A camada semi-redutora (CSR), definida como a espessura de um material absorvedor que colocado sob um feixe de raios-X reduz sua intensidade à metade, é um parâmetro que deve ser avaliado periodicamente nos programas de garantia de qualidade em radiologia médica, pois fornece informações a respeito do desempenho do feixe radiográfico produzido pelo aparelho. Todavia, sua medida é normalmente feita na região central do campo de exposição e não considera a variação da qualidade relativa do feixe ao longo de toda a sua extensão, causada essencialmente pelo efeito heel. Em vista disso, o presente trabalho propõe um algoritmo de simulação computacional para determinar a CSR de aparelhos radiográficos em qualquer posição no campo através de uma única medida na região central, para permitir uma avaliação mais completa da variação da qualidade do feixe em função do posicionamento do objeto no plano imagem. Além disso, a partir dos resultados obtidos, também é proposto um procedimento computacional capaz de determinar filtros de características específicas para compensar essas variações na qualidade da imagem causadas pelo efeito heel e também por variações na espessura do objeto radiografado. Os resultados obtidos com os programas de simulação desenvolvidos mostraram-se coerentes com os obtidos em testes práticos realizados com aparelhos radiográficos hospitalares, comprovando a validade dos algoritmos propostos. / The half-value layer (HVL) is defined as the thickness of an absorbing material which placed under an X-Ray beam reduces its intensity to half. It is a parameter that should be periodically evaluated in medical radiology quality control programs because it gives information related to the radiographic system beam performance. However, its measurement is done normally at the center of the radiation field, not taking into account the beam relative quality variation along the field, caused essentially by the heel effect. Bearing that in mind, the present work proposes a computer simulation algorithm to determine the radiographic systems HVL at any location on the field based on a single measurement at the central area, to allow a more complete evaluation of the beam quality variation due to the object location on the image plane. Furthermore, from these results, another computer simulation procedure is proposed to determine particular filter characteristics to compensate these image quality variations caused by the heel effect and also by the X-rayed object thickness variation. The results obtained from the simulation programs are consistent with the experimental results performed in medical radiographic systems, confirming therefore the validity of the proposed algorithms.

Bakgrund: Personer som insjuknar i kolorektalcancer är ofta mellan 50-70 år gamla. Colon kan undersökas med bariumundersökning, koloskopi eller datortomografi colon (DT colon). Nyttan med DT colon är att tarmen liksom strukturer utanför tarmens vägg kan avbildas samt att cancern kan stadieindelas. Syfte: Att undersöka patienters upplevelser av DT colon hos patienter som uppvisar symtom på kolorektalcancer. Dessa upplevelser kan vara fysiska och psykiska. Metod: Sökningar utfördes i databasen Pubmed där sökord kombinerades. Efter granskning av abstrakt och studier i sin helhet inkluderades 11 studier som ligger till grund för resultatet. Resultat: Patienter upplevde lite smärta i fem av sju studier. Procentuellt skattades smärta som liten till obefintlig (82-96 %) och som stark (0-3 %) i tre studier. Upplevelse av obehag varierade mellan lite och lite mer än måttligt obehag i sju studier. I en studie skattade 81 % patienter DT colon som inte till lite obehaglig. Obehag under utvidgning av tarmen upplevde majoriteten som inte till lite obehagligt och mindre andel (30,7 % och 17 %) som ganska till mycket obehagligt i två studier. I en kvalitativ studie var utvidgning den mest jobbiga delen av undersökningen. Pinsamhet skattades som låg i två studier och i en kvalitativ studie kände sig patienterna generade. Oro mättes i sju studier där majoriteten var lite eller inte oroliga. Ingen eller lite rädsla upplevdes av patienter i tre studier. I en kvalitativ studie uttryckte några patienter att de varit rädda under DT colon varav en var rädd för att inte kunna hålla andan. Slutsats: Många upplevde lite smärta under DT colon men det fanns de som upplevde större smärta. Upplevelse av obehag varierade i studierna men ett fåtal upplevde mycket obehag. Vissa upplevde mycket och extremt obehag under utvidgning av tarmen. Patienter var lite generade men 1-3 % kände större pinsamhet. Patienterna var lite oroliga. Då få studier tog upp rädsla är det svårt att dra en slutsats.

