Quantitative assessment of myocardial function is a valuable tool for clinical applications and physiological studies. This assessment can be acquired using phase based motion sensitive magnetic resonance imaging (MRI) techniques. In this thesis, the accuracy of these phase based motion sensitive MRI techniques is investigated, and modifications in acquisition and post-processing are proposed. The strain rate of the myocardium can be used to evaluate the myocardial function. However, the estimation of strain rate from the velocity data acquired with phase-contrast MRI (PC-MRI) is sensitive to noise. Estimation using normalized convolution showed, however, to reduce this sensitivity to noise and to minimize the influence of non-myocardial tissue which could impair the result. Strain of the myocardium is another measure to assess myocardial function. Strain can be estimated from the myocardial displacement acquired with displacement encoding with stimulated echo (DENSE). DENSE acquisition can be realized with several different encoding strategies. The choice of encoding scheme may make the acquisition more or less sensitive to different sources of error. Two potential sources of errors in DENSE acquisition are the influence of the FID and of  the off-resonance effects. Their influence on DENSE were investigated to determine suitable encoding strategies to reduce their influence and thereby improve the measurement accuracy acquired. The quality of the DENSE measurement is not only dependent on the accuracy, but also the precision of the measurement. The precision is affected by the SNR and thereby depends on flip angle strategies, magnetic field strength and spatial variation of the receiver coil sensitivity. A mutual comparison of their influence on SNR in DENSE was therefore performed and could serve as a guideline to optimize parameters for specific applications. The acquisition time is often an important factor, especially in clinical applications where it affects potential patient discomfort and patient through-put. A multiple-slice DENSE acquisition was therefore presented, which allows the acquisition of strain values according to the 16-segment cardiac model within a single breath-hold, instead of the conventional three breath-holds. The DENSE technique can also be adapted toward comprehensive evaluation of the heart in the form of full three-dimensional three-directional acquisition of the displacement. To estimate the full strain tensor from these data, a novel post-processing technique using a polynomial was investigated. The method yielded accurate results on an analytical model and \textit{in-vivo} strains obtained agreed with previously reported myocardial strains in normal volunteers.

Laser Doppler flowmetry (LDF) is virtually the only non-invasive technique, except for other laser speckle based techniques, that enables estimation of the microcirculatory blood flow. The technique was introduced into the field of biomedical engineering in the 1970s, and a rapid evolvement followed during the 1980s with fiber based systems and improved signal analysis. The first imaging systems were presented in the beginning of the 1990s. Conventional LDF, although unique in many aspects and elegant as a method, is accompanied by a number of limitations that may have reduced the clinical impact of the technique. The analysis model published by Bonner and Nossal in 1981, which is the basis for conventional LDF, is limited to measurements given in arbitrary and relative units, unknown and non-constant measurement volume, non-linearities at increased blood tissue fractions, and a relative average velocity estimate. In this thesis a new LDF analysis method, quantitative LDF, is presented. The method is based on recent models for light-tissue interaction, comprising the current knowledge of tissue structure and optical properties, making it fundamentally different from the Bonner and Nossal model. Furthermore and most importantly, the method eliminates or highly reduces the limitations mentioned above. Central to quantitative LDF is Monte Carlo (MC) simulations of light transport in tissue models, including multiple Doppler shifts by red blood cells (RBC). MC was used in the first proof-of-concept study where the principles of the quantitative LDF were tested using plastic flow phantoms. An optically and physiologically relevant skin model suitable for MC was then developed. MC simulations of that model as well as of homogeneous tissue relevant models were used to evaluate the measurement depth and volume of conventional LDF systems. Moreover, a variance reduction technique enabling the reduction of simulation times in orders of magnitudes for imaging based MC setups was presented. The principle of the quantitative LDF method is to solve the reverse engineering problem