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Purpose A segmented inversion-recovery module combined with the 2D ultrashort echo time radial technique is proposed that allows accurate pixel level T1 mapping of mouse lung in vivo. Methods Numerical simulations were performed to estimate T1 measurement accuracy and precision versus flip angle and signal-to-noise ratio. Phantom measurements were used for protocol validation, where the segmented inversion-recovery ultrashort echo-time sequence was compared with the reference technique (inversion-recovery rapid acquisition with refocused echoes). The in vivo experiments were carried out on free-breathing C57 mice ( n = 10), breathing first air and then oxygen. Results The simulations demonstrated the high potential of the technique for accurate and precise T1 assessment. Phantom experiments showed good agreement for T1 values measured with segmented inversion-recovery ultrashort echo-time and the reference technique. The in vivo experiment demonstrated the utility of the technique in oxygen-enhanced assessment, where small T1 changes were detected with high precision. Conclusion Segmented inversion-recovery ultrashort echo-time provides accurate, high resolution T1 mapping of the lung parenchyma. Magn Reson Med 71:2180-2185, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Tissue microcirculation can be quantified by a deconvolution analysis of concentration-time curves measured by dynamic contrast-enhanced magnetic resonance imaging. However, deconvolution is an ill-posed problem, which requires regularization of the solutions. In this work, four algebraic deconvolution/regularization methods were evaluated: truncated singular value decomposition and generalized Tikhonov regularization (GTR) in combination with the L-curve criterion, a modified LCC (GTR-MLCC), and a response function model that takes a-priori knowledge into account. To this end, dynamic contrast-enhanced magnetic resonance imaging data sets were simulated by an established physiologically reference model for different signal-to-noise ratios and measured on a 1.5-T system in the lung of 10 healthy volunteers and 20 patients. Analysis of both the simulated and measured dynamic contrast-enhanced magnetic resonance imaging datasets revealed that GTR in combination with the L-curve criterion does not yield reliable and clinically useful results. The three other deconvolution/regularization algorithms resulted in almost identical microcirculatory parameter estimates for signal-to-noise ratios > 10. At low signal-to-noise ratios levels (<10) typically occurring in pathological lung regions, GTR in combination with a modified L-curve criterion approximates the true response function much more accurately than truncated singular value decomposition and GTR in combination with response function model with a difference in accuracy of up to 76%. In conclusion, GTR in combination with a modified L-curve criterion is recommended for the deconvolution of dynamic contrast-enhanced magnetic resonance imaging curves measured in the lung parenchyma of patients with highly heterogeneous signal-to-noise ratios. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Rationale: Inhomogeneous hypoxic pulmonary vasoconstriction causing regional overperfusion and high capillary pressure is postulated for explaining how high pulmonary artery pressure leads to high-altitude pulmonary edema in susceptible (HAPE-S) individuals. Objective: Because different species of animals also show inhomogeneous hypoxic pulmonary vasoconstriction, we hypothesized that inhomogeneity of lung perfusion in general increases in hypoxia, but is more pronounced in HAPE-S. For best temporal and spatial resolution, regional pulmonary perfusion was assessed by dynamic contrast-enhanced magnetic resonance imaging. Methods: Dynamic contrast-enhanced magnetic resonance imaging and echocardiography were performed during normoxia and after 2 h of hypoxia (Fi(O2) = 0.12) in 11 HAPE-S individuals and 10 control subjects. As a measure for perfusion inhomogeneity, the coefficient of variation for two perfusion parameters (peak signal intensity, time-to-peak) was determined for the whole lung and isogravitational slices. Results: There were no differences in perfusion inhomogeneity between the groups in normoxia. In hypoxia, analysis of coefficients of variation indicated a greater inhomogeneity in all subjects, which was more pronounced in HAPE-S compared with control subjects. Discrimination between HAPE-S and control subjects was best in gravity-dependent lung areas. Pulmonary artery pressure during hypoxia increased from 22 +/- 3 to 53 +/- 9 mm Hg in HAPE-S and 24 +/- 4 to 33 +/- 6 mm Hg in control subjects (mean +/- SD; p < 0.001), respectively. Conclusion: This study shows that hypoxic pulmonary vasoconstriction is inhomogeneous in hypoxia in humans, particularly in HAPE-S individuals where it is accompanied by a greater increase in pulmonary artery pressure compared with control subjects. These findings support the hypothesis of exaggerated and uneven hypoxic pulmonary vasoconstriction in HAPE-S individuals. [ABSTRACT FROM AUTHOR]

Immunosuppressed organ transplant recipients have a markedly increased risk of neoplasia. Among these malignancies acute myeloid leukaemia (AML) is rare. However, until now no case of successful chemotherapy has been reported. We present a 39-year-old male patient who developed AML (FAB M4 Eo) 4 years after renal transplantation and achieved a stable complete remission after induction therapy with standard dose cytarabine and daunorubicin. Remission duration is now 11 months. At present the transplant is functioning well after two additional courses of consolidation chemotherapy with high-dose cytarabine combined with mitoxantrone and idarubicine respectively. Cyclosporin A was given during all cycles of chemotherapy. We conclude that intensive chemotherapy in patients with AML following renal transplantation in good performance status is feasible. [ABSTRACT FROM PUBLISHER]

Abstract 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.

