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Background To evaluate the effectiveness and feasibility of high-intensity focused ultrasound (HIFU) for the treatment of bone metastases. Methods A single-center prospective study was made involving 17 consecutive patients with symptomatic bone metastases. Patients were treated by Focused Ultrasound (FUs) performed with magnetic resonance (MR) guidance. Surgical treatment or radiotherapy treatment was not indicated for patients who underwent FUs. Lesions were located in the appendicular and axial skeleton and consisted of secondary symptomatic lesions. The clinical course of pain was evaluated using the Visual Analog Scale (VAS) before treatment, at 1 week, and at 1 month after treatment and the Oral Morphine Equivalent Daily Dose (OMEDD) was also recorded. We used Wilcoxon signed rank test to assess change in patient pain (R CRAN software V 3.1.1). Results We observed a significant decrease in the pain felt by patients between pre- procedure and 1 week post-procedure (p = 2.9.10–4), and pre-procedure and 1 month post-procedure (p = 3.10–4). The proportion of responders according to the International Bone Metastases Consensus Working Party was: Partial Response 50% (8/16) and Complete Response 37.5% (6/16). Conclusions HIFU under MR-guidance seems to be an effective and safe procedure in the treatment of symptomatic bone lesions for patients suffering from metastatic disease. A significant decrease of patient pain was observed. Trial registration NCT01091883. Registered 24 March 2010. Level of evidence: Level 3.

The Winter School on Therapeutic Ultrasound held its biennial meeting at the Ecole de Physique des Houches in Les Houches, France from March 26-31, 2017. The program brought together a globally and scientifically diverse group of faculty, clinicians, and trainees with interest in elements of therapeutic ultrasound. The meeting agenda was composed of daily lectures on various topics of relevance, supplemented with evening seminars, excursions, and networking opportunities. In anticipation of the next edition of the Winter School expected in 2019, we are nearly reaching the half way point between offerings of this unique and specialized meeting. Thus, this meeting report offers a reflection on the 2017 Winter School with the intention of setting the stage for 2019. Reviewed within this report are the lectures, student presentation series, and evening seminars encompassed within meeting agenda. It is my hope that this resource will be utilized by investigators within the therapeutic ultrasound community considering attending the Winter School in 2019.

Background Multiple sclerosis (MS) impacts approximately 400,000 in the United States and is the leading cause of disability among young to middle aged people in the developed world. Characteristic of this disease, myelin within generally focal volumes of brain tissue wastes away under an autoimmune assault, either inexorably or through a cycle of demyelination and remyelination. This centrally located damage produces central and peripheral symptoms tied to the portion of brain within the MS lesion site. Interestingly, Gibson and colleagues noted that optical activation of transgenically tagged central neurons increased the thickness of the myelin sheath around those neurons. Since ultrasound, delivered transcranially, can also activate brain focally, we hypothesized that ultrasound stimulation that followed the temporal pattern of Gibson et al. applied to MS lesions in a mouse model might either decelerate the demyelination phase or accelerate its remyelination phase. Methods We created a temporal pattern of ultrasound delivery that conformed to that of Gibson et al. and capable of activating mouse brain. We then applied ultrasound, transcranially, following that temporal pattern to separate cohorts of a mouse model of multiple sclerosis, using three different ultrasound carrier frequencies (0.625 MHz, 1.09 MHz, 2.0 MHz), during each of the demyelinating and remyelinating phases. After identifying the most promising protocol and MS brain state through qualitative analysis of myelin content, we performed additional studies for that condition then assayed for change in myelin content via quantitative analysis. Results We identified one ultrasound protocol that significantly accelerated remyelination, without damage, as demonstrated with histological analysis. Conclusion MRI-guided focused ultrasound systems exist that can, in principle, deliver the ultrasound protocol we successfully tested here. In addition, MRI, as the clinical gold standard, can readily identify MS lesions. Given the relatively low intensity values of our ultrasound protocol – close to FDA limits – we anticipate that future success with this approach to MS therapy as tested using more realistic MS mouse models may one day translate to clinical trials that help address this devastating disease.

