This procedure adheres to the ethical standards of the institutional committee on human experimentation and the Helsinki Declaration. Ultrasound is considered a minimal-risk procedure; therefore, written consent from the patient is generally not required. Patients with concerns about neurological changes in an appropriate clinical setting were included in the study. Those with open head wounds, surgical incisions, or surgical dressings at the insonation site were excluded. The consumables and equipment used in this study are listed in the Table of Materials.
1. Transducer selection
<ol>
	<li>Select the phased-array probe (1-5 MHz) for TCCD scan. This probe provides the smallest footprint for insonation of the transtemporal window. 
	NOTE: The term &#34;phased-array probe&#34; is often used to refer to the linear phased-array sector arc probe6,10. This terminology can be ambiguous, as all contemporary ultrasound transducers utilize phasing to direct the ultrasound beam. To keep things concise, this review will use &#34;phased-array probe&#34; in place of &#34;linear phased-array sector arc probe.</li>
</ol>
2. Machine settings
<ol>
	<li>Set the machine to the transcranial preset. This preset is available in most modern machines. This sets the indicator to the right of the screen. 
	NOTE: If Transcranial preset is not available, the Cardiac preset can be utilized. The indicator will be to the left of the screen for this preset.
	<ol>
		<li>Set the initial mode to B-Mode (2-dimensional grayscale11). Set Depth 13-16 cm. 
		NOTE: This depth will capture a hyperechoic convex line, which represents the ipsilateral temporal bone, usually at a depth of about 1-2 cm. Whereas the contralateral temporal bone will be seen as concave hyperechoic structure at depth of 14-16 cm.</li>
		<li>For the best scanning ergonomics, position the machine so that the ultrasound screen is directly in line with the ultrasound probe.</li>
	</ol>
	</li>
</ol>
3. Patient position
<ol>
	<li>Place the patient in a supine position with the head of the bed at 30 degrees.</li>
</ol>
4. Scanning technique
<ol>
	<li>Apply Gel to the probe.</li>
	<li>Place the probe on the transtemporal window (Figure 1), parallel to the ground with the index mark aimed towards the patient anterior. 
	NOTE: The transtemporal area lies just above the zygomatic arch and infront of the tragus of the ear6.</li>
</ol>
5. Transcranial views
<ol>
	<li>Use a sliding motion to scan through the nearby brain tissue until the intracranial structures that are relevant are identified. These act as a starting point to identify the landmarks needed for PoCUS TCCD.</li>
	<li>Identify the ipsilateral temporal bone, which is typically seen at around 1 cm11.</li>
	<li>Identify the contralateral temporal bone, which is typically around 14-16 cm11. 
	NOTE: The ipsilateral temporal window appears as a concave or linear hyperechoic structure. The contralateral temporal window is more concave looking11.</li>
	<li>Identify the third ventricle, which appears as two hyperechoic lines with a thin hypoechoic structure in between which represent cerebrospinal fluid. 
	NOTE: This is typically seen at depth of 6-8 cm11. Use sliding or sweeping motion until structure above is identified12. This is not an essential step for this protocol. If not clearly identified can proceed with the next step.</li>
</ol>
6. Color Doppler interrogation of the middle cerebral artery (MCA)
<ol>
	<li>Start with the view obtained from the step in the prior section.</li>
	<li>Start by reducing the depth to have the far field be 10 cm.</li>
	<li>On the left side of the top half of the ultrasound screen locates the large color flow sampling box. 
	NOTE: The MCA should now appear as a linear structure with blood flow directed towards the ultrasound transducer. Red color indicates flow moving towards the transducer.</li>
	<li>Initiate Pulse Wave Doppler and center the box over the MCA`s red color flow signal.</li>
	<li>Obtain a Spectral Doppler wave form. 
	NOTE: Normal MCA blood flow velocity displays a sharp systolic upstroke followed by a gradual deceleration during diastole13.
	<ol>
		<li>Trace the contour to measure the velocity time Integral for one cardiac cycle. 
		NOTE: In ultrasound with transcranial mode, multiple values will automatically be generated once the tracing is complete.</li>
		<li>Ensure that MFV or Time Average Velocity (TAV) or Time adjusted peak velocity (TAP) or Time average maximum Velocity (TAMAX) is displayed. If not, calculate2 it by (PSV + (EDV x 2))/3. 
		NOTE: Mean flow velocity above 120 could raise the concern for possible increased risks of vasospasm. The Angle of insonation must ideally be between 0-30 degrees otherwise measured velocities will be underestimated14. Mean flow velocity (MFV), Time adjusted peak velocity (TAP), Time average maximum Velocity (TAMAX) and Time Average velocity (TAV) will be used interchangeably.</li>
		<li>Ensure that Pulsatility index is displayed. If not, calculate it by using the formula PSV-EDV)/MFV15. 
		NOTE: The PI can be converted to an estimate of ICP using the following formula: ICP = (10.93 x PI)-1.28. Progression to PI &#62; 2 could raise the concern for elevated ICP16. PI is resistant to off-axis insonation as it is a relative ratio. All measurements in this value will be affected equally thus PI value will remain preserved17.</li>
	</ol>
	</li>
</ol>
7. Post-procedural steps
<ol>
	<li>Review the acquired images and Doppler spectra to ensure that they meet diagnostic quality standards.</li>
	<li>Ensure that all images and Doppler data are properly saved and labeled for future reference and analysis.</li>
	<li>Inform the patient about any follow-up steps or additional tests if required.</li>
</ol>

