Ventilation Imaging Research Articles

Integrated Cardiopulmonary MRI Assessment of Pulmonary Hypertension.

Pulmonary hypertension (PH) is a heterogeneous condition that can affect the lung parenchyma, pulmonary vasculature, and cardiac chambers. Accurate diagnosis often requires multiple complex assessments of the cardiac and pulmonary systems. MRI is able to comprehensively assess cardiac structure and function, as well as lung parenchymal, pulmonary vascular, and functional lung changes. Therefore, MRI has the potential to provide an integrated functional and structural assessment of the cardiopulmonary system in a single exam. Cardiac MRI is used in the assessment of PH in most large PH centers, whereas lung MRI is an emerging technique in patients with PH. This article reviews the current literature on cardiopulmonary MRI in PH, including cine MRI, black-blood imaging, late gadolinium enhancement, T1 mapping, myocardial strain analysis, contrast-enhanced perfusion imaging and contrast-enhanced MR angiography, and hyperpolarized gas functional lung imaging. This article also highlights recent developments in this field and areas of interest for future research including cardiac MRI-based diagnostic models, machine learning in cardiac MRI, oxygen-enhanced 1 H imaging, contrast-free 1 H perfusion and ventilation imaging, contrast-free angiography and UTE imaging. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.

A\xa0novel lung-avoidance planning strategy based on 4DCT ventilation imaging and CT density characteristics for stage\xa0III non-small-cell lung cancer patients

BackgroundFunctional planning based merely on 4DCT ventilation imaging has limitations. In this study, we proposed a radiotherapy planning strategy based on 4DCT ventilation imaging and CT density characteristics.Materials and methodsFor 20 stage III non-small-cell lung cancer (NSCLC) patients, clinical plans and lung-avoidance plans were generated. Through deformable image registration (DIR) and quantitative image analysis, a 4DCT ventilation map was calculated. High-, medium-, and low-ventilation regions of the lung were defined based on the ventilation value. In addition, the total lung was also divided into high-, medium-, and low-density areas according to the HU threshold. The lung-avoidance plan aimed to reduce the dose to functional and high-density lungs while meeting standard target and critical structure constraints. Standard and dose–function metrics were compared between the clinical and lung-avoidance plans.ResultsLung avoidance plans led to significant reductions in high-function and high-density lung doses, without significantly increasing other organ at risk (OAR) doses, but at the expense of a significantly degraded homogeneity index (HI) and conformity index (CI; p < 0.05) of the planning target volume (PTV) and a slight increase in monitor units (MU) as well as in the number of segments (p > 0.05). Compared with the clinical plan, the mean lung dose (MLD) in the high-function and high-density areas was reduced by 0.59 Gy and 0.57 Gy, respectively.ConclusionA lung-avoidance plan based on 4DCT ventilation imaging and CT density characteristics is feasible and implementable, with potential clinical benefits. Clinical trials will be crucial to show the clinical relevance of this lung-avoidance planning strategy.

An asymmetrical whole-body birdcage RF coil without RF shield for hyperpolarized 129 Xe lung MR imaging at 1.5 T.

This study describes the development and testing of an asymmetrical xenon-129 (129 Xe) birdcage radiofrequency (RF) coil for 129 Xe lung ventilation imaging at 1.5 Tesla, which allows proton (1 H) system body coil transmit-receive functionality. The 129 Xe RF coil is a whole-body asymmetrical elliptical birdcage constructed without an outer RF shield to enable 1 H imaging. field homogeneity and flip angle mapping of the 129 Xe birdcage RF coil and 1 H system body RF coil with the 129 Xe RF coil in situ were evaluated in the MR scanner. The functionality of the 129 Xe birdcage RF coil was demonstrated through hyperpolarized 129 Xe lung ventilation imaging with the birdcage in both transceiver configuration and transmit-only configuration when combined with an 8-channel 129 Xe receive-only RF coil array. The functionality of 1 H system body coil with the 129 Xe RF coil in situ was demonstrated by acquiring coregistered 1 H lung anatomical MR images. The asymmetrical birdcage produced a homogeneous field (±10%) in agreement with electromagnetic simulations. Simulations indicated an optimal detuning configuration with 4 diodes. The obtained g-factor of 1.4 for acceleration factor of R = 2 indicates optimal array configuration. Coregistered 1 H anatomical images from the system body coil along with 129 Xe lung images demonstrated concurrent and compatible arrangement of the RF coils. A large asymmetrical birdcage for homogenous transmission with high sensitivity reception for 129 Xe lung MRI at 1.5 Tesla has been demonstrated. The unshielded asymmetrical birdcage design enables 1 H structural lung MR imaging in the same exam.

