Diagnostic accuracy of perfusion-weighted phase-resolved functional lung magnetic resonance imaging in patients with chronic pulmonary embolism

PurposeThis study aimed to evaluate the diagnostic performance of perfusion-weighted phase-resolved functional lung (PW-PREFUL) magnetic resonance imaging (MRI) in patients with chronic pulmonary embolism (CPE).Materials and methodsThis study included 86 patients with suspected chronic thromboembolic pulmonary hypertension (CTEPH), who underwent PREFUL MRI and ventilation/perfusion (V/Q) single-photon emission computed tomography/computed tomography (SPECT/CT). PREFUL MRI was performed at 1.5 T using a balanced steady-state free precession sequence during free breathing. Color-coded PW images and quantitative parameters were obtained by postprocessing. Meanwhile, V/Q SPECT/CT imaging was performed as a reference standard. Hypoperfused areas in the lungs were scored for each lobe and segment using V/Q SPECT/CT images and PW-PREFUL MR images, respectively. Normalized perfusion (QN) and perfusion defect percentage (QDP) were calculated for all slices. For intra- and interobserver variability, the MRI images were analyzed 2 months after the first analysis by the same radiologist and another radiologist (11 years of lung MRI experience) blinded to the results of the first reader.ResultsOf the 86 enrolled patients, 77 met the inclusion criteria (36 diagnosed with CPE using V/Q SPECT/CT and 41 diagnosed with non-CPE etiology). For the PW-PREFUL MRI, the sensitivity, specificity, accuracy, and positive and negative predictive values for the diagnosis of CPE were 97, 95, 96, 95, and 98% at the patient level; 91, 94, 93, 91, and 94% at the lobe level, and 85, 94, 92, 88, and 94% at the segment level, respectively. The detection of segmental and subsegmental hypoperfusion using PW-PREFUL MRI revealed a moderate agreement with V/Q SPECT/CT (κ = 0.65; 95% confidence interval: 0.61–0.68). The quantitative results indicated that the QN was lower in the CPE group than in the non-CPE group [median score (interquartile range, IQR) 6.3 (2.8–9.2) vs. 13.0 (8.8–16.7), p < 0.001], and the QDP was higher [median score (IQR) 33.8 (15.7–51.7) vs. 2.2 (1.4–2.9), p < 0.001].ConclusionPREFUL MRI could be an alternative test to detect CPE without requiring breath-hold, contrast agents, or ionizing radiation

Multicenter Standardization of Phase-Resolved Functional Lung MRI in Patients With Suspected Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND Detection of pulmonary perfusion defects is the recommended approach for diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This is currently achieved in a clinical setting using scintigraphy. Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is an alternative technique for evaluating regional ventilation and perfusion without the use of ionizing radiation or contrast media. PURPOSE To assess the feasibility and image quality of PREFUL-MRI in a multicenter setting in suspected CTEPH. STUDY TYPE This is a prospective cohort sub-study. POPULATION Forty-five patients (64 ± 16 years old) with suspected CTEPH from nine study centers. FIELD STRENGTH/SEQUENCE 1.5 T and 3 T/2D spoiled gradient echo/bSSFP/T2 HASTE/3D MR angiography (TWIST). ASSESSMENT Lung signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between study centers with different MRI machines. The contrast between normally and poorly perfused lung areas was examined on PREFUL images. The perfusion defect percentage calculated using PREFUL-MRI (QDP$_{PREFUL}$ ) was compared to QDP from the established dynamic contrast-enhanced MRI technique (QDP$_{DCE}$ ). Furthermore, QDP$_{PREFUL}$ was compared between a patient subgroup with confirmed CTEPH or chronic thromboembolic disease (CTED) to other clinical subgroups. STATISTICAL TESTS t-Test, one-way analysis of variance (ANOVA), Pearson's correlation. Significance level was 5%. RESULTS Significant differences in lung SNR and CNR were present between study centers. However, PREFUL perfusion images showed a significant contrast between normally and poorly perfused lung areas (mean delta of normalized perfusion -4.2% SD 3.3) with no differences between study sites (ANOVA: P = 0.065). QDP$_{PREFUL}$ was significantly correlated with QDP$_{DCE}$ (r = 0.66), and was significantly higher in 18 patients with confirmed CTEPH or CTED (57.9 ± 12.2%) compared to subgroups with other causes of PH or with excluded PH (in total 27 patients with mean ± SD QDP$_{PREFUL}$  = 33.9 ± 17.2%). DATA CONCLUSION PREFUL-MRI could be considered as a non-invasive method for imaging regional lung perfusion in multicenter studies. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 1

