Dataset Information

Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models.

ABSTRACT: There is a clinical need for noninvasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning, and therapy monitoring. Oxygen-enhanced MRI (OE-MRI) is an emerging imaging technique for quantifying the spatial distribution and extent of tumor oxygen delivery in vivo. In OE-MRI, the longitudinal relaxation rate of protons (?R1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive ?R1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive ?R1, termed "Oxy-R fraction") would be a robust biomarker of hypoxia in models with varying vascular and hypoxic features. Here, we demonstrate that OE-MRI signals are accurate, precise, and sensitive to changes in tumor pO2 in highly vascular 786-0 renal cancer xenografts. Furthermore, we show that Oxy-R fraction can quantify the hypoxic fraction in multiple models with differing hypoxic and vascular phenotypes, when used in combination with measurements of tumor perfusion. Finally, Oxy-R fraction can detect dynamic changes in hypoxia induced by the vasomodulator agent hydralazine. In contrast, more conventional biomarkers of hypoxia (derived from blood oxygenation-level dependent MRI and dynamic contrast-enhanced MRI) did not relate to tumor hypoxia consistently. Our results show that the Oxy-R fraction accurately quantifies tumor hypoxia noninvasively and is immediately translatable to the clinic.

SUBMITTER: O'Connor JP

PROVIDER: S-EPMC4757751 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models.

O'Connor James P B JP Boult Jessica K R JK Jamin Yann Y Babur Muhammad M Finegan Katherine G KG Williams Kaye J KJ Little Ross A RA Jackson Alan A Parker Geoff J M GJ Reynolds Andrew R AR Waterton John C JC Robinson Simon P SP

Cancer research 20151209 4

There is a clinical need for noninvasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning, and therapy monitoring. Oxygen-enhanced MRI (OE-MRI) is an emerging imaging technique for quantifying the spatial distribution and extent of tumor oxygen delivery in vivo. In OE-MRI, the longitudinal relaxation rate of protons (ΔR1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygena ...[more]

PMID: 26659574

Similar Datasets

Project description:Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (?R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen. Native transverse relaxation rate (R2*) and oxygen-induced R2* change (?R2*) were measured, reflecting presence of deoxygenated hemoglobin molecules. Median and voxel-wise values of ?R1 were compared with values of R2* and ?R2*. Tumor regions with dynamic contrast agent-enhanced MRI perfusion, refractory to signal change at OE MRI (referred to as perfused Oxy-R), were distinguished from perfused oxygen-enhancing (perfused Oxy-E) and nonperfused regions. R2* and ?R2* values in each tumor subregion were compared by using one-way analysis of variance. Results Tumor-wise and voxel-wise ?R1 and ?R2* comparisons did not show correlative relationships. In xenografts, parcellation analysis revealed that perfused Oxy-R regions had faster native R2* (102.4 sec-1 vs 81.7 sec-1) and greater negative ?R2* (-22.9 sec-1 vs -5.4 sec-1), compared with perfused Oxy-E and nonperfused subregions (all P < .001), respectively. Similar findings were present in human tumors (P < .001). Further, perfused Oxy-R helped identify tumor hypoxia, measured at pathologic analysis, in both xenografts (P = .002) and human tumors (P = .003). Conclusion Intrinsic susceptibility biomarkers provide cross validation of the OE MRI biomarker perfused Oxy-R. Consistent relationship to pathologic analyses was found in xenografts and human tumors, demonstrating biomarker translation. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Project description:ObjectivesTo assess the feasibility of a CNN-based liver registration algorithm to generate difference maps for visual display of spatiotemporal changes in liver PDFF, without needing manual annotations.MethodsThis retrospective exploratory study included 25 patients with suspected or confirmed NAFLD, who underwent PDFF-MRI at two time points at our institution. PDFF difference maps were generated by applying a CNN-based liver registration algorithm, then subtracting follow-up from baseline PDFF maps. The difference maps were post-processed by smoothing (5 cm2 round kernel) and applying a categorical color scale. Two fellowship-trained abdominal radiologists and one radiology resident independently reviewed difference maps to visually determine segmental PDFF change. Their visual assessment was compared with manual ROI-based measurements of each Couinaud segment and whole liver PDFF using intraclass correlation (ICC) and Bland-Altman analysis. Inter-reader agreement for visual assessment was calculated (ICC).ResultsThe mean patient age was 49 years (12 males). Baseline and follow-up PDFF ranged from 2.0 to 35.3% and 3.5 to 32.0%, respectively. PDFF changes ranged from - 20.4 to 14.1%. ICCs against the manual reference exceeded 0.95 for each reader, except for segment 2 (2 readers ICC = 0.86-0.91) and segment 4a (reader 3 ICC = 0.94). Bland-Altman limits of agreement were within 5% across all three readers. Inter-reader agreement for visually assessed PDFF change (whole liver and segmental) was excellent (ICCs > 0.96), except for segment 2 (ICC = 0.93).ConclusionsVisual assessment of liver segmental PDFF changes using a CNN-generated difference map strongly agreed with manual estimates performed by an expert reader and yielded high inter-reader agreement.Key points• Visual assessment of longitudinal changes in quantitative liver MRI can be performed using a CNN-generated difference map and yields strong agreement with manual estimates performed by expert readers.

