Fingersomatotopy in area 3b: an fMRI-study

BACKGROUND: The primary sensory cortex (S1) in the postcentral gyrus is comprised of four areas that each contain a body map, where the representation of the hand is located with the thumb most laterally, anteriorly and inferiorly and the little finger most medially, posteriorly and superiorly. Previous studies on somatotopy using functional MRI have either used low field strength, have included a small number of subjects or failed to attribute activations to any area within S1. In the present study we included twenty subjects, who were investigated at 3 Tesla (T). We focused specifically on Brodmann area 3b, which neurons have discrete receptive fields with a potentially more clearcut somatotopic organisation. The spatial distribution for all fingers' peak activation was determined and group as well as individual analysis was performed. RESULTS: Activation maps from 18 subjects were of adequate quality; in 17 subjects activations were present for all fingers and these data were further analysed. In the group analysis the thumb was located most laterally, anteriorly and inferiorly with the other fingers sequentially positioned more medially, posteriorly and superiorly. At the individual level this somatotopic relationship was present for the thumb and little finger, with a higher variability for the fingers in between. The Euclidian distance between the first and fifth finger was 17.2 mm, between the first and second finger 10.6 mm and between the remaining fingers on average 6.3 mm. CONCLUSION: Results from the group analysis, that is both the location of the fingers and the Euclidian distances, are well comparable to results from previous studies using a wide range of modalities. On the subject level the spatial localisation of the fingers showed a less stringent somatotopic order so that the location of a finger in a single subject cannot be predicted from the group result

Physical Aspects of Thermotherapy - A study of heat transport with a view to treatment optimisation

Local treatment with the aim to destruct tissue by heating (thermotherapy) may in some cases be an alternative or complement to surgical methods, and has gained increased interest during the last decade. The major advantage of these, often minimally-invasive methods, is that the disease can be controlled with reduced treatment trauma and complications. The extent of thermal damage is a complex function of the physical properties of tissue, which influence the temperature distribution, and of the biological response to heat. In this thesis, methods of obtaining a well-controlled treatment have been studied from a physical point of view, with emphasis on interstitial laser-induced heating of tumours in the liver and intracavitary heating as a treatment for menorrhagia. Hepatic inflow occlusion, in combination with temperature-feedback control of the output power of the laser, resulted in well defined damaged volumes during interstitial laser thermotherapy in normal porcine liver. In addition, phantom experiments showed that the use of multiple diffusing laser fibres allows heating of clinically relevant tissue volumes in a single session. Methods for numerical simulation of heat transport were used to calculate the temperature distribution and the results agreed well with experiments. It was also found from numerical simulation that the influence of light transport on the damaged volume may be negligible in interstitial laser thermotherapy in human liver. Finite element analysis, disregarding light transport, was therefore proposed as a suitable method for 3D treatment planning. Finite element simulation was also used to model intracavitary heating of the uterus, with the purpose of providing an increased understanding of the influence of various treatment parameters on blood flow and on the depth of tissue damage. The thermal conductivity of human uterine tissue, which was used in these simulations, was measured. Furthermore, magnetic resonance imaging (MRI) was investigated as a method of non-invasive temperature monitoring, and an optically tissue-like phantom material, suitable for MRI, was developed. MRI thermometry in this material was shown to be an excellent method for characterisation of laser applicators and for verification of numerical calculations. Finally, a water-cooled laser applicator for the treatment of benign prostatic hyperplasia, allowing anatomically correct heating, was developed and evaluated ex-vivo. An increased understanding of the physical aspects of thermotherapy, aided by the methods and results presented in this thesis, constitutes a significant contribution to the performance of safe and efficacious treatment

Physical Aspects of Thermotherapy - A study of heat transport with a view to treatment optimisation

