Hyperspectral absorption microscopy using photoacoustic remote sensing.

An improved method of remote optical absorption spectroscopy and hyperspectral optical absorption imaging is described which takes advantage of the photoacoustic remote sensing detection architecture. A wide collection of photoacoustic excitation wavelengths ranging from 210 nm to 1550 nm was provided by a nanosecond tunable source allowing access to various salient endogenous chromophores such as DNA, hemeproteins, and lipids. Sensitivity of the device was demonstrated by characterizing the infrared absorption spectrum of water. Meanwhile, the efficacy of the technique was explored by recovering cell nuclei and oxygen saturation from a live chicken embryo model and by recovering adipocytes from freshly resected murine adipose tissue. This represents a continued investigation into the characteristics of the hyperspectral photoacoustic remote sensing technique which may represent an effective means of non-destructive endogenous contrast characterization and visualization.

Functional photoacoustic remote sensing microscopy using a stabilized temperature-regulated stimulated Raman scattering light source.

Stimulated Raman scattering (SRS) has been widely used in functional photoacoustic microscopy to generate multiwavelength light and target multiple chromophores inside tissues. Despite offering a simple, cost-effective technique with a high pulse repetition rate; it suffers from pulse-to-pulse intensity fluctuations and power drift that can affect image quality. Here, we propose a new technique to improve the temporal stability of the pulsed SRS multiwavelength source. We achieve this by lowering the temperature of the SRS medium. The results suggest that a decrease in temperature causes an improvement of temporal stability of the output, considerable rise in the intensity of the SRS peaks, and significant increase of SRS cross section. The application of the method is shown for in vivo functional imaging of capillary networks in a chicken embryo chorioallantois membrane using photoacoustic remote sensing microscopy.

Label-free, non-contact, in vivo ophthalmic imaging using photoacoustic remote sensing microscopy.

We present, to the best of our knowledge, the first label-free, non-contact, in vivo imaging of the ocular vasculature using photoacoustic remote sensing (PARS) microscopy. Both anterior and posterior segments of a mouse eye were imaged. Vasculature of the iris, sclera, and retina tissues were clearly resolved. To the best of our knowledge, this is the first study showing non-contact photoacoustic imaging conducted on in vivo ocular tissue. We believe that PARS microscopy has the potential to advance the diagnosis and treatment of ocular diseases.

Functional and structural ophthalmic imaging using noncontact multimodal photoacoustic remote sensing microscopy and optical coherence tomography.

Early diagnosis of ocular diseases improves the understanding of pathophysiology and aids in accurate monitoring and effective treatment. Advanced, multimodal ocular imaging platforms play a crucial role in visualization of ocular components and provide clinicians with a valuable tool for evaluating various eye diseases. Here, for the first time we present a non-contact, multiwavelength photoacoustic remote sensing (PARS) microscopy and swept-source optical coherence tomography (SS-OCT) for in-vivo functional and structural imaging of the eye. The system provides complementary imaging contrasts of optical absorption and optical scattering, and is used for simultaneous, non-contact, in-vivo imaging of murine eye. Results of vasculature and structural imaging as well as melanin content in the retinal pigment epithelium layer are presented. Multiwavelength PARS microscopy using Stimulated Raman scattering is applied to enable in-vivo, non-contact oxygen saturation estimation in the ocular tissue. The reported work may be a major step towards clinical translation of ophthalmic technologies and has the potential to advance the diagnosis and treatment of ocular diseases.

Partial inhibition of mitochondrial complex I ameliorates Alzheimer's disease pathology and cognition in APP/PS1 female mice.

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder without a cure. Here we show that mitochondrial respiratory chain complex I is an important small molecule druggable target in AD. Partial inhibition of complex I triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection in symptomatic APP/PS1 female mice, a translational model of AD. Treatment of symptomatic APP/PS1 mice with complex I inhibitor improved energy homeostasis, synaptic activity, long-term potentiation, dendritic spine maturation, cognitive function and proteostasis, and reduced oxidative stress and inflammation in brain and periphery, ultimately blocking the ongoing neurodegeneration. Therapeutic efficacy in vivo was monitored using translational biomarkers FDG-PET, 31P NMR, and metabolomics. Cross-validation of the mouse and the human transcriptomic data from the NIH Accelerating Medicines Partnership-AD database demonstrated that pathways improved by the treatment in APP/PS1 mice, including the immune system response and neurotransmission, represent mechanisms essential for therapeutic efficacy in AD patients.