# Validation of intraoperative functional brain mapping based on color imaging with direct electrical brain stimulation

Charly Caredda, Thiébaud Picart, Jacques Guyotat, Bruno Montcel

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Charly Caredda, Thiébaud Picart, Jacques Guyotat, Bruno Montcel. Validation of intraoperative functional brain mapping based on color imaging with direct electrical brain stimulation. European Conference on Biomedical Optics, 2025, München, France. pp.M5A.4, 10.1364/ECBO.2025.M5A.4. hal-05385077

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# Validation of intraoperative functional brain mapping based on color imaging with direct electrical brain stimulation

Charly Caredda,<fnref n="1" />,* Thiébaud Picart,<fnref n="2" /> Jacques Guyotat<fnref n="1" />,<fnref n="2" /> and Bruno Montcel,<fnref n="1" />

**Abstract:** Non-invasive functional brain mapping is an imaging technique that allows the localization of functional areas of the patient's brain. This technique is used during brain tumor resection surgery to indicate to the neurosurgeon the cortical tissues which should not be removed without neurologic or cognitive impairment. In this study, we used intraoperative color imaging for the identification of the motor function. We evaluated the sensitivity and specificity of intraoperative optics identifications on 12 patients. These identifications were compared to electrical brain stimulation and showed a good correspondence. © 2025 The Author(s)

## 1. INTRODUCTION

Non-invasive functional brain mapping is an imaging technique that allows the localization of functional areas of the patient's brain. This technique is used during brain tumor resection surgery to indicate to the neurosurgeon the cortical tissues which should not be removed without neurologic or cognitive impairment. Functional magnetic resonance imaging (fMRI) [1] is the preoperative gold standard for identifying the patient's functional areas. During neurosurgery, the patient has undergone craniotomy to allow access to the cerebral cortex. The craniotomy induces a brain shift that invalidates the relevance of neuronavigation to localize functional areas during the surgical procedure [2]. During neurosurgery, electrical brain stimulation (EBS) is the gold standard for identifying brain functions, but this technique is mainly limited by its low spatial resolution (≈ 5 mm [3]) and has the potential risk to trigger epileptic seizures.

Optical imaging is an ideal complement to EBS, as it can be seamlessly integrated into the operating theatre using surgical microscopes. Color cameras of these microscopes can be used to monitor the brain activity with quantification of the concentration changes in oxy- and deoxygenated hemoglobin (*HbO₂* and *Hb*, respectively) in brain cortex [4,5]. The aim of this work is to evaluate the sensitivity and specificity of functional identifications obtained with color imaging against EBS, which is the intraoperative gold standard.

## 2. MATERIAL AND METHODS

The study was conducted at the neurological center of the Pierre Wertheimer hospital in Bron (France) during brain tumor resection operations. 12 patients presenting a tumor close to the motor cortex area were included in the study. The experiment was approved by the local ethics committee of Lyon University Hospital (France) and the participating patients signed written consent.

After the patient's craniotomy and before the brain tumor resection surgery, a video was acquired with a wide field optical device (BASLER acA2000-165uc, Leica M530 OHX surgical microscope or Zeiss Opmi Pentero 800). In all cases, the devices were composed of an RGB camera in conjunction with a continuous wave white light source. The white light source was illuminating the patient exposed cortex and the RGB camera was collecting the reflected light. The videos were acquired with successive periods of rest and motor stimulation that could be repeated over time. Motor cortex stimulation was performed by the patient or by an external person by repetitive, alternating hand opening and closing at ≈ 1 Hz. With the collected data, videos of concentration changes of oxygenated and deoxygenated hemoglobin (ΔC<sub>HbO₂</sub> and ΔC<sub>Hb</sub> in *M*) were calculated. Then, we applied statistical parametric mapping (SPM) [6] to calculate images of Z<sub>stats</sub> values that illustrate the correlation of measured contrasts with the patient's cortical hemodynamic response. Finally, binary images of the statistical

<footnote n="1">¹ Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1294, F69100, Lyon, France</footnote>

