MRI CONTRAST

INTRODUCTION

  • MRI contrast agents are contrast agents used to improve the visibility of internal body structures in magnetic resonance imaging.

  •  improves the diagnostic accuracy of the MRI scan. For example, it improves the visibility of inflammation, tumours, blood vessels and, for some organs, blood supply.
  • The most commonly used compounds for contrast enhancement are gadolinium-based. 

  •  Gadolinium is the key component of the contrast material most often used in magnetic resonance (MR) exams. When this substance is present in the body, it alters the magnetic properties of nearby water molecules, which enhances the quality of MR images.

susceptibility

It is the degree to which a material can be magnetized in an external magnetic field.

Paramagnetic agents

  •  Gadolinium is a paramagnetic agent.
  •  They are usually positive agents but at higher doses can cause T2 shortening resulting into
  •  decreased signal on T2-W images.
  •  When paramagnetic agents initially pass through the vascular bed of brain, they cause local T2 shortening and decrease in the signal on T2-W images.
  •  This effect is used in perfusion studies.   

Superparamagnetic agents

  •  They are negative contrast agents.
  •  They cause proton dephasing leading to T2 shortening and signal loss.
  •  Example: Iron oxide (Fe3O4) ,like superparamagnetic iron oxides (SPIOs) and ultrasmall SPIO
  •  (USPIOs). 

RELAXIVITY

It is the degree to which the agent can enhance the longitudinal or transverse water relaxation rate constant[r1=1/t1 or r2=1/t2]normalized to concentration os the contrast agent.

 Positive relaxation agents (T1 agents)

  • These agents affect T1 relaxation of the tissues.
  •  T1 of the tissue in which contrast media is accumulated is reduced.
  •  Reduction in T1,results into increase in the signal intensity on T1-W images 
  • Hence , these agents are called positive relaxation agents.
  • Examples: Gadolinium, Mn-DPDP.

Negative relaxation agents (T2 agents)

  • They affect T2 relaxation and reduce T2 of the tissue where they accumulate.
  •  This results in reduction in the signal intensity of the tissue on T2-W images.
  • Examples: Iron oxide particles, Gadolinium (high doses).                                                     

 ORAL CONTRAST

 Positive Contrast

  • Example: Manganese chloride, Gd-DTPA, oil emulsions
  • Image degradation can occur with peristaltic movements of bowel.
  • For MR Enterography, sorbitol (3%) with or without barium or polyethylene glycol solutions can be used as oral contrast.

 Negative contrast

  • They decrease signal from bowel lumen reducing the motion related image degradation. 
  • They are also used in MRCP.
  • Superparamagnetic iron oxide particle reduce signal by susceptibility effects.
  • Example: Barium, blue-berry or pineapple juice (contain manganese) and perfluorochemicals are also used to reduce signals from bowel.

Mechanism of MR Contrast Enhancement

  • In MR imaging,the contrast mechanism is multi-factorial and includes:
  • Spin Density,
  • Relaxivity (T1, T2), 
  • Magnetic susceptibility,
  • Diffusion and Perfusion of contrast agent.

 DIPOLE –DIPOLE INTERACTION

  In Relaxivity ,Paramagnetic ions increase relaxation of water protons by a dipole-dipole relaxation.

  The phenomenon, in which excited protons are affected by nearby excited protons or electrons, is called

  •    The dipole-dipole interaction affects the rotational and translational diffusion of water molecules leading to   their relaxation.
  •  The more and closer the water molecules approach the paramagnetic ions, greater will be the relaxation.

  ‘dipole-dipole interaction’. 

 Gadolinium

  • Atomic Number-64
  • Paramagnetic agent
  • Reduces T1 and T2 of the tissues where it accumulates
  • Increased signal on T1-w and reduced signals (negligible) on T2-w images
  • Usual dose: 0.1 mmol/Kg
  • Median Lethal dose (LD50): 6–30 mmol/kg
  • Overall adverse reaction rate: 3–5%

  • OSMOLALITY

  • Ionic: Magnevist- 1960 mmol/kg
  • Nonionic: Omniscan – 789 mmol/kg
  • Prohance – 620 mmol/kg

  •  A T2 effect of Gd leading to reduction in signal on T2-w images is generally insignificant and clinically not relevant.
  • However, the susceptibility effect (not the relaxivity) of Gd, as it initially passes through the vascular bed leading to decreased signal on T2-w images, is used in the MR perfusion.

