Right coronary wall CMR in the older asymptomatic advance cohort: positive remodeling and associations with type 2 diabetes and coronary calcium.

Abstract

Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort.
Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03).
Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.

Full text

Page 1

RESEARCHOpen Access
Right coronary wall cmr in the older
asymptomatic advance cohort: positive
remodeling and associations with type
2 diabetes and coronary calcium
Masahiro Terashima1, Patricia K Nguyen1, Geoffrey D Rubin2, Craig H Meyer3, Ann Shimakawa4,
Dwight G Nishimura5, Shoichi Ehara1, Carlos Iribarren6, Brian K Courtney1, Alan S Go6,7,
Mark A Hlatky1,8, Stephen P Fortmann9, Michael V McConnell1,5*
Abstract
Background: Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to
assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The
purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort.
Results: Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood
coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular
disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and
wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of
these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased
coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was
the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007,
respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03).
Conclusions: Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis
in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the
noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.
Introduction
Noninvasive imaging techniques to assess subclinical
coronary atherosclerosis have the potential to identify
patients at higher risk for future coronary events and
guide lifestyle modifications and pharmacological ther-
apy to maximize cardiovascular risk reduction. Over the
last decade, significant progress has been made in the
development of coronary magnetic resonance angiogra-
phy using a variety of techniques [1-5]. However, the
assessment of coronary artery luminal narrowing has
limited value for the detection of subclinical coronary
atherosclerosis because the coronary artery lumen size is
often preserved by positive arterial remodeling[6].
Therefore, direct noninvasive imaging of the coronary
artery wall is an important target for cardiovascular
imaging.
While coronary wall imaging by cardiovascular mag-
netic resonance (CMR) is challenging due to the small
size of coronary arteries and cardiac/respiratory motion,
it has been successfully applied in patients using breath-
hold[7-9] or respiratory gating (i.e., free-breathing) tech-
niques[10-14]. Using these techniques, significant
increases in coronary wall area and wall thickness have
been found in patients with documented coronary artery
disease[10,12] and in those with type 1 diabetes mellitus
plus nephropathy [13]. The MESA study more recently
* Correspondence: mcconnell@stanford.edu
1Division of Cardiovascular Medicine, Stanford University School of Medicine,
Stanford, CA, USA
Full list of author information is available at the end of the article
Terashima et al. Journal of Cardiovascular Magnetic Resonance 2010, 12:75
http://www.jcmr-online.com/content/12/1/75
© 2010 Terashima et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Page 2

