Estimation of Cerebral Blood Flow Using the Pulse Wave Amplitude in Brain MRI.

RATIONALE AND OBJECTIVES: First, to test the feasibility of cerebral blood flow (CBF) estimation using the pulse wave amplitude in flow-related enhancement (FREE) brain MRI in comparison to pseudo-continuous arterial spin labeling (pCASL-MRI). Second, the potential for acceleration was evaluated retrospectively. MATERIALS AND METHODS: 24 healthy study participants between 20 and 61 years had cerebral MRI. Perfusion imaging was performed with a balanced steady-state free precession sequence for FREE-MRI and with pCASL-MRI for comparison. RESULTS: The value distribution of the estimated CBF showed a high overlap in the histogram between 0 and 20 mL/100 g/min. However, disparity of the values occurred with more values between 20 and 60 mL/100 g/min using pCASL-MRI and more high values > 60 mL/100 g/min applying FREE-MRI. A Kolmogorov-Smirnov test confirmed a differing probability distribution (P = 0.62). The approximated CBF from FREE-MRI remained stable until only 50% of the acquired data was used. Values from using 40% of the data increased significantly compared to 90% or more (P ≤ 0.05). Values within the white matter presented no significant change after data reduction. The global and voxel-wise correlation coefficients towards pCASL-MRI presented stability during data reduction of FREE-MRI. CONCLUSION: In conclusion, the proposed technique allows a rough approximation of the CBF compared to pCASL-MRI. Further sequence optimization must be achieved to improve the measurement of relatively lowly perfused tissues. Nevertheless, it offers large potential for imaging speed optimization and enables perfusion-weighted images similarly to the color Doppler mode in ultrasound.

PREFUL MRI for Monitoring Perfusion and Ventilation Changes after Elexacaftor-Tezacaftor-Ivacaftor Therapy for Cystic Fibrosis: A Feasibility Study.

Purpose To assess the feasibility of monitoring the effects of elexacaftor-tezacaftor-ivacaftor (ETI) therapy on lung ventilation and perfusion in people with cystic fibrosis (CF), using phase-resolved functional lung (PREFUL) MRI. Materials and Methods This secondary analysis of a multicenter prospective study was carried out between August 2020 and March 2021 and included participants 12 years or older with CF who underwent PREFUL MRI, spirometry, sweat chloride test, and lung clearance index assessment before and 8-16 weeks after ETI therapy. For PREFUL-derived ventilation and perfusion parameter extraction, two-dimensional coronal dynamic gradient-echo MR images were evaluated with an automated quantitative pipeline. T1- and T2-weighted MR images and PREFUL perfusion maps were visually assessed for semiquantitative Eichinger scores. Wilcoxon signed rank test compared clinical parameters and PREFUL values before and after ETI therapy. Correlation of parameters was calculated as Spearman ρ correlation coefficient. Results Twenty-three participants (median age, 18 years [IQR: 14-24.5 years]; 13 female) were included. Quantitative PREFUL parameters, Eichinger score, and clinical parameters (lung clearance index = 21) showed significant improvement after ETI therapy. Ventilation defect percentage of regional ventilation decreased from 18% (IQR: 14%-25%) to 9% (IQR: 6%-17%) (P = .003) and perfusion defect percentage from 26% (IQR: 18%-36%) to 19% (IQR: 13%-24%) (P = .002). Areas of matching normal (healthy) ventilation and perfusion increased from 52% (IQR: 47%-68%) to 73% (IQR: 61%-83%). Visually assessed perfusion scores did not correlate with PREFUL perfusion (P = .11) nor with ventilation-perfusion match values (P = .38). Conclusion The study demonstrates the feasibility of PREFUL MRI for semiautomated quantitative assessment of perfusion and ventilation changes in response to ETI therapy in people with CF. Keywords: Pediatrics, MR-Functional Imaging, Pulmonary, Lung, Comparative Studies, Cystic Fibrosis, Elexacaftor-Tezacaftor-Ivacaftor Therapy, Fourier Decomposition, PREFUL, Free-Breathing Proton MRI, Pulmonary MRI, Perfusion, Functional MRI, CFTR, Modulator Therapy, Kaftrio Clinical trial registration no. NCT04732910 Supplemental material is available for this article. © RSNA, 2024.

Feasibility, Repeatability, and Correlation to Lung Function of Phase-Resolved Functional Lung (PREFUL) MRI-derived Pulmonary Artery Pulse Wave Velocity Measurements.

