Additive Role of Susceptibility weighted image To Diffusion weighted image in the diagnosis Of Patients with Acute Stroke

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Additive Role of Susceptibility weighted image To Diffusion weighted image in the diagnosis Of Patients with Acute Stroke

https://doi.org/10.21203/rs.3.rs-1984157/v1

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Background

Acute ischemic stroke is defined as decrease in the brain blood supply caused by a blood vessel burst or being blocked by a thrombus, resulting in decreased oxygen and nutrients supply, causing brain tissue damage. Diffusion weighted sequences (DWI) gave us data on the pathophysiology of ischemia and may contribute to therapeutic decisions. Susceptibility weighted (SWI) sequences also have the potential to assess tissue viability. An ischemic area showed increased oxygen extraction fraction and slow flow contributed to greater level of deoxyhemoglobin and vein dilatation, which increases the prominence of vessels on SWI. This prominent vessel sign (PVS) on SWI has been reported due to increased oxygen extraction and matches well with venous and capillary deoxyhemoglobin levels. We aimed in this study to highlight the role of the addition of susceptibility weighted MR images to diffusion weighted images of the brain in the diagnosis of patients with acute stroke. Results: Prominent vessel sign (PVS) on SWI was found in 46 (76.7%) patients. Twelve (20%) patients had haemorrhage (low signals) on SWI and 2 (3.3%) patients had no SWI findings. DWI showed a sensitivity of (100%) and SWI showed a sensitivity of (96.7%) for the detection of infarct All of the 60 (100%) patients showed hyperintense signals on T2WIs, FLAIR sequences, and on DWI and hypointense signals on the ADC map. Conclusions: SWI is a potential adjunct in individuals with acute infarction, SWI may be helpful in identifying asymmetrical conspicuous hypointense arteries, positive DWI-SWI mismatch is an indicator of the ischemic penumbra and a prognostic indicator for infarct expansion.

Diffusion MRI

Susceptibility Weighted Imaging

Acute stroke

Prominent vessels sign

Stroke is defined as the abrupt onset of a focal neurological deficit secondary to an avascular event lasting more than 24 hours. An acute stroke indicates the first 24-hour period of a stroke event. It is classified as either ischemic (by thrombosis or embolism) or hemorrhagic (caused mainly by rupture of a blood vessel or aneurysm). Acute ischemic stroke is defined as decreased blood supply to the brain due to blood vessel rupture or being blocked by a thrombus, and so decreased oxygen supply and nutrients damage the brain tissue [1, 2].

Magnetic resonance imaging (MRI) is useful not only for detecting ischemic lesions but also for determining the relationship between lesions, brain anatomical and functional changes [3, 4].

Diffusion-weighted sequences (DWI) provided information on the pathophysiology of ischemia and may have implications for therapeutic plans. It is more sensitive than T2 and FLAIR in detecting acute cerebral ischemia in minor strokes [5, 6].

SWI is a relatively new and developed MRI technique that is increasingly being used to narrow the differential diagnosis of a wide range of neurological disorders. It utilises the magnetic susceptibility differences of different tissues, such as blood, iron, and calcification. It used both magnitude and phase images from a high-resolution, three-dimensional (3D) fully velocity-compensated gradient echo sequence. A phase mask was created from the MR phase images and multiplying these with the magnitude images increased the conspicuity of the smaller veins and other sources of susceptibility effects, which is outlined using minimal intensity projection (MIP) [7].

SWI enabled early detection of acute haemorrhage and intravascular clots, so SWI sequences also had the ability to assess tissue viability [8, 9].

PVS on SWI had been reported to specify increased oxygen extraction and correlated well with venous and capillary deoxyhemoglobin levels [10].

Many previous studies attempted to use SWI in the detection of micro haemorrhage or the differentiation of haemorrhage and calcification, but few studies used this sequence in early detection and compared it to DWI in the diagnosis of acute infarcts.

The goal of this study was to highlight the importance of combining susceptibility weighted MR images with diffusion weighted images of the brain in the diagnosis of patients with acute stroke.