showed positive arterial remodeling by coronary wall
CMR in 179 asymptomatic participants[14]. There are
limited data on evaluating subclinical atherosclerosis in
older patient groups, who are at increased risk for cor-
onary events.
We have investigated clinical, imaging, and genetic
abnormalities in an at-risk (i.e., older) community-based
patient cohort - the Atherosclerotic Disease, Vascular
Function, and Genetic Epidemiology (ADVANCE) study
[15,16]. Here we report on coronary wall CMR in this
older, asymptomatic cohort to assess image quality,
measurement variability, remodeling, and risk factor
associations.
Methods
Study Patients
This was an CMR sub-study of 223 participants from
the ADVANCE study of 1023 older subjects (age 60 to
72 years, 34% women) with details on the patient cohort
published previously[5,16]. Briefly, subjects without a
known history of cardiovascular disease or other major
comorbidities were randomly selected from the mem-
bership of Kaiser Permanente of Northern California.
All subjects were studied through the Stanford Preven-
tion Research Center. Coronary risk factors were mea-
sured using standardized protocols[17]. Diabetes
mellitus was defined as self-report of physician-
diagnosed diabetes, use of diabetes medication, or fasting
blood glucose ≥ 126 mg/dl at the study visit[18]. Hyper-
tension was defined as use of antihypertensive medica-
tion or blood pressure ≥ 140/90 mmHg at study visit.
Multi-detector row spiral computed tomography (CT)
was used to quantify coronary artery calcification (CAC)
by the Agatston score, as previously reported[16,19].
Written informed consent was obtained from all parti-
cipants. The study protocol was approved by the Institu-
tional Review Boards of Stanford University and the
Kaiser Foundation Research Institute.
Coronary Wall Imaging by CMR
A 1.5T Signa MR scanner (GE Healthcare, Waukesha,
WI) was used, equipped with high-performance gradi-
ents (40 mT/m, 150 mT/m/ms) and a commercial
4-channel cardiac phased-array surface coil (GE Health-
care, Waukesha, WI). A real-time interactive MR system
(iDrive, GE Healthcare, Waukesha, WI) was used for
coronary localization. For determination of the most
quiescent period of the right coronary artery (RCA)
within the cardiac cycle, a 2 D cine scan was performed
in the 4-chamber view. High-resolution bright-blood
coronary MRA, as previously reported[1,20], was per-
formed to obtain in-plane views of the right coronary
artery (RCA). Then, 3 cross-sectional coronary wall
images of a linear portion of the proximal-to-mid RCA
were acquired with 3 separate breathholds using a spiral
black-blood coronary CMR sequence, with cardiac gat-
ing and acquisition during the previously identified
patient-specific quiescent period. This sequence used an
interleaved spiral k-space trajectory technique incorpor-
ating 1) double-inversion preparation (DIR) to null the
blood signal, 2) spectral-spatial excitation for water-
selective imaging, and 3) spiral readout (field of view =
22 cm, in-plane spatial resolution = 0.7 mm, slice thick-
ness = 5 mm, slice gap = 0 mm, DIR thickness =
10 mm, TR = 1 heart beat, TE = 2.5 ms, TI = 280-350
ms adjusted for heart rate, flip angle = 90°, 18 inter-
leaves, temporal acquisition window = 34 ms, scan time
typically 20 sec per breathhold)[9].
MR Image Analysis
Using the 3 cross-sectional RCA wall images, the image
where the RCA wall exhibited the best image quality
and the most circular cross-section was identified.
Before quantitative analysis, image quality was rated on
the MR images using a 4-point scale (4 = good, 3 = fair,
2 = poor, and 1 = very poor) based on signal-to-noise
ratio (SNR), vessel border sharpness, and artifacts[21].
An image quality of 3 or above was considered adequate
for quantitative analysis (Figure 1). These images were
all pooled and then analyzed, blinded to patient infor-
mation. Cross-sectional measurements of the total vessel
area (VA) and lumen area (LA) of the RCA were per-
formed manually using a custom-designed CMR analysis
software after the images were magnified two-fold[5,22].
The coronary wall area (WA) was calculated as WA =
VA-LA. The mean wall thickness (WT) was calculated
assuming a circular vessel shape: WT = (√VA-√LA)/√π.
All MR images were re-measured to assess intra- and
inter-observer variability.
Statistical Analysis
Continuous variables are expressed as means with stan-
dard deviations or medians with inter-quartile ranges.
Differences between two groups for continuous variables
Figure 1 Representative images of spiral black-blood coronary
wall CMR (arrows) showing patients at the low and high end for
mean coronary wall thickness (left - 1.27 mm, right - 2.06 mm).
Terashima et al. Journal of Cardiovascular Magnetic Resonance 2010, 12:75
http://www.jcmr-online.com/content/12/1/75
Page 2 of 7

