Lecture 2: Clinical Tractography for Neurosurgical Planning

How diffusion MRI and tractography are used to help neurosurgeons avoid damaging important white matter pathways during surgery. The technique is especially important when lesions are close to areas responsible for movement, language, or vision.

Why Neurosurgical Planning Matters

The main aim of neurosurgery is to remove as much abnormal tissue as possible while preserving normal brain function. Surgeons therefore need detailed information about:

• where the lesion is located

• where important functional brain regions are located

• where critical white matter pathways travel

Damage to eloquent brain regions can produce severe post-surgical deficits such as:

• weakness or paralysis

• speech and language problems

• visual field loss

• sensory deficits

Standard imaging methods help identify lesions and cortical function, but they provide limited information about white matter connectivity. Tractography fills this gap by visualising white matter pathways.

Imaging Methods Used in Neurosurgical Planning

Several imaging techniques are combined during surgical planning.

Structural MRI

T1-weighted MRI

Used to identify anatomy and lesion structure. Particularly useful for tumours and cortical abnormalities.

FLAIR MRI

Provides complementary contrast and is useful for detecting abnormal white matter changes, cortical dysplasia, oedema, or calcification.

These scans define lesion morphology but do not show functional pathways.

Functional Imaging Techniques

Functional MRI (fMRI)

Measures blood oxygenation changes associated with neural activity. Used to identify functional cortex such as language or motor areas.

Magnetoencephalography (MEG)

Measures magnetic fields produced by brain activity more directly than fMRI.

Transcranial Magnetic Stimulation (TMS)

Stimulates cortex non-invasively to identify regions involved in movement or language.

Cortical and Subcortical Stimulation

Electrodes are used during surgery or epilepsy monitoring to identify eloquent tissue.

Awake Craniotomy

Allows direct monitoring of patient function during surgery.

These methods mainly focus on grey matter function rather than white matter connectivity. Tractography therefore becomes essential for understanding how regions are connected.

A major limitation of these methods is that they mainly focus on grey matter. They provide little direct information about white matter pathways. Surgeons may know approximately where major tracts such as the corticospinal tract should be located anatomically, but this is not sufficiently precise for surgery. Tractography was developed to solve this problem by visualising white matter pathways directly.

Diffusion MRI: The Basis of Tractography

Tractography is based on diffusion MRI, which measures how water molecules move through tissue.

Brownian Motion

Water molecules are constantly moving randomly due to thermal energy. This random motion is called Brownian motion. Over time, molecules spread further from their original position.

The longer water molecules are allowed to move, the further they spread from their starting point. The amount of spreading depends on both time and the diffusion coefficient, which reflects how freely water can move in a particular environment.

The diffusion coefficient depends on:

• temperature

• molecular species

• surrounding environment

In free water at body temperature, diffusion is relatively unrestricted.

How MRI Detects Diffusion

MRI scanners apply magnetic gradients during imaging.

If water molecules remain stationary:

• the effects of gradients cancel out

If water molecules move:

• signal loss occurs

Greater diffusion causes greater signal attenuation.

Diffusion-weighted imaging compares:

• a non-diffusion-weighted image (b=0)

• diffusion-weighted images (higher b-values)

Higher b-values increase sensitivity to diffusion.

Diffusion-weighted MRI compares how much signal is lost when water molecules move. Greater water movement causes greater signal loss, and this information is calculated for each voxel to create diffusion maps such as ADC maps.

Apparent Diffusion Coefficient (ADC)

In biological tissue, diffusion is restricted by:

• cell membranes

• axons

• myelin

• intracellular structures

Water therefore appears to diffuse less freely than in pure water. This measured value is called the Apparent Diffusion Coefficient (ADC).

Low ADC values indicate restricted diffusion.

High ADC values indicate freer diffusion.

Anisotropy

Diffusion in the brain is direction-dependent.

Isotropic Diffusion

Water diffuses equally in all directions.
Typical of:

• cerebrospinal fluid

• grey matter

Anisotropic Diffusion

Water diffuses preferentially in one direction.
Typical of:

• organised white matter tracts

Axons constrain water movement across fibres while allowing easier movement along fibre direction.

This directional property is fundamental for tractography because it allows estimation of fibre orientation.

Diffusion Tensor Imaging (DTI)

DTI models diffusion in three dimensions using a diffusion tensor.

The tensor:

• is a 3×3 matrix

• describes both magnitude and direction of diffusion

At least:

• 6 diffusion-weighted images

• plus 1 unweighted image

are required to estimate the tensor, although 20–30 directions are typically acquired for better accuracy.

Eigenvectors and Eigenvalues

The diffusion tensor can be decomposed into:

• 3 eigenvectors = diffusion directions

• 3 eigenvalues = diffusion magnitudes

The principal eigenvector indicates the dominant fibre orientation.

This allows white matter direction to be estimated within each voxel.

Important DTI Metrics

Fractional Anisotropy (FA)

FA measures how directional diffusion is.

High FA:

• highly organised white matter

• strong directional diffusion

Low FA:

• isotropic diffusion

• damaged or disorganised tissue

Mean Diffusivity (MD)

MD measures the overall magnitude of diffusion regardless of direction.

