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Contrast enhanced FLAIR versus contrast enhanced T1W images in evaluation of intraparenchymal brain lesions
Egyptian Journal of Radiology and Nuclear Medicine volume 53, Article number: 143 (2022)
Patients with suspected brain lesions are usually evaluated by means of intravenous contrast materials. These lesions may demonstrate enhancement through different mechanisms. At most institutions, CE-T1WI is the preferred sequence. FLAIR is a sort of inversion recovery pulse sequence with a long TR, TE and T1 and hence effectually nulls signals from CSF. The long T1 causes mild T effect and this result in lesion enhancement on post-contrast study. Therefore, lesions demonstrating enhancement on CE-T1WI will also demonstrate enhancement on CE-FLAIR images. The purpose of this work was to assess the role of CE-FLAIR versus CE-T1WI in evaluation of different intraparenchymal brain lesions.
Comparing CE-T1WI to CE-FLAIR in various brain pathologies, both observers found higher sensitivity and specificity for lesion to background contrast ratio on CE-FLAIR comparing to CE-T1WI. Observer 1 found that lesion to background contrast ratio on CE-FLAIR had sensitivity of 71.4%, specificity of 66.7% and AUC of 0.661 versus 63.3% sensitivity, 58.3% specificity and 0.634 AUC for CE-T1WI. Observer 2 found that lesion to background contrast ratio on CE-FLAIR had sensitivity of 77.6%, specificity of 66.7% and AUC of 0.719 versus 61.2% sensitivity, 50% specificity and 0.628 AUC for CE-T1WI.
On comparing CE-FLAIR to CE-T1WI, CE-FLAIR display better lesion detection and enhancement also better soft tissue contrast resolution.
The term brain lesion is commonly applied to define any lesion within the cranial cavity, which usually raises the volume of intracranial contents and causes a rise in the intracranial pressure. It includes any neoplasm (benign or malignant, primary or secondary), also any acute or chronic inflammatory lesion, any hematomas, various types of cysts, vascular malformations, traumatic and meningeal pathologies .
MRI used to assess these lesions through different sequences, the most important used sequences are non-enhanced T1-weighted image (T1WI), T2-weighted image (T2WI), FLAIR (Fluid attenuated inversion recovery), susceptibility-weighted image (SWI) and diffusion weighted image (DWI). Patients with suspected brain lesions are usually evaluated by means of intravenous contrast materials. These lesions may demonstrate enhancement through different mechanisms. At most institutions, CE-T1WI is the preferred sequence .
FLAIR is a sort of inversion recovery pulse sequence with a long TR (repetition time), TE (echo time) and TI (inversion time) and hence effectually nulls signals from cerebrospinal fluid (CSF) . The long T1 causes mild T effect and this result in lesion enhancement on post-contrast study. Therefore, lesions demostrating enhancement on contrast enhanced T1WI (CE-T1WI) will also demonstrate enhancement on contrast enhanced FLAIR (CE-FLAIR) images. Previous studies showed that CE-FLAIR provide extra information comparing to CE-T1WI [3, 4].
CE-FLAIR has a substantial role in meningeal pathologies. It is very useful in the early diagnosis of leptomeningitis resulting in reduction in the mortality rate due to early initiation of an effective treatment [5, 6]. Also it has an important role in evaluating arterial pathologies, acute stroke, subacute cortical infarct and also in assessment of post-operative changes [7,8,9,10]. In addition to that it has a substantial role in assessment of facial neuritis in which CE-T1WI has a confined role due to the normal enhancement of the facial nerve. It was found that CE-FLAIR can improve the specificity and accuracy of MRI in patients with idiopathic facial palsy . To the best of our knowledge, only few studies concentrated on the role of CE-FLAIR versus CE-T1WI in evaluation of intraparenchymal brain lesions [2, 12, 13].
Aim of the work
The aim of this study was to evaluate the role of CE-FLAIR versus CE-T1WI in evaluation of different intraparenchymal brain lesions.