of matching measured and calculated Doppler power spectra at two different source-detector separations. The forward problem of calculating the Doppler power spectra from a model is solved by mixing optical Doppler spectra, based on the scattering phase functions and the velocity distribution of the RBC, from various layers in the model and for various amounts of Doppler shifts. The Doppler shift distribution is calculated based on the scattering coefficient of the RBC:s and the path length distribution of the photons in the model, where the latter is given from a few basal MC simulations. When a proper spectral matching is found, via iterative model parameters updates, the absolute measurement data are given directly from the model. The concentration is given in g RBC/100 g tissue, velocities in mm/s, and perfusion in g RBC/100 g tissue × mm/s. The RBC perfusion is separated into three velocity regions, below 1 mm/s, between 1 and 10 mm/s, and above 10 mm/s. Furthermore, the measures are given for a constant output volume of a 3 mm3 half sphere, i.e. within 1.13 mm from the light emitting fiber of the measurement probe. The quantitative LDF method was used in a study on microcirculatory changes in type 2 diabetes. It was concluded that the perfusion response to a local increase in skin temperature, a response that is reduced in diabetes, is a process involving only intermediate and high flow velocities and thus relatively large vessels in the microcirculation. The increased flow in higher velocities was expected, but could not previously be demonstrated with conventional LDF. The lack of increase in low velocity flow indicates a normal metabolic demand during heating. Furthermore, a correlation between the perfusion at low and intermediate flow velocities and diabetes duration was found. Interestingly, these correlations were opposites (negative for the low velocity region and positive for the mediate velocity region). This finding is well in line with the increased shunt flow and reduced nutritive capillary flow that has previously been observed in diabetes.

The mechanical properties of living cells provide useful information on cellular structure and function. In the present study a micropipette aspiration technique was developed to investigate the viscoelastic parameters of isolated articular chondrocytes. The Standard Linear Solid (SLS) and the Boltzmann Standard Linear Solid (BSLS) models were used to compute the instantaneous and equilibrium moduli and viscosity based on the response to an aspiration pressure of 7 cm of water. The modulus and viscosity of the chondrocytes increased with decreasing pressure rate. For example, the median equilibrium moduli obtained using the BSLS model increased from 0.19 kPa at 5.48 cmH2O/s to 0.62 kPa at 0.35 cmH2O/s. Cell deformation during micropipette aspiration was associated with an increase in cell volume and remodelling of the cortical actin visualised using GFP-actin. Interestingly, GFP-actin transfection inhibited the increase in cell moduli observed at the slower aspiration rate. Thus actin remodelling appears to be necessary for the pressure rate-dependent behaviour. A hypothesis is proposed explaining the role of actin remodelling and interaction with the membrane in regulating cell mechanics. Further studies investigated a mechanical injury model of cartilage explants which resulted in significant increases in all three viscoelastic parameters. Treatment with IL-1β also increased the instantaneous moduli of cells treated in explants but there was no difference in equilibrium moduli or viscosity. IL-1β treatment in monolayer had no effect on cell mechanics suggesting that previously reported changes in actin associated with IL-1β may be lost during cell isolation or trypsinisation. Separate studies demonstrated increases in chondrocyte moduli and viscosity during passage indicating changes in cell structure-function associated with de-differentiation in monolayer. In conclusion, this study has developed an optimised micropipette aspiration technique which was successfully used to quantify chondrocyte viscoelastic behaviour and to elucidate the underlying role of actin dynamics and response to pathological stimuli and in vitro culture.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Medical Engineering and Medical Physics, 1984. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographical references. / by Bruce Robert Rosen. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Medical Engineering and Medical Physics, 1984. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographical references. / by Elazer Reuven Edelman. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Medical Engineering and Medical Physics, 1988. / Includes bibliographical references. / by Richard Glenn Stevens Spencer. / Ph.D.

