MRI in Stroke White Matter Disease

Question 1

Understand the basic physics of MRI and image contrast

Answer 1

Core Principles of MRI Physics

1. Magnetic Properties of Hydrogen:

• Water molecules in the body contain hydrogen protons which act like tiny magnets
• When placed in a magnetic field, these protons align with the direction of the field, creating a net magnetisation vector

2. Application of a Magnetic Field (B0)

• The primary magnetic field, B0 is a strong and constant field that aligns the hydrogen protons in one direction
• The strength of this field typically ranges from 0.5T to 3T in clinical MRIs but can be higher in research settings

3. Radiofrequency (RF) Pulse:

• An RF pulse is applied perpendicular to the direction of the primary magnetic field. This pulse provides energy that flips the alignment of the hydrogen protons, moving the magnetisation vector away from its alignment with B0
• The angle by which the protons are flipped is typically 90 degrees or 180 degrees, depending on the desired imaging technique

4. Relaxation Times (T1 and T2)

• T1 Relaxation (Longitudinal Relaxation): After the RF pulse is turned off, the protons return to their original alignment with the magnetic field. The time constant that characterise this process is called T1, which varies by the tissue type and is influenced by the molecular environment
• T2 Relaxation (Transverse Relaxation): Simultaneously, the protons lose phase coherence in the transverse plane due to interactions with neighbouring molecules, a process characterised by the time constant T2. T2 is generally shorter than T1 and also varies by tissue type

5. Image Contrast:

• T1-Weighted Imaging: Enhances contrast based on differences in T1 relaxation times. Tissues with shorter T1 relaxation times (fats) appear brighter, and those with longer T1 (like fluid) appear darker. Short TE and short TR to visualise normal anatomy and pathological changes involving fat and water content variation
• T2-Weighted Imaging: Enhances contrast based on differences in T2 relaxation times. Tissues with longer T2 times (like fluid) appear brighter, making it useful for detecting oedema, tumours and lesions. Taken with long TE and long TR
• Proton Density Weighted Imaging: Reflects the density of hydrogen protons, providing contrast based on the inherent proton density in different tissues. Taken with short TE and long TR to provide good anatomical detail.

6. Signal Decay and Acquisition:

• The signal detected by the MRI scanner comes from the RF energy released as the protons realign with the magnetic field. This signal decay occurs at a rate influenced by both T1 and T2
• The spatial distribution of this signal is encoded in the MRI data using gradients in the magnetic field, allowing for the precise localisation of the signal sources within the body

Image Acquisition Techniques

• Echo Time (TE): The time between the application of the RF pulse and the peak of the signal used to create the image. Shorter TEs are typically used for T1-weighted images and longer TEs are used for T2-weighted images
• Repetition Time (TR): The time between successive RF pulses applied to the same slice of tissue. Short TRs enhance T1 contrast and long TRs are used to enhance T2 or proton density contrast

Question 2

Understand the differences between T1- and T2-weighted images and how they are affected by pathological changes in stroke and white matter disease

Answer 2

T1-Weighted Imaging

• MRI signal intensity is primarily determined by T1 relaxation time, which is the time it takes for proton to realign with the magnetic field after the RF pulse is off
• Short TR and short TE are used. This emphasises differences in the rate at which different tissues recover their magnetisation along the direction of the magnetic field (longitudinal recovery)
• Fat appears bright (hyperintense) because it has a short T1 relaxation time
• Fluids like CSF and oedema appear dark (hypointense) because they have long T1 relaxation time
• Gray matter appears darker than white matter because its T1 time is slightly longer. White matter is bright because of shorter T1 relaxation time
• T1 is sensitive to tissue structure, particularly myelination in WM
• Dependent on how mobile the water is in the tissue and T1 increases slightly with oedema
• Paramagnetic ions reduce T1 (Fe from blood breakdown products, Gd from contrast agents)
• Ischemic Stroke: In the acute phase of an ischemic stroke, subtle changes may occur on T1 images, such as slight hyperintensity or a loss of the distinction between gray and white matter due to cytotoxic oedema
• White Matter Disease: Multiple sclerosis or leukoaraiosis show areas of demyelination or gliosis as hypointense on T1-weighted images compared to normal white matter
• T1 weighted MRI can be used to detect flow

