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PET/CT imaging evidence of FUS‐mediated (18)F‐FDG uptake changes in rat brain

Hyungmin Kim, Mi‐Ae Park, Shuyan Wang, Alan Chiu, Krisztina Fischer, Seung‐Schik Yoo

Medical Physics 2013 · 10.1118/1.4789916

rodenthealthypethistology molecular

Abstract

Purpose Transcranial focused ultrasound (FUS) delivers highly focused acoustic energy to a small region of the brain in a noninvasive manner. Recent studies have revealed that FUS, which is administered either in pulsed or continuous waves, can elicit or suppress neural tissue excitability. This neuromodulatory property of FUS has been demonstrated via direct motion detection, electrophysiological recordings, functional magnetic resonance imaging (fMRI), confocal imaging, and microdialysis sampling of neurotransmitters. This study presents new evidence of local increase in glucose metabolism induced by FUS to the rat brain using FDG (18-fludeoxyglucose) positron emission tomography (PET). Methods Sprague-Dawley rats underwent sonication to a unilateral hemispheric area of the brain prior to PET scan. The pulsed sonication (350 kHz, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, and duration of 300 ms) was applied in 2 s intervals for 40 min immediately after the FDG injection via tail vein. Subsequently, the PET was acquired in dynamic list-mode to image FDG activity for an hour, and reconstructed into a single volume representing standardized uptake value (SUV). The raw SUV as well as its asymmetry index (AI) were measured from five different volume-of-interests (VOIs) of the brain for both hemispheres, and compared between sonicated and unsonicated groups. Results Statistically significant hemispheric changes in SUV were observed only at the center of sonication focus within the FUS group [paired t-test; t(7) = 3.57, p Conclusions Spatially distinct increases in the glucose metabolic activity in the rat brain is present only at the center of sonication focus, suggesting localized functional neuromodulation mediated by the sonication.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects7 animals
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutspet, histology molecular — FDG-PET standardized uptake value and asymmetry index; H&E histology
Direction of effectexcitatorySonication raised FDG uptake (asymmetry index 7.9 percent vs -0.8 percent in controls) at the center of the focus only, interpreted as increased local glucose metabolism.
Adverse eventsnone observedBehavior monitored every two days and H&E histology in two animals at 36 days showed no tissue damage or hemorrhage.

Exposures

Exposure 1: 350 kHz pulsed FUS near unilateral thalamus for 40 min

Target: thalamus — “near the thalamic area unilaterally”
Device: custom-built · Channel Tech group, CA (ceramic element) · air-backed spherical segment single-element transducer, 6 cm diameter, 7 cm radius of curvature

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)350✓✓✓
Pulse duration (ms)0.5✓✓✓
Pulse repetition frequency (Hz)1,000✓✓✓⚑
Duty cycle (%)not reportedpulse duration × PRF gives 50%⚑
Sonication duration (s)0.3✓✓✓
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 estimatenot reported
In-situ pressure (kPa)430✓✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)3✓✓✓
Protocol, in the paper’s words

Tone bursts of 0.5 ms at 1 kHz PRF for 300 ms sonications repeated at 2 s intervals for 40 min starting immediately after FDG injection; PET acquired afterwards for 60 min.

Flags from extraction

  • exposures[0].unspecified_domain.ispta_w_cm2 — Intensity was set 'considering the pressure attenuation' of the skull (12.1 percent) but the paper does not say whether 3 W/cm2 is free-field or in situ; left unspecified.
  • exposures[0].unspecified_domain.pressure_kpa — 0.43 MPa peak negative pressure stated as corresponding to MI 0.74; domain not stated.
  • n_subjects — 17 rats enrolled; 7 in the FUS group, 7 controls; 2 for baseline, 1 excluded. A separate threshold experiment sonicated 9 more rats under ketamine/xylazine; recorded FUS group only.
  • exposures[0].timing.duty_cycle_pct — Duty cycle not stated for this protocol; not computed.
  • exposures[0].timing.pulse_repetition_frequency_hz — Threshold experiment text says 100 Hz PRF while the main protocol says 1 kHz; likely typo in the paper, main protocol recorded.
  • sham_type — Control group underwent conditions mimicking the FUS group including application of the sonication setup; whether the transducer was powered is not stated.
  • exposures[0].device.family — Transducer maker not named; only the ceramic supplier given.