This project is based on research that was partially supported by the Nebraska Agricultural Experiment Station with funding from the Hatch Act (Accession Number 0223605) through the USDA National Institute of Food and Agriculture.

All human subject research was performed in accordance with the Institutional Review Board of the University of Nebraska-Lincoln, and informed consent was obtained from all subjects.
1. Locating the MCA signal by freehand TCD
NOTE: &#8220;Freehand&#8221; TCD refers to operation of TCD with a handheld transducer to find a CBFV signal before beginning an fTCD experiment.
<ol>
	<li>Setting TCD parameters
	<ol>
		<li>Keep the power at a reasonably high value (e.g., 40...

<ol>
	<li>Buxton, R. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+physics+of+functional+magnetic+resonance+imaging+(fMRI).">The physics of functional magnetic resonance imaging (fMRI).</a> Reports on Progress in Physics. 76 (9), 096601 (2013).</li><li>Lohmann, H., Dr&#228;ger, B., M&#252;ller-Ehrenberg, S., Deppe, M., Knecht, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Language+lateralization+in+young+children+assessed+by+functional+transcranial+Doppler+sonography.">Language lateralization in young children assessed by functional transcranial Doppler sonography.</a> NeuroImage. 24 (3), 780-790 (2005).</li><li>Knecht, 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=Noninvasive+determination+of+language+lateralization+by+functional+transcranial+Doppler+sonography:+a+comparison+with+the+Wada+test.">Noninvasive determination of language lateralization by functional transcranial Doppler sonography: a comparison with the Wada test.</a> Stroke. 29 (1), 82-86 (1998).</li><li>Knecht, 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=Successive+activation+of+both+cerebral+hemispheres+during+cued+word+generation.">Successive activation of both cerebral hemispheres during cued word generation.</a> Neuroreport. 7 (3), 820-824 (1996).</li><li>Hage, B., Way, E., Barlow, S. M., Bashford, G. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-time+cerebral+hemodynamic+response+to+tactile+somatosensory+stimulation.">Real-time cerebral hemodynamic response to tactile somatosensory stimulation.</a> Journal of Neuroimaging. 28 (6), 615-620 (2018).</li><li>Hage, B., 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=Functional+transcranial+Doppler+ultrasound+for+measurement+of+hemispheric+lateralization+during+visual+memory+and+visual+search+cognitive+tasks.">Functional transcranial Doppler ultrasound for measurement of hemispheric lateralization during visual memory and visual search cognitive tasks.</a> IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. 63 (12), 2001-2007 (2016).</li><li>Meyer, G. F., Spray, A., Fairlie, J. E., Uomini, N. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inferring+common+cognitive+mechanisms+from+brain+blood-flow+lateralization+data:+a+new+methodology+for+fTCD+analysis.">Inferring common cognitive mechanisms from brain blood-flow lateralization data: a new methodology for fTCD analysis.</a> Frontiers in Psychology. 5, 552 (2014).</li><li>Uomini, N. T., Meyer, G. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shared+brain+lateralization+patterns+in+language+and+Acheulean+stone+tool+production:+a+functional+transcranial+Doppler+ultrasound+study.">Shared brain lateralization patterns in language and Acheulean stone tool production: a functional transcranial Doppler ultrasound study.</a> PLoS ONE. 8 (8), 72693 (2013).</li><li>Edvinsson, L., MacKenzie, E. T., McCulloch, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Cerebral Blood Flow and Metabolism. , (1993).</li><li>Alexandrov, A. V., 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=Practice+standards+for+transcranial+Doppler+ultrasound:+part+I--test+performance.">Practice standards for transcranial Doppler ultrasound: part I--test performance.</a> Journal of Neuroimaging. 17 (1), 11-18 (2007).</li><li>Fujioka, K. A., Douville, C. M., Newell, D. W., Aaslid, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anatomy+and+freehand+examination+techniques.">Anatomy and freehand examination techniques.</a> Transcranial Doppler. , (1992).</li><li>Alexandrov, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+Doppler+physics+and+techniques,+lecture+notes.">Transcranial Doppler physics and techniques, lecture notes.</a> American Society of Neuroimaging Conference. , (2020).</li><li>Alwatban, M., Truemper, E. J., Al-rethaia, A., Murman, D. L., Bashford, G. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+breath-hold+acceleration+index:+a+new+method+to+evaluate+cerebrovascular+reactivity+using+transcranial+Doppler.">The breath-hold acceleration index: a new method to evaluate cerebrovascular reactivity using transcranial Doppler.</a> Journal of Neuroimaging. 28 (4), 429-435 (2018).</li><li>Tiecks, F. 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=Effects+of+the+Valsalva+maneuver+on+cerebral+circulation+in+healthy+adults:+a+transcranial+Doppler+study.">Effects of the Valsalva maneuver on cerebral circulation in healthy adults: a transcranial Doppler study.</a> Stroke. 26 (8), 1386-1392 (1995).</li><li>Alwatban, M., Murman, D. L., Bashford, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebrovascular+reactivity+impairment+in+preclinical+Alzheimer's+disease.">Cerebrovascular reactivity impairment in preclinical Alzheimer's disease.</a> Journal of Neuroimaging. 29 (4), 493-498 (2019).</li><li>Twedt, M. H., 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=Most+high-intensity+transient+signals+are+not+associated+with+specific+surgical+maneuvers.">Most high-intensity transient signals are not associated with specific surgical maneuvers.</a> World Journal for Pediatric and Congenital Heart Surgery. 11 (4), 401-408 (2020).</li><li>Moehring, M. A., Spencer, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Power+M-mode+Doppler+(PMD)+for+observing+cerebral+blood+flow+and+tracking+emboli.">Power M-mode Doppler (PMD) for observing cerebral blood flow and tracking emboli.</a> Ultrasound in Medicine &amp; Biology. 28 (1), 49-57 (2002).</li><li>Poldrack, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+future+of+fMRI+in+cognitive+neuroscience.">The future of fMRI in cognitive neuroscience.</a> NeuroImage. 62 (2), 1216-1220 (2012).</li><li>Oh, H., Custead, R., Wang, Y., Barlow, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+encoding+of+saltatory+pneumotactile+velocity+in+human+glabrous+hand.">Neural encoding of saltatory pneumotactile velocity in human glabrous hand.</a> PLoS ONE. 12 (8), 0183532 (2017).</li><li>Rosner, A. O., Barlow, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+changes+in+cortical+sensorimotor+systems+following+hand+and+orofacial+motor+tasks+and+pulsed+pneumotactile+stimulation.">Hemodynamic changes in cortical sensorimotor systems following hand and orofacial motor tasks and pulsed pneumotactile stimulation.</a> Somatosensory &amp; Motor Research. 33 (3-4), 145-155 (2016).</li><li>Alexandrov, A. V., 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=High+rate+of+complete+recanalization+and+dramatic+clinical+recovery+during+tPA+infusion+when+continuously+monitored+with+2-MHz+transcranial+doppler+monitoring.">High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial doppler monitoring.</a> Stroke. 31 (3), 610-614 (2000).</li><li>Watt, B. P., Burnfield, J. M., Truemper, E. J., Buster, T. W., Bashford, G. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monitoring+cerebral+hemodynamics+with+transcranial+Doppler+ultrasound+during+cognitive+and+exercise+testing+in+adults+following+unilateral+stroke.">Monitoring cerebral hemodynamics with transcranial Doppler ultrasound during cognitive and exercise testing in adults following unilateral stroke.</a> 2012 IEEE Engineering in Medicine and Biology Society Annual Conference Proceedings. , 2310-2313 (2012).</li><li>Markus, H. S., Harrison, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estimation+of+cerebrovascular+reactivity+using+transcranial+Doppler,+including+the+use+of+breath-holding+as+the+vasodilatory+stimulus.">Estimation of cerebrovascular reactivity using transcranial Doppler, including the use of breath-holding as the vasodilatory stimulus.</a> Stroke. 23 (5), 668-673 (1992).</li><li>File:Circle of Willis en.svg. . Wikimedia Commons, the free media repository Available from: <a target="_blank" href="https://commons.wikimedia.org/w/index.php?title=File:Circle_of_Willis_en.svg">https://commons.wikimedia.org/w/index.php?title=File:Circle_of_Willis_en.svg</a> (2020)</li><li>Bode, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Pediatric Applications of Transcranial Doppler Sonography. , (1988).</li></ol>

