Gd-EOB-DTPA-enhanced T1 relaxometry for assessment of liver function determined by real-time 13C-methacetin breath test.

OBJECTIVES: To determine whether liver function as determined by intravenous administration of 13C-methacetin and continuous real-time breath analysis can be estimated quantitatively from gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) relaxometry. METHODS: Sixty-six patients underwent a 13C-methacetin breath test (13C-MBT) for evaluation of liver function and Gd-EOB-DTPA-enhanced T1-relaxometry at 3 T. A transverse 3D VIBE sequence with an inline T1 calculation based on variable flip angles was acquired prior to (T1 pre) and 20 min post-Gd-EOB-DTPA (T1 post) administration. The reduction rate of T1 relaxation time (rrT1) and T1 relaxation velocity index (∆R1) between pre- and post-contrast images was evaluated. 13C-MBT values were correlated with T1post, ∆R1 and rrT1, providing an MRI-based estimated 13C-MBT value. The interobserver reliability was assessed by determining the intraclass correlation coefficient (ICC). RESULTS: Stratified by three different categories of 13C-MBT readouts, there was a constant increase of T1 post with increasing progression of diminished liver function (p ≤ 0.030) and a constant significant decrease of ∆R1 (p ≤ 0.025) and rrT1 (p < 0.018) with progression of liver damage as assessed by 13C-methacetin breath analysis. ICC for all T1 relaxation values and indices was excellent (> 0.88). A simple regression model showed a log-linear correlation of 13C-MBT values with T1post (r = 0.57; p < 0.001), ∆R1 (r = 0.59; p < 0.001) and rrT1 (r = 0.70; p < 0.001). CONCLUSION: Liver function as determined using real-time 13C-methacetin breath analysis can be estimated quantitatively from Gd-EOB-DTPA-enhanced MR relaxometry. KEY POINTS: • Gd-EOB-DTPA-enhanced T1 relaxometry quantifies liver function • Gd-EOB-DTPA-enhanced MR relaxometry may provide parameters for assessing liver function before surgery • Gd-EOB-DTPA-enhanced MR relaxometry may be useful for monitoring liver disease progression • Gd-EOB-DTPA-enhanced MR relaxometry has the potential to become a novel liver function index.

CT after Endovascular Repair of Abdominal Aortic Aneurysms: Diagnostic Accuracy of Diameter Measurements for the Detection of Aneurysm Sac Enlargement.

PURPOSE: To evaluate the diagnostic accuracy of diameter measurements for the detection of aneurysm volume increase during follow-up after endovascular aortic repair (EVAR) of abdominal aortic aneurysms (AAAs). MATERIALS AND METHODS: This retrospective study analyzed 100 pairs of follow-up computed tomography scans randomly selected from an EVAR database (male/female ratio, 91/9; mean age, 71 y; bifurcated and aortouniiliac stent grafts, 96% and 4%, respectively; mean interval, 359 d). Five maximum diameter (Dmax) values were measured (anteroposterior, transverse, axial, coronal, and perpendicular). Aneurysm sac volume was measured by manual segmentation and used as the standard of reference. Overall, 37% of patients had a persistent type II endoleak. RESULTS: The anteroposterior, transverse, axial, coronal, and perpendicular Dmax values increased in 39 patients (mean, 4.3 mm), 30 patients (mean, 4.0), 35 patients (mean, 3.9 mm), 43 patients (mean, 3.9 mm), and 41 patients (mean, 4.3 mm), respectively. Aneurysm sac volume increased in 39 patients (mean, 25.7 cm3). The cutoff levels according to the reporting standard for aneurysm sac enlargement (diameter ≥ 5.0 mm, volume ≥ 5.0%) had sensitivity/specificity rates of 29%/95%, 33%/97%, 29%/99%, 33%/93%, and 38%/96%, respectively, for the five Dmax values. The reference standards failed to detect aneurysm volume increase in 72%, 67%, 72%, 61%, and 67% of patients, respectively, with persistent type II endoleak. CONCLUSIONS: Depending on the chosen cutoff value, diameter measurements showed low to moderate sensitivity for the detection of aneurysm volume increase. The diameter measurements failed to detect aneurysm enlargement in a large number of patients with persistent type II endoleak after EVAR of AAA.

