Spectroscopic photoacoustic imaging of cervical tissue composition in excised human samples

Abstract

Objective Cervical remodeling is an important component in determining the pathway of parturition; therefore, assessing changes in cervical tissue composition may provide information about the cervix’s status beyond the measurement of cervical length. Photoacoustic imaging is a non-invasive ultrasound-based technology that captures acoustic signals emitted by tissue components in response to laser pulses. This optical information allows for the determination of the collagen-to-water ratio (CWR). The purpose of this study was to compare the CWR evaluated by using spectroscopic photoacoustic (sPA) imaging in cervical samples obtained from pregnant and non-pregnant women. Methods This cross-sectional study comprised cervical biopsies obtained at the time of hysterectomy (n = 8) and at the scheduled cesarean delivery in pregnant women at term who were not in labor (n = 8). The cervical CWR was analyzed using a fiber-optic light-delivery system integrated to an ultrasound probe. The photoacoustic signals were acquired within the range of wavelengths that cover the peak absorption of collagen and water. Differences in the CWR between cervical samples from pregnant and non-pregnant women were analyzed. Hematoxylin and eosin and Sirius Red stains were used to compare the collagen content of cervical samples in these two groups. Results Eight cervix samples were obtained after hysterectomy, four from women ≤41 years of age and four from women ≥43 years of age; all cervical samples (n = 8) from pregnant women were obtained after 37 weeks of gestation at the time of cesarean section. The average CWR in cervical tissue samples from pregnant women was 18.7% (SD 7.5%), while in samples from non-pregnant women, it was 55.0% (SD 20.3%). There was a significantly higher CWR in the non-pregnant group compared to the pregnant group with a p-value <0.001. A subgroup analysis that compared the CWR in cervical samples from pregnant women and non-pregnant women ≤41 years of age (mean 46.3%, SD 23.1%) also showed a significantly higher CWR (p <0.01). Lower collagen content in the pregnancy group was confirmed by histological analysis, which revealed the loss of tissue composition, increased water content, and collagen degradation. Conclusion The proposed bimodal ultrasound and sPA imaging system can provide information on the biochemical composition of cervical tissue in pregnant and non-pregnant women. Photoacoustic imaging showed a higher collagen content in cervical samples from non-pregnant women as compared to those from pregnant women, which matched with the histological analysis. This novel imaging method envisions a new potential for a sensitive diagnostic tool in the evaluation of cervical tissue composition.

Progress of photoacoustic imaging combined with targeted photoacoustic contrast agents in tumor molecular imaging

“…Endogenous contrast agents are intrinsic chromophores in biological tissues, primarily hemoglobin ( Karlas et al, 2021 ), melanin ( Fan et al, 2014 ), lipids ( Ntziachristos and Razansky, 2010 ), collagen ( Wu et al, 2021 ), bilirubin ( Lee et al, 2017 ), water ( Yan et al, 2021 ), and DNA and RNA ( Yao et al, 2010 ) ( Figure 2 ). Tumor metabolism and behavior are regulated by intracellular factors and metabolites in the tumor microenvironment ( Elia and Haigis, 2021 ).…”

Recent advances in nanomaterial-driven strategies for diagnosis and therapy of vascular anomalies

“…Endogenous contrast agents for PAI are intrinsic chromophores in biological tissues, primarily including hemoglobin, lipids, melanin, bilirubin, collagen, water, DNA, RNA, etc [ 64 – 67 ]. Molecular-level changes during the development of vascular anomalies result in variations in photoacoustic signals from these molecules, forming the basis for the use of endogenous contrast agents.…”

Clinical photoacoustic/ultrasound dual-modal imaging: Current status and future trends

“…In these studies, the system designs have in common that an optimized imaging system achieved a higher spatial and temporal resolution, better penetration in tissue with reduced artifacts. Consequently, the advancements in PAT have enabled a wide applications ranging from small animal studies to clinical imaging, including imaging of breast ( Becker et al, 2018 ; Xu et al, 2019 ; Yang et al, 2020 ), thyroid ( Dima and Ntziachristos, 2016 ; Sinha et al, 2017 ; Roll et al, 2019 ), skin ( Petri et al, 2016 ; Dahlstrand et al, 2020 ), tumors ( Li et al, 2015 ; Yamada et al, 2020 ; Karmacharya et al, 2021 ; Knorring and Mogensen, 2021 ; Wang C et al, 2021 ), cardiovascular ( Taruttis et al, 2013 ; Karlas et al, 2021a ), functional neuroimaging ( Wang et al, 2003 ; Wu et al, 2019a ), eyes ( Liu and Zhang, 2016 ) and others ( Nagae et al, 2018 ; Yang et al, 2018 ; Liang et al, 2021 ; Yan et al, 2021 ). Therefore, PAT imaging has broader clinical translational potential than other forms of pure optical imaging, indicating its ability to provide potent structural, functional, and molecular information in vivo ( Yao and Wang, 2018 ; Wu M et al, 2021 ).…”