Medical Policy

This document addresses magnetic resonance imaging (MRI) guided high intensity focused ultrasound (HIFU) ablation, also known as magnetic resonance guided focused ultrasound (MRgFUS), when used to treat any non-oncologic indications, including but not limited to uterine fibroids, essential tremor (ET), or benign prostatic hyperplasia (BPH). The ultrasound beam penetrates through the soft tissues and can be focused to targeted sites, using MR for guidance and monitoring.

Note: Please see SURG.00135 Renal Sympathetic Nerve Ablation for the ablation of renal sympathetic nerves using high-intensity focused ultrasound.

Note: Please see the following related documents for additional information:

• CG-MED-81 Ultrasound Ablation for Oncologic Indications
• CG-SURG-28 Transcatheter Uterine Artery Embolization
• CG-SURG-91 Minimally Invasive Ablative Procedures for Epilepsy
• CG-SURG-108 Stereotactic Radiofrequency Pallidotomy
• SURG.00026 Deep Brain, Cortical, and Cerebellar Stimulation

Medically Necessary

1. Unilateral focused ultrasound thalamotomy is considered medically necessary for the treatment of adults with essential tremors when all of the following criteria are met:
   1. Moderate to severe tremor of the hand (as defined by a score of 2 or greater on the clinical rating scale for tremor [CRST]); and
   2. Failure of 2 or more tremor suppressant medications, as evidenced by persistent moderate to severe tremors, intolerable side effects of drug therapy or contraindications; and
   3. At least 1 of the medications failed was a first line agent (propranolol or primidone).
2. Unilateral focused ultrasound pallidotomy is considered medically necessary for the treatment of idiopathic Parkinson’s disease in individuals who meet all of the following criteria:
   1. Age 30 or older; and
   2. Unilateral pallidotomy is used as an adjunct to medication treatment of idiopathic Parkinson’s disease; and
   3. Levodopa responsive (as defined by a 30% or greater reduction in the Movement Disorder Society- Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor subscale in the on versus off levodopa medication state; and
   4. Moderate-to-severe motor complications as defined by at least one of the following:
      1. MDS-UPDRS score of 20 or greater in the meds off condition; or
      2. Motor complications on optimum medical treatment documented by at least one of the following:
         1. Dyskinesia (as defined by MDS-UPDRS item 4.2 score of 2 or greater in the meds on condition); or
         2. Motor fluctuations (as defined by MDS-UPDRS item 4.4 score of 2 or greater);
            and
   5. The individual is not a candidate for either the following procedures:
      1. Deep brain stimulation (DBS); or
      2. Radiofrequency (RF) thermoablation;
         and
   6. The absence of all of the following conditions:
      1. Central neurodegenerative disease other than Parkinson’s Disease (includes multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, and Alzheimer’s disease); or
      2. Previous deep brain stimulation; or
      3. Previous basal ganglia ablation procedure; or
      4. Coagulopathy or current anticoagulant use which cannot be reversed; or
      5. Intracranial tumor with significant anatomic distortion.

Investigational and Not Medically Necessary:

MRI guided high intensity focused ultrasound ablation is considered investigational and not medically necessary when the criteria above are not met and for all other non-oncologic indications.

Essential Tremor (ET)

The first line treatment for ET is pharmacotherapy, with propranolol and primidone considered as first line medication (Elias, 2016). Neurosurgical intervention targeted at the nucleus ventralis intermedius of the thalamus can be considered for individuals who have failed medication therapy. The targeted tissue connects the cerebellum with cortical motor pathways. Radiofrequency thalamotomy and deep brain stimulation have been used to disrupt this pathway and suppress tremors. Acceptance of these procedures by those with ET has generally been low based upon the reluctance to undergo the invasive procedures.

In July 2016, the U.S. Food and Drug Administration (FDA) approved the ExAblate Neuro^® system (InSightec, Inc., Dallas, TX) as a treatment of idiopathic ET in adults aged 22 or older whose tremor has failed pharmacological treatment. ExAblate Neuro uses focused ultrasound to induce a unilateral thalamic lesion (thalamotomy) when the ventralis intermedius has been identified and is accessible for ablation by the device. The intent of treatment is to reduce an individual’s ET and increase motor function.

Elias and colleagues (2013) reported on the results of a feasibility trial for the ExAblate Neuro unilateral transcranial MRI-guided focused ultrasound thalamotomy to treat medication-refractory ET. The study defined medication refractory tremor as failure of treatment with at least two trials of full-dose therapeutic medication, one of which had to be a first line therapy (propranolol or primidone). In this uncontrolled pilot study, 15 individuals with severe medication-refractory ET underwent a single treatment session using the ExAblate Neuro system. Assessments were performed at baseline, 1 day, 1 week, 1 month, 3 months and 12 months following treatment, with the change in hand tremor score at 3 months being the primary clinical outcome. Hand tremor was scored using a summation of eight items which graded hand tremor and ability to perform tasks. Higher scores denoted more severe tremor, and the maximum score was 32. There was significant improvement in contralateral hand tremor from baseline (20.4 ± 5.2) to 3 months (4.3 ± 3.5) and 12 months (5.2 ± 4.8). No significant difference in ipsilateral hand tremor scores from baseline to 12 months was found. Paresthesias of the face or fingers were the most common reported side effects, with 4 individuals reporting persistent paresthesias. The authors recommended that larger studies were needed to evaluate potential associated cognitive impairment and include a comparison to the current standard therapy.

Subsequent to the above pilot study, Elias and colleagues (2016) published the results of a prospective, sham-controlled, double-blind, randomized trial of 76 participants, which evaluated MRI-guided focused ultrasound thalamotomy treatment of moderate to severe medication-refractory ET. Medication refractory treatment was defined as tremor refractory to at least 2 agents, with at least one being propranolol or primidone. Participants were assigned in a 3:1 ratio to undergo either the active treatment, MRI-guided focused ultrasound thalamotomy, or sham treatment. Following evaluation of the primary endpoint at 3 months, the individuals in the sham group could cross over to the active treatment group. The change in hand tremor scores from baseline to 3 months was defined as the primary efficacy outcome measure. The hand tremor score was based upon components of the Clinical Rating Scale for Tremor (CRST) related to hand tremor, with higher scores indicating more severe tremor. At 3 months, the mean score in the contralateral hand in the active treatment group improved by 47% compared to the sham group mean score improvement of 0.1% (18.1 ± 4.8 to 9.6 ± 5.1 versus 16.0 ± 4.4 to 15.8 ± 4.9; between group change 8.3 points; 95% confidence interval [CI], 5.9-10.7; p=0.001). At 12 months, the significant improvement over baseline persisted. There was no significant change in the tremor score in the ipsilateral hand compared to baseline. The results were similar in the sham crossover group; 19 participants who crossed over to active treatment reported a significant improvement in contralateral hand tremor at 3 and 6 months respectively (16.5 ± 4.2 to 7.4 ± 3.9 and 16.5 ± 4.2 to 8.0 ± 3.9,). A total of 74 neurological adverse events (AEs) occurred in 56 individuals who underwent active treatment, including 38% with sensory alteration and 36% with cerebellar deficits such as dysmetria and ataxia and other gait disturbance, which persisted to 12 months at 14% and 9%, respectively.

