Magnetic Resonance Imaging of Lung Perfusion.

"Lung perfusion" in the context of imaging conventionally refers to the delivery of blood to the pulmonary capillary bed through the pulmonary arteries originating from the right ventricle required for oxygenation. The most important physiological mechanism in the context of imaging is the so-called hypoxic pulmonary vasoconstriction (HPV, also known as "Euler-Liljestrand-Reflex"), which couples lung perfusion to lung ventilation. In obstructive airway diseases such as asthma, chronic-obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma, HPV downregulates pulmonary perfusion in order to redistribute blood flow to functional lung areas in order to conserve optimal oxygenation. Imaging of lung perfusion can be seen as a reflection of lung ventilation in obstructive airway diseases. Other conditions that primarily affect lung perfusion are pulmonary vascular diseases, pulmonary hypertension, or (chronic) pulmonary embolism, which also lead to inhomogeneity in pulmonary capillary blood distribution. Several magnetic resonance imaging (MRI) techniques either dependent on exogenous contrast materials, exploiting periodical lung signal variations with cardiac action, or relying on intrinsic lung voxel attributes have been demonstrated to visualize lung perfusion. Additional post-processing may add temporal information and provide quantitative information related to blood flow. The most widely used and robust technique, dynamic-contrast enhanced MRI, is available in clinical routine assessment of COPD, CF, and pulmonary vascular disease. Non-contrast techniques are important research tools currently requiring clinical validation and cross-correlation in the absence of a viable standard of reference. First data on many of these techniques in the context of observational studies assessing therapy effects have just become available. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 5.

Replication of the bSTAR sequence and open-source implementation.

PURPOSE: The reproducibility of scientific reports is crucial to advancing human knowledge. This paper is a summary of our experience in replicating a balanced SSFP half-radial dual-echo imaging technique (bSTAR) using open-source frameworks as a response to the 2023 ISMRM "repeat it with me" Challenge. METHODS: We replicated the bSTAR technique for thoracic imaging at 0.55T. The bSTAR pulse sequence is implemented in Pulseq, a vendor neutral open-source rapid sequence prototyping environment. Image reconstruction is performed with the open-source Berkeley Advanced Reconstruction Toolbox (BART). The replication of bSTAR, termed open-source bSTAR, is tested by replicating several figures from the published literature. Original bSTAR, using the pulse sequence and image reconstruction developed by the original authors, and open-source bSTAR, with pulse sequence and image reconstruction developed in this work, were performed in healthy volunteers. RESULTS: Both echo images obtained from open-source bSTAR contain no visible artifacts and show identical spatial resolution and image quality to those in the published literature. A direct head-to-head comparison between open-source bSTAR and original bSTAR on a healthy volunteer indicates that open-source bSTAR provides adequate SNR, spatial resolution, level of artifacts, and conspicuity of pulmonary vessels comparable to original bSTAR. CONCLUSION: We have successfully replicated bSTAR lung imaging at 0.55T using two open-source frameworks. Full replication of a research method solely relying on information on a research paper is unfortunately rare in research, but our success gives greater confidence that a research methodology can be indeed replicated as described.

Long-term pulmonary outcome of children with congenital diaphragmatic hernia: functional lung MRI using matrix-pencil decomposition enables side-specific assessment of lung function.