Arbetet är en komplettering till ett befintligt projekt som gjorts på MT-FoU vid Norrlands Universitetssjukhus. I det befintliga projektet har ett mobilt system, MoLab, skapats för att analysera gång. Systemet har en algoritm som ska ge tidsmarkörer vid hälisättning och är baserat på tröghetsgivare. Målet med arbetet är att utvärdera noggrannheten hos den befintliga algoritmen. För att göra det skapas ett mätsystem och en testsensor används för att kunna testa om den befintliga algoritmen i det tidigare arbetet har något fel inom ett bestämt intervall, -20ms < x < 20ms. Det undersöks även om gånghastighet eller huruvida testpersonen bär skor eller inte ger någon skillnad i felet. Till mätsystemet används en Adafruit Feather MO Bluefruit LE och tester gjordes på tre testpersoner i åldrarna 28–47 år (totalt 18 test). På mätvärdena utfördes t-test och det gjordes en box plot för att analysera resultaten. Medelvärdet för normal gång, med skor för alla testpersoner och test, blev 0,42 ms. Normal gång utan skor blev 5,02 ms. Medelvärdet för rask gång, med skor, blev 0,44 ms och utan skor blev 0,87 ms. Medelvärdet för långsam gång, med skor, blev -4,68 ms och utan skor blev 2,04 ms. Resultaten från boxplotten visar att tidskillnaderna mellan systemen blev ganska spridda men att medelvärdet, ligger inom det bestämda intervallet vid alla tester. T-testen visar att nollhypotesen gäller och att det befintliga systemet därmed anses registrera hälisättningen korrekt. Algoritmen skulle därför fungera för detektion av hälisättning vid gång. / The work is a complement to an existing project done at MT-R&D at Norrlands University Hospital. In the existing project, a mobile system, MoLab, has been created for gaitanalysis. The system has an algorithm that provides time markers for heel strikes and isbased on inertial sensors. The aim of the work is to evaluate the accuracy of the existingalgorithm. To do that, a measurement system is created and a test sensor is used to testif the existing algorithm in the previous work has a difference within a certain range, -20ms <x <20ms, to the test sensor. It is also examined whether walking speed or whetherthe test person wears shoes or not give a difference in the error. The measuring systemuses an Adafruit Feather MO Bluefruit LE and tests were made on three test subjectsaged 28-47 years (a total of 18 tests). At the measured values, t-tests and box plots wereperformed to analyze the results. The mean time difference for normal walking speed,with shoes for all test subjects and tests, was 0,42 ms. The mean time difference fornormal speed, without shoes, was 5,02 ms. The mean time difference for rapid speed,with shoes, was 0,44 ms and without shoes was 0,87 ms. The mean time difference forslow walking speed, with shoes, was -4,68 ms and without shoes was 2,04 ms. Theresults from the box plot show that the time differences between the systems were quitespread but that the mean and median values are within the specified range of all tests.The T-test shows that the null hypothesis is valid and that the existing system is thusconsidered to register the heel strike correctly. The algorithm would therefore work fordetection of heel strikes in gait.

No description available.

