Professional Documents
Culture Documents
1, July 1982
over four times the efficiency of the prototype could be N-isopropyl 1-123 p-iodoamphetamine: Concise communication," I
Nucl. Med. Vol. 23, pp. 191-195, 1982.
constructed using state-of-the-art ring detectors. [6] K. A. Frey, D. M. Wieland, L. E. Brown, W. L. Rogers, and B. W. Agranoff,
"Development of a tomographic myelin scan, Ann. Neurol., Vol. 10,
LUK HU WE*UgI * ECU t1__ _ _ pp. 214-221, 1981.
[7] T. F. Budinger, "Revival of clinical nuclear medicine brain imaging."J.
This work was supported by the National Cancer Institute Nucl. Med., Vol. 22, pp. 1094-1097, 1981.
Grant#5 R01 CA32846. The authors wish to acknowledge [81 R. E. Coleman, B. P. Drager, and R. J. Jaszczak, "Studying regional brain
the work done by the Physics Instrument Shop in construc- function: A challenge for SPECT," J. Nucl. Med., Vol. 23, pp. 266-270,
1982.
ting the tomograph and the secretarial assistance of Diane [9] G. F. Knoll, and J. J. Williams, "Application of a ring pseudorandom
Vecellio in preparation of the manuscript. aperture for transverse section tomography," IEEE Trans. Nuc. Sci., Vol.
NS-245, pp. 581-586, 1977.
[10] J. J. Williams, "Design and investigation of a circular ring emission
tomograph," Doctoral Thesis, University of Michigan, 1979.
[1] D. E. Kuhl, and R. 0. Edwards, "Image separation radio-isotope scann- [11] W. P. Snapp, "Reconstruction methods for nuclear emission
ing," Radiology, Vol. 80, pp. 653-661, 1963. tomography," Systems Engineering Laboratory Technical Report #SEL-
[ 2] H. S. Winchell, R. M. Baldwin, and T. H. Lin, "Development of TR-144, Department of Electrical & Computer Engineering, University
1-123-labeled amines for brain studies: Localization of of Michigan, July 1980.
1-123-iodophenylalkyl amines in rat brain," /. Nucl. Med., Vol. 21, pp. [12] H. 0. Anger, "A scintillation camera with multichannel collimators," J.
940-946, 1980. Nucl. Med., Vol. 5, pp. 515-531, 1964.
[ 3] H. S. Winchell, W. D. Horst, L. Braun, et al., "N-isopropyl-[123] [13] C. Burnham, J. Bradshaw, D. Kaufman, D. Chesler, and G. Brownell,
p-iodoamphetamine: Single pass brain uptake and washout; binding to "One dimensional scintillation cameras for positron ECT ring
brain synaptosomes; and localization in dog and monkey brain," I. detectors," IEEE Trans. Nuc. Sci., Vol. NS-28, pp. 109-113, 1981.
Nucl. Med., Vol. 21, pp. 947-952, 1980. [14] W. L. Rogers, and R. S. Adler, "Time-coded aperture design for nuclear
[ 4] D. E. Kuhl, J. R. Barrio, S. C. Huang, et al., "Quantifying local cerebral medicine imaging: A study of signal-to-noise ratio," Applied Optics,
blood flow by N-isopropyl-p-[123] iodoamphetamine (IMP) Vol. 21, pp. 324-333, 1982.
tomography," 1. Nucl. Med., Vol. 23, pp. 196-203, 1982. [15] K. F. Koral, W. L. Rogers, and G. F. Knoll, "Digital tomographic imaging
[ 5] T. C. Hill, B. L. Holman, R. Lovett, et al., "Initial experience with SPECT with a time-modulated pseudorandom coded aperture and an Anger
(single photon computerized tomography) of the brain using camera," 1. Nucl. Med., Vol. 16, pp. 402-413, 1975.
