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A Tactile Resonance Sensor System for Detection of Prostate Cancer ex vivo: Design and Evaluation on Tissue Models and Human Prostate
Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

The most common form of cancer among males in Europe and the USA is prostate cancer, PCa. Surgical removal of the prostate is the most common form of curative treatment. PCa can be suspected by a blood test for a specific prostate antigen, a PSA-test, and a digital rectal examination, DRE where the physician palpates the prostate through the rectum. Stiff nodules that can be detected during the DRE, and elevated levels of PSA are indications for PCa, and a reason for further examination. Biopsies are taken from the prostate by guidance of a transrectal ultrasound. Superficial cancer tumours can indicate that the cancer has spread to other parts of the body. Tactile resonance sensors can be used to detect areas of different stiffness in soft tissue. Healthy prostate tissue is usually of different stiffness compared to tissue with PCa.

Aim

The general aim of this doctoral thesis was to design and evaluate a flexible tactile resonance sensor system (TRSS) for detection of cancer in soft human tissue, specifically prostate cancer. The ability to detect cancer tumours located under the surface was evaluated through measurements on tissue phantoms such as silicone and biological tissues. Finally measurements on resected whole prostate glands were made for the detection of cancer tumours.

Methods

The sensor principle was based on an oscillating piezoelectric element that was indented into the soft tissue.  The measured parameters were the change in resonance frequency, Δf, and the contact force F during indentation. From these, a specific stiffness parameter  was obtained. The overall accuracy of the TRSS was obtained and the performance of the TRSS was also evaluated on tissue models made of silicone, biological tissue and resected whole human prostates in order to detect presence of PCa. Prostate glands are generally spherical and a special rotatable sample holder was included in the TRSS. Spherically shaped objects and uneven surfaces call for special attention to the contact angle between the sensor-tip and the measured surface, which has been evaluated. The indentation velocity and the depth sensitivity of the sensor were evaluated as well as the effect on the measurements caused by the force with which spherical samples were held in place in the sample holder. Measurements were made on silicone models and biological tissue of chicken and pork muscles, with embedded stiff silicone nodules, both on flat and spherical shaped samples. Finally, measurements were made on two excised whole human prostates.

Results

A contact angle deviating ≤ 10° from the perpendicular of the surface of the measured object was acceptable for reliable measurements of the stiffness parameter. The sensor could detect stiff nodules ≤ 4 mm under the surface with a small indentation depth of 0.4 to 0.8 mm.

Measurements on the surface of resected human prostate glands showed that the TRSS could detect stiff areas (p < 0.05), which were confirmed by histopathological evaluation to be cancer tumours on, and under the surface.

Conclusions

A flexible resonance sensor system was designed and evaluated on soft tissue models as well as resected whole prostate glands. Evaluations on the tissue models showed that the TRSS can detect stiffer volumes hidden below the surface on both flat and spherical samples. The measurements on resected human prostate glands showed that PCa could be detected both on and under the surface of the gland. Thus the TRSS provides a promising instrument aimed for stiffness measurements of soft human tissue that could contribute to a future quantitative palpation method with the purpose of diagnosing cancer. 

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2014. , 47 p.
Series
Resonance Sensor Lab, ISSN 1653-6789 ; 6
National Category
Medical Equipment Engineering
Research subject
Electronics
Identifiers
URN: urn:nbn:se:umu:diva-86322ISBN: 978-91-7601-006-8 (print)OAI: oai:DiVA.org:umu-86322DiVA: diva2:698546
Public defence
2014-03-20, MA 121, MIT-huset, Umeå universitet, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2014-02-26 Created: 2014-02-24 Last updated: 2014-03-24Bibliographically approved
List of papers
1. A flexible sensor system using resonance technology for soft tissue stiffness measurements: evaluation on silicone
Open this publication in new window or tab >>A flexible sensor system using resonance technology for soft tissue stiffness measurements: evaluation on silicone
2011 (English)In: 15TH NORDIC-BALTIC CONFERENCE ON BIOMEDICAL ENGINEERING AND MEDICAL PHYSICS (NBC 2011) / [ed] K. Dremstrup, S. Rees, M.Ø. Jensen, Aalborg: Springer , 2011, 21-24 p.Conference paper, Published paper (Refereed)
Abstract [en]

One of the most common forms of cancer amongmen in Europe and the United States is prostate cancer. Thecancerous tissue is less soft, and has different biomechanicalproperties compared to healthy tissue. It has been shown thattactile sensors can be used to distinguish this difference. If apiezoelectric sensor is set to oscillate at its resonance frequencythrough a feed back circuit, a frequency shift is observed whenthe sensor comes in contact with a surface. This shift can becorrelated to the stiffness of the tissue. A flexible instrumenthas been developed, with which it is possible to scan both flatand spherical bodies and where the sensor can be tilted to havedifferent contact angles. Measurements performed in thisstudy on flat silicone discs of different stiffness showed arelationship between both the frequency shift and theimpression depth for the different silicone discs, when aconstant force was applied. The results are promising forfuture studies on silicone with different geometries and finallyon prostate tissue to complete the evaluation.

