Estimation of arterial stiffness, compliance, and distensibility from M-mode ultrasound

measurements of the common carotid artery.

G Gamble, J Zorn, G Sanders, S MacMahon and N Sharpe

Stroke. 1994;25:11-16
doi: 10.1161/01.STR.25.1.11
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Estimation of Arterial Stiffness, Compliance,
and Distensibility From M-Mode Ultrasound
Measurements of the Common Carotid Artery
G. Gamble, MSc; J. Zorn, SEN; G. Sanders, NZCS; S. MacMahon, PhD; N. Sharpe, MD
Background and Purpose Arterial stiffness may indicate
early vascular changes that predispose to the development of
major vascular disease. The repeatability of a variety of indices
of arterial stiffness calculated from a standard carotid arterial
M-mode ultrasound image was investigated.
Methods Twenty-six asymptomatic normal subjects were
imaged and had blood pressure recordings on each of two
separate occasions at least 1 day apart. Using a computer-
assisted method, the maximum and minimum internal diame-
ter and average wall thickness of the right common carotid
artery were measured over several cardiac cycles, and the
following indices of arterial stiffness and distensibility (com-
pliance) were derived: the pressure-strain elastic modulus
(Ep), Young's modulus (E), cross-sectional compliance (CC),
and the distensibility coefficient (DC).
Results The repeatability of these measures, expressed as
coefficients of variation, was as follows: Ep, 18%; E, 24%; CC,
14%; and DC, 13%. In another group of 20 subjects, the
coefficient of variation for repeat examination by different sonog-
raphers was Ep, 19%; E, 20%; CC, 14%; and DC, 17% and for
A rterial stiffness1 and its reciprocal, arterial disten-
/ \ sibility (or compliance2), may provide indices of
.Z \ . early vascular changes that predispose to the
development of major vascular disease. Localized in-
creases in wall stiffness have been documented in areas
of artery adjacent to regions of plaque.3 Men with
angiographically verified coronary artery disease have
been shown to have stiffer arteries than control sub-
jects. 46 Patients with a history of myocardial infarction
have been shown to have increased arterial stiffness,7 as
have their offspring.8 Risk factors for vascular disease
including age, 910 blood pressure,1113 blood cholesterol,8
and diabetes8 have all been shown to be positively
associated with arterial stiffness. Each of these observa-
tions is therefore consistent with the hypothesis that
increased arterial stiffness (and reduced compliance) is a
precursor, or at least a predictor, of atherosclerotic
disease. Unlike established atherosclerotic disease, how-
ever, increased arterial stiffness may be reversed quickly
by pharmacologic and dietary interventions. In hyperten-
sive subjects, it has been reported that calcium antago-
nists,214 /3,-adrenoceptor blockers,14 and angiotensin
Received March 3, 1993; final revision received September 10,
1993; accepted September 10, 1993.
From the Department of Medicine, University of Auckland,
New Zealand.
Correspondence to G.D. Gamble, Department of Medicine,
University of Auckland, Private Bag 92019, Auckland, New
Zealand.
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11
the one sonographer using two ultrasound machines was Ep,
13%; E, 13%; CC, 11%; and DC, 13%. These values indicate a
moderate level of repeatability. In a univariate analysis each of
these indices was significantly related to increasing age
(Ep=1.0+12.9xAGE, r=.8O; E=314.5 +13.9xAGE, r=.48;
CC=22.6-0.26xAGE, r = - . 6 3 ; D C = 6 4 . 0 - 0 . 6 5 x A G E ,
r=-.78) but not to wall thickness (all P>A1). Using multiple
regression techniques to adjust for age, wall thickness is a
significant predictor of distensibility (P=.O17), cross-sectional
compliance (P<.001), and the pressure-strain elastic modulus
(P=.O19). Because Young's modulus is calculated from wall
thickness, it could not be included in the multivariate analysis.
Conclusions We conclude that estimates of carotid artery
distensibility and cross-sectional compliance derived from
M-mode ultrasound recordings are moderately repeatable and
may provide useful additional end points for trials of athero-
sclerotic progression. (Stroke. 1994;25:11-16.)
Key Words atherosclerosis carotid arteries
ultrasonics
converting enzyme inhibition15-16 can reduce arterial
stiffness. In normotensive subjects it has been suggested
that sodium restriction may also reduce arterial stiff-
ness17 and that reversible increases in arterial compliance
can be seen after a brief period of exercise training.18
More evidence about the prognostic significance of
increased arterial stiffness and the effects of interventions
on this parameter would be useful. However, the conduct
of appropriate large-scale clinical and epidemiological
studies has been hampered by the absence of simple
measurement techniques. Previous studies have used a
variety of measurement methods including applanation
tonometry,19 multigated pulsed Doppler,20-21 phase-locked
echo tracking,10 magnetic resonance imaging,6 intravascu-
lar ultrasound,22 B-mode ultrasound,3 and pulsed Doppler
velocitometry,11-15-23-24 each of which requires special
equipment and training available in only a few centers. For
this reason we have assessed the usefulness of M-mode
ultrasonography of the carotid artery for assessment of
arterial stiffness and compliance. This methodology could
be applied in most cardiology or radiology departments.
Moreover, because B-mode ultrasound measurements of
carotid artery wall thickness and plaque prevalence are
already being collected in numerous epidemiological stud-
ies 2527 and randomized trials,28-29 M-mode ultrasound
measurements of arterial stiffness and compliance could
potentially provide useful additional end points with little
extra effort.
In this study we sought to determine the reproduc-
ibility of M-mode measurements of systolic and diastolic
12 Stroke Vol 25, No 1 January 1994

