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Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by obstruction of airways and emphysematous lung tissue damage, with associated hypoxic vasoconstriction in the affected lung parenchyma. In our study, we evaluate the role of oxygen-enhanced (OE) MRI and dynamic contrast enhanced (DCE)-MRI in COPD patients for assessment of ventilation and perfusion defects and compared their severity with clinical severity. A total of 60 patients with COPD (diagnosed based on clinical and spirometry findings) and 2 controls with normal spirometry and no history of COPD were enrolled. All patients underwent MRI within 1 month of spirometry. OE-MRI was performed by administering oxygen at 12 L/min for 4 min to look for ventilation defects. DCE-MRI was performed by injecting intravenous gadolinium contrast, and perfusion abnormalities were detected by subtracting the non-enhanced areas from the first pass perfusion contrast images. A total of 87% of the subjects demonstrated ventilation and perfusion abnormalities on MRI independently. The lobe-wise distribution of ventilation and perfusion abnormalities correlated well with each other and was statistically significant in all lobes (p < 0.05). The severity of ventilation-perfusion defects also correlated well with clinical severity, as their median value (calculated using a Likert rating scale) was significantly lower in patients in the Global initiative for chronic Obstructive Lung Disease (GOLD) I/II group (3.25) compared to the GOLD III/IV group (7.25). OE- and DCE-MRI provide functional information about ventilation-perfusion defects and their regional distribution, which correlates well with clinical severity in patients with COPD.

Background Although MRI is a radiation-free imaging modality, it has historically been limited in lung imaging due to inherent technical restrictions. The aim of this study is to explore the performance of lung MRI in detecting solid and subsolid pulmonary nodules using T1 gradient-echo (GRE) (VIBE, Volumetric interpolated breath-hold examination), ultrashort time echo (UTE) and T2 Fast Spin Echo (HASTE, Half fourier Single-shot Turbo spin-Echo). Methods Patients underwent a lung MRI in a 3 T scanner as part of a prospective research project. A baseline Chest CT was obtained as part of their standard of care. Nodules were identified and measured on the baseline CT and categorized according to their density (solid and subsolid) and size (> 4 mm/ ≤ 4 mm). Nodules seen on the baseline CT were classified as present or absent on the different MRI sequences by two thoracic radiologists independently. Interobserver agreement was determined using the simple Kappa coefficient. Paired differences were compared using nonparametric Mann-Whitney U tests. The McNemar test was used to evaluate paired differences in nodule detection between MRI sequences. Results Thirty-six patients were prospectively enrolled. One hundred forty-nine nodules (100 solid/49 subsolid) with mean size 10.8 mm (SD = 9.4) were included in the analysis. There was substantial interobserver agreement (k = 0.7, p  = 0.05). Detection for all nodules, solid and subsolid nodules was respectively; UTE: 71.8%/71.0%/73.5%; VIBE: 61.6%/65%/55.1%; HASTE 72.4%/72.2%/72.7%. Detection rate was higher for nodules > 4 mm in all groups: UTE 90.2%/93.4%/85.4%, VIBE 78.4%/88.5%/63.4%, HASTE 89.4%/93.8%/83.8%. Detection of lesions ≤4 mm was low for all sequences. UTE and HASTE performed significantly better than VIBE for detection of all nodules and subsolid nodules (diff = 18.4 and 17.6%, p  = < 0.01 and p  = 0.03, respectively). There was no significant difference between UTE and HASTE. There were no significant differences amongst MRI sequences for solid nodules. Conclusions Lung MRI shows adequate performance for the detection of solid and subsolid pulmonary nodules larger than 4 mm and can serve as a promising radiation-free alternative to CT.