In the spectrum of muonic X-rays ofU measured in coincidence with prompt fission events a structure has been found which is attributed to 2p→1s transitions of the muon attached to heavy fragments. The intensity I of this structure relative to the strength I observed for prompt fission has been determined to be I/ I=(6.0± 2.1) %. Although the experimental significance for the appeareance of this phenomenon is weak, this is the first experimental indication for its occuxence. [ABSTRACT FROM AUTHOR]

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., (© 2023. The Author(s).)

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., Competing Interests: Authors MW, H-UK, and CH declared advisory board membership with Boehringer Ingelheim unrelated to the present study. Authors MK, SB, HH, and FR were employed by the Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Konietzke, Triphan, Eichinger, Bossert, Heller, Wege, Eberhardt, Puderbach, Kauczor, Heußel, Heußel, Risse and Wielpütz.)

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 80 th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRM Emph ) and functional small airway disease (PRM fSAD ), 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 PRM Emph  (r = 0.70 to 0.75, p < 0.001). QDP was distinctly higher than PRM Emph  (mean difference = 35.85 to 40.40) and PRM fSAD (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 PRM Emph  and PRM fSAD . 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 PRM Emph  and PRM fSAD 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., (© 2021. The Author(s).)

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., Competing Interests: Competing interests: JC is a co-prinicipal investigator for the COPDGene study and has received grants from National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI). AG, MB, BL, CI, FR and CD are employees of Boehringer Ingelheim. DAL has received grants from NHLBI, and personal fees from Boehringer Ingelheim, Parexel, Siemens and Veracyte. In addition, DAL has a patent for ‘systems and methods for classifying severity of COPD’ pending. HW has received grants and personal fees from Boehringer Ingelheim, and personal fees from AstraZeneca, Chiesi, GSK, Menarini and Novartis. JV-C has received grants and personal fees from Boehringer Ingelheim and Novartis, and grants from GSK and Siemens Healthineers. AMT has received personal fees, payment for educational talks and expenses payments for work on the FOOTPRINTS steering committee from Boehringer Ingelheim, grants and personal fees from AstraZeneca, CSL Behring and Grifols Biotheraputics, and grants, personal fees and non-finanacial support from Chiesi. RMM has received personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Merck Sharp & Dohme, Mundipharma, Novartis and Roche. WJ has received grants from AstraZeneca and Chiesi. AL-S reports receipt of a study fee for involvement in conducting the FOOTPRINTS study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The carbodiimide-mediated amine coupling of protein ligands to sensor chips coated with anionic polycarboxylate hydrogels, such as carboxymethyl dextran, is the predominant covalent immobilization procedure utilized in optical biosensors, namely surface plasmon resonance (SPR) biosensors. Usually, electrostatic interactions at a slightly acidic pH and low ionic strength are employed to efficiently accumulate neutral and basic ligands on the chip surface, which are then covalently coupled by surface-bound active N-hydroxysuccinimide (NHS) esters. Unfortunately, this approach is not suitable for acidic proteins or other ligands with low isoelectric points (IEPs), such as nucleic acids, because the charge density of the polycarboxylates is greatly reduced at acidic pH or because electrostatic attraction cannot be achieved. To overcome these drawbacks, we have established a charge-reversal approach that allows the preconcentration of acidic proteins above their IEPs. A precisely controlled amount of tertiary amines is applied to reverse the previous anionic surface charge while maintaining carbodiimide compatibility with future protein immobilization. The mechanism of this reversed-charge immobilization approach was demonstrated employing protein A as a model protein and using attenuated total reflectance Fourier transform infrared spectroscopy, dynamic contact angle measurements, colorimetric quantification, and SPR analysis to characterize surface derivatization. Furthermore, even though it had previously proven impossible to preconcentrate DNA electrostatically and to covalently couple it to polyanionic chip surfaces, we demonstrated that our approach allowed DNA to be preconcentrated and immobilized in good yields. Graphical abstract Principle of the covalent immobilization of acidic ligands on reversed-charge zwitterionic sensor chip surfaces.

