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Background: Treatment of patients with pulmonary arterial hypertension (PAH) is conventionally based on functional plus invasive measurements obtained during right heart catheterization (RHC). Whether risk assessment during repeated measurements could also be performed on the basis of imaging parameters is unclear, as a direct comparison of strategies is lacking. Research Question: How does the predictive value of noninvasive parameters compare with that of invasive hemodynamic measurements 1 year after the diagnosis of idiopathic PAH? Study Design and Methods: One hundred and eighteen patients with idiopathic PAH who underwent RHC and cardiac MRI (CMR) were included in this study (median time between baseline evaluation and first parameter measures, 1.0 [0.8-1.2] years). Forty-four patients died or underwent lung transplantation. Forward Cox regression analyses were done to determine the best predictive functional, hemodynamic, and/or imaging model. Patients were classified as high risk if the event occurred < 5 years after diagnosis (n = 24), whereas patients without event were classified as low risk. Results: A prognostic model based on age, sex, and absolute values at follow-up of functional parameters (6-min walk distance) performed well (Akaike information criterion [AIC], 279; concordance, 0.67). Predictive models with only hemodynamic (right atrial pressure, mixed venous oxygen saturation; AIC, 322; concordance, 0.66) or imaging parameters (right ventricular ejection fraction; AIC, 331; concordance, 0.63) at 1 year of follow-up performed similarly. The predictive value improved when functional data were combined with either hemodynamic data (AIC, 268; concordance, 0.69) or imaging data (AIC, 273; concordance, 0.70). A model composed of functional, hemodynamic, and imaging data performed only marginally better (AIC, 266; concordance, 0.69). Finally, changes between baseline and 1-year follow-up were observed for multiple hemodynamic and CMR parameters; only a change in CMR parameters was of prognostic predictive value. Interpretation: At 1 year of follow-up, risk assessment based on CMR is at least equal to risk assessment based on RHC. In this study, only changes in CMR, but not hemodynamic parameters, were of prognostic predictive value during the first year of follow-up.

Background Drugs approved for pulmonary arterial hypertension have been considered for patients with heart failure with preserved ejection fraction and combined post- and precapillary pulmonary hypertension (Cpc-PH). We aimed to study changes in cardiac volumes, cardiac load and left ventricular (LV) filling pressures in patients with heart failure with preserved ejection fraction and Cpc-PH in response to pulmonary arterial hypertension-specific treatment. Methods and Results In this prospective study, 23 patients with heart failure with preserved ejection fraction and Cpc-PH underwent right-heart catheterization, including acute provocation testing (fluid loading and inhaled nitric oxide) and cardiac MRI at baseline. Right-heart catheterization and cardiac MRI were repeated after 4 months of treatment. At baseline, acutely increasing preload by fluid loading resulted in a significant increase in pulmonary arterial wedge pressure (PAWP), whereas reducing right ventricular (RV) afterload and increasing LV distensability by acute administration of inhaled nitric oxide had no effect on PAWP. After 4 months of treatment, we observed a significant reduction in RV and LV afterload and increased RV and LV stroke volume, but PAWP significantly increased. Conclusions In patients with heart failure with preserved ejection fraction and Cpc-PH, 4 months of pulmonary arterial hypertension-specific treatment increased RV and LV stroke volume at the expense of increased PAWP. This increase in PAWP was similarly observed acutely after fluid loading.

Introduction PAH impacts right ventricular (RV) structure and function but also leads to changes in the LV due to RV/LV interaction and underfilling. REPAIR, the first PAH study to use a primary endpoint assessed by cardiac MRI (cMRI), reported that RV stroke volume (RVSV) increased by 12 mL and pulmonary vascular resistance (PVR) decreased by 38% from baseline (BL) to Week 26 with macitentan. Purpose To assess the effect of macitentan on LV function in patients with PAH. Methods REPAIR (NCT02310672) was a 52-week, multicentre, open-label, single-arm, phase 4 study assessing the effect of macitentan primarily on RV structure and function, determined by cMRI and right heart catheterisation. Macitentan 10 mg was initiated in treatment-naïve patients, in patients receiving stable background phosphodiesterase type-5 inhibitor (PDE5i) at BL, or in initial combination with PDE5i. Exploratory LV endpoints were assessed by cMRI at Weeks 26 and 52. Safety was assessed up to end of study treatment +30 days in all patients who received ≥1 dose of macitentan (N=87). Patients with BL and Week 26 assessments for both PVR and RVSV were included in the modified Full Analysis Set (mFAS; N=71). Results In the mFAS, 57 (80%) patients were female. At BL, median age was 45 years; median (Q1, Q3) six-minute walk distance was 395 (323, 483) m; 48%/51% of patients were WHO functional class II/III; 59% had idiopathic PAH. Compared to BL, at Weeks 26 and 52 there were significant changes in LV cMRI parameters (table). The most common AEs were peripheral oedema (22%), headache (21%) and dizziness (14%). Conclusions Macitentan led to improvements in LV mass, volume and function, including clinically-relevant increases in LV stroke volume, at both 26 and 52 weeks in patients with PAH. Safety was consistent with other macitentan clinical trial data. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Actelion Pharmaceuticals Ltd

