Dataset Information

Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer.

ABSTRACT: Clinical tools for measuring tumor vascular hemodynamics, such as dynamic contrast-enhanced MRI, are clinically important to assess tumor properties. Here we explored the use of multispectral optoacoustic tomography (MSOT), which has a high spatial and temporal resolution, to measure the intratumoral pharmacokinetics of a near-infrared-dye-labeled 2-Deoxyglucose, 2-DG-800, in orthotropic 2-LMP breast tumors in mice. As uptake of 2-DG-800 is dependent on both vascular properties, and glucose transporter activity - a widely-used surrogate for metabolism, we evaluate hemodynamics of 2-DG-MP by fitting the dynamic MSOT signal of 2-DG-800 into two-compartment models including the extended Tofts model (ETM) and reference region model (RRM). We showed that dynamic 2-DG-enhanced MSOT (DGE-MSOT) is powerful in acquiring hemodynamic rate constants, including K^trans and K_ep, via systemically injecting a low dose of 2-DG-800 (0.5 µmol/kg b.w.). In our study, both ETM and RRM are efficient in deriving hemodynamic parameters in the tumor. Area-under-curve (AUC) values (which correlate to metabolism), and K^trans and K_ep values, can effectively distinguish tumor from muscle. Hemodynamic parameters also demonstrated correlations to hemoglobin, oxyhemoglobin, and blood oxygen level (SO₂) measurements by spectral unmixing of the MSOT data. Together, our study for the first time demonstrated the capability of DGE-MSOT in assessing vascular hemodynamics of tumors.

SUBMITTER: Han Z

PROVIDER: S-EPMC10362308 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer.

Han Zheng Z MacCuaig William M WM Gurcan Metin N MN Claros-Sorto Juan J Garwe Tabitha T Henson Christina C Holter-Chakrabarty Jennifer J Hannafon Bethany B Chandra Vishal V Wellberg Elizabeth E McNally Lacey R LR

Photoacoustics 20230709

Clinical tools for measuring tumor vascular hemodynamics, such as dynamic contrast-enhanced MRI, are clinically important to assess tumor properties. Here we explored the use of multispectral optoacoustic tomography (MSOT), which has a high spatial and temporal resolution, to measure the intratumoral pharmacokinetics of a near-infrared-dye-labeled 2-Deoxyglucose, 2-DG-800, in orthotropic 2-LMP breast tumors in mice. As uptake of 2-DG-800 is dependent on both vascular properties, and glucose tran ...[more]

PMID: 37485041

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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.

Project description:Objective: Monitoring emerging vascular-targeted photodynamic therapy (VTP) and understanding the time-dynamics of treatment effects remains challenging. We interrogated whether handheld multispectral optoacoustic tomography (MSOT) could noninvasively monitor the effect of VTP using WST11, a vascular-acting photosensitizer, on tumor tissues over time using a renal cell cancer mouse model. We also investigated whether MSOT illumination can induce VTP, to implement a single-modality theranostic approach. Materials and Methods: Eight BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells (RENCA) on the flank. Three weeks later VTP was performed (10 min continuous illumination at 753 nm following intravenous infusion using WST11 or saline as control. Handheld MSOT images were collected prior to VTP administration and subsequently thereafter over the course of the first hour, at 24 and 48 h. Data collected were unmixed for blood oxygen saturation in tissue (SO2) based on the spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen saturation over time, relative to baseline, were examined by paired t-test for statistical significance (p < 0.05). In-vivo findings were corroborated by histological analyses of the tumor tissue. Results: MSOT is shown to prominently resolve changes in oxygen saturation in tumors within the first 20 min post WST11-VTP treatment. Within the first hour post-treatment, SO2 decreased by more than 60% over baseline (p < 0.05), whereas it remained unchanged (p > 0.1) in the sham-treated group. Moreover, unlike in the control group, SO2 in treated tumors further decreased over the course of 24 to 48 h post-treatment, concomitant with the propagation of profound central tumor necrosis present in histological analysis. We further show that pulsed MSOT illumination can activate WST11 as efficiently as the continuous wave irradiation employed for treatment. Conclusion: Handheld MSOT non-invasively monitored WST11-VTP effects based on the SO2 signal and detected blood saturation changes within the first 20 min post-treatment. MSOT may potentially serve as a means for both VTP induction and real-time VTP monitoring in a theranostic approach.

Dataset Information

Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer.

Publications

Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer.

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