When performing a preload challenge using the wireless, wearable Doppler ultrasound system, there are a number of critical steps that the user should consider. Written and informed consent was obtained for this protocol; the study was reviewed and approved by the Research Ethics Board of Health Sciences North. The procedures followed were in accordance with the local ethical standards of the committee on human experimentation and with the Helsinki Declaration of 1975.
1. Identifying an appropriate patient
<ol>
	<li>Identify a patient on whom the wearable Doppler ultrasound device will be placed. Ensure that the patient is calm and relatively motionless to minimize phonation and deglutition for the duration of the assessment (1-5 min).</li>
	<li>Position the patient in the semi-recumbent or semi-Fowler position in the hospital bed or gurney. Specifically, adjust the bed such that the torso is at an angle of 30-45&#176; above horizontal.</li>
</ol>
2. Obtaining the carotid artery and internal jugular Doppler signals
<ol>
	<li>Turn on the wearable Doppler ultrasound by pressing the round button in the center of the ultrasound device. Blue lights around the periphery of the button will flash, signaling that the device is on and ready to pair with a smart device.</li>
	<li>Turn on the dedicated application on the smart device. Press the start button on the smart device application. Observe the list displayed on the application showing the discoverable, wearable, ultrasound devices within physical proximity of the smart device. Match the number affixed to the face of the desired ultrasound device to the indicated device on the application list. Press connect to pair the desired ultrasound device to the application.</li>
	<li>Confirm the desired ultrasound device is paired by observing white flashing lights around the button in the center of the device. Press correct on the smart device application to complete the pairing.</li>
	<li>Apply a small amount of ultrasound gel to the large face of the transducer wedge on the back of the ultrasound device. 
	NOTE: The gel application produces a characteristic Doppler signal artifact, which can be seen on the smart device application.</li>
	<li>Tap the large face of the transducer wedge to ensure the device is live and paired to the smart device application. Ensure that the volume on the smart device application is turned on by pressing the volume icon button in the top-right corner of the application display.</li>
	<li>With the patient&#39;s neck slightly extended, note the laryngeal prominence, and hold the ultrasound device so that the large face of the transducer wedge faces downward toward the patient&#39;s heart. Place the wedge of the device on the lateral aspect of the patient&#39;s laryngeal prominence. Look for an audio and visual response on the smart device application: the top portion of the application will display a waveform spectrum for the carotid artery and jugular vein. The bottom portion of the application quantifies the corrected flow time (ccFT) for each cardiac cycle, displayed as green bars.</li>
	<li>Slide the transducer face on the patient&#39;s neck laterally from a perpendicular plane defined by the trachea until the carotid Doppler spectrum is detected both visually and audibly on the smart device application. 
	&#8203;NOTE: In most patients, the audio and visual Doppler spectra of the carotid artery and jugular vein are detected within a few centimeters of the lateral laryngeal border.</li>
</ol>
3. Optimizing the carotid artery and internal jugular Doppler signals
<ol>
	<li>While holding the device in place, observe the carotid Doppler spectrum and its features on the top of the application display. A good carotid artery Doppler signal is identified by its characteristic sharp velocity upstroke with a good signal-to-noise ratio and a clear dicrotic notch, which demarcates the end of mechanical systole. The application will automatically begin tracing the Doppler spectrum once a strong enough signal is obtained, indicated by a white line around the maximum of the waveform.</li>
	<li>While holding the device in place, observe the velocity measurements using the scale on the top left-hand side of the smart device display. Using the auto-trace over the carotid artery maximum, ensure that the trace is in a typical range. The peak systolic velocity of the carotid artery is typically between 50 cm/s and 120 cm/s, and the end diastolic velocity is typically less than 20 cm/s.</li>
	<li>Slowly slide the ultrasound device laterally slightly by a few millimeters while looking at the dicrotic notch on the artery spectrum to ensure that a clear velocity nadir is observed reliably. If the dicrotic notch velocity becomes difficult to see, repeat this step, but slide the ultrasound device medially.</li>
	<li>Repeat steps 3.1-3.3 over the contralateral carotid artery to assess for the presence of a clearer dicrotic notch velocity.</li>
