The use of transcranial Doppler (TCD) ultrasound for the assessment of cerebral blood flow velocity (CBFV) provides an indication of cerebral blood flow assuming the diameter of the insonated vessel remains constant. Studies using TCD have traditionally described cerebrovascular hemodynamics with respect to CBFV and cerebrovascular resistance (CVRi); however, a more complete assessment of the cerebral circulation can be gleaned from the analysis of within beat characteristic of the TCD velocity waveform for the determination of cerebrovascular tone. Therefore, the general purpose of the presented studies was to assess CBFV responses and within beat characteristic for the description of cerebrovascular hemodynamics after long duration spaceflight, with sustained orthostasis, in response to changes in the partial pressure of end tidal carbon dioxide (PETCO2), and with NG stimulation. After long duration spaceflight, cerebrovascular autoregulation was found to be impaired along with a reduction in cerebrovascular CO2 reactivity (Study 1). Additionally, critical closing pressure (CrCP) was found to be increased suggesting potential remodelling of the cerebrovasculature contributing to an increase in cerebrovascular tone (Study 2). With sustained orthostasis, CBFV was found to progressively decrease and to be related to reductions in PETCO2 and increases in CrCP suggesting the contribution of changes in cerebrovascular tone leading to the development of syncope (Study 4). The CBFV reduction with the progression towards syncope was also associated with changes in waveform morphology such that the dicrotic notch point was less than the end diastolic value (Study 3). Mathematical modelling (RCKL) was used to further assess changes in cerebrovascular hemodynamics for physiological interpretation of changes in CBFV waveform morphology and found that the amplitude of the dicrotic notch and the calculation of the augmentation index were both significantly related to vascular compliance before and after stimulation with NG (Study 5). The use of quantitative assessments of common carotid artery (CCA) blood flow as an indicator of cerebral blood flow suggested the dilation of the middle cerebral artery (MCA) with NG (Study 5 and 6) and changes in MCA diameter with acute alterations in PETCO2 (Study 6). CCA and MCA velocity wave morphology were assessed showing that with changes in PETCO2, changes in CBFV velocity wave were not reflected in the CCA trace (Study 7). In addition, further assessment of the CBFV velocity trace and the calculation of CrCP and the augmentation index suggested that with changes in PETCO2 cerebrovascular compliance and cerebrovascular tension, both thought to be components of cerebrovascular tone, change independently (Study 7). Combined, the results of the presented studies suggest that changes in cerebrovascular hemodynamics can be determined from alterations in the CBFV velocity waveform morphology. However, further work is required to determine how these variations relate to specific components of cerebrovascular tone, including alterations in cerebrovascular compliance and vascular tension, and how these variables change with acute and chronic alterations in cerebrovascular hemodynamics.

In order to continue development of an ultrasound-guidance system for spinal fusion surgery, simulation and experimental research was conducted to study the effects of bone on ultrasound imaging. Simulation work examined the effect of bone volume and transducer frequency on image quality and accuracy. Experimental work utilized a 3.2MHz prototype ultrasound probe to create ultrasound images of pedicles. The simulation results, based on an idealized anatomical model, provided higher-quality images than the experimental results. It was determined that high bone volume and high transducer frequency have a detrimental effect on image quality. The experimental results suggest that the high variability in pedicle shape results in variability in ultrasound image quality. Overall, the simulation and experimental results suggest that ultrasound imaging of bone is feasible at relatively low frequencies, while highlighting the need for more experiments to take into account the substantial variability in pedicle shape and bone volume.

Endogenously, VEGF initiates angiogenesis, then later Angiopoietin (Ang)-1 matures vessels. We hypothesized that multigene therapy of VEGF before Ang1 to ischemic hindlimb tissue would result in persistent angiogenesis. At 2, 4 and 8 wks after inducing ischemia, blood flow was assessed by contrast-enhanced ultrasound. Animals were treated with VEGF at 2 wks, VEGF/Ang1 at 2 wks, or VEGF at 2 wks and Ang1 at 4 wks. In untreated controls, blood flow remained reduced. After VEGF delivery, resting flow and vessel density increased; however, flow reserve remained reduced, and vasculature was capillary-rich and eventually regressed. After VEGF/Ang1 co-delivery, flow increased marginally, flow reserve improved and vascular architecture remained normal. After separated VEGF and Ang1 delivery, flow, vessel density and flow reserve increased and were sustained, while vascular architecture remained normal. In conclusion, temporally separated VEGF and Ang1 delivery promotes sustained angiogenesis and improved vessel functionality.

In order to continue development of an ultrasound-guidance system for spinal fusion surgery, simulation and experimental research was conducted to study the effects of bone on ultrasound imaging. Simulation work examined the effect of bone volume and transducer frequency on image quality and accuracy. Experimental work utilized a 3.2MHz prototype ultrasound probe to create ultrasound images of pedicles. The simulation results, based on an idealized anatomical model, provided higher-quality images than the experimental results. It was determined that high bone volume and high transducer frequency have a detrimental effect on image quality. The experimental results suggest that the high variability in pedicle shape results in variability in ultrasound image quality. Overall, the simulation and experimental results suggest that ultrasound imaging of bone is feasible at relatively low frequencies, while highlighting the need for more experiments to take into account the substantial variability in pedicle shape and bone volume.

