Ultrasound-triggered oxygen-loaded nanodroplets enhance and monitor cerebral damage from sonodynamic therapy.

In sonodynamic therapy, cellular toxicity from sonosensitizer drugs, such as 5-aminolevulinic acid hydrochloride (5-ALA), may be triggered with focused ultrasound through the production of reactive oxygen species (ROS). Here we show that by increasing local oxygen during treatment, using oxygen-loaded perfluorocarbon nanodroplets (250 +/- 8 nm), we can increase the damage induced by 5-ALA, and monitor the severity by recording acoustic emissions in the brain. To achieve this, we sonicated the right striatum of 16 healthy rats after an intravenous dose of 5-ALA (200 mg/kg), followed by saline, nanodroplets, or oxygen-loaded nanodroplets.

Ultrasound-sensitive nanodroplets achieve targeted neuromodulation.

Focused ultrasound (FUS) offers an attractive tool for non-invasive neuromodulation, addressing a clinical need to develop more minimally invasive approaches that are safer, more tolerable and versatile. In combination with a cavitation agent, the effects of ultrasound can be amplified and localized for therapy. Using c-Fos expression mapping, we show how ultrasound-sensitive nanodroplets can be used to induce either neurosuppression or neurostimulation, without disrupting the blood-brain barrier in rats.

Novel Treatment Approaches for Brain Tumour from a Blood-Brain Barrier Perspective.

For a chemotherapeutic agent to be effective, it must conquer the presence of blood-brain barrier (BBB), which limits the penetration of drugs into the brain. Tumours in the brain compromise the integrity of BBB and result in a highly heterogeneous vasculature, known as blood-brain tumour barrier (BBTB). In this chapter, we firstly highlight the cellular and molecular characteristics of the BBB and BBTB as well as the challenges aroused by BBB/BBTB for drug delivery.

Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor.

The presence of blood-brain barrier (BBB) and/or blood-brain-tumor barriers (BBTB) is one of the main obstacles to effectively deliver therapeutics to our central nervous system (CNS); hence, the outcomes following treatment of malignant brain tumors remain unsatisfactory. Although some approaches regarding BBB disruption or drug modifications have been explored, none of them reach the criteria of success. Convention-enhanced delivery (CED) directly infuses drugs to the brain tumor and surrounding tumor infiltrating area over a long period of time using special catheters.

Chronic Cluster Headache Update and East-West Comparisons: Focusing on Clinical Features, Pathophysiology, and Management.

Purpose Of Review: This review provides an update on chronic cluster headache (CH) focusing on clinical features, pathophysiology, and management as well as comparisons between Eastern and Western populations.

Recent Findings: Chronic CH in Eastern populations was relatively rare, compared to that in Western populations. Lacrimation and/or conjunctival injection is the most frequently reported cranial autonomic symptom, and visual aura is predominant in chronic CH patients.

Novel fractionated ultrashort thermal exposures with MRI-guided focused ultrasound for treating tumors with thermosensitive drugs.

Thermosensitive liposomes represent an important paradigm in oncology, where hyperthermia-mediated release coupled with thermal bioeffects enhance the effectiveness of chemotherapy. Their widespread clinical adoption hinges upon performing controlled targeted hyperthermia, and a leading candidate to achieve this is temperature-based magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS). However, the current approach to hyperthermia involves exposures lasting tens of minutes to hours, which is not possible to achieve in many circumstances because of blood vessel cooling and respiratory motion.

MR-guided Focused Ultrasound Facilitates Sonodynamic Therapy with 5-Aminolevulinic Acid in a Rat Glioma Model.

Glioblastoma multiforme (GBM) continues to have a dismal prognosis and significant efforts are being made to develop more effective treatment methods. Sonodynamic therapy (SDT) is an emerging modality for cancer treatment which combines ultrasound with sonosensitizers to produce a localized cytotoxic effect. It has long been known that ultrasound exposure can cause both thermal and non-thermal bioeffects and it remains an open question to what degree does temperature impact the efficacy of SDT.

Microbubble-assisted MRI-guided focused ultrasound for hyperthermia at reduced power levels.

Purpose: Ultrasound contrast agent microbubbles were combined with magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) as a means to achieve mild hyperthermia at reduced power levels.

Methods: MRgFUS hyperthermia (42°C for 20 min) was evaluated in rabbit thigh muscle or Vx2 tumors using infusions of microbubbles (Definity, 20 µL/kg) or saline (sham) administered over 5 min. The impact of treatments on drug uptake was assessed with liposomal doxorubicin (Caelyx, 2.

Preliminary Investigation of Focused Ultrasound-Facilitated Drug Delivery for the Treatment of Leptomeningeal Metastases.

