Semi-quantitative Multispectral Optoacoustic Tomography (MSOT) for volumetric PK imaging of gastric emptying.
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ABSTRACT:
SUBMITTER: Morscher S
PROVIDER: S-EPMC4244636 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Accurate detection and characterization of cancers are key for providing timely intervention and effective treatments. Current imaging technologies are particularly limited when it comes to detecting very small tumors in vivo, i.e., very early cancers or metastases, differentiating viable tumor from surrounding dead tumor tissue, and evaluating tumor metabolism within tissue. Optoacoustic imaging offers potential solutions to these imaging problems because of its ability to image optical absorption properties of both intrinsic tissue chromophores and exogenous contrast agents without the involvement of ionizing radiation. Optoacoustic imaging uses pulsed laser to induce localized thermoelastic expansion that generates acoustic waves detectable by an ultrasound transducer. To date, multispectral optoacoustic tomography (MSOT) has primarily been used in preclinical research; however, its use in translational and clinical research is expanding. This review focuses on current and emerging applications of optoacoustic imaging for molecular imaging of cancer using both exogenous and endogenous contrast agents and sheds light on potential future clinical applications. Clin Cancer Res; 22(14); 3432-9. ©2016 AACR.
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Project description:PurposeThis study proposes the utilization of multispectral optoacoustic tomography (MSOT) to investigate the intratumoral distribution of polymeric micelles and effect of size on the biodistribution and antitumor efficacy (ATE).Materials and methodsDocetaxel and/or optoacoustic agent-loaded polymeric micelles (with diameters of 22, 48, and 124 nm) were prepared using amphiphilic block copolymers poly (ethylene glycol) methyl ether-block-poly (D,L lactide) (PEG2000-PDLLAx). Subcutaneous 4T1 tumor-bearing mice were monitored with MSOT imaging and IVIS® Spectrum in vivo live imaging after tail vein injection of micelles. The in vivo results and ex vivo confocal imaging results were then compared. Next, ATE of the three micelles was found and compared.ResultsWe found that MSOT imaging offers spatiotemporal and quantitative information on intratumoral distribution of micelles in living animals. All the polymeric micelles rapidly extravasated into tumor site after intravenous injection, but only the 22-nm micelle preferred to distribute into the inner tumor tissues, leading to a superior ATE than that of 48- and 124-nm micelles.ConclusionThis study demonstrated that MSOT is theranostically a powerful imaging modality, offering quantitative information on size-dependent spatiotemporal distribution patterns after the extravasation of nanomedicine from tumor blood vessels.
| S-EPMC6296692 | biostudies-literature
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.
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Project description:A handheld approach to optoacoustic imaging is essential for the clinical translation. The first 2- and 3-dimensional handheld multispectral optoacoustic tomography (MSOT) probes featuring real-time unmixing have recently been developed. Imaging performance of both probes was determined in vitro and in a brain melanoma metastasis mouse model in vivo. T1-weighted MR images were acquired for anatomical reference. The limit of detection of melanoma cells in vitro was significantly lower using the 2D than the 3D probe. The signal decrease was more profound in relation to depth with the 3D versus the 2D probe. Both approaches were capable of imaging the melanoma tumors qualitatively at all time points. Quantitatively, the 2D approach enabled closer anatomical resemblance of the tumor compared to the 3D probe, particularly at depths beyond 3 mm. The 3D probe was shown to be superior for rapid 3D imaging and, thus, holds promise for more superficial target structures.
