Use of MRI and MR markers in AAA treatment

Question 1

What is 4D-flow MRI?

Answer 1

4D-flow MRI enables the measurement and visualization of the temporal evolution of complex blood flow patterns within an acquired 3D volume as a function of time (4D).

Question 2

What are disadvantages of 4D-flow MRI?

Answer 2

• Long scan times (10 minutes compared to 10 seconds for T1)
• Large datasets, which means complex processing

Question 3

What is DCE-MRI?

Answer 3

DCE-MRI is based on dynamic T1-weighted imaging of contrast agent extravasation over several minutes often with lower time resolution than needed to track a first-pass bolus. Often, a fast spoiled gradient echo sequence is used.

Question 4

What is a pharmacokinetic map in regard to DCE-MRI?

Answer 4

A pharmacokinetic map is used to translate and understand how a drug interacts with the body. So in regard to DCE-MRI, you can monitor the distribution of the contrast agent and measure the perfusion rate based on this.

Question 5

Currently, surgery of an aneurysm is determined by the diameter of the aorta. Why is this a simplified way of determining the need for surgery?

Answer 5

Because the diameter of the aorta does not directly reflect the actual disease activity. There are for example many other factors that determine the risk for rupture of the aorta than only the diameter.

Question 6

What technique is therefore best to use to determine the need for surgery of an aneurysm? Why?

Answer 6

Dynamic MRI
- No radiation
- Various image contrast mechanisms → visualize more than just morphology

Question 7

There are three types of MRI biomarkers:
- molecular biomarkers
- flow biomarkers
- wall biomarkers

What are molecular MRI biomarkers?

Answer 7

Contrast agents targeting AAA-progression-specific mechanisms such as inflammation.

Question 8

An example of a molecular MRI-biomarker is the use of ECM collagen-specific probes.
Describe how this biomarker aids in the measurement of AAA.

Answer 8

• Degradation of the ECM in the medial wall is key to formation, progression and rupture of AAA.
• Collagen degradation and inappropriate deposition may alter vessel wall response to mechanical load → vessel wall failure.
• Imaging AAA collagen may provide information about the state of aneurysm development.

Question 9

Fill in:

A high concentration of collagen within the ECM of the medial wall of the aorta is associated with a high OR low chance of rupture.

Answer 9

low

Question 10

An example of a molecular MRI-biomarker is the use of ultrasmall superparamagnetic particles of iron oxide (USPIO).
Describe how this biomarker aids in the measurement of AAA.

Answer 10

• USPIO are taken up by tissue-resident macrophages and can be used to identify cellular inflammation within tissues.
• USPIO enhancement on MRI is associated with a more rapid AAA expansion.

Question 11

There are three types of MRI biomarkers:
- molecular biomarkers
- flow biomarkers
- wall biomarkers

What are flow MRI biomarkers?

Answer 11

Biomarkers based on the haemodynamics of the blood flow, can only be measured with 4D-flow MRI.

Question 12

Wall shear stress can be used as a flow biomarker for AAA. Describe how this biomarker can be used.

Answer 12

• Wall shear stress → the force on the wall of the aorta created by the blood flow.
• Peek systolic shear stress is lower in a dilated aorta compared to a healthy aorta.
• The location of the decreased shear stress also tells you the locaion of the aneurysm/rupture.

Question 13

The oscillatory shear index (OSI) can be used as a flow biomarker for AAA. Describe how this biomarker can be used.

Answer 13

• OSI is an indicator for the fluctuations in wall shear stress.
• An increased OSI (i.e. increased fluctuations in wall shear stress) is associated with a dilated aorta and correlates with inflammation and an increase in OH- radicals.

Question 14

There are three types of MRI biomarkers:
- molecular biomarkers
- flow biomarkers
- wall biomarkers

What are wall MRI biomarkers?

Answer 14

Biomarkers related to the properties of the aneurysm or aorta wall.

Question 15

The microcirculation can be used as a wall biomarker for AAA. Describe how this biomarker can be used.

Answer 15

• A high degree of microcirculation means a high possibility for the income of inflammatory cells. These inflammatory cells are important in the degradation of the ECM.
• This means that a high degree of microcirculation will result in the thinning of the aortic wall.

Question 16

With DCE-MRI, the parameter Ktrans can be measured. What is this parameter and how can this parameter be used as a wall biomarker for AAA?

Answer 16

• Pharmacokinetic modelling of DCE enables uantification of transfer constant Ktrans.
• Ktrans reflects microvascular flow, permeability and surface area.
• Higher Ktrans is more prone to entrance of inflammatory cells and MMPs (hypothesis)

Question 17

The wall stiffness can be used as a wall biomarker for AAA. Describe how this biomarker can be used.

Answer 17

• Changes in AAA tissue stiffness can reveal information about tissue microstructure and ECM content

Question 18