Transcranial pulsed ultrasound

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Transcranial pulsed ultrasound (TPU) uses low intensity, low frequency ultrasound (LILFU) to stimulate the brain. In 2002, Dr. Alexander Bystritsky first proposed the idea that this methodology contained therapeutic benefits. [1] Beginning in 2008, Dr. William Tyler and his research team from Arizona State University began an investigation and development of this alternative neuromodulation without the harmful effects and risks of invasive surgery. They discovered that this low-power ultrasound is able to stimulate high neuron activity which allows for the manipulation of the brain waves through an external source. Unlike deep brain stimulation or Vagus nerve stimulation, which use implants and electrical impulses, TPU is a noninvasive and focused procedure that does not require the implantation of electrodes that could damage the nervous tissue. Its use is applicable in the various fields including but not limited to medical and military science. Although this technology holds great potential to introducing new and beneficial alternatives to conventional brain manipulation, it is a relatively young science and has certain obstructions to its full development such as a lack of complete understanding and control of every safety measure. [2]

Contents

Research and applications

Most of the research as of 2010 revolved around projects to utilize TPU as a method of treating neural disorders and improving cognitive function. However, in 2012 Dr. Tyler also began research on ultrasound's potential to stopping seizures. [3] Dr. Tyler and his team still continue to improve their knowledge of brain stimulation therapy and hope to provide a strong foundation in the implementation of such methods. [4]

Medical field

Scientists continue to test a variety of mammals such as humans, monkeys [5] and mice on positively affecting the treatment of epilepsy, Parkinson's disease, chronic pain, coma, dystonia, psychoses and depression by applying safe, low-intensity, TPU. Because the potential for this technology covers a wide variety of benefits, continued research into its safety and efficacy is expected to accelerate its integration into standard medical practice. [2]

Military

Defense Advanced Research Projects Agency (DARPA) is undergoing research to develop a helmet that could control the mental stress of soldiers through the use of TPU. It could have the potential to moderate a soldier's stress and anxiety levels. [6] Sound waves would target specific areas of the brain to stimulate activity in regions only a few cubic millimeters in size. This would allow them to target very specific areas of the brain with great accuracy and without inflicting damage to its surroundings. A prototype of this device is currently being worked upon to better the ability and potential of soldiers. [7]

Testing

Conventional ultrasound used for anatomical analysis typically uses a wave frequency of about 20 MHz to penetrate the bodily tissue and produce images. In comparison, the low frequency of TPU has a sub-thermal exposure of about 5.7 MHz. By significantly reducing the wave frequency, excitable tissue can be manipulated without overexposure or detectable damage. Scientists have discovered that focusing on targeted brain regions in animals has been proven to alter their behavior, their cells' electrical properties (electrophysiology), and their synaptic plasticity, which is essentially the neuron's ability to function. [1]

For instance, when focused on the motor cortex of mice, TPU has been shown to induce paw movements without changing the structure or function of that area of the brain. This proves that this method is capable of controlling brain activity at a high cognitive level. It is clear that shorter waves are able to activate neuron activity while longer waves inhibit it. However, the mechanism responsible for this reaction is yet to be discovered. A recent leading hypothesis is the mechanical manipulation of stretch-sensitive membranes actually stimulates certain voltage-gated ion channels, such as sodium or calcium, thus modulating neuronal activity. [1]

Limitations

Clinical trials have been used to determine any outstanding harmful effects. Although no subjects have displayed long-term neurological abnormalities as a result of these tests, this is a relatively new procedure and has not been studied enough to predict long term side effects. Even though it is a safer alternative to surgery because it is non-invasive, ultrasound always holds the potential to unintentionally disarrange the neurons in a harmful way and cause minor hemorrhages after long-term exposure. [8]

Therapeutic benefits

Opposing high-frequency ultrasound, LILFU holds the following benefits: lower absorption in tissue, greater physical penetration depth in tissue, stronger particle deflections, significantly better acoustic penetration and power in bone, greater influence in kinetic effects, immediate/short-term effect results, longer/persistent effects after procedure and a higher degree of patient safety. [9]

Related Research Articles

Ultrasound Sound waves with frequencies above the human hearing range

Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies from person to person and is approximately 20 kilohertz in healthy young adults. Ultrasound devices operate with frequencies from 20 kHz up to several gigahertz.

Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil, which in turn is connected to the scalp. The stimulator generates a changing electric current within the coil which induces a magnetic field; this field then causes a second inductance of inverted electric charge within the brain itself.