Free-breathing dynamic (19)F gas MR imaging for mapping of regional lung ventilation in patients with COPD

Purpose: To quantify regional lung ventilation in patients with chronic obstructive pulmonary disease (COPD) by using free-breathing dynamic fluorinated (fluorine 19 [(19)F]) gas magnetic resonance (MR) imaging. Materials and Methods: In this institutional review board-approved prospective study, 27 patients with COPD were examined by using breath-hold (19)F gas wash-in MR imaging during inhalation of a normoxic fluorinated gas mixture (perfluoropropane) and by using free-breathing dynamic (19)F gas washout MR imaging after inhalation of the gas mixture was finished for a total of 25-30 L. Regional lung ventilation was quantified by using volume defect percentage (VDP), washout time, number of breaths, and fractional ventilation (FV). To compare different lung function parameters, Pearson correlation coefficient and Fisher z transformation were used, which were corrected for multiple comparisons with the Bonferroni method. Results: Statistically significant correlations were observed for all evaluated lung function test parameters compared with median and interquartile range of (19)F washout parameters. An inverse linear correlation of median number of breaths (r = -0.82; P < .0001) and median washout times (r = -0.77; P < .0001) with percentage predicted of forced expiratory volume in 1 second (FEV1) was observed; correspondingly median FV (r = 0.86; P < .0001) correlated positively with percentage predicted FEV1. Comparing initial with late phase, median VDP of all subjects decreased from 49% (25th-75th percentile, 35%-62%) to 6% (25th-75th percentile, 2%-10%; P < .0001). VDP at the beginning of the gas wash-in phase (VDPinitial) significantly correlated with percentage predicted FEV1 (r = -0.74; P = .0028) and FV (r = 0.74; P = .0002). Median FV was significantly increased in ventilated regions (11.1% [25th-75th percentile, 6.8%-14.5%]) compared with the defect regions identified by VDPinitial (5.8% [25th-75th percentile, 4.0%-7.4%]; P < .0001). Conclusion Quantification of regional lung ventilation by using dynamic (19)F gas washout MR imaging in free breathing is feasible at 1.5 T even in obstructed lung segments

The current status and further prospects for lung magnetic resonance imaging in pediatric radiology

Lung MRI makes it possible to replace up to 90% of CT examinations with radiation-free magnetic resonance diagnostics of the lungs without suffering any diagnostic loss. The individual radiation exposure can thus be relevantly reduced. This applies in particular to children who repeatedly require sectional imaging of the lung, e.g., in tumor surveillance or in chronic lung diseases such as cystic fibrosis. In this paper we discuss various factors that favor the establishment of lung MRI in the clinical setting. Among the many sequences proposed for lung imaging, respiration-triggered T2-W turbo spin-echo (TSE) sequences have been established as a good standard for children. Additional sequences are mostly dispensable. The most important pulmonary findings are demonstrated here in the form of a detailed pictorial essay. T1-weighted gradient echo sequences with ultrashort echo time are a new option. These sequences anticipate signal loss in the lung and deliver CT-like images with high spatial resolution. When using self-gated T1-W ultrashort echo time 3-D sequences that acquire iso-voxel geometry in the sub-millimeter range, secondary reconstructions are possible