Volume-assisted estimation of liver function based on Gd-EOB-DTPA-enhanced MR relaxometry.

OBJECTIVES: To determine whether liver function as determined by indocyanine green (ICG) clearance can be estimated quantitatively from hepatic magnetic resonance (MR) relaxometry with gadoxetic acid (Gd-EOB-DTPA). METHODS: One hundred and seven patients underwent an ICG clearance test and Gd-EOB-DTPA-enhanced MRI, including MR relaxometry at 3 Tesla. A transverse 3D VIBE sequence with an inline T1 calculation was acquired prior to and 20 minutes post-Gd-EOB-DTPA administration. The reduction rate of T1 relaxation time (rrT1) between pre- and post-contrast images and the liver volume-assisted index of T1 reduction rate (LVrrT1) were evaluated. The plasma disappearance rate of ICG (ICG-PDR) was correlated with the liver volume (LV), rrT1 and LVrrT1, providing an MRI-based estimated ICG-PDR value (ICG-PDRest). RESULTS: Simple linear regression model showed a significant correlation of ICG-PDR with LV (r = 0.32; p = 0.001), T1post (r = 0.65; p < 0.001) and rrT1 (r = 0.86; p < 0.001). Assessment of LV and consecutive evaluation of multiple linear regression model revealed a stronger correlation of ICG-PDR with LVrrT1 (r = 0.92; p < 0.001), allowing for the calculation of ICG-PDRest. CONCLUSIONS: Liver function as determined using ICG-PDR can be estimated quantitatively from Gd-EOB-DTPA-enhanced MR relaxometry. Volume-assisted MR relaxometry has a stronger correlation with liver function than does MR relaxometry. KEY POINTS: • Measurement of T1 relaxation times in Gd-EOB-DTPA-enhanced MR imaging quantifies liver function. • Volume-assisted Gd-EOB-DTPA-enhanced MR relaxometry has stronger correlation with ICG-PDR than does Gd-EOB-DTPA-enhanced MR relaxometry. • Gd-EOB-DTPA-enhanced MR relaxometry may provide robust parameters for detecting and characterizing liver disease. • Gd-EOB-DTPA-enhanced MR relaxometry may be useful for monitoring liver disease progression. • Gd-EOB-DTPA-enhanced MR relaxometry has the potential to become a novel liver function index.

IL-13 orchestrates resolution of chronic intestinal inflammation via phosphorylation of glycogen synthase kinase-3ß.

Spontaneous amelioration of inflammation (often accompanied by fibrosis) is a well-known, but poorly understood, outcome of many chronic inflammatory processes. We studied this phenomenon in a chronic trinitrobenzene sulfonic acid-induced colitis model, an experimental colitis in mice that we showed to ultimately undergo spontaneous resolution, despite continued trinitrobenzene sulfonic acid stimulation. Analysis of the mechanism of this resolution revealed that it was critically dependent on IL-13 activation of STAT6, followed by phosphorylation (inactivation) of glycogen synthase kinase-3ß, at least in part via STAT6 induction of p38 MAPK. Such glycogen synthase kinase-3ß inactivation causes changes in CREB and p65 DNA-binding activity that favors decreased proinflammatory IL-17 production and increased anti-inflammatory IL-10 production. Thus, in this case, IL-13 acts as a molecular switch that leads to resolution of inflammation.

Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist.

Peroxisome proliferator-activated receptor delta (PPARδ), a member of the nuclear receptor family, is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle, and liver. Here we show that the PPARδ agonist KD3010, but not the well-validated GW501516, dramatically ameliorates liver injury induced by carbon tetrachloride (CCl(4)) injections. Deposition of extracellular matrix proteins was lower in the KD3010-treated group than in the vehicle- or GW501516-treated group. Interestingly, profibrogenic connective tissue growth factor was induced significantly by GW501516, but not by KD3010, following CCl(4) treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for 3 wk. Primary hepatocytes treated with KD3010 but not GW501516 were protected from starvation or CCl(4)-induced cell death, in part because of reduced reactive oxygen species production. In conclusion, our data demonstrate that an orally active PPARδ agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis, suggesting a possible mechanistic and therapeutic approach in treating patients with chronic liver diseases.

Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids.

BACKGROUND & AIMS: Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. METHODS: We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2(-/-) mice. RESULTS: Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2(-/-) mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2(-/-) mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1ß in a Nod2 dependent fashion. CONCLUSIONS: Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte.

Attosecond chronoscopy of the photoemission near a bandgap of a single-element layered dielectric.

We report on the energy dependence of the photoemission time delay from the single-element layered dielectric HOPG (highly oriented pyrolytic graphite). This system offers the unique opportunity to directly observe the Eisenbud-Wigner-Smith (EWS) time delays related to the bulk electronic band structure without being strongly perturbed by ubiquitous effects of transport, screening, and multiple scattering. We find the experimental streaking time shifts to be sensitive to the modulation of the density of states in the high-energy region (E ≈ 100 eV) of the band structure. The present attosecond chronoscopy experiments reveal an energy-dependent increase of the photoemission time delay when the final state energy of the excited electrons lies in the vicinity of the bandgap providing information difficult to access by conventional spectroscopy. Accompanying simulations further corroborate our interpretation.

Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice.

BACKGROUND & AIMS: Progression of liver fibrosis in experimental models depends on gut-derived bacterial products, but little is known about mechanisms of disruption of the mucosal barrier or translocation. We used a mouse model of cholestatic liver disease to investigate mechanisms of intestinal barrier disruption following liver injury. METHODS: Liver fibrosis and bacterial translocation were assessed in Toll-like receptor 2 (TLR2)-deficient and tumor necrosis factor receptor I (TNFRI)-deficient mice subjected to bile duct ligation. Epithelial and lamina propria cells were isolated and analyzed by immunoblot analyses and flow cytometry. We analyzed bone marrow chimeras and mice with a conditional gain-of-function allele for the TNFRI receptor. By crossing TNFRI(flxneo/flxneo) mice with mice that expressed the VillinCre transgene specifically in intestinal epithelial cells, we created mice that express functional TNFRI specifically on intestinal epithelial cells (VillinCreTNFRI(flxneo/flxneo) mice). RESULTS: Following bile duct ligation, TLR2-deficient mice had less liver fibrosis and intestinal translocation of bacteria and bacterial products than wild-type mice. Mice with hematopoietic cells that did not express TLR2 also had reduced bacterial translocation, indicating that TLR2 expression by hematopoietic cells regulates intestinal barrier function. The number of TLR2(+) monocytes that produce tumor necrosis factor α increased in the intestinal lamina propria of wild-type mice following bile duct ligation; bacterial translocation was facilitated by TNFRI-mediated signals on intestinal epithelial cells. CONCLUSIONS: Intestinal inflammation and bacterial translocation contribute to liver fibrosis via TLR2 signaling on monocytes in the lamina propria and TNFRI signaling on intestinal epithelial cells in mice. Therefore, enteric TNFRI is an important mediator of cholestatic liver fibrosis.

Added value of Gd-EOB-DTPA-enhanced Hepatobiliary phase MR imaging in evaluation of focal solid hepatic lesions.

BACKGROUND: Correct characterization of focal solid hepatic lesions has always been a challenge and is of great diagnostic and therapeutic relevance. The purpose of this study was to determine the added value of hepatobiliary phase images in Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for differentiating focal solid hepatic lesions. METHODS: In this retrospective trial 84 consecutive patients underwent Gd-EOB-DTPA-enhanced MR examinations. MRI was conducted for 64 patients with malignant focal hepatic lesions (34 hepatocellular carcinoma (HCC), 30 metastases) and for 20 patients with benign hepatic lesions (14 focal nodular hyperplasia (FNH), 3 adenoma, 3 hemangioma). Five radiologists independently reviewed three sets of MR images by means of a 5-point confidence scale from score 1 (definitely benign) to score 5 (definitely malignant): set 1: unenhanced images; set 2: unenhanced and Gd-EOB-DTPA-enhanced dynamic images; set 3: hepatobiliary phase images in addition to set 2. Accuracy was assessed by the alternative free-response receiver operating characteristic curve (Az) and the index of diagnostic performance was calculated. RESULTS: Diagnostic accuracy was significantly improved by the addition of Gd-EOB-DTPA-enhanced dynamic images: Az in set 1 was 0.708 and 0.833 in set 2 (P = 0.0002). The addition of hepatobiliary phase images increased the Az value to 0.941 in set 3 (set 3 vs set 2, P < 0.0001; set 3 vs set 1, P < 0.0001). The index of diagnostic performance was lowest in set 1 (45%), improved in set 2 (71%), and highest in set 3 (94%). CONCLUSIONS: Hepatobiliary phase images obtained after Gd-EOB-DTPA-enhanced dynamic MRI improve the differentiation of focal solid hepatic lesions.

