Focal destruction of nervous tissue by focused ultrasound: biophysical factors influencing its application.
Authors: BALLANTINE HT, HUETER TF, NAUTA WJ, SOSA DM
Ultrasound at frequencies of 1.0 mcps and 2.5 mcps can be focused by a suitable lens system to produce a small region of high vibrational intensity. The concentrated energy within and around the focal region can be used to destroy structures of the central nervous system. The extent of destruction depends upon: (a) the size of the focal region, which varies inversely with the frequency, (b) the ultrasonic intensity, (c) the duration of exposure, and (d) the physical and physiologic characteristics of the tissue under irradiation. With proper choice of ultrasonic dosage, mice were rendered monoplegic by destruction of one-half of the spinal cord without demonstrable injury to the skin or subcutaneous tissues through which the converging ultrasonic beam had been transmitted. In similar fashion, focal lesions were produced in the basal ganglia of living cats by stereotaxic transdural application of a focused ultrasonic beam delivered through the superior aspect of the cerebral hemispheres. Histologic studies of mouse spinal cords and cat brains offered evidence that the fiber tracts of the central nervous system are more vulnerable to ultrasonic irradiation than aggregates of cell nuclei or vascular structures. The destructive action of the ultrasound is apparently a result of mechanical strain combined with a rise in temperature at the focus of the beam. The heating factor was found to assume greater importance under conditions of high intensity and continuous (rather than pulsed) irradiation. Trypan blue staining and radioautography using P(32) have been employed to identify the lesions 1 hour after irradiation. This has been a valuable adjunct in our attempts to determine the accuracy of placement of the lesions and their size. Perhaps more important, however, is the indication from these studies that ultrasonically produced lesions may offer a useful method for investigation of the nature of the blood-brain barrier. "Target studies" were undertaken to determine the precision with which lesions of predetermined size could be placed at predetermined sites in the basal ganglia of the cat. Results to date have been promising, but it is our opinion that further technical improvement will be necessary before ultrasound can be used as an accurate method for placing discrete lesions within the human brain.
Introduction
Purpose
Thermal ablation
Study Objective
To evaluate focused ultrasound's ability to produce precise, localized destructive lesions in the central nervous system of animal models and to characterize the factors affecting lesion size, placement accuracy, and effects on the blood–brain barrier.
Animal model / Human subject
Mice (species: Mus musculus; strain: not stated; age: not stated; sex: not stated); Cats (species: Felis catus; strain: not stated; age: not stated; sex: not stated)
MRI or image guidance method
Stereotaxic (stereotactic transdural application of focused ultrasonic beam)
Targeted brain region(s)
Basal Ganglia
Cargo name and characteristics
Trypan blue (small-molecule vital dye) and Phosphorus-32 (P-32, radioactive isotope used for radioautography)
Outcomes and Safety
Summary of Outcomes
Focused ultrasound (1.0 and 2.5 mcps) produced small, high‑intensity focal lesions that destroyed central nervous system structures (in mice causing monoplegia by unilateral spinal cord destruction and in cats producing focal basal ganglia lesions); histology indicated fiber tracts are more vulnerable than cell bodies or vasculature. Successful parameters included frequencies of 1.0 and 2.5 mcps, control of focal size (higher frequency → smaller focus), appropriate ultrasonic intensity and exposure duration, and continuous (high‑intensity) irradiation which produced greater heating/destruction than pulsed delivery.
Duration of biological effect
1 hour
Safety-related matter
Focused ultrasound deliberately produced destructive CNS lesions (mice were rendered monoplegic after destruction of half the spinal cord and focal lesions were produced in cat basal ganglia); fiber tracts were especially vulnerable and heating became more important with high-intensity continuous irradiation. There was no demonstrable injury to skin or subcutaneous tissues along the beam path, but the authors caution that further technical improvement is needed before human application.
Brain Region
Ultrasound Parameters
FUS Frequency
1.0 MHz, 2.5 MHz
FUS Mode
continuous
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
single
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