MR-Guided High-Intensity Focused Ultrasound Lesioning: MRgHIFU Breathing Life in the Lost Art of Lesioning for Movement Disorders
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.302452
Source of Support: None, Conflict of Interest: None
Keywords: Focused ultrasound, high-intensity focused ultrasound, MRgHIFU, transcranial-focused ultrasound
The concept of focused ultrasound was first introduced in 1935. Later studies done by Lynn and colleagues in the 1940s demonstrated the feasibility of creating an ablative lesion in bovine liver and animal brain tissue using focused ultrasound., It was not until Fry developed a focused ultrasound device to produce accurate lesions without damaging the surrounding tissue.
First introduced as a commercial machine, “Sonablate 200” was produced in the United States by “Focused Surgery” aiming to treat hyperplasia and prostatic gland cancer. As for the treatment of brain diseases, the “ExAblate 2000” was the first magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) system to obtain the Food and Drug Administration (FDA) market approval and was produced by the Israeli-based innovator Insightec [Figure 1].
In this paper, we will describe the current indication, studies, and future applications of MRgHIFU.
Before surgery, pretreatment brain magnetic resonance imaging (MRI) planning images are enquired. At our institution, we use either 3 T or 1.5 T images. Besides, it is mandatory to obtain thin slices computed tomography (CT) scan (0.625 mm slice thickness) to evaluate the skull density ratio (SDR). These images will be registered, merged, and used for target definition. SDR is the median ratio of the skull density between the outer and inner cortical bone. This ratio is a major criterion in patient selection with a direct correlation to procedure success, and MRgHIFU should be suggested to patients with an SDR of 0.4 or higher.
With some similarity to radiofrequency lesioning done years ago for the treatment of movement disorders, MRgHIFU surgery is done as an awake procedure. Following fixation of the hamlet which contains 1024 ultrasound beam sources, the patient's head is secured to the MRI table and acquisition scans are done. Since ultrasound waves cannot cross air, the patient's hair needs to be thoroughly shaved and degassed water is used as a barrier. A round elastic silicon membrane is stretched around the patient's head to avoid spillage of the degassed water.
Following imaging acquisition, the target for lesioning is selected by the surgeon. Since microelectrode recording is nonfeasible (as MRgHIFU is an incision-less procedure), trail sonication is done with the escalation of the temperature to a non-ablative degree. One should remember that during sonication (transfer of the ultrasonic energy to the brain), real-time thermometry is done [Figure 2]. By doing so, transitional functional damage is done to the treated tissue, and clinical examination of the patient can help the surgeon localize the efficacy and proximity to eloquent structures. Following both clinical and radiologic confirmation, a thermal lesion is done at the desired target with an elevation of the temperature to more than 55°C. This increase in temperature causes a highly accurate hyperthermic ablative necrosis that can be observed via intraoperative imaging studies during MRgHIFU [Figure 3]. Lesion volume depends on multiple factors but typically a 4–5 mm diameter lesion can be obtained at a peak sonication temperature of 57–60°C (T2-weighted-MRI [T2-WMRI] is typically used to measure the lesion size). The accuracy of MRgHIFU is less than 2 mm, which is comparable with radiosurgery and gamma knife.
With accumulating clinical and neuroradiological data from multiple experienced centers using MRgHIFU for the treatment of movement disorders, and establishing a database, outcomes will defiantly improve. Since most diseases progress with time, there might be a need to retreat a group of patients with disease progression and tremors recurrence, as the long-term durability of MRgHIFU is yet to be established.
Current and future applications of MRgHIFU are shown in [Table 1].
The introduction of MRgHIFU for the treatment of essential tremor (ET) was done by Elias and colleagues in their pilot study comprising of 15 patients treated with unilateral ventral intermediate nucleus (VIM) thermal ablation. In their study, they proved the efficacy and safety of the procedure with a marked reduction of tremors and improvement in the quality of life. Since then multiple studies and reports were done to prove and assess the efficacy, safety, and cost-effectiveness of MRgHIFU in comparison to traditional procedures for the treatment of movement disorders. Richard et al., in a systematic literature review, conducted to identify the clinical, health-related quality of life, and economics of movement disorder surgeries concluded that MRI-guided focused ultrasound (MRgFUS) has similar short-term cost-effectiveness compared to deep brain stimulation (DBS) surgery. Halpern and colleagues reported in their study that when compared to DBS and radiosurgery, MRgHIFU thalamotomy is more effective than both. In a meta-analysis, Nanda et al. reported transient dizziness as the most common complication (occurring in 45.5% of patients), followed by nausea and vomiting. He additionally reported that the most common long-term complication was ataxia (occurring in 32.8%), followed by paresthesia (occurring in 25.1% of the patients). At 1 year, the ataxia had significantly recovered, and paresthesia became the most common persisting complication, at 15.3%.
