Neurodegenerative MRI brain (an approach)

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Imaging of the brain in patients with suspected neurodegenerative conditions is common and challenging, as in patients with subtle and equivocal signs and symptoms, the imaging findings are also often subtle and equivocal. In many instances, by the time imaging findings are clear cut, then the patient has declared themselves clinically, and the diagnosis is already established or at least strongly suggested.

As such the true role of imaging is often to push clinicians towards or away from a particular diagnosis rather than making a firm unwavering diagnosis; in other words, it is an exercise in applied Bayesian thinking.

It should also be noted that although MRI is the focus of this article many of the structural and volumetric changes that are sought can be reasonably well seen on CT imaging if it is performed volumetrically and time is taken to look for them.

Main conditions

Although there are a great many conditions which fall under the neurodegenerative umbrella, and even more which can result in cognitive impairment, the majority of patients with significant cognitive impairment will have one of a relatively small group, and familiarity with them is crucial. These include:

In addition, there are a number of 'classic' albeit uncommon to rare conditions with specific imaging findings:

Unfortunately, not all these conditions have good imaging biomarkers, and understanding this is crucial in not being unnecessarily certain of a particular diagnosis.

A further group of conditions, beyond the scope of this article, are conditions which can present with neurodegenerative-like signs and symptoms, such as:

Importance of clinical history

A good clinical history is paramount if the importance of subtle findings is to be appreciated whilst not overemphasising non-specific features. Unfortunately, all too often requests contain only vague details such as "dementia?" or "cognitive impairment".

Ideally, an MRI request should include two key components:

  • pertinent clinical information
  • the working diagnosis and differential
    • Clinical information
    • patient demographics
      • age, gender, ethnicity, and perhaps occupation
    • main presenting complaint
    • characterization of cognitive symptoms
      • attentional problems
      • memory problems (e.g. short term / long term / ante-grade / retrograde)
      • language problems (e.g. receptive, expressive) 
      • visual / constructional problems
      • apraxia/acalculia
      • personality change (e.g. disinhibition, aggression) 
    • characterization of physical symptoms
      • tremor
      • rigidity
      • hyperkinesis
      • falls
      • dysphagia
      • incontinence
      • eye signs
    • time course
      • onset, duration, progression
    • any relevant family history
    • any risk factors for differential diagnosis
      • e.g. smoking, hypertension, diabetes, stroke
    • any toxic exposures
      • e.g. medications, alcohol, illicit substances, radiation, environmental poisons
    • clearly stated differential diagnosis or study question
      • e.g. ?caudate atrophy
    Working diagnosis and differential 

    It is unlikely that even a talented subspecialty neuroradiologist will be able to develop as good a working diagnosis and differential diagnosis based on the above information as a clinician who has examined the patient, spent time with them, and who has years of clinical experience to draw up. Therefore, the working diagnosis, the relevant differential diagnosis and some sense of how likely these diagnoses are is essential. That way, the MRI report can then push towards or away from a particular diagnosis rather.

    Protocol

    There are many variations on a 'neurodegenerative protocol' and much will depend upon local preferences and equipment. What is essential is that good quality three plane imaging (sagittal, coronal, and axial) with T1, T2, FLAIR, DWI, and T2* (e.g SWI) sequences.

    Some sequences are best for anatomy (e.g. T1) whereas others are better at pathology (e.g. FLAIR). Others still are useful for the detection specific of specific changes (e.g. SWI microhemorrhages). 

    For a more detailed discussion, please refer to the separate article on neurodegenerative MRI protocol.

    Scoring systems and measurements 

    Although in most instances individual scoring systems are not reported, they are useful to know even if only as guides on which features have been found useful and reliable. Some of the more common scoring systems include:

    A number of measurements/ratios are also useful:

    Signs

    In addition to systematically going through each scan, it is worth specifically looking for some signs, which will ensure you do not miss a diagnosis which will in retrospect be obvious. Having said this, many of these signs are only useful (if at all) late in the course of the disease at which time the diagnosis is often already obvious clinically.

    Nonetheless, some of the better-known signs include:

    Systematic approach

    It should be self-evident that no single approach is the 'correct one'. What is certain is that in assessing an MRI brain for neurodegenerative diseases, perhaps more so than for other indications, a careful systematic approach is needed. What that approach does not matter so much, as long as all pertinent features are sought. What is presented here is the approach used by the author.

