Thanh D Nguyen1, Jingwen Du2, Yan Wen1, Ajay Gupta1, Pascal Spincemaille1, Qi Yang2, and Yi Wang1
1Weill Cornell Medicine, New York, NY, United States, 2Xuanwu Hospital of Capital Medical University, Beijing, China
Synopsis
In this study, we used CT angiography (CTA) as a
reference standard to demonstrate that carotid quantitative susceptibility
mapping (QSM) provides accurate detection of calcified atherosclerotic plaques
in the carotid arteries. Calcification is strongly diamagnetic and appears
uniquely hypointense on carotid QSM. Inclusion of QSM in carotid MRI would aid
characterization of carotid plaque.
INTRODUCTION
Calcification is a common feature of carotid
atherosclerotic plaques, which indicates plaque stability and may reduce stroke
risk in half (1). Heavily calcified plaques are associated with less favorable
outcomes of carotid revascularization. Therefore, accurate assessment of plaque
calcification is critically important to triaging patients for medication vs.
revascularization intervention. CT angiography (CTA), currently the gold
standard for in vivo calcification detection, requires harmful radiation and a large
dose of iodine contrast agent but does not provide characterization of other
important intraplaque components including hemorrhage of high risk. Multi-contrast
MRI (mcMRI), useful for characterizing intraplaque components without CTA limitations
(2), allows detection of calcification based on hypointensity on T1w/T2w images.
However, accurate interpretation of calcification on mcMRI is difficult, as hemosiderin-rich
intraplaque hemorrhage (IPH), perivascular fat, and blood vessels also appear
hypointense on the black blood fat-suppressed mcMRI images. This mcMRI
ambiguity can be resolved on quantitative susceptibility mapping (QSM), because
calcification is a uniquely strong diamagnetic source in the body (3-5) and is
easily distinguishable from paramagnetic sources such as hemorrhage and fat. The
objective of this study was to evaluate the improvement in diagnostic accuracy
of calcification detection in carotid plaques by adding QSM to mcMRI, using CTA
as the reference standard.METHODS
Carotid plaque
mcMRI.
The clinical imaging protocol was based on ASNR Vessel Wall Imaging Study Group
recommendations (6) and consisted of 3D TOF, 2D black blood fat-suppressed
T1w/T2w TSE, and 3D magnetization-prepared rapid gradient echo (MPRAGE) sequences
with spatial resolution of 0.6x0.6x2 mm3 and 6 cm longitudinal
coverage of the carotid bifurcation.
Carotid QSM. A multi-echo 3D GRE
sequence was optimized for carotid QSM to match the spatial resolution and
coverage of mcMRI with 5 min scan time. Four echo times were acquired per TR with
4.7 ms in-phase echo spacing to allow optimal field estimation in the presence
of fat at 3T (7). A nonlinear preconditioned total field inversion algorithm
was developed to calculate the susceptibility map by minimizing the following cost
function:
$$x^*=arg min_x{\parallel}w(e^{-i\alpha f}-e^{-id*Px}){\parallel}^2_2+{\lambda\parallel}M_G{\triangledown}Px{\parallel}_1+{\lambda_{A}\parallel}M_{A}P(x-\overline{x}^{A}){\parallel}^2_2$$
Here the first
two terms are the data fidelity term and structure consistency regularization
term, where
$$$w$$$ is the
SNR weighting,
$$$d$$$ is the
dipole kernel, $$$M_G$$$
is the edge mask, and
$$$\triangledown$$$ is the
gradient operator. The third term enforces susceptibility homogeneity of the
well-mixed arterial blood (8),
$$$M_{A}$$$ is the
arterial mask (obtained
using a semi-automated region-growing algorithm), and
$$$\overline{x}^{A}$$$ is the mean susceptibility within
the mask.
$$$\alpha$$$ is a
scalar that scales down
$$$f$$$
to avoid
phase wraps. The preconditioner
$$$P$$$ is used
to accelerate convergence (9). The final
susceptibility map is $$$Px^*/\alpha$$$.
Imaging
study. Ten patients (mean age 66 years ± 5) had both
MRI and CTA scans with median follow-up interval of 3 days. A neuroradiologist with
13 years of carotid imaging experience independently reviewed CTA and mcMRI
(without and with QSM image) to identify plaque calcification on a per vessel
basis. Calcification was detected as region with high attenuation on CTA
(Hounsfield unit>100), hypointense signal (compared to the adjacent muscle)
on mcMRI, and strongly negative susceptibility (<-0.5 ppm) on QSM.RESULTS
Figure
1 shows an example of concordant depiction of a heavily calcified plaque at the
carotid bifurcation on mcMRI, QSM and CTA images. Compared to mcMRI, the
unambiguous visual contrast between calcification and the surrounding tissues
on QSM allows easy identification and improves diagnostic confidence. This
benefit is highlighted in Figs. 2 and 3, which show examples of small
calcification nodules with dark signal that could not be prospectively identified by the experienced
reader on mcMRI but well captured by QSM (approximately -2 ppm susceptibility) in
excellent agreement with CTA.
Out
of 17 vessels with calcified plaques detected by CTA, mcMRI only captured 11
calcifications (64.7% sensitivity). However, with the addition of QSM, all
calcifications were identified (100% sensitivity). Both mcMRI and QSM correctly
identified the 3 non-calcified vessels (100% specificity).
Additionally,
Figure 4 demonstrates the versatility of QSM for detecting paramagnetic intraplaque
hemorrhage consistent with low attenuation (Hounsfield unit <60) on
CTA image.DISCUSSION
Our
preliminary results suggest that QSM substantially improves the diagnostic
accuracy for detecting calcified carotid plaques. Our QSM validation study with
CTA is ongoing, and the patient cohort size will be significantly increased in
the future. QSM has the potential to become an instrumental part of noninvasive
and quantitative carotid MRI for plaque characterization. QSM is known to
provide sensitive detection of strong magnetic materials in tissue, including highly
paramagnetic iron in hemorrhage and highly diamagnetic calcification deposits. Accordingly,
QSM can reliably resolve the ambiguity of T1w hypointensity on traditional
mcMRI, which can be the result of IPH and/or calcification. Future clinical
studies with large patient sample sizes are warranted to establish the value of
including QSM in carotid MRI protocol, which would enable confident triaging
carotid patients who are at high risk and would benefit from surgical
interventions to prevent stroke, from those with lower risk who would derive a
similar risk reduction benefit from noninvasive medication treatment.Acknowledgements
No acknowledgement found.References
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