role of contrast enhanced ultrasonography in characterization of hepatobiliary disease dr. muhammad...

Role of Contrast Enhanced Ultrasonography in Characterization

of Hepatic Diseases

DR MUHAMMAD BIN ZULFIQARPGR III FCPS Services institute of Medical

Sciences/ Services Hospital Lahore

AIMS

• To assess whether characterization of solid focal liver lesions could be improved by CEUS as compared with lesion with preliminary Gray Scale and Color Doppler US.

Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935

Contrast Agents

• US contrast agents consist of microbubbles of air or perfluorocarbon gas stabilized by a protein, lipid, or polymer shell (1).

• The bubbles are sufficiently small and stable to traverse the pulmonary and cardiac circulations following peripheral venous injection.

• The bubbles are approximately the same size as red blood cells and cannot move through the vascular endothelium into the interstitium, even after an extended period of time (2)

(1)Solbiati L, Martegani A, Leen E, Correas JM, Burns PN, Becker D. Contrast-enhanced ultrasound of liver diseases. Milan, Italy: Springer, 2003(2).Becher H, Burns PN. Handbook of contrast echocardiography. Berlin, Germany: Springer, 2000. Available at: http://www.sunnybrook.utoronto.ca/EchoHandbook/.

Dose of Contrast Agent

• A typical contrast material dose for an adult patient consists of 0.2–2 mL of a suspension of bubbles in saline solution. This dose is manually injected into an arm vein, followed by a flush of 5 mL of saline solution.


Bubble Specific Imaging• Bubbles respond to the sound emitted by the imaging

transducer by changing their size in sympathy with the US pressure wave, which results in their radial oscillation at the US frequency.

• Bubbles have a natural or resonant frequency, at which their response is greatly enhanced.

• Bubbles of the size range (diameter of 3–5 um) resonate at diagnostic US frequencies and are required for transpulmonary passage following intravenous injection

• It is this phenomenon that makes contrast-specific imaging possible.

Powers JE, Burns PN, Souquet J. Imaging instrumentation for ultrasound contrast agents. In: Nanda NC, Schlief R, Goldberg BB, eds. Advances in echo imaging using contrast enhancement. 2nd ed. Dubai, United Arab Emirates: Kluwer Academic Publishers, 1997; 139–170.

• Graph illustrates microbubble behavior in an acoustic field. Bubbles respond asymmetrically to high-intensity sound waves, stiffening when compressed and yielding when expanded, a nonlinear response that produces harmonics in the scattered wave.

Burns PN, Wilson SR, Hope Simpson D. Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast. Invest Radiol 2000; 35:58–71.

Principles of CEUS Imaging

• Harmonic Imaging (rarely used)– Frequencies that are multiples of the driving

frequency• Pulse Inversion / Phase Inversion Imaging /

Coherent Contrast Imaging (commonly used)– the echo from tissue is suppressed and that from

the microbubble contrast material is enhanced


MI (Mechanical Index)

• (the MI is the ratio of the peak rarefactional pressure to the square root of the frequency and is related to the tendency of the sound to induce bubble motion.


Low Mechanical Index <0.2

• At a low MI (less than about 0.2, depending on the agent used), bubbles are stimulated into harmonic motion and can be imaged in real time,

• shows vessel morphology and the evolution of the vascular volume over time.


High Mechanical Index >0.3

• Higher MI (greater than about 0.3, again depending on the agent), the oscillation of the bubbles becomes so pronounced that the bubbles can be disrupted by the sound beam used to image them.

• So they emit a strong, highly nonlinear echo that is relatively easy to detect.

• Highly sensitive “vascular volume” image.• this “disruption” method of imaging does not allow

real-time frame rates, yet it is the most sensitive means of evaluating the vascular volume in tissue.


Combination of MI Values

• Both High(>0.3) and Low(<0.2) MI values are used in combination in to image capillary flow in myocardium (1), liver (2) and other organs (3) .

(1) Becher H, Burns PN. Handbook of contrast echocardiography. Berlin, Germany: Springer, 2000. Available at: http://www.sunnybrook.utoronto.ca/ EchoHandbook/.(2) Wilson SR, Burns PN. Liver mass evaluation with ultrasound: the impact of microbubble contrast agents and pulse inversion imaging. Semin Liver Dis 2001; 21:147–159.(3) Missouris CG, Allen CM, Balen FG, Buckenham T, Lees WR, MacGregor GA. Non-invasive screening for renal artery stenosis with ultrasound contrast enhancement. J Hypertens 1996; 14:519–524.

