Micro Spectroscopic Photoacoustic (μsPA) imaging of advanced carotid atherosclerosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Iskander-Rizk S
PROVIDER: S-EPMC8027769 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objectives: The objective of this study was to demonstrate the feasibility of using noninvasive photoacoustic imaging technology along with novel semiconducting polymer nanoparticles for in vivo identifying inflammatory components in carotid atherosclerosis and assessing the severity of inflammation using mouse models. Methods and Results: Healthy carotid arteries and atherosclerotic carotid arteries were imaged in vivo by the noninvasive photoacoustic imaging system. Molecular probes PBD-CD36 were used to label the inflammatory cells to show the inflammation information by photoacoustic imaging. In in vivo imaging experiments, we observed the maximum photoacoustic signal enhancement of 4.3, 5.2, 8 and 16.3 times between 24 h post probe injection and that before probe injection in four carotid arteries belonging to three atherosclerotic mice models. In the corresponding carotid arteries stained with CD36, the ratio of 0.043, 0.061, 0.082 and 0.113 was found between CD36 positive (CD36(+)) expression area and intima-media area (P < 0.05). For the CD36(+) expression less than 0.008 in eight arteries, no photoacoustic signal enhancement was found due to the limited system sensitivity. The photoacoustic signal reflects CD36(+) expression in plaques, which shows the feasibility of using photoacoustic imaging for in vivo assessment of carotid atherosclerosis. Conclusion: This research demonstrates a semiconducting polymer nanoparticle along with photoacoustic technology for noninvasive imaging and assessment of inflammation of carotid atherosclerotic plaques in vivo.
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Project description:Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids, and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of >90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, whereas diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear colocalization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques.
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Project description:This study presents a system-level optimization of spectroscopic photoacoustic (PA) imaging for prostate cancer (PCa) detection in three folds. First, we present a spectral unmixing model to segregate spectral system error (SSE). We constructed two noise models (NMs) for the laser spectrotemporal fluctuation and the ultrasound system noise. We used these NMs in linear spectral unmixing to denoise and to achieve high temporal resolution. Second, we employed a simulation-aided wavelength optimization to select the most effective subset of wavelengths. NMs again were considered so that selected wavelengths were not only robust to the collinearity of optical absorbance, but also to noise. Third, we quantified the effect of frame averaging on improving spectral unmixing accuracy through theoretical analysis and numerical validation. To validate the whole framework, we performed comprehensive studies in simulation and an in vivo experiment which evaluated prostate-specific membrane antigen (PSMA) expression in PCa on a mice model. Both simulation analysis and in vivo studies confirmed that the proposed framework significantly enhances image signal-to-noise ratio (SNR) and spectral unmixing accuracy. It enabled more sensitive and faster PCa detection. Moreover, the proposed framework can be generalized to other spectroscopic PA imaging studies for noise reduction, wavelength optimization, and higher temporal resolution.
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Project description:ObjectiveCervical 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.MethodsThis 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.ResultsEight 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.ConclusionThe 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.
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Project description:The movement from the subjects during in vivo confocal Raman spectral measurements could change the measurement volume, leading to non-specific signals and inaccurate interpretation of the acquired spectrum. Here we introduce a generally applicable method that includes (1) developing a multimodal system to achieve real-time monitoring of every spectral measurement with reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) imaging; (2) performing region-of-interest measurement by scanning an area of the tissue during spectral acquisition. The developed method has been validated by measuring different micro-structures of in vivo human skin. Our results demonstrated great consistency between RCM images and confocal Raman spectra. The superior quality of the images and spectra allows us to derive blood flow velocity and blood glucose level. We believe this method is valuable for realizing accurate microscopic spectral measurement and have great potential to be adapted into clinic to achieve non-invasive measurement of important biological parameters.
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Project description:Spectral photoacoustic imaging in combination with unmixing techniques may be applied to retrieve information about high-risk features present in atherosclerotic plaques, possibly providing prognostic insights into future stroke events. We present the photoacoustic spectral contrast found in 12 systematically scanned advanced atherosclerotic plaques in the near-infrared wavelength range (850-1250 nm). The main absorbers are lipid, water, and hemoglobin, with the highest photoacoustic intensities at the lipid's second overtone at 1190 and 1210 nm. Linear unmixing resulted in visualizing regions with high lipid and hemoglobin absorption, corresponding to the histological presence of lipid and intraplaque hemorrhage. A non-negative matrix factorization approach reveals differences in lipid spectral contrast, providing potential insights into the vulnerability of atherosclerotic plaque. These results provide a reference for future, more complex, in vivo photoacoustic imaging of carotid artery atherosclerosis, potentially contributing to assessing the risk of future events and treatment decision.
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Project description:Purpose: Breast cancer imaging methods lack diagnostic accuracy, in particular for patients with dense breast tissue, and improved techniques are critically needed. The purpose of this study was to evaluate antibody-indocyanine green (ICG) conjugates, which undergo dynamic absorption spectrum shifts after cellular endocytosis and degradation, and spectroscopic photoacoustic (sPA) imaging to differentiate normal breast tissue from breast cancer by imaging B7-H3, a novel breast cancer associated molecular target. Methods: Quantitative immunohistochemical staining of endothelial and epithelial B7-H3 expression was assessed in 279 human breast tissue samples, including normal (n=53), benign lesions (11 subtypes, n=129), and breast cancers (4 subtypes, n=97). After absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control-ICG (Iso-ICG) were characterized, sPA imaging in a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was performed and compared to imaging of control conditions [B7-H3-ICG in tumor negative animals (n=60), Iso-ICG (n=30), blocking B7-H3+B7-H3-ICG (n=20), and free ICG (n=20)] and validated with ex vivo histological analysis. Results: Immunostaining showed differential B7-H3 expression on both the endothelium and tumor epithelium in human breast cancer with an area under the ROC curve of 0.93 to differentiate breast cancer vs non-cancer. Combined in vitro/in vivo imaging showed that sPA allowed specific B7-H3-ICG detection down to the 13 nM concentration and differentiation from Iso-ICG. sPA molecular imaging of B7-H3-ICG showed a 3.01-fold (P<0.01) increase in molecular B7-H3-ICG signal in tumors compared to control conditions. Conclusions: B7-H3 is a promising target for both vascular and epithelial sPA imaging of breast cancer. Leveraging antibody-ICG contrast agents and their dynamic optical absorption spectra allows for highly specific sPA imaging of breast cancer.
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