Preoperative dynamic contrast-enhanced MRI correlates with molecular markers of hypoxia and vascularity in specific areas of intratumoral microenvironment and is predictive of patient outcome

Randy L. Jensen, Michael L. Mumert, David L. Gillespie, Anita Y. Kinney, Matthias Schabel, Karen L. Salzman

Research output: Contribution to journalArticle

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Abstract

BackgroundMeasures of tumor vascularity and hypoxia have been correlated with glioma grade and outcome. Dynamic contrast-enhanced (DCE) MRI can noninvasively map tumor blood flow, vascularity, and permeability. In this prospective observational cohort pilot study, preoperative imaging was correlated with molecular markers of hypoxia, vascularity, proliferation, and progression-free and overall patient survival.MethodsPharmacokinetic modeling methods were used to generate maps of tumor blood flow, extraction fraction, permeability-surface area product, transfer constant, washout rate, interstitial volume, blood volume, capillary transit time, and capillary heterogeneity from preoperative DCE-MRI data in human glioma patients. Tissue was obtained from areas of peritumoral edema, active tumor, hypoxic penumbra, and necrotic core and evaluated for vascularity, proliferation, and expression of hypoxia-regulated molecules. DCE-MRI parameter values were correlated with hypoxia-regulated protein expression at tissue sample sites.ResultsPatient survival correlated with DCE parameters in 2 cases: capillary heterogeneity in active tumor and interstitial volume in areas of peritumoral edema. Statistically significant correlations were observed between several DCE parameters and tissue markers. In addition, MIB-1 index was predictive of overall survival (P =. 044) and correlated with vascular endothelial growth factor expression in hypoxic penumbra (r = 0.7933, P =. 0071) and peritumoral edema (r = 0.4546). Increased microvessel density correlated with worse patient outcome (P =. 026).ConclusionsOur findings suggest that DCE-MRI may facilitate noninvasive preoperative predictions of areas of tumor with increased hypoxia and proliferation. Both imaging and hypoxia biomarkers are predictive of patient outcome. This has the potential to allow unprecedented prognostic decisions and to guide therapies to specific tumor areas.

Original languageEnglish (US)
Pages (from-to)280-291
Number of pages12
JournalNeuro-Oncology
Volume16
Issue number2
DOIs
StatePublished - Jan 2014

Fingerprint

Edema
Neoplasms
Glioma
Survival
Permeability
Microvessels
Blood Volume
Tumor Burden
Vascular Endothelial Growth Factor A
Cohort Studies
Biomarkers
Hypoxia
Proteins
Therapeutics
Tumor Hypoxia

Keywords

  • DCE-MRI
  • HIF-1
  • hypoxia
  • vascularity
  • VEGF

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Preoperative dynamic contrast-enhanced MRI correlates with molecular markers of hypoxia and vascularity in specific areas of intratumoral microenvironment and is predictive of patient outcome. / Jensen, Randy L.; Mumert, Michael L.; Gillespie, David L.; Kinney, Anita Y.; Schabel, Matthias; Salzman, Karen L.

In: Neuro-Oncology, Vol. 16, No. 2, 01.2014, p. 280-291.

Research output: Contribution to journalArticle

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abstract = "BackgroundMeasures of tumor vascularity and hypoxia have been correlated with glioma grade and outcome. Dynamic contrast-enhanced (DCE) MRI can noninvasively map tumor blood flow, vascularity, and permeability. In this prospective observational cohort pilot study, preoperative imaging was correlated with molecular markers of hypoxia, vascularity, proliferation, and progression-free and overall patient survival.MethodsPharmacokinetic modeling methods were used to generate maps of tumor blood flow, extraction fraction, permeability-surface area product, transfer constant, washout rate, interstitial volume, blood volume, capillary transit time, and capillary heterogeneity from preoperative DCE-MRI data in human glioma patients. Tissue was obtained from areas of peritumoral edema, active tumor, hypoxic penumbra, and necrotic core and evaluated for vascularity, proliferation, and expression of hypoxia-regulated molecules. DCE-MRI parameter values were correlated with hypoxia-regulated protein expression at tissue sample sites.ResultsPatient survival correlated with DCE parameters in 2 cases: capillary heterogeneity in active tumor and interstitial volume in areas of peritumoral edema. Statistically significant correlations were observed between several DCE parameters and tissue markers. In addition, MIB-1 index was predictive of overall survival (P =. 044) and correlated with vascular endothelial growth factor expression in hypoxic penumbra (r = 0.7933, P =. 0071) and peritumoral edema (r = 0.4546). Increased microvessel density correlated with worse patient outcome (P =. 026).ConclusionsOur findings suggest that DCE-MRI may facilitate noninvasive preoperative predictions of areas of tumor with increased hypoxia and proliferation. Both imaging and hypoxia biomarkers are predictive of patient outcome. This has the potential to allow unprecedented prognostic decisions and to guide therapies to specific tumor areas.",
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T1 - Preoperative dynamic contrast-enhanced MRI correlates with molecular markers of hypoxia and vascularity in specific areas of intratumoral microenvironment and is predictive of patient outcome

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AU - Mumert, Michael L.

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N2 - BackgroundMeasures of tumor vascularity and hypoxia have been correlated with glioma grade and outcome. Dynamic contrast-enhanced (DCE) MRI can noninvasively map tumor blood flow, vascularity, and permeability. In this prospective observational cohort pilot study, preoperative imaging was correlated with molecular markers of hypoxia, vascularity, proliferation, and progression-free and overall patient survival.MethodsPharmacokinetic modeling methods were used to generate maps of tumor blood flow, extraction fraction, permeability-surface area product, transfer constant, washout rate, interstitial volume, blood volume, capillary transit time, and capillary heterogeneity from preoperative DCE-MRI data in human glioma patients. Tissue was obtained from areas of peritumoral edema, active tumor, hypoxic penumbra, and necrotic core and evaluated for vascularity, proliferation, and expression of hypoxia-regulated molecules. DCE-MRI parameter values were correlated with hypoxia-regulated protein expression at tissue sample sites.ResultsPatient survival correlated with DCE parameters in 2 cases: capillary heterogeneity in active tumor and interstitial volume in areas of peritumoral edema. Statistically significant correlations were observed between several DCE parameters and tissue markers. In addition, MIB-1 index was predictive of overall survival (P =. 044) and correlated with vascular endothelial growth factor expression in hypoxic penumbra (r = 0.7933, P =. 0071) and peritumoral edema (r = 0.4546). Increased microvessel density correlated with worse patient outcome (P =. 026).ConclusionsOur findings suggest that DCE-MRI may facilitate noninvasive preoperative predictions of areas of tumor with increased hypoxia and proliferation. Both imaging and hypoxia biomarkers are predictive of patient outcome. This has the potential to allow unprecedented prognostic decisions and to guide therapies to specific tumor areas.

AB - BackgroundMeasures of tumor vascularity and hypoxia have been correlated with glioma grade and outcome. Dynamic contrast-enhanced (DCE) MRI can noninvasively map tumor blood flow, vascularity, and permeability. In this prospective observational cohort pilot study, preoperative imaging was correlated with molecular markers of hypoxia, vascularity, proliferation, and progression-free and overall patient survival.MethodsPharmacokinetic modeling methods were used to generate maps of tumor blood flow, extraction fraction, permeability-surface area product, transfer constant, washout rate, interstitial volume, blood volume, capillary transit time, and capillary heterogeneity from preoperative DCE-MRI data in human glioma patients. Tissue was obtained from areas of peritumoral edema, active tumor, hypoxic penumbra, and necrotic core and evaluated for vascularity, proliferation, and expression of hypoxia-regulated molecules. DCE-MRI parameter values were correlated with hypoxia-regulated protein expression at tissue sample sites.ResultsPatient survival correlated with DCE parameters in 2 cases: capillary heterogeneity in active tumor and interstitial volume in areas of peritumoral edema. Statistically significant correlations were observed between several DCE parameters and tissue markers. In addition, MIB-1 index was predictive of overall survival (P =. 044) and correlated with vascular endothelial growth factor expression in hypoxic penumbra (r = 0.7933, P =. 0071) and peritumoral edema (r = 0.4546). Increased microvessel density correlated with worse patient outcome (P =. 026).ConclusionsOur findings suggest that DCE-MRI may facilitate noninvasive preoperative predictions of areas of tumor with increased hypoxia and proliferation. Both imaging and hypoxia biomarkers are predictive of patient outcome. This has the potential to allow unprecedented prognostic decisions and to guide therapies to specific tumor areas.

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