Three-dimensional quantitative MRI of aerosolized gadolinium-based nanoparticles and contrast agents in isolated ventilated porcine lungs.

PURPOSE: The objective of this study is to evaluate the suitability and performance of ultra-short echo time (UTE) sequences for imaging and quantifying the deposition of nebulized MRI contrast agents in human-sized lungs. METHODS: Nebulization of clinically used contrast agent or gadolinium-based nanoparticles were performed using a commercial jet nebulizer in isolated and ventilated porcine lungs connected to a 3D-printed human upper airways replica. MR images of isolated lungs were acquired on a 3T clinical MR scanner using 3D UTE sequences at different flip angles. RESULTS: 3D acquisitions with isotropic millimetric resolution were obtained in less than 4 min. Images exhibit homogeneous and large MR signal enhancement (above 200%) following nebulization of both types of aerosols. Deposition of aerosol down to the level of the bronchi of secondary lobules was visualized. T1 values and the concentration of nanoparticles obtained by MRI were found to correlate with the amount of nebulized gadolinium3+ ions. CONCLUSION: The distribution of aerosolized gadolinium-based contrast agent or nanoparticles can be visualized and quantified using UTE MRI in large animal ventilated lung model on a clinical MRI scanner. This protocol can be used for assessing and quantifying aerosol regional deposition with high spatial resolution (1 mm 3D isotropic) without ionizing radiation and could be applied in the future for diagnostic or therapeutic applications in patients.

Effect of the Surrounding Magnetic Environment of Temporal Bone on the Fluid Signal Intensity in Human Inner Ear Using a Combined T2 Preparation Pulse and Fluid Attenuated Inversion Pulse Technique.

PURPOSE: Recently, the utility of non-contrast MR endolymphatic hydrops imaging was reported, but the pitfall was indicated based on T2 preparation pulse sensitiveness to local static magnetic field (B0) inhomogeneity. The purpose of this study is to clarify the effects of surrounding magnetic environment of temporal bone to lymphatic fluid signal intensity on the T2 preparation and fluid attenuated inversion recovery pulse combination (T2prep 3D-FLAIR) technique in human inner ear study. METHODS: We prepared a custom-made phantom comprising a chicken leg bone submersed in saline. To evaluate signal characteristics of saline close to bone, multiple TE gradient echoes, T2 relaxation time measurement, and T2prep 3D-FLAIR image were acquired. In the vicinity of the vestibule of a healthy volunteer, similar examinations were executed. Additionally, to investigate the influence of the magnetic environment from B0, the evaluation was performed in five head position settings relative to B0. RESULTS: In both the phantom case and volunteer case, together with T2 star signal intensity attenuation, T2 relaxation time shortening was observed on fluid around bone. Specifically, at the outer edge in the vestibule and cochlea of the volunteer, T2 relaxation time was shorter than that of center of vestibule and that of cochlea. In the T2prep 3D-FLAIR image, higher signal intensity was observed at the same location on the outer edge of them. These results showed that bone affects surrounding fluid magnetic environment. Also, for B0 influence, despite a large area variation ratio, there is no statistically significant difference correlated to orientation within B0. CONCLUSION: The surrounding magnetic environment of the temporal bone affects lymphatic fluid signals of the peripheral part of the human inner ear on T2prep 3D-FLAIR technique.

CHN1 and duane retraction syndrome: Expanding the phenotype to cranial nerves development disease.

Duane retraction syndrome is a congenital eye movement disorder characterized by a failure of abducens nerve to develop normally, resulting in restriction or absence of abduction, adduction, or both, and narrowing of the palpebral fissure and retraction of the globe on attempted adduction. There is a genetic heterogeneity in Duane retraction syndrome (DURS). DURS maps to chromosome 8q13 in some patients, and pathogenic variants in CHN1 and MAFB genes are known to lead to DURS. We report here a child and his father with Duane retraction syndrome, associated to swallowing difficulties and unilateral trapeze aplasia. A whole exome sequencing revealed a heterozygous missense variant in CHN1 gene. This gene encodes GTPase-activating protein and is involved in the assembly of neuronal locomotor circuits. A patient with a 8q deletion has previously been described with a Duane retraction syndrome associated to trapeze aplasia. We provide an additional description to support the role in cranial nerves development of the CHN1 gene.

