Keywords
cerebrovascular disease - image quality - CTA - time-of-flight MRA
Palavras-chave
doença cerebrovascular - qualidade de imagem - CTA - angiografia por tempo de voo
Introduction
Cerebrovascular disease (CVD) is a major public health concern globally, significantly
contributing to morbidity and mortality.[1] CVD encompasses a range of conditions that affect the blood vessels and blood supply
to the brain, leading to potentially severe outcomes such as stroke, transient ischemic
attacks, and other neurologic impairments.[2] The World Health Organization reports that stroke, a primary manifestation of CVD,
is the second leading cause of death and the third leading cause of disability worldwide.[1]
[3] The burden of CVD is profound, with significant implications for healthcare systems,
economies, and the quality of life of affected individuals and their families.[2]
Accurate and timely diagnosis is crucial for effective management of cerebrovascular
disease. The utilization of advanced imaging techniques has revolutionized the diagnostic
process by enabling the evaluation of cerebrovascular abnormalities.[4] Traditionally, Digital Subtraction Angiography (DSA) has been considered the gold
standard for diagnosing cerebrovascular conditions due to its high spatial resolution
and excellent visualization of the vascular anatomy.[5] DSA involves the injection of contrast material into the bloodstream and the acquisition
of detailed images, which can highlight even small vascular anomalies with high precision.
However, despite its diagnostic superiority, DSA is an invasive procedure associated
with potential complications, including bleeding, infection, and adverse reactions
to contrast agents.[6]
To mitigate the risks associated with DSA, non-invasive imaging modalities such as
Computed Tomography Angiography (CTA), Contrast-Enhanced Magnetic Resonance Angiography
(CE MRA), and Time-of-Flight Magnetic Resonance Angiography (TOF MRA) have been developed
and widely adopted in clinical practice. Each of these modalities offers distinct
advantages and limitations, influencing their use in different clinical scenarios.[7]
CTA has become a widely used and standard technique for evaluating cerebrovascular
disease. CTA involves the use of a CT scanner and intravenous administration of iodinated
contrast material to obtain detailed images of the cerebral vasculature.[8] One of the key advantages of CTA is its high spatial resolution, which enables the
accurate detection of a wide range of cerebrovascular abnormalities, including stenosis,
occlusions, aneurysms, and arteriovenous malformations.[9]
[10]
However, CTA is not without its limitations. The use of ionizing radiation in CTA
poses a risk, particularly with repeated exposures, which can be a concern for patients
requiring multiple follow-up scans.[11]
[12] Additionally, the administration of iodinated contrast agents can lead to adverse
reactions, ranging from mild allergic responses to severe nephrotoxicity, especially
in patients with pre-existing renal impairment.[13] These limitations necessitate the exploration of alternative imaging modalities
that can provide comparable diagnostic accuracy without the associated risks.
TOF MRA has emerged as a promising non-invasive alternative to CTA.[14] TOF MRA leverages the inherent properties of blood flow and magnetic resonance imaging
to generate detailed images of the cerebral vasculature without the need for contrast
agents. This technique utilizes a strong magnetic field and radiofrequency pulses
to excite hydrogen protons in the blood, producing high-contrast images of the blood
vessels.[15] One of the primary advantages of TOF MRA is the elimination of contrast-related
risks, making it a safer option for patients with renal insufficiency or contrast
allergies.[16] Additionally, TOF MRA avoids exposure to ionizing radiation, making it suitable
for repeated imaging and longitudinal follow-up studies.[15]
[17]
Despite these advantages, the diagnostic proficiency of TOF MRA compared with CTA
and CE MRA has been a subject of ongoing research and debate.[14]
[15]
[18]
[19]
[20] Some studies suggest that TOF MRA may have limitations in detecting small aneurysms
and accurately characterizing complex vascular structures due to its lower spatial
resolution and susceptibility to flow-related artifacts.[15]
[21] Conversely, other studies highlight the capability of advanced TOF MRA techniques,
such as 3-T contrast-enhanced MRA and 3D TOF MRA, to provide reliable and detailed
evaluations of cerebrovascular conditions, comparable to those obtained with CTA.[17]
[22]
The aim of this study is to investigate the diagnostic value of TOF MRA compared with
CTA in the assessment of cerebrovascular disease. Through the analysis of essential
diagnostic parameters, our objective is to assess the reliability of TOF MRA as a
non-invasive substitute for CTA.
