From the Diagnostic Radiology Department, Warren Grant Magnuson Clinical
Center, National Institutes of Health (R.M.S., J.A.-B., I.M.F., S.C.H.,
E.C.J., M.K.B., B.W., K.E.B.), and the National Heart, Lung, and Blood
Institute (B.A.R., E.T., J.M.H.), Bethesda, Md; and Children's Hospital
of Philadelphia and University of Pennsylvania School of Medicine (T.L.S.).
Correspondence to Ronald M. Summers, MD, PhD, Diagnostic Radiology Department, Bldg 10, Room 1C660, 10 Center Dr, MSC 1182, Bethesda, MD 20892-1182. E-mail rms{at}nih.gov
Methods and Results—Morphological assessment of the aortic root
was done with spin-echo and gradient-echo MRI scanning. Comparisons
were made with a number of measures of disease severity, including
cholesterol-year score, calcium score on electron-beam CT
(EBCT), and size of Achilles tendon xanthomas. Atherosclerotic plaque,
visible on fat-suppressed images but never on water-suppressed images,
was present in 9 HFH patients (53%). Supravalvular aortic
stenosis was present in 7 patients with HFH (41%). Maximum
supravalvular aortic wall thickness was significantly greater
and OD and lumen cross-sectional area (CSA) were smaller in patients
than in control subjects (P=0.006, 0.0005, and 0.06,
respectively). Maximum wall thickness was associated with a greater
calcium score on electron-beam CT (P=0.02). Although the
cumulative exposure of the aortic root to cholesterol (the
cholesterol-year score) was significantly correlated with
the Achilles tendon CSA and vascular calcification, this score did not
correlate with the wall thickness or aortic CSA.
Conclusions—This study not only demonstrates the utility of MRI
for detecting and characterizing aortic root atherosclerotic plaque and
supravalvular aortic stenosis in HFH patients but also
suggests that the LDL receptor plays a direct or indirect role in
aortic mural development and vascular growth.
Familial hypercholesterolemia is an autosomal
dominant disease characterized by elevated LDL in the blood. The
primary defect is a mutation in the gene for the receptor for plasma
LDL.2 More than 150 different mutations are known
to exist. The gene defect causes a deficiency in the number of
functioning LDL receptors. Because of this deficiency, LDL removal from
the blood is impeded and excess LDL accumulates in scavenger cells,
producing xanthomas and atheromas.2
Phenotypic homozygotes, although rare (numbering 1 in 1 million
persons), are the most severely affected because their cells take up
little or no LDL. Treatment includes cholesterol-lowering
drugs, plasmapheresis, coronary artery bypass surgery, and in
some cases, liver transplantation.5
Because atherosclerosis is such a frequent finding in
HFH, patients with HFH serve as a useful model for the understanding of
atherosclerosis. New evidence suggests that
atheromata in the aortic root may be a heretofore
unrecognized cause of cerebral ischemic
events.6 Thus, the high frequency of aortic root
lesions in HFH patients lends another rationale for the development of
techniques to detect these lesions.
In this study, we evaluated the aortic root in HFH patients and normal
volunteers by MRI to detect the presence and location of plaque, to
assess morphological (wall thickness, CSA) and
hemodynamic (valvular
regurgitation, turbulence) features, and to correlate
these findings with serum cholesterol and duration of
disease in the patients. Findings were also correlated with the
presence of aortic root calcification on EBCT and ankle xanthomas
demonstrated by CT. We investigated several MRI pulse sequences to
evaluate which ones were most efficacious for detecting plaque. The
study was done prospectively, with image analysis done by
investigators blinded to the clinical history. To the best of our
knowledge, this is the first reported MRI study of the aortic root
lesions in HFH and the first to suggest that the LDL receptor may be
important for vascular growth.
