Biological- and imaging biomarkers of oedema and fibrosis

Private
Public

Biological- and imaging biomarkers of oedema and fibrosis in a rat model of Drug-Induced Interstitial Lung Disease (DIILD) (Conference Abstract)

  • 124

Publications
Take a look

IBs of oedema and fibrosis in rat DIILD

Biological- and imaging biomarkers of oedema and fibrosis in a rat model of Drug-Induced Interstitial Lung Disease (DIILD) (Conference Abstract)

Irma Mahmutovic Persson, Hanna Falk Håkansson, Anders Örbom, Per-Ola Önnervik, Janne Persson, Karin Von Wachenfeldt, Lars E. Olsson.


European Respiratory Journal 2019 54: PA2417. doi: 10.1183/13993003.congress-2019.PA2417.

Abstract

A large number of systemically administered drugs have the potential to cause DIILD. We aim to characterize a model of DIILD in the rat and develop imaging biomarkers for detection and quantification of DIILD.

Methods: Sprague-Dawley rats received one single dose of intratracheal bleomycin and were longitudinally imaged at day 0, 3, 7, 14, 21 and 28 post dosing, applying imaging techniques MRI and PET/CT. Bronchoalveolar lavage fluid (BALF) was analyzed for total protein and inflammatory cells. Lungs were taken for further analyses by histology, and stained for inflammation and collagen deposition.

Results: Bleomycin induced significant increase in total protein concentration and total cell count in BALF, peaking at day3 (p>0.001) and day7 (p>0.001) compared to control, respectively. The lesion measured by MRI and the FDG-PET signal in the lungs of bleomycin challenged rats was significantly increased during day3-14, peaking at day7. Two subgroups of animals were identified as low- and high responders to bleomycin challenge, by their different change in total lung volume. Both groups showed signs of inflammation initially, while at later time points the low-responder group recovered towards control, and the high-responder group showed progressive fibrosis with significant increase of lesion volume (p<0.001), compared to control.

Conclusion: Bleomycin-induced lung injury with MRI and PET readout in rats, is an adequate and translational animal model for DIILD studies. The scenario comprised different disease responses, with different fractions of inflammation and fibrosis. Thereby, this study improved the understanding biological- and imaging biomarkers in DIILD.

IBS OF OEDEMA AND FIBROSIS IN RAT DIILD
Article categories

Hyperpolarised 129-xenon diffusion-weighted MRI

Private
Public

Hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

  • 123

Publications
Take a look

Conference Abstract: Hyperpolarised 129Xe diffusion-weighted MRI in ILD

Hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

James Eaden, Ho-Fung Chan, Paul Hughes, Nicholas Weatherly, Matthew Austin, Laurie Smith, Jim Lithgow, Andrew Swift, Stephen Renshaw, Maya Buch, Colm Leonard, Sarah Skeoch, Nazia Chaudhuri, Geoff Parker, Stephen Bianchi, Jim Wild


European Respiratory Journal 2019 54: PA3157. doi: 10.1183/13993003.congress-2019.PA3157.

Abstract

Introduction: Apparent diffusion coefficient (ADC) is a measure of gas diffusion in the airspaces, where restrictions by tissue boundaries provide information about lung microstructure down to the alveolar level. Diffusion-weighted (DW) MRI of the lung with hyperpolarised helium in idiopathic pulmonary fibrosis (IPF) has shown that ADC correlates with DLCO, KCO and CT fibrosis score (Chan, H-F. et al. Radiology 2019; doi:10.1148/radiol.2019181714) but to date no data are available on the utility of 129-xenon (129Xe) diffusion in interstitial lung disease (ILD). Aim: To evaluate the ability of 129Xe DW-MRI to distinguish between ILD subtypes.

