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32
Chapter 1 · Fundamental Principles
gain will lead to color overow and may obscure atheroscle-
1
rotic lesions in arteries or thrombus in a partially occluded vein (. Fig. 1.40b). is phenomenon contributes to the unreliability of planimetric stenosis grading, which is based on the cross- sectional vessel area depicted in color duplex scans.
1.1.4.6 Doppler Angle
e evaluation of an artery or vein in the B-mode image com­bined with the spectral Doppler information obtained with a dened ultrasound beam and known angle of insonation enables reliable calculation of blood ow velocity from the Doppler shi. To ensure reliable Doppler angle correction for accurate measurement, a long stretch of the vessel of
interest should be displayed in
the longitudinal plane (parallel vessel walls along the width of the monitor). e smaller the angle between the Doppler beam and the direc­tion of the owing blood, the higher the Doppler frequency shi of the reected echo and the higher the sensitivity for ow detection. At angles of 60–90°, the Doppler frequency shi decreases and ow velocity measurement becomes pro­gressively more unreliable, and no ow signals are depicted when the Doppler beam is perpendicular to the vessel wall (
. Fig.1.40c–e). Conversely, perpendicular insonation of a
reecting surface provides optimal B-mode information
With a linear-array transducer, the examiner can use beam steering (lateral beam deection) for electronically changing the direction of the beam to achieve a good Doppler angle relative to the direction of blood ow. Technically, the beam can only be steered either right or le by a maximum of 20°, resulting in a Doppler angle of 70°. erefore, beam steering can improve the angle, but does not achieve the best Doppler angle of <60° (for minimizing measurement errors) when interrogating a vessel segment running parallel to the skin surface (. Fig.1.40e).
In the clinical setting, the examiner must nd a compro-
mise between optimal B-mode imaging and optimal ow evaluation
. e usual procedure is to rst try and achieve a perpendicular beam angle for morphologic evaluation of the vessel wall and to then optimize the angle for spectral Doppler interrogation using either electronic beam steering or manual manipulation of the transducer (curved-array or sector probe). Another measure is to place the Doppler gate at the edge of the scan eld.
In the color ow image of a vessel coursing parallel to the skin surface (e.g., carotid or femoral artery) examined with a curved-array transducer held perpendicular to the body surface, the colors representing the blood ow information may change in brightness (luminosity) without this reect­ing dierent ow velocities. Under these conditions, ow near the margin of the image is displayed in brighter colors due to higher Doppler shis and in increasingly darker col­ors toward the center, where the frequency shi decreases as the insonation angle increases (and no color as the angle approaches 90°). is phenomenon is relevant only in the velocity mode and not in the power mode, as the latter is vir­tually independent of the Doppler angle.
1.1.4.7 Physical Limitations ofColor
Duplex Ultrasound
As a result of the vast amount of information to be processed, color duplex scanning has a much poorer spatial and tempo­ral resolution than pure B-mode imaging. Axial resolution is proportional to the wavelength in B-mode imaging, while it is dependent on the number of sample volumes placed along the color Doppler scan line in the color duplex mode. e use of smaller sample volumes improves axial resolution but at the expense of sensitivity and accuracy in Doppler shi evaluation as the signal-to-noise ratio deteriorates. Lateral resolution in color duplex imaging is determined by the number of color Doppler lines processed per centime­ter. e frame rate decreases as the number of Doppler lines increases, compromising temporal resolution, in particular at greater scan depths.
As a result of these limitations, the axial resolution of color duplex ultrasound is on the order of 0.4–1.0mm with a lateral resolution of only 1.0–2.0mm, which is four to ten times lower than the B-mode scan resolution (Widder 1999).
In duplex ultrasound, it takes roughly 50–200ms to cre­ate one color image, depending on the depth of the target vessel and size of the color box. is corresponds to a frame
rate
or sampling rate of 5Hz. When a low PRF is selected,
.
the speed at which the color Doppler lines sweep the sector is similar to or slightly below the mean ow velocity in arter­ies. erefore, a single color ow frame may simultaneously depict systolic ow and early diastolic ow (e.g., displayed in red and blue, respectively, see . Fig.1.37). Due to the low temporal resolution, however, the color coding does not fully reect the pulsatile character of ow.
Slow ow produces smaller Doppler frequency shis, which have to be extracted from short echo pulse packets for each scan line consisting of a number of individual pulses. e scan lines must be processed successively.
ough the insonation angle should ideally be as small as possible for optimal velocity measurement, this is not always practical because there will be a longer delay when the color
box is tilted
compromise, in particular when examining vessels deeper in the body. Tilting the color box by 20° and 30° prolongs the round trip time by 13% and 31%, respectively.
Color duplex imaging, like all diagnostic ultrasound techniques, is impaired by
ing
caused by bowel gas or calcied structures (bone or cal­cied plaques in the lumen). e examiner can circumvent such interfering structures by moving the transducer, but this oen increases the distance between the transducer and the target anatomy, and hence the round trip time.
A strong reector in the beam path can act like a mir­ror and generate a phantom image in another area of the scan. Such mirror images can be identied by angling the transducer, which will make the mirror artifacts disappear or appear in a dierent location. When the ultrasound beam strikes interfaces of high acoustic impedance at a right angle, reverberations (repeat echoes) may occur with the ultra­sound pulses being reected to and fro, resulting in a kind
(beam steering). is is why one must nd a
scattering and acoustic shadow-
1.1 · Technical Principles ofDiagnostic Ultrasound
33
1
of ping-pong eect. Slight angulation of the transducer pre­vents reverberations but will also reduce reection from the interface and thus degrade image quality.

