A magnetic resonance imaging, histological, and dose modeling comparison of focused ultrasound, radiofrequency, and Gamma Knife radiosurgery lesions in swine thalamus

Laboratory investigation

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The purpose of this study was to use MRI and histology to compare stereotactic lesioning modalities in a large brain model of thalamotomy.


A unilateral thalamotomy was performed in piglets utilizing one of 3 stereotactic lesioning modalities: focused ultrasound (FUS), radiofrequency, and radiosurgery. Standard clinical lesioning parameters were used for each treatment; and clinical, MRI, and histological assessments were made at early (< 72 hours), subacute (1 week), and later (1–3 months) time intervals.


Histological and MRI assessment showed similar development for FUS and radiofrequency lesions. T2-weighted MRI revealed 3 concentric lesional zones at 48 hours with resolution of perilesional edema by 1 week. Acute ischemic infarction with macrophage infiltration was most prominent at 72 hours, with subsequent resolution of the inflammatory reaction and coalescence of the necrotic zone. There was no apparent difference in ischemic penumbra or “sharpness” between FUS or radiofrequency lesions. The radiosurgery lesions presented differently, with latent effects, less circumscribed lesions at 3 months, and apparent histological changes seen in white matter beyond the thalamic target. Additionally, thermal and radiation lesioning gradients were compared with modeling by dose to examine the theoretical penumbra.


In swine thalamus, FUS and radiosurgery lesions evolve similarly as determined by MRI, histological examination, and theoretical modeling. Radiosurgery produces lesions with more delayed effects and seemed to result in changes in the white matter beyond the thalamic target.

Abbreviations used in this paper:CEM = cumulative equivalent minute; FUS = focused ultrasound; GFAP = glial fibrillary acidic protein; GKRS = Gamma Knife radiosurgery; LFB = Luxol fast blue.

Article Information

Address correspondence to: W. Jeff Elias, M.D., Department of Neurosurgery, Box 800212, University of Virginia Health System, Charlottesville, VA 22908. email: wje4r@virginia.edu.

Please include this information when citing this paper: published online June 7, 2013; DOI: 10.3171/2013.5.JNS122327.

© AANS, except where prohibited by US copyright law.



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    Evolution of the thalamic lesioning process depicted on T2-weighted coronal MR images obtained in the craniectomy FUS, radiofrequency (RF), and radiosurgery (RS) cohorts.

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    Volumetric measurements during the maturation of FUS (solid) and radiofrequency (speckled) lesions (Zones 1 and 2) and surrounding edema (Zone 3) as determined from T2-weighted MRI. d = days.

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    Early lesions (48 hours) produced by FUS (A–C) and radiofrequency (D–F). Both FUS and radiofrequency produced well-delineated acute infarctions characterized by central ischemic necrosis and surrounding edema (A, D, and E). The periphery of the lesions shows a moderate degree of vacuolization of the neuropil (B and E), axonal swelling (C), and ischemic neurons (F) with minimal inflammatory infiltration. LFB (A and D), H & E (B, C, E, and F); original magnifications ×20 (A, D, and E), ×100 (B), ×400 (C), and ×200 (F).

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    Subacute lesions (1 week) produced by FUS (A–C) and radiofrequency (D–F). Subacute infarction with central necrosis and dense inflammatory infiltration was seen in both groups of animals. Better delineation of the infarcts (A, D, and E) than early lesions, intense macrophage infiltration (B, C, and E), and neovascularization (C and F) were characteristic of the lesions at this stage. All H & E; original magnifications ×20 (A and D), ×200 (B), ×400 (C and F), and ×100 (E).

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    Late lesions (1 month) produced by FUS (A and B) and radiofrequency (C and D). Well-delineated subacute infarctions were characteristics of lesions 1 month after FUS or radiofrequency (A–C). A cystic infarct in the thalamus 1 month after FUS (A and B) readily demonstrates the circumscription of the lesions. The lesions are surrounded by intense reactive gliosis, as highlighted by GFAP immunopositivity (D). H & E (A–C); original magnifications ×20 (A, C, and D) and ×200 (B).

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    Photographs of specimens from the craniectomy FUS (A), radiofrequency (B), radiosurgery (C), and transcranial FUS (D) cohorts showing gross appearance at 1 week after the lesioning procedures. Specimens from the craniectomy FUS and radiofrequency cohorts showed visible lesions, whereas there was no visible lesion in animals in the radiosurgery cohort at this time point. Transcranial sonication through the intact swine skull produced thermal injury to the cortex (as shown in D) without apparent scalp burning in 2 of 3 animals.

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    Subacute (1 week [A and B]) and late (3 months [C–I]) GKRS lesions. Early infarction, with edema and hypoxicischemic red neurons, was apparent 1 week after the procedure (A and B). Poorly circumscribed lesions were seen 3 months after the procedure (C–E). LFB staining shows irregular borders of the lesion (C) with extension of demyelination to the adjacent white matter (arrows) and edema of surrounding deep gray nuclei (asterisk). Higher magnification of edema is seen in Panel I. GFAP immunostaining highlights the extension of gliosis surrounding the lesion and in the adjacent gray and white matter (E). Intensive inflammatory infiltrates with dense macrophage reaction and dystrophic calcification (D and F, arrows) were present (D and E). Note extension of the macrophage infiltration into the surrounding white matter highlighted as negative profile by GFAP immunostaining (E, arrows). Additionally, large, bizarre astrocytes (G) were observed intermixed with the inflammatory infiltrates and highlighted by GFAP immunostaining (H). H & E (A, B, D, F, G, and I) and LFB (C); original magnifications ×100 (A and F), ×200 (B, G, and I), ×20 (C and E), ×40 (D), and ×400 (H).

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    Simulated ultrasonic thermal dose (unbroken line), radiofrequency thermal dose (dashed line), and GKRS dose (dashed-dotted line) profiles as a function of distance in tissue. Zero distance thus corresponds to the center of the ultrasonic beam, the center of the radiosurgery beams, and the edge of the radiofrequency electrode. eq.min = CEM.



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