Comparison of Functional Free-Breathing Pulmonary 1H and Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Cystic Fibrosis

Rationale and Objectives: Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF). Materials and Methods: 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice. Results: The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p < 0.0001) and elevated LCI (p < 0.0001). PREFUL and HP 129Xe VDP were significantly different between the CF PEx and healthy groups (p < 0.05). In the stable CF group, PREFUL and HP 129Xe VDP were not significantly different from the healthy group (p = 0.18 and 0.08, respectively). There was a correlation between PREFUL and HP 129Xe VDP (R2 = 0.31, p = 0.004), and both parameters were significantly correlated with FEV1 and LCI. Conclusion: PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.The Hospital for Sick Children. Grant: Cystic Fibrosis Catalyst. Natural Sciences and Engineering Research Council of Canada. Grant Number: RGPIN 217015-2013. Canadian Institutes of Health Research. Grant Numbers: MOP 123431, PJT 153099, and PJT 376120. Mitacs

Comparison of phase-resolved functional lung (PREFUL) MRI derived perfusion and ventilation parameters at 1.5T and 3T in healthy volunteers.

PurposeThe purpose of this study is to evaluate the influence of different field strengths on perfusion and ventilation parameters, SNR and CNR derived by PREFUL MRI using predefined sequence parameters.MethodsData sets of free breathing 2d FLASH lung MRI were acquired from 15 healthy subjects at 1.5T and 3T (Magnetom Avanto and Skyra, Siemens Healthcare, Erlangen, Germany) with a maximum period of 3 days in between. The processed functional parameters regional ventilation (RVent), perfusion (Q), quantified perfusion (QQuant), perfusion defect percentage (QDP), ventilation defect percentage (VDP) and ventilation-perfusion match (VQM) were compared for systematic differences. Signal- and contrast-to-noise ratio (SNR and CNR) of both acquisitions were analyzed.ResultsRVent, Q, VDP, SNR and CNR presented no significant differences between 1.5T and 3T. QQuant (1.5T vs. 3T, P = 0.04), and QDP (1.5T vs. 3T, P≤0.01) decreased significantly at 3T. Consequently, VQM increased significantly (1.5T vs. 3T, P≤0.01). Skewness and kurtosis of the Q-values increased significantly at 3T (P≤0.01). The mean Sørensen-Dice coefficients between both series were 0.91 for QDP and 0.94 for VDP. The Bland-Altman analysis of both series showed mean differences of 4.29% for QDP, 1.23% for VDP and -5.15% for VQM. Using the above-mentioned parameters for three-day repeatability at two different scanners and field strengths, the retrospective power calculation showed, that a sample size of 15 can detect differences of 3.7% for QDP, of 2.9% for VDP and differences of 2.6% for VQM.ConclusionSignificant differences in QDP may be related to field inhomogeneities, which is expressed by increasing skewness and kurtosis at 3T. QQuant reveals only poor reproducibility between 1.5T and 3T. RVent, Q, VDP, SNR and CNR were not altered significantly at the used sequence parameters. Healthy participants with minimal defects present high spatial agreement of QDP and VDP

Artificially-generated consolidations and balanced augmentation increase performance of U-net for lung parenchyma segmentation on MR images.