For the treatment of non-ET tremors, Lozano in his study of three patients with Parkinson's disease (PD), two patients with dystonic tremor, and one patient with dystonia gene-associated tremor, who were treated with MRgHIFU targeting the VIM, reported a significant, immediate, and sustained improvement of the contralateral tremor.
In patients with PD, there are published reports of MRgHIFU ablation of the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Chang reported a 53% decrease in dyskinesia following unilateral MRgHIFU pallidotomy. Overall, the clinical improvement of PD patients treated with GPi or pallidothalamic tract thermal ablation is lower compared to improvement achieved with DBS surgery.
As MRgHIFU thermal ablative is the most studied mechanism, there are some clinical studies and reports of its use in the following areas:
Obsessive-compulsive disorder (OCD): Kim et al. in their report of 11 patients with treatment-refractory OCD treated via bilateral thermal ablation of the anterior limb of the internal capsule using MRgHIFU, showed a significant improvement in both depressive and anxiety symptoms. Lipsman and his group examined the safety profile, clinical response, and imaging correlates of MRgHIFU bilateral anterior capsulotomy in patients with refractory OCD and major depressive disorder (MDD). They reported no serious adverse effects with a positive response rate of 50%, with OCD patients showing a superior response rate.
Brain tumors and neuro-oncology: There have been several reports for using focused ultrasound as a thermal ablative procedure. Early in 2006, Ram reported a trial to treat patients with brain stem glioma, and later McDannols in his study reported a trial to treat three patients with high-grade brain tumors., Both studied could not be continued due to immature technical issues that did not enable sufficient accurate and volumetric thermal ablation. Further developments are needed to establish and use MRgHIFU for the treatment of brain tumors, and these are currently being investigated. These studies will probably include using microbubbles injections to enhance the efficacy of MRgHIFU.
Epilepsy and pain: The classic therapeutical approach to epilepsy is either ablation of the epileptogenic focus or disrupting the epileptogenic complex connectivity network. It is most appropriate to use MRgHIFU whenever there is an obvious target to be ablated, such as a hypothalamic hamartoma, cortical dysplasia, etc., Hoffman et al. described a computerized model for the treatment of medically refractory mesial temporal sclerosis (MTS) epilepsy patients requiring surgery. In the described model, MRgFUS surgical plans ablating sites of the posterior hippocampal disconnection were done and concluded that treatment with this modality is both feasible and safe.
Zibly et al., in a phantom experiment, tested the feasibility, safety, and efficacy of MRgFUS for treating facet joint pain. In their animal study, they proved that targeting the facet joint with energies of 150–450 J provides controlled and accurate heating at the facet joint edge without penetration to the vertebral body, spinal canal, or root foramina. Monteith et al. in a cadaver study demonstrated the feasibility of targeting the trigeminal root entry zone and was able to avoid technical obstacles such as bone and brain stem heating.
Currently, the FDA has not yet approved the use of MRgHIFU for bilateral thermal ablation, so only one side of the affected limbs can be treated. Clinical studies are being done to assess the safety and efficacy of bilateral ablation, and these are yet to be evaluated.
The present MRgHIFU systems present a narrow therapeutic area which is of 3 cm radius around the mid-commissural point. This makes treatment possible by targeting the thalamus and the basal ganglia but reduces the treatment efficacy of cortical and subcortical regions.
When passing through the inner and outer cortical table of the skull, the ultrasound waves may cause transient heating of the bone and even necrosis (asymptomatic)., Due to a similar mechanism, the scalp is also subjected to overheating and there have been rare reports of scalp burns.
Since MRgHIFU is an ablative procedure, neurological adverse effects can be immediate and long-lasting. The side effects are mainly attributed to the location of the thermal ablation and can be resolved with the resolution of perilesional edema.
Amid as a lost art, lesioning of brain tissue for the treatment of a diversity of central nervous system disorders, MRgHIFU is a promising flourishing noninvasive technology. It guarantees both patients and physicians, the ability to target deep brain areas in conjunction with the accuracy and feasibility of invasive stereotactic surgery. Future studies will undoubtfully expose new indications of its safe use in neurosurgery.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]