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.

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.

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.

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.

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.

Multi-parametric artificial neural network fitting of phase-cycled balanced steady-state free precession data.

PURPOSE: Standard relaxation time quantification using phase-cycled balanced steady-state free precession (bSSFP), eg, motion-insensitive rapid configuration relaxometry (MIRACLE), is subject to a considerable underestimation of tissue T1 and T2 due to asymmetric intra-voxel frequency distributions. In this work, an artificial neural network (ANN) fitting approach is proposed to simultaneously extract accurate reference relaxation times (T1 , T2 ) and robust field map estimates ( B1+ , ΔB0 ) from the bSSFP profile. METHODS: Whole-brain bSSFP data acquired at 3T were used for the training of a feedforward ANN with N = 12, 6, and 4 phase-cycles. The magnitude and phase of the Fourier transformed complex bSSFP frequency response served as input and the multi-parametric reference set [T1 , T2 , B1+ , ∆B0 ] as target. The ANN predicted relaxation times were validated against the target and MIRACLE. RESULTS: The ANN prediction of T1 and T2 for trained and untrained data agreed well with the reference, even for only four acquired phase-cycles. In contrast, relaxometry based on 4-point MIRACLE was prone to severe off-resonance-related artifacts. ANN predicted B1+ and ∆B0 maps showed the expected spatial inhomogeneity patterns in high agreement with the reference measurements for 12-point, 6-point, and 4-point bSSFP phase-cycling schemes. CONCLUSION: ANNs show promise to provide accurate brain tissue T1 and T2 values as well as reliable field map estimates. Moreover, the bSSFP acquisition can be accelerated by reducing the number of phase-cycles while still delivering robust T1 , T2 , B1+ , and ∆B0 estimates.

Functional lung imaging with transient spoiled gradient echo.

PURPOSE: To introduce an alternative framework for perfusion and ventilation lung imaging at 3 T using transient spoiled gradient echo (tSPGR) acquisitions. METHODS: Sets of coronal 2D time-resolved lung image series were acquired in 5 healthy volunteers using tSPGR and compared with contemporary SPGR and ultrafast balanced SSFP (uf-bSSFP) implementations at 1.5 T and 3 T. Sequence parameters and view ordering were optimized for tSPGR to yield maximum signal intensity in the lung tissue. Signal-to-noise ratio and contrast-to-noise ratio analyses were performed in all acquired tSPGR, SPGR, and uf-bSSFP data sets. Matrix pencil decomposition was applied to generate functional parameter maps, including fractional ventilation, relative perfusion, and blood arrival time. RESULTS: For the lung, the signal intensity of tSPGR imaging was maximal for minimal TR and TE settings of 0.99 ms and 0.43 ms, respectively. Moreover, low RF spoiling increments in combination with a centric view ordering resulted in a further signal-to-noise ratio increase of about 30% to 40%. The average signal-to-noise ratio in the lung parenchyma was 73.3 for uf-bSSFP, 38.1 for tSPGR, 20.7 for SPGR at 1.5 T, and 31.2 for uf-bSSFP, 35.6 for tSPGR, and 21.3 for SPGR at 3 T. The average ventilation and perfusion contrast-to-noise ratio was 33.2 and 36.2 for uf-bSSFP, 15.4 and 12.5 for tSPGR, 13.5 and 4.1 for SPGR at 1.5 T, and 16.5 and 11.3 for uf-bSSFP, 29.7 and 50.8 for tSPGR, and 22.4 and 16.5 for SPGR at 3 T, respectively. CONCLUSION: At 3 T, application of balanced SSFP is limited, so tSPGR offers an alternative framework for successful lung function assessment using matrix pencil MRI.

Three-dimensional oxygen-enhanced MRI of the human lung at 1.5T with ultra-fast balanced steady-state free precession.

PURPOSE: To assess the feasibility of 3D oxygen-enhanced (OE) MRI of the lung at 1.5T using multi-volumetric ultra-fast balanced steady-state free precession (ufSSFP) acquisitions. METHODS: Isotropic imaging of the lung for OE-MRI was performed with an adapted 3D ufSSFP sequence using five breath-hold acquisitions ranging from functional residual capacity to tidal inspiration under both normoxic (room air) and hyperoxic (100% O2 ) gas conditions. For each O2 concentration, a sponge model (which captures the parenchymal signal intensity variation as a function of the lung volume) was fitted to the acquired multi-volumetric datasets after semiautomatic lung segmentation and deformable image registration. From the retrieved model parameters, 3D oxygen-enhancement maps were calculated. RESULTS: For OE ufSSFP imaging, the maximum parenchymal signal is observed for flip angles around 23° under both normoxic and hyperoxic conditions. It is found that the sponge model accurately describes parenchymal signal at different breathing positions, thereby mitigating the confounding bias in the estimated oxygen enhancement from residual density modulations. From the model, an average lung oxygen enhancement of 7.0% ± 0.3% was found in the healthy volunteers, and the oxygen-enhancement maps indicate a ventral to dorsal gravitation-related gradient. CONCLUSION: The study demonstrates the feasibility of whole-lung OE-MRI from multi-volumetric ufSSFP in healthy volunteers. Magn Reson Med 79:246-255, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Dynamic and steady-state oxygen-dependent lung relaxometry using inversion recovery ultra-fast steady-state free precession imaging at 1.5 T.

