Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats
Andrei V. Alexandrov, Kristian Barlinn, Roger Strong, Anne W. Alexandrov, Jaroslaw Aronowski
Translational Stroke Research 2011, 2, 376-381 · 10.1007/s12975-011-0080-6
Abstract
It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long-Evans rats with permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power (128 or 10 mW) or no ultrasound (controls). We measured cerebral hemorrhage, indirect and direct infarct volume as well as edema volume at 24 h. No cerebral hemorrhages were detected in all animals. Exposure to low-power (10 mW) ultrasound resulted in a significantly decreased indirect infarct volume (p = 0.0039), direct infarct volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls. High-power (128 mW) ultrasound had no significant effects. An additional experiment with India ink showed a greater intravascular penetration of dye into ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency, low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema reduction and possible promotion of microcirculation could be used to facilitate drug and nutrient delivery to ischemic areas.
Abstract via europepmc.
Exposures
Exposure 1: 2-MHz pulsed-wave transcranial Doppler insonation at 128 mW or 10 mW power output
Target: hemisphere unspecified — “lateral brain surface / MCA territory (trans-temporal insonation)”
Device: other named manufacturer · DWL · MultiDop-T
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 5,200 | ✓✓✓ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 3,600 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Transcranial insonation was performed with a 2-MHz pulsed-wave US generated with pulse repetition frequency of 5.2 kHz (MultiDop-T®, DWL, Germany). One US transducer with an external diameter of 1.0 cm was placed at the level of temporal bone with its middle projecting between the ear and eye. The distance from the transducer surface to the brain midline structures was 5 cm (Fig. 1). The transducer emitting area covered an entire side of the rat skull, between the eye and most of the ear, thereby exposing an entire lateral brain surface to the US beam. The transducer was placed in a plastic tube, and a transmission gel was used to fill the space between the transducer and the rat skin. The gel was injected into the plastic tube without major air bubble formation. The depth of insonation was set at 5 cm with sample volume of 1 cm. Exposure to US lasted 1 h. In the first group of animals, power of 128 mW was used (estimated “best case” scenario of low attenuation via the human temporal bone). In the second group, power was decreased to 10 mW (i.e., a realistic 90% attenuation rate that could be encountered in most ageing stroke patients). Brief detection of arterial pulsations was done in all actively insonated animals at depths of insonation 4.5 to 6.5 cm which confirmed successful penetration of US through the skull for both power levels. Arterial flow signals were detected with the amplitude of pulsations reaching 100 cm/s and the heart rate of 120– 150 beats/min. Insonation began at 30 min after initiation of a permanent MCA/CCA occlusion in the first two groups and continued for 1 h (Fig. 1). Control animals also had permanent MCA occlusion but received no US exposure.
Flags from extraction
n_subjects— n_subjects reflects only animals actively exposed to US (128 mW + 10 mW groups, n=19); total study enrolment was 32 rats, including 13 unsonicated controls, and 2 additional animals died perioperatively in the high-power group before study completion.exposures[0].unspecified_domain.ispta_w_cm2— Paper reports transducer power output in mW (128 or 10 mW), not spatial intensity in W/cm2 or pressure in kPa, so no value could be placed in the provided intensity/pressure fields.direction_of_effect— Study reports a bioeffect (infarct/edema volume reduction), not a measure of neural excitability, so 'not_assessed' was used; see direction_notes for the actual finding.