Henk Stevens

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.

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.

Imaging of Stroke

In vivo demonstration of stroke-related pathological processes has evolved from scintigraphical and angiographical techniques to computer-assisted tomographic technologies. Today, computer tomography (CT) and magnetic resonance imaging (MRI) are widely available (1–5). CT is mainly used to distinguish between hemorrhagic and nonhemorrhagic pathology in the acute phase of stroke (6). Both MRI and CT visualize morphological changes in the brain; MRI, however, has a far better spatial resolution and allows visualization of other aspects of the pathology as well. To detect functional changes in both the normal and the pathological brain, additional procedures can be used such as visualization of regional cerebral blood flow with positron emission tomography (PET) or single photon emission tomography (SPECT). Both hypoperfusion of the core of the infarcted brain area and the penumbra and hyperperfusion in more peripherally located brain regions (luxury perfusion) can readily be shown (7–18). PET has the advantages of a higher resolution and absolute quantitative information on flow and metabolism of brain pathology compared to SPECT, but SPECT is cheaper and more accessible.

Long-Term Food Restriction, Deprenyl, and Nimodipine Treatment on Life Expectancy and Blood Pressure of Stroke-Prone Rats

We determined whether food restriction or the drugs nimodipine (Ca2+ antagonist) and deprenyl (a MAO-B inhibitor) prevent the development of stroke in the spontaneously hypertensive stroke-prone rat (SHR-SP). Forty male SHR-SP rats, in the age of 34 weeks, were exposed to various treatments. During a period of 27 weeks, survival and blood pressure were followed. In the control and deprenyl group, the blood pressure values remained unchanged; 50% had died after 27 weeks. All rats that were treated with nimodipine survived. After food restriction, 7/8 rats survived and showed a lower blood pressure. This study in SHR-PR rats shows the superiority of nimodipine on survival, and the potential of food restriction as a stroke-preventing measure.

Cobalt-57 as a SPET tracer in the visualization of ischaemic brain damage in patients with middle cerebral artery stroke

In PET studies we have shown the usefulness of cobalt radionuclides for the visualization and quantification of ischaemic damage in stroke. In the present study, we explored 57Co2+ as a SPET tracer. Uptake of radioactivity was estimated by using a cobalt enhancement ratio defined as the ratio of cobalt uptake in the affected region versus a similar volume in the non-affected contralateral side. Clinical status was assessed with the Orgogozo stroke score at the time of scanning and at least 60 days after admission. Nineteen patients (11 men, 8 women) with a middle cerebral artery stroke were examined with 57Co2+ SPET 0-30 days after stroke onset. Our investigations show enhanced cobalt uptake in the infarcted brain tissue in patients with a major stroke and little clinical improvement. There was a significant correlation between the cobalt enhancement ratio and the Orgogozo score at the time of scanning and discharge. Our results suggest that 57Co2+ SPET is suitable for determining the extent of (possibly calcium-mediated) damage in stroke and in the assessment of potential therapeutic interventions.

60Co and 45Ca autoradiography in cerebral ischemia in the rat

Radioisotopes of divalent Co (57Co in single photon emission tomography (SPECT)and 55Co in positron emission tomography (PET) have clinically been applied to visualize Ca related brain damage. The cerebral uptake of 45Ca and 60Co in a unilateral stroke model in the rat was compared; 100 microCi 45CaCl2 or 60 microCi 60CoCl2 was intravenously given at day 2 or 9 and the rats were killed 24 h later for autoradiography. Similarly increased uptake of 45Ca and 60Co was observed at both time points in unilaterally affected areas such as the cerebral cortex, dentate gyrus, caudate putamen of the striatum, substantia nigra pars reticulatum and corpus geniculatum. More Ca-uptake was found in the hippocampus CA1 region (at day 10) and the thalamus (ventral part at both time points). Radioactive Co but not Ca accumulated in the choroid plexus. Although the present investigation supports the idea that divalent Co-isotopes are useful to visualize stroke induced damage and choroid plexus function, these radionuclides do, however, not allow to detect excessive Ca-influx in degenerating neurones.