Background In pulmonary arterial hypertension (PAH) patients, the right ventricle (RV) stiffens due to hypertrophy, fibrosis and intrinsic (sarcomeric) stiffness. In these patients, end-diastolic elastance (stiffness, Eed) is associated with parameters of disease severity and predicts mortality. However, the effect of RV stiffness on RV filling and the effect of increased filling pressures on right atrial (RA) function remain elusive. Purpose To examine the relationship between RV diastolic stiffness and RA phasic function and the effect of diastolic dysfunction on ventricular filling in PAH patients. Methods Using single-beat pressure-volume analyses we determined Eed in controls (n=31) and baseline, treatment naive PAH patients (63 idiopathic, 9 hereditary and 25 connective tissue disease associated). We also measured RA reservoir, conduit and active strain by tissue tracking on cardiac magnetic resonance images. Furthermore, interventricular dyssynchrony was defined as a right to left difference in time to peak circumferential strain >52ms (97.5th percentile in controls). Results End-diastolic pressure was higher in PAH patients (16±7 mmHg) than in controls (8±4 mmHg; p Passive filling time of the RV (end-systole until start of atrial contraction) was shorter in patients than in controls (244±136ms vs. 365±103ms; p Conclusion Stiffening of the RV in PAH patients is accompanied by increased filling pressures and decreased RA conduit strain, while there is no correlation between Eed and RA active strain. Higher heart rate and ventricular dyssynchrony lead to shorter passive filling time of the RV, which in turn leads to lower passive filling volume. In contrast, the active filling volume is preserved in these patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organization for Scientific Research

Purpose In this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM). Materials and methods In 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2 ml/kg body weight) was injected intravenously at a speed of 3 ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T1 map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model. Results Sagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T2* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient–echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5 s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5 mm and two acquisitions. Conclusion The proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.

Background: Pharmacokinetic (PK) models can describe microvascular density and integrity. An essential component of PK models is the arterial input function (AIF) representing the time-dependent concentration of contrast agent (CA) in the blood plasma supplied to a tissue. Purpose/Hypothesis: To evaluate a novel method for subject-specific AIF estimation that takes inflow effects into account. Study Type: Retrospective study. Subjects: Thirteen clinical patients referred for spine-related complaints; 21 patients from a study into luminal Crohn's disease with known Crohn's Disease Endoscopic Index of Severity (CDEIS). Field Strength/Sequence: Dynamic fast spoiled gradient echo (FSPGR) at 3T. Assessment: A population-averaged AIF, AIFs derived from distally placed regions of interest (ROIs), and the new AIF method were applied. Tofts' PK model parameters (including v p and K trans ) obtained with the three AIFs were compared. In the Crohn's patients K trans was correlated to CDEIS. Statistical Tests: The median values of the PK model parameters from the three methods were compared using a Mann–Whitney U-test. The associated variances were statistically assessed by the Brown-Forsythe test. Spearman's rank correlation coefficient was computed to test the correlation of K trans to CDEIS. Results: The median v p was significantly larger when using the distal ROI approach, compared to the two other methods (P l 0.05 for both comparisons, in both applications). Also, the variances in v p were significantly larger with the ROI approach (P l 0.05 for all comparisons). In the Crohn's disease study, the estimated K trans parameter correlated better with the CDEIS (r = 0.733, P l 0.001) when the proposed AIF was used, compared to AIFs from the distal ROI method (r = 0.429, P = 0.067) or the population-averaged AIF (r = 0.567, P = 0.011). Data Conclusion: The proposed method yielded realistic PK model parameters and improved the correlation of the K trans parameter with CDEIS, compared to existing approaches. Level of Evidence: 3. Technical Efficacy Stage 1. J. Magn. Reson. Imaging 2018;47:1197–1204.

Cardiac magnetic resonance imaging of the pressure overloaded right ventricle (RV) of precapillary pulmonary hypertension (PH) patients, exhibits late gadolinium enhancement at the interventricular insertion regions, a phenomenon which has been linked to focal fibrosis. Native T1-mapping is an alternative technique to characterize myocardium and has the advantage of not requiring the use of contrast agents. The aim of this study was to characterize the myocardium of idiopathic pulmonary arterial hypertension (IPAH), systemic scleroderma related PH (PAH-Ssc) and chronic thromboembolic PH (CTEPH) patients using native T1-mapping and to see whether native T1-values were related to disease severity. Furthermore, we compared native T1-values between the different precapillary PH categories. Native T1-mapping was performed in 46 IPAH, 14 PAH-SSc and 10 CTEPH patients and 10 control subjects. Native T1-values were assessed using regions of interest at the RV and LV free wall, interventricular septum and interventricular insertion regions. In PH patients, native T1-values of the interventricular insertion regions were significantly higher than the native T1-values of the RV free wall, LV free wall and interventricular septum. Native T1-values at the insertion regions were significantly related to disease severity. Native T1-values were not different between IPAH, PAH-Ssc and CTEPH patients. Native T1-values of the interventricular insertion regions are significantly increased in precapillary PH and are related to disease severity. Native T1-mapping can be developed as an alternative technique for the characterization of the interventricular insertion regions and has the advantage of not requiring the use of contrast agents.