BACKGROUND: Pulse wave velocity (PWV) in the pulmonary arteries (PA) is a marker of vascular stiffening. Currently, only phase-contrast (PC) MRI-based options exist to measure PA-PWV. PURPOSE: To test feasibility, repeatability, and correlation to clinical data of Phase-Resolved Functional Lung (PREFUL) MRI-based calculation of PA-PWV. STUDY TYPE: Retrospective. SUBJECTS: 79 (26 female) healthy subjects (age range 19-78), 58 (24 female) patients with chronic obstructive pulmonary disease (COPD, age range 40-77), 60 (33 female) patients with suspected pulmonary hypertension (PH, age range 28-85). SEQUENCE: 2D spoiled gradient echo, 1.5T. ASSESSMENT: PA-PWV was measured from PREFUL-derived cardiac cycles based on the determination of temporal and spatial distance between lung vasculature voxels using a simplified (sPWV) method and a more comprehensive (cPWV) method including more elaborate distance calculation. For 135 individuals, PC MRI-based PWV (PWV-QA) was measured. STATISTICAL TESTS: Intraclass-correlation-coefficient (ICC) and coefficient of variation (CoV) were used to test repeatability. Nonparametric tests were used to compare cohorts. Correlation of sPWV/cPWV, PWV-QA, forced expiratory volume in 1 sec (FEV1 ) %predicted, residual volume (RV) %predicted, age, and right heart catheterization (RHC) data were tested. Significance level α = 0.05 was used. RESULTS: sPWV and cPWV showed no significant differences between repeated measurements (P-range 0.10-0.92). CoV was generally lower than 15%. COPD and PH patients had significantly higher sPWV and cPWV than healthy subjects. Significant correlation was found between sPWV or cPWV and FEV1 %pred. (R = -0.36 and R = -0.44), but not with RHC (P-range -0.11 - 0.91) or age (P-range 0.23-0.89). Correlation to RV%pred. was significant for cPWV (R = 0.42) but not for sPWV (R = 0.34, P = 0.055). For all cohorts, sPWV and cPWV were significantly correlated with PWV-QA (R = -0.41 and R = 0.48). DATA CONCLUSION: PREFUL-derived PWV is feasible and repeatable. PWV is increased in COPD and PH patients and correlates to airway obstruction and hyperinflation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

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.

Cerebral microcirculatory pulse wave propagation and pulse wave amplitude mapping in retrospectively gated MRI.

To analyze cerebral arteriovenous pulse propagation and to generate phase-resolved pulse amplitude maps from a fast gradient-echo sequence offering flow-related enhancement (FREE). Brain MRI was performed using a balanced steady-state free precession sequence at 3T followed by retrospective k-space gating. The time interval of the pulse wave between anterior-, middle- and posterior cerebral artery territories and the superior sagittal sinus were calculated and compared between and older and younger groups within 24 healthy volunteers. Pulse amplitude maps were generated and compared to pseudo-Continuous Arterial Spin Labeling (pCASL) MRI maps by voxel-wise Pearson correlation, Sørensen-Dice maps and in regards to signal contrast. The arteriovenous delays between all vascular territories and the superior sagittal sinus were significantly shorter in the older age group (11 individuals, ≥ 31 years) ranging between 169 ± 112 and 246 ± 299 ms versus 286 ± 244 to 419 ± 299 ms in the younger age group (13 individuals) (P ≤ 0.04). The voxel-wise pulse wave amplitude values and perfusion-weighted pCASL values correlated significantly (Pearson-r = 0.33, P < 0.01). Mean Dice overlaps of high (gray) and low (white matter) regions were 73 ± 3% and 59 ± 5%. No differences in image contrast were seen in the whole brain and the white matter, but significantly higher mean contrast of 0.73 ± 0.23% in cortical gray matter in FREE-MRI compared to 0.52 ± 0.12% in pCASL-MRI (P = 0.01). The dynamic information of flow-related enhancement allows analysis of the cerebral pulse wave propagation potentially providing information about the (micro)circulation on a regional level. However, the pulse wave amplitude reveals weaknesses in comparison to true perfusion-weighting and could rather be used to calculate a pulsatility index.

Incidental pulmonary nodules - current guidelines and management. / Inzidentelle Lungenrundherde ­ aktuelle Leitlinien und Management.