T2-Weighted Imaging

• Focuses on the T2 relaxation time, which is the time it takes for protons to lose phase coherence in the transverse plane relative to each other, leading to a loss in signal intensity.
• Long TR and long TE are used, which highlight the differences in the rate at which different tissues lose signal due to dephasing
• Signal intensity comes from phase coherence (away from B0)
• Fluids and other substances with long T2 relaxation time appear bright (hyperintense). visualise fluid accumulation such as oedema, inflammation or infection
• Fat appears less bright than in T1-weighted images and white matter appears darker than gray matter.
• T2 is reduced so less bright by the presence of paramagnetic ions, Fe from blood breakdown products & Gd
• Cell death = less cell membrane = more T2 = brighter
• Ischemic Stroke: In acute ischemic stroke, T2-weighted images can show areas of high intensity due to vasogenic oedema and tissue liquefaction. The distinction becomes clearer as the stroke evolves from the acute to the chronic stage.
• **White Matter Disease: Conditions like chronic small vessel ischemic changes appear as hyperintense on T2-weighted images. These hyperintensities, white matter hyperintensities (WMHs) are associated with increased tissue water cotent and breakdown of the normal white matter structure
• T2 weighted MRI can be used to detect perfusion using i.v. contrast agents

Stroke Imaging (Chalela et al., 2007)

White Matter Disease (Debette & Markus, 2010)

Clinical Utility

• T1-Weighted Images are particularly useful for assessing the anatomy and integrity of white matter and for identifying pathologies that alter the normal appearance of white and gray matter.
• T2-Weighted Images are invaluable in diagnosing and evaluating diseases that involve increases in fluid content within tissues, making them crucial for detecting and monitoring conditions like stroke, brain tumors, and inflammatory processes.

Question 3

Understand how white matter brain lesions can be accurately detected by MRI and their implications for future patient outcomes

Answer 3

Detection of White Matter Lesions by MRI

1. T2-Weighted MRI:

• WML will appear as hyperintense (bright) signals on T2-weighted images due to prolonged T2 relaxation time caused by an increase in water content in the tissue, from oedema, demyelination or axonal loss

2. FLAIR Imaging:

• Fluid-Attenuated Inversion Recovery is useful in detecting WML near CSF (which shows up as bright in T2). It suppresses the signal from CSF, making the hyperintense lesions more conspicuous against the suppressed background. Crucial for identifying periventricular lesions often missed by T2 due to the high brightness of nearby CSF
• See small cortical strokes close to bright CSF in T2w

(Brant-Zawadzski, 1996)

3. Diffusion Tensor Imaging (DTI):

• DTI provides further detail by measuring the diffusion of water molecules in the brain tissue. It can reveal microstructural changes in white matter that are not visible on convention MRI scans. Changes in diffusion anisotropy can indicate damage to white matter tracts, often before any visible signs appear on T2 or FLAIR
• Anisotropic diffusion = asymmetric diffusion
• Fractional anisotropy map: Measure of asymmetry, 0 = isotropic, 1 = extremely anisotropic. Grey-scale image
• Principal diffusion direction map: Measures anisotropy and direction. Degree of anisotropy = brightness; Direction = colour
• Fibre tracking map: Automatic generation of fibre tracks by software

Implication of WML for Future Patient Outcomes

1. Stroke Risk:

• The presence of WML has been associated with an increased risk of stroke. These lesions indicate underlying vascular pathology, which can predispose patients to both ischemic and haemorrhagic strokes. The extent and location of lesions can help stratify risk levels for individual patients

2. Cognitive Decline and Dementia:

• Extensive WML are linked with cognitive decline and an increased risk of developing dementia, including Alzheimer’s disease and vascular dementia. The disruption of white matter integrity affects the connectivity and functionality of neural networks involved in cognition

3. Progression of Multiple Sclerosis:

• In MS, MRI is essential for monitoring disease progression and response to therapy. New or expanding WML can indicate active disease and may influence treatment strategies

4. Mortality:

• Studies have shown that severe WML are associated with a higher mortality rate in the elderly. Correlation due to the increased likelihood of CVD and higher vulnerability to acute neurological events.