Although there was no statistical difference between the age
distributions of normal volunteers and HFH patients
(P=0.32), there were 6 patients <18 years of age and no
normal volunteers under this age. We were unable to recruit pediatric
volunteers because we were not approved to do so through our
Institutional Review Board. Written informed consent was obtained for
all subjects, and the study was done after Institutional Review Board
approval. Anthropometric data (height, weight, blood pressure, and
heart rate) were obtained from all patients and from the majority of
the volunteers (Table 1
The diagnosis of HFH was based on plasma lipoprotein analysis
and family history.7 The patients were subject to
a number of cardiovascular complications (Table 2
The severity and duration of
hypercholesterolemia in the patients were
determined by use of the "cholesterol-year score." This
score is computed by multiplying the initial serum
cholesterol value (in mg/dL) by the age at diagnosis to
compute the pretreatment score and then adding the annually determined
posttreatment total cholesterol
values.7
MRI Scanning
Oblique axial spin-echo images of the aortic root and proximal
ascending aorta transverse to the lumen were obtained with a
phased-array surface coil. The imaging sequence used ECG gating, fat
suppression, and respiratory compensation, with 5- or 7-mm slice
thickness, no interslice gap, 18-cm FOV, 256x160 matrix, NEX=2, TR=1
RR interval, and TE=12 ms. Saturation bands were placed above, below,
anterior to, and posterior to the aortic root. The superior and
inferior saturation bands suppressed MR signal from flowing
blood, which otherwise could lead to image artifacts. Nonsuppressed and
water-suppressed sequences were also done. The number of images
obtained depended on heart rate but ranged from 5 to 11 images.
Oblique axial gradient-echo cine images perpendicular to the long axis
of the aorta were obtained at 16 phases of the cardiac cycle at each of
3 contiguous levels in the supravalvular aortic root of 12
patients and 9 normal control subjects. Gradient-echo images were added
to the imaging protocol after the beginning of the study. The imaging
parameters were TR=99 ms, TE=9 ms with fractional echo,
7-mm slice thickness and 7-mm gap, 18-cm FOV, flip angle 20°,
256x160 matrix, 16-kHz bandwidth, and NEX=2. Both respiratory and flow
compensation were used. Gradient-echo images on 3 HFH patients that
were of unacceptable quality because of technical failure were
discarded from the analysis.
EBCT was done as part of a different arm of our institution's protocol
on HFH. Transaxial scans through the thorax were done with ECG gating
on an Imatron scanner with settings of 130 kV, 620 mA, 100-ms exposure,
slice thickness 3 mm, and FOV=15 cm. Calcium scores, which
represent the total amount of calcium in the coronary
arteries and thoracic aorta, were derived from region-of-interest
measurements.9 10
Achilles tendon CT was done to assess for the presence of
xanthomas.11 The ankles were scanned without the
use of intravenous contrast in the flexed position with
toes pointing straight up. Scans were obtained with 120 kVp, 280 mA,
1-second exposure, contiguous slice thickness 10 mm, and FOV as
small as possible to include both tendons. The CSAs of the tendons were
measured bilaterally at the maximal diameter by hand
tracing.7
Image Analysis
We tested the hypothesis that the aortic root is small in patients with
HFH. The CSA of the aortic root was measured just superior to the sinus
of Valsalva. This location was chosen because of the known tendency of
HFH patients to develop supravalvular aortic stenosis.
Measurements were made from the gradient-echo cine images at end
diastole (first phase after the R wave) by tracing the
outer contour of the bright signal from flowing blood. Each measurement
of CSA was made 3 times, and the mean was computed. To test the effect
of body habitus on the results, CSA was normalized to BSA or weight.
BSA was computed from weight and height.12
The presence of supravalvular aortic stenosis was
determined from the fat-suppressed images. The 2 images just above the
sinus of Valsalva were examined, and supravalvular aortic
stenosis was diagnosed if the transverse inner dimension of the
aorta on the more inferior slice (just above the sinus) was
<90% of that from the more superior slice. The choice of 90% as a
cutoff was made on the basis of our observations of the normal control
subjects.
The transverse IDs and ODs of the aortic root on the first
supravalvular section were measured from the fat-suppressed
images by a single observer as another determination of aortic root
hypoplasia. The transverse dimension was chosen because the outer wall
of the aortic root could be reliably determined there.
The presence on gradient-echo images of turbulence or jets indicative
of abnormal flow states (including aortic stenosis or
regurgitation) was recorded.
