ASYMMETRIES IN rsFMRI INTRINSIC BRAIN ACTIVITY MEASURES AS A PREDICTOR OF

EPILEPSY SURGERY SUCCESS

Carly M. Rosen, David M. Groppe, Ashesh D. Mehta

Laboratory of Multimodal Brain MappingFeinstein Institute for Medical Research

Introduction

• Epilepsy is a neurological disorder that characterized by recurrent seizures. It is estimated to affect over 70 million people worldwide.

• Surgical resection of the epileptogenic zone (EZ) is considered a standard of care for patients with seizures that cannot be controlled with antiepileptic drugs. This condition is known as intractable epilepsy.

• The success of this epilepsy surgery is highly variable (30-80%).

Question

Background

Can rs-fMRI analysis be used to determine the degree of seizure freedom after epilepsy surgery?

Methods• Prior to implantation of intracranial electrodes, structural

and functional MRIs were acquired from 13 intractable epilepsy patients

Implantation of intracranial grid and strip electrodes is used to determine EZ and

vital brain areas prior to resection surgery

• After implantation, the EZ is determined through electrocorticography (ECoG) analysis and is targeted for resection.

• The preoperative structural MRI is compared to the postoperative MRI to determine the resected area.

• The blood-oxygenation level dependent (BOLD) response, used in fMRI analysis, is a correlate of brain activity.

• Resting-state functional Magnetic Resonance Imaging (rsfMRI) may be used to identify the extent of epileptogenic tissue as well as predict cognitive changes after resection.

• Measures of intrinsic brain activity such as regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and fractional amplitude of low frequency fluctuations (fALFF) can be obtained from rsfMRI data.– In this presentation these measures are obtained for the areas

outside of the resected zone. The measure is considered significant when the value of a region on the resected hemisphere differ from the identical contralateral region by |Z|>1.65 (p<0.05)

Resting-state fMRI and its Measures

Defining the Resection ZoneFig. 1:Resection mask on pre-operativeMRI

Fig. 2:Resection mask on post-operativeMRI

Engel Epilepsy Surgery Outcome Scale

Class 1: free of disabling seizures

Class 2: rare disabling seizures

Class 3: worthwhile improvement

Class 4: no worthwhile improvement

Patient Data

RO

RT

RF

Right ResectionsRO: 1 R Occipital (3)RT: 0 R TemporalRF: 0 R Frontal

LFLO

Left ResectionsLF: 3 L Frontal (1,1,1)LT: 8 L Temporal (4,3,3,2,2,1,1,1)LO: 1 L Occipital (2) LT

Predictions

• Worse surgery outcome correlates with a greater number of brain regions of:– high ReHo outside the resection zone• A previous study (Zeng et al. 2013) proposed that

increased ReHo regions compose a network that is responsible for seizure propagation and generation.

– low ALFF/fALFF outside the resection zone• Previous PET studies (Friedman et al. 1993) have

determined that areas of hypometabolism, which is correlated with decreases ALFF, may indicate epileptogenic regions.

Regional Homogeneity (ReHo)

Resection zone

Engel 2

Engel 1

• Measures the synchronization in local brain regions.

• Increased ReHo regions may compose a network of seizure generation and propagation

• Warm areas represent the regions of which the ReHo is greater relative to the contralateral side.

Amplitude of Low Frequency Fluctuations (ALFF)

• Reflects the intensity of fluctuations of regional spontaneous brain activity.

• Thought to correlate with brain metabolism.

• Low values of ALFF (blue-colored regions) may predict seizure areas.

Engel 2

Engel 3

• fALFF is the ALFF adjusted for artifacts, such as signals in the cerebral-spinal fluid where no such signal should exist.

• Low values of fALFF (blue regions) may predict seizure propagation areas.

Fractional Amplitude of Low Frequency Fluctuations (fALFF)

Engel 4

Engel 1

Results

0 1 2 3 4-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

R² = 0.00237658804926033

R² = 0.0230955290186914

R² = 0.106563976378547

Individual Asymmetry Values for Engel Outcome

REHO

ReHo

FALFF

FALFF

ALFF

ALFF

Engel Outcome

1 2 3 4-0.015

-0.01

-0.005

0

0.005

0.01

0.015

0.02

0.025

0.03Average Asymmetry Values for Engel Outcome

REHOFALFFALFF

Engel Outcome

• ReHo and fALFF relationships to Engel are the opposite of the predicted relationships– Suggests that a priori hypotheses were incorrect

• ALFF trendline slope is very minimal– Suggests that there is no clear relationship between epilepsy surgery

success (Engel Outcome) and the ALFF hypometabolism measure

Results Summary

Conclusions

• Insignificant results may be due to– Arbitrary threshold (|z|>1.65; p<0.05 )– Relatively small sample size

• Engel outcome may not rely purely on the number of ReHo or ALFF/fALFF areas outside of the resection zone that remain after surgery– The size of the resting-state abnormality within

the resected region may be important