A study of T ₁ relaxation time as a measure of liver fibrosis and the influence of confounding histological factors

Abstract

Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non-invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the liver. Here, we extend this work to measure T1 of the whole liver and investigate the effects of additional histological factors such as steatosis, inflammation and iron accumulation on the relationship between liver T1 and fibrosis. We prospectively enrolled patients who had previously undergone liver biopsy to have MR scans. A non-breath-holding, fast scanning protocol was used to acquire MR relaxation time data (T1 and T2*), and blood serum was used to determine the enhanced liver fibrosis (ELF) score. Areas under the receiver operator curves (AUROCs) for T1 to detect advanced fibrosis and cirrhosis were derived in a training cohort and then validated in a second cohort. Combining the cohorts, the influence of various histology factors on liver T1 relaxation time was investigated. The AUROCs (95% confidence interval (CI)) for detecting advanced fibrosis (F ≥ 3) and cirrhosis (F = 4) for the training cohort were 0.81 (0.65-0.96) and 0.92 (0.81-1.0) respectively (p < 0.01). Inflammation and iron accumulation were shown to significantly alter T1 in opposing directions in the absence of advanced fibrosis; inflammation increasing T1 and iron decreasing T1. A decision tree model was developed to allow the assessment of early liver disease based on relaxation times and ELF, and to screen for the need for biopsy. T1 relaxation time increases with advanced fibrosis in liver patients, but is also influenced by iron accumulation and inflammation. Together with ELF, relaxation time measures provide a marker to stratify patients with suspected liver disease for biopsy.

Imaging the kidney using magnetic resonance techniques

“…T1 values have been shown to correlate well with fibrosis and oedema in cardiac [8] and liver imaging [9]. In an animal model of acute kidney injury (AKI) induced by 30min or 45min of ischaemia followed by reperfusion, Hueper et al demonstrated that the T1 relaxation time of renal tissue increased significantly at days 1 and 7, and was associated with renal inflammation [10].…”

Current and Future Magnetic Resonance Technologies for Assessing Liver Disease in Clinical and Experimental Medicine

“…For T 1 measures, the acquisition and analysis are highly repeatable in healthy subjects, with a coefficient of variation between visits of 1.8% and low inter-and intra-observer variability with intra-class correlation coefficients of >0.99 [13] .…”

“…Two prospective studies have shown that differing measures of liver longitudinal relaxation time (T 1 ) correlate well to histological fibrosis [12,13] . For T 1 measures, the acquisition and analysis are highly repeatable in healthy subjects, with a coefficient of variation between visits of 1.8% and low inter-and intra-observer variability with intra-class correlation coefficients of >0.99 [13] .…”

“…Architectural changes within the liver can be evaluated concurrently with portal haemodynamic changes allowing non-invasive assessment of portal hypertension and effects of interventions. A combination ultra-high field (7T) provides greater sensitivity with a potential to distinguish inflammation from fibrosis on imaging and determine specific types of fats (saturated vs. unsaturated) present within More recently, a wider range of MRI measurements have been developed to measure liver disease, including T 1 mapping of liver fibrosis [2] , MR elastography [3] , R 2 * mapping/susceptibility [4] and gradient echo fat-fraction measurements (also referred to as Dixon scanning) [5] . Also, advances in proton and multi-nuclear MR spectroscopy (MRS) have opened up a range of otherwise inaccessible parameters for examination [6,7] .…”

“…These include inflammation [13] , iron [14][15][16] , fat [17] and oedema [18,19] . Iron accumulation in liver tissue reduces T2 and T2 * relaxation times [15,16] , and an increase in iron will also reduce T 1 in the liver [14] .…”