Contrast Agents for Liver MRI

Gadolinium Chelates

• Most commonly used contrast agent
• Standard dose 0.1 mmol Gd/kg
• Bolus injection, dynamic study during arterial (20-30s) to detect hypervascular lesions, portovenous phase (60-90s) to detect hypovascular lesions, and equilibrium phase (between 2-10 min) to allow hemangiomas to fill-in and cholangiocarcinoma and inflammation to enhance

Liver-Specific Agents

• Teslascan (Mn-DPDP)
• MultiHance (gadobenate dimeglumine)
• Primovist (gadoxetic acid)
• SPIO (Endorem/Feridex)

Teslascan

• Hepatocyte-specific MR contrast agent
• Uptake into hepatocyte and partially excretes into the bile
• Drip infusion
• Increased T1 signal intensity
• Differentiate tumors of hepatocellular origin from nonhepatocellular origin

MultiHance

• 4% biliary excretion
• Can be bolus injected, images also taken 1-2 hours later for tumor detection (uptake into liver parenchyma to increase conspicuity of metastases)

Primovist

• Strong biliary excretion
• Can be bolus injected (doses 0.025 mmol/kg), images on delayed phase can be taken as early as 20 min

Superparamagnetic Iron Oxide Particles (SPIO)

• Accumulates within phagocytes in the liver (typically, there is absence of phagocytes in malignancy)
• On T2WI, normal tissues or lesions with phagocytes (ie, FNH, hepatocellular adenoma, well-differentiated HCC) appear dark
• Drip infusion
• Imaging done several hours after contrast administration

Above image: gadolinium metal, from www.emovendo.net

Reference:

Reimer P, Parizel PM, Meaney JFM, Stichnoth FA. Clinical MR Imaging, 2010

Metformin and Iodinated Contrast Agents

Facts about Metformin

• Medication for treatment of type II diabetes
• Decreases hepatic glucose production and enhance glucose uptake in peripheral tissues (by increase insulin sensitivity)
• May be in a pure form or in combination with other antihyperglycemic drugs
• Renal excretion
• Most significant reaction is lactic acidosis, which has a high mortality (up to 50%)
• Most metformin associated lactic acidosis (MALA) occured in patients with coexisting renal dysfunction (high level of metformin due to poor excretion)

Why Do We Worry About Metformin and Iodinated Contrast Agents?

• The use of iodinated contrast agents in patients with pre-existing renal dysfunction can lead to significant contrast-induced nephropathy - that could, in turn, worsen MALA.

In Whom We Should Worry?

• Patients with pre-existing renal dysfunction
• Patients with comorbidities that could give rise to lactic acidosis (liver dysfunction, alcohol abuse, heart failure, myocardial ischemia, peripheral muscle ischemia, sepsis, severe infection)

What To Do?

• Patients with normal renal function and no known comorbidities -> no need to discontinue metformin prior to IV contrast administration
• Patients with known comorbidities -> Discontinue metformin at time of IV contrast administration, and withheld for 48 hours
  
• Patients with known renal dysfunction -> suspend metformin at time of IV contrast administration, renal function follow-ups until safe reinstitution of metformin can be assured

Reference:
American College of Radiology. Manual on Contrast Media version 6 (2008).
McCartney MM, et al. Metformin and contrast media - a dangerous combination? Clin Radiol 1999;54:29.

Imaging During Pregnancy: Gadolinium?

Facts

• IV gadolinium (Gd) is teratogenic in animal studies (at high, repeated dose)
• Gd crosses placenta
• Gd is category 'C' by U.S. FDA, meaning that "It has been shown to be teratogenic (or to have an embryocidal effect or other adverse effect) in (name(s) of species) when given in doses (x) times the human dose. There are no adequate and well-controlled studies in pregnant women. (Name of drug) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus."

How To Deal
According to ACR (American College of Radiology) and U.S. FDA, Gd is only to be administered if potential benefit justifies potential risk to the fetus.

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Gadolinium มีผลทำให้เกิดความผิดปกติต่อลูกในครรภ์ของสัตว์ทดลองเมื่อใช้ในปริมาณมากและซ้ำๆ ดังนั้น จึงไม่แนะนำให้ใช้ในหญิงมีครรภ์ (U.S. FDA ถือว่าเป็นยาในกลุ่ม C ซึ่งหมายความว่ามีความเสี่ยงสูง) ข้อยกเว้นที่จะใช้ได้ก็ต่อเมื่อพิจารณาแล้วว่าประโยชน์ที่จะได้รับจากการใช้ Gd นั้นมีเหนือกว่าโทษที่อาจมีต่อทารกในครรภ์

Image source: www.britannica.com

Reference:
1. Chen MM, et al. Obst Gynecol 2008;112(2):333-340 (Aug 2008)
2. http://www.fda.gov/Cder/handbook/categc.htm

Imaging During Pregnancy: Iodinated Contrast Media?

Facts

• Iodinated contrast media can cross human placenta and enter fetus when given in clinical doses.
  
• No teratogenic or mutagenic effect was shown in animal studies.
  
• No adequate, well-controlled human studies have been performed.

What are the risks?

• Neonatal hypothyroidism: this occurred after direct instillation of ionic contrast into amniotic cavity during amniofetography. No report of effect from IV use of contrast media.

What to do?

• According to ACR (American College of Radiology), no definitive conclusion on risks of IV iodinated contrast media in pregnant women. Only use if absolutely necessary and informed consent needs to be obtained.
• If IV contrast medium was given, check thyroid function of newborn baby for possible hypothyroidism.

Reference:
1. Chen MM, et al. Obst Gynecol 2008;112(2):333-340 (Aug 2008)
2. American College of Radiology. Manual on contrast media version 6 (2008)

Guideline for Prevention of Contrast-Induced Nephropathy