Diffuse electrical currents delivered to the eye were investigated in a rat model of retinitis pigmentosa for potentially therapeutic effects. Low-level currents were passed between electrodes placed on the cornea and in the mouth during 30-min sessions two times per week from 4 to 16 weeks of age. Single-flash electroretinograms (ERG) were recorded and analyzed for amplitude and measures of sensitivity, and basic histology was performed. ERG a-wave amplitudes were slightly greater in treated vs. age-matched controls at 16 weeks of age, but the combined thicknesses of the outer nuclear layer and outer segment layer were similar at this age. Treated animals exhibited a significant preservation of b-wave amplitudes, and a striking preservation of rod sensitivity, measured as the stimulus strength required to reach half-saturation of the a-wave. Analysis of the leading edge of the a-wave using a delayed Gaussian function revealed a decrease in the parameter reflecting gain of the phototransduction cascade over the 12-week course of treatment, and no significant change in control animals over the same period. These results suggest that while the exogenous currents failed to preserve the number or gross structure of rods, the responsivity of individual photoreceptors was relatively preserved, perhaps via an increase in efficiency of photon capture (R/photon). This preserved functionality may delay the retraction of bipolar cell dendrites from degenerating photoreceptors.
Background Lung cancer is the world’s leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules. Objective The Cole relaxation frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues. Methods Human testing ex vivo was conducted with NoduleScan in freshly resected lung tissue from 30 volunteer patients undergoing resection for nonsmall cell lung cancer. The CRF of the tumor and the distant normal lung tissue relative to the tumor were compared to histopathology specimens to establish a potential algorithm for point-of-care diagnosis. For animal testing in vivo, 20 mice were implanted with xenograft human lung cancer tumor cells injected subcutaneously into the right flank of each mouse. Spectral impedance measurements were taken on the tumors on live animals transcutaneously and on the tumors after euthanasia. These CRF measurements were compared to healthy mouse lung tissue. For porcine lung testing ex vivo, porcine lungs were received with the trachea. After removal of the vocal box, a ventilator was attached to pressurize the lung and simulate breathing. At different locations of the lobes, the lung's surface was cut to produce a pocket that could accommodate tumors obtained from in vivo animal testing. The tumors were placed in the subsurface of the lung, and the electrode was placed on top of the lung surface directly over the tumor but with lung tissue between the tumor and the electrode. Spectral impedance measurements were taken when the lungs were in the deflated state, inflated state, and also during the inflation-deflation process to simulate breathing. Results Among 60 specimens evaluated in 30 patients, NoduleScan allowed ready discrimination in patients with clear separation of CRF in tumor and distant normal tissue with a high degree of sensitivity (97%) and specificity (87%). In the 25 xenograft small animal model specimens measured, the CRF aligns with the separation observed in the human in vivo measurements. The CRF was successfully measured of tumors implanted into ex vivo porcine lungs, and CRF measurements aligned with previous tests for pressurized and unpressurized lungs. Conclusions As previously shown in breast tissue, CRF in the range of 1kHz-10MHz was able to distinguish nonsmall cell lung cancer versus normal tissue. Further, as evidenced by in vivo small animal studies, perfused tumors have the same CRF signature as shown in breast tissue and human ex vivo testing. Inflation and deflation of the lung have no effect on the CRF signature. With additional development, CRF derived from spectral impedance measurements may permit point-of-care diagnosis guiding surgical resection.
Lung cancer is the world’s leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules. The Cole Relaxation Frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues. Here we show that CRF allows for diagnosis of cancer in human subjects, based on evaluation of 60 specimens obtained from 30 patients. We observed clear discrimination of CRF values in tumor and distant normal tissues, resulting in a high degree of sensitivity (97%) and specificity (87%) in cancer diagnosis. Furthermore, we tested 20 xenograft small animal model specimens, observing a similar separation of CRF values as in the human in-vivo measurements. We also obtained CRF measurements in pressurized and unpressurized lungs by implanting tumors into ex-vivo porcine lungs. CRF measurements align with previous tests in human and small animal models.
UNSTRUCTURED Lung cancer is the world’s leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules. The Cole Relaxation Frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues. Here we show that CRF allows for diagnosis of cancer in human subjects, based on evaluation of 60 specimens obtained from 30 patients. We observed clear discrimination of CRF values in tumor and distant normal tissues, resulting in a high degree of sensitivity (97%) and specificity (87%) in cancer diagnosis. Furthermore, we tested 20 xenograft small animal model specimens, observing a similar separation of CRF values as in the human in-vivo measurements. We also obtained CRF measurements in pressurized and unpressurized lungs by implanting tumors into ex-vivo porcine lungs. CRF measurements align with previous tests in human and small animal models.
Figure 1. (A) KPC pancreas sample placed on Novascan's electrode array for a series of spectral bioimpedance measurements. A zoom in of the electrode with a pancreas sample is also shown. White rectangles indicate multiple locations measured across the sample. Spectral impedance scans for a control mouse (B) and a KPC mouse (C). The examination of CRF peak properties was used for cancer identification in pancreas samples. For the control mouse the CRF peaks fall below the threshold of 1 MHz, determining no cancer. For the KPC mouse several scans have CRF peaks above the threshold of 1 MHz, determining cancer presence.
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