Name: targeted neuronal injury for the non-invasive disconnection of brain circuitry
Uploaded: 2020-09-27T13:00:00
Description: Watch this Scientific Journal Video about Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry at JoVE.com

The authors recognize Rene Jack Roy for his excellent technical support in the area of MRI. This work was supported by the National Institutes of Health (R01 NS102194 to KSL and R01 CA217953-01 to MW), the Chester Fund (KSL), and the Focused Ultrasound Foundation (KSL and JW).

All methods described here have been approved by the University of Virginia Animal Care and Use Committee.
1. Preparation of reagents
<ol>
	<li>On the day of surgery, prepare 6.0 mL of injectable quinolinic acid (QA). Dissolve 450 mg of QA in 4.0 mL of 1.0 N NaOH. Add 0.6 mL of 10x PBS, pH to 7.4, and bring to a final volume of 6.0 mL with dH2O. Filter through 0.22 &#181;m syringe filter. The solution is stable for 2 weeks at 4 &#176;C.</li>
	<li>Prepare an aqueous dispersion of m...

<ol>
	<li>Wiebe, S., Eliasziw, M., Matijevic, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+in+quality+of+life+in+epilepsy:+How+large+must+they+be+to+be+real.">Changes in quality of life in epilepsy: How large must they be to be real.</a> Epilepsia. 42, 113-118 (2001).</li><li>McClelland, S., Guo, H., Okuyemi, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Population-based+analysis+of+morbidity+and+mortality+following+surgery+for+intractable+temporal+lobe+epilepsy+in+the+United+States.">Population-based analysis of morbidity and mortality following surgery for intractable temporal lobe epilepsy in the United States.</a> Archives of Neurology. 68, 725-729 (2011).</li><li>Hynynen, K., McDannold, N., Vykhotseva, N., Jolesz, F. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+MR+imaging-guided+focal+opening+of+the+blood-brain+barrier+in+rabbits.">Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits.</a> Radiology. 220, 640-646 (2001).</li><li>McDannold, N., Vykhodtseva, N., Raymond, S., Jolesz, F. A., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI-guided+targeted+blood-brain+barrier+disruption+with+focused+ultrasound:+histological+findings+in+rabbits.">MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits.</a> Ultrasound in Medicine &amp; Biology. 31, 1527-1537 (2005).</li><li>Park, J., Zhang, Y., Vykhodtseva, N., Jolesz, F. A., McDannold, N. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+kinetics+of+blood+brain+barrier+permeability+and+targeted+doxorubicin+delivery+into+brain+induced+by+focused+ultrasound.">The kinetics of blood brain barrier permeability and targeted doxorubicin delivery into brain induced by focused ultrasound.</a> Journal of Controlled Release. 162 (1), 134-142 (2012).</li><li>Sheikov, N., McDannold, N., Vykhodtseva, N., Jolesz, F., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cellular+mechanisms+of+the+blood-brain+barrier+opening+induced+by+ultrasound+in+the+presence+of+microbubbles.">Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in the presence of microbubbles.</a> Ultrasound in Medicine &amp; Biology. 30, 979-989 (2004).</li><li>Vlachos, F., Tung, Y. S., Konofagou, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Permeability+assessment+of+the+focused+ultrasound-induced+blood-brain+barrier+opening+using+dynamic+contrast-enhanced+MRI.">Permeability assessment of the focused ultrasound-induced blood-brain barrier opening using dynamic contrast-enhanced MRI.</a> Physics in Medicine and Biology. 55 (18), 5451-5466 (2010).</li><li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=focal+disconnection+of+brain+circuitry+using+magnetic+resonance-guided+low-intensity+focused+ultrasound+to+deliver+a+Neurotoxin.">focal disconnection of brain circuitry using magnetic resonance-guided low-intensity focused ultrasound to deliver a Neurotoxin.</a> Ultrasound in Medicine &amp; Biology. 42 (9), 2261-2269 (2016).</li><li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Testing+different+combinations+of+acoustic+pressure+and+doses+of+quinolinic+acid+to+induce+focal-neuron+loss+in+mice+using+transcranial+low-intensity+focused+ultrasound.">Testing different combinations of acoustic pressure and doses of quinolinic acid to induce focal-neuron loss in mice using transcranial low-intensity focused ultrasound.</a> Ultrasound in Medicine &amp; Biology. 45, 129-136 (2018).</li><li>Foster, A. C., Miller, L. P., Oldendorf, W. H., Schwarcz, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Studies+on+the+disposition+of+quinolinic+acid+after+intracerebral+or+systemic+administration+in+the+rat.">Studies on the disposition of quinolinic acid after intracerebral or systemic administration in the rat.</a> Experimental Neurology. 84, 428-440 (1984).</li><li>Beskid, M., R&#243;&#380;ycka, Z., Taraszewska, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quinolinic+acid:+effect+on+the+nucleus+arcuatus+of+the+hypothalamus+in+the+rat+(ultrastructural+evidence).">Quinolinic acid: effect on the nucleus arcuatus of the hypothalamus in the rat (ultrastructural evidence).