Project description:BackgroundGlioblastoma (GBM) is the most aggressive type of brain cancer, with a 5-year survival rate of ~5% and most tumours recurring locally within months of first-line treatment. Hypoxia is associated with worse clinical outcomes in GBM, as it leads to localized resistance to radiotherapy and subsequent tumour recurrence. Current standard of care treatment does not account for tumour hypoxia, due to the challenges of mapping tumour hypoxia in routine clinical practice. In this clinical study, we aim to investigate the role of oxygen enhanced (OE) and blood-oxygen level dependent (BOLD) MRI as non-invasive imaging biomarkers of hypoxia in GBM, and to evaluate their potential role in dose-painting radiotherapy planning and treatment response assessment.MethodsThe primary endpoint is to evaluate the quantitative and spatial correlation between OE and BOLD MRI measurements and [18F]MISO values of uptake in the tumour. The secondary endpoints are to evaluate the repeatability of MRI biomarkers of hypoxia in a test-retest study, to estimate the potential clinical benefits of using MRI biomarkers of hypoxia to guide dose-painting radiotherapy, and to evaluate the ability of MRI biomarkers of hypoxia to assess treatment response. Twenty newly diagnosed GBM patients will be enrolled in this study. Patients will undergo standard of care treatment while receiving additional OE/BOLD MRI and [18F]MISO PET scans at several timepoints during treatment. The ability of OE/BOLD MRI to map hypoxic tumour regions will be evaluated by assessing spatial and quantitative correlations with areas of hypoxic tumour identified via [18F]MISO PET imaging.DiscussionMANGO (Magnetic resonance imaging of hypoxia for radiation treatment guidance in glioblastoma multiforme) is a diagnostic/prognostic study investigating the role of imaging biomarkers of hypoxia in GBM management. The study will generate a large amount of longitudinal multimodal MRI and PET imaging data that could be used to unveil dynamic changes in tumour physiology that currently limit treatment efficacy, thereby providing a means to develop more effective and personalised treatments.

Project description:BackgroundTumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Current positron emission tomography-based hypoxia imaging techniques are not routinely available in many centres. We investigated if an alternative technique called oxygen-enhanced magnetic resonance imaging (OE-MRI) could be performed in HNSCC.MethodsA volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was implemented on 1.5-T clinical scanners. Participants were scanned breathing room air and during high-flow oxygen administration. Oxygen-induced changes in T1 times (ΔT1) and R2* rates (ΔR2*) were measured in malignant tissue and healthy organs. Unequal variance t-test was used. Patients were surveyed on their experience of the OE-MRI protocol.ResultsFifteen patients with HNSCC (median age 59 years, range 38 to 76) and 10 non-HNSCC subjects (median age 46.5 years, range 32 to 62) were scanned; the OE-MRI acquisition took less than 10 min and was well tolerated. Fifteen histologically confirmed primary tumours and 41 malignant nodal masses were identified. Median (range) of ΔT1 times and hypoxic fraction estimates for primary tumours were -3.5% (-7.0 to -0.3%) and 30.7% (6.5 to 78.6%) respectively. Radiotherapy-responsive and radiotherapy-resistant primary tumours had mean estimated hypoxic fractions of 36.8% (95% confidence interval [CI] 17.4 to 56.2%) and 59.0% (95% CI 44.6 to 73.3%), respectively (p = 0.111).ConclusionsWe present a well-tolerated implementation of dynamic, volumetric OE-MRI of the head and neck region allowing discernment of differing oxygen responses within biopsy-confirmed HNSCC.Trial registrationClinicalTrials.gov, NCT04724096 . Registered on 26 January 2021.Relevance statementMRI of tumour hypoxia in head and neck cancer using routine clinical equipment is feasible and well tolerated and allows estimates of tumour hypoxic fractions in less than ten minutes.Key points• Oxygen-enhanced MRI (OE-MRI) can estimate tumour hypoxic fractions in ten-minute scanning. • OE-MRI may be incorporable into routine clinical tumour imaging. • OE-MRI has the potential to predict outcomes after radiotherapy treatment.

Project description:ObjectivesTo compare single parameter thresholding with multivariable probabilistic classification of ischemic stroke regions in the analysis of computed tomography perfusion (CTP) parameter maps.MethodsPatients were included from two multicenter trials and were divided into two groups based on their modified arterial occlusive lesion grade. CTP parameter maps were generated with three methods-a commercial method (ISP), block-circulant singular value decomposition (bSVD), and non-linear regression (NLR). Follow-up non-contrast CT defined the follow-up infarct region. Conventional thresholds for individual parameter maps were established with a receiver operating characteristic curve analysis. Probabilistic classification was carried out with a logistic regression model combining the available CTP parameters into a single probability.ResultsA total of 225 CTP data sets were included, divided into a group of 166 patients with successful recanalization and 59 with persistent occlusion. The precision and recall of the CTP parameters were lower individually than when combined into a probability. The median difference [interquartile range] in mL between the estimated and follow-up infarct volume was 29/23/23 [52/50/52] (ISP/bSVD/NLR) for conventional thresholding and was 4/6/11 [31/25/30] (ISP/bSVD/NLR) for the probabilistic classification.ConclusionsMultivariable probability maps outperform thresholded CTP parameter maps in estimating the infarct lesion as observed on follow-up non-contrast CT. A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions.Key points• Combining CTP parameters with a logistic regression model increases the precision and recall in estimating ischemic stroke regions. • Volumes following from a probabilistic analysis predict follow-up infarct volumes better than volumes following from a threshold-based analysis. • A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions.

Dataset Information

Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models.

Publications

Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets