Intravenous contrast agents are commonly used to evaluate patients with suspected intracranial lesions. Gadolinium is the most commonly used intravenous contrast agent for imaging the brain. It helps in improved lesion detection and better characterization [6].
No one can deny the fact of the importance of T1 post-contrast significance in detection of space-occupying lesions in the brain. Unfortunately, small groups in our practice are aware of the role of T2-FLAIR post-contrast imaging in specific situations. Although these effects are known by some expertises, it was not used commonly in the practice. So the result is that we have small studies assessing the role of post-contrast T2 FLAIR images in different brain lesions [7].
Post-contrast T2 FLAIR imaging sequences have been investigated in a variety of intracranial pathologies with the goal of increasing diagnostic sensitivity. The diagnostic value of post-contrast-T2 FLAIR has been variably reported in both veterinary, and human studies, with its use in meningeal-based disease commonly reported as beneficial [8].
A total of 85 cases with different intracranial pathologies were enrolled; they were further classified on the basis of the clinical diagnosis, pathological evaluation, and final imaging diagnosis into 3 groups as follows: tumors (either primary or metastatic) were found in 69 cases (81.2%) representing most of our studied cases, with 44 cases (63.8%) primary tumors and 25 cases (36.2%) metastatic tumors; Multiple sclerosis was observed in 10 cases (11.8%); and infection (including meningitis, meningoencephalitis, and brain abscess) was detected in 6 cases (7.1%).
In our study, we provided additional subtraction imaging between post and corresponding pre-contrast FLAIR sequences; this was beneficial and provided improvement in detection of very small enhancing lesions, or lesions of initially high signal intensity in non-enhanced FLAIR images as well as in cases where there is an improper delineation of enhancing lesion margin from the hyperintense perilesional edema. In addition, we found that the use of subtraction imaging helped avoid false-positive cases, decreased reading time, and increased the accuracy of detection of contrast enhancement in a clinical practice, and this was equivalent to the results of the study done by Zivadinov and his colleagues [9].
Results of qualitative comparison between the two sequences showed that CE-T2 FLAIR provided superior enhancement in 49 cases (57.6%), less enhancement was detected in 10 cases (11.8%), yet equivocal enhancement in both sequences was found in 26 cases (30.6%). These results are in agreement with those obtained by Athar and colleagues who demonstrated better enhancement in 19 cases (57.6%) in post-contrast T2 FLAIR weighted images, less enhancement in 6 cases (18.2%). However, in the remaining 8 cases (24.2 %), both sequences do not reveal any abnormality so considered as equal [10].
Lesion conspicuity, delineation of enhancing lesion margin from the surrounding normal brain tissue or perilesional edema as well as the ability to clearly identify enhancement and lesion outline in post-contrast FLAIR sequence were evaluated in all cases and described as either: good delineation, reported in 55 cases (64.7%), fair delineation, reported in 11 cases (12.9%) and no delineation, reported in 19 cases (22.4%). Our results for good delineation are relatively higher than the results of the study done by Athar and colleagues that reported a clear outline of a lesion in post-contrast FLAIR sequence in 13 cases (39.4%) out of 33 cases. This could be explained by different sample sizes.
In order to avoid any bias in qualitative analysis of post-contrast FLAIR images, the signal intensity of all lesions was measured in both pre- and post-contrast FLAIR images and the difference was calculated and expressed as contrast enhancement index (CEI). Our results demonstrated significantly higher signal intensity on CE-FLAIR images compared to pre-contrast ones (P < 0.001), which confirm the presence of enhancement after contrast injection.
In this study, lesion-to-background contrast percentage was assessed objectively to prevent making subjective data via visual assessment of contrast that might be affected by windows and levels, amplification, and monitor illumination.
Our study demonstrated a significant higher contrast ratio in CE-FLAIR compared to both non-enhanced FLAIR and CE-T1W sequences (P < 0.001) which allowed better delineation of lesions by CE-FLAIR. The higher contrast ratio detected by CE-FLAIR can be explained by greater inherent soft tissue contrast resolution in FLAIR compared to T1W sequence. In addition, unlike CE-T1WI, CE-FLAIR images normal vasculature and healthy meninges do not enhance. Therefore, CE-FLAIR images are considered as being most effective to assess sulcal or meningeal infection, inflammation, and metastases near the CSF side.
In our study, good agreement was found between two observers as regard signal intensity readings in pre- and post-contrast FLAIR images, contrast enhancement index as well as contrast to background ratio on post-contrast FLAIR and post-contrast T1W images with correlation coefficient more than 0.7 was considered excellent agreement.
In line with our study, Kim and colleagues stated that contrast-enhanced fast FLAIR images had higher tumor-to-background contrast ratio compared to contrast-enhanced T1W images [3].
Furthermore, ZHOU and colleagues observed that the CER and contrast-to-noise ratio (CNR) on CE T1WI was significantly higher but grey matter/white matter contrast was lower (P=0.02) than those on CE FLAIR images [11].
While another study by Tomura and colleagues in which the intensity ratios (intensity of tumor divided by intensity of peritumoral region) in contrast-enhanced spin echo T1W and contrast-enhanced multi-shot echo-planar imaging FLAIR (Ms-EPI-FLAIR), “comprising combined sequences of FLAIR and Ms-EPI” were compared, showed that the intensity ratio in Ms-EPI-FLAIR did not differ from that in spin echo T1WI.These results were in contrary to what we had observed [12]. This discrepancy could be attributed to different sample sizes, different imaging parameters, and different MRI machines with different specifications.