1.1.5 Ultrasound Contrast Agents

Color duplex imaging with a high-resolution transducer usu­ally allows adequate visualization of the peripheral arteries in the gray-scale mode; the evaluation of blood ow, however, may be impaired, either by the presence of sclerotic vascular lesions or by scattering due to edema or other localized so tissue changes. In these situations, a microbubble contrast agent, or echo enhancer, can be used to improve blood ow imaging. For vascular ultrasound examinations in the clinical setting, however, a contrast agent is rarely needed as there are only a few situations (e.g., identication of a suitable recipi­ent vessel for crural bypass graing) in which color duplex and spectral Doppler imaging are degraded by poor imaging conditions and do not provide the information required for treatment planning.
Ultrasound contrast agents are gas-lled microbubbles and enhance the contrast between blood and surrounding tissue by
partment
administration. Microbubbles can thus enable or improve the identication and evaluation of vessels with slow or low blood ow, which may be dicult to identify with conven­tional ultrasound techniques. While this is an advantage for vascular applications, ultrasound contrast agents are mainly used to evaluate organ and lesion perfusion, to characterize focal liver lesions for example. Contrast-enhanced ultra­sound (CEUS) plays virtually no role in the routine clinical examination of patients with angiologic or vascular surgical conditions. Notable exceptions are CEUS examinations of small peripheral vessels and below-the-knee arteries with slow, postocclusive ow, transcranial duplex scanning, the search for endoleaks aer stenting of the aorta, demonstra­tion of intraplaque neovascularization in the assessment of plaque vulnerability, and evaluation of inammatory activity in patients with vasculitis. With the use of contrast agents, ultrasound to some extent gives up the crucial advantages it normally has over other imaging modalities– low cost, short examination time, and noninvasiveness. Moreover, in those body regions where diagnostic improvement is achieved through the administration of an echo enhancer, competing imaging modalities are used because they provide high accu­racy and oen enable better documentation of the ndings.
and properties are commercially available from various man­ufacturers. Basically, the contrast agents consist of micro­bubbles composed of a gas core encapsulated by a thin shell or stabilized by a carrier medium.
the
producing strong reections in the vascular com-
during their lifetime of 3–5min aer intravenous
Ultrasound contrast agents with dierent compositions
ese two factors– the shell and the gas core– determine
stability of ultrasound microbubbles:
5 e microbubble gas core is stabilized by a shell
that contains surface stabilizers (palmitic acid,
phospholipids) or substances that form a capsule on the molecular level (albumins, polymers).
5 e stability of the core can be improved by using a
heavier gas instead of air (sulfur hexauoride, peruo­ropropane). Such gases have lower diusivity, higher physical density, and a lower saturation constant, reduc­ing the solubility of the microbubbles.
e more stable microbubbles used in newer ultrasound contrast agent preparations have certain advantages, such as a longer blood half-life due to lower spontaneous solubility. Bubbles containing a high-molecular-weight gas can pass the pulmonary circulation because they are more resistant to destruction when exposed to changing pressures.
1.1.5.1 Approved Ultrasound Contrast
Agents andUses
While a variety of microbubble contrast agents diering in core and shell composition were investigated around the turn of the century, only a few microbubble preparations were ultimately approved for clinical use.
Levovist was the rst ultrasound contrast agent approved
in Europe but has since been taken o the European market. e preparation consists of a suspension of galactose-based air bubbles coated with a stabilizing palmitic acid layer.
SonoVue is approved in Europe as an echo enhancer for
vascular applications. e microbubbles have a mean diam­eter of 5–10μm, contain sulfur hexauoride, and are stabi­lized by phospholipids. Being eliminated from the body by exhalation, SonoVue is not nephrotoxic.
e microbubbles are injected as a single bolus of
1–2.4mL (at a rate of 1mL/s) or as a smaller bolus of 0.5–
1.0mL followed by continuous infusion of 1mL/min over a few minutes. Aer bolus injection, enhancement of the arterial lumen begins aer 10–30s and peaks aer 30–60s, followed by a gradual decrease in intensity over 3–8 min (imaging window). e imaging window can be extended by infusion of the microbubble preparation. Depending on the infusion rate, a 15–20dB increase in intensity is observed aer 1min. Excessive enhancement with appearance of ow signals outside the vascular space (color blooming) imme­diately aer bolus administration can be counteracted by adjusting transmit gain. e slow linear decrease in intensity following the initial peak aer bolus injection ensures ade­quate enhancement for several minutes, which is long enough for most vascular applications. Dynamic contrast-enhanced ultrasound (CEUS) with generation of time-intensive curves (TIC) allows estimation of blood volume and regional blood ow in the target vasculature or a vascular segment of inter­est (Dietrich etal. 2012).
e intravascular half-life of the microbubbles primarily depends on their inherent stability and the acoustic energy applied, which in turn is determined by the ultrasound sys­tem’s output and attenuation of the ultrasound beam while passing through the tissue.