Background: To assess the prevalence of thrombophilia in patients with central (CRVO) and branch retinal vein occlusion (BRVO)., Methods: In 139 patients with CRVO (n = 88) and BRVO (n = 51) and in 40 healthy controls factor VIII, fibrinogen, antithrombin III, protein C, protein S, activated protein C resistance, anticardiolipin antibodies (ACA), homocysteine, factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T mutation were assessed retrospectively., Results: Elevated factor VIII activity and the homozygous MTHFR C677T mutation were significantly more often found in CRVO and BRVO cases compared to controls. Age-, gender- and C-reactive protein-adjusted logistic regression analysis did not show a significant additive effect of elevated factor VIII activity on the risk of developing CRVO/BRVO. Elevated fibrinogen levels and ACA were significantly more often found in CRVO than amongst controls. No significant differences were found concerning the remaining variables., Conclusions: We suggest elevated fibrinogen levels, ACA and the homozygous MTHFR C677T mutation as potential risk factors for CRVO/BRVO., (© 2014 S. Karger AG, Basel.)

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.

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., (Copyright © 2011 John Wiley & Sons, Ltd.)

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., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Assessment of lung cancer perfusion is impaired by respiratory motion. Imaging times for contrast agent wash-out studies often exceed breath hold capabilities, and respiration triggering reduces temporal resolution. Temporally resolved volume acquisition of entire tumors is required to assess heterogeneity. Therefore, we developed and evaluated an MR measurement technique that exceeds a single breath hold, and provides a variable temporal resolution during acquisition while suspending breath-dependent motion., Materials and Methods: 20 patients with suspected lung cancer were subjected to perfusion studies using a spoiled 3D gradient echo sequence after bolus injection of 0.07 mmol/kg body weight of Gd-DTPA. 10 acquisitions in expiratory breath hold were followed by 50 navigator-triggered acquisitions under free breathing. Post-processing allowed for co-registration of the 3D data sets. An ROI-based visualization of the signal-time curves was performed., Results: In all cases motion-suspended, time-resolved volume data sets (40 x 33 x 10 cm(3), voxel size: 2.1 x 2.1 x 5.0 mm(3)) were generated with a variable, initially high temporal resolution (2.25 sec) that was synchronized with the breath pattern and covered up to 8 1/2 min. In 7 / 20 cases a remaining offset could be reduced by rigid co-registration. The tumors showed fast wash-in, followed by rapid signal decay (8 / 20) or a plateau., Conclusion: The feasibility of a perfusion study with hybrid breath hold and navigator-triggered time-resolved 3D MRI which combines high initial temporal resolution during breath hold with a long wash-out period under free breathing was demonstrated., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

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.

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., ((c) 2007 Wiley-Liss, Inc.)

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.

Recently it has been shown that regional lung perfusion can be assessed using time-resolved contrast-enhanced magnetic resonance (MR) imaging. Quantification of the perfusion images has been attempted, based on definition of small regions of interest (ROIs). Use of complete lung segmentations instead of ROIs could possibly increase quantification accuracy. Due to the low signal-to-noise ratio, automatic segmentation algorithms cannot be applied. On the other hand, manual segmentation of the lung tissue is very time consuming and can become inaccurate, as the borders of the lung to adjacent tissues are not always clearly visible. We propose a new workflow for semi-automatic segmentation of the lung from additionally acquired morphological HASTE MR images. First the lung is delineated semi-automatically in the HASTE image. Next the HASTE image is automatically registered with the perfusion images. Finally, the transformation resulting from the registration is used to align the lung segmentation from the morphological dataset with the perfusion images. We evaluated rigid, affine and locally elastic transformations, suitable optimizers and different implementations of mutual information (MI) metrics to determine the best possible registration algorithm. We located the shortcomings of the registration procedure and under which conditions automatic registration will succeed or fail. Segmentation results were evaluated using overlap and distance measures. Integration of the new workflow reduces the time needed for post-processing of the data, simplifies the perfusion quantification and reduces interobserver variability in the segmentation process. In addition, the matched morphological data set can be used to identify morphologic changes as the source for the perfusion abnormalities.

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.