A study conducted by Azad and colleagues, where quantitative assessment included computation of net meningeal enhancement, using single pixel signal intensity software and comparing the results between CE-FLAIR, Magnetization Transfer Spin Echo, and Fat-Saturation T1-Weighted Sequences, observed that a significant difference was found between the net meningeal enhancement on the contrast-enhanced FLAIR sequence compared to the magnetization transfer spin echo and the T1-weighted fat saturation sequences (p < 0.001) [13]. These results seem to be consistent with the data obtained by our study.
In concordance with the previous study done by Rastogi and Jain, we found that , in 69 cases of intracranial tumors post-contrast FLAIR showed superior enhancement in 35 cases (50.7%), equal enhancement in 25 cases(36.3%), and less enhancement than post-contrast T1W images in 9 cases (13%) [7]. We had also observed that in patients with tumors, CE-T2FLAIR images were considered to be superior to CE-T1W images as it allow to reveal more widespread enhancement (rather than solid part) and denser and more nodular wall enhancement in the necrotic tumor. So after interpretation of these findings not only the differentiation of the tumor can be performed but also the site for stereotactic biopsy can be determined.
We had also observed that CE-FLAIR yielded significantly more information compared to routine CE-T1W sequence in detection of early leptomeningeal metastatic lesions and small superficial parenchymal lesions as well. There is no doubt that early identification of leptomeningeal disease affects the treatment and overall prognosis of many brain tumors. Our results were consistent with the study done by Kim and colleagues [2] who stated that in small intracerebral metastasis, lesion detection was increased when contrast-enhanced FLAIR was added to contrast-enhanced T1WI.
On the basis of our observations of 10 patients with multiple sclerosis, we found that CE-FLAIR was superior to CE-T1W sequence in 9 cases (90% of our studied MS cases), and provided better detectability and significantly more number of active lesions, this was assessed by depicting active lesions as ultra-bright relative to pre-contrast FLAIR images and confirming enhancement by FLAIR subtraction images along with measuring signal intensity of MS plaques in pre- and post-contrast FLAIR images; furthermore, these findings were supported by clinical data. So, we suggest that CE-FLAIR would be a promising diagnostic technique and should be added in diagnosis and follow-up of multiple sclerosis and can be a valuable tool in monitoring disease activity. So, our results were consistent with the findings of the study done by Abdolmohammadi and colleagues who reported that in post-contrast FLAIR images it has been observed more acute MS plaques at supratentorial area than post-contrast T1W sequence which is a gold standard sequence. Moreover, they stated that post-contrast FLAIR sequence was better at lesion visualization than the DWI and post-contrast T1W sequences [14].
Leptomeningeal infiltration (LMI) in multiple sclerosis patients in MS was firstly discovered in 2004. After that several pathological studies have established the presence of immune cell aggregations in the meninges among some groups of MS patients. Pathologically, LMI is considered as abnormal immune cell aggregations in the meninges of patients with multiple sclerosis, especially those with progressive MS either in primary or secondary forms. The presence of LMI is considered as a bad prognostic outcome with more disability and higher EDSS scores. Recently, specific MRI sequences have the ability to confirm the presence of these follicles that correspond to the pathological findings [15].
In Eisele and colleagues’ study, the pathologic control group demonstrated the sensitivity of post-contrast FLAIR images demonstrating leptomeningeal enhancement in all cases. In contrast, only 1 out of 112 examined patients with MS showed a single area of abnormal leptomeningeal contrast enhancement [16]. This was quite equivalent to our results.
In our study, it is interesting to note that appreciable abnormal leptomeningeal enhancement in post-contrast FLAIR sequence was described in all cases of multiple sclerosis and was not clearly demonstrated in post-contrast T1W sequence.
Regarding 6 cases diagnosed with infection, our results showed that CE-FLAIR demonstrated superior enhancement and additional valuable reliable information compared to conventional CE-T1W sequence in 5 cases (83.3%). We had observed that CE-FLAIR has a great capability for better detection and delineation of even subtle meningeal enhancement compared to teh CE-T1W sequence. Furthermore, in cases of pyogenic abscess (2 cases), CE-FLAIR demonstrated better wall enhancement, with greater mural thickness and more clear and sharp delineation from the surrounding. These results were consistent with the studies done by Ahmad and Rastogi and Jain [7, 17] whose supported the fact that CE-FLAIR sequence has an insignificant component of vascular enhancement compared to meningeal enhancement which makes meningeal inflammation easily detected and aids in early diagnosis of infectious meningitis which is important for a favorable clinical outcome.
On the light of previously discussed results of qualitative comparison between contrast-enhanced T2 FLAIR and contrast-enhanced T1 sequences and by reviewing the results of multiple researchers, we concluded that contrast-enhanced FLAIR is more sensitive for subtle abnormalities than either FLAIR alone or post-contrast T1-weighted imaging alone and CE-FLAIR should be used as a valuable adjunct to conventional CE-T1W sequence when an intracranial lesion is suspected in the clinical setting.
This study has some limitations as moderate overall sample size, small percentage of patients with leptomeningeal lesions, and non-representation of other brain pathological conditions associated with leptomeningeal disease as Sturge Weber syndrome and facial and optic neuritis.