RESUMO
Metabolic dysfunction-associated steatotic liver disease (MASLD) typically presents with hepatic fibrosis in advanced disease, resulting in increased liver stiffness. A subset of patients further develops liver cirrhosis and hepatocellular carcinoma. Cardiovascular disease is a common comorbidity in patients with MASLD and its prevalence is increasing in parallel. Recent evidence suggests that especially liver stiffness, whether or not existing against a background of MASLD, is associated with heart diseases. We conducted a narrative review on the role of liver stiffness in the prediction of highly prevalent heart diseases including heart failure, cardiac arrhythmias (in particular atrial fibrillation), coronary heart disease, and aortic valve sclerosis. Research papers were retrieved from major scientific databases (PubMed, Web of Science) until September 2023 using 'liver stiffness' and 'liver fibrosis' as keywords along with the latter cardiac conditions. Increased liver stiffness, determined by vibration-controlled transient elastography or hepatic fibrosis as predicted by biomarker panels, are associated with a variety of cardiovascular diseases, including heart failure, atrial fibrillation, and coronary heart disease. Elevated liver stiffness in patients with metabolic liver disease should lead to considerations of cardiac workup including N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide determination, electrocardiography, and coronary computed tomography angiography. In addition, patients with MASLD would benefit from heart disease case-finding strategies in which liver stiffness measurements can play a key role. In conclusion, increased liver stiffness should be a trigger to consider a cardiac workup in metabolically compromised patients.
Assuntos
Fibrilação Atrial , Carcinoma Hepatocelular , Doença das Coronárias , Fígado Gorduroso , Cardiopatias , Insuficiência Cardíaca , Neoplasias Hepáticas , Humanos , Peptídeo Natriurético Encefálico , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Cardiopatias/complicações , Fígado Gorduroso/complicações , Insuficiência Cardíaca/epidemiologia , Carcinoma Hepatocelular/complicações , Doença das Coronárias/complicações , Neoplasias Hepáticas/complicações , Medição de RiscoRESUMO
BACKGROUND & AIMS: Currently available non-invasive tests, including fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM by VCTE), are highly effective at excluding advanced fibrosis (AF) (F ≥3) or cirrhosis in people with non-alcoholic fatty liver disease (NAFLD), but only have moderate ability to rule-in these conditions. Our objective was to develop and validate two new scores (Agile 4 and Agile 3+) to identify cirrhosis or AF, respectively, with optimized positive predictive value and fewer indeterminate results, in individuals with NAFLD attending liver clinics. METHODS: This international study included seven adult cohorts with suspected NAFLD who underwent liver biopsy, LSM and blood sampling during routine clinical practice or screening for trials. The population was randomly divided into a training set and an internal validation set, on which the best-fitting logistic regression model was built, and performance and goodness of fit were assessed, respectively. Furthermore, both scores were externally validated on two large cohorts. Cut-offs for high sensitivity and specificity were derived in the training set to rule-out and rule-in cirrhosis or AF and then tested in the validation set and compared to FIB-4 and LSM. RESULTS: Each score combined LSM, AST/ALT ratio, platelets, sex and diabetes status, as well as age for Agile 3+. Calibration plots for Agile 4 and Agile 3+ indicated satisfactory to excellent goodness of fit. Agile 4 and Agile 3+ outperformed FIB-4 and LSM in terms of AUROC, percentage of patients with indeterminate results and positive predictive value to rule-in cirrhosis or AF. CONCLUSIONS: The two novel non-invasive scores improve identification of cirrhosis or AF among individuals with NAFLD attending liver clinics and reduce the need for liver biopsy in this population. IMPACT AND IMPLICATIONS: Non-invasive tests currently used to identify patients with advanced fibrosis or cirrhosis, such as fibrosis-4 index and liver stiffness measurement by vibration-controlled transient elastography, have high negative predictive values but high false positive rates, while results are indeterminate for a large number of cases. This study provides scores that will help the clinician diagnose advanced fibrosis or cirrhosis. These new easy-to-implement scores will help liver specialists to better identify (1) patients who need more intensive follow-up, (2) patients who should be referred for inclusion in therapeutic trials, and (3) which patients should be treated with pharmacological agents when effective therapies are approved.
Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Fibrose , BiópsiaRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to a large spectrum of liver disorders and is the most common cause of metabolic liver disease. The current gold standard for diagnosing NAFLD is liver biopsy, which can lead to severe complications. PURPOSE: Among the noninvasive diagnostic options, we chose to use a FibroScan and developed an algorithm applying the Voigt rheological model to assess the viscoelastic properties of the liver and evaluate its performance for the diagnosis of steatosis. METHODS: Twenty-two healthy volunteers and 20 patients with steatosis were included. For each subject, we used a modified FibroScan, whose data had been processed by our algorithm to separate the two viscoelastic components, stiffness µ, and viscosity η. The liver elasticity µFibroscan measured by the FibroScan was also recorded. Mann-Whitney tests and receiver operating characteristics (ROCs) curve analyses were performed to compare the parameters between the two groups, and Pearson's correlation coefficients were used to assess the correlations between the parameters. RESULTS: We found a good correlation between η and µFibroscan (r = 0.75), and poor correlations between µ and both η and µFibroscan (r = 0.33 and r = 0.03, respectively). We also showed that η and µFibroscan were higher in patients with steatosis compared to healthy volunteers, with area under the ROCs (AUROC) curve at 0.814 and 0.891, respectively. Conversely, µ was not different between the two groups (AUROC = 0.557). CONCLUSIONS: Our novel method successfully separated the two viscoelastic properties of the liver, of which the parameter η is a sensitive indicator for steatosis.
Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Biópsia , Técnicas de Imagem por Elasticidade/métodos , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Estudos Prospectivos , Curva ROC , VibraçãoRESUMO
Controlled attenuation parameter (CAP) is a measurement of ultrasound attenuation used to assess liver steatosis non-invasively. However, the standard method has some limitations. This study assessed the performance of a new CAP method by ex vivo and in vivo assessments. The major difference with the new method is that it uses ultrasound data continuously acquired during the imaging phase of the FibroScan examination. Seven reference tissue-mimicking phantoms were used to test the performance. In vivo performance was assessed in two cohorts (in total 195 patients) of patients using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as a reference. The precision of CAP was improved by more than 50% on tissue-mimicking phantoms and 22%-41% in the in vivo cohort studies. The agreement between both methods was excellent, and the correlation between CAP and MRI-PDFF improved in both studies (0.71 to 0.74; 0.70 to 0.76). Using MRI-PDFF as a reference, the diagnostic performance of the new method was at least equal or superior (area under the receiver operating curve 0.889-0.900, 0.835-0.873). This study suggests that the new continuous CAP method can significantly improve the precision of CAP measurements ex vivo and in vivo.
Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Curva ROC , UltrassonografiaRESUMO
Vibration-controlled transient elastography-based FibroScan (Echosens, Paris, France) is today considered the reference device for non-invasive assessment of liver stiffness, and has been found to be a good surrogate marker of liver fibrosis. One major issue when using VCTE™ is the necessity to find an optimal measurement window before triggering measurements. In this article, a new method called vibration-guided transient elastography (VGTE) facilitating the localization of an optimal measurement window is proposed. VGTE relies on a combination of continuous and transient vibrations used to locate the liver and to measure liver stiffness, respectively. Two studies conducted on customized phantoms and on 31 volunteers compared VGTE with standard ultrasound-based tools. VGTE performed significantly better than standard ultrasound-based tools in detection of an optimal measurement window. The operator never failed to find a valid measurement window using VGTE. VGTE can also detect artifacts such as lungs, ribs and blood vessels.