Medical ultrasound

Medical ultrasound is a diagnostic imaging technique, or therapeutic application of ultrasound. It is used to create an image of internal body structures such as tendons, muscles, joints, blood vessels, and internal organs. Its aim is often to find a source of a disease or to exclude pathology. The practice of examining pregnant women using ultrasound is called obstetric ultrasound, and was an early development and application of clinical ultrasonography.

Behavioral neuroscience, also known as biological psychology, biopsychology, or psychobiology, is the application of the principles of biology to the study of physiological, genetic, and developmental mechanisms of behavior in humans and other animals.

Sonic weapon A weapon that uses soundwaves to discomfort, capacitate or kill opponents.

Sonic and ultrasonic weapons (USW) are weapons of various types that use sound to injure, incapacitate, or kill an opponent. Some sonic weapons are currently in limited use or in research and development by military and police forces. Some of these weapons have been described as sonic bullets, sonic grenades, sonic mines, or sonic cannons. Some make a focused beam of sound or ultrasound; some make an area field of sound.

Neurotechnology is any technology that has a fundamental influence on how people understand the brain and various aspects of consciousness, thought, and higher order activities in the brain. It also includes technologies that are designed to improve and repair brain function and allow researchers and clinicians to visualize the brain.

Neural engineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.

Bioelectromagnetics, also known as bioelectromagnetism, is the study of the interaction between electromagnetic fields and biological entities. Areas of study include electromagnetic fields produced by living cells, tissues or organisms, the effects of man-made sources of electromagnetic fields like mobile phones, and the application of electromagnetic radiation toward therapies for the treatment of various conditions.

Transcranial Doppler

Transcranial Doppler (TCD) and transcranial color Doppler (TCCD) are types of Doppler ultrasonography that measure the velocity of blood flow through the brain's blood vessels by measuring the echoes of ultrasound waves moving transcranially. These modes of medical imaging conduct a spectral analysis of the acoustic signals they receive and can therefore be classified as methods of active acoustocerebrography. They are used as tests to help diagnose emboli, stenosis, vasospasm from a subarachnoid hemorrhage, and other problems. These relatively quick and inexpensive tests are growing in popularity. The tests are effective for detecting sickle cell disease, ischemic cerebrovascular disease, subarachnoid hemorrhage, arteriovenous malformations, and cerebral circulatory arrest. The tests are possibly useful for perioperative monitoring and meningeal infection. The equipment used for these tests is becoming increasingly portable, making it possible for a clinician to travel to a hospital, to a doctor's office, or to a nursing home for both inpatient and outpatient studies. The tests are often used in conjunction with other tests such as MRI, MRA, carotid duplex ultrasound and CT scans. The tests are also used for research in cognitive neuroscience.

High-intensity focused ultrasound Non-invasive therapeutic technique

High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that uses non-ionizing ultrasonic waves to heat or ablate tissue. HIFU can be used to increase the flow of blood or lymph, or to destroy tissue, such as tumors, via thermal and mechanical mechanisms. Given the prevalence and relatively low cost of ultrasound, HIFU has been subject to much research and development. The premise of HIFU is that it is a non-invasive low cost therapy that can at minimum outperform the current standard of care.

Transcranial direct-current stimulation

Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. It was originally developed to help patients with brain injuries or psychiatric conditions like major depressive disorder. It can be contrasted with cranial electrotherapy stimulation, which generally uses alternating current the same way.

Low-intensity pulsed ultrasound (LIPUS) is a technology that can be used for therapeutic purposes. It exploits low intensity and pulsed mechanical waves in order to induce regenerative and anti-inflammatory effects on biological tissues, such as bone, cartilage, and tendon. Even if the real mechanism underlying its effectiveness has not been understood yet, it is plausible that the treatment relies on non-thermal phenomena, such as microbubbles and microjets induced by cavitation, acoustic streaming, and mechanical stimulation.

Therapeutic ultrasound refers generally to any type of ultrasonic procedure that uses ultrasound for therapeutic benefit. Physiotherapeutic ultrasound was introduced into clinical practice in the 1950s, with lithotripsy introduced in the 1980s. Others are at various stages in transitioning from research to clinical use: HIFU, targeted ultrasound drug delivery, trans-dermal ultrasound drug delivery, ultrasound hemostasis, cancer therapy, and ultrasound assisted thrombolysis It may use focused ultrasound (FUS) or unfocused ultrasound.

