The Initial Measurements in the First Specifically Designed Clinical EPR Facility for Measurements in In Vivo in Human Subjects
Harold M. Swartz1, Tadeusz Walczak1,
Piotr Lesniewski1, Ildar Salikhov1, Oleg Grinberg1,
Akinori Iwasaki1, Richard J. Comi2, Jay C. Buckey2,
Eugen Hug2, David J. Gladstone2
1EPR Center for the Study of Viable Systems,
Dartmouth Medical School, Hanover, NH USA;
2Dartmouth-Hitchcock
Medical Center, Lebanon, NH USA
The clinical EPR facility has now been
constructed and tested and is being utilized in studies with human subjects.
Measurements have been made under three protocols that have been reviewed and
approved by the committee on protection
of human subjects. Protocols are under
development for two additional studies in human subjects.
The
first measurements were made in a project in which EPR oximetry is to be used
to measure oxygenation in the critical tissues
of feet of diabetic patients
with significant peripheral vascular disease. We have begun to make serial
measurements of the pO2
in the site where most clinically
significant ulcers occur in diabetics, under the metatarsal head of the foot.
We have successfully made
repeated measurements from India ink that was
injected into this area. The measurements indicate that with proper positioning
and apparatus,
repeated measurements can be made accurately and reproducibly
over a period of at least several weeks. We are now completing
the initial
studies in volunteers that are needed to develop fully the procedures for the
full study.
We then will begin systematic studies in diabetics and healthy
controls.
The
second set of measurements is being made in conjunction with the use of
EPR dosimetry for non-invasive retrospective
measurements of clinically
significant doses of ionizing radiation. These measurements are based on the
long-lived free radicals
that are induced by ionizing radiation, which are
stabilized in the hydroxyapaptite matrix of the enamel of teeth. For
development
and validation of the approach, we will utilize the EPR signals
induced in teeth from therapeutic radiation of head and neck tumors.
This
method may be of great value for making measurements in individuals after a
terrorist incident, making it feasible to reassure
people who did not receive
life-threatening doses, and getting those with significant doses into
appropriate treatment.
The
third major protocol is directed towards establishing procedures and
determining feasibility of using in vivo EPR
to measure oxygen in tumors
repeatedly, with the aim to guide radiation therapy to optimize the
effectiveness of the treatment
on an individualized basis. The ability to make
repeated measurements of the pO2 in tumors will enable the clinician
to schedule
the delivery of fractionated radiation therapy at times when there
is maximum effectiveness on the tumor.
An extension of this protocol is under
development to provide for the use of the implantable resonator, which will
make it feasible
to utilize the method for deep-seated tumors.
The
fourth protocol will use EPR oximetry to measure the effects of hyperbaric
oxygen (HBO) on tissue pO2.
This will include both direct effects
(by making measurements immediately after the completion of the HBO), and
testing the hypothesis
that HBO treatment has a longer-term effect on tissue
oxygenation, due to changes in the vasculature.
A
fifth protocol will be developed to make measurements of oxygen in wounds to
determine the adequacy of oxygenation
in the wound. This capability should
enable the clinician to determine whether a wound is likely to heal
satisfactorily or if additional
measure is needed to make healing more likely.
CONCLUSIONS
The ability to make EPR measurements in
human subjects has been demonstrated, and we now can proceed systematically
to
determine which applications will be clinically useful. It seems very likely
that in vivo EPR will become an effective clinical modality.