Introduction Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM. Methods Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group. Endpoints Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.

AIMS: This study investigated the relationship between right ventricular (RV) structure and function and survival in idiopathic pulmonary arterial hypertension (IPAH).METHODS AND RESULTS: In 64 patients, cardiac magnetic resonance, right heart catheterization, and the six-minute walk test (6MWT) were performed at baseline and after 1-year follow-up. RV structure and function were analysed as predictors of mortality. During a mean follow-up of 32 months, 19 patients died. A low stroke volume (SV), RV dilatation, and impaired left ventricular (LV) filling independently predicted mortality. In addition, a further decrease in SV, progressive RV dilatation, and further decrease in LV end-diastolic volume (LVEDV) at 1-year follow-up were the strongest predictors of mortality. According to Kaplan-Meier survival curves, survival was lower in patients with an inframedian SV index or= 84 mL/m(2), and an inframedian LVEDVCONCLUSIONS: The RV contains prognostic information in IPAH. A large RV volume, low SV, and a reduced LV volume are strong independent predictors of mortality and treatment failure.

Background— The effect of a mutation in the bone morphogenetic protein receptor 2 ( BMPR2 ) gene on right ventricular (RV) pressure overload in patients with pulmonary arterial hypertension is unknown. Therefore, we investigated RV function in patients who have pulmonary arterial hypertension with and without the BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular tissue. Methods and Results— In total, 95 patients with idiopathic or familial pulmonary arterial hypertension were genetically screened for the presence of a BMPR2 mutation: 28 patients had a BMPR2 mutation, and 67 patients did not have a BMPR2 mutation. In vivo measurements were assessed using right heart catheterization and cardiac MRI. Despite a similar mean pulmonary artery pressure (noncarriers 54±15 versus mutation carriers 55±9 mm Hg) and pulmonary vascular resistance (755 [483–1043] versus 931 [624–1311] dynes·s −1 ·cm −5 ), mutation carriers presented with a more severely compromised RV function (RV ejection fraction: 37.6±12.8% versus 29.0±9%: P −1 ·m −2 ). Differences continued to exist after treatment. To investigate the role of transforming growth factor β and bone morphogenetic protein receptor II signaling, human RV and left ventricular tissue were studied in controls (n=6), mutation carriers (n=5), and noncarriers (n=11). However, transforming growth factor β and bone morphogenetic protein receptor II signaling, and hypertrophy, apoptosis, fibrosis, capillary density, inflammation, and cardiac metabolism, as well, were similar between mutation carriers and noncarriers. Conclusions— Despite a similar afterload, RV function is more severely affected in mutation carriers than in noncarriers. However, these differences cannot be explained by a differential transforming growth factor β, bone morphogenetic protein receptor II signaling, or cardiac adaptation.

Objectives: Our aim was to validate 3-dimensional echocardiography (3DE) for assessment of left ventricular (LV) end-diastolic volume, end-systolic volume (ESV), stroke volume, and ejection fraction (EF) using the freehand-acquisition method. Furthermore, LV volumes by breath hold—versus free breathing—3DE acquisition were assessed and compared with magnetic resonance imaging (MRI). Methods: From the apical position, a fan-like 3DE image was acquired during free breathing and another, thereafter, during breath hold. In 27 patients, 28 breath hold— and 24 free breathing—3DE images were acquired. A total of 17 patients underwent both MRI and 3DE. MRI contours were traced along the outer endocardial contour, including trabeculae, and along the inner endocardial contour, excluding trabeculae, from the LV volume. Results: All 28 (100%) breath hold— and 86% of free breathing—3DE acquisitions could be analyzed. Intraobserver variation (percentual bias ± 2 SD) of end-diastolic volume, ESV, stroke volume, and EF for breath-hold 3DE was, respectively, 0.3 ± 10.2%, 0.3 ± 14.6%, 0.1 ± 18.4%, and −0.1 ± 5.8%. For free-breathing 3DE, findings were similar. A significantly better interobserver variability, however, was observed for breath-hold 3DE for ESV and EF. Comparison of breath-hold 3DE with MRI inner contour showed for end-diastolic volume, ESV, stroke volume, and EF, a percentual bias (± 2 SD) of, respectively, −13.5 ± 26.9%, −17.7 ± 47.8%, −10.6 ± 43.6%, and −1.8 ± 11.6%. Compared with the MRI outer contour, a significantly greater difference was observed, except for EF. Conclusions: 3DE using the freehand method is fast and highly reproducible for (serial) LV volume and EF measurement, and, hence, ideally suited for clinical decision making and trials. Breath-hold 3DE is superior to free-breathing 3DE regarding image quality and reproducibility. Compared with MRI, 3DE underestimates LV volumes, but not EF, which is mainly explained by differences in endocardial contour tracing by MRI (outer contour) and 3DE (inner contour) of the trabecularized endocardium. Underestimation is reduced when breath-hold 3DE is compared with inner contour analysis of the MRI dataset. (J Am Soc Echocardiogr 2003;16:101-9.)