5. Mobility and Falls:

• WML are associated with impaired mobility and a higher risk of falls in the elderly. Likely due to the effect on neural pathways that coordinate motor function (Descending pathway from motor cortex)

Clinical Management

• Early Detection: Routine MRI screening for at-risk population, early identification of WML
• Tailored Treatment: Extent and progression of white matter damage can guide the customisation of treatment plans, potentially involving pharmacological treatments, lifestyle adjustments and rehabilitation therapies
• Regular Monitoring:

(Debette and Markus, 2010):

• assesses the significance of white matter hyperintensities detected on MRI and their association with stroke, dementia, and cognitive decline.
• WMH = 3.5x stroke risk
• Pathologically associated with myelin loss, BBB breakdown, gliosis (proliferation of glial cells which can act like tumours)

Question 4

Understand what can be observed by perfusion and diffusion (advanced) MRI in stroke

Answer 4

Perfusion MRI (PWI)

Principle:

• Perfusion MRI assesses blood flow in the brain by tracking the distribution and rate of a contrast agent (gadolinium, Gd) or using arterial spin labelling (ASL)
• This technique measures parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT), which are crucial for assessing the haemodynamic status of the brain tissue.

Application in Stroke:

• Detection of Ischemic Penumbra: The ischemic penumbra is the region around the core of the infarct where tissue is at risk but potentially salvageable. PWI can identify these areas by showing reduced perfusion relative to normal brain tissue. Treatment decisions, particularly those involving reperfusion therapies like thromboylsis (aspirin and clopidogrel) or thrombectomy rely on identifying the penumbra
• Evaluating Reperfusion: After therapeutic intervention, PWI is used to assess the success of reperfusion treatments by comparing pre- and post-treatment perfusion states. Successful reperfusion is indicated by normalised or improved perfusion metrics in affected areas

(Chalela et al., 2004)

Diffusion MRI (DWI)

Principle:

• DWI measures the random Brownian motion of water molecules in brain tissue. In the context of stroke, DWI is sensitive to changes in water mobility, which can be altered by cytotoxic oedema - a cellular response to ischemia
• The apparent diffusion coefficient (ADC) map, derived from DWI, quantifies these changes in water diffusion. Lower ADC values typically indicate restricted diffusion
• Cytoxic oedema and cell swelling = restricted diffusion
• Cellular necrosis = increased diffusion

Application in Stroke:

• Early Detection of Ischemic Stroke: DWI is sensitive to ischemic changes and can detect strokes within minutes of symptom onset. Areas of ischemic stroke show up as hyperintense on DWI with corresponding hypointensity on ADC map due to restricted diffusion
• Differentiating Strokes: DWI helps distinguish acute ischemic stroke from haemorrhagic stroke and other stroke mimics, such as tumour or abscesses, which typically do not show restricted diffusion
• Assessment of Stroke Evolution: Follow-up DWI scans can monitor the progression or resolution of ischemic lesions. Increases in ADC values over days to weeks following stroke indicates the transition from acute to subacute and chronic stages, reflecting changes in tissue status and water mobility.

Combining PWI and DWI

Mismatch Concept:

• The mismatch between areas showing perfusion deficits (PWI) and those with diffusion restriction (DWI) is considered a surrogate marker for the ischemic penumbra. The PWI-DWI mistmatch model helps in identifying patients who are likely to benefit from reperfusion therapies beyond the conventional therapeutic window
• This mismatch approach guides decisions in acute stroke management, especially in selecting patients for interventions like mechanical thrombectomy up to 24 hours after stroke onset

Limitations and Challenges

• PWI: Requires rapid and precise administration of contrast agents and interpretation can be complex due to variations in haemodynamic responses among patients. ASL, a non-contrast techniques, offer an alternative but may have lower spatial resolution and signal-to-noise ratio
• DWI: While highly sensitive to early ischemic changes, can be too sensitive, detecting small lesions that are clinically insignificant. Additionally, in very acute stages of stroke, DWI may show transient normalisation, known as the fogging effect, which can complicate assessment of infarct size and extent

