MRI-guided focused ultrasound for treating Parkinson's disease with human mesenchymal stem cells.

Parkinson's disease (PD) is a progressive disorder that affects the nervous system and causes regions of the brain to deteriorate. In this study, we investigated the effects of MR-guided focused ultrasound (MRgFUS) for the delivery of human mesenchymal stem cells (MSCs) on the 6-hydroxydopamine (6-HODA)-induced PD rat model. MRgFUS-induced blood-brain barrier (BBB) permeability modulation was conducted using an acoustic controller with the targets at the striatum (ST) and SN.

Repeated 5-aminolevulinic acid mediated sonodynamic therapy using magnetic resonance guided focused ultrasound in rat brain tumour models.

Sonodynamic therapy is an emerging therapeutic approach against brain tumours. However, the treatment scheme and ultrasound parameters have yet to be explored for clinical translation. Our study aimed to optimize ultrasound parameters for sonodynamic therapy (SDT) with 5-ALA as a sonosensitizing agent and to evaluate its therapeutic outcome on the rodent 9L gliosarcoma and the human U87 glioblastoma models.

Investigating the hypotensive effect of focused ultrasound neuromodulation and barbiturate-loaded nanodroplets in healthy and hypertensive rats.

Background: Current strategies for reducing blood pressure (BP) are ineffective and unsafe for many patient populations, including drug-resistant hypertension and during pregnancy. Stimulating the periaqueductal grey (PAG) region has shown promise in treating drug-resistant hypertension in patients using deep brain stimulation.

Objective: To develop a minimally invasive neuromodulation technique for the sustained treatment of hypertension.

Transducer module apodization to reduce bone heating during focused ultrasound uterine fibroid ablation with phased arrays: A numerical study.

Background: During magnetic resonance-guided focused ultrasound (MRgFUS) surgery for uterine fibroids, ablation of fibrous tissues in proximity to the hips and spine is challenging due to heating within the bone that can cause patients to experience pain and potentially damage nerves. This far-field bone heating limits the volume of fibroid tissue that is treatable via MRgFUS.

Purpose: To investigate transducer module apodization for improving the ratio of focal-to-bone heating ( ) when targeting fibroid tissue close to the hips and spine, to enable MRgFUS treatments closer to the bone.

A Transmit-Receive Phased Array for Microbubble-Mediated Focused Ultrasound Brain Therapy in Small Animals.

Unlabelled: Focused ultrasound (FUS) combined with circulating microbubbles (MBs) can be employed for non-invasive, localized agent delivery across the blood-brain barrier (BBB). Previous work has demonstrated the feasibility of clinical-scale transmit-receive phased arrays for performing transcranial therapies under MB imaging feedback.

Objective: This study aimed to design, construct, and evaluate a dual-mode phased array for MB-mediated FUS brain therapy in small animals.

Long-Term Safety and Efficacy of Focused Ultrasound Capsulotomy for Obsessive-Compulsive Disorder and Major Depressive Disorder.

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluated the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD).

Methods: This phase 1, single-center, open-label study recruited patients with treatment-resistant OCD and MDD.

Mild hyperthermia with magnetic resonance- guided high intensity focused ultrasound combined with salvage chemoradiation for recurrent rectal cancer.

Introduction: Pelvic recurrences from rectal cancer present a challenging clinical scenario. Hyperthermia represents an innovative treatment option in combination with concurrent chemoradiation to enhance therapeutic effect. We provide the initial results of a prospective single center feasibility study (NCT02528175) for patients undergoing rectal cancer retreatment using concurrent chemoradiation and mild hyperthermia with MR-guided high intensity focused ultrasound (MR-HIFU).

Inducing cavitation within hollow cylindrical radially polarized transducers for intravascular applications.

Thrombotic occlusions of large blood vessels are increasingly treated with catheter based mechanical approaches, one of the most prominent being to employ aspiration to extract clots through a hollow catheter lumen. A central technical challenge for aspiration catheters is to achieve sufficient suction force to overcome the resistance of clot material entering into the distal tip. In this study, we examine the feasibility of inducing cavitation within hollow cylindrical transducers with a view to ultimately using them to degrade the mechanical integrity of thrombus within the tip of an aspiration catheter.

A Convolutional Neural Network for Beamforming and Image Reconstruction in Passive Cavitation Imaging.

Convolutional neural networks (CNNs), initially developed for image processing applications, have recently received significant attention within the field of medical ultrasound imaging. In this study, passive cavitation imaging/mapping (PCI/PAM), which is used to map cavitation sources based on the correlation of signals across an array of receivers, is evaluated. Traditional reconstruction techniques in PCI, such as delay-and-sum, yield high spatial resolution at the cost of a substantial computational time.

Three-dimensional super resolution ultrasound imaging with a multi-frequency hemispherical phased array.

Background: High resolution imaging of the microvasculature plays an important role in both diagnostic and therapeutic applications in the brain. However, ultrasound pulse-echo sonography imaging the brain vasculatures has been limited to narrow acoustic windows and low frequencies due to the distortion of the skull bone, which sacrifices axial resolution since it is pulse length dependent.