Our retrospective comparative study included 60 patients with clinical manifestations of acute stroke (24 females and 36 males) who aged from 36 to 88 years old (mean value 63.47±12.221 years) were referred by their neurologist to our university hospital's Radio-diagnosis & Medical Imaging department. A written informed consent was taken from every patient before participation in this study. The study was done after approval from the Ethical Committee. The duration of the study was approximately 2 years, starting from May 2020 to May 2022. : 1) over the age of 18, (2) presented within 1-24 hours (mean time bout 14h) of the onset of symptoms, with clinical manifestations of acute stroke lasting more than 1 hour (3) Primary CT scan is negative; (4) DWI is positive. Exclusion criteria were as follows: (1) patients with chronic neurological deficit due to chronic vascular insult(lacunar); and (2) any patients with MRI contraindications such as a heart pacemaker, metallic aneurysmal clip in the brain, claustrophobia, or being vitally unstable. (3) Patients who are clinically unstable and necessitate close observation. All patients underwent a history of the onset and duration of their neurological complaint, a neurological examination, and routine laboratory tests such as complete blood culture (CBC), international normalised ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT), blood sugar level, and lipid profile. Cardiologic assessment by echocardiogram.. All the patients were subjected to history taking about the onset of neurological complaint and the duration, neurological examination and routine laboratory investigations as Complete blood culture (CBC), international normalized ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT), blood sugar level and lipid profile. Cardiologic assessment by echocardiogram.

-Imaging modalities, including:

1) CT without contrast study of the brain.

2) MRI of the brain, which was performed in the study of 60 patients who presented within 6-24 hours of the onset of symptoms of brain stroke. Detachable metallic implants in the patient’s body or clothes were removed before the MRI examination. Examination was done with patients supine and the head in the neutral position with the use of a circular polarized head-array coil and ultra- gradients. All MRI scans were performed by the MRI 1.5 Tesla unit (GE Healthcare, United States) with closed magnet right-handed system. The selected patients were imaged by the MRI stroke protocol, which include the following sequences: T1WIs (TR =122, TE =18), T2WIs (TR =5278, TE =130), FLAIR sequences (TR =1110/2810, TR =135), DWIs and ADC maps (TR =3570, TE=114) and high-resolution SWI has been added with the following parameters: TR/TE 25/35, flip angle 10. Post processing had been performed and MIP images were generated during the exam. The total scan time for all protocols was less than 25 minutes.

MRI data analysis: All initial MR images were interpreted. The definition of an acute infarct area was hypersignal on T2WI, FLAIR sequence, DWI, hypo signal on ADC and hypo signals on SWI (either due to macro haemorrhage or microbleed in the form of small dark signals with a maximum diameter < 10 mm and increased size and/or number of regional veins which will appear as low signals as well).

An infarct extent on individual DWI and SWI was calculated using the Alberta Stroke Program Early CT Score (ASPECTS) system in 46 patients with MCA territorial infarct. This topographic system assigned 1 point for each of the 10 zones of the MCA territory. A score of 10 was normal, while a score of 0 indicated diffuse infarction. In this 10-point semi-quantitative CT scoring system, 1 point was subtracted from 10 zones for each area of acute infarction in DWI. Also, 1 point was subtracted from 10 for each area displaying asymmetric low signals from prominent vessels on SWI with either increased vessel number or diameter in the target area (MCA territory), when compared to the normal side [11]. The integration of the ASPECT score into DWI in stroke is extended and it is added to predict outcome and rapid risk assessment before thrombolytic therapy (figure1). We used the susceptibility-diffusion mismatch judgement method: the two physicians (with experience in neuroimaging diagnoses for more than 10 years) observed the images and made the score in consensuses with good interobserver reliability.

SWI-DWI positive mismatches were determined when DWI ASPECTS was greater than SWI ASPECTS value, SWI-DWI negative mismatches were determined when DWI ASPECTS was less than SWI ASPECTS value, and no mismatches were determined when ASPECTS on both DWI and SWI was the same.

