Introduction
LiverMultiScan is a non-invasive, MRI-based procedure for evaluating liver disease. It is an FDA-cleared and CE-marked precision imaging solution that provides validated1, standardised and quantitative metrics for a comprehensive assessment of liver health.
The metrics included are:
- Corrected T1, or cT1 - A patented measure of liver disease activity that is predictive of liver and cardiovascular outcomes.2,3 cT1 is reported in milliseconds (ms)
- Liver Fat Fraction – Measured with Proton Density Fat Fraction (PDFF), which is widely considered to be the gold standard for accurate and consistent measurement of liver steatosis. Liver fat fraction is reported in %.
- Liver Iron Concentration - A measure of the iron present in the liver, reported as mg Fe/g dry tissue.
How is cT1 generated?
cT1 is a proprietary biomarker provided only via Perspectum. It relates to the amount of extracellular fluid present in the liver parenchyma, which is in turn affected by levels of inflammation and fibrosis. Conventional T1 (ms), a standard MRI parameter, measures the amount of extracellular fluid but can be confounded by the iron stored in the liver. This could lead to an underestimation of the T1 value and hence, underestimation of disease levels.
cT1 is T1 corrected for the confounding effect of iron, which enables accurate4 measurement of liver disease activity that aids physicians in diagnosis and risk-stratification. Unlike conventional T1, Perspectum has applied its know-how in implementing and standardising cT1 across major MRI scanner manufacturer platforms (Siemens, GE and Philips at 1.5T and 3T) for repeatable and reproducible5 results, which is essential for reliably monitoring liver disease over time to guide treatment decisions. cT1 is also unaffected by body habitus6, ensuring consistent results across diverse patient profiles while remaining sensitive to dynamic changes in disease activity7.
Multiple publications evidence its use as a high-performing biomarker for use in the management of chronic liver diseases including MASLD and MASH, autoimmune hepatitis8, viral hepatitis9 and paediatric liver disease10.
Clinical Utility
EASL and AASLD guidelines recommend the use of noninvasive tests, including LiverMultiScan cT1, in individuals who are at risk of MASLD, including those with cardiometabolic risk factors, abnormal liver enzymes and radiological signs of hepatic steatosis, particularly in patients with type 2 diabetes and obesity.11-14
A decrease of 80ms in cT1 has been demonstrated to be clinically meaningful, and identifies patients with MASH on therapy who have achieved histological resolution of steatohepatitis, without worsening of fibrosis15. cT1 has also shown the ability to detect dose-dependent change in patients on therapy in MASH clinical trials16.
The following table is provided cT1 thresholds of importance:
cT1 ≥800ms: Above the upper limit of normal
cT1 800 - 874 ms: Elevated levels of disease activity,
cT1 ≥875ms: High risk of more advanced liver disease, or possible ‘at-risk’ MASH
A reduction of 80ms corresponds to resolution of MASH
A state-of-the-art clinical review noted that multi parametric MRI imaging as used in LiverMultiScan could serve as a virtual biopsy as it provides a panoramic view of liver tissue characteristics, which supports assessment of the heterogenous distribution of disease across the liver. 17
cT1 has been shown to predict relapse in patients with autoimmune hepatitis even when their blood tests and other imaging tests have been normal.8
References
1. Banerjee R, Pavlides M, Tunnicliffe EM, et al. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol 2014;60(1):69-77. DOI: 10.1016/j.jhep.2013.09.002.
2. Roca-Fernandez, A, Banerjee R, Thomaides-Brears H, et al. Liver disease is a significant risk factor for cardiovascular outcomes - AUK Biobank study. J Hepatol 2023;79(5):1085-1095. DOI:10.1016/j.jhep.2023.05.046.
3. Jayaswal ANA, Levick C, Selvaraj EA, Dennis A, BoothJC, Collier J, Cobbold J, Tunnicliffe EM, Kelly M, Barnes E, Neubauer S,Banerjee R, Pavlides M. Prognostic value of multiparametric magnetic resonance imaging, transient elastography and blood-based fibrosis markers in patients with chronic liver disease. Liver Int. 2020 Dec; 40(12):3071-3082. doi:10.1111/liv.14625. PMID: 32730664.
4. Andersson A, Kelly M, Imajo K, et al. Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter Pooled Data and Meta-Analysis. Clin Gastroenterol Hepatol 2022;20(11):2451-2461 e3. DOI:10.1016/j.cgh.2021.09.041.