	<li>After observing for the presence of a clear dicrotic notch velocity on both carotid arteries, select the side of the neck to which the device will be adhered. Choose the side with the most obvious dicrotic notch velocity. If both sides of the neck have equally acceptable dicrotic notch velocities, choose the side of the neck with the most robust internal jugular Doppler spectrum.</li>
</ol>
4. Adhering the ultrasound device to the neck
<ol>
	<li>Prepare to adhere the device to the chosen carotid artery by visually noting where on the neck the best signal was obtained. If needed, use a skin-marking pen to identify the optimal placement position. Lift the device from the neck, and remove the protective backing from the adhesive attached to the ultrasound device.</li>
	<li>Observe the transducer face on the ultrasound device, and determine if there is a sufficient amount of ultrasound gel remaining. If needed, reapply a small amount of ultrasound gel to the transducer face. Remove excess ultrasound gel from the neck that may have remained during signal discovery as this may interfere with the adhesion of the device.</li>
	<li>Return the device to the neck to the location identified in step 4.1, with the large face of the transducer wedge pointing downward toward the heart. Smooth the wings of the adhesive across the neck. Remove the protective backing from the tips of the adhesive after pulling tight; place the filming against the skin to fully secure the device to the neck. Monitor the carotid and jugular spectra throughout adhesion to ensure that the signal is not lost.</li>
</ol>
5. Performing a preload challenge&#160;&#160;via a passive leg raise (PLR)
<ol>
	<li>Ensure that the patient is in the semi-recumbent position on the hospital bed or gurney, as identified in step 1.2.</li>
	<li>Clear the smart device application data by pressing restart on the smart device application. Press begin assessment on the smart device application to obtain the baseline measures for the passive leg raise (PLR). Begin with 30-60 s of resting baseline with the patient in the semi-recumbent position on the hospital bed or gurney. Look for a marker displayed on the bottom portion of the application display to signify the beginning of the assessment.</li>
	<li>Prepare the necessary measures to perform a PLR (e.g., obtain extra nursing help as needed).</li>
	<li>Once ready to perform a PLR, press mark intervention on the smart device application to signify the beginning of the preload challenge (in this case, a PLR). Look for a marker displayed on the bottom portion of the application display to signify the beginning of the intervention. Perform a PLR; without touching the patient, reposition the hospital bed or gurney so that the torso is moved downward to the horizontal and the legs are lifted to 30-45&#176; above the horizontal. 
	NOTE: The user must take great care to keep the patient fully passive during this maneuver.</li>
	<li>Keep the patient in the PLR position for 90-120 s. 
	NOTE: Throughout the maneuver, it is imperative that the patient keep their neck completely still so as not to change the insonation angle between the transducer face and the vessels in the neck. If needed, manually stabilize the patient&#39;s neck.</li>
	<li>Observe the jugular Doppler spectrum on the smart device application during the intervention; assess for changes in the absolute jugular venous velocity and its pattern as a surrogate for the jugular venous pressure.</li>
	<li>Observe the evolution of the green bars on the smart device application during the intervention; assess for changes in the ccFT before and after the start of the preload challenge. The smart device application automatically quantifies the ccFT for each cardiac cycle and represents this as a green bar.</li>
	<li>Once the intervention is complete, press end assessment on the smart device application. Look for a marker that will be displayed on the bottom portion of the application display to signify the end of the assessment.</li>
	<li>Return the patient back to the baseline, semi-recumbent position.</li>
	<li>If desired, press save on the smart device application to save the assessment and export the data files (see additional data notes for more details).</li>
</ol>
6. Observing the changes in the carotid corrected flow time (ccFT) on the smart device application following the completed assessment
<ol>
	<li>Observe the assessed changes in the ccFT displayed in a yellow box on the lower-right side of the application. 
	NOTE: The smart device application automatically quantifies the changes in ccFT between the recorded baseline measurements and the preload challenge/intervention measurements.</li>
	<li>Press save on the application, and wait for the data to be split into the following files: two .txt format files containing IQ and Tick data from the Doppler device hardware; one PKL format file containing the spectrogram information (use this to visualize the real-time collected data online); and two .json format files containing the session information (such as the date and time, smart device hardware settings, user settings, and more) and real-time calculations per cardiac cycle.</li>
</ol>