Accelerate gas diffusion-weighted MRI for lung morphometry with deep learning.

ObjectivesMultiple b-value gas diffusion-weighted MRI (DW-MRI) enables non-invasive and quantitative assessment of lung morphometry, but its long acquisition time is not well-tolerated by patients. We aimed to accelerate multiple b-value gas DW-MRI for lung morphometry using deep learning.MethodsA deep cascade of residual dense network (DC-RDN) was developed to reconstruct high-quality DW images from highly undersampled k-space data. Hyperpolarized 129Xe lung ventilation images were acquired from 101 participants and were retrospectively collected to generate synthetic DW-MRI data to train the DC-RDN. Afterwards, the performance of the DC-RDN was evaluated on retrospectively and prospectively undersampled multiple b-value 129Xe MRI datasets.ResultsEach slice with size of 64 × 64 × 5 could be reconstructed within 7.2 ms. For the retrospective test data, the DC-RDN showed significant improvement on all quantitative metrics compared with the conventional reconstruction methods (p < 0.05). The apparent diffusion coefficient (ADC) and morphometry parameters were not significantly different between the fully sampled and DC-RDN reconstructed images (p > 0.05). For the prospectively accelerated acquisition, the required breath-holding time was reduced from 17.8 to 4.7 s with an acceleration factor of 4. Meanwhile, the prospectively reconstructed results showed good agreement with the fully sampled images, with a mean difference of −0.72% and −0.74% regarding global mean ADC and mean linear intercept (Lm) values.ConclusionsDC-RDN is effective in accelerating multiple b-value gas DW-MRI while maintaining accurate estimation of lung microstructural morphometry, facilitating the clinical potential of studying lung diseases with hyperpolarized DW-MRI.Key Points• The deep cascade of residual dense network allowed fast and high-quality reconstruction of multiple b-value gas diffusion-weighted MRI at an acceleration factor of 4.• The apparent diffusion coefficient and morphometry parameters were not significantly different between the fully sampled images and the reconstructed results (p > 0.05).• The required breath-holding time was reduced from 17.8 to 4.7 s and each slice with size of 64 × 64 × 5 could be reconstructed within 7.2 ms.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00330-021-08126-y.

VMAT Planning With Xe-CT Functional Images Enables Radiotherapy Planning With Consideration of Lung Function.

The most severe adverse event of radiotherapy in lung cancer is radiation pneumonitis (RP). Some indices commonly used to prevent RP are evaluated based on the anatomical lung volume. The irradiation dose may be more accurately assessed by using functional lung volume. We evaluated the usefulness of computed tomography (CT) incorporating functional ventilation images acquired by the inhalation of xenon (Xe) gas (Xe-CT functional images). Two plans were created for twelve patients: volumetric modulated arc therapy (VMAT) planning using conventional chest CT images (anatomical plans) and VMAT planning using Xe-CT functional images (functional plans), and the dosimetric parameters were compared. Compared to the anatomical plans, the functional plans had significantly reduced V 20Gy in the high-functional lungs (p=0.005), but significant differences were not seen in the moderate-functional and low-functional lungs. The incorporation of Xe-CT functional images into VMAT plans enables radiotherapy planning with consideration of lung function.

Functional avoidance-based intensity modulated proton therapy with 4DCT derived ventilation imaging for lung cancer.