BACKGROUND: Due to the greater use of high-resolution cross-sectional imaging, the number of incidental pulmonary nodules detected each year is increasing. Although the vast majority of incidental pulmonary nodules are benign, many early lung carcinomas could be diagnosed with consistent follow-up. However, for a variety of reasons, the existing recommendations are often not implemented correctly. Therefore, potential for improvement with respect to competence, communication, structure, and process is described. METHODS: This article presents the recommendations for incidental pulmonary nodules from the current S3 guideline for lung cancer (July 2023). The internationally established recommendations (BTS guidelines and Fleischner criteria) are compared and further studies on optimized management were included after a systematic literature search in PubMed. RESULTS AND CONCLUSION: In particular, AI-based software solutions are promising, as they can be used in a support capacity on several levels at once and can lead to simpler and more automated management. However, to be applicable in routine clinical practice, software must fit well into the radiology workflow and be integrated. In addition, "Lung Nodule Management" programs or clinics that follow a high-quality procedure for patients with incidental lung nodules or nodules detected by screening have been established in the USA. Similar structures might also be implemented in Germany in a future screening program in which patients with incidental pulmonary nodules could be included. KEY POINTS: · Incidental pulmonary nodules are common but are often not adequately managed. · The updated S3 guideline for lung cancer now includes recommendations for incidental pulmonary nodules. · Competence, communication, structure, and process levels offer significant potential for improvement. CITATION FORMAT: · Glandorf J, Vogel-Claussen J, . Incidental pulmonary nodules - current guidelines and management. Fortschr Röntgenstr 2023; DOI: 10.1055/a-2185-8714.

Influence of gadolinium, field-strength and sequence type on quantified perfusion values in phase-resolved functional lung MRI.

PURPOSE: The purpose of this study is to evaluate the influences of gadolinium-based contrast agents, field-strength and different sequences on perfusion quantification in Phase-Resolved Functional Lung (PREFUL) MRI. MATERIALS AND METHODS: Four cohorts of different subjects were imaged to analyze influences on the quantified perfusion maps: 1) at baseline and after 2 weeks to obtain the reproducibility (26 COPD patients), 2) before and after the administration of gadobutrol (11 COPD, 2 PAH and 1 asthma), 3) at 1.5T and 3T (12 healthy, 4 CF), and 4) with different acquisition sequences spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) (11 COPD, 7 healthy). Wilcoxon-signed rank test, Bland-Altman plots, voxelwise Pearson correlations, normalized histogram analyses with skewness and kurtosis and two-sample Kolmogorov-Smirnov tests were performed. P value ≤ 0.05 was considered statistically significant. RESULTS: In all cohorts, linear correlations of the perfusion values were significant with correlation coefficients of at least 0.7 considering the entire lung (P<0.01). The reproducibility cohort revealed stable results with a similar distribution. In the gadolinium cohort, the quantified perfusion increased significantly (P<0.01), and no significant change was detected in the histogram analysis. In the field-strength cohort, no significant change of the quantified perfusion was shown, but a significant increase of skewness and kurtosis at 3T (P = 0.01). In the sequence cohort, the quantified perfusion decreased significantly in the bSSFP sequence (P<0.01) together with a significant decrease of skewness and kurtosis (P = 0.02). The field-strength and sequence cohorts had differing probability distribution in the two-sample Kolmogorov-Smirnov tests. CONCLUSION: We observed a high susceptibility of perfusion quantification to gadolinium, field-strength or MRI sequence leading to distortion and deviation of the perfusion values. Future multicenter studies should strictly adhere to the identical study protocols to generate comparable results.

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.

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.

Free-breathing 3D Stack-of-Stars Gradient Echo Sequence in MR-guided Percutaneous Liver Interventions: Evaluation of Workflow and Diagnostic Quality.

PURPOSE: To evaluate workflow efficiency and diagnostic quality of a free-breathing 3D stack-of-stars gradient echo (Radial GRE) sequence compared to a breath-hold 3D Cartesian gradient echo (Cartesian GRE) sequence for needle position control in MR-guided liver interventions. MATERIALS AND METHODS: 12 MR-guided liver interventions were performed on a 1.5 T Siemens Aera and analyzed retrospectively. 15 series of the Radial GRE sequence were compared to 14 series of the Cartesian GRE sequence regarding the time interval between two consecutive live-scans for needle tracking (Tracking-2-Tracking-Time). The quality of both sequences was compared by the SNR within comparable slices in liver and tumor ROIs. The CNR was calculated by subtraction of the SNR values. Subjective image quality scores of three radiologists were assessed and inter-rater reliability was tested by Fleiss' kappa. Values are given as mean ± SD. P-values < 0.05 were considered as significant. RESULTS: The median Tracking-2-Tracking-Time was significantly shorter for the Radial GRE sequence, 185 ± 42 s vs. 212 ± 142 s (p = 0.04) and the median SNR of the liver and tumor ROIs were significantly higher in the Radial GRE sequence, 249 ± 92 vs. 109 ± 67 (p = 0.03) and 165 ± 74 vs. 77 ± 43 (p = 0.02). CNR between tumor and liver ROIs showed a tendency to be higher for the Radial GRE sequence without significance, 68 ± 48 vs. 49 ± 32 (p = 0.28). Mean subjective image quality was 3.33 ± 1.08 vs. 2.62 ± 0.95 comparing Radial and Cartesian GRE with a Fleiss' kappa of 0.39 representing fair inter-rater reliability. CONCLUSION: A free-breathing 3D stack-of-stars gradient echo sequence can simplify the workflow and reduce intervention time, while providing superior image quality. Under local anesthesia, it increases patient comfort and reduces potential risks for needle dislocations in MR-guided liver interventions by avoiding respiratory arrests for needle position control.

