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Dynamic Subtraction MR Imaging of the Liver: Advantages and Pitfalls

¹ All authors: Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215.
² Present address: Department of Diagnostic Radiology, Yonsei University College of Medicine, YongDong Severance Hospital, 146-92 Dogok-Dong, Gangnam-Gu, Seoul 135-270, South Korea.

Received September 10, 2002; accepted after revision October 31, 2002.

 
Address correspondence to N. M. Rofsky.

Introduction

Top Introduction MR Imaging Technique Advantages of Subtraction... Pitfalls of Subtraction Imaging Conclusion References

 
Gadolinium-enhanced dynamic MR imaging is a key strategy in imaging of the liver. An optimized arterial phase imaging protocol [1] implemented with three-dimensional imaging techniques yields arterial phase MR examinations that minimize partial volume artifacts and allow high-quality multiplanar reformations [2, 3]. These innovations are aimed toward achieving improved lesion detection and characterization as well as the ability to generate high-quality angiograms from a single acquisition. Subtraction of unenhanced images from gadolinium-enhanced images has been pursued in an attempt to maximize the qualitative recognition of lesion enhancement and vascular anatomy [4, 5].

MR Imaging Technique

Top Introduction MR Imaging Technique Advantages of Subtraction... Pitfalls of Subtraction Imaging Conclusion References

 
MR imaging was performed using a 1.5-T unit (Symphony or Vision; Siemens, Erlangen, Germany) with a torso phased array coil. In all patients, a three-dimensional spoiled gradient-echo sequence with fat suppression was used as previously described [2]. After an unenhanced data set was obtained during end-expiration, a timing examination was performed according to the previously described method [1] using a 1-mL test dose of gadopentetate dimeglumine (Magnevist; Berlex, Wayne, NJ). Before patients underwent scanning, they were educated about the performance of end-expiration breath-holds.

For arterial phase imaging, all patients received a 19-mL bolus of contrast material through an arm vein with an MR-compatible power injector (Spectris; Medrad, Pittsburgh, PA). After the arterial phase, imaging was repeated twice at 45-sec intervals for portal vein and equilibrium phase acquisitions. Unenhanced images were subtracted from enhanced images during arterial, portal, and equilibrium phases on the MR console, using the system's commercially available software. The arterial phase subtraction data set was also used to produce maximum intensity projections with a restricted volume of interest for MR angiography. For detailed evaluation of venous anatomy in some patients, arterial phase images were subtracted from the portal venous phase images.

Advantages of Subtraction Imaging

Top Introduction MR Imaging Technique Advantages of Subtraction... Pitfalls of Subtraction Imaging Conclusion References

 
Characterization of T1 Hyperintense Lesions
Regenerative nodules, dysplastic nodules, and hepatocellular carcinomas can all exhibit high signal intensity on unenhanced T1-weighted MR images in the cirrhotic liver. For these lesions, arterial enhancement is often difficult to detect using a subjective comparison of the unenhanced and enhanced images. The presence of arterial enhancement strongly suggests the diagnosis of hepatocellular carcinoma because contrast enhancement of other cirrhotic nodules is rare [6]. Arterial enhancement within a nodule can be visualized on the subtraction image as high signal intensity exceeding that of background parenchyma (Figs. 1A, 1B and 1C). However, for most benign and borderline cirrhotic nodules, the degree of nodular arterial enhancement is not well delineated from background parenchyma on subtraction images. Subtraction images are also helpful in assessing for enhancement and hence for the viability of treated tumors, especially in lesions that may also appear bright on T1-weighted images, such as lesions with coagulation necrosis or internal hemorrhage (Figs. 2A, 2B).

View larger version (153K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —64-year-old man with alcoholic cirrhosis complicated by multifocal hepatocellular carcinomas. Transverse unenhanced volumetric interpolated breath-hold MR image (TR/TE, 4.2/1.9; flip angle, 12°) shows hyperintense nodule (arrow) in right lobe of liver.

View larger version (145K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —64-year-old man with alcoholic cirrhosis complicated by multifocal hepatocellular carcinomas. Transverse arterial phase dynamic MR image shows hyperintense nodule (arrow) and two small enhancing lesions (arrowheads).