The primary objective is to evaluate the potential dosimetric gains of performing functional avoidance‐based proton treatment planning using 4DCT derived ventilation imaging. 4DCT data of 31 patients from a prospective functional avoidance clinical trial were evaluated with intensity modulated proton therapy (IMPT) plans and compared with clinical volumetric modulated arc therapy (VMAT) plans. Dosimetric parameters were compared between standard and functional plans with IMPT and VMAT with one‐way analysis of variance and post hoc paired student t‐test. Normal Tissue Complication Probability (NTCP) models were employed to estimate the risk of two toxicity endpoints for healthy lung tissues. Dose degradation due to proton motion interplay effect was evaluated. Functional IMPT plans led to significant dose reduction to functional lung structures when compared with functional VMAT without significant dose increase to Organ at Risk (OAR) structures. When interplay effect is considered, no significant dose degradation was observed for the OARs or the clinical target volume (CTV) volumes for functional IMPT. Using fV20 as the dose metric and Grade 2+ pneumonitis as toxicity endpoint, there is a mean 5.7% reduction in Grade 2+ RP with the functional IMPT and as high as 26% in reduction for individual patient when compared to the standard IMPT planning. Functional IMPT was able to spare healthy lung tissue to avoid excess dose to normal structures while maintaining satisfying target coverage. NTCP calculation also shows that the risk of pulmonary complications can be further reduced with functional based IMPT.

Early prediction of lung lesion progression in COVID-19 patients with extended CT ventilation imaging.

PurposeIn the prediction of COVID-19 disease progression, a clear illustration and early determination of an area that will be affected by pneumonia remain great challenges. In this study, we aimed to predict and visualize the progression of lung lesions in COVID-19 patients in the early stage of illness by using chest CT.MethodsCOVID-19 patients who underwent three chest CT scans in the progressive phase were retrospectively enrolled. An extended CT ventilation imaging (CTVI) method was proposed in this work that was adapted to use two chest CT scans acquired on different days, and then lung ventilation maps were generated. The prediction maps were obtained according to the fractional ventilation values, which were related to pulmonary regional function and tissue property changes. The third CT scan was used to validate whether the prediction maps could be used to distinguish healthy regions and potential lesions.ResultsA total of 30 patients (mean age ± SD, 43 ± 10 years, 19 females, and 2–12 days between the second and third CT scans) were included in this study. The predicted lesion locations and sizes were almost the same as the true ones visualized in third CT scan. Quantitatively, the predicted lesion volumes and true lesion volumes showed both a good Pearson correlation (R2 = 0.80; P < 0.001) and good consistency in the Bland–Altman plot (mean bias = 0.04 cm3). Regarding the enlargements of the existing lesions, prediction results also exhibited a good Pearson correlation (R2 = 0.76; P < 0.001) with true lesion enlargements.ConclusionThe present findings demonstrated that the extended CTVI method could accurately predict and visualize the progression of lung lesions in COVID-19 patients in the early stage of illness, which is helpful for physicians to predetermine the severity of COVID-19 pneumonia and make effective treatment plans in advance.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00259-021-05435-8.

Regional Gas Exchange Measured by 129 Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease.

BackgroundHyperpolarized 129Xe magnetic resonance imaging (MRI) provides a non‐invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown.PurposeTo characterize changes in 129Xe gas transfer function following administration of an inhaled long‐acting beta‐agonist/long‐acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator.Study TypeProspective.PopulationSeventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy.Field Strength/SequencesDedicated ventilation imaging used a multi‐slice 2D gradient echo sequence. Three‐dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1‐point Dixon sequence. Imaging was acquired at 3 T.Assessment129Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (vendef + low) and by barrier uptake and RBC transfer relative to a healthy reference population (bar%ref and RBC%ref). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO), were also performed before and after treatment.Statistical TestsPaired t‐test, Pearson correlation coefficient (r).ResultsBaseline vendef + low was 57.8 ± 8.4%, bar%ref was 73.2 ± 19.6%, and RBC%ref was 36.5 ± 13.6%. Following treatment, vendef + low decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC%ref decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar%ref and DLCO were correlated with the degree of post‐treatment change in vendef + low (r = −0.49, P < 0.05 and r = −0.52, P < 0.05, respectively).ConclusionLABA/LAMA therapy tended to preferentially improve ventilation in subjects whose 129Xe barrier uptake and DLCO were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy.Level of Evidence1Technical Efficacy Stage4

