Brain Pathology

Radiology - Pathology

Before You Begin

This module is intended primarily for pre-clinical studentslearning or reviewing pathophysiology.

Please note that this series will focus on how pathology presents in imaging studies. It assumes familiarity with fundamental anatomy. If you need to learn or review this core concept, please visit the “Anatomy” section of our website.

If material is repeated from another module, it will be outlined as this text is so that you are aware

Structure and function of the brain

• Layers of neurons and glial cells form the gray matter, which peripherally lines the gyri. Additional deep gray matter is present in the basal ganglia and thalami

• Deeper white matter tracts are composed of glial cells and myelinated nerve fibers, and is less densely cellular than gray matter

• Ventricles and subarachnoid space are filled with CSF. These spaces become more apparent with volume loss and some pathologic conditions

• The posterior fossa, including the brainstem and cerebellum, contain highly organized white matter tracts as well as gray matter

CT appearance of the normal brain

• Limited contrast resolution between gray and white matter; gray matter is hyperdense (whiter) compared to white matter due to cellularity

• Contrast resolution also limits evaluation of smaller white matter lesions

• X-rays must penetrate the calvarium, often leading to artifact, particularly at the skull base and in the posterior fossa

• Good for the evaluation of intracranial hemorrhage, volume loss, hydrocephalus

Normal CT appearance of the brain

*

*

Noncontrast CT demonstrates

normal gray-white differentiation

and cerebral volume

Note that the bone is white

(compare to MRI)

Streak artifact can

confound diagnosis of

pathology in the

brainstem and posterior

fossa

MR appearance of the normal brain

• Better contrast resolution allows differentiation between gray and white matter (T1 white matter = hyperintense/”whiter” than gray matter due to myelination, T2 white matter = hypointense/”grayer”)

• Fluid is T2 hyperintense

• Hemorrhage, protein, melanin is T1 hyperintense

• Not limited by photon starvation or beam hardening artifact in the posterior fossa

• Multiple pulse sequences can be used to differentiate between blood, CSF/simple fluid, etc.

• FLAIR

• Gradient/T2*/SWI

• DWI

Normal MR appearance of the brain: T1/T2

*

T2 T2 hyperinstense substances:

Water/Fluid/CSF

Fat

Gray matter is hyperintense to

white matter because of high

cellularity

CSF

Gray

White

Skull

Note that the skull bone is hypointense on

MRI whereas it was bright/radiodense on CT

The subcutaneous tissues (fat) are usually

hyperintense (bright) on MRISubcutaneous tissues

Normal MR appearance of the brain: T1/T2

*

T1 T1 hyperintense substances:

Hemorrhhage (subacute)

Fat

Protein

Melanin

Slow-flowing blood

T1 hypointense:

Highly-cellular tumors

White matter is hyperintense

to gray matter due to

myelinated nerve fibers

Normal MR appearance of the brain: FLAIR

*

*

FLAIR (fluid-attenuation

inversion recovery) images

suppress signal from normal

CSF or other simple fluid. The

image is otherwise T2-weighted

*If an area of CSF doesn’t suppress on FLAIR,

it is contaminated with something (elevated

protein, cells, blood)

FLAIR T2

Normal MR appearance of the brain: T2*

*

*

Gradient or susceptibility weighted

images (GRE/T2*/SWI) exploit local

magnetic field inhomogeneities,

making calcifications, such as in the

pineal gland, more conspicuous.

Because T2* images

increase artifacts, things

like aneurysm clips, VP

shunts, etc. can obscure

large portions of the image

due to “blooming”

Normal MR appearance of the brain: DWI

*

*

DWI (diffusion-weighted imaging)

evaluates the free flow of water. This is

disrupted when there is:

Intracellular water (cytotoxic edema)

Hypercellular tumor or abscess

Comparison is made with

the ADC (apparent diffusion

coefficient) image. True

restricted diffusion is bright

on DWI and dark on ADC

Abnormal: Restricted Diffusion

DWI—snow globe analogy

Note the Pittsburgh

reference and the large air

bubble in the snow globe.

