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Focused ultrasound modulates the level of cortical neurotransmitters: Potential as a new functional brain mapping technique

Byoung‐Kyong Min, Po Song Yang, Mark Bohlke, Shinsuk Park, David R.Vago, Timothy J. Maher, Seung‐Schik Yoo

International Journal of Imaging Systems and Technology 2011, 21, 232-240 · 10.1002/ima.20284

rodenthealthyhistology molecular

Abstract

Regional modulation of the level of cortical neurotransmitters in the brain would serve as a new functional brain mapping technique to interrogate the neurochemical actions of the brain. We investigated the utility of the application of low‐intensity, pulsed sonication of focused ultrasound (FUS) to the brain to modulate the extracellular level of dopamine (DA) and serotonin (5‐HT). FUS was delivered to the thalamic areas of rats, and extracellular DA and 5‐HT were sampled from the frontal lobe using the microdialysis technique. The concentration changes of the sampled DA and 5‐HT were measured through high‐performance liquid chromatography. We observed a significant increase of the extracellular concentrations of DA and 5‐HT in the FUS‐treated group as compared with those in the unsonicated group. Our results provide the first direct evidence that FUS sonication alters the level of extracellular concentration of these monoamine neurotransmitters and has a potential modulatory effect on their local release, uptake, or degradation. Our findings suggest that the pulsed application of FUS offers new perspectives for a possible noninvasive modulation of neurotransmitters and may have diagnostic as well as therapeutic implications for DA/5‐HT‐mediated neurological and psychiatric disorders. © 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 232–240, 2011

Abstract via crossref.

Speciesrat (Sprague-Dawley)
Subjects12 animals
Sessions per subject1
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutshistology molecularIn vivo microdialysis with high-performance liquid chromatography (HPLC) electrochemical detection of extracellular dopamine and serotonin
Direction of effectexcitatoryFUS sonication of the thalamus significantly increased extracellular dopamine (from approximately 20 min post-sonication) and serotonin (from approximately 80 min post-sonication) in frontal-lobe microdialysate compared with the unsonicated control group.
Adverse eventsnot reportedThe study reports MaxPn = 0.35 MPa and a mechanical index (MI) of 0.2 (below the FDA non-ophthalmic MI limit of 1.9) and Ispta = 175 mW/cm2 (below the 720 mW/cm2 AIUM non-obstetric diagnostic limit), and notes that cavitation-related brain tissue damage is rare below 40 MPa.

Exposures

Exposure 1: Pulsed FUS sonication of the thalamus (bilateral)

Target: thalamus — “thalamic areas / thalamus (bilateral)
Device: custom-built

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)100✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 5%
Sonication duration (s)1,200✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatederatingsingle value
In-situ pressure (kPa)350✓✓
In-situ Isppa (W/cm²)3.5✓✓
In-situ Ispta (W/cm²)0.175✓✓
Protocol, in the paper’s words

The sonication parameters were regulated by software: 0.5 ms for the tone burst duration (TBD) and 100 Hz for the pulse repetition frequency (PRF). The sonication lasted for 20 min. Sonications given at a longer TBD and higher acoustic energy were avoided as they may generate sustained increases in neural cell excitability (potentially inducing seizures).

Flags from extraction

  • exposures[0].in_situClassified as in_situ/derating because the paper states intensity was calculated 'after taking into account ultrasound attenuation through the rodent skull in situ' using a literature-derived skull attenuation factor (~87%); the link between that derating step and the specific 175 mW/cm2 / 3.5 W/cm2 / 0.35 MPa values is inferred across two paragraphs rather than stated in a single sentence.
  • exposures[0].timing.duty_cycle_pctDuty cycle is not explicitly stated as a percentage; 0.5 ms pulse duration and 100 Hz PRF are both given directly in the text but combining them into a duty cycle would require arithmetic not performed here.