Several follow-up studies have evaluated durability of MRI-guided focused ultrasound thalamotomy 2 to 3 years following treatment. Chang and colleagues (2018) reported on the 2-year follow-up outcomes of the Elias 2016 randomized controlled trial (RCT). The mean hand tremor score initially improved by 55% (from 19.8 ± 4.9 at baseline to 8.6 ± 4.5) at 6 months post procedure. At 2 years, the mean hand tremor motor score was improved by 56% over baseline (8.8 ± 5.0; change in the score from baseline to 2 years, 11 points). At 3 years post-procedure, Halpern and colleagues (2019) evaluated outcomes of this same group. The median hand tremor motor score was stable at 56% improvement over baseline (median score of 8). In a retrospective review, Meng and associates (2018) assessed the 2-year outcomes of 37 individuals who underwent unilateral MRgFUS thalamotomy to treat moderate to severe medically refractory ET. A 42.4% (95% CI, 32.0%-52.9%) improvement in the baseline dominant tremor score (20.3 ± 5.0) was maintained at 2 years (43.4%: 95% CI: 27.8%-59.0%). At 1 year post-treatment, 45.7% of the individuals had significant tremor improvement; this had decreased to 35.3% at 2 years (Halpern, 2019). These follow-up studies report substantial drop-out rates, introducing the potential for retention bias into the results. Additional studies with follow-up from 3 to 5 years post-procedure report showed sustained improvement from baseline (Cosgrove, 2022; Halpern, 2019; Park, 2019; Sinai, 2019).

The International Parkinson and Movement Disorder Society published an evidence-based review of ET treatments (Ferreira 2019). The task force noted that unilateral MRgFUS thalamotomy is “likely efficacious” (evidence suggests, but is not sufficient to show, that the intervention has a positive effect on studied outcomes). The task force concluded that unilateral MRgFUS thalamotomy is “possibly useful” for clinical practice. The society’s recommendation is based on the Elias (2016) RCT.

Miller and colleagues (2022) reported on the prevalence of worsening tremor over time following MRgFUS treatment of ET. This is the phenomenon noted above in Louis’s analysis of the pivotal trial published by Elliot et al. Miller’s meta-analysis included 17 prospective studies, 3 retrospective studies and 1 RCT. Tremor was evaluated using hand tremor scores (HTS), CRST scores, or Quality of Life in Essential Tremor Questionnaire (QUEST) using pool reported effects. The analysis showed ongoing treatment benefit but decreasing treatment effect from 3 to12 months and 24 months following treatment. The authors noted that this diminishing effect might be due to heterogeneity within the studies, disease progression, or a true waning effect over time. Diminished effects have also been reported with DBS, either due to disease progression or habituation. At this time, there are no studies which directly compare MRgFUS and DBS.

The American Society for Stereotactic and Functional Neurosurgery (ASSFN) position statement on MRgFUS (Pouratian, 2020) notes the following indications when using MRgFUS as a treatment option of ET:

1. Confirmed diagnosis of ET.
2. Failure to respond to, intolerance of, or medical contraindication to use of at least 2 medications for ET, 1 of which must be a first-line medication.
3. Appendicular tremor that interferes with quality of life (QoL) based on clinical history.
4. Unilateral treatment.

The ASSFN position statement  notes the following contraindications to MRgFUS therapy:

1. Bilateral MRgFUS thalamotomy.
2. Contralateral to a previous thalamotomy.
3. Cannot undergo magnetic resonance imaging (MRI) because of medical reasons.
4. Skull density ratio (ratio of cortical to cancellous bone) is <0.40

The ASSFN statement also notes that there is insufficient evidence to support treatment of tremors of the head, voice or neck with MRgFUS.

In 2020, Giordano and associates published a systematic review comparing unilateral MRgFUS thalamotomy to unilateral and bilateral DBS. Studies reporting on the treatment of drug-refractory ET using DBS (n=37) or MRgFUS (n=7) were included. There were no prospective randomized studies directly comparing MRgFUS to DBS. A total of 1202 individuals were included in this study’s DBS group and 477 individuals were included in the MRgFUS group. At 14.4-16.6 months follow-up, the improvement in quality of life was significantly greater in the MRgFUS group (61.9%) compared to the DBS group (52.5%). During that follow-up period, there was a significantly higher improvement in tremor severity in the DBS group (60.1%) compared to the MRgFUS group (55.6%). While a subgroup analysis showed no differences in tremor severity between unilateral DBS therapy and MRgFUS therapy, bilateral DBS therapy was superior to both unilateral treatments. The authors asserted that bilateral DBS is the current gold standard treatment for medication-resistant ET. Bilateral staged MRgFUS thalamotomy is currently undergoing feasibility testing. MRgFUS and DBS have different complication patterns. MRgFUS is associated with a higher prevalence of gait disturbances/muscle problems, nausea and paresthesias. DBS is associated with a higher prevalence of speech disturbances and local adverse symptoms. Persistent complications are more frequent with MRgFUS than with DBS therapy. This may be due to permanent tissue destruction induced by MRgFUS compared to DBS which can be reprogrammed or turned off.

MRgFUS for ET Summary

DBS has been considered the standard of care treatment for medically refractory ET. Radiofrequency ablation has been considered an option in individuals who are high risk candidates for DBS surgery. These procedures are associated with risks including intracerebral hemorrhage, post radiation necrosis, infections, and hardware malfunction. Adoption of these modalities by individuals with medically refractory ET has been limited due to the invasiveness of these procedures and their perceived risks. MRgFUS has become widely accepted by the medical community as an effective minimally invasive therapy for individuals who are not candidates for, or refuse to undergo, a more invasive procedure.

