Title Page
Advances in MR imaging for the evaluation of carotid atherosclerosis Gregory C. Makris, MD, Zhongzhao Teng PhD, Andrew J. Patterson1, Jyh-miin Lin,
MBA
Gregory Makris, MD
P
Corresponding author:
R O
O
1. University Department of Radiology, University of Cambridge
FS
Victoria Young, MBBS, PhD , Martin J. Graves, PhD, Jonathan H. Gillard, FRCR,
D
University of Cambridge School of Clinical Medicine Box 218 Cambridge Biomedical Campus
E
Cambridge CB2 0QQ, UK
O
R
R
E
C
T
[email protected]
C
Funding source:
N
This research is supported by BHF PG/11/74/29100 and the NIHR Cambridge
U
Biomedical Research Centre.
B
JR
Keywords: MRI, stroke, carotid plaque, mechanics Running title: Carotid plaque MR imaging Type of Manuscript: Review articles Word count: 4,105 Abstract: 170 Tables: 2 Figure: 5 Conflict of interest: Nothing to declare Running title: Carotid plaque MR imaging
Manuscript
Abstract Carotid artery atherosclerosis is an important source of mortality and morbidity in the western world with significant socioeconomic implications. The quest for the early
FS
identification of the vulnerable carotid plaque is already in its 3rd decade and traditional
O
measures, such as the sonographic degree of stenosis, are not selective enough to distinguish
R O
those who would really benefit from a carotid endarterectomy. Magnetic resonance imaging of the carotid plaque enables the visualisation of plaque composition and specific plaque
P
components that have been linked to a higher risk of subsequent embolic events. Blood suppressed T1- T2-and proton density -weighted fast spin echo, gradient echo and time-of-
D
flight sequences are typically used, to quantify plaque components such as lipid-rich necrotic
E
core, intraplaque haemorrhage, calcification, and surface defects including erosion, disruption
T
and ulceration The purpose of this article is to review the most important recent advances in
U
N
C
O
R
R
E
C
MRI technology to enable better diagnostic carotid imaging.
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
Introduction Internal carotid artery (ICA) atherosclerosis is a significant source of mortality and morbidity
FS
in the western world1, 2. MRI enables the visualisation of plaque composition and specific plaque constituents have been linked to a higher risk of subsequent embolic events.
O
Currently, either the sonographic or angiographic degree of carotid stenosis is used as a
R O
marker of severity for assessing carotid disease and risk of stroke3, 4. However there is mounting evidence, which suggests that the degree of stenosis is not enough to accurately
P
characterize carotid plaque burden and vulnerability.
D
High-resolution, multi-contrast carotid MRI protocols have been used to depict
T
E
atherosclerotic components within carotid plaques, the validity of these protocols have been 5-7
.
C
evaluated using histopathology and the protocols have been applied in multi-centre trials
E
Blood suppressed T1- T2-and proton density (PD)-weighted fast spin echo and gradient echo
R
Time-Of-Flight (TOF) sequences) are typically used,8 to quantify plaque components such as 5, 9-11
, intraplaque haemorrhage (IPH)
5, 12-15
, calcification 5, 9
R
lipid-rich necrotic core (LRNC)
O
and surface defects including erosions, disruption and ulceration 11, 16-18. In addition, the intra14, 19-21
and the inter-scan reproducibility 20, 22, 23 of quantitative measures
C
reader, inter-reader
U
N
associated with both morphology and composition have been reported.
Novel MR-defined plaque features of vulnerability are emerging and appear promising for the identification of the vulnerable plaque. A recent systematic review of 9 studies with 779
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
subjects demonstrated that the presence of IPH, LRNC, and thinning/rupture of the fibrous cap (FC) is linked to an increased risk of future stroke or transient ischaemic attack (TIA)24. The hazard ratios for each of them as predictors of subsequent ischaemic events were 4.59 (95% confidence interval (CI), 2.91-7.24), 3.00 (95% CI, 1.51-5.95), and 5.93 (95% CI, 2.65-
13.20), respectively. In a separate meta-analysis focusing on IPH which pooled 8 clinical studies of 689 patients, the hazard ratio of MRI-depicted IPH in symptomatic patients was
B
FS
11.725. This evidence indicates that dedicated MRI-depicted plaque composition offers stroke
O
risk information beyond measurement of luminal stenosis.