Methods
Study Design and Population
A retrospective observational study was conducted, to investigate patients with acute
neurologic symptoms and evaluate cerebrovascular disease. The study received approval
from the Ethics Committee of ……………REC.1402.146). The study population comprised 205
adult patients (mean age: 60 ± 11.67 years) who underwent both TOF MRA and CTA scans
within seven days of each other during the same admission. Demographic parameters,
including age and, gender, were collected for each patient. Clinical symptoms such
as weakness in limbs, aphasia, loss of consciousness, loss of balance, vertigo, numbness,
dysarthria, and difficulty in vision were assessed. Inclusion criteria involved patients
above 18 years of age with available TOF MRA and CTA images, while severe artifacts
hindering interpretation or incomplete imaging protocols were considered as exclusion
criteria. The imaging data obtained from the hospital's Picture Archiving and Communicating
System (PACS) underwent anonymization using unique codes. The analysis of the imaging
data revealed different cerebrovascular conditions, including vessel stenosis, vessel
occlusion, aneurysm, and arteriovenous malformation. It is important to note that
although DSA is widely considered the traditional gold standard for cerebrovascular
evaluation, its unavailability for the selected patients precluded its inclusion in
the study.
Image Acquisition
CT Angiography
CTA imaging was performed using a 16-MDCT scanner (Neusoft, Neuviz 16) to acquire
multidetector-row computed tomographic angiography (MDCTA) data. The scanning parameters
included a voltage of 120 kV, automatic mA selection, a matrix size of 512 × 512,
a pitch of 1.5, a rotation speed of 0.6 seconds, a detector collimation of 16 × 0.75 mm,
and a field of view (FOV) of 199 mm. A total of 150 mL of contrast material (Visipaqu
320 mg/mL) was administered to each patient through a 20-gauge needle in the antecubital
vein, at a flow rate of 4 mL/s. Scanning was initiated using a bolus-tracking technique,
starting when the region of interest (ROI) in the common carotid artery reached 80
Hounsfield units (HU), with a 5-second delay.
Magnetic Resonance Angiography
MRA was conducted using a 1.5 T scanner (Magnetom Vision; Avanto; I-class). The acquisition
parameters for the 3D Time-of-Flight (TOF) MRA sequence were set as follows: a repetition
time/echo time (TR/TE) of 25 milliseconds/7 milliseconds, a flip angle of 25 degrees,
and FOV of 180 mm for the read direction with a phase FOV of 100%. The slice thickness
was 0.5 mm with a slice oversampling of 14.3%. The actual bandwidth was 100 Hz/pixel,
resulting in a voxel size of 0.7 × 0.7 × 0.5 mm. The total acquisition time for the
MR imaging scan was 4 minutes and 58 seconds.
Image Interpretation
Two radiologists, blinded to the patients' clinical information, independently performed
the interpretation of the imaging datasets. Initially, the CTA images were evaluated,
followed by a separate interpretation of the TOF MRA images. To minimize recall bias,
the TOF MRA images were assessed at least four weeks after the initial CTA evaluation.
In cases of uncertain or conflicting results, the radiologists collaborated to reach
a consensus. CTA was considered the reference standard, given its established accuracy
and extensive clinical usage for evaluating cerebrovascular disease.
Statistical Analysis
The collected data were organized and stored in a database for further analysis. The
performance of TOF-MRA in detecting CVD was summarized based on sensitivity, specificity,
positive predictive value (PPV), and negative predictive value (NPV), with CTA serving
as the reference standard. All statistical analyses were performed using SPSS version
26. p < 0.05 was considered statistically significant.
Results
Patient Demographics
A total of 205 patients were included in the study (84 female, 41%). Among the patients,
the highest number of participants fell between the age range of 61–70 years, comprising
33.6% of the total patients. In terms of clinical symptoms, the most prevalent symptom
reported was weakness in limbs, affecting 59.5% of the individuals. This was followed
by loss of balance, loss of consciousness, and dysarthria as the common symptoms,
in descending order ([Table 1]).
