The applied research of MRI with ASSET-EPI-FLAIR combined with 3D TOF MRA sequences in the assessment of patients with acute cerebral infarction

Abstract

Background

To extend the time window for thrombolysis, reducing the time for diagnosis and detection of acute cerebral infarction seems to be warranted.

Purpose

To evaluate the feasibility of implementing an array spatial sensitivity technique (ASSET)-echo-planar imaging (EPI)-fluid attenuated inversion recovery (FLAIR) (AE-FLAIR) sequence into an acute cerebral infarction magnetic resonance (MR) evaluation protocol, and to assess the diagnostic value of AE-FLAIR combined with three-dimensional time-of-flight MR angiography (3D TOF MRA).

Material and Methods

A total of 100 patients (68 men, 32 women; age range, 44–82 years) with acute cerebral infarction, including 50 consecutive uncooperative and 50 cooperative patients, were evaluated with T1-weighted (T1W) imaging, T2-weighted (T2W) imaging, FLAIR, diffusion-weighted imaging (DWI), 3D TOF, EPI-FLAIR, and AE-FLAIR. Conventional FLAIR, EPI-FLAIR, and AE-FLAIR were assessed by two observers independently for image quality. The optimized group (AE-FLAIR and 3D TOF) and the control group (T1W imaging, T2W imaging, conventional FLAIR, DWI, and 3D TOF) were compared for evaluation time and diagnostic accuracy.

Results

One hundred and twenty-five lesions were detected and images having adequate diagnostic image quality were in 73% of conventional FLAIR, 62% of EPI-FLAIR, and 89% of AE-FLAIR. The detection time was 12 ± 1 min with 76% accuracy and 4 ± 0.5 min with 100% accuracy in the control and the optimized groups, respectively. Inter-observer agreements of κ = 0.78 and κ = 0.81 were for the optimized group and control group, respectively.

Conclusion

With reduced acquisition time and better image quality, AE-FLAIR combined with 3D TOF may be used as a rapid diagnosis tool in patients with acute cerebral infarction, especially in uncooperative patients.

Keywords

Acute cerebral infarction magnetic resonance imaging (MRI)three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA)image quality fluid attenuated inversion recovery (FLAIR)

Introduction

Cerebral stroke is one of the most common causes of long-term disability or death worldwide and results in a marked burden in healthcare system (1). Typically, a stroke is caused by the blood supply reduction to the brain due to cerebral artery occlusion by a clot (2). This so-called ischemic stroke (cerebral infarction), which may result from cardiogenic, lacunar, arterosclerotic, hemodynamic, or cryptogenic sources, accounts for about 80% of strokes (3). The minority of strokes is related to disruption of a cerebral artery resulting in intracerebral hemorrhage (2). Currently, early recanalization of an occluded cerebral artery with use of a neurothrombectomy device or thrombolytic drug to salvage ischemic tissue at risk of infarction and decrease the size of the infarct may lead to a better functional outcome of patients with acute ischemic stroke (4). Thus, to extend the time window for thrombolysis, reducing the time for diagnosis and detection of acute cerebral infarction seems to be warranted.

Neuroimaging has been demonstrated to play a significant role in the evaluation of patients with acute cerebral infarction (5). In order to better investigate anatomical details and pathologic lesions in the brain, routine magnetic resonance imaging (MRI) protocols include various types of sequences such as T1-weighted (T1W) and T2-weighted (T2W) imaging (5). However, adequate image quality is often impaired by motion artifacts which may sometimes obscure or mimic pathology in uncooperative patients with unconsciousness or respiratory failure symptoms (5,6). Because of longer acquisition time and limited availability, MRI has been mainly used in comprehensive stroke centers (7). With recent advances in MR technology, a comprehensive MR protocol including parenchymal imaging (diffusion-weighted imaging [DWI], gradient recalled-echo [GRE], fluid attenuated inversion recovery [FLAIR]), MR angiography (MRA), and MR perfusion can be obtained in 20 min as demonstrated in several clinical trials (5,8). The tissue contrast of DWI aids in the assessment of alterations of water diffusion related to the cytotoxic edema in the acute phase of brain ischemia (9). Besides, three-dimensional time-of-flight MRA (3D TOF MRA), an available non-invasive technique, is a commonly used pulse sequence in the MR evaluation of intracranial arteries (10). FLAIR imaging is a T2W imaging sequence and is an indispensable part of common multi-parametric stroke MRI protocols (9). Recently, introduction of fast imaging techniques, such as parallel acquisition and echo-planar imaging (EPI), has obviously enhanced the performance of MRI with regard to acquisition speed (5,7). For instance, a study has demonstrated that the application of EPI to the FLAIR sequence (EPI-FLAIR) was feasible with comparable quantitative and qualitative results to the conventional FLAIR and resulted in reduced acquisition time (5). The reduction of acquisition time may prove useful for examining the uncooperative, medically unstable, or claustrophobic patients. However, few studies have investigated the ability of the application of both EPI and parallel acquisition techniques to the FLAIR sequence in evaluation of patients with acute cerebral infarction.

