<p>There are two Gadolinium-based liver-specific contrast media for Magnetic Resonance Imaging on the market, Gd-BOPTA (MultiHance®, Bracco Imaging, Milan, Italy) and Gd-EOB-DTPA (Primovist®, Bayer Schering Pharma, Berlin, Germany). The aim of this study in two parts was to evaluate the dynamics of biliary, parenchymal and vascular enhancement using these contrast media in healthy subjects. Ten healthy volunteers were examined in a 1.5 T magnetic resonance system using three-dimensional Volumetric Interpolated Breath-Hold (VIBE) sequences for dynamic imaging with both contrast media – at two different occasions – until five hours after injection. The doses given were 0.025 mmol/kg for Gd-EOB-DTPA and 0.1 mmol/kg for Gd-BOPTA. The enhancement over time of the common biliary duct in contrast to the liver parenchyma was analyzed in the first study. This was followed by a study of the image contrasts of the hepatic artery, portal vein and middle hepatic vein versus the liver parenchyma.While Gd-EOB-DTPA gave an earlier and more prolonged enhancement of the biliary duct, Gd-BOPTA achieved higher image contrast for all vessels studied, during the arterial and portal venous phases. There was no significant difference in the maximal enhancement obtained in the liver parenchyma.At the obtained time-points and at the dosage used, the high contrast between the common biliary duct and liver parenchyma had an earlier onset and longer duration for Gd-EOB-DTPA, while Gd-BOPTA achieved higher maximal enhancement of the hepatic artery, portal vein and middle hepatic vein than Gd-EOB-DTPA. Diseases of the liver and biliary system may affect the vasculature, parenchyma, biliary excretion or a combination of these. The clinical context regarding the relative importance of vascular, hepatic parenchymal and biliary processes should determine the choice of contrast media for each patient and examination.</p><p> </p>

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There are two Gadolinium-based liver-specific contrast media for Magnetic Resonance Imaging on the market, Gd-BOPTA (MultiHance®, Bracco Imaging, Milan, Italy) and Gd-EOB-DTPA (Primovist®, Bayer Schering Pharma, Berlin, Germany). The aim of this study in two parts was to evaluate the dynamics of biliary, parenchymal and vascular enhancement using these contrast media in healthy subjects. Ten healthy volunteers were examined in a 1.5 T magnetic resonance system using three-dimensional Volumetric Interpolated Breath-Hold (VIBE) sequences for dynamic imaging with both contrast media – at two different occasions – until five hours after injection. The doses given were 0.025 mmol/kg for Gd-EOB-DTPA and 0.1 mmol/kg for Gd-BOPTA. The enhancement over time of the common biliary duct in contrast to the liver parenchyma was analyzed in the first study. This was followed by a study of the image contrasts of the hepatic artery, portal vein and middle hepatic vein versus the liver parenchyma.While Gd-EOB-DTPA gave an earlier and more prolonged enhancement of the biliary duct, Gd-BOPTA achieved higher image contrast for all vessels studied, during the arterial and portal venous phases. There was no significant difference in the maximal enhancement obtained in the liver parenchyma.At the obtained time-points and at the dosage used, the high contrast between the common biliary duct and liver parenchyma had an earlier onset and longer duration for Gd-EOB-DTPA, while Gd-BOPTA achieved higher maximal enhancement of the hepatic artery, portal vein and middle hepatic vein than Gd-EOB-DTPA. Diseases of the liver and biliary system may affect the vasculature, parenchyma, biliary excretion or a combination of these. The clinical context regarding the relative importance of vascular, hepatic parenchymal and biliary processes should determine the choice of contrast media for each patient and examination.

Sammanfattning I Sverige drabbas ca 10000 personer årligen av lungemboli (LE). En vanlig bakomliggande orsak till LE är djup ventrombos. Tromboserna brukar vanligen sitta i benets eller bäckenets djupa vener. För att påvisa LE krävs att patienten genomgår olika radiologiska metoder såsom t.ex. datortomografi (DT) eller lungscintigrafi. Syftet med denna studie är att beskriva radiologiska metodval vid utredning av LE, för- och nackdelar med de olika metoderna och i vilka fall respektive metod föredras.  I databasen Pubmed söktes vetenskapliga artiklar som analyserar vilken av de radiologiska metoderna som föredras vid LE. Åtta artiklar valdes ut. Båda metoderna, DT och lungscintigrafi, är viktiga för att ställa diagnos vid misstänkt LE.  DT är den metod som väljs som förstahandsmetod, detta på grund av stor tillgänglighet och snabbhet, vilket är en stor fördel. Lungscintigrafiteknik bör dock inte uteslutas eftersom de båda metoderna kan komplettera varandra.

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.

Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 2 uppsatser.

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.

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.

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.