Standardizing PoC TCCD Ultrasound Protocols for Critical Care in Adults

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	<li>Aaslid, R., Markwalder, T. M., Nornes, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+transcranial+Doppler+ultrasound+recording+of+flow+velocity+in+basal+cerebral+arteries.">Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries.</a> J Neurosurg. 57 (6), 769-774 (1982).</li><li>Nicoletto, H. A., Burkman, M. H. <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+series+part+II:+Performing+a+transcranial+Doppler.">Transcranial Doppler series part II: Performing a transcranial Doppler.</a> Am J Electroneurodiag Technol. 49 (1), 14-27 (2009).</li><li>Gunda, S. 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=A+comparative+study+of+transcranial+color-coded+Doppler+(TCCD)+and+transcranial+Doppler+(TCD)+ultrasonography+techniques+in+assessing+the+intracranial+cerebral+arteries+haemodynamics.">A comparative study of transcranial color-coded Doppler (TCCD) and transcranial Doppler (TCD) ultrasonography techniques in assessing the intracranial cerebral arteries haemodynamics.</a> Diagnostics (Basel). 14 (4), 387 (2024).</li><li>Caldas, J., Rynkowski, C. B., Robba, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=POCUS,+how+can+we+include+the+brain?+An+overview.">POCUS, how can we include the brain? An overview.</a> J Anesth Analg Crit Care. 2 (1), 55 (2022).</li><li>Rajajee, 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=Transcranial+color-coded+sonography+with+angle+correction+as+a+screening+tool+for+raised+intracranial+pressure.">Transcranial color-coded sonography with angle correction as a screening tool for raised intracranial pressure.</a> Crit Care Explor. 5 (9), e0953 (2023).</li><li>Bathala, L., Mehndiratta, M., Sharma, 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:+Technique+and+common+findings+(part+1).">Transcranial Doppler: Technique and common findings (part 1).</a> Ann Indian Acad Neurol. 16 (2), 174 (2013).</li><li>Barlinn, K., 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=Increased+pulsatility+of+the+intracranial+blood+flow+spectral+waveform+on+transcranial+Doppler+does+not+point+to+peripheral+arterial+disease+in+stroke+patients.">Increased pulsatility of the intracranial blood flow spectral waveform on transcranial Doppler does not point to peripheral arterial disease in stroke patients.</a> J Stroke Cerebrovas Dis. 24 (1), 189-195 (2015).</li><li>Bronshteyn, Y. S., Blitz, J., Hashmi, N., Krishnan, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Logistics+of+perioperative+diagnostic+point-of-care+ultrasound:+Nomenclature,+scope+of+practice,+training,+credentialing/privileging,+and+billing.">Logistics of perioperative diagnostic point-of-care ultrasound: Nomenclature, scope of practice, training, credentialing/privileging, and billing.</a> Int Anesthesiol Clin. 60 (3), 1-7 (2022).</li><li>Robba, C., 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=Basic+ultrasound+head-to-toe+skills+for+intensivists+in+the+general+and+neuro+intensive+care+unit+population:+Consensus+and+expert+recommendations+of+the+european+society+of+intensive+care+medicine.">Basic ultrasound head-to-toe skills for intensivists in the general and neuro intensive care unit population: Consensus and expert recommendations of the european society of intensive care medicine.</a> Intensive Care Med. 47 (12), 1347-1367 (2021).</li><li>Fischetti, A. J., Scott, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Basic+ultrasound+beam+formation+and+instrumentation.">Basic ultrasound beam formation and instrumentation.</a> Clin Tech Small Anim Pract. 22 (3), 90-92 (2007).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aium+practice+guideline+for+the+performance+of+a+transcranial+Doppler+ultrasound+examination+for+adults+and+children.">Aium practice guideline for the performance of a transcranial Doppler ultrasound examination for adults and children.</a> J Ultrasound Med. 31 (9), 1489-1500 (2012).</li><li>Lau, V. I., Arntfield, R. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Point-of-care+transcranial+Doppler+by+intensivists.">Point-of-care transcranial Doppler by intensivists.</a> Crit Ultrasound J. 9 (1), 21 (2017).</li><li>Naqvi, J., Yap, K. H., Ahmad, G., Ghosh, J. <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+ultrasound:+A+review+of+the+physical+principles+and+major+applications+in+critical+care.">Transcranial Doppler ultrasound: A review of the physical principles and major applications in critical care.</a> Int J Vasc Med. 2013, 1-13 (2013).</li><li>Lepic, 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=Importance+of+angle+corection+in+transcranial+color-coded+duplex+insonation+of+arteries+at+the+base+of+the+brain.">Importance of angle corection in transcranial color-coded duplex insonation of arteries at the base of the brain.</a> Vojnosanit Pregl. 72 (12), 1093-1097 (2015).</li><li>Gosling, R. G., King, D. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+measurement+in+peripheral+vascular+surgery:+Arterial+assessment+by+Doppler-shift+ultrasound.">The role of measurement in peripheral vascular surgery: Arterial assessment by Doppler-shift ultrasound.