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378 radiology.rsna.org n Radiology: Volume 262: Number 2—February 2012

Diffusion-weighted MR Imaging for Liver Lesion Characterization: A Critical Look 1

Bachir Taouli , MD

Published online 10.1148/radiol.11112417

Radiology 2012; 262:378–380

1 From the Department of Radiology, Body MR imaging and Translational and Molecular Imaging Institute, Mount Sinai Medical Center, One Gustave Levy Place, Box 1234, New York, NY 10029. Received November 12, 2011. Revision requested November 15. Final revision received November 23. Accepted December 3. Final version accepted Decem-ber 6. Address correspondence to the author (e-mail: bachir.taouli@mountsinai.org ).

Potential confl icts of interest are listed at the end of this article.

See also the article by Agnello et al in this issue.

q RSNA, 2012

Powered by tremendous advances in image quality over the past few years, diffusion-weighted (DW)

magnetic resonance (MR) imaging has drawn strong interest from the radio-logic community and major MR vendors. DW imaging is increasingly used in the abdomen, particularly in the liver, with promising results for liver lesion detec-tion and characterization ( 1 ). DW imag-ing can be easily implemented in clinical protocols, as it can be performed rela-tively quickly (as short as two breath-hold acquisitions) and does not require contrast agent injection, which makes it attractive in patients with decreased renal function, who cannot receive gadolinium-based contrast agents.

DW imaging can be used for liver lesion detection by using low b values (below 100 sec/mm 2 ), providing black-blood images, with high inherent tissue contrast and robust image quality. For liver applications, DW imaging provides higher sensitivity for lesion detection compared with T2-weighted imaging and inferior to equivalent sensitivity com-pared with contrast material–enhanced T1-weighted imaging (using extracellu-lar or liver-specifi c agents) ( 2–11 ). Some investigators have, in fact, proposed re-placing standard T2-weighted imaging sequences with black-blood DW images.

In addition, DW imaging has been used for lesion characterization by us-ing higher b values ( � 500 sec/mm 2 ). These images provide qualitative as-sessment of lesion signal intensity and lesion signal intensity changes compared with liver parenchyma, as well as quan-titative assessment of apparent diffu-sion coeffi cient (ADC), by using ADC maps (obtained automatically on most MR systems nowadays). Malignant le-sions (which are usually more cellular) typically demonstrate impeded diffusion, which is manifested as high residual signal intensity on images obtained with high b values compared with background

liver parenchyma, as opposed to benign nonsolid lesions, such as liver cysts and hemangiomas, with ADC of malignant lesions visually equal or lower than that of surrounding liver parenchyma. Quantitative ADC threshold values have been described extensively for lesion characterization, with variable accuracy, depending on the patient population and lesion type included. The proposed ADC cutoffs depend also on the b values used for acquisition, which is a major limitation for the widespread use of DW imaging. As a general rule, signif-icantly higher ADC values have been demonstrated for benign lesions com-pared with malignant lesions, with var-iable overlap ( 5,12–19 ). Investigators in a recent meta-analysis ( 20 ) reported an area under the curve of the sum-mary receiver operator characteristic of 0.96, with sensitivity ranging from 0.74–1.0 (mean, 0.91) and specifi city of 0.77–1.00 (mean, 0.93). However, the accuracy decreases when benign hepa-tocellular lesions such as focal nodular hyperplasia (FNH) and hepatocellular adenomas (HCAs) are included ( 5 ). Similarly, the accuracy also decreases when treated necrotic malignant lesions are included.

In this issue of Radiology , Agnello and colleagues ( 21 ) investigate the role of qualitative and quantitative DW imaging for the diagnosis of FNH and HCA. FNH and HCA are two benign liver lesions composed of hepatocytes. FNH is more frequently encountered than HCA, it has no malignant poten-tial, leads to very few complications, and surgical resection is generally not necessary. On the other hand, in HCA, there is a risk of hemorrhage and a small but described risk for malignant transformation (depending on the sub-type) ( 22 ). HCA can be either resected, or treated conservatively after stopping the potential risk factor (eg, oral con-traceptives). Because of the differences

Radiology: Volume 262: Number 2—February 2012 n radiology.rsna.org 379

EDITORIAL: Diffusion-weighted MR for Liver Lesion Characterization Taouli

and lack of liver fi brosis or cirrhosis, al-though rare cases have been described in chronic liver disease).

ADC measurement is infl uenced by water diffusion and tissue perfusion and fl ow ( 33 ). It will be interesting to de-termine the infl uence of both compo-nents by sampling multiple b values and process the data by using a biexponen-tial model (intravoxel incoherent mo-tion, or IVIM) ( 34 ). The decrease in true diffusion may be infl uenced by dif-ferences in tumor cellularity, architec-ture, and grade. Differences in perfu-sion may be attributed to different fl ow and perfusion characteristics, which may be correlated to enhancement by using routine T1-weighted imaging or to perfusion-weighted imaging. These perfusion and diffusion components could eventually prove to be useful not only for lesion characterization but also for predicting and assessing treatment response in malignant lesions. An-other interesting direction would be to examine the role of computed high b values for the diagnosis of benign ver-sus malignant liver lesions ( 35 ).

