Introduction: Stereotactic lesions of the ventral intermediate nucleus of thalamus (Vim) can provide dramatic relief for patients suffering from tremor(1). Precise lesioning can be accomplished with radiofrequency (RF) heating of an electrode or by Gamma Knife radiosurgery (GK)(2). Recently, it has become possible to use transcranial, MR-guided focused ultrasound (FUS) to produce precisely defined lesions in deep brain structures(3-5). Comparisons of the radiographic evolution and histologic characteristics of lesions produced by these techniques would help identify the relative advantages and risks of each.

Methods: Piglets are divided into lesioning cohorts: RF, GK, and FUS. Each animal is treated with a unilateral thalamotomy utilizing one of the lesioning modalities. Five cohorts are studied and each consists of five pigs: RF early stage, RF late stage, FUS early stage, FUS late stage, and GK. MRI is obtained for each group at sequential time points during the maturation of the lesion: immediately posttreatment, 48 hours, and at 3 months. GK lesions mature with a delayed latency(6) and will also be imaged at 6 months. Histology will be obtained at specific timepoints to assess for lesion volume and for the presence of edema, ischemia, inflammation, gliosis, and hemorrhage. The temporal evolution, volume, and histological changes of the lesions will be compared amongst the modalities.

Results: We have treated five FUS early stage pigs. Lesions obtained are well circumscribed on MRI at the exact target point as planned and the pigs clinically did not suffer from any side effects.

Conclusions: FUS is a viable non-invasive method for performing deep brain lesions with high target accuracy and live detection of temperature rise at the lesion site. We continue with our study for long term effect and comparison across groups.

Patient Care: While stereotactic radiofrequency heating and gamma knife radiosurgery have been utilized for decades to perform lesioning of deep subcortical nuclei, the nature of MR and histological evolution to a mature lesion remains incompletely understood. This project will provide serial information regarding the imaging and histological changes that occur with RF and GK. Furthermore, the lesioning process generated by FUS will be more completely assessed and compared with temporal, volumetric, and histological measures. This project will provide critical information regarding the incidence of hemorrhage, ischemia, and edema formation amongst the modalities; and it will also provided key preclinical data supporting the use of the non-invasive MR guided FUS in a proposed human clinical trial of ultrasound thalamotomy for the treatment of Essential Tremor.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the effect of medium frequency focused ultrasound on deep brain nuclei. 2) Discuss the advantage of real time measuring temperature rise in the target site. 3) Identify FUS as a viable non-invasive option for targeting deep brain nuclei for lesioning.

References: 1. Hirai T, Miyazaki M, Nakajima H, Shibazaki T, Ohye C. The correlation between tremor characteristics and the predicted volume of effective lesions in stereotaxic nucleus ventralisintermedius thalamotomy. Brain. 1983;106 ( Pt 4):1001-18. 2. Niranjan A, Jawahar A, Kondziolka D, Lunsford L. A comparison of surgical approaches for the management of tremor: radiofrequency thalamotomy, gamma knife thalamotomy and thalamic stimulation. Stereotactic & Functional Neurosurgery. 1999:2-4. 3. Clement GT, Hynynen K. A non-invasive method for focusing ultrasound through the humanskull. Phys Med Biol. 2002;47(8):1219-36. 4. Clement GT, White J, Hynynen K. Investigation of a large-area phased array for focused ultrasound surgery through the skull. Phys Med Biol. 2000;45(4):1071-83. 5. Clement GT, White PJ, King RL, McDannold N, Hynynen K. A magnetic resonance imagingcompatible, large-scale array for trans-skull ultrasound surgery and therapy. J Ultrasound Med. 2005;24(8):1117-25. 6. Kamiryo T, Kassell N, Thai Q, et al. Histological changes in the normal rat brain after gammairradiation. Acta Neurochirurgica. 1996;138(4):451-9.