OBJECTIVES: In patients with congenital diaphragmatic hernia (CDH) the exact functional outcome of the affected lung side is still unknown, mainly due to the lack of spatially resolved diagnostic tools. Functional matrix-pencil decomposition (MP-) lung MRI fills this gap as it measures side-specific ventilation and perfusion. We aimed to assess the overall and side-specific pulmonary long-term outcomes of patients with CDH using lung function tests and MP-MRI. METHODS: Thirteen school-aged children with CDH (seven with small and six with large defect-sized CDH, defined as > 50% of the chest wall circumference being devoid of diaphragm tissue) and thirteen healthy matched controls underwent spirometry, multiple-breath washout, and MP-MRI. The main outcomes were forced expiratory volume in 1 second (FEV1), lung clearance index (LCI2.5), ventilation defect percentage (VDP), and perfusion defect percentage (QDP). RESULTS: Patients with a large CDH showed significantly reduced overall lung function compared to healthy controls (mean difference [95%-CIadjusted]: FEV1 (z-score) -4.26 [-5.61, -2.92], FVC (z-score) -3.97 [-5.68, -2.26], LCI2.5 (TO) 1.12 [0.47, 1.76], VDP (%) 8.59 [3.58, 13.60], QDP (%) 17.22 [13.16, 21.27]) and to patients with a small CDH. Side-specific examination by MP-MRI revealed particularly reduced ipsilateral ventilation and perfusion in patients with a large CDH (mean difference to contralateral side [95%-CIadjusted]: VDP (%) 14.80 [10.50, 19.00], QDP (%) 23.50 [1.75, 45.20]). CONCLUSIONS: Data indicate impaired overall lung function with particular limitation of the ipsilateral side in patients with a large CDH. MP-MRI is a promising tool to provide valuable side-specific functional information in the follow-up of patients with CDH. CLINICAL RELEVANCE STATEMENT: In patients with congenital diaphragmatic hernia, easily applicable MP-MRI allows specific examination of the lung side affected by the hernia and provides valuable information on ventilation and perfusion with implications for clinical practice, making it a promising tool for routine follow-up. KEY POINTS: • Functional matrix pencil decomposition (MP) MRI data from a small sample indicate reduced ipsilateral pulmonary ventilation and perfusion in children with large congenital diaphragmatic hernia (CDH). • Easily applicable pencil decomposition MRI provides valuable side-specific diagnostic information on lung ventilation and perfusion. This is a clear advantage over conventional lung function tests, helping to comprehensively follow up patients with congenital diaphragmatic hernia and monitor therapy effects.

Submillimeter lung MRI at 0.55 T using balanced steady-state free precession with half-radial dual-echo readout (bSTAR).

PURPOSE: To demonstrate the feasibility of high-resolution morphologic lung MRI at 0.55 T using a free-breathing balanced steady-state free precession half-radial dual-echo imaging technique (bSTAR). METHODS: Self-gated free-breathing bSTAR (TE1 /TE2 /TR of 0.13/1.93/2.14 ms) lung imaging in five healthy volunteers and a patient with granulomatous lung disease was performed using a 0.55 T MR-scanner. A wobbling Archimedean spiral pole (WASP) trajectory was used to ensure a homogenous coverage of k-space over multiple breathing cycles. WASP uses short-duration interleaves randomly tilted by a small polar angle and rotated by a golden angle about the polar axis. Data were acquired continuously over 12:50 min. Respiratory-resolved images were reconstructed off-line using compressed sensing and retrospective self-gating. Reconstructions were performed with a nominal resolution of 0.9 mm and a reduced isotropic resolution of 1.75 mm corresponding to shorter simulated scan times of 8:34 and 4:17 min, respectively. Analysis of apparent SNR was performed in all volunteers and reconstruction settings. RESULTS: The technique provided artifact-free morphologic lung images in all subjects. The short TR of bSTAR in conjunction with a field strength of 0.55 T resulted in a complete mitigation of off-resonance artifacts in the chest. Mean SNR values in healthy lung parenchyma for the 12:50 min scan were 3.6 ± 0.8 and 24.9 ± 6.2 for 0.9 mm and 1.75 mm reconstructions, respectively. CONCLUSION: This study demonstrates the feasibility of morphologic lung MRI with a submillimeter isotropic spatial resolution in human subjects with bSTAR at 0.55 T.

Simultaneous multiple breath washout and oxygen-enhanced magnetic resonance imaging in healthy adults.

