Impact of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Children with Cystic Fibrosis and One or Two F508del Alleles.

BACKGROUND: We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children with CF and one or two F508del alleles aged 6 to 11 years. METHODS: This prospective, observational, multicenter, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and three months after initiation of ETI. RESULTS: A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the LCI in F/MF children (-1.0; IQR, -2.0 to -0.1; p<0.01) and F/F children (-0.8; IQR, -1.9 to -0.2; p<0.001) from 3 months onwards. Further, ETI improved the MRI global score in F/MF (-4.0; IQR, -9.0 to 0.0; p<0.01) and F/F children (-3.5; IQR, -7.3 to -0.8; p<0.001). CONCLUSIONS: ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one F508del alleles in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF.

Navigator-based motion compensation for liver BOLD measurement with five-echo SAGE EPI and breath-hold task.

PURPOSE: The purpose of this work is to apply multi-echo spin- and gradient-echo (SAGE) echo-planar imaging (EPI) combined with a navigator-based (NAV) prospective motion compensation method for a quantitative liver blood oxygen level dependent (BOLD) measurement with a breath-hold (BH) task. METHODS: A five-echo SAGE sequence was developed to quantitatively measure T2 and T2* to depict function with sufficient signal-to-noise ratio, spatial resolution and sensitivity to BOLD changes induced by the BH task. To account for respiratory motion, a navigator was employed in the form of a single gradient-echo projection readout, located at the diaphragm along the inferior-superior direction. Prior to each transverse imaging slice of the spin-echo EPI-based readouts, navigator acquisition and fat suppression were incorporated. Motion data was obtained from the navigator and transmitted back to the sequence, allowing real-time adjustments to slice positioning. Six healthy volunteers and three patients with liver carcinoma were included in this study. Quantitative T2 and T2* were calculated at each time point of the BH task. Parameters of t value from first-level analysis using a general linear model and hepatovascular reactivity (HVR) of Echo1, T2 and T2* were calculated. RESULTS: The motion caused by respiratory activity was successfully compensated using the navigator signal. The average changes of T2 and T2* during breath-hold were about 1% and 0.7%, respectively. With the help of NAV prospective motion compensation whole liver t values could be obtained without motion artifacts. The quantified liver T2 (34.7 ± 0.7 ms) and T2* (29 ± 1.2 ms) values agreed with values from literature. In healthy volunteers, the distribution of statistical t value and HVR was homogeneous throughout the whole liver. In patients with liver carcinoma, the distribution of t value and HVR was inhomogeneous due to metastases or therapy. CONCLUSIONS: This study demonstrates the feasibility of using a NAV prospective motion compensation technique in conjunction with five-echo SAGE EPI for the quantitative measurement of liver BOLD with a BH task.

Phenotyping of COPD with MRI in comparison to same-day CT in a multi-centre trial.

OBJECTIVES: A prospective, multi-centre study to evaluate concordance of morphologic lung MRI and CT in chronic obstructive pulmonary disease (COPD) phenotyping for airway disease and emphysema. METHODS: A total of 601 participants with COPD from 15 sites underwent same-day morpho-functional chest MRI and paired inspiratory-expiratory CT. Two readers systematically scored bronchial wall thickening, bronchiectasis, centrilobular nodules, air trapping and lung parenchyma defects in each lung lobe and determined COPD phenotype. A third reader acted as adjudicator to establish consensus. Inter-modality and inter-reader agreement were assessed using Cohen's kappa (im-κ and ir-κ). RESULTS: The mean combined MRI score for bronchiectasis/bronchial wall thickening was 4.5/12 (CT scores, 2.2/12 for bronchiectasis and 6/12 for bronchial wall thickening; im-κ, 0.04-0.3). Expiratory right/left bronchial collapse was observed in 51 and 47/583 on MRI (62 and 57/599 on CT; im-κ, 0.49-0.52). Markers of small airways disease on MRI were 0.15/12 for centrilobular nodules (CT, 0.34/12), 0.94/12 for air trapping (CT, 0.9/12) and 7.6/12 for perfusion deficits (CT, 0.37/12 for mosaic attenuation; im-κ, 0.1-0.41). The mean lung defect score on MRI was 1.3/12 (CT emphysema score, 5.8/24; im-κ, 0.18-0.26). Airway-/emphysema/mixed COPD phenotypes were assigned in 370, 218 and 10 of 583 cases on MRI (347, 218 and 34 of 599 cases on CT; im-κ, 0.63). For all examined features, inter-reader agreement on MRI was lower than on CT. CONCLUSION: Concordance of MRI and CT for phenotyping of COPD in a multi-centre setting was substantial with variable inter-modality and inter-reader concordance for single diagnostic key features. CLINICAL RELEVANCE STATEMENT: MRI of lung morphology may well serve as a radiation-free imaging modality for COPD in scientific and clinical settings, given that its potential and limitations as shown here are carefully considered. KEY POINTS: • In a multi-centre setting, MRI and CT showed substantial concordance for phenotyping of COPD (airway-/emphysema-/mixed-type). • Individual features of COPD demonstrated variable inter-modality concordance with features of pulmonary hypertension showing the highest and bronchiectasis showing the lowest concordance. • For all single features of COPD, inter-reader agreement was lower on MRI than on CT.