Parallel acquisition imaging spatial encoding from coil elements of the receiver array to compress the gradient encoding steps and hence accelerate acquisition (11). In this study, array spatial sensitivity technique (ASSET) parallel acquisition, a sensitivity encoding (SENSE)-based algorithm, was employed. The purpose of this study was to evaluate the feasibility of implementing an ASSET-EPI-FLAIR (AE-FLAIR) sequence into an acute cerebral infarction MR evaluation protocol, to assess the diagnostic value of AE-FLAIR combined with 3D TOF MRA, and to compare with the results with conventional MR protocol.

Material and Methods

Patients

From March 2010 and March 2015, 100 consecutive patients with acute ischemic stroke who had undergone computed tomography (CT) to rule out intracranial hemorrhage were recruited for this study. Consecutive selection of patients was performed in this study, and these 100 patients included 50 cooperative and 50 uncooperative patients. All these patients met the following inclusion criteria: age >40 years; within 72 h after onset of ictus; in accordance with the Chinese guidelines of diagnosis and treatment for acute ischemic stroke (2010) (12) and having ruled out intracranial hemorrhage by CT evaluation; and a National Institutes of Health Stroke Scale (NIHSS) score at admission (>20). The exclusion criteria were as follows: intracranial hemorrhage; hypoxic-ischemic encephalopathy; toxication; hypoglycemia; hypotension; hepatic encephalopathy; pulmonary encephalopathy; other intracephalic diseases such as encephalitis; tumor; and parasitosis. Besides, the clinical stages of these 100 patients with acute ischemic stroke were determined as previously described (13). Additionally, this study was approved by the local institutional review committee, and written informed consent from the patients or the closest family member of the patients was obtained before the start of the study.

MRI protocol

All MRI scans were performed on a 1.5-T MR scanner (Optima, MR360; GE Healthcare, Beijing, China) retrofitted for EPI and ASSET capabilities with a standard circularly polarized head coil. The following sequences were performed in all participants (the cooperative group and the uncooperative group of patients) in an axial plane: DWI, 3D TOF MRA, conventional FLAIR, Prol-T2W imaging, fast spin echo (FSE)-T1W imaging, EPI-FLAIR, and AE-FLAIR. The parameters used for these sequences were presented in Table 1. For each sequence, 20 contiguous sections that covered the entire brain from the foramen magnum to the vertex were acquired.

Table 1.

Summary of imaging parameters for the sequences that were applied for MRI scans

Parameter	DWI	3D TOF MRA	FLAIR	Prol-T2W imaging	FSE-T1W imaging	EPI-FLAIR	AE-FLAIR
Field of view (cm)	24 × 24	22 × 18	24 × 18	24 × 18	24 × 18	24 × 24	24 × 24
TR/TE (ms)	5000/minimum	28/6.9	8600/140	5200/126	450/minimum	9000/minimum	9000/minimum
Slice thickness/inter-slice gap (mm)	6/2	1.2/0	6/2	6/2	6/2	6/2	6/2
Matrix size	128 × 128	320 × 192	320 × 192	320 × 328	320 × 224	192 × 64	192 × 64
NEX	1	1	1	1.5	2	1	1
Asset R value	2						2
b (s/mm²)	1000/0					1000/0	1000/0
BW		15.63	27.78	31.25	31.25
TI (ms)			2000–2200			2000–2200	2000–2200
Echo train length			24	24	20

3D TOF MRA, three-dimensional time-of-flight magnetic resonance angiography; AE-FLAIR, array spatial sensitivity technique-EPI-FLAIR; BW, bandwidth; DWI, diffusion-weighted imaging; EPI-FLAIR, echo-planar imaging-FLAIR; FLAIR, fluid attenuated inversion recovery; FSE-T1W, fast spin echo-T1-weighted; NEX, number of excitations; asset R value, scan time reduction factor; TI, inversion time; TR/TE, repetition time/echo time.