Water-Fat Separated T1 Mapping in the Liver and Correlation to Hepatic Fat Fraction.

(1) Background: T1 mapping in magnetic resonance imaging (MRI) of the liver has been proposed to estimate liver function or to detect the stage of liver disease, among others. Thus far, the impact of intrahepatic fat on T1 quantification has only been sparsely discussed. Therefore, the aim of this study was to evaluate the potential of water-fat separated T1 mapping of the liver. (2) Methods: A total of 386 patients underwent MRI of the liver at 3 T. In addition to routine imaging techniques, a 3D variable flip angle (VFA) gradient echo technique combined with a two-point Dixon method was acquired to calculate T1 maps from an in-phase (T1_in) and water-only (T1_W) signal. The results were correlated with proton density fat fraction using multi-echo 3D gradient echo imaging (PDFF) and multi-echo single voxel spectroscopy (PDFF_MRS). Using T1_in and T1_W, a novel parameter FF_T1 was defined and compared with PDFF and PDFF_MRS. Furthermore, the value of retrospectively calculated T1_W (T1_W_calc) based on T1_in and PDFF was assessed. Wilcoxon test, Pearson correlation coefficient and Bland-Altman analysis were applied as statistical tools. (3) Results: T1_in was significantly shorter than T1_W and the difference of both T1 values was correlated with PDFF (R = 0.890). FF_T1 was significantly correlated with PDFF (R = 0.930) and PDFF_MRS (R = 0.922) and yielded only minor bias compared to both established PDFF methods (0.78 and 0.21). T1_W and T1_W_calc were also significantly correlated (R = 0.986). (4) Conclusion: T1_W acquired with a water-fat separated VFA technique allows to minimize the influence of fat on liver T1. Alternatively, T1_W can be estimated retrospectively from T1_in and PDFF, if a Dixon technique is not available for T1 mapping.

Diagnostic Accuracy of Indocyanine Green Clearance Test for Different Stages of Liver Fibrosis and Cirrhosis.

(1) Background: This study aimed to correlate the indocyanine green clearance (ICG) test with histopathological grades of liver fibrosis and liver cirrhosis to assess its diagnostic accuracy in differentiating normal liver parenchyma from liver fibrosis and liver cirrhosis. (2) Methods: A total of 82 patients who received a histopathological liver examination, imaging, and ICG test within three months were included in this retrospective study. The histopathological level of fibrosis was graded using the Ishak scoring system, and the patients were divided into five categories: no liver fibrosis (NLF), mild liver fibrosis (MLF), advanced liver fibrosis (ALF), severe liver fibrosis (SLF), and liver cirrhosis (LC). The non-parametric Kruskal-Wallis test with post hoc pairwise comparison utilizing Mann-Whitney U tests and Bonferroni adjustment was used to analyze differences in the ICG test results between the patient groups. Cross correlation between the individual fibrosis/cirrhosis stages and the score of the ICG test was performed, and the sensitivity, specificity, and positive and negative predictive values were calculated for each model predicting liver fibrosis/cirrhosis. (3) Results: A significant difference (p ≤ 0.001) between stages of NLF, LF, and LC was found for the ICG parameters (ICG plasma disappearance rate (ICG-PDR) and ICG retention percentage at 15 min (ICG-R15)). The post hoc analysis revealed that NLF significantly differed from SLF (ICG-PDR: p = 0.001; ICG-R15: p = 0.001) and LC (ICG-PDR: p = 0.001; ICG-R15: p = 0.001). ALF also significantly differed from SLF (ICG-PDR: p = 0.033; ICG-R15: p = 0.034) and LC (ICG-PDR: p = 0.014; ICG-R15: p = 0.014). The sensitivity for detection of an initial stage of liver fibrosis compared to no liver fibrosis (Ishak ≥ 1) was 0.40; the corresponding specificity was 0.80. The differentiation of advanced liver fibrosis or cirrhosis (Ishak ≥ 4) compared to other stages of liver fibrosis was 0.75, with a specificity of 0.81. (4) Conclusions: This study shows that the ICG test, as a non-invasive diagnostic test, is able to differentiate patients with no liver fibrosis from patients with advanced liver fibrosis and liver cirrhosis. The ICG test seems to be helpful in monitoring patients with liver fibrosis regarding compensation levels, thus potentially enabling physicians to both detect progression from compensated liver fibrosis to advanced liver fibrosis and cirrhosis and to initiate antifibrotic treatment at an earlier stage.