Clinical CEUS examinations can be performed using conventional ultrasound techniques; however, the acoustic
1
Transmitted
Received
Second harmonic
0
1
2
34
Chapter 1 · Fundamental Principles
energy will rapidly destroy the microbubbles. e life span of the bubbles is longer when contrast-specic ultrasound modes such as low-mechanical (MI) index imaging are employed. is means that the examination is performed with a lower output power or decreased MI.With this tech­nique, dynamic real-time imaging can be performed over several minutes aer administration of the microbubbles. For most indications in vascular ultrasound, it is usually suf­cient to inject an echo enhancer bolus of 1.2–2.4mL, fol­lowed by a 10-mL saline ush (0.9%).
Ultrasound microbubbles do not diuse from the blood into surrounding tissues. ey do not leave the vascular sys­tem unless blood escapes through a hole in the vessel wall (e.g., an endoleak). Hence, they have no nephrotoxic eects and a low overall rate of adverse events. Life-threatening ana­phylactic reactions have been reported to occur in less than
0.002% of cases.
ere are several contraindications to the use of SonoVue as an echo enhancer:
5 Severe pulmonary hypertension, uncontrolled arterial
hypertension, acute lung failure
5 Acute coronary syndrome, severe cardiac insuciency,
malignant arrhythmia
5 Acute respiratory distress syndrome, e.g., bronchial
asthma
5 Pregnancy and breastfeeding (safety remains to be
proven during pregnancy and lactation)
5 Patient age below 18 5 Known intolerance of sulfur hexauoride
e preparation of a patient for an ultrasound examination with use of an echo enhancer includes obtaining written informed consent and placing a venous line.
1.1.5.2 Mechanisms ofAction
Ultrasound contrast agents act by increasing the propor­tion of scattered and reected ultrasound pulses from the blood, thereby improving both the Doppler signal and the signal-to- noise ratio (SNR). How strongly the microbubbles enhance reection depends on their diameter (factor of 6), the transmit frequency used (factor of 4), and their com­pressibility. Most microbubbles used as echoenhancers con­tain gas and enhance backscatter because of the
mismatch between their gas cores and the liquid compo­nent of blood
. e intensity of backscatter is determined by
acoustic
the microbubble concentration in the blood and the reec­tion capacity of the individual bubbles, which is a function of their scatter cross-section. However, the maximum bubble size is limited by the fact that they must pass the lungs (bubble size <8μm). It has been shown that backscatter enhances the echo signal intensity of blood by 15–25dB (Kaps and Seidel
1999). Low ultrasound beam power induces linear oscil­lation of the microbubbles, transforming the bubbles into small “ultrasound transmitters.” is is another mechanism by which microbubbles enhance the ultrasound signal. e resonance frequency is inversely proportional to the bubble diameter.
ultrasound pulse
Power
f
. Fig. 1.41 The Doppler-shifted signal returning to the transducer
contains both the fundamental and harmonics, which can be extracted by comparison with the emitted pulse
nonliner
ultrasound signal
f
f
f
3
At higher power, the microbubbles oscillate in a nonlinear fashion, producing strong signals at fundamental and non­fundamental frequencies. e nonfundamental or
frequencies
are multiples of the transmitted frequency. e
harmonic
second harmonic has the highest energy and is therefore most relevant for diagnostic ultrasound (. Fig.1.41). Because the resonance frequencies of the 2–7-μm gas bubbles are within the range of the transmitted frequencies of 2.5–10 MHz typically used in diagnostic ultrasound, the bubble vibrations produce an additional signal amplication. e correspond­ing frequencies are received and processed along with the Doppler-shied frequencies. is resonance behavior of the
microbubbles
improves the SNR by a further 30–35dB, pro­vided that the bandwidth of the ultrasound system extends over a sucient range of frequencies to enable the generated harmonics to be detected (Correas etal. 1997).
Short pulses of high energy can be applied to make the microbubbles burst, producing ultrasound signals that are detected with high sensitivity. In contrast to the enhancing mechanisms outlined in the preceding sections, bursting is independent of blood ow and the resulting signals merely show the distribution of the collapsed microbubbles at the time of imaging.
Both SonoVue and Levovist are taken up and eliminated by the reticuloendothelial system of the liver. In the liver, the microbubbles can be made to burst by exposing them to a high-energy beam. In this way, they can contribute to the sonoscintigraphic identication of liver metastases, which do not have a reticuloendothelial system. Alternatively, focal liver lesions may be dierentiated on the basis of their blood supply (predominantly portal venous versus arterial) and dierences in contrast agent arrival times aer bolus injec­tion. Because of their selective uptake, the microbubbles also have the potential to be used as vehicles for the targeted local
1.1 · Technical Principles ofDiagnostic Ultrasound
delivery of chemotherapy. Other echo enhancer preparations consist of suspensions (some of which contain human albu­min) and bubbles stabilized for specic needs.
1.1.5.3 Ultrasound Techniques Using
Contrast Agents
1.1.5.3.1 Contrast-Enhanced Duplex Ultrasound
e reection of ultrasound by microbubbles present in the blood selectively enhances the vascular system, thus improving the delineation of arteries and veins from sur­rounding tissue (in color duplex and power Doppler). Blood ow velocity is not aected by the microbubbles, and therefore spectral Doppler analysis can be performed for quantication of blood ow velocity (CW/PW Doppler) in the same way as without contrast medium but with lower gain. When a frequency-based Dopppler technique is used, however, the eect of contrast enhancement can only be exploited in large and medium-sized vessels as the signals returning from slow microcirculatory ow in small vessels cannot be adequately separated from the echoes produced by moving tissue.