Place, publisher, year, edition, pages
Aalborg: Springer, 2011
Series
IFMBE Proceedings, ISSN 1680-0737 ; 34
Keyword
Resonance sensor, Piezoelectric, Prostate cancer, Detection, Frequency shift
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:umu:diva-45160 (URN)10.1007/978-3-642-21683-1 (DOI)000308452500005 ()978-3-642-21682-4 (ISBN)
Conference
15th Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC 2011), JUN 14-17, 2011, Aalborg, DENMARK
Available from: 2011-06-23 Created: 2011-06-23 Last updated: 2017-01-17Bibliographically approved
2. Stiffness measurements on spherical surfaces of prostate models using a resonance sensor
Open this publication in new window or tab >>Stiffness measurements on spherical surfaces of prostate models using a resonance sensor
2013 (English)In: World Congress on Medical Physics and Biomedical Engineering May 26-31, 2012, Beijing, China / [ed] Mian Long, Springer Berlin/Heidelberg, 2013, 1401-1404 p.Conference paper, Published paper (Refereed)
Abstract [en]

Prostate cancer is one of the most common formsof cancer among men in Europe and the United States.Piezoelectric resonance sensors can be used in medicalresearch for measurements of stiffness of human tissue.Cancer tissue is usually stiffer and has different biomechanicalproperties compared to healthy tissue. The frequency shiftobserved when a piezoelectric resonance sensor comes intocontact with a tissue surface has been suggested to correlatewith the stiffness variations, e.g. due to cancer. An instrumenthas been developed, with which it is possible to scan flat andspherical objects and where the sensor can be tilted fordifferent contact angles. Measurements performed in thisstudy on spherical tissue models made of silicone, showed theimportance of keeping the contact angle perpendicular to thesurface of the sphere. The results are promising for futurestudies on prostate tissue to complete the evaluation of theinstrument.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2013
Series
IFMBE Proceedings, ISSN 1680-0737 ; 39
Keyword
Resonance sensor, Piezoelectric, Prostate cancer, Detection, Frequency shift
National Category
Medical Engineering
Research subject
Electronics
Identifiers
urn:nbn:se:umu:diva-55888 (URN)10.1007/978-3-642-29305-4_368 (DOI)978-3-642-29304-7 (ISBN)978-3-642-29305-4 (ISBN)
Conference
WC2012 World Congress on Medical Physics and Biomedical Engineering, Beijing, China, May 26-31, 2012
Available from: 2012-06-08 Created: 2012-06-08 Last updated: 2014-03-10Bibliographically approved
3. Contact angle and indentation velocity dependency for a resonance sensor: Evaluation on soft tissue silicone models
Open this publication in new window or tab >>Contact angle and indentation velocity dependency for a resonance sensor: Evaluation on soft tissue silicone models
2013 (English)In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 37, no 3, 185-196 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keyword
Contact angle, Frequency shift, Indentation velocity, Resonance sensor, Tissue stiffness
National Category
Medical Engineering
Identifiers
urn:nbn:se:umu:diva-68970 (URN)10.3109/03091902.2013.773097 (DOI)
Available from: 2013-05-02 Created: 2013-05-02 Last updated: 2017-12-06Bibliographically approved
4. Detection of stiff nodules embedded in soft tissue phantoms, mimicking cancer tumours, using a tactile resonance sensor
Open this publication in new window or tab >>Detection of stiff nodules embedded in soft tissue phantoms, mimicking cancer tumours, using a tactile resonance sensor
2014 (English)In: Journal of Biomedical Science and Engineering, ISSN 1937-6871, E-ISSN 1937-688X, Vol. 7, 181-193 p.Article in journal (Refereed) Published
Abstract [en]

Background

Prostate cancer (PCa) is the most common form of cancer among males in Europe and in the USA and the most common curative treatment is removal of the prostate, i.e. prostatectomy. After the removal, the prostate is histopathologically analysed. One area of interest is to examine the capsule of the prostate, as tumours on and near the surface can indicate that the PCa has spread to other parts of the body. There are no current methods to examine the surface of the prostate at the time of surgery. Tactile resonance sensors can be used for detecting areas of different stiffness in soft tissue. Human prostate tissue affected by cancer is usually stiffer than healthy tissue, and for this purpose a tactile resonance sensor was developed. The aim of this study was to investigate the depth at which embedded stiffer volumes could be detected, using soft tissue phantoms.

