Hybrid lipidic and fluorinated polymer microbubbles for blood-brain barrier opening: a comparative study with SonoVue.

Microbubble-mediated focused ultrasound is a promising strategy for transient and localized blood-brain barrier (BBB) permeabilization, enabling drug delivery to the brain. Optimizing microbubble stability and acoustic response is essential to maximize treatment efficiency and minimize potential damage. This study introduces an innovative microbubble formulation with a phospholipid-fluoropolymer shell (LIP-POL), designed to enhance circulation persistence while maintaining a low cavitation threshold.

Novel transferrin receptor-mediated enzyme replacement therapy efficiently treats myogenic and neurogenic aspects of Pompe disease in mice.

Pompe disease (PD) is a multisystemic progressive disease caused by acid-alpha glucosidase (GAA) deficiency. Patients display a spectrum of phenotypes ranging from the severe, rapidly progressive infantile-onset PD (IOPD) form to the slower progressing late-onset PD (LOPD). Enzyme replacement therapies (ERTs) are the only approved treatments; they decrease mortality in IOPD while maintaining or improving motor and respiratory function in LOPD.

Enhancing oxime efficacy into brain using ultrasound to counteract nerve agent exposure.

Organophosphates (OP) found in pesticides and chemical weapons irreversibly inhibit acetylcholinesterases (AChE) and cause toxic accumulation of acetylcholine throughout the organism. Due to their lipophilicity, OP easily cross the blood-brain barrier (BBB) and affect the central nervous system (CNS), resulting in epileptic seizures and long-term cognitive impairment. The antidote includes oximes which reactivate inhibited AChE.

Preoperative PET imaging and fluorescence-guided surgery of human glioblastoma using dual-labeled antibody targeting ET receptors in a preclinical mouse model: A theranostic approach.

Glioblastoma (GBM) poses significant challenges regarding complete tumor removal due to its heterogeneity and invasiveness, emphasizing the need for effective therapeutic options. In the last two decades, fluorescence-guided surgery (FGS), employing fluorophores such as 5-aminolevulinic acid (5-ALA) to enhance tumor delineation, has gained attraction among neurosurgeons. However, some low-grade tumors do not show any accumulation of the tracers, and the lack of patient stratification represents an important limitation.

Low-boiling-point perfluorocarbon nanodroplets for adaptable ultrasound-induced blood-brain barrier opening.

Low-boiling point perfluorocarbon nanodroplets (NDs) are valued as effective sonosensitive agents, encapsulating a liquid perfluorocarbon that would instantaneously vaporize at body temperature without the NDs shell. Those NDs have been explored for both therapeutic and diagnostic purposes. Here, phospholipid-shelled nanodroplets containing octafluoropropane (CF) or decafluorobutane (CF) formed by condensation of microbubbles were thoroughly characterized before blood-brain (BBB) permeabilization.

CMUT for ultrafast passive cavitation detection during ultrasound-induced blood-brain barrier disruption: proof of concept study.

Cavitation dose monitoring plays a key role in ultrasound drug delivery to the brain. The use of capacitive micromachined ultrasonic transducer (CMUT) technology has a great potential for passive cavitation detection (PCD).Here, a circular (diameter 7 mm) CMUT centered at 5 MHz was designed to be inserted into a therapeutic transducer (1.

A longitudinal MRI analysis reveals altered brain connectivity and microstructural changes in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuropathological changes, yet the underlying neurobiological mechanisms remain elusive. Here, we employed a multimodal longitudinal neuroimaging approach, using anatomical and functional sequences on a high field magnetic resonance imaging (MRI) preclinical scanner, to investigate alterations in brain connectivity and white matter microstructure in a transgenic mouse model of AD (J20) when compared to wild-type (WT) littermates. Functional connectivity analysis revealed distinct network disruptions in J20 mice, primarily involving connections between posterior and anterior brain regions; importantly, a significant interaction between group and age highlighted an exacerbation of these connectivity changes with advancing age in J20 mice.

[F]2-fluoro-2-deoxy-sorbitol ([F]FDS) PET imaging repurposed for quantitative estimation of blood-brain barrier permeability in a rat model of Alzheimer's disease.

Numerous studies suggest that blood-brain barrier (BBB) dysfunction may contribute to the progression of Alzheimer's disease (AD). Clinically available neuroimaging methods are needed for quantitative "scoring" of BBB permeability in AD patients. [F]2-fluoro-2-deoxy-sorbitol ([F]FDS), which can be easily obtained from simple chemical reduction of commercial [F]2-fluoro-2-deoxy-glucose ([F]FDG), was investigated as a small-molecule marker of BBB permeability, in a pre-clinical model of AD using in vivo PET imaging.

No observation of DIANA signals in rats at 7.0 and 17.2 Tesla.