Nebulised Gadolinium-Based Nanoparticles for a Multimodal Approach: Quantitative and Qualitative Lung Distribution Using Magnetic Resonance and Scintigraphy Imaging in Isolated Ventilated Porcine Lungs.

PURPOSE: This study aims at determining lung distribution of gadolinium-based polysiloxane nanoparticles, AGuIX® (small rigid platform - SRP), as a potential theranostic approach by the pulmonary route. METHODS: First, the aerodynamic size distribution and the aerosol output rate were thoroughly characterized. Then, a multimodal approach using magnetic resonance (MR) and gamma-camera (GC) imaging allows to assess the deposition of the aerosolised nanoparticles in the respiratory tract using isolated ventilated porcine lungs. RESULTS: The SRP has proven to be radiolabelled by radioisotope with a good yield. Crude SRP or radiolabelled ones showed the same aerodynamic size distribution and output as a conventional molecular tracer, as sodium fluoride. With MR and GC imaging approaches, the nebulised dose represented about 50% of the initial dose of nanoparticles placed in the nebuliser. Results expressed as proportions of the deposited aerosol showed approximately a regional aerosol deposition of 50% of the deposited dose in the lungs and 50% in the upper airways. Each technique assessed a homogeneous pattern of deposited nanoparticles in Lungs. MR observed a strong signal enhancement with the SRP, similar to the one obtained with a commonly used MRI contrast agent, gadoterate meglumine. CONCLUSION: As a known theranostic approach by intravenous administration, SRP appeared to be easily aerosolised with a conventional nebuliser. The present work proves that pulmonary administration of SRP is feasible in a human-like model and allows multimodal imaging with MR and GC imaging. This work presents the proof of concept of SRP nebulisation and aims to generate preclinical data for the potential clinical transfer of SRP for pulmonary delivery.

Enhancement of blood vessel visualization in 3D time-of-flight MR angiography utilizing surface array coil.

Array coils play an important role in improving the signal-to-noise ratio (SNR) and achieving parallel imaging; however, one disadvantage of array coils is the nonuniformity of their sensitivity. We propose a simple algorithm to enhance blood vessel visualization in 3D-TOF-MRA (three-dimensional time-of-flight magnetic resonance angiography) utilizing this surface array sensitivity, and we apply it to the MRA data of normal volunteers. We have verified that visualization of peripheral vessels has been remarkably improved.

Contrast-enhanced MR imaging of the endolymphatic sac in patients with sudden hearing loss.

Our objective was to evaluate the frequency of contrast enhancement of the endolymphatic sac in patients with sudden hearing loss. Forty consecutive patients with sudden sensorineural hearing loss (20 males and 20 females; age range 11-82 years), 40 age-matched control subjects, and 5 patients with Meniere's disease were examined using the same imaging protocol on a 1.5-T MR system. Pre- and post-contrast-enhanced T1-weighted 3D spoiled gradient-echo sequence (3D SPGR; TR/TE=23/10 ms, no. of excitations=1, flip angle=30 degrees) images were obtained using a voxel size of 0.6 x 0.7 x 0.8 mm(3). Contrast enhancement in the area of the endolymphatic sac was assessed by two radiologists, and the frequency of contrast enhancement was compared between the three study groups. Enhancement of the ipsilateral endolymphatic sac was observed in 30 of the 40 patients with sudden hearing loss (75%). Twenty of these 30 patients also showed enhancement on the contralateral side, and 1 patient showed enhancement only on the contralateral side. Only 1 of the 5 patients with Meniere's disease showed enhancement. Nine of the 40 control subjects (22.5%) showed enhancement (bilateral enhancement in 5 subjects, unilateral in 4). The frequency of enhancement in patients with sudden hearing loss was significantly higher than that in control subjects ( P<0.0001) or patients with Meniere's disease ( P<0.05). The frequency of contrast enhancement of the endolymphatic sac is significantly increased in patients with sudden hearing loss, but further study is necessary to clarify the relationship between this finding and the pathophysiology of sudden hearing loss.