Popular Abstract in Swedish Lokal behandling med målsättning att förstöra kroppsvävnad genom uppvärmning (termoterapi) kan i vissa fall vara ett alternativ eller komplement till kirurgi. I avhandlingen presenteras utrustning och metoder för att, utifrån en fysikalisk synvinkel, göra sådana behandlingar säkrare och effektivare. Genom att beräkna temperaturefördelningen m.h.a. datorsimuleringar kan man i förväg bedöma hur olika applikatorer som används för uppvärmning skall placeras. Man kan t.ex. använda optiska fibrer för att leda laserljus, som sedan absorberas och övergår till värme, in i vävnaden. Hänsyn måste då tas till vävnadens fysikaliska egenskaper, t.ex. värmeledningsförmåga och optiska egenskaper. Även blodflödet har stor betydelse för temperaturfördelningen genom sin kylande inverkan och måste tas med i beräkningarna. Under behandling måste temperaturen också kunna mätas för att kontrollera att resultatet blir som man tänkt sig. Vanligtvis används termistorer, som sticks in i vävnaden, för detta ändamål. Man söker emellertid nya metoder för att kunna mäta temperaturen utan att behöva sticka in någon mätprob och för att få information om temperaturen i hela området. En sådan metod bygger på temperaturmätningar m.h.a. s.k. magnetresonanstomografi och har i detta arbetet använts för att studera temperaturfördelningen under bestrålning med laserljus i ett material som liknar vävnad. Utifrån mätresultaten kan man t.ex. kontrollera om beräkningar som gjorts är riktiga. Uppvärmning m.h.a. laserljus kan användas för att döda levertumörer, men har även studerats som en möjlig metod att behandla prostatabesvär, vilket drabbar en mycket stor andel av alla män då de blir äldre. I avhandlingen presenteras, förutom utrustning och beräkningar för behandling av levertumörer, en ny laserapplikator som är avsedd att göra prostatabehandlingar enklare. Vidare har en ny metod för behandling av alltför rikliga bödningar från livmodern studerats genom datorsimulering. Under behandlingen förs en kateter med en expanderbarballong in i livmoderkaviteten och cirkulerande vätska i ballongen värms upp till en temperatur omkring 75°C. Datorsimuleringar visar hur ballongtemperatur, behandlingstid, blodflöde m.m. påverkar temperaturfördelningen och därmed utsräckningen av det behandlade området. En ökad förståelse av de fysikaliska aspekterna på termoterapi gör att dessa nya behandlingar kan utföras på ett bättre och säkrare sätt.Local treatment with the aim to destruct tissue by heating (thermotherapy) may in some cases be an alternative or complement to surgical methods, and has gained increased interest during the last decade. The major advantage of these, often minimally-invasive methods, is that the disease can be controlled with reduced treatment trauma and complications. The extent of thermal damage is a complex function of the physical properties of tissue, which influence the temperature distribution, and of the biological response to heat. In this thesis, methods of obtaining a well-controlled treatment have been studied from a physical point of view, with emphasis on interstitial laser-induced heating of tumours in the liver and intracavitary heating as a treatment for menorrhagia. Hepatic inflow occlusion, in combination with temperature-feedback control of the output power of the laser, resulted in well defined damaged volumes during interstitial laser thermotherapy in normal porcine liver. In addition, phantom experiments showed that the use of multiple diffusing laser fibres allows heating of clinically relevant tissue volumes in a single session. Methods for numerical simulation of heat transport were used to calculate the temperature distribution and the results agreed well with experiments. It was also found from numerical simulation that the influence of light transport on the damaged volume may be negligible in interstitial laser thermotherapy in human liver. Finite element analysis, disregarding light transport, was therefore proposed as a suitable method for 3D treatment planning. Finite element simulation was also used to model intracavitary heating of the uterus, with the purpose of providing an increased understanding of the influence of various treatment parameters on blood flow and on the depth of tissue damage. The thermal conductivity of human uterine tissue, which was used in these simulations, was measured. Furthermore, magnetic resonance imaging (MRI) was investigated as a method of non-invasive temperature monitoring, and an optically tissue-like phantom material, suitable for MRI, was developed. MRI thermometry in this material was shown to be an excellent method for characterisation of laser applicators and for verification of numerical calculations. Finally, a water-cooled laser applicator for the treatment of benign prostatic hyperplasia, allowing anatomically correct heating, was developed and evaluated ex-vivo. An increased understanding of the physical aspects of thermotherapy, aided by the methods and results presented in this thesis, constitutes a significant contribution to the performance of safe and efficacious treatment

