Great Expectations:
The Multi-modal Intracranial
Imaging Appearances in Posttreatment Gliomas
{
Topple JA1, Francies O1, Krishnan A1,2,
Evanson J1
1Barts
Health Trust, London, United Kingdom
2The National Hospital for Neurology and Neurosurgery,
London, United Kingdom
Abstract number: eEdE 71
Sub number: 993
Disclosures
The authors have no
disclosures
Figure 1) Royal London Hospital, Whitechapel,
London, United Kingdom
“Take nothing on its looks;
take everything on evidence.
There’s no better rule.”
Charles Dickens, Great Expectations
Background
Epidemiology:





Gliomas are the most commonly diagnosed primary
malignant intracranial neoplasm in adults
Incidence of all gliomas is 4.67-5.73 per 100,000
population
Peak age for high grade tumours is 75-84
Low grade tumours are more common in younger
adults aged 35-44
Males are affected more frequently
(Ostrom et al 2014)
Background
Epidemiology continued:




The incidence of high grade glioblastoma (GBM) is
0.59-3.69 per 100,000
The survival rate of patients with GBM is poor (0.054.7% at 5yrs)
Risk factors include exposure to ionising radiation
Early complete surgical resection is associated with
improved survival
(Ostrom et al 2014)
World Health Organisation
(WHO) Tumour Grading
Histological Tumour Type
Tumour Grade
Astrocytoma
Grades I-IV
Oligodendroglioma
Grades II-III
Oligoastrocytoma
Grades II-III
Glioblastoma multiforme
Grade IV
Medical
Surgical
Oncological
Steroid therapy
Biopsy (Confirm
Radiotherapy
histological diagnosis)
Debulking (seizure
control and reduction of
mass effect)
Complete resection
(improves patient survival
and potential for
complete cure)
Intravascular
chemotherapy
Combined
chemoradiotherapy
Chemotherapeutic
wafer implants
Ommaya reservoirs
Anti-angiogenic
therapies
Current Treatments
Imaging Methods

Computed tomography (CT)

Magnetic resonance imaging (MRI)

Brain FDG Positron Emission Tomography
(PET)
Measuring Degree of Progression

-
-
-
The Macdonald Criteria:
Guideline for assessing response in high grade
gliomas
Two dimensional measurements on MRI of tumour
size
Tumour progression on follow-up imaging requires
>25% increase in the size of the enhancing
component
Purpose of Exhibit

To review the post medical, surgical
and oncological treatment imaging
appearances in patients with
intracranial gliomas

To showcase the diagnostic pearls and
pitfalls of these complex cases
Methods

Retrospective review of patients with
histologically confirmed glioma chosen from a
prospectively collected surgical database over
a 7 year period at a tertiary neurosurgical
referral centre

Evaluation of pre-treatment and post-treatment
imaging studies from our PACS system
Educational Objectives
After reviewing this presentation, the reader will be able to:
Recognise the post treatment multimodal imaging appearances
of medical, surgical and oncological therapies employed to treat
low and high grade intracranial gliomas
1.
Describe the possible complications of surgical and oncological
therapies for intracranial gliomas
1.
Appreciate the role of intra-operative MRI to determine extent of
residual disease prior to surgical closure
1.
Differentiate between true disease progression,
pseudoprogression and pseudoresponse
1.
Steroid Treatment-related
Changes



Dexamethasone is the steroid of choice
Used to decrease parenchymal oedema and
improve intracranial pressure prior to surgery or
chemoradiotherapy
Improves white matter oedema on serial CT or
MRI studies
Figure 2A)
Recurrent GBM previously treated
with chemoradiotherapy. Axial T2 W
MRI four weeks prior to treatment.
Figure 2B)
Axial T2 W MRI 4 weeks after
initiation of steroid treatment. The
degree of surrounding oedema
has decreased.
Steroid-related changes
Post-surgical Findings: burr holes

1.
2.
A
B
Figure 3) 39 year old patient with a cerebellar
anaplastic astrocytoma with associated
effacement of the fourth ventricle and
obstructing hydrocephalus. Underwent burr
hole and ventricular drain insertion. Scout
view of the burr hole and drain (A). Axial CT
on bone windows shows a well defined right
frontal burr hole with minimal overlying
subcutanoeus swelling (B).
3.
4.
Appearances of burr holes
post stereotactic brain
biopsy:
Well circumscribed defect in
the calvarium
Overlying subgaleal or
subdural fluid collections
Pneumocephalus
Enhancement of burr hole
tract on contrast enhanced
T1 W MRI
Post-surgical Findings: craniotomy




