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.

Denna rapport kommer att visa på hur utvecklingen av en prototyp för lagring av fysiska rörelser har gått till. Vilka komponenter som har valts och varför. Arbetet är utfört på uppdrag av Medicinsk Teknik – Forskning och Utveckling (MT-FoU) vid Umeå Universitet i Sverige. MT-FoU har även bistått med mjukvara och möjligheten till 3D-utskrift av behållare för prototypen. Prototypen kan lagra information om rörelser med hjälp av accelerometer, gyroskop och magnetometer. Informationen lagras på ett SD-kort och överförs sedan trådlöst via en nätverksrouter till klientsidan medhjälp av WiFi. Fysisk aktivitet har visat sig vara en viktigare del av människans hälsa än tidigare trott. Därför är det alltid viktigt att röra på sig mycket men och på rätt sätt. Med hjälp av denna produkt kan information om hur du exempelvis rör dig under ett träningspass registreras och analyseras. I denna rapport tas tillförlitligheten upp hos produkten med hjälp av två andra kommersiella produkter som data jämförs mot. / This report will show how the development of a prototype for the storage of physical movements has been developed. Which components that have been chosen and why. The work is performed on behalf of the Biomedical Engineering - Research and Development (MT-FoU) at Umeå University, Sweden. MT-FoU has also assisted with the software and the possibility of 3D printing of containers for the prototype. The prototype can store information about movement using the accelerometer, gyroscope and magnetometer. The information is stored on an SD card and then transmitted wirelessly via a network router to the clientside using WiFi. Physical activity has been shown to be a more important part of human health than previously thought. It´s always important to move much but it´s also important that we move in a right way as well. With the help of this product information on moves during a training session is recorded and analyzed. In this report, the reliability of the product is measured with the help of two other commercial products which data is compared against.

<p>Vevs-karakterisering med høyoppløsning MAS MR spektroskopi</p><p>Høyoppløsning MAS er en MR spektroskopisk metode som gir høyt oppløste spekter av faste materialer. I dette doktorgradsarbeidet har høyoppløsning MAS blitt anvendt på forskjellige typer humant vev. Det primære målet var å etablere en metode for å studere biokjemiske egenskaper i vevsprøver, med hovedvekt på vev fra brystkreftpasienter.</p><p>Prøvepreparering før MAS analyser er enkelt sammenlignet med ekstraksjon. Vi har funnet at oppløsningen i spektrene, og dermed den oppnåelige biokjemiske informasjonen, er tilsvarende som i spekter fra ekstrakter av vevsprøver. En viktig fordel i forhold til ekstraksjons-metoder er at vevsprøven som studeres kan bevares slik at den kan vurderes ved andre metoder etterpå. Organer er gjerne satt sammen av forskjellige typer celler og vev og en slik heterogenitet vil ha betydning for den biokjemiske profilen, siden celler av forskjellig type kan ha forskjellig metabolisme. En del av prosjektet gikk ut på å optimalisere MR eksperimentene med hensyn på biokjemisk informasjon samtidig som at vevsprøven ble bevart for en patologisk undersøkelse. Lav temperatur under analysene ble funnet å være viktig for en slik bevaring av vevet. Vi oppnådde høyt oppløste spekter og har langt på vei kartlagt den kjemiske sammensetningen av intakte vevsprøver. Den metabolske profilen i brystkreftprøver viste en sammenheng med vevs-sammensetning bestemt ved patologi.</p><p>MR spekter av biologisk materiale kan inneholde hundrevis av topper, og flere av disse kan henge sammen med sykdomsprosesser i vevet. Ved sammenligning av enkelt-topper mot kliniske funn kan man miste viktig informasjon i spektrene som er ikke er synlig for det blotte øyet. Multivariate analyser gjør det mulig å undersøke hele spektrene mot kliniske kjennetegn. I denne avhandlingen har prisipalkomponent-analyse blitt brukt til å korrelere MAS spektrene med pasientenes diagnoser og andre kliniske funn.</p><p>En studie av livmorhalskreft omfattet vevsprøver fra åtte pasienter med livmorhalskreft og åtte kontroller. Prinsipalkomponent-analyse av MAS spektrene ga to klare grupperinger av de ulike spektrene i samsvar med prøvetype. Den kjemiske profilen bestemt med MAS har en sammenheng med de makroskopiske forandringene i kreftvev fra livmorhals.</p><p>Hjerneautopsier fra pasienter med en sjelden neurodegenerativ sykdom som rammer barn (neuronal ceroid lipofuscinosis) ble undersøk på samme måte mot autopsier fra personer uten kjent sykdom i nervesystemet. To former av sykdommen var inkludert i studien som omfattet totalt 24 biopsier, og den formen som bryter ut tidligst lot seg skille fra de to andre gruppene. Vevsprøver fra denne gruppen inneholdt svært lite eller ikke påviselige mengder NAA, som syntetiseres og lagres i nevroner. Dette korrelerer med tap av nevroner som er observert hos slike pasienter.</p><p>Den største studien inkluderte vevsprøver fra svulst og ikke-infiltrert vev (n=18) fra 85 brystkreftpasienter. MAS spekter fra disse prøvene ble undersøkt med hensyn på absolutt konsentrasjon av bestemte metabolitter og ved PCA med hensyn på sammenheng med flere kliniske parametere, som pasientens diagnose, svulstens størrelse og lymfeknutestatus hos pasienten. Det ble funnet flere trender til sammenhenger mellom MAS spekter og kliniske parametere. Det mest lovende resultatet med hensyn på fremtidig klinisk verdi var en mulig korrelasjon med lymfeknutestatus hos pasientgruppen med den vanligste formene for brystkreft.</p> / Paper III is a preprint of an article published in NMR in Biomedicine. http://www.interscience.wiley.com