</a> Experimental and Toxicologic Pathology. 49, 477-481 (1997).</li><li>Schwarcz, R., K&#246;hler, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+vulnerability+of+central+neurons+of+the+rat+to+quinolinic+acid.">Differential vulnerability of central neurons of the rat to quinolinic acid.</a> Neuroscience Letters. 38, 85-90 (1983).</li><li>Schwarcz, R., Whetsell, W. O., Mangano, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quinolinic+acid:+an+endogenous+metabolite+that+produces+axon-sparing+lesions+in+rat+brain.">Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain.</a> Science. 219, 316-318 (1983).</li><li>Klibanov, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microbubble+contrast+agents:+targeted+ultrasound+imaging+and+ultrasound-assisted+drug-delivery+applications.">Microbubble contrast agents: targeted ultrasound imaging and ultrasound-assisted drug-delivery applications.</a> Investigative Radiology. 41 (3), 354-362 (2006).</li><li>Agari, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+treatment+of+epilepsy+by+resection+of+periventricular+nodular+heterotopia.">Successful treatment of epilepsy by resection of periventricular nodular heterotopia.</a> Acta Medica Okayama. 66 (6), 487-492 (2012).</li><li>Lee, K. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+genetic+animal+model+of+human+neocortical+heterotopia+associated+with+seizures.">A genetic animal model of human neocortical heterotopia associated with seizures.</a> The Journal of Neuroscience. 17 (16), 6236-6242 (1997).</li><li>Schottler, F., Couture, D., Rao, A., Kahn, H., Lee, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subcortical+connections+of+normotopic+and+heterotopic+neurons+in+sensory+and+motor+cortices+of+the+tish+mutant+rat.">Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat.</a> The Journal of Comparative Neurology. 395 (1), 29-42 (1998).</li><li>Schottler, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Normotopic+and+heterotopic+cortical+representations+of+mystacial+vibrissae+in+rats+with+subcortical+band+heterotopia.">Normotopic and heterotopic cortical representations of mystacial vibrissae in rats with subcortical band heterotopia.</a> Neuroscience. 108 (2), 217-235 (2001).</li><li>Zhang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+non-invasive,+targeted,+neuronal+lesions+on+seizures+in+a+mouse+model+of+temporal+lobe+epilepsy.">Effects of non-invasive, targeted, neuronal lesions on seizures in a mouse model of temporal lobe epilepsy.</a> Ultrasound in Medicine and Biology. 46, 1224-1234 (2020).</li><li>Holmes, E. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+serum+kynurenine+and+hepatic+tryptophan+dioxygenase+activity+by+high-performance+liquid+chromatography.">Determination of serum kynurenine and hepatic tryptophan dioxygenase activity by high-performance liquid chromatography.</a> Analytical Biochemistry. 172, 518-525 (1988).</li><li>Shibata, K., Ohno, T., Sano, M., Fukuwatari, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+urinary+ratio+of+3-hydroxykynurenine/3-hydroxyanthranilic+acid+is+an+index+of+predicting+the+adverse+effects+of+D-trytophan+in+rats.">The urinary ratio of 3-hydroxykynurenine/3-hydroxyanthranilic acid is an index of predicting the adverse effects of D-trytophan in rats.</a> Journal of Nutritional Science and Vitaminology. 60, 261-268 (2014).</li><li>Aubry, J. -. F., Tanter, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR-guided+transcranial+focused+ultrasound.">MR-guided transcranial focused ultrasound.</a> Therapeutic Ultrasound. , 97-111 (2016).</li><li>Elias, W. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Randomized+trial+of+focused+ultrasound+thalamotomy+for+essential+tremor.">A Randomized trial of focused ultrasound thalamotomy for essential tremor.</a> New England Journal of Medicine. 375, 730-739 (2016).</li><li>Ghanouni, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+MR-guided+focused+ultrasound:+a+review+of+the+technology+and+neuro+applications.">Transcranial MR-guided focused ultrasound: a review of the technology and neuro applications.</a> American Journal of Roentgenology. 205, 150-159 (2015).</li><li>Martin, E., Jeanmonod, D., Morel, A., Zadicario, E., Werner, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-intensity+focused+ultrasound+for+noninvasive+functional+neurosurgery.">High-intensity focused ultrasound for noninvasive functional neurosurgery.</a> Annals of Neurology. 66, 858-861 (2009).</li><li>Monteith, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+magnetic+resonance-guided+focused+ultrasound+for+temporal+lobe+epilepsy:+a+laboratory+feasibility+study.">Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study.</a> Journal of Neurosurgery. 12, 1-8 (2016).</li></ol>

