Oxymetry deep in tissues with low-frequency electron paramagnetic resonance.

Abstract

We have measured the oxygen concentration in the body water of murine FSa and NFSa fibrosarcomas using a new method for quantitative oxygen concentration determination deep in the tissues of a living animal. The measurement uses unusually low-frequency electron paramagnetic spectroscopy sensitive to substrate 7 cm deep in tissue, partially deuterated spin probes (spin labels of molecular mass 195, approximating that of glucose) whose distribution compartment can be targeted with facile adduct substitution, and novel analytic techniques. We show that the water-compartment oxygen concentration of the tumors decreases as the tumor size increases and also shows a trend to decrease as radiobiologic hypoxia increases. An oxymetric spectral image of the tumor is presented. The technique will improve with larger human tissue samples. It provides the potential to quantitatively assess tissue hypoxia in ischemic or preischemic states in stroke and myocardial infarction. It will allow direct assessment of tumor hypoxia to determine the usefulness of radiation and chemotherapy adjuvants directed to hypoxic cell compartments.

A parametric approach to spectral–spatial EPR imaging

“…[13] may be solved by many numerical methods; we use the interior-reflective Newton method implemented in the Matlab 1 7.1 routine lsqnonlin. Note that the cost function is quadratic in d but non-convex in τ.…”

“…At parameter values for which the log-likelihood has low curvature (i.e., is relatively flat), the cost function in Eq. [13] is not sensitive to small changes in the estimated parameters; hence, the estimation error variance due to measurement noise is relatively large. In contrast, where the log-likelihood function has high curvature, the cost is sensitive to small changes in the estimated parameters, resulting in low variance parameter estimates.…”

“…[13], and the reconstructed object is shown in Fig. 9, the estimated spin density and estimated half-linewidth are shown in the Fig.…”

“…The imaging technique that includes a spectral dimension is termed spectral-spatial imaging. An example application of spectral-spectral EPRI is oximetry based on linewidth broadening from Heisenberg spin exchange interaction between a paramagnetic EPR spin probe and unpaired electrons in molecular oxygen [13].…”

Cardiac applications of EPR imaging

“…The approach uses non-toxic redox-active free radical probes such as nitroxyls (nitroxides). 18,[46][47][48] Figure 1. Projection acquisition in EPR imaging.…”