Controlled Attenuation Parameter in Healthy Individuals Aged 8–70 Years

Purpose Controlled attenuation parameter (CAP) is a non-invasive method to assess the presence of liver steatosis. It has been evaluated in children and adults, mainly in either the obese or in subjects with suspected liver disease. Our aim was to describe CAP in healthy non-obese subjects without suspected liver steatosis and to suggest cutoff levels for steatosis. Materials and Methods We prospectively recruited 187 individuals aged 8–70 years. All underwent clinical examination, including height and weight measurement. Body mass index (BMI) was calculated and converted into z-scores. To exclude liver pathology, B-mode ultrasound and liver stiffness measurements were performed in all prior to CAP measurement. Blood was drawn for liver biochemistry in adults. Results CAP was associated with BMI z-score across all ages. CAP started to rise alongside BMI z-score already in subjects with a BMI below average. CAP values were higher in adults than in children (p<0.001), and higher in adult males than adult females (p=0.014). CAP did not correlate with age within the adult or pediatric cohorts. CAP was highly correlated with the fatty liver index. 18 and 23% of subjects showed CAP above the suggested cutoff value for children and adults, respectively. Conclusion CAP was correlated with BMI z-score, even in individuals with a below-average BMI . We found CAP above published cutoff values in a substantial proportion of presumably healthy, non-obese children and adults, warranting further research to clarify whether this represents non-obese non-alcoholic fatty liver disease or if reference values need adjustment.publishedVersio

In-vitro and in-vivo validation of ultrasound shear wave elastography for liver application

Background and aims: Ultrasound (US) elastography is a noninvasive method that is used to investigate tissue elasticity in several organs. In chronic liver disease, the predominant approach is quantitative. By measuring liver stiffness, one could possibly follow the development of fibrosis in in chronic liver diseases. The spectrum of US elastography methods has been expanding, however, there is limited validation of several of the new methods. Validation is needed for the methods to be established as tools in clinical practice. The overall aim of this theses was to validate several US shear wave elastography (SWE) methods, including point shear wave elastography (pSWE) and 2D-SWE, in vitro and in vivo aiming at liver as the primary organ. In the first study the main aim was to assess and validate the repeatability, reproducibility and interobserver agreement of several US SWE methods. This was approached in vitro using liver fibrosis phantoms with known Youngs modulus. In the second and third study we assessed in vivo; in livers of an adult healthy cohort and a cohort of patients with primary sclerosing cholangitis (PSC). Furthermore, we aimed to define normal liver elasticity, assess number of repeated measurements needed to achieve a representative median value and explore the assessment of fibrosis. Methods: Methods to estimate tissue elasticity are usually integrated in US scanners. In the first study we used transient elastography (TE) and methods integrated in GE Logiq E9 (2D-SWE), Hitachi Ascendus (pSWE), Philips iU22 (pSWE) and Samsung RS80A with prestige (pSWE). Two investigators performed non-continued measurements in parallel on four individual tissue-mimicking liver fibrosis phantoms. In the second study we obtained liver stiffness measurements (LSM) in a healthy cohort of 50 men and 50 women using TE and methods integrated in GE Logiq E9 (2D-SWE) and Samsung TS80A (pSWE). Prior to the LSM all 100 subjects underwent lab tests and US examination in B-mode. Inter- and intraobservation between two examiners were assessed in a subgroup of 24 subjects. In the third study we used the pSWE method integrated in Philips iU22 and included 55 non-transplant PSC patients and 24 matched controls. All subjects underwent US examination and lab tests were performed on patients with PSC. We evaluated inter- and intraobserver variability of the spleen and liver elasticity measurements between two examiners in 19 healthy subjects. Main results: In the first study we found that all four US SWE methods could differentiate the four individual liver fibrosis phantoms. The methods had high repeatability and reproducibility. The inter-and intraobserver agreement was excellent and there was no significant difference in mean elasticity for all the US SWE methods. Furthermore, the study demonstrated that the difference in elastography measurements acquired with US SWE was larger for the harder phantoms with higher Youngs modulus compared to the softer ones. In the second study we found that the reproducibility and repeatability of LSM in healthy livers was high, furthermore, our results showed that the mean liver elasticity in a healthy adult cohort was higher when acquired with the 2D-SWE method, than with non-imaging SWE methods such as Samsung pSWE or TE. We also found that males had higher liver elasticity than females. In addition, we demonstrated that five consecutive acquisitions may be sufficient for reliable LSM results. In the third study, we found good intra- and interobservation agreement assessing Philips iU22 pSWE measurements of the right liver lobe in the healthy subjects. We also found that the PSC patients had higher LSM than the healthy controls when measuring the right liver lobe, whereas the LSM of the left liver and spleen elasticity measurements were indifferent between PSC patients and healthy controls. Conclusions: US SWE methods used in our studies demonstrated excellent in vitro and good in vivo repeatability and interobserver agreement. Mean LSM in our healthy cohort was significantly higher when obtained with 2D-SWE, and in male participants. We found no difference across age groups 20-70 years or among non-obese BMI-groups 18-30 kg/m2. Our results indicated that five LSM may be sufficient to obtain a reliable result in healthy livers. Furthermore, we showed that PSC patients displayed higher levels of LSM compared to the healthy controls. However, the range of LSM of PSC patients was wide, which could suggest increasing stages of fibrosis through the disease development, making SWE a possible method for prospective studies evaluating SWE as a prognostic tool