Page 3

were compared using Student’s t-test or the Mann-
Whitney U test. Differences in categorical variables
among groups of interest were assessed using chi-
squared tests. Measurements variability was assessed by
both linear regression analysis and Bland-Altman analy-
sis. Multivariate regression analysis was performed to
identify predictors for increased coronary wall area and
wall thickness. Traditional coronary risk factors, such as
age, gender, body mass index (BMI), diabetes mellitus,
hypertension, total/HDL cholesterol ratio, and current
smoking were included in the final multivariate regres-
sion model. Spearman rank correlation analysis was per-
formed for the relationship between CAC (log [CAC+1])
and coronary vessel area, lumen area, wall area, and wall
thickness. A two-sided p value < 0.05 was considered
statistically significant and all analyses were performed
using StatView statistical software (SAS institute, Cary,
North Carolina).
Results
Subject Characteristics
The mean age was 66 ± 3 years, 33% were women, and
37% were non-Caucasian (Table 1). Hypertension was
common (56%), while 17% had type 2 diabetes mellitus
and <8% were cigarette smokers. CAC > 0 was present
in 78% (n = 173) of subjects.
Coronary Wall Image Quality, Measurement Variability,
Arterial Remodeling
Image quality of coronary wall CMR was >2 (fair or
good) in 67% of subjects, leaving a total of 150 subjects
for quantitative analysis. Bland-Altman analysis showed
small differences for the intra- and inter-observer mea-
surements of VA, WA, LA, and WT (Figure 2). The
intra- and inter-observer variabilities were also low by
linear regression analysis, with correlation coefficients of
0.93-0.99 (all p < 0.0001).
Mean coronary measurements by CMR were as follows:
VA = 32.1 ± 8.2 mm2, WA = 22.8 ± 5.9 mm2, LA = 9.3 ±
3.4 mm2, and WT = 1.48 ± 0.25 mm. VA increased with
increasing WT (r = 0.66, p < 0.0001, Figure 3), while LA
remained constant (r = 0.05, p = 0.6). The increase in VA,
but not LA, with an increase in WT is consistent with
positive arterial remodeling [10,14].
Subclinical Coronary Atherosclerosis by CMR and
Coronary Risk Factors
We compared coronary CMR measures to the clinical
risk factors listed in Table 1. By univariate analysis,
increased coronary WA and WT were associated with
male gender (WA: 23.6 ± 5.9 vs. 21.7 ± 6.0 mm2, p =
0.045; WT: 1.51 ± 0.24 vs. 1.43 ± 0.26 mm, p = 0.046),
diabetes (WA: 25.5 ± 6.2 vs. 22.4 ± 5.8 mm2, p = 0.04;
WT: 1.61 ± 0.25 vs. 1.46 ± 0.24 mm, p = 0.008), and
BMI (WA: r = 0.16, p = 0.046; WT: r = 0.2, p = 0.01).
Total/HDL cholesterol ratio was associated with WT
(r = 0.22, p = 0.008), but not WA. There were no signif-
icant associations between these risk factors and either
VA or LA.
In multivariate analysis (Table 2), gender and BMI
were no longer significant. Total/HDL cholesterol ratio
remained independently associated with WT (p = 0.03),
but not WA. Only diabetes was independently asso-
ciated with both coronary WA (p = 0.04) and WT (p =
0.007). Differences in coronary measures between dia-
betics and non-diabetics are shown in Figure 4.
Coronary Wall Measurements by CMR and Coronary
Artery Calcification
By Spearman rank correlation analysis, there was a sig-
nificant correlation of CAC with coronary VA (p =
0.01), WA (p = 0.01), and WT (p = 0.03) (r =
0.18~0.21), but not coronary LA (p = 0.07). All coronary
measurements were significantly increased in patients
with any calcification of the RCA (p < 0.005, Figure 5).
Discussion
We investigated coronary wall CMR in a cohort of
asymptomatic older subjects, which to our knowledge is
the largest group studied by coronary wall CMR to date
and the first to focus on patients > 60 years old. The
main findings were: 1) adequate coronary wall image
quality was achieved in two thirds of the subjects and
measurements had very good intra- and inter-observer
variability, 2) coronary wall measurements were consis-
tent with positive arterial remodeling, 3) coronary ather-
osclerosis by CMR was increased in subjects with type
2 diabetes and also 4) with increasing coronary
calcification.
While coronary wall image quality and measurement
variability have been reported in prior smaller studies,
our study extends these findings to a large older com-
munity-based cohort where image quality can be chal-
lenging. This study confirms the positive arterial
Table 1 Clinical Characteristics of Study Subjects
(n = 223)
Characteristic
Age (years)66.0 ±
2.7
149/74
27.0 ±
4.3
38 (17)
124 (56)
3.7 ± 1.0
17 (7.6)
Gender (men/women)
Body mass index (kg/m2)
Diabetes mellitus (n, %)
Hypertension (n, %)
Total/HDL cholesterol (mg/dL)
Current smoker (n, %)
Terashima et al. Journal of Cardiovascular Magnetic Resonance 2010, 12:75
http://www.jcmr-online.com/content/12/1/75
Page 3 of 7

