Comparison of Free-Breathing 3D Phase-Resolved Functional Lung (PREFUL) MRI With Dynamic 19 F Ventilation MRI in Patients With Obstructive Lung Disease and Healthy Volunteers.

BACKGROUND: Non-contrast-enhanced 1 H magnetic resonance imaging (MRI) with full lung coverage shows promise for assessment of regional lung ventilation but a comparison with direct ventilation measurement using 19 F MRI is lacking. PURPOSE: To compare ventilation parameters calculated using 3D phase-resolved functional lung (PREFUL) MRI with 19 F MRI. STUDY TYPE: Prospective. POPULATION: Fifteen patients with asthma, 14 patients with chronic obstructive lung disease, and 13 healthy volunteers. FIELD STRENGTH/SEQUENCE: A 3D gradient-echo pulse sequence with golden-angle increment and stack-of-stars encoding at 1.5 T. ASSESSMENT: All participants underwent 3D PREFUL MRI and 19 F MRI. For 3D PREFUL, static regional ventilation (RVent) and dynamic flow-volume cross-correlation metric (FVL-CM) were calculated. For both parameters, ventilation defect percentage (VDP) values and ventilation defect (VD) maps (including a combination of both parameters [VDPCombined ]) were determined. For 19 F MRI, images from eight consecutive breaths under volume-controlled inhalation of perfluoropropane were acquired. Time-to-fill (TTF) and wash-in (WI) parameters were extracted. For all 19 F parameters, a VD map was generated and the corresponding VDP values were calculated. STATISTICAL TESTS: For all parameters, the relationship between the two techniques was assessed using a Spearman correlation (r). Differences between VDP values were compared using Bland-Altman analysis. For regional comparison of VD maps, spatial overlap and Sørensen-Dice coefficients were computed. RESULTS: 3D PREFUL VDP values were significantly correlated to VDP measures by 19 F (r range: 0.59-0.70). For VDPRVent , no significant bias was observed with VDP of the third and fourth breath (bias range = -6.8:7.7%, P range = 0.25:0.30). For VDPFVL-CM , no significant bias was found with VDP values of fourth-eighth breaths (bias range = -2.0:12.5%, P range = 0.12:0.75). The overall spatial overlap of all VD maps increased with each breath, ranging from 61% to 81%, stabilizing at the fourth breath. DATA CONCLUSION: 3D PREFUL MRI parameters showed moderate to strong correlation with 19 F MRI. Depending on the 3D PREFUL VD map, the best regional agreement was found to 19 F VD maps of third-fifth breath. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Effect of CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor on pulmonary ventilation derived by 3D phase-resolved functional lung MRI in cystic fibrosis patients.

OBJECTIVES: To investigate whether 3D phase-resolved functional lung (PREFUL)-MRI parameters are suitable to measure response to elexacaftor/tezacaftor/ivacaftor (ETI) therapy and their association with clinical outcomes in cystic fibrosis (CF) patients. METHODS: Twenty-three patients with CF (mean age: 21; age range: 14-46) underwent MRI examination at baseline and 8-16 weeks after initiation of ETI. Morphological and 3D PREFUL scans assessed pulmonary ventilation. Morphological images were evaluated using a semi-quantitative scoring system, and 3D PREFUL scans were evaluated by ventilation defect percentage (VDP) values derived from regional ventilation (RVent) and cross-correlation maps. Improved ventilation volume (IVV) normalized to body surface area (BSA) between baseline and post-treatment visit was computed. Forced expiratory volume in 1 second (FEV1) and mid-expiratory flow at 25% of forced vital capacity (MEF25), as well as lung clearance index (LCI), were assessed. Treatment effects were analyzed using paired Wilcoxon signed-rank tests. Treatment changes and post-treatment agreement between 3D PREFUL and clinical parameters were evaluated by Spearman's correlation. RESULTS: After ETI therapy, all 3D PREFUL ventilation markers (all p < 0.0056) improved significantly, except for the mean RVent parameter. The BSA normalized IVVRVent was significantly correlated to relative treatment changes of MEF25 and mucus plugging score (all |r| > 0.48, all p < 0.0219). In post-treatment analyses, 3D PREFUL VDP values significantly correlated with spirometry, LCI, MRI global, morphology, and perfusion scores (all |r| > 0.44, all p < 0.0348). CONCLUSIONS: 3D PREFUL MRI is a very promising tool to monitor CFTR modulator-induced regional dynamic ventilation changes in CF patients. CLINICAL RELEVANCE STATEMENT: 3D PREFUL MRI is sensitive to monitor CFTR modulator-induced regional ventilation changes in CF patients. Improved ventilation volume correlates with the relative change of mucus plugging, suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement. KEY POINTS: • 3D PREFUL MRI-derived ventilation maps show significantly reduced ventilation defects in CF patients after ETI therapy. • Significant post-treatment correlations of 3D PREFUL ventilation measures especially with LCI, FEV1 %pred, and global MRI score suggest that 3D PREFUL MRI is sensitive to measure improved regional ventilation of the lung parenchyma due to reduced inflammation induced by ETI therapy in CF patients. • 3D PREFUL MRI-derived improved ventilation volume (IVV) correlated with MRI mucus plugging score changes suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement 8-16 weeks after ETI therapy.