Methods: A prospective, multicentre study of patients with ILD including drug induced ILD (DI-ILD), hypersensitivity pneumonitis (HP), IPF and connective tissue disease ILD (CTD-ILD). Hyperpolarised 129Xe DW-MRI was performed on a 1.5 T scanner and mean ADC was calculated. Results: To date, 33 patients (6 DI-ILD, 7 HP, 15 IPF, 5 CTD-ILD) have undergone baseline 129Xe DW-MRI. There was a significant difference in mean ADC between the ILD subtypes (p=0.011), with the significant difference occuring between the HP (median: 0.038cm2/s) and IPF (median: 0.048cm2/s) groups (p<0.01). Median FVC% predicted in the HP and IPF groups was 75.6% and 84.7% respectively. There was a correlation between mean ADC and DLCO (r=-0.39; p=0.03) as well as KCO (r=-0.58; p<0.01) but not FVC (r=0.24; p=0.19).

Conclusions: We demonstrate a correlation between mean 129Xe ADC and DLCO but not FVC. Our findings suggest significant differences in mean ADC between IPF and HP. Therefore, 129Xe DW-MRI could potentially have a role in differentiating changes in the airway microstructure in ILD subtypes.

CONFERENCE ABSTRACT: HYPERPOLARISED 129XE DIFFUSION-WEIGHTED MRI IN ILD
Article categories

Longitudinal change in hyperpolarised 129-xenon MR spectroscopy

Private
Public

Longitudinal change in hyperpolarised 129-xenon MR spectroscopy in interstitial lung disease (Conference Abstract)

  • 122

Publications
Take a look

Conference Abstract: Longitudinal change in hyperpolarised 129Xe MRS in ILD

Longitudinal change in hyperpolarised 129-xenon MR spectroscopy in interstitial lung disease (Conference Abstract)

James Eaden, Paul Hughes, Guilhem Collier, Graham Norquay, Nicholas Weatherly, Matthew Austin, Laurie Smith, Jim Lithgow, Andrew Swift, Stephen Renshaw, Maya Buch, Colm Leonard, Sarah Skeoch, Nazia Chaudhuri, Geoff Parker, Stephen Bianchi, Jim Wild


European Respiratory Journal 2019 54: PA3158 doi: 10.1183/13993003.congress-2019.PA3158 .

Abstract

Introduction: Hyperpolarised 129-xenon (129Xe) MR spectroscopy (MRS) can be used as a quantitative marker of gas exchange in interstitial lung disease (ILD). The ratio of the uptake of 129Xe in the red blood cells to the tissue/plasma (RBC:TP) has been shown to be reduced by 70% in idiopathic pulmonary fibrosis (IPF) patients when compared with healthy volunteers (Kaushik, S.S. et al. J Appl Physiol 2014; 117:577-585). In IPF, a significant decline in 129Xe RBC:TP over 12 months has been demonstrated but no significant change in DLCO or KCO (Weatherley, N.D. et al. Thorax 2018 [Epub ahead of print]).

Aim: To compare longitudinal changes in 129Xe RBC:TP with changes in FVC and DLCO between ILD subtypes.

Methods: A prospective, multicentre study of ILD patients including drug induced ILD (DI-ILD), hypersensitivity pneumonitis (HP), IPF and connective tissue disease ILD (CTD-ILD). Hyperpolarised 129Xe MRS was performed on a 1.5 T scanner.

Results: To date, 18 patients (5 DI-ILD, 5 HP, 6 IPF, 2 CTD-ILD) have undergone 129Xe MRS on two separate visits (6 weeks apart for DI-ILD/HP and 6 months apart for IPF/CTD-ILD). There was a significant difference in longitudinal change in RBC:TP between the HP and IPF groups (p=0.022). Median change in RBC:TP in the HP and IPF groups was 0.022 and -0.023 respectively. There was no significant difference in longitudinal change in FVC% predicted (p=0.79) or DLCO% predicted (p=0.39) between the ILD subtypes.

Conclusions: Our findings demonstrate that 129Xe RBC:TP has sensitivity to longitudinal change with significant differences between IPF and HP patients, whilst FVC and DLCO showed no change, suggesting that RBC:TP is more sensitive to change than PFTs in ILD.

