MR-guided high-intensity focused ultrasound for chronic pain: where do we stand?

Figures & data

Figure 1. Somatosensory and affective nuclei of the thalamus.Schematic diagram depicting the location and composition of the thalamic nuclei relevant for pain transmission. The somatosensory thalamus includes the nuclei ventromedialis (VPM) and ventrolateralis (VPL); (yellow), and the centromedian-parafascicular complex of the thalamus (CmPf), which is located in internal lamina (gray).Reproduced from [9] with permission of Springer Nature.

Figure 2. Projections of the somatosensory and affective pain circuits of the thalamus.Pain processing pathways are highlighted within the cerebral tissue. The somatosensory process and pain memory pathway originate from the brainstem and spinal cord via ascending fibers and project to the thalamic nuclei (CmPf, VPM/VPL, CLT). Signals from the VPL project to the somatosensory cortex, located in the parietal lobe, and these signals are processed in the primary (S1) and secondary (S2) regions. The affective pain processing pathways originate from the CmPF /CLT and project to the insula, the anterior cingulate cortex (ACC) and prefrontal cortex (PFC). Reproduced from [9] with permission of Springer Nature.

Table 1. Clinical trials assessing the efficacy and safety of MRgFUS for chronic pain disorders and appproaching different targets associated with sensory and limbic brain circuits.

Reference	PN	Design	Target	Indication	FU	Outcome	SAE/AE
Gallay, 2020 [15]	8	OT	MRgFUS CLT (peak 51–64°C)	TN	53 m	51% pain relief/3 m 71% pain relief/12 m 78% pain relief/53 m	None
Jeanmonod, 2012 [14]	12	OT	MRgFUS CLT (peak 51–64°C)	NP	12 m	49% pain relief/3 m 57% pain relief/12 m	1 ICH
Gallay, 2018 [13]	180 (treatments)	OT	MRgFUS CLT (peak 51–64°C)	NP	3 m	na	None
Martin, 2009 [12]	9	OT	MRgFUS VPL (Peak temperature 51–60°C)	NP	N.a.	Mean pain relief 68% after 2 d	None
NCT03111277	10	OT	MRgFUS CLT	NP PP	12 m	NRS/BPI SAE	—
NCT04579692	10	OT	MRgFUS CLT	TN	6 m	NRS/BPI/PGIC/BNI	—-
NCT03100474	500XX	OT/PR	MRgFUS thalamic nuclei/na	NP	5y	——	—–
NCT04485208	40	OT	MRgFUS VPL/VPM	NP	8w	NRS/BPI/PHQ-9	—-
NCT04649554	30	OT	MRgFUS na	NP	3-12 m	NRS/PDI/PCS/PROMIS GHQ/PROMIS SDQ/AE/QST/LEP/PGIC	—-
NCT04283643	149	RT	MRgFUS/(na) TMS	AP/CP/HS	1d	NRS/EEG/MRI	—-
NCT05122403	12	RCT	MRgFUS CLT	NP	12 m	NRS/MRI/AE	—-
NCT03309813	10	RCT	MRgFUS medial thalamus bilateral	TN	3 m	NRS/PROMIS PI/AE/PGIC

Abbreviation: MRgFUS – magnet resonance guided focused ultrasound; TMS – transcranial magnetic stimulation; OT – observation trial; RCT – randomized controlled trial; RT – randomized trial; PR – patient register; y – year; m – months; w – week; d – day; FU – follow up; m – months; AE – serious adverse event; ICH – intracranial hemorrhage; NP – neuropathic pain; TN – trigeminal neuralgia; AP/CP – acute/chronic pain; PP – phantom pain; HS – healthy subjects; CLT – posterior part of the central lateral thalamic nucleus; VPL/VPM – ventroposterolateral/ventropostero-medial nucleus of the thalamus; NRS – numbering rating scale; PDI – pain disability inventor; PCS – pain catastrophizing scale; PROMIS – patient reported outcomes measurement information system; PROMIS GHQ – general health questionnaire; PROMIS SDQ – sleep disturbance questionnaire; PROMIS PI – pain inventory; QST – quantitative sensory testing; LEP – laser evoked potential; PGIC – patient´s global impression of change; BPI – British pain inventory; BNI – Barrow neurological institute; C – degree centigrade; EEG – electroencephalogram; MRI – magnet resonance tomography; XX movement disorder/pain/psychiatric cohort, NCT – ongoing trials (results not published).

Nüssel M, Zhao Y, Knorr C, et al. Deep brain stimulation, stereotactic radiosurgery and high-intensity focused ultrasound targeting the limbic pain matrix: a comprehensive review. Pain Ther. 2022;11(2):459–476. doi: 10.1007/s40122-022-00381-1

 PubMed Web of Science ®Google Scholar

Gallay MN, Moser D, Jeanmonod D. MR-Guided focused ultrasound central lateral thalamotomy for trigeminal neuralgia. Single center experience. Front Neurol. 2020;11:271.

 PubMed Web of Science ®Google Scholar

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:E1. doi: 10.3171/2011.10.FOCUS11248

 PubMed Web of Science ®Google Scholar

Gallay MN, Moser D, Jeanmonod D. Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments. Journal Of Neurosurgery. 2018;130(4):1234–1243. doi: 10.3171/2017.12.JNS172054

 PubMed Web of Science ®Google Scholar

Martin E, Jeanmonod D, Morel A, et al. High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol. 2009;66(6):858–861. doi: 10.1002/ana.21801

 PubMed Web of Science ®Google Scholar