View larger version (147K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C. —64-year-old man with alcoholic cirrhosis complicated by multifocal hepatocellular carcinomas. Subtracted arterial phase MR image (B – A) shows distinct enhancement of hyperintense nodule (arrow) and two other smaller lesions (arrowheads).

View larger version (142K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —54-year-old man with hepatocellular carcinomas treated with percutaneous radiofrequency ablation 6 months earlier. Transverse unenhanced volumetric interpolated breath-hold MR image (TR/TE, 4.5/1.9; flip angle, 12°) shows 4.5-cm focus with very high signal intensity component in center of lesion surrounded by moderately hyperintense component (arrow) in posterior segment of right lobe of liver. Another small hyperintense lesion (arrowhead) is also visible.

View larger version (142K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —54-year-old man with hepatocellular carcinomas treated with percutaneous radiofrequency ablation 6 months earlier. Subtracted arterial phase MR image shows no evidence of contrast enhancement of treated lesion (arrow) and smaller necrotic focus (arrowhead) along transhepatic tract of electronic probe. Heterogeneously strong enhancement of surrounding liver resulted from extensive tumor invasion of right portal vein.

Detection of Hypervascular Lesions Unidentified on Contrast-Enhanced Images
Some small enhancing lesions are not identified on contrast-enhanced images because their signal intensity is similar to that of background liver. After subtraction, visual conspicuity of the enhanced lesions can be increased to facilitate the detection of focal lesions with contrast enhancement (Figs. 3A, 3B).

View larger version (141K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A. —57-year-old woman with liver metastases from breast cancer. Transverse arterial phase volumetric interpolated breath-hold MR image (TR/TE, 4.2/1.9; flip angle, 12°) shows contrast enhancement of 4-cm lesion (arrow) between area of right and left lobe of liver. On unenhanced images at same slice level (not shown), there were two more hypointense small lesions adjacent to main lesion.

View larger version (123K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B. —57-year-old woman with liver metastases from breast cancer. Subtracted arterial phase MR image shows distinct enhancement of two smaller lesions (arrowheads) as well as main lesion (arrow). Note perihepatic high-signal-intensity rim anterior to liver.

Visualization of Enhancing Pseudocapsules
The conspicuity of the marginal or peritumoral enhancing rim is increased on subtraction images generated from portal or equilibrium phase images. This finding helps characterize focal lesions with fibrotic pseudocapsules (Figs. 4A, 4B). For tumor evaluation in patients who have undergone localized ablation therapy, the integrity of the enhancing rim can be used as a marker of surrounding inflammatory reaction in the acute or subacute stage after treatment [7] (Figs. 5A, 5B). In contradistinction, residual tumor shows irregularity or partial disruption of the rim.

View larger version (145K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A. —64-year-old man with alcoholic cirrhosis complicated by multifocal hepatocellular carcinoma. Transverse portal venous phase volumetric interpolated breath-hold MR image (TR/TE, 4.2/1.9; flip angle, 12°) shows one isointense lesion (arrow) and one hypointense lesion (arrowhead), each surrounded by thin hyperintense rim.

View larger version (138K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B. —64-year-old man with alcoholic cirrhosis complicated by multifocal hepatocellular carcinoma. Subtracted portal venous phase MR image enables more conspicuous visualization of enhancing pseudocapsules (arrowheads) of two hepatocellular carcinomas.

View larger version (155K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5A. —63-year-old man with hepatocellular carcinoma treated with percutaneous radiofrequency ablation 1 month earlier. Transverse equilibrium phase volumetric interpolated breath-hold MR image (TR/TE, 4.5/1.9; flip angle, 12°) shows indistinct peritumoral rim enhancement (arrow), suggesting hyperemia without definite enhancement of tumor.

View larger version (141K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5B. —63-year-old man with hepatocellular carcinoma treated with percutaneous radiofrequency ablation 1 month earlier. Subtracted equilibrium phase MR image shows unequivocal rim enhancement (arrowheads) around treated tumor with complete integrity.