Right ventricular (RV) failure is the main determinant of short-term survival in patients with pulmonary arterial hypertension (PAH). The pathophysiology of the development of RV failure has been incompletely understood. Cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) are advanced, noninvasive imaging techniques that provide in vivo assessment of the RV. These techniques do not only allow global RV morphological and functional evaluation but also enable to study myocardial tissue processes such as perfusion and blood flow, metabolism, neurohormonal activation, and molecular processes such as angiogenesis and apoptosis. Clinical application of advanced imaging techniques have contributed to the discovery of risk factors, monitoring of therapeutic effects, and determination of prognostic factors in patients with PAH. In addition, current and future applications of MRI and PET will likely lead to a better understanding of the pathophysiological pathways that contribute to the development of RV failure. In the near future it can be expected that application of hybrid PET-MRI could be one of the most important developments in order to allow simultaneous, integrated assessment of multiple RV disease processes in vivo.

This systematic review gives an extensive overview of the current state of perfusion-weighted magnetic resonance imaging (MRI) for head and neck squamous cell carcinoma (HNSCC). Pubmed and Embase were searched for literature until July 2014 assessing the diagnostic and prognostic performance of perfusion-weighted MRI in HNSCC. Twenty-one diagnostic and 12 prognostic studies were included for qualitative analysis. Four studies used a T2(∗) sequence for dynamic susceptibility (DSC)-MRI, 29 studies used T1-based sequences for dynamic contrast enhanced (DCE)-MRI. Included studies suffered from a great deal of heterogeneity in study methods showing a wide range of diagnostic and prognostic performance. Therefore we could not perform any useful meta-analysis. Perfusion-weighted MRI shows potential in some aspects of diagnosing HNSCC and predicting prognosis. Three studies reported significant correlations between hypoxia and tumor heterogeneity in perfusion parameters (absolute correlation coefficient |ρ|>0.6, P

Until now, electrical impedance tomography (EIT) has been used for cardiac imaging with the electrodes attached transversally at the level of the fourth intercostal space at the anterior side. However, the results obtained with this electrode configuration have been disappointing. The aim of the present study was to improve the measurement design of EIT for cardiac imaging. Therefore, magnetic resonance imaging (MRI) scans were analysed in two healthy subjects to determine the optimum anatomical plane in which atria and ventricles are clearly visually separated. From these findings, we proposed a new oblique plane at the level of the ictus cordis anteriorly and 10 cm higher posteriorly. EIT pictures obtained in the oblique plane revealed a better visual separation between the ventricles and atria than with the electrodes attached in the transverse plane. Comparison between volume changes measured by means of MRI and impedance changes in different regions of interest measured with EIT were performed with the electrodes in the proposed oblique plane. Ventricular and atrial volume changes measured by MRI show the same pattern as do impedance changes measured by EIT. Furthermore, we assessed the reproducibility and validity of the oblique electrode configuration in ten healthy male volunteers during rest and during exercise compared with the currently used transverse electrode configuration. The reproducibility coefficient assessed from repeated measurements with the electrodes attached in the oblique plane was 0.98 at rest and 0.85 during exercise. For the transverse plane the reproducibility coefficient was 0.96 at rest and 0.66 during exercise. The well-known increase in stroke volume during exercise is 40% in healthy subjects. The increase in impedance change during exercise compared with rest was 34 ± 13% (20-59%) for the oblique plane and 68 ± 57% (13-140%) for the transverse plane. From these results we infer that the stroke volume is assessed more accurately by using the oblique plane. From these findings, we conclude that the oblique plane improved the cardiac measurements, because (i) a better spatial separation of the heart compartments is obtained, (ii) the results are more reliable and (iii) measurements during exercise are more accurate with the electrodes attached in an oblique plane.

End-systolic elastance (E(es)), a load-independent measure of ventricular function, is of clinical interest for studies of the right ventricle (RV) in patients with pulmonary arterial hypertension (PAH). The objective of this study was to determine whether, in PAH patients, E(es) can be estimated from mean pulmonary artery pressure (mPAP) and end-systolic volume (ESV) only.Right heart catheterization was used to measure mPAP. Maximal isovolumic pressure (P(iso)) was estimated from RV pressure curves with the so-called single-beat method. Cardiac magnetic resonance imaging (MRI) was used to assess RV end-diastolic and end-systolic volumes (EDV and ESV). E(es) was then calculated as: E(es) = (P(iso)-mPAP) / (EDV-ESV), and as E(es,V0 = 0) = mPAP/ESV (simplified method, with V0 = 0, is negligible volume at zero pressure). Right ventricular volume at zero pressure (V(0)) was then defined as the intercept of the end-systolic pressure-volume relation (single-beat method) with the horizontal axis.E(es,V0 = 0) was significantly lower compared with E(es) (0.61 vs 1.34 mm Hg/ml, respectively, p0.01). A modified Bland-Altman analysis showed a contractility-dependent difference between E(es,V0 = 0) and E(es). Moreover, V(0) ranged from-8 up to 171 ml, and a moderate and good correlation was found between V(0) and EDV, and V(0) and ESV, respectively (r = 0.65 and r = 0.87, p0.01).These findings show that V(0) is dependent on RV dilation. Therefore, the assumption that V(0) is negligible in PAH is incorrect. Consequently, for an accurate assessment of load-independent RV systolic function, RV volumes and pressure curves are required.

