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Title: Perfusion Estimated With Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely With Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study

Abstract

Purpose: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. Methods and Materials: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. Results: Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02).more » Conclusions: Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.« less

Authors:
 [1];  [2];  [3];  [2];  [4];  [5]; ;  [2];  [6];  [7]
  1. School of Cancer and Enabling Sciences, University of Manchester, Manchester (United Kingdom) and North Western Medical Physics, The Christie, Manchester (United Kingdom)
  2. School of Cancer and Enabling Sciences, University of Manchester, Manchester (United Kingdom)
  3. Department of Radiology, The Christie, Manchester (United Kingdom)
  4. (United Kingdom)
  5. Department of Clinical Oncology, The Christie, Manchester (United Kingdom)
  6. School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester (United Kingdom)
  7. School of Cancer and Enabling Sciences, University of Manchester, Manchester (United Kindgom) and Division of Medical Physics, University of Leeds, Leeds (United Kingdom)
Publication Date:
OSTI Identifier:
22054455
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 81; Journal Issue: 4; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; CARCINOMAS; GROWTH FACTORS; HEAD; INTRAVENOUS INJECTION; NECK; NMR IMAGING; PATIENTS; PERMEABILITY; POLYMERASE CHAIN REACTION; SURFACE AREA; SURGERY

Citation Formats

Donaldson, Stephanie B., E-mail: Stephanie.donaldson@physics.cr.man.ac.uk, Betts, Guy, Bonington, Suzanne C., Homer, Jarrod J., Department of Otolaryngology-Head-and-Neck Surgery, Manchester Royal Infirmary, Manchester, Slevin, Nick J., Kershaw, Lucy E., Valentine, Helen, West, Catharine M.L., and Buckley, David L.. Perfusion Estimated With Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely With Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study. United States: N. p., 2011. Web. doi:10.1016/J.IJROBP.2010.09.039.
Donaldson, Stephanie B., E-mail: Stephanie.donaldson@physics.cr.man.ac.uk, Betts, Guy, Bonington, Suzanne C., Homer, Jarrod J., Department of Otolaryngology-Head-and-Neck Surgery, Manchester Royal Infirmary, Manchester, Slevin, Nick J., Kershaw, Lucy E., Valentine, Helen, West, Catharine M.L., & Buckley, David L.. Perfusion Estimated With Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely With Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study. United States. doi:10.1016/J.IJROBP.2010.09.039.
Donaldson, Stephanie B., E-mail: Stephanie.donaldson@physics.cr.man.ac.uk, Betts, Guy, Bonington, Suzanne C., Homer, Jarrod J., Department of Otolaryngology-Head-and-Neck Surgery, Manchester Royal Infirmary, Manchester, Slevin, Nick J., Kershaw, Lucy E., Valentine, Helen, West, Catharine M.L., and Buckley, David L.. Tue . "Perfusion Estimated With Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely With Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study". United States. doi:10.1016/J.IJROBP.2010.09.039.
@article{osti_22054455,
title = {Perfusion Estimated With Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely With Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study},
author = {Donaldson, Stephanie B., E-mail: Stephanie.donaldson@physics.cr.man.ac.uk and Betts, Guy and Bonington, Suzanne C. and Homer, Jarrod J. and Department of Otolaryngology-Head-and-Neck Surgery, Manchester Royal Infirmary, Manchester and Slevin, Nick J. and Kershaw, Lucy E. and Valentine, Helen and West, Catharine M.L. and Buckley, David L.},
abstractNote = {Purpose: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. Methods and Materials: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. Results: Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02). Conclusions: Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.},
doi = {10.1016/J.IJROBP.2010.09.039},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 81,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2011},
month = {Tue Nov 15 00:00:00 EST 2011}
}
  • Purpose: Hypoxia in patients with head-and-neck cancer (HNC) is well established and known to cause radiation resistance and treatment failure in the management of HNC. This study examines the role of parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) as surrogate markers of intratumoral hypoxia, defined by using the exogenous marker of hypoxia pimonidazole and the endogenous marker carbonic anhydrase 9 (CA9). Methods and Materials: Patients with HNC underwent preoperative DCE-MRI, perfusion CT, and pimonidazole infusion. Imaging parameters were correlated with pimonidazole and CA9 staining. The strength of correlations was tested by using amore » two-tailed Spearman's rank correlation coefficient. Results: Twenty-three regions of interest were analyzed from the 7 patients who completed the DCE-MRI studies. A number of statistically significant correlations were seen between DCE-MRI parameters (volume transfer between blood plasma and extracellular extravascular space [EES], volume of EES, rate constant between EES and blood plasma, time at arrival of contrast inflow, time to peak, average gradient, and time to onset) and areas with a pimonidazole score of 4. In the case of CA9 staining, only a weak correlation was shown with wash-in rate. There were no significant correlations between perfusion CT parameters and pimonidazole staining or CA9 expression. Conclusion: Intratumoral hypoxia in patients with HNC may be predicted by using DCE-MRI; however, perfusion CT requires further investigation.« less