Quantification of dual-energy CT-derived functional parameters as potential imaging markers for progression of idiopathic pulmonary fibrosis

ObjectivesThe individual course of disease in idiopathic pulmonary fibrosis (IPF) is highly variable. Assessment of disease activity and prospective estimation of disease progression might have the potential to improve therapy management and indicate the onset of treatment at an earlier stage. The aim of this study was to evaluate whether regional ventilation, lung perfusion, and late enhancement can serve as early imaging markers for disease progression in patients with IPF.MethodsIn this retrospective study, contrast-enhanced dual-energy CT scans of 32 patients in inspiration and delayed expiration were performed at two time points with a mean interval of 15.4 months. The pulmonary blood volume (PBV) images obtained in the arterial and delayed perfusion phase served as a surrogate for arterial lung perfusion and parenchymal late enhancement. The virtual non-contrast (VNC) images in inspiration and expiration were non-linearly registered to provide regional ventilation images. Image-derived parameters were correlated with longitudinal changes of lung function (FVC%, DLCO%), mean lung density in CT, and CT-derived lung volume.ResultsRegional ventilation and late enhancement at baseline preceded future change in lung volume (R - 0.474, p 0.006/R - 0.422, p 0.016, respectively) and mean lung density (R - 0.469, p 0.007/R - 0.402, p 0.022, respectively). Regional ventilation also correlated with a future change in FVC% (R - 0.398, p 0.024).ConclusionCT-derived functional parameters of regional ventilation and parenchymal late enhancement are potential early imaging markers for idiopathic pulmonary fibrosis progression.Key Points• Functional CT parameters at baseline (regional ventilation and late enhancement) correlate with future structural changes of the lung as measured with loss of lung volume and increase in lung density in serial CT scans of patients with idiopathic pulmonary fibrosis.• Functional CT parameter measurements in high-attenuation areas (- 600 to - 250 HU) are significantly different from normal-attenuation areas (- 950 to - 600 HU) of the lung.• Mean regional ventilation in functional CT correlates with a future change in forced vital capacity (FVC) in pulmonary function tests.

Automated assessment of functional lung imaging with 68Ga-ventilation/perfusion PET/CT using iterative histogram analysis

PurposeFunctional lung mapping from Ga68-ventilation/perfusion (V/Q) PET/CT, which has been shown to correlate with pulmonary function tests (PFTs), may be beneficial in a number of clinical applications where sparing regions of high lung function is of interest. Regions of clumping in the proximal airways in patients with airways disease can result in areas of focal intense activity and artefact in ventilation imaging. These artefacts may even shine through to subsequent perfusion images and create a challenge for quantitative analysis of PET imaging. We aimed to develop an automated algorithm that interprets the uptake histogram of PET images to calculate a peak uptake value more representative of the global lung volume.MethodsSixty-six patients recruited from a prospective clinical trial underwent both V/Q PET/CT imaging and PFT analysis before treatment. PET images were normalised using an iterative histogram analysis technique to account for tracer hotspots prior to the threshold-based delineation of varying values. Pearson’s correlation between fractional lung function and PFT score was calculated for ventilation, perfusion, and matched imaging volumes at varying threshold values.ResultsFor all functional imaging thresholds, only FEV1/FVC PFT yielded reasonable correlations to image-based functional volume. For ventilation, a range of 10–30% of adapted peak uptake value provided a reasonable threshold to define a volume that correlated with FEV1/FVC (r = 0.54–0.61). For perfusion imaging, a similar correlation was observed (r = 0.51–0.56) in the range of 20–60% adapted peak threshold. Matched volumes were closely linked to ventilation with a threshold range of 15–35% yielding a similar correlation (r = 0.55–0.58).ConclusionsHistogram normalisation may be implemented to determine the presence of tracer clumping hotspots in Ga-68 V/Q PET imaging allowing for automated delineation of functional lung and standardisation of functional volume reporting.