Background Hybrid devices that combine radiation therapy and MR-imaging have been introduced in the clinical routine for the treatment of lung cancer. This opened up not only possibilities in terms of accurate tumor tracking, dose delivery and adapted treatment planning, but also functional lung imaging. The aim of this study was to show the feasibility of Non-uniform Fourier Decomposition (NuFD) MRI at a 0.35 T MR-Linac as a potential treatment response assessment tool, and propose two signal normalization strategies for enhancing the reproducibility of the results. Methods Ten healthy volunteers (median age 28 ± 8 years, five female, five male) were repeatedly scanned at a 0.35 T MR-Linac using an optimized 2D+ t balanced steady-state free precession (bSSFP) sequence for two coronal slice positions. Image series were acquired in normal free breathing with breaks inside and outside the scanner as well as deep and shallow breathing. Ventilation- and perfusion-weighted maps were generated for each image series using NuFD. For intra-volunteer ventilation map reproducibility, a normalization factor was defined based on the linear correlation of the ventilation signal and diaphragm position of each scan as well as the diaphragm motion amplitude of a reference scan. This allowed for the correction of signal dependency on the diaphragm motion amplitude, which varies with breathing patterns. The second strategy, which can be used for ventilation and perfusion, eliminates the dependency on the signal amplitude by normalizing the ventilation/perfusion maps with the average ventilation/perfusion signal within a selected region-of-interest (ROI). The position and size dependency of this ROI was analyzed. To evaluate the performance of both approaches, the normalized ventilation/perfusion-weighted maps were compared and the deviation of the mean ventilation/perfusion signal from the reference was calculated for each scan. Wilcoxon signed-rank tests were performed to test whether the normalization methods can significantly improve the reproducibility of the ventilation/perfusion maps. Results The ventilation- and perfusion-weighted maps generated with the NuFD algorithm demonstrated a mostly homogenous distribution of signal intensity as expected for healthy volunteers regardless of the breathing maneuver and slice position. Evaluation of the ROI’s size and position dependency showed small differences in the performance. Applying both normalization strategies improved the reproducibility of the ventilation by reducing the median deviation of all scans to 9.1%, 5.7% and 8.6% for the diaphragm-based, the best and worst performing ROI-based normalization, respectively, compared to 29.5% for the non-normalized scans. The significance of this improvement was confirmed by the Wilcoxon signed rank test with p < 0.01 at α = 0.05 . A comparison of the techniques against each other revealed a significant difference in the performance between best ROI-based normalization and worst ROI ( p = 0.01 ) and between best ROI-based normalization and scaling factor ( p = 0.02 ), but not between scaling factor and worst ROI ( p = 0.71 ). Using the ROI-based approach for the perfusion-maps, the uncorrected deviation of 10.2% was reduced to 5.3%, which was shown to be significant ( p < 0.01 ). Conclusions Using NuFD for non-contrast enhanced functional lung MRI at a 0.35 T MR-Linac is feasible and produces plausible ventilation- and perfusion-weighted maps for volunteers without history of chronic pulmonary diseases utilizing different breathing patterns. The reproducibility of the results in repeated scans significantly benefits from the introduction of the two normalization strategies, making NuFD a potential candidate for fast and robust early treatment response assessment of lung cancer patients during MR-guided radiotherapy.

Compared with hyperpolarized noble gas MRI, oxygen-enhanced lung imaging is a cost-effective approach to investigate lung function. In this study, we investigated the feasibility of free-breathing phase-resolved oxygen-enhanced pulmonary MRI based on a 3D stack-of-stars ultra-short echo time (UTE) sequence. We conducted both computer simulation and in vivo experiments and calculated percent signal enhancement maps of four different respiratory phases on four healthy volunteers from the end of expiration to the end of inspiration. The phantom experiment was implemented to verify simulation results. The respiratory phase was segmented based on the extracted respiratory signal and sliding window reconstruction, providing phase-resolved pulmonary MRI. Demons registration algorithm was applied to compensate for respiratory motion. The mean percent signal enhancement of the average phase increases from anterior to posterior region, matching previous literature. More details of pulmonary tissues were observed on post-oxygen inhalation images through the phase-resolved technique. Phase-resolved UTE pulmonary MRI shows the potential as a valuable method for oxygen-enhanced MRI that enables the investigation of lung ventilation on middle states of the respiratory cycle.