Assuntos
Técnicas de Imagem por Elasticidade/instrumentação , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , VibraçãoRESUMO
BACKGROUND: The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]). METHODS: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009. FINDINGS: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0. INTERPRETATION: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease. FUNDING: Echosens and UK National Institute for Health Research.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fibrose/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Biópsia , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Inglaterra/epidemiologia , Feminino , Fibrose/classificação , França/epidemiologia , Humanos , Fígado/metabolismo , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Turquia/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Esophageal varices (EVs) are among the most severe complications of cirrhosis, with a prevalence of 50% to 60% among cirrhotic patients. International guidelines therefore recommend that cirrhotic patients should be screened for the presence of EVs. The main objective of this study was to introduce a new spleen-dedicated FibroScan (Echosens, Paris, France) examination and to assess its performance in detecting large EVs (grade 2 and 3). This novel examination has been validated in simulation and phantom studies and has been used in a population of patients with chronic liver disease. The study described here suggests that the novel spleen-dedicated FibroScan examination performs better than the standard FibroScan for the detection of large EVs (area under the curve = 0.70 for the standard examination and 0.79 [p <0.01] for the spleen examination), but further clinical studies are needed to investigate the role of spleen stiffness in the management of cirrhotic patients.
Assuntos
Técnicas de Imagem por Elasticidade/instrumentação , Técnicas de Imagem por Elasticidade/métodos , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Baço/diagnóstico por imagem , Baço/patologia , Adulto , Idoso , Animais , Varizes Esofágicas e Gástricas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Purpose To evaluate the diagnostic performance and examination success rate of magnetic resonance (MR) elastography and vibration-controlled transient elastography (VCTE) in the detection of hepatic fibrosis in patients with severe to morbid obesity. Materials and Methods This prospective and HIPAA-compliant study was approved by the institutional review board. A total of 111 patients (71 women, 40 men) participated. Written informed consent was obtained from all patients. Patients underwent MR elastography with two readers and VCTE with three observers to acquire liver stiffness measurements for liver fibrosis assessment. The results were compared with those from liver biopsy. Each pathology specimen was evaluated by two hepatopathologists according to the METAVIR scoring system or Brunt classification when appropriate. All imaging observers were blinded to the biopsy results, and all hepatopathologists were blinded to the imaging results. Examination success rate, interobserver agreement, and diagnostic accuracy for fibrosis detection were assessed. Results In this obese patient population (mean body mass index = 40.3 kg/m2; 95% confidence interval [CI]: 38.7 kg/m2, 41.8 kg/m2]), the examination success rate was 95.8% (92 of 96 patients) for MR elastography and 81.3% (78 of 96 patients) or 88.5% (85 of 96 patients) for VCTE. Interobserver agreement was higher with MR elastography than with biopsy (intraclass correlation coefficient, 0.95 vs 0.89). In patients with successful MR elastography and VCTE examinations (excluding unreliable VCTE examinations), both MR elastography and VCTE had excellent diagnostic accuracy in the detection of clinically significant hepatic fibrosis (stage F2-F4) (mean area under the curve: 0.93 [95% CI: 0.85, 0.97] vs 0.91 [95% CI: 0.83, 0.96]; P = .551). Conclusion In this obese patient population, both MR elastography and VCTE had excellent diagnostic performance for assessing hepatic fibrosis; MR elastography was more technically reliable than VCTE and had a higher interobserver agreement than liver biopsy. © RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on January 25, 2017.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , VibraçãoRESUMO
We describe a novel device called the AdipoScan that was adapted from the FibroScan to specifically assess shear wave speed (SWS) in human abdominal subcutaneous adipose tissue (scAT). Measurement reproducibility was assessed on tissue-mimicking phantoms with and without repositioning, with resultant coefficients of variation of 1% and 0%, respectively, as well as in vivo (14% and 7%, respectively). The applicability of the AdipoScan was tested on 19 non-obese volunteers, and a scAT thickness >2 cm was found to be mandatory to perform a valid measurement. Abdominal scAT SWS was assessed in 73 severely obese subjects, all candidates for bariatric surgery. Subcutaneous AT SWS was positively associated with scAT fibrosis and obesity-related co-morbidities such as hypertension, glycemic status, dyslipidemia and liver dysfunction. These results suggest that the AdipoScan could be a useful non-invasive tool to evaluate scAT fibrosis and metabolic complications in obesity. Further investigation is required to evaluate the relevance of using the AdipoScan to predict patient weight trajectories and metabolic outcomes after bariatric surgery.
