Recent advances in noninvasive assessment of liver steatosis.

Due to the steatosis epidemic, noninvasive quantification of liver fat content is of great interest. Magnetic resonance (MR) techniques, including proton MR spectroscopy (MRS) and MR chemical shift imaging can quantify liver fat by measuring, directly or indirectly (the latter), the proton density fat fraction (PDFF). They have shown excellent diagnostic accuracy and are currently the reference standard for the noninvasive assessment of liver steatosis and are used in clinical trials for evaluating the change in liver fat over time. Using ultrasound (US), three different quantitative parameters can be obtained to estimate liver fat: attenuation coefficient, backscatter coefficient, and speed of sound. Controlled attenuation parameter (CAP), which estimates the attenuation of the US beam, was the first algorithm available and is performed with a non-imaging system. Currently, several other algorithms are available on B-mode imaging ultrasound systems, and they have shown an accuracy similar to or higher than the CAP. This article reports the current knowledge about their application in patients with metabolic dysfunction-associated steatotic liver disease.

Noninvasive assessment of liver fibrosis and portal hypertension.

PURPOSE OF REVIEW: The result of ongoing liver injury - and disease, regardless of cause - is fibrosis, and fibrosis appears to be a critically important result of ongoing injury. Further, in a number of different liver diseases, the presence of fibrosis has prognostic value. Therefore, the assessment of fibrosis is of critical clinical importance. Given the importance of fibrosis, there has been a rapid evolution in the use of noninvasive liver tests. This review highlights a number of the core principles surrounding. RECENT FINDINGS: The use of noninvasive test has progressed rapidly over the last decade and data are rapidly accumulating. New terminology has been adapted by the American Association for the Study of Liver Disease (AASLD) for noninvasive assessment of liver disease and termed 'NILDA' (Non-Invasive Liver Disease Assessment). Blood based such as APRI and or FIB-4 and imaging tests such as liver stiffness measurement (LSM) have moderate to high degrees of accuracy for detection of advanced liver fibrosis (≥ F2) and even higher accuracy for detection of severe fibrosis (F4 or cirrhosis). NILDA are particularly effective at the ends of the liver disease spectrum. For example, a very low LSM (less than 7 kPa) essentially excludes significant fibrosis or portal hypertension, and a very high LSM (> 25 kPa) makes significant fibrosis with portal hypertension (cirrhosis) highly likely. SUMMARY: NILDA are currently front and center in terms of assessment of the severity of liver disease. In all patients with known or suspected liver disease, noninvasive blood tests, including APRI and or FIB-4, should be the initial choice to assess the severity of liver fibrosis and/or portal hypertension. In most patients, these tests should be followed with imaging evaluation. The most commonly available imaging is LSM, which appears to be more accurate in predicting fibrosis severity, and is superior to blood tests in the assessment of portal hypertension. In situations in which there is diagnostic uncertainly, liver biopsy with or without HVPG remains an important consideration.

Novel high-resolution contrast agent ultrasound techniques HiFR CEUS and SR CEUS in combination with shear wave elastography, fat assessment and viscosity of liver parenchymal changes and tumors.

BACKGROUND: The continuous development of ultrasound techniques increasingly enables better description and visualization of unclear lesions. New ultrasound systems must be evaluated with regard to all these diagnostic possibilities. METHODS: A multifrequency C1-7 convex probe (SC7-1M) with the new high-end system Resona A20 Series was used. Modern technologies, including HiFR CEUS, SR CEUS and multimodal tissue imaging with shear wave elastography (SWE), fat evaluation and viscosity measurements (M-Ref) were applied. RESULTS: Of n = 70 (mean value 48,3 years±20,3 years, range 18-84 years) cases examined, a definitive diagnosis could be made in n = 67 cases, confirmed by reference imaging and/or follow-up. Of these, n = 22 cases were malignant changes (HCC (hepatocellular carcinoma) n = 9, CCC (cholangiocellular carcinoma) n = 3, metastases of colorectal carcinomas or recurrences of HCC n = 10). In all 12 cases of HCC or CCC, the elastography measurements using the shear wave technique (with values >2 m/s to 3.7 m/s) showed mean values of 2.3±0.31 m/s and a degree of fibrosis of F2 to F4. In n = 14 cases, changes in the fat measurement (range 0.51 to 0.72 dB/cm/MHz, mean values 0.58±0.12 dB/cm/MHz) in the sense of proportional fatty changes in the liver were detected. In the 4 cases of localized fat distribution disorders, the values were >0.7 dB/cm/MHz in the sense of significant fatty deposits in the remaining liver tissue. Relevant changes in the viscosity measurements with values >1.8 kPa were found in n = 31 cases, in n = 5 cases of cystic lesions with partially sclerosing cholangitis, in n = 13 cases of malignant lesions and in n = 9 cases post-interventionally, but also in n = 4 cases of benign foci with additional systemic inflammation. CONCLUSIONS: The results are promising and show a new quality of ultrasound-based liver diagnostics. However, there is a need for further investigations with regard to the individual aspects, preferably on a multi-center basis.

