No abstract

Purpose: Mannitol is a hyperosmolar agent for reducing intracranial pressure and inducing osmotic blood–brain barrier opening (OBBBO). There is a great clinical need for a non-invasive method to optimize the safety of mannitol dosing. The aim of this study was to develop a label-free Chemical Exchange Saturation Transfer (CEST)-based MRI approach for detecting intracranial accumulation of mannitol following OBBBO. Methods: In vitro MRI was conducted to measure the CEST properties of D-mannitol of different concentrations and pH. In vivo MRI and MRS measurements were conducted on Sprague-Dawley rats using a Biospec 11.7T horizontal MRI scanner. Rats were catheterized at the internal carotid artery (ICA) and randomly grouped to receive either 1 mL or 3 mL D-mannitol. CEST MR images were acquired before and at 20 min after the infusion. Results: In vitro MRI showed that mannitol has a strong, broad CEST contrast at around 0.8 ppm with a mM CEST MRI detectability. In vivo studies showed that CEST MRI could effectively detect mannitol in the brain. The low dose mannitol treatment led to OBBBO but no significant mannitol accumulation, whereas the high dose regimen resulted in both OBBBO and mannitol accumulation. The CEST MRI findings were consistent with 1H-MRS and Gd-enhanced MRI assessments. Conclusion: We demonstrated that CEST MRI can be used for non-invasive, label-free detection of mannitol accumulation in the brain following BBBO treatment. This method may be useful as a rapid imaging tool to optimize the dosing of mannitol-based OBBBO and improve its safety and efficacy.

Extracellular vesicles (EVs), or exosomes, are naturally occurring nano- and micro-sized membrane vesicles playing an essential role in cell-to-cell communication. There is a recent increasing interest in harnessing the therapeutic potential of these natural nanoparticles to develop cell-free regenerative medicine and manufacture highly biocompatible and targeted drug and gene delivery vectors, amongst other applications. In the context of developing novel and effective EV-based therapy, imaging tools are of paramount importance as they can be used to not only elucidate the underlying mechanisms but also provide the basis for optimization and clinical translation. In this review, recent efforts and knowledge advances on EV-based therapies have been briefly introduced, followed by an outline of currently available labeling strategies by which EVs can be conjugated with various imaging agents and/or therapeutic drugs and genes. A comprehensive review of prevailing EV imaging technologies is then presented along with examples and applications, with emphasis on imaging probes and agents, corresponding labeling methods, and the pros and cons of each imaging modality. Finally, the potential of theranostic EVs as a powerful new weapon in the arsenal of regenerative medicine and nanomedicine is summarized and envisioned.

Here we report a novel approach to detect non-labeled cationic compounds, named modulated saturation transfer (MOST)-MRI, based on their effect of modulating the exchange rate of surrounding exchangeable protons. MOST-MRI was able to detect polyethylenimine (PEI600, M.W. = 600 Da), at a high sensitivity (μM or μg/mL range) through its quenching effects on surrounding fast-exchanging protons. In animals, MOST-MRI detected the tumor uptake of PEI600 that was injected intratumorally at a low dose (50 μg/kg b.w.), indicating the potential of MOST-MRI for label-free imaging guidance that is needed for the development and clinical translation of cationic gene delivery systems.