Development of clinical EPR hardware
The whole body clinical spectrometer
For the first systematic clinical measurements by EPR, we have developed a "Clinical EPR Facility" based on a 400 gauss permanent magnet (Sumitomo Special Metals, Torrance, CA) with 60 cm pole pieces and a gap of 50 cm. We have focused our initial efforts on two specific projects:
1) measurements using EPR oximetry to monitor tissue pO2 in the foot for the evaluation of peripheral vascular disease in patients with diabetes,
2) the use of in vivo EPR dosimetry for determination of clinically significant doses of ionizing radiation "after-the-fact" from accidental or deliberate dispersal of large amounts of radiation into the environment.
There are a number of challenging requirements that must be met for a clinical spectrometer to be suitable for studies at any site within a human subject. The gap needs to be able to accommodate large human subjects comfortably and safely, and be large enough for procedures that require that the subject be placed horizontally within the gap of the magnet. Many of the clinical applications will be for oximetry. The intrinsic linewidths of suitable oximetric materials range from less than 30 mG for LiPc, to 5 gauss or more for some of the carbon based materials, so a wide range of modulation fields and precise control of the swept magnetic field are needed. In order to position the subject in the magnet, we constructed a special gantry (made from nonmagnetic material) that can be moved on rails into the magnet. As shown in Figure 1 the subject can sit or lie in the clinical spectrometer. A special flat magnet has been constructed for use in radiation dosimetry (Figure 2).
Figure 1: Measurements can be performed while the patient is comfortably seated next to the magnet (left). The distance between the poles of the magnet and a sliding bed facilitate measurements of patients in a recumbent position (right).
Figure 2: (left) The transportable spectrometer for measurement in peripheral tissues consists of a rugged cylindrical magnet, power supply, and laptop controlled modular RF bridge. (right) For in vivo dosimetry, a portable "flat magnet" as been designed and constructed. The final version will have a covered surface and an apparatus for positioning the subject comfortably and accurately at the desired relationship to the magnet. The face of the flat magnet can be rotated so that it can be used in any position.
Clinical resonator design
Surface loop resonators are the most versatile and heavily used design used at the Center. These resonators are used for oximetry in tissues near the skin surface and in exposed organs and for radiation dosimetry. These resonators are shown in Figures 8 and 15. We have continued to emphasize the development of the implantable resonator. The implantable resonator, which can make measurements at depths of perhaps 20 cm or more, may greatly facilitate some applications in human subjects. This is clearly the case for oximetry of non-superficial tumors during the course of radiation therapy. A novel implantable micro-resonator has been designed and constructed (Figure 3). Oxygen-sensitive lithium phthalocyanine was encapsulated at one end of the resonator within a loop with diameter less than 1 mm. The opposite end of the resonator terminates in a larger, 8-10 mm diameter loop that allows inductive coupling of the resonator to the RF bridge. The small loop is placed in the tissue of interest and the larger coupling loop is located subcutaneously at a depth that allows the delivery of microwaves into the resonator. As a proof of concept, this resonator has been used to measure pO2 in the in vivo rabbit myocardium (Figure 3, Table 1).
Figure 3: An implantable micro-resonator, with total length of ~5 cm, a coupling loop diameter of 7 mm, and approximately 1 mg of LiPc contained in the detection loop, was implanted in the left ventricular wall of a rabbit at the base of the left anterior descending artery. pO2 measurements under different conditions are included in Table 1.
Table 1: The measured pO2 values within the myocardium corresponded well with expected values reported in other studies using other types of measurements.