Baseline characteristics from a 3-year longitudinal study to phenotype subjects with COPD: the FOOTPRINTS study.

BACKGROUND: FOOTPRINTS® is a prospective, longitudinal, 3-year study assessing the association between biomarkers of inflammation/lung tissue destruction and chronic obstructive pulmonary disease (COPD) severity and progression in ex-smokers with mild-to-severe COPD. Here, we present baseline characteristics and select biomarkers of study subjects. METHODS: The methodology of FOOTPRINTS® has been published previously. The study population included ex-smokers with a range of COPD severities (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 1-3), ex-smokers with COPD and alpha-1-antitrypsin deficiency (A1ATD) and a control group of ex-smokers without airflow limitation (EwAL). At study entry, data were collected for: demographics, disease characteristics, history of comorbidities and COPD exacerbations, symptoms, lung function and volume, exercise capacity, soluble biomarkers, and quantitative and qualitative computed tomography. Baseline data are presented with descriptive statistical comparisons for soluble biomarkers in the individual GOLD and A1ATD groups versus EwAL. RESULTS: In total, 463 subjects were enrolled. The per-protocol set comprised 456 subjects, mostly male (64.5%). The mean (standard deviation) age was 60.7 (6.9) years. At baseline, increasing pulmonary symptoms, worse lung function, increased residual volume, reduced diffusing capacity of the lung for carbon monoxide (DLco) and greater prevalence of centrilobular emphysema were observed with increasing disease severity amongst GOLD 1-3 subjects. Subjects with A1ATD (n = 19) had similar lung function parameters to GOLD 2-3 subjects, a high residual volume comparable to GOLD 3 subjects, and similar air trapping to GOLD 2 subjects. Compared with EwAL (n = 61), subjects with A1ATD had worse lung function, increased residual volume, reduced DLco, and a greater prevalence of confluent or advanced destructive emphysema. The soluble inflammatory biomarkers white blood cell count, fibrinogen, high-sensitivity C-reactive protein and plasma surfactant protein were higher in GOLD 1-3 groups than in the EwAL group. Interleukin-6 was expressed less often in EwAL subjects compared with subjects in the GOLD and A1ATD groups. Soluble receptor for advanced glycation end product was lowest in GOLD 3 subjects, indicative of more severe emphysema. CONCLUSIONS: These findings provide context for upcoming results from FOOTPRINTS®, which aims to establish correlations between biomarkers and disease progression in a representative COPD population. TRIAL REGISTRATION NUMBER: NCT02719184, study start date 13/04/2016.

Unsupervised clustering algorithms improve the reproducibility of dynamic contrast-enhanced magnetic resonance imaging pulmonary perfusion quantification in muco-obstructive lung diseases.

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows the assessment of pulmonary perfusion, which may play a key role in the development of muco-obstructive lung disease. One problem with quantifying pulmonary perfusion is the high variability of metrics. Quantifying the extent of abnormalities using unsupervised clustering algorithms in residue function maps leads to intrinsic normalization and could reduce variability. Purpose: We investigated the reproducibility of perfusion defects in percent (QDP) in clinically stable patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Methods: 15 CF (29.3 ± 9.3y, FEV1%predicted = 66.6 ± 15.8%) and 20 COPD (66.5 ± 8.9y, FEV1%predicted = 42.0 ± 13.3%) patients underwent DCE-MRI twice 1 month apart. QDP, pulmonary blood flow (PBF), and pulmonary blood volume (PBV) were computed from residue function maps using an in-house quantification pipeline. A previously validated MRI perfusion score was visually assessed by an expert reader. Results: Overall, mean QDP, PBF, and PBV did not change within 1 month, except for QDP in COPD (p < 0.05). We observed smaller limits of agreement (± 1.96 SD) related to the median for QDP (CF: ± 38%, COPD: ± 37%) compared to PBF (CF: ± 89%, COPD: ± 55%) and PBV (CF: ± 55%, COPD: ± 51%). QDP correlated moderately with the MRI perfusion score in CF (r = 0.46, p < 0.05) and COPD (r = 0.66, p < 0.001). PBF and PBV correlated poorly with the MRI perfusion score in CF (r =-0.29, p = 0.132 and r =-0.35, p = 0.067, respectively) and moderately in COPD (r =-0.57 and r =-0.57, p < 0.001, respectively). Conclusion: In patients with muco-obstructive lung diseases, QDP was more robust and showed a higher correlation with the MRI perfusion score compared to the traditionally used perfusion metrics PBF and PBV.