Critical steps in the protocol include 1) finding the MCA, 2) placing the headband, and 3) performing the breath-holding maneuver.
Modifications may be necessary depending on the subjects in the study. For example, subjects with Alzheimer&#8217;s disease may have difficulty following instructions, necessitating the use of a capnograph to ensure compliance with breath-holding instructions15. Young children may have difficulty following i...

In neuroscience research, it is often desirable to monitor real-time brain activity noninvasively in a variety of environments. However, conventional functional neuroimaging modalities have limitations that impede the ability to capture localized and/or rapid activity changes. The true (non-jittered, non-retrospective) temporal resolution of functional magnetic resonance imaging (fMRI) is currently of the order of a few seconds1, which may not capture transient hemodynamic changes linked to transient neural activation. In another example, although functional near-infrared spectroscopy (fNIRS) has high temporal resolution (milliseconds) and reasonable spatial resolution, it can only probe hemodynamic changes within the cerebral cortex and cannot provide information about changes taking place in the larger arteries supplying the brain.
In contrast, fTCD&#8212;classified as a neuroimaging modality&#8212;&#8220;imaging&#8221; refers to the dimensions of time and space, rather than two orthogonal spatial directions that are more familiar in an &#8220;image&#8221;. fTCD provides complementary information to other neuroimaging modalities by measuring high temporal resolution (typically 10 ms) hemodynamic changes at precise locations within vessels of the basal cerebral circulation.&#160;As with other neuroimaging modalities, fTCD may be used for a variety of experiments such as studying lateralization of cerebral activation during language-related tasks2,3,4, studying neural activation in response to various somatosensory stimuli5, and exploring neural activation in various cognitive stimuli such as visual tasks6, mental tasks7, and even tool production8.
Although fTCD offers several advantages for use in functional imaging, including low cost of equipment, portability, and enhanced safety (compared to Wada test3 or positron emission tomography [PET] scans), operation of a TCD machine requires skills obtained by practice. Some of these skills, which must be learned by a TCD operator, include the ability to identify various cerebral arteries and the motor skills necessary to precisely manipulate the ultrasound probe during the search for the relevant artery. The goal of this Methods paper is to present a technique for using fTCD to perform a functional imaging experiment. First, the basic steps for identifying and optimizing the signal from the MCA, which perfuses 80% of the cerebral hemisphere9, will be listed. Next, placement of a fixation device for holding the TCD probe in place during the experiment will be described. Finally, the breath-holding experiment, which is one example of a functional imaging experiment using fTCD, will be described, and representative results will be shown.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Aquasonic</td>
			<td>Parker Laboratories, Inc., Fairfield, NJ, USA</td>
			<td>01-50</td>
			<td>Ultrasound Gel</td>
		</tr>
		<tr>
			<td>Doppler Box X</td>
			<td>DWL Compumedics Gmbh, Singen, Germany</td>
			<td>Model &#34;BoxX&#34;</td>
			<td>Transcranial Doppler with 2-MHz monitoring probes</td>
		</tr>
		<tr>
			<td>Kimwipes</td>
			<td>Kimberly-Clark Professional</td>
			<td>34256</td>
			<td>Delicate Task Wipers</td>
		</tr>
		<tr>
			<td>Transeptic&#160;</td>
			<td>Parker Laboratories, Inc., Fairfield, NJ, USA</td>
			<td>09-25</td>
			<td>Cleaning Spray</td>
		</tr>
	</tbody>
</table>

