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.

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.

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.

Compartment-specific 129Xe HyperCEST z spectroscopy and chemical shift imaging of cucurbit[6]uril in spontaneously breathing rats.

129Xe hyperpolarized gas chemical exchange saturation transfer (HyperCEST) MRI has been suggested as molecular imaging modality but translation to in vivo imaging has been slow, likely due to difficulties of synthesizing suitable molecules. Cucurbit[6]uril-either in readily available non-functionalized or potentially in functionalized form-may, combined with 129Xe HyperCEST MRI, prove useful as a switchable 129Xe MR contrast agent but the likely differential properties of contrast generation in individual chemical compartments as well as the influence of 129Xe signal drifts encountered in vivo on HyperCEST MRI are unknown. Here, HyperCEST z spectroscopy and chemical shift imaging with compartment-specific analysis are performed in a total of 10 rats using cucurbit[6]uril injected i.v. and under a protocol employing spontaneous respiration. Differences in intensity of the HyperCEST effect between chemical compartments and anatomical regions are investigated. Strategies to mitigate influence of signal instabilities associated with drifts in physiological parameters are developed. It is shown that presence of cucurbit[6]uril can be readily detected under spontaneous 129Xe inhalation mostly in aqueous tissues further away from the lung. Differences of effect intensity in individual regions and compartments must be considered in HyperCEST data interpretation. In particular, there seems to be almost no effect in lipids. 129Xe HyperCEST MR measurements utilizing spontaneous respiration protocols and extended measurement times are feasible. HyperCEST MRI of non-functionalized cucurbit[6]uril may create contrast between anatomical structures in vivo.

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.

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.

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

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

Regional investigation of lung function and microstructure parameters by localized 129 Xe chemical shift saturation recovery and dissolved-phase imaging: A reproducibility study.

PURPOSE: To evaluate the reproducibility and regional variation of parameters obtained from localized 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to compare the results to 129 Xe dissolved-phase MR imaging. METHODS: Thirteen healthy volunteers and 10 COPD patients were scanned twice using 129 Xe dissolved-phase imaging, CSSR, and ventilation imaging sequences. A 16-channel phased-array coil in combination with the regularized spectral localization achieved by sensitivity heterogeneity (SPLASH) method was used to perform a regional analysis of CSSR data. Lung function and microstructural parameters were obtained using Patz model functions and their reproducibility was assessed. RESULTS: The Patz model alveolar wall thickness parameter shows good reproducibility on a regional basis with a median coefficient of variation of 6.5% in healthy volunteers and 12.4% in COPD patients. Significant regional differences of lung function parameters derived from localized CSSR were found in healthy volunteers and correlations with spirometric indices were found. CONCLUSION: Localized 129 Xe CSSR provides reproducible estimates of alveolar wall thickness and is able to detect regional differences of lung microstructure.

Hyperpolarized gas MRI in pulmonology.

Lung diseases have a high prevalence amongst the world population and their early diagnosis has been pointed out to be key for successful treatment. However, there is still a lack of non-invasive examination methods with sensitivity to early, local deterioration of lung function. Proton-based lung MRI is particularly challenging due to short T2* times and low proton density within the lung tissue. Hyperpolarized gas MRI is aan emerging technology providing a richness of methodologies which overcome the aforementioned problems. Unlike proton-based MRI, lung MRI of hyperpolarized gases may rely on imaging of spins in the lung's gas spaces or inside the lung tissue and thereby add substantial value and diagnostic potential to lung MRI. This review article gives an introduction to the MR physics of hyperpolarized media and presents the current state of hyperpolarized gas MRI of 3Headvasd and 129Xe in pulmonology. Key applications, ranging from static and dynamic ventilation imaging as well as oxygen-pressure mapping to 129Xe dissolved-phase imaging and spectroscopy are presented. Hyperpolarized gas MRI is compared to alternative examination methods based on MRI and future directions of hyperpolarized gas MRI are discussed.