Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia

Qi, Qi; Yeung, Timothy Pok Chi; Lee, Ting‐Yim; Crukley, Cathie; Morrison, Laura; Hoffman, Lisa; Yartsev, Slav

doi:10.1371/journal.pone.0153569

Cited by 7 publications

(7 citation statements)

References 22 publications

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“…We found significant positive correlations between PN and E and C I at the tumor periphery in the SE images. These results are in apparent contradiction with Qi et al [ 11 ], since they found a significant negative correlation between PN and BV and BF, quantified from DCE CT images of the C6 glioma model. We hypothesize that this discrepancy is related to the differences in the kinetic models used to quantify the imaging parameters.…”

Section: Discussioncontrasting

confidence: 99%

“…Previous studies of the orthotopic C6 glioma model have used DE [ 14 , 15 ] or DCE imaging techniques [ 9 , 10 , 11 ], and general findings among them are in agreement with our observations in the subcutaneous C6 glioma model. Both animal models allowed to obtain CE X-ray images that improved lesion detection and reflected the heterogeneity in E, C I , or rBV values quantified in the different tumor regions, despite the presence of the BBB in the orthotopic model, which could be explained by the similarities in microvessel morphology and permeability between these two animal models [ 31 ].…”

Section: Discussionsupporting

confidence: 92%

“…CE X-ray imaging techniques have been used to assess the association of quantitative imaging parameters with histological biomarkers of angiogenesis in preclinical studies with animals [ 7 ]. Dynamic contrast-enhanced (DCE) imaging with clinical CT scanners, i.e., perfusion CT, has been the most used CE X-ray imaging technique to study angiogenesis in animal models of cancer [ 8 , 9 , 10 , 11 ]. Static single- and dual-energy techniques (SE and DE, respectively) have been used with micro-CT or clinical CT scanners [ 12 , 13 , 14 , 15 ], or with planar imaging systems, such as in mammography [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model

Ayala-Domínguez

Pérez-Cárdenas

Avilés‐Salas

et al. 2020

Cancers

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The aim of this work was to systematically obtain quantitative imaging parameters with static and dynamic contrast-enhanced (CE) X-ray imaging techniques and to evaluate their correlation with histological biomarkers of angiogenesis in a subcutaneous C6 glioma model. Enhancement (E), iodine concentration (CI), and relative blood volume (rBV) were quantified from single- and dual-energy (SE and DE, respectively) micro-computed tomography (micro-CT) images, while rBV and volume transfer constant (Ktrans) were quantified from dynamic contrast-enhanced (DCE) planar images. CI and rBV allowed a better discernment of tumor regions from muscle than E in SE and DE images, while no significant differences were found for rBV and Ktrans in DCE images. An agreement was found in rBV for muscle quantified with the different imaging protocols, and in CI and E quantified with SE and DE protocols. Significant strong correlations (Pearson r > 0.7, p < 0.05) were found between a set of imaging parameters in SE images and histological biomarkers: E and CI in tumor periphery were associated with microvessel density (MVD) and necrosis, E and CI in the complete tumor with MVD, and rBV in the tumor periphery with MVD. In conclusion, quantitative imaging parameters obtained in SE micro-CT images could be used to characterize angiogenesis and necrosis in the subcutaneous C6 glioma model.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model

Ayala-Domínguez

Pérez-Cárdenas

Avilés‐Salas

et al. 2020

Cancers

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“…46 Stroma can represent zones of hypoxia in tumors and BF and BV are negatively correlated with the degree of tumor hypoxia. 47,48 However, tumor microenvironment and its relationship with hypoxia and T A B L E 1 Median baseline perfusion parameters in different histological types of nasal tumors in dogs. vascularization in human and veterinary medicine are complex, and findings in the literature are inconsistent, and therefore assumptions should be avoided.…”