Background Dysfunction of the Sacroiliac Joint (SIJ) is one of the key sources of low back pain. For prolonged pain relief, some patients undergo fluoroscopic guided radio-frequency (RF) ablation of SIJ, during which a number of RF probes are inserted to create thermal lesions that disrupt the posterior sacral nerve supply. This procedure is minimally invasive, laborious, time-consuming and costly. To study if High Intensity Focused Ultrasound (HIFU) ablation is a feasible alternative approach to SIJ pain treatment, we performed experiments using HIFU to ablate SIJ in the swine model. Methods Three female Yorkshire swine (36, 35.2 and 34 kg) underwent bilateral Magnetic Resonance guided HIFU (MRgHIFU) ablation of the SIJs. Treatment assessment was performed using contrast-enhanced imaging, histopathology and evaluation of pain and changes in ambulation and gait. Results Contiguous lesions along the right and left SIJs were achieved in all animals. In one out of three animals, excessive heating of the muscle and skin tissue in the near-field resulted in unwanted muscle necrosis. No changes in animal behavior, ambulation or gait were detected. Conclusions The initial experiments with MRgHIFU ablation of SIJs in sub-acute swine model show promise for this ablation modality as a non invasive and more precise alternative to the currently used fluoroscopically - guided RF ablations and injections.

Background Past catheter-based and focused ultrasound renal denervation studies have indicated that procedure efficacy is related to the number of ablations performed or the amount of energy used for the ablation. This study extends those prior results and investigates energy level effects on the efficacy of MR guided focused ultrasound renal denervation performed in a porcine model. Methods Twenty-four normotensive pigs underwent unilateral denervation at three intensity levels. The applied intensity level was retrospectively de-rated to account for variability in animal size. Efficacy was assessed through evaluating the norepinephrine present in the kidney medulla and through histological analysis. The treatment was performed under MRI guidance including pre- and post-procedure T1-weighted and quantitative T1 and T2 imaging. During treatment, the temperature in the near field of the ultrasound beam was monitored in real time with MR temperature imaging. Energy delivery in the regions surrounding the renal artery was independently confirmed through an invasive fiberoptic temperature probe placed in the right renal artery. Results Animals that underwent denervation at a de-rated acoustic intensity of greater than 1.2 kW/cm2 had a significantly lower norepinephrine concentration in the kidney indicating successful denervation. Images obtained during the treatment indicated no tissue changes in the kidneys as a function of the procedure but there were significant T1 changes present in the right lumbar muscles, although only one animal had indication of muscle damage at the time of necropsy. Conclusions While MR guided focused ultrasound renal denervation was found to be safe and effective in this normotensive animal model, the results indicated the need to incorporate patient-specific details in the treatment planning of MRgFUS renal denervation procedure.

Background With an increasing number of imaging studies being done nowadays, the number of incidentally discovered thyroid nodules is expected to rise. Although many of these nodules are small and benign in nature, some do grow and may cause pressure and/or thyrotoxic symptoms. Surgical resection has traditionally been recommended for symptomatic nodules but is associated with risk of hypothyroidism, bleeding, infection, and nerve damage. High intensity focused ultrasound (HIFU) is one of the non-surgical thermal ablation techniques that may serve as an alternative in the treatment of benign thyroid nodules. The present review is to systematically evaluate the efficacy and safety of HIFU ablation. Methods We comprehensively searched all studies that evaluated the use of HIFU ablation as a treatment of benign thyroid nodules from Medline (PubMed) and Cochrane Library electronic databases using specific keywords. All titles identified by the search strategy were independently screened by two authors. Case reports, animal studies, editorials, expert opinions, reviews without original data and studies on pediatric population were excluded. Multiple reports of the same dataset were assessed and the most representative and updated report of a study was included. Results Five original studies were found. All treated thyroid nodules were confirmed to be benign cytologically and either appeared solid or predominantly (>70%) solid on ultrasonography. Only one type of commercially available US-guided device with an extracorporeal probe (3 MHz) was used in all the reported treatments. No major complications including recurrent laryngeal nerve injury, skin burn or haematoma were reported in all of the studies. The overall nodule volume reduction after single session of HIFU ablation ranged between 45 and 68%, depending on nodule size and length of follow-up. Conclusions Despite the few number of studies, our review appeared to suggest that HIFU is a safe and efficacious method of treating symptomatic benign thyroid nodules. However, larger-scale, prospective trials with longer follow-up period are indeed required to confirm this. In terms of the ablation itself, relative to other ablation techniques, there are still much room for improvements in shortening treatment duration and expanding the range of treatable nodules.