Leptomeningeal metastases (LM) are a serious complication of cancer in the central nervous system (CNS) and are diagnosed in approximately 5% of patients with solid tumors. Effective treatment using systemically administered therapeutics is hindered by the barriers of the CNS. Ultrasound can mediate delivery of drugs through these barriers.

Characterization of Different Microbubbles in Assisting Focused Ultrasound-Induced Blood-Brain Barrier Opening.

Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening.

Synergistic Effects of Nanodrug, Ultrasound Hyperthermia, and Thermal Ablation on Solid Tumors-An Animal Study.

Objective: Delivery barriers of nanodrug in large tumors due to heterogeneous blood supply, elevated interstitial pressure, and long transport distances can degrade the efficacy of cancer treatment. In this study, we proposed a therapeutic strategy to improve the tumor growth inhibition by injecting pegylated liposomal doxorubicin (PLD), and then applying a short time of ultrasound hyperthermia (HT) on the entire solid tumor, and inflicting ultrasound thermal ablation (Ab) in the low-perfused tumor region.

Methods: BALB/c female mice with an average weight of 20 g were adopted and murine breast cancer cells 4T1 were subcutaneously implanted into the flank.

Non-invasive Photodynamic Therapy in Brain Cancer by Use of Tb-Doped LaF Nanoparticles in Combination with Photosensitizer Through X-ray Irradiation: A Proof-of-Concept Study.

The use of photodynamic therapy (PDT) in the treatment of brain cancer has produced exciting results in clinical trials over the past decade. PDT is based on the concept that a photosensitizer exposed to a specific light wavelength produces the predominant cytotoxic agent, to destroy tumor cells. However, delivering an efficient light source to the brain tumor site is still a challenge.

Pulsed-wave low-dose ultrasound hyperthermia selectively enhances nanodrug delivery and improves antitumor efficacy for brain metastasis of breast cancer.

The clinical application of chemotherapeutics for brain tumors remains a challenge due to limitation of blood-brain barrier/blood-tumor barrier (BBB/BTB). In this study, we investigated the effects of low-dose focused ultrasound hyperthermia (UH) on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer cells (4T1-luc2) expressing firefly luciferase were implanted into mouse striatum as a brain tumor model.

Targeting microbubbles-carrying TGFβ1 inhibitor combined with ultrasound sonication induce BBB/BTB disruption to enhance nanomedicine treatment for brain tumors.

The clinical application of chemotherapy for brain cancer tumors remains a challenge due to difficulties in the transport of therapeutic agents across the blood-brain barrier/blood-tumor barrier (BBB/BTB). In this study, we developed des-octanoyl ghrelin-conjugated microbubbles (GMB) loaded with TGFβ1 inhibitor (LY364947) (GMBL) to induce BBB/BTB disruption for ultrasound (US) sonication with GMBL. The in-vitro stability study showed that GMB was pretty stable over one month.

Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.

The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer.

Targeted delivery of erythropoietin by transcranial focused ultrasound for neuroprotection against ischemia/reperfusion-induced neuronal injury: a long-term and short-term study.

Erythropoietin (EPO) is a neuroprotective agent against cerebral ischemia/reperfusion (I/R)-induced brain injury. However, its crossing of blood-brain barrier is limited. Focused ultrasound (FUS) sonication with microbubbles (MBs) can effectively open blood-brain barrier to boost the vascular permeability.

Detecting blood-brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: a correlation study with contrast-enhanced MRI.

Focused ultrasound combined with an intravascular ultrasound contrast agent can induce transient disruption of the blood-brain barrier, and the blood-brain barrier disruption can be detected by contrast-enhanced MRI. There is, however, no study investigating the ability of various MR methods to detect focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage. Sonication was applied to 15 rat brains with four different doses of ultrasound contrast agent (0, 10, 30, or 50 μL/kg), and contrast-enhanced T1-weighted spin echo, gradient echo images, and longitudinal relaxation rate mapping along with effective transverse relaxation time-weighted and susceptibility-weighted images were acquired.

Pulse sequence and timing of contrast-enhanced MRI for assessing blood-brain barrier disruption after transcranial focused ultrasound in the presence of hemorrhage.

Purpose: To optimize the timing of contrast-enhanced magnetic resonance imaging (MRI) that best indicates blood-brain barrier (BBB) disruption induced by focused ultrasound (FUS) along with an ultrasound contrast agent (UCA) and to verify that the contrast-enhanced spin-echo MRI sequence can indicate the degree and location of BBB disruption in the presence of hemorrhage better than a gradient-echo sequence.

Materials And Methods: Sonication was applied to 12 rat brains with four different doses of UCA to cause variable degrees of hemorrhage. Two imaging sequences were performed to acquire T1-weighted (T1W) images at two time-points after the administration of a T1-shortening contrast agent.