A camada semi-redutora (CSR), definida como a espessura de um material absorvedor que colocado sob um feixe de raios-X reduz sua intensidade à metade, é um parâmetro que deve ser avaliado periodicamente nos programas de garantia de qualidade em radiologia médica, pois fornece informações a respeito do desempenho do feixe radiográfico produzido pelo aparelho. Todavia, sua medida é normalmente feita na região central do campo de exposição e não considera a variação da qualidade relativa do feixe ao longo de toda a sua extensão, causada essencialmente pelo efeito heel. Em vista disso, o presente trabalho propõe um algoritmo de simulação computacional para determinar a CSR de aparelhos radiográficos em qualquer posição no campo através de uma única medida na região central, para permitir uma avaliação mais completa da variação da qualidade do feixe em função do posicionamento do objeto no plano imagem. Além disso, a partir dos resultados obtidos, também é proposto um procedimento computacional capaz de determinar filtros de características específicas para compensar essas variações na qualidade da imagem causadas pelo efeito heel e também por variações na espessura do objeto radiografado. Os resultados obtidos com os programas de simulação desenvolvidos mostraram-se coerentes com os obtidos em testes práticos realizados com aparelhos radiográficos hospitalares, comprovando a validade dos algoritmos propostos. / The half-value layer (HVL) is defined as the thickness of an absorbing material which placed under an X-Ray beam reduces its intensity to half. It is a parameter that should be periodically evaluated in medical radiology quality control programs because it gives information related to the radiographic system beam performance. However, its measurement is done normally at the center of the radiation field, not taking into account the beam relative quality variation along the field, caused essentially by the heel effect. Bearing that in mind, the present work proposes a computer simulation algorithm to determine the radiographic systems HVL at any location on the field based on a single measurement at the central area, to allow a more complete evaluation of the beam quality variation due to the object location on the image plane. Furthermore, from these results, another computer simulation procedure is proposed to determine particular filter characteristics to compensate these image quality variations caused by the heel effect and also by the X-rayed object thickness variation. The results obtained from the simulation programs are consistent with the experimental results performed in medical radiographic systems, confirming therefore the validity of the proposed algorithms.

Computed tomography urography (CTU) is today the imaging method used to investigate patients with suspected urinary tract malignancy, replacing the old imaging method intravenous pyelography (IVP) about a decade ago. The downside of this shift was that the effective radiation dose to the examined patient was eight times higher for CTU compared to IVP. Based on four different studies, the present thesis focused on efforts to reduce the CTU radiation dose.   In study I, the number of cysts and solid lesions in the separate scan phases was evaluated in 57 patients undergoing four-phase CTU 1997-98. The number of scans was reduced from four to three when the nephrographic scan was abolished following study I. Study II registered the diameter of renal cell carcinoma (RCC) and the presenting symptoms in the total number of patients (n=232) diagnosed with RCC between 1997 and 2003. The results from study II showed that the critical size for RCCs to cause macroscopic hematuria was ≥ 4 cm. Study III was a dose-escalation study aimed to decide the minimal possible tube load in the unenhanced and excretory phase scans if the low dose images are reviewed together with normal dose corticomedullary phase images. Study III showed that it is possible to reduce the mean effective dose in three phase CTU from 16.2 mSv to 9.4 mSv with a combined low and normal dose CTU protocol. Study IV investigated the changes in the CTU protocol between 1997 and 2008, and the development of the effective radiation dose. Study IV clarified how the CTU protocol has changed between 1997 and 2008 and as a result the mean effective radiation dose to patients undergoing CTU in 2008 is only 39% of the effective dose in 1997.   In conclusion, the findings from the studies included in this thesis have contributed to a reduced radiation dose to patients undergoing CTU. The mean effective dose from CTU is at present only three times higher compared to that from the IVP.

