Quantitative Spectral Contrast in Hyperpolarized 129Xe Pulmonary MRI

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Robertson, Scott Haile


Driehuys, Bastiaan

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Hyperpolarized (HP) 129Xe MRI has emerged as a viable tool for evaluating lung function without ionizing radiation. HP 129Xe has already been used to image ventilation and quantify ventilation defects. However, this thesis aims to further develop imaging techniques that are capable of imaging, not just ventilation, but also gas transfer within the lung. This ability to image gas transfer directly is enabled by the solubility and chemical shifts of 129Xe that provide separate MR signatures in the airspaces, barrier tissue, and red blood cells (RBCs).

While 129Xe in the airspace (referred to as gas-phase 129Xe) can be readily imaged with standard vendor-provided imaging sequences, 129Xe in the barrier and RBC compartments (collectively referred to as dissolved-phase 129Xe) has such a rapid T2* (<2 msec at 2T) that even simple gradient recalled echo (GRE) sequences are ineffective at imaging the limited signal before it decays. To minimize these losses from T2* decay, the 3D radial sequence offers much shorter TEs that can image the dissolved-phase 129Xe. Despite their ability to image dissolved-phase signal, however, 3D radial sequences have not yet been widely adopted within the hyperpolarized gas community. In order to demonstrate the potential of the 3D radial pulse sequence, chapter 3 uses standard 129Xe ventilation imaging to compare 3D radial image quality and defect conspicuity with that of the conventional GRE. Since the 3D radial sequence offered comparable performance in ventilation imaging, and also provided the ability to image dissolved-phase 129Xe, chapter 3 establishes that the 3D radial sequence is well-suited for imaging 129Xe in humans.

Though 3D radial acquisition offers clear advantages for functional 129Xe lung imaging, its non-Cartesian sampling of k-space complicates image reconstruction. Chapter 4 carefully explains the process of gridding-based reconstruction, and describes how problems arising from non-selective RF pulses and undersampling, both of which are commonly employed in hyperpolarized 129Xe imaging, can be avoided by using appropriate reconstruction techniques. Furthermore, we detail a generalized procedure to optimize reconstruction parameters, then demonstrate the benefits of our improved reconstruction methods across both 1H anatomical imaging as well as functional imaging of 129Xe in the gas- and dissolved-phases.

These dissolved-phase images are particularly interesting because they consist of separate contributions from 129Xe in the RBCs and barrier tissue. Once these two resonances are disentangled from one another, they provide a noninvasive means to measure gas exchange regionally. However, such decomposition of these two resonances is predicated on prior knowledge of their spectroscopic properties. To that end, chapter 5 describes a non-linear spectroscopic curve fitting toolbox that we developed to more accurately characterize the 129Xe spectrum in vivo. Though previously, only two dissolved-phase resonances have ever been described within the lung, our fitting tools were able to identify a third dissolved-phase resonance in both healthy volunteers and healthy controls. Furthermore, we describe several spectroscopic features that differ statistically between our healthy volunteers and IPF subjects to demonstrate that this technique is sensitive to even subtle functional changes within the lung. These spectroscopic measurements provide the basis for imaging gas transfer.

Describing lung function regionally requires phase-sensitive imaging techniques that can decompose the dissolved-phase signal into images that represent the contribution from the RBC and barrier resonances. To date, only two implementations have been demonstrated, and both suffered from poor SNR and challenges in quantifying gas transfer. Chapter 6 adds quantitative processing techniques that improve phase sensitive imaging of 129Xe gas transfer. These methods 1) normalize both the RBC and barrier uptake images by gas-phase magnetization so that intensities can be compared across subjects, 2) compress the dynamic range of these functional images to enhance their perceived SNR, and 3) derive colormap thresholds from a healthy reference population to give intensities meaningful context.

To show the value of our quantitative gas transfer imaging, chapter 7 applies these techniques to a cohort of healthy volunteers and another of IPF patients. Since patients with IPF exhibit a progressive thickening and hardening of the pulmonary interstitium that severely restricts the transport of gases between the lungs and blood, they represent an ideal population to prove out our methods. This analysis identifies several patterns to the RBC and barrier distributions which could potentially represent different stages of disease. Furthermore, we demonstrate that our MRI-based findings correlate well with DLCO and FVC, and to a lesser extent with the structural cues seen in CT. This suggests that 129Xe imaging offers complimentary functional information that can’t be derived from CT, while also describing its spatial distribution unlike PFTs.

The work in this thesis has transitioned our HP 129Xe gas transfer studies from a proof of concept to an optimized and quantitative imaging protocol with robust processing pipelines. Using these MRI methods, we have shown that we can directly and quantitatively probe pulmonary ventilation and gas transfer within a single breath hold. In IPF, such noninvasive imaging methods are desperately needed to monitor the efficacy of these new treatments to ensure that the associated medical expense is justified with positive changes in outcomes. Finally, these new functional contrasts will be useful in studying other cardiopulmonary diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension.





Robertson, Scott Haile (2016). Quantitative Spectral Contrast in Hyperpolarized 129Xe Pulmonary MRI. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/13406.


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