R O
Although MRI holds promise, the clinical application for plaque characterisation will require further consensus regarding MRI protocols and new MRI techniques. A recent overview of
P
17 studies that assessed the agreement between MRI and histology indicated that MRI could characterise calcification, FC, IPH and LRNC with moderate-to-good sensitivity and
D
specificity26. It suggests that further effort is needed to use MRI as a routinely clinical
E
C
requirement of a dedicated receiver coil.
T
E
imaging modality to assess carotid atherosclerosis characteristics. One pragmatic issue is the
R
The purpose of this article is to review the most important recent advances in MRI
R
technology to enable better diagnostic carotid imaging. This article also reviews recent
U
N
C
O
advances in material stress analysis and molecular imaging relevant to carotid atherosclerosis.
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
MR sequences for Carotid plaque composition analysis The de facto standard for blood suppressed carotid imaging is double inversion recovery
FS
(DIR) preparation. Intra-luminal blood signal is suppressed by applying a 180° non-selective pulse to invert the magnetisation within the transmit volume, which is immediately followed
O
by a 180° slice selective pulse to revert the magnetisation within the imaging plane. The
R O
magnetisation in the blood outside the imaging plane reaches a null point after a period of time defined as the Inversion Time (TI). Also after a period of time, for any given flow rate,
B
P
inflowing blood from outside the imaging plane will replace in the intra-luminal space within
D
the defined imaging plane.
T
E
DIR is typically implemented as a gated single slice technique as black blood imaging is
C
originally developed for cardiac application where gating is a fundamental prerequisite.
E
However, gated acquisitions lead to variations in T1 relaxation and the signal slice
R
implementation results in scan-times, which preclude clinical adoption. In response Yarnykh
R
and Yuan27 implemented an ungated multi-slice DIR protocol; this in effect accelerates the
O
acquisition as a function of the number of slices, which are simultaneously acquired.
C
However, DIR is known to be sensitive at producing plaque-mimicking artifacts. This is
N
understood to frequently occur at the carotid bifurcation as complex flow patterns exist where
U
blood signal within the imaging plane is not fully displaced from the imaging plane.
More advanced methods for blood suppression have subsequently been proposed which are
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
even more time efficient and can null residual blood signal. Wang, et al
28
presented a
technique known as improved motion sensitized driven equilibrium (iMSDE), in which blood suppression can be directly controlled by the size of the motion sensitizing gradients. This method effectively suppresses blood signal, however, the technique induces additional T 2
decay. In 2012, Li et al29 presented Delayed Alternating Nutation with Tailored Excitation (DANTE). This study demonstrated how blood signal could be suppressed by both a function
B
FS
of the DANTE preparation echo-train length and flip angle. To date, there are no studies, which have systematically compared all three methods, however, results of our initial
R O
O
validation studies are presented in Figure 1.
Currently the majority of MR imaging is performed on 1.5T systems. The continuous
P
advances in MR technology have allowed carotid imaging at higher magnetic strengths and multi-phase coils increase the potential for parallel imaging. Preliminary experience with
D
eight-channel coils at 3T indicates an increase in signal to noise ratio (SNR) to contrast to
T
E
noise ratio (CNR) compared with 1.5T. In a study by Young et al 30, 18 subjects with carotid
C
atherosclerosis were imaged on both 1.5 and 3 T systems using the same receiver coil. T1-,
E
T2- and PD images were obtained and multiple slices were prescribed to encompass both the
R
carotid bifurcation and the plaque. In this study the mean improvements in SNR was 1.9, 2.1
31
recently reported on 19 patients at 3T and noted significant associations
O
Yuan et al,
R
and 2.1 respectively, which were statistical significant.
C
between the presence of thin/ruptured FC (100% versus 36%, p = 0.006) and lipid-rich
N
necrotic core (100% versus 39%, p = 0.022), with a borderline association with haemorrhage
U
(86% versus 33%,p = 0.055).
