Cranial MR-Guided Focused Ultrasound: Clinical Challenges and Future Directions.

Magnetic resonance-guided focused ultrasound is a powerful new technology that is enabling development of noninvasive applications for complex brain disorders. This is currently revolutionizing the treatment of tremor disorders, and a variety of experimental applications are under active investigation. To fully realize the potential of this disruptive technology, many challenges have been identified, some of which have been addressed and others remain to be solved. As an image-based technology, optimal intraoperative imaging can be difficult to achieve and several factors can influence the quality of these images. Technical issues with current devices can also limit the effective delivery of ultrasound technology to particular targets. While lesioning is the primary approved application of magnetic resonance-guided focused ultrasound at present, the ability to transient and precisely open the blood-brain barrier has the potential to clear brain pathologies and deliver restorative therapies, but this more experimental method presents unique difficulties to overcome. Finally, regulatory and reimbursement hurdles currently remain complex and continue to limit widespread application of even approved, effective applications. Here we review many of these challenges, discuss several solutions that have already been developed, and propose potential options for addressing some of these complexities in the future.

Innovative Applications of MR-Guided Focused Ultrasound for Neurological Disorders.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a cutting-edge technology that is changing the practice of movement disorders surgery. Given the noninvasive and innovative nature of this technology, there is great interest in expanding the use of MRgFUS to additional diseases and applications. Current approved applications target the motor thalamus to treat tremor, but clinical trials are exploring or plan to study noninvasive lesions with MRgFUS to ablate tumor cells in the brain as well as novel targets for movement disorders and brain regions associated with pain and epilepsy. Although there are additional potential indications for lesioning, the ability to improve function by destroying parts of the brain is still limited. However, MRgFUS can also be applied to a brain target after intravenous delivery of microbubbles to create cavitations and focally open the blood-brain barrier (BBB). This has already proven to be safe and technically feasible in human patients with Alzheimer's disease, and this action alone has potential to clear extracellular pathology associated with this and other neurodegenerative disorders. This also provides a foundation for noninvasive intravenous delivery of therapeutic molecules to precise brain targets after transient disruption of the BBB. Certain chemotherapies for brain tumors, immunotherapies, gene, and cell therapies are all examples of therapeutic or even restorative agents that normally will not enter the brain without direct infusion but which have been shown in preclinical studies to effectively traverse the BBB after transient disruption with MRgFUS. Here we will review these novel applications of MRgFUS to provide an overview of the extraordinary potential of this technology to expand future neurosurgical treatments of brain diseases.

High-intensity focused ultrasound procedure: The rise of a new noninvasive glaucoma procedure and its possible future applications.

Glaucoma, one of the leading causes of blindness, is usually first managed medically, with incisional surgery as a second step. Noninvasive glaucoma procedures attempt to fill the gap between medical and surgical treatments and may work synergistically with them. High-intensity focused ultrasound induces a selective and controlled thermal ablation of the distal part of the ciliary body, and this effect is independent from the degree of tissue pigmentation with limited damage to adjacent structures. This selective and innovative treatment decreases intraocular pressure by reducing aqueous humor production and by increasing uveoscleral outflow. We review the current literature on the use of high-intensity focused ultrasound in glaucoma, exploring present use, safety, efficacy, and future clinical applications.

Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU): Overview of Emerging Applications (Part 2).

BACKGROUND: High-intensity focused ultrasound (HIFU) allows noninvasive heating of deep-seated tissues. Guidance under magnetic resonance imaging (MR-HIFU) offers spatial targeting based on anatomical MR images as well as MR-based near-real-time temperature maps. Temperature feedback allows delivery of a well-defined thermal dose enabling new applications such as the ablation of malignant tissue. METHODS: Peer-reviewed publications on MR-HIFU were studied and are summarized in this review. Literature was restricted to applications in oncology. RESULTS: Several MR-HIFU-based applications for the treatment of malignant diseases are currently part of clinical trials or translational research. Recent trials regarding the treatment of prostate cancer with MR-HIFU have already shown this to be a safe and patient-friendly method. For the treatment of breast cancer and malignancies within abdominal organs, MR-HIFU has been applied so far only in proof of concept studies. CONCLUSION: MR-HIFU is currently being investigated for the ablative treatment of malignant tissue in a variety of oncological applications. For example, the transrectal as well as transurethral ablation of prostate cancer using MR-HIFU was shown to be a patient-friendly, safe alternative to other local treatment options with low side effects. KEY POINTS: · MR guidance offers high soft tissue contrast for treatment planning, near-real-time temperature monitoring, and post-interventional therapy evaluation.. · Special HIFU transducers and technological solutions are available for the treatment of e. g. prostate cancer, breast cancer or abdominal malignancies.. CITATION FORMAT: · Siedek F, Yeo SY, Heijman E et al. MR-Guided High-Intensity Focused Ultrasound (MR-HIFU): Overview of Emerging Applications (Part 2). Fortschr Röntgenstr 2019; 191: 531 - 539.