Patient’s demographic data
This prospective study included 61 patients (30 male and 31 female) with an age range from 5 to 72 years (mean ± SD = 41.35 ± 15.62). MRI studies for all cases were performed in the period from June 2020 to November 2021. This study was approved by our institution ethics committee and informed written consent was obtained from each patient.
Patients presented by variable neurological conditions including:
Suspected infection (Fever, disturbed conscious level, neck stiffness).
Patients with clinical suspicion of multiple sclerosis (numbness, limb weakness, fatigue, gait disturbance and visual symptoms) or on follow-up to assess activity of disease.
Patients with suspected primary brain tumor or on post-operative / post radiotherapy follow-up.
Patients with known elsewhere primary brain tumor with underlying metastatic work up to detect metastatic brain lesions.
General contra-indications for MRI scan, for example:
Patients who have a cardiac pacemaker.
Patients with cochlear implants.
Patients having an intracranial aneurysmal clip.
Un-cooperative and claustrophobic patients.
Bad general condition.
Patients who have contraindications to contrast media as in severely impaired renal function for the fear of nephrogenic systemic sclerosis and other complications of IV Gadolinium contrast media.
MRI examinations were performed for all patients using 1.5 T. MRI unit (Philips Interna) with standard head coil and with the patient in supine position. The following sequences were obtained for all patients: fast spin echo (FSE) T1WI (TR/TE: 581/15 ms, slice thickness: 5 mm, interslice gap: 1 mm, flip angle: 69, FOV: 230 mm and matrix: 256), T2WI (TR/TE: 4000/100 ms, slice thickness: 5 mm, interslice gap: 1 mm, flip angle: 90, FOV: 230 mm and matrix: 256), FLAIR (TR/TE: 11,000/110 ms, TI: 2800 ms, slice thickness: 5 mm, interslice gap: 1 mm, flip angle: 90, FOV: 230 mm and matrix: 256) and DWI (TR/TE: 3614/160 ms, TI: 2800 ms, slice thickness: 5 mm, interslice gap: 1 mm, flip angle: 90, FOV: 230 mm and matrix: 256).
Contrast enhanced images were acquired after intravenous injection of Gadolinium (Magnevist) in the dose of 0.1 mmol/kg body weight. One minute after the injection of contrast agent, the acquisition of axial, sagittal and coronal conventional CE-T1WI were immediately done, the axial or coronal CE-FLAIR images were acquired successively with a delay time of approximately 3–4 min (the scan parameters were the same as the pre-contrast images).
MR images were analyzed independently by two experienced radiologists with about 14 and 10 years’ experience in neuroimaging.
At first the radiologists interpret the conventional MRI sequences to detect any brain lesion (e.g., tumor, infection, multiple sclerosis (MS), etc.). Then CE-T1WI and CE-FLAIR images were assessed and compared with each other’s. Images were assessed both qualitatively and quantitatively.
If CE-FLAIR images were unable to differentiate enhancing lesion from surrounding edema (as in tumors) or unable to detect lesion enhancement as in lesions with initially high signal intensity (SI) in pre contrast FLAIR images especially in cases of MS, we use subtraction MRI technique by performing a subtraction between the post-contrast and the corresponding pre-contrast FLAIR images to evaluate and confirm the presence of enhancement. Subtraction technique was added in most of the cases of our study (39 cases).
Qualitative evaluation by visual assessment includes the following:
Existence of lesion contrast enhancement.
Defining the site and pattern of lesion enhancement.
Estimation of the lesion rate of enhancement in both CE-T1WI and CE-FLAIR and classing it in CE-FLAIR images as: superior, equivocal or inferior comparing to CE-T1WI.
Assessment of lesion conspicuity which was defined as delineation of the border of the enhanced lesion in CE-FLAIR images and differentiating the lesion from the surrounding edema or from the normal appearing brain parenchyma, it was classified into: no, fair or good delineation.
Linking the images findings with the provided clinical data.