Different Ultrasound Shear Wave Elastography Techniques as Novel Imaging-Based Approaches for Quantitative Evaluation of Hepatic Steatosis-Preliminary Findings.

BACKGROUND: Modern ultrasound (US) shear-wave dispersion (SWD) and attenuation imaging (ATI) can be used to quantify changes in the viscosity and signal attenuation of the liver parenchyma, which are altered in hepatic steatosis. We aimed to evaluate modern shear-wave elastography (SWE), SWD and ATI for the assessment of hepatic steatosis. METHODS: We retrospectively analyzed the US data of 15 patients who underwent liver USs and MRIs for the evaluation of parenchymal disease/liver lesions. The USs were performed using a multifrequency convex probe (1-8 MHz). The quantitative US measurements for the SWE (m/s/kPa), the SWD (kPa-m/s/kHz) and the ATI (dB/cm/MHz) were acquired after the mean value of five regions of interest (ROIs) was calculated. The liver MRI (3T) quantification of hepatic steatosis was performed by acquiring proton density fat fraction (PDFF) mapping sequences and placing five ROIs in artifact-free areas of the PDFF scan, measuring the fat-signal fraction. We correlated the SWE, SWD and ATI measurements to the PDFF results. RESULTS: Three patients showed mild steatosis, one showed moderate steatosis and eleven showed no steatosis in the PDFF sequences. The calculated SWE cut-off (2.5 m/s, 20.4 kPa) value identified 3/4 of patients correctly (AUC = 0.73, p > 0.05). The SWD cut-off of 18.5 m/s/kHz, which had a significant correlation (r = 0.55, p = 0.034) with the PDFF results (AUC = 0.73), identified four patients correctly (p < 0.001). The ideal ATI (AUC = 0.53 (p < 0.05)) cut-off was 0.59 dB/cm/MHz, which showed a significantly good correlation with the PDFF results (p = 0.024). CONCLUSION: Hepatic steatosis can be accurately detected using all the US-elastography techniques applied in this study, although the SWD and the SWE showed to be more sensitive than the PDFF.

Volume-Assisted Estimation of Remnant Liver Function Based on Gd-EOB-DTPA Enhanced MR Relaxometry: A Prospective Observational Trial.

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction.