OBJECTIVES: Paralysis of the diaphragm is an uncommon condition, which may result in dyspnoea on excertion and in orthopnea. In patients who have symptoms, the paralysed diaphragm is often plicated to prevent its paradoxical movement on inspiration. This procedure brings relief to many patients, but the mechanism for this improvement is not well understood. METHODS: Nine symptomatic patients who underwent plication of a unilateral paralysed hemidiaphragm were prospectively evaluated. All patients underwent pulmonary function tests and cardiopulmonary exercise tests before surgery and repeated them after surgery. RESULTS: Patients with hemidiaphragm paralysis before surgery were found to have lower tidal volumes at any given ventilation rate during exercise than normal subjects. A clear and consistent change was found in the manner in which patients increased their ventilation during exercise after surgery. All patients showed an increase in tidal volume for a given ventilation rate, which was significant. The plication procedure reduced the respiratory rate for any exercise level in all patients, and this effect was more pronounced during exercise. CONCLUSIONS: In patients with hemidiaphragm paralysis who underwent a diaphragm plication exercise, tidal volumes increased and the ventilatory frequency decreased. Despite this improvement, maximal exercise capacity remained unaltered.

With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non-small cell lung cancer. Methods: Patients were evaluated using an imaging protocol including CT, F-18-FDG PET, H-2 O-15 PET, and dynamic contrast-enhanced MRI to derive measurements on tumor size, glucose metabolism, perfusion, and microvascular permeability. The percentage change in imaging parameters after 3 wk of treatment as compared with baseline was calculated and correlated with progression-free survival (PFS). Results: Forty-four patients were included, and 40 underwent CT and F-18-FDG PET at both time points. Complete datasets, containing all imaging modalities, were available for 14 patients. Bevacizumab and erlotinib treatment resulted in decreased metabolism, perfusion, and tumor size. A decrease in standardized uptake value or tumor perfusion of more than 20% at week 3 was associated with longer PFS (9.7 vs. 2.8 mo, P = 0.01, and 12.5 vs. 2.9 mo, P = 0.009, respectively). Whole-tumor K-trans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor K-trans values-that is, an increase in regions with low or high K-trans values-after 3 wk had shorter PFS (2.3 vs. 7.0 mo, P = 0.008). A partial response, according to the response evaluation criteria in solid tumors (RECIST), at week 3 was also associated with prolonged PFS (4.6 vs. 2.9 mo, P = 0.017). However, 40% of patients with a partial response as their best RECIST response still had stable disease at week 3. In these cases tumor perfusion was already decreased and K-trans heterogeneity showed no increase, indicating that the latter parameters seem to be more discriminative than RECIST at the 3-wk time point. Conclusion: PET and dynamic contrast-enhanced MRI were able to identify patients who benefit from bevacizumab and erlotinib treatment. Molecular imaging seems to allow earlier response evaluation than CT.

To the Editors: As has often been said by Dr Harold C. Urschel Jr, pneumonectomy is “a disease” in itself. It is a major procedure with frequent perioperative complications such as empyema, fistula, cardiac problems or respiratory insufficiency. Besides frequent post-operative cardiac and respiratory complications, long-term sequelae are also seen. After pneumonectomy, anatomical adaptations occur with repositioning of intrathoracic structures. Common changes are elevation of the hemidiaphragm (especially after phrenic nerve damage), mediastinal shift, diminished intercostal space and filling of the postpneumonectomy space with fluid. Infrequently, these adaptations may lead to invalidating complications. The most frequent complication is the so-called post-pneumonectomy syndrome caused by compression of the remaining bronchus against the vertebral column or aorta. Since positioning of the organs may take years, symptoms may occur even after 5–10 yrs. In this letter, we will focus on a rare complication, shunting through a patent foramen ovale (PFO), as a long-term complication of right-sided pneumonectomy or bilobectomy. Only a few cases have been published, although this complication might be under-reported since the diagnosis of PFO is difficult, especially after pneumonectomy. This letter describes three patients who were diagnosed with shunting through a PFO following lung resection. In these patients, right ventricular compression by the elevated right hemidiaphragm was the main cause of PFO and surgical plication of the right hemidiaphragm was sufficient to close the PFO. ### Patient A A 67-yr-old male underwent a right-sided pneumonectomy 14 yrs earlier because of a bronchial carcinoid. Partial resection of the pericardium with transection of the phrenic nerve were needed for complete resection He developed progressive dyspnoea during exercise and when bending down. Echocardiography demonstrated a right-to-left interatrial shunt when increasing intra-abdominal pressure (valsalva manoeuvre) with a shunt fraction of 18%. Further analysis with right heart catheterisation at our institution showed a mean right atrial resting pressure ( P ra …