Data management and statistical analysis: Data entry, processing, and statistical analysis were carried out using a statistical package (social sciences IBM SPSS software package version 22.0. Armonk, NY: IBM Corp). Numbers and percentages were used to describe qualitative data. The Shapiro-Wilk test was used to identify the normality of the distribution. Analyses were conducted using range (minimum and maximum), mean, and standard deviation. A 5% level or lower is considered significant.

Analytical statistics sensitivity: The capacity of the test to correctly identify diseased individuals in a population is “true positive”. To calculate it, divide true positives (TP) by true positives + false negatives (TP+FN).

Table 1 showed demographic data for 60 patients with clinical manifestations of acute infracts in our study. There were 48 ischemic patients and 12 heamorrhagic patients among the 60 patients with acute infracts.

All studied cases showed hyperintense signals on T2WI, FLAIR, and diffusion WI and hypointense signals on the ADC map.

SWI findings in the studied patients were prominent vessel sign in 46 patients (76.7%), haemorrhage (low signals) in 12 patients (20 .0%), and no findings in two cases (3.3%).

Twenty-eight (46.7%) patients had lesions in subcortical sites, twenty (33.3%) patients had lesions in cortical sites, and the remaining 12 (20%) patients had both cortical and subcortical lesions.

The site of PVS in the studied 48/60 patients with ischemic stroke was MCA territorial infarct in 46/48 patients (95.8%) [Fig. 3–7] and ACA territorial in 2/48 patients (4.2%) [Fig. 2] with significant P-value 0.01, zonal distribution of sites of territorial infarcts and PVS illustrated in table 3. M4, M5, and M6 where the most affected segment (41.3%) with PVS. On the other hand, the deep structure such as the internal capsule and lentiform nucleus were the least affected areas.

There was a significant difference (p-value 0.02) in semi-quantitative ASPECT scoring in different pulse sequences, including DWI and SWI. DWI score ranged between 4.0–9.0 with a mean value of 6.70 ± 1.52 while susceptibility weighted imaging SWI score ranged between 0.0–9.0 with a mean value of 4.96 ± 2.50

Thirty patients (65.2%) had positive mismatch (DWI > SWI), twelve (26.1%) had no mismatch (DWI = SWI), and four (8.7%) had negative mismatch (DWI SWI). Table 4.

The hypo intensity sign on SWI was present in 46 of the 60 patients with a sensitivity of 69.7%, specificity of 84.5%, positive predictive value of 87.9%, and negative predictive value of 61.6%.

Susceptibility-weighted imaging (SWI) is a relatively new imaging technique which is mainly based on the susceptibility effects within vessels [12].

SWI applications in the field of acute infarction are promising as they have significantly greater sensitivity and better contrast resolution for the detection of thromboembolus. Applications of SWI include detecting intracerebral hemorrhage, identifying intra-arterial thrombus, diagnosing occult vascular malformations, and evaluating cerebral hemodynamics after stroke [13].

Our study tried to find the additional role for SWI in early diagnosis of acute stroke, early detection of micro bleeding and liability for hemorrhagic transformation which, would affect the prognosis and thrombolytic therapy.

On SWI, the BOLD effect of deoxyhemoglobin made it possible to properly assess slow flowing blood in small cerebral vessels which, was hard to assess with current time of light and phase contrast magnetic resonance angiography. [14] The MIPs were used to delineate continuity of tortuous structures; therefore, they gave a venogram effect to the veins allowing better judgement of their characteristics and differentiating them from near hemorrhagic foci [15].

In this study, PVS on SWI was found in 46 (76.7%) patients, 12(20%) patients had haemorrhage (low signals) on SWI, and 2 (3.3%) patients had no SWI findings. The uncoupling between oxygen supply and demand in hypo-perfused tissue caused a relative increase of deoxygenated haemoglobin levels and a decrease of oxyhemoglobin in the capillaries and the draining veins, leading to a low signal within the draining vein on SWI, which is a useful indicator of early infarct extension. A great PVS within the large MCA territory was related to poor early-stage outcome and could be useful for early clinical assessment of stroke. This was matched with Chen et al. [10], Stefan et al. [16] and Kesavadas et al. [17].