Update on Percutaneous Local Ablative Procedures for the Treatment of Hepatocellular Carcinoma. / Aktueller Stand zu perkutanen lokalablativen Verfahren beim hepatozellulären Karzinom.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Because many hepatocellular carcinomas are already unresectable at the time of initial diagnosis, percutaneous tumor ablation has become established in recent decades as a curative therapeutic approach for very early (BCLC 0) and early (BCLC A) HCC. The aim of this paper is to provide a concise overview of the percutaneous local ablative procedures currently in use, based on their technical characteristics as well as clinical relevance, taking into account the current body of studies. MATERIALS AND METHODS: The literature search included all original papers, reviews, and meta-analyses available via MEDLINE and Pubmed on the respective percutaneous ablation procedures; the primary focus was on randomized controlled trials and publications from the last 10 years. RESULTS AND CONCLUSIONS: Radiofrequency ablation (RFA) and microwave ablation (MWA) are well-established procedures that are considered equal to surgical resection in the treatment of stage BCLC 0 and A HCC with a diameter up to 3 cm due to their strong evidence in international and national guidelines. For tumors with a diameter between 3 and 5 cm, the current S3 guidelines recommend a combination of transarterial chemoembolization (TACE) and thermal ablation using RFA or MWA as combination therapy is superior to thermal ablation alone in tumors of this size and shows comparable results to surgical resection in terms of overall survival. Alternative, less frequently employed thermal procedures include cryotherapy (CT) and laser ablation (LA). Non-thermal procedures include irreversible electroporation (IRE), interstitial brachytherapy (IBT), and most recently, electrochemotherapy (ECT). Due to insufficient evidence, these have only been used in individual cases and within the framework of studies. However, the nonthermal methods are a reasonable alternative for ablation of tumors adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods. With advances in the technology of the respective procedures, increasingly good evidence, and advancements in supportive techniques such as navigation devices and fusion imaging, percutaneous ablation procedures may expand their indications for the treatment of larger and more advanced tumors in the coming years. KEY POINTS: · RFA and MWA are considered equal to surgical resection as a first-line therapy for the curative treatment of stage BCLC 0 and A HCCs with a diameter of up to 3 cm.. · For HCCs with a diameter between 3 and 5 cm, a combination of TACE and RFA or MWA is recommended. This combination therapy yields results comparable to those of surgical resection in terms of overall survival.. · Due to insufficient evidence, alternative ablation methods have only been used in individual cases and within the framework of studies. However, nonthermal methods, such as IRE, IBT, and, most recently, ECT, are a reasonable alternative for ablation of HCCs adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods.. CITATION FORMAT: · Luerken L, Haimerl M, Doppler M et al. Update on Percutaneous Local Ablative Procedures for the Treatment of Hepatocellular Carcinoma. Fortschr Röntgenstr 2022; 194: 1075 - 1086.

High resolution flow with glazing flow for optimized flow detection in transjugular intrahepatic portosystemic stent shunt (TIPS): First results.

BACKGROUND: Ultrasound follow-up of transjugular intrahepatic portosystemic shunt (TIPS) is challenging due to the bent course of the stent-graft. OBJECTIVE: Aim of this retrospective study was to assess to which extent the combination of HR flow with Glazing Flow improves hemodynamic assessment in the ultrasound follow-up of TIPS. METHODS: Comparative studies with CCDS and High Resolution (HR)-Flow with Glazing Flow were evaluated regarding image quality and artifacts on a 5-point scale (0 = cannot be assessed up to 5 = maximum image quality without artifacts). In all cases, an experienced examiner performed the examinations with a 1-6 MHz probe (Resona 7, Mindray). RESULTS: 61 ultrasound examinations in 48 patients were performed; the mean patient age was 54±14.2 years. The use of HR-Flow with Glazing Flow resulted in an improved flow display in 55/61 cases (90.2%). Both methods correlated well (r = 0.71), but HR flow with Glazing flow values were in general higher than CCDS values. The reading resulted in an average value of 2.52±0.54 for CCDS and 3.52±0.57 for HR flow with Glazing flow (p = 0.013). CONCLUSION: The combination of HR-Flow and Glazing Flow results in improved flow representation and reduction of artifacts in the ultrasound follow-up of TIPS.

Quantitative analysis of liver function: 3D variable-flip-angle versus Look-Locker T1 relaxometry in hepatocyte-specific contrast-enhanced liver MRI.