PurposeTo improve automated lung segmentation on 2D lung MR images using balanced augmentation and artificially-generated consolidations for training of a convolutional neural network (CNN).Materials and methodsFrom 233 healthy volunteers and 100 patients, 1891 coronal MR images were acquired. Of these, 1666 images without consolidations were used to build a binary semantic CNN for lung segmentation and 225 images (187 without consolidations, 38 with consolidations) were used for testing. To increase CNN performance of segmenting lung parenchyma with consolidations, balanced augmentation was performed and artificially-generated consolidations were added to all training images. The proposed CNN (CNNBal/Cons) was compared to two other CNNs: CNNUnbal/NoCons-without balanced augmentation and artificially-generated consolidations and CNNBal/NoCons-with balanced augmentation but without artificially-generated consolidations. Segmentation results were assessed using Sørensen-Dice coefficient (SDC) and Hausdorff distance coefficient.ResultsRegarding the 187 MR test images without consolidations, the mean SDC of CNNUnbal/NoCons (92.1 ± 6% (mean ± standard deviation)) was significantly lower compared to CNNBal/NoCons (94.0 ± 5.3%, P = 0.0013) and CNNBal/Cons (94.3 ± 4.1%, P = 0.0001). No significant difference was found between SDC of CNNBal/Cons and CNNBal/NoCons (P = 0.54). For the 38 MR test images with consolidations, SDC of CNNUnbal/NoCons (89.0 ± 7.1%) was not significantly different compared to CNNBal/NoCons (90.2 ± 9.4%, P = 0.53). SDC of CNNBal/Cons (94.3 ± 3.7%) was significantly higher compared to CNNBal/NoCons (P = 0.0146) and CNNUnbal/NoCons (P = 0.001).ConclusionsExpanding training datasets via balanced augmentation and artificially-generated consolidations improved the accuracy of CNNBal/Cons, especially in datasets with parenchymal consolidations. This is an important step towards a robust automated postprocessing of lung MRI datasets in clinical routine

Free-Breathing Low-Field MRI of the Lungs Detects Functional Alterations Associated With Persistent Symptoms After COVID-19 Infection

OBJECTIVES: With the COVID-19 pandemic, repetitive lung examinations have become necessary to follow-up symptoms and associated alterations. Low-field MRI, benefiting from reduced susceptibility effects, is a promising alternative for lung imaging to limit radiations absorbed by patients during CT examinations, which also have limited capability to assess functional alterations. The aim of this investigative study was to explore the functional abnormalities that free-breathing 0.55 T MRI in combination with the phase-resolved functional lung (PREFUL) analysis could identify in patients with persistent symptoms after COVID-19 infection. MATERIALS AND METHODS: Seventy-four COVID-19 patients and 8 healthy volunteers were prospectively scanned in free-breathing with a balanced steady-state free-precession sequence optimized at 0.55 T, 5 months postinfection on average. Normalized perfusion (Q), fractional ventilation (FV), and flow-volume loop correlation (FVLc) maps were extracted with the PREFUL technique. Q, FV, and FVLc defects as well as defect overlaps between these metrics were quantified. Morphological turbo-spin-echo images were also acquired, and the extent of abnormalities was scored by a board-certified radiologist. To investigate the functional correlates of persistent symptoms, a recursive feature elimination algorithm was applied to find the most informative variables to detect the presence of persistent symptoms with a logistic regression model and a cross-validation strategy. All MRI metrics, sex, age, body mass index, and the presence of preexisting lung conditions were included. RESULTS: The most informative variables to detect persistent symptoms were the percentage of concurrent Q and FVLc defects and of areas free of those defects. A detection accuracy of 71.4% was obtained with these 2 variables when fitting the model on the entire dataset. Although none of the single variables differed between patients with and without persistent symptoms ( P &gt; 0.05), the combined score of these 2 variables did ( P &lt; 0.02). This score also showed a consistent increase from healthy volunteers (7.7) to patients without persistent symptoms (8.2) and with persistent symptoms (8.6). The morphological abnormality score showed poor correlation with the functional parameters. CONCLUSIONS: Functional pulmonary examinations using free-breathing 0.55 T MRI with PREFUL analysis revealed potential quantitative markers of impaired lung function in patients with persistent symptoms after COVID-19 infection, potentially complementing morphologic imaging. Future work is needed to explore the translational relevance and clinical implication of these findings

129Xe and Free-Breathing 1H Ventilation MRI in Patients With Cystic Fibrosis: A Dual-Center Study