Phase-resolved Functional Lung (PREFUL) MRI-derived Ventilation and Perfusion Parameters Predict Future Lung Transplant Loss.

Background Chronic lung allograft dysfunction (CLAD), the physiologic correlate of chronic rejection, remains a major barrier to long-term survival following lung transplant. Biomarkers for early prediction of future transplant loss or death due to CLAD might open a window of opportunity for early diagnosis and treatment of CLAD. Purpose To evaluate the prognostic use of phase-resolved functional lung (PREFUL) MRI in predicting CLAD-related transplant loss or death. Materials and Methods In this prospective, longitudinal, single-center study, PREFUL MRI-derived ventilation and parenchymal lung perfusion parameters of bilateral lung transplant recipients without clinically suspected CLAD were assessed 6-12 months (baseline) and 2.5 years (follow-up) after transplant. MRI scans were acquired between August 2013 and December 2018. Regional flow volume loop (RFVL)-based ventilated volume (VV) and perfused volume were calculated using thresholds and spatially combined as ventilation-perfusion (V/Q) matching. Spirometry data were obtained on the same day. Exploratory models were calculated using receiver operating characteristic analysis, and subsequent survival analyses (Kaplan-Meier, hazard ratios [HRs]) of CLAD-related graft loss were performed to compare clinical and MRI parameters as clinical end points. Results At baseline MRI examination, 132 clinically stable patients of 141 patients (median age, 53 years [IQR, 43-59 years]; 78 men) were included (nine were excluded for deaths not associated with CLAD), 24 of which had CLAD-related graft loss (death or retransplant) within the observational period of 5.6 years. PREFUL MRI-derived RFVL VV was a predictor of poorer survival (cutoff, 92.3%; log-rank P = .02; HR for graft loss, 2.5 [95% CI: 1.1, 5.7]; P = .02), while perfused volume (P = .12) and spirometry (P = .33) were not predictive of differences in survival. In the evaluation of percentage change at follow-up MRI (92 stable patients vs 11 with CLAD-related graft loss), mean RFVL (cutoff, 97.1%; log-rank P < .001; HR, 7.7 [95% CI: 2.3, 25.3]), V/Q defect (cutoff, 498%; log-rank P = .003; HR, 6.6 [95% CI: 1.7, 25.0]), and forced expiratory volume in the first second of expiration (cutoff, 60.8%; log-rank P < .001; HR, 7.9 [95% CI: 2.3, 27.4]; P = .001) were predictive of poorer survival within 2.7 years (IQR, 2.2-3.5 years) after follow-up MRI. Conclusion Phase-resolved functional lung MRI ventilation-perfusion matching parameters were predictive of future chronic lung allograft dysfunction-related death or transplant loss in a large prospective cohort who had undergone lung transplant. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Fain and Schiebler in this issue.

Absolute thermometry using hyperpolarized 129 Xe free-induction decay and spin-echo chemical-shift imaging in rats.

PURPOSE: To implement and test variants of chemical shift imaging (CSI) acquiring both free induction decays (FIDs) showing all dissolved-phase compartments and spin echoes for specifically assessing 129 $$ {}^{129} $$ Xe in lipids in order to perform precise lipid-dissolved 129 $$ {}^{129} $$ Xe MR thermometry in a rat model of general hypothermia. METHODS: Imaging was performed at 2.89 T. T 2 $$ {T}_2 $$ of 129 $$ {}^{129} $$ Xe in lipids was determined in one rat by fitting exponentials to decaying signals of global spin-echo spectra. Four rats (conventional CSI) and six rats (turbo spectroscopic imaging) were scanned at three time points with core body temperature 37/34/37 ∘ $$ {}^{\circ } $$ C. Lorentzian functions were fit to spectra from regions of interest to determine the water-referenced chemical shift of lipid-dissolved 129 $$ {}^{129} $$ Xe in the abdomen. Absolute 129 $$ {}^{129} $$ Xe-derived temperature was compared to values from a rectal probe. RESULTS: Global T 2 $$ {T}_2 $$ of 129 $$ {}^{129} $$ Xe in lipids was determined as 251 . 3 ms ± 81 . 4 ms $$ 251.3\;\mathrm{ms}\pm 81.4\;\mathrm{ms} $$ . Friedman tests showed significant changes of chemical shift with time for both sequence variants and both FID and spin-echo acquisitions. Mean and SD of 129 $$ {}^{129} $$ Xe and rectal probe temperature differences were found to be - 0 . 1 5 ∘ C ± 0 . 9 3 ∘ C $$ -0.1{5}^{\circ}\mathrm{C}\pm 0.9{3}^{\circ}\mathrm{C} $$ (FID) and - 0 . 3 8 ∘ C ± 0 . 6 4 ∘ C $$ -0.3{8}^{\circ}\mathrm{C}\pm 0.6{4}^{\circ}\mathrm{C} $$ (spin echo) for conventional CSI as well as 0 . 0 3 ∘ C ± 0 . 7 7 ∘ C $$ 0.0{3}^{\circ}\mathrm{C}\pm 0.7{7}^{\circ}\mathrm{C} $$ (FID) and - 0 . 0 6 ∘ C ± 0 . 7 6 ∘ C $$ -0.0{6}^{\circ}\mathrm{C}\pm 0.7{6}^{\circ}\mathrm{C} $$ (spin echo) for turbo spectroscopic imaging. CONCLUSION: 129 $$ {}^{129} $$ Xe MRI using conventional CSI and turbo spectroscopic imaging of lipid-dissolved 129 $$ {}^{129} $$ Xe enables precise temperature measurements in the rat's abdomen using both FID and spin-echo acquisitions with acquisition of spin echoes enabling most precise temperature measurements.