Background: Gd-EOB-DTPA, a liver specific contrast agent with T1- shortening effects, is routinely used in clinical magnetic resonance imaging (MRI) for detection and characterization of focal liver lesions. Gd-EOB-DTPA-enhanced T1 relaxometry has recently received increasing attention as a tool for the quantitative analyses of liver function. However, this T1 relaxometry technique is limited due to various artifacts caused by B1 inhomogeneities and motion artifacts. This study aims to compare two different T1 relaxometry techniques for evaluating liver function as determined using a 13C-methacetin-based breath test (13C-MBT). Methods: Ninety-six patients underwent gadoxetic acid-enhanced MRI of the liver at 3T and a 13C-MBT. Two different prototype sequences for T1 relaxometry were used, a 3D VIBE sequence using Dixon water-fat separation and variable-flip-angles (VFA), as well as a 2D Look-Locker sequence (LL). Images were acquired before (T1 pre) and 20 minutes after (T1 post) administration of liver-specific contrast agent to evaluate the reduction rates of T1 relaxation time (rrT1) in accordance with the 13C-MBT outcome. To analyze both MR sequences' performance, the intraclass correlation coefficient (ICC) between four ROI measurements within the same liver and the coefficient of repeatability (CR) were calculated. Results: T1 relaxometry measurements based on MR sequences, VFA, and LL show a constant change in line with impaired liver function progression. Simple regression models showed a log-linear correlation of 13C-MBT values with all evaluated T1 relaxometry measurements (VFA T1post, VFA rrT1, LL T1post, LL rrT1, P<0.001). Both ICC (VFA T1post, LL T1post; 0.75, 0.95) and CR (VFA T1 post, LL T1 post; 179, 101) showed a better agreement between ROI measurements using the LL sequence. Conclusions: Both T1 relaxometry sequences are suitable for the evaluation of liver function based on 13C-MBT. However, the Look-Locker sequence is less susceptible to artifacts and might be more advantageous, especially in patients with impaired liver function.

Application of A U-Net for Map-like Segmentation and Classification of Discontinuous Fibrosis Distribution in Gd-EOB-DTPA-Enhanced Liver MRI.

We aimed to evaluate whether U-shaped convolutional neuronal networks can be used to segment liver parenchyma and indicate the degree of liver fibrosis/cirrhosis at the voxel level using contrast-enhanced magnetic resonance imaging. This retrospective study included 112 examinations with histologically determined liver fibrosis/cirrhosis grade (Ishak score) as the ground truth. The T1-weighted volume-interpolated breath-hold examination sequences of native, arterial, late arterial, portal venous, and hepatobiliary phases were semi-automatically segmented and co-registered. The segmentations were assigned the corresponding Ishak score. In a nested cross-validation procedure, five models of a convolutional neural network with U-Net architecture (nnU-Net) were trained, with the dataset being divided into stratified training/validation (n = 89/90) and holdout test datasets (n = 23/22). The trained models precisely segmented the test data (mean dice similarity coefficient = 0.938) and assigned separate fibrosis scores to each voxel, allowing localization-dependent determination of the degree of fibrosis. The per voxel results were evaluated by the histologically determined fibrosis score. The micro-average area under the receiver operating characteristic curve of this seven-class classification problem (Ishak score 0 to 6) was 0.752 for the test data. The top-three-accuracy-score was 0.750. We conclude that determining fibrosis grade or cirrhosis based on multiphase Gd-EOB-DTPA-enhanced liver MRI seems feasible using a 2D U-Net. Prospective studies with localized biopsies are needed to evaluate the reliability of this model in a clinical setting.

Dynamic perfusion analysis in acute ischemic stroke: A comparative study of two different softwares.

BACKGROUND: In clinical practice, decisions often must be made rapidly; therefore, automated software is useful for diagnostic support. Perfusion computed tomography and follow-up evaluation of perfusion data are valuable tools for selecting the optimal recanalization therapy in patients with acute ischemic stroke. OBJECTIVE: This study aimed to compare commercially available software used to evaluate stroke patients prior to thrombectomy. METHODS: The performance of Olea Sphere (OlS) software vs. CT Neuro Perfusion from Syngo (Sy), as well as the electronic Alberta Stroke Program Early Computed Tomography Score (e-ASPECTS) software vs. an experienced radiologist, were compared using descriptive statistics including significance analysis, Spearman's correlation, and the Bland-Altman agreement analysis. For this purpose, 43 data sets of patients with stroke symptoms related to the middle cerebral artery territory were retrospectively post-processed with both tools and analyzed. RESULTS: The automatic e-ASPECTS showed high agreement with an expert rater assessment of the ASPECTS. Using OlS and Sy, we compared the parameters for the ischemic core (relative cerebral blood flow), Time to maximum (Tmax) for the penumbra, and the relative mismatch between these two values. Overall, both software tools achieved good agreement, and their respective values correlated well with each other. However, OlS predicted significantly smaller infarct core volumes compared with Sy. CONCLUSIONS: Although the absolute values have a certain degree of variation, both software programs have good agreement with each other.

