Single‐point (constant‐time) imaging in radiofrequency Fourier transform electron paramagnetic resonance†

Subramanian, S.; Devasahayam, Nallathamby; Murugesan, Ramachandran; Yamada, Ken Ichi; Cook, John A.; Taube, Andrew G.; Mitchell, James B.; Lohman, Joost A. B.; Krishna, Murali C.

doi:10.1002/mrm.10199

Cited by 86 publications

(91 citation statements)

References 38 publications

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“…EPRI for pO 2 The technical details of the EPR scanner and oxygen image reconstruction were described in earlier reports (25,27,38). Parallel coil resonators tuned to 300 MHz were used for EPRI and MRI.…”

Section: Animal Experimentsmentioning

confidence: 99%

In VivoImaging of Tumor Physiological, Metabolic, and Redox Changes in Response to the Anti-Angiogenic Agent Sunitinib: Longitudinal Assessment to Identify Transient Vascular Renormalization

Matsumoto

Saito

Takakusagi

et al. 2014

Antioxidants & Redox Signaling

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Aims: The tumor microenvironment is characterized by a highly reducing redox status, a low pH, and hypoxia. Anti-angiogenic therapies for solid tumors frequently function in two steps: the transient normalization of structurally and functionally aberrant tumor blood vessels with increased blood perfusion, followed by the pruning of tumor blood vessels and the resultant cessation of nutrients and oxygen delivery required for tumor growth. Conventional anatomic or vascular imaging is impractical or insufficient to distinguish between the two steps of tumor response to anti-angiogenic therapies. Here, we investigated whether the noninvasive imaging of the tumor redox state and energy metabolism could be used to characterize anti-angiogenic drug-induced transient vascular normalization. Results: Daily treatment of squamous cell carcinoma (SCCVII) tumor-bearing mice with the multityrosine kinase inhibitor sunitinib resulted in a rapid decrease in tumor microvessel density and the suppression of tumor growth. Tumor pO 2 imaging by electron paramagnetic resonance imaging showed a transient increase in tumor oxygenation after 2-4 days of sunitinib treatment, implying improved tumor perfusion. During this window of vascular normalization, magnetic resonance imaging of the redox status using an exogenously administered nitroxide probe and hyperpolarized 13 C MRI of the metabolic flux of pyruvate/lactate couple revealed an oxidative shift in tumor redox status. Innovation: Redox-sensitive metabolic couples can serve as noninvasive surrogate markers to identify the vascular normalization window in tumors with imaging techniques. Conclusion: A multimodal imaging approach to characterize physiological, metabolic, and redox changes in tumors is useful to distinguish between the different stages of anti-angiogenic treatment.

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Section: Animal Experimentsmentioning

confidence: 99%

In VivoImaging of Tumor Physiological, Metabolic, and Redox Changes in Response to the Anti-Angiogenic Agent Sunitinib: Longitudinal Assessment to Identify Transient Vascular Renormalization

Matsumoto

Saito

Takakusagi

et al. 2014

Antioxidants & Redox Signaling

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“…The actual line widths (FWHM) at 300 MHz are 180 mG and 133 mG, respectively, for oxo63 and oxo31, due to the presence of unresolved hyperfine coupling from 13 Pulsed (time domain) EPRI and oximetry. Technical details of the pulsed EPR scanner operating at 300 MHz, data acquisition based on the singlepoint imaging (SPI) modality, image reconstruction, and the oximetry calculation procedure were described in the earlier reports (25,29,46). Briefly, the SPI is a pure phase-encoding imaging technique.…”

Section: Chemicals the Triarylmethyl (Tam) Probes Oxo63 And Oxo31 Wementioning

confidence: 99%

Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice

Matsumoto¹,

Hyodo²,

Subramanian³

et al. 2008

J. Clin. Invest.

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146

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A priori knowledge of spatial and temporal changes in partial pressure of oxygen (oxygenation; pO 2 ) in solid tumors, a key prognostic factor in cancer treatment outcome, could greatly improve treatment planning in radiotherapy and chemotherapy. Pulsed electron paramagnetic resonance imaging (EPRI) provides quantitative 3D maps of tissue pO 2 in living objects. In this study, we implemented an EPRI set-up that could acquire pO 2 maps in almost real time for 2D and in minutes for 3D. We also designed a combined EPRI and MRI system that enabled generation of pO 2 maps with anatomic guidance. Using EPRI and an air/carbogen (95% O 2 plus 5% CO 2 ) breathing cycle, we visualized perfusion-limited hypoxia in murine tumors. The relationship between tumor blood perfusion and pO 2 status was examined, and it was found that significant hypoxia existed even in regions that exhibited blood flow. In addition, high levels of lactate were identified even in normoxic tumor regions, suggesting the predominance of aerobic glycolysis in murine tumors. This report presents a rapid, noninvasive method to obtain quantitative maps of pO 2 in tumors, reported with anatomy, with precision. In addition, this method may also be useful for studying the relationship between pO 2 status and tumor-specific phenotypes such as aerobic glycolysis.

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“…Pulse EPR methodologies used in vivo oxygen imaging includes single point imaging ͑SPI͒ 15,16 and electron spin echo ͑ESE͒ imaging ͑ESEI͒ developed in our group. 17 SPI utilizes phase encoding, while ESEI is based on frequency encoding of spatial information.…”

Section: Introductionmentioning

confidence: 99%

Comparison of 250 MHz electron spin echo and continuous wave oxygen EPR imaging methods for in vivo applications

Epel¹,

Sundramoorthy²,

Barth³

et al. 2011

Medical Physics

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Purpose:The authors compare two electron paramagnetic resonance imaging modalities at 250 MHz to determine advantages and disadvantages of those modalities for in vivo oxygen imaging. Methods: Electron spin echo ͑ESE͒ and continuous wave ͑CW͒ methodologies were used to obtain three-dimensional images of a narrow linewidth, water soluble, nontoxic oxygen-sensitive trityl molecule OX063 in vitro and in vivo. The authors also examined sequential images obtained from the same animal injected intravenously with trityl spin probe to determine temporal stability of methodologies. Results: A study of phantoms with different oxygen concentrations revealed a threefold advantage of the ESE methodology in terms of reduced imaging time and more precise oxygen resolution for samples with less than 70 torr oxygen partial pressure. Above ϳ100 torr, CW performed better. The images produced by both methodologies showed pO 2 distributions with similar mean values. However, ESE images demonstrated superior performance in low pO 2 regions while missing voxels in high pO 2 regions. Conclusions: ESE and CW have different areas of applicability. ESE is superior for hypoxia studies in tumors.

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Single‐point (constant‐time) imaging in radiofrequency Fourier transform electron paramagnetic resonance†

Cited by 86 publications

References 38 publications

In VivoImaging of Tumor Physiological, Metabolic, and Redox Changes in Response to the Anti-Angiogenic Agent Sunitinib: Longitudinal Assessment to Identify Transient Vascular Renormalization

In VivoImaging of Tumor Physiological, Metabolic, and Redox Changes in Response to the Anti-Angiogenic Agent Sunitinib: Longitudinal Assessment to Identify Transient Vascular Renormalization

Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice

Comparison of 250 MHz electron spin echo and continuous wave oxygen EPR imaging methods for in vivo applications

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