Quantification of pulmonary perfusion abnormalities using DCE-MRI in COPD: comparison with quantitative CT and pulmonary function.

OBJECTIVES: Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI. METHODS: We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 ± 9.0 years, patients-at-risk, and all GOLD groups) from one center of the "COSYCONET" COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu's method, k-means clustering, texture analysis, and 80th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRMEmph) and functional small airway disease (PRMfSAD), and FEV1/FVC from PFT. RESULTS: All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p < 0.001), with the highest association based on Otsu's method (r = 0.72, p < 0.001). QDP correlated significantly with all PRM indices (p < 0.001), with the strongest correlations with PRMEmph (r = 0.70 to 0.75, p < 0.001). QDP was distinctly higher than PRMEmph (mean difference = 35.85 to 40.40) and PRMfSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = - 0.54 to - 0.41, p < 0.001). CONCLUSION: QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRMEmph and PRMfSAD. We propose to use QDP based on Otsu's method for future clinical studies in COPD. KEY POINTS: • QDP quantified from DCE-MRI is associated with visual MRI perfusion score, CT PRM indices, and PFT. • The extent of QDP from DCE-MRI corresponds to the combined extent of PRMEmph and PRMfSAD from CT. • Assessing pulmonary perfusion abnormalities using DCE-MRI with QDP improved the correlations with CT PRM indices and PFT compared to the quantification of pulmonary blood flow and volume.

FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD.

INTRODUCTION: A better understanding is needed of the different phenotypes that exist for patients with chronic obstructive pulmonary disease (COPD), their relationship with the pathogenesis of COPD and how they may affect disease progression. Biomarkers, including those associated with emphysema, may assist in characterising patients and in predicting and monitoring the course of disease. The FOOTPRINTS study (study 352.2069) aims to identify biomarkers associated with emphysema, over a 3-year period. METHODS AND ANALYSIS: The FOOTPRINTS study is a prospective, longitudinal, multinational (12 countries), multicentre (51 sites) biomarker study, which has enrolled a total of 463 ex-smokers, including subjects without airflow limitation (as defined by the 2015 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report), patients with COPD across the GOLD stages 1-3 and patients with COPD and alpha1-antitrypsin deficiency. The study has an observational period lasting 156 weeks that includes seven site visits and additional phone interviews. Biomarkers in blood and sputum, imaging data (CT and magnetic resonance), clinical parameters, medical events of special interest and safety are being assessed at regular visits. Disease progression based on biomarker values and COPD phenotypes are being assessed using multivariate statistical prediction models. ETHICS AND DISSEMINATION: The study protocol was approved by the authorities and ethics committees/institutional review boards of the respective institutions where applicable, which included study sites in Belgium, Canada, Denmark, Finland, Germany, Japan, Korea, Poland, Spain, Sweden, UK and USA; written informed consent has been obtained from all study participants. Ethics committee approval was obtained for all participating sites prior to enrolment of the study participants. The study results will be reported in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02719184.

Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome.

BACKGROUND: Hereditary Hyperferritinaemia Cataract Syndrome (HHCS) is a rare autosomal dominant disease characterized by increased serum ferritin levels and early onset of bilateral cataract. The disease is caused by mutations in the Iron-Responsive Element (IRE) located in the 5' untranslated region of L-Ferritin (FTL) mRNA, which post-transcriptionally regulates ferritin expression. METHODS: We describe two families presenting high serum ferritin levels and juvenile cataract with novel mutations in the L-ferritin IRE. The mutations were further characterized by in vitro functional studies. RESULTS: We have identified two novel mutations in the IRE of L-Ferritin causing HHCS: the Badalona +36C > U and the Heidelberg +52 G > C mutation. Both mutations conferred reduced binding affinity on recombinant Iron Regulatory Proteins (IPRs) in EMSA experiments. Interestingly, the Badalona +36C > U mutation was found not only in heterozygosity, as expected for an autosomal dominant disease, but also in the homozygous state in some affected subjects. Additionally we report an update of all mutations identified so far to cause HHCS. CONCLUSIONS: The Badalona +36C > U and Heidelberg +52 G > C mutations within the L-ferritin IRE only mildly alter the binding capacity of the Iron Regulatory Proteins but are still causative for the disease.

Magnetic resonance imaging to assess the effect of exercise training on pulmonary perfusion and blood flow in patients with pulmonary hypertension.

