ResearchPad - liver-and-spleen-scan https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A pilot study of ex-vivo MRI-PDFF of donor livers for assessment of steatosis and predicting early graft dysfunction]]> https://www.researchpad.co/article/elastic_article_14544 The utility of ex vivo Magnetic resonance imaging proton density fat fraction (MRI-PDFF) in donor liver fat quantification is unknown.PurposeTo evaluate the diagnostic accuracy and utility in predicting early allograft dysfunction (EAD) of ex vivo MRI-PDFF measurement of fat in deceased donor livers using histology as the gold standard.MethodsWe performed Ex vivo, 1.5 Tesla MRI-PDFF on 33 human deceased donor livers before implantation, enroute to the operating room. After the exclusion of 4 images (technical errors), 29 MRI images were evaluable. Histology was evaluable in 27 of 29 patients. EAD was defined as a peak value of aminotransferase >2000 IU/mL during the first week or an INR of ≥1.6 or bilirubin ≥10 mg/dL at day 7.ResultsMRI-PDFF values showed a strong positive correlation (Pearson’s correlation coefficient) when histology (macro-steatosis) was included (r = 0.78, 95% confidence interval 0.57‐0.89, p<0.0001). The correlation appeared much stronger when macro plus micro-steatosis were included (r = 0.87, 95% confidence interval 0.72‐0.94, p<0.0001). EAD was noted in 7(25%) subjects. AUC (Area Under the Curve) for macro steatosis (histology) predicted EAD in 73% (95% CI: 48–99), micro plus macro steatosis in 76% (95% CI: 49–100). AUC for PDFF values predicted EAD in 67(35–98). Comparison of the ROC curves in a multivariate model revealed, adding MRI PDFF values to macro steatosis increased the ability of the model in predicting EAD (AUC: 79%, 95% CI: 59–99), and addition of macro plus micro steatosis based on histology predicted EAD even better (AUC: 90%: 79–100, P = 0.054).ConclusionIn this pilot study, MRI-PDFF imaging showed potential utility in quantifying hepatic steatosis ex-vivo donor liver evaluation and the ability to predict EAD related to severe allograft steatosis in the recipient. ]]> <![CDATA[Improved visualisation of hepatic metastases in gadoxetate disodium-enhanced MRI: Potential of contrast-optimised (phase-sensitive) inversion recovery imaging]]> https://www.researchpad.co/article/5c897740d5eed0c4847d2834

Background

Detection of metastases can have a significant impact on therapy. Nevertheless, even in gadoxetate disodium-enhanced MR scans, very small hepatic metastases may be difficult to see.

Purpose

To investigate the potential of a contrast-optimised (phase-sensitive) inversion recovery MR sequence in gadoxetate disodium-enhanced scans for detection of hepatic metastases.

Materials and methods

With institutional review board approval and after written informed consent, 40 patients (18 male, 22 female) with suspected or known hepatic metastases were examined on a 1.5 T MR system. A T1-weighted gradient-echo volumetric-interpolated-breath-hold (VIBE) sequence was acquired as part of the standard imaging protocol 20 minutes after administration of gadoxetate disodium. Additionally, an IR sequence was acquired with an inversion time to suppress native signal from metastases. Overall image quality and delineation of lesions were assessed on VIBE as well as on magnitude-reconstructed (MAG) and phase-sensitive IR (PSIR) sequences. Lesion-to-liver contrast (LLC) was compared between VIBE and MAG images.

Results

Overall image quality was high in both VIBE and MAG IR sequences (VIBE 4.275; MAG 4.313), yet significantly lower in PSIR (4.038). Subjective delineation of lesions was higher on MAG and PSIR images compared to VIBE in all size groups with an overall statistically significant difference for VIBE vs. MAG vs. PSIR (p < .001) in the variance analysis. Mean LLC was 0.35±0.01 for VIBE sequences, and 0.73±0.01 for MAG.

Conclusion

Contrast-optimised PSIR seems to improve imaging characteristics of hepatic metastases in gadoxetate disodium-enhanced scans compared to T1 gradient-echo VIBE sequences.