Evaluation of image registration algorithms for 3D phase-resolved functional lung ventilation magnetic resonance imaging in healthy volunteers and chronic obstructive pulmonary disease patients.

The purpose of the current study was to assess the influence of the registration algorithms on the repeatability of three-dimensional (3D) phase-resolved functional lung (PREFUL) ventilation magnetic resonance imaging (MRI). Twenty-three healthy volunteers and 10 patients with chronic obstructive pulmonary disease (COPD) underwent 3D PREFUL MRI during tidal breathing. The registration of dynamically acquired data to a fixed image was executed using single-step, stepwise, and group-oriented registration (GOREG) approaches. Advanced Normalization Tools (ANTs) and the Forsberg image-registration package were used for the registration. Image registration algorithms were tested for differences and evaluated by the repeatability analysis of ventilation parameters using coefficient of variation (CoV), intraclass-correlation coefficient, Bland-Altman plots, and correlation to spirometry. Also, the registration time and image quality were computed for all registration approaches. Very strong to strong correlations (r range: 0.917-0.999) were observed between ventilation parameters derived using various registration approaches. Median CoV values of the cross-correlation (CC) parameter were significantly lower (all p ≤ 0.0054) for ANTs GOREG compared with single-step and stepwise ANTs registration. The majority of comparisons between COPD patients and age-matched healthy volunteers showed agreement among the registration approaches. The repeatability of regional ventilation (RVent)-based ventilation defect percentage (VDPRVent ) and VDPCC was significantly higher (both p ≤ 0.0054) for Forsberg GOREG compared with ANTs GOREG. All 3D PREFUL-derived ventilation parameters correlated with forced expiratory volume in 1 s (FEV1 ) and the FEV1 / forced vital capacity (FVC) ratio (all |r| > 0.40, all p < 0.03). The image sharpness of RVent maps was statistically elevated (all p < 0.001) using GOREG compared with single-step and stepwise registration approaches using ANTs. The best computational performance was achieved with Forsberg GOREG. The GOREG scheme improves the repeatability and image quality of dynamic 3D PREFUL ventilation parameters. Registration time can be ~10-fold reduced to 9 min using the Forsberg method with equal or even improved repeatability and comparable PREFUL ventilation results compared with the ANTs method.

Volume-Controlled 19 F MR Ventilation Imaging of Fluorinated Gas.

BACKGROUND: 19 F MRI of inhaled gas tracers has developed into a promising tool for pulmonary diagnostics. Prior to clinical use, the intersession repeatability of acquired ventilation parameters must be quantified and maximized. PURPOSE: To evaluate repeatability of static and dynamic 19 F ventilation parameters and correlation with predicted forced expiratory volume in 1 second (FEV1 %pred) with and without inspiratory volume control. STUDY TYPE: Prospective. POPULATION: A total of 30 healthy subjects and 26 patients with chronic obstructive pulmonary disease (COPD). FIELD STRENGTH/SEQUENCE: Three-dimensional (3D) gradient echo pulse sequence with golden-angle stack-of-stars k-space encoding at 1.5 T. ASSESSMENT: All study participants underwent 19 F ventilation MRI over eight breaths with inspiratory volume control (w VC) and without inspiratory volume control (w/o VC), which was repeated within 1 week. Ventilated volume percentage (VVP), fractional ventilation (FV), and wash-in time (WI) were computed. Lung function testing was conducted on the first visit. STATISTICAL TESTS: Correlation between imaging and FEV1 %pred was measured using Pearson correlation coefficient (r). Differences in imaging parameters between first and second visit were analyzed using paired t-test. Repeatability was quantified using intraclass correlation coefficient (ICC) and coefficient of variation (CoV). Minimum detectable effect size (MDES) was calculated with a power analysis for study size n = 30 and a power of 0.8. All hypotheses were tested with a significance level of 5% two sided. RESULTS: Strong and moderate linear correlations with FEV1 %pred for COPD patients were found in almost all imaging parameters. The ICC w VC exceeds the ICC w/o VC for all imaging parameters. CoV was significantly lower w VC for initial VVP in COPD patients, FV, CoV FV, WI and standard deviation (SD) of WI. MDES of all imaging parameters were smaller w VC. DATA CONCLUSION: 19 F gas wash-in MRI with inspiratory volume control increases the correlation and repeatability of imaging parameters with lung function testing. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Molecular Imaging of Inflammation and Fibrosis in Pressure Overload Heart Failure.