Page 4

remodeling and association with coronary calcium
reported in the MESA study, but now also in a large
cohort of subjects over 60 years old. The association
with type 2 diabetes is novel.
Coronary Wall Imaging by CMR
Coronary wall CMR can be performed by breath-held
and free breathing methods. To date, it has been shown
to be reproducible in healthy volunteers[23,24] and to
detect increased wall thickness in selected patients with
known coronary artery disease, type 1 diabetes compli-
cated by diabetic nephropathy, and asymptomatic indivi-
duals from the MESA study[10,12-14,25].
In our study, the breath-held spiral black-blood coron-
ary CMR sequence provided adequate image quality in
67% of subjects (age 60-72 years). This was somewhat
lower than the 74% of coronary locations visualized that
had adequate image quality in the MESA study (where
the age ranged from 45 to 84 years[25]). There are a
number of factors that may contribute to inadequate
Intraobserver VA Differences (mm2)
VA Average (mm2)
A.
-6
-4
-2
0
2
4
6
8
152025 30354045505560
r=0.99, p<0.0001
B.
LA Average (mm2)
Intraobserver LA Differences (mm2)
-4
-3
-2
-1
0
1
2
3
4
5
6
2468 10 121416182022
r=0.94, p<0.0001
Intraobserver WA Differences (mm2)
WA Average (mm2)
C.
-8
-6
-4
-2
0
2
4
6
101520 2530 354045
r=0.97, p<0.0001
Intraobserver WT Differences (mm)
-0.5
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0.81.01.2 1.41.61.8 2.02.2 2.4 2.6
WT Average (mm)
D.
r=0.93, p<0.0001
Interobserver VA Differences (mm2)
VA Average (mm2)
-3
-2
-1
0
1
2
3
4
5
6
15 202530 3540 45 5055 60
E.
r=0.99, p<0.0001
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0
0.5
1.0
1.5
2.0
2.5
246810
LA Average (mm2)
121416 182022
Interobserver LA Differences (mm2)
F.
r=0.98, p<0.0001
-6
-4
-2
0
2
4
6
1015202530 354045
Interobserver WA Differences (mm2)
WA Average (mm2)
G.
r=0.98, p<0.0001
-0.25
-0.2
-0.15
-0.1
-0.05
0
0.05
0.1
0.15
0.2
0.25
0.811.2 1.41.6 1.822.22.4
Interobserver WT Differences (mm)
H.
r=0.96, p<0.0001
Figure 2 Bland-Altman plots of intra-observer (left panels) and inter-observer (right panels) differences in coronary CMR
measurements. The solid lines are the mean differences and the dashed lines are 2 standard deviations (SD) from the mean difference. The
linear regression analyses are also provided, with correlation coefficient and p value for each comparison.
Terashima et al. Journal of Cardiovascular Magnetic Resonance 2010, 12:75
http://www.jcmr-online.com/content/12/1/75
Page 4 of 7