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<![CDATA[A new formula to calculate the resection limit in hepatectomy based on Gd-EOB-DTPA-enhanced magnetic resonance imaging]]> https://www.researchpad.co/article/5c644885d5eed0c484c2e84f

Background and aim

Dynamic magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) can be used not only to detect liver tumors but also to estimate liver function. The aim of this study was to establish a new EOB-MRI-based formula to determine the resection limit in patients undergoing hepatectomy.

Methods

Twenty-eight patients with a normal liver (NL group) and five with an unresectable cirrhotic liver (UL group) who underwent EOB-MRI were included. Standardized liver function (SLF) was calculated based on the signal intensity (SI), the volume of each subsegment (S1–S8), and body surface area. A formula defining the resection limit was devised based on the difference in the SLF values of patients in the NL and UL groups. The formula was validated in 50 patients who underwent EOB-MRI and hepatectomy.

Results

The average SLF value in the NL and UL groups was 2038 and 962 FV/m2, respectively. The difference (1076 FV/m2) was consistent with a 70% in resection volume. Thus, the resection limit for hepatectomy was calculated as a proportion of 70%: 70×(SLF−962)/1076 (%). The one patient who underwent hepatectomy over the resection limit died due to liver failure. In other 49 patients, in whom the resection volume was less than the resection limit, procedures were safely performed.

Conclusions

Our formula for resection limit based on EOB-MRI can improve the safety of hepatectomy.

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<![CDATA[Measurement of liver iron by magnetic resonance imaging in the UK Biobank population]]> https://www.researchpad.co/article/5c26973bd5eed0c48470efe9

The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease. The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals. Magnetic resonance imaging (MRI) was undertaken at the UK Biobank imaging centre, acquiring a multi-echo spoiled gradient-echo single-breath-hold MRI sequence from the liver. All images were analysed for liver iron and fat (expressed as proton density fat fraction or PDFF) content using LiverMultiScan. Liver iron was measured in 97.3% of the cohort. The mean liver iron content was 1.32 ± 0.32 mg/g while the median was 1.25 mg/g (min: 0.85 max: 6.44 mg/g). Overall 4.82% of the population were defined as having elevated liver iron, above commonly accepted 1.8 mg/g threshold based on biochemical iron measurements in liver specimens obtained by biopsy. Further analysis using univariate models showed elevated liver iron to be related to male sex (p<10−16, r2 = 0.008), increasing age (p<10−16, r2 = 0.013), and red meat intake (p<10−16, r2 = 0.008). Elevated liver fat (>5.6% PDFF) was associated with a slight increase in prevalence of elevated liver iron (4.4% vs 6.3%, p = 0.0007). This study shows that population studies including measurement of liver iron concentration are feasible, which may in future be used to better inform patient stratification and treatment.

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<![CDATA[Semi-Supervised Feature Transformation for Tissue Image Classification]]> https://www.researchpad.co/article/5989da08ab0ee8fa60b76a30

Various systems have been proposed to support biological image analysis, with the intent of decreasing false annotations and reducing the heavy burden on biologists. These systems generally comprise a feature extraction method and a classification method. Task-oriented methods for feature extraction leverage characteristic images for each problem, and they are very effective at improving the classification accuracy. However, it is difficult to utilize such feature extraction methods for versatile task in practice, because few biologists specialize in Computer Vision and/or Pattern Recognition to design the task-oriented methods. Thus, in order to improve the usability of these supporting systems, it will be useful to develop a method that can automatically transform the image features of general propose into the effective form toward the task of their interest. In this paper, we propose a semi-supervised feature transformation method, which is formulated as a natural coupling of principal component analysis (PCA) and linear discriminant analysis (LDA) in the framework of graph-embedding. Compared with other feature transformation methods, our method showed favorable classification performance in biological image analysis.