Recent studies have demonstrated the effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of osteoid osteoma (OO), a painful, benign bone tumor. As MRgFUS is a noninvasive and radiation-free treatment, it stands to replace the current standard of care, percutaneous radiofrequency, or laser thermal ablation. Within an institution, creation of a clinical OO MRgFUS treatment program would not only provide cutting edge medical treatment at the current time but would also establish the foundation for an MRgFUS clinical service to introduce treatments currently under development into clinical practice in the future. The purpose of this document is to provide information to facilitate creation of a clinical service for MRgFUS treatment of OO by providing (1) recommendations for the multi-disciplinary management of patients and (2) guidelines regarding current best practices for MRgFUS treatment. This paper will discuss establishment of a multi-disciplinary clinic, patient accrual, inclusion/exclusion criteria, diagnosis, preoperative imaging, patient preparation, anesthesia, treatment planning, targeting and treatment execution, complication avoidance, and patient follow-up to assure safety and effectiveness.

We present here biophysical models to gain deeper insights into how an acoustic stimulus might influence or modulate neuronal activity. There is clear evidence that neural activity is not only associated with electrical and chemical changes but that an electro-mechanical coupling is also involved. Currently, there is no theory that unifies the electrical, chemical, and mechanical aspects of neuronal activity. Here, we discuss biophysical models and hypotheses that can explain some of the mechanical aspects associated with neuronal activity: the soliton model, the neuronal intramembrane cavitation excitation model, and the flexoelectricity hypothesis. We analyze these models and discuss their implications on stimulation and modulation of neuronal activity by ultrasound.

Background Already in the late 1960s and early 1970s, targeting of the “posterior subthalamic area (PSA)” was explored by different functional neurosurgical groups applying the radiofrequency (RF) technique to treat patients suffering from essential tremor (ET). Recent advances in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) technology offer the possibility to perform thermocoagulation of the cerebellothalamic fiber tract in the PSA without brain penetration, allowing a strong reduction of the procedure-related risks and increased accuracy. We describe here the first results of the MRgFUS cerebellothalamic tractotomy (CTT). Methods Twenty-one consecutive patients suffering from chronic (mean disease duration 29.9 years), therapy-resistant ET were treated with MRgFUS CTT. Three patients received bilateral treatment with a 1-year interval. Primary relief assessment indicators were the Essential Tremor Rating Scale (Fahn, Tolosa, and Marin) (ETRS) taken at follow-up (3 months to 2 years) with accent on the hand function subscores (HF16 for treated hand and HF32 for both hands) and handwriting. The evolution of seven patients with HF32 above 28 points over 32 (group 1) differentiated itself from the others’ (group 2) and was analyzed separately. Global tremor relief estimations were provided by the patients. Lesion reconstruction and measurement of targeting accuracy were done on 2-day post-treatment MR pictures for each CTT lesion. Results The mean ETRS score for all patients was 57.6 ± 13.2 at baseline and 25.8 ± 17.6 at 1 year (n = 10). The HF16 score reduction was 92 % in group 2 at 3 months and stayed stable at 1 year (90 %). Group 1 showed only an improvement of 41 % at 3 months and 40 % at 1 year. Nevertheless, two patients of group 1 treated bilaterally had an HF16 score reduction of 75 and 88 % for the dominant hand at 1 year after the second side. The mean patient estimation of global tremor relief after CTT was 92 % at 2 days and 77 % at 1-year follow-up. Conclusions CTT with MRgFUS was shown to be an effective and safe approach for patients with therapy-refractory essential tremor, combining neurological function sparing with precise targeting and the possibility to treat patients bilaterally.

INTRODUCTION: Breast fibroadenomata (FAD) are benign lesions which occur in about 10 % of all women. Diagnosis is made by triple assessment (physical examination, imaging and/or histopathology/cytology). For a definitive diagnosis of FAD, the treatment is conservative unless the patient is symptomatic. For symptomatic patients, the lumps can be surgically excised or removed interventionally by vacuum-assisted mammotomy (VAM). Ablative techniques like high-intensity focused ultrasound (HIFU), cryo-ablation and laser ablation have also been used for the treatment of FAD, providing a minimally invasive treatment without scarring or poor cosmesis. This review summarises current trials using minimally invasive ablative techniques in the treatment of breast FAD.METHODS: A comprehensive review of studies using minimally invasive ablative techniques was performed.RESULTS: There are currently several trials completed or recruiting patients using HIFU, cryo-ablation and laser ablation in the treatment of breast FAD. The results look very promising but cannot be compared at this point due to heterogeneity between studies.CONCLUSION: Minimally invasive ablative techniques like HIFU, cryo-ablation and laser ablation are promising in the treatment of breast FAD. Future trials should be randomised and contain larger numbers of patients to determine the effectiveness of ablative techniques with more precision.