</a> Proc Royal Soc Med. 67 (6P1), 447-449 (1974).</li><li>Chan, K. -. H., Miller, J. D., Dearden, N. M., Andrews, P. J. D., Midgley, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+changes+in+cerebral+perfusion+pressure+upon+middle+cerebral+artery+blood+flow+velocity+and+jugular+bulb+venous+oxygen+saturation+after+severe+brain+injury.">The effect of changes in cerebral perfusion pressure upon middle cerebral artery blood flow velocity and jugular bulb venous oxygen saturation after severe brain injury.</a> J Neurosurg. 77 (1), 55-61 (1992).</li><li>White, H., Venkatesh, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+of+transcranial+Doppler+in+the+ICU:+A+review.">Applications of transcranial Doppler in the ICU: A review.</a> Intensive Care Med. 32 (7), 981-994 (2006).</li><li>Alexandrov, A. V., Neumyer, M. M., 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=.">.</a> Cerebrovascular ultrasound in stroke prevention and treatment. , 17-32 (2004).</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+(TCD)+ultrasound.+Part+II.+Clinical+indications+and+expected+outcomes.">Practice standards for transcranial Doppler (TCD) ultrasound. Part II. Clinical indications and expected outcomes.</a> J Neuroimaging. 22 (3), 215-224 (2012).</li><li>Bellner, 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=Transcranial+Doppler+sonography+pulsatility+index+(pi)+reflects+intracranial+pressure+(icp).">Transcranial Doppler sonography pulsatility index (pi) reflects intracranial pressure (icp).</a> Surg Neurol. 62 (1), 45-51 (2004).</li><li>Czosnyka, M., Matta, B. F., Smielewski, P., Kirkpatrick, P. J., Pickard, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+perfusion+pressure+in+head-injured+patients:+A+noninvasive+assessment+using+transcranial+Doppler+ultrasonography.">Cerebral perfusion pressure in head-injured patients: A noninvasive assessment using transcranial Doppler ultrasonography.</a> J Neurosurg. 88 (5), 802-808 (1998).</li><li>Nedelmann, M., 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=Consensus+recommendations+for+transcranial+color-coded+duplex+sonography+for+the+assessment+of+intracranial+arteries+in+clinical+trials+on+acute+stroke.">Consensus recommendations for transcranial color-coded duplex sonography for the assessment of intracranial arteries in clinical trials on acute stroke.</a> Stroke. 40 (10), 3238-3244 (2009).</li><li>Rasulo, F. A., 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+Doppler+as+a+screening+test+to+exclude+intracranial+hypertension+in+brain-injured+patients:+The+impressit-2+prospective+multicenter+international+study.">Transcranial Doppler as a screening test to exclude intracranial hypertension in brain-injured patients: The impressit-2 prospective multicenter international study.</a> Critical Care. 26 (1), 110 (2022).</li><li>Robba, C., 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=Basic+ultrasound+head-to-toe+skills+for+intensivists+in+the+general+and+neuro+intensive+care+unit+population:+Consensus+and+expert+recommendations+of+the+european+society+of+intensive+care+medicine.">Basic ultrasound head-to-toe skills for intensivists in the general and neuro intensive care unit population: Consensus and expert recommendations of the european society of intensive care medicine.</a> Intensive Care Med. 47 (12), 1347-1367 (2021).</li><li>Chang, J. J., Tsivgoulis, G., Katsanos, A. H., Malkoff, M. D., 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=Diagnostic+accuracy+of+transcranial+Doppler+for+brain+death+confirmation:+Systematic+review+and+meta-analysis.">Diagnostic accuracy of transcranial Doppler for brain death confirmation: Systematic review and meta-analysis.</a> Am J Neurorad. 37 (3), 408-414 (2016).</li><li>Baumgartner, R. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+color-coded+duplex+sonography.">Transcranial color-coded duplex sonography.</a> J Neurol. 246 (8), 637-647 (1999).</li><li>Hassler, W., Steinmetz, H., Pirschel, J. <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+study+of+intracranial+circulatory+arrest.">Transcranial Doppler study of intracranial circulatory arrest.</a> J Neurosurg. 71 (2), 195-201 (1989).</li><li>Zweifel, C., 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=Reliability+of+the+blood+flow+velocity+pulsatility+index+for+assessment+of+intracranial+and+cerebral+perfusion+pressures+in+head-injured+patients.">Reliability of the blood flow velocity pulsatility index for assessment of intracranial and cerebral perfusion pressures in head-injured patients.</a> Neurosurg. 71 (4), 853-861 (2012).</li><li>Simm, R. F., De Aguiar, P. H. P., De Oliveira Lima, M., Paiva, B. L., Zuccarello, M., 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> Cerebral vasospasm: Neurovascular events after subarachnoid hemorrhage. , 75-76 (2013).</li><li>De Riva, N., 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+Doppler+pulsatility+index:+What+it+is+and+what+it+isn't.">Transcranial Doppler pulsatility index: What it is and what it isn't.</a> Neurocritic Care. 17 (1), 58-66 (2012).</li></ol>

