June 2011 Divya S Bolar, HMSIV Pre-surgical planning for brain tumor resection using functional MRI Divya S. Bolar,, HMS IV 1
Our patient: clinical history 85-year year-old right-handed handed woman presents s/p fall with occipital head strike Denies LOC or pre-syncopal symptoms. Endorses eight month history of falls secondary to progressive left-sided weakness and loss of balance. PMHx: : CAD, DM2, HTN, RCC s/p nephrectomy in 1999 Physical exam: notable for intact CN, diffuse left-sided weakness, unsteady gait. No sensory deficits. Labs unremarkable. 2
Our patient: Right parietal lesion on CT Central focus of hyper-attenuation CT head C- 3
Our patient: Surrounding edema Central focus of hyper-attenuation Substantial surrounding edema 4
Our patient: Sulci effacement Central focus of hyper-attenuation Substantial surrounding edema Mass effect with sulci effacement 5
Our patient: Other findings Central focus of hyper-attenuation Substantial surrounding edema Mass effect with sulci effacement Minimal midline shift No fractures or other acute findings 6
Our patient: Differential diagnosis Differential Dx: 1. Hemorrhagic infarct 2. Hemorrhage into underlying mass lesion Well-circumscribed lesion, chronicity of symptoms => suspect hemorrhage into mass 7
Our patient: Intracranial hemorrhage on C- C MRI Mild degree of T1 hyperintensity MRI head T1/ C- 8
Our patient: Intracranial hemorrhage on C+ MRI MRI head T1/ C+ Moderate degree of lesion enhancement Uncharacteristic of hemorrhagic infarct Consistent with contrast uptake by abnormal tumor vasculature 9
Our patient: Approach to management Additional body imaging with CT: Masses found in lung & breast No masses found in remaining kidney or at prior surgical site Etiology of brain tumor unclear Metastasis from occult RCC? New primary brain tumor? Metastasis from other site? Neurosurgical resection was recommended to decompress, reduce edema, improve local control, and biopsy 10
Frontoparietal tumors Neurosurgical resection often indicated, but carries risk of injury to: Primary motor cortex in precentral gyrus and/or descending corticospinal tract Frontal language regions if lesion is in dominant hemisphere (Broca( Broca s s area in orpeculum) Chief concern is paralysis and loss of speech and language Preoperative mapping of these areas could assist in surgical planning and reduce risk of injury 11
Pre-surgical planning: What does the neurosurgeon want to know? Distance between tumor margin and essential functional areas Golden rule says minimum distance 10 mm to preserve function Trajectory to tumor that avoids functional area (if one exists) With this information surgeon can: 1. Determine if tumor is amenable for resection 2. Decide if intraoperative cortical stimulation is needed 3. Better navigate surgical procedure itself So-called functional MRI is a noninvasive approach that can safely identify essential functional areas in advance of surgical intervention 12
What is functional MRI (fmri( fmri)? fmri is a technique for determining which parts of the brain are activated by different types of physical sensation or activity, such as sight, sound or the movement of a subject's fingers. - Steve Smith, FMRIB, Oxford 13
Approach to fmri Subjects are continuously imaged while performing specifically timed tasks Tasks are chosen based on neural system we wish to interrogate. Examples include: Motor => Finger or foot-tapping tapping Visual => Viewing flashing checkerboards Analysis of images allows creation of statistical maps that localize task-based neural activity to corresponding brain regions 14
How is neural activity reflected in the MRI signal? (i.e. how does fmri work!!)