[Figure: see text].

First experiences using transurethral ultrasound ablation (TULSA) as a promising focal approach to treat localized prostate cancer: a monocentric study.

PURPOSE: To share our experience using transurethral ultrasound ablation (TULSA) treatment for focal therapy of localized prostate cancer (PCa). MATERIALS AND METHODS: Between 10/2019 and 06/2021 TULSA treatment for localized PCa was performed in 22 men (mean age: 67 ± 7 years, mean initial PSA: 6.8 ± 2.1 ng/ml, ISUP 1 in n = 6, ISUP 2 in n = 14 and 2 patients with recurrence after previous radiotherapy). Patients were selected by an interdisciplinary team, taking clinical parameters, histopathology from targeted or systematic biopsies, mpMRI and patients preferences into consideration. Patients were thoroughly informed about alternative treatment options and that TULSA is an individual treatment approach. High-intensity ultrasound was applied using an ablation device placed in the prostatic urethra. Heat-development within the prostatic tissue was monitored using MR-thermometry. Challenges during the ablation procedure and follow-up of oncologic and functional outcome of at least 12 months after TULSA treatment were documented. RESULTS: No major adverse events were documented. In the 12 month follow-up period, no significant changes of urinary continence, irritative/obstructive voiding symptoms, bowel irritation or hormonal symptoms were reported according to the Expanded Prostate Cancer Index Composite (EPIC) score. Erectile function was significantly impaired 3-6 months (p < 0.01) and 9-12 months (p < 0.05) after TULSA. PSA values significantly decreased after therapy (2.1 ± 1.8 vs. 6.8 ± 2.1 ng/ml, p < 0.001). PCa recurrence rate was 23% (5/22 patients). CONCLUSION: Establishment of TULSA in clinical routine was unproblematic, short-term outcome seems to be encouraging. The risk of erectile function impairment requires elaborate information of the patient.

Examining lung microstructure using 19 F MR diffusion imaging in COPD patients.

PURPOSE: To examine the time-dependent diffusion of fluorinated (19 F) gas in human lungs for determination of surface-to-volume ratio in comparison to results from hyperpolarized 129 Xe and lung function testing in healthy volunteers and patients with chronic obstructive pulmonary disease. METHODS: Diffusion of fluorinated gas in the short-time regime was measured using multiple gradient-echo sequences with a single pair of trapezoidal gradient pulses. Pulmonary surface-to-volume ratio was calculated using a first-order approximation of the time-dependent diffusion in a study with 20 healthy volunteers and 22 patients with chronic obstructive pulmonary disease. The repeatability after 7 days as well as the correlation with hyperpolarized 129 Xe diffusion MRI and lung function testing was analyzed. RESULTS: Using 19 F diffusion MRI, the median surface-to-volume ratio is significantly decreased in chronic obstructive pulmonary disease patients (S/V = 126 cm-1 [87-144 cm-1 ]) compared with healthy volunteers (S/V = 164 cm-1 [160-84 cm-1 ], p < 0.0001). No significant difference was found between measurements within 7 days for healthy (p = 0.88, median coefficient of variation = 4.3%) and diseased subjects (p = 0.58, median coefficient of variation= 6.7%). Linear correlations were found with S/V from 129 Xe diffusion MRI (r = 0.85, p = 0.001) and the forced expiratory volume in 1 second (r = 0.68, p < 0.0001). CONCLUSION: Examination of lung microstructure using time-dependent diffusion measurement of inhaled 19 F is feasible, repeatable, and correlates with established measurements.

The impact of the field of view (FOV) on image quality in MDCT angiography of the lower extremities.

