Brain targeting for focused ultrasound essential tremor ablation: proceedings from the 2023 Focused Ultrasound Foundation workshop.

Essential tremor (ET) is the most common movement disorder globally and has negative impacts on quality of life. While medical treatments exist, approximately 50% of patients have tremor that is refractory to medication or experience intolerable medication side effects. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an option for these patients and while incisionless, it is still invasive, although less so than other surgical treatments such as deep brain stimulation and radiofrequency thalamotomy.

Patient-Reported Outcomes and Predictive Factors following Focused Ultrasound Thalamotomy for Essential Tremor.

Introduction: The objectives of this study were to determine long-term patient-reported outcomes with magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET) and to identify risk factors for a poor clinical outcome.

Methods: We administered a telephone or mail-in survey to patients who consecutively underwent unilateral MRgFUS thalamotomy for ET at our institution over an 8-year period. Patients were asked to self-report measures of hand tremor improvement, degree of overall postprocedure improvement, activities of daily life, side effects, and willingness to undergo the procedure again.

Thermal Neuromodulation With Focused Ultrasound: Implications for the Technique of Subthreshold Testing.

Background: During focused ultrasound ablation (FUSA), the presumed stereotactic target is tested with subthreshold sonications before permanent ablation. This testing relies on ultrasound-induced reversible clinical effects (thermal neuromodulation, TN). However, the thermal dose and spot size thresholds to induce TN are not yet defined.

Evaluation of Pseudorandom Sonications for Reducing Cavitation With a Clinical Neurosurgery HIFU Device.

Transcranial high-intensity focused ultrasound is used in clinics for treating essential tremor (ET) and proposed for many other brain disorders. This promising treatment modality requires high energy resulting eventually in undesired cavitation and potential side effects. The goals of the present work were: 1) to evaluate the potential increase of the cavitation threshold using pseudorandom gated sonications and 2) to assess the heating capabilities with such sonications.

Ultrashort echo-time MRI versus CT for skull aberration correction in MR-guided transcranial focused ultrasound: In vitro comparison on human calvaria.

Purpose: Transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) brain treatment systems compensate for skull-induced beam aberrations by adjusting the phase and amplitude of individual ultrasound transducer elements. These corrections are currently calculated based on a preacquired computed tomography (CT) scan of the patient's head. The purpose of the work presented here is to demonstrate the feasibility of using ultrashort echo-time magnetic resonance imaging (UTE MRI) instead of CT to calculate and apply aberration corrections on a clinical TcMRgFUS system.

Head phantoms for transcranial focused ultrasound.

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.

Feasibility and Safety of MR-Guided Focused Ultrasound Lesioning in the Setting of Deep Brain Stimulation.

Background: Patients treated with deep brain stimulation (DBS) often develop symptom progression. If safe, focused ultrasound (FUS) lesioning could be used for patients unable to undergo further DBS surgery.

Objective: To test the feasibility and safety of MR-guided FUS surgery in the setting of a previously implanted DBS system.

Focused ultrasound development and clinical adoption: 2013 update on the growth of the field.

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.

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound.

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.

Trans-cranial focused ultrasound without hair shaving: feasibility study in an ex vivo cadaver model.

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.

Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

FEA modeling of CMUT with membrane stand-off structures to enable selectable frequency-mode operation.

A selectable, dual-frequency, capacitive micro- machined ultrasonic transducer (CMUT) designed for both high-frequency imaging and low-frequency therapeutic effect is presented. A validated finite element analysis (FEA) CMUT model was used to examine the performance of the proposed dual-frequency transducer. CMUT device simulations were used to design a hybrid device incorporating stand-off structures that divide a large, low-frequency membrane into smaller, high-frequency sub-membranes when the membrane is partially collapsed so that the stand-offs contact the substrate.

Construction of a genetic multiplexer to toggle between chemosensory pathways in Escherichia coli.