Page 5

image quality of coronary wall CMR, including subopti-
mal breath-holding, cardiac and respiratory motion arti-
facts, and limited signal-to-noise ratio (SNR). The short
spiral readouts of this breath-held sequence limit SNR,
which is why this study focused on the more anterior
right coronary artery, as in most prior studies[9-13].
Increased BMI also likely contributed to reduced SNR,
as obese patients (BMI ≥ 30, accounting for 24% of
cohort) were less likely to have adequate image quality
(39.2% vs. 81.7% for BMI < 30). Notably, patients with
CAC≥400 were also less likely to have adequate MR
image quality (52.5% vs. 70.5% for CAC < 400), suggest-
ing that severe calcification (with low MR signal) limits
coronary wall visualization. A higher proportion of our
older cohort (78%) had evidence of coronary calcifica-
tion compared to the MESA study (46%)[14].
Importantly, in those subjects with adequate image
quality, quantitative measures had very good intra- and
inter-observer agreement, which had only been shown
previouslyin healthyvolunteers[23,24].
approaches are likely needed in combination to improve
image quality and SNR in order to make this a more
robust and reliable technique. These include optimized
multi-element surface coils, 3 D acquisition[10,23], free-
breathing methods to allow longer acquisitions[26],
radial k-space sampling[27], and higher magnetic field
strength, such as 3T[28-31].
Several
Positive Arterial Remodeling
The compensatory enlargement of artery size with
increased atherosclerosis to maintain lumen size has
been termed positive arterial remodeling. Our finding of
increased coronary vessel area and preserved lumen area
with increased coronary wall thickness confirms, in an
older population, the prior reports of positive remodel-
ing by coronary wall CMR[10,14]. Importantly, while
male gender and BMI can affect vessel size, these were
not associated with increased wall thickness on multi-
variate analysis. This identification of positive remodel-
ing is potentially valuable clinically, as it has been
associated with an increased risk of plaque rupture by
pathology[8].
60
mm2)
Areas (m
d Lumen
Vessel an
oronary V
Co
50
Vessel Area:
R=0.66, P<0.0001
,
30
40
20
10
Lumen Area:
R=0.05, P=0.6
0
0.51.0 1.5 2.02.5
Coronary Wall Thickness (mm)
Figure 3 Coronary wall thickness compared to both vessel area
(solid squares, solid line) and lumen area (open circles, dashed
line) by linear regression, showing significant positive
correlation for vessel area but no significant change in lumen
area, consistent with positive remodeling.
Table 2 Multivariate Regression Analysis of Coronary Risk
Factors and Coronary Wall CMR
Coronary WA
(p = 0.038)
b
value
Coronary WT
(p = 0.0009)
VariableSEP
Value
b
value
SEP
Value
Age (years)
Gender (men/women)
Body mass index
(kg/m2)
Diabetes mellitus (%)
Hypertension (%)
Total/HDL cholesterol
(mg/dL)
Current smoker, n (%)
-0.024 0.176
0.099
0.132
0.981
0.239
0.123
0.022
0.101
0.16
0.007
0.042
0.006
0.783
0.216
0.054
1.033
0.141
0.177
0.019
0.105
1.402
1.037
0.49
0.037
0.829
0.226
0.223
0.015
0.189
0.057
0.042
0.020
0.007
0.857
0.025
0.132 2.0370.1120.1440.082 0.073
b: standardized regression coefficients. SE: standard error.
40 40
30
35
non-DM
DM
1.6
1.8
*
*
20
25
1.0
1.2
1.4
10
15
0.4
0.6
0.8
0
(mm2)
5
VALAWA
(mm)
WT
0
0.2
Figure 4 Coronary wall CMR measurements between non-
diabetic (n = 128) and diabetic (n = 22) subjects. Both coronary
wall area and wall thickness were significantly associated with
diabetes mellitus (DM) by multivariate analysis. [* p < 0.05].
40
RCA CAC=0
RCA CAC>0
*
30
35
*
1.6
1.8
*
20
25
1.0
1.2
1.4
10
15
*
0.4
0.6
0.8
0
(mm2)
5
VALA WA
WT
0
0.2
(mm)
Figure 5 Coronary wall CMR measurements and RCA
calcification. All coronary measurements were significantly greater
in patients with positive RCA calcification (RCA CAC > 0, n = 84)
compared to those without (RCA CAC = 0, n = 66). [* p < 0.005].
Terashima et al. Journal of Cardiovascular Magnetic Resonance 2010, 12:75
http://www.jcmr-online.com/content/12/1/75
Page 5 of 7