SWI may be an effective tool for more accurate identification of the ischemic penumbra depending on the evaluation of the asymmetrical prominent vessel sign According to Abu-Samra et al., SWI is a sign of salvageable ischemic tissue that will become infarcted if blood perfusion is not restored promptly [18]. SWI could thus provide information on the status of blood vessels in patients with acute cerebral infarction in addition to that provided by other currently used imaging methods [19].

As a result, more extensive PVS on SWI is associated with lower initial NIHSS scores, smaller diffusion lesion volume, and better collateral flow (good prognostic sign), as a result, it could be a valuable substitute marker for predicting increased oxygen extraction fraction and diffusion-perfusion mismatch in acute ischemic hemispheres [20].

Two cases of acute infarction in our study did not show PVS on (SWI) and this matched with Jiang, Hf et al, who stated that the presence of PVS is independently linked to large vessel occlusion, cardioembolism, and anterior circulation infarct [13].

Our study matched with Chen et al. as regards the most affected areas by PVS (M 3, M4 and M5) and least affected areas (caudate and lentiform nucleus and internal capsule) [10]

In contrast to CT scans, SWI may also identify spontaneous hemorrhagic transformation of ischemic stroke. This hypothesis is supported by our observations (Fig. 3). The rate of symptomatic haemorrhage may be reduced by determining the presence of spontaneous hemorrhagic transformation prior to thrombolytic therapy [21].

Our study correlated the results between DWI ASPECTS and SWI ASPECTS. SWI/DWI mismatch was helpful in detecting penumbra in MCA infarct, thus acting as a prognostic factor of infarction on follow-up images. Positive mismatch was highly related to good cerebral perfusion and good outcomes and prognosis. We found positive mismatch (DWI > SWI) in 30 (65.2%) patients out of 46 patients with evidence of MCA territorial infarct. The sensitivity, specificity, positive predictive value, negative predictive value, and efficacy of a positive DWI/ SWI mismatch in predicting infarction growth were 100%, 71.43%, 60%, 100%, and 80%, respectively in this study.

These results are consistent with Abu-samra, M. [18], Wang et al. [22] and Wu et al [23], who stated that there was no significant difference between the SWI and CTP ASPECT scores, but there was a significant difference between the SWI and DWI ASPECT scores. Their findings suggest that penumbra could be detected by SWI-DWI and that mismatch might indicate the extent of the ischemic penumbra and guide patients who need thrombolytic therapy quickly [19]

Our study had many limitations, the most significant of which were the small sample size and the absences of gold standard as our diagnosis was made only by imaging and clinical, which may have influenced our results. And, apart from obvious MR contraindications such as cardiac pacemakers, the main factors leading to an exclusion from MRI were a diminished level of consciousness, vomiting, agitation, and hemodynamic compromise. We also did not perform perfusion imaging to assess the area of penumbra, and because severely affected patients were often ill-suited for MRI studies or often produced poor images. We highly recommend further studies using a large sample volume with 3 Tesla or more MRI should be considered for more accurate results and data analysis, as well as a comparative study between the SWI and perfusion MRI studies to better assess penumbra, and follow-up either clinically or by imaging is highly indicated for assessment of treatment efficacy in cases of acute stroke.

Conclusions: DWI MR images are the mainstays for assessment of patients with acute stroke, SWI shows several findings in acute stroke were observed as PVS, early detectable bleeding, and DWI-SWI mismatch. The study's findings suggest that a positive DWI/SWI mismatch is a reliable marker of ischemic penumbra and a predictor of infarct expansion, and that it may be used to direct early thrombolytic or endovascular therapies to stop the progression of stroke. Therefore, for patients with suspected acute stroke, we advise including SWI in the standard neuroimaging protocol.

