Posts By :

Eduardo Camacho

Mesa de trabajo 1Ictus

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.

Epidemiology

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.

Causes

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.

Symptoms

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.

Diagnosis

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.

Risk factors

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.

Treatment

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.

References:

  1. 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.
  2. Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016. (2018). New England Journal Of Medicine, 379(25), 2429-2437.
  3. 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.
  4. 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.
  5. 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
  6. 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).
  7. 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.
ALZ WORLD DAY

Imaging Biomarkers in Alzheimer

Alzheimer’s disease (AD) is a neurodegenerative disorder considered the most common cause of dementia worldwide. Dementia is a general term for the loss of cognitive functions –memory, thinking or reasoning- and behavioural abilities that affects the daily life of a person. According to the World Alzheimer Report, about 50 million people worldwide suffer from dementia. This number is estimated to be almost doubled every 20 years, reaching 131.5 million patients in 2050. AD is deemed the main form of dementia and contributes to 60-70% of the cases.

In this disorder, the connections between the nerve cells that make up the brain are affected, causing the death of these cells and the loss of brain tissue. In AD, abnormal levels of beta-amyloid and tau proteins are found in the brain. Evidence suggests that a complex interaction between these proteins is the main responsible of Alzheimer’s brain changes. Depending on the brain regions affected, different alterations may be presented in the patient. Some of the first regions to be altered are the entorhinal cortex and hippocampus, which are closely related to memory performance.

AD is a progressive disorder in which more parts of the brain are damaged over time. As this happens, more dementia’s symptoms are developed and the patient’s condition gradually worsens. In the early stages, people often present a reduced ability to take and remember new information; and may be accompanied by word-finding problems, vision or spatial issues, or impairment in reasoning or judgement. As AD progresses, patients suffer an increased memory and cognitive loss. They can experiment difficulties in recognizing family and friends, loss the ability to have conversations or be unable to respond to their environment. In severe cases of AD, brain tissue shrinks significantly, making people unable to communicate and completely dependent on others.

There are no effective treatment options for AD patients able to detain its progression. Nevertheless, symptoms can mitigate by means of medication and a healthy lifestyle. Some risk factors, such as age and genetics, are out of control; while others can be overcome to take care of brain-health. According to the Alzheimer’s Research & Prevention Foundation, regular physical exercise can reduce the risk of developing AD up to 50%. Others such as social engagement, healthy diet, mental work and stimulation, good sleep and stress management has proven to fortify the brain and reduce the risk of suffering any form of dementia.

As shown, prevention is the most effective way to fight this devastating disease. An early diagnosis is fundamental for this purpose. Nowadays, this is performed mainly by means of questions to the patients, blood/urine tests, and memory, attention or problem-solving exercises. Brain scans, such as computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) are also key elements in diagnosis because they allow to detect the presence of abnormal concentrations in proteins and atrophy.

In this way, our team has developed automatic brain tools for the detection and assessment of Alzheimer in a subject. Our Brain Atrophy suite and Voxel-Based Morphometry analysis modules are designed to evaluate the shrinkage of the brain by comparing its volume and morphology with a set of healthy subjects (paired in age and gender).

two examples of Brain Atrophy- Hippocampal Asymmetry analysis reports

Above there are two examples of Brain Atrophy: Hippocampal Asymmetry analysis reports over a healthy and over an Alzheimer’s brain. This analysis provides a view of the brain focused on hippocampus’s status (volume and level of asymmetry) framed in a comparison with a set of healthy people. Taking a look at them, relevant differences in the Alzheimer’s brain come to light: the left hippocampus volume falls below the normal ranges (red region in the table), while the left-right hippocampus asymmetry is also presented out of normal values.

Other important tool to assess brain atrophy is our Voxel-Based Morphometry analysis module, which gives volumes and statistical scores comparing morphology differences between the pathological brain and the previous set of healthy subjects.

QuibimStructuredReport_Voxel-Based Morphometry-01

The analysis above has been performed over the same Alzheimer’s brain than the previous Hippocampal Asymmetry evaluation. Both reports highlight alterations in the hippocampus, which is one of the first affections in AD.

Other tools we have included in the Brain Atrophy suite, such as global brain screening, frontal-temporal dementia and motor cortex evaluation can be also performed to obtain a more enlightening sight of the brain.  The combination of these brain assessment tools with traditional AD evaluation methods can lead to a better understanding and an earlier diagnosis of this terrible pathology.

MS WORLD DAY_QUIBIM

IMAGING BIOMARKERS IN MULTIPLE SCLEROSIS

Pain, depression, slurred speech and feeling of numbness, tingling, or weakness. These are just some symptoms of Multiple Sclerosis (MS) disease, a long-term condition that affects the brain and spinal cord.

In MS, the immune system confuses myelin with a foreign body and attacks it. The loss of this protective sheath that covers the nerve fibers will disrupt the messages travelling between the brain and the body. These messages may be slowed down, interrupted, or may not occur at all.

Eventually, the person sees affected the ability of controlling their own actions. The signs and symptoms of MS may vary greatly depending on the stage of the disease and the location of the affected nerve fibers. Movement affections, vision problems, altered speech and dizziness are common consequences of this condition.

It is the most widespread neurological disorder of young adults globally. The disease can be developed at any age, but its main incidence appears in the range of 20-50 years old. The National Multiple Sclerosis Society estimates that near 2.3 million people are living with this disease around the world. It also calculates that 1 million of them are placed in the United States, where 200 new cases are diagnosed every week.

Together with blood tests, medical history and neurologic exams, imaging scans have also proven to be a key element for the diagnosis of MS, concretely the Magnetic Resonance Imaging (MRI) is the reference diagnostic technique for the identification of lesions in MS.

Damaged white matter has a prolonged T2 relaxation time due to increased tissue water content and to degradation of the myelin, being well depicted on MRI and concretely on Fluid Attenuated Inversion Recovery (FLAIR) images. In this MR-sequence, MS lesions are seen as white matter hyperintensities (WMH). Nowadays, manual segmentation of WMH areas is still the gold standard to quantify the total lesion volume and to know the number of lesions in the brain. However, this methodology turns MS patient’s diagnosis and follow-up in a cumbersome and time-consuming task with high intra- and inter- observer variabilities.

Zero-click tools based on Artificial Intelligence (AI) and, more concretely, Convolutional Neural Networks (CNN) can be used to automatically segment WMH on FLAIR images in a few minutes. Novel designed architectures are composed of an ensemble of CNNs built on standard convolutional, dilated and residual layers.

Multiple Sclerosis_QUIBIM

These tools are capable of fine segmentation of the lesion avoiding the physiological WMH as the ependymal layer. Physicians can obtain quantitative information that helps them to achieve a more accurate and earlier diagnosis, thus reducing the workload and improving the time-efficiency while enhancing patient assessment.

What information does it provide?

Once WMH are segmented, relevant lesion statistics are quantified: lesion number, total lesion volume, dominant lesion volume, dissemination, or entropy among others. All this information can be summarized in a structured report along with the most characteristic slices. These processes will easily assist physicians in the diagnosis of MS patients not in the future, but now.

QuibimStructuredReport_White matter lesions

AUTHORS:

Eduardo Camacho Ramos.

Ana Jiménez Pastor.