Britt M. Andersson

Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro

Prostate cancer is the most common form of cancer in men in Europe and in the USA. Some prostate tumours are stiffer than the surrounding normal tissue, and it could therefore be of interest to measure prostate tissue stiffness. Resonance sensor technology based on piezoelectric resonance detects variations in tissue stiffness due to a change in the resonance frequency. An impression-controlled resonance sensor system was used to detect stiffness in silicone rubber and in human prostate tissue in vitro using two parameters, both combinations of frequency change and force. Variations in silicone rubber stiffness due to the mixing ratio of the two components could be detected (p<0.05) using both parameters. Measurements on prostate tissue showed that there existed a statistically significant (MANOVA test, p<0.001) reproducible difference between tumour tissue (n=13) and normal healthy tissue (n=98) when studying a multivariate parameter set. Both the tumour tissue and normal tissue groups had variations within them, which were assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces and different levels of dehydration for the prostates. Our results indicated that the resonance sensor could be used to detect stiffness variations in silicone and in human prostate tissue in vitro. This is promising for the development of a future diagnostic tool for prostate cancer.

Resonance sensor measurements of stiffness variations in prostate tissue in vitro : a weighted tissue proportion model

Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensors ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro.

Tactile sensors based on piezoelectric resonance have been adopted for medical applications. The sensor consists of an oscillating piezoelectric sensor-circuit system, and a change in resonance frequency is observed when the sensor tip contacts a measured object such as tissue. The frequency change at a constant applied force or mass load is used as a stiffness-sensitive parameter in many applications. Differential relations between force and frequency have also been used for monitoring intraocular pressure and stiffness variations in prostate tissue in vitro. The aim of this study was to relate the frequency change (Deltaf), measured force (F) and the material properties, density and elasticity to an explanatory model for the resonance sensor measurement principle and thereby to give explanatory models for the stiffness parameters used previously. Simulations of theoretical equations were performed to investigate the relation between frequency change and contact impedance. Measurements with a resonance sensor system on prostate tissue in vitro were used for experimental validation of the theory. Tissue content was quantified with a microscopic-based morphometrical method. Simulation results showed that the frequency change was dependent upon density (rho) and contact area (S) according to Deltaf proportional, variant rhoS(3/2). The experiments followed the simulated theory at small impression depths. The measured contact force followed a theoretical model with the dependence of the elastic modulus (E) and contact area, F proportional, variant ES(3/2). Measured density variations related to histological variations were statistically weak or non-significant. Elastic variations were statistically significant with contributions from stroma and cancer relative to normal glandular tissue. The theoretical models of frequency change and force were related through the contact area, and a material-dependent explanatory model was found as Deltaf proportional, variant rhoE(-1)F. It explains the measurement principle and the previously established stiffness parameters from the material properties point of view.

Resistivity of high-Tc superconductors: Linear in T at constant P, non-linear at constant V

Abstract The observed constant-pressure resistivity ϱp of most high-Tc superconductors is linear in temperature T over large ranges. We show that this is not true for the constant-volume resistivity ϱv; for 1–2–3 YBCO the correction from ϱp to ϱv is -32% at 500 K relative to the low-T value. Since theory predicts ϱv rather than ϱp, the observed linearity of ϱ probably cannot be used as a tool to choose between theories for high-Tc superconductivity.

Evaluation of applanation resonator sensors for intra-ocular pressure measurement: results from clinical and in vitro studies.

Glaucoma is an eye disease that, in its most common form, is characterised by high intra-ocular pressure (IOP), reduced visual field and optic nerve damage. For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring IOP. Recently, an applanation resonator sensor (ARS) for measuring IOP was introduced and evaluated using anin vitro pig-eye model. In the present study, the first clinical evaluation of the same probe has been carried out, with experimentsin vivo on human eyes. There was a low but significant correlation between IOPARS and the IOP measured with a Goldmann applanation tonometer (r=0.40, p=0.001, n=72). However, off-centre positioning of the sensor against the cornea caused a non-negligible source of error. The sensor probe was redesigned to have a spherical, instead of flat, contact surface against the eye and was evaluated in thein vitro model. The new probe showed reduced sensitivity to off-centre positioning, with a decrease in relative deviation from 89% to 11% (1 mm radius). For normalised data, linear regression between IOPARS and direct IOP measurement in the vitreous chamber showed a correlation of r=0.97 (p<0.001, n=108) and a standard deviation for the residuals of SD≦2.18 mm Hg (n=108). It was concluded that a spherical contact surface should be preferred and that further development towards a clinical instrument should focus on probe design and signal analysis.