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<![CDATA[Characterisation of liver fat in the UK Biobank cohort]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdbc49

Non-alcoholic fatty liver disease and the risk of progression to steatohepatitis, cirrhosis and hepatocellular carcinoma have been identified as major public health concerns. We have demonstrated the feasibility and potential value of measuring liver fat content by magnetic resonance imaging (MRI) in a large population in this study of 4,949 participants (aged 45–73 years) in the UK Biobank imaging enhancement. Despite requirements for only a single (≤3min) scan of each subject, liver fat was able to be measured as the MRI proton density fat fraction (PDFF) with an overall success rate of 96.4%. The overall hepatic fat distribution was centred between 1–2%, and was highly skewed towards higher fat content. The mean PDFF was 3.91%, and median 2.11%. Analysis of PDFF in conjunction with other data fields available from the UK Biobank Resource showed associations of increased liver fat with greater age, BMI, weight gain, high blood pressure and Type 2 diabetes. Subjects with BMI less than 25 kg/m2 had a low risk (5%) of high liver fat (PDFF > 5.5%), whereas in the higher BMI population (>30 kg/m2) the prevalence of high liver fat was approximately 1 in 3. These data suggest that population screening to identify people with high PDFF is possible and could be cost effective. MRI based PDFF is an effective method for this. Finally, although cross sectional, this study suggests the utility of the PDFF measurement within UK Biobank, particularly for applications to elucidating risk factors through associations with prospectively acquired data on clinical outcomes of liver diseases, including non-alcoholic fatty liver disease.

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<![CDATA[Feature Learning Based Random Walk for Liver Segmentation]]> https://www.researchpad.co/article/5989da82ab0ee8fa60b9b277

Liver segmentation is a significant processing technique for computer-assisted diagnosis. This method has attracted considerable attention and achieved effective result. However, liver segmentation using computed tomography (CT) images remains a challenging task because of the low contrast between the liver and adjacent organs. This paper proposes a feature-learning-based random walk method for liver segmentation using CT images. Four texture features were extracted and then classified to determine the classification probability corresponding to the test images. Seed points on the original test image were automatically selected and further used in the random walk (RW) algorithm to achieve comparable results to previous segmentation methods.

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<![CDATA[Monitoring Radiofrequency Ablation Using Ultrasound Envelope Statistics and Shear Wave Elastography in the Periablation Period: An In Vitro Feasibility Study]]> https://www.researchpad.co/article/5989da26ab0ee8fa60b80a1f

Radiofrequency ablation (RFA) is a minimally invasive method for treating tumors. Shear wave elastography (SWE) has been widely applied in evaluating tissue stiffness and final ablation size after RFA. However, the usefulness of periablation SWE imaging in assessing RFA remains unclear. Therefore, this study investigated the correlation between periablation SWE imaging and final ablation size. An in vitro porcine liver model was used for experimental validation (n = 36). During RFA with a power of 50 W, SWE images were collected using a clinical ultrasound system. To evaluate the effects of tissue temperature and gas bubbles during RFA, changes in the ablation temperature were recorded, and image echo patterns were measured using B-mode and ultrasound statistical parametric images. After RFA, the gross pathology of each tissue sample was compared with the region of change in the corresponding periablation SWE image. The experimental results showed that the tissue temperature at the ablation site varied between 70°C and 100°C. Hyperechoic regions and changes were observed in the echo amplitude distribution induced by gas bubbles. Under this condition, the confounding effects (including the temperature increase, tissue stiffness increase, and presence of gas bubbles) resulted in artifacts in the periablation SWE images, and the corresponding region correlated with the estimated final ablation size obtained from the gross pathology (r = 0.8). The findings confirm the feasibility of using periablation SWE imaging in assessing RFA.

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<![CDATA[Performance of Real-Time Elastography for the Staging of Hepatic Fibrosis: A Meta-Analysis]]> https://www.researchpad.co/article/5989da97ab0ee8fa60ba239b

Background

With the rapid development of real-time elastography (RTE), a variety of measuring methods have been developed for the assessment of hepatic fibrosis. We evaluated the overall performance of four methods based on RTE by performing meta-analysis of published literature.