Medical Radiation Physics Clinical Sciences, Lund

optimisation and quality control i

Valid Exposure Protocols Needed in Magnetic Resonance Imaging Genotoxic Research

Several in vitro and in vivo studies have investigated if a magnetic resonance imaging (MRI) examination can cause DNA damage in human blood cells. However, the electromagnetic field (EMF) exposure that the cells received in the MR scanner was not sufficiently described. The first studies looking into this could be regarded as hypothesis-generating studies. However, for further exploration into the role of MRI exposure on DNA integrity, the exposure itself cannot be ignored. The lack of sufficient method descriptions makes the early experiments difficult, if not impossible, to repeat. The golden rule in all experimental work is that a study should be repeatable by someone with the right knowledge and equipment, and this is simply not the case with many of the recent studies on MRI and genotoxicity. Here we discuss what is lacking in previous studies, and how we think the next generation of in vitro and in vivo studies on MRI and genotoxicity should be performed. Bioelectromagnetics

A two-compartment gel phantom for optimization and quality assurance in clinical BOLD fMRI

Clinical applications of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) depend heavily on robust paradigms, imaging methods and analysis procedures. In this work, as a means to optimize and perform quality assurance of the entire imaging and analysis chain, a phantom that provides a well known and reproducible signal change similar to a block type fMRI experiment is presented. It consists of two gel compartments with slightly different T(2) that dynamically enter and leave the imaged volume. The homogeneous gel in combination with a cylindrical geometry results in a well-defined T(2) difference causing a signal difference between the two compartments in T(2)-weighted MR images. From time series data obtained with the phantom, maps of percent signal change (PSC) and t-values are calculated. As an example of image parameter optimisation, the phantom is demonstrated to be useful for accurate determination of the influence of echo time (TE) on BOLD fMRI results, taking the t-value as a measure of sensitivity. In addition, the phantom is proposed as a tool for quality assurance (QA) since reproducible time series and t-maps are obtained in a series of independent repeat experiments. The phantom is relatively simple to build and can therefore be used by any clinical fMRI center

Characterization of the MRI patient exposure environment and exposure assessment methods for magnetic fields in MRI scanners [Elektronisk resurs]