High MD:

• freer diffusion

• tissue loss or oedema

Low MD:

• restricted diffusion

How Pathology Affects DTI Metrics

Pathology commonly causes:

Reduced FA

Because tissue organisation breaks down and barriers restricting diffusion are lost.

Increased MD

Because water can diffuse more freely in damaged tissue.

Examples include:

• tumours

• degeneration

• oedema

• white matter injury

Colour FA Maps

Colour-coded FA maps show fibre orientation.

Typical colour convention:

• red = left-right

• green = anterior-posterior

• blue = superior-inferior

These maps provide intuitive visualisation of major white matter tracts.

Limitations of DTI

DTI assumes only one dominant fibre orientation per voxel.

This creates problems in regions with:

• crossing fibres

• branching fibres

• kissing fibres

The tensor therefore becomes inaccurate in complex white matter regions.

Constrained Spherical Deconvolution (CSD)

• CSD is an advanced diffusion MRI method used to estimate multiple fibre directions within a single voxel, making it much more useful for tractography than standard DTI in regions where fibres cross, branch, or curve.

• Unlike DTI, which assumes there is only one dominant fibre direction in each voxel, CSD assumes that several fibre bundles may pass through the same voxel in different directions. This is important because most white matter voxels actually contain complex fibre arrangements rather than one single tract.

• CSD works by analysing the full diffusion signal measured across many directions and comparing it to an idealised diffusion pattern from a single fibre bundle, known as the response function. It then mathematically separates the mixed diffusion signal into multiple probable fibre orientations within the voxel.

• The output of CSD is called a fibre orientation distribution (FOD), which is a spherical model showing the likely directions of fibres. Each peak in the FOD represents a different fibre population travelling through the voxel.

• This allows tractography algorithms to follow pathways through crossing-fibre regions much more accurately. For example, instead of incorrectly averaging two crossing tracts into one false diagonal direction like DTI often does, CSD can separate the two directions individually.

• CSD is particularly useful for reconstructing complex pathways such as:

  • optic radiations

  • Meyer’s Loop

  • arcuate fasciculus

  • corticospinal tract.

• It is preferred over DTI for tractography because it provides:

  • more anatomically realistic pathways

  • better handling of crossing fibres

  • fewer false tract terminations

  • improved continuity of streamlines through complex white matter regions.

• In neurosurgery, this improves surgical planning because surgeons can estimate tract locations more accurately and reduce the risk of damaging important pathways during resections.

• However, CSD is more computationally demanding and requires:

  • higher quality diffusion data

  • more diffusion directions

  • better signal-to-noise ratio

  • more advanced processing pipelines.

• It is also more sensitive to noise, meaning false fibre orientations or spurious streamlines can sometimes be produced if data quality is poor.

• CSD scans often take longer to acquire than standard DTI scans, which can be difficult in:

  • children

  • unwell patients

  • intraoperative MRI settings.

• Interpretation is also more complex because fibre orientation distributions are harder to analyse than simple tensors and usually require greater expertise.

• Importantly, CSD still does not directly visualise axons. Like all tractography methods, it estimates likely fibre pathways indirectly from patterns of water diffusion.

Tractography

• Tractography reconstructs white matter pathways by connecting voxels with similar diffusion directions.

• The aim is to move beyond looking at diffusion in single voxels and instead estimate:

  • how brain regions are connected

  • where important white matter bundles travel

  • whether pathways are close to lesions or surgical targets.

• This is especially important in neurosurgery because damage to white matter tracts can produce major deficits even if cortical regions are preserved.

• For example:

  • damaging the corticospinal tract can cause paralysis

  • damaging optic radiations can cause visual field loss

  • damaging the arcuate fasciculus can impair language.

Basic Tractography Algorithm

Seed Point

• Tractography starts from a seed point or seed region.

• The algorithm:

  • takes a small step in the principal diffusion direction

  • recalculates direction in the next voxel

  • continues repeatedly through neighbouring voxels.

• This process gradually creates streamlines representing estimated white matter pathways.

• Tracking is usually performed in both directions from the seed point so that the full pathway can be reconstructed.

Why Termination Criteria are Needed

• Without stopping rules, streamlines would continue into biologically meaningless regions.

• Tractography is an estimation process, so the algorithm needs rules to prevent anatomically impossible pathways.

Low Fractional Anisotropy (FA)

• Tracking stops when FA becomes too low.

• Low FA usually means:

  • diffusion is no longer strongly directional

  • tissue is no longer organised white matter.

• This commonly occurs when entering:

  • grey matter

  • CSF

  • damaged tissue.

Why this matters

• If tracking continued into isotropic tissue, streamline directions would become random and biologically meaningless.

Exit Brain Mask

• Tracking stops when the streamline exits the brain.

Why this matters

• White matter pathways cannot continue outside brain tissue.

• This prevents false tracts extending into non-brain regions.

Sharp Turns

• Tracking stops if the next step involves a sharp turn.

• Sudden turns are biologically implausible because real white matter fibres usually follow smooth trajectories.