OBJECTIVES: To evaluate the impact of the reconstructed field-of-view (FOV) on image quality in computed-tomography angiography (CTA) of the lower extremities. METHODS: A total of 100 CTA examinations of the lower extremities were acquired on a 2 × 192-slice multidetector CT (MDCT) scanner. Three different datasets were reconstructed covering both legs (standard FOV size) as well as each leg separately (reduced FOV size). The subjective image quality was evaluated for the different vessel segments (femoral, popliteal, crural, pedal) by three readers using a semi-quantitative Likert scale. Additionally, objective image quality was assessed using an automated image quality metric on a per-slice basis. RESULTS: The subjective assessment of the image quality showed an almost perfect interrater agreement. The image quality of the small FOV datasets was rated significantly higher as compared to the large datasets for all patients and vessel segments (p < 0.05) with a tendency towards a higher effect in smaller vessels. The difference of the mean scores between the group with the large FOV and small FOV was 0.68 for the femoral level, 0.83 for the popliteal level, 1.12 for the crural level, and 1.08 for the pedal level. The objective image quality metric also demonstrated a significant improvement of image quality in the small FOV datasets. CONCLUSIONS: Side-separated reconstruction of each leg in CTA of the lower extremities using a small reconstruction FOV significantly improves image quality as compared to a standard reconstruction with a large FOV covering both legs. KEY POINTS: • In CT angiography of the lower legs, the side-separated reconstruction of each leg using a small field-of-views improves image quality as compared to a standard reconstruction covering both legs. • The side-separated reconstruction can be readily implemented at every commercially available CT scanner. • There is no need for additional hardware or software and no additional burden to the patient.

Correction of heat-induced susceptibility changes in respiratory-triggered 2D-PRF-based thermometry for monitoring of magnetic resonance-guided hepatic microwave ablation in a human-like in vivo porcine model.

PURPOSE: To develop and evaluate susceptibility corrected 2D proton resonance frequency (PRF)-based magnetic resonance (MR)-thermometry for the accurate assessment of the ablation zone of hepatic microwave ablation (MWA). METHODS AND MATERIALS: Twelve hepatic MWA were performed in five LEWE minipigs with human-like fissure-free liver. Temperature maps during ablation of PRF-based MR-thermometry were corrected by modeling heat induced susceptibility changes. Ablation zones were determined using cumulative equivalent minutes at 43 °C (CEM43) as tissue damage model. T1 weighted (w) post-ablation contrast-enhanced (CE) MR-imaging and manually segmented postmortem histology were used for validation. The agreement of uncorrected (raw) and susceptibility corrected (corr) MR-thermometry with T1w post-ablation CE MR-imaging and histology was evaluated. The Wilcoxon-signed rank test and Bland-Altman analysis were applied. RESULTS: With the susceptibility corrected MR-thermometry a significantly increased dice coefficient (raw: 77% vs. corr: 83%, p < 0.01) and sensitivity (raw: 72% vs. corr: 82%, p < 0.01) was found for the comparison to T1w-CE imaging as well as histopathology (dice coefficients: raw: 76% vs. corr: 79%, p < 0.001; sensitivity: raw: 72% vs. corr: 74%, p < 0.001). While major axis length was significantly increased (7.1 mm, p < 0.001) and minor axis length significantly decreased (2.2 mm, p < 0.001) in uncorrected MR-thermometry compared to T1w-CE MR-imaging, no significant bias was found after susceptibility correction. CONCLUSION: Using susceptibility corrected 2D PRF-based MR-thermometry to predict the ablation zones of hepatic MWA provided a good agreement in comparison to T1w post-ablation CE MR-imaging and histopathology.

Perfusion quantification using voxel-wise proton density and median signal decay in PREFUL MRI.

PURPOSE: Contrast-free lung MRI based on Fourier decomposition is an attractive method to monitor various lung diseases. However, the accuracy of the current perfusion quantification is limited. In this study, a new approach for perfusion quantification based on voxel-wise proton density and median signal decay toward the steady state for Fourier decomposition-based techniques is proposed called QQuantified (QQuant ). METHODS: Twenty patients with chronic obstructive pulmonary disease and 18 patients with chronic thromboembolic pulmonary hypertension received phase-resolved functional lung-MRI (PREFUL) and dynamic contrast-enhanced (DCE)-MRI. Nine healthy participants received phase-resolved functional lung-MRI only. Median values of QQuant were compared to a Fourier decomposition perfusion quantification presented by Kjørstad et al (QKjørstad ) and validated toward pulmonary blood flow derived by DCE-MRI (PBFDCE ). Blood fraction maps determined by the new approach were calculated. Regional and global correlation coefficients were calculated, and Bland-Altman plots were created. Histogram analyses of all cohorts were created. RESULTS: The introduced parameter QQuant showed only 2 mL/min/100 mL mean deviation to PBFDCE in the patient cohort and showed less bias than QKjørstad . Significant increases of regional correlation with PBFDCE were achieved (r = 0.3 vs. r = 0.2, P < .01*). The trend of global correlation toward PBFDCE is not uniform, showing higher values for QKjørstad in the chronic obstructive pulmonary disease cohort than for QQuant and vice versa in the chronic thromboembolic pulmonary hypertension cohort. In contrast to QKjørstad , QQuant perfusion maps indicate a physiologic dorsoventral gradient in supine position similar to PBFDCE with similar value distribution in the histograms. CONCLUSION: We proposed a new approach for perfusion quantification of phase-resolved functional lung measurements. The developed parameter QQuant reveals a higher accuracy compared to QKjørstad .