Parkinson’s Disease (PD)

Krishna and associates (2023) evaluated the safety and efficacy of focused ultrasound ablation (FUSA) of the globus pallidus internus in individuals with PD. Individuals with PD and dyskinesias or motor fluctuations and motor impairment in the off-medication state were eligible to be included in this multicenter, prospective, double-blind, randomized, sham-controlled trial. Trial eligibility was determined by scores on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Participants were randomized to receive FUSA of the globus pallidus internus (n=69) or a sham procedure (n=25). The primary outcome was a response- a decrease or improvement of at least 3 points on either of the cited scales on the treated side without a clinically meaningful worsening in either scale at 3 months. A total of 65/69 participants (94%) in the treatment group and 22/25 (88%) in the sham group completed the 3-month assessment. At 3 months, approximately one-third of participants in the FUSA group were classified as having a response resulting in improved motor function and reduced dyskinesia, one-third were classified as non-responders. Approximately one-third of participants in the sham group had a response. After the 3-month evaluation, 20 individuals in the sham group elected to undergo active treatment. The 3-month outcomes of the cross-over group were similar to the initial active treatment group. The authors of the study concluded:

The procedure has recently been approved by the FDA for unilateral treatment only, whereas most patients with Parkinson’s disease have bilateral motor signs and symptoms. There are limitations of the procedure in a condition with bilateral manifestations. Unlike deep-brain stimulation, there is no opportunity to treat progressive worsening of motor symptoms. Owing to the lack of ability to modify the lesion after the procedure, operators must prioritize safety during treatment. With deep-brain stimulation, adjustments in programming can attempt to improve the balance between a reduction in motor symptoms and a reduction in stimulation-related side effects, even years after implantation.

Schrag (2023) commented that the results of the Krishna (2023) study were promising, but noted:

given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.

The long-term clinical outcomes of focused ultrasound ablation thalamotomy to treat tremor dominant PD (TDPD) showed that therapeutic benefits might continue up to 5 years post-procedure (Sinai, 2022). Individuals with TPDP who chose surgery over DBS at a single institution (n=26) were followed for up to 60 months. The unilateral FUSA thalamotomy was used to primarily alleviate tremor in the dominant hand. Immediately following treatment, tremors completely ceased in 23 of the 26 participants and there was a 90% improvement in the remaining 3 participants. The median duration of follow-up was 36 months. Seven participants (27%) were evaluated after 5 years. In the 5-year follow-up, 1 individual experienced return of tremors to the baseline level. Five other participants had a partial return of tremors. All AEs were reported within 1 week of treatment and reported as mild and transient. The significance of these results was limited by the small number of participants and significant loss to follow-up. The authors did not report on the individuals who chose to undergo DBS rather than FUSA thalamotomy.

In an initial pilot investigation, Bond and associates (2017) evaluated the safety and efficacy of focused ultrasound thalamotomy for the treatment of medically refractory, (TDPD). In a double-blind, sham-controlled, pilot RCT, 27 individuals were treated with FUSA thalamotomy (n=20) or sham procedure (n=7). After 3 months, individuals in the sham procedure group were offered open-label treatment and 6 individuals underwent FUS thalamotomy. The primary outcome was the change from baseline to 3 months in the treated upper limb tremor subscore. Hand tremor improved 62% (interquartile range [IQR] 22%-79%) from a baseline of 17 points (IQR 10.5-27.5) following FUSA thalamotomy and 22% (IQR −11% to 29%) from a baseline of 23 points (IQR 14-27) after sham procedures (p=0.04). AEs occurred in approximately 35% of all individuals treated and included finger paresthesia, ataxia, and orofacial paresthesia. At 1 year, only 14 (47%) of the original 30 individuals in the initial treatment group were available for evaluation. Of these, 13 individuals reported a positive outcome. While this initial pilot study reported positive results, this was a small study which did not reach its planned enrollment size and lost a significant portion of the treatment group at 1 year follow-up. In addition, the authors noted a potential confounder in allowing medication dose changes during the trial. Larger trials comparing FUS thalamotomy to standard treatment with longer follow-up are needed to better evaluate long-term clinical outcomes.

Central Neurodegenerative Disease

Neurodegenerative diseases are progressive conditions which result in both physical and mental impairments. The common feature of all neurodegenerative diseases is neuronal death. The presenting symptoms are dependent on the type and position of the degenerated neurons within the brain. The etiology of neurodegenerative diseases is poorly understood, but there are similar features across all diseases: disrupted proteostasis, oxidative and endoplasmic reticulum stress, metabolic dysfunction, and neuroimmune system alterations (Bloomingdale, 2022). The blood-brain barrier has limited the effectiveness of potentially curative pathogenesis-targeting pharmacological therapies (Lamptey, 2022). Treatments are limited to symptom alleviation.

Neurodegenerative diseases, such as progressive supranuclear palsy were once considered a type of atypical Parkinsonism but is now categorized as a separate motor and behavioral syndrome (Boxer, 2017). Corticobasal degeneration is closely related to progressive supranuclear palsy and there appears to be considerable overlap between the syndromes, clinically and genetically (Boxer, 2017). Lewy body with dementia and PD dementia are currently both characterized as being under the umbrella term Lewy body dementia. There are no curative treatments available and therapy is focused on symptom management. Management is difficult as treatment aimed at addressing one symptom may worsen other symptoms (Taylor, 2020). Taylor and colleagues (2020) describe the differences between these conditions noting:

The two diseases are demarcated clinically from one another by the so-called 1-year rule, based on the temporal onset of motor relative to cognitive symptoms (ie, in Parkinson’s disease dementia the motor symptoms precede the onset of dementia by at least one year).

There are knowledge and evidence gaps regarding the pathophysiology and treatment of central neurodegenerative disorders. The presence of atypical Parkinsonism is considered a contraindication for other established treatments of PD (Fabbri 2023; Sharma, 2020). There are no studies which evaluate the clinical outcomes of focused ultrasound lesioning in treating idiopathic PD when another central neurodegenerative disease has also been diagnosed.

Anatomic Distortion

The presence of masses within the enclosed space of the cranial vault present unique challenges (Sorribes, 2019). Expanding tumor mass may cause changes within the intracranial anatomy, including compression, distortion due to brain shift and traction of intracranial structures (Khan, 2013). These changes are the result of pathological processes, including tumor cells displacing adjacent healthy tissue, tumor-induced vascular abnormalities, disruption of the blood brain barrier and cerebral edema (Sorribes, 2019). Cerebrospinal fluid displacement, cerebral blood flow decrease, and changes in the parenchyma shape may result, in order to compensate for the increasing intracranial pressure (Sorribes, 2019). There is a paucity of evidence evaluating intracranial focused ultrasound therapy in the presence of significant distortion by intracranial pathology.

MRgFUS for Parkinson’s Disease Summary

Unilateral lesioning surgery (LS) is preferred over bilateral procedures, which are associated with increased side effects. Sharma and associates (2020) note:

A major limitation of LS is increased side effects with bilateral lesions, including aphasia, dysarthria, dysphagia, and cognitive deficits about 30 to 60% for bilateral thalamotomies and hypophonia, neuropsychological, and cognitive deficits about 17% for bilateral pallidotomies.

Generally, thalamotomy is considered for tremor-predominant PD or ET, although in individuals with PD, a pallidotomy might be a better choice as it can additionally improve bradykinesia and rigidity.

