Magali Sasso

Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes.

There is a need for noninvasive methods to detect liver steatosis, which can be a factor of liver fibrosis progression. This work aims to evaluate a novel ultrasonic controlled attenuation parameter (CAP) devised to target, specifically, liver steatosis using a sophisticated process based on vibration control transient elastography (VCTE™). CAP was first validated as an estimate of ultrasonic attenuation at 3.5 MHz using Field II simulations and tissue-mimicking phantoms. Performance of the CAP was then appraised on 115 patients, taking the histological grade of steatosis as reference. CAP was significantly correlated to steatosis (Spearman ρ = 0.81, p < 10(-16)). Area under receiver operative characteristic (ROC) curve (AUC) was equal to 0.91 and 0.95 for the detection of more than 10% and 33% of steatosis, respectively. Furthermore, results show that CAP can efficiently separate several steatosis grades. These promising results suggest that CAP is a noninvasive, immediate, objective and efficient method to detect and quantify steatosis.

Novel controlled attenuation parameter for noninvasive assessment of steatosis using Fibroscan : validation in chronic hepatitis C

Summary.  A novel controlled attenuation parameter (CAP) has been developed for Fibroscan® to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan® and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S0: steatosis in <10% of hepatocytes, S1: 11–33%, S2: 34–66% and S3: 67–100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross‐validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to differentiate between steatosis grades. In multivariate analysis, CAP was related to steatosis (P < 10−15) independently of fibrosis stage (which was related to LSM). The areas under ROC curves using CAP to detect steatosis were 0.80 (95% CI, 0.75–0.84) for S ≥ S1, 0.86 (0.81–0.92) for S ≥ S2 and 0.88 (0.73–1) S = S3. CAP exhibited a good ability to differentiate steatosis grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment confirmed results from previous studies. CAP is a novel tool to assess the degree of steatosis and both fibrosis and steatosis can be evaluated noninvasively during the same procedure using Fibroscan®, in patients with CHC.

Association of Adipose Tissue and Liver Fibrosis With Tissue Stiffness in Morbid Obesity: Links With Diabetes and BMI Loss After Gastric Bypass

CONTEXT Liver and white adipose tissue (WAT) develop inflammation and fibrosis. OBJECTIVE The aim of the study was to evaluate the bioclinical relevance of WAT fibrosis in morbid obesity and diabetes and the relationships with tissue stiffness measured using a novel device. DESIGN AND SETTING Observational and longitudinal studies were conducted in a hospital nutrition department. PATIENTS Biopsies of liver and subcutaneous WAT (scWAT) and omental adipose tissue were collected from 404 obese bariatric surgery candidates, of whom 243 were clinically characterized before surgery and 3, 6, and 12 months after surgery. In 123 subjects, liver and scWAT stiffness was assessed noninvasively using vibration-controlled transient elastography (VCTE). INTERVENTIONS Bariatric surgery was performed for some patients. MAIN OUTCOME MEASURE Adipose tissue fibrosis and stiffness and their link to obesity phenotypes were measured. RESULTS scWAT fibrosis was positively associated with liver fibrosis (fibrosis score ≥2) (ϱ= 0.14; P = .01). VCTE-evaluated liver and scWAT stiffness was positively correlated with immunohistochemistry-determined liver (ϱ= 0.46; P = .0009) and scWAT fibrosis (ϱ= 0.48; P = .0001). VCTE-evaluated scWAT stiffness measures negatively associated with dual-energy x-ray absorptiometry-evaluated body fat mass (R = -0.25; P = .009) and were correlated with metabolic variables. Diabetic subjects showed increased scWAT stiffness. Participants less responsive to gastric bypass were older and more frequently diabetic, and they had increased body mass index, serum IL-6, and scWAT and liver fibrosis. Subjects with no diabetes and normal liver had higher fat mass and lower tissue fibrosis and stiffness. CONCLUSION scWAT stiffness was associated with tissue fibrosis, obesity, and diabetes-related traits. Noninvasive evaluation of scWAT stiffness might be useful in clinical practice.

Accumulation and Changes in Composition of Collagens in Subcutaneous Adipose Tissue After Bariatric Surgery.

CONTEXT Extracellular matrix (ECM) in sc adipose tissue (scAT) undergoes pathological remodeling during obesity. However, its evolution during weight loss remains poorly explored. OBJECTIVE The objective of the investigation was to study the histological, transcriptomic, and physical characteristics of scAT ECM remodeling during the first year of bariatric surgery (BS)-induced weight loss and their relationships with metabolic and bioclinical improvements. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS A total of 118 morbidly obese candidates for BS were recruited and followed up during 1 year after BS. MAIN OUTCOME MEASURES scAT surgical biopsy and needle aspiration as well as scAT stiffness measurement were performed in three subgroups before and after BS. Fourteen nonobese, nondiabetic subjects served as controls. RESULTS Significantly increased picrosirius-red-stained collagen accumulation in scAT after BS was observed along with fat mass loss, despite metabolic and inflammatory improvements and undetectable changes of scAT stiffness. Collagen accumulation positively associated with M2-macrophages (CD163(+) cells) before BS but negatively afterward. Expression levels of genes encoding ECM components (eg, COL3A1, COL6A1, COL6A2, ELN), cross-linking enzymes (eg, lysyl oxidase [LOX], LOXL4, transglutaminase), metalloproteinases, and their inhibitors were modified 1 year after BS. LOX expression and protein were significantly decreased and associated with decreased fat mass as well as other cross-linking enzymes. Although total collagen I and VI staining decreased 1 year after BS, we found increased degraded collagen I and III in scAT, suggesting increased degradation. CONCLUSIONS After BS-induced weight loss and related metabolic improvements, scAT displays major collagen remodeling with an increased picrosirius-red staining that relates to increased collagen degradation and importantly decreased cross-linking. These features are in agreement with adequate ECM adaptation during fat mass loss.