<footnote n="2">²Cranial Neurosurgical Department, Hospices Civils de Lyon, 69677 BRON, France - Lyon 1 University</footnote>

<footnote>*charly.caredda@creatis.insa-lyon.fr</footnote>
inferences (representing the delineation of the function) were calculated by thresholding the Z<sub>stats</sub> images. Two approaches were tested: (1) the random field theory [7]; (2) a manual thresholding: functional brain areas were identified as portions of patient's brain where the Z<sub>stats</sub> > μ(Z<sub>stats</sub> + 0.75σ(Z<sub>stats</sub>)). A detailed description of the processing pipeline can be found in Caredda et al., NeuroImage, 2023 [4].

After RGB imaging, the neurosurgeon performed direct electrical brain stimulation using a bipolar electrode (Nimbus Medtronic neurostimulator) to identify the eloquent cortex during the neurosurgery. When a functional area was identified by EBS, the neurosurgeon placed a colored tag on the patient cortex and an image was acquired to identify the position of the functional area in the RGB image. EBS was not performed on the entire cerebral cortex to avoid epileptic seizures. The surgeon stopped functional mapping when the epicenter of a function has been detected in a cerebral gyrus. For the motor cortex, the surgeon generally identifies three epicenters related to the hand and face, as well as the total negative motor area. The extent of the eloquent cortex was then manually delimited by the neurosurgeon using anatomical landmarks (sulci). With this procedure, a binary image representing the ground truth for the eloquent cortex was created. Binary images of functional activation obtained with RGB imaging were compared to the ground truth using sensitivity and specificity metrics [8]:

$$ 
\begin{aligned}
\text{Strict sensitivity} &= \frac{TP}{TP+FN} \\
\text{Specificity} &= \frac{TN}{TN+FP}
\end{aligned}
\qquad (1) $$

with TP the true positives (number of pixels for which the functional optics and the gold standard detected activated brain areas), FN the false negatives (number of pixels for which the ground truth detected activated brain areas but not functional optics), TN the true negatives (number of pixels for which the functional optics and the gold standard did not detect activated brain areas) and FP the false positives (number of pixels for which the functional optics detected activated brain areas but not the ground truth). A relaxed sensitivity metric was also established, where 100% indicates that a portion of brain function was identified, and 0% indicates that no brain function was identified.

### 3. RESULTS AND DISCUSSION

In Fig. 1, we represented the identification of the motor function obtained with direct electrical brain stimulation and intraoperative RGB imaging.

<figure><img src="image_2.png" /><figcaption>Fig. 1. Identification of the motor function using RGB imaging in the right hemisphere. (a) Contour of the motor (red) function delimited with electrical brain stimulation and anatomical landmarks. The white point indicated the location of the brain area tested with EBS. The terms "Anterior" and "Medial" are directional terms used to locate the surgical window in the brain anatomy. (b) Identification of the motor function using ΔC<sub>Hb</sub> contrasts calculated with intraoperative RGB imaging. The false colormap represents Z<sub>stats</sub> values calculated with SPM. The black and magenta contours indicates the extent of the brain function calculated with the random field theory and the manual thresholding procedure, respectively.</figcaption></figure>

The motor function was identified by optical imaging with a specificity of 99% and presented a good match with the ground truth. The strict sensitivity metrics calculated with identifications obtained with the random field theory and the manual thresholding procedure were 28.2% and 55.6%, respectively. In Table 1, we indicated the
sensitivity and specificity metrics of functional optics identifications calculated on 12 patients. Motor functions identified with optical imaging are detected with a strong specificity (≥ 94%) but low strict sensitivity (≤ 23.7%). This means that optical imaging has very few false positives, but that the extent of the functional maps covers only a small part of the cortex identified by the neurosurgeon.

The motor cortex is divided into several segments associated with movements of the face, hand or foot. In our study, the motor cortex was stimulated by a hand movement involving repetitive, alternating opening and closing of the hand. We can therefore assume that only a segment of the motor cortex was activated during the hand movement. This could explain why only a small part of the motor cortex was identified by optical imaging.

