The objective of this study is to develop and test a unique portable device that aims to non-invasively detect bio-electrochemical characteristics of human tissues. For this purpose, we designed and developed a new portable Bio-impedance Spectroscopy (BIS) system utilizing active probe technique as measurement technique for bioelectrical features. This BIS system includes the integrated current source and output voltage signal detection sensors. Active probes are placed on the skin surface of the targeted human organ tissues to directly detect bioimpedance signals. Bio-impedance spectrum was measured by applying electrical currents over a range of frequencies (10kHz − 3MHz). The spectrum was then quantitatively analyzed to produce new biomarkers based on bio-electrochemical characteristics of human tissues. These new bioelectrical markers aim to accurately and reproducibly predict and/or detect human diseases (including cancer). To address the feasibility of this new research technique, we conducted a comprehensive evaluation of new BIS device with its calibration techniques and phantom study. Results showed that the computed bioelectrical marker values monotonically change corresponding to tissue compositions. In this research, we demonstrated how to compute independent and dependent bioelectrical features to be implemented on machine learning (ML) models that can improve our understanding of disease or cancer risk state. The study suggested that using this new device has potential for different applications, including the noninvasive assessment of breast density and the detection of asymmetrical focal areas between two bilateral breasts, which may eventually help more accurately predict breast cancer risk.
In order to improve efficacy of screening mammography, in recent years, we have been investigating the
feasibility of applying a resonance-frequency based electrical impedance spectroscopy (REIS) technology to noninvasively
detect breast abnormalities that may lead to the development of cancer in the near-term. Despite
promising study-results, we found that REIS suffered from relatively poor reproducibility due to perturbations in
electrode placement, contact pressure variation on the breast, as well as variation of the resonating inductor. To
overcome this limitation, in this study, we propose and analyze a new paradigm of Dielectric Relaxation
Spectroscopy (DRS) that measures polarization-lag of dielectric signals in breast-capacitance when excited by the
pulses or sine waves. Unlike conventional DRS that operates using the signals at very high frequencies (GHz) to
examine changes in polarization, our new method detects and characterizes the dielectric properties of tissue at low
frequencies (≤10 MHz) due to the advent of inexpensive oscillators that are accurate to 1 pico-second (used in GPS
receivers) as well as measurement of amplitudes of 1 ppm or better. From theoretical analysis, we have proved that
the sensitivity of new DRS in detecting permittivity of water increased by ≥80 times as compared to conventional
DRS, which operates at frequencies around 4GHz. By analyzing and comparing the relationship between the new
DRS and REIS, we found that this DRS has potential advantages in enhancing repeatability from various readings,
including temperature-insensitive detection, and yielding higher resolution or sensitivity (up to 100 Femtofarads).
Glucose metabolism relates to biochemical processes in living organisms and plays an important role in diabetes and cancer-metastasis. Although many methods are available for measuring glucose metabolism-activities, from simple blood tests to positron emission tomography, currently there is no robust and affordable device that enables monitoring of glucose levels in real-time. In this study we tested feasibility of applying a unique resonance-frequency based electronic impedance spectroscopy (REIS) device that has been, recently developed to measure and monitor glucose metabolism levels using a phantom study. In this new testing model, a multi-frequency electrical signal sequence is applied and scanned through the subject. When the positive reactance of an inductor inside the device cancels out the negative reactance of the capacitance of the subject, the electrical impedance reaches a minimum value and this frequency is defined as the resonance frequency. The REIS system has a 24-bit analog-to-digital signal convertor and a frequency-resolution of 100Hz. In the experiment, two probes are placed inside a 100cc container initially filled with distilled water. As we gradually added liquid-glucose in increments of 1cc (250mg), we measured resonance frequencies and minimum electrical signal values (where A/D was normalized to a full scale of 1V). The results showed that resonance frequencies monotonously decreased from 243kHz to 178kHz, while the minimum voltages increased from 405mV to 793mV as the added amount of glucose increased from 0 to 5cc. The study demonstrated the feasibility of applying this new REIS technology to measure and/or monitor glucose levels in real-time in future.
Electrical Impedance Spectroscopy (EIS) has shown promising results for differentiating between malignant and
benign tumors, which exhibit different dielectric properties. However, the performance of current EIS systems has been
inadequate and unacceptable in clinical practice. In the last several years, we have been developing and testing a new
EIS approach using resonance frequencies for detection and classification of suspicious tumors. From this experience,
we identified several limitations of current technologies and designed a new EIS system with a number of new
characteristics that include (1) an increased A/D (analog-to-digital) sampling frequency, 24 bits, and a frequency
resolution of 100 Hz, to increase detection sensitivity (2) automated calibration to monitor and correct variations in
electronic components within the system, (3) temperature sensing and compensation algorithms to minimize impact of
environmental change during testing, and (4) multiple inductor-switching to select optimum resonance frequencies. We
performed a theoretical simulation to analyze the impact of adding these new functions for improving performance of the
system. This system was also tested using phantoms filled with variety of liquids. The theoretical and experimental test
results are consistent with each other. The experimental results demonstrated that this new EIS device possesses the
improved sensitivity and/or signal detection resolution for detecting small impedance or capacitance variations. This
provides the potential of applying this new EIS technology to different cancer detection and diagnosis tasks in the future.
Electrical impedance spectroscopy (EIS) has been investigated and emerged as a potential non-invasive, low cost,
and convenient tool for prescreening and detecting breast abnormalities that could lead to developing breast cancers.
