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Diagnostic levels of ultrasound may disrupt myelination

Mark H Ellisman, Darryl Erik Palmer, Michael P André

Experimental Neurology 1987, 98, 78-92 · 10.1016/0014-4886(87)90073-2

rodenthealthyhistology molecular

Abstract

Neonatal rats 3 to 5 days of age were exposed to the ultrasound beam from a medical ultrasound imaging system. Dorsal nerve roots were examined by electron microscopy. Comparison between exposed and sham-exposed controls revealed disruption of the nodes of Ranvier attributable to ultrasound. Morphologic changes ranged from vacuole formation in the paranodal region to frank demyelination and were still evident after 24 h of recovery. Rats of this age are at a stage of myelination similar to that of a human fetus 4 to 5 months. The ultrasound intensities used in this study are consistent with those used for human imaging (SPTA 0.135 mW/cm2, SATA 0.045 mW/cm2, SPTP 8.7 W/cm2, SPPA 1.9 W/cm2), but the relevance of these findings to clinical ultrasound will require further study.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects10 animals
Sessions per subject1
Randomisednot reported
Blindingsingle
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesiaawake
Readoutshistology moleculartransmission and high-voltage electron microscopy of nodes of Ranvier ultrastructure in dorsal/ventral lumbar spinal roots
Direction of effectnot assessedThe study assessed structural (ultrastructural) disruption of nodes of Ranvier rather than neural excitability or activity; disruption of glial-axonal junctions, microedema and demyelination were observed in exposed animals.
Adverse eventsobservedDisruption of nodes of Ranvier, ranging from paranodal vacuole formation (microedema) to frank demyelination, was observed in more than 50% of nodes examined in all exposed animals and was still present after 24 h recovery; no such changes were seen in sham-exposed or cage controls.

Exposures

Exposure 1: Diagnostic ultrasound beam directed at the dorsal surface of neonatal rat pups (spinal roots examined)

Target: lumbar spinal cord — “dorsal and ventral lumbar spinal roots
Device: other named manufacturer · ADR · ADR model 2130 real-time linear array scanner

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)3,500?
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)42✓✓
Duty cycle (%)not reported
Sonication duration (s)1,800✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)1.9✓✓
Free-field Ispta (W/cm²)0.000135✓✓
In-situ estimatenot reported
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

Rat pups were mounted dorsal-surface-toward a diagnostic linear-array scanner at 8.5 cm (just beyond the focal length) in a 37C water tank and exposed for 30 min. The linear array pulsed four elements simultaneously (10x11 mm transmitting surface), with one element added and one dropped before each sequential pulse so that several pulses contributed to the exposure at each point; pulse repetition frequency for any given set of four elements was 42 Hz. Some animals were fixed immediately after exposure, others after a 24 h recovery period.

Flags from extraction

  • exposures[0].fundamental_frequency_khzThe transducer is described as a 'nominal 3.5-MHz transducer', but later the paper states that the measured center frequency of the pulse waveform was found to be 2.4 MHz; the nominal value is recorded here, with the measured value noted as a discrepancy.
  • sham_typeControl animals were 'bound and placed in the tank for 30 min but not exposed'; the exact mechanism (transducer present but powered off vs. absent) is not fully described, so classification as inactive_transducer is inferred.
  • exposures[0].free_field.isppa_w_cm2SPPA and SPTP were calculated from hydrophone measurements made 'at the position of the rat in our exposure tank' (i.e. in water, not through animal tissue), so classified as free_field; SPTA/SATA were separately reported by the manufacturer as measured in water.