Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI

O’Connor, James P.B.; Robinson, Simon P.; Waterton, John C.

doi:10.1259/bjr.20180642

Cited by 133 publications

(138 citation statements)

References 94 publications

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“…However, the spatial resolution associated with PET imaging is low compared to the size of the hypoxic regions that can be found in tumor tissue [5]. Magnetic resonance imaging (MRI) techniques, including blood oxygen level dependent MRI (BOLD-MRI), tissue oxygen level dependent MRI (TOLD-MRI), oxygen-enhanced MRI (OE-MRI), and dynamic contrast-enhanced MRI (DCE-MRI), have also been applied to study tumor hypoxia [4,5,7,8]. MRI can be performed with substantially higher spatial resolution than PET imaging, and DCE-MRI is highly attractive because the technique is associated with a high signal to noise ratio and is routinely used to detect and characterize various types of cancer in the clinic.…”

Section: Introductionmentioning

confidence: 99%

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

Gaustad

Hauge

Wegner

et al. 2020

Cancers

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Tumor hypoxia is associated with resistance to treatment, aggressive growth, metastatic dissemination, and poor clinical outcome in many cancer types. The potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess the extent of hypoxia in tumors has been investigated in several studies in our laboratory. Cervical carcinoma, melanoma, and pancreatic ductal adenocarcinoma (PDAC) xenografts have been used as models of human cancer, and the transfer rate constant (Ktrans) and the extravascular extracellular volume fraction (ve) have been derived from DCE-MRI data by using Tofts standard pharmacokinetic model and a population-based arterial input function. Ktrans was found to reflect naturally occurring and treatment-induced hypoxia when hypoxia was caused by low blood perfusion, radiation responsiveness when radiation resistance was due to hypoxia, and metastatic potential when metastasis was hypoxia-induced. Ktrans was also associated with outcome for patients with locally-advanced cervical carcinoma treated with cisplatin-based chemoradiotherapy. Together, the studies imply that DCE-MRI can provide valuable information on the hypoxic status of cervical carcinoma, melanoma, and PDAC. In this communication, we review and discuss the studies and provide some recommendations as to how DCE-MRI data can be analyzed and interpreted to assess tumor hypoxia.

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Section: Introductionmentioning

confidence: 99%

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

Gaustad

Hauge

Wegner

et al. 2020

Cancers

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“…This suggested that when planning the combination therapy of radiation and evofosfamide, decreasing frequency of evofosfamide treatment may decrease the systemic toxicity without compromising the treatment effect. With methodologies to provide quantitative assessment of tumor oxygen with T1-weighted MRI on conventional clinical scanners implemented on human subjects 37,38 , such strategies will play a key role in tailoring therapies with evofosfamide and in combination with antiproliferative therapies such as conventional chemotherapy or radiation therapy.…”

Section: Resultsmentioning

confidence: 99%

Reoxygenation after Evofosfamide Treatment in Pancreatic Ductal Adenocarcinoma Xenografts is due to Decreased Oxygen Consumption and not Increased Oxygen Supply

Kishimoto

Brender

Saida

et al. 2020

Preprint

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Evofosfamide is designed to release a cytotoxic bromo-isophosphoramide (Br-IPM) moiety in a hypoxic microenvironment. This drug therefore preferentially attacks hypoxic regions in tumors where other standard anti-cancer treatments such as chemotherapy and radiation therapy are often ineffective. Various combination therapies with evofosfamide have been proposed and tested in preclinical and clinical settings. However, the treatment effect of evofosfamide monotherapy on tumor hypoxia has not been fully understood, partly due to the lack of quantitative methods to assess tumor pO2 in vivo. Here, we use quantitative pO2 imaging by EPR to evaluate the change in tumor hypoxia in response to evofosfamide treatment using two pancreatic ductal adenocarcinoma xenograft models; MIA Paca-2 tumors responding to evofosfamide and Su.86.86 tumors which do not respond. EPR imaging showed oxygenation improved globally after evofosfamide treatment in hypoxic MIA Paca-2 tumors, in agreement with the ex vivo results obtained from hypoxia staining by pimonidazole and in apparent contrast to the decrease in Ktrans observed in DCE MRI. This suggests reoxygenation after treatment is due to decreased oxygen demand rather than improved prefusion. Following the change in pO2 after treatment may therefore yield a way of monitoring treatment response. The observation that evofosfamide not only kills the hypoxic region of the tumor but also improves oxygenation in the residual tumor regions provides a rationale for combination therapies using radiation and anti-proliferatives post evofosfamide for improved outcomes.

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“…In the body, oxygen affects MR contrast by acting as a paramagnetic relaxation agent thus shortening the T1 relaxation time, one of the principal sources of image contrast in MRI [18]. Perfused tumours contain a much higher concentration of oxygen than non-perfused tumours, and that oxygen causes a shortening in T1 relaxation in the tumour tissue [19][20][21]. The partial pressure of oxygen within the tumour cannot be determined from the T1 alone however.…”

Section: Introductionmentioning

confidence: 99%

“…One method of using this effect to infer perfusion levels is by inducing arterial hyperoxia to further shorten T1 of arterial blood and well-perfused tissues by breathing an increased inspired fraction of oxygen [18,22,23]. By acquiring a quantitative map of T1 values in each voxel (known as a ''T1 map") under normal conditions, and then performing the scan a second time while the patient is breathing an increased inspired fraction of oxygen via a face mask, the change in T1 between the air and oxygen T1 maps provides information about both the arterial blood volume in, and perfusion of the tumour [19]. It is by this mechanism that the changes in T1 from this oxygen-enhanced MRI could potentially differentiate perfused tumours from tumours with poor vascularity or hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma

Bluemke

Bulte

Bertrand

et al. 2020

Clinical and Translational Radiation Oncology

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a b s t r a c tBackground and purpose: Oxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma. Materials and methods: T2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8-10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy. A mean T1 was extracted from manually segmented tumour regions of interest and a paired two-tailed t-test was used to compare changes across the patient population. Regions of subcutaneous fat and muscle tissue were examined as control ROIs. Results: There was a significant increase in T1 of the tumour ROIs across patients following the 8-10 fractions of chemoradiotherapy (paired t-test, p < 0.001, n = 7). At baseline, prior to receiving chemoradiotherapy, there were no significant changes in T1 across patients from breathing oxygen (n = 9). In the post-chemoRT scans (8-10 fractions), there was a significant decrease in T1 of the tumour ROIs across patients when breathing 100% oxygen (paired t-test, p < 0.001, n = 8). Out of the 12 patients from which we successfully acquired a visit 1 T1-map, only 1 patient did not respond to treatment, therefore, we cannot correlate these results with clinical outcome. Conclusions: These clinical data demonstrate feasibility and potential for T1-mapping and oxygen enhanced T1-mapping to indicate perfusion or treatment response in tumours of this nature. These data show promise for future work with a larger cohort containing more non-responders, which would allow us to relate these measurements to clinical outcome.

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Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI

Cited by 133 publications

References 94 publications

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

Reoxygenation after Evofosfamide Treatment in Pancreatic Ductal Adenocarcinoma Xenografts is due to Decreased Oxygen Consumption and not Increased Oxygen Supply

Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma

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