3.7.1 Introduction
During phylogenetic development the structural complexity of the brain increases reflect the level of organization of the brain. The microstructural organization of the brain can be investigated in vivo with difiusion weighted imaging. In this study our aim was to investigate the anisotropy of water difiusion in long standing structural abnormalities of different aetiology.
3.1.2 M ethods
3.7.2.1 Patients
Eighteen patients (mean age 35 years, range 17-49 years) with partial epilepsy of more than 5 years and a structural abnormality on standard T l- and T2-weighted magnetic resonance images and 10 control subjects (mean age 33 years, range 29-39 years) without a history of neurological disease were scanned with DTI. Patients were recruited from a tertial referral centre for epilepsy and were interviewed and examined by the investigator. The neurological defict was stable, all patients were investigated with DTI in the interictal stage. The diagnosis of the structural abnormality was based on the appearance on standard imaging and the clinical data. The structural abnormalities could be divided in three principal groups, brain damage (lesions without mass effect), dysgenesis (characterized by abnormal gyral pattern and or heterotopic grey matter) and tumours (lesions with mass effect). Brain damage included postsurgical brain damage, nonspecific brain damage, perinatal brain damage, perinatal infarct, ischemic infarct, perinatal hypoxia, traumatic brain damage (n=3), mitochondrial cytopathy with the A117786 mutation and mesiotemporal sclerosis. Dysgenetic structural abnormalities included focal cortical dysplasia in combination with subcortical high signal, widespread cortical dysplasia and heterotopia in combination with cortical dysgenesis. Tumours included meningeoma (n=2), hypothalamic hamartoma and a glioma. Tab. 4.4 shows the location, diagnosis and diffusion measurements of the structural abnormalities.
3.7.2.2 DTI parameters
Scans were performed on a 1.5T Horizon Echospeed scanner (GE, Milwaukee,USA). Maximum gradient strength = 22 mT/m, slew rate =120 T/m/s. We used a single shot difiusion-weighted spin echo planar sequence (TR = 2700ms, TE = 78ms, FOV 24 cm, acquisition matrix 96 x 96, reconstruction
matrix 128 x 128, 5mm slice thickness, 5mm interslice gap). Pulsed unipolar diSiision gradients were used for diSlision sensitisation (delta = 28ms DELTA = 35ms, difiusion time Td = 26ms). Four linearly increasing b-values were applied in 7 non-coUinear directions at 6 slice positions (bn^=703 s/mm^). Four averages were acquired.
Images were transferred to a separate workstation (Sun Microsystems, Palo Alto CA), and converted into UNC format for postprocessing. Image distortion due to the difiusion gradients were corrected with a co-registration program. Movement artefacts were reduced by using a filter algorithm which rejects outlying pixels. Maps of the mean difiusivity and the fi’actional anisotropy (FA) were generated using the method proposed by Basser and Pierpaotf ^ on a pixel by pixel basis. The mean difiusivity is a measure of the magnitude of difiusion in mmVs. The FA index is a rotationally invariant scalar index of anisotropy which scales fi*om 0 (isotropic medium) to 1 (maximum anisotropy). Structural abnormalities were identified on standard MR images and measurements were performed in regions of interests using the Displmage software. The ROI was automatically transferred fi*om mean difiusivity maps to the corresponding region on FA maps to ensure that measurements were performed in identical regions. Normal values were established by measuring FA and mean difiusivity in 2 locations (left and right) in 10 control subjects in the subcortical white matter. Differences between values of patients and of control subjects were statistically tested with a t-test (alpha 5%). Individual measurements in patients outside mean ± 3SD of normal controls were considered to be abnormal.
3,7.3 Results
FA maps provided contrast for myelinated tracts in normal controls. In the subcortical white matter of normal controls the mean FA in the white matter was 0.76 (SD 0.05). The mean difiusivity maps were uniform with values of 0.75 x 10'^ mnf/s (SD 0.05 xlO'^mm^/s). In structural abnormalities FA was significantly reduced (p<0.0001) and mean difiusivity significantly increased (p<0.0001)
compared to normal subcortical white matter (fig.3.18). Despite this finding the correlation between FA and mean difiusivity was poor (r = -0.1). In structural abnormalities of five patients the mean difiusivity was inside mean plus 3SD of normal control subjects. Two patients had dysgenetic lesions and three patients brain damage. All FA measurements in structural abnormalities were outside mean minus 3SD of normal control subjects regardless their aetiology (fig.3.19). Table 3.4 shows diagnosis and difiusion measurements.
I
a
%2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
braindamage A tumour □ dysgenesis controls H---1---1---h0.1
0.3
0.5
0.7
0.9
Fractional Anisotropy Index
Figure 3.18 - Fractional anisotropy and mean difiusivity in structural abnormalities and in the white matter of control subjects.
