KEYWORDS: Brain, Tissue optics, Diffuse reflectance spectroscopy, Epilepsy, Data analysis, Tissues, Tumors, Control systems, Statistical analysis, In vivo imaging
This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate
pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic
optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional
characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was
hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic
behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited
for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent
diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light
source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a
rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically
abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data
analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each
investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the
two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred
to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative
correlation time indices from all investigated sites were sub-grouped according to the corresponding histological
classifications. The difference between the mean indices of two subgroups was evaluated by standard t-test. These
comparison and calculation procedures were carried out for all possible wavelength combinations between 400 nm and
800 nm with 2 nm increments. The positive group consisted of seven pathologically abnormal test sites, and the negative
group consisted of 13 normal test sites from non-epileptic tumor patients. A standard t-test showed significant difference
between negative correlation time indices from the two groups at the wavelength combinations of 700-760 nm versus
550-580 nm. An empirical discrimination algorithm based on the negative correlation time indices in this range produced
100% sensitivity and 85% specificity. Based on these results time-dependent diffuse reflectance spectroscopy with
optimized data analysis methods differentiates epileptic brain tissue from normal brain tissue adequately, therefore can
be utilized for surgical guidance, and may enhance the surgical outcome of pediatric epilepsy surgery.
Optical spectroscopy for in vivo tissue diagnosis is performed traditionally in a static manner; a snap shot of the tissue
biochemical and morphological characteristics is captured through the interaction between light and the tissue. This
approach does not capture the dynamic nature of a living organ, which is critical to the studies of brain disorders such as
epilepsy. Therefore, a time-dependent diffuse reflectance spectroscopy system with a fiber-optic probe was designed
and developed. The system was designed to acquire broadband diffuse reflectance spectra (240 ~ 932 nm) at an
acquisition rate of 33 Hz. The broadband spectral acquisition feature allows simultaneous monitoring of various
physiological characteristics of tissues. The utility of such a system in guiding pediatric epilepsy surgery was tested in a
pilot clinical study including 13 epilepsy patients and seven brain tumor patients. The control patients were children
undergoing suregery for brain tumors in which measurements were taken from normal brain exposed during the surgery.
Diffuse reflectance spectra were acquired for 12 seconds from various parts of the brain of the patients during surgery.
Recorded spectra were processed and analyzed in both spectral and time domains to gain insights into the dynamic
changes in, for example, hemodynamics of the investigated brain tissue. One finding from this pilot study is that
unsynchronized alterations in local blood oxygenation and local blood volume were observed in epileptogenic cortex.
These study results suggest the advantage of using a time-dependent diffuse reflectance spectroscopy system to study
epileptogenic brain in vivo.
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