The product of resistance, R, and compliance, C ( RC time), of the entire pulmonary circulation is constant. It is unknown if this constancy holds for individual lungs. We determined R and C in individual lungs in chronic thromboembolic pulmonary hypertension (CTEPH) patients where resistances differ between both lungs. Also, the contribution of the proximal pulmonary arteries (PA) to total lung compliance was assessed. Patients ( n = 23) were referred for the evaluation of CTEPH. Pressure was measured by right heart catheterization and flows in the main, left, and right PA by magnetic resonance imaging. Total, left, and right lung resistances were calculated as mean pressure divided by mean flow. Total, left, and right lung compliances were assessed by the pulse pressure method. Proximal compliances were derived from cross-sectional area change Δ A and systolic-diastolic pressure difference ΔP (Δ A/ΔP) in main, left, and right PA, multiplied by vessel length. The lung with the lowest blood flow was defined “low flow” (LF), the contralateral lung “high flow” (HF). Total resistance was 0.57 ± 0.28 mmHg·s−1·ml−1, and resistances of LF and HF lungs were 1.57 ± 0.2 vs. 1.00 ± 0.1 mmHg·s−1·ml−1, respectively, P < 0.0001. Total compliance was 1.22 ± 1.1 ml/mmHg, and compliances of LF and HF lung were 0.47 ± 0.11 and 0.62 ± 0.12 ml/mmHg, respectively, P = 0.01. Total RC time was 0.49 ± 0.2 s, and RC times for the LF and HF lung were 0.45 ± 0.2 and 0.45 ± 0.1 s, respectively, not different. Proximal arterial compliance, given by the sum of main, right, and left PA compliances, was only 19% of total lung compliance. The RC time of a single lung equals that of both lungs together, and pulmonary arterial compliance comes largely from the distal vasculature.

Background Cardiovascular Magnetic Resonance (CMR) is an emerging modality in the diagnosis and follow-up of patients with Pulmonary Arterial Hypertension (PAH). Derivation of stroke volume (SV) from the pulmonary flow curves is considered as a standard in this respect. Our aim was to investigate the accuracy of pulmonary artery (PA) flow for measuring SV. Methods Thirty-four PAH patients underwent both CMR and right-sided heart catheterisation. CMR-derived SV was measured by PA flow, left (LV) and right ventricular (RV) volumes, and, in a subset of nine patients also by aortic flow. These SV values were compared to the SV obtained by invasive Fick method. Results For SV by PA flow versus Fick, r = 0.71, mean difference was -4.2 ml with limits of agreement 26.8 and -18.3 ml. For SV by LV volumes versus Fick, r = 0.95, mean difference was -0.8 ml with limits of agreement of 8.7 and -10.4 ml. For SV by RV volumes versus Fick, r = 0.73, mean difference -0.75 ml with limits of agreement 21.8 and -23.3 ml. In the subset of nine patients, SV by aorta flow versus Fick yielded r = 0.95, while in this subset SV by pulmonary flow versus Fick yielded r = 0.76. For all regression analyses, p < 0.0001. Conclusion In conclusion, SV from PA flow has limited accuracy in PAH patients. LV volumes and aorta flow are to be preferred for the measurement of SV.

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r= -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function. Copyright © ERS Journals Ltd 2006.

In pulmonary arterial hypertension (PAH) an increased pulmonary vascular resistance results in chronic pressure overload on the right ventricle and induces pathological right ventricular (RV) remodelling and RV failure. This causes limited exercise capacity, fatigue and increased mortality. Several treatment options have become available for PAH, and in patients given monotherapy, a second drug of a different class is given to improve symptoms and exercise capacity. Whether the addition of a second treatment reverses RV remodelling has not been described. In this study, the phosphodiesterase 5 inhibitor sildenafil was added to treatment with bosentan, an endothelin receptor antagonist. The objective of this study was to investigate whether the addition of sildenafil reverses RV remodelling and further improves RV function in patients with PAH treated with bosentan. In 15 patients with PAH receiving bosentan for one year, sildenafil was added for three months. Sildenafil was started at 50 mg twice daily and increased to 50 mg thrice daily after four weeks. At the start of the study and again after one year of bosentan, right-heart catheterisation with vasoreactivity testing, cardiac magnetic resonance (CMR) and 6 min walk test (6MWT) were performed. N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined after one year of bosentan and after three months of combination therapy. After three months of combination therapy, the effects of the addition of sildenafil were evaluated with …