CONFERENCE ABSTRACT: LONGITUDINAL CHANGE IN HYPERPOLARISED 129XE MRS IN ILD
Article categories

Quantitative CT and hyperpolarised 129-xenon

Private
Public

Quantitative CT and hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

  • 121

Publications
Take a look

Conference Abstract: Quantitative CT and hyperpolarised 129Xe dwMRI in ILD

Quantitative CT and hyperpolarised 129-xenon diffusion-weighted MRI in interstitial lung disease (Conference Abstract)

James A. Eaden, Ho-Fung Chan, Paul JC. Hughes, Nicholas D. Weatherly, Matthew Austin, Laurie J. Smith, Jim Lithgow, Smitha Rajaram, Andrew J. Swift, Stephen A. Renshaw, Ronald A. Karwoski, Brian J. Bartholmai, Colm T. Leonard, Sarah Skeoch, Nazia Chaudhuri, Geoff JM. Parker, Stephen M. Bianchi, and Jim M. Wild.


Thorax 2019;74:A79. doi: 10.1136/thorax-2019-BTSabstracts2019.131.

Abstract

Introduction: Apparent diffusion coefficient (ADC) is a diffusion-weighted (DW) MRI measure of Brownian gas diffusion in the airspaces, where restrictions by tissue boundaries provide information about lung microstructure. The mean diffusive length scale (LmD), is another DW-MRI lung microstructure measurement calculated using a stretched exponential fit method. Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) quantifies various radiological parenchymal features based on histogram signature mapping techniques and is the most widely used quantitative CT image texture analysis software in interstitial lung disease (ILD).

Aim: To evaluate the ability of hyperpolarised 129-xenon (129Xe) DW-MRI and high resolution CT (HRCT) to distinguish between ILD subtypes.

Methods: A prospective, multicentre study of patients with ILD including drug induced ILD (DI-ILD), hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF) and connective tissue disease ILD (CTD-ILD). Hyperpolarised 129Xe DW-MRI was performed on a 1.5 T scanner. The HRCT scan was performed within a year prior to the MRI scan. Quantitative CT analysis was performed using CALIPER. Semi-quantitative visual CT analysis was performed by two consultant chest radiologists using a scoring system (table 1).

Results: To date, 32 patients (7 DI-ILD, 6 HP, 14 IPF, 5 CTD-ILD) have undergone baseline 129Xe DW-MRI and CT analysis. There was a significant difference in LmD between the HP and IPF groups (p=0.048) but this was not observed with ADC (p=0.16). Quantitative CT analysis demonstrated a significant difference between the ILD subtypes in both ground glass (GG) percent (p=0.007) and honeycombing percent (p=0.023), with the significant difference in GG% occurring between the HP and IPF groups (p=0.004). There was no significant difference between the ILD subtypes in reticulation percent (p=0.15). Semi-quantitative visual CT analysis showed a significant difference between the ILD subtypes in GG score (p=0.008), with the significant difference occurring between the HP and IPF groups (p=0.007). There was no significant difference between the ILD subtypes in the reticulation score (p=0.071) or the honeycombing score (p=0.16).

Conclusions: Our findings suggest significant differences in LmD, GG score and CALIPER GG% between IPF and HP. 129Xe DW-MRI and quantitative CT could potentially have a role in differentiating between these ILD subtypes. .