diameters of the right carotid artery and of several

calculated indices of arterial stiffness and compliance.
We also sought to determine whether these indices were
related to age and artery wall thickness in a manner
consistent with their being valid measurements of arte-
rial stiffness and compliance.
Subjects and Methods
Twenty-six asymptomatic subjects (18 women; mean age, 40
years; range, 22 to 56 years) were examined by one ultrasonog-
rapher on two occasions at least 1 day but not more than 4
weeks apart. Before ultrasonography, after 5 minutes' rest in a
semidarkened room, two blood pressure recordings were made
from the right arm of the supine subject using a mercury
sphygmomanometer. A region 1.5 cm proximal to the origin of
the bulb of the right common carotid artery was identified
using B-mode ultrasonography. The transducer was manipu-
lated such that the near wall of the carotid artery was parallel
to the transducer footprint and the lumen maximized in the
longitudinal plane. An M-mode recording at 50 mm/s was
made with the M-mode cursor perpendicular to the vessel
walls, as identified using B-mode (10-MHz single crystal,
mechanical sector transducer, ATL-UM8). Three cardiac cy-
cles were recorded onto videotape and also digitized on-line
for later measurement. The sonographer maintained sufficient
pressure on the artery to allow acoustic coupling without
compressing the artery. After the examination, and with the
patient remaining supine, two additional blood pressure read-
ings were made. Average systolic and diastolic blood pressures
were calculated from four readings taken before and after the FIG 1. M-mode ultrasound recording of a right common carotid
ultrasound scan. This entire procedure was repeated at the artery approximately 2 cm proximal to the bulb showing the
second visit. typical pattern of two echoic regions separated by an anechoic
To estimate the reproducibility of measurements made from area. This pattern corresponds to the thickness of the superficial
images collected by two sonographers and to compare mea- (near) and deep (far) artery walls; the distance between repre-
surements made on different ultrasound machines, an addi- sents the arterial lumen. Also shown is the electrocardiogram
tional group of 20 subjects (mean age, 55 years; range, 41 to 64 and measuring grid calibrated to the cardiac cycle. The points
years) was studied. Subjects were imaged by two sonographers marked A and B are the periadventitia-adventitia and intima-
lumen interfaces, respectively, of the near wall, and the points
within 19 days (mean, 7 days) of each other. A third sonogra-
marked C and D are the lumen-intima and adventitia-periadven-
pher imaged the same patients twice, at least 7 days apart, titia interfaces, respectively, of the far wall. The maximum and
once using either an ATL-UM8 (10-MHz transducer) or an minimum values for each of the 10 distances from B to C were
ACUSON 128 (7-MHz transducer) on the first visit and then used as the systolic and diastolic artery diameters, and the mean
the other machine at the second visit. Regular maintenance of the 10 distances from C to D (measured from B-mode) was
and quality assurance checks using a phantom ensured that taken as the circumferential artery wall thickness. The image was
the ultrasound machines were performing to the manufactur- digitized on-line from an ATL-UM8 single crystal 10-MHz me-
er's specifications. chanical sector transducer and collected at 50 mm/s.
The digitized M-mode was analyzed off-line using a locally
developed computer program. Each image was recalled (magni-
fication x5) and the distance between two successive R waves modulus (Peterson's modulus): the change in carotid artery
measured. This distance was divided into 10 equal sections, and diameter for a change in arterial blood pressure relative to the
the measurer was able to select lumen-intima interfaces for the average diameter1; and (4) Young's modulus: artery stiffness per
near and far walls of the carotid artery by positioning a cursor centimeter of wall thickness.1 Because only the far wall of the
over the point on a computer-generated grid. The cursor was free carotid artery can be validly measured with B-mode ultrasound,31
to vary vertically, but not horizontally, along this grid line (Fig 1). this was used to provide an estimate of wall thickness. These
Thus, for each individual the cardiac cycle was divided into parameters were calculated as:
tenths, and at each tenth the distance between the lumen-intima
interface for the near and far walls was calculated and maximum lAdld,
and minimum lumen diameters detected. We have previously Distensibility Coefficient (DC) =
identified a very close association between the ultrasound repre-
sentation of the lumen and the actual lumen, measured with Ad/d,
electronic calipers, in 10 bovine arteries scanned in a water bath Cross-sectional Compliance (CC): TTd?
(95% confidence interval [CI] of the difference between caliper 'Up
and ultrasound, -0.09 to 0.75 mm). Wall thickness of the far wall
was measured from B-mode and best represents the combined
Ap
thicknesses of the intima, media, and the adventitia.30 The Pressure-Strain Elastic Modulus (Ep)= D
coefficient of variation of measurements of wall thickness is 7.2% Ad
for repeated visits (Gamble et al, unpublished data, 1994).
From these measurements the following parameters were Ap D
estimated: (1) distensibility: the change in carotid artery diame- Young's Modulus (E)=T~7XT~
ter for a change in blood pressure relative to its systolic diame-
ter20; (2) cross-sectional compliance: distensibility multiplied by where Ad is the change in diameter, d, is the systolic diameter,
the cross-sectional area of the artery20; (3) pressure-strain elastic D is the average diameter of the artery, h is the arterial wall

