Divya S Bolar, HMSIVGillian Lieberman, MD

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PrePre--surgical planning for surgical planning for brain tumor resection brain tumor resection using functional MRIusing functional MRI

DivyaDivya S. S. BolarBolar, HMS IV, HMS IVGillian Lieberman, MDGillian Lieberman, MD

June 2011

Divya S Bolar, HMSIVGillian Lieberman, MD

Our patient: clinical historyOur patient: clinical history8585--yearyear--old rightold right--handed woman presents handed woman presents s/ps/p fall fall

with occipital head strikewith occipital head strike

Denies LOC or preDenies LOC or pre--syncopalsyncopal symptoms. Endorses eight symptoms. Endorses eight month history of falls secondary to progressive leftmonth history of falls secondary to progressive left--sided sided weakness and loss of balance.weakness and loss of balance.

PMHxPMHx: CAD, DM2, HTN, RCC : CAD, DM2, HTN, RCC s/ps/p nephrectomynephrectomy in 1999in 1999

Physical exam: Physical exam: notable for intact CN, diffuse leftnotable for intact CN, diffuse left--sided sided weakness, unsteady gait. No sensory deficits. Labs weakness, unsteady gait. No sensory deficits. Labs unremarkable.unremarkable.

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Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Right parietal lesion on CTOur patient: Right parietal lesion on CT

Central focus of Central focus of hyperhyper--attenuationattenuation

CT head C-

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Surrounding edemaOur patient: Surrounding edema

Central focus of Central focus of hyperhyper--attenuationattenuation

Substantial Substantial surrounding edemasurrounding edema

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Our patient: SulciSulci effacementeffacement

Central focus of Central focus of hyperhyper--attenuationattenuation

Substantial Substantial surrounding edemasurrounding edema

Mass effect with Mass effect with sulcisulci effacement effacement

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Other findingsOur patient: Other findings

Central focus of Central focus of hyperhyper--attenuationattenuation

Substantial Substantial surrounding edemasurrounding edema

Mass effect with Mass effect with sulcisulci effacement effacement

Minimal midline shiftMinimal midline shift

No fractures or other No fractures or other acute findingsacute findings

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Differential diagnosisOur patient: Differential diagnosis

Differential Differential DxDx::1.1. Hemorrhagic infarctHemorrhagic infarct2.2. Hemorrhage into Hemorrhage into

underlying mass underlying mass lesionlesion

WellWell--circumscribed circumscribed lesion, lesion, chronicitychronicity of of symptoms => symptoms => suspect hemorrhage suspect hemorrhage into massinto mass

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Our patient: Intracranial hemorrhage on CIntracranial hemorrhage on C-- MRIMRI

Mild degree of T1 Mild degree of T1 hyperintensityhyperintensity

MRI head T1/ C-

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Our patient: Intracranial hemorrhage on C+ MRIIntracranial hemorrhage on C+ MRI

Moderate degree Moderate degree of lesion of lesion enhancement enhancement

Uncharacteristic of Uncharacteristic of hemorrhagic hemorrhagic infarctinfarct

Consistent with Consistent with contrast uptake by contrast uptake by abnormal tumor abnormal tumor vasculaturevasculature

MRI head T1/ C+

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Approach to management

Additional body imaging with CT:Additional body imaging with CT:

Masses found in lung & breastMasses found in lung & breast

No masses found in remaining kidney or at prior No masses found in remaining kidney or at prior surgical sitesurgical site

Etiology of brain tumor unclearEtiology of brain tumor unclear

Metastasis from occult RCC?Metastasis from occult RCC?

New primary brain tumor?New primary brain tumor?

Metastasis from other site?Metastasis from other site?

Neurosurgical resection was recommended to Neurosurgical resection was recommended to decompress, reduce edema, improve local decompress, reduce edema, improve local control, and biopsycontrol, and biopsy

Divya S Bolar, HMSIVGillian Lieberman, MD

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FrontoparietalFrontoparietal tumorstumors

Neurosurgical resection often indicated, but Neurosurgical resection often indicated, but carries risk of injury to:carries risk of injury to:

Primary motor cortex in Primary motor cortex in precentralprecentral gyrusgyrus and/or and/or descending descending corticospinalcorticospinal tracttract

Frontal language regions if lesion is in dominant Frontal language regions if lesion is in dominant hemisphere (hemisphere (BrocaBroca’’s area in s area in orpeculumorpeculum))

Chief concern is paralysis and loss of speech and Chief concern is paralysis and loss of speech and languagelanguage

Preoperative mapping of these areas could assist Preoperative mapping of these areas could assist in surgical planning and reduce risk of injuryin surgical planning and reduce risk of injury

Divya S Bolar, HMSIVGillian Lieberman, MD

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PrePre--surgical planning: surgical planning: What does the neurosurgeon want to know?What does the neurosurgeon want to know?