OBJECTIVES: To evaluate whether careful exercise training improves pulmonary perfusion and blood flow in patients with pulmonary hypertension (PH), as assessed by magnetic resonance imaging (MR). METHODS: Twenty patients with pulmonary arterial hypertension or inoperable chronic thromboembolic PH on stable medication were randomly assigned to control (n = 10) or training groups (n = 10). Training group patients received in-hospital exercise training; patients of the sedentary control group received conventional rehabilitation. Medication remained unchanged during the study period. Changes of 6-min walking distance (6MWD), MR pulmonary flow (peak velocity) and MR perfusion (pulmonary blood volume) were assessed from baseline to week 3. RESULTS: After 3 weeks of training, increases in mean 6MWD (P = 0.004) and mean MR flow peak velocity (P = 0.012) were significantly greater in the training group. Training group patients had significantly improved 6MWD (P = 0.008), MR flow (peak velocity -9.7 ± 8.6 cm/s, P = 0.007) and MR perfusion (pulmonary blood volume +2.2 ± 2.7 mL/100 mL, P = 0.017), whereas the control group showed no significant changes. CONCLUSION: The study indicates that respiratory and physical exercise may improve pulmonary perfusion in patients with PH. Measurement of MR parameters of pulmonary perfusion might be an interesting new method to assess therapy effects in PH. The results of this initial study should be confirmed in a larger study group.

A texture analysis approach to quantify ventilation changes in hyperpolarised ³He MRI of the rat lung in an asthma model.

In preclinical research, allergic asthma is investigated in rats sensitised with the antigen ovalbumin (OVA), followed by a challenge with aerosolised OVA to induce an inflammatory reaction of the lower airways. This causes diffuse, nonfocal ventilation defects that lead to heterogeneously distributed signal intensities in hyperpolarised (HP) (3)He MR images, which are difficult to assess directly by diagnostic grading or volumetry. Texture analysis can characterise these changes and does not require segmentation of the lung structures prior to the analysis. The aim of this work was to evaluate a texture analysis approach to quantify changes in lung ventilation in HP (3)He MRI of OVA-challenged rats. OVA-challenged animals were treated with two different compound doses to evaluate the sensitivity of the texture analysis. Four groups were investigated using HP (3)He MRI at 4.7 T: controls, vehicle-treated, and low- and high-dose budesonide-treated rats. In addition, broncho-alveolar lavage was performed and the eosinophil cell count was used as a biological reference marker. First-order texture, geometrical features and features based on second-order statistics using run-length and grey-level co-occurrence matrices were calculated. In addition, wavelet transforms were applied to compute first-order statistics on multiple scales. The texture analysis was able to show significant differences between the control and untreated vehicle groups as well as between the vehicle and treatment groups. This is in agreement with the findings of the eosinophil cell counts, which were used as a marker for the severity of inflammation. However, not all features used in the different texture analysis methods could differentiate between the treatment groups. In conclusion, texture analysis can be used to quantify changes in lung ventilation as measured with HP (3)He MRI after therapeutic intervention with budesonide.

The feasibility of low mechanical index contrast enhanced ultrasound (CEUS) in distinguishing malignant from benign thoracic lesions.

We proposed to assess the feasibility of low mechanical index (MI) contrast enhanced ultrasound (CEUS) in the characterisation of thoracic lesions. Fifty patients were prospectively examined by CEUS and images acquired on a low MI (0.17-0.24) setting following injection of SonoVue. From region-of-interest (ROI) generated signal intensity (SI) time curves, the maximum SI, bolus arrival time (BAT), time to peak intensity (TTP), wash-in slope and mean transit time (MTT) were calculated. Using the Wilcoxon rank test; parameters and threshold values for positive differentiation were determined. In addition, for the parameters that allowed positive differentiation between malignant and benign lesions receiver operator curves (ROC) were obtained. The wash-in slope, TTP and MTT (p = 0.0003, <0.0001, 0.02) allowed positive differentiation. The sensitivity and specificity was 93% and 78%, with 6.87 s(-1) threshold value for the wash-in slope, 78% and 89% with 11.84 s threshold for the TTP and 48% and 89% with 78.6 s threshold for the MTT. CEUS is a useful tool for differentiating malignant and benign thoracic lesions.

Oxygen-enhanced lung magnetic resonance imaging: influence of inversion pulse slice selectivity on inversion recovery half-Fourier single-shot turbo spin-echo signal.