Pharmacological therapy has been the primary treatment to manage symptoms in individuals with PD. DBS has been an option for individuals with disabling and medically unresponsive disease. Radiofrequency pallidotomy is considered an option in individuals who are high risk candidates for DBS surgery. DBS and radiofrequency pallidotomy are invasive procedures with potential complications such as intracerebral hemorrhage, infections, and hardware malfunction. Focused ultrasound has been evaluated as an alternative to other invasive procedures in medically refractory PD. Experts in the field advise that MRgFUS should be an option for individuals with severe, treatment-resistant, tremor predominant Parkinson’s disease who are not candidates for DBS or radiofrequency pallidotomy. Further data regarding long-term outcomes are needed regarding use of other lesioning surgery in treating PD.

Other Movement Disorders

Altinel and colleagues (2019) conducted a systematic review and meta-analysis comparing lesion surgery to DBS to treat tremor related to Parkinson’s Disease, ET or multiple sclerosis. While the analysis included 15 randomized studies, only 2 studies used MRgFUS to create the lesion. The duration of follow-up in both studies was limited to 3 months. A separate analysis found no difference in tremor severity improvement between MRgFUS, DBS and other types of lesion surgery. Over the short-term 3-month follow-up period, MRgFUS was associated with higher QOL scores than DBS. This analysis was limited by heterogeneity (tremor etiology, type of lesion surgery), limited follow-up times and lack of direct comparison groups.

In 2018, Schreglmann and associates evaluated efficacy and the prevalence of persistent side effects of different lesioning techniques in the treatment of ET, Parkinson’s disease, dystonic tremor, multiple sclerosis or lesions to the midbrain or cerebellar structures. ET was treated with MRgFUS, Gamma Knife or radiofrequency in 6 retrospective and 7 prospective studies. The primary outcome was the change in upper limb tremor severity from baseline to follow-up, with the selected follow-up time-point as the point with the largest number of individuals retained. As the follow-up times varied, the authors controlled for an effect on follow-up duration on the effect size. The authors reported that the duration of follow-up did not have a significant influence on treatment effect size. There were no significant differences over the studied time periods with regard to the mean effect on tremor severity or the rate of persistent side effects. The authors concluded that head-to-head comparisons between DBS and MRgFUS are needed to further evaluate tremor treatment and noted:

Nevertheless, this systematic review also shows how limited the evidence base is in particular for MRIgFUS ablation in conditions other than ET. It therefore highlights the need for adequately designed prospective trials to support the existing data on safety and efficacy for established targets such as V.im. and of recently rediscovered targets within the PSA. Before that, the indiscriminate application of incisionless interventions to novel indications could potentially harm the further development of this fascinating technique.

BPH

HIFU ablation is a minimally invasive procedure using a transrectal ultrasound probe to image the prostate and deliver timed bursts of heat to create coagulation necrosis in a targeted area without harming adjacent healthy tissue (Leslie, 2006). Schatzl and colleagues (2000) compared the efficacy of transurethral resection of the prostate (TURP) to four less invasive treatment options including HIFU in a small clinical trial. Randomization was attempted but could not be carried out because treatment options for each participant were limited based on specific characteristics such as prostate size, prostatic calcifications and middle lobes. The individuals who received HIFU tended to have smaller prostates and less severe symptoms than those who received TURP. A second study reported by Madersbacher and colleagues (2000) attempted to determine the long-term outcome after HIFU therapy for individuals with lower urinary tract symptoms (LUTS) due to BPH. The data collected between June 1992 and March 1995 indicated that HIFU therapy for BPH, at least in its present form, did not “stand the test of time,” as 43.8% of individuals had to undergo TURP within 4 years after initial therapy. Additional long-term studies are warranted to reliably assess the role of HIFU as an established alternative to standard treatments for BPH. In recent years, few trials evaluating the use of HIFU in BPH have been published.

Uterine Fibroids

Stewart and colleagues (2003) studied the safety and feasibility of MR-guided HIFU (referred to as focused ultrasound surgery [FUS] in this study) in a case series of 55 women with symptomatic uterine fibroids who underwent HIFU treatment and, in some cases, a planned hysterectomy within 1 month after the ultrasound treatment (n=28). In the latter group, hysterectomy specimens provided pathologic evidence of accurate levels of thermal energy delivered and revealed 3 times the volume of necrotic fibroid tissue than was targeted for treatment. Reported side effects related to HIFU were minimal. Authors concluded that “…correlation of both treatment and patient parameters with the surrogate endpoint of post-FUS MRI and, ultimately, symptom reduction will be necessary in future studies to optimize therapy for individual women.”

In the study designed for FDA approval of the ExAblate^® 2000 (InSightec, Ltd, Dallas, TX), Stewart and colleagues studied 109 women treated with MR-guided HIFU and 83 women treated with abdominal hysterectomy. The initial article published in 2004 and the follow-up article published in 2006, only reported the outcomes for the group treated with HIFU. The study’s primary outcome was change in the symptom severity score (SSS) that is part of the validated Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QOL). Symptom severity was measured on a 0 (less severe) to 100 (most severe) scale with eight questions relevant to bulk and bleeding symptoms. At the 6-month follow-up, 71% of the HIFU group achieved a 10-point or greater reduction in SSS which decreased to 51% at 12 months. It was unclear what value represented a clinically meaningful change in SSS. Furthermore, 21% of those treated by HIFU needed additional surgical treatment, and 4% underwent a repeat MRI guided HIFU within 12 months of the first treatment.

Stewart and colleagues (2007) published results from three phase III trials and one post-marketing study. A total of 416 women were enrolled who received HIFU. Quality of life outcomes, measured again by the SSS of the UFS-QOL, were assessed for 359 women who were available at the 24-month follow-up. Clinical endpoints of the trials included uterine shrinkage, the need for additional fibroid treatment and the time to additional fibroid treatment. The study found a relationship between the non-perfused volume ratio and the probability of undergoing additional fibroid treatment. There was significantly greater improvement in women who had a more complete ablation; however, for women with minimal ablation, the need for additional treatment/procedures was high.

Fennessy and colleagues (2007) evaluated MR-guided HIFU using different treatment protocols. Results from nonrandomized, consecutive participants treated with the original protocol (33% of fibroid volume with a maximum treatment time of 120 minutes, n=96) were compared to a modified protocol (50% treatment volume, 180-minute maximum treatment time, and a second treatment if within a 14-day period, n=64). In the original protocol group, the non-perfused (effectively treated) area was calculated at 17% of fibroid volume compared with 26% of fibroid volume with the modified protocol group. Overall, symptom severity was reported to have decreased from a score of 62 at baseline to 33 at 12 months, with fewer participants in the modified group choosing alternative treatment (28% versus 37%). Out of the 160 participants initially treated, 55 from the original treatment protocol and 21 from the modified protocol group were evaluated at the 12-month follow-up.