tions of the initial simple, inexpensive Doppler units [27, 2]. megaHertz (MHz) and produces peak energy levels at less
The impetus for the improvement of the technical capabili- than 5.0 W/cm2. The acoustic waves are generated when a
ties of Doppler instruments has resulted from 1) the un- piezoelectric crystal, the transducer, vibrates at its resonant
familiarity of clinicians with the physiological and dynamic frequency after the application of a controlled burst of elec-
nature of the Doppler blood velocity, 2) the uncertainty in tromagnetic energy to its surface. When the vibrating
medicine on the clinical importance of detecting multiple transducer contacts the skin, two important changes occur
grades of stenotic lesions, 3) the technical difficulties in pro- as the acoustic energy propagates through the tissue. The
ducing accurate and reproducible measurements of the energy will be absorbed to reduce its intensity at each point
Doppler flow variables required to quantitatively correlate along the beam, and it will also be reflected at points along
disturbed flow regions with atherosclerotic lesions, and 4) the beam where the acoustic impedance changes. The
the requirement of reliable and precise measurements of acoustic impedance depends on the mechanical properties
the variables needed to calculate volumetric flow (cm3/sec). of the biological tissue. If ultrasonic energy from the
Moreover, we still do not fully understand the epidemiology transducer is delivered in short bursts of energy, or pulsed,
of vascular disease, the pathophysiology of occlusive the same transducer can then be used to receive reflected
changes, the natural history of arterial lesions, or the precise energy.
mechanisms of transient ischemic attacks distal to a stenotic If the location of the interface between two tissues with
lesion. Doppler ultrasound instruments were developed in different values of acoustic impedance is stationary, the fre-
the hope of providing techniques which would help us quency of the reflected wave will be approximately the
understand these phenomena. same as the incoming wave and can be received by the
Clinical Doppler ultrasound systems which at present are same or separate transducers for dynamic structural infor-
commercially available can be listed in order of their com- mation, such as cardiac chamber [24] and blood vessel
plexity and cost: 1) directional and nondirectional portable dimensions [19, 20]. In contrast, a moving interface will
continuous wave (CW) devices, 2) continuous and pulsed cause the reflected signal frequency to be frequency-shifted
wave Doppler (PD) flow imaging scanners, and 3) real-time by a magnitude which is proportional to the velocity of the
ultrasonic sector scanners incorporating a range-gated puls- interface in the direction of the sound beam axis [2]. In the
ed Doppler identified as a duplex scanner (DS). These simplest form, this relationship is given by the classic Dop-
various methods differ not only in initial cost but also in their pler equation: A f = 2 V f cos 0
technical capabilities, limitations, versatility, and clinical C
reliability. Importantly, each Doppler procedure of nonin- where Af represents the Doppler shift expressed in kHz; V is
vasively evaluating atherosclerotic lesions requires different the velocity vector of the interface generally expressed in
degrees of operator skill and clinical interpretation of the m/sec; f is the frequency of the transmitted ultrasound; C is
raw data. Presently, it appears that no best test exists but a the velocity of sound (1400 m/sec) of the tissue media sup-
combination of various Doppler techniques (direct or in- porting the acoustic energy; and 0 is the Doppler incident
direct interrogation of a given vessel) produces the most ef- angle between the transmitted beam and the velocity vec-
fective way of diagnosis [1]. tor. Clearly, if the values of f and C are assumed constant (a
The purposes of this paper are threefold: 1) to briefly reasonable assumption in most applications) and 0 can be
describe the general, theoretical and technical aspects of measured or held constant, Af will be proportional to V.
current ultrasonic Doppler methods; 2) to discuss the impor- When the incident sound beam traverses a blood vessel
tant clinical advantages, assumptions, accuracy, reliability, and its energy is not absorbed or reflected by significant
and technical problems associated with each method; and amounts of calcium [36], small amounts of energy are ab-
3) to suggest future research and development which could sorbed by each moving red cell. Since the dimensions of the
improve the accuracy and precision of noninvasive, non- red cells are small compared to the wave length of the
ionizing Doppler ultrasound in the quantitative evaluation of acoustic energy, the reflected wave is radiated in all direc-
the anatomy, pathophysiology, and natural history of tions [26]. This phenomenon is called backscatter and allows
atherosclerosis. detection of acoustic signals with the receiving transducer
held at any angle with the backscattering particles. If the red
Methods cell is moving relative to the transducer, a backscattered
General Considerations Doppler shift can be recorded [2]. Since a distribution of
Accurate use of any Doppler ultrasound device whether blood velocities is present in each segment of a blood ves-
continuous, pulsed, flow imaging, or real-time duplex re- sel [45], a spectrum of Doppler shift frequencies will be
quires an appreciation of the hemodynamic phenomenon developed [53]. These spectra can become quite dynamic
being measured as well as an understanding of the interac- and complex in physiological states of blood flow and parti-
tion of acoustic energy with biological tissues and moving cularly within the region of atherosclerotic lesions [28, 33].