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
Assessment of carotid plaque morphology using 3D MR sequences In a 3D sequence an RF pulse is applied to excite an imaging volume, phase encoding is performed in both the convention phase encode axis and in the slice select direction. 3D
FS
sequences typically result in higher SNR efficiency. In a study by Balu et al 32 , a total of 18
O
subjects with significant carotid stenosis were imaged with 2D (2-mm slice thickness) and 3D
R O
(1-mm/0.5-mm (acquired/interpolated) slice thickness) T1 weighted fast spin-echo (FSE) black-blood imaging sequences with DIR blood suppression. Morphological measurements,
P
SNR in the wall and lumen, and wall-lumen CNR were compared between 2D and 3D images. The lumen SNR, wall SNR, and CNR were comparable between the two methods.
D
There was also no difference in average volumetric measurements between 2D/3D. In
T
E
contrast the distributions of small plaque components such as calcification were better
C
characterized by the 3D acquisition while there was a higher sensitivity to motion artifacts
E
with 3D imaging, resulting in a small number of examinations with low image quality. The
R
conclusion from this study was that 2D and 3D protocols can provide comparable
R
morphometric and volumetric measurements of the carotid artery with the 3D imaging
O
offering an advantage in terms of small plaque component visualization but with the price of
N
C
lower reliability for image quality.
U
In another study by Takano et al.33, twenty-two patients scheduled for carotid endarterectomy underwent carotid plaque MRI with both a conventional fast spin echo 2D sequence and 3D fast spin echo sequence with variable refocusing flip angles. This 3D sequence enables the
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
acquisition of longer echo train lengths whilst reducing the T 2 blurring effect that would typically accrue by attempting to maintain magnetisation across the train of refocusing pulse. Image quality and SNR were evaluated; observations were compared for each plaque component according to the histological category of the plaque between 2D and 3D
sequences (Figure 2). No significant differences were observed among the overall imaging quality scores of the two modalities, although 3D sequences allowed visualization in random
FS
orientations, as well as better depiction of small plaque components such as ulcerations and calcifications. The SNR of the plaque to the submandibular gland on T1 weighted 3D
O
sequence was significantly higher than that on the 2D sequence. In addition it was shown that
R O
the SNR of the plaque to the submandibular gland of histology-defined soft plaque components were significantly higher on T1 weighted 3D sequence than on 2D sequence.
B
P
From this study it was concluded that 3D variable-flip-angle turbo spin-echo is a promising
D
tool for diagnostic imaging.
T
E
In 2011, Balu et al34 proposed a black blood 3D gradient echo sequence (3D-MERGE), the
C
sequence was evaluated on 9 patients with carotid atheroma. The proposed sequence
E
incorporated black blood preparation using iMSDE preparation prior to 3D spoiled gradient
R
echo readout. The proposed gradient sequence enabled isotropic resolution (0.7 mm3), and is
O
R
more time efficient than the 3D fast spin echo alternatives (imaging time ~2minutes).
C
In addition the advances in MR technology allow the use of non-gated sequences instead of
N
gated sequences for atherosclerotic vessel wall imaging without compromising image quality. 35
. Other examples of
U
This may shorten examination time and improve patient comfort
technological advances include the three-dimensional (3D) diffusion-prepared segmented steady-steady free precession (DP-SSFP) cardiovascular magnetic resonance (CMR)
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
sequence for black-blood
36
which allows for 3D acquisition of thin and contiguous slices
with black-blood image contrast. Finally turbo spin-echo (TSE) based motion-sensitized driven-equilibrium (MSDE) sequence have been developed as an alternative to black-blood
(BB) carotid MRI imaging providing a more accurate depiction of the lumen boundaries by
FS
eliminating plaque mimicking artefacts in carotid plaque imaging37.