PoC ultrasound is increasingly playing a vital role in the diagnosis and management of patients with acute organ dysfunction, as seen with RUSH and FAST exams. However, when evaluating cerebral function, to date there is little published guidance for clinicians seeking to perform PoC TCCD. 
To develop this PoC protocol, we chose to adapt TCCD rather than TCD imaging. In contrast to traditional TCD, TCCD combines B-mode and color Doppler, allowing for angle correction that results in more accurate measurement of flow velocity22. Further, this protocol proposed in this manuscript abbreviated existing TCCD protocols to focus on a single sonographic window: the trans-temporal. This is because the trans-temporal window is more easily accessible with ultrasound than the alternatives such as the trans-orbital and trans-foraminal12. Further, the trans-temporal window provides the most optimal insonation location to estimate the cerebral blood flow velocity (CBFV) of the MCA, which is the largest artery in the anterior cerebral circulation and receives approximately 70% of the internal carotid artery's blood flow4.
Although the concept of PoC TCCD remains in its nascency, there is some published evidence supporting its use in clinical practice. For example, when screening for increased intra-cranial pressure in the acute setting , PoC TCCD has been shown to provide a rational screening tool for increasing ICP5,23. Based on this existing evidence, European Society of Intensive Care Medicine now lists TCCD as a tool for intensivist to consider when screening patients for elevated ICP24. For the scenario of brain death screening, a meta-analysis in 2016 of 22 published studies showed that TCD detected cerebral circulatory arrest with sensitivity 0.9% and specificity 0.9825.
Although PoCUS TCCD has its advantages, there are also important limitations. First, the exam can be technically difficult in the setting of a poor temporal bone acoustic window, especially in the elderly, with incomplete insonation occurring in 10% of patients with cerebrovascular diseases22. Second, the absolute velocities obtained from TCCD in vasospasm evaluation may misestimate true arterial blood flow velocities since the normal velocities reported are more extensively validated for non-imaging probes utilized in TCD26. Nonetheless, new emerging studies are suggesting that values are at least comparative between the two modalities3. Third, when utilizing TCCD to evaluate the progression of cerebral circulatory arrest, studies have shown that despite the presence of reassuring spectral Doppler waveforms, the mean cerebral flow may be inadequate to sustain life since patients can still qualify as brain death based on validated clinical testing25,27. Fourth, the PI used to estimate ICP level has a wide confidence interval, and thus caution should be made when utilizing the PI to correlate with a specific ICP level28. The wide confidence interval in the relationship between PI and ICP occurs because multiple factors can influence PI without impact on ICP. For instance, changes in PaCO2 or increased arterial blood pressure can affect cerebral blood flow and PI independently of ICP29. A decrease in CPP, which presents an increasing trend in PI, can be either from increased ICP or decrease in MAP. As such, PI is inversely proportional to a mean CPP or directly proportional to arterial blood pressure. Thus, it is recommended that the utilization of increasing PI be used to follow increasing ICP and decreasing CPP trends over time, and not for ICP absolute values30. Even with this in mind, confounders such as lack of pulsatile flow from V-A ECMO or LVAD makes PI uninterpretable for ICP correlate12. 
Even with these limitations, PoC TCCD has value as a bedside screening tool in the diagnosis and management of acute neurologic dysfunction. By developing this point-of-care protocol, the hope is to demystify TCCD to non-neurosonologists tasked with caring for the critically ill, especially in resource limited settings.