Lung function testing and lung imaging are commonly used techniques to monitor respiratory diseases, such as cystic fibrosis (CF). The nitrogen (N2) multiple-breath washout technique (MBW) has been shown to detect ventilation inhomogeneity in CF, but the underlying pathophysiological processes that are altered are often unclear. Dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) could potentially be performed simultaneously with MBW because both techniques require breathing of 100% oxygen (O2) and may allow for visualisation of alterations underlying impaired MBW outcomes. However, simultaneous MBW and OE-MRI has never been assessed, potentially as it requires a magnetic resonance (MR) compatible MBW equipment. In this pilot study, we assessed whether MBW and OE-MRI can be performed simultaneously using a commercial MBW device that has been modified to be MR-compatible. We performed simultaneous measurements in five healthy volunteers aged 25-35 years. We obtained O2 and N2 concentrations from both techniques, and generated O2 wash-in time constant and N2 washout maps from OE-MRI data. We obtained good quality simultaneous measurements in two healthy volunteers due to technical challenges related to the MBW equipment and poor tolerance. Oxygen and N2 concentrations from both techniques, as well as O2 wash-in time constant maps and N2 washout maps could be obtained, suggesting that simultaneous measurements may have the potential to allow for comparison and visualization of regional differences in ventilation underlying impaired MBW outcomes. Simultaneous MBW and OE-MRI measurements can be performed with a modified MBW device and may help to understand MBW outcomes, but the measurements are challenging and have poor feasibility.

Effects of elexacaftor/tezacaftor/ivacaftor therapy in children with cystic fibrosis - a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI.

BACKGROUND: With improvement in supportive therapies and the introduction of cystic fibrosis transmembrane conductance regulator (CFTR)-modulator treatment in patients with cystic fibrosis (CF), milder disease courses are expected. Therefore, sensitive parameters are needed to monitor disease course and effects of CFTR-modulators. Functional lung MRI using matrix-pencil decomposition (MP-MRI) is a promising tool for assessing ventilation and perfusion quantitatively. This study aimed to assess the treatment effect of elexacaftor/tezacaftor/ivacaftor combination regimen (ELX/TEZ/IVA) on measures of structural and functional lung abnormalities. METHODS: 24 children with CF underwent lung function tests (multiple breath washout, spirometry), functional and structural MRI twice (one year apart) before and once after at least two weeks (mean 4.7 ± 2.6 months) on ELX/TEZ/IVA. Main outcomes were changes (Δ) upon ELX/TEZ/IVA in lung function, defect percentage of ventilation (VDP) and perfusion (QDP), defect distribution index of ventilation and perfusion (DDIV, DDIQ), and Eichinger score. Statistical analyses were performed using paired t-tests and multilevel regression models with bootstrapping. RESULTS: We observed a significant improvement in lung function, structural and functional MRI parameters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ΔLCI2.5 (TO) -0.84 (-1.62 to -0.06); ΔFEV1 (z-score) 1.05 (0.56 to 1.55); ΔVDP (% of impairment) -6.00 (-8.44 to -3.55); ΔQDP (% of impairment) -3.90 (-5.90 to -1.90); ΔDDIV -1.38 (-2.22 to -0.53); ΔDDIQ -0.31 (-0.73 to 0.12); ΔEichinger score -3.89 (-5.05 to -2.72). CONCLUSIONS: Besides lung function tests, functional and structural MRI is a suitable tool to monitor treatment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in the future.

Free-breathing half-radial dual-echo balanced steady-state free precession thoracic imaging with wobbling Archimedean spiral pole trajectories.

PURPOSE: To demonstrate free-breathing thoracic MRI with a minimal-TR balanced steady-state free precession (bSSFP) technique using wobbling Archimedean spiral pole (WASP) trajectories. METHODS: Phantom and free-breathing in vivo chest imaging in healthy volunteers was performed at 1.5T with a half-radial, dual-echo, bSSFP sequence, termed bSTAR. For maximum sampling efficiency, a single analog-to-digital converter window along the full bipolar readout was used. To ensure a homogeneous coverage of the k-space over multiple breathing cycles, radial k-space sampling followed short-duration Archimedean spiral interleaves that were randomly titled by a small polar angle and rotated by a golden angle about the polar axis; depticting a wobbling Archimedean spiral pole (WASP) trajectory. In phantom and in vivo experiments, WASP trajectories were compared to spiral phyllotaxis sampling in terms of eddy currents and were used to generate in vivo thorax images at different respiratory phases. RESULTS: WASP trajectories provided artifact-free bSTAR imaging in both phantom and in vivo and respiratory self-gated reconstruction was successfully performed in all subjects. The amount of the acquired data allowed the reconstruction of 10 volumes at different respiratory levels with isotropic resolution of 1.77mm from a scan of 5.5minutes (using a TR of 1.32ms), and one high-resolution 1.16mm end-expiratory volume from a scan of 4.7minutes (using a TR of 1.42ms). The very short TR of bSTAR mitigated off-resonance artifacts despite the large field-of-view. CONCLUSION: We have demonstrated the feasibility of high-resolution free-breathing thoracic imaging with bSTAR using the wobbling Archimedean spiral pole in healthy subjects at 1.5T.