Figure 3.19 - Structural abnormalities on DTI. Tl-weighted images (left), maps of mean diffusivity (middle) and fractional anisotropy (right) are shown. Top row: A patient with traumatic brain damage affecting the right parietal and frontal lobe (1). Middle row: A patient with poly microgyria affecting the right hemisphere (2). Bottom row: A patient with a left temporal meningeoma (3). The fractional anisotropy is reduced in all structural abnormalities. However, mean diffusivity is only mildly increased in the patient with poly microgyria.
Table 3.4 DTI measurements in structural abnormalities
Pat standard M R imaging diagnosis FA (D-pp) 1 right temporal lesion postsurgical brain damage 0.47 1.63 2 left frontal lesion nonspecific brain damage 0.39 0.87 3 left hemispheral lesion perinatal brain damage 0.39 0.79
4 left ftonto-parietal lesion perinatal infarct 0.26 0.92
5 left occipital lesion ischem ic infarct 0.40 1.07
6 subcortical WML perinatal infarct 0.44 0.87 7 left hemispheral lesion traumatic brain damage 0.28 1.08 8 right fronto-parietal lesion traumatic brain damage 0.30 1.41 9 right subcortical lesion traumatic brain damage 0.42 0.85 10 WML and atrophy mitochondrial cytopathy 0.25 1.46 11 hippocampal atrophy mesiotemporal sclerosis 0.50 1.17 12 abnormal gyrification cortical dysplasia 0.27 1.05 13 abnormal gyrification cortical dysplasia 0.15 0.86 14 abnormal gyrification cortical dysplasia 0.36 0.85 15 bilateral occipital mass meningeoma 0.37 0.98 16 left temporal mass meningeoma 0.40 1.24 17 hypothalamic mass hypothalamic hamartoma 0.25 1.99 18 right mesio temporal mass glioma 0.34 0.97
FA = fractional anisotropy, (D**’’) = mean difiusivity, WML = white matter lesion, GM = grey matter.
3.7.4 Discussion
The main finding of our study was a reduction of anisotropy of water diffiision in a wide range of different structural abnormalities. In the majority of abnormalities (72%) the reduction of anisotropy was also associated with an increased diffusivity. Our finding can be interpreted by considering the physical properties of water diffusion in the brain. In the brain the molecular movement of water is restricted by membranes. Pathological processes resulting in microstructural
changes including cell swelling, shrinkage or widening of the extracellular space or the loss of tissue organization all result in transient or permanent changes of diffusion. It has also been established that water diSlision is anisotropic: water molecules can move more freely in some directions than in others. The underlying mechanisms of anisotropic difrusion are not fully understood but there is evidence that the parallel orientation of myelinated fibres in the stem of tracts is an in ^rtan t fector. Water molecules can difiuse parallel but only to a limited extent perpendicular to myelinated tracts. Unmyelinated tracts appear to impair difiusion less than myelinated tracts. A reduction of anisotropy in lesions implies that the water molecules have more freedom of movement in structurally abnormal tissue than in normal cerebral white matter. This suggests a loss of organization on the microstructural level Experimental models of wallerian degeneration for example showed that anisotropy is reduced because the damaged fibres allow perpendicular diffusion. Our finding of a reduced anisotropy implies that a reduction of the organisation is the common finding in structural abnormalities. Our finding suggests that anisotropy measurements can be a sensitive although nonspecific tool for the detection of abnormal tissue in the white matter. Further studies are necessary to assess if abnormalities can be detected in patients with normal standard MR imaging. In our study measurements of anisotropy and mean difihisivity did not correlate suggesting that both parameters maybe independent measures. In about 30% of all abnormalities a reduced anisotropy was associated with a normal mean difiusivity implying that the structural organization was different (less directional) than in normal white matter (resulting in reduced anisotropy) but the cells were still as densely packed as in normal brain tissue (resulting in normal mean difiusivity). This combination seems to be possible in gliosis (as the consequence of brain damage) and dysgenesis and may distinguish these pathologies from for example tumours. Preliminary studies in stroke, multiple s c l e r o s i s , o t h e r white matter disorders,^'*®’^'*^ malformations of cortical development^"^^ and ageing^"*^ have all shown a reduction in anisotropy suggesting that reduced anisotropy is associated with dysfunction independent of the underlying pathology. Anisotropy may even be mildly reduced in
schizophrenia^'*^ and possibly ageing/'*^
5.7.5. Conclusion
A reduced anisotropy reflecting a loss of the microstructural organisation appears to be the common denominator in structural cerebral abnormalities of different aetiologies.
3.8 Blunt Head Trauma associated with widespread Water Diffusion