First described by Aaslid et al. in 1982, transcranial Doppler (TCD) ultrasonography offered a method to evaluate intracranial blood flow and velocity1. Later, transcranial color-coded duplex ultrasound (TCCD) was developed to allow color-coded visualization of intracerebral vasculature. This permits TCCD to partly overcome a limitation of TCD: angle dependence. Specifically, as a result of Doppler shift, measurements of blood flow velocity are most accurate if the angle of the ultrasound beam and the axis of the vessel are between 0-30 degrees2. While flow velocity measurements in TCD assume an angle close to zero, TCCD allows visualization of the angle of insonation and thus angle-corrected velocity measurements3.
TCCD includes several Doppler measurements including but not limited to: pulsatility index (PI), mean flow velocities (MFV), and or time-adjusted velocity (TAV)4. Using these measurements, TCCD permits non-invasive screening for several important conditions including vasospasm, increased intracranial pressure (ICP), and cerebral circulatory arrest, each of which manifests with a unique hemodynamic and sonographic signature5.
Firstly, in the context of cerebral vasospasm following subarachnoid hemorrhage (aneurysmal or traumatic), TCCD provides real-time visualization of intracranial blood flow, allowing for the detection of narrowing or constriction of cerebral arteries. By measuring MFV (defined as end-diastolic velocity + 1/3(peak systolic velocity + end diastolic velocity)6, clinicians can quantify the severity of vasospasm up to 2.5 days prior to the onset of symptoms7. Concurrently, by measuring PI (defined as peak systolic velocity - end diastolic velocity)/mean velocity), one can detect elevated values (&#62;1.2)7. Elevated values in turn suggest increased cerebrovascular resistance, highlighting the compromised distal perfusion associated with distal vessel vasospasm7or increased intracranial&#160;pressure. The combined use of TCCD, PI, and MFV facilitates early detection and monitoring of vasospasm, enabling prompt interventions to prevent ischemic injury and improve patient outcomes.
Second, in cases of increased ICP, cerebrovascular dynamics can be assessed through PI and MFV. PI and MFV reflect changes in cerebral blood flow and vascular resistance, both of which are impacted by elevations in ICP. Increased ICP may result in elevated PI values due to impaired cerebrovascular compliance, while decreased MFV indicates reduced cerebral perfusion secondary to elevated intracranial pressures4. Monitoring these parameters allows clinicians to gauge the severity of ICP elevation, guide treatment decisions, and assess the response to interventions aimed at lowering ICP.
Third, in the event of cerebral circulatory arrest, PI and MFV assessments play a critical role in confirming the cessation of cerebral blood flow. Rapid identification of cerebral circulatory arrest using TCCD and hemodynamic parameters is essential for initiating time-sensitive interventions, such as advanced neurocritical care measures, to restore cerebral perfusion if detected in a timely manner.
In summary, TCCD offers a non-invasive bedside tool to screen for cerebral vasospasm, increased ICP, and cerebral circulatory arrest. By providing real-time visualization and quantification of cerebral hemodynamics, TCCD enables clinicians to diagnose, monitor, and manage these critical neurological conditions, with potential for improving patient outcomes and reducing morbidity and mortality. But despite the known diagnostic value of transcranial ultrasound, point-of-care utilization of TCCD in critical care medicine remains variable, in part because training in this modality across hospitals is still inconsistent due to a lack of standardized training and education.
To address these gaps, this article proposes a TCCD image acquisition protocol in adults that can be used at the point-of-care (PoC). In general, a PoC ultrasound is one that is performed and interpreted by a patient&#39;s primary treating provider8. This is in contrast to a consultative ultrasound which is requested by a patient&#39;s primary treating provider but performed by a separate specialist team. Whereas consultative TCD or TCCD typically includes Doppler interrogation of multiple cerebral arteries, this PoC protocol centers on selective interrogation of the middle cerebral artery (MCA) for two reasons: (1) the MCA is typically the easiest branch of the Circle of Willis to insonate with TCCD and (2) The MCA is responsible for approximately 70% of the flow from the internal carotid artery, therefore analysis of the MCA can bring a good information about cerebral blood flow as a whole9.
This PoC TCCD protocol includes transducer selection and placement, sequence acquisition, and image optimization. Further, use of PoC TCCD will be discussed as a means of screening for the following three conditions: vasospasm, raised intra-cranial pressure, and progression of cerebral circulatory arrest.

<table><tbody><tr><td>Low Frequency Ultrasound Probe (C35xp)</td><td>SonoSite (FujiFilm)</td><td>P19617</td><td></td></tr><tr><td>SonoSite X-porte Ultrasound</td><td>SonoSite (FujiFilm)</td><td>P19220</td><td></td></tr><tr><td>Ultrasound Gel</td><td>AquaSonic</td><td>PLI 01-08</td><td></td></tr></tbody></table>

point of care transcranial color-coded duplex ultrasound of the middle cerebral artery

In the assessment and management of many clinical problems, point-of-care (PoC) ultrasound is an emerging bedside tool. Transcranial color-coded duplex (TCCD) ultrasound can be valuable in multiple situations, including for patients who are unconscious or have an equivocal neurologic examination, as it helps rule in specific intracranial pathologies. Despite the known diagnostic value of transcranial ultrasound, its use in critical care medicine remains variable. This variability is partly due to inconsistent training across hospitals, stemming from a lack of standardized education and training. Additionally, the brain has often been overlooked in many critical care protocols, such as RUSH (Rapid Ultrasound for Shock and Hypotension) and FAST (Focused Assessment with Sonography in Trauma) exams. To address these gaps, this article proposes a protocol for PoC TCCD image acquisition in adults, detailing indications, limitations, transducer selection, placement, sequence acquisition, and image optimization. Furthermore, the use of PoC TCCD is discussed as a means of screening for three conditions: vasospasm, raised intracranial pressure, and progression of cerebral circulatory arrest.

