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.

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.

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.

Evaluation of tissue shrinkage after CT-guided microwave ablation in patients with liver malignancies using Jacobian determinant.

PURPOSE: To assess short-term tissue shrinkage in patients with liver malignancies undergoing computed tomography (CT)-guided microwave ablation (MWA) using Jacobian determinant (JD). MATERIALS AND METHODS: Twenty-nine patients with 29 hepatic malignancies (primary n = 24; metastases n = 5; median tumor diameter 18 mm) referred to CT-guided MWA (single position; 10 min, 100 W) were included in this retrospective IRB-approved study, after exclusion of five patients. Following segmentation of livers and tumors on pre-interventional images, segmentations were registered on post-interventional images. JD mapping was applied to quantify voxelwise tissue volume changes after MWA. Percentual volume changes were evaluated in the ablated tumor, a 5-cm tumor perimeter and in the whole liver and compared in different clinical conditions (tumor entity: primary vs. secondary; tumor location: subcapsular vs. non-subcapsular; tumor volume: >/<6 ml: cirrhosis: yes vs. no; prior chemotherapy: yes vs. no using Shapiro-Wilk, χ2 and Wilcoxon rank sum tests, respectively (with p < 0.05 deemed significant). RESULTS: Tissue volume change was 0.6% in the ablated tumor, 1.6% in the 5-cm perimeter and 0.3% in the whole liver. Shrinkage in the ablated tumor was pronounced in non-subcapsular located tumors, whereas tissue expansion was noted in subcapsular tumors (median -3.5 vs. 1.1%; p = 0.0195). Shrinkage in the whole liver was higher in tumor volumes >6ml, compared with smaller tumors, in which tissue expansion was noted (median -1.0 vs. 2.5%; p = 0.002). Other clinical conditions had no significant influence on the extent of tissue shrinkage (p > 0.05). CONCLUSION: 3D Jacobian analysis shows that hepatic tissue deformation following MWA is most pronounced in a 5-cm area surrounding the treated tumor. Tumor location and tumor volume may have an impact on the extent of tissue shrinkage which may affect estimation of the safety margin.

A dual center and dual vendor comparison study of automated perfusion-weighted phase-resolved functional lung magnetic resonance imaging with dynamic contrast-enhanced magnetic resonance imaging in patients with cystic fibrosis.

For sensitive diagnosis and monitoring of pulmonary disease, ionizing radiation-free imaging methods are of great importance. A noncontrast and free-breathing proton magnetic resonance imaging (MRI) technique for assessment of pulmonary perfusion is phase-resolved functional lung (PREFUL) MRI. Since there is no validation of PREFUL MRI across different centers and scanners, the purpose of this study was to compare perfusion-weighted PREFUL MRI with the well-established dynamic contrast-enhanced (DCE) MRI across two centers on scanners from two different vendors. Sixteen patients with cystic fibrosis (CF) (Center 1: 10 patients; Center 2: 6 patients) underwent PREFUL and DCE MRI at 1.5T in the same imaging session. Normalized perfusion-weighted values and perfusion defect percentage (QDP) values were calculated for the whole lung and three central slices (dorsal, central, ventral of the carina). Obtained parameters were compared using Pearson correlation, Spearman correlation, Bland-Altman analysis, Wilcoxon signed-rank test, and Wilcoxon rank-sum test. Moderate-to-strong correlations between normalized perfusion-weighted PREFUL and DCE values were found (posterior slice: r = 0.69, p < 0.01). Spatial overlap of PREFUL and DCE QDP maps showed an agreement of 79.4% for the whole lung. Further, spatial overlap values of Center 1 were not significantly different to those of Center 2 for the three central slices (p > 0.07). The feasibility of PREFUL MRI across two different centers and two different vendors was shown in patients with CF and obtained results were in agreement with DCE MRI.

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.

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.

Impact of active dose management on radiation exposure and image quality in computed tomography: An observational study in 1315 patients.

PURPOSE: To determine the clinical impact of CT dose management team on radiation exposure and image quality. METHODS: 2026 clinical routine CT examinations of 1315 patients were evaluated retrospectively. A CT dose management team was established as an integral part of the radiological department. It identified 5 CT protocols (A-E), where national reference values were exceeded the most. Those reference values included specifically the mean volumetric CT dose index (CTDIvol) and the mean dose-length product (DLP). Baseline data (period 1) and follow up data (period 2) were obtained after reduction of tube voltage and increase of pitch or noise index. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were calculated to compare image quality. Two-sided t-tests were performed. RESULTS: Mean CTDIvol and mean DLP of the chest protocol (A) decreased after reduction of tube voltage (P < 0.01). In the chest/abdomen/pelvis protocol (B), the increase of noise index resulted in a significant mean CTDIvol decrease (P < 0.02) without statistical significance of mean DLP (P < 0.12). In the abdomen/pelvis protocol (C), mean CTDIvol (P = 0.01) and mean DLP (P < 0.01) were significantly lower after noise index increase. In the staging of hepatocellular carcinoma (D), mean CTDIvol and mean DLP were significantly lower after increase of pitch and noise index (P < 0.01). The lung protocol (E) yielded no significant changes after modulation (P > 0.05). SNR (protocol A) was significantly higher in period 2 (P < 0.04). Protocol D showed significantly lower selected SNR and CNR (P < 0.02). CONCLUSIONS: Establishing an operating dose management team as a standard for good clinical practice helps to considerably reduce CT radiation dose while preserving image quality.

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.

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients.

PURPOSE: In this feasibility study, a phase-resolved functional lung imaging postprocessing method for extraction of dynamic perfusion (Q) and ventilation (V) parameters using a conventional 1H lung MRI Fourier decomposition acquisition is introduced. METHODS: Time series of coronal gradient-echo MR images with a temporal resolution of 288 to 324 ms of two healthy volunteers, one patient with chronic thromboembolic hypertension, one patient with cystic fibrosis, and one patient with chronic obstructive pulmonary disease were acquired at 1.5 T. Using a sine model to estimate cardiac and respiratory phases of each image, all images were sorted to reconstruct full cardiac and respiratory cycles. Time to peak (TTP), V/Q maps, and fractional ventilation flow-volume loops were calculated. RESULTS: For the volunteers, homogenous ventilation and perfusion TTP maps (V-TTP, Q-TTP) were obtained. The chronic thromboembolic hypertension patient showed increased perfusion TTP in hypoperfused regions in visual agreement with dynamic contrast-enhanced MRI, which improved postpulmonary endaterectomy surgery. Cystic fibrosis and chronic obstructive pulmonary disease patients showed a pattern of increased V-TTP and Q-TTP in regions of hypoventilation and decreased perfusion. Fractional ventilation flow-volume loops of the chronic obstructive pulmonary disease patient were smaller in comparison with the healthy volunteer, and showed regional differences in visual agreement with functional small airways disease and emphysema on CT. CONCLUSIONS: This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med 79:2306-2314, 2018. © 2017 International Society for Magnetic Resonance in Medicine.