Stroke and PET
In stroke the flow of blood and oxygen into the brain is blocked, either because of blocked blood vessel (ischemic stroke) or ruptured blood vessel (haemorrhagic stroke). Most strokes are ischemic, and caused by rupture of atherosclerotic plaques.
Minor failures in microvessels and tissue organization can cause failures in metabolic homeostasis, and lead to neurotoxicity cascade involving glutamate, aspartate, and glutamatergic system, and axonal damage can cause further defects in autoregulation of the vasculature. In mild case, microglia is able to restore glutamate homeostasis, but if not, overstimulation of glutamate receptors will lead to Ca2+ influx and death of neurons and oligodendrocytes (excitotoxicity) as secondary brain injury.
Primary injury to the brain compromises the blood-brain barrier (BBB), and secondary injury exacerbates the BBB breakdown. This leads to release of proteins and protein fragments from the brain to the circulation, and attracts peripheral leukocytes in to the brain. Tissue break-down products are also released to the lymphatics, where those can be identified as antigens by T and B lymphocytes leading to production of autoantibodies and accelerated inflammatory response.
Ischemic stroke is often caused by a blood clot forming in one of the arteries supplying the brain; clot then travels in the vessel until it becomes lodged and blocks blood flow (thrombotic stroke). Clot can also initially form in the heart or arteries in the upper chest and neck (embolic stroke). Transient ischemic attack (TIA) is a temporary ischemic stroke, with similar symptoms which resolve in few minutes or hours. Without treatment, TIA is often followed by full stroke within a year.
During and after ischemia, PET and MRI can be used to assess oxygen consumption as a measure of tissue viability (Duval et al., 2002; Lin & Powers, 2018). Quantitative assessment of oxygen extraction fraction could help to identify patients with increased stroke risk and for extracranial-intracranial bypass surgery (Nemoto et al., 2018).
TSPO imaging has been used to monitor the neuroinflammation following stroke. The cerebral artery occlusion model of neuroinflammation and stroke in rats has shown a localized increased uptake of [11C]PBR28 (Imaizumi et al, 2007; Tóth et al, 2016).
Permanent cortical damage in human patients after ischemic stroke can be detected as reduced uptake of [11C]Flumazenil (Heiss et al., 1998). Reduced oxygen extraction predicts stroke in carotid stenosis and occlusion (Gupta et al., 2014).
Thrombotic ischemia model in rats has shown increased BPND of CB2 receptor radioligand 24 h after the stroke surgery, while no difference was found with inflammation radioligand [11C]PK11195 (Hosoya et al., 2017).
In haemorrhagic stroke blood vessel breaks and leaks blood, causing excess pressure and swelling inside the skull and reduces blood flow to the affected regions. Similar problems are caused by tramatic brain injury (TBI). Intracerebral stroke is caused by arterial burst outside of the brain causing those tissues to be filled with blood. Subarachnoid haemorrhagic stroke is caused by blood leakage into the space between the brain cortex and membranes that cover it.
Intracerebral haemorrhage (ICH) can be classified as primary or secondary. Primary ICH is associated with arterial hypertension, and usually affects small artery deep inside the brain, while secondary ICH is caused by an existing vascular malformation or tumour. Epidural haematoma is often seen in TBI patients with skull fracture. The rupture of an arterial vessel causes bleeding into brain parenchyma, which provokes mechanical damage to surrounding blood vessels and secondary bleeds. The shear stress and mass effect of expanding haematoma leads to instant necrosis of neurons and glial cells, and destruction of BBB and extracellular matrix (ECM).
Ackerman RH, Alpert NM, Correia JA, Finkelstein S, Davis SM, Kelley RE, Donnan GA, D’Alton JG, Taveras JM. Positron imaging in ischemic stroke disease. Ann Neurol. 1984; 15(Suppl): S126-S130.
Chelluboina B, Vemuganti R. Chronic kidney disease in the pathogenesis of acute ischemic stroke. J Cerebr Blood Flow Metab. 2019. doi: 10.1177/0271678X19866733.
Derdeyn CP. Positron emission tomography imaging of cerebral ischemia. Neuroimag Clin N Am. 2005; 15: 341-350. doi: 10.1016/j.nic.2005.05.001.
Duval V, Chabaud S, Girard P, Cucherat M, Hommel M, Boissel JP. Physiologically based model of acute ischemic stroke. J Cereb Blood Flow Metab 2002; 22: 1010-1018. doi: 10.1097/00004647-200208000-00013.
Heiss W-D. PET imaging in ischemic cerebrovascular disease: current status and future directions. Neurosci Bull. 2014; 30(5): 713-732. doi: 10.1007/s12264-014-1463-y.
Powers WJ, Zazulia AR. PET in cerebrovascular disease. PET Clin. 2010; 5(1): 83106. doi: 10.1016/j.cpet.2009.12.007.
Raichle ME. The pathophysiology of brain ischemia. Ann Neurol. 1983; 13:2-10. doi: 10.1002/ana.410130103.
Updated at: 2019-05-12
Created at: 2019-02-14
Written by: Vesa Oikonen