The colorful art and science of perfusion imaging

Deconvolution in action

Do you know what deconvolution is and how it works? Although I seriously doubt that any Neurologist is richer knowing that, it certainly is reassuring to understand why CT perfusion has so many variations, interpretations and limitations.

In my view, CT perfusion has many applications in Neurology (not to speak of Oncology):

  • Determine the penumbra of a stroke: this deserves some comments. As a quantitative method CT perfusion fails. You just cannot expect to quantify the proportion of the penumbra, because there are too many unknowns in the computation and interpretation. But you can determine the mere existence of a penumbra quite reliably (and it is still the best thing we have apart from CT+CTA).
  • Distinguish status epilepticus from postictal paralysis: the former shows hyper perfusion, while the latter looks like a stroke without core (total mismatch).
  • Recognize migraines that you would otherwise treat with tPA (again, this looks like a stroke without core, but the hypoperfusion does not respect the boundaries of the arteries and the arteries are open!).
  • Prove hyperperfusion in a hyperperfusion syndrome
  • Show the downstream effects of vasospasm in SAH
  • Determine the vascular reserve with acetazolamide – ok, this is easier done with duplex ultrasound…

Here is how I use CT-perfusion in acute stroke:

  • Indications: unknown time window, stroke mimics in tpa situations
  • Require the clinician to determine the exact region where to look
  • Use MTT or TTP to screen for ANY problems in the perfusion of the brain – wherever it is slowed, you have to do the CBF/CBV magic
  • Where CBF is quite low (don’t rely on absolute values!) and CBV is also down, there is some infarct core. Now go back to the NCCT – there should be some early ischemic signs here.
  • Where CBF is not so low as in the core and CBV is only slightly down or up there is penumbra
  • If in doubt, do exact ROI comparisons (left vs. right)
  • Now decide: is the clinical picture dominated by the infarct core or the penumbra? How much cortical structures are in the core, prone to bleed if you open up the artery? Does CTA vessel occlusion (sometimes you find the occluded vessel easier, if you know where the problem sits in perfusion CT) correspond to the perfusion deficit?

Now to the gory details:

  • Arterial input function: You should use a good arterial vessel to get the arterial input function, often the ACA is in the slice studied. But the problem is that the ACA might take part in the supply of your stroke via collateralization and it might also be disturbed by stenosis (say A1 or ICA). This can lead to very bad data.
  • Without arterial input function you cannot do deconvolution (which basically shows you how your tissue perfusion would look like if the fuzzy contrast bolus would look like a perfect rectangle-shaped push of contrast agent, not a wave) properly, so you have to use things like maximum-slope-methods and so forth.
  • Same for venous outflow.
  • The choice of algorithm is quite important – there seem to be optimal ones, if you believe this paper.
  • There are plenty of assumption underlying most of the algorithms, such as intact blood brain barrier, which usually hold in acute stroke, but are violated in things like post-CEA-hyperperfusion or SAH.
  • Sometimes, the cardiac output is so bad that the perfusion curve ends too early. You can often still use TTP in that case, but all deconvolution methods must fail.

For many more details see


Cerebral air embolism

Air rarely enters the vascular system naturally, so it usually takes some medical invasive procedure to achieve it, the infamous exception being diving accidents (decompression). You can basically distinguish microscopic bubbles from macroscopic air embolism.

Microscopic bubbles can occur

  • during the PFO test
  • angiography (heart, brain)
  • ECMO and heart-lung-machines

They lead to microscopic arterial embolisms in the brain that shine brightly on T2, less so in other sequences of MRI, CT cannot show them. Depending on the emboli zed artery focal symptoms can occur, but usually only multiple small emboli lead to problems, such as encephalopathy/delirium. Note that microemboli introduced on the venous side usually don’t pass the lung, unless there is right-left shunt (PFO, Morbus Osler, …).

Macroscopic air embolism happens in typical circumstances

  • Central venous access (push and pull!)
  • Biopsies and other pulmonary procedures
  • Endoscopy (mostly EGD)
  • brain surgery (posterior fossa mainly due to the sitting position)

Now in my experience there are two possible pathophysiologic mechanisms

  • Fulminant cerebral venous embolism – this can happen (very rarely) in sitting patients; the air ascends into the jugular vein and then leads to partial occlusion of the sagittal and other sinuses with consecutive brain edema.
  • Arterial embolism: It turns out that the lung only has so much capacity for air. If enough is introduced on the venous side, air migrates to the arterial side and then embolizes to the brain where it leads to visible air in the vessels on CT.

Interestingly, these kinds of strokes seem to have better collateralization (perhaps some blood can get through the bubbles), because there are plenty of case reports with hyperbaric treatment that turned out successful. Apart from that some experts use Trendelenburg’s to try to get the bubbles out.

Literature: there are some case reports, but no proper reviews that cover the above. Even “Uncommon causes of stroke” doesn’t mention cerebral air embolism. I’d love to hear about your experiences.

Statins and their interactions

In the hypothetical polypill a statin is an essential ingredient. Although I have deep reservations against the cholesterol hypothesis per se, I do believe in the efficacy of statins, even judging their effect higher in proven arteriosclerotic strokes (such as embolism from a high grade carotid or media stenosis) than that of ASA. Their side effects are also impressive: you hear that from young strokes that receive statins as part of their prophylactic package, but then aren’t able to perform as well in sports as before.

It is (at least to me) totally unclear what dose to give to your stroke, but I titrate the dose along the arteriosclerotic burden – a pure cardioembolic stroke receives the minimum dose of, say, simvastatin 10-20 (unless he has coronary disease or PAD); a microangiopathic stroke might get some more (say 40 mg). A medium grade stenosis would receive 80 mg and a high grade or multiple stenoses gets the advanced stuff such as atorvastatin or rosuvastatin (maximum dose). Repeat offenders always get the maximum dose.

The problem with this titrated approach is that the dose given does not match the dose aimed at, because of pharmacologic interactions, of which there are plenty. E.g. some amlodipine and ticagrelor (a frequent combination after emergency stent) might lead to multiplication of the effective dose. I expect our residents to check these interactions before giving more then the minimal dose and refer them to this review for details. We also use Medscape’s interaction checker to screen in complicated regimens. Obviously, a pharmacologist would be even better, but we are poor in Germany and reduction of medication errors does not pay…

Here is a list of the standard drugs to be aware. For antibiotics and other absurd drugs refer to the above article.

Amiodarone, Amlodipine and other Ca antagonists, Cholestyramine, Cimetidine, Colchicine, Cyclosporine, Digoxine, Dronedarone, Glyburide, Fibrates/Niacin, Phenytoin, HIV drugs, Ranolazine, Ticagrelor