Magnetic Resonance Imaging of Liver Metastasis

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Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasiaā€“like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3Ā mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis.

Introduction

Liver metastasis, by definition, is a malignant lesion originating in an organ distant from the liver, which would secondarily disseminate and grow in the liver. Liver is a very common site of metastasis. Gastrointestinal tumors such as neuroendocrine tumors, colorectal cancers, esophageal and gastric tumors, and pancreatic cancers are among the most common sources for metastatic disease to the liver. Colorectal cancers (CRCs) are especially very common, with approximately 50% of the patients would have metastatic liver disease either at the time of diagnosis or in the follow-up period after surgical resection.1 Despite advances in surgery, targeted biologic therapies, and chemotherapy, the survival rates of patients with liver metastasis are still dismal, with a significant portion of these patients dying owing to their metastatic liver disease.

Disseminations through the portal venous and arterial systems are the most common routes for metastasis. Once the tumor cells detach from their original site, they travel into the vascular system and extravasate into the target organ parenchyma and proliferate. They are frequently found as multiple lesions of different sizes in both liver lobes, and several cancers often incite desmoplastic reaction when they metastasize, which gives them their hard consistency.2 Often times, internal necrotic changes give rise to their pseudocystic appearance. Central fibrous scar formation and capsular retraction (when they are located close to the liver capsule) may also be detected.3, 4

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Clinical Presentation

Most liver metastases are clinically silent and detected with cross-sectional imaging. When they are symptomatic, the disease is most often at an advanced stage and the prognosis is poor. Metastasis from hormonally active tumors may present with symptoms related to the hormonally active metabolites secreted by the metastatic cells.

Role of Cross-Sectional Imaging in the Evaluation of Metastatic Liver Disease

Imaging plays a crucial and integral role in the diagnosis and monitoring of metastatic liver disease. Several imaging modalities including ultrasonography (US), computed tomography (CT), positron emission tomography (PET), and PET-CT scans can be used for this purpose. In this article, we are going to focus on the role of MRI, which is becoming the gold standard modality in the diagnosis of hepatic metastases.

MRI for Liver Metastases

MRI offers superior soft tissue resolution, providing several advantages over other cross-sectional imaging modalities for the detection and characterization of the focal liver lesions. This superiority becomes more prominent when it comes to detection of small-sized metastases. The reported sensitivity of contrast-enhanced MRI (CE-MRI) is 91%-97% compared with 71%-73.5% for CT.5, 6, 7 The sensitivity of MRI increases, especially, in the characterization of the lesions deemed to be ā€œtoo small

Advanced MRI Techniques

Several new MRI techniques have entered clinical practice in the past few years, and they have now become essential components of standard liver MRI protocols.9 Diffusion-weighted imaging (DWI), hepatocyte-specific magnetic resonance (MR) contrast agents (HSMRCA), MR elastography, and MR perfusion may be counted among them. For the sake of brevity, we focus on DWI and HSMRCA. MR elastography and MR perfusion are less commonly used in clinical practice, and both are currently in the research

DWI of the Liver

DWI is a technique that can provide tissue contrast based on the measurement of diffusion properties of the water molecules within tissue.10 It is mainly based on the intravoxel incoherent motion and provides quantification of the water diffusion and microcapillary blood perfusion within the tissue in a noninvasive manner.11

DWI was mainly a tool for neuroimaging; however, it has become an indispensible part of the liver MRI studies. It is not only used in the detection of liver lesions but also

Hepatocyte-Specific Contrast Agents

Gadolinium chelates used as IV contrast media in MRI studies are crucial for increasing the sensitivity and specificity of the liver MRI examinations. With increasing use of MRI for the liver examinations, several HSMRCAs have been used in the past. Currently, there are 2 HSMRCAs available for clinical use, and both are gadolinium-based agents, which overcome the other shortcomings related to former HSMRCAs. These 2 agents currently used in clinical practice are gadobenate dimeglumine

Pharmacokinetics of the Gadoxetate Disodium

Owing to its unique properties, a brief discussion of the pharmacokinetics of gadoxetate disodium is warranted. It first distributes to the extracellular space after IV administration, and once in the extracellular space, it can either be excreted from the kidneys through glomerular filtration or taken up by the hepatocytes and excreted into the intrahepatic biliary canalicules.22 This dual-elimination pathway gives gadoxetate disodium its hepatocyte-specific aspect. In subjects with preserved

Use of Gadoxetate Disodium

Gadoxetate disodium was approved for clinical use in Europe in 2004, followed by United States in 2008 and Canada in 2010; there has been a massive flush of the literature regarding its clinical value and use. Several different specialties including radiology, hepatology, and surgery have contributed to the accumulation of this massive body of information.