CONFERENCE ABSTRACT: QUANTITATIVE CT AND HYPERPOLARISED 129XE DWMRI IN ILD
Article categories

Oxygen-Enhanced MRI in Cystic Fibrosis

Private
Public

Oxygen-Enhanced MRI in Cystic Fibrosis (Conference Abstract)

  • 120

Publications
Take a look

Conference Abstract: OE-MRI in Cystic Fibrosis

Oxygen-Enhanced MRI in Cystic Fibrosis (Conference Abstract)

Marta Tibiletti, Josephine H Naish, Katharina Martini, Thomas Frauenfelder, Geoff JM Parker


British Chapter of ISMRM Meeting 2019

Abstract

Introduction:

Oxygen Enhanced MRI (OE-MRI) exploits the paramagnetic properties of molecular oxygen to modify local T1 values to explore local lung function. During a dynamic OE-MRI experiment, the subject breaths varying concentrations of O2. Various parameters can be extracted, such as the ventilated volume fraction (VVF), defined as is the fraction of lung tissue showing O2 enhancement, and the oxygen wash-in time (Tup) [1]. In this work, we calculated τup, VVF, VVF-masked Tup and compared them with pulmonary function tests in a population of healthy volunteers (HV) and cystic fibrosis (CF) subjects.

Methods:

Analysis was applied retrospectively to OE-MRI data acquired from a previously published study [1]. 20 patients with CF (20 - 40 years, 13 male) and 4 HV (27-37 y, 2 male) underwent dynamic OE-MRI on a 1.5 T Philips Achieva MRI scanner. A free-breathing protocol based on an inversion-prepared centric ordered single shot 3D-turbo field echo sequence was used. The dynamic acquisition lasted 15 min (90 volumes), during which gas was delivered at 15 l/min via a disposable non-rebreathing mask and switched at minute 2 from medical air to 100% O2, and back to air at minute 10. All images were registered to correct for breathing motion using a non-linear registration algorithm [4]. Maps of Tup were derived from the signal intensity curves for each pixel by fitting to a mono-exponential recovery function. VVF was considered positive where the Akaike information criterion favours an exponential fit over a constant function. VVF fraction, median Tu and median Tup calculated only within VVF positive pixels (masked Tup) were extracted and compared to the results from conventional spirometry (FEV1, FVC and FEV1/FVC corrected for age, height and gender). Relationships between variables were evaluated with Pearson correlation with p < 0.05 considered to indicate the presence of a statistically significant correlations.

Results:

The table present the R2 and p-values of correlation between calculated parameters and corrected spirometry results.

                         FVC pred [%]     FEV1 pred [%]   FEV1/FVC pred [%]

VVF                   0.54 (p<0.001)   0.70 (p<0.001)    0.24 (p=0.02)

Tup [s]                0.00 (p=0.89)     0.01 (p=0.59)      0.12 (p=0.12)

Masked Tup [s]  0.03 (p=0.38)     0.11 (p=0.11)       0.27 (p=0.01)

Discussion:

VVF highly correlates with measurements of lung function derived from spirometry, particularly with FEV1. Oxygen wash-in time correlated significantly with FEV1/FVC pred [%] only when non-enhancing voxels are excluded.

Conclusion:

Parameters calculated from dynamic OE-MRI are highly correlated with measurement of lung function derived from spirometry.

Reference: [1] Martini K, et al. European Radiology:1-11 (2018)

CONFERENCE ABSTRACT: OE-MRI IN CYSTIC FIBROSIS
Article categories

How consistently do physicians diagnose and manage drug-induced

Private
Public

How consistently do physicians diagnose and manage drug-induced interstitial lung disease? Two surveys of European ILD specialist physicians

  • 115

Publications
Take a look

Survey: How Consistently do Physicians Diagnose DI-ILD?

How consistently do physicians diagnose and manage drug-induced interstitial lung disease? Two surveys of European ILD specialist physicians

James A. Eaden, Sarah Skeoch, John C. Waterton, Nazia Chaudhuri, Stephen M. Bianchi on behalf of the TRISTAN investigators


ERJ Open Research 2020 6: 00286-2019 doi: 10.1183/23120541.00286-2019.

Abstract

Introduction

Currently there are no general guidelines for diagnosis or management of suspected drug-induced (DI) interstitial lung disease (ILD). The objective was to survey a sample of current European practice in the diagnosis and management of DI-ILD, in the context of the prescribing information approved by regulatory authorities for 28 licenced drugs with a recognised risk of DI-ILD.

