Yuanmu Deng

In vivo imaging of changes in tumor oxygenation during growth and after treatment.

A novel procedure for in vivo imaging of the oxygen partial pressure (pO2) in implanted tumors is reported. The procedure uses electron paramagnetic resonance imaging (EPRI) of oxygen‐sensing nanoprobes embedded in the tumor cells. Unlike existing methods of pO2 quantification, wherein the probes are physically inserted at the time of measurement, the new approach uses cells that are preinternalized (labeled) with the oxygen‐sensing probes, which become permanently embedded in the developed tumor. Radiation‐induced fibrosarcoma (RIF‐1) cells, internalized with nanoprobes of lithium octa‐n‐butoxy‐naphthalocyanine (LiNc‐BuO), were allowed to grow as a solid tumor. In vivo imaging of the growing tumor showed a heterogeneous distribution of the spin probe, as well as oxygenation in the tumor volume. The pO2 images obtained after the tumors were exposed to a single dose of 30‐Gy X‐radiation showed marked redistribution as well as an overall increase in tissue oxygenation, with a maximum increase 6 hr after irradiation. However, larger tumors with a poorly perfused core showed no significant changes in oxygenation. In summary, the use of in vivo EPR technology with embedded oxygen‐sensitive nanoprobes enabled noninvasive visualization of dynamic changes in the intracellular pO2 of growing and irradiated tumors. Magn Reson Med 57:950–959, 2007.

In vivo proton electron double resonance imaging of the distribution and clearance of nitroxide radicals in mice

Proton electron double resonance imaging (PEDRI) is an emerging technique that utilizes the Overhauser effect to enable in vivo and in vitro imaging of free radicals in biological systems. Nitroxide spin probes enable measurement of tissue redox state based on their reduction to diamagnetic hydroxylamines. PEDRI instrumentation at 0.02 T was applied to assess the ability to image the in vivo distribution, clearance, and metabolism of nitroxide radicals in living mice. Using phantoms of 2,2,5,5‐tetramethyl‐3‐carboxylpyrrolidine‐N‐oxyl (PCA) in normal saline the dependence of the enhancement on RF power and spin probe concentration was determined. Enhancements of up to −23 were obtained in phantoms with 2 mM levels. Maximum enhancement of −7 was observed in vivo. Coronal images of nitroxide‐infused mice enabled visualization of the kinetics of spin probe uptake and clearance in different organs including the great vessels, heart, lungs, kidneys, and bladder with an in‐plane spatial resolution of 0.6 mm. PEDRI of living mice was also performed using 3‐carbamoyl‐proxyl and 2,2,6,6‐tetramethyl‐4‐oxopiperidine‐N‐oxyl to compare the different rate of clearance and metabolism among different nitroxide probes. PCA, due to its intravascular compartmentalization, provided the sharpest contrast for the vascular system and highest enhancement values in the PEDRI images among the three nitroxides. Magn Reson Med, 2006.

Mapping of the B1 field distribution of a surface coil resonator using EPR imaging

Surface coil resonators have been widely used to perform topical EPR spectroscopy. They are usually positioned adjacent to or implanted within the body. For EPR applications these resonators have a number of important advantages over other resonator designs due to their ease of sample accessibility, mechanical fabrication, implementation of electronic tuning and coupling functions, and low susceptibility to sample motions. However, a disadvantage is their B1 field inhomogeneity, which limits their usefulness for 3D imaging applications. We show that this problem can be addressed by mapping and correcting the B1 field distribution. We report the use of EPR imaging (EPRI) to map the B1 distribution of a surface coil resonator. We show that EPRI provides a fast, accurate, and reliable technique to evaluate the B1 distribution. 3D EPRI was performed on phantoms, prepared using three different saline concentrations, to obtain the B1 distribution. The information obtained from the phantoms was used to correct the images of living animals. With the use of this B1 correction technique, surface coil resonators can be applied to perform 3D mapping of the distribution of free radicals in biological samples and living systems. Magn Reson Med 48:1057–1062, 2002.

Proton electron double resonance imaging (PEDRI) of the isolated beating rat heart

Proton electron double resonance imaging (PEDRI) is a double resonance technique where proton MRI is performed with irradiation of a paramagnetic solute. A low‐field PEDRI system was developed at 20.1 mT suitable for imaging free radicals in biological samples. With a new small dual resonator, PEDRI was applied to image nitroxide free radicals in isolated beating rat hearts. Experiments with phantoms showed maximum image enhancement factors (IEF) of 42 or 28 with TEMPONE radical concentrations of 2–3 mM at EPR irradiation powers of 12W or 6W, respectively. In the latter case, image resolution better than 0.5 mm and radical sensitivity of 5 μM was obtained. For isolated heart studies, EPR irradiation power of 6W provided optimal compromise of modest sample heating with good SNR. Only a small increase in temperature of about 1°C was observed, while cardiac function remained within 10% of control values. With infusion of 3 mM TEMPONE an IEF of 15 was observed enabling 2D or 3D images to be obtained in 27 sec or 4.5 min, respectively. These images visualized the change in radical distribution within the heart during infusion and clearance. Thus, PEDRI enables rapid and high‐quality imaging of free radical uptake and clearance in perfused hearts and provides a useful technique for studying cardiac radical metabolism. Magn Reson Med 50:391–399, 2003.

Deconvolution algorithm based on automatic cutoff frequency selection for EPR imaging

The large line‐width associated with electron paramagnetic resonance imaging (EPRI) requires effective algorithms to deconvolve the true spatial profiles of spins from the measured projection data. The commonly used Fourier transform (FT) deconvolution algorithm is easy to implement but suffers from the division‐by‐zero problem. As a result, a couple of parameters are used to control the deconvolution performance. However, this is inconvenient and the deconvolution results are subject to the experience of the operators. In the present work we examined FT deconvolution for EPRI, and proposed an automatic algorithm to determine the cutoff frequency by calculating the piecewise variance of the division result of the Fourier amplitude spectra. The deconvolution algorithm and the filtered back‐projection image reconstruction algorithm were implemented and validated using 3D phantom and in vivo imaging data. It was clearly observed that the image resolution improved after deconvolution with the proposed algorithm. Magn Reson Med 50:444–448, 2003.

In vivo detection of gastric cancer in rats by electron paramagnetic resonance imaging

Electron paramagnetic resonance imaging (EPRI) enables noninvasive spatial mapping of free radical metabolism and has recently been shown to provide in vivo physiologic information regarding alterations in the redox state of tumors and neoplastic tissues. With the use of nitroxide spin probes, it has been shown that certain tumors possess a highly reduced state. To determine whether EPRI can be used for early detection and visualization of gastric carcinoma based on its altered redox metabolism, studies were performed in a rat gastric cancer model induced by 1-methyl-3-nitro-1-nitrosoguanidine. Using a specialized 750 MHz resonator and EPRI instrument, a technique was developed for imaging nitroxide radicals in the whole stomach. In vivo three-dimensional EPRI of the stomach of rats with continuous intravenous administration of nitroxide 3-carboxamido-2,2,5,5-tetramethylpyrrolidine-N-oxyl (3-carbamoyl-proxyl) [3-CP] was performed. Whereas electron paramagnetic resonance images from untreated controls provide a uniform visualization of the stomach mucosa and wall, in the treated rats with gastric cancer, holes were present in the image at the locations of tumors. With localized spectroscopy, it was confirmed that the tumor regions were devoid of signal, and this was largely due to the presence of a more reduced state with rapid reduction of nitroxide. Pharmacokinetic studies indicated that 3-CP in tumors was rapidly reduced to an undetectable level, whereas the 3-CP levels in normal stomach tissue persisted. Near-infrared reflectance measurements of indocyanine green dye uptake indicated that there were no significant differences in tumor versus normal mucosal perfusion. From these results, we concluded that gastric cancer tumors could be distinguished from normal tissue based primarily on the marked difference in their rate of radical metabolism. Because alterations in cellular redox state and radical metabolism are of critical importance in tumor biology and treatment, this methodology should provide an important new tool for the study and visualization of gastric carcinoma and may also be of use in other cancer models.

Automated on-the-fly detection and correction procedure for EPR imaging data acquisition

Fast and reliable data acquisition is a major requirement for successful and useful biological electron paramagnetic resonance imaging (EPRI) experiments. Even a technologically advanced and professionally supervised EPRI system can exhibit instabilities initiated by perturbations such as animal motion, microphonics, and temperature changes. As a result, part of an acquired data set may become corrupted with excessive noise and distortions, which in turn may degrade the quality of the reconstructed image. In this work an automated scheme to monitor the system performance and stability over the course of an experiment is demonstrated. This method ensures that the quality of the acquired data is maintained during the experiment. For this purpose, four parameters including noise content and integration of each acquired projection are quantified and measured against those of the zero‐gradient (ZG) projection, which is set as a quality benchmark. Projections with parameter values that differ substantially from the expected values are identified as damaged and consequently are reacquired. Therefore, the proposed technique not only effectively monitors the quality of acquisition, it also saves a substantial amount of acquisition time because it eliminates the necessity of repeating the entire experiment in cases in which only a small fraction of the data are corrupted. Magn Reson Med, 2006.