Microbubble contrast agents have been used to evaluate slow ow in peripheral vessels, including postocclusive ow, and carotid artery stenosis, and studies have shown that echo enhancers improve the accuracy of color duplex ultrasound in identifying pseudo-occlusion (Fürst et al. 1999; Ferrer et al. 2000). In the vertebral territory, ultrasound contrast agents can improve evaluation in patients with poor scan­ning conditions or with a hypoplastic vertebral artery.
Echo enhancers have also been advocated to improve the SNR in the examination of deep vessels such as the pelvic or renal arteries. Using state-of-the-art ultrasound equip­ment, however, these vascular areas rarely pose diagnostic problems. A study of duplex ultrasound with echo enhancer administration in renal artery stenosis found an increase in diagnostic yield from 64% to 84%, while the improvement in the sensitivity and specicity for identifying high-grade stenosis was negligible (Claudon etal. 2000).
1.1.5.3.2 Contrast Harmonic Imaging
is ultrasound technique can improve vascular imaging by selectively displaying the harmonics specic to microbubbles. A broadband transducer is used to detect the harmonics gen­erated by the contrast microbubbles, especially the second harmonic. e backscatter from microbubbles allows better separation of the echoes from stationary tissues, thus oering advantages in the sonographic evaluation of slow ow.
1.1.5.3.3 Stimulated Acoustic Emission Imaging
Contrast agent microbubbles are destroyed when exposed to high ultrasound energy (high mechanical index) (. Fig.1.42). e bursting bubbles emit transient ultrasound signals, which can be detected with a broadband transducer. e system registers the variation in signals from pulse to pulse. is information is displayed along with the spatial information of the B-mode image to show the contrast agent
35
. Fig. 1.42 Ultrasound techniques using contrast agents. The
amount of ultrasound energy applied determines how the micro­bubbles interact with the ultrasound beam, giving rise to dierent techniques of image generation. Exposure of microbubbles to low energy (I) causes an increase in reection and backscatter. Intermedi­ate ultrasound energy levels (II) induce nonlinear oscillation of the microbubbles, resulting in the emission of second harmonics, which selectively enhance the blood signal (contrast harmonic imaging). High ultrasound energy (III) destroys the microbubbles, releasing fre­quencies that provide information on the distribution of the contrast bubbles in the circulation (stimulated acoustic emission)
distribution in the macro- and microcirculation at a given point in time.
1.1.5.4 Summary ofTechnical Aspects
andClinical Indications
In color duplex ultrasound, the administration of echo enhancers can lead to excessive enhancement of the color Doppler signal with color overow obscuring perivascular structures and parts of the vessel wall, in particular when larger vessels are examined. is eect can be remedied by lowering the receive gain. On the other hand, the strong reection produced by the contrast bubbles can attenu­ate structures farther away from the transducer than the enhanced vessel.
A Doppler waveform obtained aer echo enhancer administration will show spectral broadening with almost complete lling-in of the systolic window. Again, the eect can be counteracted by lowering the receive gain.
Basically, all sonographic techniques exploiting the dif­ferent eects of ultrasound contrast agents in the vascular compartment aim at improving sensitivity to blood ow phenomena. However, with the sophisticated ultrasound technology available today, most vascular applications do not require use of a contrast agent. Moreover, in those rare cases where an adequate diagnostic evaluation with color duplex imaging is not possible, the use of a microbubble contrast agent is oen limited as well and oers no benets. Despite these cautionary remarks, there are a few situations in which contrast microbubbles improve diagnostic yield. e most important indications for vascular CEUS are:
1
36
Chapter 1 · Fundamental Principles
5 Transcranial duplex imaging
1
5 Evaluation for renovascular disease 5 Vein mapping for identication of a suitable recipient
segment before crural bypass gra surgery
5 Search for endoleaks in patients with an aortic stent.
the vibrating bubbles. is phenomenon is known as microstreaming and can generate very high pressures with disruption of cell membranes. In the other form of cavita-
inertial cavitation, existing bubbles or cavitation nuclei
tion, expand during the low-pressure phase and then collapse
violently. Microbubble collapse is a highly localized process It is expected, however, that ultrasound contrast agents will be used increasingly in the evaluation of microcirculation, e.g., for identifying plaque neovascularization (Seidel etal. 2006; Claudon etal. 2008).
occurring on the order of microseconds. Collapsing bubbles
can produce extremely high temperatures and pressures but
these dissipate rapidly. Bursting bubbles therefore have the
potential to destroy cells and tissues. ere is scientic evi-
dence to suggest that inertial cavitation is a threshold phe-
nomenon and will only occur if microbubbles already present
1.1.6 Safety ofDiagnostic Ultrasound
in the acoustic eld are exposed to excessive acoustic pressures
and frequencies. Pressure below the cavitation threshold will Ever since the early 1960s, when this technique was rst used for diagnostic imaging, the potential biological hazards of medical ultrasound have been discussed. Ultrasound trav­eling through the human body can have two eects known to cause changes in biological systems. Firstly there are the thermal eects resulting from the conversion of ultrasound energy into heat and secondly there are the mechanical eects arising from pressure changes associated with the propagation of sound waves in a medium.
never by itself lead to cavitation, not even during extremely
long exposure to ultrasound. Inertial cavitation induced by
diagnostic ultrasound procedures therefore remains a mere
theoretical possibility and has never been reported invivo.