We investigated the association of T1/T2 mapping values with programmed death-ligand 1 protein (PD-L1) expression in lung cancer and their potential in distinguishing between different histological subtypes of non-small cell lung cancers (NSCLCs). Thirty-five patients diagnosed with stage III NSCLC from April 2021 to December 2022 were included. Conventional MRI sequences were acquired with a 1.5 T system. Mean T1 and T2 mapping values were computed for six manually traced ROIs on different areas of the tumor. Data were analyzed through RStudio. Correlation between T1/T2 mapping values and PD-L1 expression was studied with a Wilcoxon–Mann–Whitney test. A Kruskal–Wallis test with a post-hoc Dunn test was used to study the correlation between T1/T2 mapping values and the histological subtypes: squamocellular carcinoma (SCC), adenocarcinoma (ADK), and poorly differentiated NSCLC (PD). There was no statistically significant correlation between T1/T2 mapping values and PD-L1 expression in NSCLC. We found statistically significant differences in T1 mapping values between ADK and SCC for the periphery ROI (p-value 0.004), the core ROI (p-value 0.01), and the whole tumor ROI (p-value 0.02). No differences were found concerning the PD NSCLCs.

The patterns of idiopathic pulmonary fibrosis (IPF) lung disease that directly correspond to elevated hyperpolarised gas diffusion-weighted (DW) MRI metrics are currently unknown. This study aims to develop a spatial co-registration framework for a voxel-wise comparison of hyperpolarised gas DW-MRI and CALIPER quantitative CT patterns. Sixteen IPF patients underwent 3He DW-MRI and CT at baseline, and eleven patients had a 1-year follow-up DW-MRI. Six healthy volunteers underwent 129Xe DW-MRI at baseline only. Moreover, 3He DW-MRI was indirectly co-registered to CT via spatially aligned 3He ventilation and structural 1H MRI. A voxel-wise comparison of the overlapping 3He apparent diffusion coefficient (ADC) and mean acinar dimension (LmD) maps with CALIPER CT patterns was performed at baseline and after 1 year. The abnormal lung percentage classified with the LmD value, based on a healthy volunteer 129Xe LmD, and CALIPER was compared with a Bland–Altman analysis. The largest DW-MRI metrics were found in the regions classified as honeycombing, and longitudinal DW-MRI changes were observed in the baseline-classified reticular changes and ground-glass opacities regions. A mean bias of −15.3% (95% interval −56.8% to 26.2%) towards CALIPER was observed for the abnormal lung percentage. This suggests DW-MRI may detect microstructural changes in areas of the lung that are determined visibly and quantitatively normal by CT.

Oxygen-enhanced magnetic resonance imaging (OE-MRI) enables non-invasive assessment of lung function by measuring longitudinal relaxation time (T1) changes induced by alternating inhalation of room air and pure oxygen. In this study, the pulmonary T1 and its reduction after breathing pure oxygen were quantified by using the free-breathing three-dimensional (3D) Look-Locker technique based on a stack-of-stars acquisition scheme. This method applied a continuous acquisition model to collect signals during both room-air and pure oxygen conditions without the need for breath-holding or respiratory gating. Comparative evaluations were conducted between the proposed 3D Look-Locker method and the conventional two-dimensional (2D) Look-Locker approach, using both phantom and in vivo experiments. The results demonstrate that the 3D technique yields more pronounced and reproducible T1 reductions between air and oxygen conditions compared to the 2D method. Additionally, the T1 of the average respiratory phase obtained by the 3D approach was compared with the T1 at end-expiration and end-inspiration measured by the 2D approach. A consistent decline in T1 across respiratory phases was demonstrated, from end-expiration to end-inspiration, as well as the average respiratory phase under free-breathing. These findings suggest that the proposed OE-MRI T1 measurement based on the 3D Look-Locker method provides a robust and clinically feasible approach for quantitative lung imaging.

Stroke patients are prone to life-threatening bacterial pneumonia. Previous experimental stroke studies have demonstrated that preventive antibiotic treatment (PAT) improves outcome compared with placebo treatment, which however does not model the clinical setting properly. Here we investigate whether PAT is superior to the current clinical ‘gold standard’ for treating poststroke infections. Therefore, we modeled stroke care according to the current stroke guidelines recommending early antibiotic treatment after diagnosing infections. To reliably diagnose pneumonia in living mice, we established a general health score and a magnetic resonance imaging protocol for radiologic confirmation. Compared with standard treatment after diagnosis by these methods, PAT not only abolished pneumonia successfully but also improved general medical outcome. Both, preventive and standard antibiotic treatment using enrofloxacin improved survival in a similar way compared with placebo treatment. However, in contrast to standard treatment, only PAT improved functional outcome assessed by gait analysis. In conclusion, standard and preventive treatment approach reduced poststroke mortality, however at the cost of a worse neurologic outcome compared with preventive approach. These data support the concept of PAT for treating patients at risk for poststroke infections and warrant phase III trials to prove this concept in clinical setting.