Delayed Enhancement of Tumor
Gradual and delayed enhancement in tumors resulting from diffusion of contrast medium into the tumoral interstitium or intercellular sinusoids can be easily detected on subtraction images from the equilibrium phase (Figs. 6A, 6B).

View larger version (129K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6A. —46-year-old woman with liver metastases from breast cancer. Transverse equilibrium phase volumetric interpolated breath-hold MR image (TR/TE, 4.5/1.9; flip angle, 12°) shows targetoid, inhomogeneous contrast enhancement of 3.5-cm lesion (arrow), but signal intensity is similar to that of background liver.

View larger version (125K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6B. —46-year-old woman with liver metastases from breast cancer. Subtracted equilibrium phase MR image shows distinct enhancement of lesion (arrow). Inner portion of tumor is more densely enhanced than outer portion except for central necrotic focus. This pattern is compatible with enhancement pattern of hypervascular metastatic lesion on delayed phase contrast-enhanced imaging (not shown).

Differentiation Between Malignant and Bland Thrombi in the Portal Vein
Contrast enhancement of portal vein thrombi helps distinguish malignant portal vein thrombosis from bland (nonenhancing) thrombosis in the cirrhotic liver [8]. Increased conspicuity of contrast enhancement is seen on subtraction images, which also assists in determining the extent of tumor thrombi as distinguished from bland thrombus (Figs. 7A, 7B, 7C and 7D).

View larger version (146K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7A. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Transverse portal venous phase volumetric interpolated breath-hold MR image (TR/TE, 4.2/1.9; flip angle, 12°) shows marked expansion of left portal vein by malignant tumor thrombus (arrow) with lower signal intensity distinguished from background liver.

View larger version (147K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7B. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Transverse portal venous phase MR image obtained at level 4 cm below A shows low-signal-intensity bland thrombus (arrow) in main portal vein. Inhomogeneous enhancement of hepatocellular carcinoma mass (arrowhead) is also seen in left lobe.

View larger version (165K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7C. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Subtracted portal venous phase obtained at same level as A reveals contrast enhancement in tumor thrombus (arrow) with similar degree of contrast enhancement in background liver.

View larger version (161K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7D. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Subtracted portal venous phase MR image obtained at same level as B shows dark signal of bland thrombus (arrow), representing absence of contrast enhancement, that can be easily distinguished from enhancing tumor thrombus in C.

Detailed Assessment of Vascular Anatomy
Suppression of background signals by subtraction of unenhanced images from the arterial phase images increases the vessel-to-background contrast, thus permitting better visualization of small arterial branches (Figs. 7E and 7F). Subtraction of the arterial phase data set from the venous phase data set (the latter containing both arteries and veins) can generate high-quality maximum-intensity-projection MR venograms (Figs. 7G, 7H, 7I).

View larger version (128K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7E. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Coronal nonsubtracted maximum-intensity-projection MR image obtained during arterial phase with restricted volume of interest shows celiac axis, superior mesenteric artery, and renal arteries.

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7F. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Arterial phase subtracted MR angiogram shows that suppression of background signal results in better visualization of peripheral branches of right hepatic artery (arrows) and splenic artery (arrowhead) than E.

View larger version (128K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7G. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Nonsubtracted maximum-intensity-projection MR image obtained during portal venous phase shows arterial and venous structures (arrowhead) with substantial background signal that obscures some venous anatomy. Asterisks = kidneys.

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7H. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. Subtraction image yielded from subtraction of unenhanced data set from portal venous phase data set allows improved visualization of veins (arrows) and also shows arterial structures (arrowheads) and kidneys (asterisks).

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7I. —31-year-old man with B-viral cirrhosis complicated by hepatocellular carcinoma and portal vein thromboses. This image resulted from subtraction of arterial phase data set from portal venous phase data set. It shows splenic and splanchnic venous confluence into main portal vein (black arrow) up to level of obstruction by bland thrombus better than G and H. Suppression of overlapping signals from arterial components and contrast enhancement of kidneys yield improved details of venous structures, including hepatic veins (white arrow).

