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MAPIT - MAgnetic resonance (MR) relaxometry for extracellular volume (ECV) mapPIng combined with elasTography for noninvasive characterization of diffuse liver disease

English title MAPIT - MAgnetic resonance (MR) relaxometry for extracellular volume (ECV) mapPIng combined with elasTography for noninvasive characterization of diffuse liver disease
Applicant Huber Adrian
Number 188591
Funding scheme Project funding (Div. I-III)
Research institution Universitätsinstitut für Diagnostische, Interventionelle & Pädiatrische Radiologie Inselspital
Institution of higher education University of Berne - BE
Main discipline Internal Medicine
Start/End 01.07.2020 - 30.06.2024
Approved amount 572'153.00
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Keywords (6)

MR Elastography; Chronic Liver Disease; Non-invasive Tissue Characterization; Liver Fibrosis; MR Relaxometry; T1 Mapping

Lay Summary (German)

Lead
Diffuse Lebererkrankungen sind in der Schweiz häufig. Unbehandelt führen sie zu einer Leberzirrhose mit Verlust der Leberfunktion und es kann sich Leberkrebs ausbilden. An erster Stelle steht heute die Leberverfettung, welche sich in unserer westlichen Bevölkerung bereits bei 20-30% findet und weiterhin zunimmt. Das Projekt untersucht eine neue nicht-invasive MRI-Methode, um die schweren von den weniger schweren Formen einer diffusen Lebererkrankung zu unterscheiden.
Lay summary

Lead

Diffuse Lebererkrankungen sind in der Schweiz häufig. Unbehandelt führen sie zu einer Leberzirrhose mit Verlust der Leberfunktion und es kann sich Leberkrebs ausbilden. An erster Stelle steht heute die Leberverfettung, welche sich in unserer westlichen Bevölkerung bereits bei 20-30% findet und weiterhin zunimmt. Das Projekt untersucht eine neue nicht-invasive MRI-Methode, um die schweren von den weniger schweren Formen einer diffusen Lebererkrankung zu unterscheiden.

Inhalt und Ziel des Forschungsprojekts                        

Die Ausprägung der diffusen Lebererkrankung ist vielseitig. Neben der Leberverfettung sind eine Leberfibrose, eine Entzündungsreaktion und das Absterben von Leberzellen möglich. Die Kombination und das Ausmass dieser Prozesse entscheiden über den Schweregrad, die Prognose und die mögliche Therapie der Erkrankung. Aufgrund der Umbauprozesse bildet sich zudem ein Bluthochdruck in den Pfortadergefässen der Leber, was bei gleichzeitiger Herzschwäche durch den Blutrückstau in die Leber verstärkt werden kann und die Leber zusätzlich schädigt. Mit der MRI-Elastographie kann die Steifigkeit der Leber und mit einer anderen MRI-Sequenz der Leberfettgehalt in % bestimmt werden. Die sogenannte MRI-Relaxometrie erlaubt es, Entzündungsprozesse abzubilden und die Ausdehnung der Fibrose im extrazellulären Raum zu messen. Das Ziel des Projekts ist es, alle diese Aspekte mit einer einzigen MRI-Untersuchung kombiniert zu analysieren.

Wissenschaftlicher und Gesellschaftlicher Kontext des Forschungsprojekts

Bei dem Projekt handelt es sich um eine klinische Studie. Das Ziel ist es, mittels MRI schwere von weniger schweren Formen der diffusen Lebererkrankungen zu unterscheiden und damit unnötige invasive Gewebeprobenentnahmen der Leber zu verhindern. 

Direct link to Lay Summary Last update: 23.04.2020

Responsible applicant and co-applicants

Project partner

Associated projects

Number Title Start Funding scheme
157744 Magnetic Resonance (MR) - Elastography for Characterization of Liver Disease 01.12.2014 R'EQUIP

Abstract

Quantification of liver stiffness (LS) with transient elastography (Fibroscan®) and magnetic resonance elastography (MRE) represent non-invasive surrogates to assess liver fibrosis grades. While transient elastography is widely available and relatively cheap, MRE allows whole liver volume analysis and may be combined with other MR sequences. A major drawback of both methods are false positive rates of increased LS unrelated to fibrosis due to liver congestion and inflammation. There is a need for more accurate non-invasive biomarkers to quantify liver fibrosis in early stages, especially in patients with non-alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH), where liver stiffness evaluation is increased due to fibrosis, but also due to inflammation and congestion. The latter is important, since NAFLD/NASH patients often have cardiovascular comorbidities and obesity is a major risk factor of diastolic heart failure with preserved ejection fraction (HFPEF) (1,2). The MAPIT project aims to combine MRE with MR fat quantification, relaxometry and extracellular volume (ECV) mapping as multiparametric MR (mpMR). ECV is quantified based on the haematocrit (1-haematocrit being the blood ECV) and comparison of T1 relaxation time of the liver and the blood pool (aorta), measured before and 15 minutes after administration of extracellularly distributed contrast medium. At an earlier timepoint, 2 minutes post contrast administration, comparison of T1 shortening in the liver and in the aorta gives information about the liver vascular pool, based on the hypothesis that at this timepoint, contrast medium is homogenized to the liver vessels and sinusoids, but has not yet diffused to the interstitial space. Based on these measurements, LS related to the vascular space (LSvs) can be separated from LS related to the interstitial space (LSis). MAPIT will show that LSvs is increased in liver congestion and LSis allows to grade liver fibrosis more accurately than LS alone. While the degree of steatosis can be quantified accurately with proton density fat fraction (PDFF), ECV normalized to LS (ECVkPa in % per kPa) is a promising maker for inflammation, since in inflammation we expect an ECV-expansion, but to a lesser extent LS. MAPIT therefore provides a one-stop shop mpMR to quantify liver fibrosis unrelated to inflammation and congestion and to separate NAFLD from NASH, which is now only possible based on liver biopsy NAFLD activity score (NAS) (3). As secondary mpMR biomarkers, apparent diffusion coefficient (ADC) values along with additional intravoxel incoherent motion (IVIM) parameters (D*, FP (perfusion fraction) and shifted ADC (sADC), native T1 and T2 will be analyzed as surrogates for fibrosis, congestion and inflammation. Heterogeneity of liver steatosis and inflammation will be correlated to lipid subtype composition, as measured with in vivo and ex vivo (on the biopsy samples) MR spectroscopy (MRS). MAPIT includes 3 work packages (WP). WP1 is dedicated to the mpMR protocol set up and optimization, comparing 3 different MR elastography techniques (GRE-based, SE-EPI based and multifrequency MRE) in healthy volunteers and patients with different degrees of fibrosis (f1-4). The most robust and accurate MRE technique will be selected and used in WP 2+3. WP 2 will analyze patients with liver congestion, including patients with portal venous congestion undergoing transjugular porto-systemic shunt (TIPS) and patients with liver venous congestion due to pulmonary hypertension related to obesity hypoventilation syndrome. Based on the insights gained in WP 1+2, WP 3 will compare mpMR biomarkers with histologic NAFLD activity score in NAFLD/NASH patients. MAPIT will strengthen accurate non-invasive diagnosis of chronic liver disease (CLD) using mpMR as a one-stop shop, notably to differentiate NAFLD from NASH and to grade early liver fibrosis more accurately, independent from confounding liver inflammation and congestion.
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