Improved detection of focal cortical dysplasia using a novel 3D imaging sequence: Edge-Enhancing Gradient Echo (3D-EDGE) MRI

Abstract

Epilepsy is a common neurological disorder with focal cortical dysplasia (FCD) being one of the most common lesional causes. Detection of FCD by MRI is a major determinant of surgical outcome. Evolution of MRI sequences and hardware has greatly increased the detection rate of FCD, but these gains have largely been related to the more visible Type IIb FCD, with Type I and IIa remaining elusive. While most sequence improvements have relied on increasing contrast between gray and white matter, we propose a novel imaging approach, 3D Edge-Enhancing Gradient Echo (3D-EDGE), to directly image the gray-white boundary. By acquiring images at an inversion time where gray and white matter have equal signal but opposite phases, voxels with a mixture of gray and white matter (e.g., at the gray-white boundary) will have cancellation of longitudinal magnetization producing a thin area of signal void at the normal boundary. By creating greater sensitivity for minor changes in T1 relaxation, microarchitectural abnormalities present in FCD produce greater contrast than on other common MRI sequences. 3D-EDGE had a significantly greater contrast ratio between lesion and white matter for FCD compared to MP2RAGE (98% vs 17%; p = 0.0006) and FLAIR (98% vs 19%; p = 0.0006), which highlights its potential to improve outcomes in epilepsy. We present a discussion of the framework for 3D-EDGE, optimization strategies, and analysis of a series of FCDs to highlight the benefit of 3D-EDGE in FCD detection compared to commonly used sequences in epilepsy.

Keywords: Epilepsy; Focal cortical dysplasia; MRI; Seizures.

Fig. 1

MRI sequence diagram illustrating the principles underlying the EDGE contrast. After the inversion recovery (IR) pulse is applied, magnetization recovery in the gray matter (GM) and white matter (WM) occurs at different rates. At the EDGE inversion time (TI_EDGE), WM and GM have equal signal but at opposite phases (positive versus negative, respectively). As such, voxels with a mixture of GM and WM (e.g., at the GM-WM boundary) will have cancellation of longitudinal magnetization producing an area of signal void.

Fig. 2

Theory of focal cortical dysplasia (FCD) detection with 3D-EDGE contrast. (A) Hypothetical MRI voxels (red squares) may contain entirely gray matter, white matter (WM), or a mixture. (B) Comparison to histological illustration of a normal gray matter/white matter boundary again shows sampling of gray matter, white matter, and mixture at the boundary. Given the optimized inversion times for normal gray matter and WM, those voxels with a mixture will show signal cancellation. (C) With an FCD, there is alteration in gray matter cell density along the WM boundary and abnormal ectopic neurons within the subcortical WM (arrows) producing a change in the normal inversion times and creating a “thickening” or distortion of the normal boundary line on 3D-EDGE. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Difference in contrast ratio of lesions in the 5 patients between 3D-EDGE and typical epilepsy sequences, FLAIR and MP2RAGE.

Fig. 4

MRI of focal cortical dysplasia (FCD) in two patients. In Patient 1, sagittal DIR (A) and 3D-EDGE (B) revealed left frontal FCD with transmantle sign (arrow) extending to the ependymal surface of the frontal horn. The disorganization and blurring in the cortex is much better appreciated on the 3D-EDGE image where the boundary line at the gray matter-white matter junction is blurred. In Patient 2, subtle blurring of the gray matter-white matter junction (arrowhead) is present on the MPRAGE image that is more apparent on FLAIR, as well as a “transmantle sign” with a radial band extending to the ependymal surface (arrow). The contrast of both the junctional blurring and subcortical signal change, as well as the transmantle band is greater on the corresponding 3D-EDGE image.

Fig. 5

FCD in patient 3. Four prior MRIs had been interpreted as normal; however, coronal 3D-EDGE (A) image reveals a focal thickening of the junctional band in the right cingulate (arrow), compared to the normal thin junctional band (arrowhead), that is nearly imperceptible on MP2RAGE (B) and FLAIR (C) images.

Fig. 6

Example focal cortical dysplasia in two patients. (A) In Patient 4, prior sagittal T1-weighted brain volume imaging (BRAVO) shows very subtle decreased subcortical white matter signal in the right pars opercularis (arrow) that is readily apparent on the subsequent 3D-EDGE (B) image with loss of the normal gray matter-white matter junctional stripe. In Patient 5, sagittal MP2RAGE (C) shows subtle blurring of the gray matter-white matter junction (arrow) that was not visualized on prior MPRAGE (not shown), but shows greater contrast on the sagittal 3D-EDGE (D).

Fig. 7

Effect of changing inversion time (TI) on 3D-EDGE contrast. Example images with flip angle of 8° and varying TI. (A) At a longer TI of 550 ms, gray matter and white matter show dramatic differences in signal intensity. (B) At the shorter TI of 445 ms, cortical signal intensity is brought closer to that of white matter highlighting the boundary line (arrow) in parts of the brain, but with some residual areas of incomplete cortical signal optimization, giving a thickened appearance (arrowhead). (C) Reducing TI to 425 ms creates more uniform cortical signal and 3D-EDGE boundary line (arrowhead) at the cost of slight reduction in SNR. The effect of inversion time on gray matter and white matter signal intensity is shown for (D) flip angle of 4° and (E) flip angle of 8°.