Intracranial metastasis is considered a common neoplasm representing up to 40% of all adult brain neoplasms and 25% of all types of metastases [8]. For cancer patients, both the survival time and the quality of life are determined by the good management of brain metastases. The successful brain metastases management is dependent on different factors such as the extent of the primary tumor, the extent of systemic disease, and the number as well as the location of metastases [9].
In case of cancer patients with single brain metastasis, surgical resection followed by postoperative whole-brain radiation therapy (WBRT) is the treatment of choice providing a suitable site for resection and limited progress of cancer. On the other hand, in case of patients with multiple brain metastases (> 3 lesions), the preferred treatment is the WBRT alone. However, the treatment of choice in oligometastases (2–3 lesions) remains controversial whether WBRT alone, radiosurgery alone, or both [9].
In about 20% of patients with malignancy, brain metastases are diagnosed concurrently or even before the diagnosis of the primary lesion. Although the metastases are growing rapidly, they may remain small for several years. This proposes that at the time of diagnosis of the primary tumor, the intracranial metastasis may have been already existed; however, due to the lesion small size, it could not be detected easily by the traditional radiological scans [8].
In approximately 50% of all patients with intracranial metastases, the routine radiological imaging may demonstrate only a solitary lesion. So it is necessary for optimal management of brain metastases; all the other occult lesions must be detected [8].
Recently, the era of using post-contrast FLAIR sequences in intracranial lesions has attracted the attention of neuroradiologists [10,11,12,13].
We studied 40 cases, having 99 metastatic lesions, that were subdivided into five groups according to the number and conspicuity of metastatic brain lesions with DPC-FLAIR, compared with CE-T1WI, among them 16 lesions were only detected by DPC-FLAIR, one lesion was detected only by CE-T1WI, and the remaining 82 lesions were detected by both CE-T1WI and DPC-FALIR and were further subdivided into three groups; a group with better detection with CE-T1WI (11 lesions), a group better detected by DPC-FLAIR (43 lesions) and lastly a group with equal conspicuity with both CE-T1WI and DPC-FLAIR (28 lesions).
Our results indicate that the addition of DPC-FLAIR imaging to pre- and CE-T1WI increases diagnostic confidence in the evaluation of brain metastases. DPC-FLAIR had a high AUC value of 74.5%, a sensitivity of 98.98%, and a specificity of 100% for the detection of metastatic brain lesions.
In the current study DPC-FLAIR was superior to CE-T1WI in detecting leptomeningeal and tiny cortical lesions, while the reverse is true for subependymal lesions. On the other hand, both DPC-FLAIR and CE-T1WI had more or less similar performance in subcortical and infratentorial metastatic lesions.
Regarding cortical and subcortical lesions, in our study, eight tiny cortical lesions were detected only by DPC-FLAIR, four showed more evident enhancement with DPC-FLAIR compared to CE-T1WI, and only two tiny cortical lesions were of equal enhancement intensity in both T1 and DPC-FLAIR.
Essig et al. [10] in a study including 28 patients, (57% with enhancing gliomas, and 43% with cerebral metastases), found that the small subcortical lesions were not easily detected by water-sensitive techniques such as T2-weighted fast SE or fast DPC-FLAIR imaging. Significantly more metastases were detected with contrast-enhanced fast DPC-FLAIR images than with non-enhanced fast FLAIR and T2- or proton density-weighted fast SE images; however, significantly more metastases were detected with contrast-enhanced T1-weighted SE images than with all other modalities (p < 0.01). They stated the small lesions mostly did not cause vasogenic edema or mass effect, and only showed mild enhancement with contrast. However, DPC-FLAIR was as highly sensitive as T1-weighted SE images to detect the very small cortical lesions because these enhanced lesions are easily detected on CSF suppressed background. However, they reported that lesions > 10 mm could be detected easily on all imaging sequences.
Concerning the meningeal metastases, in our study, DPC-FLAIR images were superior to CE-T1WI in 13 meningeal lesions, among them eight were detected only by DPC-FLAIR, and five lesions were better detected by DPC-FLAIR. DPC-FLAIR was inferior in two meningeal lesions which were pachymeningeal.