Quantitative evaluation includes the following items:
Calculating contrast enhancement index (CEI):
It was done by measuring the SI of the lesion in both pre and post contrast FLAIR images by using region of interest (ROI). It was calculated by using the following equation: Iˆ = I − I0 (Iˆ is CEI, I is the lesion SI on CE-FLAIR images and I0 is the lesion SI on pre-contrast FLAIR images).
Calculating lesion to background contrast ratio:
It was done by measuring the lesion SI as well as the background SI in normal appearing brain parenchyma by using ROI and applied to pre and post contrast T1W images as well as pre and post contrast FLAIR images. The lesion to background contrast ratio was calculated by using the following equation: Lesion to background contrast ratio = Lesion SI − Background SI/Background SI.
Standard of reference
In our study histopathology was used as a standard of reference in all included cases of space occupying lesions. In cases of MS we used clinical findings and CSF analysis as our standard of reference, while in cases of infection, we used the clinical and laboratory findings as a standard of reference.
Statistical analysis and data interpretation
Data were fed to the computer and analyzed using IBM SPSS Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. Qualitative data were described using number and percent. Quantitative data were described using median (minimum and maximum) for non-parametric data and mean, standard deviation for parametric data after testing normality using Kolmogorov–Smirnov test. Significance of the obtained results was judged at the (0.05) level. The diagnostic performance of a test was evaluated using Receiver Operating Characteristic (ROC) curve analysis. Sensitivity and Specificity were detected from the curve and PPV, NPV and accuracy were calculated through cross tabulation. Inter-class correlation was used to detect agreement between continuous variables with correlation coefficient more than 0.7 was considered excellent agreement. Kappa agreement was calculated by cross tabulation for categorical variables with Kappa of 0.81–0.99 was considered Perfect agreement.
This prospective study included 61 patients, 31 females (50.8) and 30 males (49.2%). Their age ranged from 5 to 72 years (mean age was 41.35 ± 15.62). According to final diagnosis in accordance with standard of reference, most of our cases were tumors (80.3%), followed by MS (8.2%) then ischemic (4.9%), infection (3.3%) and the least were traumatic and metabolic (1.6% each). As regard space occupying lesions we divided our studied cases in primary (38 cases; 62.3%) and secondary tumors (11 cases; 18%), in primary tumors we included 11 cases (18%) of Glioma (Fig. 1), 6 cases (10%) of Astrocytomas, 8 cases (13.1%) of meningiomas (Fig. 2), 8 cases (13.1%) of medulloblastomas, 3 cases (4.9%) of oligodendroglioma, one case (1.6%) of ependymoma and one case (1.6%) of central neurocytoma (Fig. 3). In secondary tumors we included 5 cases (8.3%) metastatic from breast cancer, 3 cases (4.9%) from lung cancer, one case (1.6%) from urinary bladder cancer, one case (1.6%) from rectal cancer and one case (1.6%) from high grade mucoepidermoid carcinoma.
A qualitative comparison of CE-T1WI and CE-FLAIR images was carried out, revealing the following: The first observer found that CE-FLAIR was superior to CE-T1WI in 67.2% of cases, equivocal in 24.6% of cases and inferior in 8.2% of cases. The second observer found that CE-FLAIR was superior to CE-T1WI in 70.5% of cases, equivocal in 21.3% of cases and inferior in 8.2% of cases. There was excellent agreement between both observers (Kappa = 0.930) (Table 1).
Regarding lesion conspicuity, first observer found that In CE-FLAIR images: The majority of cases (68.9%) had good delineation, 24.6% had fair delineation, and 6.6% had no delineation, while the second observer found that 75.4% of cases had good delineation, 18% had fair delineation and 6.6% had no delineation. There was excellent agreement between both observers regarding lesion conspicuity on CE-FLAIR (Kappa = 0.848) (Table 2).
Regarding the number of enhanced lesions in CE-FLAIR in comparison with CE-T1WI, the results revealed higher number of enhanced lesions detected in CE-FLAIR images comparing to CE-T1WI (Table 3; Fig. 4).