| S-EPMC4811917 | biostudies-literature
Project description:Currently, several noninvasive modalities, including MRI and PET, are being investigated to identify early intestinal inflammation, longitudinally monitor disease status, or detect dysplastic changes in patients with inflammatory bowel disease. Here, we assess the applicability and utility of multispectral optoacoustic tomography (MSOT) in evaluating the presence and severity of colitis. Methods: C57B/6 mice were untreated or treated with Bacteroides fragilis and antibiotic-mediated depletion of intestinal flora to initiate colitis. Mice were imaged using MSOT to detect intestinal inflammation. Intestinal inflammation identified with MSOT was also confirmed using both colonoscopy and histology. Results: Mice with bacterial colitis demonstrated a temporally associated increase in mesenteric and colonic vascularity with an increase in mean signal intensity of oxygenated hemoglobin (P = 0.004) by MSOT 2 d after inoculation. These findings were significantly more prominent 7 d after inoculation, with increased mean signal intensity of oxygenated hemoglobin (P = 0.0002) and the development of punctate vascular lesions on the colonic surface, which corresponded to changes observed on colonoscopy as well as histology. Conclusion: With improvements in depth of tissue penetration, MSOT may hold potential as a sensitive, accurate, noninvasive imaging tool in the evaluation of patients with inflammatory bowel disease.
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Project description:Photo-or optoacoustic imaging (OAI) allows quantitative imaging of target tissues. Using multi-wavelength illumination with subsequent ultrasound detection, it may visualize a variety of different chromophores at centimeter depth. Despite its non-invasive, label-free advantages, the precision of repeated measurements for clinical applications is still elusive. We present a multilayer analysis of n = 1920 imaging datasets obtained from a prospective clinical trial (NCT03979157) in n = 10 healthy adult volunteers. All datasets were analyzed for 13 single wavelengths (SWL) between 660 nm-1210 nm and five MSOT-parameters (deoxygenated/oxygenated/total hemoglobin, collagen and lipid) by a semi-automated batch mode software. Intraclass correlation coefficients (ICC) were good to excellent for intrarater (SWL: 0.82-0.92; MSOT-parameter: 0.72-0.92) and interrater reproducibility (SWL: 0.79-0.87; MSOT-parameter: 0.78-0.86), with the exception for MSOT-parameter lipid (interrater ICC: 0.56). Results were stable over time, but exercise-related effects as well as inter-and intramuscular variability were observed. The findings of this study provide a framework for further clinical OAI implementation.
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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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Project description:Multispectral optoacoustic tomography (MSOT) is an emerging imaging modality, which is able to capture data at high spatiotemporal resolution using rapid tuning of the excitation laser wavelength. However, owing to the necessity of imaging one wavelength at a time to the exclusion of others, forming a complete multispectral image requires multiple excitations over time, which may introduce aliasing due to underlying spectral dynamics or noise in the data. In order to mitigate this limitation, we have applied kinematic ? and ?? filters to multispectral time series, providing an estimate of the underlying multispectral image at every point in time throughout data acquisition. We demonstrate the efficacy of these methods in suppressing the inter-frame noise present in dynamic multispectral image time courses using a multispectral Shepp-Logan phantom and mice bearing distinct renal cell carcinoma tumors. The gains in signal to noise ratio provided by these filters enable higher-fidelity downstream analysis such as spectral unmixing and improved hypothesis testing in quantifying the onset of signal changes during an oxygen gas challenge.
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Project description:Although multifunctional inorganic nanoparticles have been extensively explored for effective cancer diagnosis and therapy, their clinical translation has been greatly impeded because of significant uptake in the reticuloendothelial system and concerns about potential toxicity. In this study, we uncovered the thermosensitive biodegradability of CuS nanoparticles, which have classically been considered as stable in bulk state. Polyethylene glycol (PEG)-coated CuS nanoparticles (CuS-PEG) were well preserved at 4 ºC but were rapidly degraded at 37 ºC within 1 week in both in vitro and in vivo tests. Furthermore, real-time multispectral optoacoustic tomography, which is more convenient and accurate than traditional ex vivo analysis, was successfully employed to noninvasively demonstrate the biodegradability of CuS-PEG nanoparticles and dynamically monitor their tumor imaging capacity. The temperature-dependent controllable degradation profile and excellent tumor retention of CuS-PEG nanoparticles endows them with great potential for clinical applications since it ensures that the nanoparticles remain intact during production, transportation, and storage but degrade and clear from the body at physiological temperature after accomplishing sufficient diagnosis and therapeutic operations.
| S-EPMC8075272 | biostudies-literature