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“MRI and liver fibrosis ” APASL Consensus Meeting for Liver Fibrosis June 11 th 2014

“MRI and liver fibrosis ” APASL Consensus Meeting for Liver Fibrosis June 11 th 2014 Prof Seng Gee Lim Director of Hepatology , Dept of Gastroenterology and Hepatology National University Health System Singapore. Types of MR Imaging. Contrast -Enhanced Magnetic Resonance Imaging .

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“MRI and liver fibrosis ” APASL Consensus Meeting for Liver Fibrosis June 11 th 2014

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  1. “MRI and liver fibrosis” APASL Consensus Meeting for Liver Fibrosis June 11th 2014 Prof Seng Gee Lim Director of Hepatology, Dept of Gastroenterology and Hepatology National University Health System Singapore

  2. Types of MR Imaging • Contrast-Enhanced Magnetic Resonance Imaging. • Diffusion-Weighted Magnetic Resonance Imaging (DWMRI). • Magnetic Resonance Spectroscopy (MRS) • Magnetic Resonance Elastography (MRE)

  3. Contrast-Enhanced Magnetic Resonance Imaging • Extracellular agents (eg gadolinium chelates) • Gadolinium shortens the T1 (spin-lattice) and T2 (spin-spin) relaxation times of adjacent water protons. These relaxation effects tend to cause signal enhancement at T1-weighted imaging and signal loss at T2-weighted imaging. The use of gandolinium enables visualisation of the vascular supply and vascularity of the liver. • Reticuloendothelial agents (superparamagnetic iron oxides [SPIOs]) • SPIO particles are phagocytosed by macrophages throughout the body but are preferentially entrapped by Kupffer cells, which line the hepatic sinusoids. SPIO particles act as a negative contrast agent. Their superparamagnetic properties cause local magnetic field inhomogeneity and result in considerable T2 and T2* shortening. Tissues that accumulate SPIO particles thus show reduced signal intensity, particularly on T2- and T2*-weighted images, and to a lesser extent on T1-weighted images.

  4. Gandolinium contrast MRI Arterial Porto venous Delayed

  5. Contrast MR limitations • Considerable variation in MRI of liver techniques, measurement parameters as well as few high quality studies to be certain of their utility in diagnosis of liver fibrosis. • New contrast agents are expensive and time for scanning prolonged with breath hold requirements • may not be suitable for elderly and unfit patients, making this not an optimal choice for evaluation of liver fibrosis. • Parameters are qualitative rather than quantitative making diagnostic criteria quite subjective • No good studies that document sensitivity, specificity and accuracy

  6. Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) • The principle of diffusion-weighted MR imaging (DWMRI) is that the observed signal intensity of tissue varies inversely with the freedom of water proton diffusion. • With DWMRI, tissues with reduced water proton diffusion will be brighter than those with normal water proton diffusion. • The sensitivity of the sequence for diffusion can be varied using various parameters and this is known as the diffusion weighting to “b” value. • The apparent diffusion coefficient (ADC) of water protons in tissues is determined by the slope of the log intensity versus b value. As fibrosis increases, one expects that the ADC decreases as diffusion is reduced.

  7. b value = 800 b value = 0 ADC map

  8. Magnetic Resonance Spectroscopy (MRS) • Currently MRS can be performed by analysing signals from eiether hydrogen (1H-MRS) or phosphorus (31P-MRS) atoms. • 1H-MRS provides insights into metabolism as phosphorusis associated with molecules involved in various metabolic processes. • Although not specific for liver, anatomically the concentration of highly active metabolic cells makes it ideal for 31P-MRS. • This technology does not measure fibrosis but rather metabolism. • Consequently, alterations in cell metabolism are an indirect measurement of liver fibrosis.

  9. MRS

  10. Magnetic Resonance Elastography (MRE) • Requires special software and equipment, it can be easily implemented on existing MR scanners with suitable alterations. • In contrast to other MR techniques, the generation of acoustic shear waves requires a mechanical or pneumatic driver in contact with the abdominal wall to generate mechanical waves between 40-120 Hz. • This pertubates the liver substance and a special phase contrast sequence is then use to capture images representing the displacement caused by the shear wave propagation

  11. MR elastography(MRE) 10 Normal liver has shear stiffness value of 2.9kilopascals (kPa) and below 8 6 Shear Stiffness (kPa) 4 Conventional MRI No information on mechanical properties MR Elastogram Shear stiffness map 2 Passive Driver 0 Active Driver Acoustic waves at 60Hz Imaging time: 32s Courtesy of Prof RL Ehman, Mayo Clinic, USA

