Electrical impedance
The electrical impedance spectroscopy (EIS) device consists of a handheld probe equipped with a disposable electrode that is applied directly on the skin (figure 1). This probe is connected to a small electrical device that is connected to a touch screen monitor via a cable (figure 2). The latest generation of the EIS device permits integration of dermoscopy images into the patient chart together with the EIS measurements data. This permits the clinician to integrate the clinical, dermoscopic and EIS information to augment the cognition of the operator in his/her decision making.
Electrode:
The “micro invasive” electrode of the EIS machine only penetrates to the depth of the stratum corneum (Figure 3). The surface of each electrode is furnished with small gold covered micro-invasive pins. These pins have a triangular shape and approximately 150 m high with a 170 m triangular base. These spicules penetrate into the stratum corneum and have a sand paper like feel and the application of the electrode is painless. The electrode can obtain several measurements and can be used on multiple lesions per patient. Since the electrode does penetrate the stratum corneum, it must be discarded after each patient.
Frequencies:
The EIS system measures bio-impedance of the skin at 35 different frequencies, logarithmically distributed between 1.0 kHz to 2.5 MHz, at four different depths utilizing 10 permutations. The depth selectivity is measured by using different bars of electrodes (see figure 4). The spatial localization of the sense pin and depth pin determines the four depths of penetration calculations used in EIS measurements. In general, impedance at low frequencies is related to the resistive properties of the extra-cellular environment and impedance at high frequencies is related to the resistive properties of the intra- and extra-cellular environment and the capacitive properties (reactance) of the cell membranes. The applied voltage and resulting current is limited to 150mV and 75μA respectively. The electrical current cannot be perceived by the patient and a complete electrical impedance measurement study takes under 10 seconds to perform.
Measurements:
The measurement outcome of an EIS measurement is magnitude and phase shift at each frequency included in the spectrum. The measurements are displayed as curves of magnitude (kohms, left y-axis in the figure below) and phase shift (degrees, right y-axis) at four different depths (different colors), and 10 permutations at various frequencies (x-axis). It is important to note that prior to the application of the electrode and before any measurements are taken, that the skin site of interest be moistened with 0.9% saline solution for at least 30 seconds. For each lesion being investigated, the EIS measurements must be performed twice. The first measurement is called the reference measurement and this is obtained on healthy “normal” skin located at least 2–3 cm away from the lesion of interest. This reference measurement can even be obtained on the contra lateral side. The measurements from the healthy adjacent or similar contra-lateral skin provides an intra individual reference measurement which takes into account individual variability of the skin due to both intrinsic and extrinsic factors. The second EIS measurement is obtained from lesional skin.
Discussion
Differentiating melanoma from atypical nevi can be challenging especially in patients with many atypical nevi. The clinical decision making process is complex and takes into account patient’s history, risk factors, analytical analysis of the lesion (i.e., ABCDE criteria), differential recognition (i.e., outlier lesions), comparative recognition (i.e., change over time), and gut feeling (Marghoob & Scope, 2009). However, even after taking all of the aforementioned items into account, many nevi get biopsied because of concern for melanoma and some melanomas get missed. To further assist in differentiating nevi from melanoma requires leveraging technology to improve sensitivity and specificity. These technologies include dermoscopy, reflectance confocal microscopy, and EIS, just to mention a few. EIS is intended to be used on lesions that are deemed to be suspicious for melanoma based on clinical and dermoscopic examination. In this group of lesions, EIS was able to achieve a high sensitivity (96.6%) for melanoma detection in a cohort of lesions consisting of in situ and early invasive melanoma and dysplastic nevi. The specificity was superior to the clinician’s naked eye (Malvehy et al., 2014). The observed sensitivity of the device increased as the thickness of melanoma increased. It is noteworthy that none of the invasive melanomas between x-y mm thickness were missed by the device. The overall observed specificity for atypical nevi was 34.4%. In other words, approximately one-third of the equivocal lesions submitted for biopsy in the study were accurately identified as benign/negative by EIS and theoretically a biopsy could have been avoided in these lesions. In addition, the high observed NPV of 98 2% , which was equal to the NPV of histology in the study, ensures that few melanomas were inaccurately left un-biopsied. While further work is required to determine the ability of EIS to correctly classify other lesions such as lentigines and seborrheic keratosis as benign, in the present study the seborrheic keratoses were inaccurately classified as being malignant by EIS. This observation underscores the importance that EIS should be performed by clinicians trained to correctly recognize seborrheic keratosis, thus, preventing them from be evaluated via EIS. While the sensitivity for the diagnosis of NMSC was 100% and the specificity was XYZ?, more research is required to determine the efficacy of EIS in diagnosing different subtypes and stages of non-melanoma skin cancers.
In summary, EIS is a safe device that has a high sensitivity for detecting skin cancer. The scores provided by EIS may be used in conjunction with the clinical assessment to assist in management decisions.
Link to the manufacturer: Scibase Electrical impedance