Liver Biliary Function Evaluation on a 1.5T Magnetic Resonance Imaging Scan by T1 Reduction Rate Assessment Using Variable-Flip-Angle Sequences.

OBJECTIVE: Magnetic resonance (MR) relaxometry is an absolute and reproducible quantitative method, compared with signal intensity for the evaluation of liver biliary function. This is obtainable by the T1 reduction rate (T1RR), as it carries a smaller systematic error than the pre/post contrast agent T1 measurement. We aimed to develop and test an MR T1 relaxometry tool tailored for the evaluation of liver T1RR after gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid administration on 1.5T MR. METHODS: In vitro/vivo (liver) T1RR values with two 3D FLASH variable-flip-angle sequences were calculated by a MATLAB algorithm. In vitro measurements were done by 2 physicists, in consensus. The prospective in vivo study was approved by the local ethical committee and performed on 13 normal/26 cirrhotic livers. A supplemental test in 5 normal/5 cirrhotic livers, out of the studied series, was done to compare the results of our method (without B1 inhomogeneity correction) and those of a standardized commercial tool (with B1 inhomogeneity correction). All in vivo evaluations were performed by 2 radiologists with 7 years of experience in abdominal imaging. Open-source Java-based software ImageJ was used to draw the free-hand regions of interest on liver section and for the measurement of hepatic T1RR values. The T1RR values of each group of patients were compared to assess statistically significant differences. All statistical analyses were performed with IBM-SPSS Statistics. In vivo evaluations, the intrareader and interreader reliability was assessed by intraclass correlation coefficient. RESULTS: Our method showed good accuracy in evaluating in vitro T1RR with a maximum percentage error of 9% (constant at various time points) with T1 values in the 200- to 1400-millisecond range. In vivo, a high concordance between the T1RR evaluated with the proposed method and that calculated from the standardized commercial software was verified ( P < 0.05). The median T1RRs were 74.8, 67.9, and 52.1 for the normal liver, Child-Pugh A, and Child-Pugh B cirrhotic groups, respectively. A very good agreement was found, both within intrareader and interreader reliability, with intraclass correlation coefficient values ranging from 0.88 to 0.95 and from 0.85 to 0.90, respectively. CONCLUSIONS: The proposed method allowed accurate reliable in vitro/vivo T1RR assessment evaluation of the liver biliary function after gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid administration.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats.

BACKGROUND: This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). METHODS: Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. RESULTS: In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DISCUSSION: This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