Identification of intraplaque haemorrhage
38
. The sequence was coined
R O
excitation pulse was first presented by Moody, et al in 2003
O
The characterisation of IPH using a 3D gradient echo sequence with a selective water
MRDTI (Magnetic Resonance Direct Thrombus Imaging). Their study demonstrates using
this technique was proposed by Zhu et al in 2010
39
P
histopathology validation, the sequence utility in detecting thrombus. A subsequent variant of . This sequence referred to as 3D SHINE
D
(3D Spoiled gradient recalled echo pulse sequence for haemorrhage assessment using
T
E
inversion recovery and multiple echos) enable the simultaneous detection and aging of
C
thrombus based in its respective T1 and T2* relaxation properties. The differentiation between
R
E
IPH and thrombus can be challenging and a general guide can be seen at Table 1 and 2.
R
The evaluation of fibrous cap thickness
O
Wang Y et al.40, previously demonstrated that different types of stroke can be identified using
C
standard brain MR protocols prior to invasive therapies. In this study 102 consecutive
N
subjects with and without a history of cerebrovascular events underwent contrast-enhanced
U
carotid and brain MR protocols as well as and MR angiography. This study demonstrated that of 63 patients with mild to moderate stenosis (< or =70%), 44 (69.8%) had type IV-V vulnerable plaques, which was significantly higher than those of patients with severe stenosis
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
(>70%; p < 0.001). In stroke, the number of patients with a thin or ruptured FC was twice that of those with a thick and intact fibrous cap. Contrast enhanced MRI may therefore have important applications in clinical risk evaluations in atherosclerosis.
A study by Douek P et al.41, reported on sixty-nine patients scheduled for a carotid endarterectomy using 3T contrast enhanced MRI. The carotid plaque enhancement was
FS
assessed on T1 weighted images performed pre and post contrast administration. Histological analysis was performed on the entire plaque and on an area with matched contrast
O
enhancement. Gadolinium enhancement was observed in more than 50% of the patients.
R O
There were three types of carotid plaques that were identified depending on the enhancement pattern; in other words they were grouped according to whether it was the shoulder region,
P
the shoulder and fibrous cap or the central part of the plaque enhanced most. FC rupture, IPH, and plaque gadolinium enhancement was significantly more frequent in symptomatic than in
D
asymptomatic patients (p=0.043, p
Advances in MR imaging for the evaluation of carotid atherosclerosis Gregory C. Makris, MD, Zhongzhao Teng PhD, Andrew J. Patterson1, Jyh-miin Lin,
MBA
Gregory Makris, MD
P
Corresponding author:
R O
O
1. University Department of Radiology, University of Cambridge
FS
Victoria Young, MBBS, PhD , Martin J. Graves, PhD, Jonathan H. Gillard, FRCR,
D
University of Cambridge School of Clinical Medicine Box 218 Cambridge Biomedical Campus
E
Cambridge CB2 0QQ, UK
O
R
R
E
C
T
[email protected]
C
Funding source:
N
This research is supported by BHF PG/11/74/29100 and the NIHR Cambridge
U
Biomedical Research Centre.
B
JR
Keywords: MRI, stroke, carotid plaque, mechanics Running title: Carotid plaque MR imaging Type of Manuscript: Review articles Word count: 4,105 Abstract: 170 Tables: 2 Figure: 5 Conflict of interest: Nothing to declare Running title: Carotid plaque MR imaging
Manuscript
Abstract Carotid artery atherosclerosis is an important source of mortality and morbidity in the western world with significant socioeconomic implications. The quest for the early
FS
identification of the vulnerable carotid plaque is already in its 3rd decade and traditional
O
measures, such as the sonographic degree of stenosis, are not selective enough to distinguish
R O
those who would really benefit from a carotid endarterectomy. Magnetic resonance imaging of the carotid plaque enables the visualisation of plaque composition and specific plaque
P
components that have been linked to a higher risk of subsequent embolic events. Blood suppressed T1- T2-and proton density -weighted fast spin echo, gradient echo and time-of-
D
flight sequences are typically used, to quantify plaque components such as lipid-rich necrotic
E
core, intraplaque haemorrhage, calcification, and surface defects including erosion, disruption
T
and ulceration The purpose of this article is to review the most important recent advances in
U
N
C
O
R
R
E
C
MRI technology to enable better diagnostic carotid imaging.
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
Introduction Internal carotid artery (ICA) atherosclerosis is a significant source of mortality and morbidity
FS
in the western world1, 2. MRI enables the visualisation of plaque composition and specific plaque constituents have been linked to a higher risk of subsequent embolic events.
O
Currently, either the sonographic or angiographic degree of carotid stenosis is used as a
R O
marker of severity for assessing carotid disease and risk of stroke3, 4. However there is mounting evidence, which suggests that the degree of stenosis is not enough to accurately
P
characterize carotid plaque burden and vulnerability.
D
High-resolution, multi-contrast carotid MRI protocols have been used to depict
T
E
atherosclerotic components within carotid plaques, the validity of these protocols have been 5-7
.
C
evaluated using histopathology and the protocols have been applied in multi-centre trials
E
Blood suppressed T1- T2-and proton density (PD)-weighted fast spin echo and gradient echo
R
Time-Of-Flight (TOF) sequences) are typically used,8 to quantify plaque components such as 5, 9-11
, intraplaque haemorrhage (IPH)
5, 12-15
, calcification 5, 9
R
lipid-rich necrotic core (LRNC)
O
and surface defects including erosions, disruption and ulceration 11, 16-18. In addition, the intra14, 19-21
and the inter-scan reproducibility 20, 22, 23 of quantitative measures
C
reader, inter-reader
U
N
associated with both morphology and composition have been reported.
Novel MR-defined plaque features of vulnerability are emerging and appear promising for the identification of the vulnerable plaque. A recent systematic review of 9 studies with 779
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
subjects demonstrated that the presence of IPH, LRNC, and thinning/rupture of the fibrous cap (FC) is linked to an increased risk of future stroke or transient ischaemic attack (TIA)24. The hazard ratios for each of them as predictors of subsequent ischaemic events were 4.59 (95% confidence interval (CI), 2.91-7.24), 3.00 (95% CI, 1.51-5.95), and 5.93 (95% CI, 2.65-
13.20), respectively. In a separate meta-analysis focusing on IPH which pooled 8 clinical studies of 689 patients, the hazard ratio of MRI-depicted IPH in symptomatic patients was
B
FS
11.725. This evidence indicates that dedicated MRI-depicted plaque composition offers stroke
O
risk information beyond measurement of luminal stenosis.
R O
Although MRI holds promise, the clinical application for plaque characterisation will require further consensus regarding MRI protocols and new MRI techniques. A recent overview of
P
17 studies that assessed the agreement between MRI and histology indicated that MRI could characterise calcification, FC, IPH and LRNC with moderate-to-good sensitivity and
D
specificity26. It suggests that further effort is needed to use MRI as a routinely clinical
E
C
requirement of a dedicated receiver coil.
T
E
imaging modality to assess carotid atherosclerosis characteristics. One pragmatic issue is the
R
The purpose of this article is to review the most important recent advances in MRI
R
technology to enable better diagnostic carotid imaging. This article also reviews recent
U
N
C
O
advances in material stress analysis and molecular imaging relevant to carotid atherosclerosis.
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
MR sequences for Carotid plaque composition analysis The de facto standard for blood suppressed carotid imaging is double inversion recovery
FS
(DIR) preparation. Intra-luminal blood signal is suppressed by applying a 180° non-selective pulse to invert the magnetisation within the transmit volume, which is immediately followed
O
by a 180° slice selective pulse to revert the magnetisation within the imaging plane. The
R O
magnetisation in the blood outside the imaging plane reaches a null point after a period of time defined as the Inversion Time (TI). Also after a period of time, for any given flow rate,
B
P
inflowing blood from outside the imaging plane will replace in the intra-luminal space within
D
the defined imaging plane.
T
E
DIR is typically implemented as a gated single slice technique as black blood imaging is
C
originally developed for cardiac application where gating is a fundamental prerequisite.
E
However, gated acquisitions lead to variations in T1 relaxation and the signal slice
R
implementation results in scan-times, which preclude clinical adoption. In response Yarnykh
R
and Yuan27 implemented an ungated multi-slice DIR protocol; this in effect accelerates the
O
acquisition as a function of the number of slices, which are simultaneously acquired.
