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BOLD and DTI for Presurgical MappingJay J. Pillai, M.D.

Director of Functional MRIAssociate Professor

Neuroradiology DivisionThe Russell H. Morgan Department ofRadiology and Radiological Science

Johns Hopkins Univ. School of Medicine

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What is the purpose of presurgical mapping? Why fMRI & DTI?

• Preop risk assessment• Planning surg trajectory• Planning intraop mapping• Eloquent cortex & eloquent WM---goal of neurosurgery• Added value—patient interactive (H & P, training, education

prescan), very different from volunteer research scanning

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Typical Language Paradigms• Expressive Language Tasks

– Verbal Fluency/Phonemic Fluency– Rhyming (Phonological)– Object Naming

• Receptive Language Tasks– Sentence Comprehension (V/A)/Story Listening– Sentence Completion– Semantic Decision (category, nva, s/a)

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Essential vs. Nonessential Activation

• Complementary role of intraop mapping• Role of convergent activation• Role of statistical thresholding

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Typical Motor Paradigms• Hand Motor

– Bilateral simultaneous or alternating R/L hand– AFT, hand clenching, thumb-index apposition

• Foot Motor– Toe flexion/extension– Ankle flexion/extension

• Face Motor– Tongue movement—lateral or vertical– Lip puckering

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Classical Brodmann’s areas

From Waxman SG. Correlative Neuroanatomy, 24th Ed. Lange Medical Books/McGraw-Hill, New York, 2000.

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Diffusion Tensor Imaging—Eloquent White Matter is just as important as Eloquent Cortex

• Damage to eloquent white matter similar to resection of eloquent cortex

• Water molecule diffusion is directionally dependent—anisotropy

• The direction of maximum diffusivity coincides with the WM fiber tract orientation

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The Diffusion Tensor

• The “diffusion tensor”is a matrix of numbers (mathematical model describing diffusion in 3D space) derived from diffusion measurements in several different directions (6+ directions for diffusion encoding).

• This tensor depicted as ellipsoid whose orientation is described by three eigenvectors and its shape by three eigenvalues, which are its dimensions (corresponding to diffusivity in each direction).2

1,2 Jellison BJ, Field AS, Medow J, Lazar M, Salamat MS, Alexander AL. Diffusion tensor imaging of cerebral white matter: a pictorial review of physics, fiber tract anatomy, and tumor imaging patterns. AJNR Am J Neuroradiol. 2004 Mar;25(3):356-69

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Additional white matter tracts—sagittal tractograms

Normal SLF

Adapted from Brian J. Jellison, Aaron S. Field, Joshua Medow, Mariana Lazar, M. Shariar Salamat, and Andrew L. Alexander. Diffusion Tensor Imaging of Cerebral White Matter: A Pictorial Review of Physics, Fiber Tract Anatomy, and Tumor Imaging Patterns. AJNR Am. J. Neuroradiol. 2004; 25: 356 - 369.

Arcuate Fasciculus—important for

language function/SLF

Superior Fronto-Occipital

Fasciculus

Inferior Fronto-Occipital

Fasciculus

Inferior Longitudinal

Fasciculus

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SLF

• 4 parts of SLF:– SLF I---horizontal fibers connecting superior parietal lobe to

frontal/opercular regions (premotor areas and SMA)– SLF II---horizontal fibers connecting the AG to posterior prefrontal

cortices– SLF III---horizontal fibers connecting the SMG to F lobe (pars

opercularis /ventral premotor areas [BA 44] and ventral prefrontal area [BA 46])

– SLF IV---AF--- connects STG/MTG to frontal regions (caudal dorsal prefrontal cortex, precentral gyrus but not BA as previously thought)

Bernal B, Altman N. The connectivity of the superior longitudinal fasciculus: a tractography DTI study. Magnetic Resonance Imaging 28 (2010) 217–225.

Schmahmann JD, Pandya DN, Wang R, Dai G, Darceuil HE, de Crespigny AJ, Wedeen VJ. Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 2007; 130:630-653.

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Functions of the SLF components

• SLF I: higher order control of body-centered action based on proprioception and initiation of motor activity

• SLFII: involved in focusing spatial attention (hemi-inattention/neglect w lesions)

• SLF III: involved in the gestural component of language and orofacial working memory (lesions result in cortical dysarthria, oral/buccal apraxias, impaired working memory)

• SLF IV (AF): thought that lesions result in conduction aphasia, but primate evidence suggests that ExC and MdLF rather than AF responsible; AF actually involved in spatial processing in the auditory domain (indicating location and directionality of sounds rather than symbolic repres of lang)

Schmahmann JD, Pandya DN, Wang R, Dai G, Darceuil HE, de Crespigny AJ, Wedeen VJ. Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 2007; 130:630-653.