Overview of MRI for pulmonary functional imaging.

Morphological evaluation of the lung is important in the clinical evaluation of pulmonary diseases. However, the disease process, especially in its early phases, may primarily result in changes in pulmonary function without changing the pulmonary structure. In such cases, the traditional imaging approaches to pulmonary morphology may not provide sufficient insight into the underlying pathophysiology. Pulmonary imaging community has therefore tried to assess pulmonary diseases and functions utilizing not only nuclear medicine, but also CT and MR imaging with various technical approaches. In this review, we overview state-of-the art MR methods and the future direction of: (1) ventilation imaging, (2) perfusion imaging and (3) biomechanical evaluation for pulmonary functional imaging.

Reproducibility of 19 F-MR ventilation imaging in healthy volunteers.

PurposeTo assess the reproducibility of percentage ventilated lung volume (%VV) measurements in healthy volunteers acquired by fluorine (19F)‐MRI of inhaled perfluoropropane, implemented at two research sites.MethodsIn this prospective, ethically approved study, 40 healthy participants were recruited (May 2018‐June 2019) to one of two research sites. Participants underwent a single MRI scan session on a 3T scanner, involving periodic inhalation of a 79% perfluoropropane/21% oxygen gas mixture. Each gas inhalation session lasted about 30 seconds, consisting of three deep breaths of gas followed by a breath‐hold. Four 19F‐MR ventilation images were acquired per participant, each separated by approximately 6 minutes. The value of %VV was determined by registering separately acquired 1H images to ventilation images before semi‐automated image segmentation, performed independently by two observers. Reproducibility of %VV measurements was assessed by components of variance, intraclass correlation coefficients, coefficients of variation (CoV), and the Dice similarity coefficient.ResultsThe MRI scans were well tolerated throughout, with no adverse events. There was a high degree of consistency in %VV measurements for each participant (CoVobserver1 = 0.43%; CoVobserver2 = 0.63%), with overall precision of %VV measurements determined to be within ± 1.7% (95% confidence interval). Interobserver agreement in %VV measurements revealed a high mean Dice similarity coefficient (SD) of 0.97 (0.02), with only minor discrepancies between observers.ConclusionWe demonstrate good reproducibility of %VV measurements in a group of healthy participants using 19F‐MRI of inhaled perfluoropropane. Our methods have been successfully implemented across two different study sites, supporting the feasibility of performing larger multicenter clinical studies.

Signs of tracheobronchitis may constitute the principal finding on the lung SPECT/CT images of COVID-19 patients.

BackgroundThis study aimed to analyze the rates of tracheobronchitis signs observed on the ventilation scans of COVID-19 patients with shortness of breath, with comparisons to a non-COVID population.MethodsLung scintigraphy was collected in 10 such COVID patients, as well as from a non-COVID population investigated outside the epidemic wave period, on a CZT-SPECT/CT system, with ventilation images recorded with 99mTc-labeled Technegas® and perfusion images with 99mTc-labeled albumin macroaggregates.ResultsA diffuse tracheobronchial uptake was observed on the ventilation scans from 3 COVID patients (30%), whereas this rate was 3% (3/90) in the non-COVID group (P = 0.013). These 3 patients had no laryngeal extension of Technegas® uptake and limited parenchymal lung abnormalities. Follow-up scintigraphy demonstrated the withdrawal of tracheobronchitis signs in two cases, and the advent of a severe pulmonary embolism in one.ConclusionSigns of tracheobronchitis may constitute the principal finding on lung SPECT/CT images of COVID-19 patients with shortness of breath.

Mapping lung ventilation through stress maps derived from biomechanical models of the lung.