Recently, a new method was introduced to detect neuronal activity using Magnetic Resonance Imaging (MRI). The method, referred to as DIANA, showed MRI signals with millisecond temporal resolution that correlated with local field potentials measured invasively in mice. Troublingly, attempts by other groups to detect the DIANA signals in humans at 7 Tesla and mice at 15.

Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction.

The passage of antibodies through the blood-brain barrier (BBB) and the blood-tumoral barrier (BTB) is determinant not only to increase the immune checkpoint inhibitors efficacy but also to monitor prognostic and predictive biomarkers such as the programmed death ligand 1 (PD-L1) via immunoPET. Although the involvement of neonatal Fc receptor (FcRn) in antibody distribution has been demonstrated, its function at the BBB remains controversial, while it is unknown at the BTB. In this context, we assessed FcRn's role by pharmacokinetic immunoPET imaging combined with focused ultrasounds (FUS) using unmodified and FcRn low-affinity IgGs targeting PD-L1 in a preclinical orthotopic glioblastoma model.

Imaging the impact of blood-brain barrier disruption induced by focused ultrasound on P-glycoprotein function.

The P-glycoprotein (P-gp/ABCB1) is a major efflux transporter which impedes the brain delivery of many drugs across the blood-brain barrier (BBB). Focused ultrasound with microbubbles (FUS) enables BBB disruption, which immediate and delayed impact on P-gp function remains unclear. Positron emission tomography (PET) imaging using the radiolabeled substrate [C]metoclopramide provides a sensitive and translational method to study P-gp function at the living BBB.

ImmunoPET imaging-based pharmacokinetic profiles of an antibody and its Fab targeting endothelin A receptors on glioblastoma stem cells in a preclinical orthotopic model.

Background: The resistance of glioblastoma stem cells (GSCs) to treatment is one of the causes of glioblastoma (GBM) recurrence. Endothelin A receptor (ET) overexpression in GSCs constitutes an attractive biomarker for targeting this cell subpopulation, as illustrated by several clinical trials evaluating the therapeutic efficacy of endothelin receptor antagonists against GBM. In this context, we have designed an immunoPET radioligand combining the chimeric antibody targeting ET, chimeric-Rendomab A63 (xiRA63), with Zr isotope and evaluated the abilities of xiRA63 and its Fab (ThioFab-xiRA63) to detect ET tumors in a mouse model xenografted orthotopically with patient-derived Gli7 GSCs.

Behavioral and functional assessment of mice inner ear after chronic exposure to an ultrahigh B field of 11.7 T or 17.2 T.

Purpose: Assess short-term and long-term effects of chronic exposure to an ultrahigh static magnetic (B ) field on mice inner ear in the context of MR safety of human scanning at 11.7 T.

Methods: Mice were chronically exposed to a B field of 11.

Refining the delivery and therapeutic efficacy of cetuximab using focused ultrasound in a mouse model of glioblastoma: An Zr-cetuximab immunoPET study.

Introduction: Glioblastoma (GBM) is the most common and deadly form of primary brain tumor. Between 30 % and 60 % of GBM are characterized by overexpression of the Epidermal Growth Factor Receptor (EGFR). The anti-EGFR antibody Cetuximab (CTX) showed a favorable effect for EGFR colorectal cancer but failed to demonstrate efficacy for GBM.

Retinal functional ultrasound imaging (rfUS) for assessing neurovascular alterations: a pilot study on a rat model of dementia.

Fifty million people worldwide are affected by dementia, a heterogeneous neurodegenerative condition encompassing diseases such as Alzheimer's, vascular dementia, and Parkinson's. For them, cognitive decline is often the first marker of the pathology after irreversible brain damage has already occurred. Researchers now believe that structural and functional alterations of the brain vasculature could be early precursors of the diseases and are looking at how functional imaging could provide an early diagnosis years before irreversible clinical symptoms.

Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state.

Deposits of different abnormal forms of tau in neurons and astrocytes represent key anatomo-pathological features of tauopathies. Although tau protein is highly enriched in neurons and poorly expressed by astrocytes, the origin of astrocytic tau is still elusive. Here, we used innovative gene transfer tools to model tauopathies in adult mouse brains and to investigate the origin of astrocytic tau.

Tumor-targeted superfluorinated micellar probe for sensitive F-MRI.

We describe herein the assembly and in vivo evaluation of a tailor-made micellar carrier system designed for the optimized encapsulation of a superfluorinated MRI probe and further targeting of solid tumors. The in vivo validation was carried out on MC38 tumor-bearing mice which allowed the confirmation of the efficient targeting properties of the nano-carrier, as monitored by 19F-MRI.

Acoustic Transmission Factor through the Rat Skull as a Function of Body Mass, Frequency and Position.

In many transcranial ultrasound studies on rats, the transmission factor is assumed to be independent of animal weight and losses resulting from non-normal incidence angles of the beam are not accounted for. In this study, we measured acoustic transmission factors through 13 excised skulls of male Sprague-Dawley rats weighing between 90 and 520g, at different positions on each skull and at 1, 1.25, 1.