GOLD-grade specific disease characterization and phenotyping of COPD using quantitative computed tomography in the nationwide COSYCONET multicenter trial in Germany.

INTRODUCTION: To apply quantitative computed tomography (QCT) for GOLD-grade specific disease characterization and phenotyping of air-trapping, emphysema, and airway abnormalities in patients with chronic obstructive pulmonary disease (COPD) from a nationwide cohort study. METHODS: As part of the COSYCONET multicenter study, standardized CT in ex- and inspiration, lung function assessment (FEV1/FVC) and clinical scores (BODE index) were prospectively acquired in 525 patients (192women, 327men, aged 65.7±8.5y) at risk for COPD and at GOLD1-4. QCT parameters total lung volume (TLV), emphysema index (EI), parametric response mapping (PRM) for emphysema (PRMEmph) and functional small airway disease (PRMfSAD), total airway volume (TAV), wall percentage (WP) and total diameter (TD) were computed using automated software. RESULTS: TLV, EI, PRMfSAD and PRMEmph increased incrementally with each GOLD grade (p<0.001). Aggregated WP5-10 of subsegmental airways was higher from GOLD1 to GOLD3 and lower again at GOLD4 (p<0.001), whereas TD5-10 was significantly dilated only in GOLD4 (p<0.001). 58 patients were phenotyped as 'non-airway non-emphysema type', 202 as 'airway type', 96 as 'emphysema type' and 169 as 'mixed type'. FEV1/FVC was best in 'non-airway non-emphysema type' compared to other phenotypes, while 'mixed type' had worst FEV1/FVC (p<0.001). BODE index was 0.56±0.72 in the 'non-airway non-emphysema type' and highest with 2.55±1.77 in 'mixed type' (p<0.001). CONCLUSION: QCT demonstrates increasing hyperinflation and emphysema dependent on GOLD grade, while airway wall thickening increases until GOLD 3 and airway dilatation occurs in GOLD4. QCT identifies four disease phenotypes with implications for lung function and prognosis.

[Differential diagnosis of cystic and nodular lung diseases]. / Differenzialdiagnose zystischer und nodulärer Lungenkrankheiten.

BACKGROUND: Cystic and nodular lung diseases encompass a broad spectrum of diseases with different etiologies and clinicoradiological presentations. Their differentiation is crucial for patient management but can be complex due to diseases with features of both categories and overlapping radiological patterns. OBJECTIVE: This study aims to describe the imaging features of cystic and nodular lung diseases in high-resolution computed tomography (CT) in detail-primarily based on their etiology-in order to allow a more accurate differential diagnosis of these diseases. MATERIALS AND METHODS: A narrative review based on current literature on the topic was conducted from a clinicoradiological perspective. RESULTS: This paper systematically categorizes the differential diagnosis of cystic and nodular lung disease and provides insights into their radiological patterns and etiologies. It highlights the role of CT in the diagnosis of these diseases and emphasizes the importance of multidisciplinary panels combining expertise from radiology, pulmonology, rheumatology, and pathology. CONCLUSION: Reliable differential diagnosis of cystic and nodular lung diseases, particularly based on their radiological features alone, remains difficult due to their overlapping and dynamic nature. Multidisciplinary boards should be the clinical standard for accurate work-up of these diseases, as they combine the medical history, symptoms, radiological findings, and, if necessary, histopathological examinations, thus providing a more robust framework for diagnosis and management.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis.

