Karel Strijckmans

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.

Positron emission tomography in vascular dementia.

BACKGROUND Vascular dementia (VaD) is an ill-defined entity. It is not known how acute brain failure related to stroke becomes chronic leading to dementia. PURPOSE The present study investigates whether positron emission tomography (PET) can detect different metabolic patterns in VaD. PATIENTS AND METHODS Four groups of stroke patients were selected. The PET findings of 14 stroke patients with multiple large infarcts and dementia (MID) and 14 without dementia (MS) were compared. Sixteen stroke patients with lacunes, leukoaraiosis and dementia (LD) were assessed against nine without dementia (LS). The PET examination utilised the 15-O-steady-state technique in order to determine regional cerebral blood flow (rCBF), regional oxygen extraction rate (rOER) and regional cerebral metabolic rate for oxygen (rCMRO2) in different pre-established cortical, subcortical and cerebellar regions. RESULTS Decreased coupled mean rCBF and rCMRO2 with comparable rOER values were observed in all cerebral regions except in the cerebellum of the MID compared to the MS group. In the LD group mean rCBF and rCMRO2 were decreased with increased rOER in all cerebral regions except in the cerebellum compared to the LS group. CONCLUSIONS The PET findings in demented patients with multiple large infarcts are in agreement with the concept of multi-infarct dementia. In demented patients with lacunes and leukoaraiosis, the PET pattern suggests a state of misery perfusion not only in the deep structures but also in the whole cerebral cortex. The present PET study argues that there are at least two possible mechanisms that can explain the occurrence of VaD in stroke patients.

Acetazolamide Vasoreactivity in Vascular Dementia: A Positron Emission Tomographic Study

The present study investigates the vasoreactivity of the brain in patients with large infarcts and dementia (multi-infarct dementia; MID) and in patients with microangiopathy, lacunes, white matter changes and dementia (lacunar dementia; LD) using positron emission tomography (PET) and 13NH3 as regional cerebral blood flow (rCBF) tracer. In the control group, an increase in rCBF ranging from 32 to 43% was found in all brain regions after intravenous acetazolamide administration. In both the MID group and the group with multiple infarcts without dementia, moderate loss of vasoreactivity was observed in the frontal, temporal and parietal cortex compared to the control values. Vasoreactivity was severely impaired in all cerebral regions of the LD group and restricted to the thalamus in the group with lacunes and white matter changes without dementia (lacunar stroke; LS). This suggests that global loss of vasoreactivity is not a determining factor in the occurrence of MID, but might be important in LD. The present study shows that loss of the vascular reserve leading to exhausted metabolic reserve of the whole brain is one of the possible mechanisms for the occurrence of vascular dementia.

Does the Severity of Leukoaraiosis Contribute to Senile Dementia

The present study evaluates the origin, severity and location of leukoaraiosis in senile dementia and in normal ageing. The regional white-matter lucency scores, determined on computed-tomographic scan of the brain, are compared to the regional blood flow, oxygen extraction rate and oxygen consumption, determined by the [15O] steady-state technique with positron emission tomography. Thirty patients, classified according to the presence or absence of leukoaraiosis and their mental status, are examined. The occurrence and severity of dementia appear to be mainly correlated to decreased blood flow and oxygen metabolism in the frontal, temporal and parietal cerebral cortex. Leukoaraiosis in demented and nondemented patients is associated with lowered blood flow in the frontal and parietal white matter. The regional lucency score is increased, and blood flow and oxygen consumption decreased in the frontal white matter of severely demented patients. Frontal leukoaraiosis contributes to dementia and is probably of ischemic origin, while parietal and occipital leukoaraiosis is due to wallerian degeneration.

Differential Regional Cerebral Uptake of 18F-Fluoro-2-Deoxy-D-Glucose in Alzheimer’s Disease and Frontotemporal Dementia at Initial Diagnosis

In this paper, the cerebral uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) was studied in a relatively small group of patients suffering from either clinically diagnosed Alzheimer’s disease (AD) or frontotemporal dementia during the initial differential diagnostic workup. The image analysis was done visually and semiquantitatively using three different reference regions. Visual analysis confirmed earlier literature findings on the distribution of decreased FDG uptake and demonstrated prevalent asymmetric patterns in both groups. Only semiquantitative analysis using the sensorimotor cortex as a reference region confirmed the visual findings. Moreover, there were no differences in medial temporal lobe activities between both groups, and there was no correlation of medial temporal lobe activity with dementia severity. In the AD group, a correlation of parietal FDG uptake with MMSE scores was found.