Why this matters

• Sharp turns often occur because:

  • the algorithm jumps between tracts

  • noise disrupts direction estimates

  • the streamline enters CSF or pathological tissue.

• Stopping tracking reduces false-positive pathways.

Streamlines

• Tractography outputs 3D lines called streamlines. The colourful lines. They are mathematical reconstructions based on water diffusion patterns.

• In motor tractography:

  • streamlines often travel from motor cortex to brainstem

  • most follow anatomically sensible paths.

• Some spurious streamlines still occur because:

  • diffusion models are imperfect

  • fibre crossings complicate tracking

  • MRI data contains noise.

Why this matters

• Tractography should always be interpreted cautiously.

• Individual streamlines are not proof of real anatomical fibres.

• Instead, the overall pattern of pathways is most important clinically.

Regions of Interest (ROIs)

• ROIs are binary masks used to guide tractography.

• ROI placement is one of the most important factors affecting tractography results.

Why this matters

• Different ROI strategies can produce very different tract reconstructions in the same patient.

• Poor ROI placement can:

  • miss important fibres

  • include false pathways

  • mislead surgical planning.

Types of ROIs

Seed ROI

• Starting region for streamlines.

Why it matters

• Determines which pathways are reconstructed.

• Different seed locations emphasise different parts of the tract.

Waypoint / Inclusion ROI

• Streamlines must pass through this region to be included.

Why it matters

• Removes anatomically implausible streamlines.

• Improves specificity of tract reconstruction.

• The transcript compares this to marathon checkpoints:

  • if a runner misses checkpoints, they likely took the wrong route.

Exclusion ROI

• Streamlines entering this region are discarded.

Why it matters

• Helps eliminate false-positive pathways.

• Example:

  • when reconstructing motor pathways in one hemisphere

  • exclusion ROIs can remove streamlines incorrectly crossing the midline.

Iterative Refinement

Iterative refinement means repeatedly adjusting and improving the tractography reconstruction step-by-step until the pathways look anatomically reasonable and clinically useful.

• Researchers repeatedly:

  • inspect pathways

  • adjust ROIs

  • add exclusions

  • test different thresholds.

Why this matters

• There is rarely one perfect tractography solution.

• Exploring multiple reconstructions helps avoid false conclusions.

• This is particularly important in surgical planning where missing fibres could harm patients.

ROI Definition Methods

Manual ROIs

• ROIs can be manually drawn using imaging software.

Advantages

• flexible

• tailored to individual anatomy

• useful in abnormal brains.

Limitations

• time consuming

• operator dependent.

Why this matters

• Manual methods are often essential in pathology because automated tools may fail.

Automated Parcellation

• Software such as FreeSurfer automatically segments cortical and subcortical regions.

Advantages

• fast

• reproducible

• useful in healthy anatomy.

Limitations

• relies on relatively normal brain structure

• can fail in:

  • tumours

  • previous resections

  • cortical malformations

  • severe pathology.

Why this matters

• In neurosurgical patients, anatomy is often distorted.

• Automated segmentation errors can directly affect tractography accuracy.

Functional Activation ROIs

Functional imaging activations from scans such as fMRI can be used as tractography seed regions so that white matter pathways are reconstructed from brain areas that are actually active during a task.

Why this matters

• Allows researchers to investigate white matter pathways connected to functional cortex.

Limitation

• If fMRI activation is inaccurate:

  • tractography errors become compounded.

• Some researchers therefore prefer:

  • analysing functional imaging separately

  • then comparing it with tractography to check whether findings agree.

Seed Strategy Differences

Cortical Seed

• A cortical seed means the tractography starting point is placed near the motor cortex on the brain surface.

• Because the seed starts close to cortex, the resulting streamlines spread out more broadly across cortical regions, showing detailed connections near the brain surface.

Why this matters surgically

• When surgery is close to cortex, surgeons need to know:

  • how far the motor fibres spread

  • which cortical areas are connected

  • where the safest entry route is.

• So broader projections give more detailed local information near the cortical surface.

• Deeper in the brain, tracts are usually more tightly bundled together, which is why peduncle seeds often produce narrower streamline bundles.

Peduncle Seed

• A peduncle seed means the tractography starting region is placed lower down in the corticospinal tract, usually around the cerebral peduncle in the brainstem.

• Instead of starting near the broad fan-like fibres at the cortex, the algorithm starts in a deeper region where the motor fibres are already tightly bundled together.

• Because the fibres are more compact there, the resulting streamlines are narrower and more focused.

Why this matters

• This makes it easier to visualise the main deep motor pathway without lots of broad cortical branching.

• Peduncle seeds are especially useful for deep lesions, such as thalamic tumours, because surgeons mainly need to know:

  • where the deep motor tract is travelling

  • whether it is displaced by the lesion

  • how close surgery will come to the tract.

• So:

  • cortical seeds give more detailed information near the cortical surface

  • peduncle seeds give clearer reconstruction of the deeper compact motor pathway.

Streamlines Follow the Path of Least Resistance

• Streamlines tend to follow smooth directional continuity.

Why this matters

• Algorithms naturally prefer smooth curves over abrupt directional changes.

• This can bias tracking toward some pathways while missing others.