Methods

Online journal databases and a manual search from April 2000 to April 2014 were used. Studies from different databases that meet inclusion criteria were enrolled. The statistical analysis was performed using a random-effects model and fixed-effects model for the overall effectiveness of RTE. The area under the receiver operating characteristic curve (AUROC) was calculated for various means. Fagan plot analysis was used to estimate the clinical utility of RTE, and the heterogeneity of the studies was explored with meta-regression analysis.

Results

Thirteen studies from published articles were enrolled and analyzed. The combined AUROC of the liver fibrosis index (LFI) for the evaluation of significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4) were 0.79, 0.94, and 0.85, respectively. The AUROC of the elasticity index (EI) ranged from 0.75 to 0.92 for F≥2 and 0.66 to 0.85 for F = 4. The overall AUROC of the elastic ratio of the liver for the intrahepatic venous vessels were 0.94, 0.93, and 0.96, respectively. The AUROC of the elastic ratio of the liver for the intercostal muscle in diagnosing advanced fibrosis and cirrhosis were 0.96 and 0.92, respectively. There was significant heterogeneity in the diagnostic odds ratio (DOR) for F≥2 of LFI mainly due to etiology (p<0.01).

Conclusion

The elastic ratio of the liver for the intrahepatic vein has excellent precision in differentiating each stage of hepatic fibrosis and is recommend to be applied to the clinic.

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<![CDATA[Characterization of CC-531 as a Rat Model of Colorectal Liver Metastases]]> https://www.researchpad.co/article/5989da05ab0ee8fa60b757e0

Purpose

Surgical resection of colorectal liver metastases is not achievable in more than 70% of the cases. Although the liver directed therapies have become a part of the stand of care, lack of a preclinical model impedes the assessment of toxicity and therapeutic benefits attributed several candidate drugs or treatment regimens that can be designed. In the present study we aim develop and characterize a rat colorectal liver metastasis model.

Materials and Methods

Growth characteristics of CC-531 cells were determined in vitro followed by subcapsular liver implantation in syngeneic WAG/Rij rats. Tumor growth progression was followed over 3 weeks by ultrasound (US) and magnetic resonance imaging (MRI). Growth characteristics were also assessed by histopathology and immunohistochemistry in harvested tumor tissues.

Results

The doubling time of CC-531 cells was found be under 24hrs and all the implanted rats grew tumors. US imaging showed hypoechoic masses and MRI showed contrast enhancement representing complex tumor microenvironments. Hematoxylin and Eosin staining confirmed tumor growth and uniform CD31 staining in tumor confirmed even vessel density.

Conclusion

CC-531 can be used as a metastatic rat tumor colorectal liver metastases model with well-defined characteristics that can be readily followed by imaging whilst having a therapeutic window for interventions.

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<![CDATA[Optimization of Tagged MRI for Quantification of Liver Stiffness Using Computer Simulated Data]]> https://www.researchpad.co/article/5989da30ab0ee8fa60b8427f

The heartbeat has been proposed as an intrinsic source of motion that can be used in combination with tagged Magnetic Resonance Imaging (MRI) to measure displacements induced in the liver as an index of liver stiffness. Optimizing a tagged MRI acquisition protocol in terms of sensitivity to these displacements, which are in the order of pixel size, is necessary to develop the method as a quantification tool for staging fibrosis. We reproduced a study of cardiac-induced strain in the liver at 3T and simulated tagged MR images with different grid tag patterns to evaluate the performance of the Harmonic Phase (HARP) image analysis method and its dependence on the parameters of tag spacing and grid angle. The Partial Volume Effect (PVE), T1 relaxation, and different levels of noise were taken into account. Four displacement fields of increasing intensity were created and applied to the tagged MR images of the liver. These fields simulated the deformation at different liver stiffnesses. An Error Index (EI) was calculated to evaluate the estimation accuracy for various parameter values. In the absence of noise, the estimation accuracy of the displacement fields increased as tag spacings decreased. EIs for each of the four displacement fields were lower at 0° and the local minima of the EI were found to correspond to multiples of pixel size. The accuracy of the estimation decreased for increasing levels of added noise; as the level increased, the improved estimation caused by decreasing the tag spacing tended to zero. The optimal tag spacing turned out to be a compromise between the smallest tag period that is a multiple of the pixel size and is achievable in a real acquisition and the tag spacing that guarantees an accurate liver displacement measure in the presence of realistic levels of noise.

