Dynamic and simultaneous MR measurement of R₁ and R₂* changes during respiratory challenges for the assessment of blood and tissue oxygenation

Abstract

This work presents a novel method for the rapid and simultaneous measurement of R1 and R2* relaxation rates. It is based on a dynamic short repetition time steady-state spoiled multigradient-echo sequence and baseline R1 and B1 measurements. The accuracy of the approach was evaluated in simulations and a phantom experiment. The sensitivity and specificity of the method were demonstrated in one volunteer and in four patients with intracranial tumors during carbogen inhalation. We utilized (ΔR2*, ΔR1) scatter plots to analyze the multiparametric response amplitude of each voxel within an area of interest. In normal tissue R2* decreased and R1 increased moderately in response to the elevated blood and tissue oxygenation. A strong negative ΔR2* and ΔR1 response was observed in veins and some tumor areas. Moderate positive ΔR2* and ΔR1 response amplitudes were found in fluid-rich tissue as in cerebrospinal fluid, peritumoral edema, and necrotic areas. The multiparametric approach was shown to increase the specificity and sensitivity of oxygen-enhanced MRI compared to measuring ΔR2* or ΔR1 alone. It is thus expected to provide an optimal tool for the identification of tissue areas with low oxygenation, e.g., in tumors with compromised oxygen supply.

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

“…Several preliminary studies have already shown the use of hyperoxic gas challenge to stimulate BOLD and/or TOLD MRI signal responses in tumors at distinct disease sites (breast [56, 57], cervix [49, 58, 59], brain [38, 60], prostate [61], and liver [62]). Breathing oxygen is particularly appropriate, since this is standard intervention in emergency medicine and thus it is quite straightforward to gain IRB approval.…”

“…Notably, studies in human tumor xenografts in mice [32], as well as syngeneic tumors in rats [33, 34] and rabbits [35]. The two approaches have also been assessed in humans including volunteer patients [36–38]. …”

Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology

“…The relationship observed between oxygen-induced ∆R2* and oxygen-induced ∆R1 was weak and was not described fully by the open L-shaped model predicted by the literature (24,27). No relationship was observed between native R2* and oxygen-induced ∆R1.…”

“…Voxels with greater negative gas-induced ∆R2* showed a smaller positive ∆R1, consistent with both being biomarkers of hypoxia. However, the relationship between ∆R2* and ∆R1 appeared complex and was not explained simply by the bimodal relationship predicted by the open L-shaped curve (24,27) (Fig 1). …”

“…This finding suggests that OE MRI may have a translational benefit compared with R2*-based methods. Previous studies reported complex and nonlinear relationships between ∆R1 and ∆R2* in xenografts (22–26) or patient tumors (27) (Fig 1). However, to our knowledge, no cross-validation has been performed to evaluate whether perfused Oxy-R– and R2*-based biomarkers measure the same underlying tumor biology.…”