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Hyperpolarized Gas Image Acquisition

Although imaging of hyperpolarized gases uses conventional MRI scanners, the way in which the images are acquired and the associated workflow is quite different. Here are some key principles that make hyperpolarized gas imaging different from conventional methods.

  1. Multinuclear MRI upgrade to detect nuclei other than 1H
  2. Dedicated 129Xe or 3He transmit/receive coil and switch
  3. Breath-hold rapid imaging pulse sequences
  4. Pulse sequences to exploit the unique additional contrast mechanisms
  5. Image analysis methods to quantify regional function

Here, we briefly describe each of these attributes and how best to manage them. Polarean Imaging plc. scientists and engineers are always available to support customers in getting them up and running expeditiously.

Multinuclear MRI Scanner Upgrade

Most MRI scans done today detect the hydrogen nuclei ion our bodies (protons or 1H), but for hyperpolarized gas MRI, we detect either 3He or 129Xe nuclei. These stable inert isotopes exhibit a different resonance frequency than protons. At 1.5 Tesla, protons are detected at 63.8 MHz, whereas, 3He is detected at 48.6 MHz, and 129Xe is detected at 17.66 MHz. Thus, the MRI scanner must be extended to operate outside of just the normal proton frequency range. Such extension is straight-forward and is offered commercially by all major vendors for their research platforms. This so-called multinuclear or MNS package is also used for research applications involving the detection of other nuclei of interest such as 13C, 19F, 23Na, and 31P. The multinuclear package involves primarily upgrades to the exciter board and RF amplifier of the scanner, as well as dedicated software for pulse sequence development.

3He and 129Xe Transmit/Receive Coils

The heart and soul of MRI is the radio-frequency transmit receive coil used both to excite and detect the nucleus of interest. For conventional proton MRI, coils have been designed and optimized to image specific organs such as brain, heart, shoulder, wrist, knee, etc. Similarly, for hyperpolarized gas MRI, dedicated coils are also required. Most research to date has used a dedicated flexible chest coil that wraps around the chest much like a thin life vest. Work has also been done using a rigid birdcage design, which typically offers greater RF homogeneity, but at the price of slightly lower SNR. A critically important feature of all such coils is that they are “proton blocked” to enable anatomical images to be made using the built-in body coil of the scanner right before or after hyperpolarized gas MRI. Such anatomical images are often useful for image analysis. The proton-blocked multinuclear coils are interfaced to the MRI scanner through an interface known as the transmit/receive or T/R switch. An example of a flexible torso coil and T/R switch used for 129Xe MRI is shown in the figure. This coil is produced by Clinical MR Solutions, which has a long history of making exquisitely sensitive flexible coils for hyperpolarized gas MRI applications, and partners with Polarean Imaging plc. to solve customer’s coil requirements.

Rapid Breath-hold Imaging Pulse Sequences

Fast Gradient Echo Sequences

One area where hyperpolarized gas MRI differs dramatically from “conventional” MRI is the speed with which the image can be acquired. Whereas standard MRI scans can take many minutes, a hyperpolarized gas MRI image is completed in a single breath-hold. This means that the preferred pulse sequences for image acquisition are fast gradient echo sequences that use short echo times, fast repetition times and low flip angles to best consume the hyperpolarized magnetization during the breath-hold. Such sequences have been developed and optimized for all major scanner vendors by their leading research sites and are generally shared within the research community. It is often advantageous to couple these breath-hold hyperpolarized gas MRI scans with a breath-hold anatomical scan that delineates the thoracic cavity for analysis. These sequences are already available on any scanner. Below is an example 129Xe MRI data set from a lung transplant patient with poor ventilation to the right middle and lower lobes due to limited patency of the bronchus intermedius. This ventilation deficit is readily perceived through the grey-scale 129Xe ventilation images, but is even more straight-forward to appreciate when this image is registered to the anatomical scan and quantified by linear binning thresholds. (Courtesy, Mu He, Duke University).

Undersampled 3D Radial Sequences

As efficient and simple as multi-slice 2D gradient echo images are for visualizing regional ventilation, there is an enormous opportunity to achieve fully 3D isotropic images. Such an approach has the advantage of enabling images to be visualized in any plane, which can be useful for surgical planning or registering the images to other modalities like CT, SPECT or PET. Hyperpolarized gas imaging provides unique opportunities for 3D undersampled acquisition because the lung image is inherently sparse, and thus is readily amenable to such accelerated acquisitions. Below is an example data set courtesy of Duke University that shows 3D images reconstructed in all three image planes.

