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Real-Time Resting-state fMRI for Presurgical Mapping in Patients with Brain Tumors
Kishore Vakamudi1, Mohammad Omar Chohan2, Howard Yonas2, Mona D Chaney3, and Stefan Posse1

1Neurology, Physics and Astronomy, University of New Mexico, Albuquerque, NM, United States, 2Neurosurgery, University of New Mexico, Albuquerque, NM, United States, 3Neurology, University of New Mexico, Albuquerque, NM, United States

Synopsis

We investigated the feasibility of presurgical mapping in patients with brain tumors using real-time rsfMRI analysis methodology in combination with high-speed multi-band EPI. The objective was to map sensorimotor and language resting state networks in the vicinity of brain tumors and to monitor data quality online. We validated this approach in comparison with tfMRI and intra-operative electrocorticography (ECog). The data in patients show a high degree of consistency between resting state connectivity, task-based activation and ECS localization of motor cortex and Broca’s area. Localization of Wernicke’s area was more variable, both in rsfMRI and tfMRI.

Introduction

Preoperative task-based functional MRI (fMRI) is increasingly included in neurosurgery to aid the decision-making process of treatment of patients with brain lesions1-7. However, dependence on patient’s task-compliance, which may be impaired due to disability, is a limitation for clinical applications of task-based fMRI (tfMRI). Resting state functional MRI (rsfMRI) is a promising task-free approach to delineate eloquent cortex8-14, which may complement and potentially replace tfMRI in patient who are unable to perform required tasks15,16. However, rsfMRI is highly sensitive to head movement, physiological noise and spatial-temporal non-stationarity of resting state networks (RSNs)17,18. Online monitoring of data quality is desirable to ensure scan success19. In this study, we investigated the feasibility of presurgical mapping in patients with brain tumors using our recently developed real-time rsfMRI analysis methodology20 in combination with high-speed multi-band EPI, which is increasingly used for rsfMRI due to its high sensitivity resulting from unaliased sampling of physiological signal pulsation. The objective was to map sensorimotor and language resting-state networks in the vicinity of brain tumors and to monitor data quality in real-time. We validated this approach in comparison with tfMRI and intra-operative electrocorticography (ECog).

Methods

RsfMRI (eyes open, 10min) and tfMRI (3min per task) data were acquired in 6 healthy controls (4F,2M) and in 3 patients (2F,1M) with brain tumors (1 glioblastoma, 2 low grade gliomas) using a 3T scanner equipped with 32-channel head coil. Informed written consent was obtained. Tasks were tailored to tumor location: motor (finger-tapping/fist-clenching), visual (eyes open/close), auditory (listening to syllables), and language (word/verb generation). MB8-EPI (TR/TE: 400/35ms, flip angle: 42o, voxel size: 3mm3, 32slices) was reconstructed and analyzed in real-time. Real-time seed-based connectivity analysis (SCA) of 2 RSNs and task-based correlation analysis were performed using the TurboFIRE tool20,21. Preprocessing included motion correction, 5mm isotropic Gaussian spatial filter, and spatial normalization into MNI space. SCA was performed with 8s moving average temporal low pass filter, 15s sliding window correlation analysis with running mean, and regression of 8 signal time courses from 6 rigid body motion parameters and WM and CSF ROIs. Motion parameters, true/false positive connectivity, and task-activation were monitored online. RSNs were mapped using unilateral Brodmann area (BA) based seed regions (auditory: AUN–BA41,42; default-mode: DMN–BA7,31; sensorimotor: SMN–BA01-03, visual: VSN–BA17, language: LAN-BA44,45 (Broca’s) and LAN-BA22,39,40 (Wernicke’s). Image guidance (Stealth Station Treon; Medtronic Surgical Navigation Technologies, Dublin, Ireland) for the surgical approach was based on clinical task-based presurgical fMRI obtained separately. Intraoperative brain mapping was performed using electro-cortical stimulation (ECS) and continuous electrocorticography (ECog). ECS locations were mapped onto stereotactic MRI and coordinates were recorded.

