Hyperpolarized Noble Gas MRI Detection of Radiation-Induced Lung Injury

Summary

Lung cancer is the leading cause of cancer death in the world; each year lung cancer claims over 20 000 lives in Canada and more than one million lives globally (1). Significant improvements have been made in treating many other types of cancer, but lung cancer care has not realized similar successes. Seventy percent of cancers are at an advanced stage at diagnosis, and radiation plays a standard role as a part of both radical and palliative therapy in these cases. Normal lung tissue is highly sensitive to radiation. This sensitivity poses a serious problem; it can cause radiation pneumonitis or fibrosis (RILI), which may result in serious disability and sometimes death. Thirty-seven percent of thoracic cancer patients treated with radiation develop RILI; in 20% of radiation therapy cases, injury to the lungs is moderate to severe (2). In addition, radiation-induced pneumonitis that produces symptoms occurs in 5-50% of individuals given radiotherapy for lung cancer (3, 4).

The chances of clinical radiation pneumonitis are directly related to the irradiated volume of lung (5). However, radiation planning currently assumes that all parts of the lung are equally functional. Identification of the areas of the lung that are more functional would be beneficial in order to prioritize those areas for sparing during radiation planning. In order to limit the amount of RILI to preserve lung function in patients, clinicians plan radiation treatment using conformal or intensity-modulated radiotherapy (IMRT). This makes use of computed tomography (CT) scans, which take into account anatomic locations of both disease and lung but cannot assess the functionality of the lung itself. An important component of the rationale of IMRT is that if doses of radiation entering functional tissue are constrained, radiation dose can be focused on tumours to spare functional tissues from injury to preserve existing lung function (6). Therefore, to optimally reduce toxicity, IMRT would depend on data of not only tumour location, but also regional lung function.

Pulmonary function tests (PFTs) can detect a decrease in pulmonary function due to the presence of tumours or RILI, but because the measurements are performed at the mouth, PFTs do not provide regional information on lung function. Positron emission tomography (PET) imaging may be used for radiation planning, but PET is limited in its ability to delineate functional tissue, it requires administration of a radiopharmaceutical agent, it is a slow modality, and, because it requires use of a cyclotron, it is expensive. Single-photon emission computed tomography (SPECT) imaging to measure pulmonary perfusion as a means for delineating functional tissue has been explored (7-11). Whereas SPECT can detect non-functional tissue, it offers spatial resolution that is only half that of CT or PET, and it does not possess the anatomical resolution necessary for optimal use with IMRT. Furthermore, like PET, SPECT is a slow modality. Given the limitations of existing imaging modalities, there is an urgent unmet medical need for an imaging modality that can provide complimentary data on regional lung function quickly and non-invasively, and that will limit tissue toxicity in radiotherapy for non-small cell lung cancer (NSCLC).

Hyperpolarized (HP) gas magnetic resonance imaging (MRI) has the potential to fill this unmet need. HP gas MRI, uses HP xenon-129 (129Xe) to provide non-invasive, high resolution imaging without the need for ionizing radiation, paramagnetic, or iodinated chemical contrast agents. HP gas MRI offers the tremendous advantages of quickly providing high-resolution information on the lungs that is noninvasive, direct, functional, and regional. Conventional MRI typically detects the hydrogen (1H) nucleus, which presents limitations for lung imaging due to lack of water molecules in the lungs. HP gas MRI detects 129Xe nuclei, which are polarized using spin-exchange optical pumping (SEOP) technique to increase their effective MR signal intensity by approximately 100,000 times. HP gas MRI has already been widely successful for pulmonary imaging, providing high-resolution imaging information on lung structure, ventilation function, and air-exchange function. The technology has proven useful for imaging asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, and for assessing the efficacy of therapeutics for these diseases (12 -21). In this project, the investigators propose to develop an imaging technology for delineating regions of the lung in humans that are non-functional versus those that are viable; using hyperpolarized (HP) xenon-129 (129Xe) magnetic resonance imaging (MRI), will better inform beam-planning strategies, in an attempt to reduce RILI in lung cancer patients.

Conditions

• Radiation Induced Lung Injury
• Non Small Cell Lung Cancer

Interventions

DIAGNOSTIC_TEST

Hyperpolarized xenon-129 MRI

Participants will be asked to inhale the xenon-129 contrast agent according to procedure for gas administration. The success criterion of the drug is a obtained Xe MRI lung image with reasonable signal level. The clinical MRI scanner Philips Achieva 3.0T will be equipped with 129Xe Quadrature Transreceive Lung Coil (Large and Small) to acquire 129Xe lung images. The resonator length of the large coils is equal to 122 cm, whereas the same size of the small coil is equal to 106 cm. The success criterion of the device performance is the obtained reasonable Xe MRI lung image.

Sponsors & Collaborators

• NOAMA

  collaborator UNKNOWN

• Thunder Bay Regional Health Research Institute

  lead OTHER

Principal Investigators

• Mitchell Albert, PhD · Thunder Bay Regional Health Research Institute

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-12-31

Primary Completion

2022-12-08

Completion

2022-12-08