                                             

Gadolinium Chelates

  •  Chelates are substances that have high affinity for metal ions.
  • Free Gd ions tend to accumulate in the body and do not get excreted. 
  • Free Gd ions are toxic. 
  • Therefore, Gd ions are combined with chelates such as DTPA ,that cause their rapid and total renal excretion.
  • Gadobenate  (Multihance) and Gadoxetate (Primovist/Eovist) are excreted in part by hepatobiliary system. These agents can be used to assess hepatobiliary pathology and are called as Hepatobiliary Specific Contrast Agents.

GADOLINIUM SAFETY

1. RENAL FAILURE

This is discussed under NSF. Gd chelates can be dialysed. In chronic renal disease with GFR >60 ml/min/1.73 m2, no special precautions are needed.

2.HISTORY OF ASTHMA/ALLERGY

Precautions should be taken in these patients and constant monitoring should be performed. Premedications with hydrocortisone and antihistaminic drugs may be given as clinically warranted.

 3.PREGNANCY

Gadolinium is known to cross the placenta. It is then excreted by fetal kidney and can re-circulate through amniotic fluid several times. Gadolinium can dissociate from its chelate if it stays long in the amniotic fluid. It is suggested that MR contrast medium should not be routinely injected in pregnant patient.However, a case-by-case basis decision can be done with risk-benefit analysis.

4. LACTATION

Gadolinium is excreted in human milk. Breast milk should be expressed after injection and thrown away. Baby should not be breast fed for 36–48 hours.

FERIDEX

Feridex was one of the several super paramagnetic iron oxide [SPIO] agents developed for imaging liver and reticuloendothelial system in the 1990s.

By the late 2000s,all such agents have been removed from the market,due to side effects and lack of demonstrated 

Clinical utility.

  • Not withstanding initial enthusiasm for these agents, they failed commercially because their diagnostic utility was simply not proved.
  • Although most cancers did not have SPIO uptake, several benign and malignant hepatocellular lesions including focal nodular hyperplasia, hepatic adenoma, hepatocellular carcinoma, and hemangiomas would occasionally accumulate the agents.
  • As a result, by 2012 manufacturers of both agents discontinued global production and sales. Today, Resovist is available as a liver agent only in Japan. 

 Risks/warning in feridex contrast use

  •  Dyspnea
  •  Angioedema
  •  Generalized Urticaria
  • Hypotension
  • Acute severe back
  •  Leg or groin pain

Other MR Contrast Agents

1. Iron Oxide (Fe3O4)-

It is a superparamagnetic agent. It is phagocytosed by reticulo-endothelial system (RES) with prominent uptake in liver and spleen.

Normal liver tissue takes up Iron oxide and becomes dark on T2-w images. Focal lesions such as metastases do not have RES cells within them, so they remain same and appear relatively bright.

2. Mn-DPDP (Mangafodipir trisodium)

This is a hepatobiliary specific contrast agent as 50% of the administered amount is excreted through the biliary system and other 50% by the kidneys

 It causes positive contrast enhancement of the normal liver parenchyma and lesions containing hepatocytes on T1-W images. The lesions without hepatocytes like metastasis will not show enhancement and remain relatively darker.

3. Dysprosium Chelates: Dy-HP-DO3A

These were found to be more superior to Gd chelates in perfusion studies (not in routine T1-W images) because of more T2 relaxivity and susceptibility effects.

Role of Contrast in MRI

It has been shown that there is substantial improvement in lesion identification and characterization with Gd.

CNS Neoplasm:

  •  Contrast improves identification, margin delineation and invasion in brain tumors.
  •  It is must in patients undergoing surgery.
  •  Metastases and meningiomas can appear isointense on plain scan. Contrast injection makes them more  conspicuous.
  •  Contrast is very useful in post-treatment tumors to differentiate recurrence from necrosis, especially with MR perfusion.

CNS Infection: 

Contrast enables lesion characterization and assessment of lesion activity. Acute lesions may be differentiated from chronic lesions (gliosis).

 Disease progression/regression can be monitored. 

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