J.E.S.K., S.O.G., D.J., L.M.H., E.R., G.C., J.K.E. work for Flosonics Medical, the start-up that builds the wearable Doppler ultrasound; R.A. and B.N. declare no competing interests.

The main purpose of this visual experiment is to describe a protocol for contemporaneously tracking the surrogates of cardiac preload and output during a well-validated PC using a wireless, wearable ultrasound. The goal is not to describe a specific study protocol in patients, per se. However, the description of continuous venous and arterial Doppler serves as a practical and physiological foundation for designing studies in patients both in need of resuscitation (e.g., perioperative period, sepsis) or de-resuscitation (e.g., congestive heart failure, dialysis, failure to liberate from mechanical ventilation)15,36.
The method described employs a wearable, continuous wave Doppler ultrasound that simultaneously insonates a major vein and artery to infer the cardiac function during a PC15. Critical to this method is the selection of an appropriate, cooperative patient and ensuring a minimal angle change between the vessels and the transducer throughout the assessment. Furthermore, assuring a clear and consistent dicrotic notch velocity is paramount to allow for the consistent measurement of the systolic time. Finally, the user must appreciate the venous Doppler morphology and its variation across a spectrum of jugular venous pressure (JVP), as discussed above in the representative results.
As a modification to the method described, instead of a PLR, the PC might consist of a rapid infusion of intravenous fluid9, moving a completely supine patient from horizontal to head down by 15-30&#176; (i.e., Trendelenburg positioning)10, or respiratory maneuvers such as end-expiratory occlusion34. These approaches are beneficial in that there is less patient movement and, ostensibly, a reduced risk of angle change during the assessment. In general, troubleshooting all PCs with the wearable ultrasound requires stable neck positioning, extra adhesive to secure the insonation angle, the prolongation of the assessment when phonation or deglutition artifacts occur, the repositioning of the device, or the addition of ultrasound gel to optimize the acoustic coupling to the patient31.
There are limitations to the method of cardiovascular inference described within this manuscript. With regard to the jugular venous signal, the Doppler morphology is a surrogate of the jugular venous pressure, which itself is a surrogate of the right atrial pressure37,38,39,40. Therefore, there is no certainty that the cardiac preload is increased based on the venous Doppler changes alone. Nevertheless, the venous Doppler waveform varies its morphology based upon the pressure deflections of the right atrium17,18,41; this has been observed in multiple great veins in addition to the jugular. For example, evaluations of the superior and inferior vena cava and the hepatic, portal, intrarenal, and femoral veins all qualitatively estimate the venous pressure42. More specifically, the prominent venous velocity wave during systole is formed by the x-descent of the right atrial pressure and the diastolic velocity wave by the y-descent of the right atrial pressure. The velocity nadir between systole and diastole is due to the right atrial pressure &#34;v wave&#34;16,17,18,42.
Additionally, while the duration of mechanical systole is directly proportional to the stroke volume, the systolic time, similar to SV, is mediated by the heart rate, preload, afterload, and contractility43. While the ccFT equation corrects for heart rate, a limitation of the ccFT as a surrogate for the stroke volume is that it is determined by other hemodynamic inputs. Nevertheless, increases in the ccFT by at least 7 ms24 or by +2%-4% have been shown to accurately detect a 10% rise in the SV in critically ill patients24, healthy volunteers performing a preload modifying maneuver44,45, and healthy volunteers undergoing simulated moderate-to-severe hemorrhage resuscitation27. Furthermore, ccFT has been used to accurately track changing SVs in the elective surgical population during respiratory maneuvers46. Thus, assuming that afterload and contractility are relatively constant during a focused PC, the ccFT varies primarily due to changes in the SV.
Furthermore, the absolute and relative contraindications for this approach have yet to be elaborated, especially in patients. As noted above, the most common contraindication is likely an inability to cooperate (e.g., delirious, speaking, movement, rigors). This is true for many modern vital sign monitors, though the wearable ultrasound is particularly sensitive to phonation and neck movement. Accordingly, the device works very well in intubated and paralyzed patients in the operating room; a study using the device on patients receiving elective coronary artery bypass grafting is currently enrolling. Physiological variation between the opposing carotid arteries in a particular patient is possible; however, this concern is mitigated because, in the PC paradigm, the patient acts as their own control (i.e., a pre-post intervention). Accordingly, we anticipate that while the different sides of the neck (Figure 5) may produce slightly different venous and arterial Doppler signals, the change should be consistent barring any significant unilateral abnormalities (e.g., stenosis). Physical limitations may also pose problems (e.g., central lines, cervical-spine collars, tracheotomy straps, trauma, short necks, or severe cervical kyphosis). Physiological contraindications such as moderate-to-severe carotid stenosis, aortic stenosis, arrhythmia, and abnormal respiratory patterns are also of potential concern. Generally, however, a PLR with real-time measures of cardiac output is resistant to many of these issues, including arrhythmia4,11. The device is currently being studied in both spontaneously breathing emergency department patients and in the operating room; the proportion with unusable signals will be gleaned from this data.
The significance of the method described above is that the adhered ultrasound can sample minutes of continuous data, while hand-held approaches are typically limited to a few cardiac cycles48,49. Additionally, the software for the wearable ultrasound measures the arterial Doppler coefficient of variation. From this, a &#34;smart window&#34; is implemented to sample a sufficient number of cardiac cycles at baseline and during the intervention; this statistical instrument tailors the measurement precision for each preload challenge47. Moreover, given that the wearable ultrasound remains affixed to the patient, the risk of human factors50,51 that increase the measurement variability is diminished; this holds for both arterial and venous insonation. Another significant aspect of this method is that contemporaneous venous and arterial Doppler assessment allows the clinician to indirectly assess the cardiac preload during a dynamic maneuver; this is recommended by experts in the field13 but rarely performed because measuring the right atrial pressure is cumbersome. Accordingly, continuous venous-arterial Doppler during a PC gives a deeper picture of the cardiac function at the bedside. While this method described above may be used to judge intravenous fluid resuscitation, it also holds promise for gauging &#34;de-resuscitation&#34;15,52 or predicting weaning from mechanical ventilation53 and should be explored in future clinical research. For example, the diuresis of patients with volume overload may be revealed by signs of falling right atrial pressure within the venous Doppler signal as the volume removal progresses. Further, should the patient receive a PLR before and after dialysis, the change in arterial Doppler measures should indicate increased cardiac function, as previously reported52.
A method of continuous venous-arterial Doppler during a PC is best accomplished by following the six general steps outlined above in the protocol section. A novel, wireless, wearable Doppler ultrasound system assists this paradigm by adhering to a patient and enabling a relatively fixed insonation angle during the preload change. Fundamentally, simultaneous, instantaneous, venous-arterial Doppler may elaborate the two axes of the Frank-Starling-Sarnoff relationship and, therefore, give new insights into cardiac function. This is especially important when managing acutely ill patients; both volume administration and removal could be refined by this new approach. While the above discussion is largely limited to inpatient applications, additional outpatient uses within the spheres of congestive heart failure, chronic renal failure, and pulmonary hypertension are also possibilities. Accordingly, continuous venous-arterial Doppler may unlock unforeseen channels of exploration within hemodynamics and related medical disciplines.