Aims: Alcohol septal ablation (ASA) has been successful in the treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study is to evaluate the effects of ethanol-induced myocardial infarcts on regional myocardial function using cardiac magnetic resonance (CMR) tissue tagging and 3-dimensional (3D) strain analysis. Methods and results: In nine patients (age 52±15 years) who underwent ASA, CMR was performed prior to and 6 months after the procedure. Regional myocardial mass was evaluated using cine imaging. Myocardial tagging was used to calculate systolic 3D myocardial strain values. These strain values were used to calculate the shortening index (SI), a robust parameter for myocardial contraction. Maximum end-systolic (ES) SI and systolic SI rate were quantified in three circumferential segments: septum, adjacent, and remote (lateral) myocardium. Compared with baseline, septal and non-septal mass decreased at follow-up (from 72±27 to 59±21 g; P=0.008 and from 131±34 to 109±30 g; P=0.008, respectively). In the septum, maximum ES SI and SI rate remained unchanged after ASA. In adjacent myocardium, ES SI remained unchanged, whereas SI rate improved (from -56.5±21.1 to -70.0±16.7%/s; P=0.02). Both ES SI and SI rate improved significantly in remote myocardium (from -16.9±2.8 to -18.8±3.2%; P=0.02 and from -70.3±9.2 to -86.1±15.0%/s; P=0.01, respectively). Conclusion: Reduction of left ventricular (LV) outflow tract obstruction in symptomatic HOCM is associated with a significant reduction in myocardial mass and improvement of intramural systolic function in the lateral (remote) wall, indicating reversed LV remodelling. © The European Society of Cardiology 2006. All rights reserved.

In pulmonary vascular disease, changes in the pulmonary vascular bed will lead to altered pulmonary haemodynamics. This review describes the application of several physiological principles to measure these changes noninvasively by means of novel techniques. Flow characteristics of blood through the pulmonary vascular bed alter in pulmonary vascular disease. Recent developments in magnetic resonance imaging and computed tomography make it possible to visualise and quantify these abnormal flow patterns. Information regarding pulmonary perfusion can also be obtained by measuring the electrical impedance changes in the lung by electrical impedance tomography. A more indirect approach to measure the pulmonary blood flow is the measurement of the absorption of acetylene, a perfusion limited gas. Information on the pulmonary vascular bed can also be obtained by the measurement of exhaled products of the pulmonary vascular endothelium, such as nitric oxide. Although all the techniques described offer new ways to diagnose or monitor pulmonary vascular disease, clinical data on these techniques are limited. Further improvement and evaluation of the clinical value of these techniques are therefore obligatory before they can be used in clinical practice.

Accurate values of global left ventricular (LV) dimensions and mass are important in the diagnosis and prognosis of patients with heart disease. In patients who had a myocardial infarction, it has been proven that enlargement of the LV volume shortly after infarction implies a larger risk for LV remodeling and heart failure [27]. In patients suspected of suffering from ventricular hypertrophy, it is relevant to classify the LV mass accurately as either normal or increased. Also in many other cardiac diseases, such as valvular heart diseases and cardiomyopathies, the global LV dimensions, functional parameters, and mass need to be assessed.

The purpose of the study was to investigate the resistivity change over the cardiac cycle. This is important for the correct application of thoracic impedance cardiography (TIC). The ratio of spatial mean velocity over the vessel radius of the ascending and descending aorta of two female and eight male subjects (age ranging from 23 to 69 years) were measured in supine position using MRI. Based on Visser's (1989) equation the relative resistivity change was calculated. In all subjects the authors found a change of less than 15%, which is smaller than rigid tube experiments predicted. However, the peak resistivity change occurs at the same time as the peak in the impedance signal. Thus, the effects of resistivity changes on stroke volume calculation in TIC needs further investigation.

ECG-gated electrical impedance tomography (EIT) has been developed to monitor blood volume changes. The aim of this study was to compare stroke volume measurements by EIT with established methods of thermodilution and magnetic resonance imaging (MRI). After right cardiac catheterization, EIT measurements were performed in 26 patients. Regression analysis was used to analyze the relation between the EIT results and stroke volume. From the regression line an equation was derived to estimate stroke volume (in ml) by EIT. In a group of eleven healthy subjects this equation was validated to MRI. A strong correlation was found between EIT and stroke volume measured by the thermodilution method (r=0.86). The reproducibility coefficient for EIT measurements was 0.98. The average standard deviation between stroke volume measured by EIT and MRI is 5.4 ml, the mean difference between both methods is 0.7 ml and the coefficient of variation is 8.4%. We conclude that EIT is a valid and reproducible method for the assessment of stroke volume in healthy controls and cardiological patients.

Electrical impedance (EI) measurements conducted on the thorax contain useful information about the changes in blood volume that occur in the thorax during the heart cycle. The aim of this paper is to present a new (tomographic-like) method to obtain this relevant information with electrical impedance measurements, using a linear electrode array. This method is tested on three subjects and the results are compared with results, obtained from magnetic resonance cine-images showing the cross-sectional surface area changes of the aorta, the vena cava, the carotid arteries, and the heart. This paper shows that the different sources of the thoracic EI waveform may be separated in time and location on the thoracic surface and that aortic volume changes may be estimated accurately.

Fur die Diagnose ebenso wie fur die Prognose von Patienten mit Herzerkrankungen sind genaue Werte fur die globale linksventrikulare (LV) Grose und Masse wichtig. So bedeutet bei Patienten nach Myokardinfarkt eine Vergroserung des LV-Volumens schon bald nach dem Ereignis ein groseres Risiko fur LV-Re-modeling und Herzversagen [23]. Auch bei Vermutung einer LV-Hypertrophie ist eine genaue Klassifikation der linksventrikulare Massen — normal oder vergrosert — wichtig. Bei vielen weiteren Herzerkrankungen, wie z.B. Klappenerkrankungen oder Kardiomyopathien, mussen die globalen LV-Grosen, die LV-Funktion und -Masse, quantifiziert werden.