Pitfalls of Subtraction Imaging

Top Introduction MR Imaging Technique Advantages of Subtraction... Pitfalls of Subtraction Imaging Conclusion References

 
Erroneous Coregistration Between Unenhanced and Enhanced Source Images
A certain degree of slice misregistration is physiologically inevitable, although this factor is not problematic for most examinations that are performed using end-expiration breath-holds. A hyperintense, nonenhancing lesion on unenhanced images could erroneously be designated as an enhancing lesion with poor image coregistration and could yield a false impression of a hypervascular tumor (Figs. 8 and 9A, 9B, 9C, 9D). As an alternative, hypointense lesions on unenhanced images subtracted by hepatic parenchyma on contrast-enhanced images can yield hyperintense pseudolesions on subtraction images (Figs. 8 and 10A, 10B). Adjacent slices with marked hypointense and hyperintense lesions of identical size and position on subtracted images are indicators of axial misregistration (Figs. 9A, 9B, 9C, 9D and 10A, 10B).

View larger version (70K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8. —Schema of misregistration and erroneous determination of enhancement between unenhanced and contrast-enhanced source images. On upper row images, level of contrast-enhanced image is lower than level of unenhanced image. In this case, high-signal lesion on unenhanced image (1) is subtracted from isointensely enhanced liver parenchyma on contrast-enhanced image, which can result in signal void artifact (2) on subtracted image. Also at more inferior level, normal unenhanced liver parenchyma is subtracted from hyperintense (but not enhanced) lesion that is present on contrast-enhanced image set. This results in appearance of hyperintense nodule (3) on subtracted image giving false impression of hypervascular tumor. To contrary, hypointense lesion (4) on unenhanced image when subtracted from normally enhanced parenchyma can create hyperintense signal (5) at more superior level and hypointense signal on more inferior level after subtraction. On lower row images, level of contrast-enhanced image is higher than unenhanced image, and same effect yields reciprocal result compared with upper row images.

View larger version (116K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9A. —56-year-old man with benign or borderline cirrhotic nodules unchanged during 11 months of MR imaging follow-up with slice misregistration between unenhanced and contrast-enhanced source images. Transverse unenhanced volumetric interpolated breath-hold MR image (TR/TE, 4.5/1.9; flip angle, 12°) shows small hyperintense nodule (arrow).

View larger version (94K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9B. —56-year-old man with benign or borderline cirrhotic nodules unchanged during 11 months of MR imaging follow-up with slice misregistration between unenhanced and contrast-enhanced source images. Subtracted arterial phase MR image obtained at same level as A shows low signal (arrow) corresponding to hyperintense nodule on A. Hypointense area resulted from erroneous subtraction of T1 hyperintense nodule from normal enhanced liver parenchyma on contrast-enhanced image obtained 1 cm below A (not shown).

View larger version (108K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9C. —56-year-old man with benign or borderline cirrhotic nodules unchanged during 11 months of MR imaging follow-up with slice misregistration between unenhanced and contrast-enhanced source images. Subtracted arterial phase MR image obtained 1 cm above A shows hyperintense nodule mimicking hypervascular tumor (arrow). High-signal lesion resulted from erroneous subtraction of unenhanced liver parenchyma by hyperintense (but nonenhancing) nodule on arterial phase image (not shown).

View larger version (112K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9D. —56-year-old man with benign or borderline cirrhotic nodules unchanged during 11 months of MR imaging follow-up with slice misregistration between unenhanced and contrast-enhanced source images. Six-month follow-up subtracted arterial phase MR image shows eccentric hyperintense (arrow) and hypointense (arrowheads) area corresponding to hyperintense nodule on A and arterial phase image (not shown) due to slight misregistration between source images in transverse plane.

View larger version (130K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 10A. —55-year-old man with hepatitis C viral cirrhosis. Transverse arterial phase volumetric interpolated breath-hold MR image (TR/TE, 4.5/1.9; flip angle, 12°) shows small cyst (arrow) in left lobe of liver.

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 10B. —55-year-old man with hepatitis C viral cirrhosis. Subtracted arterial phase MR image obtained 0.5 cm above A shows hyperintense nodule (arrow) mimicking hypervascular tumor. Subtracted arterial phase image (not shown) obtained at same level as A showed small signal void corresponding to small cyst on A.