Regarding quantitative measurements, there was excellent agreement between both observers regarding the CEI which represent the difference between SI of lesions in pre and post contrast FLAIR images with the mean CEI detected by observer 1 was 88 (0.5–651) and the mean CEI detected by observer 2 was 83.0 (0.5–651.0) (ICC = 0.959, 95% CI 0.933–0.975). Comparing lesion to background contrast ratio on CE-FLAIR and CE-T1WI, both observers found higher lesion to background contrast ratio on CE-FLAIR images. Observer 1 found the mean lesion to background contrast ratio on CE-FLAIR images was 0.40 (0.02–1.89) versus 0.168 (0.01–0.81) on CE-T1WI. Observer 2 found the mean lesion to background contrast ration on CE-FLAIR images was 0.428 (0.03–1.89) versus 0.177(0.02–0.81) on CE-T1WI (ICC = 0.917, 95% CI 0.865–0.949) (Table 4).
Comparing CE-T1WI to CE-FLAIR in various brain pathologies, both observers found higher sensitivity and specificity for lesion to background contrast ratio on CE-FLAIR comparing to CE-T1WI. Observer 1 found that lesion to background contrast ratio on CE-FLAIR had sensitivity of 71.4%, specificity of 66.7% and AUC of 0.661 versus 63.3% sensitivity, 58.3% specificity and 0.634 AUC for CE-T1WI. Observer 2 found that lesion to background contrast ratio on CE-FLAIR had sensitivity of 77.6%, specificity of 66.7% and AUC of 0.719 versus 61.2% sensitivity, 50% specificity and 0.628 AUC for CE-T1WI (Table 5) (Fig. 5).
The detection and characterization of brain lesions were improved by using intravenous magnetic resonance contrast materials. Gadolinium (the commonly used contrast agent), cause shortening of both T1 and T2 relaxation times of tissues in which it has accumulated. However, at clinical doses the T1-shortening effect is responsible for the lesion contrast enhancement . The shortening of the MR relaxation times caused by the injection of contrast agents causes enhanced tissue to appear hyper intense on CE-T1WI. FLAIR images are equivocal to T2WI except for dark CSF caused by the T1 effect which is due to the long TI. After contrast injection, the resultant T1 shortening will cause hyper intensity on CE-FLAIR images; therefore, lesions demonstrating enhancement on CE-T1WI will also demonstrate enhancement on CE-FLAIR images .
In this study, there was excellent agreement between both observers regarding the superiority of CE-FLAIR over CE-T1WI in lesion detection (Kappa = 0.930). This is in line with Mahale et al.  who reported that CE-FLAIR was superior over CE-T1WI in detection of lesions in 72% of the studied cases. It was also in line with Azuma et al.  who reported that there was excellent interobserver agreement regarding the superiority of CE-FLAIR over CE-T1WI in lesion detection with Kappa agreement above 0.824. Our results also were in support with the research conducted by Rastogi et al.  who found that CE-FLAIR images exhibited superior enhancement in 63.2% of the studied cases.
Regarding lesion conspicuity which refers to the ability to define the margin of the enhanced lesion in CE-FLAIR images, we found that CE-FLAIR images revealed better lesion conspicuity over CE-T1WI in 68.9% of the cases. High interobserver agreement was noted (Kappa = 0.848). Another study  stated that CE-FLAIR images revealed better lesion conspicuity only in 39.4% of the studied cases. These different ratios may be due to the additional application of subtraction imaging between post and pre contrast FLAIR in our study, which had a very important role in detection of tiny and faintly enhancing lesions. Also it had an important role in detection of lesion enhancement in lesions with initially high SI in pre contrast FLAIR images also in lesions where there is inadequate delineation of the enhancing border from the surrounding hyperintense perilesional edema. We also found that subtraction images helped to reduce false-positive cases, reduce the reading time, and raised the accuracy of detection of contrast enhancement in CE-FLAIR images, this was supported by the study done by Gao et al.  who estimated the added value and superiority of pre and post contrast FLAIR subtraction images in diagnosis of brain gliomas and distinguishing its recurrence from post-treatment changes.