Singular value decomposition-based wave extraction in axial transmission: application to cortical bone ultrasonic characterization [correspondence]

A singular value decomposition-based extraction algorithm is designed in order to recover the group velocity of an energetic contribution measured with an axial transmission device developed previously for cortical bone assessment. Its performance is evaluated on synthetic data mimicking in vivo signals, and it is compared with classical methods.

Ultrasonic velocity dispersion in bovine cortical bone: An experimental study

Cortical bone quality is determinant in bone fragility and its ultrasonic evaluation has become possible in clinical practice. However, the interaction between a broadband ultrasonic pulse and this complex multiscale medium remains poorly understood. The frequency dependence of phase velocity, which may impact clinical measurements, has been sparsely investigated. Our objective is to evaluate the determinants of the frequency dependence of phase velocity in bovine femoral cortical bone samples using an in vitro ultrasonic transmission device. The apparent phase velocity varies quasilinearly on a 1 MHz restricted bandwidth around 4 MHz. After compensating for diffraction effects, significant differences in velocity dispersion are obtained according to the anatomical location. The microstructure of each sample is determined using an optical microscope, which allows assessing the dependence of dispersion on the type of bone microstructure. Mostly positive but also negative values of dispersion are measured. Negative dispersion is mainly obtained in samples constituted of mixed microstructure, which may be explained by phase cancellation effects due to the presence of different microstructures within the same sample. Dispersion is shown to be related to broadband ultrasonic attenuation values, especially in the radial direction. Results are compared with the local Kramers-Kronig relationships.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement

Liver fibrosis is often accompanied by steatosis, particularly in patients with non‐alcoholic fatty liver disease (NAFLD), and its non‐invasive characterisation is of utmost importance. Vibration‐controlled transient elastography is the non‐invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis.

Novel Controlled Attenuation Parameter for the evaluation of fatty liver disease

There is a need for novel non-invasive methods to detect and quantify steatosis which is an intracellular accumulation of fat in the liver that can be associated in many cases with hepatitis. A novel attenuation parameter named Controlled Attenuation Parameter (CAP) has been developed to process the raw ultrasonic signals acquired by the Fibroscan® which is an ultrasound-based VCTE™ device used to diagnose liver disease. Performance of the CAP parameter to detect and quantify steatosis is assessed in a large multi-etiology cohort of 495 patients, taking the histologic staging of steatosis as a reference. CAP is found to be significantly correlated to steatosis and its values are significantly different in each steatosis stages. Diagnosis performances were assessed using the ROC curves. Areas under ROC curves were found to be equal to 0.85 and 0.90 for the diagnosis of more than 10% and 33% of fatty deposit, respectively. Results obtained in this first preliminary study are very promising. Combination of both CAP and liver stiffness measurement may improve liver diseases diagnosis performance.

AdipoScan™ - A novel transient elastography based tool to assess subcutaneous adipose tissue shear wave speed in morbidly obese patients

Subcutaneous white adipose tissue (scWAT) in human obesity undergoes severe alterations such as fibrosis accumulation. Fibrosis in scWAT is related to metabolic alterations and to less efficiency in losing weight after bariatric surgery. There is currently no non-invasive tool to assess subcutaneous white adipose tissue (scWAT) characteristics. A novel device named AdipoScan™ based on vibration controlled transient elastography (VCTE™) was developed by Echosens so as to assess scWAT shear wave speed (SWS). In the present study, the prototype and how it has been adapted to scWAT SWS evaluation was first described. Repeatability was then assessed in terms of coefficient of variation (CV) with and without repositioning on tissue mimicking phantoms (~1% and 0%, respectively) and in vivo on 41 volunteers (14% and 7%, respectively). Then, scWAT SWS was measured in vivo on 73 morbidly obese patients candidate to bariatric surgery. scWAT SWS is significantly associated with tissue fibrosis, gender, body fat mass assessed by DXA, hypertension status, and biological parameters such as glycemia, lipid profile, hepatic parameters and adiponectin. Results suggest that scWAT evaluation before surgery can be useful in clinical practice to help phenotype obese patients and the stage of adipose tissue alterations.

Development of a Multi-Dimensional SVD based Technique for Multi-Receivers Ultrasound used in Bone Status Characterization

The use of multi-dimensional wave extraction algorithm for a multi-receivers axial transmission ultrasound device used in bone evaluation is proposed. As far as we know, multi-dimensional signal processing techniques have never been implemented in this configuration. A SVD-based wavefront extraction is implemented for the characterization of an energetic low frequency contribution. Velocity accuracy is estimated on a synthetic dataset. Furthermore, the energetic low frequency removal is illustrated on in vivo signals. Results are promising as for the application of multi-dimensional techniques in medical ultrasound used in transmission