When the degree of slice misregistration is smaller than the lesion, eccentric or ringshaped pseudolesions can appear, depending on the direction of the erroneous coregistration (Figs. 9D and 11). For lesions located in the marginal subcapsular area of the liver, the lesions tend to be erroneously subtracted by extrahepatic structures. In cases of small lesions, recognition of the lesion and the corresponding high-or low-signal-intensity pseudolesions on subtraction images is more difficult in lesions in the subcapsular portion than in centrally located lesions.

View larger version (135K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 11. —Artifact resulting from erroneous misregistration on nonenhanced subtracted arterial phase volumetric interpolated breath-hold MR image (TR/TE, 4.5/1.9; flip angle, 12°) of 32-year-old woman with polycystic liver and kidney disease. All eccentrically white signals (arrowheads) on posterior portion of each hypointense lesion in right lobe of liver result from slight axial and transverse misregistration between nonenhanced and contrast-enhanced source images.

Coarsening of Background Signals in Cirrhotic Liver
In the cirrhotic liver, the gross and microscopic structural distortions of liver parenchyma and vascular systems yield inhomogeneous perfusion of the liver after contrast administration. This finding is particularly seen on the arterial phase of contrast administration. Heterogeneous parenchymal enhancement when coupled with imperfect slice coregistration can limit the confident detection of small, subcentimeter nodules on the subtraction images, even if very thin sections inherent to three-dimensional acquisitions have been used.

Conclusion

Top Introduction MR Imaging Technique Advantages of Subtraction... Pitfalls of Subtraction Imaging Conclusion References

 
Properly coregistered dynamic subtraction MR imaging can facilitate the assessment of focal liver lesions and a detailed evaluation of vascular structures. However, an inevitable limitation for evaluation of small focal hepatic lesions originates from the erroneous coregistration between the unenhanced and contrast-enhanced images. Careful review of both the source and subtraction images is crucial to avoid a false determination of focal lesion enhancement. The development of userfriendly, reliable error–correction processing strategies for subtraction imaging is needed to fully exploit the advantages of subtraction techniques and to minimize the pitfalls.

References

Top Introduction MR Imaging Technique Advantages of Subtraction... Pitfalls of Subtraction Imaging Conclusion References

 

1. Earls JP, Rofsky NM, DeCorato DR, Krinsky GA, Weinreb JC. Breath-hold single-dose gadolinium-enhanced three-dimensional MR aortography: usefulness of a timing examination and MR power injector. Radiology 1996;201:705 –710[Abstract/Free Full Text]
2. Rofsky NM, Lee VS, Laub G, et al. Abdominal MR imaging with a volumetric interpolated breath-hold examination. Radiology 1999;212:876 –884[Abstract/Free Full Text]
3. Lee VS, Lavelle MT, Rofsky NM, et al. Hepatic MR imaging with a dynamic contrast-enhanced isotropic volumetric interpolated breath-hold examination: feasibility, reproducibility, and technical quality. Radiology 2000;215:365 –372[Abstract/Free Full Text]
4. Soyer P, Spelle L, Gouhiri MH, et al. Gadolinium chelate–enhanced subtraction spoiled gradient-recalled echo MR imaging of hepatic tumors. AJR 1999;172:79 –82[Free Full Text]
5. Krinsky GA, Lee VS. MR imaging of cirrhotic nodules. Abdom Imaging 2000;25:471 –482[Medline]
6. Hayashi M, Matsui O, Ueda K, et al. Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium. AJR 1999;172:969 –976[Abstract/Free Full Text]
7. Lim HK, Choi D, Lee WJ, et al. Hepatocellular carcinoma treated with percutaneous radiofrequency ablation: evaluation with follow-up multiphase helical CT. Radiology 2001;221:447 –454[Abstract/Free Full Text]
8. Tublin ME, Dodd GD III, Baron RL. Benign and malignant portal vein thrombosis: differentiation by CT characteristics. AJR 1997;168:719 –723[Abstract/Free Full Text]

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This Article Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, J.-S. Articles by Rofsky, N. M. Search for Related Content PubMed PubMed Citation Articles by Yu, J.-S. Articles by Rofsky, N. M. Social Bookmarking                      What's this?