The emerging role of transcranial magnetic resonance imaging-guided focused ultrasound in functional neurosurgery.

To review the emerging role of transcranial MR-guided focused ultrasound as a treatment and research modality for functional neurological disorders, we summarize recent clinical and preclinical studies. Clinical trials have investigated the safety and efficacy of thermal lesions created by transcranial, high-intensity focused ultrasound. Preclinical work has additionally investigated the ability to disrupt the blood-brain barrier and to produce reversible neuromodulation with focused ultrasound utilizing lower intensities. We discuss ongoing trials and future avenues of investigation. © 2016 International Parkinson and Movement Disorder Society.

Emerging Technologies and Techniques in Radiation Therapy.

The past decade has brought an improved ability to precisely target and deliver radiation as well as other focal prostate-directed therapy. Stereotactic body radiotherapy (SBRT), proton beam radiation, high-dose-rate (HDR) brachytherapy, as well as nonradiotherapy treatments such as cryoablation and high-intensity focused ultrasound are several therapeutic modalities that have been investigated for the treatment of prostate cancer in an attempt to reduce toxicity while improving cancer control. However, high-risk prostate cancer requires a comprehensive treatment of the prostate as well as areas at risk for cancer spread. Therefore, most new radiation treatment (SBRT, HDR, and proton beam radiation) modalities have been largely investigated in combination with regional radiation therapy. Though the evidence is evolving, the use of SBRT, HDR, and proton beam radiation is promising. Nonradiation focal therapy has been proposed mainly for partial gland treatment in men with low-risk disease, and its use in high-risk prostate cancer patients remains experimental.

High intensity focused ultrasound for focal therapy of prostate cáncer / Ultrasonidos de alta frecuencia (HIFU) para el tratamiento focal del cáncer de próstata

High Intensity Focused Ultrasound (HIFU) is a heat based energy source used for tissue ablation. HIFU has several clinical applications and prostate cancer ablation is one of the uses that have been explored for more than a decade. Focal therapy is an alternative treatment option for selected patients with low/intermediate PCa, that is based on complete ablation of tumor within the prostate with preservation of normal parenchyma and better preservation of Genitourinary functions. In spite of PCa being predominantly a multi-centric disease, it is postulated that a specific dominant (large volume) 'index lesion' dictates the biological behavior of the cancer and subsequent lethality of the disease. The use of HIFU for focal ablation of PCa, have demonstrated satisfactory cancer control with fewer morbidity and better preservation of continence and erection. The aim of this article is to present the Arch. Esp. Urol. 2016; 69 (6): 311-316 311 readers with a brief review of the principles, devices available for clinical uses, published clinical experience and future directions and research opportunities in focal HIFU ablation of prostate cáncer

El HIFU (High intensity focused ultrasound) es una fuente de energía basada en calor utilizada para la ablación de tejido. El HIFU tiene varias aplicaciones clínicas y la ablación del cáncer de próstata es una de las que se ha explorado desde hace más de una década. La terapia focal es una opción de tratamiento alternativa para pacientes seleccionados con cáncer de próstata de riesgo bajo/intermedio. Se basa en la ablación completa del tumor dentro de la próstata con preservación del parénquima normal y mejor conservación de las funciones genitourinarias. A pesar de ser el cáncer de próstata una enfermedad predominantemente multicéntrica, se postula que una "lesión índice" dominante específica (gran volumen) dicta el comportamiento biológico del cáncer y la subsecuente letalidad de la enfermedad. El uso de HIFU para ablación local de cáncer de próstata ha demostrado un control del cáncer satisfactorio con menor morbilidad y mejor conservación de la continencia y la erección. El objetivo de este artículo es presentar a los lectores una breve revisión de los principios, los instrumentos disponibles para uso clínico, la experiencia clínica publicada y la dirección futura y oportunidades de investigación en la ablación focal del cáncer de próstata con HIFU

MRI methods for the evaluation of high intensity focused ultrasound tumor treatment: Current status and future needs.

Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR-guided HIFU system. The MR-based evaluation of HIFU treatment is most often restricted to contrast-enhanced T1 -weighted imaging, while it has been shown that the non-perfused volume may not reflect the extent of nonviable tumor tissue after HIFU treatment. There are multiple studies in which more advanced MRI methods were assessed for their suitability for the evaluation of HIFU treatment. While several of these methods seem promising regarding their sensitivity to HIFU-induced tissue changes, there is still ample room for improvement of MRI protocols for HIFU treatment evaluation. In this review article, we describe the major acute and delayed effects of HIFU treatment. For each effect, the MRI methods that have been-or could be-used to detect the associated tissue changes are described. In addition, the potential value of multiparametric MRI for the evaluation of HIFU treatment is discussed. The review ends with a discussion on future directions for the MRI-based evaluation of HIFU treatment.

Nanobiotechnology promotes noninvasive high-intensity focused ultrasound cancer surgery.

The successful cancer eradication in a noninvasive manner is the ultimate objective in the fight against cancer. As a "bloodless scalpel," high-intensity focused ultrasound (HIFU) is regarded as one of the most promising and representative noninvasive therapeutic modalities for cancer surgery. However, large-scale clinical applications of HIFU are still in their infancy because of critical efficiency and safety issues which remain to be solved. Fortunately, recently developed nanobiotechnology provides an alternative efficient approach to improve such important issues in HIFU, especially for cancer therapy. This Research News presents the very recent exciting progresses on the elaborate design and fabrication of organic, inorganic, and organic/inorganic hybrid nanoparticles for enhancing the HIFU ablation efficiency against tumor tissues. It is highly expected that this Research News can arouse more extensive research enthusiasm on the development of functional nanomaterials for highly efficient HIFU-based synergistic therapy, which will give a promising noninvasive therapeutic modality for the successful cancer therapy with minimal damage to surrounding normal tissues, due to the noninvasive and site-specific therapeutic features of HIFU.

[Importance of modern treatment procedures for infected and colonized wounds in dermatology]. / Stellenwert moderner physikalischer Behandlungsverfahren bei infizierten und kolonisierten Wunden in der Dermatologie.

In the coming years increasing numbers of patients with chronic ulcers and tumor wounds are to be expected, both of which are typically multifaceted diseases requiring complex and increasingly long-term ambulatory therapy. Therefore, in recent years special medical emphasis has been placed on efficacious therapies with good tolerability and also suitability regarding feasibility for outpatient treatment. Some of these methods, such as cold plasma therapy, extracorporeal shock wave therapy (ESWT), water-filtered infrared therapy (wIRA), electrostimulation (ES) and low level laser therapy (LLLT) have a good chance of success when applied as an adjuvant method in the multimodal treatment concept for patients with recalcitrant wounds. All of these methods have at least indirect antimicrobial properties which can be advantageous in cases of microbial infiltration of wounds. As for all other methods for treating recalcitrant wounds, the promising application of the aforementioned methods requires great expertise in wound healing together with a broad and continuous interdisciplinary diagnostics and therapy (wound center).

Técnicas ablativas y utilidad clínica de la ablación como primera línea de tratamiento en fase inicial del cáncer hepatocelular / Ablative techniques and the clinical utility of ablation as first-line treatment in the initial phase of hepatocellular cancer

El objetivo de los programas de cribado es diagnosticar la enfermedad en estadios iniciales asintomáticos, preferentemente cuando las lesiones no han superado los 2 cm de tamaño. En este estadio de la enfermedad se pueden aplicar tratamientos potencialmente curativos con una excelente supervivencia a largo plazo. La ablación percutánea, preferentemente la radiofrecuencia, ha demostrado una gran capacidad de inducir necrosis completa en estas lesiones de pequeño tamaño con una mínima tasa de efectos secundarios y menor coste económico que la resección hepática. Por estos motivos, en los últimos años se ha sugerido que la ablación percutánea podría constituir la primera opción terapéutica en aquellos pacientes con hepatocarcinoma en estadio muy inicial. En este documento realizaremos una revisión de la evidencia científica que apoya el uso de la ablación percutánea en este escenario. Aunque no existe ningún ensayo clínico específicamente diseñado para evaluar cuál es la mejor opción terapéutica (ablación frente a resección) en el estadio muy inicial, múltiples estudios de cohortes, un metaanálisis y un estudio de coste-eficacia usando un modelo Markov sugieren que la ablación podría constituir la primera opción terapéutica en el carcinoma hepatocelular muy inicial, reservando la resección en aquellos casos en los que la ablación fracasa o no es factible