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Martino J, De Witt Hamer PC, Berger MS, Lawton MT, Arnold CM, de Lucas EM, Duffau H. Analysis of the subcomponents and cortical terminations of the perisylvian superior longitudinal fasciculus: a fiber dissection and DTI tractography study. Brain Struct Funct. 2012 Mar 16.

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Functions of various other important eloquent tracts

• 1) SFOF—responsible for initiation and preparation of speech movements and limbic aspects of speech

• 2) IFOF—involved in language ventral stream (semantic network, distinct from phonological network mediated by SLF)

• 3) ILF—role in ventral visual stream (object recognition, discrimination and memory including facial recognition—lesion>>>prosopagnosia)—actually lateral to SS

• 4) Uncinate fasciculus– processing novel information, understanding emotional aspects of sounds, regulation of emotional responses to auditory stimuli, enables interaction between emotion and cognition, self-regulation, retrieval of past information

• 5) Cingulum bundle—dorsal limbic pathway linking caudal cingulate gyrus with HC and PHG (memory), prefrontal areas 9 & 46 (manipulating info, monitoring behavior, working memory)—critical for motivational and emotional aspects of behavior, spatial working memory (cingulotomy for OCD)

Schmahmann JD, Pandya DN, Wang R, Dai G, Darceuil HE, de Crespigny AJ, Wedeen VJ. Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 2007; 130:630-653.

Aralasmak A, Ulmer JL, Kocak M, Salvan CV, Hillis AE, Yousem DM. Association, Commissural and Projection Pathways and Their Functional Deficit Reported in Literature. J Comput Assist Tomogr 2006; 30:695-715.

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DTT Validation: Bello et al. Neuroimage 2008

• Study of 52 pts w LGG and 12 w HGG

• There was a high correlation between DT-FT and ISM(sensitivity for CST=95%, language tracts=97%).

• The combination of both methods decreased the duration of surgery, patient fatigue, and intraoperative seizures.

Bello L, Gambini A, Castellano A, et al. Motor and language DTI Fiber Tracking combined with intraoperative subcortical mapping for surgical removal of gliomas. Neuroimage. 2008 Jan 1;39(1):369-82. Epub 2007 Aug 29

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Limitations of DTT

– 4 different DTT software packages for display of CST of a single normal subject; 3 used FACT (Fiber Assignment by Continuous Tracking) method, one used Tensorline Propagation Algorithm.

– None of the software applications was able to display the CST in its full anatomical extent

– The 4 packages did not lead to comparable tracking results despite use of similar or identical tracking algorithms

Bürgel U, Mädler B, Honey CR, Thron A, Gilsbach J, Coenen VA.Fiber tracking with distinct software tools results in a clear diversity in anatomical fiber tract

portrayal. Cen Eur Neurosurg. 2009 Feb;70(1):27-35.

Clinical Value of DTT vs. color directional diffusion maps

• DTT is excellent for isolating tracts that run alongside other parallel tracts• Major limitation for clinical use is undersampling of the tract ---operator-

dependent seeding, anatomic distortion.• FA/angulation thresholds, step sizes arbitrary• Error propagation—1st vs 2nd order processing• Numerous algorithms---deterministic (discrete, subvoxel) & probabilistic

DTT with very little validation

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Validation of fMRI: studies comparing fMRI to Wada and ECS results:

Study comparing fMRI to ECS+/-Wada, 1996-2004

fMRI task (Lang/ motor)

Concordance with Wada

Concordance with ECS

Binder JR et al. 1996; Neurology 46(4): 978-984 L 22/22 lateraliz (100%) ( r=0.96 for LI)

NA

Bahn M et al., AJR 1997. 169(2):575-9.

-- 7/7 (100%) NA

Hertz-Pannier L et al. Neurology 1997. 48(4):1003-1012.

L 6/6 (100%) 1/1 (100%)

Yetkin FZ, et al. AJNR Am J Neuroradiol. 1997; 18(7): 1311-1315

L,M NA 28/28 (100% to 20mm, 87% to 10 mm)

Benson RR et al., Neurology 1999. 52(4):798-809.

L 12/12 (100%) 10/11 (91%)

Roux FE et al. Acta Neurochirurgica 1999 141(1):71-79

M NA 8/8 (100%)

Roux FE, et al. Invest Radiol 1999 34(3):225-229

M NA 14/14 (100%)

Hirsch J, et al.. Neurosurgery 2000. 47(3): 711-721.

L, M 13/13 (100%) 30/30 (100%)

Roux FE et al., Neurosurgery 2001 49(5):1145-1157

M NA 28/32 (87%)

Sabbah P et al. Neuroimage 2003; 18(2):460-7 L 19/20 (95%) NA Woermann FG et al. Neurology 2003; 61(5): 699-701.