blood particles. A brief summary will be presented here, Analysis of the Doppler shift frequencies is further compli-
and the reader is referred to the literature for a more com- cated by the inherent pulsatile motion of the blood vessel
prehensive treatment [2, 4, 13, 39, 45, 62]. [21].
The term ultrasound is used to describe mechanical vibra- Even if the velocity distributions of the interrogated blood
tions at frequencies above the limit of human audibility. vessel are well-behaved and not influenced by a focal lesion
Most nontraumatic ultrasound operates between 1-20 and/or changes in distal impedances [64], other factors
70 IEEE Transactions on Medical Imaging, Vol. MI-1, No. 1, July 1982
which affect the Doppler spectra must be known in order to preciation of the complexities involved in making the
be certain that the Doppler spectrum genuinely reflects the measurements and processing the data [5, 29, 52]. One
various blood velocities within the lumen. These factors in- must recognize that V and Q are variables that cannot be
clude the following: 1) whether there is axial migration of directly obtained with a single noninvasive measurement of
the red blood cells which would weigh the Doppler spectra one physiological variable. Noninvasive Doppler methods
toward the higher velocities, 2) whether there is a uniform of measuring V require the following three distinct steps:1)
sound beam which is required for uniform insonation of the location of the vessel, 2) determination of the Doppler inci-
vessel, and 3) whether there is distortion of the Doppler dent angle, and 3) measurement of the spatial average Af,
signal due to nonlinearities and overall band-pass which represents V. To calculate Q, a measurement of the
characteristics of the device. lumen diameter is also required.
If the mean frequency shift (At) can be electronically ex- The third step, determination of the value of Af and hence
tracted from the Doppler spectrum generated from a uni- V, can be quite difficult. Technological improvements have
provided more control of the blood velocity sensing region
formly insonified velocity profile, the spatial average veloci-
ty(V) as a function of time can be measured [4]. Volumetric known as the sample volume. Consequently, specific loca-
blood flow (Q) can then be determined from an indepen- tions of blood velocities can be more uniformly insonated
dent ultrasonic measurement of lumen diameter (D) (assum- to provide Doppler spectra which accurately reflect the true
mean velocity or distribution of velocities within the vessel
ing a circular cross-section) by the equation: [4, 46]. From these spectra, appropriate signal processing
D2 can yield a more reliable display of a normal or disturbed
4 velocity profile or a more accurate calculation of Q.
The Doppler ultrasound methods of calculating V and Q A summary of important design parameters and opera-
are deceivingly simple. This has led some investigators to tional controls of either CW or PD units which influence the
use simple, commercially available, noninvasive Doppler extraction of Doppler audio spectra from the received
systems to arrive at quantitative measurements without ap- ultrasonic signal is given in Table 1.