The objective of screening programs is to diagnose the disease in the initial asymptomatic stages, preferably when the lesions have not exceeded 2 cm in size. In this disease stage, potentially curative treatments can be applied with excellent long-term survival. Percutaneous ablation (preferentially radiofrequency) has shown a considerable capacity for inducing complete necrosis in these small lesions, with a minimal rate of adverse effects and a lower financial cost than hepatic resection. For these reasons, in recent years it has been suggested that percutaneous ablation could constitute the first therapeutic option in patients with hepatocarcinoma in very early stages. In this study, we conducted a review of the scientific evidence that supports the use of percutaneous ablation in this scenario. Although there are no clinical trials specifically designed to evaluate the better therapeutic option (ablation vs. resection) in the initial stages, numerous cohort studies, a metaanalysis and a cost-effectiveness study using a Markov model suggest that ablation could constitute the first therapeutic option in early stages of hepatocellular carcinoma, reserving resection for those cases in which ablation fails or is not feasible

Focused ultrasound: relevant history and prospects for the addition of mechanical energy to the neurosurgical armamentarium.

Although the concept of focused ultrasonography emerged more than 70 years ago, the need for a craniectomy obviated its development as a noninvasive technology. Since then advances in phased array transducers and magnetic resonance imaging technology have resurrected the ultrasound as a noninvasive therapeutic for a plethora of neurological conditions ranging from embolic stroke and intracranial hemorrhage to movement disorders and brain neoplasia. In the same way that stereotactic radiosurgery has fundamentally changed the scope and treatment paradigms of tumor and specifically skull base surgery, focused ultrasound has a similar potential to revolutionize the field of neurological surgery. In addition, focused ultrasound comes without the general complexity or the risks of ionizing radiation that accompany radiosurgery. As the quest for minimally invasive and noninvasive therapeutics continues to define the new neurosurgery, the focused ultrasound evolves to join the neurosurgical armamentarium.

Clinical applications for magnetic resonance guided high intensity focused ultrasound (MRgHIFU): present and future.

It has been well known for decades that high intensity focused ultrasound (HIFU) generates heat in tissues resulting in coagulative necrosis. Implementation, however, has been slow, due to difficulties with finding an appropriate imaging modality that could not only guide treatment, but also provide real-time thermal feedback. These problems have been overcome with the newest magnetic resonance-guided high intensity focused ultrasound systems (MRgHIFU). With its superior spatial resolution enabling accurate image guidance coupled with its ability to provide real-time thermography during treatments, MRI is moving further into the realm of therapeutics for oncologic patient care. This article will discuss the implementation of an MR-guided HIFU system, current clinical indications and touch on future directions.

[MR-guided focused ultrasound. Current and future applications]. / MR-gesteuerter fokussierter Ultraschall. Aktuelle und potenzielle Indikationen.

STANDARD RADIOLOGICAL METHODS: High-intensity focused ultrasound (synonyms FUS and HIFU) under magnetic resonance imaging (MRI) guidance (synonyms MRgFUS and MR-HIFU) is a completely non-invasive technology for accurate thermal ablation of a target tissue while neighboring tissues and organs are preserved. METHODICAL INNOVATIONS: The combination of FUS with MRI for planning, (near) real-time monitoring and outcome assessment of treatment markedly enhances the safety of the procedure. ACHIEVEMENTS: The MRgFUS procedure is clinically established in particular for the treatment of symptomatic uterine fibroids, followed by palliative ablation of painful bone metastases. Furthermore, promising results have been shown for the treatment of adenomyosis, malignant tumors of the prostate, breast and liver and for various intracranial applications, such as thermal ablation of brain tumors, functional neurosurgery and transient disruption of the blood-brain barrier.

