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Else TR et al., J Biomed Opt. 2024 Jan;29(Suppl 1):S11506.

Clinical

MSOT

Other applications

Integumentary

Melanin, Hemglobin

Anatomical

Significance: Photoacoustic imaging (PAI) provides contrast based on the concentration of optical absorbers in tissue, enabling the assessment of functional physiological parameters such as blood oxygen saturation (sO2). Recent evidence suggests that variation in melanin levels in the epidermis leads to measurement biases in optical technologies, which could potentially limit the application of these biomarkers in diverse populations.
Aim: To examine the effects of skin melanin pigmentation on PAI and oximetry.
Approach: We evaluated the effects of skin tone in PAI using a computational skin model, two-layer melanin-containing tissue-mimicking phantoms, and mice of a consistent genetic background with varying pigmentations. The computational skin model was validated by simulating the diffuse reflectance spectrum using the adding-doubling method, allowing us to assign our simulation parameters to approximate Fitzpatrick skin types. Monte Carlo simulations and acoustic simulations were run to obtain idealized photoacoustic images of our skin model. Photoacoustic images of the phantoms and mice were acquired using a commercial instrument. Reconstructed images were processed with linear spectral unmixing to estimate blood oxygenation. Linear unmixing results were compared with a learned unmixing approach based on gradient-boosted regression.
Results: Our computational skin model was consistent with representative literature for in vivo skin reflectance measurements. We observed consistent spectral coloring effects across all model systems, with an overestimation of sO2 and more image artifacts observed with increasing melanin concentration. The learned unmixing approach reduced the measurement bias, but predictions made at lower blood sO2 still suffered from a skin tone-dependent effect.
Conclusion: PAI demonstrates measurement bias, including an overestimation of blood sO2, in higher Fitzpatrick skin types. Future research should aim to characterize this effect in humans to ensure equitable application of the technology.

Preclinical

MSOT

Cancer

Digestive

Nanoparticle

Molecular

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.

Clinical

RSOM

Ischemia, Metabolic disease

Integumentary

Hemoglobin

Functional

Skin microangiopathy has been associated with diabetes. Here we show that skin-microangiopathy phenotypes in humans can be correlated with diabetes stage via morphophysiological cutaneous features extracted from raster-scan optoacoustic mesoscopy (RSOM) images of skin on the leg. We obtained 199 RSOM images from 115 participants (40 healthy and 75 with diabetes), and used machine learning to segment skin layers and microvasculature to identify clinically explainable features pertaining to different depths and scales of detail that provided the highest predictive power. Features in the dermal layer at the scale of detail of 0.1-1 mm (such as the number of junction-to-junction branches) were highly sensitive to diabetes stage. A ‘microangiopathy score’ compiling the 32 most-relevant features predicted the presence of diabetes with an area under the receiver operating characteristic curve of 0.84. The analysis of morphophysiological cutaneous features via RSOM may allow for the discovery of diabetes biomarkers in the skin and for the monitoring of diabetes status.

Clinical

MSOT

Ischemia, Cardiovascular

Musculoskeletal

Hemoglobin

Functional

Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.

Preclinical

MSOT

Cancer

Reproductive

Nanoparticle

Molecular

Multifunctional phototheranostics, employing precise and non-invasive techniques, is widely developed to enhance theranostic efficiency of breast cancer (BC), reduce side-effects, and improve quality of life. Integrating all phototheranostic modalities into a single photosensitizer for highly effective BC treatment is particularly challenging due to the potential inefficiency and time consumption associated with repeated switching of multiple-wavelength lasers. Herein, a novel single NIR-II laser-triggered three-in-one nanosystem(PdCu NY) is rationally designed, which enables dual-modal (NIR-II FL/NIR-II PA) imaging-guided self-enhancing photothermal-photodynamic therapy (PTT-PDT) in NIR-II window. The PdCu NY based on optimal Pd/Cu molar-ratio(1:11) can be easily fabricated and large-scale production for simultaneous PTT-PDT against BC under a single 1064nm laser irradiation. Significantly, the PdCu NY acted as a promising photocatalyst for decomposition of H2 O into O2 upon the same laser irradiation. In addition, the inherent catalase (CAT)-like activity of PdCu NYs enables photo-enzyme dual-catalytic O2 supply to effectively alleviate hypoxia, achieving self-enhanced PDT efficiency. These PTT-PDT self-enhanced nanosystems demonstrate precise lesion localization and complete tumor ablation using a single 1064nm laser source by “one-laser, multi-functions” strategy. More importantly, this study not only reports a three-in-one PdCu-based phototheranostic agent, but also sheds light on the exploration of versatile biosafety nanosystems for clinical applications.