Unpaired 2-tailed t tests were performed to determine the
significance of comparisons between data from the control group and the
patients, with P<0.05 considered significant. Pearson's
correlation (r value) was computed to test significance of
cholesterol-year score and calcium score with MRI
morphometry of wall thickness, diameter, and CSA. Intraobserver and
interobserver variabilities were expressed as a coefficient of
variation computed from 3 measurements by a single observer and
measurements from 3 different observers of a
representative random subset of the data from 6
patients.13
The fat-suppressed images were best for measuring wall thickness
(Figures 2
Plaques were visible on MRI studies from 9 patients and appeared as
irregular focal or diffuse wall thickening (Figure 3
The average wall thickness measured on the first supravalvular
section was 3.3±1.2 mm (range, 1.8 to 6.9 mm) in the
patients and 2.3±0.5 mm (range, 1.7 to 3.3 mm) in the normal
control subjects (P=0.004). The maximum wall thickness
measured on the first supravalvular section was also greater in
the patients than in the normal control subjects (Table 1
Analysis of regional wall thickness showed that the wall
thickness of the patients' aortas was uniformly greater on average
than that of the control subjects at all positions around the clock
face. The greatest statistically significant difference was on the left
side, at the 3 o'clock position (P=0.001), and the least
significant difference was at the 11 o'clock position
(P=0.2). When patients who had plaque were compared with
those without plaque, the wall thicknesses in the supravalvular
aortic root were also uniformly greater.
Seven HFH patients had evidence of supravalvular aortic
stenosis. Of these 7 patients, 6 also had evidence of plaque in
the aortic root.
Measurements of supravalvular aortic CSA showed that the aortic
cross section is smaller in patients than in control subjects, although
this result was not statistically significant (P=0.06)
(Table 1
Both the IDs and ODs of the supravalvular aortic root were
significantly smaller in patients than in normal control subjects
(P<0.0005; Figure 6
Turbulence was identified at the level of the aortic valve in 2
patients and no control subjects. Turbulent flow was identified on the
cine images by the presence of flow void that entirely filled the lumen
during peak systole. Very high flow rates can also produce this flow
void. One patient with turbulence had an aortic root graft and aortic
valve prosthesis in place. The second patient had aortic
valvular stenosis and marked thickening of the aortic
valve leaflets. Jets of aortic insufficiency were identified in 5
patients and no control subjects.
There was a mild correlation between aortic OD corrected for BSA and
cholesterol-year scores, although the correlation was not
statistically significant (P=0.06, r=-0.46;
Figure 7
There was a strong correlation between aorta calcium score and
cholesterol-years (r=0.80, P=0.0002).
The combined Achilles tendon CSA was also strongly correlated with
cholesterol-years (r=0.88,
P=0.000003).
For the patients, no associations were found with age or sex for either
maximum wall thickness or aorta CSA (P
The coefficients of variability for intraobserver and interobserver
measurements were 10% (95% CI, 8% to 12%) and 24% (20% to 28%),
respectively, reflecting a mean SD of wall thickness of 0.3 and
0.8 mm, respectively.
We found a significant correlation between maximum wall thickness
measured on MRI and the aortic root calcium score determined from EBCT.
This finding is not surprising, because plaques can cause an apparent
focal thickening of the wall (detectable on MRI) and plaques can
calcify (detectable on EBCT).
A correlation between severity and duration of
hypercholesterolemia and volume of plaque
calcification on EBCT has previously been demonstrated in the setting
of HFH.8 We confirmed the correlation between
disease severity (cholesterol-years) and calcium score in a
larger patient population, and we detected plaques in the aortic root,
but we were unable to confirm a statistically significant correlation
between disease severity and either presence of plaque or thickness of
the aortic wall.
We found that plaques tended to be on the left side, although the wall
thickness was greater at all locations along the aortic wall. The
reason for this discrepancy is unknown. Studies have shown that
atherosclerotic plaque and intimal thickening tend to form in areas of
recirculation and low wall shear stress,14 15
possibly because of differential gene
expression.16 Geometric factors, such as the
curvature of the aortic arch, are also known to be
important.17 18 Perhaps the aortic annular
abnormalities and supravalvular aortic stenosis modify
the blood flow velocity profiles into a pathological configuration that
predisposes to plaque formation in these locations.
Supravalvular aortic stenosis was present in 41%
of patients. Overall, the CSA of the supravalvular aortic root
was 23% smaller, the ID was 22% smaller, and the OD was 19% smaller
in the patients than in the control subjects, although these
differences disappeared when the measurements were corrected for body
weight or surface area. Plaques were found in 86% of the patients with
supravalvular aortic stenosis, although the plaques
were not always present on the section just above the sinus of
Valsalva, on which the diagnosis of stenosis was made. We did
not measure the outer CSA of the aorta. Therefore, the smaller inner
CSA in the patients could be due to wall thickening encroaching on the
lumen or to a small aorta. The lumen diameter data, however, suggest
that the aorta is small.