Section: Discussionmentioning

confidence: 99%

Dynamic contrast‐enhanced computed tomography in dogs with nasal tumors

Mortier

Maddox

Blackwood

et al. 2023

Veterinary Internal Medicne

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Background Treatment of nasal tumors in dogs is associated with high morbidity and reliable prognostic factors are lacking. Dynamic contrast‐enhanced computed tomography (DCECT) can be used to assess tumor perfusion. Objectives To assess perfusion parameters of nasal tumors (correlating with tumor type) before and during radiotherapy (RT) and find potential correlation with survival. Animals Twenty‐four client‐owned dogs with nasal tumors, including 16 epithelial tumors and 8 sarcomas. Methods Prospective cross‐sectional study. All dogs had baseline DCECT to assess fractional vascular volume (BV), blood flow (BF), and transit time (TT). Thirteen dogs had repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated. Results Median BV was 17.83 mL/100 g (range, 3.63‐66.02), median BF was 122.63 mL/100 g/minute (range, 23.65‐279.99), and median TT was 8.91 seconds (range, 4.57‐14.23). Sarcomas had a significantly lower BF than adenocarcinomas (P = .002), carcinomas (P = .01), and other carcinomas (P = .001), and significantly lower BV than adenocarcinomas (P = .03) and other carcinomas (P = .004). Significant associations were found between epithelial tumors and sarcoma for change in tumor volume (P = .01), width (P = .004), and length (P = .02) in that epithelial tumors decreased in volume whereas sarcomas increased in volume. Perfusion parameters were not correlated with survival. Conclusions and Clinical Importance Nasal sarcomas have lower BV and BF than nasal carcinomas, and sarcomas have a lower size reduction than carcinomas early on during RT. Baseline results and changes in perfusion parameters may not be correlated with survival.

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“…To facilitate improved evaluation of treatments and to better understand tumor progression in the C6 model, numerous groups have used clinically relevant imaging tools such as positron emission tomography ( 20 ), computed tomography ( 21 ), and magnetic resonance imaging (MRI) ( 22 ). MRI has become the standard of care for the detection, staging, and assessment of treatment response in patients with glioma ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of an Orthotopic Rat Model of Glioblastoma Using Multiparametric Magnetic Resonance Imaging and Bioluminescence Imaging

Lim

Hamilton

et al. 2018

Tomography

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Glioblastoma multiforme (GBM) is the most common primary brain tumor, with most patients dying within 15–18 months of diagnosis despite aggressive therapy. Preclinical GBM models are valuable for exploring GBM progression and for evaluating new therapeutics or imaging approaches. The rat C6 glioma model shares similarities with human GBM, and application of noninvasive imaging enables better study of disease progression. Here, multiparametric magnetic resonance imaging (mpMRI) and bioluminescence imaging (BLI) were applied to characterize longitudinal development of orthotopic luciferase-expressing C6 tumors. Across all rats (n = 11), a large variability was seen for BLI signal, a relative measure of C6 cell viability, but in most individuals, BLI signal peaked at day 11 and decreased thereafter. T2 and contrast-enhanced T1 tumor volumes significantly increased over time (P < .05), and volume measures did not correlate with BLI signal. After day 11, tumor regions of noncontrast enhancement appeared in postcontrast T1-weighted magnetic resonance imaging, and had significantly higher apparent diffusion coefficient values compared with contrast-enhanced regions (P < .05). This suggests formation of ill-perfused, necrotic regions beyond day 11, which were apparent at end-point–matched tissue sections. Our study represents the first combined use of BLI and mpMRI to characterize the progression of disease in the orthotopic C6 rat model, and it highlights the variability in tumor growth, the complementary information from BLI and mpMRI, and the value of multimodality imaging to better characterize tumor development. Future application of these imaging tools will be useful for evaluation of treatment response, and should be pertinent for other preclinical models.

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Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia

Cited by 7 publications

References 22 publications

Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model

Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model

Dynamic contrast‐enhanced computed tomography in dogs with nasal tumors

Characterization of an Orthotopic Rat Model of Glioblastoma Using Multiparametric Magnetic Resonance Imaging and Bioluminescence Imaging

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