Detection of hepatic steatosis with ultrasound attenuation imaging compared to MRI

doi:10.21203/rs.3.rs-5341525/v1

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Detection of hepatic steatosis with ultrasound attenuation imaging compared to MRI

https://doi.org/10.21203/rs.3.rs-5341525/v1

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Purpose: The main objective of this study was to evaluate the utility of a novel ultrasound technique, Attenuation Imaging (ATI), for detecting hepatic steatosis, comparing the results with magnetic resonance imaging (MRI) as the reference standard. ATI is a non-invasive, lower-cost, and potentially more available method with a shorter examination time than MRI.

Materials and Methods: A diagnostic test design was employed in a sample of 143 randomly selected patients who underwent both MRI and ATI. This diagnostic test study was conducted and reported in accordance with the STARD (Standards for Reporting of Diagnostic Accuracy) initiative. Pearson's correlation was used to compare the values obtained through ATI and MRI, and regression models was applied to assess interaction and confounding variables. Diagnostic performance was analyzed using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUROC).

Results: The ATI and MRI measurements showed a strong correlation (R-squared = 0.9841, p < 0.001). The non-linear regression analysis generated a formula to estimate the percentage of steatosis in MRI based on the steatosis measured by ATI. The ROC analysis revealed an AUROC of 0.8251 (95% CI: 0.75457-0.89565).

Conclusion: The ATI technique demonstrated a strong correlation with MRI for the detection of hepatic steatosis. The non-linear regression used in the study allowed for generating a formula that estimates the percentage of steatosis in MRI based on the steatosis measured by ATI. This indicates that ATI may serve as a more accessible and cost-effective alternative to MRI in detecting and monitoring hepatic steatosis in patients with non-alcoholic liver disease. Clinical Relevance: ATI offers a cost-effective, non-invasive, and accurate diagnostic method for detecting hepatic steatosis, potentially improving access to early diagnosis and treatment.

Nuclear Medicine & Medical Imaging

Abdomen

Liver Cirrhosis

Ultrasonography

Magnetic Resonance Imaging

prospective study

Non-alcoholic Fatty Liver Disease

Diagnostic Tests

Chile

Non-alcoholic fatty liver disease (NAFLD) is the primary cause of Chronic Liver Disease/Cirrhosis in developed and developing nations [1,2]. The condition encompasses a broad spectrum of liver abnormalities, including simple steatosis, steatohepatitis, and varying levels of fibrosis [3–5]. These changes may progress to cirrhosis and thus increase the risk of developing hepatocellular carcinoma [1]. NAFLD accounts for around 20% of cases of cirrhosis and is a significant contributor to the burden of disability-adjusted life years in men within our country (Chile) [6]. Liver biopsy, which has long been considered the “gold standard”, is an invasive, expensive, intervention with potential risks. The histological examination of the liver sample focuses on analyzing a small portion of the parenchyma, which represents approximately 0.00001% of the total liver volume [2]. The inherent variability in the sampling process makes it difficult to assess the consistency between different observations; furthermore, this method is expensive and not feasible for screening and monitoring a broad population [2]. In this context, non-invasive alternatives for diagnosing NAFLD are emerging [7].

Currently, non-invasive approaches are recommended for diagnosing patients who do not show clinical signs of steatohepatitis. Conventional B-mode ultrasonography is the most often used imaging method for diagnosis and monitoring the condition. It is a non-invasive, readily available, and cost-effective tool. However, it has limitations in accurately assessing steatosis, particularly in moderate instances, due to its subjective nature and limited sensitivity [6–9]. Computed tomography (CT) is a viable method for diagnosing steatosis, although it is not effective in detecting early stages, not to mention that it involves exposure to radiation [7]. Various non-invasive studies have arisen as promising solutions in this context for diagnosing a categorizing NAFLD. Magnetic resonance imaging (MRI) is a method that enables the determination of the degree of steatosis through morphological analysis and spectroscopy. This method has been validated against histological analysis, demonstrating its reliability as a diagnostic reference standard [2–5,10–12]. The specialized software “LiverLab” enables the analysis in three steps. Firstly, a qualitative assessment (Yes/No) is conducted to determine the presence of steatosis, utilizing the Dixon method with two acquisitions with a 3D T1 echo gradient sequence, revealing in-phase and out-phase images (step 1). Only if the preceding analysis is positive, the quantitative assessment is conducted by means of two different methods: the first involves a morphological analysis utilizing advanced Dixon multi-echo sequences that examine the hepatic parenchyma (step 2), the second involves a spectral analysis using voxel technique (step 3). Currently, the MRI detection mode has the highest amount of favorable evidence, achieving a good level of diagnostic accuracy, based on a recent meta-analysis that examined 82 studies and included 14,609 patients9. However, it should be noted that MRI is an expensive and somewhat limited test in terms of availability, particularly in developing countries [13].

Attenuation Imaging is a recently FDA-approved ultrasound technique that measures echogenicity in large samples of liver tissue. It provides a quick and noninvasive way to determine the level of steatosis. This technique utilizes an objective calculation to determine the echogenicity coefficient, which is then expressed in decibels per megahertz (dB/cm/MHz). It is not affected by interposing blood vessels, artifacts, or the ultrasound settings at the time of acquisition, nor is it altered by postprocessing tools. This parameter allows for an objective investigation of both intraand inter- observer concordance. Although the evidence for ATI is not as extensive as for MRI, this non-invasive method shows promise in accurately assessing the degree of liver steatosis. It offers the advantages of lower cost and potentially greater accessibility compared to magnetic resonance imaging [9,14,15]. At present, there have been only preliminary studies conducted using this technique. This study aimed to evaluate the utility of the Attenuation Imaging (ATI) ultrasoundbased technique for detecting and grading of hepatic steatosis compared to Magnetic Resonance Imaging (MRI) using as the diagnostic reference standard [16,17].

