J.T. Marcus

Monitoring Response to Antiangiogenic Therapy in Non–Small Cell Lung Cancer Using Imaging Markers Derived from PET and Dynamic Contrast-Enhanced MRI

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, 18F-FDG PET, H215O 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 18F-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 Ktrans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor Ktrans values—that is, an increase in regions with low or high Ktrans 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 Ktrans 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.

The Right Ventricle Explains Sex Differences in Survival in Idiopathic Pulmonary Arterial Hypertension

BACKGROUND Male sex is an independent predictor of worse survival in pulmonary arterial hypertension (PAH). This finding might be explained by more severe pulmonary vascular disease, worse right ventricular (RV) function, or different response to therapy. The aim of this study was to investigate the underlying cause of sex differences in survival in patients treated for PAH. METHODS This was a retrospective cohort study of 101 patients with PAH (82 idiopathic, 15 heritable, four anorexigen associated) who were diagnosed at VU University Medical Centre between February 1999 and January 2011 and underwent right-sided heart catheterization and cardiac MRI to assess RV function. Change in pulmonary vascular resistance (PVR) was taken as a measure of treatment response in the pulmonary vasculature, whereas change in RV ejection fraction (RVEF) was used to assess RV response to therapy. RESULTS PVR and RVEF were comparable between men and women at baseline; however, male patients had a worse transplant-free survival compared with female patients (P = .002). Although male and female patients showed a similar reduction in PVR after 1 year, RVEF improved in female patients, whereas it deteriorated in male patients. In a mediator analysis, after correcting for confounders, 39.0% of the difference in transplant-free survival between men and women was mediated through changes in RVEF after initiating PAH medical therapies. CONCLUSIONS This study suggests that differences in RVEF response with initiation of medical therapy in idiopathic PAH explain a significant portion of the worse survival seen in men.

Improvement of cardiac imaging in electrical impedance tomography by means of a new electrode configuration

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 mate 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.

Imaging of thoracic blood volume changes during the heart cycle with electrical impedance using a linear spot-electrode array

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.

The influence of pulsatile flow on blood resistivity in impedance cardiography

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 Vissers (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.

A validation study of stroke volume measurement by means of electrical impedance tomography

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.