Assessment of transient elastography in diagnosing MAFLD and the early effects of sleeve gastrectomy on MAFLD among the Chinese population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease among patients with obesity. Bariatric surgery, such as sleeve gastrectomy (SG), shows promise in improving the unfavorable condition of MAFLD. Transient elastography (TE) can be utilized to assess the extent of steatosis and liver fibrosis, providing a noninvasive method for preoperative prediction and postoperative evaluation of MAFLD. This study aims to investigate the effectiveness of TE in diagnosing MAFLD by evaluating liver steatosis and tissue stiffness, as well as assessing the early impact of SG in the treatment of obesity-associated MAFLD. METHODS: In this study, the authors collected preoperative and 6-month postoperative data from patients with obesity who were diagnosed with MAFLD by intraoperative liver biopsy. The patients underwent SG at our hospital between August 2021 and April 2023. The authors estimated the diagnostic accuracy for the steatosis and fibrosis categories using the area under the receiver operating characteristic curve (AUROC). The authors also evaluated the influence of disease prevalence on the positive predictive value and negative predictive value. MAFLD diagnosis was based on the liver steatosis activity and fibrosis scoring system. The authors used univariate and multivariate logistic regression analyses to identify factors contributing to severe MAFLD. To visualize the results, the authors created a nomogram and enhanced it with bootstrap resampling for internal validation. Additionally, the authors plotted receiver operating characteristic and calibration curves. The authors compared preoperative and postoperative data, including general information, laboratory tests, and TE results, to assess the early impact of SG in the treatment of obesity-associated MAFLD. RESULTS: Based on the results of liver biopsy, the AUROC for controlled attenuation parameter (CAP) in identifying steatosis was found to be 0.843 (95% CI: 0.729-0.957) for S≥S1, 0.863 (95% CI: 0.786-0.940) for S≥S2, and 0.872 (95% CI: 0.810-0.934) for S=S3. The Youden limits for S≥S1, S≥S2, and S≥S3 were determined to be 271 dB/m, 292 dB/m, and 301 dB/m, respectively. Similarly, the AUROC for liver stiffness measurement (LSM)/E in detecting liver fibrosis was 0.927 (95% CI: 0.869-0.984) for F≥F2, 0.919 (95% CI: 0.824-0.979) for F≥F3, and 0.949 (95% CI: 0.861-0.982) for F=F4, with Youden cutoff values of 7.5 kPa, 8.3 kPa, and 10.4 kPa, respectively. Patients with A≥3 and/or F≥3 were classified as having severe MAFLD. Multivariate logistic regression analysis identified CAP, E, LDL, and AST as the best diagnostic factors for severe MAFLD, and a nomogram was constructed based on these factors. The AUROC of the nomogram for the assessment of severe MAFLD was 0.824 (95% CI: 0.761-0.887), which was further validated by 1000 bootstrap resamplings with a bootstrap model area under curve of 0.823. Finally, after a 6-month follow-up period, the steatosis grade and fibrosis stage of the patients were graded based on the optimal cutoff values for CAP and LSM. Significant reductions in BMI, waist circumference, HbA1c, fasting glycemia, triglycerides, high density lipoprotein (HDL), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), gamma glutamyl transpeptidase (GGT), CAP, LSM, steatosis grade, and fibrosis stage were observed compared to the preoperative values. CONCLUSION: In this prospective study, the authors investigated the use of CAP and LSM as alternatives to liver biopsy for evaluating hepatic steatosis and fibrosis in patients with obesity combined with MAFLD. Furthermore, the authors examined the impact of SG on metabolic indicators and the progression of fatty liver disease during the early postoperative period, and observed significant improvements in both aspects.

Liver fibrosis assessment in pediatric population - can ultrasound elastography be an alternative method to liver biopsy? A systematic review.

Liver diseases of various etiologies are becoming increasingly common in the pediatric population. So far, the gold diagnostic standard in these disorders is liver biopsy. This procedure is invasive, painful and requires general anesthesia in this group of patients. Due to the continuous development of new research techniques, such as liver elastography, it is necessary to evaluate them in the context of their diagnostic usefulness. Ultrasound elastography, as a quick and effective method, is being used more and more often in the assessment and monitoring of liver dysfunction in both adults and children. There are several techniques of liver elastography, such as transient elastography, shear wave elastography consisting of various subtypes such as two-dimensional shear wave elastography, acoustic radiation force impulse and point shear wave elastography, which differ in terms of the measurement technique and the achieved results. The purpose of our review was to determine whether techniques of liver elastography could replace liver biopsy. Although now, based on the analyzed papers, elastography cannot replace liver biopsy, in our opinion, the role of this tool in monitoring pediatric patients with liver diseases will grow in the coming years.

Assessment of early anthracycline-induced cardiotoxicity and liver injury with T2 and T2* mapping in rabbit models.

