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.

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.

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.

Alveolar membrane and capillary function in COVID-19 convalescents: insights from chest MRI.

OBJECTIVES: To investigate potential presence and resolution of longer-term pulmonary diffusion limitation and microvascular perfusion impairment in COVID-19 convalescents. MATERIALS AND METHODS: This prospective, longitudinal study was carried out between May 2020 and April 2023. COVID-19 convalescents repeatedly and age/sex-matched healthy controls once underwent MRI including hyperpolarized 129Xe MRI. Blood samples were obtained in COVID-19 convalescents for immunophenotyping. Ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP), and gas phase (GP) as well as lung surface-volume ratio were quantified and correlations with CD4+/CD8+ T cell frequencies were assessed using Pearson's correlation coefficient. Signed-rank tests were used for longitudinal and U tests for group comparisons. RESULTS: Thirty-five participants were recruited. Twenty-three COVID-19 convalescents (age 52.1 ± 19.4 years, 13 men) underwent baseline MRI 12.6 ± 4.2 weeks after symptom onset. Fourteen COVID-19 convalescents underwent follow-up MRI and 12 were included for longitudinal comparison (baseline MRI at 11.5 ± 2.7 weeks and follow-up 38.0 ± 5.5 weeks). Twelve matched controls were included for comparison. In COVID-19 convalescents, RBC-TP was increased at follow-up (p = 0.04). Baseline RBC-TP was lower in patients treated on intensive care unit (p = 0.03) and in patients with severe/critical disease (p = 0.006). RBC-TP correlated with CD4+/CD8+ T cell frequencies (R = 0.61/ - 0.60) at baseline. RBC-TP was not significantly different compared to matched controls at follow-up (p = 0.25). CONCLUSION: Impaired microvascular pulmonary perfusion and alveolar membrane function persisted 12 weeks after symptom onset and resolved within 38 weeks after COVID-19 symptom onset. CLINICAL RELEVANCE STATEMENT: 129Xe MRI shows improvement of microvascular pulmonary perfusion and alveolar membrane function between 11.5 ± 2.7 weeks and 38.0 ± 5.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease. KEY POINTS: • The study aims to investigate long-term effects of COVID-19 on lung function, in particular gas uptake efficiency, and on the cardiovascular system. • In COVID-19 convalescents, the ratio of 129Xe in red blood cells/tissue plasma increased longitudinally (p = 0.04), but was not different from matched controls at follow-up (p = 0.25). • Microvascular pulmonary perfusion and alveolar membrane function are impaired 11.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease at 38.0 weeks.

Photon Counting Computed Tomography with the Radiation Dose of a Chest X-Ray: Feasibility and Diagnostic Yield.

INTRODUCTION: Photon counting (PC) detectors allow a reduction of the radiation dose in CT. Chest X-ray (CXR) is known to have a low sensitivity and specificity for detection of pneumonic infiltrates. The aims were to establish an ultra-low-dose CT (ULD-CT) protocol at a PC-CT with the radiation dose comparable to the dose of a CXR and to evaluate its clinical yield in patients with suspicion of pneumonia. METHODS: A ULD-CT protocol was established with the aim to meet the radiation dose of a CXR. In this retrospective study, all adult patients who received a ULD-CT of the chest with suspected pneumonia were included. Radiation exposure of ULD-CT and CXR was calculated. The clinical significance (new diagnosis, change of therapy, additional findings) and limitations were evaluated by a radiologist and a pulmonologist considering previous CXR and clinical data. RESULTS: Twenty-seven patients (70% male, mean age 68 years) were included. With our ULD-CT protocol, the radiation dose of a CXR could be reached (mean radiation exposure 0.11 mSv). With ULD-CT, the diagnosis changed in 11 patients (41%), there were relevant additional findings in 4 patients (15%), an infiltrate (particularly fungal infiltrate under immunosuppression) could be ruled out with certainty in 10 patients (37%), and the therapy changed in 10 patients (37%). Two patients required an additional CT with contrast medium to rule out a pulmonary embolism or pleural empyema. CONCLUSIONS: With ULD-CT, the radiation dose of a CXR could be reached while the clinical impact is higher with change in diagnosis in 41%.

Doppler-derived pulmonary pulse transit time measurements in chronic obstructive pulmonary disease: Reproducibility and cardiopulmonary function.

