Pitt Shield

A NEW METHOD FOR THE GENERATION AND USE OF FOCUSED ULTRASOUND IN EXPERIMENTAL BIOLOGY.

Authors: Lynn JG, Zwemer RL, Chick AJ, Miller AE

1. An efficient generator of focused ultrasound has been designed, built, and successfully operated. 2. The generator has been used to produce focal heating in the centers of paraffin blocks, and in a similar manner, focal areas of destruction were obtained deep in fresh liver tissue with minimal effects at the surface and no effects on the intervening tissue. 3. In animals, focused ultrasound of high intensity produced local cerebral changes as inferred from behavior disabilities and as demonstrated at autopsy. This local brain effect was achieved through intervening scalp, skull, and meninges. The resulting behavior disabilities disappeared in from 2 to 16 hours. 4. To date, it has not been possible to produce such brain changes without incidental injury to the skin and subcutaneous tissue lying at the base of the cone of radiation. 5. Improvements in generation and application of the focused supersonic beam are suggested whereby it should be possible to increase still further the focal effects in the brain, with a corresponding decrease or elimination of complicating surface injury.

Introduction

Purpose other
Study Objective Develop a focused ultrasound generator and apply it to produce focal changes deep in tissues (paraffin, liver, brain) with minimal damage to intervening tissues
Animal model / Human subject cat, dog, beef liver (ex vivo), paraffin blocks
Disease model healthy
Targeted brain region(s) Cerebral cortex

Outcomes and Safety

Summary of Outcomes ocused ultrasound (835 kHz, concave quartz crystal) produced conical melting defects in paraffin blocks and focal destruction in beef liver with minimal surface effects. In living cats and dogs, high-intensity FUS applied through scalp and skull caused temporary neurological deficits (hind limb weakness, transient blindness) lasting 2-16 hours, with scalp injury observed. The study demonstrated feasibility of transcranial focused ultrasound but noted skin damage as a limitation.
Duration of biological effect 2-16hours
Safety-related matter Scalp ulcerations and skin injury occurred; brain effects were temporary with no permanent damage reported; skin contact medium (transformer oil) may have been irritating.

Brain Region

Ultrasound Parameters

Ultrasound instrument in-house designed focused ultrasound generator; concave quartz crystal, 5.08 cm diameter, frequency 835 kHz, curved to focus at 5.5 cm in oil, mounted in bakelite container with transformer oil, air chamber behind crystal, cellophane diaphragm
FUS Frequency 835kHz
FUS Mode continuous
Duration of a single FUS session 10-30 seconds (for paraffin/liver blocks); up to 24 minutes (in vivo)
Focal Characteristics focal distance: 5.5 cm in oil, but effective focus in tissue ~3.4 cm from crystal due to refraction
Treatment frequency single session

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