Objective: We aimed to develop a user-friendly image-analysis pipeline to simultaneously generate perfusion and ventilation maps derived from Fourier decomposition of free-breathing pulmonary 1H magnetic resonance imaging (FDMRI). Methods: Free-breathing 1H MR images were non-rigidly deformed to a 1H reference image selected halfway between inspiration and expiration, using modality independent neighbourhood descriptor-based registration. The 1H reference image was segmented using multi-region coupled continuous max-flow. The co-registered image sequence was Fourier transformed on a voxel-by-voxel basis to generate images of the voxel-wise power spectrum. The two largest intensity peaks in the power spectrum corresponded to respiratory and cardiac frequencies, which were used to generate ventilation and perfusion maps, respectively. Perfusion and ventilation defects were measured using fuzzy c-means clustering in 15 asthmatics who provided written-informed-consent to pulmonary function tests and MRI. Results: The proposed FDMRI pipeline was used to generate perfusion maps in 15 asthma patients for direct comparison with 3He and FDMRI ventilation maps. FDMRI perfusion measurements were significantly correlated with FDMRI (r2=0.48, p=0.03) and 3He MRI ventilation (r2=0.44, p=0.05). Conclusion: Ventilation and perfusion free-breathing 1H MRI maps were generated in asthmatics with clinicallyacceptable accuracy and minimal user interaction using a pipeline compatible with high throughput clinical workflows.
Objective: Hyperpolarized noble gas magnetic resonance imaging (MRI) provides valuable insights on lung function, and yet is not widely available, whereas thoracic x-ray computed tomography (CT) protocols are nearly universally accessible. Our aim was to develop a texture analysis pipeline to train and test machine learning classifiers, predicting MRI-based ventilation metrics from single-volume thoracic CT in patients with chronic obstructive pulmonary disease (COPD). Methods: MR ventilation maps were generated and registered to thoracic CT datasets. Images were segmented into volumes of interest (15x15x15mm), resulting in approximately 6,000 volumes-of-interest per subject participant. 85 firstorder and texture features were calculated to describe each volume, including a new texture feature based on the size and occurrence of CT clusters (we called the cluster volume matrix), which is similar to run-length-matrix. A Logistic Regression, Linear Support Vector Machine and Quadratic Support Vector Machine were trained using 5-fold crossvalidation on a cohort of seven subjects. The highest performing classification model was then applied to a test cohort of three subjects. Results: There was qualitative spatial agreement for the experimental MRI ventilation maps and the CT-predicted functional maps. The training set was classified with 71% accuracy, while the test set was classified with 66% accuracy and area under the curve (AUC) = 0.72. Conclusions: This proof-of-concept study demonstrated feasibility in a small group of patients with moderate classification accuracy. Novel insights will be used to optimize this approach with future application to a larger heterogeneous patient cohort.
Objective: Our aim was to develop and evaluate multi-parametric response maps derived from pulmonary x-ray computed tomography (CT), 1H and hyperpolarized 3He static ventilation and diffusion-weighted magnetic resonance imaging (MRI). These maps were generated to phenotype patients with chronic obstructive pulmonary disease (COPD) based on the presence of airways disease, air trapping, emphysema, alveolar distension, and ventilation defects. Methods: To generate thoracic imaging multi-parametric response maps (mPRM), multispectral 1H, 3He and CT images were segmented and co-registered. 1H and 3He MR images were segmented using a semi-automated segmentation algorithm, the diffusion weighted MR images were segmented using a threshold-based algorithm and CT images were segmented using Pulmonary Workstation 2.0 (VIDA Diagnostics, Coralville, IA). The volume-matched segmented 1H/3He maps were registered using landmark rigid registration. The 3He maps/the diffusion weighted images were registered using an intensity-based rigid registration. CT-to-MRI co-registration was achieved using modality-independent neighborhood descriptor (MIND) deformable registration; inspiratory and expiratory CT were co-registered using an affine registration with a deformable step provided by the NiftyReg toolkit. The co-registered thoracic maps were used to generate multiparametric maps. Results: mPRM maps were generated for six different voxel classifications with increasing disease abnormality/severity as follows: 1) ventilated voxels with >-856HU/>-950HU and normal apparent diffusion coefficient (ADC) values, 2) ventilated voxels with <-856HU/<-950HU and abnormal ADC values, 3) ventilated voxels with >-856HU/>-950HU and normal ADC values, 4) ventilated voxels with <-856HU/<-950HU and abnormal ADC values, 5) unventilated voxels with >-856HU/>-950HU, and, 6) unventilated voxels with <-856HU/<-950HU. Conclusion: mPRM measurements were automated in a dedicated pipeline for MRI and CT measurements to phenotype COPD patients.
We designed and generated pulmonary imaging biomarker pipelines to facilitate high-throughput research and point-of-care use in patients with chronic lung disease. Image processing modules and algorithm pipelines were embedded within a graphical user interface (based on the .NET framework) for pulmonary magnetic resonance imaging (MRI) and x-ray computed-tomography (CT) datasets. The software pipelines were generated using C++ and included: (1) inhaled He3 / Xe129 MRI ventilation and apparent diffusion coefficients, (2) CT-MRI coregistration for lobar and segmental ventilation and perfusion measurements, (3) ultrashort echo-time H1 MRI proton density measurements, (4) free-breathing Fourier-decomposition H1 MRI ventilation/perfusion and free-breathing H1 MRI specific ventilation, (5) multivolume CT and MRI parametric response maps, and (6) MRI and CT texture analysis and radiomics. The image analysis framework was implemented on a desktop workstation/tablet to generate biomarkers of regional lung structure and function related to ventilation, perfusion, lung tissue texture, and integrity as well as multiparametric measures of gas trapping and airspace enlargement. All biomarkers were generated within 10 min with measurement reproducibility consistent with clinical and research requirements. The resultant pulmonary imaging biomarker pipeline provides real-time and automated lung imaging measurements for point-of-care and high-throughput research.