Neste projeto foi desenvolvido um método computacional para verificação da melhor combinação tela intensificadora - filme para exames mamográficos através do estudo de suas características sensitométricas. O software, desenvolvido em ambiente Delphi para windows, apresenta na tela do microcomputador a imagem a ser obtida para cada tipo de combinação tela intensificadora - filme, utilizando imagens de \"Phantoms\" e de mamas reais. Em razão da ampla quantidade de fatores que influenciam a imagem mamográfica final, tais como magnificação, característica dos filmes e telas intensificadoras e condições da processadora, o método proposto pode proporcionar uma ampla avaliação da qualidade dos sistemas de imagem mamográfica de uma forma simples, rápida e automática, através de procedimentos de simulação computacional. A simulação investigou a influência que um determinado sistema de registro exerce sobre a qualidade da imagem, possibilitando conhecer previamente a imagem final a ser obtida com diferentes equipamentos e sistemas de registro. Dentre os sistemas investigados, três filmes (Kodak Min R 2000, Fuji UM MA-HC e Fuji ADM) e duas telas intensificadoras (Kodak Min R 2000 e Fuji AD Mammo Fine), aquele que apresentou melhores resultados, com melhor qualidade de imagens e menor exposição à paciente foi o de tela Min R 2000 com filme Min R 2000 da Kodak. / The present research has as main objective the development of a computational method for verification of the best combination screen-film for mammographic examinations through the study of its sensitometric characteristics. The software interface was developed in Delphi for windows and display the image to be gotten for each type of combination screen-film, using images of Phantoms and real breasts. Because several factors influence the final mammographic image, such as magnification, characteristic of the films and screens and conditions of the processing, the method can provide an ample evaluation of the quality of the systems of mammographic image of a simple, fast and automatic form, through procedures of computational simulation. The simulation investigates the influence of a register system on the quality of the image, making it possible to know the final image previously to be gotten with different equipment and register systems. Three films (Kodak Min R 2000, Fuji UM MA-HC and Fuji ADM) and two screens (Kodak Min R 2000 and Fuji AD Mammo Fine) was avaliable and the screen Min R 2000 with film Min R 2000 was the best result with less exposure.

The aim of this doctoral thesis was to study the influence of memory, pain, age and education on the regional cerebral blood flow (rCBF), i.e. brain function, in early Alzheimer's disease (AD) and in chronic neck pain patients in comparison to healthy controls and in healthy elderly per se. This was done by optimizing single photon emission computed tomography (SPECT) as a method to study rCBF with the tracer Technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and by matching all image data to a brain atlas before evaluation. The rCBF-SPECT was evaluated and developed to obtain higher diagnostic accuracy in AD and in chronic neck pain patients it was used to study basic pain related cerebral processes in chronic pain of different origin. A new semimanual registration method, based on fiducial marker, suitable for investigations with low spatial resolution was developed. The method was used to reconstruct images with an improved attenuation and scatter correction by using an attenuation-map calculated from the patients' previously acquired CT images. The influence of age and education on rCBF was evaluated with statistical parametric mapping, SPM in healthy elderly. The main findings were age related changes in rCBF in regions close to interlobar and interhemispheric space but not in regions typically affected in early AD, except for the medial temporal lobe. The theory of a 'cognitive reserve' in individuals with a longer education was supported with findings in the lateral temporal lobe, a region related to semantic memory, and in the frontal lobe. A cross-sectional study of chronic neck pain patients showed extensive rCBF changes in coping related regions in a non-traumatic pain patients compared to both healthy and a pain group with a traumatic origin, i.e. whiplash syndrome. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. This suggests different pain mechanisms in these groups. The AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus. These changes were associated to episodic memory performance, and especially to face recognition. The diagnostic sensitivity for AD was high. The face recognition test (episodic memory) was used in AD patients to improve the sensitivity of method, i.e. memory-provoked rCBF-SPECT (MP-SPECT). The results were compared to healthy controls and the reductions of rCBF in temporoparietal regions were more pronounced in mild AD during provocation. Memory provocation increased the sensitivity of AD-related rCBF changes at group level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might then be of help to set diagnosis earlier. In conclusion rCBF in temporoparietal regions are associated to an impaired episodic memory in early AD. Changes in these regions do not have a strong connection to chronological age. The diagnostic sensitivity of rCBF-SPECT in AD is high and there is a potentially higher sensitivity if memory provoked investigations are used. The findings in this thesis have given an increased knowledge of underlying cerebral pain processing in non-traumatic and traumatic (whiplash) neck pain. Preliminary results supporting the theory of 'cognitive reserve' by showing a correlation between long education and preserved rCBF was found in healthy elderly.