Background: After transmural myocardial infarction (MI), changes occur in intramural myocardial function. This has been described in anterior MI only. The aim of this study was to determine the relation between variable infarct locations and intramural deformation in patients with a first MI. Methods: Forty patients (33 men and 7 women aged 57 ± 11 years) with different infarct-related coronary arteries (25 left anterior descending, 7 circumflex, and 8 right coronary) were studied 6 ± 3 days after infarction with magnetic resonance tissue tagging and 2-dimensional finite element analysis of myocardial deformation. Short-axis tagged images were acquired at base, mid, and apical level. Intramural deformation was measured in 6 circumferential segments per level. Results were compared with 9 age-matched healthy controls. Results: Each infarct area demonstrated a significant reduction of intramural deformation. At mid-ventricular level, segments with maximum impaired intramural function were the anteroseptal segment for left anterior descending-related MI (stretch: 16% vs 33% for controls, P < .001), the posterolateral segment for related MI (stretch: 20% vs 34%, P < .01); and the inferior segment for right coronary artery related MI (stretch: 18% vs 25%, P = .082). In these infarct segments, the intramural regional systolic stretch was more circumferentially oriented compared with radially oriented stretch in the same segments in controls (P < .05). Conclusion: The infarct area can be recognized by a specific spatial pattern of intramural deformation. In infarcted compared with noninfarcted myocardium, deformation is significantly reduced and systolic stretch deviates from the radial direction. Left anterior descending related infarcts were found to have larger regional differences in intramural deformation than circumflex or right coronary artery related MI of enzymatically the same size.

Study objective: The development of right ventricular (RV) hypertrophy in emphysema is accompanied by involvement of the left ventricle (LV) and its systolic function. Our objective was to study the relation between RV hypertrophy and LV ejection fraction in emphysema by means of MRI. Patients: Ten emphysematous patients (FEV1, 0.99±0.32 L; FEV1/vital capacity (VC), 0.32±0.11 [mean±SD]) and 10 age-matched control subjects were included. Exclusion criteria were any history of systemic hypertension, ischemic or valvular heart disease, or episodes of right- and/or left-sided cardiac failure. Measurements and results: Rapid scout imaging was used to measure RV and LV wall mass, wall thickness, and end-diastolic volume. Stroke volume was derived from the main pulmonary artery flow. RV wall volume, RV wall thickness, and the ratio of RV to LV wall thickness were significantly larger in the patient group than in the control group (p

Background: Left ventricular (LV) torsion is an essential component of cardiac contraction in normal heart function, but is impaired in patients with dilated cardiomyopathy. The aim of this study is to determine the predictive value of impaired torsion for the acute response to cardiac resynchronization therapy (CRT) in these patients. Methods: In 35 CRT candidates and 12 controls, basal and apical LV rotations were calculated using MRI tagging. Impaired torsion was quantified by the correlation between both rotations, where a negative value indicates normal torsion and a positive value indicates a torsion disorder: basal and apical rotations follow the same path. This value was called ‘Torcor’. In patients, LV pressure was measured under atrial-sensed ventricular stimulation, using different pacing combinations. Acute response to CRT was defined by >10% increase in invasively measured dP/dtmax from the best pacing configuration relative to baseline. Torcor was compared between responders, non-responders and controls, and ROC-analysis was performed. Results: Torcor was significantly higher in responders (n=18) than in non-responders (n=17) and controls (0.60±0.55, -0.45±0.55 and 0.68±0.22, resp., p

8055 Background: In advanced NSCLC, E and B either as a single agent (E) or in combination with chemotherapy (B) have shown to improve survival. Combinations of targeted agents may prove to be effe...

Objectives: to evaluate cine MRI as a means of determining the two-dimensional pulsatile wall motion (2D-PWM) of abdominal aortic aneurysm (AAA). Design: prospective study of 21 patients with AAA. 2D-PWM was defined as change in cross-sectional area. Results: the median diastolic area was 28cm 2 (intraquartile range, IQR, 22-31 cm2) and the median (IQR) 2D-PWM was 0.25 (0.10-0.40) cm2. Assuming that the AAA is circular in cross-section this represents a median (IQR) diameter increase of 0.3 (0.1-0.4) mm. However, local wall displacements up to 2 mm were present in varying directions, without significant change in surface area. Conclusion: AAA PWM is negligible and may not therefore be a potential tool to assess efficacy of endovascular aneurysm exclusion.

The influence of gravity load on the vestibular system in man was investigated in a centrifuge operating on the free swing principle. The vertical vestibular nystagmus induced by acceleration to 3G was analyzed and compared with reference measurements during 1G. Our data indicate that the effects of increased gravity load include a prolonged decay time constant of upbeat nystagmus and a subject-dependent persisting upbeat nystagmus. In an attempt to explain these findings, an extension of the velocity storage model is proposed, with gravity as a second stimulus function in addition to angular acceleration.