5. Beyer C, Andersson A, Shumbayawonda E, Alkouri N,Banerjee A, Pandya P, Harisinghani M, Corey K, Dennis A, Pansini M.Quantitative MRI for Monitoring Metabolic Dysfunction-Associated Steatotic Liver Disease: A Test-Retest Repeatability Study. J Magn Reson Imaging. 2024Sep 25. doi: 10.1002/jmri.29610. Epub ahead of print. PMID: 39319470.
6. Pavlides M, Banerjee R, Tunnicliffe EM,Kelly C, Collier J, Wang LM, Fleming KA, Cobbold JF, Robson MD, Neubauer S,Barnes E. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver Int. 2017 Jul;37(7):1065-1073.doi: 10.1111/liv.13284. Epub 2017 May 30. PMID: 27778429; PMCID: PMC5518289.
7. Harrison SA, Rossi SJ, Paredes AH, Trotter JF,Bashir MR, Guy CD, Banerjee R, Jaros MJ, Owers S, Baxter BA, Ling L, DePaoliAM. NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients WithNonalcoholic Steatohepatitis. Hepatology. 2020 Apr;71(4):1198-1212. doi:10.1002/hep.30590. Epub 2019 Apr 10. PMID: 30805949; PMCID: PMC7187438.
8. Arndtz K, Shumbayawonda E, Hodson J, et al. Multiparametric Magnetic Resonance Imaging, Autoimmune Hepatitis, andPrediction of Disease Activity. Hepatol Commun 2021;5(6):1009-1020. DOI:10.1002/hep4.1687.
9. Jayaswal ANA, Levick C, Collier J, et al. Liver cT(1)decreases following direct-acting antiviral therapy in patients with chronic hepatitis C virus. Abdom Radiol (NY) 2021;46(5):1947-1957. DOI:10.1007/s00261-020-02860-5.
10. Janowski, K., Shumbayawonda, E., Cheng, L. et al. Quantitative multiparametric MRI as a non-invasive stratification tool in children and adolescents with autoimmune liver disease. Sci Rep 11,15261 (2021). https://doi.org/10.1038/s41598-021-94754-9
11. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLDPractice Guidance on the clinical assessment and management of non alcoholic fatty liver disease. Hepatology 2023;77(5):1797-1835.DOI:10.1097/HEP.0000000000000323.
12. Wattacheril JJ, Abdelmalek MF, Lim JK, Sanyal AJ. AGA Clinical Practice Update on the Role of Noninvasive Biomarkers in the Evaluation and Management of Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology. 2023 Oct;165(4):1080-1088. doi: 10.1053/j.gastro.2023.06.013. Epub 2023 Aug 4. PMID: 37542503.
13. Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline forthe Diagnosis and Management of Nonalcoholic Fatty Liver Disease in PrimaryCare and Endocrinology Clinical Settings: Co-Sponsored by the AmericanAssociation for the Study of Liver Diseases (AASLD). Endocr Pract. 2022May;28(5):528-562. doi: 10.1016/j.eprac.2022.03.010. PMID: 35569886.
14. European Association for the Study of the Liver (EASL). Electronic address: easloffice@easloffice.eu; European Association for theStudy of Diabetes (EASD); European Association for the Study of Obesity (EASO);European Association for the Study of the Liver (EASL). EASL-EASD-EASO ClinicalPractice Guidelines on the management of metabolic dysfunction-associatedsteatotic liver disease (MASLD). J Hepatol. 2024 Sep;81(3):492-542. doi:10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7. PMID: 38851997.
15. Alkhouri N, Beyer C, Shumbayawonda E, Andersson A, Yale K, Rolph T, Chung RT, Vuppalanchi R, Cusi K, Loomba R, Pansini M, Dennis A. Decreases incT1 and liver fat content reflect treatment-induced histological improvements in MASH. J Hepatol. 2024 Sep 19:S0168-8278(24)02559-5. doi:10.1016/j.jhep.2024.08.031. Epub ahead of print. PMID: 39326675.
16. Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J,Bugianesi E, Yoneda M, Behling C, Cummings OW, Tang Y, Brouwers B, Robins DA,Nikooie A, Bunck MC, Haupt A, Sanyal AJ; SYNERGY-NASH Investigators. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with LiverFibrosis. N Engl J Med. 2024 Jul 25;391(4):299-310. doi: 10.1056/NEJMoa2401943.Epub 2024 Jun 8. PMID: 38856224.
17. Muratori L, Lohse AW, Lenzi M. Diagnosis and management of autoimmune hepatitis. BMJ 2023;380:e070201. DOI:10.1136/bmj-2022-070201