• In oedema or distorted anatomy:

  • streamlines may “wrap around” lesions

  • pathways may become artificially displaced.

Validation of Tractography

• One major limitation is that tractography has no perfect gold standard.

Why this matters

• Researchers cannot directly prove every reconstructed tract is anatomically correct.

• Validation studies are therefore extremely important.

Lawes et al. (2008)

• Compared tractography of the inferior fronto-occipital fasciculus with anatomical dissection.

Findings

• Similar:

  • tract curves

  • bends

  • shapes

  • posterior anatomy.

Importance

• Provided evidence that tractography can reflect real white matter anatomy.

• Increased confidence that reconstructed pathways are biologically meaningful.

Limitation

• Similarity does not prove perfect accuracy.

• Tractography remains an indirect estimation method.

Important Conceptual Point

• Tractography does NOT visualise individual axons.

• Instead:

  • it estimates the average direction of fibre bundles across many axons.

Why this matters

• Tractography is a probabilistic reconstruction technique, not a microscopic imaging method.

Clinical Tractography

Main Clinical Tracts

Motor Pathways

• preserve movement.

Optic Radiations

• preserve vision.

Arcuate Fasciculus

• preserve language.

Why these matter

• These functions have major impacts on quality of life.

• Neurosurgical planning focuses heavily on avoiding injury to these pathways.

Kinoshita et al. (2005)

• Early glioma tractography study.

Findings

• One patient developed severe deficits after surgery.

• Tractography underestimated tract extent.

Important technical issue

• Used a very high FA threshold (0.3).

• the algorithm only allows tracking through voxels with fairly strong directional diffusion.

So:

• FA > 0.3 → tracking continues

• FA < 0.3 → tracking stops.

Example:

• a crossing-fibre voxel with FA = 0.25 might still contain important fibres

• but tractography would stop there if the threshold is 0.3.

An FA threshold of 0.3 is relatively strict because tractography will only continue through voxels with strongly directional diffusion, meaning real fibres in crossing-fibre, curved, or damaged regions may be excluded and tracts may appear smaller than they really are.

Why This Matters Clinically

In the glioma study:

• the high FA threshold likely caused tractography to underestimate the motor tract extent

• surgeons may have thought fibres were further away from the tumour than they actually were

• one patient developed severe deficits after surgery.

So choosing the FA threshold is a balance between:

• avoiding false-positive tracts

• but not accidentally removing real fibres.

Clinical implication

• Incorrect tractography parameters can directly affect patient outcomes.

• Demonstrated the importance of:

  • careful parameter selection

  • testing multiple reconstructions

  • understanding limitations of the method.

FA THRESHOLD

• An FA threshold is a cutoff value used during tractography to decide whether tracking should continue through a voxel or stop.

• FA (fractional anisotropy) measures how directional diffusion is:

  • high FA = water mainly moves in one direction

  • low FA = water moves more equally in all directions.

FA Range

FA values always range from:

• 0 → completely isotropic diffusion

• 1 → perfectly directional diffusion.

In reality, brain tissue usually falls somewhere between these extremes.

There is no single “correct” FA value because it depends on the tissue and brain region, but roughly:

• CSF → around 0.0–0.1
  (very isotropic)

• Grey matter → around 0.1–0.2
  (less organised)

• Crossing-fibre regions → often around 0.2–0.4
  (real white matter but diffusion directions are mixed)

• Healthy major white matter tracts → often around 0.4–0.8
  (strongly directional)

• Very coherent white matter (e.g. corpus callosum) → can be even higher.

During tractography, the algorithm checks the FA value in each voxel.

If the FA:

• stays above the threshold → tracking continues

• falls below the threshold → tracking stops.

Why This Is Needed

• Low FA means the diffusion direction is less reliable.

• If tracking continued through very low FA regions:

  • streamlines would become random

  • false pathways would appear.

So thresholds help prevent biologically unrealistic tracts.

Mikuni et al. (2007)

• Mikuni et al. (2007) investigated whether tractography accurately reflected real motor pathways in patients with gliomas undergoing surgery.

• The study included 40 glioma patients and compared:

  • pre-operative motor tractography

  • with intraoperative subcortical stimulation during surgery.

• During surgery, surgeons electrically stimulated tissue near the tumour to test whether it was functionally connected to motor pathways.

• If stimulation produced a motor evoked potential (MEP), such as movement or muscle activity, this indicated the tissue was functionally important motor white matter.

• The study found that in 18 out of 40 patients, motor evoked potentials occurred within 1 cm of the tractography-defined motor pathways.

Why this is important

• This showed reasonably strong agreement between:

  • tractography predictions

  • and real functional motor tissue identified during surgery.

• In other words, the reconstructed corticospinal tracts were often close to the actual motor pathways.

• This was important because one major criticism of tractography is that it is only an indirect estimate based on water diffusion.

• By comparing tractography with direct electrical stimulation, the study provided evidence that tractography can reflect clinically meaningful anatomy.

Clinical implication

• Suggested tractography is clinically useful rather than purely experimental.

• Also showed tractography and direct stimulation complement each other rather than replacing one another.

