Faculty Bibliography

Skin injury is a common side effect of breast-cancer radiation therapy. Although physicians often observe skin toxicity, quantifying its severity remains a challenge. We present a novel quantitative ultrasonic technique to evaluate skin changes associated with radiotherapy. An in vivo study with twelve breast-cancer patients was conducted. All patients received a standard course of post-surgery radiation therapy. Each patient received ultrasound scans to the irradiated breast and the untreated (contra-lateral) breast. Radio-frequency (RF) backscatter signals and B-mode images were acquired simultaneously. To quantify the severity of skin injury, two metrics were calculated from the RF signals: skin thickness and Pearson correlation coefficient of the subcutaneous layer. Comparing to the non-irradiated skin, the average thickness of the irradiated skin increased by 40% (p=0.005) and the average correlation coefficient of the irradiated hypodermis decreased by 35% (p=0.02). This study demonstrates the feasibility of using a non-invasive ultrasonic technique to detect and quantify radiation-induced skin changes

PURPOSE: To investigate how the performance characteristics of ultrasound tissue typing (UTT) affect the design of a population-based prostate dose-painting protocol. METHODS AND MATERIALS: The performance of UTT is evaluated using the receiver operating characteristic curve. As the imager's sensitivity increases, more tumors are detected, but the specificity worsens, causing more false-positive results. The UTT tumor map, obtained with a specific sensitivity and specificity setup, was used with the patient's CT image to guide intensity-modulated radiotherapy (IMRT) planning. The optimal escalation dose to the UTT positive region, as well as the safe dose to the negative background, was obtained by maximizing the uncomplicated control (i.e., a combination of tumor control probability and weighted normal tissue complication probability). For high- and low-risk tumors, IMRT plans guided by conventional ultrasound or UTT with a one-dimensional or two-dimensional spectrum analysis technique were compared with an IMRT plan in which the whole prostate was dose escalated. RESULTS: For all imaging modalities, the specificity of 0.9 was chosen to reduce complications resulting from high false-positive results. If the primary tumors were low risk, the IMRT plans guided by all imaging modalities achieved high tumor control probability and reduced the normal tissue complication probability significantly compared with the plan with whole gland dose escalation. However, if the primary tumors were high risk, the accuracy of the imaging modality was critical to maintain the tumor control probability and normal tissue complication probability at acceptable levels. CONCLUSION: The performance characteristics of an imager have important implications in dose painting and should be considered in the design of dose-painting protocols

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

Isaacson, Cheney and Seager have demonstrated that simultaneously applying trigonometric patterns of current to a circular electrode array optimizes the sensitivity of EIT to inner structure. We have found that it is less desirable to measure voltage at an electrode that also applies a current due to variable contact impedance. In order to preserve the optimum sensitivity while minimizing the effect of electrode artefacts, we have devised an approach where we sequentially apply a current between each individual electrode and a separate, fixed ground while measuring voltages at all other electrodes for each consecutive current impulse. By adding weighted sums of both the applied currents and corresponding measured voltages from individual passes, we can synthesize trigonometric patterns of any spatial frequency. Since only one of the electrodes in any given acquired data set is used as a source, this approach significantly dilutes the effect of contact impedance on the resulting voltage measurements. We present simulated data showing the equivalency between the synthesized and actual trigonometric excitation patterns. In addition, we report experimental data, both in vitro and in vivo, that show improved results using this data acquisition technique

Our previous system covered the frequency range of 0 to 1 MHz. In this new design we propose to cover the range from 0 to 10 MHz. The higher frequencies have forced us to reconsider several design decisions in view of both the physics of the problem and the performance of available electronic components. In this presentation we examine in detail the constraints faced by the designer, starting from wiring consideration to measurement techniques. We will also present the solutions we selected to overcome the limitations we discovered. The problems include phase detection, amplitude measurements, system organization and layout and finally system calibration

The authors describe what is, to the best of their knowledge, the first quantitative hemoglobin concentration images of the female breast that were formed with model-based reconstruction of near-infrared intensity-modulated tomographic data. The results in 11 patients, including two with breast tumors with pathologic correlation, are summarized. Hemoglobin concentration appears to correlate with tumor vascularity without the need for exogenous contrast material and thereby has intrinsic diagnostic value

We have deployed a recently completed spectroscopic electrical impedance tomography (EITS) imaging system in a small series of women (13 participants accrued to date) in order to investigate the feasibility of delivering EITS breast examinations on a routine basis. Hardware is driven with sinusoidally varying spatial patterns of applied voltage delivered to 16 electrodes over the 10 kHz to 1 MHz spectral range using a radially translating interface which couples the electrodes to the breast through direct contact. Imaging examinations have consisted of the acquisition of multi-channel measurements at ten frequencies on both breasts. Participants lie prone on an examination table with the breast to be imaged pendant in the electrode array that is located below the table. Examinations were comfortable and easy to deliver (about 10 minutes per breast including electrode-positioning time). Although localized near-surface electrode artefacts are evident in the acquired images, several findings have emerged. Permittivity images have generally been more informative than their conductivity counterparts, except in the case of fluid-filled cysts. Specifically, the mammographically normal breast appears to have characteristic absolute EITS permittivity and conductivity images that emerge across subjects. Structural features in the EITS images have correlated with limited clinical information available on participants with benign and malignant abnormality, cysts and scarring from previous lumpectomy and follow-up radiation therapy. Several cases from this preliminary experience are described