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Measuring Septal Wall Thickness Using Rapid 1D Hyperpolarized Xenon-129 CSSR Acquisitions
Kai Ruppert1, Yi Xin1, Faraz Amzajerdian1, Hooman Hamedani1, Luis Loza1, Tahmina Achekzai1, Ryan J. Baron1, Ian F. Duncan1, Harrilla Profka1, Sarmad Siddiqui1, Mehrdad Pourfathi1, Federico Sertic1, Maurizio F. Cereda2, and Rahim R. Rizi1

1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, United States

Synopsis

Septal wall thickness measurements using hyperpolarized xenon-129 MRI are sensitive to inflammatory or fibrotic pathologies but currently require multi-second breath-holds. We investigated the feasibility of sampling the recovery of the xenon dissolved-phase magnetization in the lung parenchyma in real time using a rapid 1D acquisition technique combined with periodic saturation of the xenon dissolved-phase magnetization, allowing us to extract the septal wall thickness during short breath holds or even in free-breathing rabbits. Our measurements indicate that the correlation between the derived septal wall thickness and the respiratory cycle are low enough to obtain consistent wall-thickness measurements in free-breathing, non-cooperative subjects.

Purpose

Septal wall thickness measurements obtained using hyperpolarized xenon-129 (HXe) Chemical Shift Saturation Recovery (CSSR) MR spectroscopy1-4 and imaging5-8 are sensitive to inflammatory or fibrotic pathologies in the lung parenchyma. However, these assessments currently require multi-second breath holds, making them unsuitable for use in uncooperative or severely diseased subjects. In addition, physiological variations throughout the breath hold, which may impact the resulting measurements, cannot be accounted for. Kern et al7 already proposed to sample the xenon dissolved-phase magnetization throughout recovery subsequent to saturation9. In this work, we advanced this approach by investigating the use of a rapid 1D HXe MRI technique that allows for real-time monitoring of xenon gas uptake, making it feasible to characterize septal wall thickness in free-breathing subjects. We evaluated the feasibility of this method in a rabbit model.

Methods

Imaging experiments were performed in sedated New Zealand rabbits (approx. 4 kg). Animals were ventilated with room air until imaging began, at which point the gas mix was switched to 20% oxygen and 80% HXe, either for 3 breaths (6 ml/kg tidal volume) followed by a 4-s breath-hold or for 8 breaths without breath-hold. All studies were approved by the Institutional Animal Care and Use Committee.

MR imaging was conducted using a 1D-projection gradient-echo sequence with left-to-right frequency encoding that employed a non-selective 700-ms Gaussian RF excitation pulse centered 3,530 Hz downfield from the gas-phase resonance. Taking advantage of the large frequency difference between the two phases combined with a sufficiently small acquisition bandwidth, HXe in the pulmonary air spaces and dissolved in the lung tissue were imaged simultaneously, side-by-side10. The following sequence parameters were used: matrix size 28×80; TE 2.6 ms; FOV 230 mm; receiver bandwidth 110 Hz/pixel; breath hold studies: flip angle 11°, TR 20 ms (TR90°,equiv 1.10 s)11; free breathing studies: flip angle 7°, TR 10 ms (TR90°,equiv 1.34 s)11. For the breath hold studies, the dissolved-phase magnetization was saturated every 25 TRs (0.5 s) with 2-ms frequency-selective Gaussian RF pulses centered at the dissolved-phase resonance. A more rapid saturation rate of every 20 TRs (0.2 s) was used for the free-breathing studies. Septal wall thickness was calculated using the analytical uptake model of Patz et al12 for each pixel in a left-right direction based on the recovery of the dissolved-phase signal following each saturation pulse. All MR studies were performed at 1.5T (Avanto; Siemens) using a custom xenon-129 transmit/receive birdcage coil (Stark Contrast, Erlangen, Germany). Enriched xenon gas (87% xenon-129) was polarized using a prototype commercial system (XeBox-E10, Xemed LLC, Durham, NH).

Results and Discussion

Figure 1 illustrates the temporal dynamics of the 1D signal projection during a breath hold study (unlike humans, only a single, broad dissolved-phase resonance is discernible in rabbits). The dark, equidistantly-spaced bands running across the dissolved-phase signal reflect the periodic saturation of the dissolved-phase magnetization. Figure 2 depicts the spatially-averaged dissolved-phase magnetization as a function of time. The magnetization drops rapidly at around 0.6 s when the first saturation pulse is applied, and recovers over the course of the next 0.5 s as fresh magnetization enters the parenchyma from the alveolar gas pool. Similarly, Fig. 3 shows the whole-lung dissolved-phase signal as a function of time in a free-breathing rabbit with the whole-lung gas-phase signal superimposed in red. The corresponding septal wall thickness for the left and right lung throughout the respiratory cycle are displayed in Fig. 4. While the wall thickness fluctuates throughout the measurement, it does not appear to be strongly correlated with respiration. However, the average wall thickness in the left lung in this animal was approximately 1.5 μm higher than in the right lung (12.9 ± 1.6 μm vs. 11.3 ± 0.8 μm). This difference seems to correspond to the lower gas-phase and dissolved-phase signal amplitudes in the left lung relative to the right lung, and was likely caused by a reduced inflation of the left lung. If the latter assessment is correct, some degree of correlation between wall thickness and the respiratory cycle would be expected. Future studies with wall measurements during extended xenon ventilation periods will address this question.