Electrical brain stimulation

Electrical brain stimulation (EBS), also referred to as focal brain stimulation (FBS), is a form of electrotherapy and technique used in research and clinical neurobiology to stimulate a neuron or neural network in the brain through the direct or indirect excitation of its cell membrane by using an electric current. It is used for research or for therapeutic purposes.

LILFU stands for low intensity, low frequency ultrasound. It is a new technique devised by the team of William J. Tyler from Arizona State University to manipulate neuronal circuits using transcranial pulsed ultrasound. This could make the need of invasive (surgical) neuromodulation for some treatments and therapies unnecessary.

Electroanalgesia is a form of analgesia, or pain relief, that uses electricity to ease pain. Electrical devices can be internal or external, at the site of pain (local) or delocalized throughout the whole body. It works by interfering with the electric currents of pain signals, inhibiting them from reaching the brain and inducing a response; different from traditional analgesics, such as opiates which mimic natural endorphins and NSAIDs that help relieve inflammation and stop pain at the source. Electroanalgesia has a lower addictive potential and poses less health threats to the general public, but can cause serious health problems, even death, in people with other electrical devices such as pacemakers or internal hearing aids, or with heart problems.

Microbubbles (MBs) are bubbles smaller than one hundredth of a millimetre in diameter, but larger than one micrometre. They have widespread application in industry, life science, and medicine. The composition of the bubble shell and filling material determine important design features such as buoyancy, crush strength, thermal conductivity, and acoustic properties.

Neurostimulation is the purposeful modulation of the nervous system's activity using invasive or non-invasive means. Neurostimulation usually refers to the electromagnetic approaches to neuromodulation.

Transcranial random noise stimulation (tRNS) is a non-invasive brain stimulation technique and a form of transcranial electrical stimulation (tES). Terney et al from Göttingen University was the first group to apply tRNS in humans in 2008. They showed that by using an alternate current along with random amplitude and frequency in healthy subjects, the motor cortex excitability increased for up to 60 minutes after 10 minutes of stimulation. The study included all the frequencies up to half of the sampling rate i.e. 640 Hz, however the positive effect was limited only to higher frequencies. Although tRNS has shown positive effects in various studies the optimal parameters, as well as the potential clinical effects of this technique, remain unclear.

Functional ultrasound imaging

Functional ultrasound imaging (fUS) is a medical ultrasound imaging technique of detecting or measuring changes in neural activities or metabolism, for example, the loci of brain activity, typically through measuring blood flow or hemodynamic changes. The method can be seen as an extension of Doppler imaging.

References

  1. 1 2 3 Hameroff, Stewart (2013). "Transcranial ultrasound (TUS) effects on mental states: A pilot study" (PDF). Brain Stimulation. Elsevier. 6 (3): 409–15. doi:10.1016/j.brs.2012.05.002. PMID   22664271. S2CID   206354818. Archived from the original (PDF) on 22 March 2013. Retrieved 25 October 2013.
  2. 1 2 "Ultrasound Shown To Exert Remote Control Of Brain Circuits". ScienceDaily. Brain Circuits. Retrieved 23 October 2013.
  3. ↑ Tyler, William. "Our Research in the News". Tyler Laboratory. Retrieved 10 November 2013.
  4. ↑ Tyler, William. "Research Program Summary". The Virginia Tech Carilion School of Medicine and Research Institute. Archived from the original on 3 November 2013. Retrieved 23 October 2013.
  5. ↑ Deffieux, T., Younan, Y., Wattiez, N., Tanter, M., Pouget, P., & Aubry, J. F. (2013). Low-intensity focused ultrasound modulates monkey visuomotor behavior. Current Biology, 23(23), 2430-2433
  6. ↑ Dillow, Clay. "DARPA Wants to Install Transcranial Ultrasonic Mind Control Devices in Soldiers' Helmets". Popular Science. Bonnier Corporation. Retrieved 21 February 2016.
  7. ↑ Tyler, Dr. William J. "Remote Control of Brain Activity Using Ultrasound". Armed with Science. U.S. Defense Department. Retrieved 21 February 2016.
  8. ↑ Daffertshofer, M. (2005). "Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial". Stroke. 36 (7): 1441–6. doi: 10.1161/01.STR.0000170707.86793.1a . PMID   15947262.
  9. ↑ "Why low-frequency Ultrasound?". UltraPuls. Retrieved 13 November 2013.
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