MRI Shows Lung Perfusion Changes after Vaping and Smoking.

Background Evidence regarding short-term effects of electronic nicotine delivery systems (ENDS) and tobacco smoke on lung ventilation and perfusion is limited. Purpose To examine the immediate effect of ENDS exposure and tobacco smoke on lung ventilation and perfusion by functional MRI and lung function tests. Materials and Methods This prospective observational pilot study was conducted from November 2019 to September 2021 (substudy of randomized controlled trial NCT03589989). Included were 44 healthy adult participants (10 control participants, nine former tobacco smokers, 13 ENDS users, and 12 active tobacco smokers; mean age, 41 years ± 12 [SD]; 28 men) who underwent noncontrast-enhanced matrix pencil MRI and lung function tests before and immediately after the exposure to ENDS products or tobacco smoke. Baseline measurements were acquired after 2 hours of substance abstinence. Postexposure measurements were performed immediately after the exposure. MRI showed semiquantitative measured impairment of lung perfusion (RQ) and fractional ventilation (RFV) impairment as percentages of affected lung volume. Lung clearance index (LCI) was assessed by nitrogen multiple-breath washout to capture ventilation inhomogeneity and spirometry to assess airflow limitation. Absolute differences were calculated with paired Wilcoxon signed-rank test and differences between groups with unpaired Mann-Whitney test. Healthy control participants underwent two consecutive MRI measurements to assess MRI reproducibility. Results MRI was performed and lung function measurement was acquired in tobacco smokers and ENDS users before and after exposure. MRI showed a decrease of perfusion after exposure (RQ, 8.6% [IQR, 7.2%-10.0%] to 9.1% [IQR, 7.8%-10.7%]; P = .03) and no systematic change in RFV (P = .31) among tobacco smokers. Perfusion increased in participants who used ENDS after exposure (RQ, 9.7% [IQR, 7.1%-10.9%] to 9.0% [IQR, 6.9%-10.0%]; P = .01). RFV did not change (P = .38). Only in tobacco smokers was LCI elevated after smoking (P = .02). Spirometry indexes did not change in any participants. Conclusion MRI showed a decrease of lung perfusion after exposure to tobacco smoke and an increase of lung perfusion after use of electronic nicotine delivery systems. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kligerman in this issue.

MRI lung lobe segmentation in pediatric cystic fibrosis patients using a recurrent neural network trained with publicly accessible CT datasets.

PURPOSE: To introduce a widely applicable workflow for pulmonary lobe segmentation of MR images using a recurrent neural network (RNN) trained with chest CT datasets. The feasibility is demonstrated for 2D coronal ultrafast balanced SSFP (ufSSFP) MRI. METHODS: Lung lobes of 250 publicly accessible CT datasets of adults were segmented with an open-source CT-specific algorithm. To match 2D ufSSFP MRI data of pediatric patients, both CT data and segmentations were translated into pseudo-MR images that were masked to suppress anatomy outside the lung. Network-1 was trained with pseudo-MR images and lobe segmentations and then applied to 1000 masked ufSSFP images to predict lobe segmentations. These outputs were directly used as targets to train Network-2 and Network-3 with non-masked ufSSFP data as inputs, as well as an additional whole-lung mask as input for Network-2. Network predictions were compared to reference manual lobe segmentations of ufSSFP data in 20 pediatric cystic fibrosis patients. Manual lobe segmentations were performed by splitting available whole-lung segmentations into lobes. RESULTS: Network-1 was able to segment the lobes of ufSSFP images, and Network-2 and Network-3 further increased segmentation accuracy and robustness. The average all-lobe Dice similarity coefficients were 95.0 ± 2.8 (mean ± pooled SD [%]) and 96.4 ± 2.5, 93.0 ± 2.0; and the average median Hausdorff distances were 6.1 ± 0.9 (mean ± SD [mm]), 5.3 ± 1.1, 7.1 ± 1.3 for Network-1, Network-2, and Network-3, respectively. CONCLUSION: Recurrent neural network lung lobe segmentation of 2D ufSSFP imaging is feasible, in good agreement with manual segmentations. The proposed workflow might provide access to automated lobe segmentations for various lung MRI examinations and quantitative analyses.