Supravalvular aortic stenosis is a characteristic
feature of HFH.4 19 20 The cause of the
supravalvular aortic stenosis in HFH is unknown. One
possible explanation is that it is due to altered growth of the vessel
wall, because the atherosclerosis of HFH occurs at such
an early age (E.C.J. et al, unpublished observations). High LDL
concentrations might repress the expression of genes related to aortic
growth. The lack of correlation of the lumen CSA and
cholesterol-year scores would seem to refute these
hypotheses. However, it may be the levels of LDL
cholesterol during childhood that are important, rather
than cumulative cholesterol-years. Alternatively, LDL
receptor expression may be important for cellular growth and
proliferation. Rapidly dividing cells express high levels of LDL
receptors.21 22 23 In the absence of normal LDL
receptors, the growth of the ascending aorta may be arrested in these
patients.
We were able to see aortic root thickening consistent with
atherosclerotic plaques on MRI of 9 patients with HFH. In the
evaluation of clinical atherosclerotic disease, the role of MRI has
been primarily to detect stenoses and occlusions of the
arteries rather than to visualize the plaque itself. However,
atherosclerotic plaques can also be visualized on
MRI,24 and the first in vivo MRI studies of
atherosclerotic plaques in patients are beginning to
appear.25 26
In our study, plaques were seen only on fat-suppressed images and
never on water-suppressed images. This finding is consistent
with results of other studies. For example, 1 study showed that plaques
are well seen on fat-suppressed images and better discriminated from
periadventitial fat than on conventional spin-echo
images.27 In that study, the plaques became
invisible after water suppression. This was attributed to the
negligible amount of isotropic (liquidlike) signal from
immobilized lesion lipids. Spectroscopy showed the lipid
resonance to be broad and ill-defined. A later study of excised human
arteries with atherosclerotic plaque also found that fat suppression
did not significantly change the appearance of the
plaque.28 Because the spectral width of the
fat-suppression pulse is relatively narrow, the lipids in plaque (some
of which have a broad peak) are not suppressed, but the
triglycerides in periadventitial fat (which have a
relatively narrow peak) are suppressed.
In our study, the plaques had a relatively bland appearance, with
little apparent structure. Calcific plaques were poorly seen at MRI,
and the size of plaque calcifications on EBCT corresponded poorly with
the MRI appearance. Our results suggest that MR shows wall thickening
better when calcifications are absent in contrast to CT.
This study has several limitations. The spin-echo images were all
parallel to one another. Therefore, some of the images were oblique to
the true cross section of the aorta. This could cause an artifactual
thickening of the aortic wall as the aorta curves relative to the plane
of section. We compensated for this limitation by orienting the slices
correctly for the supravalvular aortic root and using only 3 to
5 of the 9 images in the spin-echo data set, thus spanning only 2 to 4
cm of aorta. Images in which the aorta was grossly oblique to the
imaging plane were discarded from further analysis, but subtle
biases in the data due to this effect could still occur. Another
limitation was that, although gated to the ECG, each image was obtained
at a different phase of the cardiac cycle. Thus, some images of the
aortic root were obtained during systole and others during
diastole. However, both the patients and the control
subjects were scanned by the same technique. Also, one would not expect
the appearance of plaque to change significantly between systole and
diastole. These limitations were due to constraints imposed
by limited MRI scanning time and the duration of scanning tolerable to
patients in 1 sitting. Gradient-echo imaging was begun after the
beginning of the study, and 3 HFH patients had gradient-echo images of
unacceptable quality. Therefore, only a subset (two thirds) of the
subjects had CSA measurements. This limitation is reflected in the
poorer correlations for the CSA data. Diameter measurements were not
subject to this limitation, however. There were significant
anthropometric (age, BSA) differences between patient and control
groups, and thus, they were not perfectly matched. This was unavoidable
because HFH strikes patients when they are young, and we were not
allowed to scan normal children. We controlled for these differences by
performing subgroup analyses.
To date, detection of aortic root and arch
atherosclerosis is not a standard part of a
cardiovascular workup and is often an incidental
finding. For example, calcified plaques are often detected on CT scans
of the chest in elderly patients. However, a recent study has shown
that increased aortic wall thickness is a risk factor for recurrent
ischemic stroke.6 We have shown that MRI
scanning with a standard clinical MRI scanner can detect such wall
thickening in the setting of HFH, a model system for the study of
atherosclerosis.
