BackgroundCerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the... Show moreBackgroundCerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients.MethodsThe BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics.DiscussionThe results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers. Show less
The locus coeruleus, a small brainstem nucleus, is the main source of the chemical norepineprine in the brain and is involved in a number of cognitive functions as well as several neurological and... Show moreThe locus coeruleus, a small brainstem nucleus, is the main source of the chemical norepineprine in the brain and is involved in a number of cognitive functions as well as several neurological and psychiatric disorders. In this dissertation we study the human LC-NE system, the anatomy of this tiny brainstem nucleus and the involvement of the LC-NE system in stress, arousal, cognitive flexibility and physiology (hormones & pupil responses). To date, the LC-NE system has been studied in animals or ex vivo (dead donors). This dissertation is among the first ones to study and visualize the LC-NE system in humans in vivo (alive volunteers) and to approach the human cognition and the study of the LC-NE system in a holistic manner: from central neuromodulators to hormones that are secreted in the body, from anatomy to physiology and cognition. To this end, all chapters were written by taking into consideration theoretical knowledge about the LC-NE system with regard to brain anatomy, cognitive functions, neuromodulation, physiological responses, and clinical applications. Chapters 2 and 3 deal mainly with the anatomy of the LC, while Chapters 4, 5 and 6 concentrate on cognition and human physiology. Additionally Chapters 5 and 6 take also a clinical approach. Show less
Purpose Imaging the carotid arteries at 7T ideally requires a flexible multichannel array that allows B1-shimming and conforms to different neck sizes. The major challenge is to minimize coupling... Show morePurpose Imaging the carotid arteries at 7T ideally requires a flexible multichannel array that allows B1-shimming and conforms to different neck sizes. The major challenge is to minimize coupling between closely spaced coils and to make the coupling relatively insensitive to loading conditions.Methods We have designed a five-channel flexible transceive array composed of shielded-coaxial-cable coils placed on the anterior part of the neck and conforming to the anatomy. In vivo imaging of the carotid arteries in three subjects has been performed.Results The measured noise correlation matrices show the decoupling level between the individual elements to be -12.5 dB and better. Anatomical localizer imaging of the carotids shows both carotids in every subject well visualized after B1-shimming. In vivo black-blood, carotid images were acquired with very high in-plane spatial resolution (0.25 x 0.25 mm(2)) with clear depiction of the vessel walls.Conclusions The flexibility of the proposed coil has been demonstrated by imaging subjects with different neck circumferences. To the best of our knowledge, the in-plane resolution of 0.25 x 0.25 mm(2) is the highest reported at 7T. Show less
Colon, A.J.; Osch, M.J.P. van; Buijs, M.; Grond, J. van der; Hillebrand, A.; Schijns, O.; ... ; Boon, P. 2018
The general aim of this thesis was to explore the possibility to detect changes related to amyloid deposition in vivo using ultra-high field MRI. The central finding of the work presented in this... Show moreThe general aim of this thesis was to explore the possibility to detect changes related to amyloid deposition in vivo using ultra-high field MRI. The central finding of the work presented in this thesis is the cortical phase change on T2*-weighted sequences that we observed in AD patients using this novel ultra-high field imaging approach at 7T. It has been demonstrated that such phase measurements are a reliable indicator of iron content in the brain. It is known that amyloid depositions co-localize with iron accumulations. However, in autopsy material of AD patients, in addition to amyloid deposition, neurofibrillary tangles as well as tau deficiency were also found to co-localize with neuronal iron accumulation. In addition to iron, myelin and deoxy-hemoglobin can also contribute to phase changes. Although the exact origin of the observed phase changes in AD is not completely clear, these changes could have value for diagnostic purposes and as a biomarker. Show less
Dzyubachyk, O.; Lelieveldt, B.P.F.; Blaas, J.; Reijnierse, M.; Webb, A.; Geest, R.J. van der 2013