Although the strict sensitivity metric was low, the relaxed sensitivity was 100% for all patients, indicating that motor function was identified for all patients. Since optical functional identifications are obtained with high specificity, we propose to expand the functional identification masks over the entire gyrus detected, stopping at adjacent sulci. This would give a sensitivity close to 100%, while guaranteeing high specificity. The detection of the motor function with a great sensitivity is crucial. Indeed, motor function is known to be part of the "minimum common brain" which defines brain areas with low plasticity and compensatory capabilities [9]. It means that the motor cortex cannot be resected without inducing permanent deficit. In a future work, we plan to compare functional identifications obtained by intraoperative optical imaging and pre-operative fMRI with the use of an optics to MRI registration pipeline that we introduced in a companion paper entitled "Automated registration of intraoperative optical images with preoperative MRI".

<table><caption>Table 1. Sensitivity and specificity metrics of functional optics identifications calculated on 12 patients.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Strict sensitivity (%)</th><th colspan="2">Relaxed sensitivity (%)</th><th colspan="2">Specificity</th></tr><tr><th>SPM</th><th>Manual thresh.</th><th>SPM</th><th>Manual thresh.</th><th>SPM</th><th>Manual thresh.</th></tr></thead><tbody><tr><th>ΔC<sub>HbO<sub>2</sub></sub></th><td>7.2 ± 12.8</td><td>23.7 ± 14.7</td><td>100</td><td>100</td><td>99.3 ± 1.7</td><td>94.8 ± 3.8</td></tr><tr><th>ΔC<sub>Hb</sub></th><td>8.6 ± 13.5</td><td>23.3 ± 13.6</td><td>100</td><td>100</td><td>99.5 ± 1</td><td>95.4 ± 3.2</td></tr></tbody></table>

## Acknowledgments

These works were funded by the European Union's Horizon Europe research and innovation programme under grant agreement No 101071040 – project HyperProbe; LABEX PRIMES (ANR-11-LABX-0063) of Université de Lyon, within the program "Investissements d'Avenir" (ANR-11-IDEX-0007), operated by the French National Research Agency (ANR); Infrastructures d'Avenir en Biologie Santé (ANR-11-INBS-000), within the program "Investissements d'Avenir" operated by the French National Research Agency (ANR) and France Life Imaging (ANR-11-INBS-0006). This material is based upon work done on the ISO 9001:2015 PILoT facility.

## References

1. S. Ogawa et al. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. *Proceedings of the National Academy of Sciences*, 87(24):9868–9872, 12 1990.

2. Ian J. Gerard et al. Brain shift in neuronavigation of brain tumors: A review. *Medical Image Analysis*, 35:403–420, 1 2017.

3. J. Pallud et al. Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy. *Neurochirurgie*, 63(3):158–163, 6 2017.

4. Charly Caredda et al. Intraoperative identification of functional brain areas with rgb imaging using statistical parametric mapping: Simulation and clinical studies. *NeuroImage*, 278:120286, 2023.

5. Charly Caredda et al. Intraoperative quantitative functional brain mapping using an RGB camera. *Neurophotonics*, 6(4):045015, 2019.

6. K. J. Friston, editor. *Statistical parametric mapping: the analysis of functional brain images*. Elsevier/Academic Press, Amsterdam; Boston, 1st ed edition, 2007.

7. K. J. Friston, K. J. Worsley, R. S. J. Frackowiak, J. C. Mazziotta, and A. C. Evans. Assessing the significance of focal activations using their spatial extent. *Human Brain Mapping*, 1(3):210–220, 1994.

8. Rajul Parikh, Annie Mathai, Shefali Parikh, G Chandra Sekhar, and Ravi Thomas. Understanding and using sensitivity, specificity and predictive values. *Indian journal of ophthalmology*, 56(1):45, 2008.

9. Tamara Ius, Elsa Angelini, Michel Thiebaut de Schotten, Emmanuel Mandonnet, and Hugues Duffau. Evidence for potentials and limitations of brain plasticity using an atlas of functional resectability of who grade ii gliomas: Towards a “minimal common brain”. *NeuroImage*, 56(3):992–1000, 2011.