| 1. |
- Lindberg, Frida, 1982-
(författare)
-
Ultrasonic Quantification of Skeletal Muscle Dynamics : Feasibility and Limitations
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pain and disorders of the human skeletal muscles are one of the most common reasons for medical consultations in the western countries today and there is a great need to improve both the understanding and treatment of several different muscular conditions.Techniques describing the muscle function in vivo are often limited by either their invasiveness or lack of spatial resolution. Electromyography (EMG) is the most common approach to assess the skeletal muscle function in vivo, providing information on the neurological input. However, the spatial resolution is in general limited and there are difficulties reaching deep musculature without using invasive needles. Moreover, it does not provide any information about muscle structure or mechanical aspects.Quantitative ultrasound techniques have gained interest in the area of skeletal muscles and enables non-invasive and in-vivo insight to the intramuscular activity, through the mechanical response of the activation. However, these techniques are developed and evaluated for cardiovascular applications and there are important considerations to be made when applying these methods in the musculoskeletal field. This thesis is based on the work from four papers with the main focus to investigate and describe some of these considerations in combination with the development of processing and analyzing methods that can be used to describe the physiological characteristics of active muscle tissue.In the first paper the accuracy of the Doppler based technique Tissue Velocity Imaging (TVI) was evaluated in a phantom study for very low tissue velocities and the effect of the pulse repetition frequency was considered. The second paper presents a biomechanical model to describe the TVI strain’s dependency on the muscle fiber pennation angle. In the third and fourth papers the intramuscular activity pattern was assessed through the regional tissue deformation by motion mode (M-mode) strain imaging. The activity patterns were analyzed during force regulation and for the effects of fatigue.The work of this thesis show promising results for the application of these methods on skeletal muscles and indicate high clinical potential where quantitative ultrasound may be a valuable tool to reach a more multifaceted and comprehensive insight in the musculoskeletal function. However, the methodological considerations are highly important for the optimized application and further evaluation and development of analyzing strategies are needed.
|
|
| 2. |
- Candefjord, Stefan
(författare)
-
Combining the tactile resonance method and Raman spectroscopy for tissue characterization towards prostate cancer detection
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PCa) is the most common male cancer in Europe and the US, and only lung and colorectal cancer have a higher mortality among European men. In Sweden, PCa is the most common cause of cancer-related death for men.The overall aim of this thesis was to explore the need for new and complementary methods for PCa detection and to take the rst step towards a novel approach: combining the tactile resonance method (TRM) and Raman spectroscopy (RS). First, the main methods for PCa detection were reviewed. Second, to establish a robust protocol for RS experiments in vitro, the eects of snap-freezing and laser illumination on porcine prostate tissue were studied using RS and multivariate statistics. Third, measurements on porcine and human tissue were performed to compare the TRM and RS data via multivariate techniques, and to assess the accuracy of classifying healthy and cancerous tissue using a support vector machine algorithm.It was concluded through the literature review that the gold standard for PCa detection and diagnosis, the prostate specic antigen test and systematic biopsy, have low sensitivity and specicity. Indolent and aggressive tumors cannot be reliably dierentiated, and many men are therefore treated either unnecessarily or too late. Clinical benets of the state-of-the-art in PCa imaging - advanced ultrasound and MR techniques - have still not been convincingly shown. There is a need for complementary and cost-eective detection methods. TRM and RS are promising techniques, but hitherto their potential for PCa detection have only been investigated in vitro.In the RS study no evidence of tissue degradation due to 830 nm laser illumination at an irradiance of ∼3 · 1010 W m-2 were found. Snap-freezing and subsequent storage at -80° C gave rise to subtle but signicant changes in Raman spectra, most likely related to alterations in the protein structure. The major changes due to PCa do not seem to be related to the protein structure, hence snap-freezing may be applied in our experiments.The combined measurements on porcine and human prostate tissue showed that RS provided additional discriminatory power to TRM. The classication accuracy for healthy porcine prostate tissue, and for healthy and cancerous human prostate tissue, was > 73%. This shows the power of the support vector machine applied to the combined data.In summary, this work indicates that an instrument combining TRM and RS is a promising complementary method for PCa detection. Snap-freezing of samples may be used in future RS studies of PCa. A combined instrument could be used for tumor-border demarcation during surgery, and potentially for guiding prostate biopsies towards lesions suspicious for cancer. All of this should provide a more secure diagnosis and consequently more effcient treatment of the patient.
