Methods: Cerebral blood flow velocity; Curve fitting

A regular reader of this blog had an excellent idea. She suggested discussing methods related to cerebrovascular physiology. I will thus try to come up with posts related to specific methods used to study cerebral blood flow, cerebral oxygenation, cerebral autoregulation, etc.  This new section will also be used to answer your questions (to the best of my knowledge) regarding methods used in this research field. I don’t pretend to know everything. So if you have any comments to add to the discussion, it will be very appreciated!

In this first post, I am answering Jess Inskip’s questions.

Question: Why do some researchers describe mean CBFV as the arithmetic mean, while others use the integral under the envelope of the CBFV tracing? Surely the latter is more important, as it is the waveform that seems to be sensitive to perturbations rather than the raw SBF and DBF.

Answer: Mean cerebral blood flow velocity (Vmean) is measured using velocity associated with maximal frequencies of the Doppler shifts (envelope). Vmean can be used as an index of cerebral blood flow if we assume that: 1) maximal velocity is proportional to the mean velocity of the blood flow in the vessel; 2) the vessel’s cross-sectional area remains constant. Although Vmean in the MCA increases in parallel with the inflow of the internal carotid artery, with the initial slope index of the 133Xenon clearance-determined cerebral blood flow, and with regional cerebral blood flow measurements by positron emission tomography during exercise for example, some argue that changes in velocities associated with the maximal frequencies of the Doppler shift doesn’t necessarily reflect changes in flow. These authors use the intensity-weighted mean velocity (VIWM), which is based on the complete velocity spectrum. The latter represents a mean velocity averaged over the entire cross section of the blood vessel. However, while small changes in the angle of insonation of a cerebral artery is of no consequence for the maximal velocity, the average flow velocity is affected by the angle of insonation. So, other investigators such as Secher et al. (J Appl Physiol 2006) argue that changes in cerebral flow velocity during exercise are essentially lost when attention is not on Vmean.

Interesting reads:

Willie CK et al. J Neurosci Methods 196:221-237, 2011

Lohmann H et al. in Baumgartner RW (ed): Handbook on Neurovascular Ultrasound. Front Neurol Neurosci. Basel, Karger, 2006, vol 21, pp 1–10

Aaslid R et al. J Neurosurg 57:769-774, 1882

Poulin MJ et al. J Appl Physiol 86:1632-1637, 1999

Question: Is there a way to determine how to curve fit the relationship between PETCO2 and cerebral blood flow. Many seem to continue to define this as a linear relationship, yet other recent research groups have shown that this should be a sigmoidal relationship (even when these two groups seem to be working in the same PETCO2 ranges).

Answer: The utilization of the right model to study this relationship remains ambiguous to me. First, you need to choose the technique to evaluate the cerebrovascular reactivity to CO2.  Accordingy to Ainslie (see Interesting reading for the reference), you need to choose the method to evaluate cerebrovascular reactivity to CO2 according to your experimental question, and a clear choice of method to study it (steady-state changes in CO2 vs. modified rebreathing) is problematic until the physiology of cerebrovascular control is better understood.

I think that, for the moment, it is the same for the determination of the right model to study the relationship between PaCO2/PetCO2 and cerebral blood flow, since there exists a plethora of models. Indeed, you can model steady-state cerebrovascular CO2 reactivity using a least squares linear regression, a biasymptotic curve analysis;, a dynamic single-compartment model, an exponential function, etc. When using modified CO2 rebreathing, a lot of studies used linear regression although some investigators demonstrated a non-linear relationship between PaCO2 and cerebral blood flow.

So, it is true that several studies are quantifying cerebrovascular reactivity to CO2 using a linear regression. One simple reason is that more complex modeling of cerebrovascular reactivity to CO2 is too complicated for clinical use.  Also, more data points are needed with an exponential model vs. a linear model…Still, an interesting benefit with exponential models = more precise data fitting. This being acknowledged, a recent study suggests that the fitting strategy doesn’t seem to influence results…at least for the estimated PaCO2 range of interest (20-60 mmHg). So, is there a way to determine how to curve fit this relationship? It depends, most likely, on the aim of your study…

Question: Furthermore, if you are looking at CO2 reactivity at resting conditions and after perturbation X, what if one of the effects of the perturbation x is in fact altering the shape of the relationship between PETCO2 and CBF.

Answer: You have an excellent point. I don’t necessarily have the answer. What I can tell is that reactivity to CO2 is higher during hypercapnia vs. hypocapnia (potential mechanism: more important impact of vasodilator vs. vasoconstrictor mediators on vascular tone). In addition, factors such as hydration, caffeine, time of day, posture, etc. have an influence on the relationship between cerebral blood flow and reactivity to CO2. Finally, this relationship could also be affected by CO2-induced changes in arterial pressure.

Interesting read:

Ainslie P et al. Am J Physiol Regul Integr Comp Physio 296: R1473-R1495, 2009


11 thoughts on “Methods: Cerebral blood flow velocity; Curve fitting

  1. Thanks for the wonderful periodic articles. I am wondering if you have come across a paper in your readings that discusses continuous monitoring of cerebral venous blood oxygenation, and flow rates invasively, through catheterization, during exercise? It would be of much interest to me, and I can’t seem to find a definitive study elucidating the response.

    Thank you kindly again, and please keep up the great articles.

  2. Thank you very much for the good words. This is very appreciated. Unfortunately, I haven’t come across a paper that discusses continuous invasive monitoring of SjvO2/cerebral blood flow during exercise. As I am also following the anesthesia literature, I know that a fiberoptic catheter is used for continuous SjvO2 monitoring (Schell and Cole Anesth Analg 2000;90:559–66) during anesthesia or neurointensive care. I have never read a paper using that technology during exercise. I will ask my Danish friends if they have already worked with such a catheter in their invasive exercise studies…I will keep you posted.

    1. Thanks again Pat, you are really wonderful for curating the field is such an accessible way. Very admirable. If I come across anything, I will be sure to let you know. There may be something from way back (like the 50’s, when NO techniques, and catheterization was more commonly used).

  3. Kory: Unfortunately, my Danish colleagues are unaware of exercise studies where they used continuous SjvO2 monitoring. However, one of them told me about the following study performed at rest in healthy volunteers:

    Olsen KS et al. J Neurosurg Anesthesiol. 1994 Oct;6(4):233-8.

    I hope that it will be of some help!

    1. Pat: thanks so much for checking with the peers around the world. It is quite surprising to me that something like that has not been monitored, so I will continue looking and searching, and if anything comes up, I will let you know.

      Even if it was just cerebral blood flow measurement during exercise with a bulb… or monitoring venous flow somewhere else…

  4. When you say “cerebral blood flow measurement during exercise’, you are still talking about continuous measurement, aren’t you? Because I know some studies where the authors took blood from the jugular vein at different time points during exercise and CBF was calculated according to the Fick principle from the CMRO2 and the jugular venous (a-v) oxygen content difference….but these measurements are not continuous.

    1. While that is more sampled, and maybe not as pseudo-continuous, that is somewhat interesting I am sure. Was the AV difference reported? I would be interested in papers like there… have you posted on them before?

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