At its foundation, the Frank-Starling-Sarnoff curve describes the relationship between cardiac preload and output1,2,3,4. Historically, this curve is depicted by plotting the right atrial pressure on the abscissa and the cardiac output or stroke volume (SV)5 on the ordinate. Assessing the slope of this curve is clinically important because the relationship between cardiac filling and output is dynamic; thus, the slope of the curve informs the resuscitation strategy1,4. Specifically, if the slope of the Frank-Starling-Sarnoff (i.e., &#34;cardiac function&#34;) curve is steep, then increasing the preload (e.g., administering intravenous fluid) augments the output. By contrast, if the slope of the cardiac function curve is shallow, then providing intravenous (IV) fluid does not increase the SV2.
Knowing when IV fluid does or does not increase the SV is important so that the treating clinician can avoid physiologically ineffective fluid4,6, in other words, the scenario in which giving IV fluid to a patient does not increase the SV7,8. Identifying this relatively common clinical state is achieved via a preload challenge (PC), which is a clinical maneuver that &#34;tests&#34; the slope of the cardiac function curve3. A PC is achieved by rapidly increasing the cardiac filling and measuring the change in SV9. As above, IV fluid can act as a PC, as can gravitational maneuvers such as moving the head below the level of the heart (i.e., Trendelenburg positioning)10 or moving from a semi-recumbent position to supine with the legs elevated (i.e., a passive leg raise)11. In fact, the passive leg raise (PLR) is a well-accepted and well-validated PC that is employed in modern intensive care units and recommended by experts prior to IV fluid administration during sepsis resuscitation4,12. Importantly, it is suggested that during the PLR, the clinician should measure both the cardiac preload (e.g., the change in right atrial pressure) and the output (e.g., the change in SV) to adequately test the cardiac function curve13. However, the former is rarely performed as simultaneous measures are cumbersome and an invasive catheter placed into the right atrium is often required.
Ultrasonographic surrogates of cardiac filling and output have grown in popularity over the last few decades, especially in emergency departments and intensive care units2,14. Specifically, the simultaneous assessment of both a great vein and large artery acts as a surrogate for cardiac preload and output, respectively2,15. For example, morphological changes in great vein Doppler have been found to track right atrial pressure-this is true for the internal jugular16,17,18, hepatic, and portal veins19, superior vena cava20, inferior vena cava21, femoral veins22, and even intrarenal veins23. Thus, great vein Doppler velocimetry operates as a surrogate for cardiac filling2. However, the Doppler of a large artery can transiently track changes in cardiac output. For instance, measures of common carotid artery systolic time24,25, velocity26,27,28, and flow 29,30 have shown promise for detecting SV changes.
A novel, wireless, wearable, continuous wave Doppler ultrasound that simultaneously insonates both the internal jugular vein and common carotid artery has previously been described14,15,27,28,31,32,33,34,35,36. Herein, a method using this device during a commonly employed, clinical PC-the passive leg raise-is illustrated. Further, the internal jugular and common carotid arterial Doppler morphologies during the PC are described as possible surrogates of cardiac preload and output, respectively. This protocol is clinically important because it provides both a practical and physiological foundation for future patient study. For example, inpatients (e.g., perioperative setting, sepsis, critically ill) and outpatients (e.g., congestive heart failure, dialysis) could be monitored by the method, or modifications thereof, described below.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>FloPatch</td>
			<td>Flosonics</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>iPad</td>
			<td>Apple</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ultrasound gel</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

continuous venous-arterial doppler ultrasound during a preload challenge

A preload challenge (PC) is a clinical maneuver that, first, increases the cardiac filling (i.e., preload) and, second, calculates the change in cardiac output. Fundamentally, a PC is a bedside approach for testing the Frank-Starling-Sarnoff (i.e., "cardiac function") curve. Normally, this curve has a steep slope such that a small change in the cardiac preload generates a large change in the stroke volume (SV) or cardiac output. However, in various disease states, the slope of this relationship flattens such that increasing the volume into the heart leads to little rise in the SV. In this pathological scenario, additional cardiac preload (e.g., intravenous fluid) is unlikely to be physiologically effective and could lead to harm if organ congestion evolves. Therefore, inferring both the cardiac preload and output is clinically useful as it may guide intravenous (IV) fluid resuscitation. Accordingly, the goal of this protocol is to describe a method for contemporaneously tracking the surrogates of cardiac preload and output using a novel, wireless, wearable ultrasound during a well-validated preload challenge.

