Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT04537611 |
Other study ID # |
20-5598 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
August 2021 |
Est. completion date |
March 2022 |
Study information
Verified date |
April 2021 |
Source |
University Health Network, Toronto |
Contact |
Joseph Fisher |
Phone |
416-710-6908 |
Email |
joe.fisher[@]utoronto.ca |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
To investigate a new method to rapidly modulate pulmonary venous hemoglobin oxygen saturation
to enable the use of deoxyhemoglobin concentration in arterial blood as an intra-arterial MRI
contrast agent for cerebral tissue perfusion imaging.
Description:
Cerebral tissue perfusion can be examined by tracking a tracer through the cerebral
vasculature. Currently, This requires an infusion of the contrast agent. However,
advancements have been made in developing non-invasive imaging techniques to evaluate tissue
perfusion. Magnetic resonance imaging (MRI) is a highly attractive imaging approach as it
does not rely on ionizing radiation and has high spatial resolution. The common contrast
agent used to study cerebral tissue perfusion in MRI is gadolinium-based contrast agents.
However, these contrast agents tend to have several disadvantages including invasiveness,
renal toxicity, tissue accumulation, and allergic reactions. As they are injected
intravenously, they become highly dispersed in the arteries, requiring a complex computation
of the arterial input function. In addition, although they remain predominantly
intravascular, they tend to diffuse extravascular in neurovascular conditions which have a
breakdown of the blood brain barrier leading to measurement inaccuracies.
Recently we have determined a way to generate an abrupt change in deoxyhemoglobin
concentration [dHb] as the blood passes the lungs, resulting in a precise and rapid targeted
change of [dHb] in the arterial blood. We hypothesize that such changes in [dHb] may be used
as a suitable MRI contrast agent for the measurement of cerebral blood flow, cerebral blood
volume, and mean transit time (CBF, CBV and MTT respecrively) in comparison to that with
gadolinium. If suitable, dOHb would provide a non-invasive, inexpensive, and safe alternative
to perfusion imaging.
A total of 25 patients with neurovascular disease who are clinically referred to the TWH
Joint Department of Medical Imaging for gadolinium perfusion imaging will be recruited. Prior
to the imaging study each subject will be familiarized with the respiratory gas control
experimental setup. A plastic face mask and breathing circuit will be applied to the
subject's face and fitted to form an airtight seal with medical adhesive tape. Gas supply to
the mask and breathing circuit will be supplied by a programmable computer-controlled gas
delivery system (RespirActâ„¢ RA-MR System, Thornhill Research Inc., Toronto, Canada). The
sequence of gas delivery and changes in PCO2 and PO2 will be applied to familiarize the
subject with the sensations related to changes in the gases. Subjects will then be placed
supine in the MRI scanner. In addition to their prescribed clinical scans, two additional
scans will be obtained. The additional MRI scans will include: 1) a structural (anatomical)
sequence (4.30 minutes), followed by 2) a BOLD-EPI sequence while inducing changes of PO2.
PO2 will be held at a baseline of 45-50 mmHg (hemoglobin O2 saturation, SaO2 ~75%) for 60s.
For 10 s, the lung PO2 will be transiently raised to peak PO2 of 90-120 mmHg (normoxia)
within 2 s transition, reaching a SaO2 of ~100%, and then returned to baseline.
Alternatively, the baseline may be at normoxia and the gas challenges will target PO2 of
45-50 mmHg. A total of 4 such ventilatory challenges will be applied over 6 min while
maintaining normocapnia.
During each PO2 stimulus, the BOLD signal will change in synchrony and inverse proportion to
[dOHb]. An arterial input function will be measured by separating arterial, tissue, and
venous voxels based on differences in [dOHb] bolus arrival times, amplitude of change, and
correlation to changes in [dOHb] measured from [Hb] and calculation of SaO2 from end-tidal
PO2. Arterial voxels, the first in the sequence of structures to receive the bolus, will be
averaged to yield an arterial input function that will be deconvolved with the tissue signal.
Whole brain maps of relative CBF, CBV, and MTT will be generated. Whole brain segmented gray
matter and white matter average values for these metrics will be calculated and compared
against the same metric values obtained using gadolinium perfusion imaging.