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 Gamble et al Carotid Stiffness From M-Mode 13

1 0 1 0
~| Systolic lumen diameter (cm) ~| Diastolic lumen diameter (cm)

(M
Z OS 0.5 -

0 OS 1.0 0 0.5 1.0

2000 -| young's Modulus (kP*/cm) 120 npressure-strain elastic modulus (kPa)

1500 -

FIG 2. Scatterplots show comparison

CM of lumen diameters and stiffness indi-
IOOO - 60 - ces obtained by M-mode ultrasound
of the right common carotid artery on
each of two visits. The least-squares
regression line for visit 1 versus visit 2
is shown.
500 -

0 500 1000 1500 2000 0 60 120

30 80
ICross-sectional compliance HO'W/kPa) "pistensibility coefficient (10-'/kPal

CM
30 -

15 30 30 60

Visit 1 Visit 1

thickness, and Ap is the difference between the average
systolic and the average diastolic blood pressures. Each pa-
rameter was calculated for each of the cardiac cycles and
averaged for each subject.
Data were analyzed using the statistical package SAS.32
Spearman's rank correlation coefficient, coefficients of varia-
tion and reproducibility (95% confidence intervals),33 and
simple absolute and mean differences were used to compare
intermeasurer and intrameasurer reproducibility. A sample
size of 26 would provide more than 80% power (a=.O5)34 to
detect "almost perfect"35 agreement between pairs of mea-
surements. Intraclass correlation coefficients were calculated
from the between- and within-person mean squares for a
one-way ANOVA.36 The standard deviation of the intermea-
surer error was calculated as the standard deviation of the
differences over V5. Stepwise and maximum R2 techniques
were used to fit multiple regression models of the data. A 5%
significance level was maintained throughout these analyses.
Results
The associations between measurements of systolic
and diastolic lumen diameters made at the first and
second visits and the least-squares regression lines are