Most existing computed tomography (CT)-ventilation imaging techniques are based on deformable image registration (DIR) of different respiratory phases of a four-dimensonal CT (4DCT) scan of the lung, followed by the quantification of local breathing-induced changes in Hounsfield Units (HU) or volume. To date, only moderate correlations have been reported between these CT-ventilation metrics and standard ventilation imaging modalities for adaptive lung radiation therapy. This study evaluates the use of stress maps derived from biomechanical model-based DIR as an alternative CT-ventilation metric. Six patients treated for lung cancer with conventional radiation therapy were retrospectively analyzed. For each patient, a 4DCT scan and Tc-99m SPECT-V image acquired for treatment planning were collected. Biomechanical model-based DIR was applied between the inhale and exhale phase of the 4DCT scans and stress maps were calculated. The voxel-wise correlation between the reference SPECT-V image and map of the maximum principal stress was measured with a Spearman correlation coefficient. The overlap between high (above the 75th percentile) and low (below the 25th percentile) functioning volumes extracted from the reference SPECT-V and the stress maps was measured with Dice similarity coefficients (DSC). The results were compared to those obtained when using two classical CT-ventilation metrics: the change in HU and Jacobian determinant. The mean Spearman correlation coefficients were: 0.37±18 and 0.39±13 and 0.59±0.13 considering the changes in HU, Jacobian and maximum principal stress, respectively. The corresponding mean DSC coefficients were 0.38±0.09, 0.37±0.07 and 0.52±0.07 for the high ventilation function volumes and 0.48±0.13, 0.44±0.09 and 0.52±0.07 for the low ventilation function volumes. For presenting a significantly stronger and more consistent correlation with standard SPECT-V images than previously proposed CT-ventilation metrics, stress maps derived with the proposed method appear to be a promising tool for incorporation into functional lung avoidance strategies.

Improved preclinical hyperpolarized 129 Xe ventilation imaging with constant flip angle 3D radial golden means acquisition and keyhole reconstruction.

Hyperpolarized (HP) 129 Xe MRI is increasingly used to noninvasively probe regional lung structure and function in the preclinical setting. As in human imaging, the primary barrier to quantitative imaging with HP gases is nonequilibrium magnetization, which is depleted by T1 relaxation and radio frequency excitation. Preclinical HP gas imaging commonly involves mechanically ventilating small animals and encoding k-space over tens or hundreds of breaths, with small subsets of k-space data collected within each breath. Breath-to-breath magnetization renewal enables the use of large flip angles, but the resulting magnetization decay generates large view-to-view differences in within-breath signal intensity, leading to artifacts and degraded image quality. This deleterious signal decay has motivated the use of variable flip angle (VFA) sampling schemes, in which the flip angle is progressively increased to maintain constant view-to-view signal intensity. However, VFA imaging complicates data acquisition and provides only a global correction that fails to compensate for regional differences in signal dynamics. When constant flip angle (CFA) imaging is used alongside 3D radial golden means acquisition, the center of k-space is sampled with every excitation, thereby encoding signal dynamics alongside imaging data. Here, keyhole reconstruction is used to generate multiple images to capture in-breath HP 129 Xe signal dynamics in mice and thus provide flip angle maps to quantitatively correct images without extra data collection. These CFA images display SNR that is not significantly different from VFA images, and further, high frequency k-space scaling can be used to mitigate decay-induced image artifacts. Results are supported by point spread function calculations and simulations of radial imaging with preclinical signal dynamics. Together, these results show that CFA 3D radial golden means ventilation imaging provides comparable image quality with VFA in small animals and allows for keyhole reconstruction, which can be used to generate flip angle maps and correct images for signal depletion.

Pulmonary Ventilation Maps Generated with Free-breathing Proton MRI and a Deep Convolutional Neural Network.

