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Tactile sensing of prostate cancer: a resonance sensor method evaluated using human prostate tissue in vitro
Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Prostate cancer is the most frequent type of cancer in men in Europe and the USA. The methods presently used to detect and diagnose prostate cancer are inexact, and new techniques are needed. Prostate tumours can be regarded as harder than the surrounding normal healthy glandular tissue, and therefore it is of interest to be able to reliably measure prostate tissue stiffness. In this dissertation the approach was to evaluate tactile resonance sensor technology and its ability to measure mechanical properties and to detect cancer in human prostate tissue.

The tactile resonance sensor is based on a piezoelectric transducer element vibrating at its resonance frequency through a feedback circuit. A change in the resonance frequency is observed when the sensor contacts an object. This feature has been utilized to measure tissue stiffness variations due to various pathophysiological conditions.

An impression-controlled tactile resonance sensor system was first used to quantify stiffness and evaluate performance on silicone. Then the sensor system was used on fresh human prostate tissue in vitro to measure stiffness using a combination of frequency change and force measurements. Significant differences in measured stiffness between malignant and healthy normal tissue were found, but there were large variations within the groups.

Some of the variability was explained by prostate tissue histology using a tissue stiffness model. The tissue content was quantified at four depths in the tissue specimens with a microscope-image-based morphometrical method involving a circular grid. Numerical weights were assigned to the tissue data from the four depths, and the weighted tissue proportions were related to the measured stiffness through a linear model which was solved with a least-squares method. An increase in the proportion of prostate stones, stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Stroma and cancer had the greatest effect and accounted for 90 % of the measured stiffness (45% and 45%, respectively).

The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. A sensing depth was extrapolated from the numerical weights for the measurements performed at different impression depths. Horizontal surface tissue variations were studied by altering the circular grid size relative to the contact area between the sensor tip and the tissue. The results indicated that the sensing area was greater than the contact area. The sensor registered spatial tissue variations.

Tissue density-related variations, as measured by the frequency change, were weakly significant or non-significant. The measured force registered elastic-related tissue variations, to which stroma and cancer were the most important variables.

A theoretical material-dependent linear relation was found between frequency change and force from theoretical models of frequency change and force. Tactile resonance sensor measurements on prostate tissue verified this at small impression depths. From this model, a physical interpretation was given to the parameters used to describe stiffness.

These results indicate that tactile resonance sensor technology is promising for assessing soft tissue mechanical properties and especially for prostate tissue stiffness measurement with the goal of detecting prostate cancer. However, further studies and development of the sensor design must be performed to determine the full potential of the method and its diagnostic power. Preferably, measurements of tissue mechanical properties should be used in combination with other methods, such as optical methods, to increase the diagnostic power.

Place, publisher, year, edition, pages
Umeå: Tillämpad fysik och elektronik , 2007. , 70 p.
Series
Resonance Sensor Lab, ISSN 1653-6789 ; 4
Keyword [en]
tactile resonance sensor, prostate tissue, prostate cancer, stiffness, density, elastic, variations, tissue histology
National Category
Medical Laboratory and Measurements Technologies
Identifiers
URN: urn:nbn:se:umu:diva-1445ISBN: 978-91-7264-461-8 (print)OAI: oai:DiVA.org:umu-1445DiVA: diva2:141087
Public defence
2007-12-14, N430, Naturvetarhuset, Umeå universitet, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2011-03-30Bibliographically approved
List of papers
1. Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro.
Open this publication in new window or tab >>Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro.
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2006 (English)In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 44, no 7, 593-603 p.Article in journal (Refereed) Published
Abstract [en]

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.

Keyword
prostate tissue, stiffness, resonance sensor
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:umu:diva-19125 (URN)10.1007/s11517-006-0069-6 (DOI)16937195 (PubMedID)
Available from: 2009-03-04 Created: 2009-03-04 Last updated: 2017-12-13Bibliographically approved
2. Resonance sensor measurements of stiffness variations in prostate tissue in vitro: a weighted tissue proportion model
Open this publication in new window or tab >>Resonance sensor measurements of stiffness variations in prostate tissue in vitro: a weighted tissue proportion model
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2006 (English)In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 27, no 12, 1373-86 p.Article in journal (Refereed) Published
Abstract [en]

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 sensor's 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.

Keyword
image analysis, prostate tissue, resonance sensor
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:umu:diva-19116 (URN)10.1088/0967-3334/27/12/009 (DOI)17135706 (PubMedID)
Available from: 2009-03-04 Created: 2009-03-04 Last updated: 2017-12-13Bibliographically approved
3. Spatial variations in prostate tissue histology as measured by a tactile resonance sensor
Open this publication in new window or tab >>Spatial variations in prostate tissue histology as measured by a tactile resonance sensor
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2007 (English)In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 28, no 10, 1267-81 p.Article in journal (Refereed) Published
Abstract [en]

In recent years, tactile sensors based on piezoelectric resonance sensor technology have been used for medical diagnosis where the sensor's 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.

Keyword
prostate tissue, tactile sensor
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-19113 (URN)10.1088/0967-3334/28/10/011 (DOI)17906393 (PubMedID)
Available from: 2009-03-04 Created: 2009-03-04 Last updated: 2017-12-13Bibliographically approved
4. Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro
Open this publication in new window or tab >>Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro
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2008 (English)In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 29, no 7, 729-745 p.Article in journal (Refereed) Published
Abstract [en]

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 (Δf), 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 (ρ) and contact area (S) according to Δf ∝ ρS3/2. 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, FES3/2. 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 Δf ∝ ρE−1F. It explains the measurement principle and the previously established stiffness parameters from the material properties point of view.

Place, publisher, year, edition, pages
Bristol: IOP Publ. Ltd, 2008
Keyword
tactile resonance sensor, density, elastic, variations, prostate tissue, stiffness, parameters, explanatory, models
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:umu:diva-10349 (URN)10.1088/0967-3334/29/7/003 (DOI)18560055 (PubMedID)
Note
Tidigare titel: Elastic and density-related variations of prostate tissue in vitro as measured by a tactile resonance sensorAvailable from: 2008-08-15 Created: 2008-08-15 Last updated: 2011-09-02Bibliographically approved

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