Technology Development

Multi-spectral PAM

We have developed a novel optical-acoustic microscope objective by integrating a customized high-frequency ultrasonic transducer and a commercial reflective optical objective (also known as Schwarzschild objective). Capitalizing on the consistent performance of this objective over the ultraviolet, visible and near-infrared range, our multispectral PAM has enabled label-free concurrent imaging of cell nucleus (DNA/RNA contrast at 270 nm), blood vessel (hemoglobin contrast at 532 and 558 nm) and sebaceous gland (lipid contrast at 1210 nm) at the same spatiotemporal scale in vivo.

Reference:

R. Cao, J. P. Kilroy, B. Ning, T. Wang, J. A. Hossack, and S. Hu, “Multispectral photoacoustic microscopy based on an optical-acoustic objective,” Photoacoustics, 3(2), 55-59 (2015)


Multi-parametric PAM

We have developed a set of novel algorithms for statistical, spectral, and correlation analysis of the same dataset acquired by PAM, enabling simultaneous quantification of the total concentration of hemoglobin (CHb), oxygen saturation of hemoglobin (sO2), and cerebral blood flow (CBF) at the microscopic level in vivo.

Reference:

B. Ning, M. J. Kennedy, A. J. Dixon, N. Sun, R. Cao, B. T. Soetikno, R. Chen, Q. Zhou, K. K. Shung, J. A. Hossack, and S. Hu, “Simultaneous photoacoustic microscopy of microvascular anatomy, oxygen saturation, and blood flow,” Optics Letters, 40(6), 910-913 (2015).


All-optical PAM

Capitalizing on the effect of surface plasmon resonance (SPR) for optical detection of ultrasound, we have developed a novel implementation of all-optical PAM. The SPR sensor in our all-optical PAM shows a linear response to the acoustic pressure from 5.2 kPa to 2.1 MPa, an ultra-flat frequency response (±0.7 dB) from 680 kHz to 126 MHz, and a noise-equivalent pressure sensitivity of 3.3 kPa. With the broadband ultrasonic detection, our SPR-PAM has achieved high spatial resolution with relatively low anisotropy (2.0 µm laterally and 8.4 µm axially).

Reference:

T. Wang, R. Cao, B. Ning, A. J. Dixon, J. A. Hossack, A. L. Klibanov, Q. Zhou, A. Wang and S. Hu, “All-optical photoacoustic microscopy based on plasmonic detection of broadband ultrasound,” Applied Physics Letters. 107, 153702 (2015)


Ultrahigh-speed PAM

Capitalizing on a self-developed high-repetition dual-wavelength Raman fiber laser and an optical-mechanical hybrid-scan configuration, we have developed a new generation of multi-parametric PAM with an unprecedented A-line rate of 300 kHz. This technical innovation has led to a 20-fold increase in the imaging speed over our first-generation multi-parametric PAM, which is based on pure mechanical scanning.

Reference:

T. Wang, N. Sun, R. Cao, B. Ning, R. Chen, Q. Zhou, and S. Hu, “Multi-parametric photoacoustic microscopy of the mouse brain with 300-kHz A-line rate”, Neurophotonics, 3(4), 045006 (2016).

Brain Imaging

Ultrasound-guided Multi-parametric PAM of the Mouse Brain

The three-dimensional skull and vascular anatomies delineated by the dual-contrast (i.e., ultrasonic and photoacoustic) system provide important guidance for dynamically focused contour scan and vessel orientation-dependent correction of CBF, respectively. Moreover, bi-directional raster scan allows determining the direction of blood flow in individual vessels. Capable of imaging CHb, sO2 and CBF at the same spatiotemporal scale, our ultrasound-aided PAM fills a critical gap in preclinical neuroimaging and lays the foundation for high-resolution mapping of the cerebral metabolic rate of oxygen (CMRO2), a quantitative index of cerebral oxygen metabolism.

Reference:

B. Ning, N. Sun, R. Cao, R. Chen, K. K. Shung, J. A. Hossack, J.-M. Lee, Q. Zhou, and S. Hu, “Ultrasound-aided multi-parametric photoacoustic microscopy of the mouse Brain,” Scientific Reports, 5, 18775 (2015).


Multi-parametric PAM of the Awake Mouse Brain

A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. We have developed first-of-a-kind head-restrained PAM, which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice.

Reference:

R. Cao, J. Li, B. Ning, N. Sun, T. Wang, Z. Zuo, and S. Hu, “Functional and Oxygen-metabolic Photoacoustic Microscopy of the Awake Mouse Brain”, NeuroImage, 150, 77-87 (2017).


Hemodynamic and Oxygen-metabolic Dysfunctions in Brain Disorders

We have been applying our pioneering multi-parametric PAM technology to study the dysfunction of cerebral hemodynamics and oxygen metabolism in multiple devastating brain disorders, including ischemic stroke, Alzheimer’s disease, traumatic brain injury, and epilepsy.

Reference:

R. Cao, J. Li, C. Zhang, Z. Zuo, S. Hu. “Photoacoustic microscopy of obesity-induced cerebrovascular alterations,” NeuroImage, 188:369-379 (2019).

Cardiovascular Imaging

Vascular remodeling

We have been applying our pioneering multi-parametric PAM technology to study both angiogenesis and arteriogenesis in the context of ischemia, would healing, obesity, and diabetes.

Reference:

B. DeGeorge Jr., B. Ning, L. Salopek, A. Pineros-Fernandez, G. Rodeheaver, S. Peirce-Cottler, S. Hu, P. Cottler, C. Campbell, “Advanced imaging techniques for the investigation of acellular dermal matrix biointegration”, Plastic and Reconstructive Surgery, 139(2), 395-405 (2017).

Cancer Imaging

Metabolic Reprogramming

We are integrating multi-parametric PAM and multiphoton fluorescence lifetime imaging microscopy to study metabolic reprogramming, the shift from oxidative to glycolytic metabolism, in cancer.

Research Sponsors

CAREER: Transforming Multi-parametric Photoacoustic Microscopy

R01 NS099261: Photoacoustic Microscopy of the Awake Mouse Brain

R01 AG067048: Nutrient-induced Mitochondrial Activity (NIMA): A Novel Lysosome to Mitochondria Signaling Pathway, Its Mechanisms and Role in Alzheimer’s Disease

R01 NS099118: Obesity-induced Cerebral Vascular Remodeling and Poor Brain Ischemic Tolerance

Single-Cell Photoacoustic Molecular Imaging at Centimeter Depth

Reversibility of Amyloid-induced Mitochondrial Dysfunction in Alzheimer’s Disease