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What Diseases & Therapeutics Can Be Studied?

During the past two decades, Hyperpolarized Gas MRI technology has been used in research settings to detect and monitor lung disease, and to assess the performance of pulmonary therapeutics. Hyperpolarized Gas MRI technology is useful in these applications for the following four reasons:

  1. Hyperpolarized gas MR imaging allows the quantification of several structural/functional components of the lung. The most established of these biomarkers are the ventilation defect percentage, and the apparent diffusion coefficient (ADC) that reports on airspace enlargement.
  2. Hyperpolarized Gas MRI technology is unique in its ability to visualize the small airways and pulmonary gas exchange regions of the lung. By imaging lung function as well as lung structure, HP Xe MRI provides a unique way to assess the pathology of the distal pulmonary spaces where disease originates. HP Xe MRI detects xenon that has successfully traversed all 23 branches of human lung to reach the gas exchange tissues. By comparison, a CT scan, even with its exquisite spatial resolution, can visualize only the first six airway branches. It is this significantly greater regional functional information provided by HP Xe MRI that is so important to detecting early disease and monitoring it over time.
  3. One of the main strengths of Hyperpolarized Gas MRI is in its ability to safely evaluate lung function longitudinally, without ionizing radiation. This is of particular importance for pediatric patients where the risk of cancer induced by repeated medical radiation from CT scans is thought to be of importance.
  4. An emerging and exciting area of research interest is driven by the solubility of 129Xe and its associated shift in detection frequency when it diffuses from the airspaces and dissolves into pulmonary blood and tissues. Once fully developed, the ability to visualize gas transfer into red blood cells opens a broader set of diseases or disease phenotypes that can be studied by HP 129Xe MRI. The most significant of these are pulmonary hypertension and interstitial lung diseases.

Hyperpolarized Gas MRI has been used to study a number of disease areas, as well as interventional procedures and therapeutic compounds to treat those diseases. These investigational studies include:

Chronic Obstructive Pulmonary Disease (COPD):
  1. HP Gas MRI has been used to observe and quantify functional ventilatory changes of patients with COPD (undetectable by CT), and to provide a quantitative determination of emphysematous damage.
  2. HP Gas ADC also has been use to evaluate reductions in regional gas trapping following treatment in COPD patients.
  3. HP Gas ventilation imaging shows regional response to bronchodilator administration, even as pulmonary function testing fails to detect changes.
  4. HP gas MRI has been used to show delayed filling of distal lung units by collateral pathways.
Cystic Fibrosis:
  • Dramatic improvements in gas distribution were visualized in children with CF following treatment with Ivacaftor, the first investigation to use HP Gas MRI to demonstrate efficacy.
  • HP Gas MRI demonstrated that ventilation defect measurements changed significantly, without any change in therapy, and these changes could not always be detected using spirometry.
  • Photo courtesy of Dr. Tallissa Altes, University of Virginia.
  • HP Gas MRI detected the movement of mucus plugs and subsequent alterations of airway patency that is not uncommon in patients with CF over short periods of time before changes in standard measures of lung function could be detected.
  • HP Gas MRI has demonstrated regional changes in gas distribution in children following chest physiotherapy, following treatment with a bronchodilator and after mechanical airway clearance treatment.
Asthma:
  • HP Gas MRI in asthmatics also demonstrated ventilation defects and showed that these defects increased in number and extent following an exercise challenge and methacholine administration.
  • HP Gas MRI has been used to guide smooth muscle ablation treatments in asthma, to identify large sub-segmental and even segmental ventilation defects in asthmatics,many before symptoms appear.
  • Another recent HP Gas MRI study showed that the ADC was increased post-methacholine compared to postsalbutamol in the gravity-dependent lung slices, suggesting that the ADC gravity-dependent gradient of lung expansion (ADC anterior-posterior (AP) gradient) detected regional gas trapping following methacholine inhalation.
Stent placement:
  • HP Gas MRI has been used to evaluate the effectiveness of bronchial stents in improving ventilation COPD patients
Radiotherapy:
  • HP Gas MRI has been used to guide so-called “dose painting” in radiotherapy treatment planning.
  • Response to therapy, including radiation-induced lung injury or inflammation (RILI) has also been monitored by HP Gas MRI.