Assuntos
Técnicas de Imagem por Elasticidade/instrumentação , Técnicas de Imagem por Elasticidade/métodos , Obesidade/diagnóstico por imagem , Gordura Subcutânea/diagnóstico por imagem , Gordura Abdominal/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Reprodutibilidade dos TestesRESUMO
To assess liver steatosis, the controlled attenuation parameter (CAP; giving an estimate of ultrasound attenuation â¼3.5 MHz) is available with the M probe of the FibroScan. We report on the adaptation of the CAP for the FibroScan XL probe (center frequency 2.5 MHz) without modifying the range of values (100-400 dB/m). CAP validation was successfully performed on Field II simulations and on tissue-mimicking phantoms. In vivo performance was assessed in a cohort of 59 patients spanning the range of steatosis. In vivo reproducibility was good and similar with both probes. The area under receiver operative characteristic curve was equal to 0.83/0.84 and 0.92/0.91 for the M/XL probes to detect >2% and >16% liver fat, respectively, as assessed by magnetic resonance imaging. Patients can now be assessed simultaneously for steatosis and fibrosis using the FibroScan, regardless of their morphology.
Assuntos
Fígado Gorduroso/diagnóstico por imagem , Ultrassonografia/instrumentação , Ultrassonografia/métodos , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Projetos Piloto , Curva ROC , Reprodutibilidade dos TestesRESUMO
Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young's modulus over the range of normal and cirrhotic liver stiffnesses. The Young's modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.
Assuntos
Biomimética , Módulo de Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Técnicas de Imagem por Elasticidade/normas , Imagens de Fantasmas , Humanos , Padrões de Referência , Resistência ao Cisalhamento , UltrassonografiaRESUMO
Ultrasonic transient elastography (TE), enables to assess, under active mechanical constraints, the elasticity of the liver, which correlates with hepatic fibrosis stages. This technique is routinely used in clinical practice to assess noninvasively liver stiffness. The Fibroscan system used in this work generates a shear wave via an impulse stress applied on the surface of the skin and records a temporal series of radio-frequency (RF) lines using a single-element ultrasound probe. A shear wave propagation map (SWPM) is generated as a 2-D map of the displacements along depth and time, derived from the correlations of the sequential 1-D RF lines, assuming that the direction of propagation (DOP) of the shear wave coincides with the ultrasound beam axis (UBA). Under the assumption of pure elastic tissue, elasticity is proportional to the shear wave speed. This paper introduces a novel approach to the processing of the SWPM, deriving the maximum likelihood estimate of the shear wave speed when comparing the observed displacements and the estimates provided by the Green's functions. A simple parametric model is used to interface Green's theoretical values of noisy measures provided by the SWPM, taking into account depth-varying attenuation and time-delay. The proposed method was evaluated on numerical simulations using a finite element method simulator and on physical phantoms. Evaluation on this test database reported very high agreements of shear wave speed measures when DOP and UBA coincide.