Table 1
Relationship of Doppler Design Parameter and Operational
Controls with Measurement Characteristics
Design Parameters
or Operational Controls Relationship Measurement Characteristics
1. Transmitter frequency Direct Resolution, scattering power
(all units) attenuation
Inverse Near field longitudinal
dimension
Inverse Resolution
6. Pulse repetition fre- Direct Processed power, maximum measur-
quency (pulsed units) able frequency (Nyquist)
Inverse Range
Greene et a/.: Quantitative Evaluation of Atherosclerosis 71
calculation, the mode, displays the frequency with the angiography is reserved only for surgical candidates. In addi-
highest energy level at any time (an estimate of Af and V). tion, unique baseline physiological data (segmental
Even in this example of narrow band spectra associated with pressures, qualitative flows, and vascular reserve) of signifi-
normal flow patterns, note the variation in gray scale cant importance to patient management are also obtained
presentation of the spectra. These variations may influence in a cost-effective manner. Few limitations are present in the
the calculations of various correlative indices associated application of continuous wave units to peripheral vascular
with spectral width. The effect of this and other controls on disease. In advanced occlusive arterial disease, no Doppler
the audio spectra display is even more pronounced in high shifts may be generated due to lack of blood velocity which
energy, broad band spectra generated from disturbed flow will not create high enough Doppler shifts to pass the band-
regions. Clearly, if one is to quantitatively analyze Doppler pass output filters of the unit. In addition, Doppler determin-
spectra generated from flow velocity fields created by dif- ed cuff blood pressures may be artificially elevated (>200
ferent degrees of arterial narrowings, careful attention to mmHg) due to arterial calcification. Generally, these condi-
the control and display settings of the instruments is most tions are self-evident and do not compromise the accuracy
important. As with all applications of noninvasive diagnostic of the noninvasive diagnosis.
ultrasound, optimal instrument control settings will vary The genuine success of simple, nonimaging continuous
with application and patient habitus. wave units in peripheral vascular disease can be attributed
The preceding theoretical comments and operational to the advanced state of the occlusive arterial disease
suggestions have been general to all three categories of (hemodynamically significant) in most patients presenting
Doppler ultrasonic instruments regardless of clinical applica- with resting or intermittent claudication. Significant flow and
tion. Each modality has specific characteristics, capabilities, pressure reduction can be detected reliably and correlated
and limitations which will now be discussed. to stenotic lesions demonstrated angiographically. Reliable
detection of nonhemodynamically significant lesions (ar-
Critique and Discussion_ bitrarily defined as <50% maximum diameter reduction in
Continuous Wave Devices any angiographic plane) which do not significantly reduce
Simple, inexpensive continuous wave (CW) devices are flow and pressure clearly put unresolvable technical
certainly the most versatile and widely used Doppler in- demands on simple continuous wave devices in peripheral
struments in clinical practice [7, 44]. Initial systems were and other applications.
nondirectional but more recent versions were designed to Application in Cerebrovascular Disease
differentiate flow directionality which is often of clinical im- Although their relative importance remains controversial,
portance. The major technical deficiency of the CW units is nonhemodynamically significant but emboligenic lesions in
their lack of depth resolution. Consequently, if two distinct the extracranial cerebrovascular system have been implicat-
flow fields (vessels) are insonated by the relatively large ed in cerebral ischemia (transient ischemic attacks) and in-
sample volume (created by the three dimensional overlap farcts (strokes) (10, 29, 48). Consequently, attempts to
of the beam patterns of the transmitting and receiving crys- noninvasively detect hemodynamically and nonhemody-
tals), unspecific Doppler audio spectra will be developed. As namically significant stenosis using continuous wave units
an example, overlapping veins and arteries, a common ana-
were undertaken. Due to inherent physiological and ana-
tomical situation, can distort the CW Doppler spectra. Direc- tomical complexities of the cerebral circulation, simple in-
tional units have helped differentiate flow fields, but they direct periorbital Doppler techniques are not accurate
have not completely resolved this problem. Although no enough to detect all hemodynamically significant lesions
range resolution is possible, continuous wave units allow
and can detect very few nonhemodynamically significant le-
ultrasonic Doppler signals to be continuously sampled. Con- sions in the extracranial vasculature [16]. Generally, total oc-
sequently, no artificial distortion (aliasing) of the audio signal clusion of the internal carotid gives a positive test result (par-
is produced by high frequency shifts associated with ticularly with compression maneuvers) and thus allows this
elevated blood velocities and/or small Doppler angles [4]. simple indirect procedure to be a useful and commonly ap-
This distortion can be created by pulsed units which sample plied adjunct to more direct methods [1].