School-age structural and functional MRI and lung function in children following lung resection for congenital lung malformation in infancy.

BACKGROUND: The management of asymptomatic congenital lung malformations is debated. Particularly, there is a lack of information regarding long-term growth and development of the remaining lung in children following lung resection for congenital lung malformations. In addition to conventional pulmonary function tests, we used novel functional magnetic resonance imaging (MRI) methods to measure perfusion and ventilation. OBJECTIVE: To assess functionality of the remaining lung expanded into the thoracic cavity after resection of congenital lung malformations. MATERIALS AND METHODS: A prospective, cross-sectional pilot study in five children who had surgery for congenital lung malformations during infancy. Participants had structural and functional MRI as well as spirometry, body plethysmography and multiple breath washout at school age. RESULTS: Structural MRI showed an expansion of the remaining lung in all cases. Fractional ventilation and relative perfusion of the expanded lung were locally decreased in functional MRI. In all other parts of the lungs, fractional ventilation and relative perfusion were normal in all children. There was an association between overall impairment of perfusion and elevated lung clearance index. The results of spirometry and body plethysmography varied between patients, including normal lung function, restriction and obstruction. CONCLUSION: Fractional ventilation and relative perfusion maps from functional MRI specifically locate impairment of the remaining lung after lung resection. These changes are not captured by conventional measures such as structural MRI and standard pulmonary function tests. Therefore, following lung resection for congenital lung malformation, children should be investigated more systematically with functional lung MRI.

Synthetic 4DCT(MRI) lung phantom generation for 4D radiotherapy and image guidance investigations.

PURPOSE: Respiratory motion is one of the major challenges in radiotherapy. In this work, a comprehensive and clinically plausible set of 4D numerical phantoms, together with their corresponding "ground truths," have been developed and validated for 4D radiotherapy applications. METHODS: The phantoms are based on CTs providing density information and motion from multi-breathing-cycle 4D Magnetic Resonance imagings (MRIs). Deformable image registration (DIR) has been utilized to extract motion fields from 4DMRIs and to establish inter-subject correspondence by registering binary lung masks between Computer Tomography (CT) and MRI. The established correspondence is then used to warp the CT according to the 4DMRI motion. The resulting synthetic 4DCTs are called 4DCT(MRI)s. Validation of the 4DCT(MRI) workflow was conducted by directly comparing conventional 4DCTs to derived synthetic 4D images using the motion of the 4DCTs themselves (referred to as 4DCT(CT)s). Digitally reconstructed radiographs (DRRs) as well as 4D pencil beam scanned (PBS) proton dose calculations were used for validation. RESULTS: Based on the CT image appearance of 13 lung cancer patients and deformable motion of five volunteer 4DMRIs, synthetic 4DCT(MRI)s with a total of 871 different breathing cycles have been generated. The 4DCT(MRI)s exhibit an average superior-inferior tumor motion amplitude of 7 ± 5 mm (min: 0.5 mm, max: 22.7 mm). The relative change of the DRR image intensities of the conventional 4DCTs and the corresponding synthetic 4DCT(CT)s inside the body is smaller than 5% for at least 81% of the pixels for all studied cases. Comparison of 4D dose distributions calculated on 4DCTs and the synthetic 4DCT(CT)s using the same motion achieved similar dose distributions with an average 2%/2 mm gamma pass rate of 90.8% (min: 77.8%, max: 97.2%). CONCLUSION: We developed a series of numerical 4D lung phantoms based on real imaging and motion data, which give realistic representations of both anatomy and motion scenarios and the accessible "ground truth" deformation vector fields of each 4DCT(MRI). The open-source code and motion data allow foreseen users to generate further 4D data by themselves. These numeric 4D phantoms can be used for the development of new 4D treatment strategies, 4D dose calculations, DIR algorithm validations, as well as simulations of motion mitigation and different online image guidance techniques for both proton and photon radiation therapy.