Particles can freely

diffuse/move around when

shaken (normal brain)

In the NYC snow globe, there is a

tiny air bubble. It is more difficult for

particles to move around when

shaken (cytotoxic edema to brain

tissue after a stroke)

Basic Intracranial PathologyApproach to evaluation of

intracranial lesions:

1. Intra-axial vs extra-axial2. Enhancement3. Edema4. Mass effect5. Other findings:

hemorrhage, hydrocephalus, additional lesions, etc.

Intra- vs Extra-axial

EXTRA-axial masses demonstrate:

-CSF cleft

-Gray Matter “buckling”

-Intervening gray matter between

mass and white matter

T1 +C T1 -CT2

*This extra-axial mass is a meningioma.

Differential Diagnosis (extra-axial mass):

Metastasis

Lymphoma

Schwannoma

Plasmacytoma

Intra- vs Extra-axial

INTRA-axial masses:

NOT surrounded by CSF or gray matter

T1 +C T1 +C

*This intra-axial mass is a lung cancer

metastasis.

Differential Diagnosis (intra-axial mass):

Metastasis (if multiple, think mets!)

Primary brain neoplasms

Abscess

Enhancement

Metastases and high grade primary tumors

enhance due to disruption of the blood-

brain barrier (BBB) and neovascularity.

Low grade primary neoplasms typically do

not enhance, as the BBB is intact.

*Make sure to look at the

precontrast T1-weighted

images to ensure that

what you are calling

“enhancement” isn’t

intrinsic T1 shortening

T1 +C T1 -C

EnhancementT1 +C Ring Enhancing Mass Differential

“MAGICAL DR”:

M – metastasis

A – abscess

G – glioblastoma

I – infarction (subacute)

C – contusion

A – AIDS

L – lymphoma (immunosuppressed)

D – demyelination

R – radiation necrosis

Vasogenic vs Cytotoxic Edema

Vasogenic edema, (extracellular) due

to capillary permeability, predominantly

affects the white matter and can be

seen with tumors, infection, or

infarction

Cytotoxic edema, (intracellular) due to

failure of the Na/K ATPase pump,

affects dead/dying cells secondary to

infarction

T2 T2

Mass Effect

Types of mass effect:

Sulcal or ventricular effacement

Subfalcine herniation/”midline shift”

Uncal herniation

Tonsillar herniation

In this left MCA territory infarction:

1) Sulcal effacment (less CSF in sulci)

2) Partial effacement of the left lateral

ventricle (smaller than right)

3) Rightward midline shift

1

2

3

T2 T2

Masses Crossing the Corpus Callosum

Differential Diagnosis:

Glioblastoma (“butterfly glioma”)

Lymphoma

*Difficult to differentiate on imaging,

though GBM are more likely to be

necrotic or hemorrhagic

T1 +C FLAIR

Enhancing right parietal mass

with surrounding FLAIR signal

abnormality extending across

the splenium of the corpus

callosum

Other Findings

Hemorrhage

Most sensitive sequence = T2*

Can also see loss of FLAIR suppression in subarachnoid or

intraventricular hemorrhage

T1/T2-weighted signal characteristics are complex and depend on age of

blood

T2* FLAIR

Other Findings

Hydrocephalus

Can occur due to mass effect from a lesion (obstructive) or impaired

CSF reabsorption (communicating)

Bonus: Can you see a potential cause of this patient’s hydrocephalus

on this image?

CT -C

Other Findings

Can you see a potential cause of this patient’s hydrocephalus on this

image?

Intraventricular Hemorrhage layering in the occipital horns

CT -C

Other Findings

Multiple enhancing lesions

Raise suspicion for metastasis, particularly when lesions are

centered at the gray-white junction, though satellite lesions

remain a consideration.

