Original contribution
Respiratory motion-corrected proton magnetic resonance spectroscopy of the liver

https://doi.org/10.1016/j.mri.2008.08.008Get rights and content

Abstract

Purpose

To develop a post-processing, respiratory-motion correction algorithm for magnetic resonance spectroscopy (MRS) of the liver and to determine the incidence and impact of respiratory motion in liver MRS.

Materials and Methods

One hundred thirty-two subjects (27 healthy, 31 with nonalcoholic fatty liver disease and 74 HIV-infected with or without hepatitis C) were scanned with free breathing MRS at 1.5 T. Two spectral time series were acquired on an 8-ml single voxel using TR/TE=2500 ms/30 ms and (1) water suppression, 128 acquisitions, and (2) no water suppression, 8 acquisitions. Individual spectra were phased and frequency aligned to correct for intrahepatic motion. Next, water peaks more than 50% different from the median water peak area were identified and removed, and remaining spectra averaged to correct for presumed extrahepatic motion. Total CH2+CH3 lipids to unsuppressed water ratios were compared before and after corrections.

Results

Intrahepatic-motion correction increased the signal to noise ratio (S/N) in all cases (median=11-fold). Presumed extrahepatic motion was present in 41% (54/132) of the subjects. Its correction altered the lipids/water magnitude (magnitude change: median=2.6%, maximum=290%, and was >5% in 25% of these subjects). The incidence and effect of respiratory motion on lipids/water magnitude were similar among the three groups.

Conclusion

Respiratory-motion correction of free breathing liver MRS greatly increased the S/N and, in a significant number of subjects, changed the lipids/water ratios, relevant for monitoring subjects.

Introduction

Hepatic steatosis (the presence of excessive fat within hepatocytes) is becoming increasingly prevalent [1]. Nonalcoholic fatty liver disease (NAFLD) is currently estimated to affect 20–30% of the US population and is integrally related to obesity and insulin resistance [1], [2]. NAFLD is fundamentally defined by excessive hepatic steatosis in the absence of significant alcohol use and can progress from simple steatosis through steatohepatitis to cirrhosis and end-stage liver disease, even requiring liver transplantation. Steatosis has also been associated with viral infections. Both hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection have been associated with steatosis; HIV therapy has also been associated [3]. The prevalence of steatosis may be higher in HIV/HCV-coinfected than HCV-monoinfected patients [4]. Both steatosis and HCV can separately lead to further liver necroinflammation and fibrosis [5], [6], [7], which may confound the noninvasive assessment of steatosis.

Liver biopsy is the current gold standard to determine the severity of steatosis [8]. With the increased prevalence of steatosis and awareness of its implications in the development and progression of diverse liver diseases [1], there is increased need to noninvasively and precisely quantify hepatic steatosis. Diet, exercise and therapeutic interventions are being suggested to reduce the amount of lipids in the liver [9], [10], [11]. To properly monitor change in patients and the effectiveness of such interventions, an accurate, reliable, noninvasive measure of steatosis is required.

Magnetic resonance spectroscopy (MRS) has the potential to provide such a noninvasive assessment of steatosis. Ex vivo and animal studies have shown MRS to give an accurate measurement of liver fat [12], [13], [14], [15], [16]. In studies of fatty liver disease of diverse causes, MRS has demonstrated the ability to discriminate elevated hepatic lipids from normal [17], [18], [19], [20]. However, the lack of any respiratory motion correction is a limitation of these studies, leading to relatively low signal to noise ratio (S/N), MRS spectra and the potential for less accuracy, possibly limiting the utility of this modality.

Acquisitions with greater S/N, and potentially with water suppression, are required to monitor small changes in hepatic fat, to analyze the effect of interventions and to have the potential to measure additional peaks beyond the dominant lipid peak [due to (CH2)n]. Invariably, these acquisition requirements would lead to longer acquisition times and thus greater potential for motion artifacts. In earlier studies, the effect of respiratory motion on MRS measured lipids/water ratio has not been investigated. Respiratory motion may have differing effects in different disease populations. The high hepatic lipid content in patients with NAFLD and the common co-existence of inflammation and/or fibrosis in the HCV-infected patients may lead to greater variability in the measured MRS signals within the liver and between liver parenchyma and extrahepatic tissues (such as vessels) as compared to healthy controls.

Therefore, the aims of this study were (1) to develop a post-processing, respiratory motion-correction algorithm for liver MRS and (2) to determine the incidence and impact of respiratory motion on free-breathing, liver MRS lipids/water measures in three groups: healthy controls, NAFLD patients and HIV-infected patients with or without HCV infection.

Section snippets

Study subjects

MR imaging and spectroscopy were performed in 132 subjects: 27 healthy volunteers, 31 patients undergoing assessment of NAFLD and 74 HIV-infected patients, 44 of whom were coinfected with HCV. Demographics of the subjects are given in Table 1. Healthy volunteers had no evidence of fatty liver disease by in- and out-of-phase MR imaging and were free of HIV and HCV disease by report. The subjects with NAFLD all had histological confirmation of pathologic steatosis — greater than 5% of hepatocytes

Results

Fig. 1 shows example images of the spectral location and the resultant spectra. The acquisition of a time series of spectra allowed the evaluation of respiratory or other temporal variations. In all cases, the phase varied greatly among individual spectra, with some spectra 180° out of phase with other spectra. Correcting for such phase differences greatly increased the S/N of the resultant summed spectrum. In an example case, shown in Fig. 2, the S/N of the CH2 lipid peak (as compared to the

Discussion

Respiratory motion-associated movement of the liver can potentially cause MR data to originate from different locations within liver parenchyma, a vessel or even outside the liver. A study of abdominal motion showed the diaphragm typically moved 15–20 mm during free breathing [30]. Even with a metabolic liver disease like NAFLD in which steatosis has been shown histologically to be diffusely and equally distributed [31], respiration will affect the MR spectra, causing phase shifts [32]. In

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    This work was supported in part by grants R01 DK061738-SI, RO1 DK074718-01, K23-AI 66943 and P01 HD40543 from the NIH, as well as funding from the Society of Gastrointestinal Radiologists, the UCSF Academic Senate, the GCRC Clinical Research Feasibility Fund Award and the UCSF Hellman Early Career Faculty Award. The Women's Interagency HIV Study (WIHS) is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993 and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). WIHS is co-funded by the National Cancer Institute, the National Institute on Drug Abuse and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (MO1-RR-00071, MO1-RR-00079, MO1-RR-00083).

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