Magnetic Resonance Imaging of the Lung: Non-Oncological Applications
Non-neoplastic pulmonary proliferative diseases are characterized by a complex interaction between proliferating lung cells and a variety of resident and infiltrating host cells, secreted factors, and extracellular matrix proteins, collectively referred to as the microenvironment. Idiopathic pulmonary fibrosis (IPF) refers to a specific condition characterized by chronic interstitial pneumonia and fibrosis of unknown cause, for which there are still no effective treatments. According to the current pathogenetic perspective, the aberrant proliferative events in IPF resemble those occurring during malignant transformation in tumors. Growing evidence supports the neoplasm-like molecular profile of IPF, and this fascinating hypothesis is beginning to be exploited for therapeutic purposes. Tyrosine kinase receptors (RTKs) are known to be major players in the onset and progression of cancer. Among these, the proto-oncogene MET is a key regulator of the invasive growth program. MET encodes the TK receptor for the "dispersion factor" or hepatocyte growth factor (HGF), a sensor of adverse microenvironmental conditions (e.g., hypoxia and ionizing radiation) that drives cellular invasion and metastasis through transcriptional activation of the "invasive growth signature." We and others have previously reported that both myofibroblasts and epithelial cells in fibroblastic foci (FFs) in IPF express MET in its activated form (MACTIF study). MRI technology will help identify hypoxic areas and thus those patients who may potentially benefit from anti-MET therapeutic lockade. Magnetic resonance imaging (MRI) has an incredible ability to distinguish between different tissue components. Advanced techniques such as diffusion, mapping, ventilation, and perfusion allow for even more precise tissue characterization.
For example, perfusion imaging can quantify the spatial distribution and extent of oxygen delivery to tissues in vivo and is therefore the best method for assessing vascular oxygenation. On the other hand, ventilation imaging allows for a quantitative analysis of pulmonary physiology, in vivo pulmonary ventilation, and oxygen sensitivity; in this way, the "alveolar" aspect of the oxygenation process will be explored.
Since the introduction of MRI imaging for the evaluation of lung diseases, various limitations, primarily related to the relatively low proton density of the lung parenchyma and respiratory motion artifacts, have hindered the clinical application of this technique. In recent decades, technical advances have addressed many of these limitations.
MRI could enable the assessment of hypoxic areas in IPF and thus lead to the identification of patients at risk of disease progression and validate MET as a new therapeutic target. No attempts have yet been reported in the literature regarding the study of pulmonary microenvironment characteristics using advanced MRI imaging.
Study Overview
Status
Conditions
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
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Lombardy
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Pavia, Lombardy, Italy, 27100
- Recruiting
- Fondazione IRCCS Policlinico San Matteo di Pavia
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Contact:
- Chandra Bortolotto, MD
- Phone Number: 0382503761
- Email: c.bortolotto@smatteo.pv.it
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Clinical and radiological diagnosis of early-stage IPF
Exclusion Criteria:
- Absolute contraindications to bronchoalveolar lavage or magnetic resonance imaging
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Assessment of the ability of advanced magnetic resonance imaging techniques to assess tissue oxygenation and local hypoxia in early interstitial pulmonary fibrosis (proliferative stage)
Time Frame: up to 36 months
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up to 36 months
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P_113422
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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