Different studies have demonstrated the superiority of MRI with hepatocyte-specific contrast agents, in particular gadoxetic acid, relative

Colorectal Cancer Metastases

CRC is a very common cause of morbidity and mortality, and liver is a very common site for tumor metastasis. Approximately 30% of the cases have metastatic liver disease at initial presentation, with almost 14.5% of the cases showing development of liver involvement during chemotherapy.46, 47 Early detection and characterization of liver metastases are of crucial importance for optimal triage of patients who may benefit from hepatic resection from those who need chemotherapy, to improve 5-year

Imaging After Locoregional Therapy for Liver Metastases

Locoregional treatments with ablative technologies and intraarterial chemoembolization or radioembolization are commonly used methods in the treatment of liver metastases. Cross-sectional imaging is the main tool for the evaluation of early-stage assessment of procedural success and follow up. US, CT, PET-CT, and MRI may all be used for this purpose. As other modalities except for MRI is out of the scope of this article, we focus on the role of MRI. Subtraction images may be helpful, especially

Imaging Findings After Ablative Locoregional Liver Therapy

The imaging specialist should be familiar with the postprocedural imaging findings to prevent the potential diagnostic confusion. Radiofrequency ablation and microwave ablation are the 2 most commonly used local ablative technologies.

The term ā€œablation zoneā€ refers to the area undergoing coagulative necrosis after ablative therapy. This encompassess the actual tumor zone as well as the 5-10Ā mm around the tumor, which is akin to disease-free resection margin aimed after conventional surgical

Imaging Findings After Transarterial Chemotherapy or Radiotherapy

Intraarterial treatments take advantage of the dual vascular supply of the liver. As the metastatic foci in the liver mostly derive their blood supply from hepatic artery and the rest of the liver from the portal vein, theoretically, by using the transarterial way, the metastases may be selectively treated by sparing the liver parenchyma. Metastatic liver disease from several different malignant neoplasms may be treated by transarterial approaches, but most of the information accumulated is on

Atypical Presentations of Liver Metastases and Challenging Findings

Typical imaging findings in metastatic liver disease may not be challenging to the imagers, and diagnosis is relatively straightforward. However, it is well known that liver metastases may mimick other benign and malignant clinical conditions, and awareness to these findings is crucial for the right diagnosis.

Diffuse infiltrative metastatic disease may be highly challenging to recognize in some patients. This pattern is less common, and hematologic malignancies are known to metastasize in this

Role of MRI in Prognosis and Predicting Response of Liver Metastases to Chemotherapy

In addition to its high sensitivity in diagnosing liver metastases, MRI may also have a role, by using DWI and other sequences, in predicting prognosis and tumor response to chemotherapy. Koh et al107 have demonstrated in their study that the detection of high ADC values in pretreatment metastatic liver foci secondary to CRCs may be an indicator of poor prognosis. The authors postulated that the presence of necrosis and loss of cell membrane integrity, causing high ADC values, in the

Future Directions

Several new state-of-art developments in MRI have a potential of opening new horizons for imaging specialists including more quantitative approaches in MRI (MR fingerprinting), the combination of MRI with PET (PET-MRI), and metabolic approaches such as glucose chemical exchange saturation transfer (glucoCEST) assessing the glucose metabolism with MRI.

In MR fingerprinting, the quantitative assessment of the tissue T1 and T2 relaxivity has a great potential, in addition to conventional

Conclusion

Metastatic liver disease is very common in the course of cancer. The presence of hepatic metastatic disease is commonly a sign of advanced stage malignancy, and early detection and proper follow up is mandatory for optimal management. Although all cross-sectional imaging modalities including US, CT, and PET-CT may be used, MRI appears to be most successful modality with its superior soft tissue resolution. This advantage of MRI became even more pronounced with the advances in

References (114)

  • B. Knowles et al.

    Detailed liver-specific imaging prior to pre-operative chemotherapy for colorectal liver metastases reduces intra-hepatic recurrence and the need for a repeat hepatectomy

    HPB (Oxford)

    (2012)
  • G. Spolverato et al.

    Hepatic resection for disappearing liver metastasis: A cost-utility analysis

    J Gastrointest Surg

    (2015)
  • A. Goldhirsch et al.

    Progress and promise: Highlights of the international expert consensus on the primary therapy of early breast cancer 2007

    Ann Oncol

    (2007)
  • R. Diaz et al.

    Hepatic resection in breast cancer metastases: Should it be considered standard treatment?

    Breast

    (2004)
  • D. Elias et al.

    An attempt to clarify indications for hepatectomy for liver metastases from breast cancer

    Am J Surg

    (2003)
  • S.M. Maksan et al.

    Curative liver resection for metastatic breast cancer

    Eur J Surg Oncol

    (2000)
  • M. Pocard et al.

    Hepatic resection in metastatic breast cancer: Results and prognostic factors

    Eur J Surg Oncol

    (2000)
  • E. Senkus et al.

    Time for more optimism in metastatic breast cancer?

    Cancer Treat Rev

    (2014)
  • S.A. Chikarmane et al.

    Metastatic patterns of breast cancer subtypes: What radiologists should know in the era of personalized cancer medicine

    Clin Radiol

    (2015)
  • A. Qayyum et al.

    Frequency of hepatic contour abnormalities and signs of portal hypertension at CT in patients receiving chemotherapy for breast cancer metastatic to the liver

    Clin Imaging

    (2007)
  • H.A. Farley et al.