This section will describe the analysis and interpretation of data obtained from the protocol above and its clinical utility. Figure 1 shows the physical location on the head where the TCCD is performed: in the transtemporal window. Figure 2 demonstrates this transtemporal window showing the ipsilateral MCA being interrogated with pulse-wave Doppler (PWD). With the PWD box placed at a depth of 45-65 mm18, a velocity profile should emerge that can be used to calculate MFW and PI. In this particular case, the Doppler data demonstrate a normal MFV (&#60;80 cm/s) and normal PI (&#60;1.2)19. In contrast, an MFV greater than 120 cm/s is abnormal. Such a value would be suggestive of vasospasm in patients with intracranial pathology at risk of causing vasospasm (e.g., subarachnoid hemorrhage).
For example, Figure 3 shows a PoC TCCD obtained on a patient with acute neurological changes on day 8 following right middle cerebral artery aneurysm coiling for subarachnoid hemorrhage. The PoC TCCD revealed elevated mean flow velocity in the ipsilateral MCA compared to prior studies. Subsequently CT angiography of the head was performed, which confirmed vasospasm in the right anterior circulation.
In patients with intracranial pathology that could lead to intracranial hypertension, PoC TCCD can measure the PI to non-invasively screen for a high Intracranial pressure16,20,21. For example, Bellener et al. developed a simplified formula to estimate the relationship20: ICP = 10.93 &#215; PI &#8722; 1.28.
Figure 4 shows a patient initially presented with intracranial hemorrhage and initial PoC TCCD had a normal PI. Later, the patient was noted to have worsening mental status, PoC TCCD was repeated and revealed elevated PI concerning for possible elevation in intracranial pressure. To treat this, hypertonic fluids were given and subsequent CT imaging revealed that the patient&#39;s hemorrhage was worsening.
PoC TCCD can also be used to screen for progression to cerebral circulatory arrest that precedes brain death. The progression to brain death typically includes a regression in cerebro-arterial flow with an increase in resistivity (Figure 5). These PoC TCCD findings should lead clinicians to obtain further ancillary testing including a comprehensive TCCD study for the purpose of definitive determination of circulatory arrest in accordance with institution-specific guidelines. As an example, Figure 6 is a PoC TCCD of a patient few hours after a prolonged cardiac arrest and subsequent return of cardiac circulation. The immediate trigger for the PoC TCCD exam was the physical exam finding of fixed and non-reactive pupils. Although no consultative TCCD service was available at facility and the patient was too unstable for apnea testing, the PoC TCCD findings were supported by a subsequent CT of the head which revealed diffuse cerebral edema.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/67288/67288fig01.jpg" /> 
Figure 1: Transtemporal window. Transtemporal window with simplified schematic of circle of Willis. The numbers represent the depth that the ipsilateral MCA will be visualized on the ultrasound. The arrow represents the directionality of blood flow. The blue circle represents the location where the probe should be placed. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/67288/67288fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/67288/67288fig02.jpg" /> 
Figure 2: Normal TCCD. TCCD of the Ipsilateral MCA at Depth of 47 mm. The image reveals normal TAV and Normal PI. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/67288/67288fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/67288/67288fig03.jpg" /> 
Figure 3: TCCD with elevated mean flow velocity. TCCD of the Ipsilateral MCA at Depth of 50 mm. This image reveals elevated TAP: Time adjusted peak velocity (equivalent for MFV or TAV or TAMAX) and Normal PI. In appropriate clinical setting, this suggests vasospasm. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/67288/67288fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/67288/67288fig04.jpg" /> 
Figure 4: TCCD with elevated pulsatility index. TCCD shows worsening PI with clinical correlation concerning for increasing intracranial pressure in appropriate clinical setting. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/67288/67288fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/67288/67288fig05.jpg" /> 
Figure 5: Transcranial Doppler progression in cerebral circulatory arrest. Schematic representation of the expected progressive changes in the waveform morphology of the middle cerebral artery as seen on TCD/TCCD in progression to cerebral circulatory arrest. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/67288/67288fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/67288/67288fig06.jpg" /> 
Figure 6: TCCD of cerebral circulatory arrest. Small systolic spikes with small diastolic reversal concerning progression toward cerebral circulatory arrest. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/67288/67288fig06large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Point of Care Transcranial Color-Coded Duplex Ultrasound of the Middle Cerebral Artery

Transcranial ultrasound is an essential tool for monitoring patients with various neurological conditions. Although it is commonly used in a protocolized fashion in consultative studies, the brain has been overlooked in many protocols utilizing point-of-care ultrasound (PoCUS). This study proposes a PoCUS image acquisition protocol.

In the assessment and management of many clinical problems, point-of-care (PoC) ultrasound is an emerging bedside tool. Transcranial color-coded duplex ...

point-care-transcranial-color-coded-duplex-ultrasound-middle-cerebral

Nanyang Technological University

Research

JoVE Journal

Medicine

507 Views.  University of Southern California, Keck school of Medicine. Transcranial ultrasound is an essential tool for monitoring patients with various neurological conditions. Although it is commonly used in a protocolized fashion in consultative studies, the brain has been overlooked in many protocols utilizing point-of-care ultrasound (PoCUS). This study proposes a PoCUS image acquisition protocol.

Video: Point of Care Transcranial Color-Coded Duplex Ultrasound of the Middle Cerebral Artery

Mouse Model of Middle Cerebral Artery Occlusion

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the brain (ischemic stroke) 2. Since most ischemic strokes (~80%) occur in the territory of middle cerebral artery (MCA) 3, many animal stroke models that have been developed have focused on this artery. The intraluminal monofilament model of middle cerebral artery occlusion (MCAO) involves the insertion of a surgical filament into the external carotid artery and threading it forward into the internal carotid artery (ICA) until the tip occludes the origin of the MCA, resulting in a cessation of blood flow and subsequent brain infarction in the MCA territory 4. The technique can be used to model permanent or transient occlusion 5. If the suture is removed after a certain interval (30 min, 1 h, or 2 h), reperfusion is achieved (transient MCAO); if the filament is left in place (24 h) the procedure is suitable as a model of permanent MCAO. This technique does not require craniectomy, a neurosurgical procedure to remove a portion of skull, which may affect intracranial pressure and temperature 6. It has become the most frequently used method to mimic permanent and transient focal cerebral ischemia in rats and mice 7,8. To evaluate the extent of cerebral infarction, we stain brain slices with 2,3,5-triphenyltetrazolium chloride (TTC) to identify ischemic brain tissue 9. In this video, we demonstrate the MCAO method and the determination of infarct size by TTC staining.

We demonstrate in the video a method for producing a middle cerebral artery occlusion in adult mice using an intraluminal monofilament. We also show how to evaluate the extent of cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) staining.

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the ...