Table 1
Participant characteristics
|
Demographic Data
|
Frequency (%)
|
|
Gender
|
|
Male
|
121(59%)
|
|
Female
|
84(41%)
|
|
Age
|
|
≤50 years
|
44(21.4%)
|
|
51–60 years
|
57(28%)
|
|
61–70 years
|
69(33.6%)
|
|
> 70 years
|
35(17%)
|
|
Chief complaint
|
|
Weakness in limbs
|
122(59.5%)
|
|
Aphasia
|
73(35%)
|
|
Loss of consciousness
|
45(21.9%)
|
|
Loss of balance
|
35(17%)
|
|
Vertigo
|
51(24.8%)
|
|
Numbness
|
19(9%)
|
|
Dysarthria
|
104(50%)
|
|
Difficulty in vision
|
25(12.1%)
|
|
Clinical history
|
|
Diabetes mellitus
|
71(34%)
|
|
Hypertension
|
102(49.7%)
|
|
CAD
|
28(13%)
|
|
Cancer
|
6(3%)
|
|
CVA
|
14(7%)
|
Abbreviations: CAD, Coronary artery disease; CVA, Cerebrovascular accident.
Imaging Findings
Based on the imaging results represented in [Table 2], it was observed that the prevalence of vessel occlusion was higher in the 3D TOF
MRA group (45.9%) compared with the CTA group (39%). Conversely, CTA exhibited a higher
detection rate for aneurysms with 2.9%, whereas 3D TOF MRA had a detection rate of
1.5%, respectively.
Table 2
Comparative imaging results of TOF MRA and CTA techniques
|
Finding
|
CTA
|
3D TOF MRA
|
|
Normal
|
64(31.2%)
|
66(32.2%)
|
|
Vessel stenosis
|
54(26.3%)
|
42(20.5%)
|
|
Vessel occlusion
|
80(39%)
|
94(45.9%)
|
|
Aneurysm
|
6(2.9%)
|
3(1.5%)
|
|
Arteriovenous malformation
|
1(0.5%)
|
0(0%)
|
Comparison of TOF MRA and CTA
Among 139 cases where TOF MRA detected CVD, 124 were confirmed by CTA. Conversely,
17 out of 66 cases that were negative on TOF MRA showed CVD on CTA. A significant
association between CVD changes detected by MRA and CTA was observed ([Table 3]). To evaluate TOF MRA's diagnostic performance against CTA, various parameters were
calculated. MRA showed a sensitivity of 88%, a specificity of 76%, and an overall
diagnostic efficacy of 84%, demonstrating its strong capability in diagnosing cerebrovascular
disease ([Table 4]).
Table 3
Comparison of MRA and CTA in detecting cardiovascular disease in participants
|
3D TOF MRA
|
CTA (Gold standard)
|
Total
|
p-value
|
|
Absent, n(%)
|
Present, n(%)
|
|
Present, n(%)
|
15(7%)
|
124(60%)
|
139(67%)
|
<0.001
|
|
Absent, n(%)
|
49(24%)
|
17(8%)
|
66(33%)
|
|
Total
|
64(32%)
|
141(68%)
|
205
|
Table 4
Performance metrics of the TOF MRA
|
Diagnostic parameter
|
value
|
95% CI
|
|
Sensitivity
|
88%
|
(83–92%)
|
|
Specificity
|
76%
|
(70–81%)
|
|
PPV
|
89%
|
(84–93%)
|
|
NPV
|
74%
|
(68–78%)
|
|
Diagnostic efficacy
|
84%
|
(78–88%)
|
Discussion
Cerebrovascular disease is a significant global health concern, and precise diagnosis
is crucial for effective management. While CTA has been the standard imaging modality,
TOF MRA offers non-invasive imaging without radiation exposure. This study was aimed
to assess the diagnostic performance of TOF MRA compared with CTA in a clinical setting.
Our study included 205 patients (mean age: 60 ± 11.67 years) with a slight male predominance.
