Viscoelastic modulus reconstruction using time harmonic vibrations

This paper presents a new iterative reconstruction method to provide high-resolution images of shear modulus and viscosity via the internal measurement of displacement fields in tissues. To solve the inverse problem, we compute the Fr\'echet derivatives of the least-squares discrepancy functional with respect to the shear modulus and shear viscosity. The proposed iterative reconstruction method using this Fr\'echet derivative does not require any differentiation of the displacement data for the full isotropic linearly viscoelastic model, whereas the standard reconstruction methods require at least double differentiation. Because the minimization problem is ill-posed and highly nonlinear, this adjoint-based optimization method needs a very well-matched initial guess. We find a good initial guess. For a well-matched initial guess, numerical experiments show that the proposed method considerably improves the quality of the reconstructed viscoelastic images.Comment: 15 page

Spring-damper equivalents of the fractional, poroelastic, and poroviscoelastic models for elastography

In MR elastography it is common to use an elastic model for the tissue's response in order to properly interpret the results. More complex models such as viscoelastic, fractional viscoelastic, poroelastic, or poroviscoelastic ones are also used. These models appear at first sight to be very different, but here it is shown that they all may be expressed in terms of elementary viscoelastic models. For a medium expressed with fractional models, many elementary spring-damper combinations are added, each of them weighted according to a long-tailed distribution, hinting at a fractional distribution of time constants or relaxation frequencies. This may open up for a more physical interpretation of the fractional models. The shear wave component of the poroelastic model is shown to be modeled exactly by a three-component Zener model. The extended poroviscoelastic model is found to be equivalent to what is called a non-standard four-parameter model. Accordingly, the large number of parameters in the porous models can be reduced to the same number as in their viscoelastic equivalents. As long as the individual displacements from the solid and fluid parts cannot be measured individually the main use of the poro(visco)elastic models is therefore as a physics based method for determining parameters in a viscoelastic model.Comment: 11 pages, 7 figures. Changed inconsistent notation in Eqs 1, 5, 8, 10 and corrected mistakes in Eqs 2, 4, 12, 3

MR Elastography-Based Assessment of Matrix Remodeling at Lesion Sites Associated With Clinical Severity in a Model of Multiple Sclerosis

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum-a region with predominant inflammation in this model-is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme

elastography in primary open-angle glaucoma

Objective: The aim of this study was to compare sonoelastographic findings in the retina-choroid-sclera (RCS) complex and vitreous in glaucomatous and healthy eyes.Methods: For this cross-sectional comparative study, 20 patients with primary open-angle glaucoma and 20 healthy volunteers were recruited. Ultrasound elastography measurements were taken with a sonographic scanner of the RCS complex, anterior vitreous (AV), posterior vitreous (PV), retrobulbar fat tissue (RFT), optic disc (OD) and optic nerve (ON) in each eye.Results: The elasticity index of the RCS complex, RFT, OD, ON, AV and PV was similar in both groups (p > 0.05), although the AV/PV strain ratio in the group of patients with glaucoma was significantly higher (p = 0.04).Conclusion: Glaucoma increases the AV/PV strain ratio. In providing reproducible and consistent values, the real-time elastography (RTE) technique may be helpful in elucidating the mechanisms of glaucoma in some aspects.Advances in knowledge: This study can help to evaluate the elasticity of the RCS complex and vitreous in glaucomatous eyes with RTE

Mandatory multidisciplinary approach for the evaluation of the lymph node status in rectal cancer

Colorectal cancer is the third most frequently reported malignancy and also the third leading cancer-related cause of death worldwide. Lymph node evaluation, both preoperatively and postoperatively, represents an important aspect of the diagnosis and therapeutic strategy in colorectal cancer, such that an accurate preoperative staging is required for a correct therapeutic strategy. Treatment of rectal cancer with positive lymph nodes, a very important predictive prognostic parameter, is currently based on neoadjuvant chemoradiotherapy followed by total/ surgical mesorectal excision and adjuvant regimen. Preoperative evaluation of the lymph node status in rectal cancer is based on endoscopic ultrasound and magnetic resonance imaging, but their accuracy, specificity, and sensitivity still require improvement. Postoperative evaluation also presents points of debate, especially related to the role of sentinel lymph node mapping and their final implication, represented by detection of micrometastases and isolated tumor cells. The pathologic interpretation of tumor deposits represents other points in discussion. From a surgical perspective, extended lateral lymph node dissection vs. abstinence and (neo)adjuvant therapeutic approach represent another unresolved issue. This review presents the major controversies existing today in the treatment and pathologic interpretation of the lymph nodes in rectal cancer, the role/ indication and value of the lateral pelvic lymph node dissection, and the postoperative interpretation of the value of the micrometastatic disease and tumor deposits