high flow rates. The distortion due to aliasing can mimic ab- Direct, continuous wave Doppler interrogation of the
normal spectra created by anatomical lesions [60]. carotid bifurcation using audio interpretation [61], zero-
Application in Peripheral Vascular Disease crossing detection [55] and FFT methods [8] have allowed
In spite of its technical limitations, the simple hand-held useful differentiation between angiographically determined
continuous wave device (with or without sophisticated spec- significant and nonsignificant lesions. One of the difficulties
tral analysis) has found wide acceptance in the diagnosis of with these nonimaging methods is the critical problem of
hemodynamically significant (flow and pressure reducing) le- the proper identification of the three major vessels (com-
sions in the peripheral arteries during rest and exercise mon, internal, and external carotids) in a small region
[7, 31, 44]. In this application, the procedure can be under- [11, 50]. Consequently, Doppler flow imaging systems with
taken by a technician without extensive training in the inter- and without audio spectra analysis were developed.
pretation of Doppler spectra. Unpublished results from our
laboratory with over 100 angiographic correlates support Doppler Flow Imaging
published results with an overall accuracy of 98% compared Continuous Wave Flow Imaging
with angiography. Thus, in our institution, peripheral In order to meet the need of proper vessel identification in
Greene et al.: Quantitative Evaluation of Atherosclerosis 73
Fig. 4. Angiographic (top) and freeze frame DS images (bottom) with FFT
spectra of a normal carotid bifurcation with the sample volume (SV)
placed in the external carotid (EC) and later in the internal carotid
(IC) distal to the common carotid (CC). Note the high diastolic flow
velocity in the IC compared to the EC. In our experience, real-time
noninvasive images of the carotid bifurcation which are similar to
angiographic presentation are not easily obtained. Often the far
walls of the EC and IC are nonvisualized, hence calibration of the
spectra into V and Q is not always feasible.
points in space independently and simultaneously (multi- SERIX_Xg t 'Ett<FFfPNOZY A NCWWASIE &F 0 jA A
gated), PD flow imaging units theoretically provide more cn- $EN $&.o4t y
ff ii0 t00
U
aging and Doppler spectral analysis are encouraging [37]
and their pitfalls can be delineated [11]. Generally, imaging :e
errors caused by calcification can be overcome by sono- PNAtff f
graphic spectral analysis. It is important to note that
nonoperable occlusive disease can be reliably separated
from operable, highly stenotic lesions. Due to the finite
spatial and velocity resolution of Doppler flow imaging in-
struments (either CW or PD), improvements in image reso- Fig. 6. Serial clinical results in our laboratory using different Doppler
lution (even at higher frequencies) seem unlikely. Conse- methods to identify angiographically demonstrated IC lesions of
quently, improved quantitative evaluation of atherosclerotic >20% diameter reduction and occlusions. See test for details.
Greene et al.: Quantitative Evaluation of Atherosclerosis 75
vascular system. Spectral analysis techniques to identify velocity and flow data. Consequently, a better clinical and
pathophysiological understanding of the true hemodynamic
arterial lesions can be applied to any of the ve.ssels. Gray severity of an atherosclerotic lesion can be obtained.
scale [18] and color-coded, real-time, multigaited, echo-
Doppler images [23] have also been develope u irom u1 J - AL.A..
technology to demonstrate the immense amoun t of physio- The authors would like to thank Drs. U. C. Luft, Jack Loep-
logical information and display formats that can b)e obtained pky, Neal Halpern, Jonathan Sands, Robert jahnke, David
from pulsed Doppler ultrasound. Sommerville, Robert Croke, Emmett Mathews, Pratap
Second, it is the opinion of this laboratory that technologi- Avasthi, David Hoekenga, and Richard Conn for their profes-
cal innovations associated with the DS have allov ved reliable sional expertise. John Adams, Treva Miller, Pat Reilly, Arthur
noninvasive estimates of cardiac output [42] ar id regional Witt, Ruth Graham, Linda Bernhardt, and Isidora Miranda
blood flow rates [32]. These measurements will become in- provided excellent technical support. The work was sup-
creasingly important for the following reasons: The hemo- ported by grants from the American Heart Association and
dynamic severity and clinical consequences of irnpared gas NHLBI grants 5-R01HL26025- 02 and 1-R01HL27095-01.
exchange due to an anatomical lesion depencI on many References
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