Robust Pre-Operative Language Mapping in Patients with

Brain Tumors: A Feasibility Study

Mohammad Fakhri, MD
Diagnostic Radiology Resident Physician, Research Track
Mallinckrodt Institute of Radiology at Washington University in St. Louis
Single Subject Language Mapping in Patients with Frontal
Lobe Brain Tumors: Mapping with a Supervised Classifier

Mohammad Fakhri, MD
Diagnostic Radiology Resident Physician, Research Track
Mallinckrodt Institute of Radiology at Washington University in St. Louis
Background
• Tumor in eloquent cortex: Maximize extent of resection with
minimal postoperative adverse outcomes.

• Task-fmri (tfMRI) Vs. Resting-State fMRI (rsfMRI).

• rsfMRI image analysis methods: Seed-based correlation,

Independent component analysis (ICA)
Challenges
•Where is the language system?

•Seed-based correlation is biased with a priori seed

•ICA is stochastic with run-to-run variability

•How many components to estimate? How to “label” results?

Cole DM, Front Syst Neurosci. 2010

Sair, HI, Neuroimaging Clin N Am. 2017
 • A supervised classifier (multi-layer
Proposed solution: perceptron; MLP) was trained to
A Trained Classifier associate blood oxygen level
dependent (BOLD) correlation
maps corresponding to pre-defined
seeds with specific RSN identities.

• Hard classification of maps

obtained from a priori seeds was
highly reliable across new
participants.

Hacker CD, Neuroimage, 2013

Aim
Objective comparison:
MLP Vs. standard seed-based correlation

Measure: Diagnostic value

Methods/Subjects
• Cases: 38 patients with a primary glial tumor in the left
frontal lobe
National Institutes of Health (NIH)–funded tumor database grant
(NIH 5R01NS066905).

• Controls: n=692,
Harvard-MGH Brain Genomics Superstruct Project , Yeo et al., 2011.
Methods/comparison
• Results from the two methods (MLP vs seed-based correlation)
were compared in expressive (Broca’s) language ROIs.

• Evaluation language masks: meta-analysis of 40 task-fMRI

language studies

• “Control” masks: spherical 10 mm radius ROIs in non-language

gray matter, lateral ventricle (CSF) and bilateral anterior corona
radiate (white matter)
Sample size/Null-hypothesis
• Sample size : anticipated values of the two ROCs, 0.6 and 0.85,
power of 80% and a 2-sided alpha value of 0.05: 29 patients.

• The null hypothesis for the ROC curve was defined as similar MLP
and Seed-correlation performance in distinguishing language ROIs
from the “Control ROI”.

• Variability of the language areas between the patients with left

frontal tumors and a large cohort of healthy subjects: modified
signed-likelihood ratio test.
Findings
Both seed-based correlation and the MLP
are able to successfully map the expressive
language area in all patients.

The LAN MLP score was found to be

significantly correlated to the correlation
coefficient from the seed-based
connectivity in all four evaluations masks
(p<0.001, Spearman correlation).
 Findings
The receiver operating curve analysis
demonstrates MLP’s performance to be
superior to that of the seed-based
correlation

MLP AUC=0.89,
Seed-correlation AUC: 0.62.
 How patients are
different?
The degree of variation between the two
groups is compared using Krishnamoorthy
and Lee’s modified signed-likelihood ratio
test.

Patients show more variability (P<0.001)

possibly due to their altered
anatomy/function.
What to learn?
• MLP-based language maps are comparable to the results obtained
using conventional seed-based correlation mapping.

• ROC analysis demonstrates better diagnostic value of a supervised

classifier to map expressive language areas in patients with primary
glial tumors in the left frontal lobe.
Limitations, how to proceed?
• The trained MLP is robust to anatomical shifts owing to mass
effects and focal, tumor-related neural dysfunction, hence, is
suitable for use in patients with brain tumors.

• Within the limitations of this study, the findings may have

important implications for clinical application.

• MLP is a promising tool to overcome challenges of rsfMRI in

presurgical language mapping.
• Thanks to NIH T32 TOP-TIER program directors awarded to
Mallinckrodt Institute of Radiology at Washington University
School of Medicine in St. Louis