However, one must also be aware that invivo evidence of potential bioeects of ultrasound is very dicult, if not impossible, to obtain: cavitation can occur anywhere in the body, and the damage it produces may be very local, involv­ing only a few cells. Modern ultrasound equipment incor­porates safety mechanisms allowing the user to limit the
1.1.6.1 Thermal Eects
Exposure to diagnostic ultrasound can increase tissue tem­perature because sound energy is absorbed and converted
average acoustic output, thus avoiding peak pressures that could theoretically lead to cavitation or other mechanical bioeects.
to heat. e ability to absorb energy varies with the tissue; it is low in body uids (amniotic uid, blood, urine) and high in bones. Adult bones absorb 60–80% of the incident
1.1.6.3 Specic Risks ofIndividual Ultrasound
Techniques
ultrasound energy. In addition, absorption in the body is also aected by technical parameters, most notably the output frequency of the transducer. Higher frequencies are absorbed more rapidly. A temperature increase of 2.5°C can severely damage biological tissues, while an increase of 1°C is gen­erally considered harmless. Experimental evidence suggests that the thermal eects of diagnostic ultrasound procedures pose no health hazard.
1.1.6.3.1 B-Mode
B-mode imaging is generally performed at very low acoustic output, resulting in intensities below 10mW/cm2. e indi­vidual pulses are very short (<1ms) and are emitted at a PRF of less than 5kHz to achieve high resolution. As the energy transmitted into the body is dissipated over a large volume, the resulting rise in tissue temperature is so small that it remains below the limit of detection. Diagnostic B-mode
1.1.6.2 Mechanical Eects
Most of the mechanical eects of ultrasound that are poten-
ultrasound is considered absolutely safe in terms of potential hazards to patients.
tially harmful to living tissues are related to the formation, growth, and possible collapse of tiny gas bubbles in the ultrasound eld, a process known as cavitation. Recall that ultrasound propagates through tissue in waves of alternating high and low pressure. Bubble formation or the expansion of existing bubbles occurs when the negative pressure is large enough. e occurrence of cavitation and its eects depend on the frequency and intensity of the transmitted ultrasound
1.1.6.3.2 M-Mode
is technique uses higher energies and may theoretically cause tissue heating. In this mode, a stationary beam is emitted repeatedly to evaluate moving structures. e scan volume is smaller than in B-mode imaging, but the PRF is much lower (only approx. 1kHz). M-mode sonography is also considered safe.
waves as well as on the focus of the acoustic eld. Two types of cavitation are commonly described: stable and inertial (or transient).
Stable cavitation refers to the continuous oscillation of
gas-lled bodies in response to the alternating positive and negative pressures to which they are exposed in an ultra­sound eld. Such cyclic expansions and contractions result in an increased ow in the uid-like medium surrounding
1.1.6.3.3 CW Doppler
As with M-mode techniques, the scan volume is small and there is continuous exposure. e power output can reach up to 100mW, and some procedures have the potential to produce biologically signicant temperature rises. Possible mechanical eects are much less of a concern than in B-mode or M-mode scanning, despite the higher acoustic output. e
PP
()
()
12
r
××
×
h
p
1.2 · Hemodynamic Principles
37
1
transmit power depends on the depth of the target anatomy. It is the operator’s responsibility to keep the overall examina­tion time as short as is consistent with achieving diagnosti­cally useful results.
1.1.6.3.4 PW Doppler
Again, the exposed volume is relatively small and the PRF is high. e individual pulses are oen twice as long as with B-mode or M-mode techniques. Taken together, the machine settings used in PW Doppler applications can result in considerable exposure, and the risk of tissue heating is far greater. Conversely, mechanical eects are negligible because the intensity of the emitted pulses is the same as in B-mode and M-mode imaging.
1.1.6.3.5 Color Doppler
e acoustic output in color Doppler imaging is intermediate between that of B-mode and PW Doppler. Mechanical eects are negligible. e emitted ultrasound pulses are distributed over a relatively large tissue volume. Temperature rises are higher than with B-mode imaging but lower than with PW Doppler techniques.
1.1.6.4 Conclusion
Current uses of diagnostic ultrasound expose the body to intensities that do not exceed 100mW/cm2. ere is no evi­dence that these intensities damage living tissues.
Nevertheless, the examiner should always seek to mini­mize exposure by limiting both the power output and the duration of scanning to what is absolutely necessary to obtain the desired diagnostic information. is approach is known as the ALARA principle (as low as reasonably achievable) and applies to all diagnostic imaging modalities. Doppler ultrasound, which uses higher intensities, should not be employed during the rst three months of pregnancy.

1.2 Hemodynamic Principles

1.2.1 Laminar Flow

Although blood ow is subject to specic conditions due to the solid components in plasma and the elasticity of the ves­sel wall, it basically follows the laws of ow dynamics. ese laws govern the ow of a uid in tubes and apply to watery or oily solutions of a constant viscosity (Newtonian uid) and assume that ow velocity under these conditions is primar­ily a function of the pressure dierence that exists between the two ends of the tube. ese ideal conditions for continu­ous laminar ow are typically not met in a living organism because various factors such as elasticity of the vessel wall, pulsatility resulting from cardiac activity, curving of vessels, and branching aect blood ow, resulting in changing veloc­ity distributions in the moving layers of the blood.
