Abstract

Tissue oximetry can assist in diagnosis and prognosis of many diseases and enable personalized therapy. Previously, we reported the ability of hexamethyldisiloxane (HMDSO) for accurate measurements of tissue oxygen tension (pO2) using Proton Imaging of Siloxanes to map Tissue Oxygenation Levels (PISTOL) magnetic resonance imaging. Here we report the feasibility of several commercially available linear and cyclic siloxanes (molecular weight 162–410 g/mol) as PISTOL-based oxygen reporters by characterizing their calibration constants. Further, field and temperature dependence of pO2 calibration curves of HMDSO, octamethyltrisiloxane (OMTSO) and polydimethylsiloxane (PDMSO) were also studied. The spin-lattice relaxation rate R1 of all siloxanes studied here exhibited a linear relationship with oxygenation (R1 = A′ + B′*pO2) at all temperatures and field strengths evaluated here. The sensitivity index η( = B′/A′) decreased with increasing molecular weight with values ranged from 4.7 × 10−3–11.6 × 10−3 torr−1 at 4.7 T. No substantial change in the anoxic relaxation rate and a slight decrease in pO2 sensitivity was observed at higher magnetic fields of 7 T and 9.4 T for HMDSO and OMTSO. Temperature dependence of calibration curves for HMDSO, OMTSO and PDMSO was small and simulated errors in pO2 measurement were 1–2 torr/°C. In summary, we have demonstrated the feasibility of various linear and cyclic siloxanes as pO2-reporters for PISTOL-based oximetry.

Highlights

  • Tissue oximetry can assist in diagnosis and prognosis of many diseases and enable personalized therapy

  • Many qualitative and quantitative oximetry techniques have been developed for oximetry such as polarographic needle electrode[23], fiber optic probes[23], Near Infrared (NIR) spectroscopy[24], fluorescence[25], immunohistochemical probes[26], positron emission tomography (PET)[27] and single photon emission computed tomography (SPECT)[28]

  • The current magnetic resonance imaging (MRI) based oximetry techniques can be further sub-divided into a) qualitative techniques: Blood Oxygen Level Dependent (BOLD)[32], Tissue Oxygen Level Dependent (TOLD)[33], oxygen-enhanced MRI34, hypoxia targeted MRI35 and b) quantitative oximetry techniques: Electron Paramagnetic Resonance (EPR36), 19F NMR of perfluorocarbon emulsions, Fluorocarbon Relaxometry using Echoplanar imaging for Dynamic Oxygen Mapping (FREDOM, 19F MRI of hexafluorobenzene)[37] and Proton Imaging of Siloxanes for mapping Tissue Oxygenation Levels (PISTOL)38,39)

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Summary

Introduction

Tissue oximetry can assist in diagnosis and prognosis of many diseases and enable personalized therapy. EPR and MR oximetry (19F and 1H) techniques are minimally invasive and provide quantitative oxygenation information via measuring the change in linewidth or spin lattice relaxation time, respectively, of an exogenously administered paramagnetic spin probe as it interacts with the molecular oxygen. While HMDSO has been shown to be a reliable pO2 reporter and has a large dynamic range and high pO2 sensitivity[38], the values of spin lattice relaxation time T1 (= 1/R1) under hypoxic conditions can be as long as 11 s, leading to long measurement times This raises the question whether any of the other siloxanes could be used as pO2 reporter molecules and how chain length and structure (linear versus cyclic) influence the pO2 sensitivity and dynamic range of T1 exhibited under different oxygenation conditions. Field and temperature dependence of the pO2 calibration curves of HMDSO, OMTSO and PDMSO were studied

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