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The most common form of cancer among men in Europe and the US is prostate cancer. When a radical prostatectomy has been found necessary, it is of interest to examine the prostate, as tumour tissue on the capsule might indicate that the cancer has metastased. This is commonly done by a microscope-based morphometric investigation. Tumour tissue is normally stiffer than healthy tissue. Sensors based on piezoelectric resonance technology have been introduced into the medical field during the last decade. By studying the change in resonance frequency when a sensor comes into contact with a material, conclusions can be drawn about the material.

A new and flexible measurement system using a piezoelectric resonance sensor has been evaluated. Three translation stages, two for horizontal movements and one for vertical movement, with stepper motors are controlled from a PC. A piezoelectric resonance element and a force sensor are integrated into a sensor head that is mounted on the vertical translation stage. The piezoelectric element is connected to a feed-back circuit and resonating at its resonance frequency until it comes into contact with a material, when a frequency shift can be observed. The force sensor is used to measure the applied force between the sensor and the material. These two parameters are combined into a third, called the stiffness parameter, which is important for stiffness evaluation. For measurements on objects with different geometries, the vertical translation stage can be aimed at a platform for flat objects or a fixture for spherical objects. The vertical translation stage is mounted on a manual rotational stage with which the contact angle between the sensor and the measured surface can be adjusted. The contact angles covered are between 0° and 35° from a line perpendicular to the surface of the measured object. The measured objects used were made from silicones of different stiffness and in the shape of flat discs and spheres. The indentation velocity of the sensor can be set at 1 mm/s to 5 mm/s. In the three papers that are the base for this licentiate thesis, we have investigated the dependence of the frequency shift, the applied force and the stiffness parameter on the contact angle, and the indentation velocity at different impression depths. The maximum error for the measurement system has also been determined.

The results of the measurements indicate that great care must be taken when aiming the sensor against the surface of the point where the measurements are to be performed. Deviations in contact angle of more than iv±10° from a line perpendicular to the surface will result in an underestimation of the frequency shift, meaning that the tissue will be regarded as stiffer than it really is. This result is important as the flat silicone models have a very even surface, which makes a controlled contact angle possible. Biological tissue can have a rough and uneven surface, which can lead to unintentional deviations in the contact angle. The magnitude of the stiffness parameter is favoured by a high indentation velocity compared to a low.

The evaluation of this measurement system has shown that it is possible to distinguish between soft and stiff silicone models, which have been used in this initial phase of the study. A new feature in this measurement system is the fixture that makes measurements on spherical objects possible and the possibility to vary the angle of contact. This is promising for future studies and measurements on whole prostate in vitro. A future application for this measurement system is to aid surgeons performing radical prostatectomy in the search for tumour tissue on the capsule of the prostate, as the presence of tumour tissue can indicate that the cancer has spread to the surrounding tissue.

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.