Morphologic and Functional Assessment of Sarcoidosis Using Low-Field MRI.

Online supplemental material is available for this article.

Effect of Salbutamol on Lung Ventilation in Children with Cystic Fibrosis: Comprehensive Assessment Using Spirometry, Multiple-Breath Washout, and Functional Lung Magnetic Resonance Imaging.

BACKGROUND: Inhalation therapy is one of the cornerstones of the daily treatment regimen in patients with cystic fibrosis (CF). Recommendations regarding the addition of bronchodilators, especially salbutamol are conflicting due to the lack of evidence. New diagnostic measures such as multiple-breath washout (MBW) and functional magnetic resonance imaging (MRI) have the potential to reveal new insights into bronchodilator effects in patients with CF. OBJECTIVE: The objective of the study was to comprehensively assess the functional response to nebulized inhalation with salbutamol in children with CF. METHODS: Thirty children aged 6-18 years with stable CF performed pulmonary function tests, MBW, and matrix pencil-MRI before and after standardized nebulized inhalation of salbutamol. RESULTS: Lung clearance index decreased (improved) by -0.24 turnover (95% confidence interval [CI]: -0.53 to 0.06; p = 0.111). Percentage of the lung volume with impaired fractional ventilation and relative perfusion decreased (improved) by -0.79% (CI: -1.99 to 0.42; p = 0.194) and -1.31% (CI: -2.28 to -0.35; p = 0.009), respectively. Forced expiratory volume (FEV1) increased (improved) by 0.41 z-score (CI: 0.24-0.58; p < 0.0001). We could not identify specific clinical factors associated with a more pronounced effect of salbutamol. CONCLUSIONS: There is a positive short-term effect of bronchodilator inhalation on FEV1 in patients with CF, which is independent of ventilation inhomogeneity. Heterogeneous response between patients suggests that for prediction of a therapeutic effect this should be tested by spirometry in every patient individually.

Pure balanced steady-state free precession imaging (pure bSSFP).

PURPOSE: To show that for tissues the conspicuous asymmetries in the frequency response function of bSSFP can be mitigated by using a short enough TR. THEORY AND METHODS: Configuration theory indicates that bSSFP becomes apparently "pure" (i.e., exhibiting a symmetric profile) in the limit of TR → 0 . To this end, the frequency profile of bSSFP was measured as a function of the TR using a manganese-doped aqueous probe, as well as brain tissue that was shown to exhibit a pronounced asymmetry due to its microstructure. The frequency response function was sampled using N = 72 (phantom) and N = 36 (in vivo) equally distributed linear RF phase increments in the interval [ 0 , 2 π ) . Imaging was performed with 2.0 mm isotropic resolution over a TR range of 1.5-8 ms at 3 and 1.5 T. RESULTS: As expected, pure substances showed a symmetric TR-independent frequency profile, whereas brain tissue revealed a pronounced asymmetry. The observed asymmetry for the tissue, however, decreases with decreasing TR and gives strong evidence that the frequency response function of bSSFP becomes symmetric in the limit of TR → 0 , in agreement with theory. The limit of apparently pure bSSFP imaging can thus be achieved for a TR ∼ 1.5 ms at 1.5 T, whereas at 3 T, tissues still show some residual asymmetry. CONCLUSION: In the limit of short enough TR, tissues become apparently pure for bSSFP. This limit can be reached for brain tissue at 1.5 T with TR ∼ 1-2 ms at clinically relevant resolutions.

Defect distribution index: A novel metric for functional lung MRI in cystic fibrosis.

