Tuan M. Le

We have developed an epi-detected multimodal nonlinear optical microscopy platform based on a compact and cost-effective laser source featuring simultaneous acquisition of signals arising from hyperspectral coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence, and second harmonic generation. The laser source is based on an approach using a frequency-doubled distributed Bragg reflector-tapered diode laser to pump a femtosecond Ti:sapphire laser. The operational parameters of the laser source are set to the optimum trade-off between the spectral and temporal requirements for these three modalities, achieving sufficient spectral resolution for CARS in the lipid region. The experimental results on a biological tissue reveal that the combination of the epi-detection scheme and the use of a compact diode-pumped femtosecond solid-state laser in the nonlinear optical microscope is promising for biomedical applications in a clinical environment.

The implementation of multilayer optics for the compression and delivery of few-cycle femtosecond pulses will be discussed in the case of several cutting-edge applications.

In neurosurgery, the goal of any intracranial intervention is to provide accurate localization, diagnosis, and an appropriate treatment of intracranial abnormalities, while causing minimal damage to the intact brain. During open-skull surgery, the boundaries of some lesions, in particular some gliomas, as well as the presence and location of small brain tumors may be difficult to determine by means of visual inspection or microscopic imaging of the tissue surface. In the past a number of nonoptical imaging methods^{1 2 3 4 5 6 7 8 9} such as magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT) have been used to identify the margins of large brain tumors and to locate clusters of tumor cells positioned farther away. Although these imaging modalities enable noninvasive tumor diagnostics, they suffer from two major disadvantages: poor spatial resolution (hundreds of micrometers to a few millimeters), insufficient for resolving small brain tumors, and misalignment between the imaged and actual positions of the tumor due to tissue movement during surgery.¹⁰ Recently, there has been a constant demand for the development of noninvasive or minimally invasive optical imaging techniques that can be applied in neurosurgery as guiding tools and as an alternative to standard excisional biopsy. Imaging methods such as diffuse optical tomography, reflectance imaging, near-IR and Raman spectroscopy, fluorescence, and confocal microscopy^{11 12 13 14 15} have enabled visualization of single tumor cells as well as better delineation of brain tumor borders. Despite all these advantages, each of these imaging modalities possesses some inherent limitation related to image resolution, acquisition time, specificity, and accuracy of the acquired image/information, etc., which motivates the constant search for novel more precise and less invasive imaging modalities.

In recent years there has been a constant demand for development of noninvasive or minimally invasive imaging techniques that can be applied in neurosurgery as guiding tools and as an alternative to standard excisional biopsy. So far a vast variety of imaging methods^{1 2 3 4} ranging from magnetic resonance imaging (MRI) to optical microscopy have been used at different stages in the diagnostics, treatment, and postoperative monitoring of various neuropathologies. Despite all their advantages, each of these methods possesses some inherent limitation related to image resolution, acquisition time, specificity and accuracy of the acquired image or information, etc., which motivates the constant search for new more precise and less invasive imaging modalities.