However, the performance of conventional EIS is unacceptable in clinical practice. In our laboratory, we developed a
new EIS approach based on resonance frequency measurements. This system relies on parameters generated by
resonating breast capacitance with a fixed inductor in six different directions using the nipple as a reference electrode.
The system detects breast tissue abnormalities due to capacitance changes caused by angiogenesis. Although preliminary
testing results from a prospective clinical study were encouraging, we found that detection results were not robust. One
of the primary reasons is that the measured EIS signals, in particular, resonance frequencies vary with lesion-depth.
Using circuit theory we investigated and derived analytical expressions between the sensitivity of capacitance changes
and parallel resistances to pathologies with respect to distances of the lesions from the nipple electrode. The resistance
shorts the measured EIS signal thereby decreasing amplitudes of waveforms at resonance frequency. The theoretical
analysis is consistent with our experimental observation, which provides valuable data and guidelines for us to develop
and construct a new resonance-frequency based EIS system using a lumped parameter (resistance and multi-layer
capacitance) based breast model, resulting in an optimal electrical circuit for future studies.
A new resonance-frequency based electronic impedance spectroscopy (REIS) system with multi-probes,
including one central probe and six external probes that are designed to contact the breast skin in a circular form with a
radius of 60 millimeters to the central ("nipple") probe, has been assembled and installed in our breast imaging facility.
We are conducting a prospective clinical study to test the performance of this REIS system in identifying younger
women (< 50 years old) at higher risk for having or developing breast cancer. In this preliminary analysis, we selected a
subset of 100 examinations. Among these, 50 examinations were recommended for a biopsy due to detection of a highly
suspicious breast lesion and 50 were determined negative during mammography screening. REIS output signal sweeps
that we used to compute an initial feature included both amplitude and phase information representing differences
between corresponding (matched) EIS signal values acquired from the left and right breasts. A genetic algorithm was
applied to reduce the feature set and optimize a support vector machine (SVM) to classify the REIS examinations into
"biopsy recommended" and "non-biopsy" recommended groups. Using the leave-one-case-out testing method, the
classification performance as measured by the area under the receiver operating characteristic (ROC) curve was 0.816 ±
0.042. This pilot analysis suggests that the new multi-probe-based REIS system could potentially be used as a risk
stratification tool to identify pre-screened young women who are at higher risk of having or developing breast cancer.
In our previous study, we reported on the development and preliminary testing of a prototype resonance
electrical impedance spectroscopy (REIS) system with a pair of probes. Although our pilot study on 150 young women
ranging from 30 to 50 years old indicated the feasibility of using REIS output sweep signals to classify between the
women who had negative examinations and those who would ultimately be recommended for biopsy, the detection
sensitivity was relatively low. To improve performance when using REIS technology, we recently developed a new
multi-probe based REIS system. The system consists of a sensor module box that can be easily lifted along a vertical
support device to fit women of different height. Two user selectable breast placement "cups" with different curvatures
are included in the system. Seven probes are mounted on each of the cups on opposing sides of the sensor box. By
rotating the sensor box, the technologist can select the detection sensor cup that better fits the breast size of the woman
being examined. One probe is mounted in the cup center for direct contact with the nipple and the other six probes are
uniformly distributed along an outside circle to enable contact with six points on the outer and inner breast skin surfaces.
The outer probes are located at a distance of 60mm away from the center (nipple) probe. The system automatically
monitors the quality of the contact between the breast surface and each of the seven probes and data acquisition can only
be initiated when adequate contact is confirmed. The measurement time for each breast is approximately 15 seconds
during which time the system records 121 REIS signal sweep outputs generated from 200 KHz to 800 KHz at 5 KHz
increments for all preselected probe pairs. Currently we are measuring 6 pairs between the center probe and each of six
probes located on the outer circle as well as two pairs between probe pairs on the outer circle. This new REIS system has
been installed in our clinical breast imaging facility. We are conducting a prospective study to assess performance when
using this REIS system under an approved IRB protocol. Over 200 examinations have been conducted to date. Our
experience showed that this new REIS system was easy to operate and the REIS examination was fast and considered
"comfortable" by examinees since the women presses her breast into the cup herself without any need for forced breast
compression, and all but a few highly sensitive women have any sensation of an electrical current during the
measurement.
KEYWORDS: Amplifiers, Capacitors, Capacitance, Radiography, Signal to noise ratio, Optical amplifiers, Calibration, Temperature metrology, Medical imaging, Silicon
The effect of finite open-loop gain in charge amplifiers in digital radiography (DR) is analyzed. Practical charge amplifiers are usually integrated into silicon chips and commonly cater to 128 columns. High gains in charge amplifiers have a cost that is associated with greater chip count, greater power dissipation, and sometimes, reduced bandwidth. Even an open-loop gain of 1000 in a charge amplifier can lead to visible artifacts in a DR system, for temperature drifts of a fraction of a degree between calibration of a panel and subsequent usage, while acquiring a radiographic image. Furthermore, small gains in a charge amplifier can rob charge from the pixel capacitor and create residual charge, predominantly in the column capacitances. This can reduce the effective signal-to-noise ratios (SNRs). Analytical models are developed to illustrate the effects of the finite gain in charge amplifiers. Methods are suggested to decrease the deleterious effects of finite gains in charge amplifiers.
With the proliferation of various new modalities, in Medical Imaging, there has been a need for compatible hardcopy. In order to render color or colorized images, for diagnostic imaging, it is necessary to have high quality hardcopy. Thermal media has the necessary characteristics to display images emanating from most of the new medical imaging modalities. Furthermore, new image presentation techniques are enabling the display of some medical images, which could only be displayed using silver halide media.
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