Publications in therapeutic ultrasound have been growing exponentially for the past four decades, n = 2 exp((t-1970)/6), R² = 0.965, and reached approximately 1440 papers in 2011. Adoption of new International Electrotechnical Commission standards by regulatory agencies such as the United States Food and Drug Administration will enable more rapid approval of devices and therefore more clinical applications. Thus the exponential growth is likely to continue with a predicted output of 3600 papers by 2015. In order to serve this growing demand, the Journal of Therapeutic Ultrasound (JTU) has been launched. JTU is an online, open access journal designed to accelerate the adoption of focused ultrasound.

In managing women with large uterine fibroids, GnRH agonists can be used to reduce fibroid volume and decrease vascularity to enhance treatment outcomes with MRgFUS. GnRH agonists have been shown to reduce fibroid volume by as much as 30-40%. The purpose of this study was to examine the responsiveness of fibroids to pre-treatment with a GnRH agonist in relation to their appearance on T2 weighted images and MRgFUS treatment outcomes.

Temporal lobe epilepsy (TLE) is the most common pharmacologically refractory form of epilepsy. While it can often be effectively treated by temporal lobe surgery, that does not always eliminate seizures, and many patients are not suitable candidates for surgery. A non-invasive method to augment surgical or medical treatment of TLE would be highly useful. Low-intensity focused ultrasound pulsation (LIFUP) offers the potential for non-invasive neuromodulation, and in animal studies has not shown any evidence of tissue damage. However, the technology has not yet been tested in humans. We are currently testing the safety and feasibility of using a LIFUP device on humans to modulate brain activity in the temporal lobe.

In this work we will present our plan for an (MR)-guided, high-intensity focused ultrasound (FUS) uterine fibroid registry, with the goal of providing large-scale evidence on the safety and long-term efficacy of FUS for the treatment of symptomatic uterine fibroids.

The movement of the target challenges the application of high intensive focused ultrasound (HiFU/MRgFUS) for the treatment of malignancies in moving abdominal organs such as liver and kidney. Moreover, the anatomical location of the lesion is often behind the rib cage. The physiology of the organs, the dynamic and complex blood perfusion impairs the energy disposition in the tissue due to the heat transfer within the organ. To explore the full potential of extracorporeal FUS to safely and precisely destroy tissue in the depth of a moving organ requires sophisticated software and advanced hardware. In the EU project FUSIMO (http://www.fusimo.eu) a software demonstrator for the patient specific planning of FUS in the liver has been developed in order to empower the physician to perform safe, effective and efficient ablation of tumours and to facilitate prediction of the outcome. The new EU project TRANS-FUSIMO (http://www.trans-fusimo.eu) aims at the translation of this software demonstrator into a fully integrated system for the FUS treatment of the liver.

The purpose of this study was to investigate the thresholds for inducing two possible means of tissue destruction with low frequency Magnetic Resonance guided Focused Ultrasound (MRgFUS): either mechanical lesioning in presence of ultrasonic cavitation or pure thermal lesioning (without cavitation).

The combination of focused ultrasound and an intravenously-injected microbubble ultrasound contrast agent offers the ability to reduce the power needed to ablate tissue, which is particularly important for targets in the brain since it can eliminate skull heating. When applied at a low duty cycle so that bulk tissue heating does not occur, the mechanical effects induced by inertial cavitation result in ablation via the destruction of blood vessels. This alternative method for tissue ablation may have advantages for the treatment of brain tumors.

Ultrasonic propulsion is a new technology we have developed which uses focused ultrasound to transcutaneously reposition kidney stones. Two applications are expelling small stones or fragments and dislodging obstructing stones. We report preliminary, investigative findings from the first use of this technology in humans.