Distance between tumor margin and essential functional Distance between tumor margin and essential functional areasareas

““Golden ruleGolden rule”” says minimum distance 10 mm to preserve says minimum distance 10 mm to preserve functionfunction

Trajectory to tumor that avoids functional area (if one Trajectory to tumor that avoids functional area (if one exists)exists)

With this information surgeon can:With this information surgeon can:1.1. Determine if tumor is amenable for resectionDetermine if tumor is amenable for resection2.2. Decide if Decide if intraoperativeintraoperative cortical stimulation is needed cortical stimulation is needed 3.3. Better navigate surgical procedure itselfBetter navigate surgical procedure itself

SoSo--called called ““functional MRIfunctional MRI”” is a noninvasive approach is a noninvasive approach that can safely identify essential functional areas in that can safely identify essential functional areas in advance of surgical interventionadvance of surgical intervention

Divya S Bolar, HMSIVGillian Lieberman, MD

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What is functional MRI (What is functional MRI (fMRIfMRI)?)?

““ fMRIfMRI is a technique for determining is a technique for determining which parts of the brain are activated by which parts of the brain are activated by different types of physical sensation or different types of physical sensation or activity, such as sight, sound or the activity, such as sight, sound or the movement of a subject's fingers.movement of a subject's fingers.””

-- Steve Smith, FMRIB, OxfordSteve Smith, FMRIB, Oxford

Divya S Bolar, HMSIVGillian Lieberman, MD

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Approach to Approach to fMRIfMRI

Subjects are continuously imaged while Subjects are continuously imaged while performing specifically timed performing specifically timed ““taskstasks””

Tasks are chosen based on neural system we Tasks are chosen based on neural system we wish to interrogate. Examples include:wish to interrogate. Examples include:

Motor => Finger or footMotor => Finger or foot--tappingtapping

Visual => Viewing flashing checkerboardsVisual => Viewing flashing checkerboards

Analysis of images allows creation of statistical Analysis of images allows creation of statistical maps that maps that localize tasklocalize task--based neural activity to based neural activity to corresponding brain regionscorresponding brain regions

Divya S Bolar, HMSIVGillian Lieberman, MD

How is neural activity reflected How is neural activity reflected in the MRI signal?in the MRI signal?

(i.e. how does (i.e. how does fMRIfMRI work!!)work!!)

Divya S Bolar, HMSIVGillian Lieberman, MD

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Contents of brain MRI voxel: Parenchyma

ParenchymaParenchyma

Van Zijl et al, Nat Med, 1998

Voxel = volumetric picture element

Divya S Bolar, HMSIVGillian Lieberman, MD

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Contents of brain MRI voxel: Microvasculature

Van Zijl et al, Nat Med, 1998

©2008 Sinauer Associates, Inc.

Voxel = volumetric picture element

Divya S Bolar, HMSIVGillian Lieberman, MD

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From neural activity to MRI signal: From neural activity to MRI signal: Microvasculature in brain Microvasculature in brain voxelvoxel

©2008 Sinauer Associates, Inc.

Arterial circulation

Venous circulation

Capillary Bed

Divya S Bolar, HMSIVGillian Lieberman, MD

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From neural activity to MRI signal: From neural activity to MRI signal: Oxygen delivery via cerebral blood flow IOxygen delivery via cerebral blood flow I

At baseline, cerebral At baseline, cerebral blood flow (CBF) supplies blood flow (CBF) supplies oxygenoxygen--rich blood to rich blood to capillary bedcapillary bedO2

O2

©2008 Sinauer Associates, Inc.