Magnetic resonance imaging (MRI) has become one of the most common imaging modalities available in modern medicine, and it is an indispensable diagnostic tool thanks to the unparalleled soft-tissue contrast and high image resolution. It is also a unique exposure environment consisting of a complex mix of magnetic fields. During an MRI scan, the patient is simultaneously exposed to a strong static magnetic field, a fast-switching gradient magnetic field, and a pulsed radiofrequency (RF) magnetic field. Transient acute effects, such as nerve excitation and tissue heating, are well known and limited by universal safety guidelines. Long-term health effects related to MRI exposure have, however, not been scientifically established, and no interaction mechanisms have been verified, despite a growing body of research on electromagnetic field exposure. Further epidemiological and experimental research on MRI exposure has been recommended but the lack of a common definition of dose or exposure metric makes evaluation of past research and the design of future experiments difficult.The objectives of this thesis were to characterize the MRI patient exposure environment in terms of the magnetic fields involved, suggest relevant exposure metrics, and introduce exposure assessment methods suitable for epidemiological and experimental research on MRI and long-term health effects.In Paper I, we discussed the MRI exposure environment and its complexity and gave an overview of the current scientific situation. In Paper II, we investigated the exposure variability between different MRI sequences and suggested patient-independent exposure metrics that describe different characteristics of the magnetic field exposure, including mean, peak, and threshold values. In Paper III, we presented three exposure assessment methods, specifically suited to the complex MRI exposure environment: a measurement-based method, a calculation-based method, and a proxy method.Papers I and II showed that MRI exams are not homogenous in terms of exposure, and exposure variability exists between the individual sequences that comprise an exam. Differences in mean exposure between sequences were several-fold, peak exposure differences up to 30-fold, and differences in threshold exposure were in some cases more than 100-fold. Furthermore, within-sequence exposure variability, related to the parameter adjustments that can be made at the scanner console before the start of a scan, gave rise to 5-to-8-fold exposure increases. Paper III showed that magnetic field models could be used to approximate the exposure at arbitrary locations inside the scanner, with slight underestimation of gradient field metrics and large variability in some RF field metrics. With improvements in accuracy and efficiency, the method could become a useful exposure assessment tool for in vitro and in vivo research as well as clinical work on medical implant safety. Our search for suitable exposure metric proxies resulted in a limited selection with low correlation between proxies and their counterpart metrics, but, with further development, the proxy method has the potential to allow for much needed exposure classification relevant to large-scale epidemiological research.The work in this thesis has contributed to increased awareness of the unique MRI exposure environment, the characteristics of the magnetic fields involved, and the inherent exposure variability in MRI exams. The metrics and methods presented are specifically suited to exposure assessment of the unique MRI environment, and may contribute to improved research quality by allowing for meaningful comparisons between study results and for experimental conditions to be easily replicated in future studies.Magnetisk resonanstomografi (MR), som är en av de vanligaste medicinska avbildningsmetoderna idag, är ett oumbärligt diagnostiskt verktyg tack vare den oöverträffade mjukvävnadskontrasten och höga bildupplösningen. MR-kameran är också en unik exponeringsmiljö bestående av en komplex blandning av magnetfält med olika frekvenser och fältstyrkor. Under en vanlig MR-undersökning exponeras patienten för ett starkt statiskt magnetfält på 1,5 eller 3 Tesla, ett snabbt växlande gradientmagnetfält och ett pulsat radiofrekvent (RF) magnetfält. Gradientfältet kan ibland generera en pirrande känsla i huden på armarna och benen och RF-fältet kan orsaka vävnadsuppvärmning. Dessa övergående effekter är välkända och begränsas av allmänna säkerhetsriktlinjer. Långsiktiga hälsoeffekter relaterade till MR-exponering är dock inte vetenskapligt fastställda och det finns inga vedertagna interaktionsmekanismer. Det finns en hel del forskning på magnetfältsexponering och biologiska effekter, men resultaten är blandade och svåra att tyda. Till skillnad från joniserande strålning (används i bl.a. röntgenundersökningar), som vi vet kan skada DNA-molekylerna i våra celler och som medför en ökad risk att utveckla cancer vid alltför höga doser, så har vi inga etablerade mått på dos och exponering när det gäller låg- och radiofrekventa magnetfält. Därför kan kvaliteten på exponerings-bedömningarna skilja betydligt mellan olika forskningsstudier, vilket innebär att det är svårt att jämföra resultat från olika studier