T2WIs: T2-weighted images, FLAIR: Fluid attenuated inversion recovery, DWI: Diffusion weighted imaging, ADC map: Apparent Diffusion Coefficient map; SWI Susceptibility-Weighted Imaging; 3D three-dimensional; MIP Minimal Intensity Projection; PVS Prominent Vessels Sign; Complete Blood Culture (CBC), International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Alberta Stroke Program Early CT Score (ASPECTS) system.

Ethics approval and consent to participate

Informed written consents taken from the patients; the study approved from ethical committee of faculty of medicine Tanta University number 13-2022

Consent for publication: not applicable

Availability of data and material: all data generated or analyzed during our study are included in this published article.

Competing interests. The authors declare that they have no conflict of interests.

Funding: No funding was obtained for this study.

Authors' contribution: M.N correlated the study concept and design and had the major role in analysis, collected data in all stage of manuscript, performed data for analysis and R.A supervised the study with significant contribution to design the methodology, manuscript revision and preparation. H.N correlated the finding with clinical finding and managed the cases. All authors have and approved the manuscript

Acknowledgements: staff member of Tanta University hospital especially radiology department .

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Table 1: Age, sex, risk factors, laboratory results in the studied patients (n = 60).

		Number of patients (%)
Age (years)	≤60	22 (36.7%)
	>60	28 (63.3%)
	Mean±S.D.	63.47±12.221
Sex	Male	36 (60.0%)
	Female	24 (40.0%)
Hypertension		34 (56.7%)
Diabetes Mellitus		32 (53.3%)
Smoking		10 (16.7%)
Hypercholesterolemia		8 (13.3%)
Hb		11.28±1.413
WBCs		11.81±2.630
Platelets		160.10±48.325
INR		2.17±0.655
PT		10.61±0.456
PTT		58.83±5.826

Data are presented as mean ± SD or frequency (%). Hb: Hemoglobin, WBCs: White blood cells, INR: International normalized ratio, PT: Prothrombin time, PTT: Partial thromboplastin time.

Table 2: Distribution according to type of stroke, side of lesion and SWI findings in the studied patients (n = 60).

Type of stroke	Ischemic stroke	48 (80 %)
Type of stroke	Hemorrhagic stroke	12 (20 %)
Side of lesion	Left-sided	40 (66.7%)
	Right-sided	14 (23.3%)
	Bilateral	6 (10%)
SWI findings	Prominent vessels sign	46 (76.7%)
	Macro hemorrhage (low signals)	12 (20 .0%)
	No findings	2 (3.3%)

Table 3: Zonal distribution of site of territorial infarcts and PVS.

Territory	number of patients 60	Patients with PVS 48	P-value
**ACA	4 6.6%	2 4.3%	0.01*
**MCA	56 93.3%	46 95.8%
-caudate nucleus	4 6.6%	3 6.5%
-lentiform nucleus	3 5%	2 4.3%
-Internal capsule	2 3.3%	2 4.3 %
-Insula	4 6.6%	3 6.5 %
-caudate nucleus	2 3.3%	1 2.1%
-M1	5 8.3%	5 10.8%
-M2	8 13.3%	7 15.2 %
-M3	5 8.3%	4 8.6 %
-M4	7 11.6%	6 13.0 %
-M5	9 15%	7 15.2%
-M6	7 11.6%	6 13.0%

N.B infarcts in M1 to M6(zones of middle cerebral artery) were estimated by (ASPECTS)

Table 4: Diffusion weighted imaging (DWI) score and susceptibility weighted imaging (SWI) score and DWI/SWI mismatch in the studied 46 patients with manifestations of acute ischemic stroke due to middle cerebral artery occlusion.

	Mean± S.D. (Number of patients (%))	p-value
DWI score	6.70 ± 1.52		0.02*
SWI score	4.96 ± 2.50
DWI/SWI mismatch
DWI > SWI	15 (65.2%)
DWI = SWI	6 (26.1%)
DWI < SWI	2 (8.7%)
Total	23 (100%)

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Additive Role of Susceptibility weighted image To Diffusion weighted image in the diagnosis Of Patients with Acute Stroke

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