PURPOSE: To demonstrate the feasibility of oxygen-dependent relaxometry in human lung using an inversion recovery ultra-fast steady-state free precession (IR-ufSSFP) technique. METHODS: Electrocardiogram-triggered pulmonary relaxometry with IR-ufSSFP was performed in 7 healthy human subjects at 1.5 T. The data were acquired under both normoxic and hyperoxic conditions. In a single breath-hold of less than 9 seconds, 30 transient state IR-ufSSFP images were acquired, yielding longitudinal (T1) and transversal (T2) relaxometry parameter maps using voxel-wise nonlinear fitting. Possible spatial misalignments between consecutive IR-ufSSFP parameter maps were corrected using elastic image registration. Furthermore, dynamic relaxometry oxygen wash-in and wash-out scans were performed in one volunteer. From this, T1 -related wash-in and wash-out time constants (τwi , τwo ) were calculated voxel-wise on registered maps using an exponential fitting model. RESULTS: For healthy lung, observed T1 values were 1399 ± 77 and 1290 ± 76 ms under normoxic and hyperoxic conditions, respectively. Oxygen-related reduction of T1 was statistically significant in every volunteer. No statistically significant change, however, was observed in T2, with normoxic and hyperoxic T2 values of 55 ± 16 and 56 ± 17 ms, respectively. The observed average τwi was 87.0 ± 28.7 seconds, whereas the average τwo was 73.5 ± 21.6 seconds. CONCLUSION: IR-ufSSFP allows fast, steady-state, and dynamic oxygen-dependent relaxometry of the human lung. Magn Reson Med 79:839-845, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Signal enhancement ratio imaging of the lung parenchyma with ultra-fast steady-state free precession MRI at 1.5T.

BACKGROUND: Lung perfusion MRI after i.v. gadolinium (Gd) contrast administration is commonly based on spoiled gradient-echo acquisitions, such as volume-interpolated breath-hold examinations (VIBE), suffering from low signal-to-noise in the parenchyma. PURPOSE: To investigate the lung signal enhancement ratio (SER) with ultra-fast steady-state free precession (ufSSFP) after Gd-administration. STUDY TYPE: Retrospective. SUBJECTS: Ten subjects with healthy lungs; nine patients with pulmonary diseases (chronic obstructive pulmonary disease [COPD], lung cancer, pulmonary fibrosis, lung contusion). FIELD STRENGTH/SEQUENCE: VIBE and ufSSFP imaging of the chest was performed at 1.5T before and 3 minutes after i.v. gadobenate dimeglumine. ASSESSMENT: A workflow including deformable image registration and median filtering was used to compute 3D SER maps. SER was analyzed in the lung, blood pool, liver, muscles, and fat. The artifacts were assessed by a radiologist. In the COPD patients, ufSSFP-SER was compared to 99m Tc-MAA-SPECT/CT by visual scoring of lung enhancement deficits. STATISTICAL TESTS: Mean signal, standard deviation (SD), intersubject SD, and coefficient of variation (CV) were calculated for SER. Statistical significance of differences in signal and artifacts were determined using Wilcoxon signed-rank paired test. Intermodality agreement between ufSSFP-SER and SPECT/CT was calculated by Cohen's kappa (κq ). RESULTS: In healthy lungs, ufSSFP-SER (99% ± 23%, mean ± pooled intrasubject SD, CV = 23%) was significantly higher (P < 10-3 ) and more homogeneous (P < 10-3 ) than VIBE (47% ± 26%, CV = 57%). UfSSFP-SER was significantly higher (P < 10-3 ) for the lungs (99% ± 9%, mean ± intersubject SD) than for the blood (81% ± 7%) and other tissues (liver 33% ± 8%, muscle 26% ± 5%, fat 2% ± 1%). In the lung ufSSFP-SER exhibits homogeneity on iso-gravitational planes, and an anterior-posterior gradient. In COPD patients, ufSSFP-SER was reduced and less homogeneous compared to the control group (73% ± 33%, mean ± pooled intrasubject SD, CV = 42%). ufSSFP-SER had moderate intermodality agreement with SPECT/CT (κq = 0.64). DATA CONCLUSION: UfSSFP-SER of the lung is a rapid and simple method. Our preliminary data show plausible results in different pulmonary diseases, motivating further evaluation in larger cohorts. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Novel magnetic resonance technique for functional imaging of cystic fibrosis lung disease.