PURPOSE: Lung impairment from functional MRI is frequently assessed as defect percentage. The defect distribution, however, is currently not quantified. The purpose of this work was to develop a novel measure that quantifies how clustered or scattered defects in functional lung MRI appear, and to evaluate it in pediatric cystic fibrosis. THEORY: The defect distribution index (DDI) calculates a score for each lung voxel categorized as defected. The index increases according to how densely and how far an expanding circle around a defect voxel contains more than 50% defect voxels. METHODS: Fractional ventilation and perfusion maps of 53 children with cystic fibrosis were previously acquired with matrix pencil decomposition MRI. In this work, the DDI is compared to a visual score of 3 raters who evaluated how clustered the lung defects appear. Further, spearman correlations between DDI and lung function parameters were determined. RESULTS: The DDI strongly correlates with the visual scoring (r = 0.90 for ventilation; r = 0.88 for perfusion; P < .0001). Although correlations between DDI and defect percentage are moderate to strong (r = 0.61 for ventilation; r = 0.75 for perfusion; P < .0001), the DDI distinguishes between patients with comparable defect percentage. CONCLUSION: The DDI is a novel measure for functional lung MRI. It provides complementary information to the defect percentage because the DDI assesses defect distribution rather than defect size. The DDI is applicable to matrix pencil MRI data of cystic fibrosis patients and shows very good agreement with human perception of defect distributions.

The impact of segmentation on whole-lung functional MRI quantification: Repeatability and reproducibility from multiple human observers and an artificial neural network.

PURPOSE: To investigate the repeatability and reproducibility of lung segmentation and their impact on the quantitative outcomes from functional pulmonary MRI. Additionally, to validate an artificial neural network (ANN) to accelerate whole-lung quantification. METHOD: Ten healthy children and 25 children with cystic fibrosis underwent matrix pencil decomposition MRI (MP-MRI). Impaired relative fractional ventilation (RFV ) and relative perfusion (RQ ) from MP-MRI were compared using whole-lung segmentation performed by a physician at two time-points (At1 and At2 ), by an MRI technician (B), and by an ANN (C). Repeatability and reproducibility were assess with Dice similarity coefficient (DSC), paired t-test and Intraclass-correlation coefficient (ICC). RESULTS: The repeatability within an observer (At1 vs At2 ) resulted in a DSC of 0.94 ± 0.01 (mean ± SD) and an unsystematic difference of -0.01% for RFV (P = .92) and +0.1% for RQ (P = .21). The reproducibility between human observers (At1 vs B) resulted in a DSC of 0.88 ± 0.02, and a systematic absolute difference of -0.81% (P < .001) for RFV and -0.38% (P = .037) for RQ . The reproducibility between human and the ANN (At1 vs C) resulted in a DSC of 0.89 ± 0.03 and a systematic absolute difference of -0.36% for RFV (P = .017) and -0.35% for RQ (P = .002). The ICC was >0.98 for all variables and comparisons. CONCLUSIONS: Despite high overall agreement, there were systematic differences in lung segmentation between observers. This needs to be considered for longitudinal studies and could be overcome by using an ANN, which performs as good as human observers and fully automatizes MP-MRI post-processing.

Liver-ultrasound-guided lung tumour tracking for scanned proton therapy: a feasibility study.