This thesis presents the non-invasive use of diffuse reflectance spectroscopy (DRS) to provide information about the biochemical composition of living tissue. During DRS measurements, the incident, visible light is partially absorbed by chromophores but also scattered in the tissue before being remitted. Human skin and heart, the main tissue objects in this thesis, are dependent on a sufficient inflow of oxygenized blood, and outflow of metabolic byproducts. This process could be monitored by DRS using the spectral fingerprints of the most important tissue chromophores, oxyhemoglobin and deoxyhemoglobin. The Beer-Lambert law was used to produce models for the DRS and has thus been a foundation for the analyses throughout this work. Decomposition into the different chromophores was performed using least square fitting and tabulated data for chromophore absorptivity. These techniques were used to study skin tissue erythema induced by a provocation of an applied heat load on EMLA-treated skin. The absorbance differences, attributed to changes in the hemoglobin concentrations, were examined and found to be related to, foremost, an increase in oxyhemoglobin. To estimate UV-induced border zones between provoked and nonprovoked tissue a modified Beer-Lambert model, approximating the scattering effects, was used. An increase of chromophore content of more than two standard deviations above mean indicated responsive tissue. The analysis revealed an edge with a rather diffuse border, contradictory to the irradiation pattern. Measuring in the operating theater, on the heart, it was necessary to calculate absolute chromophore values in order to assess the state of the myocardium. Therefore, a light transport model accounting for the optical properties, and a calibrated probe, was adopted and used. The absolute values and fractions of the chromophores could then be compared between sites and individuals, despite any difference of the optical properties in the tissue. A hyperspectral imaging system was developed to visualize the spatial distribution of chromophores related to UV-provocations. A modified Beer-Lambert approximation was used including the chromophores and a baseline as an approximate scattering effect. The increase in chromophore content was estimated and evaluated over 336 hours. In conclusion, advancing from a restricted Beer-Lambert model, into a model estimating the tissue optical properties, chromophore estimation algorithms have been refined progressively. This has allowed advancement from relative chromophore analysis to absolute values, enabling precise comparisons and good prediction of physiological conditions.

The contents of this thesis consider new methods for generating ultrasound beams for enhanced image quality in medical imaging. The results presented are produced through computer simulations. The thesis consists of an introductory chapter and four papers, which are all intended to be individually readable. Chapter 1 gives a brief overview of ultrasound and medical ultrasound imaging, as well as different aspects of ultrasound image quality and acoustic noise. A non-linear wave equation is presented and analyzed. This equation describes ultrasound propagation within, and interaction with tissue. In Paper A, a transducer annular array design method is presented. The method involves a geometric pre-focusing, which may vary between the array elements. This is useful for producing narrow receive beams within a large imaging depth window. It is advantageous for avoiding problems that occur when combining high frequencies and large receive apertures when utilizing the conventional equal-area design method. Paper B introduces a method to produce synthetic transmit beams that are useful for suppression of reverberation noise caused by multiple scattering of the forward-propagating imaging pulse. This is done through combination of two transmit pulse complexes denoted Second order UltRasound Field (SURF). Each such complex consists of a conventional high-frequency imaging pulse added to a low-frequency sound-speed manipulation pulse. The SURF transmit beam is generated by forming the difference between the propagated fields, filtered around the imaging frequency. This beam has suppressed amplitude near the transducer, where a reflection-generating body-wall is often present during in vivo imaging. Furthermore, a method to produce a combined second-harmonic pulse inversion (PI) and SURF beam is also presented, here denoted SURF-PI. Two imaging setups are defined for which the feasibility of the method is tested through simulations in case of propagation through homogeneous tissue. SURF beams and combined SURF-PI beams are compared to fundamental imaging and PI imaging beams for the two setups. The SURF-PI beams are the most suppressed in the near-field, followed by the approximately equally suppressed SURF and PI beams. The signal level within the imaging depth region becomes higher for SURF than for PI. In Paper C, two signal processing methods for further adjustment of the SURF beams are introduced. This is achieved through post-processing, either by application of a time-shift, or of a general filter, to one of the propagated fields. The processing is done prior to carrying out the subtraction that is done to form the SURF beam. This provides a flexible way of adjustment to choose the depth position where the scattering sources wished to be suppressed are located. Different adjustments may be realized without need for re-transmission or resumed propagation of the SURF pulse complexes. The post-processing methods are applied to a dataset generated for Paper B. Adjusted transmit beam examples are presented and their reverberation suppression abilities are compared to non-adjusted SURF. In Paper D, the feasibility study of the SURF beam generation as presented in Paper B, and its post-processing adjustment as presented in Paper C, are enlarged to include propagation within an inhomogeneous medium where a body-wall model producing severe aberration delays is present. It is shown that both the generation of the SURF beams and the post-processing adjustment are attainable under the modeled conditions. / artikle I: "This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible."