Yuanliang Jiang1, Chengcheng Zhu2, Andrew J Degnan3, Wenjia Peng1, Luguang Chen1, Xinrui Wang1, Qi Liu1, Yang Wang4, Zhenzhen Xiang4, Zhongzhao Teng5, David Saloner2, and Jianping Lu1
1Radiology, Changhai Hospital, Shanghai, China, People's Republic of, 2Radiology, University of California, San Francisco, San Francisco, CA, United States, 3Radilogy, University of Pittsburgh, Pittsburgh, PA, United States, 4Pathology, Changhai Hospital, Shanghai, China, People's Republic of, 5Radiology, University of Cambridge, Cambridge, United Kingdom
Synopsis
The
first ex vivo measurement of T1, T2, and T2* relaxation times of intracranial
plaque components at 3T is reported. The ability of multi-contrast MRI to characterize
plaque type was evaluated with histological validation. Plaque components could
be differentiated based on relaxation times. Specifically, lipid core had
significantly lower T2 values than fibrous cap. MRI and histology correlation
was consistent across specimens and locations, and MRI showed a high sensitivity
and specificity for identifying plaque features previously associated with high-risk.
Therefore, MRI has the potential to characterize intracranial plaque composition
and improve patient risk stratification. Purpose
Intracranial
artery atherosclerotic plaque is a major cause of stroke. The development of
black blood MRI techniques has allowed the visualization of the intracranial
artery wall in vivo. Composition of
extracranial carotid plaque such as intra-plaque haemorrhage (IPH), fibrous cap
and lipid core has been extensively studied as predictors of ischemic stroke
1. Characterizing intracranial plaque composition
in vivo, however, is still challenging
given its small size and the lack of histological validation. Previous post-mortem
studies have reported the T1/T2/T2* relaxation times of plaque components at
ultra-high field strengths (7T
2 and 17.6T
3). However, most prior in vivo studies of
intracranial plaque were undertaken using 3T clinical scanners, but relaxation
times at 3T have not been reported. This study aims: 1) to quantify the
relaxation times of intracranial plaque components ex vivo at 3T; and 2) to evaluate
the ability of multi-contrast MRI for intracranial plaque type classification
in comparison with histology.
Methods
Study population: Specimens of the circle of Willis (CoW) were obtained from 20
cadavers (11 male; mean age 73.8 ±10.9 years) with atherosclerotic plaques. All
specimens were rinsed with saline to remove blood clots.
MRI acquisition: MRI scanning was undertaken in a
Siemens 3T Skyra scanner using a loop coil (4cm diameter) within 24 hours after
excising specimen. Specimens were embedded within Fomblin (a fluorinated fluid
with no MR signal) during imaging. Quantitative T1/T2/T2* mapping sequences and
multi-contrast fast-spin echo (FSE) sequences were acquired (Table 1).
Image
analysis: Specimens were stained with haematoxylin and eosin (H&E)
and Masson trichrome. MRI images were co-registered with histology slices.
Plaque components including IPH, fibrous cap, lipid core, fibrous tissue,
calcification and healthy wall were segmented on histology, and their relaxation
times were recorded on MR images. Plaque types were classified on histology by
two experienced pathologists according to the American Heart Association (AHA)
definitions 4. Two radiologists also classified the plaque types using
multi-contrast MRI 4, blinded to the histology results.
Statistics: Considering
that multiple measurements were obtained from each subject, a linear
mixed-effect model was used to assess the difference between the relaxation
times of different components. Cohen’s kappa was used to estimate the agreement
of plaque type classification using MRI vs. histology.
Results
In total, 53 atherosclerotic arteries were excised. 229 slices
with matched MRI and histology locations were included in the analysis. Sample
images are shown in Figures 1&2. Quantitative mapping results are shown in
Table 2, and the agreement between MRI and histology is shown in Table 3. There
are significant differences among the relaxation times of different components
(p<0.05). T2 and T2* value of lipid core are lower than fibrous cap
(p<0.001), but are comparable with fibrous tissue and healthy wall
(p>0.05). Lipid core has less proton density compared with fibrous cap and
fibrous tissue (p<0.001). Calcium has the lowest relaxation times and proton
density. There is good agreement between MRI and histology for plaque type
classification (κ = 0.69) with an overall accuracy of 80.7%. The sensitivity
and specificity using MRI to identify fibro-lipid atheroma (type V-VI) is 95.8%
and 77.1% respectively. Good inter-observer agreement was also found between
two radiologists (κ = 0.77).
Discussion
To our
knowledge, this is the first study to report the relaxation times of
intracranial plaque components at 3T. The reported relaxation times can be used
in protocol design and for the characterization of plaque components on
multi-contrast imaging at 3T. We found lipid core has significantly lower T2
values than fibrous cap, such that they could be clearly distinguished on T2
weighted images. These findings agreed with previous carotid studies at 3T. However,
previous intracranial plaque studies
2 3 did not show a significant difference between the T2 values of
fibrous cap and lipid core at ultra-high field strengths. We also demonstrate that
multi-contrast MRI can identify high-risk plaques with high sensitivity and
specificity ex-vivo.
Conclusion
Intracranial plaque components have distinct and
different relaxation times at 3T. High-resolution MRI is able to characterize
intracranial plaque composition and classify plaque types ex vivo at 3T. This
study provides a basis for the development of in vivo MRI techniques to evaluate
intracranial plaque vulnerability and improve risk stratification of patients.
Acknowledgements
This study is supported by
NIH grants R01HL114118 and
R01NS059944.References
1. Underhill,
H. R., Hatsukami, T. S., Fayad, Z. A., Fuster, V. & Yuan, C. MRI of carotid
atherosclerosis: clinical implications and future directions. Nat Rev Cardiol 7, 165-173, (2010).
2. Harteveld,
A. et al. Quantitative MR imaging of
ex vivo intracranial atherosclerotic plaques at 7.0 tesla. Proc. Intl. Soc. Mag. Reson. Med. 23, 2661 (2015).
3. Zhang,
S. et al. Ultrahigh-resolution MRI
Imaging of Intracranial atherosclerosis at 17.6 Tesla: an ex vivo Study with
Histological Comparison. Proc. Intl. Soc.
Mag. Reson. Med. 23, 0553
(2015).
4. Cai, J. M. et al. Classification of human carotid
atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 106, 1368-1373 (2002).