Moreover, blood is not a watery or oily solution of con­stant viscosity but a suspension of solid blood cells in plasma. Blood viscosity is primarily dependent on the hematocrit level
and is only constant when hematocrit is below 10, increasing exponentially at higher levels. Other factors aecting blood viscosity are plasma viscosity and vessel diameter. In the terminal capillary bed, viscosity is additionally inuenced by the deformation of red blood cells. Despite these specic features of blood ow, some basic hemodynamic terms and laws are useful and will make it easier to understand nor­mal and abnormal ow in arteries and veins. In addition, invitro experiments and invivo blood ow measurements using duplex scanning have provided new insights into the ow behavior in specic vessels under normal and abnormal conditions as well as under the inuence of pharmacologic agents.
Laminar ow is characterized by a constant velocity over
time. Flow in a tube is brought about by a pressure dier­ence between the two ends of the tube. e pressure dier­ence (P
– P2) is proportional to the volume ow rate. e
1
volume ow rate (I) is proportional to the tube diameter (r) and inversely proportional to its length (l) and the viscosity of the uid (η). Mathematically, this relationship is expressed in the
Hagen–Poiseuille law:
4
-
12
××
8ph
l
××
-
=
R
PP r
I
=
By analogy with Ohm’s law, ow resistance can be calculated from the Hagen–Poiseuille equation:
8
l
R
=
4
It follows that resistance is proportional to the length of the tube (l) and the viscosity of the liquid (η). Overall resistance is most strongly aected by the radius (r) of the tube, which appears in the equation raised to the fourth power. is means that decreasing the vessel radius by one half, for exam­ple, increases ow resistance by a factor of 16. Peripheral resistance in the vascular system is regulated according to demand, primarily by the tone of the arterioles, and aects the pulsatility of blood ow in the large arteries supplying these territories. erefore, it is also reected in spectral Doppler tracings from these arteries.
e ow prole of continuous ow is determined by
inertial and frictional forces. Friction produces a laminar
or, in the 3D model, parabolic ow prole. Flow is fastest in the center of a vessel and decreases toward the wall, where it approximates zero.
In color duplex images, this decrease in blood ow velocity from midstream to the vessel wall is indicated by brighter colors in the center and darker colors near the wall (. Fig.1.43a). e following factors determine the shape of the ow prole of blood:
5 Velocity 5 Viscosity (internal friction) 5 Adhesion of the blood to the vessel wall (external friction) 5 Cohesion (forces that occur between adjacent molecules
of like composition).
38
Chapter 1 · Fundamental Principles
1
. Fig. 1.43 a Typical triphasic Doppler waveform of the popliteal artery. In the color ow image, laminar ow is characterized by brighter color-
ing in the center with darker colors representing slow ow near the wall. Red indicates blood ow toward the transducer. A vein closer to the transducer is displayed in blue, indicating blood ow away from the transducer. The triphasic waveform consists of a steep upslope (A) to peak systolic velocity (PSV) (B), a deceleration phase (C), a short phase of early diastolic backward ow (D), and forward ow from the middle to the end of diastole (E). The magnitude and duration of diastolic forward ow (E) depend on peripheral resistance (sympathetic tone) and the thrust gener­ated by the compliant aorta (windkessel eect). Blood ow toward the transducer is displayed above the baseline, and ow away from it below the line. The Doppler angle of insonation is 59°, and PSV is 85cm/s. The dierent intensities of the individual pixels in the Doppler waveform reect the number of red blood cells moving at a given velocity. The amplitude can also be represented in the form of a histogram. b Use of a low pulse repetition frequency (PRF) to ensure good color lling of arteries with slow ow below the knee. In the rst color image (left), the anterior tibial artery (blue, ow toward the periphery, away from the transducer) is depicted with central aliasing (color change from blue to yellow to red). This example illustrates a laminar ow prole with fast ow in the center of the artery and lower ow velocities near the wall due to friction. The second color image depicts early diastolic blood ow at the same site, which is due to the fast image generation. In the center, arterial reux due to high peripheral resistance is seen as a superimposed wave (red, toward transducer) while ow toward the periphery predominates nearer the walls (blue, away from transducer). The view illustrates true ow reversal relative to the ultrasound beam rather than aliasing. True ow reversal is characterized by a color change from blue to black to red. The third color ow image depicts blood ow (blue, away from transducer) toward the periphery without aliasing in mid-diastole. While each of the three color ow images depicts peripheral arterial blood ow at a specic time dur­ing the cardiac cycle, the corresponding Doppler waveform (right) displays the ow changes over time
Blood diers from Newtonian uid in that its viscosity is not an inherent property that only varies with tempera­ture but is mainly determined by the hematocrit level and other factors such as plasma viscosity (which in turn is pre­dominantly dependent on the brinogen concentration), red blood cell deformability, and the degree of shearing. In an artery or vein with laminar ow, shear stress, like thrust, is weakest in the center and strongest near the wall (. Fig.1.43b).