|
|
| 3. |
- Jalkanen, Ville, 1978-
(författare)
-
Tactile sensing of prostate cancer : a resonance sensor method evaluated using human prostate tissue in vitro
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
|
|
| 4. |
|
|
| 5. |
- Nyberg, Morgan
(författare)
-
Dual-modality probe for prostate cancer detection by combining Raman spectroscopy and tactile resonance technology
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate adenocarcinoma, or prostate cancer (PCa), is the most common type of cancer and the leading cause of cancer-related deaths for men in Sweden and Europe. Radical prostatectomy (RP) is the most common curative treatment for PCa. This is a surgical procedure where the entire prostate is removed. The surgeons strive to minimise postoperative side-effects, and will use nerve-sparing techniques if possible. The final decision on how much tissue to remove around the prostate is taken during surgery. After the prostate is resected it is histopathologically analysed. The risk of PCa recurrence is elevated when cancer cells are found in the surgical margin. Currently, there is no viable method to detect and localise PCa tumours near the resection margin during surgery. The general aim of this thesis was to develop a medical instrument with the ability to detect PCa tumours near the tissue surface.Datasets from the resonance sensor and from the Raman spectroscopy obtained on porcine model tissue were compared. Principal component analysis (PCA) was used to reduce the Raman spectroscopic dataset, and groups of tissue content were formed by a hierarchical cluster analysis (HCA) of the PCA results. The correlation of the two datasets was evaluated by a model using the PCA results for describing the stiffness of the groups.A support vector machine was evaluated as a method to combine the datasets of the two modalities. The method was used for classifying three types of porcine prostate tissues and to discern healthy vs. cancerous human prostate tissue. The cross-validation accuracy for the SVM classification was 87% for the porcine prostate and 77% for the human prostate tissue types for highly homogeneous tissue samples (>83%). Several important aspects regarding design and methods to be used for combining the two modalities into one probe were investigated. The effects of using different amounts of rubber latex for combining a TRM sensor an a fibre optic Raman probe substitute were determined. A description of the heat produced by the laser at the fibre optic tip was established, and the temperature dependence of Δf was investigated. Methods and conditions, e.g. instrument settings and light shields, for performing Raman spectroscopy with ambient light present were investigated.The dual-modality probe prototype was used to perform the first measurements on porcine model tissue. Methods for using the Raman spectroscopic modality of the combined probe with ambient light present were evaluated. The TRM modality could discern tissue with significantly different stiffness. Raman spectroscopy could be performed with ambient fluorescent light present. The first measurements on fresh human prostate tissue using the dual-modality probe were performed. Prostates with different average stiffnesses could be compared by calculating stiffness contrast. The TRM modality could discern tissue with significantly different stiffness contrast (p < 0.05). The background fluorescence in the Raman spectra of fresh human prostate tissue was higher than expected. The high-wavenumber region, 2700 cm−1 to 3200 cm−1, of the Raman spectra could be used to discern tissue characteristics using HCA of the PCA results. In this thesis, methods and design considerations for the development of a dualmodality probe, combining Raman spectroscopy and tactile resonance sensor technology, were identified and evaluated. In addition, methods for how to use the dual-modality probe for tissue classification and for combining of the datasets of the two modalities, were studied. The resonance sensor swiftly evaluates the tissue stiffness, like the palpation with a finger. The Raman spectroscopy would be applied when malignancy is suspected and adds detailed knowledge of the molecular content. This makes the dual-modality probe a promising instrument for use during RP.