och ofta omöjligt att reproducera och verifiera tidigare forskningsresultat. Ytterligare epidemiologisk och experimentell forskning om MR-exponering behövs, men för att kunna genomföra den på ett meningsfullt sätt behövs tydliga exponeringsmått och metoder för exponeringsbedömning som är anpassade till den komplexa blandning av magnetfält som finns i MR-kameran.Syftet med denna avhandling var att karakterisera MR-patientens exponerings-miljö med avseende på de tidsvarierande magnetfälten, föreslå lämpliga exponeringsmått och presentera exponeringsbedömningsmetoder som är relevanta för epidemiologisk och experimentell forskning om MR och långsiktiga hälsoeffekter.I artikel I diskuterade vi MR-kamerans exponeringsmiljö och dess komplexitet och gav en översikt av det nuvarande vetenskapliga läget gällande MR och exponering. I artikel II undersökte vi hur exponeringen kan variera mellan de olika bildtagningssekvenserna som ingår i en MR-undersökning, och föreslog patient-oberoende exponeringsmått (olika typer av medelvärden, maxvärden och tröskelvärden) för att beskriva magnetfältens egenskaper. I artikel III presenterade vi tre metoder för att bedöma exponering, särskilt lämpade för den komplexa MR-exponeringsmiljön: en metod för mätningar av magnetfälten inne i kameran, en metod som simulerar kamerans magnetfält, och en metod för att identifiera mer lättillgängliga magnetfältsrelaterade parametrar som korrelerar starkt med de egentliga exponeringsmåtten.I artiklar I och II visade vi att MR-undersökningar inte är homogena med avseende på exponering, så det går inte att enkelt klassificera en undersökning baserat på hur länge den pågår eller vilken kroppsdel som avbildas. Exponeringen kan variera betydligt mellan de olika sekvenserna som ingår ett undersöknings-protokoll. För vissa exponeringsmått är det bara några procents skillnad mellan olika sekvenser, medan det i andra fall kan vara mer än 100-faldig skillnad i exponering. Dessutom fann vi att exponeringen för en enskild sekvens kan varieras genom att MR-kamerans inställningar justeras inför en bildtagning. Detta innebär att det finns väldig många variabler som påverkar exponeringen i en MR-undersökning, och en medvetenhet om detta är viktigt om vi ska kunna genomföra meningsfulla exponeringsbedömningar. I artikel III visade vi hur simulerade magnetfält kan användas för att beräkna exponeringen på godtyckliga platser inuti MR-kameran. Modellen av gradient-fältet var stabil och fungerade bra för olika exponeringsmått, trots en liten underskattning av exponeringen. RF-fältets exponering visade sig vara svårare att simulera och resultaten varierade mer i jämförelsen med uppmätta värden. Med förbättringar i noggrannhet och effektivitet kan metoden bli ett användbart verktyg för exponeringsbedömning i framtida in vitro- och in vivo-studier samt i kliniska säkerhetsbedömningar, till exempel vid utvärdering av medicinska implantat. Jakten på lämpliga ersättningsparametrar för magnetfältens exponeringsmått resulterade i ett begränsat urval med relativt låg korrelation mellan parametrar och motsvarande mätvärden, så sökandet fortsätter. Med fortsatt utveckling har den här metoden potential att möjliggöra välbehövlig exponeringsklassificering som är relevant för storskalig epidemiologisk forskning.Denna avhandling har belyst MR-kamerans unika exponeringsmiljö med fokus på de tidsvarierande magnetfältens egenskaper, och de många variabler som påverkar exponeringen under en MR-undersökning. De exponeringsmått och bedömningsmetoder som presenterats i detta arbete är särskilt lämpade för den unika exponeringsmiljö som finns i MR-kameror, och kan bidra till förbättrad forskningskvalitet genom att möjliggöra meningsfulla jämförelser mellan olika studiers resultat och upprepning av experimentella förhållanden i framtida studier.</p

Numerical calculations of temperature distribution resulting from intracavitary heating of the uterus

Objective To estimate, using numerical calculations, the depth of tissue damage in the uterus following balloon thermal endometrial destruction. Design A parameter, therapeutic depth, was defined. This was the maximum depth into the uterine myometrium, from the uterine cavity, at which a predefined temperature was reached after a certain time and with a constant intracavitary temperature. Setting Departments of radiation physics and gynaecology at a university hospital. Results After 30 min of treatment with an intracavitary temperature of 75°C, the maximum depth into the myometrium at which the tissue had been exposed to a temperature of 55°C, when blood flow was neglected, was 8.9 mm. Taking into account blood flow the depth was 3.4 mm, and including the pressure because of the balloon it was 5.6 mm. With the inclusion of a local increase in blood flow because of elevated tissue temperature the depth was 4.4mm. Finally when damage to blood vessels due to coagulation was also accounted for, the depth was 5.2mm. The therapeutic depth decreased only slightly when the treatment time was shortened to 15 min. Conclusions Numerical calculations provide a basis for estimation of the optimal intracavitary temperature and treatment time when performing thermal endometrial destruction by means of a balloon catheter