The Introduction of an MR-Conditional Prototype for Cardiopulmonary Bypass Support: Technical Aspects and System Requirements.

Introduction: The use of cardiopulmonary bypass (CBP; also known as a heart-lung machine) in newborns with complex congenital heart defects may result in brain damage. Magnetic resonance imaging (MRI) assessments cannot be performed safely because the metal components used to construct CBP devices may elicit adverse effects on patients when they are placed in a magnetic field. Thus, this project aimed to develop a prototype MR-conditional circulatory support system that could be used to perform cerebral perfusion studies in animal models.

Consensus Statement on High-Intensity Focused Ultrasound for Functional Neurosurgery in Switzerland.

Magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) has evolved into a viable ablative treatment option for functional neurosurgery. However, it is not clear yet, how this new technology should be integrated into current and established clinical practice and a consensus should be found about recommended indications, stereotactic targets, patient selection, and outcome measurements. To sum up and unify current knowledge and clinical experience of Swiss neurological and neurosurgical communities regarding MRgHiFUS interventions for brain disorders to be published as a national consensus paper.

Bilateral staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of essential tremor: a case series study.

Background: Unilateral magnetic resonance-guided focused ultrasound (FUS) thalamotomy is efficacious for the treatment of medically refractory essential tremor (ET). Viability of bilateral FUS ablation is unexplored.

Methods: Patients diagnosed with medically refractory ET and previously treated with unilateral FUS thalamotomy at least 5 months before underwent bilateral treatment.

Investigating the Mechanism of Cyclodextrins in the Treatment of Niemann-Pick Disease Type C Using Crosslinked 2-Hydroxypropyl-β-cyclodextrin.

Niemann-Pick disease type C (NPC) is a severe disorder that is characterized by intracellular transport abnormalities leading to cytoplasmic accumulation of lipids such as cholesterol and sphingolipids. The compound 2-hydroxypropyl-β-cyclodextrin (HPβCD) has high cholesterol complexation capacity and is currently under clinical investigation for the NPC treatment. However, due to its short blood half-life, high doses are required to produce a therapeutic effect.

In-vivo validation of interpolation-based phase offset correction in cardiovascular magnetic resonance flow quantification: a multi-vendor, multi-center study.

Background: A velocity offset error in phase contrast cardiovascular magnetic resonance (CMR) imaging is a known problem in clinical assessment of flow volumes in vessels around the heart. Earlier studies have shown that this offset error is clinically relevant over different systems, and cannot be removed by protocol optimization. Correction methods using phantom measurements are time consuming, and assume reproducibility of the offsets which is not the case for all systems.

Closed-loop cavitation control for focused ultrasound-mediated blood-brain barrier opening by long-circulating microbubbles.

Focused ultrasound (FUS) exposure in the presence of microbubbles (MBs) has been successfully used in the delivery of various sizes of therapeutic molecules across the blood-brain barrier (BBB). While acoustic pressure is correlated with the BBB opening size, real-time control of BBB opening to avoid vascular and neural damage is still a challenge. This arises mainly from the variability of FUS-MB interactions due to the variations of animal-specific metabolic environment and specific experimental setup.

Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes.

In glioblastoma, the benefit from temozolomide chemotherapy is largely limited to a subgroup of patients (30-35%) with tumors exhibiting methylation of the promoter region of the O-methylguanine-DNA methyltransferase (MGMT) gene. In order to allow more patients to benefit from this treatment, we explored magnetic resonance image-guided microbubble-enhanced low-intensity pulsed focused ultrasound (LIFU) to transiently open the blood-brain barrier and deliver a first-in-class liposome-loaded small molecule MGMT inactivator in mice bearing temozolomide-resistant gliomas. We demonstrate that a liposomal O-(4-bromothenyl)guanine (OBTG) derivative can efficiently target MGMT, thereby sensitizing murine and human glioma cells to temozolomide in vitro.

[Focused ultrasound ablation as tremor treatment].

