Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand 11C-PIB

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand ¹¹C-PIB Accumulation of beta amyloid (Abeta) in the brain is characteristic for Alzheimer’s disease (AD). Carbon-11 labeled 2-(4’-methylaminophenyl)-6-hydroxybenzothiazole (¹¹C-PIB) is a novel positron emission tomography (PET) amyloid imaging agent that appears to be applicable for in vivo Abeta plaque detection and quantitation. The biodistribution and radiation dosimetry of ¹¹C-PIB were investigated in 16 healthy subjects. The reproducibility of a simplified ¹¹C-PIB quantitation method was evaluated with a test-retest study on 6 AD patients and 4 healthy control subjects. Brain ¹¹C-PIB uptake and its possible association with brain atrophy rates were studied over a two-year follow-up in 14 AD patients and 13 healthy controls. Nine monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment and 9 unrelated controls were examined to determine whether brain Abeta accumulation could be detected with ¹¹C-PIB PET in cognitively intact persons who are at increased genetic risk for AD. The highest absorbed radiation dose was received by the gallbladder wall (41.5 mjuGy/MBq). About 20 % of the injected radioactivity was excreted into urine, and the effective whole-body radiation dose was 4.7 mjuSv/MBq. Such a dose allows repeated scans of individual subjects. The reproducibility of the simplified ¹¹C-PIB quantitation was good or excellent both at the regional level (VAR 0.9-5.5 %) and at the voxel level (VAR 4.2-6.4 %). ¹¹C-PIB uptake did not increase during 24 months’ follow-up of subjects with mild or moderate AD, even though brain atrophy and cognitive decline progressed. Baseline neocortical ¹¹C-PIB uptake predicted subsequent volumetric brain changes in healthy control subjects (r = 0.725, p = 0.005). Cognitively intact monozygotic co-twins – but not dizygotic co-twins – of memory-impaired subjects exhibited increased ¹¹C-PIB uptake (117-121 % of control mean) in their temporal and parietal cortices and the posterior cingulate (p<0.05), when compared with unrelated controls. This increased uptake may be representative of an early AD process, and genetic factors seem to play an important role in the development of AD-like Abeta plaque pathology. ¹¹C-PIB PET may be a useful method for patient selection and follow-up for early-phase intervention trials of novel therapeutic agents. AD might be detectable in high-risk individuals in its presymptomatic stage with ¹¹C-PIB PET, which would have important consequences both for future diagnostics and for research on disease-modifying treatments.

Development of advanced silicon radiation detectors for harsh radiation environment

This thesis describes the development of advanced silicon radiation detectors and their characterization by simulations, used in the work for searching elementary particles in the European Organization for Nuclear Research, CERN. Silicon particle detectors will face extremely harsh radiation in the proposed upgrade of the Large Hadron Collider, the future high-energy physics experiment Super-LHC. The increase in the maximal fluence and the beam luminosity up to 1016 neq / cm2 and 1035 cm-2s-1 will require detectors with a dramatic improvement in radiation hardness, when such a fluence will be far beyond the operational limits of the present silicon detectors. The main goals of detector development concentrate on minimizing the radiation degradation. This study contributes mainly to the device engineering technology for developing more radiation hard particle detectors with better characteristics. Also the defect engineering technology is discussed. In the nearest region of the beam in Super-LHC, the only detector choice is 3D detectors, or alternatively replacing other types of detectors every two years. The interest in the 3D silicon detectors is continuously growing because of their many advantages as compared to conventional planar detectors: the devices can be fully depleted at low bias voltages, the speed of the charge collection is high, and the collection distances are about one order of magnitude less than those of planar technology strip and pixel detectors with electrodes limited to the detector surface. Also the 3D detectors exhibit high radiation tolerance, and thus the ability of the silicon detectors to operate after irradiation is increased. Two parameters, full depletion voltage and electric field distribution, is discussed in more detail in this study. The full depletion of the detector is important because the only depleted area in the detector is active for the particle tracking. Similarly, the high electric field in the detector makes the detector volume sensitive, while low-field areas are non-sensitive to particles. This study shows the simulation results of full depletion voltage and the electric field distribution for the various types of 3D detectors. First, the 3D detector with the n-type substrate and partial-penetrating p-type electrodes are researched. A detector of this type has a low electric field on the pixel side and it suffers from type inversion. Next, the substrate is changed to p-type and the detectors having electrodes with one doping type and the dual doping type are examined. The electric field profile in a dual-column 3D Si detector is more uniform than that in the single-type column 3D detector. The dual-column detectors are the best in radiation hardness because of their low depletion voltages and short drift distances.

Design and characterization of large area position sensitive radiation detectors

Planar, large area, position sensitive silicon detectors are widely utilized in high energy physics research and in medical, computed tomography (CT). This thesis describes author's research work relating to development of such detector components. The key motivation and objective for the research work has been the development of novel, position sensitive detectors improving the performance of the instruments they are intended for. Silicon strip detectors are the key components of barrel-shaped tracking instruments which are typically the innermost structures of high energy physics experimental stations. Particle colliders such as the former LEP collider or present LHC produce particle collisions and the silicon strip detector based trackers locate the trajectories of particles emanating from such collisions. Medical CT has become a regular part of everyday medical care in all developed countries. CT scanning enables x-ray imaging of all parts of the human body with an outstanding structural resolution and contrast. Brain, chest and abdomen slice images with a resolution of 0.5 mm are possible and latest CT machines are able to image whole human heart between heart beats. The two application areas are presented shortly and the radiation detection properties of planar silicon detectors are discussed. Fabrication methods and preamplifier electronics of the planar detectors are presented. Designs of the developed, large area silicon detectors are presented and measurement results of the key operating parameters are discussed. Static and dynamic performance of the developed silicon strip detectors are shown to be very satisfactory for experimental physics applications. Results relating to the developed, novel CT detector chips are found to be very promising for further development and all key performance goals are met.