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  • Burton, Neal C.  (2)
  • Driessen, Wouter H.  (2)
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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4310-4310
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4310-4310
    Abstract: Pharmacokinetic imaging is a powerful platform for evaluating new candidate drugs and imaging agents, and multitude of applications have been demonstrated in DCE MRI. Interesting parameters such as Ktrans, half-life and Tmax can be retrieved for a tumor region after injection of a perfusion agent, allowing one to draw important conclusions on tumor growth, vascularization or therapy response. DCE MRI however is to a certain extent limited to magnetic agents and provides limited spatial and temporal resolution. Multispectral Optoacoustic Imaging (MSOT) is an emerging modality that combines ultrasound resolution of 150 µm and acquisition times of a few microseconds with optical contrast in the near infrared (NIR) spectral region. Multispectral imaging allows the localization of injected fluorophores without necessity of a baseline scan before injection, while a core imaging rate of 10 images/second allows the acquisition of a multispectral image within a second or even less. This enables fast image acquisition to support pharmacokinetic imaging, where the temporal profile of individual pixels is fit to a model equation and resulting parameters are plotted as parametric maps. Using targeted agents, binding specificity and its kinetics can be evaluated, while perfusion agents allow the assessment of perfusion and tissue uptake through Ktrans. One advantage in regards to DCE-MRI is the ability to extract the arterial input function from the data itself by monitoring a single cross-section with maximal temporal resolution. Another important feature is the use of intrinsic contrast that allows blood oxygenation quantification, enabling the co-registration of functional oxygenation measurements with DCE perfusion measurements. In particular, various algorithms can be applied in order to visualize blood oxygenation as a result from tissue intrinsic optoacoustic contrast without the injection of additional agents. These can be evaluated for pixel dependent temporal changes using the fast image acquisition techniques described above, which allows for tumor delineation and assessment of perfusion in a CO2 challenge experiment by visualizing the localized change in blood oxygenation. This can be cross-validated by the subsequent injection of a perfusion agent and evaluation of its transfer coefficient using DCE-MSOT techniques to paint a complete picture of the evaluated tumor microenvironment. The presented work uses the U87-MG glioblastoma and 4T1 tumors to illustrate the abilities of the technique in both subcutaneous and orthotopic settings. The extension of contrast-enhanced kinetic modeling to the optoacoustic imaging regime allows access to a library of optical probes that are otherwise unavailable to traditional DCE-MRI, while maintaining high spatial resolution and providing access to functional hemodynamic parameters. Citation Format: Stefan Morscher, Wouter HP Driessen, Neal C. Burton, Thomas Sardella, Daniel Razansky, Vasilis Ntziachristos. Assessing PK parameters using dynamic contrast enhanced multispectral optoacoustic tomography (DCE-MSOT). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4310. doi:10.1158/1538-7445.AM2014-4310
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 737-737
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 737-737
    Abstract: Apoptosis is an important mechanism in cellular homeostasis and imbalances in the apoptotic process are associated with various disease states. An important example is the acquired ability of cancer cells to resist their own programmed cell death and therefore it is the aim of many tumor therapies to either reestablish pro-apoptotic signaling pathways or induce apoptosis through activation of existing mechanisms within the cell. Therefore, visualizing and quantifying the apoptotic process in vivo has great value in monitoring therapy response, diagnosis and staging disease. By being able to detect subtle changes in perfusion and tissue oxygenation, the small animal Multispectral Optoacoustic Tomography (MSOT) scanner offers unprecedented performance in cross-sectional imaging of tumor heterogeneity as well as a powerful capacity to simultaneously image molecular processes such as apoptosis by utilizing novel molecular probes. In this study, apoptotic regions within a mouse mammary tumor where visualized using a dye-conjugated caspase probe and compared to the hypoxia status of each tumor region. The temporal resolution of the MSOT small animal scanner (generation of multispectral cross-sectional data in less than 1 second) allows for the dynamic imaging of targeted and control probe simultaneously. To illustrate this point apoptosis probe was co-injected with a control dye with similar physical and chemical properties, but a different absorbance maximum after which the tumor region was imaged over 1 hour with multi-spectral image acquisition. Next, mice were imaged by MSOT immediately before and 24 hours post treatment with the chemotherapeutic Doxorubicin and the induction of apoptosis was visualized and quantified. Doxorubicin treatment led to a significant increase in signal resulting from the DyLight 747-conjugated apoptosis probe. In summary, MSOT can be used to determine the extent of apoptosis in tumors in vivo and thus has great value in monitoring therapy response, diagnosis and staging disease. Citation Format: Wouter H. Driessen, Neal C. Burton, Thomas Sardella, Stefan Morscher, Daniel Razansky, Vasilis Ntziachristos. Multispectral Optoacoustic Tomography (MSOT) imaging and quantification of apoptosis in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 737. doi:10.1158/1538-7445.AM2013-737
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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