Xenon-Enhanced Computed Tomography

Homework Problem 28 in Chapter 16 of Intermediate Physics for Medicine and Biology analyzes xenon-enhanced computed tomography.

Section 16.8

Problem 28. An experimental technique to measure cerebral blood perfusion is to have the patient inhale xenon, a noble gas with Z = 54, A = 131 (Suess et al. 1995). The solubility of xenon is different in red cells than in plasma. The equation used is

(arterial enhancement) = 5.15θ_Xe/[(μ/ρ)_w/(μ/ρ)_Xe]C_Xe(t),

where the arterial enhancement is in Hounsfield units, C_Xe is the concentration of xenon in the lungs (end tidal volume), and

θ_Xe = (0.011)(Hct) + 0.10.

Hct is the hematocrit: the fraction of the blood volume occupied by red cells. Discuss why the equation has this form.

I found an article that reviews using xenon as a contrast agent to monitor blood flow; Hrvoje Lusic and Mark Grinstaff discuss “X-ray-Computed Tomography Contrast Agents” (Chemical Reviews, Volume 113, Pages 1641–1666, 2013). I will quote the section on xenon, with references removed and comments added.

7.0 Xenon gas in CT imaging applications

“High Z” [high atomic number] noble gasses also represent a class of contrast media used in certain applications of X-ray CT [computed tomography] imaging. The most commonly used noble gas for CT imaging is xenon (Z_Xe = 54; absorption edge k_Xe = 34.6 keV) [compare this to other widely used contrast agents: iodine (Z_I = 53, k_I = 33.2 keV) and barium (Z_Ba = 56, k_Ba = 37.4 keV)]. Xenon is a readily diffusible monoatomic gas with low but not insignificant solubility in blood and fairly good solubility in adipose [fat] tissue. Xenon gas can pass across cell membranes, exchange between blood and tissue, and can cross the blood-brain barrier. Drawbacks to xenon gas use are related to its anesthetic properties, and may include respiratory depression, headaches, nausea, and vomiting. [Xenon-enhanced CT uses stable isotopes of xenon, so there is no dose from radioactive decay, although there is a dose from the X-rays used in CT. Other imaging methods use Xe-133, a radionuclide.]… Undesired side-effects can be adequately managed by controlling the xenon gas concentration and the length of time xenon is inhaled for. In several countries the stable xenon gas (non-radioactive 131Xe) is approved for clinical use in X-ray CT imaging. In the U.S., xenon-CT is not FDA [Food and Drug Administration] approved (as of the writing of this document) and is only available under investigational new drug (IND) status [as best I can tell, this remains true today; I’m not sure why].

Xenon-CT has been used for several decades to evaluate cerebral blood flow and perfusion in patients experiencing cerebrovascular disorders (e.g., following a brain injury, brain surgery, or stroke). It is considered a valuable imaging modality used as an alternative or complement to PET [positron emission tomography], SPECT [single photon emission computed tomography], MRI [magnetic resonance imaging], etc. Current standard for the xenon-CT cerebral blood flow evaluation calls for inhalation of 28 ± 1% medical grade xenon gas with at least 25% oxygen, for the duration of ~4.5 minutes. Following the procedure, xenon is rapidly washed out from cerebral tissues due to its short half-life of iodinated [containing iodine] small molecule contrast agents, frequently in combination with vasodilatory challenge [the widening of blood vessels] (e.g., acetazolamide) to measure brain hemodynamics…

Outlook

Xenon gas has X-ray attenuating properties similar to iodine. Xenon is chemically inert, biocompatible, and non-allergenic and can be safely used in patients with renal dysfunction. The undesired side-effects of xenon inhalation, related to its anesthetic properties, can be minimized by controlling the concentration of xenon gas being inhaled and the duration of the procedure. The rapid rate of xenon clearance from the body can be advantageous and conducive to repeat examinations. Xenon-CT has so far gained clinical approval in a number of countries, where the technique is most frequently used for cerebral blood flow assessment. Overall, xenon-CT is a useful clinical alternative to CT imaging using iodinated imaging media, especially when and where the diagnostic equipment is readily available.

The next noble gas in the rightmost column of the periodic table is radon (Z_Rn = 86, k_Rn = 98.4 keV), which has no stable isotopes. Being a noble gas, it should be diffusible and cross the blood-brain barrier like xenon. Would radon be a more effective contrast agent than xenon? For x-ray energies when the photoelectric effect dominates the interaction of photons with tissue, the cross section increases a Z⁴ (see Eq. 15.8 in IPMB), indicating that radon should be almost seven times more effective that xenon at increasing the x-ray absorption. Its k-edge is significantly higher than xenon’s, so its advantages would be realized only for x-ray energies above 100 keV. The key question is if the disadvantage of exposure to radiation (alpha decay in the lungs, which could cause lung cancer) would outweigh the advantage of its higher atomic number. If the risk from radon could be made much smaller than the risk of ionizing radiation from the CT scan itself, the use of radon might make sense. I suspect the expense of producing and handling radon, and public fears of even slight radioactivity, would tip the balance toward xenon over radon. Still, it’s an interesting idea.