Publications by authors named "Kassell N"

Article Synopsis
  • MR-guided focused ultrasound (MRgFUS) enables outpatient, incisionless treatment for brain lesions.
  • Currently, it’s approved for essential tremor and Parkinson's disease, but new technology is expanding its use to other brain conditions.
  • Ongoing advancements are enhancing the safety, ease, and effectiveness of MRgFUS treatments.
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The Focused Ultrasound Foundation was created to improve the lives of millions of people worldwide by accelerating the development of this noninvasive technology. The Foundation works to clear the path to global adoption by organizing and funding research, fostering collaboration, and building awareness among patients and professionals. Since its establishment in 2006, the Foundation has become the largest nongovernmental source of funding for focused ultrasound research.

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Objective: Histotripsy is an ultrasound-based treatment modality relying on the generation of targeted cavitation bubble clouds, which mechanically fractionate tissue. The purpose of the current study was to investigate the in vivo feasibility, including dosage requirements and safety, of generating well-confined destructive lesions within the porcine brain utilizing histotripsy technology.

Methods: Following a craniectomy to open an acoustic window to the brain, histotripsy pulses were delivered to generate lesions in the porcine cortex.

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Oncology and cerebrovascular disease constitute two of the most common diseases afflicting the central nervous system. Standard of treatment of these pathologies is based on multidisciplinary approaches encompassing combination of interventional procedures such as open and endovascular surgeries, drugs (chemotherapies, anti-coagulants, anti-platelet therapies, thrombolytics), and radiation therapies. In this context, therapeutic ultrasound could represent a novel diagnostic/therapeutic in the armamentarium of the surgeon to treat these diseases.

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Thermal dose and absorbed radiation dose have historically been difficult to compare because different biological mechanisms are at work. Thermal dose denatures proteins and the radiation dose causes DNA damage in order to achieve ablation. The purpose of this paper is to use the proportion of cell survival as a potential common unit by which to measure the biological effect of each procedure.

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OBJECTIVE In appropriate candidates, the treatment of medication-refractory mesial temporal lobe epilepsy (MTLE) is primarily surgical. Traditional anterior temporal lobectomy yields seizure-free rates of 60%-70% and possibly higher. The field of magnetic resonance-guided focused ultrasound (MRgFUS) is an evolving field in neurosurgery.

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Purpose: In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focused ultrasound (tcMRgFUS), ex-vivo studies wlkiith whole human skulls are of great use in improving the underlying technology guiding the accurate and precise thermal ablation of clinically relevant targets in the human skull. Described here are the designs, methods for fabrication, and notes on utility of three different ultrasound phantoms to be used for brain focused ultrasound research.

Methods: Three different models of phantoms are developed and tested to be accurate, repeatable experimental options to provide means to further this research.

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The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significant growth, particularly over the past decade. The eventual widespread clinical adoption of this non-invasive therapeutic modality require continued progress, in a multitude of activities including technical, pre-clinical, and clinical research, regulatory approval and reimbursement, manufacturer growth, and other commercial and public sector investments into the field, all within a multi-stakeholder environment. We present here a snapshot of the field of focused ultrasound and describe how it has progressed over the past several decades.

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Article Synopsis
  • The study investigates the potential safety risks of acoustic inertial cavitation during a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery, highlighting the need for animal studies before clinical trials.
  • The research was conducted using ten piglets that underwent sonication to analyze the effects of varying acoustic energy and power on the brain.
  • Results showed two distinct types of lesions: thermal ablation lesions linked to ischemic infarction and hemorrhagic lesions caused by inertial cavitation, indicating the complexity of safety concerns in ultrasound procedures.
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Background And Purpose: The vasoconstrictor endothelin-1 (ET-1) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Previous results showed that CGS 26303, an endothelin converting enzyme (ECE) inhibitor, effectively prevented and reversed arterial narrowing in animal models of SAH. In the present study, we assessed the effect of CGS 26303 on neurological deficits in SAH rats.

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Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve temperatures capable of inducing coagulative necrosis at acceptable power deposition levels. CT is usually used for this refocusing but requires a separate study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to determine whether MRI using an appropriate sequence would be a viable alternative to CT for planning ultrasound refocusing in TcMRgFUS.

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Background: Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using in vivo porcine and ex vivo human skull models to provide a clinically relevant proof of concept.

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Purpose: To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement.

Materials And Methods: With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included.

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Background And Purpose: MR imaging-guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue. The goal of this study was to describe MR imaging findings pre- and post-ventralis intermedius nucleus lesioning by MR imaging-guided focused sonography as a treatment for essential tremor and to determine whether there was an association between these imaging features and the clinical response to MR imaging-guided focused sonography.

Materials And Methods: Fifteen patients with medication-refractory essential tremor prospectively gave consent; were enrolled in a single-site, FDA-approved pilot clinical trial; and were treated with transcranial MR imaging-guided focused sonography.

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Background: Intracranial hemorrhage has a mortality rate of up to 40-60% due to the lack of effective treatment. Magnetic resonance-guided focused ultrasound may offer a breakthrough noninvasive technology, by allowing accurate delivery of focused ultrasound, under the guidance of real-time magnetic resonance imaging.

Aim: The purpose of the current study was to optimize the acoustic parameters of magnetic resonance-guided focused ultrasound for effective clot liquefaction, in order to evaluate the feasibility of magnetic resonance-guided focused ultrasound for thrombolysis.

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Object: Intravenous sodium nitrite has been shown to prevent and reverse cerebral vasospasm in a primate model of subarachnoid hemorrhage (SAH). The present Phase IIA dose-escalation study of sodium nitrite was conducted to determine the compound's safety in humans with aneurysmal SAH and to establish its pharmacokinetics during a 14-day infusion. Methods In 18 patients (3 cohorts of 6 patients each) with SAH from a ruptured cerebral aneurysm, nitrite (3 patients) or saline (3 patients) was infused.

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Intracerebral hemorrhage remains a significant cause of morbidity and mortality. Current surgical therapies aim to use a minimally invasive approach to remove as much of the clot as possible without causing undue disruption to surrounding neural structures. Transcranial MR-guided focused ultrasound (MRgFUS) surgery is an emerging technology that permits a highly concentrated focal point of ultrasound energy to be deposited to a target deep within the brain without an incision or craniotomy.

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Objective: Gamma Knife radiosurgery (GKRS) is a minimally invasive technique employed in the treatment of intracranial arteriovenous malformations (AVMs). Patients experience a low incidence of complications following treatment. As long-term follow-up data became available, some late adverse effects have been reported.

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Object: Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube.

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Objective: Despite the frequency with which ventriculoperitoneal shunts are placed, ventricular catheter revision rates remains as high as 30%-40% at 1 year. Many neurosurgeons place ventricular catheters "blindly" depending on anatomical landmarks and personal experience. To determine whether intraoperative ultrasonography is beneficial for ventricular catheter placement, we performed a historical cohort study comparing shunts placed with intraoperative ultrasound (US) guidance to those placed blindly.

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In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient's head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220- and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer.

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