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14 Stroke Vol 25, No 1 January 1994
TABLE 1. Estimates of the Reproducibility of M-Mode
Ultrasound Measurements of Systolic and Diastolic
Lumen Diameters of the Right Common Carotid Artery
Visit 1 Visit 2
Systolic internal diameter, cm 0.640.02 0.630.02
Pooled 0.64 0.02
Difference 0.01 0.01
Absolute difference 0.04 0.01
95% Confidence interval 0.02
Coefficient of variation 5.6%
Intraclass correlation coefficient r=.88
Diastolic Internal diameter, cm 0.580.02 0.560.02
Pooled 0.570.02
Difference 0.020.01
Absolute difference 0.040.01
95% Confidence interval 0.02
Coefficient of variation 6.3%
Intraclass correlation coefficient r=.83
Values are meanSEM where indicated. Difference and
pooled data were calculated for each subject (n=26).
plotted in Fig 2. These show a close linear association
between replicate measurements of each parameter.
The intraclass correlation coefficients for systolic and
diastolic diameters were both > .8, and the coefficients
of variation were both approximately 6% (Table 1). For
these two parameters, the mean absolute difference
between measurements at the first and second visits was
only 0.04 cm (approximately 6% to 7%). Intrameasurer
reproducibility assessed by repeat measurements of all
scans recorded at the first visit was high, with the
correlation coefficients >.8 for both systolic and dia-
stolic diameters. Intermeasurer reproducibility assessed
by comparison of measurements from the same scans
made by two observers yielded similar correlation coef-
ficients (>.8).
The associations between replicate estimates of the
four indices of stiffness or compliance at the first and
second visits and the least-squares regression lines are
also plotted in Fig 2. There were significant linear
relations of moderate magnitude (r=.41 to .73) for each
of the parameters (Table 2). The coefficients of varia-
tion for the replicate measurements ranged from 12.5%
for the distensibility coefficient to 24.2% for Young's
modulus. Accordingly, the mean absolute difference
between the first and second estimates of these param-
eters ranged from 21% for the distensibility coefficient
to 34% for Young's modulus.
The coefficients of variation for measurements made
from images collected from the same person by different
sonographers were 18.5%, 20.2%, 14%, and 17% for the
pressure-strain elastic modulus, Young's modulus, the
distensibility coefficient, and cross-sectional compli-
ance, respectively. Comparison of the difference in
images collected by one sonographer on two ultrasound
machines produced coefficients of variation of 13.1%,
12.8%, 11.3%, and 13% for the pressure-strain elastic
modulus, Young's modulus, the distensibility coeffi-
cient, and cross-sectional compliance, respectively.
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Both the pressure-strain elastic modulus and Young's
modulus increased significantly with increasing age
(Ep=1.0+12.9xAGE, r=.80; E=314.5 +13.9xAGE,
r=.48), whereas the distensibility coefficient and cross-
sectional compliance decreased significantly with in-
creasing age (DC=64.0-0.67xAGE, r=.78; CC=
22.6-0.26xAGE,/-=-.63). Carotid artery wall thickness
was not significantly correlated with any of the stiffness
or compliance indices (all P>A1). Wall thickness was,
however, found to be a significant independent predictor
of the distensibility coefficient, cross-sectional compli-
ance, and the pressure-strain elastic modulus when in-
cluded in a multiple regression model that adjusted for
age (all P<.017). The association with Young's modulus
was not examined because this index is calculated from
wall thickness.
Discussion
The results of this study demonstrate that systolic and
diastolic lumen diameters of the common carotid artery
can be measured reproducibly with M-mode ultrasound
using standard equipment and techniques. Reproduc-
ibility is not affected by using different sonographers or
different ultrasound machines. Correlation coefficients
for replicate scans and replicate measurements by the
same or different observers were all approximately .8 or
greater. The coefficients of variation for the lumen
diameters from repeated scans were both approximately
6%. The reproducibility of the four indices of arterial
stiffness or compliance was also reasonable, although
less than that for the lumen diameters themselves.
Because each of these indices is calculated from blood
pressure as well as lumen diameter (plus arterial wall
thickness in the case of Young's modulus), their repro-
ducibility reflects the sum of the variability of the
constituents (which is necessarily greater than the vari-
ability of any one constituent, such as lumen diameter,
alone). An additional source of variation results from
local irregularities in arterial stiffness. Barth et al3 have
demonstrated increased arterial stiffness in areas adja-
cent to plaques. The M-mode method can only measure
dimensions in one region of the artery at a time,
although by using B-mode to position the cursor it is
possible to obtain consistent sampling. Thus, careful
comparison of regions adjacent to plaques or examina-
tion of early atherosclerotic disease at regions where
plaque development is likely, such as the carotid bifur-
cation, is possible. An advantage in using M-mode to
detect systolic and diastolic diameters is that only a
single image needs to be captured, stored, and mea-
sured. To obtain the same information from B-mode
would require sequential images to be captured
throughout the cardiac cycle and compared with one
another.
The coefficients of variation for the four indices
studied indicate that within individuals only marked
changes in arterial stiffness or compliance (greater than
25% to 50%) could be detected reliably with this
method. However, small37 differences between individ-
uals in stiffness or compliance (10%) could be detected
reliably in studies involving just a few hundred partici-
pants. Clinical and epidemiological studies of carotid
artery wall thickness measured with B-mode ultrasound
generally require the involvement of at least several
hundred participants to detect plausible treatment ef-
 Gamble et al Carotid Stiffness From M-Mode 15