functional transcranial doppler ultrasound for monitoring cerebral blood flow

Functional transcranial Doppler ultrasound (fTCD) is the use of transcranial Doppler ultrasound (TCD) to study neural activation occurring during stimuli such as physical movement, activation of tactile sensors in the skin, and viewing images. Neural activation is inferred from an increase in the cerebral blood flow velocity (CBFV) supplying the region of the brain involved in processing sensory input. For example, viewing bright light causes increased neural activity in the occipital lobe of the cerebral cortex, leading to increased blood flow in the posterior cerebral artery, which supplies the occipital lobe. In fTCD, changes in CBFV are used to estimate changes in cerebral blood flow (CBF).
With its high temporal resolution measurement of blood flow velocities in the major cerebral arteries, fTCD complements other established functional imaging techniques. The goal of this Methods paper is to give step-by-step instructions for using fTCD to perform a functional imaging experiment. First, the basic steps for identifying the middle cerebral artery (MCA) and optimizing the signal will be described. Next, placement of a fixation device for holding the TCD probe in place during the experiment will be described. Finally, the breath-holding experiment, which is a specific example of a functional imaging experiment using fTCD, will be demonstrated.

Figure 3 shows sample Doppler spectra and color M-modes from the midpoint of the M1 segment of the MCA. Figure 3A,B were taken at the same position on the scalp, but at different angles. Note how a very small change in angle, without changing the contact position on the scalp, can greatly improve Doppler signal strength, as shown by the higher-intensity yellow coloring of the spectrogram in Figure 3B. Note ...

Watch this Scientific Journal Video about Functional Transcranial Doppler Ultrasound for Monitoring Cerebral Blood Flow at JoVE.com

Functional Transcranial Doppler Ultrasound for Monitoring Cerebral Blood Flow

Functional transcranial Doppler ultrasound complements other functional imaging modalities, with its high temporal resolution measurement of stimulus-induced changes in cerebral blood flow within the basal cerebral arteries. This Methods paper gives step-by-step instructions for using functional transcranial Doppler ultrasound to perform a functional imaging experiment.&#160;

Functional transcranial Doppler ultrasound (fTCD) is the use of transcranial Doppler ultrasound (TCD) to study neural activation occurring during stimuli ...