Lung function tests are commonly used to monitor lung disease in cystic fibrosis (CF). While practical, they cannot locate the exact origin of functional impairment. Contemporary magnetic resonance imaging (MRI) techniques provide information on the location of disease but the need for contrast agents constrains their repeated application. We examined the correlation between functional MRI, performed without administration of contrast agent, and lung clearance index (LCI) from nitrogen multiple-breath washout (N2-MBW).40 children with CF (median (range) age 12.0 (6-18) years) and 12 healthy age-matched controls underwent functional and structural MRI and lung function tests on the same day. Functional MRI provided semiquantitative measures of perfusion (RQ) and ventilation (RFV) impairment as percentages of affected lung volume. Morphological MRI was evaluated using CF-specific scores. LCI measured global ventilation inhomogeneity.MRI detected functional impairment in CF: RFV 19-38% and RQ 16-35%. RFV and RQ correlated strongly with LCI (r=0.76, p<0.0001 and r=0.85, p<0.0001, respectively), as did total morphology score (r=0.81, p<0.0001). All indices differed significantly between patients with CF and healthy controls (p<0.001).Noninvasive functional MRI is a promising method to detect and visualise perfusion and ventilation impairment in CF without the need for contrast agents.

Pulmonary relaxometry with inversion recovery ultra-fast steady-state free precession at 1.5T.

PURPOSE: To present a technique for simultaneous mapping of T1 , T2 , and relative spin density (M0 ) in human lung using inversion recovery ultra-fast steady-state free precession (IR-ufSSFP) imaging. METHODS: Pulmonary relaxometry with IR-ufSSFP is based on an interleaved time series acquisition of 2D images acquired at 1.5T. The technique was tested in a phantom and in four healthy volunteers using breath-hold and electrocardiogram triggering. Typically, 30 transient state images were acquired in a single breath-hold within < 10 s. From the signal time course, voxel-wise nonlinear fitting yielded T1 , T2 , and M0 parameter maps. Furthermore, off-resonance and B1 effects were investigated in a phantom. RESULTS: In the phantom, the observed T1 of 829 ± 2 ms and T2 of 105 ± 4 ms were in agreement with the reference T1 of 858 ± 1 ms and T2 of 104 ± 1 ms using spin echo methods. In volunteers, the average T1 of 1375 ± 102 ms and T2 of 66 ± 26 ms of lung tissue were in good agreement with the literature and were observed to be independent of the respiratory phase. Overall, high reproducibility was shown in a volunteer, yielding coefficient of variations of 0.03 for M0 , 0.004 for T1 , and 0.04 for T2 measurements. CONCLUSION: IR-ufSSFP allows for fast and simultaneous quantitative mapping of the human lung. Magn Reson Med 77:74-82, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Rapid 3D in vivo 1H human lung respiratory imaging at 1.5 T using ultra-fast balanced steady-state free precession.

PURPOSE: To introduce a reproducible, nonenhanced 1H MRI method for rapid in vivo functional assessment of the whole lung at 1.5 Tesla (T). METHODS: At different respiratory volumes, the pulmonary signal of ultra-fast steady-state free precession (ufSSFP) follows an adapted sponge model, characterized by a respiratory index α. From the model, α reflects local ventilation-related information, is virtually independent from the lung density and thus from the inspiratory phase and breathing amplitude. Respiratory α-mapping is evaluated for healthy volunteers and patients with obstructive lung disease from a set of five consecutive 3D ultra-fast steady-state free precession (ufSSFP) scans performed in breath-hold and at different inspiratory volumes. For the patients, α-maps were compared with CT, dynamic contrast-enhanced MRI (DCE-MRI), and Fourier decomposition (FD). RESULTS: In healthy volunteers, respiratory α-maps showed good reproducibility and were homogeneous on iso-gravitational planes, but showed a gravity-dependent respiratory gradient. In patients with obstructive pulmonary disease, the functional impairment observed in respiratory α-maps was associated with emphysematous regions present on CT images, perfusion defects observable on DCE-MRI, and impairments visualized on FD ventilation and perfusion maps. CONCLUSION: Respiratory α-mapping derived from multivolumetric ufSSFP provides insights into functional lung impairment and may serve as a reproducible and normative measure for clinical studies. Magn Reson Med 78:1059-1069, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Ultra-fast Steady-State Free Precession Pulse Sequence for Fourier Decomposition Pulmonary MRI.

