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Activatable probes for diagnosing and positioning liver injury and metastatic tumors by multispectral optoacoustic tomography.

ABSTRACT: Optoacoustic tomography (photoacoustic tomography) is an emerging imaging technology displaying great potential for medical diagnosis and preclinical research. Rationally designing activatable optoacoustic probes capable of diagnosing diseases and locating their foci can bring into full play the role of optoacoustic tomography (OAT) as a promising noninvasive imaging modality. Here we report two xanthene-based optoacoustic probes (C¹X-OR¹ and C²X-OR²) for temporospatial imaging of hepatic alkaline phosphatase (or ?-galactosidase) for evaluating and locating drug-induced liver injury (or metastatic tumor). The probes rapidly respond to the disease-specific biomarkers by displaying red-shifted NIR absorption bands and generate prominent optoacoustic signals. Using multispectral optoacoustic tomography (MSOT), we can precisely localize the focus of drug-induced liver injury in mice using C¹X-OR¹, and the metastatic tumors using C²X-OR². This work suggests that the activatable optoacoustic chromophores may potentially be applied for diagnosing and localizing disease foci, especially smaller and deeper ones.

SUBMITTER: Wu Y

PROVIDER: S-EPMC6162313 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Activatable probes for diagnosing and positioning liver injury and metastatic tumors by multispectral optoacoustic tomography.

Wu Yinglong Y Huang Shuailing S Wang Jun J Sun Lihe L Zeng Fang F Wu Shuizhu S

Nature communications 20180928 1

Optoacoustic tomography (photoacoustic tomography) is an emerging imaging technology displaying great potential for medical diagnosis and preclinical research. Rationally designing activatable optoacoustic probes capable of diagnosing diseases and locating their foci can bring into full play the role of optoacoustic tomography (OAT) as a promising noninvasive imaging modality. Here we report two xanthene-based optoacoustic probes (C1X-OR1 and C2X-OR2) ...[more]

PMID: 30266905

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Project description:ImportanceDifferential diagnosis of congenital vascular anomalies is challenging, and misdiagnosis is frequent. Vascular malformations are considered one of the most difficult vascular diseases to treat. A new imaging approach that visualizes anatomical features and quantitatively assesses molecular biomarkers noninvasively would aid diagnosis and monitoring of treatment response of vascular malformations.ObjectiveTo evaluate multispectral optoacoustic tomography (MSOT) for noninvasive assessment of molecular biomarkers for diagnosis and therapeutic monitoring of vascular malformations.Design, setting, and participantsThis pilot study examined 6 patients with arteriovenous malformation (AVM) and 6 patients with venous malformation (VM) diagnosed according to the classification system of the International Society for the Study of Vascular Anomalies. All patients underwent clinical hybrid MSOT/ultrasonographic (US) imaging before and after treatment at an interdisciplinary vascular malformations clinic by trained MSOT and US examiners. Examiners were blinded to the patient history and stage of disease. Data were collected from April 11 to 25, 2017, and analyzed from May 1 to October 31, 2017.InterventionsClinical hybrid MSOT/US imaging was performed before or within 1 week after endovascular embolization (for AVM) or percutaneous sclerotherapy (for VM).Main outcomes and measuresRegion-of-interest analysis of the lesion and contralateral healthy tissue revealed quantitative values for oxygenated (HbO2) and deoxygenated (HbR) hemoglobin by spectral unmixing of optoacoustic data acquired at multiple wavelengths. The HbO2:HbR ratio was calculated for healthy tissue and for AVM and VM before and after treatment.ResultsTwelve patients (9 female and 3 male; mean [SD] age, 23 [18] years; age range, 6-59 years) with vascular malformations (6 with AVMs and 6 with VMs) were included. Significantly higher HbO2:HbR ratios for AVMs (mean [SEM], 1.82 [0.08] vs 0.89 [0.03]; P < .001) and for VMs (mean [SEM], 1.12 [0.04] vs 0.89 [0.03]; P = .001) were found on MSOT tissue compared with healthy tissue. Significantly higher HbO2:HbR ratios for AVMs compared with VMs (mean [SEM], 1.82 [0.08] vs 1.12 [0.04]; P < .001) were also found. Therefore, MSOT provided intrinsic biomarker patterns to distinguish both vascular malformations. After therapy, the HbO2:HbR ratio dropped in correlation to treatment success validated by magnetic resonance imaging or angiography.Conclusions and relevanceThis study suggests that different types of vascular malformations are clearly distinguished by MSOT-based, noninvasive assessment of hemoglobin levels in vascular malformations. The therapy effects found in this study could be instantly visualized, and this may offer a new tool for noninvasive diagnosis and monitoring of vascular malformations.

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Activatable probes for diagnosing and positioning liver injury and metastatic tumors by multispectral optoacoustic tomography.

Publications

Activatable probes for diagnosing and positioning liver injury and metastatic tumors by multispectral optoacoustic tomography.

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