The relevance of skull density ratio in selecting candidates for transcranial MR-guided focused ultrasound

Abstract

OBJECTIVETranscranial MR-guided focused ultrasound (MRgFUS) is a minimally invasive treatment for movement disorders. Considerable interpatient variability in skull transmission efficiency exists with the current clinical devices, which is thought to be dependent on each patient’s specific skull morphology. Lower skull density ratio (SDR) values are thought to impede acoustic energy transmission across the skull, attenuating or preventing the therapeutic benefits of MRgFUS. Patients with SDR values below 0.4 have traditionally been deemed poor candidates for MRgFUS. Although considerable anecdotal evidence has suggested that SDR is a reliable determinant of procedural and clinical success, relationships between SDR and clinical outcomes have yet to be formally investigated. Moreover, as transcranial MRgFUS is becoming an increasingly widespread procedure, knowledge of SDR distribution in the general population may enable improved preoperative counseling and preparedness.METHODSA total of 98 patients who underwent MRgFUS thalamotomy at the authors’ institutions between 2012 and 2018 were analyzed (cohort 1). The authors retrospectively assessed the relationships between SDR and various clinical outcomes, including tremor improvement and adverse effects, as well as procedural factors such as sonication parameters. An SDR was also prospectively obtained in 163 random emergency department patients who required a head CT scan for various clinical indications (cohort 2). Patients’ age and sex were used to explore relationships with SDR.RESULTSIn the MRgFUS treatment group, 17 patients with a thalamotomy lesion had an SDR below 0.4. Patients with lower SDRs required more sonication energy; however, their low SDR did not influence their clinical outcomes. In the emergency department patient group, about one-third of the patients had a low SDR (< 0.4). SDR did not correlate with age or sex.CONCLUSIONSAlthough lower SDR values correlated with higher energy requirements during MRgFUS thalamotomy, within the range of this study population, the SDR did not appreciably impact or provide the ability to predict the resulting clinical outcomes. Sampling of the general population suggests that age and sex have no relationship with SDR. Other variables, such as local variances in bone density, should also be carefully reviewed to build a comprehensive appraisal of a patient’s suitability for MRgFUS treatment.

Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study

“…It is known that transkull transmission will make the focus both shallower and broader than it is when measured in degassed water [ 2 ]. This effect is dependent on the skull density ratio, which was not measured [ 56 ]. Therefore, it is possible that some subjects did not receive stimulation of the anterior thalamus at all.…”

Sonoselective transfection of cerebral vasculature without blood–brain barrier disruption

“…As the field of FUS-mediated therapeutic delivery to the brain gains momentum and moves closer to regulatory approval in human patients, there remains an ongoing concern over the potential dangers of neuroinflammation and petechiae due to damage caused by oscillating MBs. Additionally, variability in skull shape and thickness can result in variability in the bioeffects and treatment efficacy of FUS with MBs across and within test subjects (93)(94)(95). The concern over inflammation and treatment variability led to the development of monitoring systems to assess MB activity within the brain and the use of these observations to inform treatments.…”

Echo‐Focusing in Transcranial Focused Ultrasound Thalamotomy for Essential Tremor: A Feasibility Study

“…7 Despite the considerable progress made to date to enable transcranial treatments, 8 the skull remains a major limiting factor because high focal temperatures are difficult to achieve in patients with unfavorable skull characteristics (eg, low skull density ratio [SDR = mean ratio of trabecular to cortical bone computed tomography (CT) Hounsfield intensity], large skull thickness). [9][10][11] Benchtop studies have revealed considerable variability in human skull transmission efficiency, [12][13][14] and a wide range of acoustic energy levels are required during clinical procedures. 1,15 Although repeated high-energy low focal temperature sonications can promote lesion formation, 16 lesioning is not always feasible with current TcMRgFUS technology, leading to the exclusion of some patients (eg, SDR < 0.40-0.45).…”

“…Transcranial magnetic resonance–guided focused ultrasound (TcMRgFUS) thermoablation has been approved by the US Food and Drug Administration for essential tremor (ET) 1,2 and tremor‐dominant Parkinson's disease 3 and is under clinical testing for neuropathic pain 4 and psychiatric disorders 5,6 among other indications 7 . Despite the considerable progress made to date to enable transcranial treatments, 8 the skull remains a major limiting factor because high focal temperatures are difficult to achieve in patients with unfavorable skull characteristics (eg, low skull density ratio [SDR = mean ratio of trabecular to cortical bone computed tomography (CT) Hounsfield intensity], large skull thickness) 9‐11 . Benchtop studies have revealed considerable variability in human skull transmission efficiency, 12‐14 and a wide range of acoustic energy levels are required during clinical procedures 1,15 …”

“…1,15 Although repeated high-energy low focal temperature sonications can promote lesion formation, 16 lesioning is not always feasible with current TcMRgFUS technology, leading to the exclusion of some patients (eg, SDR < 0.40-0.45). 2,9,10 In addition, peripheral targets (eg, capsulotomy) tend to be more difficult to treat than central targets (eg, thalamotomy) with clinical TcMRgFUS systems as a result of decreased sonication efficiency at these locations. 11,17 Intraoperative changes in skull properties from heating 18,19 may further reduce sonication efficiency during the course of a single treatment.…”