IMAGING BIOMARKERS IN STROKE
Stroke is a disease that occurs when a blood vessel that carries oxygen and nutrients to the brain is blocked by a clot or bursts. As the blood supply is diminished or interrupted, the affected region of the brain does not receive the necessary nutrients and its cells begin to die in minutes.
At present, stroke is a leading cause of death and disability worldwide, especially in low- and middle-income countries. In 2017, there was around 6.2 million of deaths and 132.1 million DALYs (Disability-Adjusted Life Year) due to this pathology. The burden of stroke is expected to increase in the coming years, both in terms of absolute numbers of incidents and deaths. This suggests that continuous monitoring of stroke burden is critical to informing healthcare delivery and resources.
There are two main causes of stroke: a blocked artery (ischemic stroke) or a leaking or bursting blood vessel (hemorrhagic stroke). Some patients may have only a temporary interruption of blood flow to the brain, known as a transient ischemic attack (TIA), which causes no lasting symptoms.
Ischemic stroke is the most common (approximately 87% of cases). It occurs when blood vessels in the brain become narrowed or blocked, causing a severe reduction in blood flow (ischemia). The blockage of these blood vessels is usually due to deposits of fat that accumulate in the blood vessels or by blood clots that travel through the bloodstream and lodge in the blood vessels of the brain. On the other hand, hemorrhagic strokes are caused by a weakened vessel that ruptures and bleeds into the surrounding brain. The blood collects and compresses the surrounding brain tissue. This vessel rupture may be due to uncontrolled high blood pressure, excessive treatment with anticoagulants, or trauma, among others.
In most cases, stroke is a disease that develops very quickly, causing a brain injury in a few minutes. The effects on the patient depend on several factors as the lesion location and the amount of brain tissue damaged. However, neurological complications such as the paralysis of one side of the body, speech issues, memory loss and erratic behaviors are common consequences of stroke incidents. A good guide for remembering the main symptoms of stroke can be remembered with the word FAST: Face, the face may have fallen on one side, the person may not be able to smile, or their mouth or eye may have fallen out; Arms, the person may not be able to raise both arms and keep them; Speech, the speech may be confused, or even not be able to speak at all or understand another person; Time, it is extremely important to call the emergency phone as soon as any of these symptoms are noticed. The Cincinnati Prehospital Stroke Scale (CPSS) is a system used to diagnose potential stroke patients in pre-hospital settings by evaluating their facial drop, arms drift and speech following the previous considerations.
Medical imaging plays a crucial role in the diagnosis and treatment of stroke patients, being Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) the preferred modalities as they provide the highest discrimination of stroke lesions. Current guidelines for the emergency diagnosis of acute strokes are based on CT scanners due to its shorter acquisition time and higher availability. If imaging occurs within hours of stroke onset, it provides sufficient information to differentiate between ischemic and hemorrhagic stroke. MRI usually provides higher sensitivity and specificity in the diagnosis of acute ischemic stroke but is not typically available for emergency diagnosis.
The use of post-processing techniques can provide a range of quantitative image biomarkers to aid in the diagnosis and evaluation of stroke patients. Some of the most widespread tools for this purpose are the automatic identification and classification of stroke lesions by using Artificial Intelligence techniques, or the automatic segmentation of the stroke volume. These are very useful tools for emergency diagnosis since they allow reducing time and workload of health personnel in these situations where a rapid response is essential.
Other imaging post-processing tools can be very useful to evaluate brain integrity and its evolution over time, such as brain tractography and functional connectivity. Brain tractography reconstructs the white matter tracts and extracts metrics relating to the structural integrity of the tissue. On the other hand, functional connectivity allows the evaluation of functional integrity in the gray matter to identify those functional connections affected by the injury. These imaging biomarkers offer a guide to determine the degree of severity of the stroke lesion.
The risk factors for stroke are similar to those for coronary heart disease and other vascular pathologies: hypertension, elevated lipids, and diabetes. Risks due to lifestyle factors can also be addressed: smoking, lack of physical activity, unhealthy diet, and obesity. Combining these prevention strategies has been shown to be effective in reducing stroke incidence even in low-income countries.
The disease is more frequent in people over 55 years old and the risk is higher as age increases. The World Health Organization (WHO) estimates that in 2050 the population over 65 years will represent 46% of the population, of which approximately half may suffer a stroke. For this reason, early detection and monitoring of people at risk of suffering from this disease is very important for prevention and anticipation.
Once a stroke has occurred, treatment varies greatly depending on its type. The main treatment for ischemic stroke is intravenous tissue plasminogen activator (tPA) within 3 hours after stroke onset. The administration of tPA helps to restore blood flow to brain regions affected by a stroke, thereby limiting the risk of further damage and functional impairment. In the case of hemorrhagic strokes, the actions are focused on controlling the bleeding and reducing the pressure in the brain. Further surgery may be required to repair blood vessels. It is critical to make a correct diagnosis, since administering tPA to a patient suffering a hemorrhagic stroke has a high probability of causing further damage that may even lead to death.
- Krishnamurthi, R., Ikeda, T., & Feigin, V. (2020). Global, Regional and Country-Specific Burden of Ischaemic Stroke, Intracerebral Haemorrhage and Subarachnoid Haemorrhage: A Systematic Analysis of the Global Burden of Disease Study 2017. Neuroepidemiology, 54(Suppl. 2), 171-179.
- Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016. (2018). New England Journal Of Medicine, 379(25), 2429-2437.
- O’Donnell, M., Chin, S., Rangarajan, S., Xavier, D., Liu, L., & Zhang, H. et al. (2016). Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. The Lancet, 388(10046), 761-775.
- O’Donnell, M., Xavier, D., Liu, L., Zhang, H., Chin, S., & Rao-Melacini, P. et al. (2010). Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. The Lancet, 376(9735), 112-123.
- Johnston, S., Mendis, S., & Mathers, C. (2009). Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. The Lancet Neurology, 8(4), 345-354. doi: 10.1016/s1474-4422(09)70023-7
- Powers, W., Rabinstein, A., Ackerson, T., Adeoye, O., Bambakidis, N., & Becker, K. et al. (2018). 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke, 49(3).
- Puig J, Blasco G, Schlaug G, Stinear CM, Daunis-I-Estadella P, Biarnes C, Figueras J, Serena J, Hernández-Pérez M, Alberich-Bayarri A, Castellanos M, Liebeskind DS, Demchuk AM, Menon BK, Thomalla G, Nael K, Wintermark M, Pedraza S. Diffusion tensor imaging as a prognostic biomarker for motor recovery and rehabilitation after stroke. Neuroradiology. 2017 Apr;59(4):343-351.