Based on our observations higher number of enhanced lesions were detected in CE-FLAIR images comparing to CE-T1WI, for example in patients with multiple sclerosis (MS) included in our study, we noticed that CE-FLAIR was superior to CE-T1WI in 90% of the studied cases of MS. CE-FLAIR offered better lesion detection and detected larger number of active MS plaques. This was determined by describing active plaques as ultra-bright in comparison with pre-contrast FLAIR images and using subtraction images to confirm the presence of enhancement. Our findings were in line with another study  which concluded that CE-FLAIR had the highest sensitivity comparing to CE-T1WI, DWI & ADC in detection of active MS plaques due to the CSF signal suppression in FLAIR, thus offering enough TR time recovery in active enhanced plaques. In their study higher number of active MS plaques in supratentorial region was found on CE-FLAIR comparing to CE-T1WI.
Regarding quantitative analysis, CEI was calculated for all cases. Our results showed significantly higher lesion SI on CE-FLAIR images compared to pre contrast ones and this proved the presence of lesion enhancement on CE-FLAIR images, for observer one, the mean CEI was 88 ranging from 0.5 to 651, for observer two, the mean CEI was 83 ranging from 0.5 to 651 (ICC = 0.959, 95% CI 0.933–0.975). These results were in line with another study  which found higher CEI in CE-FLAIR in comparison with pre-contrast FLAIR images with CEI ~ 262 ranging from 40 up to 1708.
In addition to that, our study included contrast to background ratio which was objectively calculated with a view to avert creating delusive data by visual assessment of contrast enhnacement, which may be influenced by windows and levels, magnification and monitor brightness. In our study both observers found significantly higher contrast to background ratio in CE-FLAIR in comparison with CE-T1WI (ICC = 0.917 & 95% CI 0.865–0.949) which allowed better delineation of lesions by CE-FLAIR. The higher contrast to background ratio on CE-FLAIR can be explained by higher inherent soft tissue contrast resolution in FLAIR compared to T1W sequence. These results were supported by the results of study conducted by Mustafa et al.  who found higher contrast to background ratio in CE-FLAIR than in CE-T1WI. They found the contrast to background enhancement ratio ranging from 0.2 to 3 in CE-FLAIR compared to 0.05 to 1.2 in CE-T1WI. Our study also agreed with the results of Kim et al.  who found that CE-FLAIR images had higher tumor to background contrast ratio in comparison with CE-T1WI. On their study the contrast to background ratio on CE-FLAIR was about 97.7 in comparison with 29.3 in CE-T1WI.
The limitations of this study was the limited number of patients especially those with brain infections and metabolic disorders.
On comparing CE-FLAIR to CE-T1WI, CE-FLAIR display better lesion detection and enhancement also better soft tissue contrast resolution. It can provide additional information that affect disease management and progression. So we recommend CE-FLAIR to be integrated as a routine pulse sequence in MRI examination of different intraparenchymal brain lesions.
Availability of data and material
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Magnetic resonance imaging
T1 weighted image
T2 weighted image
Fluid attenuated inversion recovery
Diffusion weighted image
Contrast enhanced T1WI
Contrast enhanced FLAIR
Field of view
Fast spin echo
Region of interest
Contrast enhancement index
Space occupying lesion
Interclass correlation coefficient
Area under curve
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The study was approved by our institution’s ethics committee (Mansoura Faculty of Medicine Institutional Research Board) (ethics committee reference number is MS/19.09.819) and all patients gave their written informed consent before inclusion in the study.
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EL-Adalany, M.A., Bilal, M.M.Z., Rihan, Y.A.M. et al. Contrast enhanced FLAIR versus contrast enhanced T1W images in evaluation of intraparenchymal brain lesions. Egypt J Radiol Nucl Med 53, 143 (2022). https://doi.org/10.1186/s43055-022-00817-w
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