Pulmonary MR angiography and perfusion imaging—A review of methods and applications

The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology

Diffusion weighted imaging in cystic fibrosis disease: beyond morphological imaging

To explore the feasibility of diffusion-weighted imaging (DWI) to assess inflammatory lung changes in patients with Cystic Fibrosis (CF) METHODS: CF patients referred for their annual check-up had spirometry, chest-CT and MRI on the same day. MRI was performed in a 1.5 T scanner with BLADE and EPI-DWI sequences (b = 0-600 s/mm(2)). End-inspiratory and end-expiratory scans were acquired in multi-row scanners. DWI was scored with an established semi-quantitative scoring system. DWI score was correlated to CT sub-scores for bronchiectasis (CF-CTBE), mucus (CF-CTmucus), total score (CF-CTtotal-score), FEV1, and BMI. T-test was used to assess differences between patients with and without DWI-hotspots

Quantification of perfusion abnormalities using dynamic contrast-enhanced magnetic resonance imaging in muco-obstructive lung diseases

Pulmonary perfusion is regionally impaired in muco-obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) due to the destruction of the alveolar-capillary bed and hypoxic pulmonary vasoconstriction in response to alveolar hypoxia. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an established technique for assessing regional perfusion abnormalities by exploiting contrast enhancement in the lung parenchyma during the first pass of an intravenously injected contrast agent bolus. Typically, perfusion abnormalities are assessed in clinical studies by visual scoring or by quantifying pulmonary blood flow (PBF) and pulmonary blood volume (PBV). Automated quantification can help to address inter-reader variability issues with human reader, facilitate detailed perfusion analyses and is time efficient. However, currently used absolute quantification of PBF and PBV is highly variable. For this reason, an algorithm was developed to quantify the extent of pulmonary perfusion in percent (QDP) using unsupervised clustering algorithms, which leads to an intrinsic normalisation and can reduce variability compared to absolute perfusion quantification. The aims of this work were to develop a robust algorithm for quantifying QDP, to investigate the midterm reproducibility of QDP, and to validate QDP using MRI perfusion scoring, quantitative computed tomography (CT) parameters, and pulmonary function testing (PFT) parameters. Furthermore, the performance of QDP was compared to the performance of PBF and PBV. The development of QDP and its technical and clinical validation were performed using data from two studies, which utilise DCE-MRI. First, the algorithm was developed using data of 83 COPD subjects from the ‘COSYCONET’ COPD cohort by comparing different unsupervised clustering approaches including Otsu´s method, k-means clustering, and 80th percentile threshold. Second, the reproducibility of QDP was investigated using data from a study of 15 CF and 20 COPD patients who underwent DCE-MRI at baseline and one month later (reproducibility study). According to the indicator dilution theory, impulse response function maps were calculated from DCE-MRI data, which formed the basis for the quantification of QDP, PBF and PBV. Overall, QDP based on Otsu´s method showed the highest agreement with the MRI perfusion score, quantitative CT parameters and PFT parameters in the COSYCONET study and was therefore selected for further evaluations. QDP correlated moderately with the MRI perfusion score in CF (r=0.46, p<0.05) and moderately to strongly in COPD (r=0.66 and r=0.72, p<0.001) in both studies. PBF and PBV correlated poorly with the MRI perfusion score in CF (r=-0.29, p=0.132 and r=-0.35, p=0.067, respectively) and moderately in COPD (r=-0.49 to -0.57, p<0.001). QDP correlated strongly with the CT parameter for emphysema (r=0.74, p<0.001) and weakly with the CT parameter for functional small airway disease (r=0.35, p<0.001) in COPD. The extent of perfusion defects from DCE-MRI corresponded to extent of abnormal lung (emphysema+functional small airway disease) from CT, with a mean difference of 6.03±16.94. QDP correlated moderately with PFT parameters in both studies and patient groups, with one exception in the reproducibility study where no correlation was observed in the COPD group. The use of unsupervised clustering approaches increased the reproducibility (±1.96SD related to the median) of QDP (CF: ±38%, COPD: ±37%) compared to PBF(CF: ±89%, COPD: ±55%) and PBV(CF: ±55%, COPD: ±51%) and reduced outliers. These results demonstrate that the quantification of pulmonary perfusion using unsupervised clustering approaches in combination with the mathematical models of the indicator dilution theory improves the reproducibility and the correlations with visual MRI perfusion scoring, quantitative CT parameters and PFT parameters. QDP based on Otsu´s method showed high agreement with the MRI perfusion score, suggesting that in future clinical studies pulmonary perfusion can be assessed objectively by computer algorithms replacing the time-consuming visual scoring. Concordance between the extent of QDP from MRI and the extent of abnormal lung from CT indicates that pulmonary perfusion abnormalities themselves may contribute to, or at least precede, the development of irreversible emphysema. The findings of both studies show that QDP is clinically meaningful in muco-obstructive lung diseases as it is significantly associated with the MRI perfusion score, quantitative CT parameters, and PFT parameters

