Hyperpolarized 3He MR for sensitive imaging of ventilation function and treatment efficiency in young cystic fibrosis patients with normal lung function.

PURPOSE: To assess the sensitivity of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging for the detection of peripheral airway obstruction in younger cystic fibrosis (CF) patients showing normal spirometric results (mean forced expiratory volume in 1 second [FEV(1)], 112% +/- 14.5 [standard deviation]) and to observe the immediate effects of a single chest physical therapy (CPT) session, thereby comparing two image quantification techniques. MATERIALS AND METHODS: Ten pediatric CF patients (age range, 8-16 years) with normal spirometric results were included in this study after approval from the local research ethics committee. Spirometry followed by proton and hyperpolarized (3)He three-dimensional lung imaging were performed with a 1.5-T MR unit before and after 20 minutes of CPT. The number of ventilation defects per image (VDI) and the ventilated lung fraction (VF), defined as the ratio of ventilated lung volume divided by total lung volume, were quantified. RESULTS: Ventilation defects were found in all patients (mean VDI, 5.1 +/- 1.9; mean global VF, 78.5% +/- 12.3; and mean peripheral VF, 75.5% +/- 17.1) despite normal spirometric results. After CPT, disparate changes in the distribution of ventilation defects were observed but the average VDI and VF did not change significantly (mean VDI, 5.1 +/- 1.1; mean global VF, 83.5% +/- 12.2; and mean peripheral VF, 80.3% +/- 12.2). There was no correlation between FEV(1) and VDI (rho = -0.041, P = .863) or global VF (rho = -0.196, P = .408) values but peripheral VF and VDI were correlated (rho = -0.563, P = .011). CONCLUSION: Although spirometric results indicate normal lung function, the mean VDI in patients (5.1) found in this study is well above the VDI in healthy subjects (1.6) reported in the literature. A single CPT session induces disparate changes in the distribution and extent of ventilation defects.

Spatially resolved assessment of serotonin-induced bronchoconstrictive responses in the rat lung using 3He ventilation MRI under spontaneous breathing conditions.

The effect on lung ventilation of bronchoconstriction induced by serotonin (intravenous injection of 50 microg/kg of serotonin) was imaged using a hyperpolarized (3)He MR ventilation protocol in spontaneously breathing rats. Lung function maps assessing airflow obstruction, a key feature in clinical pneumology, were derived from dynamic image series acquired after inhalation of (3)He gas. Dynamic ventilation (3)He MR images spanning a respiratory cycle were obtained using a retrospective cine image reconstruction procedure. Two parameters, defined as signal amplitude and maximum signal decay rate, were derived from the time course of the MR signal for each pixel. These parameters were averaged over regions of interest placed in the lower part of the right and left lungs and submitted to statistical analysis. A homogeneous and significant decrease of signal amplitude and maximum signal decay rate after serotonin injection was observed for each rat on the parametric color maps. The data indicate that dynamic ventilation HP (3)He MRI can be used to assess, in a spatially resolved manner, the ventilation function of spontaneously breathing rats and the effects of agents eliciting short-lasting bronchoconstriction.

Bevacizumab and paclitaxel for breast cancer patients with central nervous system metastases: a case series.

Central nervous system (CNS) metastases are a major concern in patients with stage IV breast cancer. Recent studies have shown the efficacy of anti-vascular endothelial growth factor drugs on brain tumors, in particular glioblastoma, but none has explored their efficacy and tolerance in breast cancer patients with CNS metastases. We report 4 cases of patients with CNS metastases treated with bevacizumab and paclitaxel. All but 1 had previous whole-brain radiation therapy, performance status 0-2, and radiographic evidence of progressive CNS metastases. Patients received paclitaxel 80 mg/m2 on days 1, 8, and 15, and bevacizumab 10 mg/kg on days 1 and 15. Response was evaluated according to the World Health Organization criteria. Three patients had brain metastases, and 1 had meningeal lesions. Only 1 patient was chemotherapy-naive. Significant antitumor activity was observed, with 1 complete response and 3 partial responses in the CNS metastases. With a mean follow-up of 9 months, duration of response was 11, 10, 8, and 6 months. No patient had extra-CNS progression. This observed antitumor activity suggests efficiency of the combination of bevacizumab and paclitaxel and warrants further evaluation of this combination as an alternative option for the treatment of multiple CNS metastases in breast cancer.

Aerosols and gaseous contrast agents for magnetic resonance imaging of the lung.

Magnetic resonance imaging of lungs and the investigation of pulmonary pathologies with this technique are limited by low proton spin density, degraded magnetic homogeneity and motion. Inhaled contrast agents (gases or aerosols) can improve the diagnostic value of MRI for lung. Paramagnetic contrast agents such as gadolinium chelates aerosol or dioxygen gas increase the relaxivity of proton in lung parenchyma and can be used to assess the ventilated fraction of the bronchoalveolar space. Similarly, inhalation of non proton-MRI nuclei such as perfluorinated gas or hyperpolarized gases ((3)He or (129)Xe) can provide functional ventilation image. In this review paper, the principles, the practical implementation, the limitations and possible safety issues of these different techniques are summarized. The main pre-clinical and clinical applications of these approaches based on oral contrast agents are reviewed and illustrated with cutting-edge lung MRI studies.

Quantitative measurements of regional lung ventilation using helium-3 MRI in a methacholine-induced bronchoconstriction model.

PURPOSE: To demonstrate ventilation changes in an animal model of methacholine-induced bronchoconstriction using hyperpolarized (HP) helium-3 (He-3) MRI. MATERIALS AND METHODS: Bronchoconstriction was induced in 11 healthy rats using an intravenous injection of methacholine. The He-3 was laser-polarized using a custom-built system. MRI studies were performed on a 2-Tesla bore magnet. Coronal dynamic ventilation images were obtained using a single inhalation of the laser-polarized He-3 gas before and after methacholine injection. Ventilation image series were processed on a pixel-by-pixel basis to generate three regional ventilation parameters: gas flow rate, filling time, and maximum gas volume. Student's paired t-test was used for analysis. RESULTS: Ventilation image series with a temporal resolution of 5 msec were obtained before and after methacholine challenge. Quantitative regional gas dynamic information demonstrated statistically significant differences between the baseline and constricted states. Following methacholine injection, the mean flow values were significantly lower for the right lung (RL) (P = 0.006) and left lung (LL) (P = 0.024), while the mean filling time was found to be greater (RL: P = 0.08, LL: P = 0.021). Gas volume values at maximum inspiration were found to be significantly lower after methacholine (RL: P = 0.002; LL: P = 0.036). CONCLUSION: He-3 MRI demonstrated and quantified regional ventilation changes in bronchoconstriction conditions in rats.