3D phase-resolved functional lung ventilation MR imaging in healthy volunteers and patients with chronic pulmonary disease.

PURPOSE: To test the feasibility of 3D phase-resolved functional lung (PREFUL) MRI in healthy volunteers and patients with chronic pulmonary disease, to compare 3D to 2D PREFUL, and to investigate the required temporal resolution to obtain stable 3D PREFUL measurement. METHODS: Sixteen participants underwent MRI using 2D and 3D PREFUL. Retrospectively, the spatial resolution of 3D PREFUL (4 × 4 × 4 mm3 ) was decreased to match the spatial resolution of 2D PREFUL (4 × 4 × 15 mm3 ), abbreviated as 3Dlowres . In addition to regional ventilation (RVent), flow-volume loops were computed and rated by a cross-correlation (CC). Ventilation defect percentage (VDP) maps were obtained. RVent, CC, VDPRVent , and VDPCC were compared for systematic differences between 2D, 3Dlowres , and 3D PREFUL. Dividing the 3D PREFUL data into 4- (≈ 20 phases), 8- (≈ 40 phases), and 12-min (≈ 60 phases) acquisition pieces, the ventilation parameter maps, including the heterogeneity of ventilation time to peak, were tested regarding the required temporal resolution. RESULTS: RVent, CC, VDPRVent , and VDPCC  presented significant correlations between 2D and 3D PREFUL (r = 0.64-0.94). CC and VDPCC  of 2D and 3Dlowres  PREFUL were significantly different (P < .0113). Comparing 3Dlowres  and 3D PREFUL, all parameters were found to be statistically different (P < .0045). CONCLUSION: 3D PREFUL MRI depicts the whole lung volume and breathing cycle with superior image resolution and with likely more precision compared to 2D PREFUL. Furthermore, 3D PREFUL is more sensitive to detect regions of hypoventilation and ventilation heterogeneity compared to 3Dlowres  PREFUL, which is important for early detection and improved monitoring of patients with chronic lung disease.

Repeatability of dynamic 3D phase-resolved functional lung (PREFUL) ventilation MR Imaging in patients with chronic obstructive pulmonary disease and healthy volunteers.

BACKGROUND: A previous study has demonstrated the feasibility of 3D phase-resolved functional lung (PREFUL) MRI in healthy volunteers and patients with chronic pulmonary disease. Before clinical use, the repeatability of the ventilation parameters derived from 3D PREFUL MRI must be determined. PURPOSE: To evaluate repeatability of 3D PREFUL and to compare with pulmonary functional lung testing (PFT). STUDY TYPE: Prospective. POPULATION: Fifty-three healthy subjects and 13 patients with chronic obstructive pulmonary disease (COPD). FIELD STRENGTH/SEQUENCE: A prototype 3D stack-of-stars spoiled-gradient-echo sequence at 1.5 T. ASSESSMENT: Study participants underwent repeated MRI examination (median time interval between scans COPD/healthy subjects [interquartile range]: 7/0 days [6-8/0-0 days]) and one PFT carried out at the time of the baseline MRI. For 3D PREFUL, regional ventilation (RVent) and flow-volume loops were computed and rated by cross-correlation (CC). Also, ventilation time-to-peak (VTTP) was computed. Ventilation defect percentage (VDP) maps were obtained for RVent and CC. STATISTICAL TESTS: Repeatability of 3D PREFUL parameters was evaluated using Bland-Altman analysis, coefficient of variation (COV) and intraclass correlation coefficient (ICC). The relation between 3D PREFUL and PFT measures (forced expiratory volume in 1 second (FEV1 ) and forced vital capacity (FVC) was assessed using the Pearson correlation coefficient (r). RESULTS: In healthy subjects and COPD patients, no significant bias (all P range: 0.09-0.77) and a moderate to good repeatability of RVent, VTTP, and VDPRVent were found (COV range: 0.1%-18.2%, ICC range: 0.51-0.88). For CC and VDPCC moderate repeatability was found (COV range: 0.6%-43.6%, ICC: 0.38-0.60). CC, VDPRVent , and VDPCC showed a good correlation with FEV1 (all |r| > 0.58, all P < 0.05) and FEV1 /FVC ratio (all |r| > 0.62, all P < 0.05). DATA CONCLUSION: 3D PREFUL provided a good repeatability of RVent, VTTP, and VDPRVent and moderate repeatability of CC and VDPCC in healthy volunteers and COPD patients, and correlated well with FEV1 and FEV1 /FVC. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

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

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

Echo Time-Dependent Observed Lung T1 in Patients With Chronic Obstructive Pulmonary Disease in Correlation With Quantitative Imaging and Clinical Indices.