A positron emission tomography study of patients with acute carbon monoxide poisoning treated by hyperbaric oxygen

Seven patients with an acute and severe carbon monoxide intoxication were treated with hyperbaric oxygen and underwent a positron emission tomographic examination 2–5 days after the acute event. Although the final clinical outcome was good in all patients, ischaemic changes were observed. Three patients with temporary sequelae after hyperbaric oxygen treatment showed the most severe changes, mainly in striatum and thalamus. Although positron emission tomographic examination cannot predict the final outcome, it can show the regions at risk for development of late complications following carbon monoxide poisoning.

Cobalt-55 positron emission tomography in vascular dementia: significance of white matter changes

BACKGROUND Vascular dementia (VaD) is still used as a covering term to indicate the relationship between cerebrovascular disease and the progressive cognitive disorder. The contribution of white matter changes (WMCs), seen with computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, to dementia had not been fully elucidated. Cobalt-55 (55Co) positron emission tomography (PET) allows us to distinguish between recent and old infarcts. PURPOSE The present study investigates whether 55Co PET can detect the lesions responsible for the progression of the cognitive disorder in VaD patients. PATIENTS AND METHODS 20 consecutive patients with a previous history of repeated strokes occurring more than 6 months before and with multiple cortical infarcts, lacunes and WMCs on CT and 5 age-matched controls were investigated with 55Co PET. The stroke patients were divided in two groups: 8 with and 12 without VaD. Average 55Co counts in cerebral cortex, deep gray nuclei and white matter were compared to the value in the cerebellum used as reference. RESULTS In the control group, the 55Co uptake was identical in the cerebral cortex and in the cerebellum, but lower in the deep gray nuclei and the cerebral white matter. When comparing the stroke groups with the control, the 55Co uptake was similar for the cerebral cortex and deep gray nuclei, but significantly increased in the cerebral white matter. The 55Co uptake was also more increased in the stroke group with VaD compared to the non-demented group. CONCLUSION 55Co PET shows that the WMCs are due to the ongoing damage of probably ischaemic origin which is more prominent in stroke patients with progressive cognitive decline.

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI

Several studies have shown the feasibility of divalent cobalt (Co)-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerosis, cerebral tumors and traumatic brain injury. Little is known how regional Co uptake relates to other pathophysiological changes after stroke. Therefore, we compared 55Co-PET with functional parameters such as regional cerebral blood flow (rCBF) using C(15)O(2), regional oxygen metabolism (rCMRO(2)) using 15O(2), regional cerebral blood volume (rCBV) and post-gadolinium (Gd) T(1)w-MRI to assess the permeability of the blood-brain-barrier (BBB). Sixteen patients (10 female; six male) aged 43 to 84 (mean 69) years with first ever stroke, as shown by CT or MRI, were examined with 55Co-PET and C(15)O(2)-, 15O(2)- and C(15)O-PET in one single session, in a period varying from 0 to 30 days after stroke-onset. Regions of infarction on C(15)O(2)- and 15O(2)-PET (defined by rCMRO(2)<65% or rCBF<45% of the contralateral value) were subsequently superimposed on the 55Co-PET scan. Clinical status was established using the Orgogozo stroke scale, which was assessed both at day 1 and at discharge (at least 6 weeks after day 1). Accumulation of 55Co was seen in eight out of 16 patients, occurring in areas showing a diminished oxygen metabolism, was only partially related to blood flow, and was located mainly outside the extent of the infarction or luxury perfusion as seen on post-Gd T(1)w-MRI. Statistical analysis showed a negative correlation between the Orgogozo score at discharge and the uptake of radioactive cobalt.

Late-onset epileptic seizures in patients with leukoaraiosis: a positron emission tomographic study.

Leukoaraiosis, found on computed tomographic scans of the brain, is suspected to be of ischemic origin and is frequently associated with progressive decline of cognitive functions in elderly persons. Some of them also develop late-onset epilepsy. The present positron emission tomographic study investigates if these seizures in mentally nonaffected patients with leukoaraiosis are related to an underlying ischemic process. Patients with leukoaraiosis and late-onset seizures have a more important decline of regional blood flow and oxygen consumption in the cortical areas, compared to normal age-matched controls, to patients with cryptogenic symptomatic late-onset epilepsy and to patients with a similar degree of leukoaraiosis but without epilepsy. The present study suggests that both the late-onset seizures and the leukoaraiosis in patients with, at that time, no obvious mental deterioration are premonitory signs of an encephalopathy of unknown origin, possibly leading to cognitive decline.