Methods

With the tactile resonance sensor used in this study, the shift of the resonance frequency and the force at contact with tissue can be measured, and combined into a tissue stiffness parameter. The detection sensitivity of the sensor at impression depths, 0.4 and 0.8 mm, was measured for detection of an inserted nodules of stiff silicone in softer silicone and in chicken muscle tissue, mimicking prostate tissue with cancer tumours.

Results

Measurements on the silicone samples detected the hidden stiffer object at a depth of 1-4 mm with a difference in the stiffness parameter of 80 – 900 mN/kHz (p < 0.028, n = 48). At the depth 5-6 mm the difference was smaller but still significant < 30 mN/kHz (p < 0.05, n = 24). For the measurements on chicken muscle, the detectable depth was 4 mm (p < 0.05, n = 24).

Conclusion

This model study suggests that, with only a small impression depth of ≤ 1 mm, the resonance sensor system described here can detect stiffness variations located at least 4 mm in silicone and chicken muscle, mimicking tumours in prostate tissue.

Keyword
Tissue stiffness, Resonance sensor, Prostate cancer, Piezoelectric, Depth sensitivity, Tactile sensor
National Category
Other Medical Biotechnology
Research subject
Electronics
Identifiers
urn:nbn:se:umu:diva-86284 (URN)10.4236/jbise.2014.74022 (DOI)
Available from: 2014-02-21 Created: 2014-02-21 Last updated: 2017-04-22Bibliographically approved
5. The first study on whole human prostate ex vivo using a tactile resonance sensor for cancer detection
Open this publication in new window or tab >>The first study on whole human prostate ex vivo using a tactile resonance sensor for cancer detection
Show others...
(English)Article in journal (Other academic) Submitted
Abstract [en]

Prostate cancer (PCa) is the most common form of cancer among males in Europe and the USA. A prostatectomy i.e. the removal of the prostate is the most common form of curative treatment. Prostate cancer can be suspected by a blood test for a prostate specific antigen (PSA) and a digital rectal examination (DRE) where a physician palpates the prostate through the rectum and where stiff nodules on the prostate is an indication for PCa. The final diagnosis of PCa is made by microscopic evaluation of ultrasound-guided biopsies taken from suspicious parts of the gland. After a prostatectomy the entire prostate is histopathologically analysed. One area of interest is the superficial part of the prostate gland as tumour growth on the surface suggests that the cancer has spread to other parts of the body.

 

Tactile resonance sensors can be used to detect areas of different stiffness in soft tissue through a stiffness parameter. It is suggested that tactile resonance sensors can be used to detect prostate cancer since tumours in the human prostate usually is stiffer compared to surrounding healthy glandular tissue.

 

The aim of the study was to detect tumours on, and beneath the surface, of whole human prostate glands ex vivo using a tactile resonance sensor system (TRSS). Model studies on spherical shaped tissue phantoms made of silicone and porcine tissue were performed to evaluate the ability of the TRSS to detect stiffer volumes at a distance beneath the surface. Finally two resected human prostate glands ex vivo from patients undergoing surgery for prostate cancer were studied.

 

From the results it was concluded that the clamping force from the rotatable sample holder did not affect the magnitude of the stiffness parameter for the silicone samples. For the porcine muscle samples, the stiffness parameter showed to be affected by clamping forces larger than about 800 mN. The embedded stiff silicone nodules placed about 4 mm under the surface could be detected in both the silicone and biological tissue models with a sensor indentation distance of 0.6 mm. The measurements on resected whole human prostates showed that areas with elevated stiffness parameter values correlated (p < 0.05) with areas where cancer tumours were detected using histolopathological evaluation of the prostate. The tumours were significantly stiffer than the healthy tissue in the dorsal region. This is promising for the development of a clinically useful instrument to detect superficial prostate cancer.

Keyword
Tissue stiffness, Resonance sensor, Prostate cancer, Piezoelectric, Depth sensitivity, Tactile sensor
National Category
Medical Biotechnology
Research subject
Electronics
Identifiers
urn:nbn:se:umu:diva-86288 (URN)
Available from: 2014-02-21 Created: 2014-02-21 Last updated: 2014-02-25

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Åstrand, Anders P

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