Developing Safe Breathing Protocols for Hyperpolarized
Noble Gas MFU
M.P. Ramirez, L.V. Kubatina, K.C.E. Sigaloff, M.A. Donahue, A.K. Venkatesh, and M.S. Albert
Department of Radiology, Brigham and Women ‘s Hospital, Harvard Medical School, Boston, MA
Introduction
Aniial and human studies indicate that hyperpolarized noble
gas MRI could have profound diagnostic and therapeutic
implications, especially for the treatment of lung diseases.
Unrestricted noble gas breathing protocols, however, can have
dangerouseffects to human subjects, particularly patients with
compromised ventilation[ 11. We designed and tested specific
MI&compatible breathing protocols with helium and xenon using
Sprague-Dawleyrats. We also conducted a preliiinaty
investigation in humans. With the knowledge gained from these
animal and human studies, our goal is to determine safe ventilation
protocols for hyperpolarized noble gas MRI studies in humans.
Methods
Sprague-Dawleyrats (200-300 g) were anesthetizedwith intramuscular injections of a Ketamme (SOmgAnl)and Xylazine
(2Omg/ml). The rats were intubated by tracheostomy,randomly
assignedto ventilation with either xenon or helium, and were
continuously monitored for blood oxygen saturation,heart rate,
EKG, temperature,and endotrachealpressure. The noble gas
breathing protocols included alternatebreaths with oxygen,
continuous breaths,breath-holds, and helium breath-holds
precededby two helium rinses.
Human experiments were conducted on 3 informed and
consentinghealthy subjects, in the presenceof a certified
physician. Subjects sat upright in a chair, while their blood oxygen
saturation,heart rate, and EKG were monitored continuously.
Upon verbal cue, the subject was asked to inhale and hold 1L of
100% helium gas or air for 5 s, 10 s, 15 s, or 20 s, after which they
were instructed to breathe normally. Between each protocol,
subjectsbreathed air for five minutes.
Results
The animal experiments show that alternate-breathsof noble gas
and oxygen up to 128 breaths causea <5% decreasein oxygen
saturation. 16 continuous-breathscauseddecreasein oxygen
saturation of 31.5% f 2.3% for helium and 30.7% + 1.3% for
xenon. Breath-hold protocols up to 25 s reduce the blood oxygen
saturationto 90% for both gases,and at 30 s it drops to 82% +
0.6% with helium, and to 76.5% f 7.4% with xenon. Breath-hold
protocols with oxygen show no significant changein oxygen
saturationfrom baseline values. Figure 1 shows the decreasein
oxygen saturation for 10 s, 15 s, 20 s, 25 s, and 30 s breath-hold
protocols with oxygen, xenon, helium, and helium breath-holds
precededby two helium rinses.
For the human experiments,helium breath-holds for 5 s, 10 s, 15
s, and 20 s show a decreasein oxygen saturation values of 1.29%,
3.62%, 4.30%, and 10.55% respectively. The control breath-holds
with air show a decreaseof oxygen saturation of <I%. For the 5 s
helium breath-hold, a miniium oxygen saturationwas reached at 2
s afler the start of the protocol. For the 10 s, 15 s, and 20 s breathholds with helium, the minimum oxygen saturationvalue was
reachedat 52 s, 30 s, and 20 s after the end of the procedure. After
the 20 s breath-hold, the subject reported slight dizziness. Figure 2
shows the decreasein oxygen saturation for 5 s, 10 s, and 15 s
breath-holdswith helium and oxygen.
Discussion
We have conducted a controlled study with rats using a variety
of breathing protocols, and with quantitative ventilation and
monitoring procedures. The results of this study have been
extendedto preliminary hmnan studies using breath-hold protocols
and similarphysiological monitoring procedures.The range of
oxygen saturation values that are considerednormal for young,
Proc. Intl. Sot. Mag. Reson. Med. 8 (2000)
healthy adults is 95-lOO%, and values below 90% are considered
clinically pathological[2].
We fmd that protocols employing alternating breaths of noble
gas and oxygen, delivered to rats for extended periods of time, do
not causean unsafe decreasein oxygen saturation, and can safely
be used for imaging in rats. Gur results show that the continuousbreaths protocol should not be employed, as the oxygen saturation
drops precipitously below 90% after only eight consecutive
breaths.We fmd that breath-hold protocols up to 25 s are safe for
use in rats; oxygen saturation does not fall below about 90% during
this protocol. It is important to note that during breath-hold
procedures,the oxygen saturation remains high, near baseline
values, but suddenly drops aftr the completion of the breath-hold.
The results for helium breath-holds precededby two helium rinses
indicate that breath-holds of 10 s and longer should not be
precededby pre-rinsesof a noble gas.
The results for the human studies suggestthat breath-holds
shorter than 20 s may be safe for healthy individuals. Similar to the
experimentswith animals, we found that the detectable drop in
oxygen saturation for 10 s to 20 s breath-holds occurs Tom 20 s to
60 s aftr the completion of the protocol. This time lag to the
induction of hypoxia, which was also observed in the animal
studies, indicates that monitoring the heart rate and oxygen
saturation,by themselves,to observe in real-time, that these levels
remain within a normal range coot be reliably used to determine
the maximum length for safe breath-hold. We are in the process of
investigating the health implications of this pattern and examining a
greater number of subjects. Further researchis necessaryto
identify safe breath-hold procedures for oatients with lung
functioning impairment.
Figure 1
References
1. E. Durand,et al. EuropeanRadiol. 9, B26 (1999).
2. J.B. West, PulmonaryPathophysiology:
the essentials,3rd edition.
Williams andWilkins, Baltimore(1987).