BACKGROUND: There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1 (TE)) depends on the echo-time (TE) and reflects regional pulmonary function. PURPOSE: To investigate the potential diagnostic value of T1 (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT. STUDY TYPE: Prospective non-randomized diagnostic study. POPULATION: Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference. FIELD STRENGTH/SEQUENCE: Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for T1 (TE) mapping at TE1-5  = 70 µsec, 500 µsec, 1200 µsec, 1650 µsec, and 2300 µsec. ASSESSMENT: Perfusion images were scored by three radiologists. T1 (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired. STATISTICAL TESTS: Spearman rank correlation coefficients (ρ) were calculated between T1 (TE) and perfusion scores, clinical parameters and qCT. A P-value <0.05 was considered statistically significant. RESULTS: Median values were T1 (TE1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2 , with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ < 0.70), mean lung density (MLD, ρ < 0.72) and the perfusion score (ρ > -0.69) were found. Overall, correlations were strongest at TE2 , weaker at TE1 and rarely significant at TE4 -TE5 . DATA CONCLUSION: In COPD patients, the increase of T1 (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1 (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T1 (TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Effect of intravenously injected gadolinium-based contrast agents on functional lung parameters derived by PREFUL MRI.

PURPOSE: To evaluate the influence of intravenously administered gadolinium-based contrast agents on functional ventilation and perfusion parameters derived by phase-resolved functional lung (PREFUL) MRI. METHODS: Fourteen participants underwent functional MRI at 1.5T using a 2D spoiled gradient echo sequence during free breathing. Three data sets of PREFUL images were obtained-the 1st data set was acquired in mean 33:46 min (SD = 6:20 min) prior, the 2nd and 3rd data sets 43 and 91 s (both SD = 1.9 s), respectively, after i.v. application of gadobutrol. Full respiratory and cardiac cycles were reconstructed and functional parameters of regional ventilation (RV), perfusion (Q), and quantified perfusion (QQuant ) together with perfusion-defected percentages (QDP), ventilation-defected percentages (VDP), and ventilation-perfusion match (VQM) were calculated and compared for systematic differences between the acquired data sets. RESULTS: RV- and Q-values presented no significant alteration after gadobutrol administration. Consequently, QDP, VDP, and VQ maps were not significantly different. Sørensen-Dice coefficients of QDP and VDP maps between the different series varied up to ±9%. QQuant was significantly increased after the application of gadobutrol (1st vs. 2nd series, P = 0.0021; 1st vs. 3rd, P = 0.0188), which can be explained by the velocity-dependent signal in the completely blood-filled voxel (ROI of the aorta) after shortening of T1 relaxation time (1st vs. 2nd series, P = 0.0003; 1st vs. 3rd series, P = 0.0008). CONCLUSION: Except for quantified perfusion, all evaluated functional parameters including ventilation- and perfusion-weighted maps derived by PREFUL MRI were independent of gadolinium-based contrast agents, which is important for the design of MRI protocols in future studies.

Investigating short-time diffusion of hyperpolarized 129 Xe in lung air spaces and tissue: A feasibility study in chronic obstructive pulmonary disease patients.

PURPOSE: To investigate the diffusion of hyperpolarized 129 Xe in air spaces at short-time scales for determination of lung surface-to-gas-volume ratio in comparison to results from chemical shift saturation recovery, CT, and established clinical measures. METHODS: A pulse sequence for measurement of time-dependent diffusion of 129 Xe in air spaces at short diffusion times was developed. Gas uptake into lung tissue was measured in the same breathhold using chemical shift saturation recovery spectroscopy in the short-time regime. The potential to obtain the surface-to-gas-volume ratio using a first-order and second-order approximation of the short-time expansion of time-dependent diffusion according to Mitra et al11 and its diagnostic relevance were tested in a study with 9 chronic obstructive pulmonary diseases patients. RESULTS: Surface-to-gas-volume ratios obtained from time-dependent diffusion were correlated with results from chemical shift saturation recovery, r = 0.840, P = .005 (first-order fits), and r = 0.923, P < .001 (second-order fits), and from CT results for second-order fits, r = 0.729, P = .026. Group means ± SD were 75.0 ± 15.5 cm-1 (first-order fits) and 122.3 ± 32.8 cm-1 (second-order fits) for time-dependent diffusion, 125.9 ± 43.3 cm-1 for chemical shift saturation recovery, and 159.5 ± 50.9 cm-1 for CT. Surface-to-gas-volume ratios from time-dependent diffusion with first-order fits correlated significantly with carbon monoxide diffusing capacity as percent of prediction, r = 0.724, P = .028. CONCLUSION: Time-dependent diffusion measurements of 129 Xe at short-time scales down to ~1 ms are feasible in chronic obstructive pulmonary patients and provide clinically relevant information on lung microstructure.