Question 5

Understand how multimodal MRI can be used to monitor treatment success in thrombectomy

Answer 5

thrombectomy, a procedure used to remove a blood clot from an occluded cerebral artery

Components of Multimodal MRI in Monitoring Thrombectomy

1. DWI

• Pre-Thrombectomy: Helps in identifying the ischemic core rapidly after stroke onset. DWI shows area of restricted diffusion indicative of tissue that has suffered significant ischemic damage.
• Post-Thrombectomy: Monitoring with DWI can assess the extent to which the ischemic regions have evolved following reperfusion. A decrease or stability in the size of DWI hyperintense areas can suggest effective reperfusion and salvage of the penumbral tissues.

2. PWI:

• Pre-Thrombectomy: Identifies tissue at risk of infarction (ischemic penumbra) by showing areas of delayed or reduced perfusion surrounding the core lesion
• Post-Thrombectomy: PWI can be used to verify the restoration of blood flow to the affected areas. Improvement in perfusion parameters like cerebral blood flow (CBF) and mean transit time (MTT) = successful reperfusion

3. MRA:

• Pre-Thrombectomy: Provides a visual map of the cerebral arteries to identify the location and extent of the occlusion, aiding in planning the thrombectomy procedure
• Post-Thrombectomy: MRA is crucial for assessing the recanalization of previously occluded arteries.

4. T2-weighted Gradient Recall Echo (GRE)

• Used to identify haemorrhagic transformations, which occur as a complication of reperfusion injury after thrombectomy. The detection of microhaemorrhages or larger haematomas is vital for managing post-procedural care.

(Campbell et al., 2017) uses PWI and DWI to select patients for late window thrombectomy, emphasizing the role of advanced MRI techniques in extending treatment time frames.

Question 6

What can be observed by Blood flow imaging (MRA) in stroke

Answer 6

Magnetic Resonance Angiography (MRA) is a specialised type of MRI technique that is used specifically to visualise the blood vessels and to assess blood flow within them.

Principles of MRA

• Time-of-Flight (TOF) MRA: This non-contrast technique exploits the flow-related enhancement of moving blood. It is most effective for visualising the flow in arteries because the inflowing blood appears white against a dark background. TOF MRA is sensitive to the speed and direction of blood flow and is commonly used for examining the circle of Willis in the brain.
• With Short TR, signal from blood stays bright due to continual in-flow of blood so there is no T1 saturation
• Phase Contrast MRA: Uses phase shifts caused by blood movement to create flow-quantifiable images and can provide information about flow direction and velocity. It’s more complex and time-consuming than TOF but can be advantageous for quantitative blood flow analysis
• Contrast-Enhanced MRA (CE-MRA): Involves the injection of a gadolinium-based contrast agent to enhance the visibility of blood vessels. CE-MRA provides high-resolution images and is particularly useful for evaluating the venous system and for cases where TOF MRA may be limited such as presence of slow or turbulent flow.

Application in Stroke

1. Detection of Vascular Occlusions and Stenosis:

• MRA is effective at identifying blockages or narrowing in the arteries, which are common causes of ischemic strokes. Can pinpoint the location and extent of an occlusion.

2. Evaluation of Intracranial Aneurysms:

• MRA is used to detect and characterise aneurysms, which if ruptured can lead to haemorrhagic strokes. It helps in assessing the size, shape and orientation of aneurysms.

3. Identification of Arterial Dissections:

• Arterial dissections (tearing along inside lining of artery) in the neck and brain can lead to ischemic strokes, particularly in younger patients. MRA can visualise the false lumen or the intimal flap characteristics of dissections.

4. Monitoring Treatment Effects:

• Post-treatment MRA is crucial in assessing the success of interventions such as thrombectomy or angioplasty. Provide immediate feedback on the restoration of flow

Limitations

• Flow Artifacts: MRA may produce artifacts related to rapid or turbulent flow, mimicking stenosis or occlusion
• Sensitivity to Patient Movement: MRA can require longer acquisition times, patient movement can affect the quality of the images
• Overestimation of Stenosis: Particularly in TOF MRA, slow flow adjacent to stenosis can lead to overestimation of the degree of narrowing