MRI of Lung Structure and Function in Preterm Children

The MRI tools developed by the investigators are well positioned for assessing regional changes in lung structure and function in preterm children with bronchopulmonary dysplasia (BPD), in which airway limitation similar to asthma, alveolar simplification similar to emphysema and pulmonary vascular stunting are expected. To the investigator's knowledge, the combination of ultra short echo time (UTE) proton, pulmonary vascular proton and hyperpolarized 129Xe MRI have not yet been explored in BPD, either clinically or preclinically. The investigators propose that a comprehensive MRI examination may be useful from a diagnostic perspective, MRI of preterm children without BPD may reveal changes which are otherwise clinically 'silent' yet still place children at risk for future chronic lung disease in later life.

Study Overview

• Status: Terminated
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Diagnostic test: Lung MRI

Detailed Description

Briefly, at the beginning of an approximate three hour study visit, the qualified investigator (QI) / delegate will explain the study procedure to the participants and the participants will have an opportunity to ask questions regarding the study procedure. Following the explanation of the study, written informed consent will be collected at the beginning of visit 1. Participants who are deemed unable to provide consent will be provided an assent form and consent will be acquired from their parents/ legal guardians. During the study visit, participants will undergo: 1) brief medical history and clinical examination including questionnaires, 2) full pulmonary function tests, lung clearance testing (LCI), forced oscillation technique (FoT) and exercise testing, 3) proton MRI, 4) spin-density and/or diffusion-weighted 129Xe MRI, 5) Multiple-breath washout imaging. Qualified research team members will perform a clinical examination on the participant to record their vital statistics like age, gender, height, weight, heart rate, respiratory rate, oral temperature and blood pressure. The QI/delegate, during a brief conversation with the participant, will collect relevant medical history from the participant to make sure the participant meets all the inclusion/exclusion criteria for the study. The QI will also make sure that the participant understands the study procedure and is willing to participate in the study. Based on the clinical examination results, medical history and the pulmonary function test results, the QI/delegate will determine if all the inclusion/exclusion criteria are met to proceed with the MRI part of the study visit.

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

• Study Contact: Name: Sharon Braganza, MSc; Phone Number: 307937 4168137654; Email: sharon.braganza@sickkids.ca
• Study Contact Backup: Name: Giles Santyr, PhD; Phone Number: 301394 4168137654; Email: giles.santyr@sickkids.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 9 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Healthy volunteers will be selected from the general population and the BPD and non-BPD cohorts will be selected from patients from clinics seen at the Hospital for Sick Children, Toronto

Description

Inclusion Criteria:

- Children born pre-term at less than 28 weeks' gestation, currently aged 6-9 years, with and without BPD will be included.

For the preterm non-BPD cohort, inclusion will include

• no requirement of supplementary oxygen beyond 28 days from birth. For the BPD preterm cohort, inclusion criteria will include
• need for oxygen at 36 weeks' postmenstrual age, which includes those with moderate-severe disease .

For the healthy cohort, inclusion will include

-absence of any diagnosed pulmonary disease and term birth.

Exclusion Criteria: Children with

• known interstitial lung disease, congenital lung anomalies, cystic fibrosis, ciliary dysfunction, immunodeficiency, neuromuscular disease or structural heart disease, which may have associated pulmonary function tests (PFT) and/or MRI findings;
• genetic syndromes which may have other associated structural lung anomalies;
• any contraindications for MRI
• severe neurosensory deficits which would prevent test completion;
• viral or bacterial respiratory infection within 6 weeks will be excluded. For all three groups (healthy, preterm non-BPD and preterm BPD), we will exclude
• those with congenital lung disease (i.e. Congenital diaphragmatic hernia (CDH), lung cysts) or non BPD acquired chronic lung disease as defined by need for any routine supplementary oxygen
• if the participant has an MRI incompatible device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bio prosthetic, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy; Healthy Participants	Diagnostic test: Lung MRI; Participants will be undergoing hyperpolarized xenon and proton lung MRI
BPD cohort; Participants born prematurely with a diagnosis of BPD	Diagnostic test: Lung MRI; Participants will be undergoing hyperpolarized xenon and proton lung MRI
Non-BPD cohort; Participants born prematurely without a diagnosis of BPD	Diagnostic test: Lung MRI; Participants will be undergoing hyperpolarized xenon and proton lung MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI ventilation and 1H MRI thoracic cavity volume and tissue density	Ventilation defect percent (VDP) (%) will be generated for whole lung and individual lung slices using manual or semi-automated segmentation. For proton (1H) thoracic cavity images, the thoracic cavity volume (TCV) will be calculated by manual or semi-automated segmentation.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apparent Diffusion Coefficients (ADC) and ADC maps	Diffusion weighted images from each visit will be reviewed and compared with the proton anatomical images. Mean, whole lung, and center slice ADC (and standard deviation) will be calculated and recorded.	2 years
Multiple breath washout testing:	VDP will be calculated as described above based on the first image data set prior to wash-out breaths. A pixel-by-pixel fit of images as a function of washout breath number will then be used to calculate the fractional ventilation map defined as the volume of expired gas leaving a volume divided by its end-inspiratory volume.	2 years

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): March 20, 2024
• Study Completion (Actual): March 20, 2024

Study Registration Dates

• First Submitted: February 6, 2018
• First Submitted That Met QC Criteria: March 16, 2018
• First Posted (Actual): March 23, 2018

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Lung MRI, Bronchopulmonary Dysplasia, hyperpolarized xenon,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia
• Other Study ID Numbers: 1000055897

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared with other researchers outside of the institutions

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No