T1 based oxygen-enhanced MRI in tumours; a scoping review of current research

Abstract

Objective: Oxygen-enhanced MRI (OE-MRI) or tissue oxygen-level dependent (TOLD) MRI is an imaging technique under investigation for its ability to quantify and map oxygen distributions within tumours. The aim of this study was to identify and characterise the research into OE-MRI for characterising hypoxia in solid tumours.

Methods: A scoping review of published literature was performed on the PubMed and Web of Science databases for articles published before 27 May 2022. Studies imaging solid tumours using proton-MRI to measure oxygen-induced T₁/R₁ relaxation time/rate changes were included. Grey literature was searched from conference abstracts and active clinical trials.

Results: 49 unique records met the inclusion criteria consisting of 34 journal articles and 15 conference abstracts. The majority of articles were pre-clinical studies (31 articles) with 15 human only studies. Pre-clinical studies in a range of tumour types demonstrated consistent correlation of OE-MRI with alternative hypoxia measurements. No clear consensus on optimal acquisition technique or analysis methodology was found. No prospective, adequately powered, multicentre clinical studies relating OE-MRI hypoxia markers to patient outcomes were identified.

Conclusion: There is good pre-clinical evidence of the utility of OE-MRI in tumour hypoxia assessment; however, there are significant gaps in clinical research that need to be addressed to develop OE-MRI into a clinically applicable tumour hypoxia imaging technique.

Advances in knowledge: The evidence base of OE-MRI in tumour hypoxia assessment is presented along with a summary of the research gaps to be addressed to transform OE-MRI derived parameters into tumour hypoxia biomarkers.

Figure 1.

Example images from a patient with head and neck squamous cell carcinoma illustrating the difference between conventional T ₁ weighted imaging, quantitative T ₁ mapping and oxygen induced quantitative ΔT ₁ maps. (A) T ₁ weighted anatomical image (3D SPGR, TR/TE = 10/1.27 ms, FA = 18°). (B) Corresponding quantitative T ₁ map derived using the variable flip angle methodology from image A and a corresponding proton density weighted image (not shown, acquired with same parameters but FA = 2°). (C) Oxygen induced ΔT ₁ map obtained following a supplemental oxygen challenge administered using 15 L/min oxygen via a non-rebreather mask. Within the highlighted malignant nodal mass, regions of oxygen induced T ₁ shortening implying normoxia are clearly seen. Distinct oxygen refractory regions are also identifiable which imply either hypoxic or non-perfused areas. FA, flip angle; TE, echo time; TR, repetition time.

Figure 2.

Flowchart showing the results of the search strategy.

Figure 3.

Histogram of publication year for journal article articles and conference abstracts identified in the search.