Exploiting Other Contrast Mechanisms

One of the truly powerful aspects of MRI is the wide range of soft-tissue contrast that it can provide. This range of contrast is no less wide for hyperpolarized gas MRI, and a large body of research has begun to exploit the unique properties of the gases. Several contrast mechanisms have been developed to specifically exploit the gas-phase properties of 3He and 129Xe to highlight particular types of physiology. They include:

  1. Dynamic acquisition – Images are taken in rapid succession during inspiration and exhalation to observe slow filling compartments and or gas trapping upon exhalation.
  2. Diffusion-Weighted Acquisition – Diffusion-weighting contrast enables us to measure how normal lung architecture restricts the motion of inert gas atoms. However, when conditions like emphysema destroy lung microstructure, the gas atoms become more mobile within the distal lung and this mobility is readily detected on diffusion-weighted imaging.
  3. Long-Range Diffusion Weighted Acquisition – More recently, techniques have been developed to observe the long-range diffusion of inert gases. These techniques are particularly intriguing because they appear to reveal gas transport by “collateral pathways” that circumvent the conventional lung architecture to communicate between adjacent lung units.
  4. Oxygen-Weighted Hyperpolarized Gas MRI – Regional measurements of 129Xe or 3He signal loss over time are caused by the presence of paramagnetic oxygen. By carefully monitoring such signal loss it is possible measure not only local oxygen concentration, but also its depletion from the lung airspaces, to provide a measure of pulmonary gas exchange.
  5. 129Xe Gas Transfer and Chemical Shift Imaging – Arguably, the most interesting and powerful contrast mechanisms now emerging are those exploiting the solubility of 129Xe in tissues and fluids and the accompanying frequency shifts. Exploiting these properties is likely to be a major area of research focus and clinical opportunity in the coming years. Some recent applications are discussed below.

129Xe Transfer Imaging

The most common applications of hyperpolarized gases are to visualize their 3-dimensional distribution within the lung’s airspaces to report on regional ventilation. But 129Xe has far more to report. Upon reaching the distal alveoli, 129Xe diffuses across the blood gas-barrier and into the red blood cells moving through the capillary beds. But more importantly, when 129Xe enters these compartments its detection frequency shifts dramatically away from the frequency of 129Xe remaining in the airspaces. In fact, 129Xe exhibits a unique detection frequency in both interstitial barrier space and when it interacts with red blood cells (see figure).

Although the 129Xe signal in red blood cells at any given instant represent only a small fraction of the 129Xe, this compartment is in rapid diffuse exchange with the gas in the alveolar compartment. Hence it becomes possible to produce high-quality images of 129Xe as it transfers across the blood gas barrier and into the pulmonary blood. Such gas transfer imaging has the potential to serve as a powerful probe to detect and monitor interstitial lung diseases. (Image courtesy Sivaram Kaushik, Duke University).

Quantitative Image Analysis

A critically important aspect of all pulmonary functional imaging, is not just to sensitively image regional function, but to translate those functional images into truly quantitative information. By quantifying the images, we have the ability to better detect early disease, but perhaps more importantly, observe changes over time in response to disease progression or therapy response. In this regard, significant research has been developed to integrate both the structural 1H images and functional 3He and 129Xe images, to generate quantitative maps of pulmonary ventilation. The approach exploits co-registration of the anatomical and functional image, and rescaling the image histograms such that basic thresholds can be developed to identify regions of absent ventilation, hypoventilation, normal, and hyper ventilation. The workflow is shown below (Courtesy Mu He, Duke University).

Such analysis methods now make it straightforward to quickly identify and quantify different degrees of pulmonary ventilation in health and disease as well as over time.

Integrated 1H and 129Xe Structural/Functional Imaging Protocols

The advent of hyperpolarized gas MRI technology provides the missing link to enable magnetic resonance to play a pivotal role in the diagnosis and management of pulmonary disease. Significant progress has been made in recent years to improve the quality of structural MRI of the lung via ultra-short-echo time (UTE) imaging, as well as perfusion imaging using rapid acquisitions after intravenous contrast injection. These methods, in combination with hyperpolarized gas imaging of pulmonary ventilation, microstructure, and gas exchange now truly position MRI as the modality of choice for studying the lung.