Background Hyperpolarized noble gas MRI helps measure lung ventilation, but clinical translation remains limited. Free-breathing proton MRI may help quantify lung function using existing MRI systems without contrast material and may assist in providing information about ventilation not visible to the eye or easily extracted with segmentation methods. Purpose To explore the use of deep convolutional neural networks (DCNNs) to generate synthetic MRI ventilation scans from free-breathing MRI (deep learning [DL] ventilation MRI)-derived specific ventilation maps as a surrogate of noble gas MRI and to validate this approach across a wide range of lung diseases. Materials and Methods In this secondary analysis of prospective trials, 114 paired noble gas MRI and two-dimensional free-breathing MRI scans were obtained in healthy volunteers with no history of chronic or acute respiratory disease and in study participants with a range of different obstructive lung diseases, including asthma, bronchiectasis, chronic obstructive pulmonary disease, and non-small-cell lung cancer between September 2013 and April 2018 (ClinicalTrials.gov identifiers: NCT03169673, NCT02351141, NCT02263794, NCT02282202, NCT02279329, and NCT02002052). A U-Net-based DCNN model was trained to map free-breathing proton MRI to hyperpolarized helium 3 (3He) MRI ventilation and validated using a sixfold validation. During training, the DCNN ventilation maps were compared with noble gas MRI scans using the Pearson correlation coefficient (r) and mean absolute error. DCNN ventilation images were segmented for ventilation and ventilation defects and were compared with noble gas MRI scans using the Dice similarity coefficient (DSC). Relationships were evaluated with the Spearman correlation coefficient (rS). Results One hundred fourteen study participants (mean age, 56 years ± 15 [standard deviation]; 66 women) were evaluated. As compared with 3He MRI, DCNN model ventilation maps had a mean r value of 0.87 ± 0.08. The mean DSC for DL ventilation MRI and 3He MRI ventilation was 0.91 ± 0.07. The ventilation defect percentage for DL ventilation MRI was highly correlated with 3He MRI ventilation defect percentage (rS = 0.83, P < .001, mean bias = -2.0% ± 5). Both DL ventilation MRI (rS = -0.51, P < .001) and 3He MRI (rS = -0.61, P < .001) ventilation defect percentage were correlated with the forced expiratory volume in 1 second. The DCNN model required approximately 2 hours for training and approximately 1 second to generate a ventilation map. Conclusion In participants with diverse pulmonary pathologic findings, deep convolutional neural networks generated ventilation maps from free-breathing proton MRI trained with a hyperpolarized noble-gas MRI ventilation map data set. The maps showed correlation with noble gas MRI ventilation and pulmonary function measurements. © RSNA, 2020 See also the editorial by Vogel-Claussen in this issue.

Regional ventilation characteristics during non-invasive respiratory support in preterm infants

ObjectivesTo determine the regional ventilation characteristics during non-invasive ventilation (NIV) in stable preterm infants. The secondary aim was to explore the relationship between indicators of ventilation homogeneity and other clinical...

Flow Volume Loop and Regional Ventilation Assessment Using Phase-Resolved Functional Lung (PREFUL) MRI: Comparison With 129 Xenon Ventilation MRI and Lung Function Testing.

Regional flow volume loop ventilation-weighted noncontrast-enhanced proton lung MRI in free breathing has emerged as a novel technique for assessment of regional lung ventilation, but has yet not been validated with 129 Xenon MRI (129 Xe-MRI), a direct visualization of ventilation in healthy volunteers, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) patients. To compare regional ventilation and regional flow volume loops measured by noncontrast-enhanced ventilation-weighted phase-resolved functional lung MRI (PREFUL-MRI) with 129 Xe-MRI ventilation imaging and with lung function test parameters. Retrospective study. Twenty patients with COPD, eight patients with CF, and six healthy volunteers. PREFUL and 129 Xe-MRI gradient echo sequences were acquired at 1.5T. Coronal slices of PREFUL-MRI (free breathing) and 129 Xe-MRI (single breath-hold) were acquired on the same day, matched by their ventrodorsal position and coregistered for evaluation. Ventilation defect percentage (VDP) was calculated based on regional ventilation (RV), regional flow volume loops (RFVL), or 129 Xe-MRI with two different threshold methods. A combined VDP was calculated for RV and RFVL. Additionally, lung function testing was performed (such as the forced expiratory volume in 1 second [FEV1 ]) was used. The obtained parameters were compared using Wilcoxon tests, correlated using Spearman's correlation coefficient (r), and agreement between PREFUL and 129 Xe-MRI parameters was assessed using Bland-Altman analysis and Dice coefficients. VDP measured by PREFUL and 129 Xe were significantly correlated with both thresholding techniques (r = 0.62-0.69, P < 0.05 for all) and with lung function test parameters. Combined RV and RFVL PREFUL defect maps correlated with lung function testing (eg, with FEV1 r = -0.87 P < 0.05), and showed better regional agreement to 129 Xe-MRI ventilation defects (Dice coefficient defect 0.413) with significantly higher VDP values (10.2 ± 27.3, P = 0.04) than either PREFUL defect map alone. Combined RV and RFVL PREFUL defect maps likely increase sensitivity to mild airway obstruction with increased VDP values compared to 129 Xe-MRI, and correlate strongly with lung function test parameters. 3 TECHNICAL EFFICACY STAGE: 2.