With respect to interpreting the continuous venous-arterial Doppler ultrasound during a preload challenge, general physiological responses are illustrated in Figure 1, Figure 2, Figure 3, and Figure 4.
First, in a patient with a normal, upright cardiac function curve, a small increase in the cardiac preload (e.g., as inferred by jugular venous Doppler) is accompanied by a relatively large rise in the stroke volume (e.g., as indicated by ccFT augmentation)2,14,36; this is exemplified by Figure 1. Inferring changes in the jugular venous pressure (JVP) from the jugular Doppler spectrum during the preload challenge deserves some elaboration. Again, this physiological variable is a surrogate for cardiac preload or filling. Normally, the jugular vein is collapsed in the upright position when the jugular venous pressure is less than the atmospheric pressure. In the Doppler spectrum, this translates to a relatively high velocity (i.e., usually more than 50 cm/s) with minimal pulsations and low amplitude (i.e., the intensity or &#34;brightness&#34; of the jugular signal). Then, if the jugular venous pressure rises during the maneuver, the vein rounds out in diameter, its velocity falls (i.e., usually to less than 50 cm/s), the intensity (i.e., &#34;brightness&#34;) increases, and the waveform becomes more pulsatile2,14,36. As shown in Figure 1, the change in the venous Doppler morphology indicates that the jugular vein has increased in diameter (i.e., falling velocity, rising amplitude) and is beginning to follow the right atrial pressure deflections. Though not pictured, with increased right atrial pressure, the &#34;v&#34; wave during late systole can cleave the monophasic wave seen in Figure 1 into a systolic &#34;s&#34; velocity wave and a diastolic &#34;d&#34; velocity wave2,14,36. In as-of-yet unpublished data in healthy volunteers, we observed that jugular venous Doppler morphology was the most accurate venous ultrasonographic measure for distinguishing low from high preload states.
In contrast, an abnormal response is depicted in Figure 2. A clinical example of this pathophysiology is a hypovolemic, veno-dilated, septic patient with evolving septic cardiac dysfunction2,15,36. Such a patient has diminished venous return (which reduces the cardiac preload, i.e., the right atrial or jugular venous pressure) and simultaneously depressed cardiac function2,15,35,36. Therefore, at baseline, this patient demonstrates a continuous, low-JVP venous Doppler morphology that increases (i.e., becomes more pulsatile) during the preload challenge without a significant rise in the ccFT. This effectively describes a flattened slope of the cardiac function curve.
The results from continuous venous-arterial Doppler could also alert the treating clinician to problems with the PLR itself. For example, in some situations, the PLR may not recruit enough venous blood from the lower extremities and splanchnic circulation to generate a physiologically effective preload challenge4. Without assessing the cardiac filling, this could result in a &#34;false negative&#34; PLR. However, if the clinician sees little ccFT response (i.e., as a stroke volume surrogate) coupled with no change in the venous Doppler (i.e., as a surrogate for preload), this could herald an ineffective PLR, as seen in Figure 3.
Lastly, it is critical that the PLR maneuver is true to its namesake, meaning that there is no exertion by the patient when the torso falls and the legs elevate13. This avoids adrenergic discharge, which may increase the cardiac function independently of the venous return; however, as described in Figure 4, this undesired scenario may be indicated by the parameters of a rising stroke volume in the arterial signal coupled with a venous Doppler morphology, suggesting diminished venous pressure.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/64410/64410fig01.jpg" /> 
Figure 1: Increased slope of the cardiac function curve. In an example of a &#34;normal&#34; or &#34;expected&#34; result, the venous waveform progresses from being high velocity, low amplitude, and non-pulsatile to being lower velocity, higher amplitude, and pulsatile in character. The pulsatile venous waveform can be marked by a monophasic signal, as seen here. Concomitantly, the arterial Doppler waveform shows an increase in the ccFT from baseline, suggesting that the increase in the cardiac preload is met by a rising cardiac output. These responses, taken together, indicate a &#34;cardiac function&#34; curve with a steep slope. The y-axis on the spectrum represents the velocity in centimeters per second. The positive velocity is toward the brain (e.g., the carotid artery), while the negative velocity is toward the heart (e.g., the jugular velocity). The x-axis on the spectrum is time. <a href="https://www.jove.com/files/ftp_upload/64410/64410fig01large.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/64410/64410fig02.jpg" /> 
Figure 2: Flattened slope of the cardiac function curve. An &#34;abnormal&#34; response during a preload challenge is marked by a venous Doppler waveform that evolves as above but with an arterial response that reveals no significant change or even a decrease in the ccFT as compared to baseline, as seen here. This constellation of venous and arterial findings implies a flat or, potentially, impaired cardiac function curve with increased preload. <a href="https://www.jove.com/files/ftp_upload/64410/64410fig02large.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/64410/64410fig03.jpg" /> 
Figure 3: No change in the venous Doppler. A preload challenge that shows no significant change in the venous Doppler waveform could represent an inadequate change in cardiac filling, meaning no change in the arterial spectrum is expected. <a href="https://www.jove.com/files/ftp_upload/64410/64410fig03large.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/64410/64410fig04.jpg" /> 
Figure 4: Falling preload during a preload challenge. A preload challenge that shows rising venous velocity and a significant increase in arterial Doppler measures may mean augmented adrenergic tone (i.e., sympathetic stimulation) such that the cardiac function increases independently of the venous return. This circumstance could be the result of a &#34;non-passive&#34; leg raise, for example, if the patient strains to change their body position. <a href="https://www.jove.com/files/ftp_upload/64410/64410fig04large.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/64410/64410fig05.jpg" /> 
Figure 5: The device on a volunteer. <a href="https://www.jove.com/files/ftp_upload/64410/64410fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Continuous Venous-Arterial Doppler Ultrasound During a Preload Challenge at JoVE.com

Continuous Venous-Arterial Doppler Ultrasound During a Preload Challenge

The Frank-Starling-Sarnoff curve is clinically important and describes the relationship between cardiac preload and output. This report illustrates a novel method of simultaneous jugular venous and carotid arterial Doppler velocimetry as transient surrogates of cardiac preload and output, respectively; this approach is enabled by wireless, wearable Doppler ultrasound.

A preload challenge (PC) is a clinical maneuver that, first, increases the cardiac filling (i.e., preload) and, second, calculates the change in cardiac ...

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3.2K Views.  Health Sciences North Research Institute. The Frank-Starling-Sarnoff curve is clinically important and describes the relationship between cardiac preload and output. This report illustrates a novel method of simultaneous jugular venous and carotid arterial Doppler velocimetry as transient surrogates of cardiac preload and output, respectively; this approach is enabled by wireless, wearable Doppler ultrasound.