[Bronchial carcinoma: metastatic pathways with involvement of hilar and mediastinal lymph nodes]. / Bronchialkarzinom: Metastasierungspfade und Involvierung hilärer und mediastinaler Lymphknoten.

SIGNIFICANCE OF LUNG CANCER: Lung cancer has enormous socioeconomical impact on our society due to its high prevalence and mortality. About 59,700 new cases of lung cancer were forecasted for 2022. TNM SCHEME FOR STAGING: Correct staging is the basis for therapy planning, prognosis estimation, and future analyses. Staging is performed using the TNM scheme from the Union for International Cancer Control (UICC). Involvement of lymph nodes is used to differentiate between stage IIB and IIIC. LYMPH NODE LEVELS FOR LUNG CANCER: Knowledge of the intrathoracic lymph node levels is crucial for the exact classification and its involvement has direct implications on therapy. The International Association for the Study of Lung Cancer (IASLC) proposed a unified lymph node map with exact anatomic definitions, which is recommended by the German national lung cancer guideline. The extent of lymph node involvement is stratified into N0-N3. Different metastatic paths are known depending on the location of the primary tumor, but the burden of disease has a greater influence on survival, than the location of metastases. ASSESSING THE SPREAD OF LUNG CANCER: Computed tomography can assess operability of the primary tumor safely in most cases. Invasive procedures to confirm the diagnosis by sampling tissue should be performed after noninvasive diagnostics. PRACTICAL RECOMMENDATION: Systematic lymph node dissection for all patients with non-small cell lung cancer intended for curative resection is recommended in the current German national guideline for lung cancer.

Feasibility of flow-related enhancement brain perfusion MRI.

PURPOSE: Brain perfusion imaging is of enormous importance for various neurological diseases. Fast gradient-echo sequences offering flow-related enhancement (FREE) could present a basis to generate perfusion-weighted maps. In this study, we obtained perfusion-weighted maps without contrast media by a previously described postprocessing algorithm from the field of functional lung MRI. At first, the perfusion signal was analyzed in fast low-angle shot (FLASH) and balanced steady-state free precession (bSSFP) sequences. Secondly, perfusion maps were compared to pseudo-continuous arterial spin labeling (pCASL) MRI in a healthy cohort. Thirdly, the feasibility of the new technique was demonstrated in a small selected group of patients with metastases and acute stroke. METHODS: One participant was examined with bSSFP and FLASH sequences at 1.5T and 3T, different flip angles and slice thicknesses. Twenty-five volunteers had bSSFP imaging and pCASL MRI. Three patients with cerebral metastases and one with acute ischemic stroke had bSSFP imaging and were compared to T1 post-contrast images and CT perfusion. Frequency analyses, SNR and perfusion contrast were compared at different flip angles and slice thicknesses. Regional correlations and Sorensen-Dice overlap were calculated in the healthy cohort. Dice overlap of the pathologies in the patient cohort were calculated. RESULTS: The bSSFP sequence presented detectable perfusion signal within brain vessel and parenchyma together with superior SNR compared to FLASH. Perfusion contrast and its corticomedullary differentiation increased with flip angle. Mean regional correlation was 0.36 and highly significant between FREE maps and pCASL and grey and white matter Dice match were 72% and 60% in the healthy cohort. Pathologies presented good overlap between FREE perfusion-weighted and T1 post-contrast images. CONCLUSION: The feasibility of FREE brain perfusion imaging has been shown in a healthy cohort and selected patient cases with brain metastases and acute stroke. The study demonstrates a new approach for non-contrast brain perfusion imaging.

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.

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 .

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.

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.

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

PURPOSE: The 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. METHODS: Data 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. RESULTS: RVent, 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. CONCLUSION: Significant 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.

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.