep)) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system. RESULTS: Area under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for K (Hep), LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for K (Hep) (borderline), LSC_N10 and LSC_N20. CONCLUSIONS: Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and K (Hep) will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

Sinogram-affirmed iterative reconstruction of low-dose chest CT: effect on image quality and radiation dose.

OBJECTIVE. The purpose of this study is to compare sinogram-affirmed iterative reconstruction (SAFIRE) and filtered back projection (FBP) reconstruction of chest CT acquired with 65% radiation dose reduction. MATERIALS AND METHODS. In this prospective study involving 24 patients (11 women and 13 men; mean [± SD] age, 66 ± 10 years), two scan series were acquired using 100 and 40 Quality Reference mAs over a 10-cm scan length in the chest with a 128-MDCT scanner. The 40 Quality Reference mAs CT projection data were reconstructed with FBP and four settings of SAFIRE (S1, S2, S3, and S4). Six image datasets (FBP with 100 and 40 Quality Reference mAs, and S1, S2, S3, S4 with 40 Quality Reference mAs) were displayed on a DICOM-compliant 55-inch 2-megapixel monitor for blinded evaluation by two thoracic radiologists for number and location of lesions, lesion size, lesion margins, visibility of small structures and fissures, and diagnostic confidence. Objective noise and CT values were measured in thoracic aorta for each image series, and the noise power spectrum was assessed. Data were analyzed with analysis of variance and Wilcoxon signed rank tests. RESULTS. All 186 lesions were seen on 40 Quality Reference mAs SAFIRE images. Diagnostic confidence on SAFIRE images was higher than that for FBP images. Except for the minor blotchy appearance on SAFIRE settings S3 and S4, no significant artifacts were noted. Objective noise with 40 Quality Reference mAs S1 images (21.1 ± 6.1 SD of HU) was significantly lower than that for 40 Quality Reference mAs FBP images (28.5 ± 8.1 SD of HU) (p < 0.001). Noise power spectra were identical for SAFIRE and FBP with progressive noise reduction with higher iteration SAFIRE settings. CONCLUSION. Iterative reconstruction (SAFIRE) allows reducing the radiation exposure by approximately 65% without losing diagnostic information in chest CT.

Mathematical models for biomarker calculation of drug-induced liver injury in humans and experimental models based on gadoxetate enhanced magnetic resonance imaging.

BACKGROUND: Drug induced liver injury (DILI) is a major concern when developing new drugs. A promising biomarker for DILI is the hepatic uptake rate of the contrast agent gadoxetate. This rate can be estimated using a novel approach combining magnetic resonance imaging and mathematical modeling. However, previous work has used different mathematical models to describe liver function in humans or rats, and no comparative study has assessed which model is most optimal to use, or focused on possible translatability between the two species. AIMS: Our aim was therefore to do a comparison and assessment of models for DILI biomarker assessment, and to develop a conceptual basis for a translational framework between the species. METHODS AND RESULTS: We first established which of the available pharmacokinetic models to use by identifying the most simple and identifiable model that can describe data from both human and rats. We then developed an extension of this model for how to estimate the effects of a hepatotoxic drug in rats. Finally, we illustrated how such a framework could be useful for drug dosage selection, and how it potentially can be applied in personalized treatments designed to avoid DILI. CONCLUSION: Our analysis provides clear guidelines of which mathematical model to use for model-based assessment of biomarkers for liver function, and it also suggests a hypothetical path to a translational framework for DILI.

Radiation dose reduction with Sinogram Affirmed Iterative Reconstruction technique for abdominal computed tomography.