1 H-guided reconstruction of 19 F gas MRI in COPD patients.

PURPOSE: To reduce acquisition time and improve image quality and robustness of ventilation assessment in a single breath-hold using 1 H-guided reconstruction of fluorinated gas (19 F) MRI. METHODS: Reconstructions constraining total variation in the image domain, L1 norm in the wavelet domain, and directional total variation between 19 F and 1 H images were compared in order to accelerate 19 F ventilation imaging using retrospectively undersampled data from a healthy volunteer. Using the optimal constrained reconstruction in 8 patients with chronic obstructive pulmonary disease (16-seconds breath-hold), ventilation maps of various acceleration factors (2-fold to 13-fold) were compared with maps of the full data set using the Dice coefficient, difference in volume defect percentage and overlap percentage, as well as hyperpolarized 129 Xe gas MRI. RESULTS: The reconstruction constraining total variation and directional total variation simultaneously performed best in the healthy volunteer (RMS error = 0.07, structural similarity index = 0.77) for a measurement time of 2 seconds. Using the same reconstruction in the patients with chronic obstructive pulmonary disease, the Dice coefficient of defect volumes was 0.86 ± 0.05, the mean difference in volume defect percentage was -1.0 ± 1.7 percentage points, and the overlap percentage was 87% ± 2% for a measurement time of 6 seconds. Between volume defect percentage of 19 F and 129 Xe, a linear correlation (r = 0.75; P = .03) was found, with 19 F volume defect percentage being significantly higher (mean difference = 11%; P = .04). CONCLUSION: 1 H-guided reconstruction of pulmonary 19 F gas MRI enables reduction of acquisition time while maintaining image quality and robustness of functional parameters.

Validation of Automated Perfusion-Weighted Phase-Resolved Functional Lung (PREFUL)-MRI in Patients With Pulmonary Diseases.

BACKGROUND: Perfusion-weighted (Qw) noncontrast-enhanced proton lung MRI is a promising technique for assessment of pulmonary perfusion, but still requires validation. PURPOSE: To improve perfusion-weighted phase-resolved functional lung (PREFUL)-MRI, to validate PREFUL with perfusion single photon emission computed tomography (SPECT) as a gold standard, and to compare PREFUL with dynamic contrast-enhanced (DCE)-MRI as a reference. STUDY TYPE: Retrospective. POPULATION: Twenty patients with chronic obstructive pulmonary disease (COPD), 14 patients with cystic fibrosis (CF), and 21 patients with chronic thromboembolic pulmonary hypertension (CTEPH) were included. FIELD STRENGTH/SEQUENCE: For PREFUL-MRI, a spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories sequence were used at 1.5T. ASSESSMENT: PREFUL-MRI coronal slices were acquired in free-breathing. DCE-MRI was performed in breath-hold with injection of 0.03 mmol/kg bodyweight of gadoteric acid at a rate of 4 cc/s. Perfusion SPECT images were obtained for six CTEPH patients. Images were coregistered. An algorithm to define the appropriate PREFUL perfusion phase was developed using perfusion SPECT data. Perfusion defect percentages (QDP) and Qw-values were calculated for all methods. For PREFUL quantitative perfusion values (PREFULQ ) and for DCE pulmonary blood flow (PBF) was calculated. STATISTICAL TESTS: Obtained parameters were assessed using Pearson correlation and Bland-Altman analysis. RESULTS: Qw-SPECT correlated with Qw-DCE (r = 0.50, P < 0.01) and Qw-PREFUL (r = 0.47, P < 0.01). Spatial overlap of QDP maps showed an agreement ≥67.7% comparing SPECT and DCE, ≥64.1% for SPECT and PREFUL, and ≥60.2% comparing DCE and PREFUL. Significant correlations of Qw-PREFUL and Qw-DCE were found (COPD: r = 0.79, P < 0.01; CF: r = 0.77, P < 0.01; CTEPH: r = 0.73, P < 0.01). PREFULQ /PBF correlations were similar/lower (CF, CTEPH: P > 0.12; COPD: P < 0.01) compared to Qw-PREFUL/DCE correlations. PREFULQ -values were higher/similar compared to PBF-values (COPD, CF: P < 0.01; CTEPH: P = 0.026). DATA CONCLUSION: The automated PREFUL algorithm may allow for noncontrast-enhanced pulmonary perfusion assessment in COPD, CF, and CTEPH patients comparable to DCE-MRI. Level of Evidence 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:103-114.