Pulmonary imaging

Our research focus is the application of magnetic resonance imaging (MRI) techniques to pulmonary diseases, with an overarching aim of developing novel imaging biomarkers that can be used to better understand the pathophysiology of lung disease.

Hyperpolarised gas ventilation images from different patients

Sheffield has pioneered the use of HP gas MRI over the last 20 years, and is a world leader in the field. In 2015 our centre was licensed for the manufacture of hyperpolarised 3He and 129Xe gas for clinical lung investigations, a world first for this technology.

This work has expanded significantly over recent years with the advent of a new imaging laboratory and now attracts clinical referrals from respiratory physicians across the UK.

Whilst inexpensive and simple to perform, spirometry is insufficiently sensitive to detect early functional changes associated with lung disease. More sensitive methods are needed to allow for early therapy and better patient management, and so we focus on applying hyperpolarised gas MRI to study lung microstructure, and ventilation and gas exchange function; high resolution structural MRI to visualise the lung macrostructure; and dynamic contrast enhanced MRI to assess lung perfusion. These methods can be applied to assess lung structure and function in a range of pulmonary disorders.

Research into these techniques is ongoing and areas of interest include:

  • Chronic obstructive pulmonary disease (COPD)
  • Asthma
  • Interstitial lung disease (ILD), including Idiopathic Pulmonary Fibrosis (IPF)
  • Cystic fibrosis (CF)
  • Pulmonary vascular disease
  • Pre-term birth-related lung disease and primary ciliary dyskinesia (PCD)

Overarching projects in clinical translation:

COPD and Asthma

Asthma and COPD are among the most common respiratory diseases, with COPD being the third leading cause of death worldwide. We use hyperpolarised gas MRI to visualise the distribution of ventilation in the lung and obtain imaging biomarkers of ventilation that show increased sensitivity over spirometry in COPD and asthma. Diffusion imaging can be used to measure enlarged alveolar airspaces in emphysema, and dynamic contrast enhanced perfusion imaging can visualise the distribution of blood perfusion in the lung microvasculature.  In patients with severe COPD, time-resolved ventilation imaging can detect collateral ventilation, the key factor that determines the success or failure of lung volume reduction surgery (LVRS) using endobronchial valves.

Hyperpolarised gas ventilation images in COPD and asthma
Hyperpolarised gas ventilation images from four patients with COPD (top) and four patients with asthma (bottom).

Hyperpolarised gas MRI does not involve ionising radiation exposure and therefore can be performed repeatedly; e.g. multiple times in a single day to assess treatment response to bronchodilator therapy, or over longer time-periods to evaluate longer-term therapies. We have carried out studies to assess treatment response to novel drugs in patients suffering from these diseases. Furthermore, we have obtained Medicines and Healthcare products Regulatory Agency (MHRA) approval to perform these scans as part of routine clinical practice, to aid clinicians in managing those patients with challenging diagnoses. Our clinician collaborators report that visualising regional lung ventilation provides a greater clinical insight than spirometry alone.

Hyperpolarised gas mapping of ventilation response
Mapping of ventilation response to bronchodilator in a patient with asthma. ∆VVF = change in ventilated volume fraction.

Projects, Collaborators & Publications

Current Projects / Grants
  • ADPro NOVELTY study - Observational study of obstructive lung disease in patients with COPD and asthma (funded by AstraZeneca)
Past Projects / Grants
  • Study to assess the effect of Indacaterol/Glycopyrronium on ventilation and perfusion in COPD (funded by Novartis), EUDRACT # 2013-004461-13
  • EU FP7 AirPROM - Airway Disease Predicting Outcomes through Patient Specific Computational Modelling
  • Fevipripant asthma study with the University of Leicester (funded by EU FP7 Air PROM and Novartis)
  • Investigation of the use of MRI to detect changes in ventilation-perfusion relationships in COPD (funded by GSK)
Key Publications

Interstitial lung disease

Interstitial lung disease (ILD) covers a wide range of pulmonary disorders, including idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP), which can present as progressive fibrosis (scarring) of the lung tissue. ILD, whether fibrotic or not, is typically characterised by gas exchange functional impairment in the lung. The imaging methods that we use to help better assess the progression of disease in these patients include: diffusion-weighted MRI with hyperpolarised 3He or 129Xe, MR spectroscopy / spectroscopic imaging of 129Xe dissolved in the lung tissue and blood, and 1H dynamic contrast-enhanced (DCE) MRI. DW-MRI provides information on the microstructure of the alveoli, while 129Xe spectroscopy / spectroscopic imaging measures provide information on fibrosis and tissue thickening, and their influence on gas exchange. DCE MRI provides information on the passage of blood through the lung and its change over time in these patients. In addition, through recent collaborations with Wisconsin and the Mayo Clinic, we have implemented a high-resolution UTE MRI sequence for macrostructural assessment of the lung of comparable quality to CT, and have investigated quantitative CT biomarkers, in patients with ILD.