Tractography

• provides a pre-operative anatomical estimate of pathway location

• helps surgeons plan surgical approach

• shows how tracts may be displaced by tumours.

Subcortical stimulation

• provides real-time functional confirmation during surgery

• tests whether tissue is actually involved in motor function at that exact moment.

Stimulation:

• Intraoperative stimulation is the broad category of electrical stimulation performed during brain surgery to map brain function. It includes two phases: cortical (mapping the surface of the brain) and subcortical (mapping deeper white matter tracts).

• Interoperative Subcortical stimulation is a specific type of intraoperative stimulation used to measure the distance to critical motor or language pathways deep inside the brain while a surgeon removes a tumor.

Kamada et al. (2007)

• Kamada et al. (2007) investigated whether tractography of the arcuate fasciculus (AF) accurately reflected real language pathways during neurosurgery.

• The arcuate fasciculus is a major white matter tract involved in language, particularly communication between frontal and temporal language regions.

• The researchers reconstructed the arcuate fasciculus using tractography before surgery and imported it into the neuronavigation system used by the surgeons. This meant the surgeons could see the estimated language tract location during the operation itself.

• During surgery, electro-cortical stimulation was performed. This involves electrically stimulating regions of cortex while monitoring the patient for language disruption.

• If stimulation caused speech arrest or language problems, the stimulated area was assumed to be functionally important for language.

• The study found that stimulation sites producing language disruption were within 6 mm of the reconstructed arcuate fasciculus pathways.

Why this matters

• Demonstrated close agreement between tractography and functional language mapping.

Clinical implication

• Supports use of tractography for protecting language pathways during surgery.

Why stimulation is still needed

• Tractography estimates anatomy indirectly from water diffusion.

• Electrical stimulation tests real functional tissue directly in the patient during surgery.

• Therefore:

  • tractography provides anatomical guidance

  • stimulation provides functional confirmation.

• The two techniques are most effective when combined together.

Epilepsy Surgery Case

Clinical Background

• Patient had:

  • left frontal polymicrogyria

  • seizures

  • right hemiparesis before surgery.

• Required left frontal lobectomy.

Surgical Outcome

• Patient became seizure free.

• Right arm strength improved significantly.

Why this is important

• Demonstrates that removing epileptic tissue can improve function rather than worsen it.

• Seizure activity itself had likely been disrupting motor cortex recovery.

Clinical implication

• Careful tractography-guided surgery can preserve function while improving neurological outcome.

Why Intraoperative MRI is Needed → Brain Shift

• Before surgery, patients usually have a high-quality pre-operative MRI with CST (corticospinal tract) tractography to map important motor pathways relative to the lesion.

• These tractography maps are loaded into neuronavigation systems so surgeons can avoid damaging critical white matter during surgery.

Brain Shift

• During surgery:

  • the skull is opened

  • pressure changes

  • CSF drains

  • tissue is removed

  • gravity affects the brain.

• Because brain tissue is soft and deformable, the brain physically moves during surgery. This is called brain shift.

Why This Matters

• Pre-operative tractography only reflects anatomy before surgery begins.

• As the brain shifts:

  • tract locations may no longer align with the real anatomy

  • neuronavigation becomes less accurate.

• A motor tract that originally appeared safely away from the lesion may move closer to the surgical cavity during resection.

• This increases the risk of damaging important pathways.

Intraoperative MRI

• Intraoperative MRI acquires updated scans during surgery so surgeons can see the brain’s current anatomy after brain shift has occurred.

• Updated intraoperative CST tractography can then be generated using the new scan, improving:

  • tract localisation

  • surgical guidance

  • safety.

Challenges of Intraoperative Tractography

• Intraoperative diffusion MRI is difficult because:

  • scans must be very fast

  • image quality is lower

  • surgical cavities cause distortions

  • patient positioning is unusual

  • real-time processing is required.

• Despite these challenges, intraoperative MRI helps reduce navigation errors caused by brain shift and improves preservation of important white matter tracts during surgery.

Thalamic Pilocytic Astrocytoma Case

Clinical Problem

• Deep tumour close to motor pathways.

Why this is challenging

• White matter anatomy becomes distorted.

• Internal capsule location may be unclear.

• Surgeons need tractography to estimate:

  • pathway displacement

  • safest surgical entry route.

Tractography Findings

• Streamlines displaced posteriorly.

• Pathways wrapped around the tumour.

• Oedema caused streamlines to corkscrew around the lesion.

Why this matters

• Pathology can distort tractography dramatically.

• Requires iterative testing of different ROI strategies and thresholds.

Outcome of Astrocytoma Case

• Tumour successfully debulked.

• Patient showed:

  • improved strength

  • better hand use

  • good functional recovery.

Why this matters

• Demonstrates how tractography can help:

  • guide safer surgical approaches

  • preserve important pathways

  • improve post-operative outcomes.

Streamline Density Maps

• Streamline density refers to how many streamlines pass through a particular brain region on a tractography map.

• Areas with more streamlines are shown as brighter or denser regions on the image.

Brighter colours

• more streamlines

• greater confidence in tract location.

Limitation

• Density naturally decreases with distance from the seed region.