Pencil beam scanned (PBS) proton therapy of lung tumours is hampered by respiratory motion and the motion-induced density changes along the beam path. In this simulation study, we aim to investigate the effectiveness of proton beam tracking for lung tumours both under ideal conditions and in conjunction with a respiratory motion model guided by real-time ultrasound imaging of the liver. Multiple-breathing-cycle 4DMRIs of the thorax and abdominal 2D ultrasound images were acquired simultaneously for five volunteers. Deformation vector fields extracted from the 4DMRI, referred to as ground truth motion, were used to generate 4DCT(MRI) data sets of two lung cancer patients, resulting in 10 data sets with variable motion patterns. Given the 4DCT(MRI) and the corresponding ultrasound images as surrogate data, a patient-specific motion model was built. The model consists of an autoregressive model and Gaussian process regression for the temporal and spatial prediction, respectively. Two-field PBS plans were optimised on the reference CTs, and 4D dose calculations (4DDC) were used to simulate dose delivery for (a) unmitigated motion, (b) ideal 2D and 3D tracking (both beam adaption and 4DDC based on ground truth motion), and (c) realistic 2D and 3D tracking (beam adaption based on motion predictions, 4DDC on ground truth motion). Model-guided tracking retrieved clinically acceptable target dose homogeneity, as seen in a substantial reduction of the D5%-D95% compared to the non-mitigated simulation. Tracking in 2D and 3D resulted in a similar improvement of the dose homogeneity, as did ideal and realistic tracking simulations. In some cases, however, the tracked deliveries resulted in a shift towards higher or lower dose levels, leading to unacceptable target over- or under-coverage. The presented motion modelling framework was shown to be an accurate motion prediction tool for the use in proton beam tracking. Tracking alone, however, may not always effectively mitigate motion effects, making it necessary to combine it with other techniques such as rescanning.

[Assessment of lung impairment in patients with cystic fibrosis : Novel magnetic resonance imaging methods]. / Detektion von Lungenveränderungen bei Patienten mit Mukoviszidose : Innovationen der Magnetresonanztomographie des Thorax.

CLINICAL/METHODOLOGICAL ISSUE: The differentiated assessment of respiratory mechanics, gas exchange and pulmonary circulation, as well as structural impairment of the lung are essential for the treatment of patients with cystic fibrosis (CF). Clinical lung function measurements are often not sufficiently specific and are often difficult to perform. STANDARD RADIOLOGICAL METHODS: The standard procedures for pulmonary imaging are chest X­ray and computed tomography (CT) for assessing lung morphology. In more recent studies, an increasing number of centers are using magnetic resonance imaging (MRI) to assess lung structure and function. However, functional imaging is currently limited to specialized centers. METHODOLOGICAL INNOVATIONS: In patients with CF, studies showed that MRI with hyperpolarized gases and Fourier decomposition/matrix pencil MRI (FD/MP-MRI) are feasible for assessing pulmonary ventilation. For pulmonary perfusion, dynamic contrast-enhanced MRI (DCE-MRI) or contrast-free methods, e.g., FD-MRI, can be used. PERFORMANCE: Functional MRI provides more accurate insight into the pathophysiology of pulmonary function at the regional level. Advantages of MRI over X­ray are its lack of ionizing radiation, the large number of lung function parameters that can be extracted using different contrast mechanisms, and ability to be used repeatedly over time. ACHIEVEMENTS: Early assessment of lung function impairment is needed as the structural changes usually occur later in the course of the disease. However, sufficient experience in clinical application exist only for certain functional lung MRI procedures. PRACTICAL RECOMMENDATIONS: Clinical application of the aforementioned techniques, except for DCE-MRI, should be restricted to scientific studies.

Liver-ultrasound based motion modelling to estimate 4D dose distributions for lung tumours in scanned proton therapy.

Motion mitigation strategies are crucial for scanned particle therapy of mobile tumours in order to prevent geometrical target miss and interplay effects. We developed a patient-specific respiratory motion model based on simultaneously acquired time-resolved volumetric MRI and 2D abdominal ultrasound images. We present its effects on 4D pencil beam scanned treatment planning and simulated dose distributions. Given an ultrasound image of the liver and the diaphragm, principal component analysis and Gaussian process regression were applied to infer dense motion information of the lungs. 4D dose calculations for scanned proton therapy were performed using the estimated and the corresponding ground truth respiratory motion; the differences were compared by dose difference volume metrics. We performed this simulation study on 10 combined CT and 4DMRI data sets where the motion characteristics were extracted from 5 healthy volunteers and fused with the anatomical CT data of two lung cancer patients. Median geometrical estimation errors below 2 mm for all data sets and maximum dose differences of [Formula: see text] = 43.2% and [Formula: see text] = 16.3% were found. Moreover, it was shown that abdominal ultrasound imaging allows to monitor organ drift. This study demonstrated the feasibility of the proposed ultrasound-based motion modelling approach for its application in scanned proton therapy of lung tumours.