Fig 1.
A) The first step during the creation of the Brain-Grid is illustrated on the sagittal or axial slices: The anterior insular point (the most anterior landmark of the insular sulcus) is identified on both sides and the first line is drawn on the sagittal plane (MNI: Y 28, Talairach: Y25). The second line (drawn as well on the sagittal plane) is parallel to the previous one, crossing the posterior insular point (MNI: Y-23; Talairach: Y-24). On the midline (with sagittal view) the point where the calcarine fissure (V1) meets the most anterior portion of the parieto-occipital sulcus should be identified in order to track the third parallel line on the sagittal plane (MNI: Y-68; Talairach: Y-66). The same line crosses the temporo-occipital junction between the posterior portion of the fusiform gyrus and the inferior occipital sulcus more basally on the axial plane. The 3 lines on the sagittal plane will segment the whole brain into 4 grid voxels. The S1 voxel is the pre-insular/prefrontal portion of both hemispheres. The S2 is enclosed within the anterior insular point and posterior insular point (landmark for the second sagittal line). The S3 includes the retro-insular region and the parietal lobe, and the S4 includes primarily the occipital lobe and the border with the parieto-occipital sulcus. B) The second step during the creation of the Brain-Grid system is the identification of the right slice on the coronal plane (Into the MNI space: Y-5; Talairach Y -7). The first of the 2 parallel lines crosses the inferior insular point (the lowest limit of the insular sulcus) and the floor of the third ventricle that leads to the rounded shape of the mammillary bodies. In most patients, this horizontal line usually crosses the superior temporal sulcus on both sides (MNI: X0, Y-5, Z-13; Talairach: X0, Y-7, Z-7). The second line passes through the cistern/space between the cingular gyrus and the callosal body in the midline (MNI:X0, Y-5, Z33; Talairach: X0, Y-4, Z 31). C) Third step: Once the coronal segments and the sagittal segments are created, one should identify the middle frontal sulcus bilaterally, which is easily recognizable on the axial slice that shows the level of the lateral ventricle on the coronal reference (shown on the side). The 2 lines should be parallel to the midline, connecting this sulcus with the middle occipital gyrus crossing the white matter of the external capsule without invading the periventricular ependyma (right line, MNI: X33; Talairach: X32. left line, MNI:X-33; Talairach: X-32). The third and last line follows the midline along the falx and/or the septum pellucidum (MNI: X0; Talairach: X0). In this way 4 longitudinal segments are created, termed A1 to A4, from the right lateral side to the left lateral side.
Fig 2.
Example of how each segment can be identified according to the lines drawn on the 3 axes within the PACS clinical image client (upper part) and within the MNI space using FSLeyes (lower part). The tumor seems to invade the lateral left axial segment, thus A4, but even the second medial segment is invaded, involving A3. Two coronal units are involved in the more anterior part of the grid (C2-C3). According to the sagittal subdivision, the second and third segments are invaded by the hyperintensity but only in the more lateral quadrants. The results on this slice are A3C2S1 + A3C3S1, plus A4C1S1, A4C1S2, A4C3S1, a total of 5 units.
Fig 3.
The illustration shows the reference white matter atlas reconstructed from the HCP-template and analyzed with the Brain-Grid system. The major commissural (CC, AC, and Fo, first row), projection pathways (CST, IC, OR, TR, second row), and associative pathways (cingulum, SLF components, VOF, ILF, MLF, IFOF, UF, and FAT, third row) of both hemispheres are displayed in a left sagittal view (first column), anterior coronal view (second column), and superior-axial view (third column). The white matter bundles were tracked from the HCP-488 template within the MNI space and then analyzed using the Brain-Grid system with the number and letters for the grid voxels displayed for each projection. (See main text and the S1 and S2 Appendices for details on the single white matter bundles).
Table 1.
Summary of the clinical, histological, and radiological information on each patient enrolled in this study.
M: Male; F: Female; Histo: histology; O: Oligodendroglioma; A: Astrocytoma; R: right; L: Left; P: Parietal; F: Frontal; T: Temporal; O: Occipital; I: Insular; D: Diffuse; B: Bulky; PAR: Partial seizure; GEN: Generalized seizure; ICH: Intracerebral Hematoma; R: Surgical resection; B: Biopsy.
Fig 4.
The picture shows the trend in the frequency of Brain-Grid voxels in patients with left- or right-sided tumors according to a color gradient from white (0–5%) to dark red (more than 80% of the cases). The cut-off for a high frequency (intense orange) was set at 50% of the lesions. The A1C2S2 and A2C2S2 are most frequently involved on the right side, while A3C1S2, A3C2S2, and A4C2S2 are most frequently involved in patients with left-sided tumors, with the highest incidence being displayed by the median and central voxels bilaterally (subcortical insular regions-basal ganglia), both involved in over 80% of the cases (dark red).
Fig 5.
Radiological follow-up of Illustrative case #1.
The figure illustrates the way in which the Brain-Grid system can add some important information about the white matter bundles infiltrated during a longitudinal follow-up. Axial and coronal slices show tumor evolution on morphological T2/ FLAIR MR sequences from 2002 and onwards. The signal hyperintensity evolved from 1 BG voxel to 7 BG voxels in both the coronal and axial direction. On the right side, the BG Atlas was used as a reference for the tractographic reconstructions, summarizing the major white matter bundles involved during the tumor progression. The genu of the corpus callosum (light blue), IFOF (red), cingulum (dark red), anterior thalamic radiation (dark blue).
Fig 6.
The radiological course of Illustrative case #2.
A) Axial slices showing morphological FLAIR MR sequences during a longitudinal follow-up from 2010 and onwards. The signal hyperintensity evolved from 6 Brain-Grid units to 12 units, with a clear morphological transformation from a bulky shape to a diffuse and digitated shape infiltrating along the subcortical white matter. On the right, tractographic reconstructions from the Brain-Grid atlas revealed the major white matter involved during the progression. External capsule (light blue), UF (violet), IFOF (red), anterior thalamic radiation (dark blue), MLF (purple), AC (salmon). Follow-up MRIs in 2012 and 2013 demonstrated increased tumor volume involving also a radial extension of hyperintensity from the insula through the extreme and external capsule. Eight grid voxels were infiltrated in 2012, 9 voxels in 2013, with involvement of the S3 areas on both the lateral side (A4) and medial side (A3) within the intermediate coronal area (C2). The invasion at this time point, as shown in A–B, is more prominent through the posterior portion of the insula and sub-insular white matter. The potential pathways of infiltration are represented by the MLF fibers on the lateral (A4) grid voxel and the IFOF fibers medially (A3), caudally through the periventricular white matter (within the C3 area). After radiotherapy, the tumor volume as well as the infiltration along the longitudinal posterior pathways decreased significantly. The number of segments decreased to 8 due to a reduction of the hyperintensity in the A3C3S3 voxel. B) Details of the radiological follow-up between 2011 and 2016 that capture the switch from a bulky shape to a more diffuse and infiltrative appearance. On the right side, the Brain-Grid tractographic reconstructions summarizing the major white matter bundles involved during tumor progression. External capsule (light blue), UF (violet), IFOF (red), anterior thalamic radiation (dark blue), MLF (purple), AC (salmon). The sagittal projection shows that further infiltration along the antero-ventral pathways (UF) was not prevented by radiotherapy and that slow but continuous tumor growth occurred during the 3 years following radiotherapy. In 2016, when the entire anterior temporo-basal area was infiltrated, the number of infiltrated grid voxels was 12, showing also interhemispheric spread through the anterior commissure to the medial (A2) and intermediate coronal (C2) S2 and S3 grid voxels.