KEYWORDS: Signal detection, In vivo imaging, Tumors, Frequency modulation, 3D image processing, Oxygen, Amplifiers, Image filtering, Continuous wave operation
The work described in this presentation relates to a novel approach to Electron Paramagnetic Resonance
imaging in vivo. The method employs a continuous wave approach to spectral detection without the
conventional low frequency modulation and phase sensitive detection. A combination of direct detection
and rapid field scan in the simultaneous presence of rotating gradients enables imaging with high temporal
resolution. Since CW detection is not limited to free radical spin probes with narrow spectral lines, unlike
the time-domain case, this novel approach uniquely accomplishes ultra fast functional imaging and is
applicable to common redox-sensitive spin probes without line-width restriction.
KEYWORDS: Tumors, Magnetic resonance imaging, In vivo imaging, Oxygen, Resonators, 3D image processing, Magnetism, Spectroscopy, Computer programming, Tissues
Electron Paramagnetic Resonance is an emerging technique finding applications in functional physiological imaging.
Traditionally EPR imaging developed as a CW (continuous wave) technique involving the measurement of free radical
distribution in vivo using constant frequency and field-sweep modality almost identical to the early developments of
MRI. As in CT and PET this involved the generation of projections in presence of gradients and the reconstruction of
images via filtered back-projection. The large line-width and the concomitant short relaxation times posed a serious
challenge for the development of time-domain methods akin to modern pulsed NMR & MRI. With the recent availability of narrow line stable non-toxic radicals based on triarylmethyl (TAM), ultra fast data acquisition systems (signal digitizer and summer), very fast electronic switches and low-noise amplifiers, we have developed time-domain imaging schemes in EPR operating in the radiofrequency region Using a novel pure-phase encoding scheme, we are
able to generate 2 and 3 dimensional spatial images and spectral-spatial images that adds an additional functional
dimension to these images. The special space-encoding scheme with fast gradient ramping allow rapid in vivo imaging
of small animals with superior spatial and functional information with good temporal resolution that can provide
valuable physiological and pharmacokinetic insight. Our main thrust has been in the investigation of tumor hypoxia and
tumor reoxygenation for the purpose of minimizing the radiation dose for maximum tumor cell killing. These and some
of the allied imaging methods, and results from tumor investigation will be presented.
Electron paramagnetic resonance imaging (EPRI) is one of the recent functional imaging modalities that can provide
valuable in vivo physiological information on its own merit and aids as a complimentary imaging technique to MRI and
PET of tissues especially with respect to in vivo pO2 (oxygen partial pressure), redox status and pharmacology. EPR
imaging mainly deals with the measurement of distribution and in vivo dynamics and redox changes using special nontoxic
paramagnetic spin probes that can be infused into the object of investigation. These spin probes should be
characterized by simple EPR spectra, preferably with narrow EPR lines. The line width should be reversibly sensitive
to the concentration of in vivo pO2 with a linear dependence. Several non-toxic paramagnetic probes, some particulate
and insoluble and others water-soluble and infusible (by intravenous or intramuscular injection) have been developed
which can be effectively used to quantitatively assess tissue redox status, and tumor hypoxia. Quantitative assessment
of the redox status of tissue in vivo is important in investigating oxidative stress, and that of tissue pO2 is very important
in radiation oncology. Other areas in which EPR imaging and oxymetry may help are in the investigation of tumorangiogenesis,
wound healing, oxygenation of tumor tissue by the ingestion of oxygen-rich gases, etc. The correct choice
of the spin probe will depend on the modality of measurement (whether by CW or time-domain EPR imaging) and the
particular physiology interrogated. Examples of the available spin probes and some EPR imaging applications
employing them are presented.
Electron Paramagnetic Resonance (EPR) allows for the non-invasive imaging of free radicals in biological systems. Although a number of physical factors have hindered the development of EPR as an imaging modality, EPR offers the potential for tissue oxymetry. EPR images are typically reconstructed using a traditional filtered back-projection technique. We are attempting to improve the quality of EPR images by using maximum-entropy based iterative image reconstruction algorithms. Our investigation has so far focused on two methods, the multiplicative algebraic reconstruction technique (MART), and an algorithm that is motivated by interior-point reconstruction. MART is a row-action method that maintains strict equality in the constraints while minimizing the entropy functional. The latter method, which we have named Least-Squares Barrier Entropy (LSBEnt), transforms the constrained problem into an unconstrained problem and maximizes entropy at a prescribed distance from the measured data. EPR studies are frequently characterized by low signal-to-noise ratios and wide line widths. The effect of the backprojection streaking artifact can be quite severe and can seriously compromise a study. We have compared the iterative results with filtered backprojection on two-dimensional (2-D) EPR acquisitions of various phantoms. Encouraging preliminary results have demonstrated that one of the clear advantages of the iterative methods is their lack of streaking artifacts that plague filtered backprojection.
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