Hyperpolarized MRI of Lung Transplants

Lung Transplant Rejection Clinical Trial

Official title:

Hyperpolarized 129 Xenon MRI in a Pediatric Population With Lung Transplant

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04941573
• Other study ID #: 18-015796
• Status: Recruiting
• Phase: Phase 1
• Start date: July 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: Xemed LLC
• Contact: David M Biko, MD
• Phone: 267-425-7189
• Email: bikod[@]email.chop.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic complications such as chronic lung allograft dysfunction (CLAD) remain the leading cause of death and the primary limitation to long-term survival for lung transplant recipients. CT is currently use for longitudinal assessment in the pediatric population with lung transplant. However, it uses radiation that has been related to increase cancer risk. MRI has played a limited role in the evaluation of lung pathologies. To overcome these limitations, the use of inhaled, hyperpolarized (HP) noble gases such as helium-3 (3He) and xenon-129 (129Xe) has come into play. Filling the air spaces within the lungs with either of these HP gases provides enough signal and contrast to obtain quality images on MRI. The primary objective of this study is to evaluate the diagnostic performance of hyperpolarized xenon MRI for the assessment of CLAD in pediatric patients with lung transplant.

Description:

This is a prospective interventional study of 15 evaluable pediatric patients following a lung transplant that will be studied at the Children's Hospital of Philadelphia in association with the functional and metabolic imaging group of the Perelman School of Medicine from the University of Pennsylvania. Potential subjects will be identified by their pediatric pulmonologist during the follow-up clinic visit for referral to the study. These patients are part of the Lung Transplant Program at CHOP. Before discussing participation in the study, potential subjects will be screened using the protocol inclusion and exclusion criteria. Participation will be discussed between the PI and the referring pediatric pulmonologist. Participation will be discussed with the parents/guardian by the pediatrician and/or radiologist after identification and confirmation of eligibility. Consent will be obtained at the physician's office prior to imaging. A total of approximately 20 patients with ages 8-20 years will be recruited and enrolled to produce up to 15 evaluable subjects.

Hyperpolarized xenon is a novel contrast agent for imaging human lungs using non-invasive Magnetic Resonance Imaging for producing high quality 3D maps of lung structure and function. The xenon gas is inhaled by the subject while inside the MRI scanner and during a short breath-hold the image is acquired. Different MRI techniques can be used to provide regional lung function and structure such as: ventilation, local alveolar oxygen concentration (PAO2) and oxygen uptake rate, apparent diffusion coefficient (ADC), etc. Xenon is soluble in lung tissue and blood with a Chemically Shifted MRI resonant frequency, property which can be quantified through MRI into maps and global parameters related to lung parenchyma and blood exchange.

Early detection of lung transplant complications, such as CLAD, can have life-saving benefit for patients. CLAD is usually diagnosed by spirometry measurements, which are typically not sensitive until late onset of the disease. Longitudinal studies and patient monitoring using HRCT is not desirable due to ionizing radiation and potential long term health hazards. Also, HRCT detects only structural changes of the lung tissue and airways. HP xenon MRI can detect ventilation defects and abnormal gas exchange, which likely can be more sensitive to incipient abnormal lung function.

This study is designed as an open label longitudinal study. Post lung transplant pediatric patients will have two sessions of HP xenon MRI separated by six months. Following parental or legally authorized representative informed consent, the subjects will undergo HP Xenon MR imaging that will be performed in an MRI scanner in at the Hospital of the University of Pennsylvania. Additional conventional proton images of the chest are typically acquired for localization and to assist with interpreting the xenon MR images. These are acquired at the same time and space. After six months, the participant will undergo another hyperpolarized gas MRI as described above to evaluate their progress and evolution.

HP Xenon MRI data will provide high resolution 3D information about the ventilation, oxygen exchange (PAO2), and structural integrity of the alveoli and small airways (ADC). Gas exchange and transport will be assessed from property of xenon to dissolve in lung parenchyma and blood. The signal of the xenon dissolved in the lung tissue and blood compared to the signal of the xenon within the airspaces can be used to extract the septal wall thickness and capillary transit time in the pulmonary vasculature. Data will be used for evaluation of patients for potential lung transplant complications, such as Chronic Lung Allograft Dysfunction (CLAD). This is a longitudinal clinical study. Investigators will study correlations of HP Xenon MRI metrics with CT images and spirometry.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 20 Years

Eligibility

Inclusion Criteria:

• Males or females age 8 - 20 years of age at enrollment

• Subjects with history of lung transplant

• Available clinically indicated pulmonary function test

Exclusion Criteria:

• Any contraindication to the safe performance of MRI (metallic foreign bodies, non-safety rated implanted devices including but not limited to vascular clips, pacemaker, stent, infusion pump, neuro-stimulator, prosthesis)

• Subject unable to perform a spirometry

• Individuals requiring conscious sedation or anesthesia

• Severe claustrophobia

• Pregnant females

Related Conditions & MeSH terms

• Lung Transplant Rejection

Intervention

Combination Product:
• Hyperpolarized 129-Xenon (MagniXene) MRI of the lung
Hyperpolarized xenon is a contrast imaging agent for lung MR imaging. Inert noble gas xenon is hyperpolarized using Xemed developed technology. The gas is administered to the human subjects as a short seconds-long breath-hold while inside the MRI scanner. Once the gas is inhaled, lung images of HP Xenon distributed within the lung spaces can be acquired. Additionally, xenon follows a similar path to oxygen, dissolving in lung tissue and further in bloodstream.

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Xemed LLC	Children's Hospital of Philadelphia, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Ventilation Defect Percent (VDP) from baseline to 6-month follow-up.	129Xe MRI can reveal unventilated regions of the lungs where the gas cannot reach after being inhaled.	baseline to 6-month follow-up
Secondary	Changes in oxygen partial pressure (PAO2) maps from baseline to 6-month follow-up.	Oxygen partial pressure (PAO2) maps can be extracted from 129Xe MRI maps in a single breath-hold. Regions of the lungs that show abnormal PAO2 values are susceptible of improper ventilation or gas exchange.	baseline to 6-month follow-up
Secondary	Changes in gas exchange to lung tissue and blood and transport coefficient maps from baseline to 6-month follow-up.	Xenon is soluble in lung tissue and blood presenting specific MRI frequencies and this property can be used for imaging gas exchange properties at the alveolar level.	baseline to 6-month follow-up