Disclosures of Potential Confl icts of Interest: Financial activities related to the present ar-ticle: none to disclose. Financial activities not related to the present article: received payment for board membership from Siemens Healthcare and GE Healthcare, institution received grants from Bayer Healthcare and GE Healthcare, re-ceived payment for lectures including service on speakers bureaus from Bayer Healthcare and GE Healthcare. Other relationships: none to disclose.

References 1 . Taouli B , Koh DM . Diffusion-weighted MR

imaging of the liver . Radiology 2010 ; 254 ( 1 ): 47 – 66 .

2 . Nasu K , Kuroki Y , Nawano S , et al . Hepatic metastases: diffusion-weighted sensitivity-encoding versus SPIO-enhanced MR imag-ing . Radiology 2006 ; 239 ( 1 ): 122 – 130 .

3 . Coenegrachts K , Delanote J , Ter Beek L , et al . Improved focal liver lesion detection: comparison of single-shot diffusion-weighted echoplanar and single-shot T2 weighted turbo spin echo techniques . Br J Radiol 2007 ; 80 ( 955 ): 524 – 531 .

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standard deviation , 1.75 3 10 2 3 mm 2 /sec 6 0.46 vs 1.83 3 10 2 3 mm 2 /sec 6 0.36, with use of b values of 0 and 500 sec/mm 2 ). Parikh et al ( 5 ) found no difference between ADC of benign hepatocellular lesions (fi ve HCAs and four FNHs; mean 6 standard devi-ation for ADC of 1.49 3 10 2 3 mm 2 /sec 6 0.49) (using 0, 50, 500 s/mm 2 ) compared with metastases (1.50 6 0.42 3 10 2 3 mm 2 /s) and HCC (1.31 6 0.33 3 10 2 3 mm 2 /s). This was later confi rmed by Sandrasegaran et al ( 19 ) who also found no difference between ADC values of solid benign liver lesions and malignant lesions. Sandrasegaran et al concluded that DW imaging had minimal additional value over standard MR imaging sequences for liver lesion characterization.

The results in the large series of Agnello et al corroborate fi ndings from these previous series ( 5,15,19 ), which included a smaller number of benign hepatocellular lesions, and validate the need for the use of standard MR se-quences to correctly characterize liver lesions, especially FNH and HCA. The MR protocol should include in- and opposed-phase imaging (for detection of intravoxel fat in certain HCA subtypes) and contrast-enhanced T1-weighted im-aging, including an arterial phase and a delayed hepatobiliary phase (when us-ing liver-specifi c agents).

In my opinion, even if DW imaging has shown limited usefulness for the characterization of solid liver lesions, and for diagnosis of FNH and HCA, it still has a role in detecting liver lesions, as shown previously in many publica-tions ( 3,5–7,29–32 ). At a minimum, DW imaging should be used clinically as an alternate to T2-weighted imaging sequence; as in our experience DW im-aging surpasses standard T2-weighted imaging for benign and malignant liver lesion detection ( 5 ). Further charac-terization of detected lesions would re-quire contrast-enhanced imaging. It is also important to remember that the diagnosis of FNH and HCA requires an appropriate clinical context even with the use of conventional imaging se-quences (sex, age, predisposing factors such as oral contraceptives in HCAs,

in treatment and prognosis, it is impor-tant to distinguish FNH and HCA from each other and from malignant liver le-sions, such as hepatocellular carcinoma (HCC) and hypervascular metastases. Recently, pathologic nomenclature has revealed heterogeneity of HCA by using advanced gene expression methods ( 23 ), with corresponding imaging phenotypic expression ( 24,25 ).

The diagnosis of FNH and HCA gen-erally requires the use of gadolinium-based contrast agents, including extracel-lular agents or preferably liver-specifi c agents, such as gadobenate dimeglu-mine ( 26,27 ) or gadoxetic acid ( 28 ). The latter agents have proved to be highly accurate for the diagnosis of FNH and HCA. Data for the characterization of HCA subtypes by using liver-specifi c agents is still lacking.

To our knowledge, Agnello et al ( 21 ) report the largest series to date de-scribing diffusion characteristics of FNH and HCA. They assessed 90 benign he-patocellular lesions (54 FNHs and 36 HCAs) diagnosed in 67 patients with free-breathing single-shot echo-planar DW imaging with three b values (0, 150, 600 sec/mm 2 ). They observed that 87% of these lesions were hyperintense at b of 600 sec/mm 2 , with ADC values sig-nifi cantly lower than liver ADC, mak-ing these benign lesions indistinguish-able from malignant lesions. They also observed that FNH had a higher ADC than did HCA, and fi nally they found no correlation between ADC and HCA subtypes. Interestingly, when applying criteria described by Parikh et al ( 5 ), 49% of lesions would have been consid-ered malignant, and the rest (51%) would have been considered indeterminate. None of these lesions would have been characterized as benign by using DW imaging. Agnello and colleagues con-cluded that benign hepatocellular lesions often demonstrate impeded diffusion.

These results come as no surprise to radiologists performing DW imaging routinely, as a number of more prelimi-nary studies have shown similar results. Previously, Taouli et al ( 15 ) found no sig-nifi cant difference between ADC of solid benign hepatocellular lesions ( n = 15) compared with normal liver (mean 6

380 radiology.rsna.org n Radiology: Volume 262: Number 2—February 2012

EDITORIAL: Diffusion-weighted MR for Liver Lesion Characterization Taouli

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