Hypertension was the most prevalent risk factor in our cohort, emphasizing its well-established
association with CVD. A related study by Kazumitsu Nawata[1] found that age significantly influences CVD risk, with individuals aged 70 having
nearly double the risk compared with those aged 50. Furthermore, a history of heart
disease more than doubles the risk. The study conducted by Antoine Raberin et al.[23] highlights the influence of sex on the development of adverse cardiovascular disease
effects. It was observed that as individuals age, men tend to be more susceptible
to CVD compared with females. This difference in risk can be attributed to the effects
of testosterone in elderly males, which can increase the risk of CVD. In contrast,
estrogen in females has a vasodilatory effect, which contributes to a lower risk of
CVD. In this study, approximately half of the cases (49.7%) had high blood pressure,
which is known to increase the chances of stroke, atrial fibrillation, heart attack,
and the formation of clots in the left ventricle.[24]
[25] Likewise, the study conducted by Huimin Fan et al. found that hypertension was an
independent risk factor for silent cerebrovascular disease in young patients who had
their first-ever stroke.[26]
The imaging results from our study revealed distinct patterns in the detection rates
of various cerebrovascular conditions when comparing TOF MRA and CTA. TOF MRA identified
a higher prevalence of vessel occlusion (45.9%) than CTA (39%). However, it is important
to consider the potential for misclassification in detecting vessel stenosis. TOF
MRA detected fewer stenosis cases compared with CTA (20.5% versus 26.3%), indicating
a possible overestimation of stenosis as occlusions in MRA. This observation is in
line with the findings of the study conducted by Yukunori Korogi et al.,[27] which emphasize the importance of interpreting source images rather than maximum
intensity projection (MIP) images in MR angiography to reduce the overestimation of
stenosis and improve the sensitivity for detecting significant stenosis. In contrast,
previous studies[9]
[14] found that CTA exhibited higher sensitivity and positive predictive value than TOF
MRA for detecting intracranial stenosis and occlusion. These differences may arise
from varying examination methods and post-processing techniques employed in different
studies. M. Lell et al.[28] highlighted the influence of these factors on stenosis grading, noting that CTA
and TOF MRA showed the highest concordance when evaluated using multiplanar reconstruction
(MPR). These insights highlight the importance of considering methodological variations
and the expertise of observers in interpreting imaging results, which significantly
impact the diagnostic accuracy of each modality.
Furthermore, our study revealed that CTA exhibited a higher detection rate for aneurysms
(2.9%) compared with MRA (1.5%). These findings align with previous studies, which
have consistently demonstrated the superior ability of CTA to detect aneurysms compared
with MRA.[29]
[30] This advantage can be attributed to CTA's higher spatial resolution and enhanced
contrast capabilities, allowing for better visualization of small vascular abnormalities
like aneurysms.[8]
[10] However, advancements in MRI technology have led to the development of 3-T contrast-enhanced
and 3D TOF MRA, which have shown reliability in evaluating and characterizing intracranial
aneurysms. Previous studies[31]
[32]
[33] have demonstrated that these advanced MRI techniques produce results comparable
to those of CTA in detecting and assessing aneurysms. These findings suggest that
with state-of-the-art MRI techniques, clinicians may have viable alternatives to CTA
for the evaluation of intracranial aneurysms.
One of the key strengths of this study lies in the considerable sample size, which
consisted of 205 patients. This large cohort enhances the study's statistical power
and lends credibility to the findings. Nevertheless, it is crucial to acknowledge
certain limitations. First, the absence of DSA as a reference standard comparative
modality restricts the comprehensive assessment of diagnostic accuracy. Additionally,
the study's single-center design may limit the generalizability of the results to
broader populations. To overcome these limitations, future research endeavors should
focus on incorporating multicenter studies with larger and more diverse cohorts. Furthermore,
the inclusion of DSA in the evaluation of diagnostic modalities would provide a more
comprehensive analysis.
Conclusion
In conclusion, this study found that TOF MRA had a higher detection rate for vessel
occlusions, while CTA was more effective in detecting vessel stenosis and aneurysms.
TOF MRA has the advantage of being safer for repeated use and in patients with renal
insufficiency due to its lack of contrast agents and ionizing radiation. However,
its lower spatial resolution compared with CTA may lead to misclassification issues.