According to the continuity law, a decrease in the cross-
sectional area
in the course of a vessel segment leads to an
increase in mean ow velocity. Blood ow through a vessel
segment with an abrupt change in caliber becomes attened (plug ow) upon entering the narrower vessel segment. In plug ow, inertial forces are stronger than frictional forces, resulting in the same ow velocity of all uid layers in the vessel except for a thin layer near the wall. So-called turbu­lent ow results when the inertial forces become even stron­ger than the frictional forces, which bring order to the course of ow. Turbulent ow is characterized by an irregular ow pattern with ow in dierent directions. e typical para­bolic ow pattern develops aer a certain stretch along which
=+
1.2 · Hemodynamic Principles
A
Continuity equation
1
A
2
39
V
2
=
V
1
A = Vascular cross-sectional area
V = Mean flow velocity
Stenosis
Marginal zone of turbulent flow
1
v
1
a
Outer wall
Lateral angle α
b
A
1
Separation
v
2
point
A
2
Inner wall
Flow divider
Separation
zone
v
3
Reattachment
point
A
3
c
PressureFlow velocity
Turbulent flow
Distance
Distance
Artery
Additional loss due to turbulent flow
Additional loss due to turbulent flow
. Fig. 1.44 a When a uid such as blood enters a narrower lumen, parabolic ow changes into plug ow and returns to its original prole only
after having traveled some distance under the inuence of shear stress. According to the continuity equation, ow velocity increases in propor­tion to the decrease in diameter. b Flow in a vessel branching. Thrust and shearing are highest at the inner wall of the branching. Separation occurs at the outer wall, where thrust is rather low. Physiologic ow separation occurs in the carotid bulb (see . Fig. 5.49 (Atlas)). c Diagram of ow in a vessel segment with higher-grade stenosis and corresponding curves (solid blue lines) representing the eects of the stenosis on pres­sure (top) and ow velocity (bottom) in the stenotic and poststenotic segment. The law of conservation of energy predicts that static energy (blood pressure) is converted to kinetic energy (ow velocity) (Bernoulli equation). It thus follows that the intrastenotic increase in ow velocity results in a proportional drop in pressure (neglecting other factors such as blood viscosity and systolic-diastolic ow variation). The actual pres­sure and ow velocity measured in a poststenotic vessel segment (dotted lines) are lower than theoretically predicted because the equation does not consider losses resulting from turbulence and friction
frictional forces predominate. Physiologically, this occurs when blood leaves the le ventricle and enters the ascend­ing aorta. e sharp velocity gradient between ow in the center and the thin boundary layer near the wall in plug ow is associated with strong shear stress.
e law of conservation of energy states that the total
amount of energy
in a closed system remains constant. Applied to blood ow, this means that the total energy in a stenotic vessel is the same before and aer the stenosis (unless there is loss of energy from the system) and that there is an inversely proportional relationship between static and dynamic components (. Fig.1.44):
It follows from this law that increasing ow velocity within a stenosis (E intravascular pressure (E
) is associated with decreasing tangential
kinetic
). e reverse applies to the
static
poststenotic segment: increasing pressure results in turbu­lent ow with slow ow components near the wall and can promote intramural hematoma formation.
An abrupt decrease in the cross-sectional area in a ste­notic vessel segment and the resulting increase in ow veloc­ity are associated with progressive disturbance of laminar ow, which will nally become turbulent. Turbulent ow above a critical velocity is characterized on color duplex ultrasound by a mosaic of colors reecting the dierent ow directions. e transition from laminar to turbulent ow
EEE
totalstatic kinetic
can be calculated by means of the dimensionless Reynolds
40
××
Chapter 1 · Fundamental Principles
number, which depends on mean ow velocity (v), vessel
1
diameter (d), density of the uid (p), and viscosity (η):
vd p
Re =
h
to changes in pressure. e pressure amplitude generated by le ventricular activity is smoothed out by the
of the aorta and other large elastic, or conducting, arteries
compliance
(windkessel eect), resulting in a more steady ow. Another factor aecting the ow prole is the peripheral resistance.
Flow is highly pulsatile in the extremity arteries because Data from invitro model experiments show blood ow to be fairly laminar for Reynolds numbers up to 2000 and to become increasingly turbulent as the number exceeds 2000.
Turbulent blood ow is characterized by a pattern of ran-
dom ow directions, seen in color ow images as color shis (indicating retrograde ow components) or a mosaic of col­ors.
In turbulent ow, part of the kinetic energy is converted into acoustic energy, producing a characteristic bruit, which can be detected by auscultation.
In vessels with pulsatile ow, which normally is lami­nar, turbulent ow may occur at specic phases of the car­diac cycle under physiologic conditions. is phenomenon depends on the ow prole (high pulsatility) and pulse rate.
A sudden increase in the vessel diameter results in a longer ow prole and greater velocity gradient across the
peripheral resistance is high at rest, giving rise to the char­acteristic triphasic Doppler waveform. An increase in the peripheral blood demand leads to dilatation of the arterioles, and the resulting decrease in peripheral resistance changes the Doppler waveform. Peripheral resistance may decrease under normal (muscle activity) or abnormal conditions (local inammation, postocclusive ischemia, tumor perfu­sion). A decrease in pheripheral resistance leads to an
increase in the diastolic ow component. Moreover, the
character of the waveform is aected by central regulatory processes (increase in heart rate, blood pressure) and vessel wall elasticity (diabetes mellitus).
As peripheral resistance is a crucial factor inuencing blood ow and hence the Doppler waveform, a distinction is made between low-resistance ow and high-resistance ow (
. Fig.1.45).
vessel lumen. If the dierence between a narrow and wide (poststenotic) segment exceeds a certain value, ow separa-
tion
and eddy currents will occur near the wall. Flow separa­tion near the wall is also observed in branching blood vessels (. Fig.1.44).