In 2009, Taran and colleagues reported outcomes for the hysterectomy group in the 2006 Stewart study. The Taran article did not use the original primary outcome measure (SSS scores) and instead reported findings using the SF-36 quality of life measure as well as safety data. A significantly higher proportion of women in the hysterectomy group (82 of 83, 99%) reported at least one AE compared to women in the MR-guided HIFU group (88 of 109, 81%). Pain or discomfort, AEs associated with the gastrointestinal tract, dermatological system, nervous system, and cardiovascular system were significantly more common in the hysterectomy group. However, a similar proportion reported a serious AE, 9 of 109 (8%) in the HIFU group and 8 of 83 (10%) in the hysterectomy group. The authors concluded that the results of their study showed that HIFU treatment of uterine fibroids leads to clinical improvement with fewer significant clinical complications and AEs compared to hysterectomy during the 6-month follow-up period. The authors did acknowledge important limitations of the study--factors that were consistent with more severe disease. The women undergoing hysterectomy had increased body mass index (BMI), were less likely to be Caucasian, had higher symptom severity scores and had an increased use of medication for fibroid-related symptoms. They also pointed out the possibility of potential data collection bias between the novel-treatment group and the control group. Although this study proposes HIFU as a treatment alternative to hysterectomy for symptomatic fibroids, it did not demonstrate clinical efficacy when compared to the current accepted treatments of uterine fibroids.

Kim and colleagues (2011) reported a 3-year follow-up on a prospective study of 40 women with symptomatic fibroids. A total of 51 fibroids were treated with MR-guided HIFU. Clinical assessments were obtained at 3 months, 6 months, and 1, 2, and 3 years after HIFU treatment, as well as the SSS from the UFS-QOL. An MRI was performed at each follow-up to assess the efficacy of the treatment at 6 months, 1 year, 2 years, and 3 years. The mean baseline volume of treated fibroids was 336.9 cm³. The mean improvement scores for transformed SSS was 47.8 (p<0.001) and for transformed UFS-QOL was 39.8 (p<0.001) at 3 years. The mean volume decrease in treated fibroids was 32.0% (p<0.001) and in the uterus, the volume decrease was 27.7% (p<0.001) at 3 years. There were no complications. The authors noted that although these results are preliminary, MR-guided HIFU for the treatment of uterine fibroids may be an acceptable treatment option.

Ikink (2013) conducted a nonrandomized uncontrolled study to assess the clinical efficacy of MR-guided ultrasound techniques for the treatment of symptomatic uterine fibroids (n=46 premenopausal women). Clinical outcomes were measured using the SSS of the UFS-QOL questionnaire. Results showed that HIFU treatment resulted in a significant reduction in fibroid volume compared with baseline measurements (p<0.001), corresponding to a volume reduction of about 29%. In addition, 25 of 46 women (54%) reported a significant improvement in mean transformed SSS compared with baseline values (p<0.001). This study was also characterized by significant limitations, including lack of randomization and lack of a control arm.

Clark and colleagues (2014) conducted a systematic review of the efficacy of MRgFUS, specifically on its performance preserving fertility in women. A total of 10 studies, representing 589 women, were chosen for inclusion in the meta-analysis. Study inclusion criteria included a report of mean SSS at baseline and 6-month follow-up. The overall mean improvement in SSS 6 months after MRgFUS was estimated at 31.0% (95% CI, 23.9-38.2%). Authors concluded that, “Given the minimally invasive approach, MRgFUS could become the treatment of choice for patients desiring future fertility; however, further investigation is needed.”

Another 2014 systematic review completed by Gizzo and colleagues evaluated the safety, feasibility, indications, complications, impact on UFS-QOL and fertility associated with myomectomy performed by MRgFUS. This review included 38 studies and a total of approximately 2500 women. While the authors concluded that MRgFUS was a safe and efficient technique, it was noted that comparisons with other traditional techniques have not yet been performed.

Pron (2015) reviewed the published evidence related to MRgHIFU to treat uterine fibroids. The evidence used in the review included two systematic reviews, two RCTs, 45 cohort study reports, and 19 case reports. This evaluation did not include any randomized trials comparing MRgFUS to other guidance methods, other minimally invasive treatments, or surgeries for symptomatic uterine fibroids. The author concluded MRgHIFU can be a safe and effective non-invasive, uterine preserving treatment alternative to hysterectomy for individuals failing medical therapy. However, the author also noted there is limited information regarding treatment durability. In addition, there is a lack of existing evidence comparing MRgHIFU to the current standard treatment.

Well-designed clinical studies evaluating the safety and efficacy of MRgFUS using relevant outcome measures are lacking. Studies have generally lacked comparison to the current accepted treatments of uterine fibroids. Additionally, based on the prevalence of uterine fibroids, a relatively small number of women have been studied in clinical trials. The published evidence regarding MRgFUS does not adequately address the potential for regrowth of treated uterine fibroids over time, particularly beyond 3 to 5 years. In order to demonstrate MRgFUS as a safe and effective treatment option for uterine fibroids, well-designed RCTs with sufficient follow-up periods and appropriate clinical outcome measures are needed to compare therapy with alternative treatments.

The American College of Radiology (ACR) Appropriateness Criteria^® Treatment of Uterine Leiomyomas (2017) states that:

To date, there is little long-term information on the efficacy of this technology. It has been reported that myomas treated with HIFU have nearly 50% volume reduction at 1 year, but viable cells are present at biopsy in nearly 26% of specimens. Funaki et al. report a 24-month volume reduction of 40% with significant symptomatic improvement at 6 months that remained stable at 24-month follow-up. In a multicenter trial, Stewart et al. demonstrated significant reduction in fibroid-related symptoms in 70% of patients at 6 months and 51% of patients at 12 months.

The American College of Obstetricians and Gynecologists (ACOG) stated in their practice bulletin, Management of Symptomatic Uterine Leiomyomas (2021):

Limited, low-quality data suggest that magnetic resonance-guided focused ultrasound and high-intensity focused ultrasound are associated with a reduction in leiomyoma and uterine size. However, small randomized comparative trial data suggest that compared with UAE, magnetic resonance-guided focused ultrasound is associated with less improvement in symptoms and quality-of-life measures and a higher risk of reintervention.

Other Conditions

MRgFUS is being studied for a variety of conditions, including but not limited to benign thyroid nodules, chronic neuropathic pain, desmoid tumors, obsessive compulsive disorder or primary hyperparathyroidism (Chung, 2020; Jeanmonod, 2012; Jung, 2015; Kovatcheva, 2014; Martin, 2009; Monteith, 2016). These preliminary studies are in the early stages of evaluating the feasibility, efficacy and safety of the use of MRgFUS for the treatment of these conditions.