Endogenously, VEGF initiates angiogenesis, then later Angiopoietin (Ang)-1 matures vessels. We hypothesized that multigene therapy of VEGF before Ang1 to ischemic hindlimb tissue would result in persistent angiogenesis. At 2, 4 and 8 wks after inducing ischemia, blood flow was assessed by contrast-enhanced ultrasound. Animals were treated with VEGF at 2 wks, VEGF/Ang1 at 2 wks, or VEGF at 2 wks and Ang1 at 4 wks. In untreated controls, blood flow remained reduced. After VEGF delivery, resting flow and vessel density increased; however, flow reserve remained reduced, and vasculature was capillary-rich and eventually regressed. After VEGF/Ang1 co-delivery, flow increased marginally, flow reserve improved and vascular architecture remained normal. After separated VEGF and Ang1 delivery, flow, vessel density and flow reserve increased and were sustained, while vascular architecture remained normal. In conclusion, temporally separated VEGF and Ang1 delivery promotes sustained angiogenesis and improved vessel functionality.

Polycystic ovary syndrome (PCOS) is an endocrine abnormality with multiple diagnostic criteria due to its heterogenic manifestations. One of the diagnostic criterion includes analysis of ultrasound images of ovaries for the detection of number, size, and distribution of follicles within the ovary. This involves manual tracing of follicles on the ultrasound images to determine the presence of a polycystic ovary (PCO). A novel method that automates PCO morphology detection is described. Our algorithm involves automatic segmentation of follicles from ultrasound images, quantifying the attributes of the segmented follicles using stereology, storing follicle attributes as feature vectors, and finally classification of the feature vector into two categories. The classification categories are PCO morphology present and PCO morphology absent. An automatic PCO diagnostic tool would save considerable time spent on manual tracing of follicles and measuring the length and width of every follicle. Our procedure was able to achieve classification accuracy of 92.86% using a linear discriminant classifier. Our classifier will improve the rapidity and accuracy of PCOS diagnosis, and reduce the chance of the severe health implications that can arise from delayed diagnosis.

Shoulder pain is very common, affecting 14-21 % of the population at some time during their lifetime. The aims of this thesis were to improve the understanding of various aspects concerning the pathogenesis and treatment of subacromial pain and rotator cuff tears. Patients and healthy individuals were examined and compared in five studies: Study I) Seventy patients were retrospectively examined, clinically and with ultrasound, 15 years after arthroscopic subacromial decompression. All patients had an intact rotator cuff at surgery. Ultrasound showed significantly fewer rotator cuff tears compared to the prevalence of asymptomatic tears reported in the literature for the same age group. This indicates that arthroscopic subacromial decompression might protect the rotator cuff. Study II) Forty-two patients were retrospectively examined, clinically and with ultrasound, 39 months (mean) after an acute rotator cuff repair. All patients had pseudoparalysis after trauma, a full thickness tear and no previous history of shoulder symptoms. A delay in surgical treatment of three months and the number of tendons injured did not affect the outcome. Age affected outcome negatively. Study III) Plasma samples from 17 patients with cuff tears and 16 plasma samples from healthy age- and gender-matched controls were collected and analysed regarding the levels of matrix metalloproteinases and their inhibitors, TIMP1-4. Elevated levels of TIMP-1 were found in the patients with cuff tears compared to controls. Higher levels of TIMP-1, TIMP-3 and MMP-9 were found in patients with full-thickness tears compared to patients with partial-thickness tears. Study IV) Ninety-seven patients with longstanding subacromial pain, on the waiting-list for arthroscopic subacromial decompression, were prospectively randomised to specific shoulder exercises or control exercises for three months. Thereafter they were clinically examined and asked if they still wanted surgery. The specific shoulder exercises focusing on eccentric exercise for the rotator cuff and scapula stabilisers were found to be effective in reducing subacromial pain and improving shoulder function, thereby reducing the need for surgery. Study V) All patients including those operated, in Study IV were re-examined after one year using clinical assessment scores. The option of surgery was continuously available up to the one-year follow-up. Ultrasound and radiological examinations performed at inclusion were analysed in relation to the choice of surgery. The positive effects of the specific exercise programme were maintained after one year and significantly fewer patients in this group chose surgery. Surgery was significantly more often chosen by patients who had a low baseline shoulder score, and/or a full thickness rotator cuff tear.  All patients showed significant improvement in the clinical scores one year after inclusion or one year after surgery. These results support the concept that subacromial pain has a multifactorial aetiology and that the first line of treatment should be specific shoulder exercises. When conservative treatment fails, an acceptable result can be achieved with arthroscopic subacromial decompression. The rotator cuff status is important to consider when treating and studying these patients.