INTRODUCTION: Doppler-derived pulmonary pulse transit time (pPTT) is an auspicious hemodynamic marker in chronic pulmonary diseases. The aim is to compare four distinct pPTT measurements and its relation to right cardiac and pulmonary function. METHODS: Prospectively, 25 chronic obstructive pulmonary disease (COPD) patients (four patients excluded) and 32 healthy subjects underwent repeated distinct pPTT measurements, standard echocardiography, and pulmonary function testing on the same day. pPTT was defined as the interval from the R or Q-wave in the electrocardiogram to the corresponding pulse wave Doppler peak late systolic (S) 2 or diastolic (D) pulmonary vein flow velocity (pPTT R-S, Q-S, R-D, Q-D). Reproducibility was assessed using Bland-Altman analysis, coefficient of variation (COV), intraclass correlation coefficient (ICC), and power calculations. Associations with right ventricular RV tissue and pulse wave Doppler velocities (RV E', RV S', RV A', RV E, RV A, RV E/E', RV E/A), TAPSE, right ventricular fractional area change, left ventricular systolic and diastolic function (LV ejection fraction, E, A, E/A, E/E', septal E', lateral E'), LA diameters, as well as forced expiratory volume in 1 s, forced vital capacity (FVC) predicted (%), and in liters were analyzed. RESULTS: There was no significant difference and no bias between pPTT measures (p range: .1-.9). COV was in COPD 1.2%-2.3%, in healthy subjects 1.0%-3.1%. ICC ranged from .92 (COPD) to .96 (healthy subjects). In COPD significant correlations were found for pPTT R-S, Q-S and R-D with RV E`, (all > ρ: .49, < p = .0364), pPTT R-S, Q-S with RV E/E` (both > ρ: .49, < p = .0291), pPTT Q-S with RV S´ (ρ: .58, p = .0134), RV A (ρ: .59, p = .0339) and heart rate > ρ: -.39, < p = .0297). pPTT R-S, R-D showed significant correlations with FVC predicted (%) (ρ: .48 p = .0224) and FVC (l) (ρ:.47 p = .0347). CONCLUSIONS: All pPTT measures exhibited high reproducibility. In COPD patients pPTT measures correlate with diastolic right ventricular function. Defining Q as starting point seems clinically advantageous considering electromechanical desynchrony in patients with conduction disorders.

Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial.

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high risk (>3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening.

Regional Pulmonary Morphology and Function: Photon-counting CT Assessment.

Background Experience with functional CT in the lungs without additional equipment in clinical routine is limited. Purpose To report initial experience and evaluate the robustness of a modified chest CT protocol and photon-counting CT (PCCT) for comprehensive analysis of pulmonary vasculature, perfusion, ventilation, and morphologic structure in a single examination. Materials and Methods In this retrospective study, consecutive patients with clinically indicated CT for various known and unknown pulmonary function impairment (six subgroups) were included between November 2021 and June 2022. After administration of an intravenous contrast agent, inspiratory PCCT was followed by expiratory PCCT after a delay of 5 minutes. Advanced automated postprocessing was performed, and CT-derived functional parameters were calculated (regional ventilation, perfusion, late contrast enhancement, and CT angiography). Mean intravascular contrast enhancement in the mediastinal vessels and radiation dose were determined. Using analysis of variance, the mean values of lung volumes, attenuation, ventilation, perfusion, and late contrast enhancement were tested for differences between subgroups of patients. Results In 166 patients (mean age, 63.2 years ± 14.2 [SD]; 106 male patients), all CT-derived parameters could be acquired (84.7% success rate; 166 of 196 patients). At the inspiratory examination, mean density was 325 HU in the pulmonary trunk, 260 HU in the left atrium, and 252 HU in the ascending aorta. The mean dose-length product for inspiration and expiration was 110.32 mGy · cm and 109.47 mGy · cm, respectively; the mean CT dose index for inspiration and expiration was 3.22 mGy and 3.09 mGy, respectively (less than the mean total radiation dose of 8-12 mGy, which is diagnostic reference level). Significant differences (P < .05) between the subgroups were found for all assessed parameters. Visual inspection allowed for voxelwise assessment of morphologic structure and function. Conclusion The proposed PCCT protocol allowed for a dose-efficient and robust simultaneous evaluation of pulmonary morphologic structure, ventilation, vasculature, and parenchymal perfusion in a procedure requiring advanced software but no additional hardware. © RSNA, 2023.

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.

Fully Integrated Laser Guidance for CT-Based Punctures: A Study in Phantoms and Patients.

