Permeability Flashcards
What is the BBB?
In the normal brain, endothelial cells form tight junctions creating a ‘blood-brain barrier’
This barrier allows access to essential molecules, such as glucose, while keeping out toxins
Unfortunately, it also severely impedes drug delivery
Breakdown of the blood brain barrier can occur in various disease states, e.g. tumours, multiple sclerosis, small vessel disease etc
What is permeability imaging?
A way to quantify the permanility of the blood vessel endothelial wall.
In normal subjects blood vessel integrity is maintained and no leakage occurs.
Imperfections in the vessel wall can occur in various disease states, e.g. tumours, small vessel disease.
Measurable parameters of interest include:
-permeability-surface area product per unit
-volume of tissue
-extravascular extracellular space volume fraction
How to we aquire permiability images?
Acquire baseline pre-contrast images.
Inject a contrast agent ‘bolus’.
Observe signal change for a period up to 30 minutes after injection.
Convert signal change into contrast agent concentration.
T1-weighted sequence
Why do we use a T1 weighted sequence for permeability imaging?
Its sensitive to leakage of contrast agent into the extravascular extracellular space (EES) and less sensitive to contrast agent withtin the vessel
- with BBB imaging were not interested in contrast agnet within the vessel, we’re interested in what leaks out
What is dynamic contrast enhanced MRI?
A single post-contrast image provides information on the ‘amount’ of leakage at a specific time.
Measuring permeability requires dynamic information.
What are contrast uptake curves for tumours in the brain with permeability imaging?
Typical trends observed in the brain are:
Malignant tumour tissue: large and fast uptake with washout
Benign / necrotic tumour tissue: large, but more progressive uptake
Normal tissue: minimal contrast uptake
Great for imaging tumours and for many use is its primary clinical application
What is an issue with permeability imaging?
Signal enhancement is not linearly realted to contrast agent concentration
It exhibits a high dependecy on the pre-contrast tissue (T1) so if the original T1 tissue was bright, it shows a lot less enhancement than something else that was dark
-so we need a mathematical model to describe this relationship and relate the signal enhancement to concentration and correct for this- makes the results as quantitive as possible
How can we quantify this?
Use the pharmacokinetic model
-this describes the interaction between the blood plasma and extravascular extracellular space (EES)
Appears to provide a reasonable model of the contrast agent uptake curves observed in human tissues.
What is the application of permeability imaging to brain tumours?
Without a blood supply, tumours are limited to about 1–2 mm in diameter. In order to grow, cancer cells send out signalling molecules that stimulate new blood vessel formation. This process is called ‘angiogenesis’.
The new vessels are often formed imperfectly and without tight endothelial junctions. The degree of impairment to the BBB can then be measured using MR permeability imaging- because they have poor junctions more contrast leaks out
Higher grade, more aggressive tumours tend to be more vascular and faster growing. The aggressiveness of tumours may therefore be observed using MR permeability imaging
What are tumour microvessels?
Vessels formed during angiogenesis are imperfect
The ‘pore’ size can be up to 2000nm in diameter.
In contrast, standard endothelial pore size is 4nm