OBJECTIVES: To evaluate the early prevalence of anthracycline-induced cardiotoxicity (AIC) and anthracycline-induced liver injury (AILI) using T2 and T2* mapping and to explore their correlations. MATERIALS AND METHODS: The study included 17 cardiotoxic rabbits that received weekly injections of doxorubicin and magnetic resonance imaging (MRI) every 2 weeks for 10 weeks. Cardiac function and T2 and T2* values were measured on each period. Histopathological examinations for two to five rabbits were performed after each MRI scan. The earliest sensitive time and the threshold of MRI parameters for detecting AIC and AILI based on these MRI parameters were obtained. Moreover, the relationship between myocardial and liver damage was assessed. RESULTS: Early AIC could be detected by T2 mapping as early as the second week and focused on the 7th, 11th, and 12th segments of left ventricle. The cutoff value of 46.64 for the 7th segment had the best diagnostic value, with an area under the curve (of 0.767, sensitivity of 100%, and specificity of 52%. T2* mapping could detect the change in iron content for early AIC at the middle interventricular septum and AILI as early as the sixth week (p = 0.014, p = 0.027). The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver (r = 0.39, p = 0.002). CONCLUSION: T2 and T2* mapping showed value one-stop assessment of AIC and AILI and could obtain the earliest MRI diagnosis point and optimal parameter thresholds for these conditions. CLINICAL RELEVANCE STATEMENT: Anthracycline-induced cardiotoxicity could be detected by T2 mapping as earlier as the second week, mainly focusing on the 7th, 11th, and 12th segments of left ventricle. Combined with T2* mapping, hepatoxicity and supplementary cardiotoxicity were assessed by one-stop scan. KEY POINTS: • MRI screening time of cardiotoxicity was as early as the second week with focusing on T2 values of the 7th, 11th, and 12th segments of left ventricle. • T2* mapping could be used as a complement to T2 mapping to evaluate cardiotoxicity and as an effective index to detect iron change in the early stages of chemotherapy. • The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver, indicating that iron content in the liver and heart increased with an increase in the chemotherapeutic drugs.

Two-Dimensional Ultrasound Assessment of Long-Term Intra-Abdominal Organ Changes in Children with Sickle Cell Anemia during Steady State: A Comparative Study.

BACKGROUND: Sickle cell anemia (SCA) is a hereditary blood disorder with global prevalence, including in Nigeria. Despite advancements in SCA care management, understanding the long-term impact on organs during steady state has remained inconclusive. AIM: This study aimed to investigate the long-term changes in intra-abdominal organs of SCA children compared with non-SCA children during steady state using two-dimensional ultrasound assessment. MATERIALS AND METHODS: A total of 116 children (58 SCA and 58 controls) were enrolled between June 2021 and July 2022. Clinico-demographic data were collected through an interviewer-administered questionnaire. Two-dimensional ultrasound was used to measure the liver, spleen, kidneys, and inferior vena cava in all subjects. Age-matched controls had AA or AS genotypes. RESULTS: Of the 58 patients with SCA, 65.5% were males with an overall mean age of 8.1 ± 3.4 years, while among the non-SCA cohort (n = 58), 48.3% were males with an overall mean age of 8.7 ± 3.9 years. There was no statistically significant difference in the age and gender distribution between the SCA and non-SCA cohorts (P = 0.390 and P = 0.091, respectively). SCA subjects had a larger mean hepatic size than non-SCA subjects (12.09 cm ± 2.23 vs. 11.67 cm ± 1.96; P = 0.276) but smaller mean splenic size (8.01 cm ± 1.89 vs. 8.19 cm ± 1.61; P = 0.577) and inferior vena cava diameter (1.16 cm ± 0.29 vs. 1.25 cm ± 0.33; P = 0.100). Left kidney length and breadth were significantly greater in SCA patients (8.91 ± 1.16 vs. 8.27 ± 1.30; P = 0.006 and 4.15 ± 0.92 vs. 3.79 ± 0.48; P = 0.008, respectively). CONCLUSION: This study highlights the utility of two-dimensional ultrasound assessment in monitoring intra-abdominal organ changes in SCA children, suggesting its cost-effective benefits in monitoring health outcomes in SCA patients.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

Four-dimensional Flow MRI Assessment of Portal Hemodynamics and Hepatic Regeneration after Portal Vein Embolization.