Measuring human subcutaneous fat is useful for assessing health risks due to obesity and for monitoring athletes’ health status, body shapes and weight for various sports competitions such as gymnastics and wrestling. Our aim is to investigate the use of ultrasound imaging in automatically measuring human subcutaneous fat thickness. We proposed to use the spectrum properties extracted from the raw radio frequency (RF) signals of ultrasound for the purpose of fat boundary detection. Our fat detection framework consists of four main steps. The first step is capturing RF data from 11 beam steering angles and at four focal positions. Secondly, two spectrum properties (spectrum variance and integrated backscatter coefficient) are calculated from the local spectrum of RF data using the short time Fourier transform and moment analysis. The values of the spectrum properties are encoded as gray-scale parametric images. Thirdly, spatial compounding is used to reduce speckle noise in the parametric images and improve the visualization of the subcutaneous fat layer. Finally, we apply Rosin’s thresholding and Random Sample Consensus boundary detection on the parametric images to extract the fat boundary. The detection framework was tested on 36 samples obtained at the suprailiac, thigh and triceps of nine human participants in vivo. When compared to manual boundary detection on ultrasound images, the best result was obtained from segmenting the spatial compounded spectrum variance values averaged over multiple focuses. A reasonable result could also be obtained by using a single focus. Further, our automatic detection results were compared with the results using skinfold caliper measurements. We found that the correlation is high between our automatic detection and skinfold caliper measurement, and is similar to the previous studies which are not automatic. Our work has shown that the spatial compounded spectrum properties of RF data can be used to segment the subcutaneous fat layer. Based on our results, it is feasible to detect fat at the suprailiac, thigh and triceps sites using the spectrum variance. The values of spectrum variance change more rapidly in the fat tissue than the non-fat tissue.

This thesis is based on observations of the physical properties of wheat flour dough using ultrasonic measurements. Three frequency ranges were used in the study, low frequencies (near 40 kHz), intermediate frequencies (1 to 5 MHz, where bubble resonance effects are apparent), and high frequencies (near 20 MHz). Doughs mixed under different head space air pressures, from vacuum to atmospheric pressure, as well as under nitrogen, were studied at low frequency to investigate their relaxation behavior. Subsamples from ambient dough and vacuum dough displayed differences in the dependence of velocity and attenuation on time after compression, but no post mixing relaxation effect was apparent. A critical headspace pressure of approximately 0.16 atmospheres determined whether vacuum-like or ambient-like relaxation was observed. A peak in attenuation and changes in ultrasonic velocity were observed around the bubble resonance frequency, and these ultrasonic parameters changed substantially as a function of time. A bubble resonance model was used to interpret the results around the bubble resonance frequency, and bubble size distributions were estimated for ambient and vacuum dough from the ultrasonic data. For the high frequency range, a molecular relaxation model was used to interpret the results. Different fast relaxation times were observed for ambient dough (5 ns) and vacuum dough (1 ns). This relaxation time may be associated with conformational rearrangements in glutenin inside the dough matrix. These experiments have enabled dough relaxation to be probed over a very wide range of time scales (from ns to hours), and will lead to a better understanding of the role of dough matrix and gas cell effects on the physical properties of wheat flour doughs. / October 2007

Measuring human subcutaneous fat is useful for assessing health risks due to obesity and for monitoring athletes’ health status, body shapes and weight for various sports competitions such as gymnastics and wrestling. Our aim is to investigate the use of ultrasound imaging in automatically measuring human subcutaneous fat thickness. We proposed to use the spectrum properties extracted from the raw radio frequency (RF) signals of ultrasound for the purpose of fat boundary detection. Our fat detection framework consists of four main steps. The first step is capturing RF data from 11 beam steering angles and at four focal positions. Secondly, two spectrum properties (spectrum variance and integrated backscatter coefficient) are calculated from the local spectrum of RF data using the short time Fourier transform and moment analysis. The values of the spectrum properties are encoded as gray-scale parametric images. Thirdly, spatial compounding is used to reduce speckle noise in the parametric images and improve the visualization of the subcutaneous fat layer. Finally, we apply Rosin’s thresholding and Random Sample Consensus boundary detection on the parametric images to extract the fat boundary. The detection framework was tested on 36 samples obtained at the suprailiac, thigh and triceps of nine human participants in vivo. When compared to manual boundary detection on ultrasound images, the best result was obtained from segmenting the spatial compounded spectrum variance values averaged over multiple focuses. A reasonable result could also be obtained by using a single focus. Further, our automatic detection results were compared with the results using skinfold caliper measurements. We found that the correlation is high between our automatic detection and skinfold caliper measurement, and is similar to the previous studies which are not automatic. Our work has shown that the spatial compounded spectrum properties of RF data can be used to segment the subcutaneous fat layer. Based on our results, it is feasible to detect fat at the suprailiac, thigh and triceps sites using the spectrum variance. The values of spectrum variance change more rapidly in the fat tissue than the non-fat tissue.