Page 6

Diabetes and Subclinical Coronary Atherosclerosis
Among coronary risk factors, type 2 diabetes was the
strongest predictor by multivariate analysis of increased
coronary wall area and wall thickness by CMR in the
present study. These results are consistent with autopsy
and CT studies that have documented a higher preva-
lence of coronary atherosclerosis among patients with
diabetes, even in the absence of symptoms or clinical
evidence of coronary artery disease[32-34]. CMR of the
RCA wall has been applied previously to a subset of 61
patients from a cohort of asymptomatic type 1 diabetics,
with wall thickness found to be greater in patients who
also had nephropathy[13]. In the MESA study, HDL and
smoking history were associated with increased coronary
wall thickness on univariate analysis, but no multivariate
analysis data were provided[25]. The number of dia-
betics reported in MESA (n = 4) was likely too small for
analysis of this association. Given the increasing inci-
dence of type 2 diabetes, data on the prognostic utility
of coronary wall CMR to identify diabetic patients at
increased risk of progression to clinical coronary heart
disease would clearly be valuable.
Coronary Wall CMR and Coronary Artery Calcification
CAC measured by CT has been the most widely used
direct noninvasive measure of coronary atherosclerosis
[35] and is associated with the extent of coronary ather-
osclerosis by pathology and clinical events[33,36]. Black-
blood CMR can assess coronary wall thickness, but does
so over a more limited region. Thus, CAC by CT and
coronary wall thickness by CMR provide different mea-
sures of coronary atherosclerosis. We found a significant
association of RCA coronary wall thickness with both
total CAC and CAC of the RCA, similar to the MESA
study[14]. Further studies comparing coronary CMR to
CAC, as well as CT angiography, are clearly needed.
Study Limitations
There is a growing literature of coronary wall CMR stu-
dies, but limited validation with intravascular ultra-
sound, which cannot be justified in asymptomatic
subjects. We imaged only a single region of the RCA, as
in most prior studies, as the RCA is closer to the chest
wall providing higher SNR and good reproducibility
[10,23]. Atherosclerosis is a systemic disease that can
cause a diffuse increase in coronary wall thickness, but
more comprehensive imaging to also detect and charac-
terize focal lesions would be desirable. The MESA study
did include selected left main and left anterior descend-
ing artery locations, but ideally whole-heart coronary
wall CMR methods are needed. Finally, the ultimate
value of coronary wall CMR will be in predicting clinical
events and guiding therapy.
Conclusions
Noninvasive right coronary wall CMR was successfully
performed in a community-based cohort of older sub-
jects, demonstrating positive arterial remodeling and
association with type 2 diabetes and coronary artery cal-
cification. Coronary wall CMR warrants further study in
the detection of subclinical coronary atherosclerosis and
prediction of clinical cardiovascular events.
Acknowledgements
We thank the staff at the Kaiser Permanente of Northern California Division
of Research and the Stanford Prevention Research Center for their assistance
in patient recruitment and evaluation.
This study was supported by the Donald W. Reynolds Foundation (Las
Vegas, NV), National Heart, Lung, and Blood Institute, R01-HL39297
(Bethesda, MD) and GE Healthcare (Waukesha, WI). The funding bodies did
not influence any of the following: study design; collection, analysis, and
interpretation of data; writing of the manuscript; and the decision to submit
the manuscript for publication.
Author details
1Division of Cardiovascular Medicine, Stanford University School of Medicine,
Stanford, CA, USA.2Department of Radiology, Stanford University School of
Medicine, Stanford, CA, USA.3Department of Biomedical Engineering,
University of Virginia, Charlottesville, VA, USA.4Applied Science Laboratory-
West, GE Healthcare, Menlo Park, CA, USA.5Magnetic Resonance Systems
Research Laboratory, Department of Electrical Engineering, Stanford
University School of Medicine, Stanford, CA, USA.6Division of Research,
Kaiser Permanente of Northern California, Oakland, CA, USA.7Departments of
Epidemiology, Biostatistics, and Medicine, University of California, San
Francisco, San Francisco, CA, USA.8Department of Health Research and
Policy, Stanford University School of Medicine, Stanford, CA, USA.9Stanford
Prevention Research Center, Stanford University School of Medicine,
Stanford, CA, USA.
Authors’ contributions
MT performed CMR studies, data analysis, and drafted the manuscript. PKN
performed CMR studies and data analysis. GDR participated in the study
design and supervised the coronary CT exams and data analysis. CHM, AS,
and DGN helped develop and implement the CMR methods. SE contributed
to the data analysis. BC contributed to the CMR image analysis methods. CI,
ASG, MAH, and SPF participated in the study design and contributed to data
analysis methods. MVM participated in the study design, patient studies, and
data analysis. All authors have participated in critical review of the
manuscript and have read and approved the final version.
Competing interests
MVM and DGN receive research support from GE Healthcare. MVM has been
an advisor for Philips Healthcare and Kowa, Inc. MT has received honoraria
from Philips Healthcare. GDR has been an advisor for TeraRecon, Inc. and
Siemens Medical Solutions. AS is an employee of GE Healthcare.
Received: 18 May 2010 Accepted: 30 December 2010
Published: 30 December 2010
References
1.Yang PC, Meyer CH, Terashima M, Kaji S, McConnell MV, Macovski A,
Pauly JM, Nishimura DG, Hu BS: Spiral magnetic resonance coronary
angiography with rapid real-time localization. J Am Coll Cardiol 2003,
41:1134-1141.
2.Sakuma H, Ichikawa Y, Chino S, Hirano T, Makino K, Takeda K: Detection of
coronary artery stenosis with whole-heart coronary magnetic resonance
angiography. J Am Coll Cardiol 2006, 48:1946-1950.
3.Weber OM, Martin AJ, Higgins CB: Whole-heart steady-state free
precession coronary artery magnetic resonance angiography. Magn
Reson Med 2003, 50:1223-1228.
Terashima et al. Journal of Cardiovascular Magnetic Resonance 2010, 12:75
http://www.jcmr-online.com/content/12/1/75
Page 6 of 7