  12. Normal 10 10 Significant Fibrosis 8 8 Shear Stiffness (kPa) Shear Stiffness (kPa) 6 6 4 4 2 2 0 0 43-year old obese female normal volunteer 55-year old male with chronic hepatitis B

  13. Acoustic Radiation Force Impulse • Acoustic radiation force impulse (ARFI) imaging is a new and promising ultrasound-based diagnostic technique that, evaluating the wave propagation speed, allows the assessment of the tissue stiffness. • ARFI is implemented in the ultrasound scanner and by using a conventional probe, without any need for external compression so reducing the operator dependency, it evaluates deep tissues stiffness providing complementary informationspotentially useful for the diagnosis. • By short-duration acoustic radiation forces (less than 1 ms), it generates localized displacements in a selected region of interest (ROI; a box with dimension of 1 cm × 0.5 cm), identified on a conventional B-model. • Depending on the interactions with the transducer, the generated wave scan provides qualitative (imaging) or quantitative (wave velocity values, measured in m/s) responses, by Virtual Touch Tissue Imaging and Virtual Touch Tissue Quantification, respectively (Siemens, Erlangen, Germany).

  14. Advantages of ARFI • Can be used during conventional US evaluations, without requiring additional transducers or other equipment • They performed measurement in the right lobe, by means of an intercostal scan, a condition which offers high inter-observer reproducibility (r= 0.874) • Failure rate is low, better than TE • Quantification may not be limited by narrow intercostal spaces or even by moderate excess weight • Only requires the visible liver is not deeper than a fixed distance from the skin surface (in order to put the ROI in the parenchyma), while with TE the liver must not be more than 25 mm from the skin

  15. Acoustic radiation force impulse . ROI: Region of interest.

  16. Normal liver Cirrhosis

  17. Search Strategy • Pubmed clinical queries • Search terms “MRI, elastography” AND “liver fibrosis” • Also search under related items • Manual sort for “systematic review” or “meta-analysis” • Only 2 suitable articles: • Guo et al, Abdominal imaging 2014 (Epub ahead of print) • Wang et al, Hepatology 2012;56:239-247 .

  18. Evaluation of the 2 Systematic Reviews

  19. Interpreting Likelihood Ratios Positive Likelihood Ratio Negative Likelihood Ratio LR(-) = 1 No effect = 0.9-0.2 Moderate effect < 0.1 Large effects LR(+) = 1 No effect = 2-9 Moderate effect > 10 Large effects Users' Guides to the Medical Literature: A Manual of Evidence-Based Clinical Practice. Guyatt GH, Rennie D, eds. Chicago, IL: AMA Press; 2002.

  20. DWMRI pooled estimates • Wang et al, Hepatology 2012;56:239-247

  21. MRE pooled estimates • Guo et al, Abdominal imaging 2014 (Epub ahead of print)

  22. ARPI pooled estimates • Guo et al, Abdominal imaging 2014 (Epub ahead of print)

  23. TE pooled estimates • Bota, Liver Int. 2013: 33: 1138–1147

  24. Wang study Based on our original question, group 2 and group 4 analyses were of particular interest. • Wang et al, Hepatology 2012;56:239-247

  25. MRE pooled estimates • Wang et al, Hepatology 2012;56:239-247

  26. Conclusions • DWMRI is inferior to MRE based on the diagnostic parameters although no direct comparison was made • LR(+) <10, LR(-) >0.1 • MRE performed remarkably well in both meta analyses with accuracy >95% • In the key questions of whether they can accurately diagnose different stages of cirrhosis, they performed >95% (AUROC) • In the key question of whether then can accurately diagnose ≥F2, they were 98% accurate, LR(+) 20 • In the key question of whether then can accurately exclude <F2, LR(-) 0.06 • In the key question of whether they can distinguish cirrhosis (F4) versus other stages, the were 99% accurate, LR (+) was 16 • In the key question of whether then can accurately exclude <F4, LR(-) 0.02

  27. Recommendations Previous Consensus New recommendation MRE has been shown to have high degree of accuracy to diagnose all stages of liver fibrosis and can be used as a replacement for liver biopsy in situations where there is minimal inflammation of the liver (A1). However, availability of the software and pneumatic driver, considerable cost of the MR equipment, and cost of the test makes this less suitable for routine use in developing countries. • None

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