Results

Online data quality monitoring enabled rapid optimization of scan protocols, early identification of task non-compliance and head-movement related false-positive connectivity prompting scan-repetition. Motor, sensory, and language networks in healthy controls were identifiable within 1min of scan time, stabilized within 5-10min and did not significantly change at 20min. Resting-state connectivity and task-based activation in the motor cortex in a patient with glioblastoma were localized within 5mm of the intra-operative ECS localization of the motor cortex (Figure 1). Resting-state language connectivity and task-based activation in Broca’s area in this patient were localized within ~10mm. Resting-state language connectivity and task-based activation in Wernicke’s area in a patient with low grade glioma were localized within 5mm of intra-operative ECS of speech arrest (Figure 2). Resting-state language connectivity and task-based activation in Broca’s area in a second patient with low grade glioma were localized within 5mm of intra-operative ECS of speech arrest (Figure 3). Resting-state connectivity in Wernicke’s area in this patient was more than 30mm posterior to the ECS based localization and 17mm posterior to (clinical) task-based fMRI. Resting-state connectivity and task-based activation in motor cortex in this patient were co-localized within 3mm.

Discussion and Conclusions

The data in patients show a high degree of consistency between resting state connectivity, task-based activation and ECS localization of motor cortex and Broca’s area. Localization of Wernicke’s area was more variable, both in rsfMRI and tfMRI, and in the third patient discordant with intra-operative ECS localization, which may in part reflect cortical reorganization. Limitations of this study include small number of patients studied, atlas-based seed selection, which needs to be adapted to possible cortical reorganization due to neuroplasticity, and large spatial extent of sensorimotor and language connectivity in Broca’s area along the inferior-superior direction. Future work will include: iterative subject-specific seed optimization and intra-RSN functional parcellation combining rfMRI and tfMRI.

Acknowledgements

Research reported in this publication was supported by NIH grant numbers 1R41NS090691 and R21EB018494. We thank Kimball Malherbe (Medtronics), Alam Syed, Troy Hutchins, and Abraham Dominguez for their support of data acquisition and analysis. Special thanks to Arvind Caprihan, Catherine Smith, and Diana South of Mind Research Network for their expert support in scanner operations.

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Figures

Figure 1: Localization of motor cortex in patient with glioblastoma. a) Intra-operative mapping of motor cortex with T-indicating the tumor location; b) intra-operative ECS mapping of the motor cortex in reference to clinical fMRI; c) sensorimotor resting-state network (SMN) with T2-MRI overlay at a 0.6 meta-mean correlation threshold; d) task-based activation during right hand finger tapping at 0.6 correlation threshold; e) resting-state connectivity in Broca’s area; f) task activation of the verb generation task in Broca’s area.

Figure 2: Language mapping in patient with low grade glioma. a) Intra-operative mapping of motor cortex and language function with T indicating the tumor location and S indicating the location of speech arrest; b) resting-state connectivity in Wernicke’s area at 0.5 meta-mean correlation threshold; c) task activation of the verb generation task in Wernicke’s area at 0.5 meta-man correlation threshold. Localization of Wernicke’s area in resting-state and task-based fMRI was consistent with intra-operative mapping.

Figure 3: Language mapping in second patient with low grade glioma. a) Intra-operative mapping of motor cortex and language function with B indicating Broca’s area and W indicating Wernicke’s area; b-c) intra-operative ECS mapping of Broca’s (b) and Wernicke’s (c) areas in reference to clinical fMRI; d,g) mapping of the ECS coordinates onto FLAIR scan; e) resting-state connectivity in Broca’s area; f) task activation of the verb generation task in Broca’s area; h,i) resting-state connectivity in Wernicke’s area is displaced by more than 25mm with respect to ECS coordinates. Task-based fMRI did not show activation in Wernicke’s area.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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