In summary, we have shown that patients with HFH have a thicker-walled
aortic root, supravalvular aortic narrowing, and smaller aortas
than normal age-matched control subjects and that conventional
fat-suppressed ECG-gated spin-echo MRI was optimal for visualizing wall
thickening due to atherosclerotic plaque. Moreover, the significant
reduction in the OD in these patients implies a direct or indirect role
for the LDL receptor in aortic growth and development.
Received October 13, 1997;
revision received March 23, 1998;
accepted April 5, 1998.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Evaluation of the Aortic Root by MRI
Insights From Patients With Homozygous Familial Hypercholesterolemia
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—In homozygous familial
hypercholesterolemia (HFH), the aortic root is
prone to develop atherosclerotic plaque at an early age. However, the
aortic wall and plaque have not yet been assessed in this condition by
MRI. We evaluated the aortic root by use of MRI in 17 HFH patients and
12 normal control subjects in a prospective, blinded, controlled
study.
Key Words: atherosclerosis • magnetic resonance imaging • vasculature • cholesterol • aorta
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Homozygous familial
hypercholesterolemia is an uncommon inherited
form of hypercholesterolemia that serves as a
model for our understanding of the development of
atherosclerosis. Patients with HFH have extremely high
serum cholesterol levels and may develop advanced
atherosclerotic plaque before 10 years of age.1
The plaque formation can occur at unusual sites, including the
ascending aorta and around the coronary
ostia.2 These atheromata can
interfere with aortic valve function3 and cause
patients to present with angina, myocardial infarction, and even
sudden death.4
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Patient Population
Seventeen HFH patients and 12 normal, healthy volunteers were
studied. Demographic data are summarized in Table 1
. The HFH patients
represent a consecutive series referred to our center for
treatment. We estimate that our institution (National Institutes of
Health, Bethesda, Md) sees one third to one half of all patients with
HFH in the United States. Other characteristics of some of these HFH
patients have been reported previously.7 8 Two
patients and 2 normal volunteers were scanned more than once. For these
subjects, only data from the first complete MR imaging session were
used.
View this table:
[in a new window]
Table 1. Summary of Clinical and MRI
Data 
). ). Patients and control
subjects were not similar with regard to history of hypertension,
smoking history, or diabetes, and we did not attempt to control for
these factors.
View this table:
[in a new window]
Table 2. Cardiovascular Disease of HFH Patient
Group
All MRI scanning was done on a 1.5-T Signa MR unit (General
Electric Medical Systems). Imaging included spin-echo and gradient-echo
sequences.
Measurements of aortic wall thickness were made on the first
image of the supravalvular ascending aorta above the sinus of
Valsalva. Additional images through the ascending aorta were evaluated
for focal abnormalities; the number of useful additional images
depended on the length of the ascending aorta and its curvature,
because the images were all parallel and contiguous. If a focal area of
thickening was present, it was measured and its location
recorded. The aorta appears round on oblique axial cross-sectional
images and can be represented as a clock face, with 12
o'clock and 3 o'clock representing the anterior and left
walls, respectively. Measurements were made at the 12 positions around
this clock face to assess regional variations in wall thickness. A
measurement could be made only if both sides of the vessel wall were
delineated. Occasionally, the outer wall could not be detected if there
was insufficient contrast with mediastinal tissue (eg,
myocardium, adjacent vessels, mediastinal soft tissues).
The position of the outer wall was revealed best by suppression of the
adjacent fat. A visual approach was used to determine wall position.
These measurements were made by a single observer blinded to the
clinical data by use of random code numbers assigned to each MRI study.
Average and maximum wall thicknesses on the first supravalvular
section and regional wall thickness averaged on the first 2
supravalvular sections at each of the 12 positions around the
clock face were determined. Focal or diffuse areas of wall thickening
were designated as areas of plaque formation.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
A typical image of the ascending aorta is shown in both a normal
volunteer and a patient with HFH (Figure 1). Note the thickening of the wall of
the aorta and narrowing of the lumen in the patient study. The patient
and the normal volunteer are the same age and sex, yet the diameter of
the patient's ascending aorta is one half that of the normal
volunteer. The BSA for the patient was 29% less than that of the
normal volunteer, however (1.5 versus 2.1
m2).
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Figure 1. Comparison of 21-year-old male normal
volunteer (left) and 21-year-old male HFH patient (right).