PURPOSE: The purpose of this study was to evaluate in vivo the influence of inversion pulse slice selectivity on oxygen-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirteen healthy volunteers were studied with a two-dimensional cardiac- and respiratory-gated adiabatic inversion-recovery half-Fourier single-shot turbo spin-echo (HASTE) sequence with either slice-selective or non-slice-selective inversion recovery (IR) pulse at inversion times increasing from 300 to 1400 ms. The signal-to-noise ratio (SNR) at every inversion time (TI), real signal difference (ΔSI), and relative enhancement ratio of lung parenchyma at TI ≥ 800 ms were statistically compared for oxygen-enhanced and non-oxygen-enhanced MR images with slice-selective or non-slice-selective IR pulses. RESULTS: The SNRs of acquisitions with slice-selective IR pulses were significantly higher than those of non-slice-selective IR pulses (P < 0.05). At TI 800 ms, the ΔSI of lung parenchyma on IR-HASTE images with slice-selective inversion pulse type was significantly higher than on that with the non-slice-selective type (P < 0.05). Relative enhancement ratios of the slice-selective IR pulses were significantly lower than those of non-slice-selective IR pulses at TIs between 800 and 1400 ms (P < 0.05). CONCLUSION: Slice selectivity of inversion pulse type affects oxygen-enhanced MRI in vivo.

Repeatability and reproducibility of quantitative whole-lung perfusion magnetic resonance imaging.

PURPOSE: Magnetic resonance imaging (MRI) allows for quantitative evaluation of pulmonary perfusion and has shown high clinical usefulness for the evaluation and differentiation of different lung pathologies. The reproducibility of quantitative analysis of whole-lung perfusion has not been investigated previously. Our aim was to assess the intraobserver and interobserver repeatability and reproducibility of perfusion MRI to prove the concept that perfusion is suitable for therapy monitoring. MATERIALS AND METHODS: The study was approved by the International Review Board. Fourteen healthy volunteers were examined using a time-resolved FLASH 3-dimensional perfusion sequence (1.5-T MRI, TREAT, GRAPPA 2, coronal orientation, voxel size 3.9×3.9×6.3 mm(3)). Perfusion was assessed initially and after 24 hours during an inspiratory and an expiratory breath hold. For each examination, 0.05 mmol/kg BW of Gd-DTPA was injected. Perfusion parameters such as pulmonary blood flow (PBF), pulmonary blood volume, and mean transit time were calculated. The evaluation was performed independently by 2 blinded observers. Intraobserver and interobserver differences were determined. RESULTS: The intraobserver differences between the initial and follow-up examinations for pulmonary blood volume, mean transit time, and time to peak were not significantly different for observers 1 and 2. PBF showed a significant difference for both observers only on inspiration (P<0.006 for observer 1 and P<0.009 for observer 2). For interobserver evaluation, all parameters, except inspiratory PBF, were significantly different (P<0.0001). CONCLUSIONS: Intraobserver quantitative perfusion MRI showed reproducible results. However, the evaluation is highly dependent on the observer. Therefore, quantitative analysis of the serial examinations should be performed by the same observer.

Improved visualization of delayed perfusion in lung MRI.

INTRODUCTION: The investigation of pulmonary perfusion by three-dimensional (3D) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was proposed recently. Subtraction images are generated for clinical evaluation, but temporal information is lost and perfusion defects might therefore be masked in this process. The aim of this study is to demonstrate a simple analysis strategy and classification for 3D-DCE-MRI perfusion datasets in the lung without omitting the temporal information. MATERIALS AND METHODS: Pulmonary perfusion measurements were performed in patients with different lung diseases using a 1.5 T MR-scanner with a time-resolved 3D-GRE pulse sequence. 25 3D-volumes were acquired after iv-injection of 0.1 mmol/kg KG Gadolinium-DTPA. Three parameters were determined for each pixel: (1) peak enhancement S(n,max) normalized to the arterial input function to detect regions of reduced perfusion; (2) time between arterial peak enhancement in the large pulmonary artery and tissue peak enhancement τ to visualize regions with delayed bolus onset; and (3) ratio R=S(n,max)/τ was calculated to visualize impaired perfusion, irrespectively of whether related to reduced or delayed perfusion. RESULTS: A manual selection of peak perfusion images is not required. Five different types of perfusion can be found: (1) normal perfusion; (2) delayed non-reduced perfusion; (3) reduced non-delayed perfusion; (4) reduced and delayed perfusion; and (5) no perfusion. Types II and IV could not be seen in subtraction images since the temporal information is necessary for this purpose. CONCLUSIONS: The analysis strategy in this study allows for a simple and observer-independent visualization and classification of impaired perfusion in dynamic contrast-enhanced pulmonary perfusion MRI by using the temporal information of the datasets.