  • Purpose: To correlate proton magnetic resonance spectroscopy ({sup 1}H-MRS), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and {sup 18}F-labeled fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG PET) of nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging was evaluated for its efficacy in predicting short-term response to treatment. Methods and Materials: Metastatic neck nodes were imaged with {sup 1}H-MRS, DCE-MRI, and [{sup 18}F]FDG PET in 16 patients with newly diagnosed HNSCC, before treatment. Short-term patient radiological response was evaluated at 3 to 4 months. Correlations among {sup 1}H-MRS (choline concentrationmore » relative to water [Cho/W]), DCE-MRI (volume transfer constant [K{sup trans}]; volume fraction of the extravascular extracellular space [v{sub e}]; and redistribution rate constant [k{sub ep}]), and [{sup 18}F]FDG PET (standard uptake value [SUV] and total lesion glycolysis [TLG]) were calculated using nonparametric Spearman rank correlation. To predict short-term responses, logistic regression analysis was performed. Results: A significant positive correlation was found between Cho/W and TLG ({rho} = 0.599; p = 0.031). Cho/W correlated negatively with heterogeneity measures of standard deviation std(v{sub e}) ({rho} = -0.691; p = 0.004) and std(k{sub ep}) ({rho} = -0.704; p = 0.003). Maximum SUV (SUVmax) values correlated strongly with MRI tumor volume ({rho} = 0.643; p = 0.007). Logistic regression indicated that std(K{sup trans}) and SUVmean were significant predictors of short-term response (p < 0.07). Conclusion: Pretreatment multimodality imaging using {sup 1}H-MRS, DCE-MRI, and [{sup 18}F]FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and [{sup 18}F]FDG PET parameters were predictive of short-term response to treatment.« less
  • Purpose: To generate a population-averaged arterial input function (PA-AIF) for quantitative analysis of dynamic contrast-enhanced MRI data in head and neck cancer patients. Methods and Materials: Twenty patients underwent dynamic contrast-enhanced MRI during concurrent chemoradiation therapy. Imaging consisted of 2 baseline scans 1 week apart (B1/B2) and 1 scan after 1 week of chemoradiation therapy (Wk1). Regions of interest (ROIs) in the right and left carotid arteries were drawn on coronal images. Plasma concentration curves of all ROIs were averaged and fit to a biexponential decay function to obtain the final PA-AIF (AvgAll). Right-sided and left-sided ROI plasma concentration curves were averagedmore » separately to obtain side-specific AIFs (AvgRight/AvgLeft). Regions of interest were divided by time point to obtain time-point-specific AIFs (AvgB1/AvgB2/AvgWk1). The vascular transfer constant (K{sub trans}) and the fractional extravascular, extracellular space volume (V{sub e}) for primaries and nodes were calculated using the AvgAll AIF, the appropriate side-specific AIF, and the appropriate time-point-specific AIF. Median K{sub trans} and V{sub e} values derived from AvgAll were compared with those obtained from the side-specific and time-point-specific AIFs. The effect of using individual AIFs was also investigated. Results: The plasma parameters for AvgAll were a{sub 1,2} = 27.11/17.65 kg/L, m{sub 1,2} = 11.75/0.21 min{sup −1}. The coefficients of repeatability (CRs) for AvgAll versus AvgLeft were 0.04 min{sup −1} for K{sub trans} and 0.02 for V{sub e}. For AvgAll versus AvgRight, the CRs were 0.08 min{sup −1} for K{sub trans} and 0.02 for V{sub e}. When AvgAll was compared with AvgB1/AvgB2/AvgWk1, the CRs were slightly higher: 0.32/0.19/0.78 min{sup −1}, respectively, for K{sub trans}; and 0.07/0.08/0.09 for V{sub e}. Use of a PA-AIF was not significantly different from use of individual AIFs. Conclusion: A PA-AIF for head and neck cancer was generated that accounts for differences in right carotid artery versus left carotid artery, day-to-day fluctuations, and early treatment-induced changes. The small CRs obtained for K{sub trans} and V{sub e} indicate that side-specific AIFs are not necessary. However, a time-point-specific AIF may improve pharmacokinetic accuracy.« less
  • Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. Methods and Materials: Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters weremore » related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables. Results: At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. K{sup trans} is volume transfer constant. In a stepwise Cox regression, skewness of K{sup trans} (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p <0.001). Conclusion: Our study shows that skewness of K{sup trans} was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter K{sup trans} as a predictor of outcome in these patients.« less
  • Purpose: To compare pretreatment scans with perfusion computed tomography (pCT) vs. dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rectal tumors. Methods and Materials: Nineteen patients diagnosed with rectal cancer were included in this prospective study. All patients underwent both pCT and DCE-MRI. Imaging was performed on a dedicated 40-slice CT-positron emission tomography system and a 3-T MRI system. Dynamic contrast enhancement was measured in tumor tissue and the external iliac artery. Tumor perfusion was quantified in terms of pharmacokinetic parameters: transfer constant K{sup trans}, fractional extravascular-extracellular space v{sub e}, and fractional plasma volume v{sub p}. Pharmacokinetic parameter values and theirmore » heterogeneity (by 80% quantile value) were compared between pCT and DCE-MRI. Results: Tumor K{sup trans} values correlated significantly for the voxel-by-voxel-derived median (Kendall's tau correlation, tau = 0.81, p < 0.001) and 80% quantile (tau = 0.54, p = 0.04), as well as for the averaged uptake (tau = 0.58, p = 0.03). However, no significant correlations were found for v{sub e} and v{sub p} derived from the voxel-by-voxel-derived median and 80% quantile and derived from the averaged uptake curves. Conclusions: This study demonstrated for the first time that pCT provides K{sup trans} values comparable to those of DCE-MRI. However, no correlation was found for the v{sub e} and v{sub p} parameters between CT and MRI. Computed tomography can serve as an alternative modality to MRI for the in vivo evaluation of tumor angiogenesis in terms of the transfer constant K{sup trans}.« less