Surgical excision of a piece
of the calvarium which is
replaced at the end of the
procedure
Reattached with stainless
steel wires, screw/plate
systems or titanium clamps
Skin closed with
staples/scalp clips
The dura mater deep to the
craniotomy site will normally
enhance on post contrast
studies
A
B
Figure 4) 63 yr old female with a biopsy proven
GBM. Underwent craniotomy and debulking.
Axial (A) and coronal (B) non-contrast CT on
bone windows reveals satisfactory alignment of
the craniotomy. Post-operative pneumocephalus
is noted in the intracranial compartment and
there is surgical emphysema deep to the scalp
staples.
Post-surgical Findings: craniectomy




Figure 5) 60 yr old female with a biopsy proven
right frontal lobe GBM. Craniectomy and
lobectomy performed. Axial non-contrast CT
study reveals a right frontal craniotomy and
lobectomy with cerebral contents herniating
through the calvarial defect. There is a small
post surgical meningocoele.
Excision of a section of the
calvarium which is not
replaced at the end of the
procedure
Unilateral or bilateral
Used to treat medically
refractory increased
intracranial pressure in
glioma patients
Dura mater open – brain
contents herniate through
the defect with or without
pseudomeningocoele
Post-surgical Findings:
haemorrhage

1.
2.
3.
4.
Types of haemorrhagic
complications post
biopsy include:
Intraparenchymal
haematoma
Extradural haematoma
Subdural haematoma
Subarachnoid
haemorrhage
A
B
Figure 6) 32 yr old female presenting to accident and
emergency with left-sided headache and a right upper
quadrantanopia. Axial non-contrast CT (A) revealed a
large intraparenchymal mass lesion in the left
temporoparietal lobe with perilesional oedema.
Craniotomy and biopsy were 2 weeks later. Post-biopsy
the patient developed a unilateral hemiparesis and a
fixed dilated left pupil. An urgent non contrast CT (B)
revealed a post-biopsy intratumoral haemorrhage with
uncal herniation and progressive midline shift.

1.
2.
3.
4.
5.
6.
Signs of Intracranial
infection on CT/MRI:
Leptomeningeal
enhancement (meningitis)
Ring enhancing extra-axial
fluid collection (extradural
abscess)
Ring enhancing subdural
collection (subdural
empyema)
Ring enhancing
intraparenchymal collection
(intracerebral abscess)
Bone flap infection
Persistent pneumocephalus
within fluid collections
A
B
C
Figure 7) 32 yr old male with a recurrent astrocytoma. Underwent
repeat surgical resection. Axial contrast enhanced post-operative
CT studies at day three (A), day seven (B) and day twelve (C)
reveal enlarging subgaleal and subdural fluid collections in the
operative bed. Locules of gas persist in keeping with infection.
Post-surgical Findings: infection



Aim is to reduce the
symptoms due to
mass effect by the
tumour
Not a curative
proceure
Residual tumour will
be identified on post
surgical MRI studies
as enhancing tissue
at the tumour
margins
A
B
Figure 8) 26 yr old man who presented with headache
and papilloedema. Axial contrast enhanced CT (A)
demonstrates a large heterogeneous GBM in the left
frontal lobe with midline shift, ventricular effacement
and perilesional edema. Axial post contrast CT post
left-frontal craniotomy and debulking (B). There is an
overlying subgaleal haematoma. An isodense
subdural haematoma is noted measuring 11mm in
depth. Dural enhancement is identified. Patchy
intraparenchymal post surgical haemorrhage is seen.
A rind of hypodense tumour remains in the left-frontal
lobe (arrows).
Surgical Debulking
Complete Surgical Resection
A
B
Figure 9) 44yr old female with a known
pilocytic astrocytoma. Pre-operative axial T2
W MRI demonstrating a well defined lesion in
the deep white matter of the right frontal lobe
(A). Post-operative axial T2 W MRI (B) reveals
haemosiderin staining and a cavity at the
surgical site following complete resection of
the astrocytoma.

Potential for complete cure
in low grade gliomas and
improved survival in high
grade tumours

A cavity will be seen at the
resection site on initial
follow-up imaging
Intra-operative MRI
A
B
C
D D
Figure 10) 69 yr old female with a GBM. Intra-operative MRI performed to guide
resection. Pre-op volumetric T1 W post-contrast (A), intra-operative non-contrast T1
W (B) and intra-operative T2 W images (C) showing surgical resection cavity and
surgical packs at the craniotomy site ( blue arrows). Post-contrast T1 W study during
the surgical procedure (D). Enhancement in the cavity (green arrow) does not
correspond to the enhancing tumor on the pre-op scan (orange arrow). The surgeon
explored the wound and discovered that the enhancing material was surgical
packing material.