PURPOSE: To assess whether ultra-fast steady-state free precession (ufSSFP) can improve image quality in Fourier decomposition (FD) MRI of lung ventilation and perfusion. METHODS: Series of two-dimensional time-resolved lung images were acquired in healthy volunteers at 1.5 Tesla (T) and 3T using an FD adapted ufSSFP. For comparison, the imaging protocol was complemented by a standard implementation of the FD MRI technique using balanced steady-state free precession (bSSFP). Imaging parameters were evaluated to optimize the ufSSFP FD MRI protocol with respect to the signal intensity of the lung parenchyma and the severity of image artifacts. RESULTS: FD MRI with the adapted ufSSFP pulse sequence resulted in increased signal intensity in the lung tissue by 19% and significantly decreased banding artifacts due to shorter repetition times: 1.46 ms for ufSSFP and 1.90 ms for bSSFP. Despite improved image quality FD MRI is still problematic at 3T. CONCLUSION: MRI of the lung with ufSSFP performs better than bSSFP in terms of signal and banding artifacts, and can be used to either increase resolution or overall image quality of FD images.

Technical note: Towards more realistic 4DCT(MRI) numerical lung phantoms.

BACKGROUND: Numerical 4D phantoms, together with associated ground truth motion, offer a flexible and comprehensive data set for realistic simulations in radiotherapy and radiology in target sites affected by respiratory motion. PURPOSE: We present an openly available upgrade to previously reported methods for generating realistic 4DCT lung numerical phantoms, which now incorporate respiratory ribcage motion and improved lung density representation throughout the breathing cycle. METHODS: Density information of reference CTs, toget her with motion from multiple breathing cycle 4DMRIs have been combined to generate synthetic 4DCTs (4DCT(MRI)s). Inter-subject correspondence between the CT and MRI anatomy was first established via deformable image registration (DIR) of binary masks of the lungs and ribcage. Ribcage and lung motions were extracted independently from the 4DMRIs using DIR and applied to the corresponding locations in the CT after post-processing to preserve sliding organ motion. In addition, based on the Jacobian determinant of the resulting deformation vector fields, lung densities were scaled on a voxel-wise basis to more accurately represent changes in local lung density. For validating this process, synthetic 4DCTs, referred to as 4DCT(CT)s, were compared to the originating 4DCTs using motion extracted from the latter, and the dosimetric impact of the new features of ribcage motion and density correction were analyzed using pencil beam scanned proton 4D dose calculations. RESULTS: Lung density scaling led to a reduction of maximum mean lung Hounsfield units (HU) differences from 45 to 12 HU when comparing simulated 4DCT(CT)s to their originating 4DCTs. Comparing 4D dose distributions calculated on the enhanced 4DCT(CT)s to those on the original 4DCTs yielded 2%/2 mm gamma pass rates above 97% with an average improvement of 1.4% compared to previously reported phantoms. CONCLUSIONS: A previously reported 4DCT(MRI) workflow has been successfully improved and the resulting numerical phantoms exhibit more accurate lung density representations and realistic ribcage motion.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis.

Background: Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration. Objectives: To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF. Methods: Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8-45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP). Results: MP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = -0.75 and r = -0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01). Conclusion: MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.

Retrospective reconstruction of four-dimensional magnetic resonance from interleaved cine imaging - A comparative study with four-dimensional computed tomography in the lung.

Background and purpose: Imaging of respiration-induced anatomical changes is essential to ensure high accuracy in radiotherapy of lung cancer. We expanded here on methods for retrospective reconstruction of time-resolved volumetric magnetic resonance (4DMR) of the thoracic region and benchmarked the results against 4D computed tomography (4DCT). Materials and method: MR data of six lung cancer patients were collected by interleaving cine-navigator images with 2D data frame images, acquired across the thorax. The data frame images have been stacked in volumes based on a similarity metric that considers the anatomical deformation of lungs, while addressing ambiguities in respiratory phase detection and interpolation of missing data. The resulting images were validated against cine-navigator images and compared to paired 4DCTs in terms of amplitude and period of motion, assessing differences in internal target volume (ITV) margin definition. Results: 4DMR-based motion amplitude was on average within 1.8 mm of that measured in the corresponding 2D cine-navigator images. In our dataset, the 4DCT motion and the 4DMR median amplitude were always within 3.8 mm. The median period was generally close to CT references, although deviations up to 24 % have been observed. These changes were reflected in the ITV, which was generally larger for MRI than for 4DCT (up to 39.7 %). Conclusions: The proposed algorithm for retrospective reconstruction of time-resolved volumetric MR provided quality anatomical images with high temporal resolution for motion modelling and treatment planning. The potential for imaging organ motion variability makes 4DMR a valuable complement to standard 4DCT imaging.

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.

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.