Nebulized liposomal gadobenate dimeglumine contrast formulation for magnetic resonance imaging of larynx and trachea

Abstract

Background: To develop a lipid-stabilized contrast formulation containing gadobenate dimeglumine for clear visualization of the mucosal surfaces of the larynx and trachea for early diagnosis of disease by magnetic resonance imaging.

Methods: The contrast formulation was prepared by loading gadobenate dimeglumine into egg phosphotidylcholine, cholesterol, and sterylamine nanoliposomes using the dehydration-rehydration method. The liposomal contrast formulation was ultrasonically nebulized, and the deposition and coating pattern on explanted pig laryngeal and tracheal segments was examined by inductively coupled plasma atomic emission spectroscopy. The sizes of the nebulized droplets were characterized by photon correlation spectroscopy. The contrast-enhanced mucosal surface images of the larynx and trachea were obtained in a 3.0T magnetic resonance scanner using a T1-weighted spectral presaturation inversion recovery sequence.

Results: Various cationic liposome formulations were compared for their stabilization effects on the droplets containing gadobenate dimeglumine. The liposomes composed of egg phosphotidylcholine, cholesterol, and sterylamine in a molar ratio of 1:1:1 were found to enable the most efficient nebulization and the resulting droplet sizes were narrowly distributed. They also resulted in the most even coating on the laryngeal and tracheal lumen surfaces and produced significant contrast enhancement along the mucosal surface. Such contrast enhancement could help clearer visualization of several disease states, such as intraluminal protrusions, submucosal nodules, and craters.

Conclusion: This lipid-stabilized magnetic resonance imaging contrast formulation may be useful for improving mucosal surface visualization and early diagnosis of disease originating in the mucosal surfaces of the larynx and trachea.

Keywords: gadolinium; lipid; magnetic resonance imaging; mucoadhesion; nebulization; upper airway.

Figure 1

Schematic illustration of the sampling operation for the deposition study of nebulized lipid-stabilized contrast agent on the luminal surface of ex vivo pig laryngeal and tracheal segments.

Figure 2

Average diameter (A), diameter distribution (B), and percentage of small droplets (C) of lipid-stabilized droplets and the control after ultrasonic nebulization. In B, the blue columns represent the volume frequency percentage and the red curve represents the cumulative volume percentage; in the cumulative volume overlay graph, pink indicates L1, black indicates L2, green indicates L3, blue indicates L4 and red indicates the control.

Figure 3

Gadolinium concentrations at different sites on pig tracheal luminal surfaces after nebulization delivery of lipid-stabilized contrast agent and the control.

Figure 4

Transverse magnetic resonance images of ex vivo pig laryngeal (A1 and B1) and tracheal (A2 and B2) segments before and after nebulization delivery of lipid-stabilized contrast agent and the control. Left images, before nebulization; right images, after nebulization.

Figure 5

Transverse magnetic resonance images of ex vivo pig laryngeal and tracheal lumen in successive scanning layers after nebulization delivery of the lipid-stabilized contrast agent. In each image, the left is the larynx, and the right is the tracheal lumen.

Figure 6

Transverse magnetic resonance images of three diseased tissue models before (left column) and after (right column) contrast enhancement by the nebulized lipid-stabilized contrast formulation. (A) Intraluminal protrusion, (B) submucosal nodule, and (C) submucosal crater.