FUS coupled with the systemic administration of microbubbles has been proved to open the Blood-Brain Barrier (BBB) locally, transiently and non-invasively in non-human primates (NHP). However, the complexity of the NHP brain constitutes an obstacle in relating the volume size of the induced opening (VBBB) to the geometric aspects of the method as well as the physiologic characteristics of the targeted areas. The objective of the current study is to quantify the correlation between the VBBB, the FUS pressure and the incidence angle. Additionally, the dependence of the opening shift on the gray-to-white-matter ratio at the targeted area is studied.

Bone is highly relevant to focused ultrasound therapy, both as a potential treatment target and because it interferes with treatment of other organs such as the brain. It is challenging to image cortical bone using MRI, however, due to low water density and fast signal decay in bony tissues. Ultrashort echo time (UTE) imaging is a specialized MR technique that allows the weak, short-lived signal from cortical bone to be imaged despite these limitations. Potential applications of UTE bone imaging in MR-guided focused ultrasound include direct MR thermometry of bone heating, which is not possible using standard proton resonance shift (PRFS) techniques, and in situ skull imaging during brain treatment procedures, which could replace the separate CT scan currently required for transcranial focused ultrasound.

The Kona Medical Surround Sound™ System is a fully non-invasive system for renal denervation which employs ultrasound based imaging for targeting and tracking as well as a phased array therapeutic ultrasound transducer. To date, 69 patients have been treated under three different protocols (WAVE I, WAVE II, and WAVE III). Follow up ranges from 3 months to over 2 years. A subset of 18 patients (WAVE II) was chosen for detailed analysis using numerical simulation. Aims: To evaluate safety, feasibility, and a specific dose strategy using a computational model in a Virtual Acoustic Patient (VAP) model and validate these simulations with human data.

Thermal therapy has tremendous potential to augment the benefits of immunotherapy. The ability of heat to stimulate both general and tumor specific responses, in part through heat shock protein mediated mechanisms has been known for over two decades. Significant challenges persist however in translating these effects into predictable and meaningful clinical responses. More recently the association of radiation with immune stimulation and in some cases specific anti-tumor immune response has been defined.

Soft tissue tumors are a heterogeneous group of tumors arising from connective tissues. These tumors may be benign, benign but locally aggressive, or malignant. Surgery either alone or in combination with adjuvant therapies such as radiation or chemotherapy can potentially cure a patient with a soft tissue tumor. The morbidity and complications associated with treatment can have significant and lasting adverse effects on limb function and quality of life. In some situations, patients develop local recurrence of disease and require further surgery, which can result in further treatment-associated morbidity. We have adapted MR guided focused ultrasound (MRgFUS) techniques to the treatment of benign and malignant soft tissue tumors of the extremities with the goal of safely and effectively performing MRgFUS ablation on human subjects. This presentation describes the use of MRgFUS for the treatment of desmoid fibromatosis, arteriovenous malformations, and malignant sarcomas.

MRgFUS offers unambiguous advantages over other current treatment modalities, as it is noninvasive and does not use ionizing radiation. Further, ultrasonically-controlled stable and inertial microbubble oscillations exert forces that can, among others, activate cell’s mechanoreceptors, disrupt cellular and vascular membranes, accelerate the dissolution of blood clots, enhance thermal ablation, and induce localized tissue erosionetc. FUS can also be used transcranially for tumor ablation, blood-brain barrier disruption, neuromodulation, etc. Harnessing and, potentially, combining these abilities holds great promise for therapy and diagnosis of cancer and cardiovascular and central nervous system diseases and disorders. For the wide-spread use of these approaches, development of methods and technology to enable precise planning, monitoring and control, and assessment of their outcome are essential.

NANOPORATION project sets out to explore specific solutions to overcome the current challenges of targeted drug delivery (TDD) to tumours using magnetic resonance imaging guided focused ultrasound (MRgFUS) to cavitate microbubbles (MBs) for increasing cell permeability and to open ‘drug nano-capsules’ for releasing proven active anticancer drugs directly to the tumour site with reduction of drug dosage needed for the desired therapeutic effect.

With regards to MR-HIFU ablation of uterine fibroids, there have been no screening MR criteria that comprehensively consider multiple influencing factors. The aims of this study was to generate screening MRI-based prediction model for therapeutic responses of MR-guided high-intensity focused ultrasound (MR-HIFU) ablation of uterine fibroids comprehensively considering multiple influencing factors.