C
However, DIR is known to be sensitive at producing plaque-mimicking artifacts. This is
N
understood to frequently occur at the carotid bifurcation as complex flow patterns exist where
U
blood signal within the imaging plane is not fully displaced from the imaging plane.
More advanced methods for blood suppression have subsequently been proposed which are
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
even more time efficient and can null residual blood signal. Wang, et al
28
presented a
technique known as improved motion sensitized driven equilibrium (iMSDE), in which blood suppression can be directly controlled by the size of the motion sensitizing gradients. This method effectively suppresses blood signal, however, the technique induces additional T 2
decay. In 2012, Li et al29 presented Delayed Alternating Nutation with Tailored Excitation (DANTE). This study demonstrated how blood signal could be suppressed by both a function
B
FS
of the DANTE preparation echo-train length and flip angle. To date, there are no studies, which have systematically compared all three methods, however, results of our initial
R O
O
validation studies are presented in Figure 1.
Currently the majority of MR imaging is performed on 1.5T systems. The continuous
P
advances in MR technology have allowed carotid imaging at higher magnetic strengths and multi-phase coils increase the potential for parallel imaging. Preliminary experience with
D
eight-channel coils at 3T indicates an increase in signal to noise ratio (SNR) to contrast to
T
E
noise ratio (CNR) compared with 1.5T. In a study by Young et al 30, 18 subjects with carotid
C
atherosclerosis were imaged on both 1.5 and 3 T systems using the same receiver coil. T1-,
E
T2- and PD images were obtained and multiple slices were prescribed to encompass both the
R
carotid bifurcation and the plaque. In this study the mean improvements in SNR was 1.9, 2.1
31
recently reported on 19 patients at 3T and noted significant associations
O
Yuan et al,
R
and 2.1 respectively, which were statistical significant.
C
between the presence of thin/ruptured FC (100% versus 36%, p = 0.006) and lipid-rich
N
necrotic core (100% versus 39%, p = 0.022), with a borderline association with haemorrhage
U
(86% versus 33%,p = 0.055).
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
Assessment of carotid plaque morphology using 3D MR sequences In a 3D sequence an RF pulse is applied to excite an imaging volume, phase encoding is performed in both the convention phase encode axis and in the slice select direction. 3D
FS
sequences typically result in higher SNR efficiency. In a study by Balu et al 32 , a total of 18
O
subjects with significant carotid stenosis were imaged with 2D (2-mm slice thickness) and 3D
R O
(1-mm/0.5-mm (acquired/interpolated) slice thickness) T1 weighted fast spin-echo (FSE) black-blood imaging sequences with DIR blood suppression. Morphological measurements,
P
SNR in the wall and lumen, and wall-lumen CNR were compared between 2D and 3D images. The lumen SNR, wall SNR, and CNR were comparable between the two methods.
D
There was also no difference in average volumetric measurements between 2D/3D. In
T
E
contrast the distributions of small plaque components such as calcification were better
C
characterized by the 3D acquisition while there was a higher sensitivity to motion artifacts
E
with 3D imaging, resulting in a small number of examinations with low image quality. The
R
conclusion from this study was that 2D and 3D protocols can provide comparable
R
morphometric and volumetric measurements of the carotid artery with the 3D imaging
O
offering an advantage in terms of small plaque component visualization but with the price of
N
C
lower reliability for image quality.
U
In another study by Takano et al.33, twenty-two patients scheduled for carotid endarterectomy underwent carotid plaque MRI with both a conventional fast spin echo 2D sequence and 3D fast spin echo sequence with variable refocusing flip angles. This 3D sequence enables the
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
acquisition of longer echo train lengths whilst reducing the T 2 blurring effect that would typically accrue by attempting to maintain magnetisation across the train of refocusing pulse. Image quality and SNR were evaluated; observations were compared for each plaque component according to the histological category of the plaque between 2D and 3D
sequences (Figure 2). No significant differences were observed among the overall imaging quality scores of the two modalities, although 3D sequences allowed visualization in random
FS
orientations, as well as better depiction of small plaque components such as ulcerations and calcifications. The SNR of the plaque to the submandibular gland on T1 weighted 3D
O
sequence was significantly higher than that on the 2D sequence. In addition it was shown that
R O
the SNR of the plaque to the submandibular gland of histology-defined soft plaque components were significantly higher on T1 weighted 3D sequence than on 2D sequence.