Background: Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration. Objectives: To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF. Methods: Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8-45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP). Results: MP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = -0.75 and r = -0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01). Conclusion: MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.

Magnetic Resonance Imaging of Pulmonary and Paranasal Sinus Abnormalities in Children with Primary Ciliary Dyskinesia Compared to Children with Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z-score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF (r = -0.523 and -0.687; P < 0.01) and with lung clearance index in children with CF (r = 0.650; P < 0.001) but not in PCD (r = 0.353; P = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD (r = 0.075-0.157; P = 0.557-0.788) but correlated moderately with MRI morphology score in CF (r = 0.437; P < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Non-contrast free-breathing liver perfusion imaging using velocity selective ASL combined with prospective motion compensation.

PURPOSE: To apply velocity selective arterial spin labeling (VSASL) combined with a navigator-based (NAV) prospective motion compensation method for a free-breathing liver perfusion measurement without contrast agent. METHODS: Sinc-modulated Velocity Selective Inversion (sinc-VSI) pulses were applied as labeling and control pulses. In order to account for respiratory motion, a navigator was employed in the form of a single gradient-echo projection readout, located at the diaphragm along the inferior-superior direction. Prior to each transverse imaging slice of the spin-echo EPI based readouts, navigator and fat suppression were incorporated. Motion data was obtained from the navigator and transmitted back to the sequence, allowing real-time adjustments to slice positioning. The sinc-VSI without velocity-selective gradients during the control condition but with velocity-selective gradients along all three directions during labeling was chosen for the VSASL. The VSASL was compared with pseudo-continuous ASL (pCASL) methods, which selectively tagged the moving spins using a tagging plane placed at the portal vein and hepatic artery. RESULTS: The motion caused by respiratory activity was effectively computed using the navigator signal. The coefficients of variation (CoV) of average liver voxel in NAV were significantly decreased when compared to breath-hold (BH), with an average reduction of 29.4 ±â€¯18.44% for control images, and 29.89 ±â€¯20.83% for label images (p < 0.001). The resulting maps of normalized ASL signal (normalized to M0) showed significantly higher perfusion weightings in the NAV-compensated VSASL, when compared to the NAV-compensated pCASL techniques. CONCLUSIONS: This study demonstrates the feasibility of using a navigator-based prospective motion compensation technique in conjunction with VSASL for the measurement of liver perfusion without the use of contrast agents while allowing for free-breathing.

Postoperative Management of Portal Vein Arterialization: An Interdisciplinary Institutional Approach.

Portal vein arterialization (PVA) is a surgical procedure that plays a crucial role in hepatic vascular salvage when hepatic artery flow restoration remains elusive. Dedicated diagnostic vascular imaging and the timely management of PVA shunts are paramount to preventing complications, such as portal hypertension and thrombosis. Regrettably, a lack of standardized postoperative management protocols for PVA has increased morbidity and mortality rates post-procedure. In response to this challenge, we developed a PVA standard operating procedure (SOP) tailored to the needs of interventional radiologists. This SOP is designed to harmonize postoperative care, fostering scientific comparability across cases. This concise brief report aims to offer radiologists valuable insights into the PVA technique and considerations for post-PVA care and foster effective interdisciplinary collaboration.

Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor.

INTRODUCTION: Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of chronic rhinosinusitis (CRS) from infancy to school age, and response to lumacaftor/ivacaftor (LUM/IVA) therapy in children with cystic fibrosis (CF). However, the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CRS detected by MRI in children with CF and at least one F508del mutation, and potential incremental effects of ELX/TEZ/IVA compared to LUM/IVA in F508del homozygous children have not been studied. METHODS: 30 children with CF with at least one F508del mutation underwent three longitudinal paranasal sinus MRI before (MRI1), without (n = 16) or with LUM/IVA therapy (n = 14, MRI2), and with ELX/TEZ/IVA therapy (MRI3, mean age at therapy initiation 11.1 ± 3.4y, range 6-16y). MRI were evaluated using the CRS-MRI score. RESULTS: After therapy initiation with ELX/TEZ/IVA, the prevalence and in maxillary and sphenoid sinuses the dominance of mucopyoceles decreased (35% vs. 0 %, p<0.001 and 26% vs. 8 %, p < 0.05, respectively). This leads to a reduction in mucopyocele subscore (-3.4 ± 1.9, p < 0.001), and sinus subscores in MRI3 (maxillary sinus: -5.3 ± 3.1, p < 0.001, frontal sinus: -1.0 ± 1.9, p < 0.01, sphenoid subscore: -2.8 ± 3.5, p < 0.001, ethmoid sinus: -1.7 ± 1.9, p < 0.001). The CRS-MRI sum score decreased after therapy initiation with ELX/TEZ/IVA by -9.6 ± 5.5 score points (p < 0.001). The strength in reduction of mucopyoceles subscore and CRS-MRI sum score was independent of a pretreatment with LUM/IVA from MRI1-MRI2 (p = 0.275-0.999). CONCLUSIONS: ELX/TEZ/IVA therapy leads to improvement of CRS in eligible children with CF. Our data support the role of MRI for comprehensive monitoring of CRS disease severity and response to therapy in children with CF.

Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2 Through 5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial.

RATIONALE: Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age. OBJECTIVE: To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2 through 5 years. METHODS: This phase 2 trial had two parts: Part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2 through 5 years (previously reported) was followed by a 48-week open-label treatment period where all children received LUM/IVA (Part 2; reported here). Endpoints assessed in Part 2 included absolute changes from baseline in chest magnetic resonance imaging (MRI) global score at week 96; weight-for-age, stature-for-age, and body mass index (BMI)-for-age z-scores at week 96; lung clearance index (LCI2.5) through week 96; chest MRI morphological score, chest MRI perfusion score, weight, stature, BMI, and microbiology cultures (oropharyngeal swabs) at week 96; sweat chloride, serum levels of immunoreactive trypsinogen, fecal elastase-1 levels, and fecal calprotectin through week 96; and number of pulmonary exacerbations (PEx), time-to-first PEx, and number of CF-related hospitalizations. RESULTS: Forty-nine children received ≥1 dose of LUM/IVA in the open-label period (33 in the LUM/IVA to LUM/IVA group and 16 in the placebo to LUM/IVA group); mean exposure 47.1 (SD, 5.2) weeks. The mean absolute change in MRI global score (negative value = improvement) from baseline at Week 96 was -2.7 (SD 7.0; 95% CI, -5.2 to -0.1) in the LUM/IVA to LUM/IVA group and -5.6 (SD 6.9; 95% CI, -9.2 to -1.9) in the placebo to LUM/IVA group. Improvements in LCI2.5, sweat chloride concentration, and markers of pancreatic function and intestinal inflammation were also observed in both groups. Growth parameters remained stable in both groups. The majority of children had adverse events (AEs) considered mild (38.8%) or moderate (40.8%). Two (4.1%) children discontinued LUM/IVA treatment due to AEs (distal intestinal obstruction syndrome [n=1] and alanine aminotransferase increase [n=1]). CONCLUSION: These findings confirm the potential for early LUM/IVA treatment to alter the trajectory of CF disease progression, including CF lung disease, in children as young as 2 years of age. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03625466.

Simultaneous T1, T2 and T2⁎ mapping of the liver with multi-shot MI-SAGE.

PURPOSE: To apply multi-shot high-resolution multi inversion spin and gradient echo (MI-SAGE) acquisition for simultaneous liver T1, T2 and T2* mapping. METHODS: Inversion prepared spin- and gradient-echo EPI was developed with ascending slice order across measurements for efficient acquisition with T1, T2, and T2⁎ weighting. Multi-shot EPI was also implemented to minimize distortion and blurring while enabling high in-plane resolution. A dictionary-matching approach was used to fit the images to quantitative parameter maps, which were compared to T1 measured by modified Look-Locker (MOLLI), T1 measured by variable flip angle (VFA), T2 measured by multiple echo time-based Half Fourier Single-shot Turbo spin-Echo (HASTE), T2 measured by radial turbo-spin-echo (rTSE) and T2⁎ measured by multiple gradient echo (MGRE) sequences. RESULTS: The multi-shot variant of the sequence achieved higher in-plane resolution of 1.7 × 1.7 mm2 with good image quality in 28 s. Derived quantitative maps showed comparable values to conventional mapping methods. As measured in phantom and in vivo, MOLLI, MESE and MGRE give closest values to MISAGE. VFA, HASTE and rTSE show obvious overestimation. CONCLUSIONS: The proposed multi-shot inversion prepared spin- and gradient-echo EPI sequence allows for high-resolution quantitative T1, T2 and T2 liver tissue characterization in a single breath-hold scan.