Suppression of pulmonary vasculature in lung perfusion MRI using correlation analysis.

The purpose of the study was to evaluate the feasibility of suppressing the pulmonary vasculature in lung perfusion MRI using cross-correlation analysis (CCA). Perfusion magnetic resonance imaging (MRI) (3D FLASH, TR/TE/flip angle: 0.8 ms/2.1 ms/40 degrees ) of the lungs was performed in seven healthy volunteers at 1.5 Tesla after injection of Gd-DTPA. CCA was performed pixel-wise in lung segmentations using the signal time-course of the main pulmonary artery and left atrium as references. Pixels with high correlation coefficients were considered as arterial or venous and excluded from further analysis. Quantitative perfusion parameters [pulmonary blood flow (PBF) and volume (PBV)] were calculated for manual lung segmentations separately, with the entire left and right lung with all intrapulmonary vessels (IPV) included, excluded manually or excluded using CCA. The application of CCA allowed reliable suppression of hilar and large IPVs. Using vascular suppression by CCA, perfusion parameters were significantly reduced (p

Intraindividual comparison between gadopentetate dimeglumine and gadobutrol for magnetic resonance perfusion in normal brain and intracranial tumors at 3 Tesla.

BACKGROUND: In vitro studies have shown that the 3-Tesla (T) magnetic resonance (MR) characteristics of high- and standard-molar gadolinium-based contrast agents differ. Such differences may indicate that high-molar (1.0 M) agents offer advantages for perfusion-weighted imaging (PWI) at 3T, as has been previously reported at 1.5 T. PURPOSE: To investigate possible intraindividual differences of high- versus low-molar contrast agents on PWI at 3T in patients with intracranial space-occupying lesions. MATERIAL AND METHODS: Six patients with intraaxial and five patients with extraaxial tumors underwent two MR examinations at 3T, separated by at least 48 hours. On each occasion, an exogenous contrast-based, T2*-weighted, gradient-recalled echo-planar imaging (EPI) technique was used to determine the intracranial perfusion characteristics using one of two intravenous contrast agents: either 5 ml of 1.0 M gadobutrol or 10 ml of 0.5 M gadopentetate dimeglumine. The primary PWI outcome measure was region-of-interest maximal signal change (C(max)). RESULTS: The difference in C(max) for gray and white matter (Delta C(max)) was significantly higher for gadobutrol compared to gadopentetate dimeglumine (P<0.01). The ratio of C(max) between gray and white matter (rC(max) = C(maxGray)/C(maxWhite)) was also significantly higher (median 24.6%, range 13.7-36.5%) for gadobutrol (P<0.01). The ratio of C(max) between the whole tumor and whole normal side hemisphere was higher in five out of the six intraaxial tumor cases. A significantly higher ratio (Delta C(max)/C(max)) in the difference between C(max) of gray and white matter (from hemisphere without brain lesion) compared to C(max) for the hemisphere containing the neoplasm (hemisphere with brain lesion) was demonstrated for gadobutrol in intraaxial tumors (P<0.05). CONCLUSION: Higher-concentration 1.0 M gadobutrol can offer advantages over standard 0.5 M gadopentetate dimeglumine, particularly with respect to delineation between gray and white matter and for the demarcation of highly vascularized tumor tissue on brain PWI performed at 3T.

In vivo Gd-DTPA concentration for MR lung perfusion measurements: assessment with computed tomography in a porcine model.