Methods

Consultant physicians working in specialist ILD centres across Europe were emailed two surveys via a website link. Initially, opinion was sought regarding various diagnostic and management options based on seven clinical ILD case vignettes and five general questions regarding DI-ILD. The second survey involved 29 statements regarding the diagnosis and management of DI-ILD, derived from the results of the first survey. Consensus agreement was defined as 75% or greater.

Results

When making a diagnosis of DI-ILD, the favoured investigations used (other than computed tomography) included pulmonary function tests, bronchoscopy and blood tests. The preferred method used to decide when to stop treatment was a pulmonary function test. In the second survey, the majority of the statements were accepted by the 33 respondents, with only four of 29 statements not achieving consensus when the responses “agree” and “strongly agree” were combined as one answer.

Conclusion

The two surveys provide guidance for clinicians regarding an approach to the diagnosis and management of DI-ILD in which the current evidence base is severely lacking, as demonstrated by the limited information provided by the manufacturers of the drugs associated with a high risk of DI-ILD that we reviewed.

SURVEY: HOW CONSISTENTLY DO PHYSICIANS DIAGNOSE DI-ILD?
Article categories

Oxygen enhanced MRI biomarkers of lung function in interstitial lung disease

Private
Public

Oxygen enhanced MRI biomarkers of lung function in interstitial lung disease (Conference Abstract)

  • 114

Publications
Take a look

Conference Abstract: OE-MRI biomarkers of lung function in ILD

Oxygen enhanced MRI biomarkers of lung function in interstitial lung disease (Conference Abstract)

Tibiletti M, Naish JH, Heaton MJ, Waterton JC, Hughes PJC, Eaden JA, Skeoch S, Chaudhuri N, Bruce I, Stephen SM, Wild JM, Parker GJM


Abstract OA4330 - ERS 30th International Congress held virtually 7–9 September, 2020.

CONFERENCE ABSTRACT: OE-MRI BIOMARKERS OF LUNG FUNCTION IN ILD
Article categories

Collagen I-PET and MRI in a Rat Lung Injury Model

Private
Public

Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model

  • 110

Publications
Take a look

Collagen I-PET and MRI in a Rat Lung Injury Model

Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model

by Irma Mahmutovic Persson, Nina Fransén Pettersson, Jian Liu, Hanna Falk Håkansson, Anders Örbom, René In ’t Zandt, Ritha Gidlöf, Marie Sydoff, Karin von Wachenfeldt and Lars E. Olsson on behalf of the TRISTAN Consortium


J. Clin. Med. 2020, 9(11), 3706. doi: 10.3390/jcm9113706

Abstract

Non-invasive imaging biomarkers (IBs) are warranted to enable improved diagnostics and follow-up monitoring of interstitial lung disease (ILD) including drug-induced ILD (DIILD). Of special interest are IB, which can characterize and differentiate acute inflammation from fibrosis. The aim of the present study was to evaluate a PET-tracer specific for Collagen-I, combined with multi-echo MRI, in a rat model of DIILD. Rats were challenged intratracheally with bleomycin, and subsequently followed by MRI and PET/CT for four weeks. PET imaging demonstrated a significantly increased uptake of the collagen tracer in the lungs of challenged rats compared to controls. This was confirmed by MRI characterization of the lesions as edema or fibrotic tissue. The uptake of tracer did not show complete spatial overlap with the lesions identified by MRI. Instead, the tracer signal appeared at the borderline between lesion and healthy tissue. Histological tissue staining, fibrosis scoring, lysyl oxidase activity measurements, and gene expression markers all confirmed establishing fibrosis over time. In conclusion, the novel PET tracer for Collagen-I combined with multi-echo MRI, were successfully able to monitor fibrotic changes in bleomycin-induced lung injury. The translational approach of using non-invasive imaging techniques show potential also from a clinical perspective.

Collagen I-PET and MRI in a Rat Lung Injury Model
Article categories
Subscribe to Lung