Magnetization transfer contrast (MTC) experiments using off-resonance irradiation have been performed with an agar gel model by systematically varying offset frequency, amplitude of the RF irradiation and gel concentration. The experimental results are shown to be quantitatively modelled by a two-pool system consisting of a liquid pool with a Lorentzian line shape and a small semisolid pool with a Gaussian lineshape. The fitted model yields physically realistic fundamental parameters with a T2 of the semisolid pool of 13 microseconds. Further analysis shows that the off-resonance irradiation MTC experiment had significant limitations in its ability to saturate the semisolid pool without directly affecting the liquid component.
A powerful magnetic nanoprobe with folic acid (FA)‐targeting ligands is fabricated by dendrimer functionalization of Fe3O4 nanoparticles (NPs) precoated with crosslinkable and biocompatible polymer multilayer shells. This magnetic probe allows for magnetic resonance imaging of FA receptor‐overexpressing tumor cells in vitro and of an early‐stage tumor model in vivo (see picture).
We demonstrated a unique approach that combines a layer‐by‐layer (LbL) self‐assembly method with dendrimer chemistry to functionalize Fe3O4 nanoparticles (NPs) for specific targeting and imaging of cancer cells. In this approach, positively charged Fe3O4 NPs (8.4 nm in diameter) synthesized by controlled co‐precipitation of FeII and FeIII ions were modified with a bilayer composed of polystyrene sulfonate sodium salt and folic acid (FA)‐ and fluorescein isothiocyanate (FI)‐functionalized poly(amidoamine) dendrimers of generation 5 (G5.NH2‐FI‐FA) through electrostatic LbL assembly, followed by an acetylation reaction to neutralize the remaining surface amine groups of G5 dendrimers. Combined flow cytometry, confocal microscopy, transmission electron microscopy, and magnetic resonance imaging studies show that Fe3O4/PSS/G5.NHAc‐FI‐FA NPs can specifically target cancer cells overexpressing FA receptors. The present approach to functionalizing Fe3O4 NPs opens a new avenue to fabricating various NPs for numerous biological sensing and therapeutic applications.
The feasibility of brain MRI with laser-polarized 129Xe in a small animal model is demonstrated. Naturally abundant 129Xe is polarized and introduced into the lungs of Sprague-Dawley rats. Polarized xenon gas dissolves in the blood and is transported to the brain where it accumulates in brain tissue. Spectroscopic studies reveal a single, dominant, tissue-phase NMR resonance in the head at 194.5 ppm relative to the gas phase resonance. Images of 129Xe in the rat head were obtained with 98-microliter voxels by 2D chemical shift imaging and show that xenon is localized to the brain. This work establishes that nuclear polarization produced in the gas phases survives transport to the brain where it may be imaged. Increases in polarization and delivered volume of 129Xe will allow clinical measurements of regional cerebral blood flow.
Rationale and Objectives
Acoustic droplet vaporization (ADV) shows promise for spatial control and acceleration of thermal lesion production. Our hypothesis was that microbubbles generated by ADV could enhance high intensity focused ultrasound (HIFU) thermal ablation by controlling and increasing local energy absorption.
Materials and Methods
Thermal lesions were produced in tissue-mimicking phantoms using focused ultrasound (1.44 MHz) with a focal intensity of 4000 W·cm-2 in degassed water at 37°C. The average lesion volume was measured by visible change in optical opacity and by T2-weighted MRI. In addition, in vivo HIFU lesions were generated in a canine liver before and after an intravenous injection of droplets with a similar acoustic setup.
Results
Thermal lesions were seven-fold larger in phantoms containing droplets (3×105 droplets/mL) compared to phantoms without droplets. The mean lesion volume with a 2 s HIFU exposure in droplet-containing phantoms was comparable to that made by a 5 s exposure in phantoms without droplets. In the in vivo study, the average lesion volumes without and with droplets were 0.017 ± 0.006 cm3 (n = 4, 5 s exposure) and 0.265 ± 0.005 cm3 (n = 3, 5 s exposure), respectively – a factor of 15 difference. The shape of ADV bubbles imaged with B-mode ultrasound was very similar to the actual lesion shape as measured optically and by MRI.
Conclusion
ADV bubbles may facilitate clinical HIFU ablation by reducing treatment time or requisite in situ total acoustic power, and provide ultrasonic imaging feedback of the thermal therapy.
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