    1. T1 sagittal

    Begin by looking at the midline sagittal image and assess the following:

    • corpus callosum
      • ​the anterior half of the body should be thicker, and certainly not thinner than the posterior half. If thinner a degree of frontal lobe atrophy should be immediately suspected. ​
      • upward bowing may suggest hydrocephalus, including normal pressure hydrocephalus
    • midbrain shape, size and midbrain to pons area ratio
      • it is often easier to note abnormalities of the midbrain in the sagittal plane
      • roughly the area of the midbrain should be about a quarter of the pons, and with a little practice this can be easily eyeballed
      • don't overcall the hummingbird sign of PSP
    • pons shape
      • the pons should be plump and rounded and about 4 times as large as the midbrain. Be prepared to look for pontine atrophy if it looks small or flattened (e.g. multiple system atrophy) 
    • general morphology of the rest of the brain: many congenital anomalies have midline changes

    Next, move slightly to the left and right of the midline to assess the following:

    • medial surfaces of the frontal, parietal and occipital lobes
      • all the sulci should be about the same size
      • significant parietal sulcal widening with atrophy of the precuneus and posterior cingulate suggests Alzheimer disease
      • anterior-to-posterior gradient of sulcal size (bigger anteriorly) seen in frontotemporal lobar degeneration
      • mammillary bodies
        • should be about the same size. Atrophic or asymmetrical mammillary bodies may imply hippocampal pathology or Wernicke-Korsakoff syndrome 
      • hippocampal volume: sagittal is a surprisingly good plane for the hippocampi provided you have thin enough imaging. You should see them to be plump grey matter signal intensity sausage-shaped structures with the choroidal fissure above them, which may contain small cysts or focal expansions containing choroid. The hippocampi slightly taper as you progress from anterior to posterior. Reversal of this tapering may be seen in FTLD. In contrast, general atrophy is seen Alzheimer disease. 

    Finally, move all the way to the lateral surfaces of the brain and examine the following:

    • Sylvian fissure and cistern size
      • are they out of keeping with the rest of the brain? 
      • left to right asymmetry?
    • general sulcal and gyral size looking for regional atrophy

    Don't forget to look at everything else too. Sagittal T1 is often your largest field of view sequence and will be the only one to image the oral cavity, TMJ, and upper cervical spine and cord.

    2. Coronal sequences

    Coronal sequences are essential in the assessment of the hippocampi and careful attention must be paid not only to their size but also the distribution of change. On these sequences assess:

    • hippocampal, choroidal fissure and temporal horn size (see medial temporal lobe atrophy score)
      • don't forget to ask yourself whether the temporal horn is big or the hippocampus is small
    • symmetry
      • left > right atrophy favors FTLD
      • equal involvement favors Alzheimer disease
    • anterior to posterior gradient
      • anterior atrophy > posterior atrophy favors FTLD
    • involvement of the temporal lobe generally favors FTLD
    • atrophy largely restricted to the hippocampus and parahippocampal gyrus favors Alzheimer disease
    • mammillary body size, signal and symmetry
    3. Axial FLAIR & T2

    Start with the FLAIR axial sequences and examine:

    • gyral atrophy, particularly useful for the frontal lobes
    • widening of the Sylvian fissures
    • hippocampal volume and signal
    • posterior fossa morphology
    • Wernicke pattern high T2 signal (ventromedial thalamus, mammillary bodies, periaqueductal grey matter) 
    • degree of white matter signal and pattern
      • subcortical/deep white matter in chronic small vessel ischemia (common); consider multi-infarct dementia
      • periventricular in demyelination (uncommon in this setting) 
    • ventricular size: is it commensurate with sulcal widening?
    • evidence of old cortical infarcts
      • especially of cognitively important areas :
        • bilateral thalamic infarcts
        • inferomedial temporal lobe (especially dominant side) 
        • association areas (parietotemporal, temporo-occipital and angular gyrus)
        • borderzone (watershed) infarcts (superior frontal and parietal)

    T2 axial imaging is often better for basal ganglia structures and posterior fossa. Assess for:

    • reversal of normal T2 signal of putamen vs globus pallidus of MSA-P
    • atrophic caudate heads of Huntington disease
    • size and flow void in aqueduct (usually prominent in NPH) 

    Don't forget that T2 sequences usually give you the best look at the intracranial arteries, so make sure you look for aneurysms or vascular malformations.

    4. T2* sequences

    Sequences susceptible to blood products are particularly useful in assessing:

    5. DWI 

    DWI has a limited role in the assessment of a patient with a suspected neurodegenerative disease, but is crucial particularly for Creutzfeldt-Jakob disease: look for cortical, basal ganglia and thalamic restricted diffusion.

    Always look carefully for evidence of acute ischemia, although this is uncommonly seen in elective outpatient scans.

    Putting it all together

    Having gone through the scan systematically hopefully a definite pattern conforming to one of the suspected pathologies has become evident. In such cases, your conclusion should state which entity is most likely, but do so in a way that explicitly acknowledges that this opinion takes into account clinical context.

    • e.g. "In this age group and in the setting of visual symptoms and apraxias, bilateral relatively subtle parietal volume loss supports the clinical diagnosis of posterior cortical atrophy". 

    This is particularly important if findings are subtle or contradictory or if adequate clinical information is absent. In the latter scenario, an attempt to obtain it should be made and the author of the request card gently chastised :)

    In either case, it is often important to not appear to be overly certain, as in most instances imaging features are not pathognomonic. Once a label has been applied, shrugging it off is very difficult and can lead to long delays in a correct diagnosis.

    It is better to state that findings are non-specific and not strongly indicative of any single entity and recommend repeat imaging in 12 months at which time both the clinical and imaging features may be more convincing than arguing strongly for a particular diagnosis on the basis of flimsy evidence.