Background: Free-breathing 1H ventilation MRI shows promise but only single-center validation has yet been performed against methods which directly image lung ventilation in patients with cystic fibrosis (CF). Purpose: To investigate the relationship between 129Xe and 1H ventilation images using data acquired at two centers. Study type: Sequence comparison. Population: Center 1; 24 patients with CF (12 female) aged 9–47 years. Center 2; 7 patients with CF (6 female) aged 13–18 years, and 6 healthy controls (6 female) aged 21–31 years. Data were acquired in different patients at each center. Field Strength/Sequence: 1.5 T, 3D steady-state free precession and 2D spoiled gradient echo. Assessment: Subjects were scanned with 129Xe ventilation and 1H free-breathing MRI and performed pulmonary function tests. Ventilation defect percent (VDP) was calculated using linear binning and images were visually assessed by H.M., L.J.S., and G.J.C. (10, 5, and 8 years' experience). Statistical Tests: Correlations and linear regression analyses were performed between 129Xe VDP, 1H VDP, FEV1, and LCI. Bland–Altman analysis of 129Xe VDP and 1H VDP was carried out. Differences in metrics were assessed using one-way ANOVA or Kruskal–Wallis tests. Results: 129Xe VDP and 1H VDP correlated strongly with; each other (r = 0.84), FEV1 z-score (129Xe VDP r = −0.83, 1H VDP r = −0.80), and LCI (129Xe VDP r = 0.91, 1H VDP r = 0.82). Bland–Altman analysis of 129Xe VDP and 1H VDP from both centers had a bias of 0.07% and limits of agreement of −16.1% and 16.2%. Linear regression relationships of VDP with FEV1 were not significantly different between 129Xe and 1H VDP (P = 0.08), while 129Xe VDP had a stronger relationship with LCI than 1H VDP. Data Conclusion: 1H ventilation MRI shows large-scale agreement with 129Xe ventilation MRI in CF patients with established lung disease but may be less sensitive to subtle ventilation changes in patients with early-stage lung disease. Evidence Level: 2. Technical Efficacy: Stage 2

Multiparametric MRI for organ quality assessment in a porcine Ex-Vivo lung perfusion system.

IntroductionEx-vivo lung perfusion (EVLP) is an emerging technique promising an expansion of the donor pool and improvements in the outcome after lung transplantation. Reliable biomarkers for local assessment of organ function in the EVLP system are intensely sought after. This study aims to evaluate the feasibility of multiparametric functional magnetic resonance imaging (fMRI) in an EVLP system in a porcine aspiration model.Material and methodsSeven female pigs were anesthetized and gastric juice was instilled in the right lower lobe bronchus to simulate aspiration. Left lungs served as control. Lungs were removed and installed in a modified EVLP system. In the 12-hour EVLP run three sequential MRI scans were performed. Oxygen-washout time, Fourier Decomposition derived ventilation and perfusion, and dynamic contrast enhanced imaging derived perfusion were calculated. PaO2:FiO2 ratio was determined and correlated. End-point histology and computed tomography served as control.ResultsAll animals completed the protocol. MRI structural images showed infiltrates in lungs after aspiration comparable to CT scans. Ventilation was significantly (p = 0.016) reduced while perfusion was increased (p = 0.016) in lungs after aspiration. Non-contrast dependent Fourier decomposition perfusion showed good correlation (R2 = 0.67) to dynamic contrast enhanced derived perfusion. Oxygen washout time was significantly increased (p = 0.016) in lungs after aspiration and showed a correlation with the PaO2:FiO2 ratio (R2 = 0.54).ConclusionMultiparametric fMRI for local assessment of organ function is feasible in EVLP and detects alterations in lung function following aspiration with correlation to clinical parameters. fMRI may improve organ assessment in ex-vivo perfusion systems, leading to a better selection of segments suitable for transplant