Gene expression changes in male and female rhesus macaque 60 days after irradiation.

PURPOSE: Transcriptome changes can be expected in survivors after lethal irradiation. We aimed to characterize these in males and females and after different cytokine treatments 60 days after irradiation. MATERIAL AND METHODS: Male and female rhesus macaques (n = 142) received a whole-body exposure with 700 cGy, from which 60 animals survived. Peripheral whole blood was drawn pre-exposure and before sacrificing the surviving animals after 60 days. RESULTS: We evaluated gene expression in a three-phase study design. Phase I was a whole-genome screening (NGS) for mRNAs using five pre- and post-exposure RNA samples from both sexes (n = 20). Differential gene expression (DGE) was calculated between samples of survivors and pre-exposure samples (reference), separately for males and females. 1,243 up- and down-regulated genes were identified with 30-50% more deregulated genes in females. 37 candidate mRNAs were chosen for qRT-PCR validation in phase II using the remaining samples (n = 117). Altogether 17 genes showed (borderline) significant (t-test) DGE in groups of untreated or treated animals. Nine genes (CD248, EDAR, FAM19A5, GAL3ST4, GCNT4, HBG2/1, LRRN1, NOG, SYT14) remained with significant changes and were detected in at least 50% of samples per group. Panther analysis revealed an overlap between both sexes, related to the WNT signaling pathway, cell adhesion and immunological functions. For phase III, we validated the nine genes with candidate genes (n = 32) from an earlier conducted study on male baboons. Altogether 14 out of 41 genes showed a concordantly DGE across both species in a bilateral comparison. CONCLUSIONS: Sixty days after radiation exposure, we identified (1) sex and cytokine treatment independent transcriptional changes, (2) females with almost twice as much deregulated genes appeared more radio-responsive than males, (3) Panther analysis revealed an association with immunological processes and WNT pathway for both sexes.

Quantification of contrast agent uptake in the hepatobiliary phase helps to differentiate hepatocellular carcinoma grade.

This study aimed to assess the degree of differentiation of hepatocellular carcinoma (HCC) using Gd-EOB-DTPA-assisted magnetic resonance imaging (MRI) with T1 relaxometry. Thirty-three solitary HCC lesions were included in this retrospective study. This study's inclusion criteria were preoperative Gd-EOB-DTPA-assisted MRI of the liver and a histopathological evaluation after hepatic tumor resection. T1 maps of the liver were evaluated to determine the T1 relaxation time and reduction rate between the native phase and hepatobiliary phase (HBP) in liver lesions. These findings were correlated with the histopathologically determined degree of HCC differentiation (G1, well-differentiated; G2, moderately differentiated; G3, poorly differentiated). There was no significant difference between well-differentiated (950.2 ± 140.2 ms) and moderately/poorly differentiated (1009.4 ± 202.0 ms) HCCs in the native T1 maps. After contrast medium administration, a significant difference (p ≤ 0.001) in the mean T1 relaxation time in the HBP was found between well-differentiated (555.4 ± 140.2 ms) and moderately/poorly differentiated (750.9 ± 146.4 ms) HCCs. For well-differentiated HCCs, the reduction rate in the T1 time was significantly higher at 0.40 ± 0.15 than for moderately/poorly differentiated HCCs (0.25 ± 0.07; p = 0.006). In conclusion this study suggests that the uptake of Gd-EOB-DTPA in HCCs is correlated with tumor grade. Thus, Gd-EOB-DTPA-assisted T1 relaxometry can help to further differentiation of HCC.