• Baseline conventional US image obtained with a high mechanical index (MI) of 1.2 [1]) shows a large, highly echogenic focal mass with a hypoechoic rim. The echogenicity of the lesion is related to its tissue properties. (b) Pulse inversion US image (MI 0.1) shows suppression of the tissue echoes. The entire image now appears black

Continued

• On an arterial phase US image obtained moments after a small (0.1-mL) bolus injection of a suspension of microbubbles into a peripheral vein, the lesion enhances far more than the adjacent liver, a finding that is consistent with a hypervascular mass. The microbubbles within the vasculature now account for the echogenicity of the lesion. (d) Portal venous phase US image shows enhancement of the liver parenchyma. The lesion is less echogenic than the liver (ie, has “washed out”), a finding that is consistent with a hypervascular malignancy. Hepatocellular carcinoma (HCC) was confirmed at biopsy.

CEUS in Hepatocellular Carcinoma

• Although many malignant liver tumors are readily seen at US, surveillance US can be difficult in patients with chronically diseased livers who are at risk for HCC.

• In addition, nonenhanced US has low specificity because a variety of nonmalignant lesions such as hemangioma, FNH, and regenerative nodules may appear similar to HCC.

• In many cases, CT or MR imaging is required for further characterization.


CEUS in Hepatocellular Carcinoma

• The addition of microbubble contrast agents has greatly improved the ability to diagnose HCC with US. Hypervascularity with frequent vessel dysmorphology and washout during the portal venous phase are characteristic


Pitfalls

• Problems with adequately scanning the entire cirrhotic liver because of its small size.

• Difficulty in differentiating regenerative nodularity from malignant tumors,

• Problems related to the alteration of liver blood flow in cirrhosis, including increased relative hepatic arterial supply.

• All these are also encountered in MRI and CT Hepatobiliary Imaging.


• (Right) Arterial phase US image shows a lesion whose echogenicity exceeds that of the liver, a finding that is consistent with a hypervascular mass. There is a central nonenhancing area that suggests scar or necrosis. (Left) On a portal venous phase US image, the lesion is washed out, appearing less echogenic than the adjacent liver.

Continued

• Arterial phase (right) and portal venous phase (Left) CT scans show the hypervascular mass with necrosis and with washout on the portal venous phase image.

• This was proved to be HCC

• Small HCC. (Right) Arterial phase US image shows a hypervascular lesion with avid enhancement. (Left) On a portal venous phase US image, the lesion is hypoechoic relative to the enhanced background liver. This washout is strongly suggestive of the malignant nature of the mass.

CEUS in Metastasis• Contrast-enhanced US shows lesion blood flow in

metastases as a reflection of the vascularity of the primary tumor.

• Considerable variation is seen during the arterial phase of enhancement.– Hypovascular– Hypervascular

• Regardless of their appearance during the arterial phase, however, metastases have consistently shown less enhancement than the liver during the portal venous phase of contrast-enhanced US.


Hpovascular Metastasis

• Hypovascularity and rim enhancement (Fig 9), both typical of metastatic lesions, including those from the breast, lung, and colon.

• Tumor enhancement may be inhomogeneous because of necrosis.


• Figure 9. Metastasis from primary carcinoma of the anal canal with rim enhancement. Baseline US (right) image shows an expansive mass in the left lobe of the liver. (mid) Arterial phase US image demonstrates the mass with rim enhancement. (Left) On a portal venous phase US image, the lesion is completely washed out and appears black.

• Figure 9. Metastasis from primary carcinoma of the anal canal with rim enhancement. (a, b) Baseline US (a) and CT (b) images show an expansive mass in the left lobe of the liver. (c, d) Arterial phase US (c) and CT (d) images demonstrate the mass with rim enhancement. (e) On a portal venous phase US image, the lesion is completely washed out and appears black. (f) Portal venous phase CT scan shows continued rim enhancement of the tumor, a finding that probably represents interstitial contrast material.

Hypervascualr Metastasis

• Hypervascular primary tumors, including those from the kidney and thyroid gland and those of neuroendocrine origin, show hypervascular metastases with enhancement features that overlap with those of HCC (Fig 10


• Hypervascular metastases from carcinoid tumor. (Right) Baseline US image shows the liver with high fat content and hypoechoic lesions. (Mid) On an arterial phase US image, the lesions enhance avidly, appearing more echogenic than the adjacent liver. (Left) On a portal venous phase US image, the liver remains brightly enhanced, and the lesions have washed out and appear hypoechoic. The patient was allergic to iodinated contrast material. Wilson SR, Burns PN. Liver mass evaluation with ultrasound: the impact of microbubble contrast agents and

pulse inversion imaging. Semin Liver Dis 2001; 21:147–159.