Why this matters

• High density does not necessarily mean the tract is biologically stronger.

• Interpretation requires caution.

Optic Radiations

• The optic radiations are major white matter pathways involved in vision.

• Visual information travels:

  • from the eyes

  • through the optic nerves

  • into the optic chiasm

  • through the optic tracts

  • into the optic radiations

  • finally reaching primary visual cortex (V1).

• Visual fields are crossed:

  • left visual field projects mainly to the right hemisphere

  • right visual field projects mainly to the left hemisphere.

Why this matters clinically

• Damage to optic radiations can produce visual field deficits.

• Even if surgery successfully removes a lesion, injury to visual pathways may significantly affect quality of life.

Meyer’s Loop

• One particularly important part of the optic radiation is Meyer’s Loop.

• Meyer’s Loop:

  • curves sharply anteriorly through the temporal lobe

  • then loops back toward occipital cortex.

Why this is important

• Temporal lobe resections are common in epilepsy surgery.

• If surgeons resect too far posteriorly or laterally:

  • they may cut Meyer’s Loop

  • causing visual field deficits.

• This makes accurate tractography extremely important during temporal lobe surgery.

Why Optic Radiation Tractography is Difficult

• Segmentation of optic radiations is particularly challenging.

Main reasons

Sharp Curvature

• Meyer’s Loop bends sharply.

• Tractography algorithms prefer smoother trajectories.

Crossing Fibres

• Complex fibre architecture exists near the lateral geniculate nucleus (LGN).

Path of Least Resistance Problem

• Streamlines tend to continue in straighter directions.

• Instead of following the sharp curve of Meyer’s Loop, streamlines may incorrectly continue forwards.

Why this matters

• Tractography may underestimate the anterior extent of Meyer’s Loop.

• Surgeons could falsely assume tissue is safe to remove.

Epilepsy Case: Right Parietal Occipital Craniotomy

Clinical Background

• Patient required:

  • right parietal-occipital craniotomy

  • removal of a tuber associated with epilepsy.

• The lesion was close to the optic radiation.

Why this is important

• Surgery near visual pathways risks post-surgical visual deficits.

• Surgeons therefore needed tractography to estimate tract location before surgery.

Tractography Findings

• Optic radiation tractography was reconstructed around the lesion.

• The posterior part of the tract was particularly important in this case.

• Post-operative imaging suggested:

  • most of the optic radiation was preserved

  • only a small region appeared affected.

Surgical Outcome

• Patient had:

  • no post-operative seizures

  • reasonably preserved unaided vision.

• Unfortunately:

  • no formal visual field map was available post-operatively.

• A formal visual field map is a detailed clinical test that measures exactly which parts of a person’s visual field they can or cannot see.

• After surgery near the optic radiations, doctors ideally perform this test to check whether any visual pathways were damaged.

• The patient may feel their vision is “mostly normal,” but subtle visual field deficits can still exist.

• Some deficits are difficult for patients to notice themselves.

Why this case is important

• Demonstrates how tractography can guide resections near critical visual pathways.

• Shows that preserving most of the tract may help preserve visual function.

Limitation

• Without formal visual field testing:

  • exact visual outcome cannot be fully confirmed.

In This Case

• The surgeons believed most of the optic radiation had been preserved because:

  • tractography suggested only small overlap with the surgical area

  • the patient reported reasonably good vision.

• However, without a formal visual field test:

  • they could not objectively confirm whether small visual deficits were present.

Lacerda et al. (2020)

Aim of the Study

• Investigated visual pathway damage following paediatric epilepsy surgery.

• Researchers:

  • reconstructed optic radiations using tractography

  • segmented resection cavities

  • “Segmented” means the researchers used imaging software to identify and outline that cavity on the MRI scan.

  • measured overlap between the two.

Methodology

• The optic radiation was rotated into the axial plane to allow measurement of:

  • cross-sectional overlap area

  • between the tract and resection cavity.

• The study then compared:

  • overlap percentage

  • with post-surgical visual field deficits.

Findings

• Patients with greater overlap between:

  • optic radiation

  • and resection cavity

  were more likely to develop visual field deficits.

• Examples from the table:

  • Patient 15 had 100% overlap and persistent right homonymous hemianopia

  • Patients with 0% overlap often retained normal vision.

Why this study is important

• Provides evidence that tractography findings relate to real clinical outcomes.

• Supports the idea that:

  • damage predicted by tractography

  • corresponds to actual visual deficits after surgery.

Clinical implication

• Surgeons can potentially estimate visual risk before surgery.

• Helps guide:

  • surgical planning

  • patient counselling

  • informed consent discussions.

Broader significance

• This is important because one criticism of tractography is that it lacks a gold standard.

• Outcome studies like this help validate its clinical usefulness.

Arteriovenous Malformations (AVMs)

What is an AVM?

An AVM (arteriovenous malformation) is an abnormal tangle of blood vessels where blood flows directly from arteries into veins without passing through normal capillaries.

• This creates a high-pressure shortcut called a shunt, causing the vessels to become fragile and increasing the risk of bleeding, seizures, and neurological problems.

• The central tangled mass of abnormal vessels is called the nidus.

