Measuring cerebral hypoperfusion with Doppler ultrasound

I've been trying to organise this test for my daughter for some time, so we've read as much on it as we can. Gets a bit technical sometimes.

In the literature, I've noticed that some groups measure at the carotid (and sometimes also vertebral) artery, and some groups measure at the middle cerebral artery.

For example, Visser et al. in the Netherlands use the carotid artery.
Video lecture of Prof. Visser discussing and showing his preferred technique

And Novak uses the middle cerebral artery (which makes it transcranial Doppler, as you are "looking" through the skull).

I haven't been able to find out why one or the other position is preferred.

The one possible explanation that I noticed for preferring to measure in the neck is that about 10% of people don't have a suitable "window" in their skull for transcranial sonography. It's also possible that the carotid artery measurement is easier to acquire and does not require a headset (making it less expensive/difficult?).

I wish I could write to the researchers and ask them, but without an academic email address and letters after my name I doubt I would get a reply.

Does anyone know the answer?

 

@Hutan , thank you very much for the suggestion. I will give it a try and report back.

 

I was about to write to some of the researchers and ask them about the different placement of the ultrasound probes when they sent a letter to the editor of a journal that answers my question.

They say that both methods are good, but placing the probe on the cartotid or vertebral artery has the advantage of "being able to control for vessel diameter, which can be affected by hypocapnea and gravitational fluid shifts during HUTT [head up tilt testing]".

I don't really understand the technicalities, but am reassured that either option works.

Here is the thread on the letter to the editor:
https://www.s4me.info/threads/is-it...ing-head-up-tilt-testing-2024-mitchell.38582/

 

@Ken Turnbull ,

I am wondering how reliable this test is as clinical information. Novak seems to have created this category of orthostatic cerebral hypo perfusion but I do not see any clear indication that it is meaningful. About 10% of a retrospective series were designated as this, having showed a greater drop in perfusion measured by doppler than the others, but it is not clear to me whether this is more than just natural variation in results on a population. It is also unclear to me whether it means anything clinically.

There is a study from 1995 that confirms that doppler measures blood flow in a way that correlates with a more reliable PET method but it did not correlate with brain metabolism, so it may not tell you anything about availability of oxygen.

I know very little about this field but wonder if it is really validated. Has anyone other than Novak confirmed the validity of the concept and the clinical relevance of the test?

 

We have some older studies using near infrared spectroscopy to measure frontal lobe oxygenation, eg with orthostatic or exercise challenge. Ideally you'd want to do both modalities and correlate the Doppler US vascular flow/velocity readings with oxygenation. I can't recall this having been done to date.* Nobody's made an upright PET scanner to my knowledge so that probably won't be able to help, but upright MRIs are progressing so in theory it might become possible to measure oxygenation and blood flow at the same time via MR, both supine and sitting/standing.

Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance (2002)
Hidetaka Tanaka; Reiko Matsushima; Hiroshi Tamai; Yoshinaga Kajimoto

OBJECTIVES
To measure postural changes in cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance.

STUDY DESIGN
We studied 28 patients (age, 10 to 22 years) and 20 healthy control subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and deoxygenated Hb were noninvasively and continuously measured with near infrared spectroscopy during active standing. Beat-to-beat arterial pressure was monitored by Finapres.

RESULTS
Orthostatic intolerance determined by cardiovascular responses to standing was observed in 16 of 28 patients: instantaneous orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance but only in 2 of 20 control subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing.

CONCLUSIONS
Impaired cerebral hemodynamics in patients with chronic fatigue syndrome and postural orthostatic tachycardia suggest a link between impaired cerebral oxygenation and chronic fatigue. However, this cannot explain the symptoms in patients meeting the criteria of chronic fatigue without orthostatic intolerance.

Link | PDF (The Journal of Pediatrics)


Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome (2008)
J. Patrick Neary; Andy D. W. Roberts; Nina Leavins; Michael F. Harrison; James C. Croll; James R. Sexsmith

This study examined the effects of maximal incremental exercise on cerebral oxygenation in chronic fatigue syndrome (CFS) subjects. Furthermore, we tested the hypothesis that CFS subjects have a reduced oxygen delivery to the brain during exercise.