Fat-suppressed spin-echo MR images transverse to supravalvular
aortic root shown in same magnification. Small ascending aorta and
thickened wall (arrows) are dramatic in this patient. Bar (right) =1
cm. and 3). The nonsuppressed and the
water-suppressed sequences were less useful. On nonsuppressed images,
the mediastinal fat overlapped a portion of the vessel wall, obscuring
it and making it difficult to measure its thickness, because of
chemical shift artifact. On water-suppressed images, only the
mediastinal fat remained in the images; the aortic wall and plaques
became invisible. The fat-suppressed sequence was best because it
avoided the chemical shift artifact and did not suppress the
plaques.
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Figure 2. Effect of MR imaging parameters on
visualization of aortic root. Transverse spin-echo MR image of
supravalvular aortic root in a normal 27-year-old female
volunteer. Nonsuppressed (left), fat-suppressed (middle), and
water-suppressed (right) images are shown. On the nonsuppressed images,
chemical-shift artifact causes periaortic fat to overlap vessel wall,
limiting delineation of wall. On water-suppressed images, aortic wall
is invisible. Greatest circumference of aortic wall (arrows) is
delineated best on fat-suppressed image.
View larger version (168K):
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Figure 3. Effect of MR imaging parameters on
visualization of aortic root and plaque. Top and bottom left,
Transverse spin-echo MR images of supravalvular aortic root in
a 4-year-old female HFH patient. Nonsuppressed (top left),
fat-suppressed (top right), and water-suppressed (bottom left) images
are shown. Right main coronary artery is visible (small arrow).
Aortic wall is asymmetrically thickened on patient's left side (large
arrow). Thickened wall, presumably due to plaque, is invisible on
water-suppressed images. Bottom right, EBCT at same level also shows
right main coronary artery (small arrow) and thickened wall of
aorta (large arrow). ). All involved the
left wall of the aorta and were similar in signal intensity to and
indistinguishable from the wall. Comparison of nonsuppressed and
fat-suppressed images showed no obvious fat within the plaques. In 2
patients with known calcific plaque, there was reduced signal intensity
within the plaque on MRI (Figure 4).
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Figure 4. Forty-eight-year-old female
HFH patient with focal wall thickening corresponding to calcified
plaque. Top, Transverse spin-echo MR images of supravalvular
aortic root. Nonsuppressed (left) and fat-suppressed (right) images
show focal aortic wall thickening on patient's left (arrows). Bottom,
EBCT at same level shows circumferential calcified plaque that is
thickest on patient's left (arrow), corresponding with MR finding in
same location. In this example, plaque signal intensity is suppressed
by calcification. Note that EBCT images are obtained axially with
respect to patient, whereas MR images are oblique to patient and axial
with respect to aorta, accounting for differing appearance of main
pulmonary artery (open
arrow). and Figure 5). The latter measurement would tend to
reflect the presence of a focal lesion or plaque.
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Figure 5. Maximum wall thickness for normal control subjects
vs HFH patients. Some data points reflect multiple patients. ). Six patients had CSA <400 mm2,
but only 1 control subject did. When these data were normalized to BSA
or body weight, the correlation was poorer and the normalized CSA
values were larger in patients than in control subjects
(P=0.91 and 0.20, respectively). Normalization to BSA or
body weight heavily weighted data from children <12 years old. In
addition, HFH patients were shorter, weighed less, and had lower BSA
than normal control subjects. Because of these characteristics of the
HFH patients, we did a subgroup analysis comparing the 8 adult
HFH patients 
18 years of age with the normal control subjects. Only
patients who had had gradient-echo MR images were included in this
subgroup. For the subgroup, CSA, CSA corrected for body weight, and CSA
corrected for BSA were also not statistically significant
(P>0.25), although the normalized values were smaller than
those for the normal control subjects. ). On
average, the IDs and ODs were 5.5 and 5.8 mm smaller in patients
than in normal subjects, respectively. The disparity in diameter
between patients and control subjects held true if adult patients alone
were considered (P=0.03) but not for BSA-corrected diameter
measurements for adults (P<0.09).
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Figure 6. ODs of supravalvular aorta for normal
control subjects vs HFH patients. Some data points reflect multiple
patients. ). Wall thickness (both maximum
and average) and lumen CSA were not associated with
cholesterol-year scores (P0.23). When MRI
studies on HFH patients were segregated into 2 groups, those with (n=9)
and those without (n=8) plaque on MRI, there was still no statistically
significant association with cholesterol-year score
(plaque: 17 300±10 100; range, 3100 to 32 300; without plaque:
10 100±7000; range, 4200 to 23 200; P=0.11).