Why AVMs are Dangerous

• AVMs are fragile and prone to bleeding.

• Surgical removal is extremely delicate because surgeons must:

  • disconnect feeding arteries first

  • disconnect draining veins afterwards.

Why order matters

• If venous drainage is removed first:

  • pressure builds within the nidus

  • the AVM may rupture catastrophically.

AVM Tractography Case

• In this case:

  • the AVM was close to the left optic radiation.

• Tractography included:

  • left optic radiation

  • right optic radiation for comparison.

Why the Contralateral Side Was Included

• Researchers noticed signal dropout near the AVM.

• Signal dropout means part of the MRI image loses signal and appears darker or missing.

• Near an AVM, this can happen because:

  • blood is flowing very fast

  • the abnormal vessels distort the magnetic field

  • MRI signals become unstable or disappear.

• This is especially common in diffusion MRI because diffusion scans are very sensitive to magnetic distortions.

Why this matters

• Streamlines appeared artificially displaced away from the AVM.

• This could falsely suggest the tract was safer than it really was.

• Including the opposite hemisphere allowed:

  • comparison with normal anatomy

  • checking whether tract displacement was biologically plausible.

Important implication

• Tractography can be distorted by pathology itself.

• Absence of streamlines does not necessarily mean absence of fibres.

Clinical Importance of the AVM Case

• Tractography helped surgeons assess:

  • proximity of visual pathways

  • risk to patient vision.

Important point

• The tractography itself did not directly guide the surgical dissection.

• Instead, it improved:

  • surgical planning

  • risk assessment

  • patient counselling.

• Surgeons could explain:

  • where the AVM was

  • where the visual pathways were

  • what level of visual risk existed.

Focal Epilepsy Case Near Three Major Tracts

Clinical Background

• Patient had focal epilepsy with a lesion near:

  • arcuate fasciculus

  • motor tract

  • optic radiation.

Why this is difficult

• Multiple eloquent pathways were crowded around the lesion.

• Damaging any of them could impair:

  • language

  • movement

  • vision.

Surgical Planning

• Surgeons reconstructed all three tracts simultaneously using tractography so they could visualise:

  • where each pathway travelled

  • how close they were to the lesion

  • which surgical routes might avoid them.

• “All three tracts simultaneously” means the surgeons reconstructed and viewed all three white matter pathways together at the same time on the tractography images.

• It lets surgeons see how the pathways are positioned relative to each other and to the lesion.

Why this matters

• Demonstrates that neurosurgical planning often requires preserving multiple systems simultaneously.

• Surgeons do not only protect one tract in isolation.

• By visualising all three pathways together, the surgeon identified a narrow route between the tracts that allowed access to the lesion while minimising damage to surrounding white matter.

Outcome

• Patient became seizure free one week after surgery.

• Mild weakness remained in the:

  • left hand

  • left foot.

• Post-operative imaging showed:

  • the motor tract was very close to the resection cavity.

Why this is important

• Demonstrates that even careful surgery near eloquent pathways still carries risk.

• Small shifts in anatomy or tractography inaccuracies may still produce subtle deficits.

Clinical implication

• Tractography reduces risk but cannot eliminate it completely.

Major Limitations and Challenges of Tractography

Technical Challenges

• crossing fibres

• low resolution

• susceptibility artefacts

• image distortion

Biological Confounds

• oedema

• degeneration

• compression

• tumour infiltration

Interpretation Challenges

• no true gold standard

• false positives

• false negatives

Clinical Challenges

• requires expert knowledge

• time consuming

• difficult integration into surgical workflows

Important Conceptual Point

Tractography does NOT show individual axons.

Instead, it estimates likely pathways based on average diffusion patterns across many fibres. This is a major misconception.

Overall Significance

Tractography has become an increasingly important tool in neurosurgery because it allows surgeons to visualise critical white matter pathways before operating. It improves surgical planning and helps reduce functional deficits by identifying pathways that must be preserved.

What does ADC measure?
The overall magnitude of water diffusion within tissue.

What is fractional anisotropy (FA)?
A measure of how directional diffusion is within a voxel.

What does high FA indicate?
Highly organised white matter with strongly directional diffusion.

What does low FA indicate?
More isotropic diffusion, often seen in grey matter, CSF, oedema, or damaged tissue.

What is DTI?
A diffusion MRI model that estimates the main direction and magnitude of diffusion in 3D.

How many directions are minimally needed for DTI?
At least 6 diffusion-weighted directions plus 1 unweighted image.

What are eigenvectors in DTI?
The main diffusion directions within a voxel.

What are eigenvalues in DTI?
The magnitude of diffusion along each eigenvector.

What does the principal eigenvector represent?
The dominant fibre orientation in a voxel.

What is tractography?
A technique that reconstructs estimated white matter pathways using diffusion directions.

What are streamlines?
Computer-generated 3D lines representing estimated white matter pathways.

What is CST tractography?
Tractography of the corticospinal tract used to map motor pathways.

What is a seed region in tractography?
The starting region from which streamlines are generated.

What is a waypoint ROI?
A region that streamlines must pass through to be included.

What is an exclusion ROI?
A region where any streamline entering it is discarded.

