Rapid multiexposure in vivo brain imaging system using vertical cavity surface emitting lasers as a light source.

We demonstrate an imaging technique implementing vertical cavity lasers with extremely low transient times for a greatly simplified realization of a multiexposure laser speckle contrast imaging system. Data from multiexposure laser speckle imaging was observed to more closely agree with absolute velocity measurements using time of flight technique, when compared to long-exposure laser speckle imaging. Furthermore, additional depth information of the vasculature morphology was inferred by accounting for the change in the static scattering from tissue above vessels with respect to the total scattering from blood flow and tissue.

Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor.

Molecular optical imaging is a widespread technique for interrogating molecular events in living subjects. However, current approaches preclude long-term, continuous measurements in awake, mobile subjects, a strategy crucial in several medical conditions. Consequently, we designed a novel, lightweight miniature biosensor for in vivo continuous optical sensing. The biosensor contains an enclosed vertical-cavity surface-emitting semiconductor laser and an adjacent pair of near-infrared optically filtered detectors. We employed two sensors (dual sensing) to simultaneously interrogate normal and diseased tumor sites. Having established the sensors are precise with phantom and in vivo studies, we performed dual, continuous sensing in tumor (human glioblastoma cells) bearing mice using the targeted molecular probe cRGD-Cy5.5, which targets αVß3 cell surface integrins in both tumor neovasculature and tumor. The sensors capture the dynamic time-activity curve of the targeted molecular probe. The average tumor to background ratio after signal calibration for cRGD-Cy5.5 injection is approximately 2.43±0.95 at 1 h and 3.64±1.38 at 2 h (N=5 mice), consistent with data obtained with a cooled charge coupled device camera. We conclude that our novel, portable, precise biosensor can be used to evaluate both kinetics and steady state levels of molecular probes in various disease applications.

Rapid monitoring of cerebral ischemia dynamics using laser-based optical imaging of blood oxygenation and flow.

Imaging blood flow or oxygenation changes using optical techniques is useful for monitoring cortical activity in healthy subjects as well as in diseased states such as stroke or epilepsy. However, in order to gain a better understanding of hemodynamics in conscious, freely moving animals, these techniques must be implemented in a small scale, portable design that is adaptable to a wearable format. We demonstrate a novel system which combines the two techniques of laser speckle contrast imaging and intrinsic optical signal imaging simultaneously, using compact laser sources, to monitor induced cortical ischemia in a full field format with high temporal acquisition rates. We further demonstrate the advantages of using combined measurements of speckle contrast and oxygenation to establish absolute flow velocities, as well as to statistically distinguish between veins and arteries. We accomplish this system using coherence reduction techniques applied to Vertical Cavity Surface Emitting Lasers (VCSELs) operating at 680, 795 and 850 nm. This system uses minimal optical components and can easily be adapted into a portable format for continuous monitoring of cortical hemodynamics.

Multi-modality optical neural imaging using coherence control of VCSELs.

Neural optical imaging can evaluate cortical hemodynamic fluctuations which reflect neural activity and disease state. We evaluate the use of vertical-cavity surface-emitting lasers (VCSELs) as illumination source for simultaneous imaging of blood flow and tissue oxygenation dynamics ex vivo and in vivo and demonstrate optical imaging of blood flow changes and oxygenation changes in response to induced ischemia. Using VCSELs we show a rapid switching from a single-mode to a special multi-mode rapid current sweep operation and noise values reduced to within a factor of 40% compared to non-coherent LED illumination. These VCSELs are promising for long-term portable continuous monitoring of brain dynamics in freely moving animals.