A FEM-based method using harmonic overtones to determine the effective elastic, dielectric, and piezoelectric parameters of freely vibrating thick piezoelectric disks

To gain an understanding of the electroelastic properties of tactile piezoelectric sensors used in the characterization of soft tissue, the frequency-dependent electric impedance response of thick piezoelectric disks has been calculated using finite element modeling. To fit the calculated to the measured response, a new method was developed using harmonic overtones for tuning of the calculated effective elastic, piezoelectric, and dielectric parameters. To validate the results, the impedance responses of 10 piezoelectric disks with diameterto- thickness ratios of 20, 6, and 2 have been measured from 10 kHz to 5 MHz. A two-dimensional, general purpose finite element partial differential equation solver with adaptive meshing capability run in the frequency-stepped mode, was used. The equations and boundary conditions used by the solver are presented. Calculated and measured impedance responses are presented, and resonance frequencies have been compared in detail. The comparison shows excellent agreement, with average relative differences in frequency of 0.27%, 0.19%, and 0.54% for the samples with diameter-to-thickness ratios of 20, 6, and 2, respectively. The method of tuning the effective elastic, piezoelectric, and dielectric parameters is an important step toward a finite element model that describes the properties of tactile sensors in detail.

Spatial variations in prostate tissue histology as measured by a tactile resonance sensor

In recent years, tactile sensors based on piezoelectric resonance sensor technology have been used for medical diagnosis where the sensors stiffness-measuring properties can reflect tissue pathology. The change in the frequency of the resonating system and the change in force when contact is made with tissue are used as a stiffness parameter. Earlier stiffness measurements of prostate tissue in vitro demonstrate variations related to tissue composition. In this study, measured stiffness from two human prostate specimens was compared to histological composition of prostate tissue below and around the measurement points. Tissue stiffness was measured with the resonance sensor system. Tissue composition was measured at four different depths in the tissue specimen using a microscopic-image-based morphometrical method. With this method, the proportion of tissue types was determined at the points of intersections in a circular grid on the images representing each measurement point. Numerical values were used for weighting the tissue proportions at different depths in the tissue specimen. For an impression depth of 1.0 mm, the sensing depth in this study was estimated to be 3.5-5.5 mm. Stiffness variations due to horizontal tissue variations were investigated by studying the dependence of the size of the circular grid area relative to the contact area of the sensor tip. The sensing area (grid radius) was estimated to be larger than the contact area (contact radius) between the sensor tip and the tissue. Thus, the sensor tip registers spatial variations in prostate tissue histology, both directly below and lateral to the tip itself. These findings indicate that tumours around the sensor tip could be detected, which in turn supports the idea of a future resonance-sensor-based clinical device for detecting tumours and for guiding biopsies.

Formation of the 124-phase superconductor YBa2Cu4O8 by retaining oxygen in a reaction HIP sintering process

The ceramic superconductor YBa2Cu4O8 has been produced by high temperature sintering of a mixture of CuO and YBa2Cu3O7 in a glass capsule under high hydrostatic argon pressure. The resulting highly dense material is investigated by X-ray diffraction, optical and electron microscopy, resistance measurements and hardness measurements, and shown to be a homogeneous High transition temperature superconductor.

Indentation loading response of a resonance sensor : discriminating prostate cancer and normal tissue

Abstract Prostate cancer is the most common type of cancer among men worldwide. Mechanical properties of prostate tissue are promising for distinguishing prostate cancer from healthy prostate tissue. The aim was to investigate the indentation loading response of a resonance sensor for discriminating prostate cancer tissue from normal tissue. Indentation measurements were done on prostate tissue specimens ex vivo from 10 patients from radical prostatectomy. The measurement areas were analysed using standard histological methods. The stiffness parameter was linearly dependent on the loading force (average R2 = 0.90) and an increased loading force caused a greater stiffness contrast of prostate cancer vs normal tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with the area under the curve being 0.941 for a loading force of 12.8 mN. The results are promising for the development of a resonance sensor instrument for detecting prostate cancer.

Contact angle and indentation velocity dependency for a resonance sensor—Evaluation on soft tissue silicone models

Abstract Human tissue stiffness can vary due to different tissue conditions such as cancer tumours. Earlier studies show that stiffness may be detected with a resonance sensor that measures frequency shift and contact force at application. Through the frequency shift and the contact force, a tissue stiffness parameter can be derived. This study evaluated how the probe application angle and indentation velocity affected the results and determined the maximum parameter errors. The evaluation was made on flat silicone discs with specified hardness. The frequency shift, the force and the stiffness parameter all varied with contact angle and indentation velocity. A contact angle of ≤10° was acceptable for reliable measurements. A low indentation velocity was recommended. The maximum errors for the system were <1.1% of the measured values. It was concluded that contact angle and indentation velocity have to be considered in the clinical setting. The angular dependency is especially important in clinical use for studying stiffness of human soft tissue, e.g. in prostate cancer diagnosis.