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Physical Factors Involved in Ultrasonically Induced Changes in Living Systems: II. Amplitude Duration Relations and the Effect of Hydrostatic Pressure for Nerve Tissue

W. J. Fry, D. Tucker, F. J. Fry, V. J. Wulff

The Journal of the Acoustical Society of America 1951 · 10.1121/1.1906774

other vertebratehealthybehaviour

Abstract

The results of experiments with frogs under a hydrostatic pressure demonstrate that cavitation is not an important factor in the mechanism of production of paralysis of the hind legs of frog by ultrasonic (frequency one megacycle) irradiation over the lumbar enlargement region of the spinal cord. Experimental results indicate that a linear relation exists between the reciprocal of the minimum exposure time for paralysis and the acoustic amplitude. This result is readily described in terms of a one factor rate process. On the basis of this experimentally determined relation, it is shown that time rate of change of temperature cannot be correlated with the observations. It is concluded on the basis of a theoretical calculation that absorption of ultrasound at interfaces in the spinal cord does not result in minute hot regions. Further work on summation of subparalytic doses, spaced apart at various time intervals, indicates that the recovery process following exposure to a subparalytic dose of ultrasonic radiation may not be a monotonic function of time.

Abstract via crossref.

Speciesfrog (species not stated; average weight about 23 g, range 15-32 g)
Subjects500 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesianot reported
Readoutsbehaviourhind-limb paralysis (all-or-none) as the functional endpoint following ultrasound irradiation of the lumbar spinal cord.
Direction of effectinhibitoryUltrasound above a threshold acoustic amplitude produced permanent paralysis of the frog hind limbs after a duration that decreased linearly with amplitude (1/time proportional to amplitude minus threshold); the effect persisted at 13 atmospheres hydrostatic pressure sufficient to suppress cavitation, and was argued not to be caused by bulk or localised temperature rise.
Adverse eventsobservedUltrasound at sufficient amplitude/duration produced permanent paralysis of the frog hind limbs; effect was not prevented by suppressing cavitation with hydrostatic pressure.

Exposures

Exposure 1: Intact frog, lumbar enlargement of the spinal cord, under atmospheric or 13-atmosphere hydrostatic pressure

Target: lumbar spinal cord — “lumbar enlargement of the spinal cord, intact frog, sound beam incident on the dorsal surface
Device: custom-built

Pulse timing
Waveformcontinuous
Fundamental frequency (kHz)980✓✓
Pulse duration (ms)not applicable
Pulse repetition frequency (Hz)not applicable
Duty cycle (%)not applicable
Sonication duration (s)5.4, 7.8swept✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)1,013, 1,216swept✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurement
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Frogs at atmospheric pressure or under 13 atmospheres hydrostatic pressure (sufficient to suppress cavitation) were irradiated on the dorsal surface over the lumbar enlargement with a single continuous sonication; the reciprocal of the minimum exposure time for paralysis increased linearly with acoustic amplitude, with a definite threshold in each case. In a separate summation experiment at 10 atmospheres acoustic pressure amplitude, an initial subparalytic dose of 5.4 s (paralysis time for a single irradiation at this level was 7.8 s) was followed by a second dose after a variable interval to study recovery.

Flags from extraction

  • exposures[0].free_field.pressure_kpaList combines two explicitly stated free-field pressure-amplitude calibration points (about 12 atmospheres at 5.5 kV, used for the main amplitude-duration data of Fig. 2/3; and 10 atmospheres, held constant for the summation experiment of Fig. 4); the source quote given is only for the first.
  • exposures[0].in_situ.pressure_kpaPaper reports that the average acoustic pressure amplitude measured directly in the cord (via an inserted probe) is 0.8 of the free-field amplitude, but gives no absolute in-situ figure; per the no-derating rule this ratio is not converted into a number here.
  • n_subjectsPaper states 'about 500 frogs' were needed for the main amplitude-duration dataset (Figs. 2-3); this excludes additional frogs used in the separate summation sub-experiments (stated only as '12 to 15 frogs ... per point').