Johan Keppens

PET visualization of microglia in multiple sclerosis patients using [11C] PK11195

Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on microglia and up‐regulated after neuronal injury. [11C]PK11195 is a positron emission tomography (PET) radioligand for the PBR. The objective of the present study was to investigate [11C]PK11195 imaging in MS patients and its additional value over magnetic resonance imaging (MRI) concerning the immuno‐pathophysiological process. Seven healthy and 22 MS subjects were included. Semiquantitative [11C]PK11195 uptake values were assessed with normalization on cortical grey matter. Uptake in Gadolinium‐lesions was significantly increased compared with normal white matter. Uptake in T2‐lesions was generally decreased, suggesting a PBR down‐regulation. However, uptake values increased whenever a clinical or MR‐relapse was present, suggestive for a dynamic process with a transient PBR up‐regulation. During disease progression, an increase of normal‐appearing white matter (NAWM) uptake was found, propagating NAWM as the possible real burden of disease. In conclusion, [11C]PK11195 and PET are able to demonstrate inflammatory processes with microglial involvement in MS.

Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis : a correlative study

Objective: The objectives of the present study were to assess brain atrophy in multiple sclerosis (MS) patients during different disease stages and to investigate by PET and [11C]PK11195, a marker of microglial activation, the relationship between inflammation, atrophy and clinically relevant measures. Methods: Eight healthy subjects and 22 MS patients were included. Semiquantitative [11C]PK11195 uptake values, with normalization on cortical grey matter, were measured for magnetic resonance imaging T2- and T1-lesions and normal appearing white matter (NAWM). As atrophy index we used the ratio of the amount of white and grey matter divided by the ventricular size, using an optimized a priori based segmentation algorithm (SPM99). Results: Atrophy was significantly greater in MS patients compared to age-matched controls. A significant correlation was found between brain atrophy and both disease duration and disability, as measured with the Expanded Disability Status Scale. For NAWM, [11C]PK11195 uptake increased with the amount of atrophy, while T2-lesional [11C]PK11195 uptake values decreased according to increasing brain atrophy. Conclusions: The present study suggests that brain atrophy, correlating with disease duration and disability, is directly related to NAWM and T2-lesional inflammation as measured by microglial activation.

The significance of cobalt-55 positron emission tomography in ischemic stroke

Cobalt-55 ((55)Co) has been shown to be an interesting positron emission tomography (PET) tracer that may reflect calcium (Ca) influx in damaged cerebral tissue. Because Ca load is important in the ischemic cascade, the exact meaning of (55)Co PET in stroke patients has to be shown. The present study compares the degree of (55)Co uptake to regional cerebral blood flow (rCBF) and regional cerebral metabolic rate for oxygen (rCMRO(2)) values in brains of patients with ischemic stroke. Eighteen patients with an ischemic event in the middle cerebral artery territory were examined with PET using, in the same session, (55)Co and the (15)O steady state technique. The (55)Co ratio was assessed in ischemic and infarcted regions and compared with the corresponding rCBF and rCMRO(2) values. The average (55)Co ratio is inversely correlated to the rCBF and rCMRO(2) values. Also (55)Co accumulation tends to increase during the weeks after the onset of stroke and decreases down to normal levels after 6 months. The degree of (55)Co uptake corresponds to the severity of the ischemic damage within the first month after stroke. As it increases with time, it probably reflects the Ca accumulation caused by the progression of the inflammatory response within and around the infarct core.

Cobalt-55 Positron Emission Tomography of Ipsilateral Thalamic and Crossed Cerebellar Hypometabolism after Supratentorial Ischaemic Stroke

Cobalt-55 (55Co) is a positron emission tomography (PET) tracer used to demonstrate brain damage, possibly associated to calcium-mediated processes. The degree of 55Co accumulation correlates with the severity of ischaemia in stroke patients. It is still a matter of debate whether ipsilateral thalamic hypometabolism (ITH) and crossed cerebellar hypometabolism (CCH), occurring after middle cerebral artery (MCA) infarcts, represent only a metabolic depression of these remote regions or can lead to structural damage. The present study investigates whether an increased 55Co influx can be demonstrated with PET in ITH and CCH after MCA infarcts. About half of the patients with ITH and CCH had a significant degree of 55Co uptake in, respectively, the ipsilateral thalamus and the contralateral cerebellar hemisphere. It was observed in patients with severe signs of stroke on admission and poor clinical outcome, and correlated well with the degree of 55Co influx within the supratentorial infarct. The present study demonstrates that ITH and CCH after MCA infarction can represent structural damage in these remote areas that occurs during the second week after stroke onset.

F-18 FDG-PET in children: do we have enough counts?

PurposeThe aim of the study was to find out whether in [18F]fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG-PET) performed in children in our department, the number of counts were sufficiently high to guarantee optimal image quality. MethodsPhantom data with negative and positive lesions were acquired with an increasing count density and the relationship between image quality and counts per voxel was analyzed. On PET images obtained in 28 children aged 4–17 years and using a standard administered activity of 6.5 MBq/kg with a minimum of 74 MBq, the maximum counts per voxel in 10 regions of interest were noted and compared with those obtained on phantoms. ResultsPhantom data showed clearly the effect of higher count on image quality. Moreover, when high counts were available, reconstruction could be done using 2 mm3 voxel size, which improved the quality of the images further. In children, the counts per voxel in all the regions of interest, with the exception of the brain, were at a level of suboptimal image quality. ConclusionBy following the official guidelines, the counts per voxel observed in children with our gadolinium oxyorthosilicate-PET system were lower than the minimal required to produce optimal quality images. More efficient PET systems or higher F-18 FDG dose or increasing the acquisition time or combination of these factors are needed to improve the image quality and lesion detection.