Noninvasive Assessment of Tumor Vasculature Response to Radiation-Mediated, Vasculature-Targeted Therapy Using Quantified Power Doppler Sonography

Kim, Dong Wook Nathan; Huamani, Jessica; Niermann, Kenneth J.; Lee, Haakil; Geng, Li; Leavitt, Lauren; Baheza, Richard A.; Jones, Cameron; Tumkur, S.; Yankeelov, Thomas E.; Fleischer, Arthur C.; Hallahan, Dennis E.

doi:10.7863/jum.2006.25.12.1507

Cited by 30 publications

(14 citation statements)

References 24 publications

(44 reference statements)

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“…At day 20 after irradiation, most blood vessel perfusion resumed in vessels around the tumor periphery. Others have reported similar vascular perfusion kinetics in bulk subcutaneous xenograft tumors following single 10–20 Gy doses using Doppler ultrasound and immunohistochemistry [13]–[16]; however, the methods reported here provide the first opportunity to directly visualize and quantify these functional and structural changes in vessels in vivo within the tumor at high resolution (∼10 µm) in the same animal over time.…”

Section: Resultsmentioning

confidence: 68%

In Vivo Optical Imaging of Tumor and Microvascular Response to Ionizing Radiation

et al. 2012

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Radiotherapy is a widely used cancer treatment. However, understanding how ionizing radiation affects tumor cells and their vasculature, particularly at cellular, subcellular, genetic, and protein levels, has been limited by an inability to visualize the response of these interdependent components within solid tumors over time and in vivo. Here we describe a new preclinical experimental platform combining intravital multimodal optical microscopy for cellular-level longitudinal imaging, a small animal x-ray microirradiator for reproducible spatially-localized millimeter-scale irradiations, and laser-capture microdissection of ex vivo tissues for transcriptomic profiling. Using this platform, we have developed new methods that exploit the power of optically-enabled microscopic imaging techniques to reveal the important role of the tumor microvasculature in radiation response of tumors. Furthermore, we demonstrate the potential of this preclinical platform to study quantitatively - with cellular and sub-cellular details - the spatio-temporal dynamics of the biological response of solid tumors to ionizing radiation in vivo.

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Section: Resultsmentioning

confidence: 68%

In Vivo Optical Imaging of Tumor and Microvascular Response to Ionizing Radiation

et al. 2012

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“…Endothelial cells have been shown to be particularly sensitive to high doseper-fraction radiation (>8 Gy per fraction as opposed to low conventional doses of 1.8-3.0 Gy per fraction) resulting in endothelial apoptosis and microvascular dysfunction (19,20). Angiogenic factors like vascular endothelial growth factor and fibroblast growth factor (FGF2) have been shown to be upregulated after high-dose radiation exposure in normal brain tissue (21), and repeated administration of high-dose radiation serves to enhance vascular destruction and endothelial apoptosis and compromise blood flow (22). The hypofractionated regimen used by our center (14 Gy per fraction) poises the tissue in the high-dose volume (tumor, surrounding retina, and optic nerve) to develop tumor vasculopathy, radiation retinopathy, and optic neuropathy, Hyalinization of blood vessels 0 3 (50%) Retinal exudation 2 (50%) 4 (67%)…”

Section: Discussionmentioning

confidence: 98%

Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

Fernandes¹,

Weisbrod²,

Yücel³

et al. 2011

International Journal of Radiation Oncology*Biology*Physics

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“…On the other hand, irradiation of mouse adenocarcinoma in window chambers with 20-50 Gy in a single exposure caused progressive narrowing of blood vessels (32). Irradiation of Lewis lung carcinoma of mice grown in window chambers in dorsal skin with 20 Gy in a single exposure led to uniformly complete destruction and hemorrhage of the tumor blood vessels in 2 days (57).…”

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confidence: 99%

Radiation-Induced Vascular Damage in Tumors: Implications of Vascular Damage in Ablative Hypofractionated Radiotherapy (SBRT and SRS)

et al. 2012

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We have reviewed the studies on radiation-induced vascular changes in human and experimental tumors reported in the last several decades. Although the reported results are inconsistent, they can be generalized as follows. In the human tumors treated with conventional fractionated radiotherapy, the morphological and functional status of the vasculature is preserved, if not improved, during the early part of a treatment course and then decreases toward the end of treatment. Irradiation of human tumor xenografts or rodent tumors with 5-10 Gy in a single dose causes relatively mild vascular damages, but increasing the radiation dose to higher than 10 Gy/fraction induces severe vascular damage resulting in reduced blood perfusion. Little is known about the vascular changes in human tumors treated with high-dose hypofractionated radiation such as stereotactic body radiotherapy (SBRT) or stereotactic radiosurgery (SRS). However, the results for experimental tumors strongly indicate that SBRT or SRS of human tumors with doses higher than about 10 Gy/fraction is likely to induce considerable vascular damages and thereby damages the intratumor microenvironment, leading to indirect tumor cell death. Vascular damage may play an important role in the response of human tumors to high-dose hypofractionated SBRT or SRS.

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Noninvasive Assessment of Tumor Vasculature Response to Radiation-Mediated, Vasculature-Targeted Therapy Using Quantified Power Doppler Sonography

Abstract: This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.

Cited by 30 publications

References 24 publications

In Vivo Optical Imaging of Tumor and Microvascular Response to Ionizing Radiation

In Vivo Optical Imaging of Tumor and Microvascular Response to Ionizing Radiation

Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

Radiation-Induced Vascular Damage in Tumors: Implications of Vascular Damage in Ablative Hypofractionated Radiotherapy (SBRT and SRS)

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