A linear relationship between MR signal and contrast-agent concentration (CAC) of the arterial-input function (AIF) is crucial for MR lung-perfusion quantification. The aim was to determine the in-vivo real maximum CAC of the AIF, using cine CT measurements in a porcine model. A dilution series (Gd-DTPA, 0-20 mM) was examined by clinical time-resolved 3D-GRE MRI and by MDCT in cine CT mode. Using the CT setup, data were acquired in five pigs immediately after the injection of 0.05 mmol and 0.07 mmol/kg BW Gd-DTPA. For phantom measurements, mean signal values were determined using a region-of-interest (ROI) analysis and for animal measurements, a ROI was placed in the pulmonary trunk of the cine CT perfusion data sets. The CT phantom measurements were used to calculate the in-vivo maximum CAC corresponding to the HU values obtained in the pulmonary trunk by the cine CT study. Linearity of the AIF of the CT perfusion measurements was verified using the MR phantom measurement results. MR phantom measurements demonstrated linearity for concentrations of 0-4 mM. CT phantom measurements showed linear relation for the entire CAC range. Comparing in-vivo and in-vitro measurements, three of five CA injections at 0.05 mmol/kg and all 0.07 mmol/kg injections exceeded the range of linearity in MRI. The CA dose for quantification of lung perfusion with time-resolved MR studies must be chosen carefully since even with low doses (0.05 mmol/kg) the CAC may exceed the range of linearity in the AIF.

New method for 3D parametric visualization of contrast-enhanced pulmonary perfusion MRI data.

Three-dimensional (3D) dynamic contrast-enhanced magnetic resonance imaging (3D DCE-MRI) has been proposed for the assessment of regional perfusion. The aim of this work was the implementation of an algorithm for a 3D parametric visualization of lung perfusion using different cutting planes and volume rendering. Our implementation was based on 3D DCE-MRI data of the lungs of five patients and five healthy volunteers. Using the indicator dilution theory, the regional perfusion parameters, tissue blood flow, blood volume and mean transit time were calculated. Due to the required temporal resolution, the volume elements of dynamic MR data sets show a reduced spatial resolution in the z-direction. Therefore, perfusion parameter volumes were interpolated. Linear interpolation and a combination of linear and nearest-neighbor interpolation were evaluated. Additionally, ray tracing was applied for 3D visualization. The linear interpolation algorithm caused interpolation errors at the lung borders. Using the combined interpolation, visualization of perfusion information in arbitrary cutting planes and in 3D using volume rendering was possible. This facilitated the localization of perfusion deficits compared with the coronal orientated source data. The 3D visualization of perfusion parameters using a combined interpolation algorithm is feasible. Further studies are required to evaluate the additional benefit from the 3D visualization.

Navigator-triggered oxygen-enhanced MRI with simultaneous cardiac and respiratory synchronization for the assessment of interstitial lung disease.

PURPOSE: To evaluate an optimized method for oxygen-enhanced MRI of the lung, using simultaneous electrocardiograph (ECG) and navigator triggering. To correlate oxygen-enhanced MRI with lung function tests assessing alveolar-capillary gas exchange. MATERIALS AND METHODS: A total of 12 healthy volunteers (aged 20-32 years) and 10 patients (aged 37-87 years) with interstitial lung diseases (ILD) underwent oxygen-enhanced MRI and pulmonary functional tests (PFTs) assessing alveolar-capillary gas exchange. The paradigm room-air-oxygen-room-air was acquired with a nonselective inversion-recovery half-Fourier single-shot turbo spin-echo sequence (inversion time = 1200 msec; acquisition time = 134.5 msec; slice thickness = 20 mm; matrix size = 128 x 128), using simultaneous double triggering (navigator plus ECG trigger). Cross-correlation was performed in regions of interest (ROIs) encompassing both lungs. The number of oxygen-activated pixels over the total number of pixels in the ROIs (OAP%) of volunteers and patients was compared. OAP%s were correlated with PFTs. RESULTS: The mean OAP% of patients was significantly lower than that of volunteers (36.7 vs. 81.7, P = 0.001). OAP% correlated with the transfer lung factor for carbon monoxide (Tlco) (r = 0.64; P = 0.002), the transfer coefficient (Kco) (r = 0.75; P = 0.001), the arterial partial pressure (r = 0.77; P < 0.001), and the saturation (r = 0.70; P < 0.001) of oxygen. CONCLUSION: Navigator-triggered oxygen-enhanced MRI of the lung may have a potential role in the quantitative assessment of lung function in ILD.

[An experimental organ model for magnetic resonance imaging]. / Ein experimentelles Organmodell für die MR-Bildgebung.

