Ziyi Wang1, Leith Rankine2, Joseph Mammarappallil3, Sudarshan Rajagopal4, and Bastiaan Driehuys1,2,3
1Biomedical Engineering, Duke University, Durham, NC, United States, 2Medical Physics Graduate Program, Duke University, Durham, NC, United States, 3Radiology, Duke University Medical Center, Durham, NC, United States, 4Division of Cardiology, Duke University Medical Center, Durham, NC, United States
Synopsis
Hyperpolarized 129Xe MRI is emerging as a unique means of
imaging pulmonary gas exchange, enabling separate 3D encoding of 129Xe
in the gas-phase, interstitial barrier, and red blood cells (RBC). In patients
where diffusion limitation is not significant, defects in RBC
transfer and perfusion deficits should more closely reflect diminished
capillary blood volume or perfusion limitation. Here we establish an initial
approach to correlate RBC transfer images against an accepted perfusion imaging
reference— 99mTc scintigraphy. We demonstrate in patients with
pulmonary arterial hypertension and COPD that RBC transfer projections compare
both qualitatively and quantitatively with 99mTc scintigraphy.
INTRODUCTION
Hyperpolarized 129Xe MRI is emerging as a unique means to
image pulmonary gas exchange. 1 Its solubility and distinct chemical shift make it possible to
produce separate 3D images of ventilation, interstitial barrier uptake and red
blood cell (RBC) transfer in a single breath. 1, 2 This capability has
already provided unique insights in COPD, asthma, and interstitial lung
disease. However, the unique nature of 129Xe gas exchange MRI also
complicates its technical validation. While the global ratio of RBC:barrier correlates
strongly with DLCO, 3 there is no gold standard
for regionally resolved barrier uptake or RBC transfer. However, in the absence
of diffusion limitation, 4 regionally impaired
RBC transfer should more closely reflect diminished capillary blood volume or
perfusion limitation. 5 This provides a
potential means to perform validation of RBC transfer images against an
accepted perfusion imaging standard — 99mTc scintigraphy. As an
initial test of this idea we sought to evaluate regional correlation between RBC
transfer MRI and 99mTc perfusion scintigraphy in a cohort of
patients with pulmonary vascular disease and COPD.METHODS
The study enrolled 4 patients with type-1 PAH, one type-4 patient with
chronic thromboembolic disease (CTEPH) and one patient with COPD. All had a
routine 99mTc perfusion scan (140keV). All underwent 129Xe
gas exchange MRI after inhaling a dose of ~110ml 129Xe on a 3T SIEMENS
MAGNETOM Trio. The acquisition used an interleaved 1-point Dixon method as
described previously to decompose the images of the 3 compartments. 1 Briefly, the dissolved-
and gas-phase 129Xe signals were alternately encoded using a 0.69ms,
1-lobe sinc pulse, flip-angles = 0.5/20°, TR/TE = 7.5ms/TE90, FOV = 36cm3,
1000 views with 64 points, and bandwidth = 399Hz/sample. The 3D RBC image was
then divided by the gas-phase image to calculate RBC transfer. To depict RBC
transfer in the same format as 99mTc perfusion scintigraphy, the
standard 8 projections were produced as follows: we emulated attenuation from
lung parenchyma and body tissue as well as distance-dependent emission solid
angle that affects scintigraphy. Each
pixel was then weight for the 2 effects according to its position relative to
the chest walls, using a registered proton MRI (Figure 1). The resulting
projections were qualitatively compared between the two modalities. They were also
compared quantitatively with the clinical 6-zone analysis to derive the
relative function contributed by each zone on a coronal projection (Figure 4(a)). 6 For perfusion
scintigraphy, this projection was the geometric mean of the coronal and
anterior views. For RBC transfer it was the mean of the original 3D volume. For
each modality, the lungs were manually divided into 6 zones and its relative functional
fraction was calculated by the sum of pixel intensities relative to the whole
lung. For each patient the Pearson correlation coefficient was calculated for
the 6 zones, and P-values were generated to test the null hypothesis of no correlation (P<0.05 significant).RESULTS
Figure 2 shows the 129Xe gas exchange images from the CTEPH
patient, processed as previously described. 2 For this patient, Figure
3 compares the perfusion scintigraphy and RBC transfer projections. Note the
RBC projections are intensity-reversed to match the scintigraphy display format.
Qualitatively, both modalities delineate regions of high and low intensity in
similar ways (red arrows). Figure 4(b) shows the 6-zone analysis. Each patient
showed a significant correlation, ranging from 0.81 to 0.95.DISCUSSION
Perfusion scintigraphy is routinely used to evaluate patients with
pulmonary vascular disease as well as COPD patients (for transplant). This
provided a unique opportunity to conduct initial validation of RBC transfer
imaging using an accepted imaging standard. This was done on a quantitative and
spatially resolved basis by using the clinical 6-zone analysis that is
routinely used to plan surgical procedures. The relatively strong qualitative
and quantitative agreement between RBC transfer and scintigraphy in this cohort
suggests that in certain patient populations RBC transfer simply reflects
capillary-level perfusion. However, it should be noted that the delivery for
RBC transfer is by inhalation, not injection, thus defects can also be caused
by diffusion limitation, such as in interstitial lung disease. This provides a
second unique aspect to 129Xe gas exchange MRI not correlated to
conventional perfusion scintigraphy, and must be carefully considered in future
studies. Moreover, the higher resolution of 129Xe MRI provides opportunities
for clear 3D isotropic visualization that may ultimately allow for more
sophisticated surgical planning. In summary, we demonstrated a workflow that
enables 129Xe MRI derived RBC transfer images to be compared to 99mTc
perfusion scintigraphy, qualitatively and quantitatively, as a step towards
validating this unique method.Acknowledgements
R01HL126771,
R01HL105643, HHSN268201700001C, P41 EB015897References
- Kaushik,
S.S., et al., Single-breath clinical
imaging of hyperpolarized (129)Xe in the airspaces, barrier, and red blood
cells using an interleaved 3D radial 1-point Dixon acquisition. Magn Reson
Med, 2016. 75(4): p. 1434-43.
- Wang, Z., et al., Quantitative analysis of hyperpolarized 129
Xe gas transfer MRI. Med Phys, 2017. 44(6):
p. 2415-2428.
- Wang, J.M., et al., Using hyperpolarized 129Xe MRI to quantify
regional gas transfer in idiopathic pulmonary fibrosis. Thorax, 2017.
- Kaushik, S.S., et al., Measuring diffusion limitation with a
perfusion-limited gas--hyperpolarized 129Xe gas-transfer spectroscopy in
patients with idiopathic pulmonary fibrosis. J Appl Physiol (1985), 2014. 117(6): p. 577-85.
- Barst, R.J., et al., Diagnosis and differential assessment of
pulmonary arterial hypertension. J Am Coll Cardiol, 2004. 43(12 Suppl S): p. 40S-47S.
- Ball, W.C., Jr., et al., Regional pulmonary function studied with
xenon 133. J Clin Invest, 1962. 41:
p. 519-31.
- International Commission on
Radiation Units and Measurements., Tissue
substitutes in radiation dosimetry and measurement. ICRU report. 1989,
Bethesda, Md., U.S.A.: International Commission on Radiation Units and
Measurements. vii, 189 p.