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

Maeda, Azusa; Leung, M.; Conroy, Leigh; Chen, Yonghong; Bu, Jiachuan; Lindsay, Patricia; Mintzberg, Shani; Virtanen, Carl; Tsao, Jeffrey; Winegarden, Neil; Wang, Yanchun; Morikawa, Lily; Vitkin, I. Alex; Jaffray, David A.; Hill, Richard P.; DaCosta, Ralph S.

doi:10.1371/journal.pone.0042133

Cited by 41 publications

(49 citation statements)

References 54 publications

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“…The OCT probe insertion-induced edema should be much lower or absent in humans due to availability of dedicated esophageal OCT catheters that can be inserted in a deflated state 32 and because of the larger size of the organ. Previous studies investigated the use of OCT in esophageal and radiation-induced damages, 20,[33][34][35][36][37][38][39][40][41][42][43][44][45][46] the visibility of esophageal layers in OCT images, and the differentiation between healthy and cancerous esophagus. [39][40][41] Esophageal OCT has been used to detect Barrett's esophagus in various studies.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of using optical coherence tomography to detect acute radiation-induced esophageal damage in small animal models

et al. 2018

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"Feasibility of using optical coherence tomography to detect acute radiation-induced esophageal damage in small animal models," J. Biomed. Opt. 23(4), 046004 (2018), doi: 10.1117/1.JBO.23.4.046004. Abstract. Lung cancer survival is poor, and radiation therapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to acute radiation-induced esophageal damage (ARIED). We investigated the feasibility of optical coherence tomography (OCT) for minimally invasive imaging of the esophagus with high resolution (10 μm) to detect ARIED in mice. Thirty mice underwent cone-beam computed tomography imaging for initial setup assessment and dose planning followed by a single-dose delivery of 4.0, 10.0, 16.0, and 20.0 Gy on 5.0-mm spots, spaced 10.0 mm apart in the esophagus. They were repeatedly imaged using OCT up to three months postirradiation. We compared OCT findings with histopathology obtained three months postirradiation qualitatively and quantitatively using the contrast-to-background-noise ratio (CNR). Histopathology mostly showed inflammatory infiltration and edema at higher doses; OCT findings were in agreement with most of the histopathological reports. We were able to identify the ARIED on OCT as a change in tissue scattering and layer thickness. Our statistical analysis showed significant difference between the CNR values of healthy tissue, edema, and inflammatory infiltration. Overall, the average CNR for inflammatory infiltration and edema damages was 1.6-fold higher and 1.6-fold lower than for the healthy esophageal wall, respectively. Our results showed the potential role of OCT to detect and monitor the ARIED in mice, which may translate to humans. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Section: Discussionmentioning

confidence: 99%

Feasibility of using optical coherence tomography to detect acute radiation-induced esophageal damage in small animal models

et al. 2018

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“…Single high-dose RT (10-30 Gy) is known to have antiangiogenic effects with disappearance of small tumor vessels in the acute phase and stimulation of tumor angiogenesis at long term (after 14 days) [24]. Yet, nothing is known about the effect of fractionated RT and cediranib on tumor microvasculature in CRC.…”

Section: Discussionmentioning

confidence: 99%

The VEGFR Inhibitor Cediranib Improves the Efficacy of Fractionated Radiotherapy in a Colorectal Cancer Xenograft Model

Melsens

Verberckmoes²,

Rosseel³

et al. 2016

Eur Surg Res

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Background/Purpose: Radiotherapy (RT) increases local tumor control in locally advanced rectal cancer, but complete histological response is seen in only a minority of cases. Antiangiogenic therapy has been proposed to improve RT efficacy by “normalizing” the tumor microvasculature. Here, we examined whether cediranib, a pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, improves microvascular function and tumor control in combination with RT in a mouse colorectal cancer (CRC) model. Methods: CRC xenografts (HT29) were grown subcutaneously in mice. Animals were treated for 5 consecutive days with vehicle, RT (1.8 Gy daily), cediranib (6 mg/kg po), or combined therapy (cediranib 2 h prior to radiation). Tumor volume was measured with calipers. Vascular changes were analyzed by dynamic contrast-enhanced MRI, oxygenation and interstitial fluid pressure probes and histology. To investigate vascular changes more in detail, a second set of mice were fitted with titanium dorsal skinfold window chambers, wherein a HT29 tumor cell suspension was injected. In vivo fluorescence microscopy was performed before and after treatment (same treatment protocol). Results: In vivo microscopy analyses showed that VEGFR inhibition with cediranib led to a “normalization” of the vessel wall, with decreased microvessel permeability (p < 0.0001) and tortuosity (p < 0.01), and a trend to decreased vessel diameters. This seemed to lead to lower tumor hypoxia rates in the cediranib and combination groups compared to the control and RT groups. This led to an increased tumor control in the combination group compared to controls or monotherapy (p < 0.0001). Conclusions: The combination of RT with cediranib enhances tumor control in a CRC xenograft mouse model. Microvascular analyses suggest that cediranib leads to vascular normalization and improved oxygenation.

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“…Preclinical studies aim to highlight the biological mechanisms governing radiotherapy response in many radiation applications. [8][9][10][11] With more complex radiotherapy techniques being investigated comes a need for a high-resolution 3D measurement of dose distributions given by small animal microirradiators such as the X-Rad 225Cx (Precision X-Ray, N. Banford, CT). Current procedures for small animal treatment planning involve obtaining beam-on-time necessary for a prescribed dose from tabulated radiation output factors.…”

Section: Introductionmentioning

confidence: 99%

Investigating the accuracy of microstereotactic‐body‐radiotherapy utilizing anatomically accurate 3D printed rodent‐morphic dosimeters

et al. 2015

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Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1-15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm 3 ) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180• continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. Results: Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ∼10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. Conclusions: T...

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

Cited by 41 publications

References 54 publications

Feasibility of using optical coherence tomography to detect acute radiation-induced esophageal damage in small animal models

Feasibility of using optical coherence tomography to detect acute radiation-induced esophageal damage in small animal models

The VEGFR Inhibitor Cediranib Improves the Efficacy of Fractionated Radiotherapy in a Colorectal Cancer Xenograft Model

Investigating the accuracy of microstereotactic‐body‐radiotherapy utilizing anatomically accurate 3D printed rodent‐morphic dosimeters

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