The PING method is designed to produce non-invasive, targeted neuronal lesions. The method derives from a strong and growing foundation of research in the field of focused ultrasound3,4,5,6,7. The ability to provide focal access to specific areas of the brain parenchyma via transient opening of the BBB has created an avenue for delivering a wide variety of age...

The purpose of this method is to provide a means for producing non-invasive neuronal lesions in a targeted region of the brain. The rationale for developing such an approach is to disconnect neuronal circuitry contributing to neurological disorders. For instance, surgery can be quite effective in treating certain medically intractable neurological disorders, such as drug resistant epilepsy (DRE)1. However, each of the available surgical modalities possess limitations in terms of producing undesirable collateral damage to the brain. Traditional resective surgery can be highly invasive with the risk of bleeding, infection, blood clots, stroke, seizures, swelling of the brain, and nerve damage2. Alternatives to resective surgery that are minimally invasive or non-invasive include laser interstitial thermal therapy and radiosurgery, which have also proved to be effective in suppressing seizures in DRE. More recently, thermal lesions produced by high-intensity focused ultrasound (HIFU) have shown promise in reducing seizures. HIFU is non-invasive; however, its treatment window is currently limited to more central areas of the brain because of the risk of thermal injury to non-target tissue located in the vicinity of the skull. Despite such limitations, the benefits of surgery often outweigh the potential risks. For instance, although surgery for DRE can produce collateral brain damage, its beneficial effects in suppressing seizures and improving quality of life typically prevail over the surgical risks.
The method described herein, Precise Intracerebral Non-invasive Guided surgery (PING), was developed for the purpose of disconnecting neural circuitry, while limiting collateral brain damage. The method utilizes low intensity focused ultrasound combined with intravenous injection of microbubbles to open the BBB, in order to deliver a neurotoxin. This approach does not produce thermal lesions to the brain3,4,5,6,7, and the period of BBB opening can be exploited to deliver BBB-impermeable compounds to the brain parenchyma. The opening of the BBB is transient, and can be produced in a targeted manner using magnetic resonance imaging guidance. In our studies, the period of BBB opening has been utilized to deliver a circulating neurotoxin to a targeted area of the brain parenchyma in rats and mice8,9. Quinolinic acid is a neurotoxin that is well tolerated when administered intravenously10, intraarterially10, or intraperitoneally8,9,11. The lack of QA toxicity is due to its poor BBB permeability, which has been reported to be negligible10. In contrast, direct injection of QA into the brain parenchyma produces neuronal lesions that spare neighboring axons12,13. Thus, when circulating QA gains access to the brain parenchyma in the targeted area of BBB opening, neuronal death is produced8,9. The present method thus produces focal neuronal loss in a precisely targeted and non-invasive manner.

