Brandon Zanette1, Samal Munidasa1,2, Yonni Friedlander1,2, Felix Ratjen1,3, and Giles Santyr1,2
1Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada, 2Medical Biophysics, University of Toronto, Toronto, ON, Canada, 3Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
Synopsis
A rapid 3D stack-of-spirals (3D-SoS) sequence was used for hyperpolarized 129Xe ventilation imaging in pediatric cystic fibrosis and healthy controls, allowing for 5x reduction in scan duration and breath-hold compared to a commonly used 2D gradient echo (2D-GRE) sequence. The ventilation defect percent (VDP) measured with 3D-SoS was not significantly different from VDP measured with 2D-GRE. Additionally, the transient drop in SpO2 associated with xenon breath-holds was reduced with the shorter breath-hold afforded by 3D-SoS. In future, the reduced acquisitions durations offered by 3D-SoS may allow for improved tolerability, or may be traded for improved resolutions.
Introduction
MRI
with hyperpolarized (HP) 129Xe gas is a promising approach for
imaging pediatric cystic fibrosis (CF). Previous work has shown HP 129Xe
MRI to be safe, reproducible, and sensitive to early disease and treatment1–4. Xenon in the airspaces is
typically evaluated with slice-selective 2D gradient recalled echo (2D-GRE)
acquisitions yielding measures of ventilation defect percent (VDP). Though
widely adopted for 129Xe MRI, 2D-GRE scans typically require
breath-hold durations of 8-12 seconds5, and usually no longer than 16 seconds,
due to the Cartesian nature of k-space acquisition. Such breath-holds may be
increasingly difficult for subjects to perform, especially for very sick and/or
younger patients.
Non-Cartesian
image acquisitions such as spirals acquire k-space data more efficiently per
excitation, reducing overall scan duration, presenting a faster alternative
to standard GRE imaging6. More recently, spiral-based
acquisitions have enabled dynamic 129Xe ventilation acquisitions7,8 or 3D isotropic imaging9. Nevertheless, these methods
generally remain underutilized for this application. Previously, our group
demonstrated preliminary 129Xe ventilation data using a fast 3D
stack-of-spirals (3D-SoS) acquisition compared to typical 2D-GRE. However, this was limited to a small number of healthy adult
participants10.
In
this study we present a similar HP 129Xe imaging comparison using
the same 3D-SoS sequence in a group of healthy control and stable CF pediatric
participants.Methods
Thirteen
pediatric participants were imaged with informed consent under institutional
and Health Canada approval. Of these, 5 were healthy controls (2M, 3F, ages=13.8±2.2
years) and 8 were CF participants (3M, 5F, ages=15.4±1.6 years). Imaging was
performed on a clinical 3T MRI system (Siemens Prisma, Erlangen, Germany). HP 129Xe
MRI was performed with a flexible transmit/receive vest coil (Clinical MR
Solutions, Brookfield, WI). 129Xe was polarized to 28.5±2.7% (9820,
Polarean, Durham, NC). Both naturally abundant and isotopically enriched (~85% 129Xe)
sources of xenon were used. Xenon was dosed to 10% of total lung capacity (TLC)
calculated based on height and sex11, then balanced with N2 bringing
the total inhaled volume to 1/6 TLC. 2D-GRE imaging was performed with acquisition
parameters adherent to guidelines recently suggested by the Xenon MRI Clinical Trials
Consortium (XeMRI-CTC)5. The acquisition time ranged from
6.2-8.8 seconds depending on the number of slices required (10-14 slices). Previously described 3D-SoS imaging10 was performed in the same participants with
acquisition times ranging from 1.2-1.8 seconds. Detailed imaging parameters for
both sequences are found in Table 1. 2D-GRE and 3D-SoS datasets were acquired
with individual breath-holds of xenon. The transient SpO2 drop (lowest value within two
minutes post-inhalation) was expressed as a percent change relative to the SpO2
immediately after inhalation.
3D-SoS
images were reconstructed using a non-uniform FFT12, and both 2D-GRE and 3D-SoS were
interpolated to a resolution of 2×2×15mm3. 129Xe images
were bias corrected and registered to the segmented 1H thoracic
cavity mask. Defect regions were identified as voxels with signal intensity
less than 60% of the whole-lung mean11. Linear regression and
Bland-Altman analysis were used to compare VDP measures between acquisitions. Results
Representative
ventilation images for both acquisitions are shown for a healthy and CF participant
(Figures 1 and 2, respectively). Figure 3 shows VDP analysis and defect cluster
mapping for a representative CF participant for both acquisitions. 2D-GRE and
3D-SoS VDPs were 5.02±1.06% and 5.28±1.08% respectively for healthy
participants, and 18.05±8.26% and 18.75±6.74% respectively for CF participants.
The VDPs measured with 2D-GRE and 3D-SoS were not significantly different in
either the healthy or CF groups (p>0.05). Both 2D-GRE and 3D-SoS VDPs were
able to differentiate between healthy and CF participants (p<0.01 and p<0.001
respectively). Linear regression of 3D-SoS VDP against 2D-GRE VDP is shown in
Figure 4a. Bland-Altman analysis of these VDP measures is shown in Figure 4b. The percent change in SpO2
was reduced (p<0.05) between 2D-GRE and 3D-SoS breath-holds (−5.2±3.5% and −2.1±2.7%
respectively).Discussion
In
this work we present an alternative 3D-SoS approach to typical 2D-GRE
acquisitions for HP 129Xe MRI in pediatric
participants that is approximately 5× faster. The transient SpO2 drop associated with xenon
inhalation was reduced with the shorter 3D-SoS breath-hold, suggesting
improved tolerability. Ventilation defect patterns were observed to be
very similar between acquisitions (Figure 3). Quantitative comparison of VDP
analysis between 2D-GRE and 3D-SoS shows good agreement between the two approaches.
Linear regression indicates 3D-SoS VDP is highly linearly correlated with
2D-GRE VDP. Bland-Altman analysis shows a low bias between measures (<1%)
and a reasonably low variability. Most of the variability observed was related
to registration of 129Xe data to 1H thoracic cavity masks,
likely due to each dataset requiring separate breath-holds.
Improvements to the image registration, or the acquisition of 129Xe/1H
data within the same breath-hold (leveraging the speed of non-Cartesian
approaches) should help mitigate this source of variability in the future. Nevertheless,
these results are comparable to previously reported intrascan reproducibility in a similar
population (Bias=-0.04, 95% Limits of Agreement=[-3.10, 3.03])3.
Conclusion
In conclusion, VDP values measured with 3D-SoS were acquired faster and were not significantly different from those measured with 2D-GRE, indicating potential for more widespread adoption for 129Xe MRI. The reductions in scan duration affords the flexibility to prioritize speed/tolerability (as is the case here), trade-off for improved resolution, or perform multiple imaging acquisitions in the same breath-hold.Acknowledgements
The
authors thank Jacky Au, Sharon Braganza, Daniel Li, Leslie Burns, Tammy Rayner,
and Ruth Weiss for assistance with imaging experiments. This work was supported
by CIHR project PJT-1530399 and the Cystic Fibrosis Foundation.References
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