PURPOSE: To test the hypothesis of equal or even superior applicability and accuracy of a fully integrated, laser-based computed tomography (CT) navigation system compared with conventional CT guidance for percutaneous interventions. MATERIALS AND METHODS: CT-guided punctures were first performed in phantoms. Four radiologists with different experience levels (2 residents (L.B., C.D.) and 2 board-certified radiologists (B.M., K.R.) performed 48 punctures using both conventional image-guided and laser-guided approaches. Subsequently, 12 punctures were performed in patients during a clinical pilot trial. Phantom targets required an in-plane or a single-/double-angulated, out-of-plane approach. Planning and intervention time, control scan number, radiation exposure, and accuracy of needle placement (measured by deviation of the needle tip to the designated target) were assessed for each guidance technique and compared (Mann-Whitney U test and t test). Patient interventions were additionally analyzed for applicability in a clinical setting. RESULTS: The application of laser guidance software in the phantom study and in 12 human patients in a clinical setting was both technically and clinically feasible in all cases. The mean planning time (P = .009), intervention time (P = .005), control scan number (P < .001), and radiation exposure (P = .013) significantly decreased for laser-navigated punctures compared with those for conventional CT guidance and especially in punctures with out-of-plane-trajectories. The accuracy significantly increased for laser-guided interventions compared with that for conventional CT (P < .001). CONCLUSIONS: Interventional radiologists with differing levels of experience performed faster and more accurate punctures for out-of-plane trajectories in the phantom models, using a new, fully integrated, laser-guided CT software and demonstrated excellent clinical and technical success in initial clinical experiments.

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.

Left Ventricular Wall Reconstruction with Autologous Vascularized Tunica Muscularis of Stomach in a Porcine Pilot Model.

INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. METHODS: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. RESULTS: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. CONCLUSIONS: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications.

Intraarterial embolizations in life-threatening spontaneous retroperitoneal and rectus sheath hemorrhage (SRRSH): a three-center experience.

PURPOSE: To retrospectively evaluate the technical and clinical success of interventional treatments employed in three University medical centers and to develop work-flow recommendations for intra-arterial embolizations in patients with life-threatening spontaneous retroperitoneal and rectus sheath hemorrhage (SRRSH). MATERIALS AND METHODS: Retrospective evaluation of all patients with contrast-enhanced CT and digital subtraction angiography (DSA) for SRRSH from 01/2018 to 12/2022, amounted to 91 interventions in 83 patients (45f, 38m) with a mean age of 68.1 ± 13.2 years. Analysis of the amount of bleeding and embolized vessels, choice of embolization material, technical success, and 30-day mortality was performed. RESULTS: Pre-interventional contrast-enhanced CT demonstrated active contrast extravasation in 79 cases (87%). DSA identified a mean of 1.4 ± 0.88 active bleeds in all but two interventions (98%), consisting of 60 cases with a singular and 39 cases of >1 bleeding artery, which were consecutively embolized. The majority of patients underwent embolization with either n-butyl-2-cyanoacrylate (NBCA; n=38), coils (n=21), or a combination of embolic agents (n=23). While the technical success rate was documented at 97.8%, 25 patients (30%) died within 30 days after the initial procedure, with mortality rates ranging from 25 to 86% between the centers, each following different diagnostic algorithms. CONCLUSION: Embolotherapy is a safe therapy option with high technical success rates in patients with life-threatening SRRSH. To maximize clinical success and survival rates, we propose a standardized approach to angiography as well as a low threshold for re-angiography.

Visual impression and texture analysis of advanced modeled iterative reconstruction (ADMIRE): improved assessment of image quality in CT for better estimation of dose reduction potential.

To evaluate the image quality (IQ) of advanced modeled iterative reconstruction (ADMIRE; Siemens Healthcare, Forchheim, Germany) applying image texture and image visual impression as a supplement to physical parameters such as noise level and spatial resolution. An ACR-phantom with four modules was examined at different radiation dose levels. To characterise the image texture, two Haralick texture parameters, contrast and entropy, were assessed at different dose levels and reconstruction algorithms. The visual impression of images and the low-contrast detectability were evaluated by the structural similarity index (SSIM). The spatial resolution was determined by the modulation transfer functions and the line spread function. The Haralick texture parameters, contrast and entropy, decreased with increasing ADMIRE levels. ADMIRE III, IV and V offered a comparable contrast and entropy to those calculated by filtered back projection (FBP) with a radiation dose reduction up to 50%. SSIM (low-contrast detectability) improved with increasing ADMIRE levels. SSIM calculated by ADMIRE IV and V revealed comparable IQ to FBP with a decreased CTDIvolup to 50%. Spatial resolution was retained up to 90% dose reduction. Compared to FBP at the same dose level, the image noise decreased up to 61% with higher ADMIRE levels (σFBP= 17.3 HU andσADMIREV= 10.6 HU at 6.65 mGy). Taking texture analysis and visual perception into account, a more realistic assessment of the dose reduction potential of ADMIRE can be achieved than quality metrics based alone on physical measurements.