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<![CDATA[Is MR Spectroscopy Really the Best MR-Based Method for the Evaluation of Fatty Liver in Diabetic Patients in Clinical Practice?]]> https://www.researchpad.co/article/5989db49ab0ee8fa60bd9717

Objective

To investigate if magnetic resonance spectroscopy (MRS) is the best Magnetic Resonance (MR)-based method when compared to gradient-echo magnetic resonance imaging (MRI) for the detection and quantification of liver steatosis in diabetic patients in the clinical practice using liver biopsy as the reference standard, and to assess the influence of steatohepatitis and fibrosis on liver fat quantification.

Methods

Institutional approval and patient consent were obtained for this prospective study. Seventy-three patients with type 2 diabetes (60 women and 13 men; mean age, 54±9 years) underwent MRI and MRS at 3.0 T. The liver fat fraction was calculated from triple- and multi-echo gradient-echo sequences, and MRS data. Liver specimens were obtained in all patients. The accuracy for liver fat detection was estimated by receiver operator characteristic (ROC) analysis, and the correlation between fat quantification by imaging and histolopathology was analyzed by Spearman's correlation coefficients.

Results

The prevalence of hepatic steatosis was 92%. All gradient-echo MRI and MRS findings strongly correlated with biopsy findings (triple-echo, rho = 0.819; multi-echo, rho = 0.773; MRS, rho = 0.767). Areas under the ROC curves to detect mild, moderate, and severe steatosis were: triple-echo sequences, 0.961, 0.975, and 0.962; multi-echo sequences, 0.878, 0.979, and 0.961; and MRS, 0.981, 0.980, and 0.954. The thresholds for mild, moderate, and severe steatosis were: triple-echo sequences, 4.09, 9.34, and 12.34, multi-echo sequences, 7.53, 11.75, and 15.08, and MRS, 1.71, 11.69, and 14.91. Quantification was not significantly influenced by steatohepatitis or fibrosis.

Conclusions

Liver fat quantification by MR methods strongly correlates with histopathology. Due to the wide availability and easier post-processing, gradient-echo sequences may represent the best imaging method for the detection and quantification of liver fat fraction in diabetic patients in the clinical practice.

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<![CDATA[Non-Rigid Registration of Liver CT Images for CT-Guided Ablation of Liver Tumors]]> https://www.researchpad.co/article/5989dab3ab0ee8fa60bac11d

CT-guided percutaneous ablation for liver cancer treatment is a relevant technique for patients not eligible for surgery and with tumors that are inconspicuous on US imaging. The lack of real-time imaging and the use of a limited amount of CT contrast agent make targeting the tumor with the needle challenging. In this study, we evaluate a registration framework that allows the integration of diagnostic pre-operative contrast enhanced CT images and intra-operative non-contrast enhanced CT images to improve image guidance in the intervention. The liver and tumor are segmented in the pre-operative contrast enhanced CT images. Next, the contrast enhanced image is registered to the intra-operative CT images in a two-stage approach. First, the contrast-enhanced diagnostic image is non-rigidly registered to a non-contrast enhanced image that is conventionally acquired at the start of the intervention. In case the initial registration is not sufficiently accurate, a refinement step is applied using non-rigid registration method with a local rigidity term. In the second stage, the intra-operative CT-images that are used to check the needle position, which often consist of only a few slices, are registered rigidly to the intra-operative image that was acquired at the start of the intervention. Subsequently, the diagnostic image is registered to the current intra-operative image, using both transformations, this allows the visualization of the tumor region extracted from pre-operative data in the intra-operative CT images containing needle. The method is evaluated on imaging data of 19 patients at the Erasmus MC. Quantitative evaluation is performed using the Dice metric, mean surface distance of the liver border and corresponding landmarks in the diagnostic and the intra-operative images. The registration of the diagnostic CT image to the initial intra-operative CT image did not require a refinement step in 13 cases. For those cases, the resulting registration had a Dice coefficient for the livers of 91.4%, a mean surface distance of 4.4 mm and a mean distance between corresponding landmarks of 4.7 mm. For the three cases with a refinement step, the registration result significantly improved (p<0.05) compared to the result of the initial non rigid registration method (DICE of 90.3% vs 71.3% and mean surface distance of 5.1 mm vs 11.3 mm and mean distance between corresponding landmark of 6.4 mm vs 10.2 mm). The registration of the preoperative data with the needle image in 16 cases yielded a DICE of 90.1% and a mean surface distance of 5.2 mm. The remaining three cases with DICE smaller than 80% were classified as unsuccessful registration. The results show that this is promising tool for liver image registration in interventional radiology.