Background Percutaneous transhepatic portal vein (PV) embolization (PVE) is a standard preoperative procedure for advanced biliary cancer when the future liver remnant (FLR) is insufficient, yet the effect of this procedure on portal hemodynamics is still unclear. Purpose To assess whether four-dimensional (4D) MRI flowmetry can be used to estimate FLR volume and to identify the optimal time for this measurement. Materials and Methods This prospective single-center study enrolled consecutive adult patients with biliary cancer who underwent percutaneous transhepatic PVE for the right liver between June 2020 and November 2022. Portal hemodynamics were assessed using 4D flow MRI before PVE and within 1 day (0-day group) or 3-4 days (3-day group) after PVE. FLR volume was measured using CT before PVE and after PVE but before surgery. Blood flow changes were analyzed with the Wilcoxon signed rank test, and correlations with Spearman rank correlation. Results The 0-day group included 24 participants (median age, 72 years [IQR, 69-77 years]; 17 male participants), and the 3-day group included 13 participants (median age, 71 years [IQR, 68-78 years]; eight male participants). Both groups showed increased left PV (LPV) flow rate after PVE (0-day group: from median 3.72 mL/sec [IQR, 2.83-4.55 mL/sec] to 9.48 mL/sec [IQR, 8.12-10.7 mL/sec], P < .001; 3-day group: from median 3.65 mL/sec [IQR, 2.14-3.79 mL/sec] to 8.16 mL/sec [IQR, 6.82-8.98 mL/sec], P < .001). LPV flow change correlated with FLR volume change relative to the number of days from PVE to presurgery CT only in the 3-day group (ρ = 0.62, P = .02; 0-day group, P = .11). The output of the regression equation for estimating presurgery FLR volume correlated with CT-measured volume (ρ = 0.78; P = .002). Conclusion Four-dimensional flow MRI demonstrated increased blood flow in residual portal branches 3-4 days after PVE, offering insights for estimating presurgery FLR volume. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Roldán-Alzate and Oechtering in this issue.

Novel approach using [18F]FTHA-PET and de novo synthesized VLDL for assessment of FFA metabolism in a rat model of diet induced NAFLD.

BACKGROUND AND AIMS: The worldwide prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) raises concerns about associated risk factors, such as obesity and type 2 Diabetes Mellitus, for leading causes of disability and death. Besides Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS), functional imaging with Positron Emission Tomography (PET) could contribute to a deeper understanding of the pathophysiology of NAFLD. Here we describe a novel approach using the PET tracer [18F]FTHA, which is an analog of long-chain free fatty acids (FFA) and is taken up by tissues to enter mitochondria or to be incorporated into complex lipids for further export as very-low-density lipoprotein (VLDL). METHODS: Male Sprague Dawley rats, after 6 weeks on a high-fat diet (HFD), were used as a model of diet induced NAFLD, while a standard diet (SD) served as a control group. Liver fat was estimated by MR spectroscopy at a 9.4 T system for phenotyping. To measure hepatic FFA uptake, rats underwent 60 min dynamic [18F]FTHA-PET scans after unrestricted access to food (HFD: n = 6; SD: n = 6) or overnight (≤16h) fasting (HFD: n = 6; SD: n = 5). FFA removal was assessed from incorporated 18F-residual in de novo synthesized VLDL out of plasma. RESULTS: MRS of the liver confirmed the presence of NAFLD (>5.6% fat). Under non-fasting conditions, hepatic [18F]FTHA uptake was significantly increased in NAFLD: SUVmean (p = 0.03) within [0; 60] min interval, SUVmean (p = 0.01) and SUVmax (p = 0.03) within [30; 60] min interval. SUVs for hepatic uptake under fasting conditions were not significantly different between the groups. Analysis of FFA removal demonstrated elevated values of 18F-residue in the VLDL plasma fraction of the healthy group compared to the NAFLD (p = 0.0569). CONCLUSION: Our novel approach for assessing FFA metabolism using [18F]FTHA demonstrated differences in the hepatic FFA uptake and FFA incorporation into VLDL between healthy and NAFLD rats. [18F]FTHA-PET could be used to study metabolic disturbances involved in the progression of NAFLD.

Multimodal assessment of non-alcoholic fatty liver disease with transmission-reflection optoacoustic ultrasound.