Computed tomography (CT) lung nodule assessment is routinely performed and appears very promising for lung cancer screening. However, the radiation exposure through time remains a concern. With the overall goal of an optimal management of indeterminate lung nodules, the objective of this prospective study was therefore to evaluate the potential of optimized ultra-short echo time (UTE) MRI for lung nodule detection and volumetric assessment. Eight (54.9 ± 13.2 years) patients with at least 1 non-calcified nodule ≥4 mm were included. UTE under high-frequency non-invasive ventilation (UTE-HF-NIV) and in free-breathing at tidal volume (UTE-FB) were investigated along with volumetric interpolated breath-hold examination at full inspiration (VIBE-BH). Three experienced readers assessed the detection rate of nodules ≥4 mm and ≥6 mm, and reported their location, 2D-measurements and solid/subsolid nature. Volumes were measured by two experienced readers. Subsequently, two readers assessed the detection and volume measurements of lung nodules ≥4mm in gold-standard CT images with soft and lung kernel reconstructions. Volumetry was performed with lesion management software (Carestream, Rochester, New York, USA). UTE-HF-NIV provided the highest detection rate for nodules ≥4 mm ( = 66) and ≥6 mm ( = 32) (35 and 50%, respectively). No dependencies were found between nodule detection and their location in the lung with UTE-HF-NIV ( > 0.4), such a dependency was observed for two readers with VIBE-BH ( = 0.002 and 0.03). Dependencies between the nodule's detection and their size were noticed among readers and techniques ( < 0.02). When comparing nodule volume measurements, an excellent concordance was observed between CT and UTE-HF-NIV, with an overestimation of 13.2% by UTE-HF-NIV, <25%-threshold used for nodule's growth, conversely to VIBE-BH that overestimated the nodule volume by 28.8%. UTE-HF-NIV is not ready to replace low-dose CT for lung nodule detection, but could be used for follow-up studies, alternating with CT, based on its volumetric accuracy.

Validation of functional free-breathing MRI involves a comparison to more established or more direct measurements. This procedure is cost-intensive, as it requires access to patient cohorts, lengthy protocols, expenses for consumables, and binds working time. Therefore, the purpose of this study is to introduce a synthetic lung model (ASYLUM), which mimics dynamic MRI acquisition and includes predefined lung abnormalities for an alternative validation approach. The model is evaluated with different registration and quantification methods and compared with real data. A combination of trigonometric functions, deformation fields, and signal combinations were used to create 20 synthetic image time series. Lung voxels were assigned either to normal or one of six abnormality classes. The images were registered with three registration algorithms. The registered images were further analyzed with three quantification methods: deformation-based or signal-based regional ventilation (JVent/RVent) analysis and perfusion amplitude (QA). The registration results were compared with predefined deformations. Quantification methods were evaluated regarding predefined amplitudes and with respect to sensitivity, specificity, and spatial overlap of defects. In addition, 36 patients with chronic obstructive pulmonary disease were included for verification of model interpretations using CT as the gold standard. One registration method showed considerably lower quality results (76% correlation vs. 92/97%,  ≤ 0.0001). Most ventilation defects were correctly detected with RVent and QA (e.g., one registration variant with sensitivity ≥78%, specificity ≥88). Contrary to this, JVent showed very low sensitivity for lower lung quadrants (0-16%) and also very low specificity (1-29%) for upper lung quadrants. Similar patterns of defect detection differences between RVent and JVent were also observable in patient data: Firstly, RVent was more aligned with CT than JVent for all quadrants (  ≤ 0.01) except for one registration variant in the lower left region. Secondly, stronger differences in overlap were observed for the upper quadrants, suggesting a defect bias in the JVent measurements in the upper lung regions. The feasibility of a validation framework for free-breathing functional lung imaging using synthetic time series was demonstrated. Evaluating different ventilation measurements, important differences were detected in synthetic and real data, with signal-based regional ventilation assessment being a more reliable method in the investigated setting.