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<![CDATA[Assessment of Vascularity in Hepatic Alveolar Echinococcosis: Comparison of Quantified Dual-Energy CT with Histopathologic Parameters]]> https://www.researchpad.co/article/5989db0bab0ee8fa60bca47f

Purpose

To investigate whether dual-energy computer tomography(DECT) could determine the angiographic vascularity of alveolar echinococcosis lesions by comparing the quantitative iodine concentration (IC) with the microvascular density (MVD).

Material and Methods

Twenty-five patients (16 men, 9 women; mean age, 40.9 ± 13.8 years) with confirmed hepatic alveolar echinococcosis (HAE) underwent DECT of the abdomen, consisting of arterial phase (AP), portal venous phase (PVP), and delayed phase (DP) scanning, in dual-source mode (100 kV/140 kV). Image data were processed with a DECT software algorithm that was designed for the evaluation of iodine distribution in the different layers (marginal zone, solid and cystic) of the lesions. The CT patterns of HAE lesions were classified into three types: solid type, pseudocystic type and ‘geographic map’ (mixed) type. The IC measurements in different layers and different types of lesions were statistically compared. MVD was examined using CD34 immunohistochemical staining of the resected HAE tissue and scored based on the percentage of positively stained cells and their intensity. Pearson’s correlation analysis was used to evaluate the potential correlation between DECT parameters and MVD.

Results

A total of 27 HAE lesions were evaluated, of which 9 were solid type, 3 were pseudocystic type and 15 were mixed type. The mean lesion size was 100.7 ± 47.3 mm. There was a significant difference in the IC measurements between different layers of HAE lesions during each scan phase (p < 0.001). The IC in the marginal zone was significantly higher than in the solid and cystic components in AP (2.15 mg/mL vs. 0.17 or 0.01 mg/mL), PVP (3.08 mg/mL vs. 0.1 or 0.02 mg/mL), and DP (2.93 mg/mL vs. 0.04 or 0.02 mg/mL). No significant difference was found among the different CT patterns of HAE lesions. Positive expression of CD34 in the marginal zones surrounding HAE lesions was found in 92.5% (25/27) of lesions, of which 18.5% (5/27) were strongly positive, 62.7% (17/27) were moderately positive, and 11.1% (3/27) were weakly positive. In contrast, 7.4% (2/27) of the lesions were negative for CD34. There was a positive correlation between IC measurements and MVD in the marginal zone of HAE lesions (r = 0.73, p < 0.05).

Conclusions

The DECT quantitative iodine concentration was significantly correlated with MVD in the marginal zones surrounding HAE lesions. Dual-energy CT using a quantitative analytic methodology can be used to evaluate the vascularity of AE.