Image analysis

All datasets were transferred to a workstation. Image analysis was done by a fully trained neuroradiologist and a neurologist who were experienced in reading of brain images from patients with stroke. The two observers were masked to clinical information including the final extent of infarction. The readers were asked to grade FLAIR, EPI-FLAIR, and AE-FLAIR maps using a scale (range, 0–3) scoring system in terms of the presence of image motion artifacts, visualization of infarction, delineation of major structures, susceptibility mediated distortion at tissue interfaces: 0, poor image quality for diagnosis, not interpretable; 1, evident distortion, lesions with visible, limited detail of delineation of lesions with surrounding brain tissue, acceptable image quality for diagnosis; 2, minimal distortion with detailed delineation of all structures, moderate diagnostic image quality; and 3, excellent image quality for confident diagnosis and sharply defined borders, no distortion. A score of 2 or 3 was considered as overall adequate diagnostic image quality. The readers were also asked to assess the clinical value of the MRI results in the optimized group (AE-FLAIR and 3D TOF MRA) and the control group (T1W imaging, T2W imaging, conventional FLAIR, DWI, and 3D TOF). Individual observer’s judgments were used only for the calculation of inter-observer agreement.

Statistical evaluation

All statistical analyses were performed with the SPSS 13.0 software (SPSS Inc., Chicago, IL, USA). A kappa coefficient (κ) test was used to assess inter-observer agreement, and the median score of these two observers was used in the follow-up analysis. Good inter-observer agreement was noted between the two readers when κ ≥ 0.75. A χ² test was carried out to determine differences in the ratio of good image quality (score of 2 or 3) in the optimized group and the control group. The differences with a value of P < 0.05 were regarded as statistically significant.

Results

Baseline characteristics

The age of these 100 patients (68 men, 32 women) was in the range of 44–82 years (mean age, 63 ± 0.5 years). The NIHSS score was 25 ± 3. The 100 patients were also categorized into hyperacute phase (n = 18) and acute phase (n = 82).

Clinical imaging findings and image quality

As shown in Table 2, a total of 125 brain lesions (acute infarction) were identified by both observers in these 100 patients with conventional FLAIR, EPI-FLAIR, or AE-FLAIR. Among these 125 brain lesions, 20 lesions were in the fronto-parietal region, 22 in the temporo-parietal region, 18 in the parieto-occipital region, 30 in the corona radiata region, 14 in the pons, 11 in the cerebellum, and 10 in the temporal lobe. Images were rated as having adequate diagnostic image quality (score of 2 or 3) in 73% (92/125) of conventional FLAIR, 62% (78/125) of EPI-FLAIR, and 89% (101/125) of AE-FLAIR for both the group of cooperative patients and the group of uncooperative patients. In the uncooperative group of patients, the ratio of good image quality of the AE-FLAIR sequences (48/55, 87%) was higher than those of the conventional FLAIR (25/55, 45%) and EPI-FLAIR (36/55, 65%) sequences in all the cases (P < 0.05).

Table 2.

Summary of the results of the quantitative comparison between the cooperative group and the uncooperative group of patients.

	Sequences	Score of 3	Score of 2	Score of 1	Score of 0	Ratio of good image quality	Group comparison	χ²	df	P value
Cooperative group (n = 50)	1. FLAIR	62	5	3	0	96%	1 and 2	1.723	1	0.326
	2. AE-FLAIR	8	55	7	0	90%	1 and 3	25.895	1	0.0005
	3. EPI-FLAIR	2	40	26	2	60%	2 and 3	16.800	1	0.0005
Uncooperative group (n = 50)	1. FLAIR	5	20	18	12	45%	1 and 2	21.544	1	0.0005
	2. AE-FLAIR	10	38	6	1	87%	1 and 3	4.453	1	0.055
	3. EPI-FLAIR	4	32	12	7	65%	2 and 3	7.253	1	0.013
Total patients (n = 100)	1. FLAIR	67	25	21	1	73%	1 and 2	9.459	1	0.003
	2. AE-FLAIR	18	93	13	1	89%	1 and 3	3.603	1	0.078
	3. EPI-FLAIR	6	72	38	9	62%	2 and 3	23.614	1	0.0005

AE-FLAIR, array spatial sensitivity technique-EPI-FLAIR; df, degrees of freedom; EPI-FLAIR, echoplanar imaging-FLAIR; FLAIR, fluid attenuated inversion recovery.

