Magnetic resonance cavitation imaging for the monitoring of ultrasound therapies.

Focused ultrasound (FUS) is a promising non-invasive therapeutic approach that can be used to generate thermal and non-thermal bioeffects. Several non-thermal FUS therapies rely on FUS-induced oscillations of microbubbles (MBs), a phenomenon referred to as cavitation. Cavitation monitoring in real time is essential to ensure both the efficacy and the safety of FUS therapies.

FUS-mediated BBB opening leads to transient perfusion decrease and inflammation without acute or chronic brain lesion.

The permeabilization of the BBB to deliver therapeutics with MR-guided FUS redefines therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, the evaluation of hemodynamic modifications in the CNS is necessary to refine treatment parameters. MR-guided FUS was applied at 1.

Optimal low-intensity pulsed ultrasound stimulation for promoting anti-inflammatory effects in macrophages.

In this paper, we stimulated M1-like macrophages (obtained from U937 cells) with low-intensity pulsed ultrasound (LIPUS) to lower pro-inflammatory cytokine production. A systematic screening of different frequencies, intensities, duty cycles, and exposure times was performed. The optimal stimulation conditions leading to a marked decrease in the release of inflammatory cytokines were determined to be 38 kHz, 250 mW/cm, 20%, and 90 min, respectively.

Simultaneous proton resonance frequency T - MR shear wave elastography for MR-guided focused ultrasound multiparametric treatment monitoring.

Purpose: To develop an efficient MRI pulse sequence to simultaneously measure multiple parameters that have been shown to correlate with tissue nonviability following thermal therapies.

Methods: A 3D segmented EPI pulse sequence was used to simultaneously measure proton resonance frequency shift (PRFS) MR thermometry (MRT), T relaxation time, and shear wave velocity induced by focused ultrasound (FUS) push pulses. Experiments were performed in tissue mimicking gelatin phantoms and ex vivo bovine liver.

Mechanical high-intensity focused ultrasound creates unique tumor debris enhancing dendritic cell-induced T cell activation.

Introduction: tumor ablation releases a unique repertoire of antigens from a heterogeneous population of tumor cells. High-intensity focused ultrasound (HIFU) is a completely noninvasive ablation therapy that can be used to ablate tumors either by heating (thermal (T)-HIFU) or by mechanical disruption (mechanical (M)-HIFU). How different HIFU ablation techniques compare with respect to their antigen release profile, their activation of responder T cells, and their ability to synergize with immune stimuli remains to be elucidated.

A new versatile MR-guided high-intensity focused ultrasound (HIFU) device for the treatment of musculoskeletal tumors.

Magnetic Resonance (MR) Imaging-guided High Intensity focused Ultrasound (MRgHIFU) is a non-invasive, non-ionizing thermal ablation therapy that is particularly interesting for the palliative or curative treatment of musculoskeletal tumors. We introduce a new modular MRgHIFU device that allows the ultrasound transducer to be positioned precisely and interactively over the body part to be treated. A flexible, MR-compatible supporting structure allows free positioning of the transducer under MRI/optical fusion imaging guidance.

Simulation, Implementation and Measurement of Defined Sound Fields for Blood-Brain Barrier Opening in Rats.

The blood-brain barrier (BBB) is the most important obstacle to delivery of therapeutics to the central nervous system. Low-intensity pulsed focused ultrasound (FUS) in combination with microbubbles applied under magnetic resonance imaging (MRI) control provides a non-invasive and safe technique for BBB opening (BBBo). In rodent models, however, settings and application protocols differ significantly.

Noninvasive disconnection of targeted neuronal circuitry sparing axons of passage and nonneuronal cells.

Objective: Surgery can be highly effective for the treatment of medically intractable, neurological disorders, such as drug-resistant focal epilepsy. However, despite its benefits, surgery remains substantially underutilized due to both surgical concerns and nonsurgical impediments. In this work, the authors characterized a noninvasive, nonablative strategy to focally destroy neurons in the brain parenchyma with the goal of limiting collateral damage to nontarget structures, such as axons of passage.

Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry.

Surgical intervention can be quite effective for treating certain types of medically intractable neurological diseases. This approach is particularly useful for disorders in which identifiable neuronal circuitry plays a key role, such as epilepsy and movement disorders. Currently available surgical modalities, while effective, generally involve an invasive surgical procedure, which can result in surgical injury to non-target tissues.

A Breast-Specific MR Guided Focused Ultrasound Platform and Treatment Protocol: First-in-Human Technical Evaluation.

Objective: This paper presents and evaluates a breast-specific magnetic resonance guided focused ultrasound (MRgFUS) system. A first-in-human evaluation demonstrates the novel hardware, a sophisticated tumor targeting algorithm and a volumetric magnetic resonance imaging (MRI) protocol.

Methods: At the time of submission, N = 10 patients with non-palpable T0 stage breast cancer have been treated with the breast MRgFUS system.

Empirical and Theoretical Characterization of the Diffusion Process of Different Gadolinium-Based Nanoparticles within the Brain Tissue after Ultrasound-Induced Permeabilization of the Blood-Brain Barrier.

Low-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the diffusion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. Three compounds were tested (MultiHance, Gadovist, and Dotarem).

Real-time 3D ultrasound based motion tracking for the treatment of mobile organs with MR-guided high-intensity focused ultrasound.

Introduction: Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatments of mobile organs require locking the HIFU beam on the targeted tissue to maximise heating efficiency. We propose to use a standalone 3 D ultrasound (US)-based motion correction technique using the HIFU transducer in pulse-echo mode. Validation of the method was performed in vitro and in vivo in the liver of pig under MR-thermometry.