|
|
| 6. |
- Olofsson, Mona, 1952-
(författare)
-
Heart failure in elderly with focus on diagnosis and prognosis
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients older than 75 years with heart failure (HF) are at increased risk for mortality and hospital admissions. Echocardiography and brain natriuretic peptides (BNP, NTproBNP) are important diagnostic tools but sparsely evaluated in elderly PHC patients. Aims: Validate the clinical diagnosis of HF, investigate the types of HF and underlying cardiovascular disorders with focus on sex and age differences. Explore the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of BNP and NT-proBNP in patients with systolic HF. Study the associations of HF or NTproBNP on all-cause and cardiovascular mortality. Study the prognostic value of different biomarkers and HF, on all-cause and cardiovascular hospitalizations. Methods: Patients with suspected HF were recruited from one selected PHC and registered on a prespecified record and referred for an echocardiographic examination and a final cardiologist consultation. Blood samples for natriuretic peptides were stored frozen at – 70° C. Death certificates were used to register all-cause mortality and cardiovascular mortality. To register hospitalisations, medical records were used and classification was defined according to ICD-10. Results The GPs identified 121 women and 49 men with suspected HF of whom 39% (51 women and 16 men) were above 80 years. Myocardial infarction (OR:4,3 CL: 1,8-10,6) hypertension (OR:3,4 CI:1,6-6,9) atrial fibrillation (OR:2,8 CL:1,0-7,9) predicted a confirmed diagnosis of HF. Confirmed HF was verified in 45% of the patients and was significantly more common in men than women (p=0,02). The best NPV was 88 % for NT-proBNP (200 ng/L) and 87 % for BNP (20 pg/ml). Age and male gender were independently associated with higher levels of NT-proBNP. During the 10-year follow up, 71 out of 144 patients died. In univariate Cox regression analysis, significant associations were found for overall HF (hazard ratio [HR]: 1.86; 95% confidence interval [CI]:1.15- 3.01), isolated systolic HF (HR:1.95; 95% CI:1.06-3.61), and combined (systolic and diastolic) HF (HR:3.28; 95% CI:1.74-6.14) with all-cause mortality, but not for isolated diastolic HF. In multivariable analysis, age (HR: 1.11; 95% CI: 1.06-1.17), kidney dysfunction (HR:1.91; 95% CI:1.11- 3.29), smoking (HR:3.70; 95% CI:2.02-6.77), and NTproBNP (HR:1.01; 95% CI:1.00-1.02), but not any type of HF, significantly predicted all-cause mortality. During ten years, 136 (80%) patients were hospitalised with 660 and 207 for all-cause and cardiovascular hospitalisations, respectively. Age (OR:1.1; 95% CI:1.01-1.15) and underlying heart disease (OR:3.5; 95% CI:1.00-11.89), significantly predicted all-cause hospitalisation. Overall HF (HR:1.8; 95% CI:1.06-2.94) significantly predicted time to first all-cause hospitalisations. For cardiovascular hospitalisations age (OR:1.1;95%CI:1.01-1.12), underlying heart disease (OR:3.4;95%CI:1.04-11.40) and NTproBNP ≥800 ng/L (OR:4,3;95%CI:1.5-12.50) were significant predictors. Conclusion: A confirmed diagnosis of HF was present in 45% of the patients. NPV was high, but not as high as in younger patients with HF. Patients with systolic HF had a higher mortality than patients with diastolic HF compared to patients with no HF. Patients with combined HF were at even higher risk for all-cause mortality and cardiovascular mortality. Age, kidney dysfunction, NTproBNP and smoking predicted mortality. Age and underlying heart diseases were predictors for all-cause hospitalisations and together with NTproBNP they also predicted cardiovascular hospitalisations.
|
|