Utilizing a Cranial Window to Visualize the Middle Cerebral Artery During Endothelin-1 Induced Middle Cerebral Artery Occlusion

Creation of a cranial window is a method that allows direct visualization of structures on the cortical surface of the brain1-3. This technique can be performed in many locations overlying the rat cerebrum, but is most easily carried out by creating a craniectomy over the readily accessible frontal or parietal bones. Most frequently, we have used this technique in combination with the endothelin-1 middle cerebral artery occlusion model of ischemic stroke to quantify the changes in middle cerebral artery vessel diameter that occur with injection of endothelin-1 into the brain parenchyma adjacent to the proximal MCA4, 5. In order to visualize the proximal portion of the MCA during endothelin -1 induced MCAO, we use a technique to create a cranial window through the temporal bone on the lateral aspect of the rat skull (Figure 1). Cerebral arteries can be visualized either with the dura intact or with the dura incised and retracted. Most commonly, we leave the dura intact during visualization since endothelin-1 induced MCAO involves delivery of the vasoconstricting peptide into the brain parenchyma. This bypasses the need to incise the dura directly over the visualized vessels for drug delivery. This protocol will describe how to create a cranial window to visualize cerebral arteries in a step-wise fashion, as well as how to avoid many of the potential pitfalls pertaining to this method.

This article describes a method for visualizing rat cerebral arteries through a cranial window using temporal craniectomy in order to view proximal portions of the middle cerebral artery (Figure 1). This versatile method can be combined with various techniques of drug delivery to measure cerebral artery reactivity in vivo.

Creation of a cranial window is a method that allows direct visualization of structures on the cortical surface of the brain1-3. This technique can be ...

Optimized System for Cerebral Perfusion Monitoring in the Rat Stroke Model of Intraluminal Middle Cerebral Artery Occlusion

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal models of acute ischemic stroke allows to confirm successful arterial occlusion and exclude subarachnoid hemorrhage. Cerebral perfusion monitoring can also be used to study intracranial collateral circulation, which is emerging as a powerful determinant of stroke outcome and a possible therapeutic target. Despite a recognized role of Laser Doppler perfusion monitoring as part of the current guidelines for experimental cerebral ischemia, a number of technical difficulties exist that limit its widespread use. One of the major issues is obtaining a secure and prolonged attachment of a deep-penetration Laser Doppler probe to the animal skull. In this video, we show our optimized system for cerebral perfusion monitoring during transient middle cerebral artery occlusion by intraluminal filament in the rat. We developed in-house a simple method to obtain a custom made holder for twin-fibre (deep-penetration) Laser Doppler probes, which allow multi-site monitoring if needed. A continuous and prolonged monitoring of cerebral perfusion could easily be obtained over the intact skull.

Cerebral perfusion monitoring has been demonstrated to improve accuracy in ischemic stroke models. Technical difficulties often limit the use of this essential tool for cerebrovascular research. In this video, an optimized system is shown to obtain a single or multi-site hemodynamic monitoring during intraluminal middle cerebral artery occlusion in rats.

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal ...

State of the Art Cranial Ultrasound Imaging in Neonates

Cranial ultrasound (CUS) is a reputable tool for brain imaging in critically ill neonates. It is safe, relatively cheap and easy to use, even when a patient is unstable. In addition it is radiation-free and allows serial imaging. CUS possibilities have steadily expanded. However, in many neonatal intensive care units, these possibilities are not optimally used. We present a comprehensive approach for neonatal CUS, focusing on optimal settings, different probes, multiple acoustic windows and Doppler techniques. This approach is suited for both routine clinical practice and research purposes. In a live demonstration, we show how this technique is performed in the neonatal intensive care unit. Using optimal settings and probes allows for better imaging quality and improves the diagnostic value of CUS in experienced hands. Traditionally, images are obtained through the anterior fontanel. Use of supplemental acoustic windows (lambdoid, mastoid, and lateral fontanels) improves detection of brain injury. Adding Doppler studies allows screening of patency of large intracranial arteries and veins. Flow velocities and indices can be obtained. Doppler CUS offers the possibility of detecting cerebral sinovenous thrombosis at an early stage, creating a window for therapeutic intervention prior to thrombosis-induced tissue damage. Equipment, data storage and safety aspects are also addressed.

Cranial ultrasound (CUS) is a valuable tool for brain imaging in critically ill neonates. This video shows a comprehensive approach for neonatal (Doppler) CUS for both clinical and research purposes, including a bedside demonstration of the technique.

Cranial ultrasound (CUS) is a reputable tool for brain imaging in critically ill neonates. It is safe, relatively cheap and easy to use, even when a ...

Non-invasive Parenchymal, Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive performance-competitive means for cortical and internal brain imaging, retaining a significant potential in many neurologic fields.

The present work describes a new protocol to perform non-invasive high-frequency ultrasound and photoacoustic based imaging on rat brain, to efficiently visualize deep subcortical regions and their vascular patterns by directing signals on skull foramina naturally present on animal cranium.

Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central ...