Symptomatic localized adenomyosis is generally treated conservatively, or with more radical treatments such as hysterectomy. An effective non-invasive therapy is needed, especially for those who wish to preserve their fertility. MR-guided Focused Ultrasound ablation (MRgFUS) has been shown as an effective treatment for symptomatic uterine leiomyomas with a large non-perfused volume (NPV) immediately after treatment. Our specific aim was to compare the change in NPV in subjects with localized adenomyomas treated with MRgFUS, with the change in NPV in subjects treated with MRgFUS for symptomatic uterine leiomyomas to determine if similar results were achieved in the localized adenomyoma cohort.

Previous works by Fry et al. and others demonstrated that ultrasound exposures on the optic tract and/or the lateral geniculate nucleus (LGN) can temporarily block visually-evoked potentials in small animals. We attempted to repeat these experiments in a rhesus macaque using the ExAblate Neuro system (InSightec) operating at 650 kHz.

Transcranial MRI-guided focused ultrasound is a rapidly advancing field for delivering therapeutic and imaging agents to the brain. It has the ability to facilitate the passage of therapeutics from the vasculature to the brain parenchyma, which is normally protected by the blood-brain barrier (BBB). Its main advantages are that it is targeted, noninvasive, and readily repeatable in nature. Studies have shown that it can deliver liposomal doxorubicin (DOX), a chemotherapy agent with promise for tumors in the central nervous system, into the brain across BBB. However, prior studies have suggested that this agent may be significantly neurotoxic, even at small concentrations. Here, we studied whether multiple sessions of DOX administered after FUS-induced BBB disruption (FUS-BBBD) caused adverse events in the normal brain. First, we used fluorometry to measure the doxorubicin concentrations in the brain after FUS-BBBD. Next, we performed three weekly sessions with FUS-BBBD ± DOX administration.

Objective The blood-brain barrier (BBB) protects the brain by preventing the entry of large molecules; this poses a major obstacle for the delivery of drugs to the brain. A novel technique using focused ultrasound (FUS) energy combined with microbubble contrast agents has been widely used for non-invasive trans-cranial BBB opening. Traditionally, FUS research is conducted with magnetic resonance imaging (MRI) guidance, which is expensive and poses physical limitations due to the magnetic field. A system that could allow researchers to test brain therapies without MR intervention could facilitate and accelerate translational research. Methods In this study, we present a novel FUS system that uses a custom-built FUS generator mounted on a motorized stereotaxic apparatus with embedded brain atlas to locally open the BBB in rodents. The system was initially characterized using a tissue-mimicking phantom. Rodent studies were also performed to evaluate whether non-invasive, localized BBB opening could be achieved using brain atlas-based targeting. Brains were exposed to pulsed focused ultrasound energy at 1.06 MHz in rats and 3.23 MHz in mice, with the focal pressure estimated to be 0.5–0.6 MPa through the skull. BBB opening was confirmed in gross tissue sections by the presence of Evans blue leakage in the exposed region of the brain and by histological assessment. Results The targeting accuracy of the stereotaxic system was better than 0.5 mm in the tissue-mimicking phantom. Reproducible localized BBB opening was verified with Evans blue dye leakage in 32/33 rats and had a targeting accuracy of ±0.3 mm. The use of higher frequency exposures in mice enabled a similar precision of localized BBB opening as was observed with the low frequency in the rat model. Conclusions With this dedicated small-animal motorized stereotaxic-FUS system, we achieved accurate targeting of focused ultrasound exposures in the brain for non-invasive opening of the BBB. This system can be used as an alternative to MR-guided FUS and offers researchers the ability to perform efficient studies (30 min per experiment including preparation) at a reduced cost in a conventional laboratory environment.