-- 91/100 domin (91%) NA

Meneses MS et al. Arquivos de Neuro-Psiquiatria 2004; 62(1):61-7.

L 5/5 (100%) NA

• FROM: Pillai JJ, Language fMRI IN Holodny AI (Ed), Functional Neuroimaging: A Clinical Approach,

2008, Informa Healthcare (New York, NY)

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Giussani, Carlo; Roux, Frank-Emmanuel; MD, PhD; Ojemann, Jeffrey; Sganzerla, Erik; Pirillo, David; Papagno, CostanzaIs Preoperative Functional Magnetic Resonance Imaging Reliable for Language Areas Mapping in Brain Tumor Surgery? Review of Language Functional Magnetic

Resonance ImagingNeurosurgery. 66(1):113-120, January 2010.

BOLD validation:

Studies comparing

preop language fMRI to ECS—

Giussani et al.,

Neurosurgery Jan 2010

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Impact of preop fMRI on surgical planning:

Petrella et al., Radiology, Sept. 2006;240:793-802 • Functional MRI performed on 39 consecutive patients with brain tumors.

• Change in neurosurgical treatment plans (as a result of preoperative fMRI) occurred in 19 patients (P < .05), with a more aggressive approach recommended after imaging in 18 patients.

• Functional MR imaging resulted in reduced surgical time (estimated reduction, 15–60 minutes) in 22 patients who underwent surgery, a more aggressive resection in six, and a smaller craniotomy in two.

• In four patients, sparing of patients from additional testing (e.g., Wada) because of the functional MRI result.

Petrella JR, Shah LM, Harris KM et al. Preoperative functional MR imaging localization of language and motor areas: Effect on therapeutic decision making in patents with potentially resectable brain tumors. Radiology. 2006;240:793-802

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Impact of preop fMRI on postoperative clinical outcome

Roessler et al. J Neurol Neurosurg Psychiatry 2005

• Twenty two patients with gliomas near motor cortex evaluated with both motor 3T fMRI and intraoperative motor cortex stimulation (MCS).

• FMRI motor foci were successfully detected in all patients preoperatively, whereas MCS was possible in only 17 of 22 patients (77.3%). In those 17 patients, 100% agreement was found between MCS and fMRI for localization of primary motor cortex within 10 mm.

• Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity).

Roessler K, Donat M, Lanzenberger R, Novak K, Geissler A, Gartus A, Tahamtan AR, Milakara D, Czech T, Barth M, Knosp E, Beisteiner R. Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative

outcome. J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1152-7

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Impact of preop DTI on Postsurgical Clinical Outcome

Wu JS et al., Neurosurgery 2007

• Studied 238 pts—118 underwent DTI, 120 std 3D struct scans only for neuronavigation.

• Postoperative motor deterioration occurred in 32.8% of control cases, compared to 15.3% of the study cases (P < 0.001).

• The 6-month Karnofsky Performance Scale score of study cases was significantly higher than that of control cases, P < 0.001; greater difference for HGG than LGG.

• For 81 HGGs, the median survival of study cases was 21.2 months compared with 14.0 months of control cases (P = 0.048).

• Wu JS, Zhou LF, Tang WJ, Mao Y, Hu J, Song YY, Hong XN, Du GH. Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in

patients with gliomas involving pyramidal tracts. Neurosurgery. 2007 Nov;61(5):935-48; discussion 948-9

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Preop BOLD fMRI may serve as a prognostic indicator—recent paper by Wood et al., AJNR

2011• 74 patients w primary or met tumor underwent BOLD motor mapping

• 77 patients underwent BOLD language mapping

• Motor (p<0.001) and lang (P=0.009)LAD signif a/w pre or postop deficits

• Pre and postop deficits, grade, tumor loc and LAD predicted mortality

• Motor deficits increased linearly as dist from tumor to PSMC decreased, while lang deficits incr exponentially as dist from tumor to lang areas decr below 1 cm.

Wood JM, Kundu B, Utter A, et al. Impact of Brain Tumor Location on Morbidity and Mortality: A Retrospective Functional MR Imaging Study. AJNR Am J Neuroradiol 2011; 32(8): 1420-5.

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Clinical impact of BOLD fMRI—relationship between LAD and motor/lang deficits

Linear relationship (R2=0.99) between distance from the tumor to the area of activation and the existence of motor deficits (red) and an asymptotic relationship (exponential fit, R2=0.88) between the distance from the tumor to the area of activation and the existence of language deficits. Error bars depict 95% CIs calculated for a proportion.

Wood JM, Kundu B, Utter A, et al. Impact of Brain Tumor Location on Morbidity and Mortality: A Retrospective Functional MR Imaging Study. AJNR Am J Neuroradiol 2011; 32(8): 1420-5.