In Vivo Dual-Modal Photoacoustic and Ultrasound Imaging of Sentinel Lymph Nodes Using a Solid-State Dye Laser System

Abstract

<jats:p>Photoacoustic imaging (PAI) is being actively investigated as a non-invasive and non-radioactive imaging technique for sentinel lymph node (SLN) biopsy. By taking advantage of optical and ultrasound imaging, PAI probes SLNs non-invasively with methylene blue (MB) in both live animals and breast cancer patients. However, these PAI systems have limitations for widespread use in clinics and commercial marketplaces because the lasers used by the PAI systems, e.g., tunable liquid dye laser systems and optical parametric oscillator (OPO) lasers, are bulky in size, not economical, and use risky flammable and toxic liquid dyes. To overcome these limitations, we are proposing a novel dual-modal photoacoustic and ultrasound imaging system based on a solid-state dye laser (SD-PAUSI), which is compact, convenient, and carries far less risk of flammability and toxicity. Using a solid-state dye handpiece that generates 650-nm wavelength, we successfully imaged the MB tube positioned deeply (~3.9 cm) in chicken breast tissue. The SLNs were also photoacoustically detected in the in vivo rats beneath a 2.2-cm-thick layer of chicken breast, which is deeper than the typical depth of SLNs in humans (1.2 ± 0.5 cm). Furthermore, we showed the multispectral capability of the PAI by switching the dye handpiece, in which the MB-dyed SLN was selectively highlighted from the surrounding vasculature. These results demonstrated the great potential of the SD-PAUSI as an easy but effective modality for SLN detection.</jats:p>

Nanotheranostics: Molecular Diagnostics and Nanotherapeutic Evaluation by Photoacoustic/Ultrasound Imaging in Small Animals

“…The rat sentinel lymph node stacked under a chicken breast layer of 2.2 cm thickness was imaged by PAI. Multispectral images were acquired at 532, 650, and 1064 nm wavelengths that specifically recognized vasculature, methylene blue-dyed sentinel lymph node and lymphatic vessel, and rib cage, respectively …”

“…Multispectral images were acquired at 532, 650, and 1064 nm wavelengths that specifically recognized vasculature, methylene blue-dyed sentinel lymph node and lymphatic vessel, and rib cage, respectively. 147 Early tissue damage was identified and tracked across various stages using PAI in the murine model. Laser-based PAI was used to assess the depth of injury and variations in the photoacoustic signal with excitation at 690 nm.…”

Recent Advances in Contrast-Enhanced Photoacoustic Imaging: Overcoming the Physical and Practical Challenges

“…Despite its relatively short history in biomedical imaging, PAI research has grown impressively quickly, motivated by its attractive features as a noninvasive, nonionizing, and multiparametric imaging modality. Like the generation of thunder by lightning, in PAI, temporally confined optical illumination on a target creates acoustic waves carrying information about the photothermal conversion efficiency (amplitude) and spatial geometry (frequency) of the target. ,,, Based on the characteristic optical absorption spectra of different molecules in the body, PAI describes the concentration and distribution of these molecules without using any ionizing energy or invasive procedures. − PAI can take advantage of either the optical or the acoustic focus, whichever provides better resolution, and thus its implementation is scalable in the optical ballistic regime (i.e., up to 1 mm depth in biological tissues) and beyond (in the optical diffusive regime). ,,− Analogous to the diagnostic synergy realized by combining positron emission tomography (PET) and computed tomography (CT) for functional and structural images, respectively, PAI adds molecular and functional information to US imaging while preserving high spatiotemporal resolution. − Its potential applications are rapidly expanding, particularly for imaging diseases in crucial organs, including (but not limited to) tumors, e.g., breast, − sentinel lymph node, − prostate, − …”

High-speed photoacoustic microscopy: A review dedicated on light sources

“…The PACT typically uses multi-element US transducers with various geometries such as linear [ [17] , [18] , [19] ], arc [ [20] , [21] , [22] ], hemisphere [ [23] , [24] , [25] ], or planar [ 26 ] array to obtain tomographic or cross-sectional images. The PACT systems take advantages of real-time imaging capability (typically 5–20 Hz) and deep imaging depth (up to ∼5 cm) and have been used for several clinical applications [ [27] , [28] , [29] , [30] , [31] , [32] , [33] ], such as breast [ [34] , [35] , [36] ], prostate [ [37] , [38] , [39] ], thyroid [ 40 , 41 ], and melanoma [ 42 , 43 ]. In addition to the human clinical applications, PACT systems also have been applied to small animal studies, including brain imaging [ 44 ], whole-body dynamics monitoring [ 45 ], and deep-tissue imaging [ 46 ].…”