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<![CDATA[Liver Stiffness Measurement among Patients with Chronic Hepatitis B and C: Results from a 5-Year Prospective Study]]> https://www.researchpad.co/article/5989db40ab0ee8fa60bd66b7

Liver stiffness measurement (LSM) is widely used to evaluate liver fibrosis, but longitudinal studies are rare. The current study was aimed to monitor LSM during follow-up, and to evaluate the association of LSM data with mortality and liver-related outcomes. We included all patients with chronic viral hepatitis and valid LSM using Fibroscan. Information about liver biopsy, antiviral treatment, and clinical outcome was obtained from medical records and national registers. The study included 845 patients: 597 (71%) with hepatitis C virus (HCV), 235 (28%) with hepatitis B virus (HBV) and 13 (2%) with dual infection. The initial LSM distribution (<7/7–9.9/10–16.9/≥17 kPa) was 58%/16%/14%/12%. Among patients with initial LSM values of 7–9.9 kPa, 60% of HCV patients and 83% of HBV patients showed LSM values of <7 kPa at the latest follow-up. Progression rates (defined as >20% and >2 kPa increase, with one measure >7 kPa) were 3.4/100 person years (PY) for HCV and 1.5/100 PY for HBV infected patients. Patients with LSM values of ≥17 kPa had the same liver-related complication incidence as patients with biopsy-proven cirrhosis (11.1 versus 12.1/100 PY). Thirteen liver-related deaths occurred among HCV patients (0.6/100 PY), but none among HBV patients. Among patients who died of liver-related causes, all but one had baseline LSM values of ≥17 kPa. Overall, patients with LSM values <17 kPa were not associated with adverse outcomes. In contrast, LSM values ≥17 kPa were associated with significant risk of liver-related problems. The results of the current study suggest that clinical decisions should not be taken based on a single LSM measurement.

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<![CDATA[Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdba0b

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness.

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<![CDATA[DCE-MRI of the Liver: Reconstruction of the Arterial Input Function Using a Low Dose Pre-Bolus Contrast Injection]]> https://www.researchpad.co/article/5989d9fdab0ee8fa60b728fb

Purpose

To assess the quality of the arterial input function (AIF) reconstructed using a dedicated pre-bolus low-dose contrast material injection imaged with a high temporal resolution and the resulting estimated liver perfusion parameters.

Materials and Methods

In this IRB–approved prospective study, 24 DCE-MRI examinations were performed in 21 patients with liver disease (M/F 17/4, mean age 56 y). The examination consisted of 1.3 mL and 0.05 mmol/kg of gadobenate dimeglumine for pre-bolus and main bolus acquisitions, respectively. The concentration-curve of the abdominal aorta in the pre-bolus acquisition was used to reconstruct the AIF. AIF quality and shape parameters obtained with pre-bolus and main bolus acquisitions and the resulting estimated hepatic perfusion parameters obtained with a dual-input single compartment model were compared between the 2 methods. Test–retest reproducibility of perfusion parameters were assessed in three patients.

Results

The quality of the pre-bolus AIF curve was significantly better than that of main bolus AIF. Shape parameters peak concentration, area under the time activity curve of gadolinium contrast at 60 s and upslope of pre-bolus AIF were all significantly higher, while full width at half maximum was significantly lower than shape parameters of main bolus AIF. Improved liver perfusion parameter reproducibility was observed using pre-bolus acquisition [coefficient of variation (CV) of 4.2%–38.7% for pre-bolus vs. 12.1–71.4% for main bolus] with the exception of distribution volume (CV of 23.6% for pre-bolus vs. 15.8% for main bolus). The CVs between pre-bolus and main bolus for the perfusion parameters were lower than 14%.

Conclusion

The AIF reconstructed with pre-bolus low dose contrast injection displays better quality and shape parameters and enables improved liver perfusion parameter reproducibility, although the resulting liver perfusion parameters demonstrated no clinically significant differences between pre-bolus and main bolus acquisitions.

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<![CDATA[An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be011a

Background

In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET).

Patients and methods

We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients.

Results

Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017).