Six female CFS and eight control (CON) subjects (similar in height, weight, body mass index and physical activity level) performed an incremental cycle ergometer test to exhaustion, while changes in cerebral oxy-haemoglobin (HbO2 ), deoxy-haemoglobin (HHb), total blood volume (tHb = HbO2 + HHb) and O2 saturation [tissue oxygenation index (TOI), %)] was monitored in the left prefrontal lobe using a near-infrared spectrophotometer. Heart rate (HR) and rating of perceived exertion (RPE) were recorded at each workload throughout the test.

Predicted VO2 peak in CFS (1331 ± 377 ml) subjects was significantly (P ≤ 0.05) lower than the CON group (1990 ± 332 ml), and CFS subjects achieved volitional exhaustion significantly faster (CFS: 351 ± 224 s; CON: 715 ± 176 s) at a lower power output (CFS: 100 ± 39 W; CON: 163 ± 34 W). CFS subjects also exhibited a significantly lower maximum HR (CFS: 154 ± 13 bpm; CON: 186 ± 11 bpm) and consistently reported a higher RPE at the same absolute workload when compared with CON subjects. Prefrontal cortex HbO2 , HHb and tHb were significantly lower at maximal exercise in CFS versus CON, as was TOI during exercise and recovery.

The CFS subjects exhibited significant exercise intolerance and reduced prefrontal oxygenation and tHb response when compared with CON subjects. These data suggest that the altered cerebral oxygenation and blood volume may contribute to the reduced exercise load in CFS, and supports the contention that CFS, in part, is mediated centrally.

Link | PDF (Clinical Physiology and Functional Imaging)

---
* It was done with muscle: US, MR spectroscopy and NIRS in Muscle metabolism with blood flow restriction in chronic fatigue syndrome (2004, Journal of Applied Physiology)

 

Great finds! 2002, 2004 and 2008 and still a long way to go. Not only in exercise, I think, but who am I?
OI (also with normal BP like me) leads to less oxygen in the brain leads to brainfog.
With a questionmark. Not enough oxygen in the brain can lead to inflammation even without viruses?

 

possibly unrelated --- at best tangential --- the interest in cerebrospinal fluid & ME/CFS revolves around intracranial pressure - which is difficult to measure but high (correct?) intercranial pressure would result in headaches (correct?) and other symptoms (like what?). Low intercranial pressure would result in ---
I guess hypoperfusion might be in some way related to ME/CFS but you'd need some indicators like difference in those with ME/CFS & controls. Also, are there any drugs which regulate cerebrospinal fluid production/perfusion?
We might see something via DecodeME* and/or a rare variant genetic study (NIH have indicated they may fund one*)

*DecodeME is a common variant genetic study - results due to be published 2025
**NIH roadmap & webiars

 

Van Campen, Visser (2020) found 90% of ME/CFS patients had hypoperfusion during the tilt table test with doppler, not the healthy controls.
The NIH found no difference between groups but had POTS patients in the HC group. They compared patients with patients

 

I am wondering whether reduced cerebral perfusion on standing with a normal blood pressure in ME/CFS reflects a greater vasoconstrictive response needed to maintain BP because of peripheral blood pooling in the context of a shifted venous pool distribution and maybe reduced blood volume secondary to spending a lot of time lying down. In other words that the problem is not due to ME/CFS itself but to the acclimatisation to lying flat.

That would have significant implications for management in terms of advice on positioning.

 

would reduced cerebral perfusion lead to my "seeing stars" & everything momentarily going black, just for a split second, when i stand up?

 

It would. I always get that after getting up from a sofa if I have been sitting upright, but I don't get it getting up from a sofa if I have been lying down - which makes me think that things are complicated and maybe when I am sitting venous return is poorer because of the 'kink' in my body at the hips.

I have learnt over the years to avoid the blackout by getting up in two stages. But if I forget it always happens. It lasts about five seconds for me usually.

It also happened to me when I had a Stokes-Adams attack when my pulse went down to 20bpm after pushing a car in the snow. That time I just had time to lie on the floor and wait. It took about a minute for my heart rate to return, during which I couldn't speak or move. It didn't seem to do me any harm!!

 

interesting, because id not noticed that it happens after i've been sitting rather than lying, but i had noticed that it weirdly (to me) seems to happen more often when i'm in better patches, rather than when i am worse off and bed bound more.