Flow separation gives rise to recirculation zones, in which relative stasis of ow, in conjunction with shear stress, induces platelet aggregation with release and adhesion of procoagulative agents, which in turn can trigger local athero­genic processes. is is a possible mechanism contributing to the preferred occurrence of atherosclerotic lesions in divid­ing and branching vessel segments.
e most notable example of ow separation can be encountered when imaging the origin of the internal carotid artery (ICA), where it occurs as a result of both widening in the bulb area and branching (see . Fig. 5.49 (Atlas)). e
1.2.2.1 Low-Resistance Flow
Arteries supplying parenchymal organs and the brain are characterized by a fairly steady blood ow as a result of low
peripheral resistance
. In these arteries, a moderate systolic rise is followed by a steady ow that persists throughout dias­tole. is ow prole is typical of the renal, hepatic, splenic, internal carotid, and vertebral arteries.
Continuous diastolic ow in the arteries supplying paren­chymal organs is necessary to ensure constant perfusion of these organs. is is accomplished by the lower peripheral resistance of these vascular beds and the windkessel function of the large conducting arteries including the aorta, which jointly produce a more continuous ow than would result from the action of the le ventricle and aortic valve alone (. Fig.1.45).
high wall pressure in this area, in conjunction with slow ow in separation zones, contributes to the preferred develop­ment of carotid bulb plaque on the wall opposite the exter­nal carotid artery origin (. Figs.1.44b, 5.49 (Atlas), and 5.56 (Atlas)). Flow separation can also occur downstream of a ste­nosis, where the vascular cross-sectional area increases again (see . Fig.1.46a, b), and increased wall pressure can cause poststenotic dilatation.
Poststenotic vascular dilatation or even aneurysm is rare in atherosclerotic stenosis; it is more common in patients with other vascular conditions not causing wall sclerosis such as compression syndromes (see . Figs. 3.101, 2.105, and
2.106 (all Atlas)) or bromuscular dysplasia.
1.2.2.2 High-Resistance Flow
High peripheral resistance results in a more pulsatile ow
with a steep systolic upslope during the acceleration phase, followed by deceleration and a signicant reux in early dias­tole, short backward ow in mid-diastole, and typically zero ow in late diastole. is pattern is referred to as triphasic
ow
.
e systolic pulse wave is in part reected by the high peripheral resistance and thus moves backward through the arterial system until the ow is again redirected toward the periphery by the inux of blood during the next cardiac cycle. is ow component is small due to the high periph­eral resistance.
As a result of the high pressure in the arterioles supplied
1.2.2 Flow Proles andPerfusion Regulation
by the limb arteries, signicant blood ow in these vessels occurs only during systole when systemic pressure is higher
Unlike laminar ow, pulsatile ow changes periodically over time. Phases of acceleration and deceleration vary in relation
than peripheral pressure. e pressure during diastole is too low to produce blood ow toward the periphery.
1.2 · Hemodynamic Principles
LowerPeripheral resistanceHigher
Arteriolar diameter Arteriolar diameter
Autoregulation
Adaptive regulation
+ p
Pressure pulse generated by the heart
Reflected pressure wave
- p
D pa
41
1
Normotensive
Rest
c
. Fig. 1.45 a Eect of peripheral resistance on the Doppler waveform. Pulsatility increases with peripheral resistance. b Flow pulse curves
resulting from superimposition of the pressure pulse generated by the heart and the pressure waves reected by the distal vascular bed in arter­ies with high peripheral resistance (left) and low peripheral resistance (right). For an identical pressure pulse generated by the heart (above the baseline), the pulse curve resulting from interaction with the reected pulse (below the baseline) is highly pulsatile when peripheral resistance is high and less pulsatile when peripheral resistance is low. The pressure gradient (p) calculated by subtracting the reected pulse wave from the pulse wave emitted by the heart is directly proportional to blood ow velocity (according to the Hagen–Poiseuille law). c Changes in arteriolar diameter in response to blood pressure changes (autoregulation, left) and in response to exercise (adaptive regulation, right). d Simplied sche­matic illustration of changes in blood pressure (with ow velocity changing in proportion), peripheral resistance, and total area of the vascular bed through the circulatory system (arteries, capillaries, veins)
Blood pressure
Exercise
Cross-sectional area
High Low
b
Aorta
Pressure
Resistance
d
Peripheral resistance
Arteries
Systolic
Diastolic
Capillaries
Arterioles
Vena cava
Veins
Venules
High-resistance ow occurs in the arteries supplying the muscles and the skin, such as the arteries of the arms and legs, and the external carotid artery. e ratio of skin to mus­cle supply determines the amount of diastolic forward ow. When peripheral demand increases (muscle activity, inam­mation), the arterioles dilate to reduce local vascular resis­tance, and forward ow, primarily during diastole, increases.
Transitions between these two ow patterns may
occur under normal and abnormal conditions. Besides, there are vessels with mixed patterns. An example is the superior mesenteric artery, which has pulsatile ow like a limb artery but also has a signicant end-diastolic ow component. e
amount of end-diastolic ow is regulated adaptively and increases with demand aer ingestion of food. Adaptive adjustment of diastolic ow through arteriolar vasodilation occurs in all arteries with high-resistance ow. Other factors inuencing late diastolic ow include systemic factors such as sympathetic tone and the windkessel function of the aorta. is is why loss of aortic compliance and of vascular elasticity results in more pulsatile ow.
An arteriovenous (AV) stula turns high-resistance ow into low-resistance ow. A change from low-resistance to high-resistance ow in a transplant renal artery is an impor­tant diagnostic criterion in the diagnosis of gra rejection.