Liver elasticity in healthy individuals by two novel shear-wave elastography systems-Comparison by age, gender, BMI and number of measurements.

OBJECTIVE:Establishing normal liver stiffness (LS) values in healthy livers is a prerequisite to differentiate normal from pathological LS values. Our aim was to define normal LS using two novel elastography methods head-to-head and to assess the number of measurements, variability and reproducibility. MATERIALS AND METHODS:We evaluated shear wave elastography (SWE) methods integrated in Samsung RS80A and GE S8 by obtaining LS measurements (LSM) in 100 healthy subjects (20-70 years). Transient Elastography (TE) was used as reference method. Data were analyzed according to age, sex, BMI and 5 vs. 10 measurements. All subjects underwent B-mode ultrasound examination and lab tests to exclude liver pathology. Interobserver variation was evaluated in a subset (n = 24). RESULTS:Both methods showed excellent feasibility, measuring LS in all subjects. LSM-mean for GE S8 2D-SWE was higher compared to TE (4.5±0.8 kPa vs. 4.2±1.1, p<0.001) and Samsung RS80A (4.1±0.8 kPa, p<0.001). Both methods showed low intra- and interobserver variation. LSM-mean was significantly higher in males than females using 2D-SWE, while a similar trend for Samsung SWE did not reach significance. No method demonstrated statistical significant difference in LSM across age and BMI groups nor between LSM-mean based on 5 vs. 10 measurements. CONCLUSION:LSM was performed with high reproducibility in healthy adult livers. LSM-mean was significantly higher for GE S8 2D-SWE compared to Samsung RS80A and TE in healthy livers. Males had higher LSM than females. No method demonstrated statistical significant difference in LSM-mean across age- and non-obese BMI groups. Our results indicate that five LSM may be sufficient for reliable results

Strain Ratio as a Quantification Tool in Strain Imaging

Ultrasound-based strain imaging is available in several ultrasound (US) scanners. Strain ratio (SR) can be used to quantify the strain recorded simultaneously in two different user-selected areas, ideally exposed to the same amount of stress. The aim of this study was to evaluate SR variability when assessed in an in-vitro setup with a tissue-mimicking phantom on resected tissue samples and in live tissue scanning with endoscopic applications. We performed an in vivo retrospective analysis of SR variability used for quantification of elastic contrasts in a tissue-mimicking phantom containing four homogenous inclusion in 38 resected bowel wall lesions and 48 focal pancreatic lesions. Median SR and the inter-quartile range (IQR) were calculated for all external and endoscopic ultrasound (EUS) applications. The IQR and median provide a measure of SR variability focusing on the two percentiles of the data closest to the median value. The overall SR variability was lowest in a tissue-mimicking phantom (mean QR/median SR: 0.07). In resected bowel wall lesions representing adenomas, adenocarcinomas, or Crohn lesions, the variability increased (mean IQR/Median: 0.62). During an in vivo endoscopic examination of focal pancreatic lesions, the variability increased further (mean IQR/Median: 2.04). SR variability increased when assessed for different targets with growing heterogeneity and biological variability from homogeneous media to live tissues and endoscopic application. This may indicate a limitation for the accuracy of SR evaluation in some clinical applications