There were no discrepancies between FLAIR, EPI-FLAIR, and AE-FLAIR in identification of the anatomic location of infarctions (Figs. 1 –3). Nevertheless, 28 lesions detected by conventional FLAIR sequences, 47 lesions by EPI-FLAIR sequences, and 14 lesions by AE-FLAIR sequences were deemed non-diagnostic (image quality <2). More specifically, in the group of the uncooperative patients, the AE-FLAIR sequences had higher scores in image quality, where motion artifacts and other artifacts such as susceptibility artifacts had been most eliminated (Fig. 3). In other words, the 28 lesions with non-diagnostic value of conventional FLAIR sequences because of significant motion artifacts could be distinctly visible by EPI-FLAIR and AE-FLAIR sequences (Fig. 3). Of the 47 lesions (12 in the frontal lobe, 14 in the pons, 10 in the cerebellopontine angle, and nine in the cerebellum) that were shown with distortion and susceptibility artifacts using EPI-FLAIR sequence, 13 could be detectable using AE-FLAIR and be clearly visible using conventional FLAIR sequence (Fig. 1). Additionally, the 14 lesions (six in the pons, two in the cerebellopontine angle, and eight in the cerebellum) that was affected by susceptibility artifacts using AE-FLAIR sequence, could be clearly visible using conventional FLAIR sequence. In addition, higher contrast obtained between the infarctions and other brain tissues was found in AE-FLAIR sequences compared with those in the EPI-FLAIR or conventional FLAIR sequences.

Inter-observer reliability and evaluation time comparison

Out of the 125 lesions, 100 were deemed to have clinical value and 25 were deemed not to have clinical value by two observers in the control group of MRI. On the other hand, 98 were regarded to be with clinical value and 27 without clinical value by the two observers in the optimized group of MRI. Moreover, the inter-observer reproducibility was moderate for the control imaging group with κ = 0.75 and good as well for the optimized imaging group with κ = 0.81.

The detection time for patients in the MRI control group was 12 ± 1 min, and the diagnostic accuracy was 76%. While the detection time for patients in the optimized group was 4 ± 0.5 min, and the diagnostic accuracy was 100% (χ²= 61.782, df = 1, P = 0.0005).

Discussion

In this study, the examined AE-FLAIR sequences were applied both on groups of cooperative and uncooperative patients, whose clinical characteristics have significant difference in order to explore the clinical impact of AE-FLAIR sequences. We demonstrated a feasibility of AE-FLAIR sequences for the detection of acute cerebral infarction especially in terms of better image quality and reduced detection time. The use of the AE-FLAIR sequences may serve as a surrogate marker to identify patients with acute cerebral infarction who are eligible for thrombolysis. Moreover, our study showed an integration between AE-FLAIR sequences and 3D TOF MRA to demonstrate the acute infarctions.

Numerous investigations have reported that combined use of DWI and perfusion-weighted imaging (PWI) is increasingly used in hyperacute stroke in order to determine the infarct core and the ischemic penumbra (defined as functionally impaired yet still viable tissue surrounding the ischemic core) prior to intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) treatment (14,15). DWI can demonstrate the changes of ischemic tissue within minutes after vessel occlusion with a reduction of the apparent diffusion coefficient (ADC). However, it is demonstrated that DWI lesions can be at least partially reversible in the early phase of ischemia but do not reflect necessarily irreversibly lesions only (2,16). More recently, it had been shown that several cases of hyperacute stroke represented an absence of changes on the initial diffusion changes, nevertheless, subsequent images of the same patients represented relatively large infarctions in the regions compatible with the clinical presentation (17,18). These studies indicate that normal findings on DWI in patients with suspected cerebral ischemia do not rule out brewing infarction at the hyperacute stage. On the other hand, FLAIR can reveal arterial hyperintensity in the affected vascular regions immediately after the onset of symptom, which provides an additional information for the early diagnosis of impending infarction, especially for the hyperacute cerebral infarction (19). Collectively, the FLAIR image could represent an early sign of infarction and the FLAIR could act as a significant complementary examination for MRI.

