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Project

A multidisciplinary approach for a better diagnosis and understanding of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown origin characterized by increased matrix deposition, resulting in functional impairment and ultimately respiratory failure. HRCT findings characteristic of UIP consist of bilateral basilar subpleural reticulation often accompanied by traction bronchiectasis and architectural distortion and honeycomb cysts. A minor presence of groundglass opacity is possible. In general, these findings gradually decrease in extent from base to apex. IPF is histopathologically characterised by a heterogeneous appearance with alternating areas of normal parenchyma, fibrosis, and honeycomb cysts. Key-characteristics are dense fibrosis that causes architectural destruction with frequent honeycombing, scattered fibroblast foci, and patchy lung involvement, usually with a pleural and paraseptal distribution. Fibrotic areas contain dense acellular collagen, abundant smooth muscle proliferation, and discrete foci of proliferating fibroblasts, which are referred to as fibroblastic foci. As the prognosis of IPF is far worse than the other idiopatic interstitial pneumonias, it is extremely important to make a confident diagnosis; this however is until now dreadfully troublesome. Diagnosis is hampered by the gap between the 2 techniques where HRCT scans generate data on the structural level, but conventional light microscopy provides data on the cellular level. The aim of this project is to close the gap between HRCT and conventional light microscopy by analysing IPF explants lungs by mean of micro computed tomography (microCT). Using explant lungs of patients with IPF undergoing lung transplantation and none used or rejected donors as control will allow us to correlate abnormalities seen on HRCT with histopathology by using the same sample for both techniques. Recently micro computed tomography was developed, which can be used for the non-destructive evaluation of the internal three-dimensional structure of biological specimens. Currently micro CT is mainly used for imaging of skeletal tissue, but it can also been used for evaluation of soft tissues. IPF explanted lungs and control lung will be frozen in liquid nitrogen at total lung capacity (TLC). Each lung is cut into 2 cm-thick slices and a core of frozen tissue approximately 1 cm in diameter and 2 cm in length is removed from each slice and processed for micro-CT examination. Using micro-CT we can detect and study zones of normal appearing lung, zones of active fibrosis formation and zones of end stage fibrosis, and compare with abnormalities seen on micro CT scan. Micro CT can help us to unravel some of the main mysteries of IPF. This is a new technique, which will be extremely helpful in tackling our specific research questions. Until now only the group of professor Jim Hogg (department of pathology and laboratory Medicine, University of British Columbia, Vancouver Canada) is highly experienced using this technique in human explants lungs. Answering our research questions is only possible with the help of professor J Hogg, who has adapted the technique of micro CT to study airways and parenchyma in COPD lungs. It is a privilege that he is prepared to guide us during our study in diffuse parenchymal lung diseases and IPF specifically.
Date:1 Sep 2009 →  30 Sep 2009
Keywords:Idiopathic pulmonary fibrosis
Disciplines:Physiology