Background Radiofrequency (RF) subthalamotomies have been proposed since the 1960s to treat patients suffering from Parkinson's disease (PD). Recently, the magnetic resonance (MR)-guided focused ultrasound technology (MRgFUS) offers the possibility to perform subthalamic thermocoagulations with reduced risks and optimized accuracy. We describe here the initial results of the MRgFUS pallidothalamic tractotomy (PTT), an anatomical and physiological update of the earlier subthalamotomies. Methods Thirteen consecutive patients suffering from chronic (mean disease duration 9.7 years) and therapy-resistant PD were treated unilaterally with an MRgFUS PTT. Primary relief assessment indicators were the score reduction of the Unified Parkinson Disease Rating Scale (UPDRS) and the patient estimation of global symptom relief (GSR) taken at 3 months follow-up. Final temperatures at target were between 52°C and 59°C. The MR examinations were performed before the treatment, 2 days and 3 months after it. The accuracy of the targeting was calculated on 2 days post-treatment MR pictures for each PTT lesion. Results The first four patients received a PTT using the lesional parameters applied for thalamotomies. They experienced clear-cut recurrences at 3 months (mean UPDRS relief 7.6%, mean GSR 22.5%), and their MR showed no sign of thermal lesion in T2-weighted (T2w) images. As a consequence, the treatment protocol was adapted for the following nine patients by applying repetition of the final temperatures 4 to 5 times. That produced thermocoagulations of larger volumes (172 mm3 against 83 mm3 for the first four patients), which remained visible at 3 months on T2w images. These nine patients enjoyed a mean UPDRS reduction of 60.9% and a GSR of 56.7%, very close to the results obtained with radiofrequency lesioning. The targeting accuracy for the whole patient group was 0.5, 0.5, and 0.6 mm for the anteroposterior (AP), mediolateral (ML), and dorsoventral (DV) dimensions, respectively. Conclusions This study demonstrated the feasibility, safety, and accuracy of the MRgFUS PTT. To obtain similar results as the ones of RF PTT, it was necessary to integrate the fact that white matter, in this case, the pallidothalamic tract, requires repeated thermal exposition to achieve full lesioning and thus full therapeutic effect.

Background Potential peripheral sources of deep pain can require invasive evocative tests for their assessment. Here we perform research whose ultimate goal is development of a non-invasive evocative test for deep painful tissue. Methods We used a rat model of inflammation to show that intense focused ultrasound (iFU) differentially stimulates inflamed versus control tissue and can identify allodynia. To do so we applied iFU to inflamed and normal tissue below the skin of rats’ hind paws and measured the amount of ultrasound necessary to induce paw withdrawal. Results iFU of sufficient strength (spatial and temporal average intensities ranged from 100–350 W/cm2) caused the rat to withdraw its inflamed paw, while the same iFU applied to the contralateral paw failed to induce withdrawal, with sensitivity and specificity generally greater than 90%. iFU stimulation of normal tissue required twice the amount of ultrasound to generate a withdrawal than did inflamed tissue, thereby assessing allodynia. Finally, we verified in a preliminary way the safety of iFU stimulation with acute histological studies coupled with mathematical simulations. Conclusions Given that there exist systems to guide iFU deep to the skin, image-guided iFU may one day allow assessment of patient’s deep, peripheral pain generators.

Background Uterine fibroids are common among women at the reproductive age. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel and a conservative treatment for symptomatic cases. The aim of the study was to evaluate the efficacy of MRgFUS in African-American (AA) women compared with that in non-African-Americans (non-AA). Methods A single-armed phase IV study was conducted to establish the efficacy of treatment in AA women. Comparison of patient, fibroid, and treatment characteristics from this trial was compared with that of the previously published phase III trial. Both studies were approved by the IRB of each medical center. Results Sixty-three AA and 59 non-AA women were treated with MRgFUS. Although AA women had a different pattern of disease, outcomes were similar in both groups. AA patients had a significant higher total number of fibroids compared with non-AA (median 6.0, interquartile range (IQR) 3.0–10.0 vs. 2.0, IQR 1.0–4.0, respectively, p < 0.001), although their total fibroid volume was significantly smaller (median 196.9 cm3, IQR 112.8–415.3 cm3 vs. 394.8 cm3, IQR 189.8–674.4 cm3, respectively, p < 0.001). AA women were younger compared with non-AA (mean ± SD 43.4 ± 5.1 vs. 46.3 ± 4.1 years of age, respectively, p = 0.001) when they presented for treatment. The rate of alternative treatments as well as fibroid-associated symptoms at follow-up time points (3, 6, 12, 24, and 36 months, period following MRgFUS treatment) did not differ according to race (p ≥ 0.62). Conclusion Despite differences in the pattern of fibroid disease, MRgFUS for uterine fibroids has a similar efficacy for AA women compared with non-AA women.

The U.S. Food and Drug Administration (FDA) has automatically classified focused ultrasound (FUS) devices Class III, which requires sponsors to demonstrate the safety and effectiveness of a device through clinical trials. This requirement adds significant time and cost to the device development process; reclassification to Class II would be highly beneficial for the future of FUS.