Page 7

4.Manning WJ, Edelman RR: Magnetic resonance coronary angiography.
Magn Reson Q 1993, 9:131-151.
Terashima M, Nguyen PK, Rubin GD, Iribarren C, Courtney BK, Go AS,
Fortmann SP, McConnell MV: Impaired coronary vasodilation by magnetic
resonance angiography is associated with advanced coronary artery
calcification. JACC Cardiovasc Imaging 2008, 1:167-173.
Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ:
Compensatory enlargement of human atherosclerotic coronary arteries.
N Engl J Med 1987, 316:1371-1375.
Fayad ZA, Fuster V, Fallon JT, Jayasundera T, Worthley SG, Helft G,
Aguinaldo JG, Badimon JJ, Sharma SK: Noninvasive in vivo human
coronary artery lumen and wall imaging using black-blood magnetic
resonance imaging. Circulation 2000, 102:506-510.
Fernandes JL, Serrano CV Jr, Blotta MH, Coelho OR, Nicolau JC, Avila LF,
Rochitte CE, Parga Filho JR: Regression of coronary artery outward
remodeling in patients with non-ST-segment acute coronary syndromes:
a longitudinal study using noninvasive magnetic resonance imaging. Am
Heart J 2006, 152:1123-1132.
McConnell MV, Meyer CH, Putz EJ, Nishimura DG, Hu BS: Spiral coronary
wall imaging: Patient studies. Ninth annual meeting of the International
Society for Magnetic Resonance in Medicine; Glasgow, Scotland 2001, 1969.
Kim WY, Stuber M, Bornert P, Kissinger KV, Manning WJ, Botnar RM: Three-
dimensional black-blood cardiac magnetic resonance coronary vessel
wall imaging detects positive arterial remodeling in patients with
nonsignificant coronary artery disease. Circulation 2002, 106:296-299.
Botnar RM, Stuber M, Kim WY, Danias PG, Manning WJ: Magnetic
resonance coronary lumen and vessel wall imaging. Rays 2001,
26:291-303.
Botnar RM, Stuber M, Kissinger KV, Kim WY, Spuentrup E, Manning WJ:
Noninvasive coronary vessel wall and plaque imaging with magnetic
resonance imaging. Circulation 2000, 102:2582-2587.
Kim WY, Astrup AS, Stuber M, Tarnow L, Falk E, Botnar RM, Simonsen C,
Pietraszek L, Hansen PR, Manning WJ, et al: Subclinical coronary and aortic
atherosclerosis detected by magnetic resonance imaging in type 1
diabetes with and without diabetic nephropathy. Circulation 2007,
115:228-235.
Miao C, Chen S, Macedo R, Lai S, Liu K, Li D, Wasserman BA, Vogel-
Claussen J, Lima JA, Bluemke DA: Positive remodeling of the coronary
arteries detected by magnetic resonance imaging in an asymptomatic
population: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll
Cardiol 2009, 53:1708-1715.
Hlatky MA, Ashley E, Quertermous T, Boothroyd DB, Ridker P, Southwick A,
Myers RM, Iribarren C, Fortmann SP, Go AS: Matrix metalloproteinase
circulating levels, genetic polymorphisms, and susceptibility to acute
myocardial infarction among patients with coronary artery disease. Am
Heart J 2007, 154:1043-1051.
Fair JM, Kiazand A, Varady A, Mahbouba M, Norton L, Rubin GD, Iribarren C,
Go AS, Hlatky MA, Fortmann SP: Ethnic differences in coronary artery
calcium in a healthy cohort aged 60 to 69 years. Am J Cardiol 2007,
100:981-985.
Go AS, Iribarren C, Chandra M, Lathon PV, Fortmann SP, Quertermous T,
Hlatky MA: Statin and beta-blocker therapy and the initial presentation
of coronary heart disease. Ann Intern Med 2006, 144:229-238.
Iribarren C, Go AS, Husson G, Sidney S, Fair JM, Quertermous T, Hlatky MA,
Fortmann SP: Metabolic syndrome and early-onset coronary artery
disease: is the whole greater than its parts? J Am Coll Cardiol 2006,
48:1800-1807.
Iribarren C, Husson G, Go AS, Lo JC, Fair JM, Rubin GD, Hlatky MA,
Fortmann SP: Plasma leptin levels and coronary artery calcification in
older adults. J Clin Endocrinol Me tab 2007, 92:729-732.
Terashima M, Meyer CH, Keeffe BG, Putz EJ, de la Pena-Almaguer E,
Yang PC, Hu BS, Nishimura DG, McConnell MV: Noninvasive assessment of
coronary vasodilation using magnetic resonance angiography. J Am Coll
Cardiol 2005, 45:104-110.