Assuntos
Algoritmos , Técnicas de Imagem por Elasticidade/métodos , Simulação por Computador , Técnicas de Imagem por Elasticidade/instrumentação , Processamento de Imagem Assistida por Computador/métodos , Funções Verossimilhança , Imagens de FantasmasRESUMO
BACKGROUND: In contrast with other elastographic techniques, ascites is considered an exclusion criterion for assessment of fibrosis stage by transient elastography. However, a normal liver stiffness could rule out hepatic causes of ascites at an early stage. The aim of the present study was to determine whether liver stiffness can be generally determined by transient elastography through an ascites layer, to determine whether the ascites-mediated increase in intra-abdominal pressure affects liver stiffness, and to provide initial data from a pilot cohort of patients with various causes of ascites. METHODS AND RESULTS: Using the XL probe in an artificial ascites model, we demonstrated (copolymer phantoms surrounded by water) that a transient elastography-generated shear wave allows accurate determination of phantom stiffness up to a water lamella of 20 mm. We next showed in an animal ascites model that increased intra-abdominal pressure does not affect liver stiffness. Liver stiffness was then determined in 24 consecutive patients with ascites due to hepatic (n = 18) or nonhepatic (n = 6) causes. The cause of ascites was eventually clarified using routine clinical, imaging, laboratory, and other tools. Valid (75%) or acceptable (25%) liver stiffness data could be obtained in 23 patients (95.8%) with ascites up to an ascites lamella of 39 mm. The six patients (25%) with nonhepatic causes of ascites (eg, pancreatitis, peritoneal carcinomatosis) had a significantly lower liver stiffness (<8 kPa) as compared with the remaining patients with hepatic ascites (>30 kPa). Mean liver stiffness was 5.4 kPa ± 1.3 versus 66.2 ± 13.3 kPa. CONCLUSION: In conclusion, the presence of ascites and increased intra-abdominal pressure does not alter underlying liver stiffness as determined by transient elastography. We suggest that, using the XL probe, transient elastography can be used first-line to identify patients with nonhepatic ascites at an early stage.
RESUMO
Understanding the mechanical properties of human liver is one of the most critical aspects of its numerical modeling for medical applications or impact biomechanics. Generally, model constitutive laws come from in vitro data. However, the elastic properties of liver may change significantly after death and with time. Furthermore, in vitro liver elastic properties reported in the literature have often not been compared quantitatively with in vivo liver mechanical properties on the same organ. In this study, both steps are investigated on porcine liver. The elastic property of the porcine liver, given by the shear modulus G, was measured by both Transient Elastography (TE) and Dynamic Mechanical Analysis (DMA). Shear modulus measurements were realized on in vivo and in vitro liver to compare the TE and DMA methods and to study the influence of testing conditions on the liver viscoelastic properties. In vitro results show that elastic properties obtained by TE and DMA are in agreement. Liver tissue in the frequency range from 0.1 to 4 Hz can be modeled by a two-mode relaxation model. Furthermore, results show that the liver is homogeneous, isotropic and more elastic than viscous. Finally, it is shown in this study that viscoelastic properties obtained by TE and DMA change significantly with post mortem time and with the boundary conditions.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fígado/fisiologia , Animais , Elasticidade , Feminino , Suínos , ViscosidadeRESUMO
AIM: To develop and validate a transient micro-elastography device to measure liver stiffness (LS) in mice. METHODS: A novel transient micro-elastography (TME) device, dedicated to LS measurements in mice with a range of measurement from 1-170 kPa, was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston. The novel probe was validated in a classical fibrosis model (CCl(4)) and in a transgenic murine model of systemic amyloidosis. RESULTS: TME could be successfully performed in control mice below the xiphoid cartilage, with a mean LS of 4.4 ± 1.3 kPa, a mean success rate of 88%, and an excellent intra-observer agreement (0.98). Treatment with CCl(4) over seven weeks drastically increased LS as compared to controls (18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa). Moreover, fibrosis stage was highly correlated with LS (Spearman coefficient = 0.88, P < 0.01). In the amyloidosis model, much higher LS values were obtained, reaching maximum values of > 150 kPa. LS significantly correlated with the amyloidosis index (0.93, P < 0.0001) and the plasma concentration of mutant hapoA-II (0.62, P < 0.005). CONCLUSION: Here, we have established the first non-invasive approach to measure LS in mice, and have successfully validated it in two murine models of high LS.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fígado/patologia , Amiloidose/induzido quimicamente , Amiloidose/patologia , Animais , Tetracloreto de Carbono/toxicidade , Feminino , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos EndogâmicosRESUMO
Vibration-controlled transient elastography (VCTETM) technique is routinely used in clinical practice to assess non-invasively the liver stiffness which is correlated to hepatic fibrosis. Adequate use of the VCTETM probe requires the knowledge of the distance between the skin and the liver parenchyma. This paper compares two methods to estimate this distance using spatial variations of the spectral content of ultrasound radiofrequency (RF) lines, obtained from a probe consisting of a single element ultrasound transducer placed in front of the liver right lobe. Results on a database of 188 patients, including normal-weight and obese persons, show that the spectral variance can accurately discriminate the subcutaneous fat from the liver tissue. The proposed algorithm works in real-time and is suitable for VCTETM scanning protocol setup.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Interpretação de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Fígado/fisiologia , Fenômenos Fisiológicos da Pele , Pele/diagnóstico por imagem , Módulo de Elasticidade/fisiologia , Humanos , Aumento da Imagem/métodos , Ondas de Rádio , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fígado Gorduroso/diagnóstico por imagem , Algoritmos , Área Sob a Curva , Doença Crônica , Estudos de Coortes , Progressão da Doença , Fígado Gorduroso/etiologia , Humanos , Imagens de Fantasmas , Projetos Piloto , Curva ROC , Reprodutibilidade dos Testes , Estatísticas não ParamétricasRESUMO
The noninvasive quantitation of liver stiffness (LS) by ultrasound based transient elastography using FibroScan® has revolutionized the diagnosis of liver diseases, namely liver cirrhosis. Alternative techniques such as acoustic radiation impulse frequency imaging or magnetic resonance elastography are currently under investigation. LS is an excellent surrogate marker of advanced fibrosis (F3) and cirrhosis (F4) outscoring all previous noninvasive approaches to detect cirrhosis. LS values below 6 kPa are considered as normal and exclude ongoing liver disease. LS of 8 and 12.5 kPa represent generally accepted cut-off values for F3 and F4 fibrosis. LS highly correlates with portal pressure, and esophageal varices are likely at values >20 kPa. Many other factors may also increase LS such as hepatic infiltration with tumor cells, mast cells (mastocytosis), inflammatory cells (all forms of hepatitis) or amyloidosis. In addition, LS is directly correlated with the venous pressure (eg, during liver congestion) and is increased during mechanic cholestasis. Thus, LS should always be interpreted in the context of clinical, imaging and laboratory findings. Finally, LS has helped to better understand the molecular mechanisms underlying liver fibrosis. The novel pressure-stiffness-fibrosis sequence hypothesis is introduced.
RESUMO
Ultrasound biomicroscopy (UBM) of mice can provide a testing ground for new imaging strategies. The UBM system presented in this paper facilitates the development of imaging and measurement methods with programmable design, arbitrary waveform coding, broad bandwidth (2-80 MHz), digital filtering, programmable processing, RF data acquisition, multithread/multicore real-time display, and rapid mechanical scanning (Assuntos
Microscopia Acústica/instrumentação
, Microscopia Acústica/métodos
, Processamento de Sinais Assistido por Computador
, Software
, Algoritmos
, Animais
, Feminino
, Rim/diagnóstico por imagem
, Região Lombossacral/diagnóstico por imagem
, Camundongos
, Imagens de Fantasmas
, Transdutores
RESUMO
Ultrasound-based transient elastography (TE) and magnetic resonance elastography (MRE) are increasingly used methods for the clinical evaluation of soft tissue mechanical properties and their alteration under diseased conditions. This study proposes a comparison between magnetic resonance elastography (MRE) and ultrasound-based transient elastography (TE). Both methods were tested on the same soft tissue-mimicking gels in a common frequency range in order to allow for direct quantitative comparison. For the four gels tested, relatively good agreement was found between the shear moduli measured by both methods, with an averaged relative difference of 23%. This study demonstrates that under the assumption of homogeneous media that are significantly more elastic than viscous, quantitative results obtained by both methods are comparable.