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term referring to a group of conditions associated to fat deposition and damage of liver tissue. Early detection of fat accumulation is essential to avoid progression of NAFLD to serious pathological stages such as liver cirrhosis and hepatocellular carcinoma. Methods: We exploited the unique capabilities of transmission-reflection optoacoustic ultrasound (TROPUS), which combines the advantages of optical and acoustic contrasts, for an early-stage multi-parametric assessment of NAFLD in mice. Results: The multispectral optoacoustic imaging allowed for spectroscopic differentiation of lipid content, as well as the bio-distributions of oxygenated and deoxygenated hemoglobin in liver tissues in vivo. The pulse-echo (reflection) ultrasound (US) imaging further provided a valuable anatomical reference whilst transmission US facilitated the mapping of speed of sound changes in lipid-rich regions, which was consistent with the presence of macrovesicular hepatic steatosis in the NAFLD livers examined with ex vivo histological staining. Conclusion: The proposed multimodal approach facilitates quantification of liver abnormalities at early stages using a variety of optical and acoustic contrasts, laying the ground for translating the TROPUS approach toward diagnosis and monitoring NAFLD in patients.

Impact of fat on the apparent T1 value of the liver: assessment by water-only derived T1 mapping.

OBJECTIVES: To determine the impact of fat on the apparent T1 value of the liver using water-only derived T1 mapping. METHODS: 3-T MRI included 2D Look-Locker T1 mapping and proton density fat fraction (PDFF) mapping. T1 values of the liver were compared among T1 maps obtained by in-phase (IP), opposed-phase (OP), and Dixon water sequences using paired t-test. The correlation between T1 values of the liver on each T1 map and PDFF was assessed using Spearman correlation coefficient. The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were also correlated with PDFF. RESULTS: One hundred sixty-two patients (median age, 70 [range, 24-91] years, 90 men) were retrospectively evaluated. The T1 values of the liver on each T1 map were significantly different (p < 0.001). The T1 value of the liver on IP images was significantly negatively correlated with PDFF (r = - 0.438), while the T1 value of the liver on OP images was slightly positively correlated with PDFF (r = 0.164). The T1 value of the liver on Dixon water images was slightly negatively correlated with PDFF (r = - 0.171). The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were significantly correlated with PDFF (r = 0.606, 0.722; p < 0.001). CONCLUSION: Fat correction for the apparent T1 value by water-only derived T1 maps will be helpful for accurately evaluating the T1 value of the liver. CLINICAL RELEVANCE STATEMENT: Fat-corrected T1 mapping of the liver with the water component only obtained from the 2D Dixon Look-Locker sequence could be useful for accurately evaluating the T1 value of the liver without the impact of fat in daily clinical practice. KEY POINTS: • The T1 values of the liver on the conventional T1 maps are significantly affected by the presence of fat. • The apparent T1 value of the liver on water-only derived T1 maps would be slightly impacted by the presence of fat. • Fat correction for the apparent T1 values is necessary for the accurate assessment of the T1 values of the liver.

Joint EANM/SNMMI/IHPBA procedure guideline for [99mTc]Tc-mebrofenin hepatobiliary scintigraphy SPECT/CT in the quantitative assessment of the future liver remnant function.

PURPOSE: The aim of this joint EANM/SNMMI/IHPBA procedure guideline is to provide general information and specific recommendations and considerations on the use of [99mTc]Tc-mebrofenin hepatobiliary scintigraphy (HBS) in the quantitative assessment and risk analysis before surgical intervention, selective internal radiation therapy (SIRT) or before and after liver regenerative procedures. Although the gold standard to estimate future liver remnant (FLR) function remains volumetry, the increasing interest in HBS and the continuous request for implementation in major liver centers worldwide, demands standardization. METHODS: This guideline concentrates on the endorsement of a standardized protocol for HBS elaborates on the clinical indications and implications, considerations, clinical appliance, cut-off values, interactions, acquisition, post-processing analysis and interpretation. Referral to the practical guidelines for additional post-processing manual instructions is provided. CONCLUSION: The increasing interest of major liver centers worldwide in HBS requires guidance for implementation. Standardization facilitates applicability of HBS and promotes global implementation. Inclusion of HBS in standard care is not meant as substitute for volumetry, but rather to complement risk evaluation by identifying suspected and unsuspected high-risk patients prone to develop post-hepatectomy liver failure (PHLF) and post-SIRT liver failure.