Liu X, Zhao X, Huang J, Francois CJ, Tuite D, Bi X, Li D, Carr JC: Comparison
of 3 D free-breathing coronary MR angiography and 64-MDCT
angiography for detection of coronary stenosis in patients with high
calcium scores. AJR Am J Roentgenol 2007, 189:1326-1332.
Nguyen PK, Meyer C, Engvall J, Yang P, McConnell MV: Noninvasive
assessment of coronary vasodilation using cardiovascular magnetic
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
resonance in patients at high risk for coronary artery disease. J
Cardiovasc Magn Reson 2008, 10:28.
Desai MY, Lai S, Barmet C, Weiss RG, Stuber M: Reproducibility of 3 D free-
breathing magnetic resonance coronary vessel wall imaging. Eur Heart J
2005, 26:2320-2324.
Hazirolan T, Gupta SN, Mohamed MA, Bluemke DA: Reproducibility of
black-blood coronary vessel wall MR imaging. J Cardiovasc Magn Reson
2005, 7:409-413.
Macedo R, Chen S, Lai S, Shea S, Malayeri AA, Szklo M, Lima JA,
Bluemke DA: MRI detects increased coronary wall thickness in
asymptomatic individuals: the multi-ethnic study of atherosclerosis
(MESA). J Magn Reson Imaging 2008, 28:1108-1115.
Schar M, Kim WY, Stuber M, Boesiger P, Manning WJ, Botnar RM: The
impact of spatial resolution and respiratory motion on MR imaging of
atherosclerotic plaque. J Magn Reson Imaging 2003, 17:538-544.
Katoh M, Spuentrup E, Buecker A, Manning WJ, Gunther RW, Botnar RM: MR
coronary vessel wall imaging: comparison between radial and spiral k-
space sampling. J Magn Reson Imaging 2006, 23:757-762.
Koktzoglou I, Simonetti O, Li D: Coronary artery wall imaging: initial
experience at 3 Tesla. J Magn Reson Imaging 2005, 21:128-132.
Botnar RM, Stuber M, Lamerichs R, Smink J, Fischer SE, Harvey P,
Manning WJ: Initial experiences with in vivo right coronary artery human
MR vessel wall imaging at 3 tesla. J Cardiovasc Magn Reson 2003,
5:589-594.
Priest AN, Bansmann PM, Kaul MG, Stork A, Adam G: Magnetic resonance
imaging of the coronary vessel wall at 3 T using an obliquely oriented
reinversion slab with adiabatic pulses. Magn Reson Med 2005,
54:1115-1122.
Priest AN, Bansmann PM, Mullerleile K, Adam G: Coronary vessel-wall and
lumen imaging using radial k-space acquisition with MRI at 3 Tesla. Eur
Radiol 2007, 17:339-346.
Goraya TY, Leibson CL, Palumbo PJ, Weston SA, Killian JM, Pfeifer EA,
Jacobsen SJ, Frye RL, Roger VL: Coronary atherosclerosis in diabetes
mellitus: a population-based autopsy study. J Am Coll Cardiol 2002,
40:946-953.
Hoff JA, Quinn L, Sevrukov A, Lipton RB, Daviglus M, Garside DB, Ajmere NK,
Gandhi S, Kondos GT: The prevalence of coronary artery calcium among
diabetic individuals without known coronary artery disease. J Am Coll
Cardiol 2003, 41:1008-1012.
Arad Y, Newstein D, Cadet F, Roth M, Guerci AD: Association of multiple
risk factors and insulin resistance with increased prevalence of
asymptomatic coronary artery disease by an electron-beam computed
tomographic study. Arterioscler Thromb Vasc Biol 2001, 21:2051-2058.
Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K, Shea S,
Szklo M, Bluemke DA, et al: Coronary calcium as a predictor of coronary
events in four racial or ethnic groups. N Engl J Med 2008, 358:1336-1345.
Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS: Coronary
artery calcium area by electron-beam computed tomography and
coronary atherosclerotic plaque area. A histopathologic correlative
study. Circulation 1995, 92:2157-2162.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
doi:10.1186/1532-429X-12-75
Cite this article as: Terashima et al.: Right coronary wall cmr in the older
asymptomatic advance cohort: positive remodeling and associations
with type 2 diabetes and coronary calcium. Journal of Cardiovascular
Magnetic Resonance 2010 12:75.
Terashima et al. Journal of Cardiovascular Magnetic Resonance 2010, 12:75
http://www.jcmr-online.com/content/12/1/75
Page 7 of 7