What are termination criteria in tractography?
Rules that determine when streamline tracking should stop.

Why does tracking stop at low FA?
Because diffusion is no longer strongly directional and fibre orientation becomes unreliable.

Why is DTI limited in crossing-fibre regions?
Because DTI assumes only one dominant fibre direction per voxel.

What is CSD?
An advanced diffusion model that estimates multiple fibre directions within a voxel.

Why is CSD better than DTI for tractography?
Because it handles crossing fibres more accurately and produces more realistic pathways.

What is a fibre orientation distribution (FOD)?
A spherical model showing likely fibre directions within a voxel.

What is Meyer’s Loop?
A sharply curving part of the optic radiation that travels through the temporal lobe.

Why is Meyer’s Loop clinically important?
Damage during temporal lobe surgery can cause visual field deficits.

What is brain shift?
Movement and deformation of brain tissue during surgery.

Why is brain shift a problem for tractography?
Pre-operative tractography may no longer align with the real anatomy during surgery.

Why is intraoperative MRI used?
To update anatomy and tractography after brain shift occurs.

What is an AVM?
An abnormal tangle of blood vessels where arteries connect directly to veins without capillaries.

What is the nidus in an AVM?
The central tangled mass of abnormal vessels.

What is signal dropout?
Loss of MRI signal causing regions to appear dark or missing.

Why is signal dropout problematic in tractography?
It can make tracts appear falsely absent or displaced.

What is segmentation?
Separating and labelling brain regions or structures on MRI images.

What is a resection cavity?
The empty space left after surgical removal of brain tissue.

What does “segmented resection cavity” mean?
The cavity has been outlined and labelled on MRI for analysis.

What is a cortical seed?
A tractography seed placed near cortex, producing broader cortical projections.

What is a peduncle seed?
A seed placed lower in the corticospinal tract, producing narrower deep tract reconstructions.

Why are cortical seeds useful?
They provide detailed information about pathways near cortical surgical targets.

Why are peduncle seeds useful?
They better visualise deep compact motor pathways near deep lesions.

What is iterative refinement in tractography?
Repeatedly adjusting ROIs and parameters to improve tract reconstruction.

What did Mikuni et al. (2007) show?
Motor stimulation sites were often within 1 cm of tractography-defined motor tracts, showing good agreement with functional anatomy.

What did Kamada et al. (2007) show?
Language stimulation sites were within 6 mm of arcuate fasciculus tractography, supporting tractography for language preservation surgery.

What did Lacerda et al. (2020) show?
Greater overlap between optic radiations and resection cavities predicted visual field deficits after surgery.

What is the major limitation of tractography?
It estimates pathways indirectly from water diffusion and does not directly visualise axons.

• Tractography uses diffusion MRI to estimate white matter pathways by following the direction water diffuses through organised axonal fibres.

• Water diffuses anisotropically in white matter because axons and myelin restrict movement across fibres but allow easier movement along them.

• DTI models diffusion in 3D using tensors and produces measures such as:

  • FA = directionality of diffusion

  • MD = overall magnitude of diffusion.

• High FA indicates organised white matter; low FA indicates isotropic or damaged tissue.

• The principal eigenvector represents the dominant diffusion direction and is used to estimate fibre orientation.

• Tractography reconstructs pathways as streamlines by following diffusion directions voxel-to-voxel.

• Tracking stops when diffusion direction becomes unreliable, such as in low-FA regions.

• ROIs guide tractography:

  • seed ROIs start tracking

  • waypoint ROIs force streamlines through regions

  • exclusion ROIs remove false pathways.

• Cortical seeds produce broader cortical projections useful near the brain surface; peduncle seeds produce narrower deep motor tract reconstructions useful for deep lesions.

• DTI is limited because it assumes one fibre direction per voxel and performs poorly in crossing-fibre regions.

• CSD improves tractography by estimating multiple fibre directions within a voxel using fibre orientation distributions (FODs).

• CSD provides more anatomically realistic tractography and better reconstruction of complex pathways such as Meyer’s Loop and arcuate fasciculus.

• Tractography is used clinically to preserve:

  • motor pathways

  • optic radiations

  • language pathways during neurosurgery.

• Optic radiation tractography is important because damage to Meyer’s Loop during temporal lobe surgery can cause visual field deficits.

• Brain shift occurs during surgery because tissue moves after the skull is opened and tissue is removed, reducing the accuracy of pre-operative tractography.

• Intraoperative MRI can update anatomy and tractography during surgery but has challenges including lower image quality, distortion, and limited processing time.

• Tractography is useful but indirect:

  • it estimates pathways from water diffusion

  • it does not directly visualise axons.

• Validation studies showed good agreement between tractography and intraoperative stimulation:

  • Mikuni et al. (2007) → motor pathways

  • Kamada et al. (2007) → language pathways.

• Lacerda et al. (2020) showed greater overlap between optic radiations and resection cavities predicted post-surgical visual field deficits.

• Major tractography limitations include:

  • crossing fibres

  • noise

  • signal dropout

  • brain shift

  • lack of a true gold standard

  • dependence on ROI placement and tracking parameters.