Quantitative Assessment of Hepatic Steatosis Using Label-Free Multiphoton Imaging and Customized Image Processing Program.

Nonalcoholic fatty liver disease is rapidly becoming one of the most common causes of chronic liver disease worldwide and is the leading cause of liver-related morbidity and mortality. A quantitative assessment of the degree of steatosis would be more advantageous for diagnostic evaluation and exploring the patterns of disease progression. Here, multiphoton microscopy, based on the second harmonic generation and 2-photon excited fluorescence, was used to label-free image the samples of nonalcoholic fatty liver. Imaging results confirm that multiphoton microscopy is capable of directly visualizing important pathologic features such as normal hepatocytes, hepatic steatosis, Mallory bodies, necrosis, inflammation, collagen deposition, microvessel, and so on and is a reliable auxiliary tool for the diagnosis of nonalcoholic fatty liver disease. Furthermore, we developed an image segmentation algorithm to simultaneously assess hepatic steatosis and fibrotic changes, and quantitative results reveal that there is a correlation between the degree of steatosis and collagen content. We also developed a feature extraction program to precisely display the spatial distribution of hepatocyte steatosis in tissues. These studies may be beneficial for a better clinical understanding of the process of steatosis as well as for exploring possible therapeutic targets.

Factors associated with discordance in the assessment of fibrosis stage between transient elastography and liver biopsy in NAFLD patients.

BACKGROUND AND AIMS: Few studies focus on the concordance of fibrosis stage assessment between transient elastography (TE) and liver biopsy (LB) in non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the rate of discordance and factors associated with discordance in the fibrosis stage assessment between TE and LB. METHODS: LB-proven NAFLD patients were enrolled retrospectively. Liver fibrosis was assessed via TE and LB based on Steatosis-Activity-Fibrosis (SAF) criteria. Cohen's kappa was used to estimate the discordance between the fibrosis stage assessment by TE and LB. Logistic regression was utilized to determine the factors associated with discordance. RESULTS: A total of 172 eligible patients were included. The concordance of fibrosis staging between TE and LB was moderate (kappa = 0.446, p < 0.001). The overall rate of discordance was 52.90% (91/172) and highest in the F2 stage (66.28%) and F3 stage (60.42%), moderate in the F1 stage (23.81%), and lowest in the F4 stage (0.00%). The rate of overestimation and underestimation was 23.66% and 38.71% in patients detected by M-probe, while the rate of overestimation and underestimation was 33.87% and 19.35% in patients detected by XL-probe, respectively. BMI [OR=1.494, p = 0.017] and type 2 diabetes mellitus (T2DM) (OR=4.678, p = 0.008) were significantly associated with the overestimation in fibrosis stage assessment when the M-probe was applied. CONCLUSIONS: The discordance between TE and LB in fibrosis stage assessment was unexpectedly high and mainly observed in F1-F3 patients. BMI and T2DM were the factors associated with overestimation using the M-probe.

Simultaneous imaging of ultrasonic relative backscatter and attenuation coefficients for quantitative liver steatosis assessment.

Prevalence of liver disease is continuously increasing and nonalcoholic fatty liver disease (NAFLD) is the most common etiology. We present an approach to detect the progression of liver steatosis based on quantitative ultrasound (QUS) imaging. This study was performed on a group of 55 rats that were subjected to a control or methionine and choline deficient (MCD) diet known to induce NAFLD. Ultrasound (US) measurements were performed at 2 and 6 weeks. Thereafter, animals were humanely euthanized and livers excised for histological analysis. Relative backscatter and attenuation coefficients were simultaneously estimated from the US data and envelope signal-to-noise ratio was calculated to train a regression model for: (1) fat fraction percentage estimation and (2) performing classification according to Brunt's criteria in grades (0 <5%; 1, 5-33%; 2, >33-66%; 3, >66%) of liver steatosis. The trained regression model achieved an [Formula: see text] of 0.97 (p-value < 0.01) and a RMSE of 3.64. Moreover, the classification task reached an accuracy of 94.55%. Our results suggest that in vivo QUS is a promising noninvasive imaging modality for the early assessment of NAFLD.

[Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection].

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.