BPH

BPH, the nonmalignant growth of the smooth muscle and epithelial cells within the prostate, is a common age-related manifestation. While almost all men will develop histologic BPH, this condition will not require treatment unless it is associated with subjective symptoms, such as LUTS. LUTS symptoms can be divided into two categories. Obstructive symptoms include hesitancy, straining, weak flow, prolonged voiding, partial or complete urinary retention or overflow incontinence. Irritative symptoms include frequency, urgency with urge incontinence, nocturia, and painful urination or voiding small amount (Roehrborn, 2005). The primary goal of treatment is to alter disease progression and prevent complications (AUA, 2014). If BPH has advanced to the point of causing obstruction, interventions may be aimed at removing excessive tissue and relieving the obstruction. HIFU has been proposed as a means of removing excessive prostate tissue.

ET

ET is a progressive, disabling movement disorder, affecting as much as 4% of the population (Elias, 2013). ET does not reduce life expectancy but does adversely affect QOL. While there does appear to be a familial component, the cause of this disorder is not known. Medication is the initial treatment when the symptoms interfere with function and QOL, with propranolol and primidone considered first-line agents. Second-line agents, such as gabapentin or carbamazepine are considered less effective. Approximately 30- 50% of individuals treated for ET cannot tolerate or fail medication therapy. Surgical treatments include radiofrequency thalamotomy, surgical resection and deep brain stimulation. MRgFUS is considered a minimally invasive treatment option. Similar to radiofrequency thalamotomy and surgical resection, MRgFUS creates a thalamic lesion which can reduce tremor, but can also result in permanent neurologic deficits (Elias, 2016). While creation of a lesion does reduce tremor and larger lesions can result in more enduring efficacy, larger lesions have a higher incidence of side effects (Elias, 2016).

Tremor severity is quantified using a tremor rating assessment scale. Fahn–Tolosa–Marin Clinical Rating Scale and the Essential Tremor Rating Assessment Scale (TETRAS) rate tremors on a scale from 0 to 4. The initial tool, the Fahn–Tolosa–Marin Tremor clinical rating scale was not specific to ET. TETRAS, developed specifically for ET, correlates strongly with the Fahn–Tolosa–Marin Clinical Rating Scale. TETRAS was developed for use to evaluate ET severity in clinical trials and to monitor disease progression. The following table excerpt represents the upper limb tremor as defined by the Essential Tremor Rating Assessment Scale (Elble, 2012):

Parkinson’s Disease (PD)

PD is a heterogeneous neurodegenerative disorder which is associated with age (average onset age of 70), biological sex (more men than women are affected), heredity and environmental factors (increased risk with pesticide exposure). The majority of PD cases (85-90%) are categorized as idiopathic, with the remaining having a genetic or family risk (Kouli, 2018). The primary symptoms of PD are tremor, rigidity, bradykinesia and postural instability. The early presenting symptoms of PD are generally asymmetrical. The presence of atypical PD symptoms (cerebellar signs, early severe autonomic dysfunction, vertical supranuclear palsies, or cortical sensory loss) are indicative a possible alternative diagnosis (Kouli, 2018). The initial treatment of PD is generally pharmacological, such as levodopa and dopamine agonists. Deep brain stimulation (DBS) is considered the standard treatment to control symptoms in individuals with advanced disease who have not adequately responded to or are intolerant of medications. DBS typically results in improvements in motor skills, function and movement. Focused ultrasound ablation is limited to treating tremors.

Uterine Fibroids

The cause of fibroid tumors, also known as leiomyomas, of the uterus is unknown. However, it is suggested that fibroids may enlarge with estrogen therapy (such as oral contraceptives) or with pregnancy. Fibroid growth seems to depend on regular estrogen stimulation, and rarely affects women younger than 20 years of age or postmenopausal women. As long as a woman with fibroids is menstruating, the fibroids will probably continue to grow, although growth is usually quite slow.

Hysterectomy and various myomectomy procedures are considered the gold standard of treatment. However, there has been a longstanding research interest in developing minimally invasive alternatives. There has been interest in using HIFU treatment as a noninvasive approach to ablation of uterine fibroids. Treatment involves the use of focused high-intensity convergent ultrasound beam which increases the temperature within the targeted area to 60-95°C to destroy tissue without causing damage to adjacent tissue. During the procedure, individuals are typically placed under conscious sedation with or without epidural anesthesia, although general anesthesia may be used. Proposed advantages of HIFU include the noninvasive nature of the procedure that spares surrounding tissue, reducing postoperative morbidity, and hastening recovery.

The U.S. Food and Drug Administration (FDA) approved, via the Premarket Application (PMA) process, the ExAblate 2000 System for ablation of uterine fibroid tissue in pre- or peri-menopausal women with symptomatic uterine fibroids who desire a uterine sparing procedure. The 2004 FDA approval letter stated that women must have a uterine gestational size of less than 24 weeks and must have completed childbearing (FDA, 2004).

Benign prostate hyperplasia (BPH): A condition that causes an increase in the size of the prostate gland in men, commonly causing difficulty in urination; also referred to as benign prostatic hypertrophy.

Desmoid tumor: A type of benign, locally invasive fibrous tumor capable of growing anywhere in the body.

Essential tremor (ET): A chronic, incurable condition with unknown cause characterized by involuntary, rhythmic tremor of a body part, most typically the hands and arms.

High intensity focused ultrasound (HIFU): A surgical noninvasive procedure that uses focused high energy sound waves to destroy target tissues in the body.

Leiomyoma: A benign tumor that can be found in the uterus, commonly called a fibroid.

Menorrhagia: Excessive uterine bleeding occurring at the expected intervals of the menstrual periods.

MRI (magnetic resonance imaging): The use of a nuclear magnetic resonance spectrometer to produce electronic images of specific atoms and molecular structures in solids, especially human cells, tissues, and organs.

Myomectomy: A surgical procedure to remove only fibroids; is frequently the chosen treatment for premenopausal women who want to bear more children, because it usually can preserve fertility.

Neurodegenerative Disease: Progressive age-related disease when the neurons in the central nervous system or the peripheral nervous system lose function and die. The most common diseases are Alzheimer’s disease and Parkinson’s disease.

Uterine Fibroids: Benign fibrous tissue collected in the uterine wall.

Ventralis intermediate nucleus of the thalamus (Vim): A part of the brain involved with movement.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure code listed above when criteria are not met and for all other non-oncologic diagnoses.