Preclinical

MSOT

Other Applications

Cylindrical organs, e.g., blood vessels, airways, and intestines, are ubiquitous structures in biomedical optical imaging analysis. Image segmentation of these structures serves as a vital step in tissue physiology analysis. Traditional model-driven segmentation methods seek to fit the structure by constructing a corresponding topological geometry based on domain knowledge. Classification-based deep learning methods neglect the geometric features of the cylindrical structure and therefore cannot ensure the continuity of the segmentation surface. In this paper, by treating the cylindrical structures as a 3D graph, we introduce a novel contour-based graph neural network for 3D cylindrical structure segmentation in biomedical optical imaging. Our proposed method, which we named CylinGCN, adopts a novel learnable framework that extracts semantic features and complex topological relationships in the 3D volumetric data to achieve continuous and effective 3D segmentation. Our CylinGCN consists of a multiscale 3D semantic feature extractor for extracting inter-frame multiscale semantic features, and a residual graph convolutional network (GCN) contour generator that combines the semantic features and cylindrical topological priors to generate segmentation contours. We tested the CylinGCN framework on two types of optical tomographic imaging data, small animal whole body photoacoustic tomography (PAT) and endoscopic airway optical coherence tomography (OCT), and the results show that CylinGCN achieves state-of-the-art performance. Code will be released at https://github.com/lzc-smu/CylinGCN.git.

Wu ZH et al., J Am Chem Soc. 2023 Dec 6;145(48):26487-26493.

Preclinical

MSOT

Cancer

Digestive, Reproductive, Integumentary

Nanoparticle

Molecular

A terrylenedicarboximide-anthraquinone dyad, FTQ, with absorption in the second near-infrared region (NIR-II) is obtained as a high-performance chromophore for photothermal therapy (PTT). The synthetic route proceeds by C-N coupling of amino-substituted terrylenedicarboximide (TMI) and 1,4-dichloroanthraquinone followed by alkaline-promoted dehydrocyclization. FTQ with extended π-conjugation exhibits an optical absorption band peaking at 1140 nm and extending into the 1500 nm range. Moreover, as determined by dielectric spectroscopy in dilute solutions, FTQ achieves an ultrastrong dipole moment of 14.4 ± 0.4 Debye due to intense intramolecular charge transfer. After encapsulation in a biodegradable polyethylene glycol (DSPE-mPEG2000), FTQ nanoparticles (NPs) deliver a high photothermal conversion efficiency of 49% under 1064 nm laser irradiation combined with excellent biocompatibility, photostability, and photoacoustic imaging capability. In vitro and in vivo studies reveal the great potential of FTQ NPs in photoacoustic-imaging-guided photothermal therapy for orthotopic liver cancer treatment in the NIR-II window.

Preclinical

MSOT

Cancer

Reproductive

Nanoparticle

Molecular

For the integration of targeted diagnosis and treatment of tumor, we innovatively designed and synthesized a single-molecule hetero-multinuclear Er(III)-Cu(II) complex (ErCu2) and then constructed an ErCu2@apoferritin (AFt) nanoparticle (NP) delivery system. ErCu2 and ErCu2@AFt NPs not only provided an evident photoacoustic imaging (PAI) signal of the tumor but also effectively inhibited tumor growth by integrating photothermal therapy, chemotherapy, and immunotherapy. ErCu2@AFt NPs improved the targeting ability and decreased the systemic toxicity of ErCu2 in vivo. Furthermore, we confirmed that ErCu2 and ErCu2@AFt NPs inhibited tumor growth by inducing apoptosis and autophagy of tumor cells and activating the immune system. The study not only provides a novel strategy to develop therapeutic metal agents but also reveals their potential for targeted accurate diagnosis and multimodality therapy of cancer.