Hemangioma• Hemangioma is the most frequently encountered benign liver

tumor and is reported to occur in 5%–20% of the population. • Contrast enhanced US use to confirm the nature of a

hemangioma that is incidentally detected at nonenhanced US. • Lesions show peripheral puddles and pools of enhancement that

expand in a centripetal pattern during the portal venous phase and beyond, often progressing to complete fill-in of the lesion (Fig 11).

• Sustained enhancement, in which the lesion has an echogenicity equal to or greater than that of the liver through the portal venous phase and beyond is requisite to confident diagnosis.


• Hemangioma. (Right) Baseline conventional US image shows a heterogeneous, bulbous, slightly exophytic lesion that extends from the posterior right lobe. (Left) Early arterial phase vascular US image shows no linear vessels. There is peripheral nodular enhancement.

Continued

• (Right) Late arterial phase US image shows centripetal progression of the enhancement. (Left) On a portal venous phase US image, the lesion appears uniformly enhanced and brighter than the background liver. This sustained enhancement is consistent with a benign condition

• Rapidly enhancing hemangioma in a patient with known neuroendocrine tumor. Baseline US failed to show a mass that had been detected previously at CT performed as part of a metastasis survey. Sequential arterial phase US images obtained over a 2-second interval show a thin rim of marginal enhancement (right), peripheral nodular enhancement (Left) and Continued

• Centripetal progression of enhancement to complete fill in the lesion (Right). (Left) Arterial phase CT scan shows a brightly enhancing mass. Both images showing a hypervascular mass. The peripheral nodular enhancement and the centripetal progression of enhancement are appreciated only on the US images.

• Hemangioma. Arterial phase US image (right) and CT scan (left) show classic features of hemangioma, with bright peripheral nodules and a typical bridge across the lesion with pools of contrast material along its margins.

Focal Nodular Hyperplasia• FNH is not a tumor but a hyper plastic liver lesion.• FNH differentials include hypervascular masses such as HCC

and its fibrolamellar variety. • Noninvasive confirmation of FNH without the need for liver

biopsy is important.• Like HCC, FNH manifests as a hypervascular liver mass during

the arterial phase of contrast-enhanced US. • However, the specific morphologic features of these two

entities during the arterial phase are often different. FNH is uniformly enhanced without the frequent occurrence of necrosis and heterogeneity seen in HCC.

Continued


• Figure 14. FNH. (a) Sagittal conventional US image shows a fatty liver with an expansive hypoechoic mass in the caudate lobe. (b) Arterial phase US image shows a hypervascular mass with a stellate vascular pattern

• (Right) On a portal venous phase US image, the lesion remains equal in enhancement to the liver and contains a central nonenhancing scar. (left) Confirmatory portal venous phase CT scan also demonstrates sustained enhancement of the lesion and the nonenhancing scar.

Focal Nodular Hyperplasia• FNH shows stellate lesion vascularity and, frequently, a

central nonenhancing scar.• A tortuous feeding artery is also commonly seen with

FNH.• Portal venous phase imaging is critical to confident

confirmation of the diagnosis. As opposed to HCC, in which washout is generally seen, FNH continues to show enhancement equal to or greater than that of the adjacent liver into the portal venous phase and beyond.

• This phenomenon constitutes a major criterion for diagnosis of FNH, without which we still recommend further evaluation with CT or MR imaging.Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in

Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935

• FNH. (right) Baseline conventional US image of the right lobe shows a subtle echogenic mass. (middle) Arterial phase US image shows a hypervascular mass with some stellate vascularity, a small nonenhancing scar (arrow), and a typical tortuous feeding artery. (left) Confirmatory arterial phase CT scan also demonstrates the hypervascular mass and nonenhancing scar (arrow).

CEUS in Adenoma• Hepatic adenoma benign liver lesion. This hepatocytic

tumor frequently manifests with spontaneous rupture and hemorrhage.

• Malignant potential has been documented, and diagnosis is therefore important.

• These lesions have been vascular during the arterial phase.• The documentation of portal venous behavior has been

complicated by the higher baseline echogenicity of these tumors, which commonly contain a significant volume of fat.

• Adenoma in a young female. (A) Gray scale sonogram shows an oval hypoechoic lesion in liver. (B) CEUS-arterial phase shows

• diffuse heterogeneous enhancement, which on portovenous phase (C) is isoechoic to liver parenchyma.