Purpose: To overcome the detect limit, a large aperture 256-module sparse hemispherical transmit/receive array was used to visualize the acoustic emissions of ultrasound-vaporized lipid-coated decafluorobutane nanodroplets flowing through tube phantoms and within rabbit cerebral vasculature in vivo via passive acoustic mapping and super resolution techniques.

A Fully Electronically Steerable Therapeutic Ultrasound Phased Array With MR-Guidance.

Unlabelled: Recently, MRI-guided focused ultrasound (FUS) has shown great promise in treating various conditions non-invasively.

Objective: The focus of this article is to introduce an MRI-guided FUS device, which can provide full electronic steering range without mechanical movement and with low near-field heating. A pilot study was conducted in order to investigate the feasibility, and safety of the device in a large animal model and a pilot clinical trial.

Physical Characterization to Improve Scalability and Potential of Anesthetic-Loaded Nanodroplets.

Drug-loaded perfluorocarbon nanodroplets (NDs) can be activated non-invasively by focused ultrasound (FUS) and allow for precise drug-delivery. Anesthetic-loaded NDs and transcranial FUS have previously achieved targeted neuromodulation. To assess the clinical potential of anesthetic-loaded NDs, in depth physical characterization and investigation of storage strategies and triggered-activation is necessary.

A dataset of rodent cerebrovasculature from in vivo multiphoton fluorescence microscopy imaging.

We present MiniVess, the first annotated dataset of rodent cerebrovasculature, acquired using two-photon fluorescence microscopy. MiniVess consists of 70 3D image volumes with segmented ground truths. Segmentations were created using traditional image processing operations, a U-Net, and manual proofreading.

A PVDF Receiver for Acoustic Monitoring of Microbubble-Mediated Ultrasound Brain Therapy.

The real-time monitoring of spectral characteristics of microbubble (MB) acoustic emissions permits the prediction of increases in blood-brain barrier (BBB) permeability and of tissue damage in MB-mediated focused ultrasound (FUS) brain therapy. Single-element passive cavitation detectors provide limited spatial information regarding MB activity, greatly affecting the performance of acoustic control. However, an array of receivers can be used to spatially map cavitation events and thus improve treatment control.

Anesthetic-loaded nanodroplets with focused ultrasound reduces agitation in Alzheimer's mice.

Objective: Alzheimer's disease (AD) is often associated with neuropsychiatric symptoms, including agitation and aggressive behavior. These symptoms increase with disease severity, ranging from 10% in mild cognitive impairment to 50% in patients with moderate-to-severe AD, pose a great risk for self-injury and injury to caregivers, result in high rates of institutionalization and great suffering for patients and families. Current pharmacological therapies have limited efficacy and a high potential for severe side effects.

Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting.

Diffuse Intrinsic Pontine Glioma (DIPG), now known as Diffuse Midline Glioma (DMG) is a devastating pediatric brain tumor with limited treatment options and a very poor prognosis. Despite more than 250 clinical trials aimed to treat children diagnosed with DMG, no curative therapies currently exist for this patient population. A major obstacle has been the intact blood brain barrier (BBB) which prevents most therapeutics from crossing into the tumor bed.

Blood-brain barrier opening of the default mode network in Alzheimer's disease with magnetic resonance-guided focused ultrasound.

The blood-brain barrier (BBB) protects the brain but is also an important obstacle for the effective delivery of therapeutics in Alzheimer's disease and other neurodegenerative disorders. Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly disrupt the BBB. However, treatment of diffuse regions across the brain along with the effect on Alzheimer's disease relevant pathology need to be better characterized.

Cavitation Feedback Control of Focused Ultrasound Blood-Brain Barrier Opening for Drug Delivery in Patients with Parkinson's Disease.

Magnetic resonance-guided focused ultrasound (MRgFUS), in conjunction with circulating microbubbles, is an emerging technology that can transiently enhance the permeability of the blood-brain barrier (BBB) locally and non-invasively to facilitate targeted drug delivery to the brain. In this clinical trial, the feasibility and safety of BBB modulation in the putamen were evaluated for biweekly therapeutic agent delivery in patients with Parkinson's disease. The performance of the clinical MRgFUS system's cavitation feedback controller for active power modulation throughout the exposures was examined.

The engineered AAV2-HBKO promotes non-invasive gene delivery to large brain regions beyond ultrasound targeted sites.

Magnetic resonance imaging-guided focused ultrasound combined with microbubbles injected in the bloodstream (MRIgFUS) temporarily increases the permeability of the blood-brain barrier (BBB), which facilitates the entry of intravenously administered adeno-associated viruses (AAVs) from the blood to targeted brain areas. To date, the properties of the AAVs used for MRIgFUS delivery resulted in cell transduction limited to MRIgFUS-targeted sites. Considering future clinical applications, strategies are needed to deliver genes to multiple locations and large brain volumes while creating minimal BBB modulation.