Ultrasound Delivery Through the Intact Skull
The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the need for a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, researchers examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.
With Dr. Kullervo Hynynen at the University of Toronto, the NCIGT, led by Drs. Nathan McDannold and Greg Clement, has more recently been investigating the use of MRI-guided focused ultrasound (MRgFUS) for transcranial thermal ablation.
Publications
- Vykhodtseva N, McDannold N, Hynynen K. Progress and problems in the application of focused ultrasound for blood-brain barrier disruption. Ultrasonics. 2008 Aug;48(4):279-96. PMID: 18511095.
- McDannold N, Vykhodtseva N, Hynynen K. Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol. 2008 May;34(5):834-40. PMID: 18207311.
- McDannold N, Vykhodtseva N, Hynynen K. Effects of acoustic parameters and ultra-sound contrast agent dose on focused-ultrasound induced blood-brain barrier disruption. Ultrasound Med Biol. 2008 Jun;34(6):930-7. PMID: 18294757.
- Sheikov N, McDannold N, Sharma S, Hynynen K. Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. Ultrasound Med Biol. 2008 Jul;34(7):1093-104. PMID: 18378064.
- Sassaroli E, Hynynen K. Cavitation threshold of microbubbles in gel tunnels by focused ultrasound. Ultrasound Med Biol. 2007 Oct;33(10):1651-60. PMID: 17590501.
- McDannold N, Vykhodtseva N, Hynynen K. Use of ultrasound pulses combined with Definity for targeted blood-brain barrier disruption: A feasibility study. Ultrasound Med Biol. 2007 Apr;33(4):584-90. PMID: 17337109.
- Sheikov N, McDannold N, Jolesz F, Zhang YZ, Tam K, Hynynen K. Brain arterioles show more active vesicular transport of blood-borne tracer molecules than capillaries and venules after focused ultrasound-evoked opening of the blood-brain barrier. Ultrasound Med Biol. 2006 Sep;32(9):1399-409. PMID: 16965980.
- Treat L, McDannold N, Vykhodtseva N, Zhang Y, Tam K, Hynynen K. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer. 2007 Aug 15;121(4):901-7. PMID: 17437269.
- Hynynen K, Clement G. Clinical applications of focused ultrasound-the brain. Int J Hyperthermia. 2007 Mar;23(2):193-202. PMID: 17578343.
- Vykhodtseva N, McDannold N, Hynynen K. Induction of apoptosis in vivo in the rabbit brain with focused ultrasound and Optison. Ultrasound Med Biol. 2006 Dec;32(12):1923-9. PMID: 17169704.
- White PJ, Clement GT, et al. Local frequency dependence in transcranial ultrasound transmission. Phys Med Biol 2006; 51(9): 2293-305. PMID: 16625043 PMCID: 1560343