Characterization of transient and progressive pulmonary fibrosis by spatially correlated phase contrast microCT, classical histopathology and atomic force microscopy.

Pulmonary fibrosis (PF) is a severe and progressive condition in which the lung becomes scarred over time resulting in pulmonary function impairment. Classical histopathology remains an important tool for micro-structural tissue assessment in the diagnosis of PF. A novel workflow based on spatial correlated propagation-based phase-contrast micro computed tomography (PBI-microCT), atomic force microscopy (AFM) and histopathology was developed and applied to two different preclinical mouse models of PF - the commonly used and well characterized Bleomycin-induced PF and a novel mouse model for progressive PF caused by conditional Nedd4-2 KO. The aim was to integrate structural and mechanical features from hallmarks of fibrotic lung tissue remodeling. PBI-microCT was used to assess structural alteration in whole fixed and paraffin embedded lungs, allowing for identification of fibrotic foci within the 3D context of the entire organ and facilitating targeted microtome sectioning of planes of interest for subsequent histopathology. Subsequently, these sections of interest were subjected to AFM to assess changes in the local tissue stiffness of previously identified structures of interest. 3D whole organ analysis showed clear morphological differences in 3D tissue porosity between transient and progressive PF and control lungs. By integrating the results obtained from targeted AFM analysis, it was possible to discriminate between the Bleomycin model and the novel conditional Nedd4-2 KO model using agglomerative cluster analysis. As our workflow for 3D spatial correlation of PBI, targeted histopathology and subsequent AFM is tailored around the standard procedure of formalin-fixed paraffin-embedded (FFPE) tissue specimens, it may be a powerful tool for the comprehensive tissue assessment beyond the scope of PF and preclinical research.

Comparative sensitivity of early cystic fibrosis lung disease detection tools in school aged children.

BACKGROUND: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. METHODS: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). RESULTS: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. CONCLUSIONS: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.

Echo time-dependent observed T1 and quantitative perfusion in chronic obstructive pulmonary disease using magnetic resonance imaging.

Introduction: Due to hypoxic vasoconstriction, perfusion is interesting in the lungs. Magnetic Resonance Imaging (MRI) perfusion imaging based on Dynamic Contrast Enhancement (DCE) has been demonstrated in patients with Chronic Obstructive Pulmonary Diseases (COPD) using visual scores, and quantification methods were recently developed further. Inter-patient correlations of echo time-dependent observed T1 [T1(TE)] have been shown with perfusion scores, pulmonary function testing, and quantitative computed tomography. Here, we examined T1(TE) quantification and quantitative perfusion MRI together and investigated both inter-patient and local correlations between T1(TE) and quantitative perfusion. Methods: 22 patients (age 68.0 ± 6.2) with COPD were examined using morphological MRI, inversion recovery multi-echo 2D ultra-short TE (UTE) in 1-2 slices for T1(TE) mapping, and 4D Time-resolved angiography With Stochastic Trajectories (TWIST) for DCE. T1(TE) maps were calculated from 2D UTE at five TEs from 70 to 2,300 µs. Pulmonary Blood Flow (PBF) and perfusion defect (QDP) maps were produced from DCE measurements. Lungs were automatically segmented on UTE images and morphological MRI and these segmentations registered to DCE images. DCE images were separately registered to UTE in corresponding slices and divided into corresponding subdivisions. Spearman's correlation coefficients were calculated for inter-patient correlations using the entire segmented slices and for local correlations separately using registered images and subdivisions for each TE. Median T1(TE) in normal and defect areas according to QDP maps were compared. Results: Inter-patient correlations were strongest on average at TE2 = 500 µs, reaching up to |ρ| = 0.64 for T1 with PBF and |ρ| = 0.76 with QDP. Generally, local correlations of T1 with PBF were weaker at TE2 than at TE1 or TE3 and with maximum values of |ρ| = 0.66 (from registration) and |ρ| = 0.69 (from subdivision). In 18 patients, T1 was shorter in defect areas than in normal areas, with the relative difference smallest at TE2. Discussion: The inter-patient correlations of T1 with PBF and QDP found show similar strength and TE-dependence as those previously reported for visual perfusion scores and quantitative computed tomography. The local correlations and median T1 suggest that not only base T1 but also the TE-dependence of observed T1 in normal areas is closer to that found previously in healthy volunteers than in defect areas.