But what you've said would fit - because of course the better i am the more time i spend sitting rather than lying.

 

The shift in plasma protein level is almost certainly part of a long term mechanism to re-adjust the blood volume needed for perfusion requirements in a continuing recumbent state. It is presumably a way of saving energy that otherwise would be spent on maintaining homeostatic mechanisms for shifting volumes around on rapid demand.

I presume something similar happens to astronauts, or at least did in the early days before they had methods for countering it.

 

I respecfully disagree. Normally I just accept what you post, because of your vast knowledge and experience; now I disagree.

I don't faint and have no problem getting upright. Only when I have been upside down in my garden, stretched legs because of a busted knee; on coming up again the light goes out and the world starts tilting. I was very close to fainting twice. Because I figure things out on my own; I timed how long I could stay down and placed a few bamboo sticks to grab onto, just in case.

I do think OI is the problem in ME/CFS. Mine probably caused by reduced blood volume. I tried to get that tested 3 times, but I always bump into specialists without knowledge about ME/CFS but they always know "better" and block access to testing. That really hurts. I always stay friendly, but the next one?

I'm a slow flow (Systrom), not enough blood available, chronotropic incompetence, shunting and diverting of blood and that damages muscles and cells because they "run on empty". When "on empty" tissues can release already replicated viruses and when you are vulnerable you'll get "ït" again. Muscle aches during the time of repair and too much muscle use or just at the wrong time that causes PEM (GET). Slow muscles become fast muscles (Appelmans Wüst, 2024) No Krebs cycle, hardly fatty acids, just amino acids, muscles have to adapt.
I am short, no long arteries I supppose, just available what is in the pipeline, that's 1 minute 26 sec in my CPET of aerobic energy. After that the damaging starts and so does the pain, already during the test.

Being upright means not enough blood and oxygen to my head. Brainfog gets worse second part of the day. So I won't change my mortgage in the second half of the day. That could become costly.
It won't be the - 25% CBF drop of the tilt table test because I can use my coping mechanisms but always too low a blood flow. My learning capacity is badly affected. I'm up most of the day, certainly not lying down all day.
Advice on positioning, no thank you. That even sounds CBT, sorry.

Fire away as much as you can. But please don't start with "How do we"? I felt the recipient cringe. I won't cringe, because I have never been a medical student. Let me have it.

 

This seems like a reasonable explanation for some of the orthostatic issues that pw ME/CFS face. However, from my own experience I think it is unlikely that spending time laying down significantly contributes to orthostatic symptoms in all but some severe cases.

As with Hutan, my orthostatic symptoms began while I was still very fit and active. Over the course of a few weeks I went from feeling normal to being very dizzy and lightheaded when sitting and standing up. During this time I was still trying to exercise, spending lots of time sitting upright in classes and only lay down slightly more than typical. I would get quite severe palpitations and headaches after cardio that would slowly improve with lying down.

I very much agree that there has to be some peripheral blood pooling going on. After I go for a short walk my feel will be red or purple, especially when it is hot out. I have been tested for small fiber neuropathy and it appears to not be the cause in my case. I have also tried all of the POTS drugs with no real positive impact on blood pooling or orthostatic symptoms. I would be interested to hear what else could shift venous pooling distribution. Vascular defects, damage to small vessels, improper nervous signaling, a chemical deficit?

In my case, I do think that whatever is driving the orthostatic issues is my primary problem. However, I don't think my experience is that broadly applicable. I am not sure I am a standard ME/CFS case as I often get extreme headaches and don't experience PEM in the way that some other describe.

 

Ditto here. My first symptoms were orthostatic/autonomic and I was very active. Onset after just having sailed 30NM doing all the rig handling. Admittedly this was cruising not racing, but there is no way for me that deconditioning happened first, I was pretty fit, and even more so (and younger) were @Kiwipom and @CovidSpice.

To my mind the vascular dysfunction comes on first. Recovering after becoming severe and bedbound, improvements in orthostatic tolerance seemed to follow rest/pacing, with any reconditioning (which I suspect is modest subsequently) seeming to follow that.

 

That is what I would have predicted, but we don't have good evidence for the changes in cerebral perfusion reported on tilt table tests are actually the primary cause of the OI. SO things can easily get complicated.