Radionuclide molecular imaging is an emerging multidisciplinary technique that is used in modern medicine to visualise diseases at cellular and molecular levels. This thesis is based on five papers (I-V) and focuses on the development of site-specific radiolabelled recombinant anti-HER2 Affibody molecules and preclinical evaluations in vitro and in vivo of the labelled conjugates. This work is part of a preclinical development of an Affibody molecule-based tracer for molecular imaging of HER2 expressing tumours. Papers I and II report the evaluation of the Affibody molecule ZHER2:2395-C, site-specifically labelled with the radiometals 111In (for SPECT) and 57Co (as a surrogate for 55Co, suitable for PET applications) using a thiol reactive DOTA derivative as a chelator. Both conjugates demonstrated very suitable biodistribution properties, enabling high contrast imaging just a few hours after injection. Papers III and IV report the development and optimization of a technique for site-specific labelling of ZHER2:2395-C with 99mTc using an N3S chelating peptide sequence. 99mTc-ZHER2:2395-C demonstrated high and specific tumour uptake and rapid clearance of non-bound tracer from the blood, resulting in high tumour-to-non-tumour ratios shortly after injection, enabling high contrast imaging. In addition, in the study described in paper IV, freeze-dried kits previously developed for 99mTc-labelling were optimised, resulting in the development of a kit in which all the reagents and protein needed for labelling of ZHER2:2395-C with 99mTc were contained in a single vial. Paper V reports the evaluation of an anti-HER2 Affibody molecule, ABY-025, with a fundamentally re-engineered scaffold. Despite the profound re-engineering, the biodistribution pattern of 111In-ABY-025 was very similar to that of two variants of the parental molecule. It seems reasonable to believe that these results will also be applicable to Affibody molecules towards other targets. Hopefully, this work will also be helpful in the development of other small proteinaceous tracers.

Accurate dosimetry is a fundamental requirement for the safe and efficient use of radiation in medical applications. International Codes of Practice, such as IAEA TRS-398 (2000) for radiotherapy beams and IAEA TRS-457 (2007) for diagnostic radiology beams, provide the necessary formulation for reference and relative dosimetry and the data required for their implementation. Research in recent years has highlighted the shortage of such data for radiotherapy small photon beams and for surface dose estimations in diagnostic and interventional radiology, leading to significant dosimetric errors that in some instances have jeopardized patient’s safety and treatment efficiency. The aim of this thesis is to investigate and determine key data for the reference and relative dosimetry of radiotherapy and radiodiagnostics beams. For that purpose the Monte Carlo system PENELOPE has been used to simulate the transport of radiation in different media and a number of experimental determinations have also been made. A review of the key data for radiotherapy beams published after the release of IAEA TRS-398 was conducted, and in some cases the considerable differences found were questioned under the criterion of data consistency throughout the dosimetry chain (from standards laboratories to the user). A modified concept of output factor, defined in a new international formalism for the dosimetry of small photon beams, requires corrections to dosimeter readings for the dose determination in small beams used clinically. In this work, output correction factors were determined, for Varian Clinac 6 MV photon beams and Leksell Gamma Knife Perfexion 60Co gamma-ray beams, for a large number of small field detectors, including air and liquid ionization chambers, shielded and unshielded silicon diodes and diamond detectors, all of which were simulated by Monte Carlo with great detail. Backscatter factors and ratios of mass energy-absorption coefficients required for surface (skin) determinations in diagnostic and interventional radiology applications were also determined, as well as their extension to account for non-standard phantom thicknesses and materials. A database of these quantities was created for a broad range of monoenergetic photon beams and computer codes developed to convolve the data with clinical spectra, thus enabling the determination of key data for arbitrary beam qualities. Data presented in this thesis has been contributed to the IAEA international dosimetry recommendations for small radiotherapy beams and for diagnostic radiology in paediatric patients. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 6: Manuscript.</p>

