**7. Multi-modality approaches**

The brain mapping techniques described above, both direct and indirect, can be combined, such that the information gained by their combination surpasses their advantages individually. The most beneficial combinations usually involve compensating for limitations of one technique with another, or concurrently measuring different aspects of the same response to better understand its physiological basis. For example, combined OISI-fMRI studies have also contributed to our knowledge of the etiology of these signals [101, 130- 131]. The recent development of a system that allows simultaneous fMRI and OIS spectroscopy [132] promises to further this endeavor. This combination has also been used to test the clinical utility of intraoperative human OISI for neurosurgical guidance by comparing intraoperative OISI maps with pre-surgical fMRI maps [101, 130-131].

## **8. Conclusions**

92 Advances in Brain Imaging

saying that they experience more scattering. To properly account for the optical pathlength

Mayhew and colleagues performed Monte Carlo simulations to calculate the distribution of differential pathlength factors in the visible spectrum [71]. Since then, several studies have incorporated wavelength dependency into the Beer-Lambert model to more accurately simulate the behavior of light transport through highly scattering biological tissue [28, 33, 114-115]. Their results have shown that accounting for wavelength dependency is critical,

In 1977 Jobsis showed that the intact human skull was not necessarily a barrier for light [116]. He found that wavelengths of light beyond the visible spectrum in the near-infrared range (~670-900 nm) can penetrate through several centimeters of skin and skull. This range is ideally situated between the strong absorption spectra of hemoglobin (<~630 nm) and water (>~950 nm), and has therefore been dubbed the "biological window" for noninvasive

NIRS is based on the same principles as visible range spectroscopy described above. Changes in light attenuation are fit to a modified Beer-Lambert law incorporating scattering and absorption by hemoglobin. The wavelength dependency of the pathlength must be taken into account. Differential pathlength factors can also be calculated using a Monte Carlo simulation, but another method exists in the case of NIRS. Pathlengths can be directly measured using time-resolved spectroscopy systems [113, 119]. These instruments have very fast (picosecond) detectors that are capable of measuring the time of flight of photons traveling through the head, which is directly related to the distance traveled. Alternatively, frequency domain systems can measure the phase difference between incident and remitted light [120-121].

The main difference between NIRS and visible spectroscopy is the way in which light is emitted and collected. Because the cortex is not exposed, light cannot illuminate the entire area. Instead, light is directed into the head through fiber optic guides and diffuses through the skin, skull, and cortex. A detector fiber guide is positioned a few centimeters from the emitter, and captures photons that have scattered through the head in an arc-shaped path from emitter to detector. The greater the distance between emitter and detector, the more likely it is that photons will travel through a deeper arc. On the other hand, a greater separation reduces the number of photons detected. Studies have theoretically and experimentally determined the optimal spacing (2.5-4 cm) to allow the photons to "sample" the top layers of cortex [122-123]. Because functional activation is not expected to produce changes in the skull or scalp, any differences in measured light intensity are attributed to

NIRS can be performed using broadband or laser illumination. The former situation is directly analogous to visible spectroscopy: remitted light is spectrally decomposed and captured by a camera. This approach affords excellent spectral resolution, but the emitted power per wavelength band is low. In contrast, laser diodes produce more power in a narrow wavelength band, but the number of wavelengths is limited to a few (2-4 in conventional systems), decreasing spectral resolution. Detectors for laser illumination are

cortical hemodynamic processes, i.e., changes in oxygenation or volume.

usually photodiodes, which are much more sensitive than CCDs.

and scattering, therefore, this dependency must be taken into account.

**6.1 Near-infrared spectroscopy (NIRS)** 

optical imaging [117-118].

especially when assessing small transients in the response such as the initial dip.

A central tenet in neurosurgery is avoidance of new postoperative neurological deficit. This goal is especially challenging when operating in or near "eloquent cortex", or regions subserving known specific functions, such as sensation, motor control, or language. Given individual neuroanatomical variations, eloquent regions must be delineated at the time of surgery, within the individual patient. The conventional method for identifying eloquent cortex intraoperatively is electrical stimulation mapping (ESM), during which regions of cortex are directly stimulated with a small electrical current using a hand-held probe. However, ESM has several limitations including limited spatial resolution, lengthy protocol time which places the patient at increased anesthesia and infection risk and increases costs, and a higher risk of seizure due to direct electrical stimulation of the cortex. Intraoperative OISI can provide maps of cortical function rapidly and without contacting the brain, therefore reducing operative time and seizure likelihood. These maps will be complementary to ESM for the localization of eloquent cortex. Furthermore, these maps can

Intraoperative Human Functional Brain Mapping Using Optical Intrinsic Signal Imaging 95

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also be used for basic research, including the fine-scale determination of the functional organization of the brain. Optical imaging thus presents a powerful new avenue for the advancement of clinical neurosurgery and neuroscience research.

Although intraoperative OISI has only been used for research purposes, it has significant potential as a clinical mapping tool as well. Although it is unlikely to replace ESM, it may, if used in conjunction with conventional intraoperative mapping techniques, decrease mapping time, provide high spatial resolution cortical maps, and allow mapping of multiple tasks.

#### **9. References**


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**6** 

*1,2,3Israel 4Spain 5USA*

**Functional Holography and Cliques** 

*1The Sackler School of Medicine, Tel Aviv University, Tel Aviv,* 

*3School of Physics and Astronomy, Tel Aviv University, Tel Aviv,* 

*Universidad Politécnica de Madrid, Pozuelo de Alarcón, Madrid,* 

*2Functional Brain Imaging Unit, Wohl Institute for Advanced Imaging,* 

Yael Jacob1,2,3, David Papo1,4, Talma Hendler1,2 and Eshel Ben-Jacob3,5

The brain is a complex spatially extended biological system, where a great number of neurons (~1011) interact to carry out extremely sophisticated tasks. Alongside a wellestablished tradition of studies of single neuron activity, a wealth of neuroimaging techniques has been developed where brain activity at various spatial scales is observed in

Early neuroimaging studies of brain activity mainly focused on the functional specialization of segregated brain modules. The main concern of these studies was that of finding which brain areas change their activity as subjects carry out well-controlled tasks. A robust statistical underpinning for the quantitative analysis of results was offered by the general linear model and Gaussian field theory (Worsley & Friston, 1995), which allowed delineating a collection of significant cortical *activations* and *deactivations* associated with the execution of these tasks. From a computational point of view, this general univariate

While the brain developed largely segregated modules, communication between and within these modules is essential to the transfer and processing of information. Accordingly, neuroimaging studies started incorporating the idea that the neural activity associated with the execution of given cognitive tasks is indeed diffuse, and that the influence that one brain region exerts over the others cannot be neglected. As a consequence, over the past few years, the neuroimaging literature has seen a shift towards a focus on measures of functional integration of brain activity. Many methods were developed to estimate functional and effective connectivity (Friston, 1994). These methods were designed to investigate how a

terms of multichannel recordings of the dynamics of its components.

framework treated the brain as a collection of independent brain regions.

**1. Introduction** 

**in Brain Activation Patterns** 

*Tel Aviv Sourasky Medical Center, Tel Aviv ,* 

*5The Center for Theoretical and Biological Physics, University of California San Diego, La Jolla, California* 

*4Center for Biomedical Technology,* 