<table>
	<tbody>
		<tr>
			<td>7T-ClinScan MRI System</td>
			<td>Bruker Biospin, Ettinglen, Germany</td>
			<td></td>
			<td>MR Image Acquisition</td>
		</tr>
		<tr>
			<td>Acoustic Gel</td>
			<td>Litho CLEAR</td>
			<td>11-601</td>
			<td>High Viscosity Accoustic Transmission Gel</td>
		</tr>
		<tr>
			<td>DPX Mounting Medium</td>
			<td>Electron Microscopy Sciences</td>
			<td>13512</td>
			<td>Resin Based Cover Glass Mountant</td>
		</tr>
		<tr>
			<td>Fluoro-Jade B</td>
			<td>EDM Millipore</td>
			<td>AG310</td>
			<td>High Affinity Stain For Degenerating Neurons</td>
		</tr>
		<tr>
			<td>Fluovac anesthetic adsorber</td>
			<td>Harvard Apparatus</td>
			<td>34-0388</td>
			<td>Organic Anaesthesia Scavenger</td>
		</tr>
		<tr>
			<td>FUS System</td>
			<td>Image Guided Therapy, Pessac, France</td>
			<td>LabFUS</td>
			<td>MR Compatible Small Animal Focused Ultrasound System</td>
		</tr>
		<tr>
			<td>Gadodiamide</td>
			<td>GE Healthcare AS, Oslo, Norway</td>
			<td>Omniscan</td>
			<td>MR Contrast Agent</td>
		</tr>
		<tr>
			<td>Heparin</td>
			<td>SAGENT</td>
			<td>NDC2502140010</td>
			<td>Anti-Coagulant</td>
		</tr>
		<tr>
			<td>Hypodermic needle 30G x 1/2</td>
			<td>Becton-Dickinson</td>
			<td>26027</td>
			<td>Tail Vein Catheterization</td>
		</tr>
		<tr>
			<td>Insulin syringe 28G1/2 (1ml)</td>
			<td>EXEL</td>
			<td>26027</td>
			<td>Administration of Injectables to Tail Vein Catheter</td>
		</tr>
		<tr>
			<td>Isofluorane atomizer</td>
			<td>SurgiVet</td>
			<td>VCT302</td>
			<td>Anaesthesia Administration</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Henry Schein</td>
			<td>NDC1169567762</td>
			<td>Anaesthesia</td>
		</tr>
		<tr>
			<td>KMnO4</td>
			<td>Sigma</td>
			<td>223468</td>
			<td>Reagent Used in Fluoro-Jade B Staining</td>
		</tr>
		<tr>
			<td>Microbubbles</td>
			<td>Produced internally: A. Klibanov</td>
			<td>305106</td>
			<td>Blood Brain Barrier Disrupting Agent</td>
		</tr>
		<tr>
			<td>Microbubbles (commercial source)</td>
			<td>Lantheus Medical Imaging, North Billerica, MA</td>
			<td>Definity microbubbles</td>
			<td>Blood Brain Barrier Disrupting Agent</td>
		</tr>
		<tr>
			<td>Monitoring &#38; Gating System</td>
			<td>Small Animal Instruments</td>
			<td>Model 1030</td>
			<td>Respiration Monitoring</td>
		</tr>
		<tr>
			<td>Multisizer 3 Coulter counter</td>
			<td>Beckman-Coulter, Hialeah, FL</td>
			<td>Multisizer 3</td>
			<td>Used to Determine Average Size of Microbubbles</td>
		</tr>
		<tr>
			<td>Optixcare EYE LUBE</td>
			<td>CLC MEDICA, Ontario, Canada</td>
			<td>11611</td>
			<td>Corneal Protectant-Eye Lube</td>
		</tr>
		<tr>
			<td>PE10 tubing</td>
			<td>Becton-Dickinson</td>
			<td>427401</td>
			<td>Tail Vein Catheter Component</td>
		</tr>
		<tr>
			<td>Quinolinic Acid</td>
			<td>Santa Cruz Biotechnology, Dallas, TX</td>
			<td>CAS 89-00-9</td>
			<td>Neurotoxin</td>
		</tr>
		<tr>
			<td>Sprague-Dawley Rats</td>
			<td>Taconic Biosciences</td>
			<td>SD-M</td>
			<td>Rat Model</td>
		</tr>
		<tr>
			<td>Syringe Pump</td>
			<td>Carnegie Medicin</td>
			<td>CMA 100</td>
			<td>Controlled Delivery of Quinolinic Acid</td>
		</tr>
		<tr>
			<td>Thermoguide Software</td>
			<td>Image Guided Therapy, Pessac, France</td>
			<td>Thermoguide</td>
			<td>Drives Lab FUS System</td>
		</tr>
		<tr>
			<td>Tish Rats</td>
			<td>In-house colony</td>
			<td></td>
			<td>Rat Model</td>
		</tr>
		<tr>
			<td>Veet depilatory cream</td>
			<td>Reckitt Benckiser</td>
			<td></td>
			<td>Removal of Scalp Hair</td>
		</tr>
	</tbody>
</table>