The investigation of reperfusion of organs after an ischaemic phase is of great interest in transplantation medicine. This work presents an experimental organ model for the examination of isolated canine livers by means of magnetic resonance imaging in reperfusion experiments. The perfusion of the organs inside a perfusate container in the scanner's head coil was performed with approximately physiological conditions for 1.5 hours. The pumps for the perfusate circulation were installed outside the scanner's room, where oxygenation and heating of the perfusate was also performed. In the MR examinations, T1- and T2-weighted sequences could be used to display the morphology of the organs and the spatial perfusion distribution after administration of contrast media. The images revealed oedema development during reperfusion and an inhomogenous perfusion distribution. Thus, the model allows for the non-invasive investigation of morphology and perfusion distribution in isolated reperfused organs.

Impact of oxygen inhalation on the pulmonary circulation: assessment by magnetic resonance (MR)-perfusion and MR-flow measurements.

PURPOSE: Oxygen-enhanced magnetic resonance (MR)-ventilation imaging of the lung is based on the inhalation of a high concentration of oxygen (hyperoxia). However, the effect of hyperoxia on the pulmonary circulation is not yet fully understood. In this study the impact of hyperoxia on the pulmonary circulation was evaluated. MATERIALS AND METHODS: Ten healthy volunteers were examined in a 1.5 T MRI system with contrast-enhanced perfusion MRI (saturation recovery 2D turboFLASH) of the lung and phase-contrast flow measurements in the pulmonary trunk. Both measurements were performed breathing room air (RA) and, subsequently, 100% oxygen (15 L/min) (O(2)). RESULTS: The perfusion measurements showed a significant difference between RA and O(2) for the pulmonary blood flow (181 vs. 257 mL/min/100 mL, P = 0.04) and blood volume (14 vs. 21 mL/100 mL, P = 0.008). The mean transit time of the contrast bolus was not changed (P = 0.4) in the dorsal part of the lung, whereas it was significantly prolonged (P = 0.006) in the central part. The mean heart rate during flow measurements breathing RA (67 +/- 11 beats/min) and O(2) (61 +/- 12 beats/min) were not significantly different (P = 0.055). The average cardiac output (pulmonary trunk) was not significantly lower while breathing O(2) (RA: 5.9 vs. O(2): 5.5 L/min, P = 0.054). CONCLUSION: Hyperoxia causes a significant increase and redistribution of the pulmonary perfusion, whereas it leads to a not significant decrease in cardiac output. Thus, for MR-perfusion and MR-flow measurements oxygen inhalation should be avoided, if possible. In the context of oxygen-enhanced MR-ventilation imaging of the lung the contribution of this effect needs to be further evaluated.

Quantitative 3D pulmonary MR-perfusion in patients with pulmonary arterial hypertension: correlation with invasive pressure measurements.

PURPOSE: Pathological changes of the peripheral pulmonary arteries induce pulmonary arterial hypertension (PAH). Aim of this study was to quantitatively assess the effect of PAH on pulmonary perfusion by 3D-MR-perfusion techniques and to compare findings to healthy controls. Furthermore, quantitative perfusion data were correlated with invasive pressure measurements. MATERIAL AND METHODS: Five volunteers and 20 PAH patients (WHO class II or III) were examined using a 1.5T MR scanner. Measurement of pulmonary perfusion was done in an inspiratory breathhold (FLASH3D; 3.5 mm x 1.9 mm x 4mm; TA per 3D dataset 1.5s). Injection of contrast media (0.1 mmol Gd-DTPA/kg BW) and image acquisition were started simultaneously. Evaluation of 3D perfusion was done using singular value decomposition. Lung borders were outlined manually. Each lung volume was divided into three regions (anterior, middle, posterior), and the following parameters were assessed: Time-to-Peak (TTP), blood flow (PBF), blood volume (PBV), and mean transit time (MTT). In 10 patients invasive pulmonary artery pressure measurements were available and correlated to the perfusion measurements. RESULTS: In both, controls and patients, an anterior-to-posterior gradient with higher PBF and PBV posterior was observed. In the posterior lung region, a significant difference (p<0.05) was found for TTP (12s versus 16s) and MTT (4s versus 6s) between volunteers and patients. PBF and PBV were lower in patients than in volunteers (i.e. dorsal regions: 124 versus 180 ml/100 ml/min and 10 versus 12 ml/100 ml), but the difference failed to be significant. The ratio of PBF and PBV between the posterior and the middle or ventral regions showed no difference between both groups. A moderate linear correlation between mean pulmonary arterial pressure (mPAP) and PBV (r=0.51) and MTT (r=0.56) was found. CONCLUSION: The only measurable effect of PAH on pulmonary perfusion is a prolonging of the MTT. There is only a moderate linear correlation of invasive mPAP with PBV and MTT.