The application of advanced imaging techniques for the assessment of paediatric chest disease

Introduction – Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) both result in chronic suppurative lung disease with significant resulting morbidity and early mortality. Many clinical and academic groups advocate biennial or even annual CT surveillance from as early as 2 years of age, but new therapies and increasing life expectancy lead to concerns over the use of repeated CT imaging. There are many recent studies showing promise of MRI for structural lung imaging MRI based measures of lung function. Both CF and PCD result in multisystem disease and whilst much of the morbidity results from lung disease, monitoring of extrathoracic disease is likely also relevant. Aims and objectives – 1) To set up a clinically feasible, multisystem (lung, sinonasal and upper abdominal visceral) quantitative MRI examination for the investigation and follow up of CSLD 2) To evaluate novel imaging biomarkers of CF and PCD disease severity Hypotheses – 1) Combined structural and quantitative MRI assessment of the thorax can provide comparable information to CT such that follow up imaging via CT could be replaced with MRI. 2) Quantitative MR measures of ventilation correlate with established clinical measures of ventilation (LCI and FEV1) and provide additional spatial information. 3) A multisystem MRI assessment can provide new extra-thoracic imaging biomarkers of CF and PCD disease severity whilst being better tolerated by patients than current multimodality imaging follow up. Methods – People with CF or PCD referred for clinically indicated lung CT were prospectively recruited to undergo MR imaging of the lungs, liver and paranasal sinuses. Structural lung imaging was optimised for speed of acquisition using T2 BLADE imaging, in axial and coronal plane, during breath holds rather than more conventional respiratory triggering. Images were scored by two observers using the Eichinger scoring system and compared to CT structural scores using the CFCT scoring system. Lung T1 mapping was performed via free breathing IR-HASTE and T1 and T2 mapping performed via breath hold ufbSSFP imaging. Functional lung imaging was performed via pre and post hyperoxygenation ufbSSFP T1 mapping, free breathing dynamic oxygen enhanced IR-HASTE imaging (OE-MRI) and non-contrast ufbSSFP-based matrix pencil decomposition imaging of ventilation and pulmonary perfusion. Lung T1 maps included the superior portion of the liver enabling simultaneous liver T1 mapping. A multiparametric paranasal sinus protocol was devised containing structural (T1 and T2 TSE), susceptibility and diffusion weighted sequences for the calculation of sinus volume, mucus volume and mucosal volume, presence or absence of artefact associated with infective micro-organisms and calculation of mucus and mucosal diffusion. Participant tolerability of MR imaging assessed via a bespoke questionnaire, completed before and after both CT and MR imaging. Multiple breath wash-out testing was performed on the day of the MRI and spirometry, antibiotic usage, abdominal ultrasound and sheer wave elastography collected retrospectively from the electronic patient record. Results – 22 participants were recruited, all of whom completed the hour-long MRI protocol. The median age was 14 years (range 6 – 35). 2-plane structural lung imaging was acquired in a total of 2 minutes 4 seconds with only a single participant reporting difficulties with the required breath holds. Interclass Correlation Coefficients of interobserver variability in MRI scores were comparable to CT (0.877-0.965 compared to 0.877-0.989 respectively) suggesting good image quality with strong correlation between MR and CT component scores (bronchiectasis/bronchial wall thickening r=0.828,p<0.001; mucus plugging r=0.812, p<0.001; parenchymal score r=0.564 – 0.729, p<0.001 – 0.006). Median lung T1 did not correlate with clinical markers of disease severity, but median lung T2 demonstrated strong correlation with CT bronchial wall thickening (r=-0.655, p=0.001) and LCI2.5 (r=-0.540, p=0.046), most likely representing a surrogate of pulmonary perfusion (most pulmonary T2 signal likely originates from the pulmonary blood pool). Significant ufbSSFP enhancement was demonstrated post hyperoxygenation, but the degree of enhancement did not correlate significantly with clinical measures of disease severity. There was, however, very strong correlations between matrix pencil decomposition ventilation fraction and LCI2.5 (r=0.831, p=0.001) and CFCT scores (r= up to 0.731, p=<0.001). Significant correlation was also demonstrated between measures of ventilation heterogeneity (oxygen wash-out time skew and kurtosis) and both LCI2.5 (r=0.591, p=0.013) and CFCT component scores (r= up to 0.718, p<0.001). Liver T1 values did not correlate with evidence of liver disease on liver function tests or ultrasound imaging, but interpretation was severely limited by the very small number of recruits with CF liver disease. Sinus imaging was the last part of the protocol with failed analysis in only one patient from too much motion (a 6 year old). Association was demonstrated between exacerbation frequency and opacification of maxillary sinuses by mucusa (p=0.074), between CT hyperinflation score and increasing levels of mucus susceptibility artefact (0=0.028), between exacerbation frequency, CT bronchial wall thickening and mucus plugging and increased sinus mucus diffusion (r=0.581, p=0.048, r=0.744, p=0.006 and r=0.633, p=0.019 respectively) and between CT hyperinflation, bronchiectasis and bronchial wall thickening scores and increased sinus mucosal diffusion (r=-0.847, p=0.016; r=-0.542, p=0.017 and r=-0.427, p=0.069 respectively). A third of recruits stated that they would opt for MR imaging over CT imaging in the future and whilst 41% reported difficulties staying still for the MRI, respiratory image post processing was successful in all participants, with no parts of the MRI studies repeated. Conclusion – Multisystem lung, liver and sinus MRI is feasible, well tolerated by people with CF or PCD, down to the age of 6 years, and provides gross structural imaging of sufficient quality to replace CT for lung imaging surveillance. Furthermore, the addition of functional lung imaging provides quantitative outputs which correlate well with clinically established lung function tests with the benefit of spatially localised lung function and additional quantitative measures of relevant extrapulmonary disease, within a single ionising radiation free examination. The data from this study have supported funding for future work addressing short, medium and long-term repeatability and longitudinal trends both in times of disease stability and over the course of an infective exacerbation.Open Acces