Background: The development of high-intensity magnetic resonance imaging (MRI)-guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of interventional techniques for stereotactic functional neurosurgery of lesions. This has resulted in novel incisionless intervention approaches for the therapy of tremor disorders. The safety and efficacy is documented by recent study data.

Functional lesional neurosurgery for tremor: back to the future?

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson's disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions.

Preparation of PEGylated liposomes incorporating lipophilic lomeguatrib derivatives for the sensitization of chemo-resistant gliomas.

Liposomal delivery is a well-established approach to increase the therapeutic index of drugs, mainly in the field of cancer chemotherapy. Here, we report the preparation and characterization of a new liposomal formulation of a derivative of lomeguatrib, a potent O-methylguanine-DNA methyltransferase (MGMT) inactivator. The drug had been tested in clinical trials to revert chemoresistance, but was associated with a low therapeutic index.

Spatially-segmented undersampled MRI temperature reconstruction for transcranial MR-guided focused ultrasound.

Background: Volumetric thermometry with fine spatiotemporal resolution is desirable to monitor MR-guided focused ultrasound (MRgFUS) procedures in the brain, but requires some form of accelerated imaging. Accelerated MR temperature imaging methods have been developed that undersample k-space and leverage signal correlations over time to suppress the resulting undersampling artifacts. However, in transcranial MRgFUS treatments, the water bath surrounding the skull creates signal variations that do not follow those correlations, leading to temperature errors in the brain due to signal aliasing.

Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound.

Objective: To report results of a prospective trial of unilateral transcranial MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract in essential tremor (ET).

Methods: This was a prospective, uncontrolled, single-center interventional study. Patients with ET fulfilling criteria for interventional therapy received unilateral ablation of the cerebellothalamic tract (CTT) by MRIgFUS.

Feasibility of Diffusion Tractography for the Reconstruction of Intra-Thalamic and Cerebello-Thalamic Targets for Functional Neurosurgery: A Multi-Vendor Pilot Study in Four Subjects.

Functional stereotactic neurosurgery by means of deep brain stimulation or ablation provides an effective treatment for movement disorders, but the outcome of surgical interventions depends on the accuracy by which the target structures are reached. The purpose of this pilot study was to evaluate the feasibility of diffusion tensor imaging (DTI) based probabilistic tractography of deep brain structures that are commonly used for pre- and perioperative targeting for functional neurosurgery. Three targets were reconstructed based on their significance as intervention sites or as a no-go area to avoid adverse side effects: the connections propagating from the thalamus to (1) primary and supplementary motor areas, (2) to somatosensory areas and the cerebello-thalamic tract (CTT).

Minimizing eddy currents induced in the ground plane of a large phased-array ultrasound applicator for echo-planar imaging-based MR thermometry.

Background: The study aims to investigate different ground plane segmentation designs of an ultrasound transducer to reduce gradient field induced eddy currents and the associated geometric distortion and temperature map errors in echo-planar imaging (EPI)-based MR thermometry in transcranial magnetic resonance (MR)-guided focused ultrasound (tcMRgFUS).

Methods: Six different ground plane segmentations were considered and the efficacy of each in suppressing eddy currents was investigated in silico and in operando. For the latter case, the segmented ground planes were implemented in a transducer mockup model for validation.

Correcting heat-induced chemical shift distortions in proton resonance frequency-shift thermometry.

Purpose: To reconstruct proton resonance frequency-shift temperature maps free of chemical shift distortions.

Theory And Methods: Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off-resonance distortions if left uncorrected. We propose an online-compatible algorithm to correct these distortions in 2DFT and echo-planar imaging acquisitions, which is based on a k-space signal model that accounts for proton resonance frequency change-induced phase shifts both up to and during the readout.

Full-wave acoustic and thermal modeling of transcranial ultrasound propagation and investigation of skull-induced aberration correction techniques: a feasibility study.

Background: Transcranial focused ultrasound (tcFUS) is an attractive noninvasive modality for neurosurgical interventions. The presence of the skull, however, compromises the efficiency of tcFUS therapy, as its heterogeneous nature and acoustic characteristics induce significant distortion of the acoustic energy deposition, focal shifts, and thermal gain decrease. Phased-array transducers allow for partial compensation of skull-induced aberrations by application of precalculated phase and amplitude corrections.