targeted neuronal injury for the non-invasive disconnection of brain circuitry

Surgical intervention can be quite effective for treating certain types of medically intractable neurological diseases. This approach is particularly useful for disorders in which identifiable neuronal circuitry plays a key role, such as epilepsy and movement disorders. Currently available surgical modalities, while effective, generally involve an invasive surgical procedure, which can result in surgical injury to non-target tissues. Consequently, it would be of value to expand the range of surgical approaches to include a technique that is both non-invasive and neurotoxic.
Here, a method is presented for producing focal, neuronal lesions in the brain in a non-invasive manner. This approach utilizes low-intensity focused ultrasound together with intravenous microbubbles to transiently and focally open the Blood Brain Barrier (BBB). The period of transient BBB opening is then exploited to focally deliver a systemically administered neurotoxin to a targeted brain area. The neurotoxin quinolinic acid (QA) is normally BBB-impermeable, and is well-tolerated when administered intraperitoneally or intravenously. However, when QA gains direct access to brain tissue, it is toxic to the neurons. This method has been used in rats and mice to target specific brain regions. Immediately after MRgFUS, successful opening of the BBB is confirmed using contrast enhanced T1-weighted imaging. After the procedure, T2 imaging shows injury restricted to the targeted area of the brain and the loss of neurons in the targeted area can be confirmed post-mortem utilizing histological techniques. Notably, animals injected with saline rather than QA do demonstrate opening of the BBB, but dot not exhibit injury or neuronal loss. This method, termed Precise Intracerebral Non-invasive Guided surgery (PING) could provide a non-invasive approach for treating neurological disorders associated with disturbances in neural circuitry.

This section describes the effect of PING on neurons located in a neocortical dysplasia. Tissue dysplasias are a common feature in the brains of patients with drug resistant epilepsy, and surgical removal of seizure-genic dysplasias can provide excellent control of seizures15. Defining the effect of PING on dysplastic brain tissue is therefore an important priority. A rat model of genetic cortical dysplasia, the tish rat, was selected for studying this issue because the tish brain exhibits dysplas...

Watch this Scientific Journal Video about Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry at JoVE.com

Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry

The goal of the protocol is to provide a method for producing non-invasive neuronal lesions in the brain. The method utilizes Magnetic Resonance-guided Focused Ultrasound (MRgFUS) to open the Blood Brain Barrier in a transient and focal manner, in order to deliver a circulating neurotoxin to the brain parenchyma.

Surgical intervention can be quite effective for treating certain types of medically intractable neurological diseases. This approach is particularly ...

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