When services are Investigational and Not Medically Necessary:

When services are also Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Altinel Y, Alkhalfan F, Qiao N, Velimirovic M. Outcomes in lesion surgery versus deep brain stimulation in patients with tremor: A systematic review and meta-analysis. World Neurosurg. 2019; 123:443-452.e8.
2. Avedian RS, Bitton R, Gold G, et al. Is MR-guided high-intensity focused ultrasound a feasible treatment modality for desmoid tumors? Clin Orthop Relat Res. 2016; 474(3):697-704.
3. Bachmann G. Expanding treatment options for women with symptomatic uterine leiomyomas: timely medical breakthroughs. Fertil Steril. 2006; 85(1):46-47.
4. Bloomingdale P, Karelina T, Ramakrishnan V, et al. Hallmarks of neurodegenerative disease: A systems pharmacology perspective. CPT Pharmacometrics Syst Pharmacol. 2022; 11(11):1399-1429.
5. Bond AE, Shah BB, Huss DS, et al. Safety and efficacy of focused ultrasound thalamotomy for patients with medication-refractory, tremor-dominant Parkinson disease: a randomized clinical trial. JAMA Neurol. 2017; 74(12):1412-1418.
6. Boxer AL, Yu JT, Golbe LI, et al. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Lancet Neurol. 2017; 16(7):552-563.
7. Chang JW, Park CK, Lipsman N, et al. A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up. Ann Neurol. 2018; 83(1):107-114.
8. Chung SR, Baek JH, Suh CH, et al. Efficacy and safety of high-intensity focused ultrasound (HIFU) for treating benign thyroid nodules: a systematic review and meta-analysis. Acta Radiol. 2020; 61(12):1636-1643.
9. Clark NA, Mumford SL, Segars JH. Reproductive impact of MRI-guided focused ultrasound surgery for fibroids: a systematic review of the evidence. Curr Opin Obstet Gynecol. 2014; 26(3):151-161.
10. Cosgrove GR, Lipsman N, Lozano AM, et al. Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results. J Neurosurg. 2022; 138(4):1028-1033.
11. Elias WJ, Huss D, Voss T, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013; 369(7):640-648.
12. Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016; 375(8):730-739.
13. Elble R, Comella C, Fahn S, et al. Reliability of a new scale for essential tremor. Mov Disord. 2012; 27(12):1567-1569.
14. Fabbri M, Barbosa R, Rascol O. Off-time Treatment Options for Parkinson's Disease. Neurol Ther. 2023; 12(2):391-424.
15. Fennessy FM, Tempany CM, McDannold NJ, et al. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery: results of different treatment protocols. Radiology. 2007; 243(3):885-893.
16. Ferreira JJ, Mestre TA, Lyons KE, et al; MDS Task Force on Tremor and the MDS Evidence Based Medicine Committee. MDS evidence-based review of treatments for essential tremor. Mov Disord. 2019; 34(7):950-958.
17. Frieben RW, Lin HC, Hinh PP, et al. The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function: a systematic review. Asian J Androl. 2010; 12(4):500-508.
18. Giordano M, Caccavella VM, Zaed I, et al. Comparison between deep brain stimulation and magnetic resonance-guided focused ultrasound in the treatment of essential tremor: a systematic review and pooled analysis of functional outcomes. J Neurol Neurosurg Psychiatry. 2020; 91(12):1270-1278.
19. Gizzo S, Saccardi C, Patrelli TS, et al. Magnetic resonance-guided focused ultrasound myomectomy: safety, efficacy, subsequent fertility and quality-of-life improvements, a systematic review. Reprod Sci. 2014; 21(4):465-476.
20. Halpern CH, Santini V, Lipsman N, et al. Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor. Neurology. 2019; 93(24):e2284-e2293.
21. Harary M, Segar DJ, Hayes MT, Cosgrove GR. Unilateral thalamic deep brain stimulation versus focused ultrasound thalamotomy for essential tremor. World Neurosurg. 2019; 126:e144-e152.
22. Iacopino DG, Gagliardo C, Giugno A, et al. Preliminary experience with a transcranial magnetic resonance-guided focused ultrasound surgery system integrated with a 1.5-T MRI unit in a series of patients with essential tremor and Parkinson's disease. Neurosurg Focus. 2018; 44(2):E7.
23. Ikink ME, Voogt MJ, Verkooijen HM, et al. Mid-term clinical efficacy of a volumetric magnetic resonance-guided high-intensity focused ultrasound technique for treatment of symptomatic uterine fibroids. Eur Radiol. 2013; 23(11):3054-3061.
24. Jeanmonod D, Werner B, Morel A, et al. Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus. 2012; 32(1):E1.
25. Ji Y, Hu K, Zhang Y, et al. High-intensity focused ultrasound (HIFU) treatment for uterine fibroids: a meta-analysis. Arch Gynecol Obstet. 2017; 296(6):1181-1188.
26. Jung HH, Chang WS, Rachmilevitch I, et al. Different magnetic resonance imaging patterns after transcranial magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus of the thalamus and anterior limb of the internal capsule in patients with essential tremor or obsessive-compulsive disorder. J Neurosurg. 2015; 122(1):162-168.
27. Khan RB, Merchant TE, Boop FA, et al. Headaches in children with craniopharyngioma. J Child Neurol. 2013; 28(12):1622-1625.
28. Kim HS, Baik JH, Pham LD, Jacobs MA. MR-guided high-intensity focused ultrasound treatment for symptomatic uterine leiomyomata: long-term outcomes. Acad Radiol. 2011; 18(8):970-976.
29. Kouli A, Torsney KM, Kuan WL. Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects [Internet]. Brisbane (AU): Codon Publications; 2018 Dec 21. Chapter 1.
30. Kovatcheva R, Vlahov J, Stoinov J, et al. US-guided high-intensity focused ultrasound as a promising non-invasive method for treatment of primary hyperparathyroidism. Eur Radiol. 2014; 24(9):2052-2058.
31. Krishna V, Fishman PS, Eisenberg HM, et al. Trial of globus pallidus focused ultrasound ablation in Parkinson's disease. N Engl J Med. 2023; 388(8):683-693.
32. Krishna V, Sammartino F, Agrawal P, et al. Prospective tractography-based targeting for improved safety of focused ultrasound thalamotomy. Neurosurgery. 2019; 84(1):160-168.
33. Lamptey RNL, Chaulagain B, Trivedi R, et al. A review of the common neurodegenerative disorders: current therapeutic approaches and the potential role of nanotherapeutics. Int J Mol Sci. 2022; 23(3):1851.
34. Lennon JC, Hassan I. Magnetic resonance-guided focused ultrasound for Parkinson's disease since ExAblate, 2016-2019: a systematic review. Neurol Sci. 2021; 42(2):553-563.
35. Leslie TA, Kennedy JE. High-intensity focused ultrasound principles, current uses, and potential for the future. Ultrasound Q. 2006; 22(4):263-272.
36. Lipsman N, Schwartz ML, Huang Y, et al. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol. 2013; 12(5):462-468.
37. Louis ED. Treatment of medically refractory essential tremor. N Engl J Med. 2016; 375(8):792-793.
38. Madersbacher S, Schatzl G, Djavan B, et al. Long-term outcome of transrectal high-intensity focused ultrasound therapy for benign prostatic hyperplasia. Eur Urol. 2000; 37(6):687-694.
39. Martin E, Jeanmonod D, Morel A, et al. High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol. 2009; 66(6):858-861.
40. Meng Y, Solomon B, Boutet A, et al. Magnetic resonance-guided focused ultrasound thalamotomy for treatment of essential tremor: A 2-year outcome study. Mov Disord. 2018; 33(10):1647-1650.
41. Miller WK, Becker KN, Caras AJ, et al. Magnetic resonance-guided focused ultrasound treatment for essential tremor shows sustained efficacy: a meta-analysis. Neurosurg Rev. 2022; 45(1):533-544.
42. Monteith S, Snell J, Eames M, et al. Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study. J Neurosurg. 2016:125(8):1557-1564.
43. Park YS, Jung NY, Na YC, Chang JW. Four-year follow-up results of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. Mov Disord. 2019; 34(5):727-734.
44. Rabinovici J, Inbar Y, Revel A, et al. Clinical improvement and shrinkage of uterine fibroids after thermal ablation by magnetic resonance-guided focused ultrasound surgery. Obstet Gynecol. 2007; 30(5):771-777.
45. Roehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol. 2005; 7 Suppl 9:S3-S14.
46. Schatzl G, Madersbacher S, Djavan B, et al. Two-year results of transurethral resection of the prostate versus four ‘less invasive’ treatment options. Eur Urol. 2000; 37(6):695-701.
47. Schrag A. Focused ultrasound ablation of the globus pallidus internus for Parkinson's disease. N Engl J Med. 2023; 388(8):759-760.
48. Schreglmann SR, Krauss JK, Chang JW, et al. Functional lesional neurosurgery for tremor: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2018; 89(7):717-726.
49. Sharma VD, Patel M, Miocinovic S. Surgical treatment of Parkinson's Disease: Devices and lesion approaches. Neurotherapeutics. 2020; 17(4):1525-1538.
50. Sinai A, Nassar M, Eran A, et al. Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: a 5-year single-center experience. J Neurosurg. 2019: 1-8.
51. Sinai A, Nassar M, Sprecher E, et al. Focused ultrasound thalamotomy in tremor dominant Parkinson's Disease: Long-term results. J Parkinsons Dis. 2022;12(1):199-206.
52. Sorribes IC, Moore MNJ, Byrne HM, Jain HV. A biomechanical model of tumor-induced intracranial pressure and edema in brain tissue. Biophys J. 2019; 116(8):1560-1574.
53. Stacy MA, Elble RJ, Ondo WG, et al; TRS study group. Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Mov Disord. 2007; 22(6):833-838.
54. Stewart EA, Gedroyc WM, Tempany CM, et al. Focused ultrasound treatment of uterine fibroid tumors: safety and feasibility of a noninvasive thermoablative technique. Am J Obstet Gynecol. 2003; 189(1):48-54.
55. Stewart EA, Gostout B, Rabinovici J, et al. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol. 2007; 110(2 Pt 1):279-287.
56. Stewart EA, Rabinovici J, Tempany CM, et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Fertil Steril. 2006; 85(1):22-29.
57. Taran FA, Tempany CM, Regan L, et al. Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal hysterectomy for treatment of uterine leiomyomas. Ultrasound Obstet Gynecol. 2009; 34(5):572-578.
58. Taylor JP, McKeith IG, Burn DJ, et al. New evidence on the management of Lewy body dementia. Lancet Neurol. 2020; 19(2):157-169.
59. Welton T, Cardoso F, Carr JA, et al. Essential tremor. Nat Rev Dis Primers. 2021; 7(1):83.
60. Yuen J, Miller KJ, Klassen BT, et al. Hyperostosis in combination with low skull density ratio: A potential contraindication for magnetic resonance imaging-guided focused ultrasound thalamotomy. Mayo Clin Proc Innov Qual Outcomes. 2021; 6(1):10-15.