Purpose: To evaluate a dual-bolus approach to pulmonary perfusion MRI., Materials and Methods: The dual-bolus approach uses a separate low-dose measurement for the arterial input function (AIF) to ensure linearity. The measured AIF is constructed according to a subsequent higher dose used for the tissue concentration curves in the lung. In this study a prebolus of 0.01 mmol/kg followed by doses of 0.04 mmol/kg and 0.08 mmol/kg was used. Measurements were performed using time-resolved two-dimensional fast low-angle shot (2D FLASH) MRI (TE/TR = 0.73 msec/1.73 msec; flip angle = 40 degrees ; generalized autocalibrating partially parallel acquisitions (GRAPPA) factor = 3; temporal resolution = 400 msec) in end-inspiratory breath-hold., Results: The combination of prebolus/0.04 mmol/kg resulted in a pulmonary blood flow (PBF) of 211 +/- 77 mL/min/100 mL, and a pulmonary blood volume (PBV) of 20 +/- 3 mL/100 mL. The combination of prebolus/0.08 mmol/kg resulted in approximately 50% lower perfusion values, most likely due to saturation effects in the lung tissue., Conclusion: A dual-bolus approach to pulmonary perfusion MRI is feasible and may reduce the problem of lacking linear relationship between the contrast-agent concentration and signal intensity.

Objectives: We sought to assess the agreement between lung perfusion ratios calculated from pulmonary perfusion magnetic resonance imaging (MRI) and those calculated from radionuclide (RN) perfusion scintigraphy., Materials and Methods: A retrospective analysis of MR and RN perfusion scans was conducted in 23 patients (mean age, 60 +/- 14 years) with different lung diseases (lung cancer = 15, chronic obstructive pulmonary disease = 4, cystic fibrosis = 2, and mesothelioma = 2). Pulmonary perfusion was assessed by a time-resolved contrast-enhanced 3D gradient-echo pulse sequence using parallel imaging and view sharing (TR = 1.9 milliseconds; TE = 0.8 milliseconds; parallel imaging acceleration factor = 2; partition thickness = 4 mm; matrix = 256 x 96; in-plane spatial resolution = 1.87 x 3.75 mm; scan time for each 3D dataset = 1.5 seconds), using gadolinium-based contrast agents (injection flow rate = 5 mL/s, dose = 0.1 mmol/kg of body weight). The peak concentration (PC) of the contrast agent bolus, the pulmonary blood flow (PBF), and blood volume (PBV) were computed from the signal-time curves of the lung. Left-to-right ratios of pulmonary perfusion were calculated from the MR parameters and RN counts. The agreement between these ratios was assessed for side prevalence (sign test) and quantitatively (Deming-regression)., Results: MR and RN ratios agreed on side prevalence in 21 patients (91%) with PC, in 20 (87%) with PBF, and in 17 (74%) with PBV. The MR estimations of left-to-right perfusion ratios correlated significantly with those of RN perfusion scans (P < 0.01). The correlation was higher using PC (r = 0.67) and PBF (r = 0.66) than using PBV (r = 0.50). The MR ratios computed from PBF showed the highest accuracy, followed by those from PC and PBV. Independently from the MR parameter used, in some patients the quantitative difference between the MR and RN ratios was not negligible., Conclusions: Pulmonary perfusion MRI can be used to assess the differential blood flow of the lung. Further studies in a larger group of patients are required to fully confirm the clinical suitability of this imaging method.

Background and Purpose: Radiofrequency ablation (RFA) is an attractive minimally invasive treatment option for small renal masses. The purpose of this study was to investigate the morphologic imaging appearance of RF lesions immediately after the ablation of kidney tissue using standard clinical MR sequences, as well as to investigate the correlation between MR and gross lesion size., Materials and Methods: Ablations were performed 17 times in a standardized model of ex-vivo perfused porcine kidneys using a resistance-controlled RF device (250 W, 470 kHz) and a nonexpandable bipolar applicator inserted into the center of healthy renal parenchyma. The RF current was applied for 9 minutes at 20 W. Imaging was performed after ablation using standard clinical MR sequences: morphologic T(1)/T(2)- weighted images and an isotropic post-contrast T(1) high-resolution measurement (VIBE). Maximum lesion diameters were measured in three directions and were compared with the measurements of the gross lesions. Histologic (hematoxylin + eosin and nicotinamide adenine dinucleotide staining) and statistical analyses were performed., Results: The gross pathologic examination showed a firm, white-yellow ablation zone sharply demarcated from the untreated tissue. The histologic examination confirmed cellular viability outside but not in the treatment zone. The RF lesions were hyperintense on T(1)-weighted images and hypointense on T(2)-weighted images. The lesion size measured in the VIBE images correlated best with the macroscopic lesion size (N = 16)., Conclusions: Morphologic MR T(1) and T(2) sequences of RF lesions immediately after ablation produce reliable and consistent imaging characteristics. The post-contrast, high-resolution sequence (VIBE) enables the extent of the lesion to be determined accurately. The potential uses of this imaging strategy in clinical practise warrant further investigation on human renal-cell carcinoma.