Many applications require cells to switch between discrete phenotypic states. Here, we harness the FimBE inversion switch to flip a promoter, allowing expression to be toggled between two genes oriented in opposite directions. The response characteristics of the switch are characterized using two-color cytometry.

Filled and unfilled temperature-dependent epoxy resin blends for lossy transducer substrates.

In the context of our ongoing investigation of low-cost 2-dimensional (2-D) arrays, we studied the temperature- dependent acoustic properties of epoxy blends that could serve as an acoustically lossy backing material in compact 2-D array-based devices. This material should be capable of being machined during array manufacture, while also providing adequate signal attenuation to mitigate backing block reverberation artifacts. The acoustic impedance and attenuation of 5 unfilled epoxy blends and 2 filled epoxy blends - tungsten and fiberglass fillers - were analyzed across a 35 degrees C temperature range in 5 degrees C increments.

Wavelength band optimization in spectral near-infrared optical tomography improves accuracy while reducing data acquisition and computational burden.

Multispectral near-infrared (NIR) tomographic imaging has the potential to provide information about molecules absorbing light in tissue, as well as subcellular structures scattering light, based on transmission measurements. However, the choice of possible wavelengths used is crucial for the accurate separation of these parameters, as well as for diminishing crosstalk between the contributing chromophores. While multispectral systems are often restricted by the wavelengths of laser diodes available, continuous-wave broadband systems exist that have the advantage of providing broadband NIR spectroscopy data, albeit without the benefit of the temporal data.

Wavelength dependence of sensitivity in spectral diffuse optical imaging: effect of normalization on image reconstruction.

Near Infrared Diffuse Optical Tomography has the potential to be used as a non-invasive imaging tool for biological tissue specifically for the diagnosis and characterization of breast cancer. Most model based reconstruction algorithms rely on calculating and inverting a large Jacobian matrix. Although this method is flexible for a wide range of complex problems, it usually results in large image artifacts from hypersensitivity around the detectors.

Near infrared optical tomography using NIRFAST: Algorithm for numerical model and image reconstruction.

Diffuse optical tomography, also known as near infrared tomography, has been under investigation, for non-invasive functional imaging of tissue, specifically for the detection and characterization of breast cancer or other soft tissue lesions. Much work has been carried out for accurate modeling and image reconstruction from clinical data. NIRFAST, a modeling and image reconstruction package has been developed, which is capable of single wavelength and multi-wavelength optical or functional imaging from measured data.

Fabrication and evaluation of fully-sampled, two-dimensional transducer array for "Sonic Window" imaging system.

A low-cost, fully-sampled, 3600 element 2D transducer array operating at 5 MHz and designed for use in a hand-held ultrasound system is described here. Four array configurations are presented--(1) array with both matching and pedestal backing layers, (2) array with a matching layer but no backing pedestal, (3) array with a backing pedestal but no matching layer, and (4) array with neither matching layer nor backing pedestal. Each array was characterized in terms of impedance measurements, pulse-echo response, and experimental beamprofile.

High-resolution high-speed panoramic cardiac imaging system.

A panoramic cardiac imaging system consisting of three high-speed CCD cameras has been developed to image the surface electrophysiology of a rabbit heart via fluorescence imaging using a voltage-sensitive fluorescent dye. A robust, unique mechanical system was designed to accommodate the three cameras and to adapt to the requirements of future experiments. A unified computer interface was created for this application - a single workstation controls all three CCD cameras, illumination, stimulation, and a stepping motor that rotates the heart.

An efficient Jacobian reduction method for diffuse optical image reconstruction.

Model based image reconstruction in Diffuse Optical Tomography relies on both the numerical accuracy of the forward model as well as the computational speed and efficiency of the inverse model. Most model based image reconstruction algorithms rely on Newton type inversion methods, whereby the inverse of a large Jacobian is approximated. In this work we present an efficient Jacobian reduction method which takes into account the total sensitivity of the imaging domain to the measured boundary data.