Quantitative Gd-DOTA-based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE-MRI.

Asthma is a chronic respiratory disease, commonly treated with inhaled therapy. Better understanding of the mechanisms of aerosol deposition is required to improve inhaled drug delivery. Three-dimensional ultrashort echo time (UTE) MRI acquisitions at 1.5 T were combined with spontaneous nose-only inhalation of aerosolized gadolinium (Gd) to map the aerosol deposition and to characterize signal enhancement in asthmatic rat lungs. The rats were sensitized to ovalbumin (OVA) to develop asthmatic models and challenged before imaging by nebulization of OVA to trigger asthmatic symptoms. The negative controls were not sensitized or challenged by nebulization of saline. The animal lungs were imaged before and after administration of Gd-based aerosol in freely breathing rats, by using a T1 -weighted 3D UTE sequence. A contrast-enhanced quantitative analysis was performed to assess regional concentration. OVA-sensitized rats had lower signal enhancement and lower deposited aerosol concentration. Their enhancement dynamics showed large inter-subject variability. The signal intensity was homogeneously enhanced for controls while OVA-sensitized rats showed heterogeneous enhancement. Contrast-enhanced 3D UTE was applied with aerosolized Gd to efficiently measure spatially resolved deposition in asthmatic lungs. The small administered dose (around 1 µmol/kg body weight) and the use of standard clinical MRI suggest a potential application for the exploration of asthma.

A Novel Microflow Phantom Dedicated to Ultrasound Microvascular Measurements.

Tumor microvascularization is a biomarker of response to antiangiogenic treatments and is accurately assessed by ultrasound imaging. Imaging modes used to visualize slow flows include Power Doppler imaging, dynamic contrast-enhanced ultrasonography, and more recently, microvascular Doppler. Flow phantoms are used to evaluate the performance of Doppler imaging techniques, but they do not have a steady flow and sufficiently small channels. We report a novel device for robust and stable microflow measurements and the study of the microvascularization. Based on microfluidics technology, the prototype features wall-less cylindrical channels of diameters ranging from as small as 147 up to 436 µm, cast in a soft silicone polymer and perfused via a microfluidic flow pressure controller. The device was assessed using flow rates from 49 to 146 µL/min, with less than 1% coefficient of variation over three minutes, corresponding to velocities of 6 to 142 mm/s. This enabled us to evaluate and confirm the reliability of the Superb Microvascular Imaging Doppler mode compared with the Power Doppler mode at these flow rates in the presence of vibrations mimicking physiological motion.

Aerosol deposition in the lungs of spontaneously breathing rats using Gd-DOTA-based contrast agents and ultra-short echo time MRI at 1.5 Tesla.

PURPOSE: Aerosol toxicology and drug delivery through the lungs, which depend on various parameters, require methods to quantify particle deposition. Intrapulmonary-administered MRI contrast agent combined with lung-specific imaging sequences has been proposed as a high performance technique for aerosol research. Here, aerosol deposition is assessed using ultra-short echo (UTE) sequences. METHODS: Before and after administration of Gd-DOTA-based aerosol delivered nose-only in free-breathing healthy rats, a T1 -weighted 3D UTE sequence was applied in a clinical 1.5 Tesla scanner. Administration lasted 14 min, and the experiment was performed on six rats. A contrast-enhanced quantitative analysis was done. RESULTS: Fifty percent signal enhancement was obtained in the lung parenchyma. Lung clearance of the contrast agent was evaluated to be 14% per h (corresponding to a characteristic clearance time of 3.6 h) and aerosol deposition was shown to be homogeneous throughout the lung in healthy rats. The total deposited dose was estimated to be 1.05 µmol/kg body weight, and the concentration precision was 0.02 mM. CONCLUSION: The UTE protocol with nebulized Gd-DOTA is replicable to significantly enhance the lung parenchyma and to map aerosol deposition. This functional strategy, applied in a clinical system with a clinical nebulization setup and a low inhaled dose, suggests a feasible translation to human.

A temperature-controlled cryogen free cryostat integrated with transceiver-mode superconducting coil for high-resolution magnetic resonance imaging.

Small-sized High Temperature Superconducting (HTS) radiofrequency coils are used in a number of micro-magnetic resonance imaging applications and demonstrate a high detection sensitivity that improves the signal-to-noise ratio. However, the use of HTS coils could be limited by the rarity of cryostats that are suitable for the MR environment. This study presents a magnetic resonance (MR)-compatible and easily operated cryogen-free cryostat based on the pulse tube cryocooler technology for the cooling and monitoring of HTS coils below the temperature of liquid nitrogen. This cryostat features a real-time temperature control function that allows the precise frequency adjustment of the HTS coil. The influence of the temperature on the electrical properties, resonance frequency (f0), and quality factor (Q) of the HTS coil was investigated. Temperature control is obtained with an accuracy of over 0.55 K from 60 K to 86 K, and the sensitivity of the system, extracted from the frequency measurement from 60 K to 75 K, is of about 2 kHz/K, allowing a fine retuning (within few Hz, compared to 10 kHz bandwidth) in good agreement with experimental requirements. We demonstrated that the cryostat, which is mainly composed of non-magnetic materials, does not perturb the electromagnetic field in any way. MR images of a 10 × 10 × 15 mm3 liquid phantom were acquired using the HTS coil as a transceiver with a spatial resolution of 100 × 100 × 300 µm3 in less than 20 min under experimental conditions at 1.5 T.

Design of a fast field-cycling magnetic resonance imaging system, characterization and methods for relaxation dispersion measurements around 1.5 T.

The dependence of the nuclear magnetic resonance relaxation rate on the magnetic field has been widely studied, in particular, in biomedical areas with the objectives to better understand the underlying microscopic mechanisms in tissues and provide biomarkers of diseases. By combining fast-field cycling (FFC) and magnetic resonance imaging (MRI), it is possible to provide localized relaxation dispersion measurements in heterogeneous systems with recent demonstrations in solutions, biological samples, human beings, and small animals. We report here the developments and performances of a device designed for small animal FFC-MRI comprising a resistive insert technology operating inside a 1.5 T MRI system. Specific measurement methods were developed to characterize the system efficiency, response time, homogeneity, stability, and compensation. By adding a non-linear element in the system and using a dual amplifier strategy, it is shown that large field offsets can be produced during relaxation periods while maintaining precise field control during detection periods. The measurement of longitudinal nuclear magnetic relaxation dispersion (NMRD) profiles in the range of 1.08 T-1.92 T is reported, essentially displaying a linear variation in this range for common MRI contrast agents. The slopes of both the longitudinal and transverse relaxation dispersion profiles at 1.5 T are measured and validated, extending the capabilities of previous approaches. The performances of a longitudinal relaxation dispersion mapping method are finally reported, opening the way to quantitative preclinical dispersion imaging studies at a high FFC-MRI field.