A few abnormal cells found in a small piece of prostate tissue are most consequential for a man’s future. The prevalence of prostate cancer (PCa) is increasing globally. The main instigating factor for this cancer is not yet known, but it appears to be the consequence of many variables such as an increasingly older population, more frequent PSA-testing, and factors involving lifestyle. Prostate cancer screening, as an equivalent for breast cancer screening, has been suggested but unfortunately there are no accurate diagnostic tools available for this type of screening. The reason for this is simply that the prostate is one of the most difficult organs to diagnose and, consequently, PCa screening would generate far too many false-positive and false-negative results.  The prostate is not easily accessible as it is deeply-seated in the male pelvic area, wrapped around the urethra and surrounded by sensitive vital organs.  Furthermore, PCa is frequently multi-focal, and the cancer cells have a tendency of assimilating among normal cells and, thus, do not always form solid lumps.  Therefore, prostate tumors are often not felt by digital rectal examination (DRE) or identified by imaging.  The PSA-test is not reliable as it is more prostate-specific than cancer-specific.  Due to increasing prostate awareness, more early-stage and locally confined PCa are being detected. This is saving lives, although there is a high risk of over treatment and unnecessary side-effects.  The increased detection of PCa requires sophisticated diagnostic methods and highly skilled clinicians who can discern between indolent and aggressive cancers.  The current “gold-standard” for PCa diagnosis is biopsy grading by pathologists using the Gleason score system, which is a difficult task.  Therefore, innovative methods to improve the precision of prostate diagnosis, by increased biopsy sensitivity and tumor localization, are of essence. In light of these difficulties, the metabolomic approach using 1D and 2D high-resolution magic angle spinning (HRMAS) NMR spectroscopy combined with histopathology on intact prostatectomy specimens was evaluated in this research project.  The non-destructive nature of HRMAS NMR enables spectroscopic analysis of intact tissue samples with consecutive histological examinations under light microscope. Metabolomics aids in the unraveling and the discovery of organ-specific endogenous metabolites that have the potential to be reliable indicators of organ function and viability, extrinsic and intrinsic perturbations, as well as valuable markers for treatment response. The results may, therefore, be applied clinically to characterize an organ by utilizing biomarkers that have the capacity to distinguish between disease and health. The aim was to characterize the human and the rat prostate in terms of its intermediary metabolism, which I show here to differ between species and anatomical regions.  Furthermore, the aim is to seek the verification of HRMAS NMR derived metabolites which are known to be a part of the prostate metabolome such as, citrate, choline, and the polyamines which were performed, but also the identification of metabolites not previously identified as part of the local prostate metabolism, such as Omega-6, which was detected in tumors.  The extended aim was to elucidate novel bio-markers with clinical potential. In this study, the common phyto-nutrient, inositol, which appears to possess protective properties, was identified as being a potentially important PCa bio-marker for the distinction between the more indolent Gleason score 6 and the more aggressive Gleason score 7 in non-malignant prostate tissues with tumors elsewhere in the organ. Further studies in this area of PCa research are therefore warranted.

Neste projeto foi desenvolvido um método computacional para verificação da melhor combinação tela intensificadora - filme para exames mamográficos através do estudo de suas características sensitométricas. O software, desenvolvido em ambiente Delphi para windows, apresenta na tela do microcomputador a imagem a ser obtida para cada tipo de combinação tela intensificadora - filme, utilizando imagens de \"Phantoms\" e de mamas reais. Em razão da ampla quantidade de fatores que influenciam a imagem mamográfica final, tais como magnificação, característica dos filmes e telas intensificadoras e condições da processadora, o método proposto pode proporcionar uma ampla avaliação da qualidade dos sistemas de imagem mamográfica de uma forma simples, rápida e automática, através de procedimentos de simulação computacional. A simulação investigou a influência que um determinado sistema de registro exerce sobre a qualidade da imagem, possibilitando conhecer previamente a imagem final a ser obtida com diferentes equipamentos e sistemas de registro. Dentre os sistemas investigados, três filmes (Kodak Min R 2000, Fuji UM MA-HC e Fuji ADM) e duas telas intensificadoras (Kodak Min R 2000 e Fuji AD Mammo Fine), aquele que apresentou melhores resultados, com melhor qualidade de imagens e menor exposição à paciente foi o de tela Min R 2000 com filme Min R 2000 da Kodak. / The present research has as main objective the development of a computational method for verification of the best combination screen-film for mammographic examinations through the study of its sensitometric characteristics. The software interface was developed in Delphi for windows and display the image to be gotten for each type of combination screen-film, using images of Phantoms and real breasts. Because several factors influence the final mammographic image, such as magnification, characteristic of the films and screens and conditions of the processing, the method can provide an ample evaluation of the quality of the systems of mammographic image of a simple, fast and automatic form, through procedures of computational simulation. The simulation investigates the influence of a register system on the quality of the image, making it possible to know the final image previously to be gotten with different equipment and register systems. Three films (Kodak Min R 2000, Fuji UM MA-HC and Fuji ADM) and two screens (Kodak Min R 2000 and Fuji AD Mammo Fine) was avaliable and the screen Min R 2000 with film Min R 2000 was the best result with less exposure.