These results are in agreement with a study conducted by Park and Ahn [14], who compared between DPC-FLAIR and contrast-enhanced 3D T1 black-blood fast spin echo (FSE) imaging regarding the diagnosis of leptomeningeal metastases. The visual conspicuity of DPC-FLAIR was significantly greater than that of 3D T1-BB FSE (p = 0.014 for reviewer 1 and p = 0.023 for reviewer 2). They suggested the higher sensitivity of DPC-FLAIR over the conventional contrast-enhanced T1 sequence in terms of visualization of leptomeningeal metastases due to the greater ability of DPC-FLAIR to demonstrate lower contrast concentrations than T1W1 images. This is due to the fact that, through the damaged vessels, gadolinium leakage into the adjacent CSF occurred resulting in contrast dilution and accordingly its low concentration. Hence, they concluded the predilection of post-contrast DPC-FLAIR over the standard contrast-enhanced T1.
Yet we disagree with the study conducted by Singh et al. [15] who stated that for diagnosis of intracranial neoplastic leptomeningeal disease, DPC-FLAIR sequences are of lower sensitivity than the conventional contrast-enhanced T1W1 images. The sensitivity and specificity for DPC-FLAIR images for detecting leptomeningeal metastases were 41% and 88%, respectively, and those of contrast-enhanced T1-weighted MR images were 59% and 93%. They supposed that this is because of using standard contrast-enhanced T1W1 MRI instead of magnetization transfer saturation with the T1W1 MRI in the previous studies [11].
Additionally, DPC-FLAIR is highly effective in the diagnosis of parenchymal metastasis. In our study, DPC-FLAIR, regarding parenchymal lesions, was superior in 34 lesions, inferior in nine lesions, and equal in 19 as compared to contrast T1WI.
Similarly, the significance of DPC-FLAIR imaging in the detection of superficial parenchymal lesions was reported by Lee et al. [3] who studied the DPC-FLAIR in several pathological diseases, including intracranial metastases. CSF signal intensity suppression, minimal blood vessels enhancement, diminished phase shift artifacts caused by blood vessels or dural sinuses enhancement, as well as easy detection of peritumoral edema are the causes that appreciate the use of the DPC-FLAIR images in the diagnosis of the superficial and deep metastatic tumors over CE-T1WI [3].
This was in agreement with Ercan et al. [16] who compared between DPC-FLAIR and T1WI in patients with identified or suspected brain metastases. Concerning the number, conspicuity, and parenchymal metastases enhancement, the DPC-FLAIR images were more sensitive than the CE-T1WIimages in five patients. However, these results were allocated to the delayed enhancement as in all patients, the CE-T1WI was firstly performed followed by the DPC-FLAIR.
It was hypothesized that in some patients, with a delay in the imaging time, the intracranial metastatic lesions are filled up with the gadolinium contrast agent, allowing better visualization of more small lesions. The more the imaging time the more leakage of the contrast material through the BBB leading to intralesional gadolinium accumulation with subsequent higher signal intensity [7].
Kushnirsky et al. [17] proposed the delay in imaging could lead to increase signal intensity as the imaging delay permits a longer time for the aberrant and leaky neovasculature inside the metastasis to be perfused with the contrast agent. The minute metastatic foci have a small vascular surface making the contrast diffusion very limited in the first-pass kinetics. However, by the time the contrast material recirculates through the cerebral vasculature leading to additional contrast extravasation [17].
Notwithstanding, the accuracy of CE-T1WI for the diagnosis of subependymal enhancing lesions remains higher than that of the DPC-FLAIR images [6]. In our study, the only lesion which was detected by post-contrast T1 and not by DPC-FLAIR was a tiny subependymal nodule.
So, due to the probability of the presence of leptomeningeal abnormalities with intra-parenchymal or subependymal lesions, it is clear that both CE-T1W1 and DPC-FLAIR sequences should be acquired within the same acquisition protocols.
Furthermore, concerning the CSF flow artifacts, it is well established that T1W1 images are less sensitive to this type of artifact predominantly in the posterior fossa rather than DPC-FLAIR images. Subsequently, to avoid the false-positive diagnosis of leptomeningeal abnormalities, these artifacts must be taken into consideration.
Limitation of our study included relatively small sample size and lack of comparison between delayed CE-T1WI and DPC-FLAIR to obviate the effect of the delay on the contrast concentration within the lesions; however, we still believe that the effect of delay is not the major factor of the higher accuracy of DPG-FALIR because it is more sensitive for detecting enhancing tiny cortical and leptomeningeal lesions by avoiding the confusion caused by enhancing cortical vessels that can be seen on CE-T1WI as well as omitting the bright signal of CSF.