High-intensity focused ultrasound in prostate cancer: today's outcomes and tomorrow's perspectives.

High-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied for prostate cancer that capitalizes on the coagulation necrosis that occurs at temperatures greater than 60°C. Owing to a lack of long-term follow-up data the procedure is still considered experimental treatment. As primary therapy, HIFU is indicated in patients aged ≥70 years with clinical organ-confined disease, although it has also been used, with encouraging results, as first line salvage therapy after definitive treatment, and in locally advanced (T3-4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated with this treatment method appears to be low and includes urinary retention (1-9%), urethral stricture (4-14%), incontinence (1-15%), erectile dysfunction (13-53%) and rectourethral fistulae (0-3%). The risk of complications increases with repeated treatments. A few studies have recently been published on HIFU as focal therapy. HIFU technology can be enhanced using means such as ultrasound microbubble contrast agents for assessment of therapy efficacy, magnetic resonance imaging to guide the enhancement of heat rate, and localized drug and gene delivery.

Clinical application of extracorporeal shock wave therapy in orthopedics: focused versus unfocused shock waves.

For the past decade extracorporeal shock wave therapy has been applied to a wide range of musculoskeletal disorders. The many promising results and the introduction of shock wave generators that are less expensive and easier to handle has added to the growing interest. Based on their nature of propagation, shock waves can be divided into two types: focused and unfocused. Although several physical differences between these different types of shock waves have been described, very little is known about the clinical outcome using these different modalities. The aim of the present review is to investigate differences in outcome in select orthopaedic applications using focused and unfocused shock waves.

Novel methods for renal tissue ablation.

PURPOSE OF REVIEW: To provide an overview of the current research on renal tissue ablation, highlighting novel ablation techniques and technologies. RECENT FINDINGS: As long-term data on renal radio frequency ablation (RFA) and cryoablation confirming their oncologic efficacy emerge, ongoing research aims at improving the treatment profiles of these techniques as well as developing novel methods for renal tissue ablation. SUMMARY: Although nephron-sparing surgery is the gold standard treatment for small renal masses confirmed malignant, ablative therapies are an option in elderly patients, who may be poor surgical candidates. RFA and cryoablation have each been used for renal tissue ablation for over a decade but their efficacy in ablation of central lesions or lesions more than 3 cm in size is limited. Increasing ablation size and improving efficiency of thermal energy delivery are the goals of research in RFA and cryoablation. Novel ablation technologies including microwave ablation, irreversible electroporation and high-intensity focused ultrasound among others have undergone preliminary preclinical and clinical evaluation in select series but require further development and assessment of outcomes prior to routine clinical use for renal tumor ablation.

MRIgHIFU: a tool for image-guided therapeutics.

High-intensity focused ultrasound (HIFU) provides focal delivery of mechanical energy deep into the body. This energy can be used to elevate the tissue temperature to such a degree that ablation is achieved. The elevated temperature can also be used to release drugs from temperature-sensitive carriers or activate therapeutic molecules using mechanical or thermal energy. Lower dose exposures modify the vasculature to allow large molecules to diffuse from blood in the surrounding tissue for local drug delivery. The energy delivery can be targeted and monitored using magnetic resonance imaging (MRI). The online image guidance and monitoring provides treatment delivery that is customized to each patient such that optimal, effective treatment can be achieved. This ability to localize and customize treatment delivery may further enhance the future potential of targeted drugs that are personalized for each patient. This review examines the rapid development of MRI-guided HIFU (MRIgHIFU) methods over the past few years and discuss their future potential.

High-intensity focused ultrasound in the management of prostate cancer.

The treatment of localized prostate cancer with high-intensity focused ultrasound (HIFU) has been researched since the 1990s and today the treatment is an actively used therapy for the disease. HIFU works in two ways to destroy tissue, namely thermal and mechanical effects. The most recent data on the Ablatherm HIFU device come from an international registry (@-Registry) and indicate a 5-year biochemical survival rate of 85%. HIFU is commonly used in conjunction with transurethral resection of the prostate in order to reduce prostate gland size and facilitate effective tissue destruction. An additional benefit of HIFU is that it can be used as salvage therapy after radical prostatectomy and external-beam radiotherapy. A new area of research with HIFU involves focal therapy, where tumor sites within the gland are directly targeted with the objective of reducing morbidity.