A randomized trial of risk-adapted screening for prostate cancer in young men-Results of the first screening round of the PROBASE trial.

There is no generally accepted screening strategy for prostate cancer (PCa). From February 2014 to December 2019 a randomized trial (PROBASE) recruited 46 642 men at age 45 to determine the efficacy of risk-adapted prostate-specific antigen-based (PSA) screening, starting at either 45 or 50 years. PSA tests are used to classify participants into a low (<1.5 ng/mL), intermediate (1.5-2.99 ng/mL) or high (≥3 ng/mL) risk group. In cases of confirmed PSA values ≥3 ng/mL participants are recommended a prostate biopsy with multiparametric magnetic resonance imaging (mpMRI). Half of the participants (N = 23 341) were offered PSA screening immediately at age 45; the other half (N = 23 301) were offered digital rectal examination (DRE) with delayed PSA screening at age 50. Of 23 301 participants who accepted baseline PSA testing in the immediate screening arm, 89.2% fell into the low, 9.3% into intermediate, and 1.5% (N = 344) into the high risk group. Repeat PSA measurement confirmed high-risk status for 186 men (0.8%), of whom 120 (64.5%) underwent a biopsy. A total of 48 PCas was detected (overall prevalence 0.2%), of which 15 had International Society of Uropathology (ISUP) grade 1, 29 had ISUP 2 and only 4 had ISUP ≥3 cancers. In the delayed screening arm, 23 194 participants were enrolled and 6537 underwent a DRE with 57 suspicious findings, two of which showed PCa (both ISUP 1; detection rate 0.03%). In conclusion, the prevalence of screen-detected aggressive (ISUP ≥3) PCa in 45-year-old men is very low. DRE did not turn out effective for early detection of PCa.

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.

Validation of Phase-Resolved Functional Lung (PREFUL) Magnetic Resonance Imaging Pulse Wave Transit Time Compared to Echocardiography in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) pulmonary pulse wave transit time (pPTT) is a contrast agent free, vascular imaging biomarker, but has not been validated in chronic obstructive pulmonary disease (COPD). PURPOSE: To validate PREFUL with echocardiographic pPTT as a reference standard and to compare arterial/venous pPTT mapping with spirometry and clinical parameters. STUDY TYPE: Prospective. POPULATION: Twenty-one patients (62% female) with COPD and 44 healthy participants (50% female). FIELD STRENGTH/SEQUENCE: 1.5 T; 2D-spoiled gradient-echo sequence. ASSESSMENT: Three coronal PREFUL MRI slices, echocardiography, and spirometry including forced expiratory volume in 1 second (FEV1, liter) and predicted defined as FEV1 in% divided by the population average FEV1%, were performed. Pulmonary pulse transit time from the main artery to the microvasculature (PREFUL pPTT), to the right upper lobe vein (PREFUL pPTTav , echo pPTTav ), from microvasculature to right upper lobe vein (PREFULvein ) and the ratio of PREFUL pPTT to PREFUL pPTTvein were calculated. Body mass index (BMI), Global Initiative for COPD (GOLD) stage 1-4, disease duration, and cigarette packs smoked per day multiplied by the smoked years (pack years) were computed. STATISTICAL TESTS: Shapiro-Wilk-test, paired-two-sided-t-tests, Bland-Altman-analysis, coefficient of variation, Pearson ρ were applied, pPTT data were compared between 21 subjects from the 44 healthy subjects who were age- and sex-matched to the COPD cohort, P < 0.05 was considered statistically significant. RESULTS: PREFUL pPTTav significantly correlated with echo pPTTav (ρ = 0.95) with 1.85 msec bias, 95% limits of agreement: 55.94 msec, -52.23 msec in all participants (P = 0.59). In the healthy participants, PREFUL and echo pPTTav significantly correlated with age (ρ = 0.81, ρ = 0.78), FEV1 (ρ = -0.47, ρ = -0.34) and BMI (ρ = 0.56, ρ = 0.51). In COPD patients, PREFUL pPTT significantly correlated with FEV1 predicted (ρ = -0.59), GOLD (ρ = 0.53), disease duration (ρ = 0.54), and pack years (ρ = 0.49). DATA CONCLUSION: Arteriovenous PTT measured by PREFUL MRI corresponds precisely to echocardiography and appears to be feasible even in severe COPD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.