View larger version (14K):
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Figure 7. Cholesterol-year score vs OD corrected
for BSA. Line through data represents result of linear
regression fit (r=-0.46, P=0.06). 0.27). The combined
Achilles tendon CSA measurements were not correlated with either
maximum wall thickness, aorta CSA, or average wall thickness
(P0.07). Aortic calcium score was correlated with maximum
wall thickness (r=0.59, P=0.02) but with neither
aortic root CSA nor average wall thickness (P0.09). The
calcium score/wall thickness correlation was heavily weighted by 3
outliers. Neither tendon size nor calcium scores were associated with
the presence of plaque (P0.09).
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
Our results demonstrate that the wall thickness of the ascending
aorta is increased in patients with HFH. Although this was partly
because of the presence of focal plaques, there may be a generalized
component of wall thickening that is consistent with the known
medial hyperplasia present in this disorder. Generalized wall
thickening was most apparent in the youngest patients, for unknown
reasons (Figure 3). Because plaques can regress with treatment, serial
MRI of the aortic root may be useful in HFH patients to determine
prognosis and response to therapy.
Selected Abbreviations and Acronyms
BSA
=
body surface area
CSA
=
cross-sectional area
EBCT
=
electron-beam CT
FOV
=
field of view
HFH
=
homozygous familial hypercholesterolemia
NEX
=
number of excitations
Acknowledgments
We thank Andrew Dwyer, MD, for critical review of the manuscript
and Kim Gallagher for assistance with data entry and manuscript
preparation.
Footnotes
Presented at the Fourth Scientific Meeting of the International Society for Magnetic Resonance in Medicine, New York, NY, April 27–May 3, 1996, and NIH Clinical Center Grand Rounds, Bethesda, Md, April 9, 1997.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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  V. L. Wright, W. Olan, B. Dick, H. Yu, N. Alberts-Grill, L. L. Latour, and A. E. Baird Assessment of CE-MRA for the rapid detection of supra-aortic vascular disease Neurology, July 12, 2005; 65(1): 27 - 32. [Abstract] [Full Text] [PDF]
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 A. E. Li, I. Kamel, F. Rando, M. Anderson, B. Kumbasar, J. A. C. Lima, and D. A. Bluemke Using MRI to Assess Aortic Wall Thickness in the Multiethnic Study of Atherosclerosis: Distribution by Race, Sex, and Age Am. J. Roentgenol., March 1, 2004; 182(3): 593 - 597. [Abstract] [Full Text] [PDF]
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 L. L. Demer and Y. Tintut Mineral Exploration: Search for the Mechanism of Vascular Calcification and Beyond: The 2003 Jeffrey M. Hoeg Award Lecture Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1739 - 1743. [Abstract] [Full Text] [PDF]
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 M. Podbregar, B. Krivec, and G. Voga Impact of Morphologic Characteristics of Central Pulmonary Thromboemboli in Massive Pulmonary Embolism* Chest, September 1, 2002; 122(3): 973 - 979. [Abstract] [Full Text] [PDF]
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 Z. A. Fayad and V. Fuster Clinical Imaging of the High-Risk or Vulnerable Atherosclerotic Plaque Circ. Res., August 17, 2001; 89(4): 305 - 316. [Abstract] [Full Text] [PDF]
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 Z. A. Fayad, T. Nahar, J. T. Fallon, M. Goldman, J. G. Aguinaldo, J. J. Badimon, M. Shinnar, J. H. Chesebro, and V. Fuster In Vivo Magnetic Resonance Evaluation of Atherosclerotic Plaques in the Human Thoracic Aorta : A Comparison With Transesophageal Echocardiography Circulation, May 30, 2000; 101(21): 2503 - 2509. [Abstract] [Full Text] [PDF]
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A. Russo, M. De Luca, C. Vigna, Vincenzo De Rito, M. Pacilli, A. Lombardo, M. Armillotta, R. Fanelli, and F. Loperfido Central Pulmonary Artery Lesions in Chronic Obstructive Pulmonary Disease : A Transesophageal Echocardiography Study Circulation, October 26, 1999; 100(17): 1808 - 1815. [Abstract] [Full Text] [PDF]
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