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1.
  • Hallberg, Per, 1965- (author)
  • Applanation Resonance Tonometry for Intraocular Pressure Measurement
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma. Since glaucoma is a leading cause of blindness, reliable methods for measuring the IOP are important. This doctoral dissertation presents a new method, applanation resonance tonometry (ART), for measurement of IOP. The method is based on resonance sensor technology combined with the novel multipoint analysis of continuously sampled data of both contact force and contact area. The ART was evaluated in in vitro porcine-eye studies as well as in clinic on both healthy volunteers and patients. A new symmetric probe with a larger sensor tip and improved aligning light was developed and evaluated in vitro. It showed that the error from off-centring was highly reduced. The new ART probe, used as a biomicroscope device (ARTBiom) and as a handheld device (ARTHand), was further evaluated in a clinical study designed in accordance with the International Standard Organisation’s (ISO) requirement. Both the ARTBiom and the ARTHand met the precision set by the requirements. Laser surgery is a common way to correct vision. The biomechanical effect of photorefractive keratectomy (PRK) on IOP measurements was evaluated using Goldmann applanation tonometry (GAT) and ART in an in vitro study. Both methods were affected, but to a different extent. The flat contact probe of GAT, as compared with the convex tip of ART, and single point vs. multipoint approach, provide explanation to the ART advantage regarding measurement error of IOP after PRK. In conclusion, resonance sensor technology has made it possible to introduce a new multipoint method for measuring IOP, and the method is relevant for measuring IOP in humans. It may be possible to reduce errors in the clinical measurement of IOP with this new method, especially after corneal surgery. The ART has the potential to become a useful clinical instrument for IOP measurement.
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2.
  • Jalkanen, Ville, 1978- (author)
  • Resonance sensor technology for detection of prostate cancer
  • 2006
  • Licentiate thesis (other academic/artistic)abstract
    • Prostate cancer is the most common type of cancer in men in Europe and the USA. Some prostate tumours are regarded as stiffer than the surrounding normal tissue, and therefore it is of interest to be able to reliably measure prostate tissue stiffness. The methods presently used to detect prostate cancer are inexact, and new techniques are needed. In this licentiate thesis resonance sensor technology, with its ability to measure tissue stiffness, was applied to normal and cancerous prostate tissue. A piezoelectric transducer element in a feedback system can be set to vibrate at 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 pathophysiological conditions. An impression-controlled resonance sensor system was used to quantify stiffness in human prostate tissue in vitro using a combination of frequency change and force measurements. Measurements on prostate tissue showed statistically significant (p < 0.001) and reproducible differences between normal healthy tissue and tumour tissue when using a multivariate parameter analysis. Measured stiffness varied in both the normal tissue and tumour tissue group. One source of variation was assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces, different levels of dehydration of the prostates, and actual differences between patients. The prostate 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 coefficient of determination was R2 ≥ 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. It is concluded that prostate cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differentiate from cancer. Furthermore, the results of this study indicated that the resonance sensor could be used to detect stiffness variations in human prostate tissue in vitro, and especially due to prostate cancer. This is promising for the development of a future diagnostic tool for prostate cancer.
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3.
  • Jalkanen, Ville, 1978- (author)
  • Tactile sensing of prostate cancer : a resonance sensor method evaluated using human prostate tissue in vitro
  • 2007
  • Doctoral thesis (other academic/artistic)abstract
    • 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.
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4.
  • Jonsson, Ulf G, 1950- (author)
  • Detecting Inclusions in a Silicone Rubber Phantom Using Standing Lamb Waves and Multiple Frequency Footprints
  • 2014
  • Doctoral thesis (other academic/artistic)abstract
    • The thesis deals with one major question: is it possible, using one piezoelectric sensor/vibrator, to detect a hard inclusion in a silicone rubber phantom? The question was approached with an open mind and the task was subdivided into three clearly identifiable parts: characterization of the piezoelectric sensor/vibrator (paper I), creating a model of the visco-elastic properties of a tissue-like material (phantom) in contact with the sensor/vibrator (paper II), and to detect the presence of a hard inclusion in the phantom (paper III). All vibrations of the sensor/vibrator and phantom was modeled using a finite element method (FEM). To minimize the computational time and to maximize the FEM model's ability to correctly reproduce the vibrations, a two-dimensional model system consisting of a cylindrical piezoelectric sensor/vibrator, emitting radial elastic waves in to a cylindrical disk-shaped phantom, was chosen. The piezoelectric sensor/vibrator was characterized using a parameter tuning procedure using harmonic overtones. The procedure enables tuning of the electro-elastic parameters of the sensor/vibrator so that the measured and calculated impedance frequency responses match. Silicone rubber was chosen as a phantom to mimic soft tissue. The properties of the phantom was modeled using a fractional derivative visco-elastic model. The hyperelastic effect at the first radial resonance of the sensor vibrator was corrected for by a compensating function. The high frequency complex visco-elastic modulus of the silicone rubber was determined using the transitions of standing Lamb waves in the phantom. The presence of a ring-shaped inclusion in the phantom, of polyamide, was detected using the change of the transitional Lamb wave patterns in the phantom. The tuning of the PZT5A1 sensor/vibrator parameters yielded a match between the calculated and the measured impedance spectra better than 0.54%. The average, complex, elastic modulus of three silicone rubber, Silgel 612, samples were: (0.97 + 0.009i) GPa  at 100 kHz and (0.97 + 0.005i) GPa at 250 kHz. The presence of a polyamide inclusion, PA6GPE, was detected in the phantom using multiple frequency footprints.
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5.
  • Åstrand, Anders P. (author)
  • A flexible resonance sensor system for detection of cancer tissue : evaluation on silicon
  • 2012
  • Licentiate thesis (other academic/artistic)abstract
    • 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.
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6.
  • Åstrand, Anders P, 1961- (author)
  • A Tactile Resonance Sensor System for Detection of Prostate Cancer ex vivo : Design and Evaluation on Tissue Models and Human Prostate
  • 2014
  • Doctoral thesis (other academic/artistic)abstract
    • 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.AimThe 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.ResultsA 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. 
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