B
P
From this study it was concluded that 3D variable-flip-angle turbo spin-echo is a promising
D
tool for diagnostic imaging.
T
E
In 2011, Balu et al34 proposed a black blood 3D gradient echo sequence (3D-MERGE), the
C
sequence was evaluated on 9 patients with carotid atheroma. The proposed sequence
E
incorporated black blood preparation using iMSDE preparation prior to 3D spoiled gradient
R
echo readout. The proposed gradient sequence enabled isotropic resolution (0.7 mm3), and is
O
R
more time efficient than the 3D fast spin echo alternatives (imaging time ~2minutes).
C
In addition the advances in MR technology allow the use of non-gated sequences instead of
N
gated sequences for atherosclerotic vessel wall imaging without compromising image quality. 35
. Other examples of
U
This may shorten examination time and improve patient comfort
technological advances include the three-dimensional (3D) diffusion-prepared segmented steady-steady free precession (DP-SSFP) cardiovascular magnetic resonance (CMR)
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
sequence for black-blood
36
which allows for 3D acquisition of thin and contiguous slices
with black-blood image contrast. Finally turbo spin-echo (TSE) based motion-sensitized driven-equilibrium (MSDE) sequence have been developed as an alternative to black-blood
(BB) carotid MRI imaging providing a more accurate depiction of the lumen boundaries by
FS
eliminating plaque mimicking artefacts in carotid plaque imaging37.
Identification of intraplaque haemorrhage
38
. The sequence was coined
R O
excitation pulse was first presented by Moody, et al in 2003
O
The characterisation of IPH using a 3D gradient echo sequence with a selective water
MRDTI (Magnetic Resonance Direct Thrombus Imaging). Their study demonstrates using
this technique was proposed by Zhu et al in 2010
39
P
histopathology validation, the sequence utility in detecting thrombus. A subsequent variant of . This sequence referred to as 3D SHINE
D
(3D Spoiled gradient recalled echo pulse sequence for haemorrhage assessment using
T
E
inversion recovery and multiple echos) enable the simultaneous detection and aging of
C
thrombus based in its respective T1 and T2* relaxation properties. The differentiation between
R
E
IPH and thrombus can be challenging and a general guide can be seen at Table 1 and 2.
R
The evaluation of fibrous cap thickness
O
Wang Y et al.40, previously demonstrated that different types of stroke can be identified using
C
standard brain MR protocols prior to invasive therapies. In this study 102 consecutive
N
subjects with and without a history of cerebrovascular events underwent contrast-enhanced
U
carotid and brain MR protocols as well as and MR angiography. This study demonstrated that of 63 patients with mild to moderate stenosis (< or =70%), 44 (69.8%) had type IV-V vulnerable plaques, which was significantly higher than those of patients with severe stenosis
B
JR
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
(>70%; p < 0.001). In stroke, the number of patients with a thin or ruptured FC was twice that of those with a thick and intact fibrous cap. Contrast enhanced MRI may therefore have important applications in clinical risk evaluations in atherosclerosis.
A study by Douek P et al.41, reported on sixty-nine patients scheduled for a carotid endarterectomy using 3T contrast enhanced MRI. The carotid plaque enhancement was
FS
assessed on T1 weighted images performed pre and post contrast administration. Histological analysis was performed on the entire plaque and on an area with matched contrast
O
enhancement. Gadolinium enhancement was observed in more than 50% of the patients.
R O
There were three types of carotid plaques that were identified depending on the enhancement pattern; in other words they were grouped according to whether it was the shoulder region,
P
the shoulder and fibrous cap or the central part of the plaque enhanced most. FC rupture, IPH, and plaque gadolinium enhancement was significantly more frequent in symptomatic than in
D
asymptomatic patients (p=0.043, p
