Diffusion Tensor Imaging 12/06/2013

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1 12/06/2013 Beate Diehl, MD PhD FRCP University College London National Hospital for Neurology and Neurosurgery Queen Square London, UK American Epilepsy Society Annual Meeting

2 Disclosure None

3 Learning Objectives To understand the basis of Diffusion Tensor Imaging (DTI), how it can be used to reconstruct white matter tracts (Diffusion Tensor Tractography, DTT) and its technical limitations. To appraise opportunities to improve our knowledge about the epileptic brain using DTI, and how structure and function relate to each other. To appraise the utility of DTT for surgical planning and resection.

4 Impact on Clinical Care and Practice Indications for obtaining DTI and DTT in clinical practice. Opportunity for translational clinical research for better prognostication of postoperative deficits and their prevention.

5 OUTLINE From DWI to DTI and DTT, Introduction to technique DWI and DTI abnormalities in the epileptic network DTI abnormalities and structure/function relationship Role of DTT in perusing pathways of seizure spread Role of DTI/DTT in planning epilepsy surgery Postoperative findings of DTI after epilepsy surgery

6 Diffusion-weighted Imaging (DWI): Non-invasive MR-technique that allows the measurement of molecular motion of water in tissue. Diffusion Tensor Imaging (DTI): Modification of DWI that measures water diffusion in more than 6 directions.

7 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

8 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

9 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

10 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

11 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

12 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

13 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

14 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

15 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

16 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

17 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

18 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

19 Unrestricted Isotropic Diffusion Restricted Anisotropic Diffusion

20 Amplitude of diffusion: ADC (10-4 mm 2 /s) Directionality of diffusion: anisotropy. 1= complete anisotropy (l1); 0= isotropy (l1=l2=l3) l1 l2+l3 2 l1+l2+l3 3 Parallel diffusion Radial diffusion Mean diffusivity l3 Can be used to reconstruct tracts: Diffusion Tensor Tractography DTT l2 l1 FA Map Red: left-right Green: a-p Blue: sup-inf

21 For each voxel, main direction of diffusion is determined. Diffusion tensor model The information used to reconstruct the tracts. PROBLEM: Image resolution. Typical voxel size 10mm 3 ~ axons

22 Diffusion Tensor Tractography (DTT): Techniques Tractography based on Diffusion Tensor with Deterministic tractography Tractography constrained by Spherical deconvolution with Deterministic tractography Probabilistic tractography Reflects uncertainty of The estimated fiber orientation Fiber orientation best estimate to propagate streamlines Tournier JD et al 2011

23 Validating DTT of the Arcuate Fasciculus Reconstruction using methodology by Catani M et al., 2005 Diehl et al, y/o RH man, non-lesional left TLE, determining co localisation between AF and cortical stimulation

24 Validating DTT of the Arcuate Fasciculus with direct cortical electrical stimulation Green good colocalization Blue poor colocalization Colocalization significantly better in anterior than posterior language regions. Diehl et al, 2010

25 Validating DTT of the Arcuate Fasciculus Comparison with CCEPs Conner CR et al., 2011

26 OUTLINE From DWI to DTI and DTT, Introduction to technique DWI and DTI abnormalities in the epileptic network DTI abnormalities and structure/function relationship Role of DTT in perusing pathways of seizure spread Role of DTI/DTT in planning epilepsy surgery Postoperative findings of DTI after epilepsy surgery

27 Aim: To obtain an estimate of white matter diffusion characteristics and relate these to the distance from the seizure focus. Methods: Studies included comparing TLE with control group. White matter region of interest approach. Results: 13 cross-sectional studies Compared to controls significant: FA reduction in ipsilateral > contralateral WM. MD increase Diffusion Tensor Imaging Metaanalysis: DTI in TLE in ipsi- and contralateral WM. Tracts closely connected to sz onset zone most affected. Otte WM et al, 2012 FA and mean diffusivity compared to controls

28 Widespread DTI abnormalities in patients with Epilepsy : Mechanism Hypothesis: Axonal packing and myelin content are the primary predictors of FA (Beaulieu, 2002) Correlations between in vivo DTI and histology in humans: Fimbria/fornix TLE resection Pos. correlation FA and cumulative axon membrane circumference. (Concha et al.,2010)

29 Widespread DTI abnormalities in patients with Epilepsy : Mechanism Most commonly seen pattern of DTI changes associated with focal epilepsy: Unchanged parallel diffusivity Increased perpendicular diffusivity as can be seen in Wallerian degeneration (Gross DW, 2011) Changes already present in new onset epilepsy in children (Widjaja et al., 2013)

30 Structure-Function Relationship: Memory Memory performance in TLE: 28 patients (18 L) L TLE: Evidence of damage of the uncinate fasciculus. Abnormal ADC and/or FA measures relate to auditory memory (L UF) and visual memory (R UF) performance. Deterministic tractography Diehl et al., 2008