Divya S Bolar, HMSIVGillian Lieberman, MD

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From neural activity to MRI signal: From neural activity to MRI signal: Oxygen delivery via cerebral blood flow IIOxygen delivery via cerebral blood flow II

Chief oxygenChief oxygen--carrier is carrier is macromolecule macromolecule hemoglobinhemoglobin in red blood in red blood cell (RBC)cell (RBC)

Oxygenated hemoglobin Oxygenated hemoglobin is called is called oxyoxyhemoglobinhemoglobin (HbO(HbO 22 ))

O2

O2

RBC with HbO2

©2008 Sinauer Associates, Inc.

Divya S Bolar, HMSIVGillian Lieberman, MD

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From neural activity to MRI signal: From neural activity to MRI signal: Oxygen extraction and consumptionOxygen extraction and consumption

As blood traverses As blood traverses capillary bed, oxygen is capillary bed, oxygen is extractedextracted from HbOfrom HbO 22 into into tissue and consumedtissue and consumed

RBC with HbO2

©2008 Sinauer Associates, Inc.

O2

O2

Divya S Bolar, HMSIVGillian Lieberman, MD

Deoxygenated Deoxygenated hemoglobinhemoglobin ((dHbdHb) ) subsequently results on subsequently results on venous sidevenous side

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From neural activity to MRI signal: From neural activity to MRI signal: Venous deoxygenated hemoglobin (Venous deoxygenated hemoglobin (dHbdHb))

RBC with RBC with dHbdHb

RBC with RBC with HbOHbO22

©2008 Sinauer Associates, Inc.

Divya S Bolar, HMSIVGillian Lieberman, MD

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From neural activity to MRI signal: From neural activity to MRI signal: Effects of Effects of dHbdHb on MRI signalon MRI signal

RBC with RBC with dHbdHb

RBC with RBC with HbOHbO22

©2008 Sinauer Associates, Inc.

dHbdHb is paramagnetic andis paramagnetic and perturbsperturbs the magnetic the magnetic fieldfield

DecreasesDecreases baselinebaseline MR MR signalsignal

Divya S Bolar, HMSIVGillian Lieberman, MD

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From neural activity to MRI signal: From neural activity to MRI signal: Stimulation increases neuronal activityStimulation increases neuronal activity

©2008 Sinauer Associates, Inc.

During stimulation (e.g. from a task) neuronal activity increases

Divya S Bolar, HMSIVGillian Lieberman, MD

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©2008 Sinauer Associates, Inc.

From neural activity to MRI signal: From neural activity to MRI signal: Secondary increase in CBF flushes out Secondary increase in CBF flushes out dHbdHb

O2

O2

A secondary increase in A secondary increase in CBF followsCBF follows

Increased CBF delivers Increased CBF delivers more HbOmore HbO 2 2 and and flushes flushes out venous out venous dHbdHb

Divya S Bolar, HMSIVGillian Lieberman, MD

©2008 Sinauer Associates, Inc.

O2

O2

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From neural activity to MRI signal: From neural activity to MRI signal: Reduction in Reduction in dHbdHb increases MR signalincreases MR signal

Decreased Decreased dHbdHb results in results in aa smaller smaller field field perturbation perturbation and and an an increaseincrease in MR signalin MR signal

Divya S Bolar, HMSIVGillian Lieberman, MD

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MR signal intensity:MR signal intensity: Baseline StateBaseline State

[dHb] = 40%©2008 Sinauer Associates, Inc.

© 2011 IMAIOS

Divya S Bolar, HMSIVGillian Lieberman, MD

MR signal intensity:MR signal intensity: Activated Activated StateState

This is the blood oxygen level dependent (BOLD) effect and is the basis for fMRI!

Slight intensity increase in corresponding region

[dHb] = 20%©2008 Sinauer Associates, Inc.

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© 2011 IMAIOS

Divya S Bolar, HMSIVGillian Lieberman, MD

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SampleSample““blockblock--designdesign”” fMRIfMRI task:task:Right handed fingerRight handed finger--tappingtapping

1 min1 min X 3Acquire low-resolution MR images every two seconds

1 min1 minREST

TAP!

MR signal from left motor cortex

Divya S Bolar, HMSIVGillian Lieberman, MD

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Generation of statistical map shows “activated voxels”

Map overlaid on high-resolution T1-weighted anatomical

Divya S Bolar, HMSIVGillian Lieberman, MD

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Central voxel with highly significant activation

Divya S Bolar, HMSIVGillian Lieberman, MD

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Peripheral voxel with less significant activation

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Our patient: fMRIfMRI protocolprotocol

Use similar Use similar ““blockblock--designdesign”” fMRIfMRI paradigmparadigm

Include:Include:

Motor task: LH fingerMotor task: LH finger--tappingtapping

Language: Verb repetitionLanguage: Verb repetition

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Activation from LH finger-tapping

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Primary motor cortex

Primary motor cortex

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Supplementary motor cortex(?)