    Treatment of neuroendocrine liver metastases

    Surg Oncol Clin N Am

    (2016)
  • A. Kamaya et al.

    Hypervascular liver lesions

    Semin Ultrasound CT MR

    (2009)
  • D.S. Rigel et al.

    The incidence of malignant melanoma in the United States: Issues as we approach the 21st century

    J Am Acad Dermatol

    (1996)
  • N. Ghanem et al.

    Detectability of liver metastases in malignant melanoma: Prospective comparison of magnetic resonance imaging and positron emission tomography

    Eur J Radiol

    (2005)
  • V. Vandecaveye et al.

    Detection of head and neck squamous cell carcinoma with diffusion weighted MRI after (chemo)radiotherapy: Correlation between radiologic and histopathologic findings

    Int J Radiat Oncol Biol Phys

    (2007)
  • J.D. Jaskolka et al.

    Needle tract seeding after radiofrequency ablation of hepatic tumors

    J Vasc Interv Radiol

    (2005)
  • J.M. Llovet et al.

    Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma

    Hepatology

    (2001)
  • I.R. Kamel et al.

    Functional MR imaging assessment of tumor response after 90Y microsphere treatment in patients with unresectable hepatocellular carcinoma

    J Vasc Interv Radiol

    (2007)
  • S.R. Alberts et al.

    Chemotherapy for colorectal cancer liver metastases

    Oncologist

    (2008)
  • J.A. Conti et al.

    The desmoplastic reaction surrounding hepatic colorectal adenocarcinoma metastases aids tumor growth and survival via alphav integrin ligation

    Clin Cancer Res

    (2008)
  • D. Da Ines et al.

    Hepatic capsular retraction: Spectrum of diagnosis at MRI

    Acta Radiol Short Rep

    (2014)
  • V.O. Chan et al.

    Diagnostic performance of MDCT, PET/CT and gadoxetic acid (Primovist((R)))-enhanced MRI in patients with colorectal liver metastases being considered for hepatic resection: Initial experience in a single centre

    Ir J Med Sci

    (2012)
  • D.V. Sahani et al.

    Detection of liver metastases from adenocarcinoma of the colon and pancreas: Comparison of mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET

    AJR Am J Roentgenol

    (2005)
  • J. Ward et al.

    Liver metastases in candidates for hepatic resection: Comparison of helical CT and gadolinium- and SPIO-enhanced MR imaging

    Radiology

    (2005)
  • N.S. Holalkere et al.

    Characterization of small liver lesions: Added role of MR after MDCT

    J Comput Assist Tomogr

    (2006)
  • P.G. Kele et al.

    Diffusion weighted imaging in the liver

    World J Gastroenterol

    (2010)
  • B. Taouli et al.

    Advanced MRI methods for assessment of chronic liver disease

    AJR Am J Roentgenol

    (2009)
  • H.J. Kim et al.

    Incremental value of liver MR imaging in patients with potentially curable colorectal hepatic metastasis detected at CT: A prospective comparison of diffusion-weighted imaging, gadoxetic acid-enhanced MR imaging, and a combination of both MR techniques

    Radiology

    (2015)
  • V.S. Katabathina et al.

    Genetics and imaging of hepatocellular adenomas: 2011 update

    Radiographics

    (2011)
  • E.M. Charles-Edwards et al.

    Diffusion-weighted magnetic resonance imaging and its application to cancer

    Cancer Imaging

    (2006)
  • M. Bruegel et al.

    Characterization of focal liver lesions by ADC measurements using a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging technique

    Eur Radiol

    (2008)
  • F.H. Miller et al.

    Utility of diffusion-weighted MRI in distinguishing benign and malignant hepatic lesions

    J Magn Reson Imaging

    (2010)
  • B. Taouli et al.

    Diffusion-weighted imaging of the liver: Comparison of navigator triggered and breathhold acquisitions

    J Magn Reson Imaging

    (2009)
  • B. Taouli et al.

    imaging of the liver

    Radiology

    (2010)
  • N.K. Lee et al.

    Biliary MR imaging with Gd-EOB-DTPA and its clinical applications

    Radiographics

    (2009)
  • K.I. Ringe et al.

    Gadoxetate disodium-enhanced MRI of the liver: Part 1, protocol optimization and lesion appearance in the noncirrhotic liver

    AJR Am J Roentgenol

    (2010)
  • I. Cruite et al.

    Gadoxetate disodium-enhanced MRI of the liver: Part 2, protocol optimization and lesion appearance in the cirrhotic liver

    AJR Am J Roentgenol

    (2010)
  • R.B. Schwope et al.

    Gadoxetic acid: Pearls and pitfalls

    Abdom Imaging

    (2015)
  • M.K. Seale et al.

    Hepatobiliary-specific MR contrast agents: Role in imaging the liver and biliary tree

    Radiographics

    (2009)
  • S. Gschwend et al.

    Pharmacokinetics and imaging properties of Gd-EOB-DTPA in patients with hepatic and renal impairment

    Invest Radiol

    (2011)
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