A microsurgical bifurcation rabbit model to investigate the effect of high-intensity focused ultrasound on aneurysms: a technical note.

Background: Recent clinical studies confirmed the high potential of MR-guided focused ultrasound (MRgFUS) in the field of functional neurosurgery. While its ability for precise thermo-ablation within soft tissue is widely recognized, the impact of high-intensity focused ultrasound (HIFU) on larger vessels is less explored. We used a bifurcation aneurysm model in rabbits to investigate the possible effects on the walls of vascular aneurysms and to assess the risk and prospect of this procedure for managing neurovascular disorders.

Prolonged survival upon ultrasound-enhanced doxorubicin delivery in two syngenic glioblastoma mouse models.

Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans with a very poor prognosis. Chemotherapeutical treatment of GBMs is limited by the blood-brain barrier (BBB). This physical and metabolic barrier separates the blood from the brain parenchyma and prevents the entry of toxins but also of potentially useful chemotherapeutics from the blood into the brain.

Numerical simulations of clinical focused ultrasound functional neurosurgery.

A computational model utilizing grid and finite difference methods were developed to simulate focused ultrasound functional neurosurgery interventions. The model couples the propagation of ultrasound in fluids (soft tissues) and solids (skull) with acoustic and visco-elastic wave equations. The computational model was applied to simulate clinical focused ultrasound functional neurosurgery treatments performed in patients suffering from therapy resistant chronic neuropathic pain.

A review of numerical and experimental compensation techniques for skull-induced phase aberrations in transcranial focused ultrasound.

The development of phased array transducers and their integration with magnetic resonance (MR) guidance and thermal monitoring has established transcranial MR-guided focused ultrasound (tcMRgFUS) as an attractive non-invasive modality for neurosurgical interventions. The presence of the skull, however, compromises the efficiency of transcranial FUS (tcFUS) therapy, as its heterogeneous nature and acoustic characteristics induce significant phase aberrations and energy attenuation, especially at the higher acoustic frequencies employed in tcFUS thermal therapy. These aberrations may distort and shift the acoustic focus as well as induce heating at the patient's scalp and skull bone.

Noninvasive functional neurosurgery using transcranial MR imaging-guided focused ultrasound.

Unlabelled: Transcranial magnetic resonance imaging-guided focused ultrasound (tcMRgFUS) is a novel technique to supplement the spectrum of established neurosurgical interventions. In contrast to traditional ablative procedures, tcMRgFUS is noninvasive and entirely imaging-guided with continuous temperature measurements at and around the target in real time. It has no trajectory restrictions and does not involve ionizing radiation.

Comparison of temperature processing methods for monitoring focused ultrasound ablation in the brain.

Purpose: To investigate the performance of different reconstruction methods for monitoring temperature changes during transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS).

Materials And Methods: Four different temperature reconstruction methods were compared in volunteers (without heating) and patients undergoing transcranial MRgFUS: single baseline subtraction, multibaseline subtraction, hybrid single baseline/referenceless reconstruction, and hybrid multibaseline/referenceless reconstruction. Absolute temperature error and temporal temperature uncertainty of the different reconstruction methods were analyzed and compared.

Application of Zernike polynomials towards accelerated adaptive focusing of transcranial high intensity focused ultrasound.

Purpose: To study the phase aberrations produced by human skulls during transcranial magnetic resonance imaging guided focused ultrasound surgery (MRgFUS), to demonstrate the potential of Zernike polynomials (ZPs) to accelerate the adaptive focusing process, and to investigate the benefits of using phase corrections obtained in previous studies to provide the initial guess for correction of a new data set.

Methods: The five phase aberration data sets, analyzed here, were calculated based on preoperative computerized tomography (CT) images of the head obtained during previous transcranial MRgFUS treatments performed using a clinical prototype hemispherical transducer. The noniterative adaptive focusing algorithm [Larrat et al.