title: Non-invasive assessment of radiation injury with electrical impedance spectroscopy.
abstract: A detailed understanding of non-targeted normal tissue response is necessary for the optimization of radiation treatment plans in cancer therapy. In this study, we evaluate the ability of electrical impedance spectroscopy (EIS) to non-invasively determine and quantify the injury response in soft tissue after high dose rate (HDR) irradiation, which is characterized by large localized dose distributions possessing steep spatial gradients. The HDR after-loading technique was employed to irradiate small volumes of muscle tissue with single doses (26-52 Gy targeted 5 mm away from the source). Impedance measurements were performed on 29 rats at 1, 2 and 3 month post-irradiation, employing 31 frequencies in the 1 kHz to 1 MHz range. Over the first 3 months, conductivity increased by 48% and 26% following target doses of 52 Gy and 26 Gy 5 mm from the HDR source, respectively. Injury, assessed independently through a grid-based scoring method showed a quadratic dependence on distance from source. A significant injury (50% of cells atrophied, necrotic or degenerating) in 1.2% of the volume, accompanied by more diffuse injury (25% of cells atrophied, necrotic or degenerating) in 9% of the tissue produced a conductivity increase of 0.02 S m(-1) (8% over a baseline of 0.24 S m(-1)). This was not statistically significant at p = 0.01. Among treatment groups, injury differences in 22% of the volume led to statistically significant differences in conductivity of 0.07 S m(-1) (23% difference in conductivity). Despite limitations, the success of EIS in detecting responses in a fraction of the tissue probed, during these early post-irradiation time-points, is encouraging. Electrical impedance spectroscopy may provide a useful metric of atrophy and the development of fibrosis secondary to radiation that could be further developed into a low-cost imaging method for radiotherapy monitoring and assessment.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, USA. kso2003@columbia.edu
authors.forename: K Sunshine
authors.initials: KS
authors.lastname: Osterman
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
authors.forename: Christine
authors.initials: C
authors.lastname: DeLorenzo
authors.forename: David J
authors.initials: DJ
authors.lastname: Gladstone
authors.forename: Keith D
authors.initials: KD
authors.lastname: Paulsen
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004553:Electric Conductivity; D017097:Electric Impedance; D005355:Fibrosis; D006614:Hindlimb / Q000528:radiation effects; D009132:Muscles / Q000473:pathology / Q000528:radiation effects*; D009336:Necrosis; D011832:Radiation Injuries / Q000175:diagnosis*; D011833:Radiation Injuries, Experimental; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D051381:Rats; D013057:Spectrum Analysis / Q000379:methods*