This protocol forms the basis for a functional TCD experiment because almost all functional TCD experiments require placement of a fixation device to record a stable signal over an extended period of time. The main advantage of functional TCD is its high temporal resolution measurement of changes in cerebral blood flow. Finding the middle cerebral artery using TCD takes practice.It is crucial to hold the transducer steady and move very slowly. The fine motor control needed for making small adjustments in transducer position and direction takes time to develop. Practice on as many volunteers as you can find.Visual demonstration is important for two reasons. First, it is helpful to see exactly where to place the transducer. Second, a crucial part of learning functional TCD is learning the sounds associated with the different arteries.Begin by setting the parameters for a transcranial Doppler ultrasound or TCD. Keep the power at a reasonably high value during the initial search for the middle cerebral artery or MCA. Once the MCA signal is located, reduce the power as much as possible while still maintaining a good signal.Set the sample volume to eight to 12 millimeters during the initial search for the MCA signal. If the signal is difficult to find, increase the gate size to increase the intensity of the signal. Set the gain at a medium level, with the goal of keeping background noise at a minimum.Set the high pass filter cutoff between 50 and 150 hertz. If the subject is an adult, set the depth to 50 millimeters, which is the average midpoint depth for the M1 segment of the MCA. Apply enough ultrasound gel to cover the surface of the transducer.Alert the subject that the gel may feel cold, then place the transducer on the temporal window. After placing the transducer on the scalp, search for the MCA signal, which will generally be located slightly anterior and rostral from the location of the initial transducer placement. If the TCD spectral signal is not immediately obvious, adjust the angle of the transducer while keeping it in the same location relative to the scalp.Slowly angle the probe from rostral to caudal and posterior to anterior. If a signal is still absent, check the color M mode display for flow in the MCA, which is indicated by red color. Increment or decrement the signal depth in five millimeter steps and continue searching.If flow was visible in M mode but not in the Doppler spectra, increase or decrease the depth until the flow signal is visible on the Doppler spectra. If a satisfactory signal is still not obtained, move the transducer to a nearby slightly more anterior position on the scalp, and repeat the search. When an optimal MCA signal is obtained, note the depth and maximum velocity.Using a washable makeup pen, place a mark on the scalp where the optimal signal was found. Next, search for the bifurcation. Increase the depth until the signal from the bifurcation of the internal carotid artery into the middle cerebral artery and anterior cerebral artery is noted, typically at a depth of 51 to 65 millimeters.Search for the optimum bifurcation spectral signal, striving for the highest velocity spectral signal possible. When an optimal bifurcation signal is obtained, note the depth of the bifurcation. Adjust the fixation device to the subject's approximate head size.Alert the subject before placing the headset on his or her head. After placing the headset, adjust the fixation device's fit. And ask the subject if the device is too tight.Loosen the mechanism of the fixation device so that the transducer can move freely. Apply enough ultrasound gel to the transducer to cover the face of the transducer. Adjust the fixation device so that the transducer is located over the top of the previously made mark.Search for the optimal MCA spectral signal, striving for the highest velocity spectral signal possible. When the optimal MCA signal is found, tighten the mechanism of the fixation device to lock the transducer in place. Note the depth and all other settings.Decrease the power as much as possible while still maintaining a spectral envelope that traces the maximum velocity accurately. Begin recording on the TCD software. Instruct the subject to breathe normally for three minutes to achieve a good baseline recording and allow cerebral blood flow velocity to stabilize from any previous experiments or stimuli.Countdown slowly from three. On the count of one, ask the subject to begin breath holding after a normal inspiration. Place a marker in the TCD recording to signify the start of breath holding.Have the subject hold their breath for 30 seconds or until they're no longer comfortable holding their breath. When the subject inhales, place a marker in the TCD recording to signify the end of breath holding. Continue monitoring cerebral blood flow velocity using TCD for at least 30 seconds following the end of breath holding to ensure that the velocity returns to baseline values.Doppler spectra and color M modes from the midpoint of the M1 segment of the middle cerebral artery or MCA are shown here. The spectra were taken at the same position on the scalp, but at different angles. It's important to note that a very small change in angle can greatly improve Doppler signal strength.A simple Doppler spectrum and M mode from the bifurcation of the ICA into the ACA and MCA is shown here. The overlapping red and blue shaded regions and the M mode image denote the MCA and ACA respectively. Doppler spectra and M mode images we're taken at different time points in the breath hold maneuver.The mean blood flow velocity at baseline was 56 centimeters per second, increasing to 70 centimeters per second by the end of breath holding, and undershooting to 47 centimeters per second after breath holding ended. The entire breath holding experiment is shown here. The envelope shown by the white line increases gradually during breath holding remains elevated for approximately 15 seconds after breath holding ends, undershoots for approximately 20 seconds, and then recovers to baseline values.Several examples of bilateral TCD spectra and M mode suitable for bilateral FTCD are shown here. It is important to remember that finding the MCA signal involves very controlled, fine motor movements. The only way to become proficient at finding the MCA is to practice on as many different people as possible.This technique paved the way for researchers to measure brain activity in environments that were previously inaccessible. For example, unlike within MRI, subjects wearing TCD fixation devices can move freely, so brain lateralization during active tasks can be studied.

functional-transcranial-doppler-ultrasound-for-monitoring-cerebral

Research

JoVE Journal

Bioengineering

7.1K 次观看.  University of Nebraska-Lincoln. 此协议构成了功能性 TCD 实验的基础，因为几乎所有功能性 TCD 实验都需要放置固定装置来长时间记录稳定的信号。功能性TCD的主要优点是其高时间分辨率测量脑血流量的变化。使用 TCD 查找中脑动脉需要练习。保持传感器稳定且移动非常缓慢至关重要。在传感器位置和方向上进行小调整所需的精细电机控制需要时间来开发。尽可能多地练习志愿者。视觉演示很重要...