<p>A global mapping of early stage medical technology companies has been implemented. The companies have emerging products within neurology and have undergone an evaluation by clinicians concerning the ability to provide clinical value for Swedish health care. The evaluation process has been executed by discussion with neurologists and neurosurgeons in combination with a literature survey. To limit the evaluation process, areas of stroke, traumatic brain injury, Parkinson’s disease, multiple sclerosis and epilepsy were chosen.</p><p>Some companies turn up to develop more requested products than others. Medfield Diagnostics AB, with their microwave screening product could in the future address the need for fast, accurate and accessible diagnosis of stroke and head trauma. The NBS system from Nexstim Ltd. has potential to provide clinical value by the ability of the products TMS technology to navigate in the brain. Elminda Ltd. product built of an evidence based rehabilitation platform could enhance recovery of patients with neurological disorders on an individual basis. BrainsGate Ltd. product to deliver drugs over the blood brain barrier provides totally new treatment options and NeuroSonix Ltd. ultrasound based product could assist the surgeon and decrease damageable embolic debris. Neurolife non-invasive solutions innovative device, which non-invasively measured the intracranial pressure, would be a totally new way to monitor patients.</p><p>A symposium was organized and three top ranked companies with stroke care products were invited to present their technology for Swedish clinicians in Stockholm. Participating companies were Nexstim Ltd., Elminda Ltd. and Medfield Diagnostics AB, who were all well received and considered to have interesting technologies with ability to provide clinical value.</p>

No description available.

No description available.

Vevs-karakterisering med høyoppløsning MAS MR spektroskopi Høyoppløsning MAS er en MR spektroskopisk metode som gir høyt oppløste spekter av faste materialer. I dette doktorgradsarbeidet har høyoppløsning MAS blitt anvendt på forskjellige typer humant vev. Det primære målet var å etablere en metode for å studere biokjemiske egenskaper i vevsprøver, med hovedvekt på vev fra brystkreftpasienter. Prøvepreparering før MAS analyser er enkelt sammenlignet med ekstraksjon. Vi har funnet at oppløsningen i spektrene, og dermed den oppnåelige biokjemiske informasjonen, er tilsvarende som i spekter fra ekstrakter av vevsprøver. En viktig fordel i forhold til ekstraksjons-metoder er at vevsprøven som studeres kan bevares slik at den kan vurderes ved andre metoder etterpå. Organer er gjerne satt sammen av forskjellige typer celler og vev og en slik heterogenitet vil ha betydning for den biokjemiske profilen, siden celler av forskjellig type kan ha forskjellig metabolisme. En del av prosjektet gikk ut på å optimalisere MR eksperimentene med hensyn på biokjemisk informasjon samtidig som at vevsprøven ble bevart for en patologisk undersøkelse. Lav temperatur under analysene ble funnet å være viktig for en slik bevaring av vevet. Vi oppnådde høyt oppløste spekter og har langt på vei kartlagt den kjemiske sammensetningen av intakte vevsprøver. Den metabolske profilen i brystkreftprøver viste en sammenheng med vevs-sammensetning bestemt ved patologi. MR spekter av biologisk materiale kan inneholde hundrevis av topper, og flere av disse kan henge sammen med sykdomsprosesser i vevet. Ved sammenligning av enkelt-topper mot kliniske funn kan man miste viktig informasjon i spektrene som er ikke er synlig for det blotte øyet. Multivariate analyser gjør det mulig å undersøke hele spektrene mot kliniske kjennetegn. I denne avhandlingen har prisipalkomponent-analyse blitt brukt til å korrelere MAS spektrene med pasientenes diagnoser og andre kliniske funn. En studie av livmorhalskreft omfattet vevsprøver fra åtte pasienter med livmorhalskreft og åtte kontroller. Prinsipalkomponent-analyse av MAS spektrene ga to klare grupperinger av de ulike spektrene i samsvar med prøvetype. Den kjemiske profilen bestemt med MAS har en sammenheng med de makroskopiske forandringene i kreftvev fra livmorhals. Hjerneautopsier fra pasienter med en sjelden neurodegenerativ sykdom som rammer barn (neuronal ceroid lipofuscinosis) ble undersøk på samme måte mot autopsier fra personer uten kjent sykdom i nervesystemet. To former av sykdommen var inkludert i studien som omfattet totalt 24 biopsier, og den formen som bryter ut tidligst lot seg skille fra de to andre gruppene. Vevsprøver fra denne gruppen inneholdt svært lite eller ikke påviselige mengder NAA, som syntetiseres og lagres i nevroner. Dette korrelerer med tap av nevroner som er observert hos slike pasienter. Den største studien inkluderte vevsprøver fra svulst og ikke-infiltrert vev (n=18) fra 85 brystkreftpasienter. MAS spekter fra disse prøvene ble undersøkt med hensyn på absolutt konsentrasjon av bestemte metabolitter og ved PCA med hensyn på sammenheng med flere kliniske parametere, som pasientens diagnose, svulstens størrelse og lymfeknutestatus hos pasienten. Det ble funnet flere trender til sammenhenger mellom MAS spekter og kliniske parametere. Det mest lovende resultatet med hensyn på fremtidig klinisk verdi var en mulig korrelasjon med lymfeknutestatus hos pasientgruppen med den vanligste formene for brystkreft. / Paper III is a preprint of an article published in NMR in Biomedicine. http://www.interscience.wiley.com

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."