Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma

Bluemke, Emma; Bertrand, Ambre; Chu, Kwun-Ye; Syed, Nigar; Murchison, Andrew G.; Cooke, Rosie; Greenhalgh, Tessa; Burns, Brian; Craig, Martin; Taylor, Nia; Shah, Ketan; Gleeson, Fergus; Bulte, Daniel P.

doi:10.1016/j.ctro.2022.100563

Cited by 3 publications

(4 citation statements)

References 56 publications

(113 reference statements)

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“…Although our study and the previous two studies all used volumetric acquisitions, the 3-T study by Bluemke et al [ 38 ] made single T1 measurements before and after oxygen to determine tumour Δ R 1 rates whereas our study and that of the previous 1.5-T study by Dubec et al [ 37 ] used dynamic acquisitions with multiple T1 measurement time points before and after oxygen administration. These dynamic measurements allow voxel-wise oxygen-induced ΔT1/Δ R 1 maps to be produced following image coregistration to control for participant motion.…”

Section: Discussionmentioning

confidence: 98%

“…All 15 primary tumours in the current study showed statistically significant shortening of VOI median ΔT1 times mirroring the observed oxygen-induced prolongation of all VOI averaged ΔR 1 rates in the previous 1.5-T study [ 37 ]. In contrast, a study at 3-T in five patients with oropharyngeal cancers reported tumour Δ R 1 rates ranging from -0.001 to 0.108/s with two of the mean baseline R 1 rates failing to show statistically significant change with oxygen [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…These dynamic measurements allow voxel-wise oxygen-induced ΔT1/Δ R 1 maps to be produced following image coregistration to control for participant motion. Bluemke et al [ 38 ] acknowledge that patient motion was a significant difficulty encountered in their study and focus their OE-MRI analysis on describing oxygen-induced changes to tumour region of interest R 1 histograms. We feel that dynamic OE-MRI acquisitions with appropriate image registration allow greater characterisation of tumour oxygenation status; however, standardisation of imaging parameters and data processing approaches is clearly required for ready comparison of OE-MRI studies [ 39 ] as has been developed in other quantitative MRI techniques [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

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Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

McCabe,

Martin,

Rowe

et al. 2024

Eur Radiol Exp

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Background Tumour 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. Methods A 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. Results Fifteen 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). Conclusions We 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 registration ClinicalTrials.gov, NCT04724096. Registered on 26 January 2021. Relevance statement MRI 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. Graphical Abstract

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

McCabe,

Martin,

Rowe

et al. 2024

Eur Radiol Exp

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“…OE-MRI has also been utilized to identify hypoxic changes between fractionated radiotherapy in many different histologic types of tumors, including brain metastasis [ 186 ], HNSCCs [ 187 ], NSCLC [ 188 ], renal cell carcinoma (RCC) [ 189 ], glioblastoma [ 190 ] and hepatocellular carcinoma [ 191 ]. This has led to the development of a hybrid MRI-radiotherapy linear accelerator (MR Linac) system, which was validated in human subjects [ 97 ].…”

Section: Imaging Hypoxia In Cancermentioning

confidence: 99%

Functional Imaging of Hypoxia: PET and MRI

Perez

Kim

Maxwell

et al. 2023

Cancers

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Molecular and functional imaging have critical roles in cancer care. Existing evidence suggests that noninvasive detection of hypoxia within a particular type of cancer can provide new information regarding the relationship between hypoxia, cancer aggressiveness and altered therapeutic responses. Following the identification of hypoxia inducible factor (HIF), significant progress in understanding the regulation of hypoxia-induced genes has been made. These advances have provided the ability to therapeutically target HIF and tumor-associated hypoxia. Therefore, by utilizing the molecular basis of hypoxia, hypoxia-based theranostic strategies are in the process of being developed which will further personalize care for cancer patients. The aim of this review is to provide an overview of the significance of tumor hypoxia and its relevance in cancer management as well as to lay out the role of imaging in detecting hypoxia within the context of cancer.

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Optimization and validation of low‐field MP2RAGE T₁ mapping on 0.35T MR‐Linac: Toward adaptive dose painting with hypoxia biomarkers

Park,

Warner,

Kaza

et al. 2024

Medical Physics

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BackgroundStereotactic MR‐guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low‐field MR‐Linac faces substantial challenges due to dramatically lower signal‐to‐noise ratio (SNR) characteristics. While quantitative MRI and T1 mapping of hypoxia biomarkers show promise, T1‐to‐noise ratio (T1NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen‐enhanced (OE)‐MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T1‐weighted contrast images with simultaneous T1 mapping.PurposeTo optimize MP2RAGE for low‐field T1 mapping; conduct experimental validation in a ground‐truth phantom; establish feasibility and reproducibility of low‐field MP2RAGE acquisition and T1 mapping in healthy volunteers.MethodsThe MP2RAGE optimization was performed to maximize the contrast‐to‐noise ratio (CNR) of T1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low‐field MP2RAGE images were acquired on a 0.35T MR‐Linac (ViewRay MRIdian) using a multi‐channel head coil. Validation of T1 mapping was performed with a ground‐truth Eurospin phantom, containing inserts of known T1 values (400–850 ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T1 maps. Mean (± SD) T1 relative error, T1NR, and intersession coefficient of variation (CV) were determined. Whole‐brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T1 maps were generated. Mean (± SD) T1 values for WM and GM were determined. Whole‐brain T1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel‐by‐voxel T1 difference maps were generated to evaluate 3D spatial variation.ResultsLow‐field MP2RAGE optimization resulted in parameters: MP2RAGETR of 3250 ms, inversion times (TI1/TI2) of 500/1200 ms, and flip angles (α1/α2) of 7/5°. Eurospin T1 maps exhibited a mean (± SD) relative error of 3.45% ± 1.30%, T1NR of 20.13 ± 5.31, and CV of 2.22% ± 0.67% across all inserts. Whole‐brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (± SD) T1 values: 435.36 ± 10.01 ms for WM and 623.29 ± 14.64 ms for GM across subjects, showing excellent concordance with literature. Whole‐brain T1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel‐level WM and GM T1 values. Reproducibility analysis revealed a CV of 0.46% ± 0.31% and 0.35% ± 0.18% for WM and GM, respectively. Voxel‐by‐voxel T1 difference maps show a normal 3D spatial distribution of noise in WM and GM.ConclusionsLow‐field MP2RAGE proved effective in generating accurate, reliable, and reproducible T1 maps with high T1NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE‐MRI, this study establishes a foundation for TOLD T1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR‐guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging‐to‐treat cancers.

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Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma

Cited by 3 publications

References 56 publications

Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

Functional Imaging of Hypoxia: PET and MRI

Optimization and validation of low‐field MP2RAGE T₁ mapping on 0.35T MR‐Linac: Toward adaptive dose painting with hypoxia biomarkers

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Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma

Cited by 3 publications

References 56 publications

Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

Functional Imaging of Hypoxia: PET and MRI

Optimization and validation of low‐field MP2RAGE T1 mapping on 0.35T MR‐Linac: Toward adaptive dose painting with hypoxia biomarkers

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Product

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Optimization and validation of low‐field MP2RAGE T₁ mapping on 0.35T MR‐Linac: Toward adaptive dose painting with hypoxia biomarkers