In Vivo pO2 Imaging of Tumors

Epel, Boris; Halpern, Howard J.

doi:10.1016/bs.mie.2015.08.017

Cited by 42 publications

(19 citation statements)

References 77 publications

(79 reference statements)

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“…Measurement tools are needed for diagnosis and optimization of treatment strategies for diseases such as cancer and ischemic heart disease [1–4]. In vivo electron paramagnetic resonance (EPR) imaging of O 2 concentration in tissues uses the O 2 effect on the relaxation of paramagnetic probes such as triarylmethyl radicals, lithium phthalocyanine and related compounds [2, 3, 5].…”

Section: Introductionmentioning

confidence: 99%

Triarylmethyl Radical: EPR Signal to Noise at Frequencies between 250 MHz and 1.5 GHz and Dependence of Relaxation on Radical and Salt Concentration and on Frequency

Shi

Quine

Rinard

et al. 2016

Zeitschrift Für Physikalische Chemie

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In vivo oximetry by pulsed electron paramagnetic resonance is based on measurements of changes in electron spin relaxation rates of probe molecules, such as the triarylmethyl radicals. A series of experiments was performed at frequencies between 250 MHz and 1.5 GHz to assist in the selection of an optimum frequency for oximetry. Electron spin relaxation rates for the triarylmethyl radical OX063 as a function of radical concentration, salt concentration, and resonance frequency were measured by electron spin echo 2-pulse decay and 3-pulse inversion recovery in the frequency range of 250 MHz–1.5 GHz. At constant OX063 concentration, 1/T1 decreases with increasing frequency because the tumbling dependent processes that dominate relaxation at 250 MHz are less effective at higher frequency. 1/T2 also decreases with increasing frequency because 1/T1 is a significant contribution to 1/T2 for trityl radicals in fluid solution. 1/T2–1/T1, the incomplete motional averaging contribution to 1/T2, increases with increasing frequency. At constant frequency, relaxation rates increase with increasing radical concentration due to contributions from collisions that are more effective for 1/T2 than 1/T1. The collisional contribution to relaxation increases as the concentration of counter-ions in solution increases, which is attributed to interactions of cations with the negatively charged radicals that decrease repulsion between trityl radicals. The Signal-to-Noise ratio (S/N) of field-swept echo-detected spectra of OX063 were measured in the frequency range of 400 MHz–1 GHz. S/N values, normalized by √Q, increase as frequency increases. Adding salt to the radical solution decreased S/N because salt lowers the resonator Q. Changing the temperature from 19 to 37 °C caused little change in S/N at 700 MHz. Both slower relaxation rates and higher S/N at higher frequencies are advantageous for oximetry. The potential disadvantage of higher frequencies is the decreased depth of penetration into tissue.

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Section: Introductionmentioning

confidence: 99%

Triarylmethyl Radical: EPR Signal to Noise at Frequencies between 250 MHz and 1.5 GHz and Dependence of Relaxation on Radical and Salt Concentration and on Frequency

Shi

Quine

Rinard

et al. 2016

Zeitschrift Für Physikalische Chemie

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“…Systems for reliable monitoring could lead not only to an improved understanding for O 2 -mediated biological processes but also to important insights in clinical diagnostics and therapeutic guidance. Existing methods for the direct (in the form of O 2 partial pressure) or indirect (in the form of changes in the concentration of oxygenated hemoglobin, [HbO 2 ], and deoxygenated hemoglobin, [Hb]) assessments of localized tissue oxygenation in animal models have some combination of limitations associated with inability to operate at substantial depths beneath the body surface [near-infrared spectroscopy (NIRS) or cerebral oximeters], requirements for physical tethers (O 2 electrodes, optical fibers, or bulky head stages), and/or need for anesthetics or special apparatus [brain oxygenation level–dependent magnetic resonant imaging (BOLD-MRI) and electron paramagnetic resonant spectroscopy (EPR)] ( 6 , 7 ). These disadvantages can lead to confounding effects associated with altered oxygenation levels due to anesthesia ( 8 ) and/or with physical constraints ( 9 , 10 ) on the natural behaviors of animal models, and associated inability to perform studies during social interactions.…”

Section: Introductionmentioning

confidence: 99%

Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

et al. 2019

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Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

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“…Fluorocarbon contrast agent-based 19 F MRI is a recently developed approach for quantitative oxygen imaging [5, 6]. Electron paramagnetic resonance (EPR) - based approaches with use of specially designed paramagnetic spin probes also allow for direct pO 2 determination with high resolution but suffer a lack of anatomical information [7–9]. The combination of 1 H MRI and EPR imaging (EPRI) techniques allows for co-registration of both anatomical and functional information and are, therefore excellent tools for visualization of oxygen concentration with high spatial and temporal resolution [10–12].…”

Section: Introductionmentioning

confidence: 99%

Oxygen-induced leakage of spin polarization in Overhauser-enhanced magnetic resonance imaging: Application for oximetry in tumors

Gorodetskii

Eubank

Driesschaert

et al. 2018

Journal of Magnetic Resonance

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Overhauser-enhanced Magnetic Resonance Imaging (OMRI) is a double resonance technique applied for oxygen imaging in aqueous samples and biological tissues. In this report, we present an improved OMRI approach of oxygen measurement using the single line “Finland” trityl spin probe. Compared to a traditional approach, we introduced an additional mechanism of leakage of spin polarization due to an interaction of a spin system with oxygen. The experimental comparison of the new approach with an oxygen-dependent leakage factor to a traditional approach performed in phantom samples in vitro, and mouse tumor model in vivo, shows improved accuracy of determination of oxygen and contrast agent concentrations.

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In Vivo pO2 Imaging of Tumors

Cited by 42 publications

References 77 publications

Triarylmethyl Radical: EPR Signal to Noise at Frequencies between 250 MHz and 1.5 GHz and Dependence of Relaxation on Radical and Salt Concentration and on Frequency

Triarylmethyl Radical: EPR Signal to Noise at Frequencies between 250 MHz and 1.5 GHz and Dependence of Relaxation on Radical and Salt Concentration and on Frequency

Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

Oxygen-induced leakage of spin polarization in Overhauser-enhanced magnetic resonance imaging: Application for oximetry in tumors

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