Video: Continuous Venous-Arterial Doppler Ultrasound During a Preload Challenge

Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction

Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ultrasound and fetal echocardiography. Increasingly, these imaging modalities are being employed clinically to examine cardiac function and assess wellbeing in utero, thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR that allows analysis of cardiac function in a clinically relevant way. Using isoflurane induced anesthesia, IUGR is surgically created at gestational age day 25 by performing a laparotomy, exposing the bicornuate uterus and then ligating 40-50% of uteroplacental vessels supplying each gestational sac in a single uterine horn. The other horn in the rabbit bicornuate uterus serves as internal control fetuses. Then, after recovery at gestational age day 30 (full term), the same rabbit undergoes examination of fetal cardiac function. Anesthesia is induced with ketamine and xylazine intramuscularly, then maintained by a continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic effects on fetal cardiac function. A repeat laparotomy is performed to expose each gestational sac and a microultrasound examination (VisualSonics VEVO 2100) of fetal cardiac function is performed. Placental insufficiency is evident by a raised pulsatility index or an absent or reversed end diastolic flow of the umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery Doppler is then examined. Fetal echocardiography is performed by recording B mode, M mode and flow velocity waveforms in lateral and apical views. Offline calculations determine standard M-mode cardiac variables, tricuspid and mitral annular plane systolic excursion, speckle tracking and strain analysis, modified myocardial performance index and vascular flow velocity waveforms of interest. This small animal model of IUGR therefore affords examination of in utero cardiac function that is consistent with current clinical practice and is therefore useful in a translational research setting.

We describe examination of fetal cardiac function with contemporary functional fetal echocardiography and fetoplacental Doppler ultrasound using the VisualSonics VEVO 2100 microultrasound in a surgically induced model of intrauterine fetal growth restriction in a rabbit.

Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ...

Laser Doppler: A Tool for Measuring Pancreatic Islet Microvascular Vasomotion In Vivo

As a functional status of microcirculation, microvascular vasomotion is important for the delivery of oxygen and nutrients and the removal of carbon dioxide and waste products. The impairment of microvascular vasomotion might be a crucial step in the development of microcirculation-related diseases. In addition, the highly vascularized pancreatic islet is adapted to support endocrine function. In this respect, it seems possible to infer that the functional status of pancreatic islet microvascular vasomotion might affect pancreatic islet function. Analyzing the pathological changes of the functional status of pancreatic islet microvascular vasomotion may be a feasible strategy to determine contributions that pancreatic islet microcirculation makes to related diseases, such as diabetes mellitus, pancreatitis, etc. Therefore, this protocol describes using a laser Doppler blood flow monitor to determine the functional status of pancreatic islet microvascular vasomotion, and to establish parameters (including average blood perfusion, amplitude, frequency, and relative velocity of pancreatic islet microvascular vasomotion) for evaluation of the microcirculatory functional status. In a streptozotocin-induced diabetic mouse model, we observed an impaired functional status of pancreatic islet microvascular vasomotion. In conclusion, this approach for assessing pancreatic islet microvascular vasomotion in vivo may reveal mechanisms relating to pancreatic islet diseases.

Laser Doppler: A Tool for Measuring Pancreatic Islet Microvascular Vasomotion In Vivo

Pancreatic islet microvascular vasomotion regulates islet blood distribution and maintains the physiological function of islet &#946; cells. This protocol describes using a laser Doppler monitor to determine the functional status of pancreatic islet microvascular vasomotion in vivo and to assess the contributions of pancreatic islet microcirculation to pancreatic-related diseases.

As a functional status of microcirculation, microvascular vasomotion is important for the delivery of oxygen and nutrients and the removal of carbon ...

Evaluation of Cerebral Blood Flow Autoregulation in the Rat Using Laser Doppler Flowmetry

When investigating the body&#39;s mechanisms for regulating cerebral blood flow, a relative measurement of microcirculatory blood flow can be obtained using laser Doppler flowmetry (LDF). This paper demonstrates a closed skull preparation that allows cerebral blood flow to be assessed without penetrating the skull or installing a chamber or cerebral window. To evaluate autoregulatory mechanisms, a model of controlled blood pressure reduction via graded hemorrhage can be utilized while simultaneously employing LDF. This enables the real time tracking of the relative changes in the blood flow in response to reductions in arterial blood pressure produced by the withdrawal of circulating blood volume. This paradigm is a valuable approach to study cerebral blood flow autoregulation during reductions in arterial blood pressure and, with minor modifications in the protocol, is also valuable as an experimental model of hemorrhagic shock. In addition to evaluating autoregulatory responses, LDF can be used to monitor the cortical blood flow when investigating metabolic, myogenic, endothelial, humoral, or neural mechanisms that regulate cerebral blood flow and the impact of various experimental interventions and pathological conditions on cerebral blood flow.

This article demonstrates the use of laser Doppler flowmetry to evaluate the ability of the cerebral circulation to autoregulate its blood flow during reductions in arterial blood pressure.

When investigating the body&#39;s mechanisms for regulating cerebral blood flow, a relative measurement of microcirculatory blood flow can be obtained ...

Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration

Coronary artery spasm (CAS) can be diagnosed in a large proportion of patients with recurrent angina with non-obstructive coronary artery disease (ANOCA) using acetylcholine (ACh) spasm provocation testing. CAS can further be divided into different subtypes (e.g., focal, diffuse epicardial, or microvascular spasm), each with different pathophysiological mechanisms that may require tailored drug treatment. The evidence behind the role of nitrates in the setting of each CAS subtype is lacking, and the effectivity can vary on a per-patient basis. In order to assess on a per-patient level whether nitroglycerine (NTG) can prevent inducible spasm, the vasospastic ACh dose can be readministered after NTG administration as part of the spasm provocation test. The preventive effect of NTG is assessed by evaluating improvements in the severity of induced symptoms, ischemic ECG changes, and by reassessing the site and mode of spasm on angiography. This technique can therefore be used to assess the nitrate responsiveness on a per-patient level and unmask co-existing microvascular spasm in patients with epicardial spasm that is prevented with NTG. The NTG rechallenge, therefore, allows to further guide targeted therapy for CAS and provide new insights into the pathophysiological mechanism behind vasospastic disorders.

This protocol presents the acetylcholine rechallenge after nitroglycerine as an add-on procedure to spasm provocation testing. The purpose of this technique is to unmask co-existing microvascular spasm&#160;in patients with epicardial spasm&#160;and to assess the protective efficacy of nitroglycerine on a per-patient level to guide medical therapy.

Coronary artery spasm (CAS) can be diagnosed in a large proportion of patients with recurrent angina with non-obstructive coronary artery disease (ANOCA) ...

Providing Visual Biofeedback Using Brightness Mode Ultrasound During a Golf Swing

Using ultrasound biofeedback in conjunction with verbal cueing can increase muscle thickness more than verbal cueing alone and may augment traditional rehabilitation techniques in an athletic, physically active population. Brightness mode (B-mode) ultrasound can be applied using frame-by-frame analysis synchronized with video to understand muscle thickness changes during these dynamic tasks. Visual biofeedback with ultrasound has been established in static positions for the muscles of the lateral abdominal wall. However, by securing the transducer to the abdomen using an elastic belt and foam block, biofeedback can be applied during more specific tasks prevalent in lifetime sports, such as golf. To analyze muscle activity during a golf swing, muscle thickness changes can be compared. The thickness must increase throughout the task, indicating that the muscle is more active. This methodology allows clinicians to immediately replay ultrasound videos for patients as a visual tool to instruct proper activity of the muscles of interest. For example, ultrasound can be used to target the external and internal obliques, which play an important role in swinging a golf club or any other rotational sport or activity. This methodology aims to increase oblique muscle thickness during the golf swing. Additionally, the timing of muscle contraction can be targeted by instructing the patient to contract the abdominal muscles at specific time points, such as the beginning of the downswing, with the goal of improving muscle firing patterns during tasks.

Brightness mode ultrasound can be used to provide visual biofeedback of the muscles of the lateral abdominal wall during a golf swing. Post-swing visual and verbal instruction can increase the muscle activation and timing of the external and internal obliques.

Using ultrasound biofeedback in conjunction with verbal cueing can increase muscle thickness more than verbal cueing alone and may augment traditional ...

Muscle Function Obtained with Motion Mode Ultrasound and Surface Electromyography during Core Endurance Exercise

Motion mode (M-mode) ultrasound allows researchers and clinicians to measure the change of muscle thickness across time. Muscle thickness can be measured between fascial borders at a given time point during an exercise. This selected time point produces a one-dimensional image resulting in real-time, live observation of anatomy. Ultrasound used during functional movement can be referred to as dynamic ultrasound; this is feasible and reliable with the use of a linear transducer, elastic belt, and foam block to secure consistent transducer placement. The lateral abdominal wall is commonly investigated using ultrasound due to the overlapping nature of the muscles. Surface electromyography (sEMG) can complement M-mode ultrasound imaging because it measures the electrical representation of muscle activation. There is minimal evidence using M-mode ultrasound and sEMG simultaneously during core exercise. Exercises that challenge the core musculature involve both isometric holds (e.g., side plank), as well as oscillatory extremity movements (e.g., dead bug). In this study, both instruments will be used simultaneously to measure core muscle function during exercise. Ultrasound measurements will be obtained using a linear transducer and ultrasound unit, and sEMG measurements will be acquired from a wireless sEMG system. To make comparisons between participants and exercises, normalization methods using static, exercise starting positions for both instruments will be used. An activation ratio will be used for ultrasound and calculated by dividing the contracted thickness (thickness during a time point of exercise) by the rested (starting position) thickness. Muscle thickness will be measured in centimeters from the superior inferior fascial border to inferior superior fascial border. These methods aim to offer an innovative and practical measurement of muscle function with M-mode ultrasound and sEMG during core endurance exercises.

This protocol uses motion mode ultrasound and surface electromyography simultaneously to measure muscle function of the core. Muscle thickness and activation of the local stabilizers (e.g., transverse abdominis, internal oblique) and global movers (e.g., external oblique) is achievable during specific time points of the side plank and dead bug exercises.

Motion mode (M-mode) ultrasound allows researchers and clinicians to measure the change of muscle thickness across time. Muscle thickness can be measured ...