Reconstruction of nonlinear ultrasound field of an annular therapeutic array from acoustic holograms of its individual elements.

Acoustic holography method has been shown to provide accurate reconstruction of 3D ultrasound fields generated by various medical transducers including multi-element arrays as well as to set a boundary condition for nonlinear field modeling at high pressure levels. Here an approach of measuring holograms of individual array elements for modeling of an entire array field is proposed and tested for a 3 MHz 16-element annular array (48 mm diameter and 35 mm radius of curvature). The array is a part of a high intensity focused ultrasound system with magnetic resonance guidance used for developing thermal and mechanical methods of tissue ablation in mouse tumors.

Supersonic transient magnetic resonance elastography for quantitative assessment of tissue elasticity.

Non-invasive, quantitative methods to assess the properties of biological tissues are needed for many therapeutic and tissue engineering applications. Magnetic resonance elastography (MRE) has historically relied on external vibration to generate periodic shear waves. In order to focally assess a biomaterial or to monitor the response to ablative therapy, the interrogation of a specific region of interest by a focused beam is desirable and transient MRE (t-MRE) techniques have previously been developed to accomplish this goal.

Real-time monitoring of tissue displacement and temperature changes during MR-guided high intensity focused ultrasound.

Purpose: The therapy endpoint most commonly used in MR-guided high intensity focused ultrasound is the thermal dose. Although namely correlated with nonviable tissue, it does not account for changes in mechanical properties of tissue during ablation. This study presents a new acquisition sequence for multislice, subsecond and simultaneous imaging of tissue temperature and displacement during ablation.

Non-Invasive, Focal Disconnection of Brain Circuitry Using Magnetic Resonance-Guided Low-Intensity Focused Ultrasound to Deliver a Neurotoxin.

Disturbances in the function of neuronal circuitry contribute to most neurologic disorders. As knowledge of the brain's connectome continues to improve, a more refined understanding of the role of specific circuits in pathologic states will also evolve. Tools capable of manipulating identified circuits in a targeted and restricted manner will be essential not only to expand our understanding of the functional roles of such circuits, but also to therapeutically disconnect critical pathways contributing to neurologic disease.

In vivo MR guided boiling histotripsy in a mouse tumor model evaluated by MRI and histopathology.

Boiling histotripsy (BH) is a new high intensity focused ultrasound (HIFU) ablation technique to mechanically fragmentize soft tissue into submicrometer fragments. So far, ultrasound has been used for BH treatment guidance and evaluation. The in vivo histopathological effects of this treatment are largely unknown.

Magnetic resonance-guided motorized transcranial ultrasound system for blood-brain barrier permeabilization along arbitrary trajectories in rodents.

Background: Focused ultrasound combined with microbubble injection is capable of locally and transiently enhancing the permeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) guidance enables to plan, monitor, and characterize the BBB disruption. Being able to precisely and remotely control the permeabilization location is of great interest to perform reproducible drug delivery protocols.

Concurrent Visualization of Acoustic Radiation Force Displacement and Shear Wave Propagation with 7T MRI.

Manual palpation is a common and very informative diagnostic tool based on estimation of changes in the stiffness of tissues that result from pathology. In the case of a small lesion or a lesion that is located deep within the body, it is difficult for changes in mechanical properties of tissue to be detected or evaluated via palpation. Furthermore, palpation is non-quantitative and cannot be used to localize the lesion.

Development of a high-field MR-guided HIFU setup for thermal and mechanical ablation methods in small animals.

Background: Thermal and mechanical high intensity focused ultrasound (HIFU) ablation techniques are in development for non-invasive treatment of cancer. However, knowledge of in vivo histopathologic and immunologic reactions after HIFU ablation is still limited. This study aims to create a setup for evaluation of different HIFU ablation methods in mouse tumors using high-field magnetic resonance (MR) guidance.

Magnetic resonance imaging assessment of effective ablated volume following high intensity focused ultrasound.

Under magnetic resonance (MR) guidance, high intensity focused ultrasound (HIFU) is capable of precise and accurate delivery of thermal dose to tissues. Given the excellent soft tissue imaging capabilities of MRI, but the lack of data on the correlation of MRI findings to histology following HIFU, we sought to examine tumor response to HIFU ablation to determine whether there was a correlation between histological findings and common MR imaging protocols in the assessment of the extent of thermal damage. Female FVB mice (n = 34), bearing bilateral neu deletion tumors, were unilaterally insonated under MR guidance, with the contralateral tumor as a control.

Defining the optimal age for focal lesioning in a rat model of transcranial HIFU.

This study aimed at determining the optimal age group for high-intensity focused ultrasound (HIFU) experiments for producing lesions in rats. Younger rats have thinner skulls, allowing for the acoustic waves to propagate easily through the skull without causing burns of the skin and brain surface. Younger rats however, have a smaller brain that can make HIFU focusing in the brain parenchyma challenging because of the focus size.

Magnetic resonance thermometry at 7T for real-time monitoring and correction of ultrasound induced mild hyperthermia.

While Magnetic Resonance Thermometry (MRT) has been extensively utilized for non-invasive temperature measurement, there is limited data on the use of high field (≥7T) scanners for this purpose. MR-guided Focused Ultrasound (MRgFUS) is a promising non-invasive method for localized hyperthermia and drug delivery. MRT based on the temperature sensitivity of the proton resonance frequency (PRF) has been implemented in both a tissue phantom and in vivo in a mouse Met-1 tumor model, using partial parallel imaging (PPI) to speed acquisition.