Diffusion-weighted MRI in ILD
CT images (top) and helium-3 (3He) diffusion-weighted MRI acquired in a 74-year-old male with IPF. ADC: apparent diffusion coefficient; LmD: mean diffusive length scale.
129Xe MR Spectroscopic Imaging in IPF
129Xe spectroscopic imaging (a, b) and spectroscopy (c) in a patient with IPF. Arrows highlight a region of reduced gas transfer to the red blood cells. FA = flip angle, G = residual gas contamination, TP = tissue and plasma, RBC = red blood cells.
Dynamic contrast enhanced perfusion MRI in ILD
Parametric transit time (FWHM) maps from two participants with ILD at baseline (A and C) and follow up (B and D) scans. Colour bar denotes FWHM in seconds.
High resolution CT (left) and UTE MRI (right) of a patient with connective tissue disease interstitial lung disease (CTD-ILD). UTE = ultra-short echo time.

We are using high resolution UTE MR images to study patients with a number of subtypes of interstitial lung disease (ILD) as part of the TRISTAN study, and we are able to detect changes similar to those seen on CT.

Projects, Collaborators & Publications

Current Projects / Grants
Key Publications

Cystic fibrosis

One key issue in monitoring patients with CF is the global information provided from lung function, rather than the locality and regional extent of lung disease, which can only be accessed with imaging. CT is often used clinically when managing patients with CF, however repeated exposure to ionising radiation, particularly in children, is a concern and has led our centre and others to pursue MRI for lung functional assessment of patients with CF.

We were the first centre to perform paediatric studies in CF, and have applied hyperpolarised gas and structural UTE MRI in CF in a number of studies, scanning patients as young as 6 years old. These imaging methods can detect subclinical changes in lung function and involve no ionising radiation, so are well-suited to longitudinal follow-up / monitoring of disease in these patients.

Hyperpolarised gas MRI is sensitive to early CF lung disease
Hyperpolarised gas MRI is sensitive to early CF lung disease in patients with normal FEV1 (left), and also to worsening and improving lung disease when FEV1 is unchanged (right).

We are also involved in a number of collaborative studies investigating structure-function relationships in CF and evaluating novel proton MRI methods developed by our partners. 

Linking structure with function in CF
Linking structure with function in CF with various MRI techniques.

Projects, Collaborators & Publications

Current Projects / Grants
  • MMAVIC study - MRI & multiple breath washout to assess ventilation in cystic fibrosis
  • VIPS study - Validation of bi- and three-dimensional Fourier Decomposition to assess lung ventilation and perfusion compared to CT, hyperpolarized gases and contrast-enhanced MRI
Key Publications

Pulmonary vascular disease

Pulmonary vascular disease is diagnosed using invasive techniques such as right heart catheter or nuclear medicine imaging. Our research focus is the use of MRI for non-invasive diagnostic and prognostic markers in pulmonary vascular disease. We have developed image processing techniques and software to allow for analysis of quantitative metrics of cardiopulmonary function, such as pulmonary VQ matching and T1 relaxation time.

See also: Cardiovascular Imaging

Dynamic contrast enhanced perfusion images
Dynamic contrast enhanced perfusion images in a healthy volunteer, a patient with chronic thromboembolic pulmonary hypertension (CTEPH) and a patient with pulmonary arterial hypertension (PAH).
Inspiration breath hold and free breathing lung T1 maps
a) Inspiration breath hold and b) free breathing lung T1 maps using a Look-Locker acquisition in pulmonary hypertension subgroups.

Projects, Collaborators & Publications

Current Projects / Grants
Key Publications

Pre-term Birth Related Lung Disease and PCD

In addition to our extensive research in to paediatric CF, we have utilised hyperpolarised gas MRI to study the lung ventilation and microstructural changes associated with pre-term birth related lung disease (Rhino study) and congenital diaphragmatic hernia (CDH).

Hyperpolarised gas images of children born preterm
Hyperpolarised 129Xe ventilation images from 3 children born preterm with obstructive lung disease (left). 129Xe ADC and LmD maps from 3 children born preterm with chronic lung disease of prematurity (right).

In a study using ventilation MRI in children with primary ciliary dyskinesia (PCD), we found ventilation defects even in the presence of normal lung clearance index and FEV1, suggesting that ventilation MRI is a sensitive method for detecting lung disease in children with PCD.

Ventilation images of children with primary ciliary dyskinesia
Ventilation images of children with primary ciliary dyskinesia

Projects, Collaborators & Publications

Current Projects / Grants
Key Publications


  • Smitha Rajaram (Consultant Radiologist)

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