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Science to Practice |
Department of Radiology,
New York University Medical Center
110 W 3rd St, Suite 1401
New York, NY 10016
Vivian.lee@med.nyu.edu
SUMMARY
Aguirre et al found that the combined use of gadolinium-based and SPIO contrast agents yields high sensitivity (93%) for the diagnosis of hepatic fibrosis. Their findings lead the way for further developments to improve the sensitivity of noninvasive imaging methods for diagnosing cirrhosis. With continued advances in this field, liver biopsy may someday become obsolete.
THE SETTING
The estimated prevalences of hepatitis B and hepatitis C virus infections in the United States are 4.9% (1) and 1.8% (2), respectively, and rising. Approximately 5%–10% of individuals infected with viral hepatitis B and over 50% of those infected with viral hepatitis C become chronically infected (3,4). Like other causes of cirrhosis, chronic viral infection can lead to complications such as portal hypertension, end-stage liver disease, and hepatocellular carcinoma. In chronic viral hepatitis, the definitive evaluation of disease severity, which includes an assessment of fibrosis, relies on histologic findings. However, liver biopsy is an invasive and expensive procedure with a measurable risk of complications, poor patient tolerance, and possible interpretation and sampling errors. The development of noninvasive markers of liver fibrosis, by facilitating an earlier diagnosis and improved monitoring of disease progression, could obviate biopsy and may have important clinical consequences.
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THE SCIENCE
Gadolinium chelates show a delayed distribution into fibrotic tissue, thereby causing delayed enhancement of hepatic septal fibrosis at T1-weighted imaging. SPIOs, on the other hand, accumulate within the reticuloendothelial cells of the liver, causing T2* shortening and signal intensity loss; these changes are particularly well seen on gradient-echo images obtained with longer echo times. With SPIOs, fibrotic bands are spared. When both agents are administered and imaging is performed by using a gradient-echo sequence with an echo time of about 4.8 msec (at 1.5 T), the synergistic effects become readily apparent: The gadolinium-based contrast agents enhance the fibrosis, while the SPIOs darken the spared liver. While SPIOs alone showed high diagnostic accuracy (93% for total score based on reticularity and nodularity) compared with histopathologic scores of fibrosis, Aguirre et al (5) found that the combination of gadolinium-based and SPIO contrast agents yielded superior results overall, taking into consideration reticularity, nodularity, contrast-to-noise ratios, and corrected coefficient of variation scores (see table 8 in Aguirre et al article). Their results are compatible with a growing body of literature that demonstrates improved detection of hepatocellular carcinoma with use of the combination of agents based on a similar mechanism: The conspicuity of gadolinium-enhanced lesions is increased in the setting of decreased signal intensity from the uninvolved liver parenchyma following SPIO injection (6,7).
THE PRACTICE
Clinical Use:
To date, conventional imaging techniques such as ultrasonography, computed tomography (CT), and MR imaging have proved to be relatively insensitive for the diagnosis of mild fibrosis associated with early cirrhosis. CT and MR imaging typically involve the use of the morphologic consequences of fibrosis and the stigmata of portal hypertension to diagnose cirrhosis. The diagnosis of early fibrosis, therefore, relies on liver biopsy, which itself is invasive and imperfect owing to limited sampling of liver tissue. While the combined use of two contrast agents may be considered prohibitively expensive for routine use, the findings of Aguirre et al support the selective application of this method where the alternative may be a more invasive and riskier biopsy procedure (5). In addition, this noninvasive imaging method provides the added advantage of evaluation of the entire liver, enabling more accurate assessment of disease severity in cases where the fibrosis is not uniform across the entire organ.
Future Opportunities and Challenges:
In addition to the use of exogenous contrast agents, MR imaging offers alternative approaches to the early diagnosis of cirrhosis and fibrosis that remain to be explored more fully. Diffusion-weighted imaging, which is widely used in brain imaging, may have the potential to depict subtle restriction of water diffusion in patients with chronic hepatitis before gross morphologic changes become evident (8). With early fibrosis, deposition of collagen in the space of Disse and alteration of sinusoidal architecture result in a decrease in portal venous flow, which is counteracted by an increase in hepatic arterial flow, a process known as the hepatic arterial buffer response (9). Measurements of these perfusion changes with techniques such as gadolinium-enhanced MR imaging offer yet another strategy for detecting the early pathophysiologic changes of fibrosis and cirrhosis (9). How these alternative approaches compare to or complement the combined contrast agent method described in this issue of Radiology remains to be determined.
FOOTNOTES
See also the article by Aguirre et al in this issue.
References
Related Article
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