So how does one analyse a MCE study qualitatively?
This requires a sound grasp of microbubble and capillary physiology! Here is a step-by-step explanation through the theory:
- Microbubbles display the same rheology as red blood cells (RBCs) and thus effectively act as RBC tracers in the intravascular compartment
- Microbubbles flow through capillaries at a very slow rate (approx 1mm/sec)
- The ‘elevation’ or depth of an ultrasound beam in a conventional 2D adult transthoracic probe is 5mm
- At a speed of 1mm/sec, this means that approximately 5 seconds would be required for the entire ultrasound beam to refill with bubbles after high MI-impulse destruction
- With a resting heart rate of 60-80bpm, there is roughly one heart beat (or cardiac cycle) / second, meaning that it would take 5 cycles for bubble replenishment at rest
- A normal individual with no coronary artery disease should be able to increase resting myocardial blood flow up to 4-5 times normal at peak hyperaemia (i.e. normal coronary flow reserve)
- If that were the case, the RBCs (and thus microbubbles) would now have a speed of 5mm/sec, meaning that they would replenish the ultrasound beam width in 1 second (as opposed to the five at rest)
- If a vasodilator (e.g. dipyridamole) has been used for stress, there will be little change in heart rate, so 1 second = 1 cycle, so one would expect to see complete microbubble replenishment within 1 second (or 1 cycle)
However, if exercise or dobutamine have been used, the heart rate will have increased (e.g. from 60bpm to 120bpm) meaning that there are now 2 cardiac cycles per second, so one would allow 2-3 cycles/beats to see complete bubble replenishment.
In the presence of a coronary stenosis, during hyperaemia (stress), the perfusion / driving pressure in the capillary bed supplied by the diseased artery falls significantly and these capillaries close, known as derecruitment. Consequently, there is an absolute reduction in blood flow through the subtended myocardial segment(s) and this is detected by MCE as a filling or perfusion defect (interested readers are directed at this point to an excellent paper by Jayaweera et al [Am J Physiol Heart Circ Physiol 1999; 277; H2363-H2372] which discusses the prominent role of capillaries in determining myocardial blood flow and flow reserve).
Figure: The elevation (E) or thickness of the ultrasound beam is depicted in A after a flash has destroyed all microbubbles within this field. New microbubbles will then re-enter this ultrasound beam elevation (replenishment B-E), with increasing concentration after each second (i.e. t1 represents the first second after flash destruction, t2 represents two seconds after flash destruction etc). The speed of this replenishment depends in part upon the microbubble velocity.
Therefore, when interpreting MCE images qualitatively, rest and stress images should be analysed by:
Freeze the cine loop on the frame exactly after the flash frames and ensure that there has been adequate bubble destruction (i.e. myocardium should be black)
If there has been inadequate destruction, the first thing to do is ensure that background tissue signals are not high as this will give a false impression of perfusion (if so, reduce the gain). Other options include increasing the MI of the flash frames (e.g. from 0.6 to 0.8) or increasing the number of flash frames (e.g. from 8 to 15)
Analyse each cine-loop frame-by-frame to ensure that there is normal perfusion at rest and stress. At rest, complete bubble replenishment is expected within 5 seconds and, at peak stress, within 1 second
The degree to which the CFR is reduced is directly proportional to the degree to which refilling will be delayed (in the presence of a significant coronary stenosis)
Wei K et al Circulation 1998.
Figure 6: Examples of flash replenishment imaging
Top left: PRE FLASH image (apical 4Ch view) showing homogenous contrast intensity in the septal (S) and lateral (L) walls. Note the low MI of 0.08.
Top right: FLASH image. High MI (0.5) bubble destruction.
Bottom left: First frame immediately post bubble destruction showing complete bubble destruction throughout the LV walls and apex (A).
Bottom right: An example of poor / incomplete bubble destruction: note the apex appears black but the basal and mid segments are still opacified by contrast, implying that the bubbles were not destroyed and thus replenishment cannot be assessed.
More moving clips and further examples are available in the Atlas of Clinical Cases – Chapter 5. Below is a link to a normal (triggered imaging) perfusion image (note rapid and homogenous contrast opacification immediately after flash destruction of microbubbles).