|
Research in the Functional Optical Imaging Lab is focused on the development of advanced in-vivo optical microscopy techniques
for functional imaging of tissues. An area of particular interest is applications to functional brain imaging. We seek to integrate
innovative photonics and computational techniques to understand basic neurophysiological mechanisms and to address clinically relevant
research questions in areas such as stroke, migraine, functional mapping during neurosurgery, and Alzheimer’s disease. Current research
projects inlude development of a system for imaging of brain function during neurosurgery, evaluation of drugs designed to
improve blood flow following stroke using laser speckle contrast imaging
Laser speckle contrast imaging (LSCI) is a simple and powerful technique for high resolution imaging of blood flow. This technique works
particularly well in the exposed cortex since the majority of the vasculature is near the surface. We have used laser speckle contrast
imaging to image blood flow changes in the cortex during a number of physiological conditions including stroke and migraine headache
models as well as functional activation of the normal brain. Laser speckle is a random interference pattern produced when coherent
light that has traveled different pathlengths is combined together on a detector such as a CCD camera. The blood flow in the cortex
alters the speckle pattern and as a result, the spatial variations in the raw speckle image are encoded with information about the blood flow.
The images below illustrate the concept of speckle contrast imaging. A 785 nm laser diode was expanded to illuminate a 6x4mm area of rat
cortex (skull removed, dura intact) and the area was imaged onto an CCD camera. The image below shows a single raw speckle image. Upon
careful inspection, some of the larger blood vessels can be seen in the raw speckle image. When the speckle contrast is computed using the
equation above, detailed spatial heterogeneities in blood flow are immediately visible.
The image below shows how we can use LSCI to image changes in flow during an induced stroke.
Two photon microscopy is ideally suited for 3 dimensional
functional imaging of the cortex in animal models. Because two photon absorption is confined to a very
small focal volume, very good axial resolution can be achieved with collection efficiency much greater
than that of confocal microscopy. Two photon microscopy also has the advantage that it uses long wavelength
excitation sources (700nm - 1000nm) that penetrate tissue much deeper than conventional flourescence microscopy.
|
 |
 |
Currently we are finalizing the construction and characterization of our microscope.
In addition to producing broad images of the vasculature in the brain as seen above, we have the capability of monitoring
individual vessels as seen on the left.
|
During many types of brain surgery, the surgeon must balance the tradeoff between sufficient resection of malignant tissue and
preservation of function such as motor, language or sensory function. Therefore intraoperative mapping of functional areas of the
cortex is essential. Two of the standard methods for intraoperative mapping are electrostimulation mapping (ESM) and pre-operative
fMRI. Although ESM provides real-time feedback to the surgeon, its spatial resolution is limited to approximately 1 cm. Pre-operative
fMRI on the other hand provides decent spatial resolution, but does not provide real-time feedback. In this project we are developing
a dual-CCD based optical imaging system capable of real-time, quantitative imaging of brain function during neurosurgery. This system
will image changes in cerebral blood flow, blood volume, hemoglobin oxygenation and oxygen metabolism by combining laser speckle
contrast imaging with multi-wavelength reflectance imaging.
|