Quantification of pulmonary perfusion abnormalities using DCE-MRI in COPD: comparison with quantitative CT and pulmonary function

Objectives Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI. Methods We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 +/- 9.0 years, patients-at-risk, and all GOLD groups) from one center of the COSYCONET COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu's method, k-means clustering, texture analysis, and 80(th) percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRMEmph) and functional small airway disease (PRMfSAD), and FEV1/FVC from PFT. Results All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p < 0.001), with the highest association based on Otsu's method (r = 0.72, p < 0.001). QDP correlated significantly with all PRM indices (p < 0.001), with the strongest correlations with PRMEmph (r = 0.70 to 0.75, p < 0.001). QDP was distinctly higher than PRMEmph (mean difference = 35.85 to 40.40) and PRMfSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = - 0.54 to - 0.41, p < 0.001). Conclusion QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRMEmph and PRMfSAD. We propose to use QDP based on Otsu's method for future clinical studies in COPD

Lung Imaging and Function Assessment using Non-Contrast-Enhanced Magnetic Resonance Imaging

Measurement of pulmonary ventilation and perfusion has significant clinical value for the diagnosis and monitoring of prevalent lung diseases. To this end, non-contrast-enhanced MRI techniques have emerged as a promising alternative to scintigraphical measurements, computed tomography, and contrast-enhanced MRI. Although these techniques allow the acquisition of both structural and functional information in the same scan session, they are prone to robustness issues related to imaging artifacts and post-processing techniques, limiting their clinical utilization. In this work, new acquisition and post-processing techniques were introduced for improving the robustness of non-contrast-enhanced MRI based functional lung imaging. Furthermore, pulmonary functional maps were acquired in 2-year-old congenital diaphragmatic hernia (CDH) patients to demonstrate the feasibility of non-contrast-enhanced MRI methods for functional lung imaging. In the first study, a multi-acquisition framework was developed to improve robustness against field inhomogeneity artifacts. This method was evaluated at 1.5T and 3T field strengths via acquisitions obtained from healthy volunteers. The results demonstrate that the proposed acquisition framework significantly improved ventilation map homogeneity p<0.05. In the second study, a post-processing method based on dynamic mode decomposition (DMD) was developed to accurately identify dominant spatiotemporal patterns in the acquisitions. This method was demonstrated on digital lung phantoms and in vivo acquisitions. The findings indicate that the proposed method led to a significant reduction in dispersion of estimated ventilation and perfusion map amplitudes across different number of measurements when compared with competing methods p<0.05. In the third study, the free-breathing non-contrast-enhanced dynamic acquisitions were obtained from 2-year-old patients after CDH repair, and then processed using the DMD to obtain pulmonary functional maps. Afterwards, functional differences between ipsilateral and contralateral lungs were assessed and compared with results obtained using contrast-enhanced MRI measurements. The results demonstrate that pulmonary ventilation and perfusion maps can be generated from dynamic acquisitions successfully without the need for ionizing radiation or contrast agents. Furthermore, lung perfusion parameters obtained with DMD MRI correlate very strongly with parameters obtained using dynamic contrast-enhanced MRI. In conclusion, the presented work improves the robustness and accuracy of non-contrast-enhanced functional lung imaging using MRI. Overall, the methods introduced in this work may serve as a valuable tool in the clinical adaptation of non-contrast-enhanced imaging methods and may be used for longitudinal assessments of pulmonary functional changes