Objective

This study aimed to evaluate the utility of the Attenuation Imaging (ATI) ultrasoundbased technique for detecting and grading of hepatic steatosis compared to Magnetic Resonance Imaging (MRI) using as the diagnostic reference standard.

Study Design

The study was designed as a prospective cohort study for diagnostic tests. The sample size calculation was estimated with a statistical power of 90%, to detect changes in sensitivity from 0.75 to 0.90, considering a two-tailed statistical significance value of 0.05. The minimal calculated sample size was 140 participants who would be subjected to both MRI and ATI for detection of hepatic steatosis.

Recruitment of participants and data collection

145 participants were randomly selected from the population attending an abdominal ultrasound in Clínica Alemana de Santiago that were potentially at risk for liver steatosis (patients with overweight or obesity, metabolic syndrome, insulin resistance, and/or diabetes). Participants were recruited from 2021 to 2022. Inclusion criteria were age older than 15 years and one or more of the following conditions: overweight, obesity, metabolic syndrome, insulin resistance, and diabetes. Participants were excluded if they had a prior history of significant alcohol consumption, known secondary causes of liver steatosis, autoimmune or viral hepatitis, HIV infection, and/or genetic disorders. Informed written consent was obtained following a detailed explanation. The initial assessment included an interviewer- administered questionnaire in addition to standard MRI questionnaires. Studied variables included age, sex, comorbidities, ultrasound echogenicity coefficient (index test), percentage of steatosis estimated by MRI (clinical reference standard).

Evaluation of NAFLD by ATI

Abdominal ultrasound using the ATI technique was performed on all participants in Canon Aplio i800 Ultrasound Machines with Liver Package software (Canon Medical Systems, Otawara, Japan).

Evaluation of NAFLD by MRI

Magnetic Resonance Imaging analyses were performed on 3 Tesla Siemens MAGNETOM Skyra MRI with LiverLab software (Siemens Healthineers, Erlangen, Germany).

Statistical análisis

All statistical analyses were conducted using STATA 14. Descriptive analysis of the epidemiological characteristics of the study group was carried out using the ShapiroWilk normality test, considering the central limit theorem, for the variables studied. According to the distribution, averages as measures of central trend and standard deviation were used as a measure of dispersion in normal distribution variables and inter-quartil ranges and variances otherwise. Qualitative variables were expressed in absolute values and summarized in percentages. Pearson’s correlation coefficient was used to compare ATI vs MRI values in addition to multivariate regression analysis to evaluate variable interaction and confounding variables. The diagnostic performance was evaluated using ROC (receiver operating characteristic) curve analysis and area under the ROC curve (AUROC).

Participant demographics

Participant characteristics are shown in Table 1.

Table 1: Characteristics of study participants.

Of the 145 participants recruited, 2 were rejected due to secondary causes of steatosis. Eventually, 143 participants were recruited who underwent both ATI and MRI and were included in the analysis. The mean age of the cohorts was 40.4 years (var: 160, IQR: 29-51). Of the participants recruited, 117 were women with a mean age of 41.1 (var: 158.7, IQR: 30-51). 26 were men with a mean age of 36.9 (var: 162.4 IQR: 29-40).

Evaluation of NAFLD by MRI and ATI

MRI LiverLab evaluation is summarized in Table 2 and Figure 1.

Table 2: Liver steatosis detected on MRI.

The mean value of liver steatosis detected by MRI as a % of fat infiltration was 9,3%. Attenuation Imaging ultrasound evaluation is summarized in Table 3 and Figure 2

Table 3: Steatosis analysis on Attenuation Imaging US.

Multivariate análisis

A Pearson's - Check correlation analysis using a correlation matrix indicated a lack of substantial link between age or sex with either ATI values or MRI steatosis percentage estimation.

Non-linear regression análisis

When a non-linear regression analysis was performed, a formula was generated to estimate the percentage of steatosis in MRI based on the measurements obtained by ATI. This formula showed a strong correlation as seen in Figure 4 with an R-squared of 0.9841 (p < 0.001). Diagnostic performance was analyzed using Receiver Operating Characteristics (ROC) curves and area under the ROC curve (AUROC), revealing an AUROC of 0.8251 (95% CI: 0.75457 to 0.89565).

This study found that the ATI values obtained from the sonographic evaluation rose in tandem with the percentage of steatosis found by the LiverLab evaluation performed on MRI. The ATI technique demonstrated a strong correlation with MRI for the detection of hepatic steatosis. The non-linear regression used in the study allowed for the generation of a formula that estimates the percentage of steatosis in MRI based on the steatosis measured by ATI.

To date, this study is one of the largest evaluations of ATI ultrasound imaging compared to MRI or biopsy, and while relatively few studies have been published to date, the cumulative data is aligned and appears to show that ATI may serve as a more accessible and cost effective alternative to MRI in detecting and monitoring hepatic steatosis in patients with non-alcoholic liver disease, potentially improving access to early diagnosis and treatment.

Limitations

Single center study. Single population with possible selection bias and unblinded patients. Single technology type was used for US and MRI evaluations.

For the study titled "Detection of hepatic steatosis with ultrasound attenuation imaging compared to MRI," I confirm that the study was conducted in accordance with the ethical standards outlined in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Ethics approval was obtained from the Ethics Committee of the Faculty of Medicine of the Universidad del Desarrollo – Clínica Alemana de Santiago, and informed consent was obtained from all participants.

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The authors declare no competing interests.

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Detection of hepatic steatosis with ultrasound attenuation imaging compared to MRI

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