Government Agency, Medical Society and Other Authoritative Publications:

1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 228. Management of Symptomatic Uterine Leiomyomas. 2021.
2. Burke CT, Funaki BS, Ray CE. American College of Radiology (ACR) Appropriateness Criteria^® treatment of uterine leiomyomas. Revised in 2017. Available at: https://acsearch.acr.org/docs/69508/Narrative/. Accessed on July 22, 2023.
3. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Other Treatments for Fibroids. Last Reviewed: November 2, 2018. Available at: http://www.nichd.nih.gov/health/topics/uterine/conditioninfo/treatments/Pages/radiological.aspx. Accessed on July 13, 2023.
4. Health Quality Ontario. Magnetic Resonance-Guided Focused Ultrasound Neurosurgery for Essential Tremor: A Health Technology Assessment. Ont Health Technol Assess Ser. 2018; 18(4):1-141.
5. Pouratian N, Baltuch G, Elias WJ, Gross R. American Society for Stereotactic and Functional Neurosurgery Position Statement on Magnetic Resonance-Guided Focused Ultrasound for the Management of Essential Tremor. Neurosurgery. 2020; 87(2):E126-E129.
6. Pron G. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids: an evidence-based analysis. Ont Health Technol Assess Ser. 2015; 15(4):1-86.
7. U.S. Food and Drug Administration (FDA) Center for Devices and Radiologic Health (CDRH) 510 (k) Premarket Notification Database. InSightec Exablate Neuro. Summary of Safety and Effectiveness. No. P150038. Rockville, MD: FDA. July 11, 2016. Available at http://www.accessdata.fda.gov/cdrh_docs/pdf15/P150038B.pdf. Accessed on July 13, 2023.

1. American Parkinson Disease Association (APDA). Parkinson’s disease vs. Parkinsonism: what’s the difference? December 18, 2018. Available at: https://www.apdaparkinson.org/article/atypical-parkinsonism/.
2. National Institute of Health (NIH): National Institute of Diabetes and Digestive and Kidney Diseases. Prostate Enlargement: Benign Prostatic Hyperplasia. September 2014. Available at: https://www.niddk.nih.gov/health-information/urologic-diseases/prostate-problems/prostate-enlargement-benign-prostatic-hyperplasia. Accessed on July 13, 2023.
3. NIH: National Institute of Environmental Health Sciences. Neurodegenerative Diseases. Last reviewed June 9, 2022. Available at: https://www.niehs.nih.gov/research/supported/health/neurodegenerative/index.cfm. Accessed on October 31, 2023.
4. NIH: National Institute of Neurological Disorders and Stroke (NINDS). Accessed on October 18, 2023.
   • Deep Brain Stimulation for Movement Disorders. Available at: https://www.ninds.nih.gov/health-information/disorders/deep-brain-stimulation-movement-disorders?search-term=essential%20tremor.
   • Parkinson’s Disease. Available at: https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease?search-term=essential%20tremor.
5. U.S. National Library of Medicine. Uterine fibroids. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000914.htm. Accessed on July 13, 2023.

Estrogen Therapy
ExAblate 2000 System
ExAblate Neuro
Fibroids
Myomectomy
Thalamotomy

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member’s contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

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