Neuroscience

Transient Middle Cerebral Artery Occlusion Model of Neonatal Stroke in P10 Rats

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature and mature brain. Stroke occurs commonly in the perinatal period in humans, and transient ischemia-reperfusion is the most common form of stroke in neonates. The reperfusion phase is a critical component of injury progression, which occurs over a period of days to weeks, and of the endogenous response to injury. This postnatal day 10 (p10) rat model of transient middle cerebral artery occlusion (tMCAO) creates a unilateral, non-hemorrhagic focal ischemia-reperfusion injury that can be utilized to study the mechanisms of focal injury and repair in the full-term-equivalent brain. The injury pattern that is produced by tMCAO is consistent and highly reproducible and can be confirmed with MRI or histological analyses. The severity of injury can be manipulated through changes in occlusion time and other methods that will be discussed.

Neonatal stroke is a significant cause of early brain injury requiring a translational model with consistent focal injury patterns and high reproducibility in order to enable study. This study describes the detailed surgical procedure for creating a non-hemorrhagic, unilateral focal ischemia-reperfusion injury in full-term-equivalent rodents.

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature ...

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.

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 ...

Bioengineering

Analysis of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage with High Frequency Transcranial Duplex Ultrasound

Cerebral vasospasm that occurs in the weeks after subarachnoid hemorrhage, a type of hemorrhagic stroke, contributes to delayed cerebral ischemia. A problem encountered in experimental studies using murine models of SAH is that methods for in vivo monitoring of cerebral vasospasm in mice are lacking. Here, we demonstrate the application of high frequency ultrasound to perform transcranial Duplex sonography examinations on mice. Using the method, the internal carotid arteries (ICA) could be identified. The blood flow velocities in the intracranial ICAs were accelerated significantly after induction of SAH, while blood flow velocities in the extracranial ICAs remained low, indicating cerebral vasospasm. In conclusion, the method demonstrated here allows functional, noninvasive in vivo monitoring of cerebral vasospasm in a murine SAH model.

The aim of this manuscript is to present a sonography-based method that allows in vivo imaging of blood flow in cerebral arteries in mice. We demonstrate its application to determine changes in blood flow velocities associated with vasospasm in murine models of subarachnoid hemorrhage (SAH).

Cerebral vasospasm that occurs in the weeks after subarachnoid hemorrhage, a type of hemorrhagic stroke, contributes to delayed cerebral ischemia. A ...

Modeling Stroke in Mice: Transient Middle Cerebral Artery Occlusion via the External Carotid Artery

Stroke is the third most common cause of mortality and the leading cause of acquired adult disability in developed countries. To date, therapeutic options are limited to a small proportion of stroke patients within the first hours after stroke. Novel therapeutic strategies are being extensively investigated, especially to prolong the therapeutic time window. These current investigations include the study of important pathophysiological pathways after stroke, such as post-stroke inflammation, angiogenesis, neuronal plasticity, and regeneration. Over the last decade, there has been increasing concern about the poor reproducibility of experimental results and scientific findings among independent research groups. To overcome the so-called &#8220;replication crisis&#8221;, detailed standardized models for all procedures are urgently needed. As an effort within the &#8220;ImmunoStroke&#8221; research consortium (https://immunostroke.de/), a standardized mouse model of transient middle cerebral artery occlusion (MCAo) is proposed. This model allows the complete restoration of the blood flow upon removal of the filament, simulating the therapeutic or spontaneous clot lysis that occurs in a large proportion of human strokes. The surgical procedure of this &#8220;filament&#8221; stroke model and tools for its functional analysis are demonstrated in the accompanying video.

Different models of middle cerebral artery occlusion (MCAo) are used in experimental stroke research. Here, an experimental stroke model of transient MCAo via the external carotid artery (ECA) is described, which aims to mimic human stroke, in which the cerebrovascular thrombus is removed due to spontaneous clot lysis or therapy.

Stroke is the third most common cause of mortality and the leading cause of acquired adult disability in developed countries. To date, therapeutic options ...

A Model of Transient Cerebral Ischemia by Occlusion of Middle Cerebral Artery

Transient Middle Cerebral Artery Occlusion Model of Stroke

Stroke stands as a major cause of death or chronic disability globally. Nevertheless, existing optimal treatments are limited to reperfusion therapies during the acute phase of ischemic stroke. To gain insights into stroke physiopathology and develop innovative therapeutic approaches, in vivo rodent models of stroke play a fundamental role. The availability of genetically modified animals has particularly propelled the use of mice as experimental stroke models.
In stroke patients, occlusion of the middle cerebral artery (MCA) is a common occurrence. Consequently, the most prevalent experimental model involves intraluminal occlusion of the MCA, a minimally invasive technique that doesn't require craniectomy. This procedure involves inserting a monofilament through the external carotid artery (ECA) and advancing it through the internal carotid artery (ICA) until it reaches the branching point of the MCA. After a 45 min arterial occlusion, the monofilament is removed to allow reperfusion. Throughout the process, cerebral blood flow is monitored to confirm the reduction during occlusion and subsequent recovery upon reperfusion. Neurological and tissue outcomes are evaluated using behavioral tests and magnetic resonance imaging (MRI) studies.

Author Spotlight: Assessing Ischemic Stroke Damage Through Middle Cerebral Artery Occlusion Model 

This protocol describes the model of transient focal cerebral ischemia in mice through intraluminal occlusion of the middle cerebral artery. Additionally, examples of outcome assessment are shown using magnetic resonance imaging and behavioral tests.

Stroke stands as a major cause of death or chronic disability globally. Nevertheless, existing optimal treatments are limited to reperfusion therapies ...