Conclusions

Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

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<![CDATA[Development of Bifunctional Gadolinium-Labeled Superparamagnetic Nanoparticles (Gd-MnMEIO) for In Vivo MR Imaging of the Liver in an Animal Model]]> https://www.researchpad.co/article/5989db28ab0ee8fa60bd0bfa

Liver tumors are common and imaging methods, particularly magnetic resonance imaging (MRI), play an important role in their non-invasive diagnosis. Previous studies have shown that detection of liver tumors can be improved by injection of two different MR contrast agents. Here, we developed a new contrast agent, Gd-manganese-doped magnetism-engineered iron oxide (Gd-MnMEIO), with enhancement effects on both T1- and T2-weighted MR images of the liver. A 3.0T clinical MR scanner equipped with transmit/receiver coil for mouse was used to obtain both T1-weighted spoiled gradient-echo and T2-weighted fast spin-echo axial images of the liver before and after intravenous contrast agent injection into Balb/c mice with and without tumors. After pre-contrast scanning, six mice per group were intravenously injected with 0.1 mmol/kg Gd-MnMEIO, or the control agents, i.e., Gd-DTPA or SPIO. The scanning time points for T1-weighted images were 0.5, 5, 10, 15, 20, 25, and 30 min after contrast administration. The post-enhanced T2-weighted images were then acquired immediately after T1-weighted acquisition. We found that T1-weighted images were positively enhanced by both Gd-DTPA and Gd-MnMEIO and negatively enhanced by SPIO. The enhancement by both Gd-DTPA and Gd-MnMEIO peaked at 0.5 min and gradually declined thereafter. Gd-MnMEIO (like Gd-DTPA) enhanced T1-weighted images and (like SPIO) T2-weighted images. Marked vascular enhancement was clearly visible on dynamic T1-weighted images with Gd-MnMEIO. In addition, the T2 signal was significantly decreased at 30 min after administration of Gd-MnMEIO. Whereas the effects of Gd-MnMEIO and SPIO on T2-weighted images were similar (p = 0.5824), those of Gd-MnMEIO and Gd-DTPA differed, with Gd-MnMEIO having a significant T2 contrast effect (p = 0.0086). Our study confirms the feasibility of synthesizing an MR contrast agent with both T1 and T2 shortening effects and using such an agent in vivo. This agent enables tumor detection and characterization in single liver MRI sections.

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<![CDATA[Application and Evaluation of Interactive 3D PDF for Presenting and Sharing Planning Results for Liver Surgery in Clinical Routine]]> https://www.researchpad.co/article/5989dad3ab0ee8fa60bb6d67

Background & Objectives

The Portable Document Format (PDF) is the de-facto standard for the exchange of electronic documents. It is platform-independent, suitable for the exchange of medical data, and allows for the embedding of three-dimensional (3D) surface mesh models. In this article, we present the first clinical routine application of interactive 3D surface mesh models which have been integrated into PDF files for the presentation and the exchange of Computer Assisted Surgery Planning (CASP) results in liver surgery. We aimed to prove the feasibility of applying 3D PDF in medical reporting and investigated the user experience with this new technology.

Methods

We developed an interactive 3D PDF report document format and implemented a software tool to create these reports automatically. After more than 1000 liver CASP cases that have been reported in clinical routine using our 3D PDF report, an international user survey was carried out online to evaluate the user experience.

Results

Our solution enables the user to interactively explore the anatomical configuration and to have different analyses and various resection proposals displayed within a 3D PDF document covering only a single page that acts more like a software application than like a typical PDF file (“PDF App”). The new 3D PDF report offers many advantages over the previous solutions. According to the results of the online survey, the users have assessed the pragmatic quality (functionality, usability, perspicuity, efficiency) as well as the hedonic quality (attractiveness, novelty) very positively.

Conclusion

The usage of 3D PDF for reporting and sharing CASP results is feasible and well accepted by the target audience. Using interactive PDF with embedded 3D models is an enabler for presenting and exchanging complex medical information in an easy and platform-independent way. Medical staff as well as patients can benefit from the possibilities provided by 3D PDF. Our results open the door for a wider use of this new technology, since the basic idea can and should be applied for many medical disciplines and use cases.

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