31 Control DTT in Epilepsy Structure-Function Relationship: Memory Left Right Group maps of parahippocampal gyrus tracts (left TLE patients controls) L TLE Significant correlations L TLE between left and right FA, and verbal and non-verbal memory. Probabilistic tractography Yogarajah M et al., 2009

32 Structure-Function Relationship: Language DTT from FL R DTT of AF R R Left FLE, MRI negative: Streamline DTT. Right language dominant. Number of L arcuate fasciculus (AF) fibers reduced by 50%. Modified from Vollmar and Diehl, chapter in Extratemporal Lobe Epilepsy Surgery, ed Koubeissi and Maciunas DTI /FA of the AF predicted language laterality (determined by WADA test) in the majority (19 of 23) of patients. Ellmore TM et al., 2009

33 Structure-Function Relationship Predictive value of AF DTI for naming difficulties following dominant anterior temporal lobectomy. Powell R et al., 2008 Positive correlation between lateralisation (asymmetry index, AI) of language connections and postoperative naming change.

34 Diffusion changes and epileptogenicity Diffusion abnormalities in cortex and white matter in different depths in the seizure onset zone of children undergoing intracranial EEG recordings. 18 children, focal neocortical epilepsy, normal MRI compared to 18 age-matched healthy controls. Analysis of ADC and FA of cortex and white matter in different depths (surface based laminar analysis). Govindan RM et al., 2013

35 OUTLINE From DWI to DTI and DTT, Introduction to technique DWI and DTI abnormalities in the epileptic network DTI abnormalities and structure/function relationship Role of DTT in perusing pathways of seizure spread Role of DTI/DTT in planning epilepsy surgery Postoperative findings of DTI after epilepsy surgery

36 DTT and pathways of seizure spread Left inferior temporal sulcus cortical dysplasia (FCD). Ictal onset Slow and contiguous propagation DTT from a ROI underlying the ictal onset zone with reduction of connectivity underlying FCD. Diehl B et al., 2010

37 DTT and pathways of rapid seizure spread

38 a Courtesy C Vollmar

39

40

41 b

42 b

43 OUTLINE From DWI to DTI and DTT, Introduction to technique DWI and DTI abnormalities in the epileptic network DTI abnormalities and structure/function relationship Role of DTT in perusing pathways of seizure spread Role of DTI/DTT in planning epilepsy surgery Postoperative findings of DTI after epilepsy surgery

44 DTT and presurgical planning: at Detailed atlases Catani M et al., 2012

45 DTT for presurgical planning 28 y/o, RH, sz onset age 7, R parietal epilepsy Seizure semiology: left sensory aura (pins and needles in L arm/ face-> left hemibody). R parietal focal cortical dysplasia Hand fmri

46 DTT for presurgical planning

47 DTT and presurgical planning

48 DTT for presurgical planning Outcome: 12 months seizure free, minimal hand numbness Type IIB CD

49 OUTLINE From DWI to DTI and DTT, Introduction to technique DWI and DTI abnormalities in the epileptic network DTI abnormalities and structure/function relationship Role of DTT in perusing pathways of seizure spread Role of DTI/DTT in planning epilepsy surgery Postoperative findings of DTI after epilepsy surgery

50 DTT for presurgical planning, optic radiation Visual fields: European driving regulations the horizontal visual field should be at least 120 degrees, the extension should be at least 50 degrees left and right and 20 degrees up and down. DTT of the optic radiation to plan lesionectomy of cavernous haemangioma

51 DTT for presurgical planning, Optic Radiation DTT of the optic radiation to plan temporal lobectomy Winston G et al., 2012

52 Daga P et al., 2012 Significant brain shift needs to be taken into account American Epilepsy Society 2013

53 DTT for presurgical planning

54 Before and after surgery Little is known what happens to diffusion changes after surgery. TLE: Preop FA reductions in fornix, cingulate, external capsules, did not normalise (Concha et al., 2007) Several reports of FA increase postoperatively contralateral fornix (Nygen et al., 2011) inferior and superior longitudinal fasciculi (Faber et al., 2013) Significance of such increases is currently not well understood Structural reorganization? Artifact?

55 26 left, 20 R TLE patients, before and after ant. TL resection (mean 4.5 months) Whole-brain analysis, tract-based spatial statistics Postop compared to preop: Decreased FA in tracts adjacent to resection (R and L TLE) Increased FA in areas corresponding to ventro-medial language network (L TLE only)? structural reorganization Diffusion Tensor Imaging Before and after surgery Yogarajah M et al., 2010

56 Conclusions DTI is a novel imaging technique that provides insight into the structural integrity of cerebral white matter. There are significant technical limitations to reconstruct tracts from DTI, and validation of findings is an ongoing effort. Widespread abnormalities have been found in patients with focal epilepsy, and tracts closely connected to sz onset zone are most affected in TLE. Some structure function relationship exists, but networks underpinning cognition are complex. DTT may contribute to our understanding of ictal onset and spread. DTT has the potential to improve prediction of post surgical outcome and improve functional outcome.

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