Small-animal whole-body photoacoustic tomography

Multi-spectral optoacoustic tomography (MSOT) is an imaging technology that generates high-resolution optical images in scattering media, including biological tissues. MSOT illuminates tissue with light of transient energy, typically light pulses lasting 1-100 nanoseconds.

The tissue absorbs the light pulses, and as a result undergoes thermo-elastic expansion, a phenomenon known as the optoacoustic or photoacoustic effect. This expansion gives rise to ultrasound waves (photoechoes) that are detected and formed into an image. Image formation can be done by means of hardware (e.g. acoustic focusing or optical focusing) or computed tomography (mathematical image formation). Unlike other types of optoacoustic imaging, MSOT involves illuminating the sample with multiple wavelengths, allowing it to detect ultrasound waves emitted by different photoabsorbing molecules in the tissue, whether endogenous (oxygenated and deoxygenated hemoglobin, melanin) or exogenous (imaging probes, nanoparticles).

Computational techniques such as spectral unmixing deconvolute the ultrasound waves emitted by these different absorbers, allowing each emitter to be visualized separately in the target tissue. In this way, MSOT can allow visualization of hemoglobin concentration and tissue oxygenation or hypoxia. Unlike other optical imaging methods, MSOT is unaffected by photon scattering and thus can provide high-resolution optical images deep inside biological tissues.

With the wide use of small animals for biomedical studies, in vivo small-animal whole-body imaging plays an increasingly important role. Photoacoustic tomography (PAT) is an emerging whole-body imaging modality that shows great potential for preclinical research. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous tissue chromophores, such as oxy-hemoglobin and deoxy-hemoglobin, or exogenous contrast agents. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Using near-infrared light, which has relatively low blood absorption, PAT can image through the whole body of small animals with acoustically defined spatial resolution. Anatomical and vascular structures are imaged with endogenous hemoglobin contrast, while functional and molecular images are enabled by the wide choice of exogenous optical contrasts. This paper reviews the rapidly growing field of small-animal whole-body PAT and highlights studies done in the past decade.

Researchers working at Duke University and Washington University in St. Louis developed a new photoacoustic technique called single-impulse photoacoustic computed tomography (SIP-PACT) that provides an amazing high resolution look inside small living animals such as mice. Photoacoustic imaging involves shining a laser light into tissue, which gene

Image result for Full Body Optoacoustic Functional Imaging of Small

Small Animals, especially mice, are widely used in biomedical research for studying and modeling the progression of human diseases and the response to potential therapies. During the past thirty years, there has been an exponential increase in the number of scientific publications on small-animal models . Compared with slicing and staining numerous sacrificed animals at multiple time points, in vivo whole-body imaging allows researchers to follow biological processes and disease progression more accurately . In response, many clinical whole-body imaging modalities, such as magnetic resonance imaging (MRI), positron electron tomography (PET), and X-ray computed tomography (CT), have evolved preclinical counterparts with higher spatial resolution. However, these techniques have their own limitations on small-animal research. For instance, micro MRI requires a costly high magnetic field to achieve high spatial resolution and suffers from slow data acquisition; micro X-ray CT and PET utilize ionizing radiation, which may confound longitudinal observations; and ultrasound biomicroscopy (UBM) [5] has low acoustic-impedance contrast among soft tissues. Pure optical imaging modalities have also been widely used in small-animal whole-body research; however, they are afflicted with either limited penetration depth, requiring slicing sacrificed animals, or very poor spatial resolution (>1 mm) [7].

Recently, there has been increasing interest in whole-body photoacoustic tomography (PAT). PAT utilizes non-ionizing laser illumination to generate an internal temperature rise, which is subsequently converted to pressure via thermoelastic expansion. The pressure waves are detected by ultrasonic transducers, and the temporal signals are reconstructed to form an image of the optical absorbers. The conversion to acoustic waves enables photoacoustic tomography to generate high-resolution images in both the optically ballistic and diffusive regimes . Combining endogenous and exogenous contrasts, PAT can provide anatomical, functional, and molecular assessments in a single modality. Anatomical structures can be imaged based on endogenous hemoglobin contrast. Hemoglobin can also serve as a functional contrast for imaging hemoglobin oxygen saturation (sO2), speed of blood flow, and metabolic rate of oxygen. Molecular imaging is enabled by the broad choice of labeling dyes, nanoparticles , and proteins . These unique advantages position whole-body PAT to make a broad impact in preclinical medical research and life sciences.

Over the past few years, several small-animal whole-body PAT systems, employing different light illumination and detection schemes, have been developed. In this paper, we review different photoacoustic whole-body imaging techniques and highlight studies done in the past decade. While whole-body imaging includes both brain and trunk imaging, this review focuses on trunk imaging. Recent reviews on photoacoustic brain imaging can be found in references . Nevertheless, most of the systems discussed in this review can image the brain with little or no modifications.

Credit: Duke University

Washington University

National Library of Meicine

 

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