Contents of brain MRI voxel: Parenchyma Parenchyma Van Zijl et al, Nat Med, 1998 Voxel = volumetric picture element 16
Contents of brain MRI voxel: Microvasculature 2008 Sinauer Associates, Inc. Van Zijl et al, Nat Med, 1998 Voxel = volumetric picture element 17
From neural activity to MRI signal: Microvasculature in brain voxel Arterial circulation Capillary Bed Venous circulation 2008 Sinauer Associates, Inc. 18
From neural activity to MRI signal: Oxygen delivery via cerebral blood flow I O 2 At baseline, cerebral blood flow (CBF) supplies oxygen-rich blood to capillary bed O 2 2008 Sinauer Associates, Inc. 19
From neural activity to MRI signal: Oxygen delivery via cerebral blood flow II RBC with HbO 2 O 2 O 2 Chief oxygen-carrier is macromolecule hemoglobin in red blood cell (RBC) Oxygenated hemoglobin is called oxyhemoglobin (HbO 2 ) 2008 Sinauer Associates, Inc. 20
From neural activity to MRI signal: Oxygen extraction and consumption RBC with HbO 2 O 2 As blood traverses capillary bed, oxygen is extracted from HbO 2 into tissue and consumed O 2 2008 Sinauer Associates, Inc. 21
From neural activity to MRI signal: Venous deoxygenated hemoglobin (dhb( dhb) RBC with HbO 2 Deoxygenated hemoglobin (dhb) subsequently results on venous side RBC with dhb 2008 Sinauer Associates, Inc. 22
From neural activity to MRI signal: Effects of dhb on MRI signal RBC with HbO 2 dhb is paramagnetic and perturbs the magnetic field Decreases baseline MR signal RBC with dhb 2008 Sinauer Associates, Inc. 23
From neural activity to MRI signal: Stimulation increases neuronal activity During stimulation (e.g. from a task) neuronal activity increases 2008 Sinauer Associates, Inc. 24
From neural activity to MRI signal: Secondary increase in CBF flushes out dhb O 2 A secondary increase in CBF follows Increased CBF delivers more HbO 2 and flushes out venous dhb O 2 2008 Sinauer Associates, Inc. 25
From neural activity to MRI signal: Reduction in dhb increases MR signal O 2 Decreased dhb results in a smaller field perturbation and an increase in MR signal O 2 2008 Sinauer Associates, Inc. 26
MR signal intensity: Baseline State Divya S Bolar, HMSIV 2008 Sinauer Associates, Inc. [dhb] = 40% 2011 IMAIOS 27
MR signal intensity: Activated State Divya S Bolar, HMSIV Slight intensity increase in corresponding region 2008 Sinauer Associates, Inc. [dhb] = 20% This is the blood oxygen level dependent (BOLD) effect and is the basis for fmri! 2011 IMAIOS 28
Sample block block-design fmri task: Right handed finger-tapping Divya S Bolar, HMSIV REST 1 min TAP! X 3 1 min Acquire low-resolution MR images every two seconds MR signal from left motor cortex 29
Generation of statistical map shows activated voxels Map overlaid on high-resolution T1-weighted anatomical 30
Central voxel with highly significant activation 31
Peripheral voxel with less significant activation 32
Our patient: fmri protocol Use similar block-design fmri paradigm Include: Motor task: LH finger-tapping Language: Verb repetition 33
Our patient: Activation from LH finger-tapping Divya S Bolar, HMSIV 34
Our patient: Primary motor cortex Primary motor cortex 35
Our patient: Supplementary motor cortex(?) Supplementary motor cortex(?) 36
Our patient: Activation from Verb repetition Operculum frontale Activation seen in operculum frontale; location consistent with Broca s s Area Suggests patient has left hemispheric dominance Reduced risk of language impairment with resection of right-sided lesion. 37
Our patient: Surgical planning Tumor margin 5 mm away from motor activation strip Unobscured oblique trajectory available for direct approach 5 mm 38
Our patient: Pre-post op comparison PRE POST 39
Our patient: Post-operative changes T1 hyperintensity consistent with post- operative blood and proteinaceous material Thin rim of enhancement could be post-op op change, but residual tumor cannot be excluded 40
Our patient: Outcome Patient initially had increased left-sided weakness post-operatively operatively Not surprising given proximity of tumor to motor cortex Improved over time Preliminary pathology suggested metastasis from renal cell carcinoma She was discharged and will see oncology to discuss chemotherapy options 41
Summary Functional MRI can be useful tool for preoperative planning and assessment for brain tumor resection fmri creates activation maps which correlate to neural activity patterns Link between neural activity and MRI signal arises from increased blood flow flushing out paramagnetic dhb during stimulation Use of maps allow surgeons to: 1. Assess resectability of tumors near essential functional areas 2. Decide if intraoperative cortical stimulation is needed 3. Better navigate surgical procedure 42
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. 43
Thanks to: Acknowledgements Rafael Rajos MD, Neuroradiology, BIDMC Ted Brewer MD, Neuroradiology, BIDMC Gillian Lieberman MD, Radiology, BIDMC Emily Hanson, Radiology, BIDMC 44