Point-of-Care Ultrasound: A Review of Ultrasound Parameters for Predicting Difficult Airways

Airway management remains a crucial part of perioperative care. The conventional approach to assessing potentially difficult airways emphasizes the LEMON method, which looks for and evaluates the Mallampati classification, signs of obstruction, and neck mobility. Clinical findings help predict a higher likelihood of difficult tracheal intubation, but no clinical result reliably excludes difficult intubation. Ultrasound as an adjunct to clinical examination can provide the clinician with a dynamic anatomical airway assessment, which is impossible with clinical examination alone. In the hands of anesthesiologists, ultrasound is becoming more popular in the perioperative period. This method is particularly applicable for identifying proper endotracheal tube positioning in specific patient populations, such as those who are morbidly obese and patients with head and neck cancer or trauma. The focus is on identifying the normal anatomy, correctly positioning the endotracheal tube, and refining the parameters that predict difficult intubation. Several ultrasound measurements are clinical indicators of difficult direct laryngoscopy in the literature. A meta-analysis revealed that the distance from the skin to the epiglottis (DSE) is most associated with a difficult laryngoscopy. An ultrasound of the airway could be applied in routine practice as an adjunct to the clinical examination. A full stomach, rapid sequence intubation, gross visual anatomical abnormalities, and restricted neck flexibility prevent using ultrasound to assess the airway. The airway evaluation is performed with a linear array transducer of 12-4 MHz, with the patient in the supine position, with no pillow, and with the head and neck in a neutral position. The central axis of the neck is where the ultrasound parameters are measured. These image acquisitions guide the standard ultrasound examination of the airway.

A point-of-care ultrasound (POCUS) is a simple, non-invasive, and portable tool that enables dynamic airway assessment. Several studies have attempted to determine the role of ultrasound parameters as an adjunct to clinical examination in predicting difficult laryngoscopies.

Airway management remains a crucial part of perioperative care. The conventional approach to assessing potentially difficult airways emphasizes the LEMON ...

Reduction of Radiation Exposure during Endovascular Treatment of Peripheral Arterial Disease Combining Fiber Optic RealShape Technology and Intravascular Ultrasound

Vascular surgeons and interventional radiologists face chronic exposure to low-dose radiation during endovascular procedures, which may impact their health in the long term due to their stochastic effects. The presented case shows the feasibility and efficacy of combining Fiber Optic RealShape (FORS) technology and intravascular ultrasound (IVUS) to reduce operator exposure during the endovascular treatment of obstructive peripheral arterial disease (PAD). 
FORS technology enables real-time, three-dimensional visualization of the full shape of guidewires and catheters, embedded with optical fibers that use laser light instead of fluoroscopy. Hereby, radiation exposure is reduced, and spatial perception is improved while navigating during endovascular procedures. IVUS has the capacity to optimally define vessel dimensions. Combining FORS and IVUS in a patient with iliac in-stent restenosis, as shown in this case report, enables passage of the stenosis and pre- and post-percutaneous transluminal angioplasty (PTA) plaque assessment (diameter improvement and morphology), with a minimum dose of radiation and zero contrast agent. The aim of this article is to describe the method of combining FORS and IVUS stepwise, to show the potential of merging both techniques in view of reducing radiation exposure and improving navigation tasks and treatment success during the endovascular procedure for the treatment of PAD.

Described here is a stepwise method of combining Fiber Optic RealShape technology and intravascular ultrasound to show the potential of merging both techniques, in view of the reduction of radiation exposure and improvement of navigation tasks and treatment success during an endovascular procedure for the treatment of peripheral arterial disease.

Vascular surgeons and interventional radiologists face chronic exposure to low-dose radiation during endovascular procedures, which may impact their ...

Doppler Ultrasound Scan and Blood Flow Quantitation in Leg-Extension Exercises

Assessing Leg Blood Flow in Training Workloads

Doppler Ultrasound-Based Leg Blood Flow Assessment During Single-Leg Knee-Extensor Exercise in an Uncontrolled Setting

Doppler ultrasound has revolutionized the assessment of organ blood flow and is widely used in research and clinical settings. While Doppler ultrasound-based assessment of contracting leg muscle blood flow is common in human studies, the reliability of this method requires further investigation. Therefore, this study aimed to investigate the within-day test-retest, between-day test-retest, and inter-rater reliability of Doppler ultrasound for assessing leg blood flow during rest and graded single-leg knee-extensions (0 W, 6 W, 12 W, and 18 W), with the ultrasound probe being removed between measurements. The study included thirty healthy subjects (age: 33 &#177; 9.3, male/female: 14/16) who visited the laboratory on two different experimental days separated by 10 days. The study did not control for major confounders such as nutritional state, time of day, or hormonal status. Across different exercise intensities, the results demonstrated high within-day reliability with a coefficient of variation (CV) ranging from 4.0% to 4.3%, acceptable between-day reliability with a CV ranging from 10.1% to 20.2%, and inter-rater reliability with a CV ranging from 17.9% to 26.8%. Therefore, in a real-life clinical scenario where controlling various environmental factors is challenging, Doppler ultrasound can be used to determine leg blood flow during submaximal single-leg knee-extensor exercise with high within-day reliability and acceptable between-day reliability when performed by the same sonographer.

Author Spotlight: Assessing the Reliability of Doppler Ultrasound in Measuring Leg Blood Flow 

This test-retest study evaluated leg blood flow measured by the Doppler ultrasound technique during single-leg knee-extensor exercise. The within-day, between-day, and inter-rater reliability of the method was investigated. The approach demonstrated high within-day and acceptable between-day reliability. However, the inter-rater reliability was unacceptably low during rest and at low workloads.