Conclusion

We demonstrated the implementation of a rapid 1D acquisition technique combined with periodic saturation of the xenon dissolved-phase magnetization within the lung parenchyma to conduct CSSR measurements in real time. The correlation between the derived septal wall thickness and the respiratory cycle appeared to be low enough to obtain consistent measurement values even in a free-breathing rabbit. Hence, septal wall thickness measurements seem feasible even in non-cooperative subjects.

Acknowledgements

Supported by NIH grants R01 EB015767, R01 HL129805, S10 OD018203 and R01 CA193050.

References

[1] Ruppert K et al. NMR of hyperpolarized 129Xe in the canine chest: spectral dynamics during a breath-hold. NMR Biomed 2000;13:220-228. [2] Butler JP et al. Measuring surface-area-to-volume ratios in soft porous materials using laser-polarized xenon interphase exchange nuclear magnetic resonance. J Phys Condens Matter 2002;14:L297-L304. [3] Qing et al. Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI. NMR in Biomed 2014;27(12):1490-1501. [4] Zhong et al. Simultaneous assessment of both lung morphometry and gas exchange function within a single breath‐hold by hyperpolarized 129Xe MRI. NMR in Biomed 2017 (epub). [5] Doganay et al. Quantification of regional early stage gas exchange changes using hyperpolarized 129Xe MRI in a rat model of radiation-induced lung injury. Med Phys 2016;43(5):2410-2420. [6] Kern et al. Regional investigation of lung function and microstructure 129Xe chemical shift saturation recovery parameters by localized and dissolved‐phase imaging: A reproducibility study. MRM 2018 (epub). [7] Kern et al. Mapping of regional lung microstructural parameters using 129 Xe dissolved‐phase MRI in healthy volunteers hyperpolarized and patients with chronic obstructive pulmonary disease. MRM 2018 (epub). [8] Zanette et al. Physiological gas exchange mapping of hyperpolarized 129Xe using spiral-IDEAL and MOXE in a model of regional radiation-induced lung injury. Med Phys 2018;45(2):803-816. [9] Look DC, Locker DR. Time saving in measurement of NMR and EPR relaxation times. Rev Sci Instrum 1970;41:250– 251. [10] Mugler et al. Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129. Proc Natl Acad Sci USA 2010;107(50):21707-21712. [11] Ruppert et al. Assessment of flip angle-TR equivalence for standardized dissolved-phase imaging of the lung with hyperpolarized 129Xe MRI. MRM 2018 (epub). [12] Patz et al. Diffusion of hyperpolarized 129Xe in the lung: a simplified model of 129Xe septal uptake and experimental results. New J Physics 2011;13:015009.

Figures

Figure 1. Characterization of the temporal xenon-129 signal dynamics in a 1D projection of a rabbit lung during breath hold. The measurement was performed with a left-to-right spatial resolution of 3 mm and a temporal resolution of 20 ms. The horizontal dark bands in the dissolved-phase signal indicate the application of dissolved-phase RF saturation pulses every 500 ms, while the gas-phase magnetization remained undisturbed.

Figure 2. Temporal dynamics of the total dissolved-phase (blue) signal as a function of time during a 4-s breath hold. The dissolved-phase magnetization was saturated every 500 ms and the subsequent recovery of the dissolved-phase signal was sampled with a temporal resolution of 20 ms to extract the septal wall thickness.

Figure 3. Temporal dynamics of the total gas-phase (red) and dissolved-phase (blue) signal as a function of time from a measurement in a free breathing rabbit. The dissolved-phase magnetization was saturated every 200 ms and the subsequent recovery of the dissolved-phase signal was sampled with a temporal resolution of 10 ms to extract the septal wall thickness.

Figure 4. Temporal dynamics of gas-phase signal (dashed lines) and septal wall thickness (solid) in the left and right lung of a free-breathing rabbit, derived from the measurement shown in Fig. 3. Once steady state had been reached after approximately 4-5 breaths, the septal wall thickness measurements stabilized and did not appear to be strongly correlated with respiration.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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