Hyperpolarized Imaging for New Treatments

Hyperpolarized Imaging for New Treatments

Publication date: Feb 07, 2020

The introduction of triple combination CFTR modulator therapy for patients with Cystic Fibrosis (CF) with at least one copy of the deltaF508 mutation is expected to provide major health benefits, but will also require novel outcome measures that can detect CF lung disease at an early stage, capture the efficacy of new therapies when disease manifestations are limited, as well as determine whether stopping existing chronic maintenance therapies does not have negative effects. In the past decade, research has focused on the multiple breath washout (MBW) test, as a sensitive outcome measure, especially if highly-effective modulator therapies are initiated in early childhood. Even LCI, however, may not adequately capture early lung function changes, thus warranting investigation of even more sensitive outcome measures. Magnetic resonance imaging (MRI) has the advantage of being a radiation-free modality, making it more suitable for assessing response to therapy in a shorter time frame with repeated imaging. Inhalation of a hyperpolarized gas enables the visualization and quantification of regional ventilation in the lung and can be combined with structural MRI to assess both structure and function in parallel. The main Investigator and others have recently formed an international consortium (the 129Xe MRI Clinical Trial Consortium), comprised of both imaging experts and pulmonary clinicians to standardize imaging procedures, thus facilitating multi-site implementations. Data from this proposed study (HyPOINT; Hyperpolarized Imaging for New Treatments) will inform the future utility of MRI for both longitudinal studies to track disease progression over time as well as for future interventional trials. Further, the current study could inform the design of future trials of interventions of patients for whom currently no effective CFTR modulator therapy is available and for patients with rare genotypes thus laying the groundwork for a more personalized medicine approach in the near-term future.

Concepts Keywords
Allele Branches of biology
Antibiotic Medical specialties
Canada RTT
CFTR Health
Chloride Radiation
Cincinnati Experts pulmonary clinicians
Claustrophobia Mutations cystic fibrosis
Cystic Fibrosis Resonance imaging
FDA Channelopathies
FEV1 Cystic fibrosis
Functional MRI Magnetic resonance imaging
Genotype Clinical trial
Genotypes Radiation therapy
Heart Rate Radiation
Hyperpolarized Magnetic resonance imaging
Informed Consent MRI
Iontophoresis Genotype
IRB
LCI
Lung
Magnetic Resonance Imaging
Maintenance Therapies
MEq
Modality
MRI
Mutation
Nadir
Phenotype
Pilocarpine
Pregnancy Test
Primary Endpoint
Protocol
Pulmonary
Radiation
Recording
Reliant
Reproducibility
SickKids
Spirometry
SPO2
Toronto
Urine
VDP
Virginia
Vital Signs
Washout
Wisconsin

Semantics

Type Source Name
disease MESH Cystic Fibrosis
disease MESH lung disease
disease MESH disease progression
disease MESH diagnosis
drug DRUGBANK Chloride ion
drug DRUGBANK Aspartame
drug DRUGBANK Pilocarpine
disease MESH claustrophobia

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