TABLE 2. Estimates of the Reproducibility of Four Indices of Arterial Stiffness or

Compliance Calculated From M-Mode Ultrasound Measurements of the Right Common
Carotid Artery

Visit 1 Visit 2
Young's modulus, kPa/cm 885.586.3 846.473.7
Pooled 865.968.8
Mean difference 39.1 82.7
Mean absolute difference 297.058.1
95% Confidence interval 113.9
Coefficient of variation 24.2%
Pressure-strain elastic modulus, kPa 54.73.6 51.63.5
Pooled 53.1 3.0
Mean difference 3.1 3.9
Mean absolute difference 14.02.7
95% Confidence interval 5.3
Coefficient of variation 18.4%
Distenslbility coefficient, 10 3 /kPa 36.1 2.1 38.32.3
Pooled 37.22.0
Mean difference -2.22.0
Mean absolute difference 7.81.3
95% Confidence interval 2.5
Coefficient of variation 12.5%
Cross-sectional compliance, 10~7m2/kPa 12.21.1 12.31.0
Pooled 12.21.0
Mean difference -0.030.8
Mean absolute difference 2.80.5
95% Confidence interval 1.0
Coefficient of variation 14.4%
Values are meanSEM where indicated. Difference and pooled data were calculated for each
subject (n=26).

fects. Therefore, with little extra effort, these studies
could provide useful additional data from M-mode
ultrasound on the determinants and consequences of
increased arterial stiffness and reduced compliance and
the effects of treatments, including reduction of blood
pressure and blood cholesterol.
Although this study was not designed to assess di-
rectly the validity of these indices of arterial distensibil-
ity and compliance, the results do provide indirect
evidence of relevance to this. The observations that the
pressure-strain elastic modulus and Young's modulus
were directly related to age, while the distensibility
coefficient and cross-sectional compliance were in-
versely related to age, are consistent with other evi-
dence obtained with various techniques indicating that
arterial stiffness increases838 and compliance decreas-
es 911 with age. Moreover, the observations that the
pressure-strain elastic modulus was positively related to
carotid artery wall thickness, while the distensibility
coefficient and cross-sectional compliance were in-
versely related to carotid artery wall thickness after
adjustment for age, are consistent with other evidence
that suggests that increased arterial stiffness is the result
of changes in the composition of the artery wall.39"41
Taken together these results suggest that the carotid
M-mode-derived indices of arterial stiffness and com-
pliance are valid. However, studies comparing these
indices with those derived from other methods such as
applanation tonometry or pulsed Doppler velocitome-
try would be useful to further establish the validity of
this simple method.
Acknowledgments
This study was supported by a grant from the National Heart
Foundation of New Zealand. Dr MacMahon is the recipient of
a Senior Research Fellowship from the Health Research
Council of New Zealand. The technical assistance of Colleen
Ciobo and Sue Flett is gratefully acknowledged.
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