Shruti Thakur, Anupam Jhobta, D.S. Dhiman, R.G. Sood, Arun Chauhan,Charu S. Thakur. Role of contrast enhanced ultrasound in characterization of focal liver lesions. The Egyptian Journal of Radiology and Nuclear Medicine (2014) 45, 7–17

• Contrast-enhanced ultrasound images of a hepatic adenoma (HA) in a 23- year old asymptomatic man with no history of hormone use. (A) Hypoechoic HA visualized in two-dimensional sonography; lines ‘A’ and ‘B’ were used to measure diameter in the maximum section. (B) Hypervascular enhancement of HA with contrast ‘fast-in’ in the arterial phase. (C) Lesion (arrow) appearing isoechoic or slightly hyperechoic compared with normal-surrounding liver parenchyma in the portal venous phase. (D) Lesion (arrow) showing persistent enhancement with slight washing out and visualization of the borderline in the delayed phase

XL ZHU1,*, P CHEN2,*, H GUO3,*, N ZHANG3, WJ HOU4, XY LI1 AND Y XU1. Contrast-enhanced Ultrasound for the Diagnosis of Hepatic Adenoma. The Journal of International Medical Research 2011; 39: 920 – 928

A B C D

Imaging Phase

HCC HypovascularMetastasis

Hypervascular Metastasis

Hemangioma FNH

Arterial (vascularpattern)

Hypervascular,dysmorphicvessels

Hypovascular,marginalvessels

Hypervascular Marginal vessels,peripheralpuddles andpools, no linearvessels

Hypervascular, stellatevessels, tortuousfeedingartery

EnhancementArterial

Greater than that of liver, diffuse, often heterogeneous

Less than thatof liver, marginal,often heterogeneous

More thanthat of liver

Greater than thatof liver, peripheralnodules,often heterogeneous

Greater than that ofliver, diffuse andhomogeneous,nonenhancingscar

Portal venous–late

Less than that ofliver

Less than thatof liver

Less than thatof liver

Equal to or greaterthan that ofliver, centripetalprogression

Greater than orequal to that ofliver, nonenhancingscar

Change in enhancementover time

Washout Washout Washout Sustained enhancement

Sustained enhancement


Characteristics pattern in Other Lesions

Jae Young Jang, et al. Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions. Clinical and Molecular Hepatology 2013;19:1-16

Role in Cholangiocarcinoma

• The enhancement patterns of ICC correlate with tumor size. That is, most small ICCs (≤ 3 cm) are homogeneously enhancing, while those > 3 cm enhance heterogeneously or show a peripherally enhancing rim.

• In portal and late phase on CEUS, most ICCs show up as hypo-enhancing, which is a prominent feature of malignancy on CEUS.

• However, on enhanced CT or MRI, most ICCs show delayed hyper-enhancement in the late phase.

Xu HX. Contrast-enhanced ultrasound in the biliary system: Potential uses and indications. World J Radiol 2009 December 31; 1(1): 37-44

• Intrahepatic cholangiocarcinoma. (right) Baseline ultrasound shows an isoechoic mass in segment 5 of the liver; (left): The lesion shows peripheral rim-like hyper-enhancement 26 s after contrast agent injection on CEUS;

• (Right) The lesion becomes hypo-enhanced 52 s after contrast agent injection; (left) The lesion continues to be hypo-enhanced 121 s after contrast agent injection.

Characteristics of malignant lesions of the liver in CEUS

Jae Young Jang, et al. Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions. Clinical and Molecular Hepatology 2013;19:1-16

CEUS in Hepatic Abscess

• Hepatic abscess shows perilesional vascularity on arterial phase, ring enhancement on portal venous phase and retained their enhancement pattern on late parenchymal phase.

• Hepatic abscess shows dense rim of opacification with a persistent hypoechoic center.

• Both the external and internal margins became sharper after contrast administration

Shruti Thakur, Anupam Jhobta, D.S. Dhiman, R.G. Sood, Arun Chauhan,Charu S. Thakur. Role of contrast enhanced ultrasound in characterization of focal liver lesions. The Egyptian Journal of Radiology and Nuclear Medicine (2014) 45, 7–17

http://dx.doi.org/10.3350/cmh.2013.19.1.1

• Hepatic abscess in a 22-year-old man. (right) Gray scale shows a well defined heterogeneous hypoechoic lesion in right lobe. (left) Color Doppler shows no vascularity.

Continued

• (Right) CEUS-arterial phase shows intense peritumoral enhancement. (Left) CEUS-portal venous phase shows persisting rim enhancement.

Take Home Message

Microbubble enhanced US of the liver provides enhancement information comparable to that provided by contrast enhanced CT and MR imaging, along with real-time morphologic evaluation of lesion vascularity.

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role of contrast enhanced ultrasonography in characterization of hepatobiliary disease dr. muhammad...

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