CT +C CT +C

Differential Diagnosis Intra-axial Mass:ADULT

Supratentorial

Metastases

>> Primary Glial Neoplasm

Abscess

Infratentorial

Metastases

>> Hemangioblastoma

PEDIATRIC

Supratentorial

Primary Glial Neoplasm

Primitive Neuroectodermal tumor

Dysembryoplastic Neuroepithelial tumor

>>Metastases

Infratentorial

Juvenile Pilocytic Astrocytoma

Meduolloblastoma

Ependymoma

Hemangioblastoma

>> Metastases

*Age is important, with metastases most common in adults, though

narrowing the differential requires a thorough step-wise approach to

imaging and subsequent tissue sampling

Remember this approach:Approach to evaluation of

intracranial lesions:

1. Intra-axial vs extra-axial2. Enhancement3. Edema4. Mass effect5. Other findings:

hemorrhage, hydrocephalus, additional lesions, etc.

Cases

Use this approach to try to make the following diagnoses

Case 1

57M with dizziness, intermittent left sided paresthesia, and cognitive decline

Case 1T1 +C T2

Case 1

Avidly enhancing, dural-

based extra-axial mass

adjacent to the left temporal

lobe

Vasogenic edema and mass effect with

buckling of the left temporal gray matter

T1 +C T2

Meningioma

• Avidly enhancing extra-axial, dural-based mass

• Dural tail

• May see susceptibility artifact if calcified

• Benign WHO grade 1, but can have substantial mass effect and vasogenic edema in adjacent parenchyma, which is typically the reason for symptoms and resection.

Case 2

51M with vertigo and ataxia

Case 2T1 +C FLAIR

Case 2

Homogeneously enhancing mass in

the left periventricular white matter

with surrounding vasogenic edema

and mass effect

T1 +C FLAIR

Case 2

DWI ADC

Case 2

Restricted diffusion of the mass, with

surrounding edema

DWI ADC

CNS lymphoma

• Enhancing masses, typically in the periventricular white matter, thalamus, or basal ganglia

• Solid enhancement in immunocompetent patients, can be rim enhancing in immunocompromised patients

• Surrounding mass effect and vasogenic edema• Restricted diffusion due to hypercellularity• Can cross midline (ddx glioblastoma)

Case 3

65M with lung cancer and altered mental status

Case 3T2 T2

T1 +C

Case 3

Enlarged third and lateral ventricles

with normal size of the 4th ventricle

Obstructive hydrocephalus secondary

to enhancing metastatic mass at the

level of the cerebral aqueduct.

T2 T2

T1 +C

Metastases with hydrocephalus• Most metastases are parenchymal and frequently

centered at the gray-white junction due to highly-branching vasculature

• Multiple enhancing masses → high suspicion for metastatic disease

• Will enhance due to BBB disruption and neovascularity

• Mass effect with vasogenic edema → in this case, resulting in effacement of the cerebral aqueduct and hydrocephalus

Case 4

44yo F with altered mental status, left facial droop, and weakness

Case 4T1 +C T1 +C

Case 4

Diffuse pachymeningial (dural) enhancement

T1 +C T1 +C

Case 4T1 +C T2

Case 4

Multiple supra- & infra-tentorial ring enhancing masses with vasogenic edema

T1 +C T2

Case 4DWI ADC

Case 4

Masses demonstrate restricted diffusion

DWI ADC

Meningitis with abscess• CT: usually normal, may see hyperdensity in basilar

cisterns or sylvian fissures. If +C, may see meningeal enhancement

• MR: loss of FLAIR suppression in sulci, meningeal enhancement

• Complications: sinus thrombosis, abscess, empyema

Challenge Case

Don’t fall victim to satisfaction of search!

Challenge CaseFLAIR

Challenge CaseT1 +CT2* DWI ADC

Glioblastoma + Meningioma• Right frontal avidly enhancing dural based mass with

susceptibility on T2* images compatible with calcifcation. Mild local mass effect and edema. No restricted diffusion

• Right parietal enhancing mass with restricted diffusion and surrounding T2/FLAIR signal abnormality extending into the splenium of the corpus callosum. No hemorrhage or calcification

Glioblastoma + Meningioma• The glioblastoma was resected, but recurred, and the

right frontal meningioma remains stable (2 yrs later)

ConclusionImaging findings and localization can help narrow the differential diagnosis of intracranial pathologies, though tissue sampling is frequently necessary

END