Objectives: Our aim was to develop a clinically-practical and physiologically-relevant approach for regional structure-function measurements of the lung using Fourier decomposition of free-breathing pulmonary magnetic resonance imaging (FDMRI). Methods: Ten patients with chronic obstructive pulmonary disease provided written informed consent to a study protocol approved by Health Canada and completed pulmonary function tests, 1H/hyperpolarized noble gas and free-breathing pulmonary magnetic resonance imaging (MRI) during a single 2-hour visit. Free-breathing 1H MRI was simultaneously segmented using a multi-region coupled continuous max-flow approach by exploring primal/dual analysis and convex optimization techniques. The segmented free-breathing 1H MRI lung was registered using deformable registration approach that was developed using dual and convex optimization methods to compensate for respiratory/cardiac motion. Fourier decomposition of the co-registered lung was used to generate pulmonary functional information that was quantified as ventilation-defect-percent (VDP). The pipeline was implemented on a GPU for speed-up. Lung segmentation accuracy was measured by comparing algorithm and manual lung masks using Dice-similarity-coefficient (DSC). FD-VDP was compared to 3He-VDP using Pearson correlation coefficient and Bland-Altman analysis. The reproducibility of our algorithm was measured using coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for DSC and FD-VDP. Results: The pipeline yielded a whole lung DSC of 95.7±1.7% and FD-VDP that were correlated with 3He-VDP (r = 0.81, p = 0.004). CoV (ICC) were 0.4% (0.98) and 4.1% (0.98) for whole lung DSC and FD-VDP, respectively. The proposed approach requires ~45 min for parallel implementation with minimal user interaction. Conclusion: The proposed approach provides a clinically-practical pipeline to generate regional pulmonary structure-function measurements using free-breathing pulmonary 1HMRI with promising potential for widespread clinical translation.
Fourier-decomposition of free-breathing pulmonary magnetic resonance imaging (FDMRI) was recently piloted as a way to provide rapid quantitative pulmonary maps of ventilation and perfusion without the use of exogenous contrast agents. This method exploits fast pulmonary MRI acquisition of free-breathing proton (1H) pulmonary images and non-rigid registration to compensate for changes in position and shape of the thorax associated with breathing. In this way, ventilation imaging using conventional MRI systems can be undertaken but there has been no systematic evaluation of fundamental image quality measurements based on linear systems theory. We investigated the performance of free-breathing pulmonary ventilation imaging using a Fourier-based linear system description of each operation required to generate FDMRI ventilation maps. Twelve subjects with chronic obstructive pulmonary disease (COPD) or bronchiectasis underwent pulmonary function tests and MRI. Non-rigid registration was used to co-register the temporal series of pulmonary images. Pulmonary voxel intensities were aligned along a time axis and discrete Fourier transforms were performed on the periodic signal intensity pattern to generate frequency spectra. We determined the signal-to-noise ratio (SNR) of the FDMRI ventilation maps using a conventional approach (SNRC) and using the Fourier-based description (SNRF). Mean SNR was 4.7 ± 1.3 for subjects with bronchiectasis and 3.4 ± 1.8, for COPD subjects (p>.05). SNRF was significantly different than SNRC (p<.01). SNRF was approximately 50% of SNRC suggesting that the linear system model well-estimates the current approach.
Pulmonary x-ray computed tomography (CT) may be used to characterize emphysema and airways disease in patients with chronic obstructive pulmonary disease (COPD). One analysis approach – parametric response mapping (PMR) utilizes registered inspiratory and expiratory CT image volumes and CT-density-histogram thresholds, but there is no consensus regarding the threshold values used, or their clinical meaning. Principal-component-analysis (PCA) of the CT density histogram can be exploited to quantify emphysema using data-driven CT-density-histogram thresholds. Thus, the objective of this proof-of-concept demonstration was to develop a PRM approach using PCA-derived thresholds in COPD patients and ex-smokers without airflow limitation. Methods: Fifteen COPD ex-smokers and 5 normal ex-smokers were evaluated. Thoracic CT images were also acquired at full inspiration and full expiration and these images were non-rigidly co-registered. PCA was performed for the CT density histograms, from which the components with the highest eigenvalues greater than one were summed. Since the values of the principal component curve correlate directly with the variability in the sample, the maximum and minimum points on the curve were used as threshold values for the PCA-adjusted PRM technique. Results: A significant correlation was determined between conventional and PCA-adjusted PRM with 3He MRI apparent diffusion coefficient (p<0.001), with CT RA950 (p<0.0001), as well as with 3He MRI ventilation defect percent, a measurement of both small airways disease (p=0.049 and p=0.06, respectively) and emphysema (p=0.02). Conclusions: PRM generated using PCA thresholds of the CT density histogram showed significant correlations with CT and 3He MRI measurements of emphysema, but not airways disease.
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