129Xe MRI as a measure of clinical disease severity for pediatric asthma

Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. Children with asthma had higher VDP (P= .002) and number of defects per image slice (defects/slice) (P= .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r= 0.48; P= .03) and oral corticosteroid use (r= 0.43; P= .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r= -0.35; P= .04) and FEV1/forced vital capacity ratio (r= -0.41; P= .01). 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.

CT Ventilation Image-Guided Lung Functional Avoidance Radiotherapy: A Single-Arm Prospective Pilot Clinical Trial

Lung functional avoidance radiotherapy (RT) that preferentially avoids irradiating functionally normal lung regions has the potential to reduce pulmonary toxicity after RT. The primary objective of this single-arm prospective pilot clinical trial (NCT02308709) was to assess the safety and feasibility of computed tomography (CT) ventilation image-guided functional avoidance RT. We herein report on the feasibility and dosimetric results. Patients with primary lung cancer or metastatic disease to the lungs to be treated with either conventionally fractionated RT (CFRT) or stereotactic body RT (SBRT) were eligible for this trial. All patients underwent 4-dimensional (4D) CT ventilation imaging during RT simulation based on a 4D CT scan, deformable image registration, and image analysis to quantify regional volume changes as surrogates for ventilation. Each patient required clinically-approved intensity-modulated RT plans for both standard anatomic RT and CT ventilation image-guided functional avoidance RT without compromising target coverage or adherence to constraints of organs at risk (OARs). The lung dose-function metrics were compared between the two plans using the paired two-tailed t test. The primary endpoint was the rate of grade ≥3 toxicities that occurred within 12 months after treatment, to be compared with predefined acceptable rates determined based on published toxicity data. Between May 2015 and November 2019, 34 patients were enrolled (25 patients with stage II-III NSCLC to be treated with CFRT with concurrent chemotherapy and 9 patients with stage I-II NSCLC to be treated with SBRT). One patient died before initiating RT. Of 33 evaluable patients, 32 patients received full dose (CFRT 60 Gy in 2 Gy daily fractions; SBRT 54 Gy in 3 fractions or 55 Gy in 5 fractions) and 1 patient chose to discontinue concurrent chemoradiotherapy due to grade 4 esophagitis. Compared with standard RT planning, functional avoidance RT planning significantly reduced the functional mean lung dose by 0.9 Gy (95% confidence interval [CI] 0.6-1.2 Gy; P < 0.01) (relative reduction 5.2%; 95% CI 3.5-6.8%) and the percentage of total lung function receiving ≥20 Gy by 4.2% (95% CI 3.0-5.4%; P < 0.01) (relative reduction 13.2%; 95% CI 10.5-15.9%) without compromising target coverage or adherence to constraints of OARs in patients treated with CFRT. In patients treated with SBRT, functional avoidance RT planning also significantly reduced the functional mean lung dose by 0.9 Gy (95% confidence interval [CI] 0.7-1.1 Gy; P < 0.01) (relative reduction 9.6%; 95% CI 6.6-12.7%). This pilot study demonstrates the feasibility of CT ventilation image-guided functional avoidance RT that significantly reduces the dose to functionally normal lung regions. Final toxicity results will be reported upon completion of the follow-up phase.