PURPOSE: The objective of this study was to assess the effect of Sinogram Affirmed Iterative Reconstruction (SAFIRE) and filtered back-projection (FBP) techniques on abdominal computed tomography (CT) performed with 50% and 75% radiation dose reductions. METHODS: Twenty-four patients (mean age, 64 ± 14 years; male-female ratio, 10:14) gave informed consent for an institutional review board-approved prospective study involving acquisition of additional research images through the abdomen on 128-slice multi-detector-row CT (SOMATOM Definition Flash) at quality reference mAs of 100 (50% lower dose) and 50 (75% lower dose) over a scan length of 10 cm using combined modulation (CARE Dose 4D). Standard-of-care abdominal CT was performed at 200 quality reference mAs, with remaining parameters held constant. The 50- and 100-mAs data sets were reconstructed with FBP and at 4 SAFIRE settings (S1, S2, S3, S4). Higher number of SAFIRE settings denotes increased strength of the algorithm resulting in lower image noise. Two abdominal radiologists independently compared the FBP and SAFIRE images for lesion number, location, size and conspicuity, and visibility of small structures, image noise, and diagnostic confidence. Objective noise and Hounsfield units (HU) were measured in the liver and the descending aorta. RESULTS: All 43 lesions were detected on both FBP and SAFIRE images. Minor blocky, pixelated appearance of 50% and 75% reduced dose images was noted at S3 and S4 SAFIRE but not at S1 and S2 settings. Subjective noise was suboptimal in both 50% and 75% lower-dose FBP images but was deemed acceptable on all SAFIRE settings. Sinogram Affirmed Iterative Reconstruction images were deemed acceptable in all patients at 50% lower dose and in 22 of 24 patients at 75% lower dose. As compared with 75% reduced dose FBP, objective noise was lower by 22.8% (22.9/29.7), 35% (19.3/29.7), 44.3% (16.7/29.3), and 54.8% (13.4/29.7) on S1 to S4 settings, respectively (P < 0.001). CONCLUSIONS: Sinogram Affirmed Iterative Reconstruction-enabled reconstruction provides abdominal CT images without loss in diagnostic value at 50% reduced dose and in some patients also at 75% reduced dose.

ON THE POSSIBILITY TO RESOLVE GADOLINIUM- AND CERIUM-BASED CONTRAST AGENTS FROM THEIR CT NUMBERS IN DUAL-ENERGY COMPUTED TOMOGRAPHY.

Cerium oxide nanoparticles with integrated gadolinium have been proved to be useful as contrast agents in magnetic resonance imaging. Of question is their performance in dual-energy computed tomography. The aims of this work are to determine (1) the relation between the computed tomography number and the concentration of the I, Gd or Ce contrast agent and (2) under what conditions it is possible to resolve the type of contrast agent. Hounsfield values of iodoacetic acid, gadolinium acetate and cerium acetate dissolved in water at molar concentrations of 10, 50 and 100 mM were measured in a water phantom using the Siemens SOMATOM Definition Force scanner; gadolinium- and cerium acetate were used as substitutes for the gadolinium-integrated cerium oxide nanoparticles. The relation between the molar concentration of the I, Gd or Ce contrast agent and the Hounsfield value was linear. Concentrations had to be sufficiently high to resolve the contrast agents.

Vertebral Axial Asymmetry in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate parameters of axial vertebral deformation in patients with scoliosis compared to a control group, and to determine whether these parameters correlated with the severity of spine curvature, measured as the Cobb angle. SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity. Many studies have investigated vertebral deformation, in terms of wedging and pedicle deformations, but few studies have investigated actual structural changes within vertebrae. METHODS: This study included 20 patients with AIS (Lenke 1-3, mean age: 15.6 years, range: 11-20). We compared preoperative low-dose computed tomography (CT) examinations of patients with AIS to those of a control group matched for age and sex. The control individuals had no spinal deformity, but they were admitted to the emergency department for trauma CTs. We measured the Cobb angles and the axial vertebral rotation (AVR), axial vertebral body asymmetry (AVBA), and frontal vertebral body rotation (FVBR) for the superior end, inferior end, and apical vertebrae, with in-house-developed software. Correlations between entities were investigated with the Pearson correlation test. RESULTS: The average Cobb angles were 49.3° and 1.3° for the scoliotic and control groups, respectively. The patient and control groups showed significant differences in the AVRs of all three vertebra levels (p < .01), the AVBAs of the superior end and apical vertebrae (p < .008), and the FVBR of the apical vertebra (p = .011). Correlations were only found between the AVBA and FVBR in the superior end vertebra (r = 0.728, p < .001) and in the apical vertebra (r = 0.713, p < .001). CONCLUSIONS: Compared with controls, patients with scoliosis showed clear morphologic differences in the midaxial plane vertebrae. Differences in AVR, AVBA, and FVBR were most pronounced at the apical vertebra. The FVBR provided valuable additional information about the internal rotation and deformation of vertebrae. LEVEL OF EVIDENCE: Level III.

