In vivo imaging of carbon nanotube biodistribution using magnetic resonance imaging

International audienceAs novel engineered nanoparticles such as carbon nanotubes (CNTs) are extensively used in nanotechnology due to their superior properties, It becomes critical to fully understand their biodistribution and effect when accidently inhaled. A noninvasive follow-up study would be beneficial to evaluate the blodistribution and effect of nanotube deposition after exposure directly in vivo. Combined helium-3 and proton magnetic resonance resonance (MRI) were used In a rat model to evaluate the biodistribution and biological impact of raw single-wall CNTs (raw-SWCNTs) and superpurified SWCNTs (SP-SWCNTs). The susceptibility effects induced by metal impurity in the intrapulmonary instilled raw-SWCNT samples were large enough to induce a significant drop in magnetic field homogeneity detected In He-3 MR Image acquired under spontaneous breathing conditions using a multiecho radial sequence. No MRI susceptibility variation was observed with SP-SWCNT exposition even though histological analysis confirmed their presence In Instilled lungs. Proton MRI allowed detection of Intravenously injected raw-SWCNTs In spleen and kidneys using gradient echo sequence sensitive to changes of relaxation time values. No signal modifications were observed In the SP-SWCNT Injected group. In Instilled groups, the contrast-to-noise ratio in liver, spleen, and kidneys stayed unchanged and were comparable to values obtained In the control group. Histological analysis confirms the absence of SWCNTs In systemic organs when SWCNTs were Intrapulmonary instilled. In conclusion, the presence of SWCNTs with associated metal Impurities can be detected in vivo by noninvasive MR techniques. Hyperpolarized He-3 can be used for the Investigation of CNT pulmonary biodistribution while standard proton MR can be performed for systemic investigation following injection of CNT solution

Long-term follow-up of lung biodistribution and effect of instilled SWCNTs using multiscale imaging techniques

International audienceDue to their distinctive properties, single-walled carbon nanotubes (SWCNTs) are being more and more extensively used in nanotechnology, with prospects in nanomedicine. It would therefore appear essential to develop and apply appropriate imaging tools for detecting and evaluating their biological impacts with the prospect of medical applications or in the situation of accidental occupational exposure. It has been shown recently that raw SWCNTs with metallic impurities can be noninvasively detected in the lungs by hyperpolarized (3)helium (HP-He-3) MRI. Moreover raw and purified SWCNTs had no acute biological effect. The purpose of the present longitudinal study was to investigate long-term follow-up by imaging, as well as chronic lung effects. In a 3-month follow-up study, multiscale imaging techniques combining noninvasive HP-He-3 and proton (H) MRI to ex vivo light (histopathological analysis) and transmission electron microscopy (TEM) were used to assess the biodistribution and biological effects of intrapulmonary instilled raw SWCNTs. Specific in vivo detection of carbon nanotubes with MRI relied on their intrinsic metal impurities. MRI also has the ability to evaluate tissue inflammation by the follow-up of local changes in signal intensity. MRI and ex vivo microscopy techniques showed that granulomatous and inflammatory reactions were produced in a time and dose dependent manner by instilled raw SWCNTs

Metastability exchange optical pumping low field polarizer for lung magnetic resonance imaging

An extensive improvement of our low field polarizer is described. It produces 3He gas polarized up to 40% in a 6 h decay time storage cell. Production rate was raised by a factor of 10 to 4–5 scc/min thanks to the implementation of a new 10 W laser and a new design of a peristaltic compressor, easier to handle. Some applications of polarized gas are also presented: dynamic images of gas inhalation in the rat as well as a static image of human lungs using hyperpolarized gas were obtained

Free breathing hyperpolarized 3He lung ventilation spiral MR imaging.

International audienceOBJECTIVES: Current clinical hyperpolarized He lung ventilation MR imaging protocols rely on the patient's ability to control inhalation and exhalation and hold their breath on demand. This is impractical for intensive care unit patients under ventilation or for pediatric populations under the age of 3 to 4 years. To address this problem, we propose a free-breathing protocol for hyperpolarized He lung ventilation spiral imaging. This approach was evaluated in vitro and on rabbits. MATERIALS AND METHODS: The protocol was implemented on a clinical 1.5-T magnetic resonance imaging scanner. Ventilation images were acquired using a spiral sequence, in vitro on a lung phantom and in vivo on rabbits, the animal breathing freely from a gas reservoir. Dynamic spiral ventilation images were reconstructed using retrospective Cine synchronization. Magnetic resonance (MR) signal dynamics was modeled taking account of gas inflow and outflow, radiofrequency depolarization and oxygen-induced relaxation. RESULTS: Cine ventilation images acquired in spontaneously breathing rabbits were reconstructed with a temporal resolution of 50 milliseconds. Gas volume variations and time-to-maximum maps were obtained. The numerical model was validated in vitro and in vivo with various gas mixtures. Ventilation parameters (functional residual capacity, tidal volume, and alveolar pO2) were extracted from the MR signal dynamics. CONCLUSIONS: Ventilation imaging can be performed at tidal volume using a simple experimental protocol, without any ventilation device or breath-hold period. Acquisition time, SNR and pO2 decay can be optimized using the developed numerical model. Free-breathing ventilation images can be obtained without artifacts related to motion or gas flow. Lastly, parametric maps can be derived from the time-resolved ventilation images and physiological parameters extracted from the global signal dynamics

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

International audiencePURPOSE: 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