Supplementary motor cortex(?)

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Activation from Verb repetition

Activation seen in Activation seen in operculum operculum frontalefrontale; ; location consistent with location consistent with BrocaBroca’’s Areas Area

Suggests patient has Suggests patient has left left hemispheric dominancehemispheric dominance

Reduced risk of language Reduced risk of language impairment with resection impairment with resection of rightof right--sided lesion. sided lesion.

Operculum frontale

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Surgical planning

Tumor margin Tumor margin 5 mm 5 mm away from motor away from motor activation stripactivation strip

UnobscuredUnobscured oblique oblique trajectory trajectory available available for direct approachfor direct approach

5 mm

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Pre-post op comparison

PRE

POST

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Post-operative changes

T1 T1 hyperintensityhyperintensity consistent with postconsistent with post-- operative blood and operative blood and proteinaceousproteinaceous material material

Thin rim of Thin rim of enhancement could enhancement could be postbe post--op change, op change, but residual tumor but residual tumor cannot be excludedcannot be excluded

Divya S Bolar, HMSIVGillian Lieberman, MD

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Our patient: Outcome

Patient initially had increased leftPatient initially had increased left--sided sided weakness postweakness post--operativelyoperatively

Not surprising given proximity of tumor to motor Not surprising given proximity of tumor to motor cortexcortex

Improved over timeImproved over time

Preliminary pathology suggested metastasis Preliminary pathology suggested metastasis from renal cell carcinomafrom renal cell carcinoma

She was discharged and will see oncology to She was discharged and will see oncology to discuss chemotherapy optionsdiscuss chemotherapy options

Divya S Bolar, HMSIVGillian Lieberman, MD

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Summary

Functional MRI can be useful tool for preoperative Functional MRI can be useful tool for preoperative planning and assessment for brain tumor resectionplanning and assessment for brain tumor resection

fMRIfMRI creates creates ““activation mapsactivation maps”” which correlate to which correlate to neural activity patternsneural activity patterns

Link between neural activity and MRI signal arises from Link between neural activity and MRI signal arises from increased blood flow flushing out paramagnetic increased blood flow flushing out paramagnetic dHbdHb during stimulationduring stimulation

Use of maps allow surgeons to: Use of maps allow surgeons to: 1.1. Assess Assess resectabilityresectability of tumors near essential functional areasof tumors near essential functional areas2.2. Decide if Decide if intraoperativeintraoperative cortical stimulation is neededcortical stimulation is needed3.3. Better navigate surgical procedureBetter navigate surgical procedure

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References

Buxton RB. Introduction to Functional Magnetic Resonance Imaging. Second Edition. New York, NY: Cambridge University Press; 2009.

Hoa D. Functional MRI of the Brain. http://www.imaios.com/en/e-Courses/e- MRI/Functional-MRI/introduction, Accessed 6/16/2011.

Holodny AI. Functional Neuroimaging: A Clinical Approach. New York, NY: Informa Healthcare; 2008.

Purves, Augustine, Fitzpatric, Hall, LaMantia, McNamara, White. Neuroscience. Fourth Edition. http://www.sinauer.com/neuroscience4e/animations1.1.html, Accessed 6/16/2011.

Smith S. Brief Introduction to FMRI. http://www.uib.no/med/avd/miapr/arvid/bfy- 361/fmri_smith_1998.pdf. Accessed 6/16/2011.

Sunaert S. Presurgical planning for tumor resectioning. JMRI. 2006; 23:887-095.

van Zijl PC, Eleff SM, Ulatowski JA, Oja JM, Ulug AM, Traystman RJ, Kauppinen RA. Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging. Nat Med 1998;4:159–167.Brugge WR, Van Dam J.

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Acknowledgements

Thanks to:

Rafael Rajos MD, Neuroradiology, BIDMC

Ted Brewer MD, Neuroradiology, BIDMC

Gillian Lieberman MD, Radiology, BIDMC

Emily Hanson, Radiology, BIDMC