CLINICAL AUDIT OF IMAGE QUALITY IN RADIOLOGY USING VISUAL GRADING CHARACTERISTICS ANALYSIS.

The aim of this work was to assess whether an audit of clinical image quality could be efficiently implemented within a limited time frame using visual grading characteristics (VGC) analysis. Lumbar spine radiography, bedside chest radiography and abdominal CT were selected. For each examination, images were acquired or reconstructed in two ways. Twenty images per examination were assessed by 40 radiology residents using visual grading of image criteria. The results were analysed using VGC. Inter-observer reliability was assessed. The results of the visual grading analysis were consistent with expected outcomes. The inter-observer reliability was moderate to good and correlated with perceived image quality (r(2) = 0.47). The median observation time per image or image series was within 2 min. These results suggest that the use of visual grading of image criteria to assess the quality of radiographs provides a rapid method for performing an image quality audit in a clinical environment.

A randomized trial of cold-exposure on energy expenditure and supraclavicular brown adipose tissue volume in humans.

OBJECTIVE: To study if repeated cold-exposure increases metabolic rate and/or brown adipose tissue (BAT) volume in humans when compared with avoiding to freeze. DESIGN: Randomized, open, parallel-group trial. METHODS: Healthy non-selected participants were randomized to achieve cold-exposure 1hour/day, or to avoid any sense of feeling cold, for 6weeks. Metabolic rate (MR) was measured by indirect calorimetry before and after acute cold-exposure with cold vests and ingestion of cold water. The BAT volumes in the supraclavicular region were measured with magnetic resonance imaging (MRI). RESULTS: Twenty-eight participants were recruited, 12 were allocated to controls and 16 to cold-exposure. Two participants in the cold group dropped out and one was excluded. Both the non-stimulated and the cold-stimulated MR were lowered within the group randomized to avoid cold (MR at room temperature from 1841±199 kCal/24h to 1795±213 kCal/24h, p=0.047 cold-activated MR from 1900±150 kCal/24h to 1793±215 kCal/24h, p=0.028). There was a trend towards increased MR at room temperature following the intervention in the cold-group (p=0.052). The difference between MR changes by the interventions between groups was statistically significant (p=0.008 at room temperature, p=0.032 after cold-activation). In an on-treatment analysis after exclusion of two participants that reported ≥8days without cold-exposure, supraclavicular BAT volume had increased in the cold-exposure group (from 0.0175±0.015l to 0.0216±0.014l, p=0.049). CONCLUSIONS: We found evidence for plasticity in metabolic rate by avoiding to freeze compared with cold-exposure in a randomized setting in non-selected humans.

Visual assessment of biliary excretion of Gd-EOB-DTPA in patients with suspected diffuse liver disease - A biopsy-verified prospective study.

OBJECTIVES: To qualitatively evaluate late dynamic contrast phases, 10, 20 and 30 min, after administration of Gd-EOB-DTPA with regard to biliary excretion in patients presenting with elevated liver enzymes without clinical signs of cirrhosis or hepatic decompensation and to compare the visual assessment of contrast agent excretion with histo-pathological fibrosis stage, contrast uptake parameters and blood tests. METHODS: 29 patients were prospectively examined using 1.5 T MRI. The visually assessed presence or absence of contrast agent for each of five anatomical regions in randomly reviewed time-series was summarized on a four grade scale for each patient. The scores, including a total visual score, were related to the histo-pathological findings, the quantitative contrast agent uptake parameters, expressed as K Hep or LSC_N, and blood tests. RESULTS: No relationship between the fibrosis grade or contrast uptake parameters could be established. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found. Comparing a sub-group of cholestatic patients with fibrosis score and Gd-EOB-DTPA dynamic parameters did not add any additional significant correlation. CONCLUSIONS: No correlation between visually assessed biliary excretion of Gd-EOB-DTPA and histo-pathological or contrast uptake parameters was found. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found.

Physiologically realistic and validated mathematical liver model reveals [corrected] hepatobiliary transfer rates for Gd-EOB-DTPA using human DCE-MRI data.

OBJECTIVES: Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required. METHODS: A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA. RESULTS: The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data. CONCLUSIONS: We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.