Studies have depicted that more rapid fast-FLAIR sequences may prove more useful in the diagnostic MRI of patients who cannot tolerate long scanning times, to reduce the discomfort of MS patients enrolled and to improve image quality by reducing motion artifacts (20). In this study, we demonstrated that an optimized cerebral infarction MR protocol was feasible while maintaining a high degree of diagnostic image quality. Across all 100 patients, we obtained good diagnostic image quality (89%) in AE-FLAIR sequence compared with EPI-FLAIR and conventional FLAIR. In particular, the 70 acute infarctions detected in the 50 cooperative patients displayed image qualities of 96%, 90%, and 60% in FLAIR, AE-FLAIR, and EPI-FLAIR, respectively. The results suggested that in the cooperative group, the application value of AE-FLAIR was comparable to that of conventional FLAIR and superior to that of EPI-FLAIR. Furthermore, the above findings were also verified for in a subset of uncooperative patients (n = 50) in our study, where the AE-FLAIR sequences additionally minimized the motion artifacts and had improved image quality. Besides, a high inter-observer agreement (κ = 0.81) to demonstrate the reproducibility of our technique was identified. In this regard, we were able to suggest that AE-FLAIR provided some comparable even higher qualitative and quantitative values to those obtained from conventional FLAIR and EPI-FLAIR, especially for the patients who are claustrophobic or unable to cooperate.

The main clinical use of FLAIR sequence imaging in the setting of acute stroke is to focus recognition of acute ischemic infarcts within the thrombolytic time window. In addition, evidence has reported a time dependency of visibility of the acute ischemic lesions on FLAIR imaging (21). Additionally, studies have demonstrated that patients should not be offered thrombolysis treatment beyond a time from onset of symptoms during which thrombolysis is effective and safe (9). For the patients within the therapeutic time window, a study had estimated that for every minute during which acute ischemic stroke was left untreated, about 1.9 million neurons were lost (22), indicating a possibly critical role of the reduction of imaging diagnostic time before the thrombolysis decision. The findings demonstrate the importance for saving valuable acquisition time in patients with acute cerebral infarction. In this study, we obtained an optimized MR stroke protocol in 4 ± 0.5 min, a three-fold reduction in scan time instead of conventional MRI protocol as demonstrated in the control group (12 ± 1 min). We suggest that the application of AE-FLAIR combined with MRA may enhance image acquisition and postprocessing speed, in accordance with the previous study which demonstrated that the integration of parallel imaging could act its complementary effects with EPI and improve the image quality of EPI-FLAIR technique (5).

3D TOF MRA has been traditionally performed in routine stroke MR protocols to evaluate the status of brain arteries (23,24). Some of the potential disadvantages of TOF MRA have been reported to include long acquisition time in the range of 5–7 min. Nevertheless, evidence has shown that by introduction of MR scanners with fast imaging tools, such as 3.0-T highly accelerated parallel acquisition, MRA images of the entire head could be obtained with greatly reduced acquisition times (25). Also, a study demonstrated that the addition of parallel imaging had a two-fold synergistic effect to EPI (7). In the present study, we showed an integration between AE-FLAIR sequences and 3D TOF MRA to demonstrate the acute infarctions.

The present study had several limitations. The first was a relatively small sample size drawn from a single institution, which may possibly introduce a sample bias and the subjective nature of our image quality scoring system. Further larger case series and future studies of other imaging parameters are needed. Second, though AE-FLAIR and EPI-FLAIR has enhanced the acquisition speed with the introduction of fast imaging techniques, AE-FLAIR and EPI-FLAIR were often associated with image abnormality compared with the conventional FLAIR. In this study, high image quality scores and inter-observer agreement in defining adequate image quality of the optimized imaging group indicated that the effect on image was not a limiting factor for the diagnostic interpretation. Larger clinical investigations are likely needed to fully determine the clinical usefulness of the described AE-FLAIR combined with 3D TOF technique.

In conclusion, with reduced acquisition time and better image quality, AE-FLAIR combined with 3D TOF may be used as a rapid diagnosis tool in patients with acute cerebral infarction, especially in uncooperative patients.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Guangdong Province’s science and technology planning projects (no. 2013B022000011 and no. 21612428), Education Ministry of Guangdong province’s science and technology innovation fund projects (no. 2013KJCX0025), and Guangdong medical scientific research projects (no. A2014387).

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