Controlled Attenuation Parameter in Healthy Individuals Aged 8–70 Years

Purpose Controlled attenuation parameter (CAP) is a non-invasive method to assess the presence of liver steatosis. It has been evaluated in children and adults, mainly in either the obese or in subjects with suspected liver disease. Our aim was to describe CAP in healthy non-obese subjects without suspected liver steatosis and to suggest cutoff levels for steatosis. Materials and Methods We prospectively recruited 187 individuals aged 8–70 years. All underwent clinical examination, including height and weight measurement. Body mass index (BMI) was calculated and converted into z-scores. To exclude liver pathology, B-mode ultrasound and liver stiffness measurements were performed in all prior to CAP measurement. Blood was drawn for liver biochemistry in adults. Results CAP was associated with BMI z-score across all ages. CAP started to rise alongside BMI z-score already in subjects with a BMI below average. CAP values were higher in adults than in children (p<0.001), and higher in adult males than adult females (p=0.014). CAP did not correlate with age within the adult or pediatric cohorts. CAP was highly correlated with the fatty liver index. 18 and 23% of subjects showed CAP above the suggested cutoff value for children and adults, respectively. Conclusion CAP was correlated with BMI z-score, even in individuals with a below-average BMI . We found CAP above published cutoff values in a substantial proportion of presumably healthy, non-obese children and adults, warranting further research to clarify whether this represents non-obese non-alcoholic fatty liver disease or if reference values need adjustment

Repeatability of shear wave elastography in liver fibrosis phantoms—Evaluation of five different systems

<div><p>This study aimed to assess and validate the repeatability and agreement of quantitative elastography of novel shear wave methods on four individual tissue-mimicking liver fibrosis phantoms with different known Young’s modulus. We used GE Logiq E9 2D-SWE, Philips iU22 ARFI (pSWE), Samsung TS80A SWE (pSWE), Hitachi Ascendus (SWM) and Transient Elastography (TE). Two individual investigators performed all measurements non-continued and in parallel. The methods were evaluated for inter- and intraobserver variability by intraclass correlation, coefficient of variation and limits of agreement using the median elastography value. All systems used in this study provided high repeatability in quantitative measurements in a liver fibrosis phantom and excellent inter- and intraclass correlations. All four elastography platforms showed excellent intra-and interobserver agreement (interclass correlation 0.981–1.000 and intraclass correlation 0.987–1.000) and no significant difference in mean elasticity measurements for all systems, except for TE on phantom 4. All four liver fibrosis phantoms could be differentiated by quantitative elastography, by all platforms (p<0.001). In the Bland-Altman analysis the differences in measurements were larger for the phantoms with higher Young’s modulus. All platforms had a coefficient of variation in the range 0.00–0.21 for all four phantoms, equivalent to low variance and high repeatability.</p></div

Liver elastography in healthy children using three different systems - how many measurements are necessary?

Purpose Liver elastography is increasingly being applied in screening for and follow-up of pediatric liver disease, and has been shown to correlate well with fibrosis staging through liver biopsy. Because time is of the essence when examining children, we wanted to evaluate if a reliable result can be achieved with fewer acquisitions. Materials and Methods 243 healthy children aged 4–17 years were examined after three hours of fasting. Participants were divided into four age groups: 4–7 years; 8–11 years; 12–14 years and 15–17 years. Both two-dimensional shear wave elastography (2D-SWE; GE Logiq E9) and point shear wave elastography (pSWE; Samsung RS80A with Prestige) were performed in all participants, while transient elastography (TE, Fibroscan) was performed in a subset of 87 children aged 8–17 years. Median liver stiffness measurement (LSM) values of 3, 4, 5, 6, 7, and 8 acquisitions were compared with the median value of 10 acquisitions (reference standard). Comparison was performed for all participants together as well as within every specific age group. We investigated both the intraclass correlation coefficient (ICC) with absolute agreement and all outliers more than 10 %, 20 % or ≥ 0.5 or 1.0 kPa from the median of 10 acquisitions. Results For all three systems there was no significant difference between three and ten acquisitions, with ICCs ≥ 0.97. All systems needed 4 acquisitions to achieve no LSM deviating ≥ 1.0 kPa of a median of ten. To achieve no LSM deviating ≥ 20 % of a median of ten acquisitions, pSWE and TE needed 4 acquisitions, while 2D-SWE required 6 acquisitions. Conclusion Our results contradict recommendations of 10 acquisitions for pSWE and TE and only 3 for 2D-SWE.acceptedVersio

Hitachi (SWM).

<p>Hitachi SWM was applied on liver fibrosis phantom 3. The ROI is represented by the blue box (centre). The shear wave velocity measurements are presented in the histogram, and the median is given as Vs in m/s. Stiffness is based on this value expressed in kPa as well as the IQR (m/s), VsN (Reliability Index for shear wave velocity measurement) and the depth of the sample.</p

IQR/Median (%) for all systems and both observers.

<p>IQR/Median (%) is presented on the vertical axis for both observers (blue). The phantoms 1–4 are numbered on the horizontal axis.</p

IQR/Median (%) for all systems and both observers.

<p>IQR/Median (%) is presented on the vertical axis for both observers (blue). The phantoms 1–4 are numbered on the horizontal axis.</p