Allows for real-time localisation of residual tumour at the
periphery of the lesion during surgical excision
Utilises 1.5 Tesla scanner
At the National Hospital for Neurology and Neurosurgery
we incorporate Pre and post contrast T1, T2 and DWI
axial intra-operative sequences
Has been shown to improve resection results
(Schneider JP et al 2001)
Intra-operative MRI
Continued
Post Radiotherapy Changes –
white matter signal change


-
A
B
Figure 11) 44 yr old female with a right temporal GBM.
Completed chemotherapy in October 2009. An axial T2 W
MRI prior to chemoradiotherapy (A) demonstrates a small
volume of white matter change in the centrum semiovale. A
follow up axial T2 W MRI 8 months later (B) showed
marked bilateral deep white matter signal change in
keeping with radiotherapy.
May be acute, subacute,
delayed or late
Imaging features:
Increased white matter
signal change within the
radiotherapy field
Post Radiotherapy Changes microhaemorrhages
A
Figure 12) 39 yr old female with a history
of pontine glioma treated with radiotherapy
in 1992. Sagittal T2 W MRI reveals a soft
tissue lesion in the pons.
B
Figure 12) Axial gradient echo T2* sequence
shows susceptibility artefact in the left occipital
lobe at the site of a previous intraparenchymal
haemorrhage. Several microbleeds are
visualised elsewhere in the basal ganglia,
corpus callosum and periventricular white
matter due to previous radiotherapy treatment.





-
-
Occurs 18-24 months
post radiotherapy
treatment
Mostly confined to white
matter
Deep gray matter affected
post intra-arterial
chemotherapy earlier at
2-23 months
Difficult to distinguish
from progression or
recurrence
Imaging signs:
Loss of central
enhancement
increased T2 signal
change and enhancement
A
B
Figure 13) 59 year old female presenting with syncope and
retrograde amnesia. Diagnosed with a grade II glioma.
Radiotherapy completed. Image A – Pre-treatment axial T2
W MRI showing a lesion with surrounding oedema in the
right perisylvian region. Image B – An MRI performed at 5
months post radiotherapy shows an increase in signal
change throughout the right hemisphere.
Post Radiotherapy Changes –
radiation necrosis
Post-radiotherapy Changes –
New Enhancement
Progressive confluent high T2 signal changes in
the white matter
 Periventricular enhancing foci distant from the
resection cavity lying within the irradiated field
 Distant enhancement away from the primary site
 Cut green pepper or soap bubble sign

Radiation Necrosis
A
B
Figure 14) Imaging of radiation necrosis in a patient with a grade II astrocytoma treated with high
dose radiotherapy using A) T1 W MRI post contrast B) MRI perfusion cerebral blood volume map C)
NM Brain FDG PET D) Single voxel MR spectroscopy. Axial T1 W image shows irregular
enhancement in the pre-treatment phase. The cerebral blood volume map post treatment shows
areas of decreased perfusion centrally in the lesion (necrosis). A photopenic area is identified
centrally on the PET study (necrosis). The spectroscopy demonstrates an elevated lipid and lactate
peak.

Definition:
An increase in the contrast
enhancing area after combined
chemoradiotherapy followed by
subsequent reduction in the
enhancing volume without
further treatment

Clinically asymptomatic

Occurs in the first 3 months
post treatment

Higher incidence in patients
with O6-methylguanine
methyltransferase (MGMT)
MRI techniques:
- DWI/ADC maps
- Diffusion tensor imaging (DTI)
- Hydrogen-1 MRI spectroscopy
- Perfusion MR / Cerebral blood
volume studies

Nuclear Medicine techniques:
- FDG-PET, FLT-PET
- Follow up imaging
- Re-biopsy

Pseudoprogression
Pseudoprogression - Case 1
A
A
B
B
C
D
Figure 15) 53 yr old male with a known GBM on second line chemotherapy. Initial
post-contrast T1 W study pre-treatment (A), an immediate post-treatment
contrast enhanced T1 W study (B) shows thick peripheral enhancement in the left
parietal lobe with surrounding white matter oedema. Repeat follow-up imaging
shows progressive decreased in the size of the enhancing lesion (C). A fused
cerebral blood volume map and post contrast T1 study (D) shows that there is no
increased perfusion at the site of the enhancing tumour. The appearances are in
keeping with pseudoprogression.
Differentiating True Progression
from Pseudoprogression - Case 2
A
B
C
Figure 16) 31 yr old female with a low grade glioma. Tumour resected and subsequently
treated with chemoradiotherapy. Fused post contrast T1 W sequences and cerebral blood
volume maps prior to temazolamide treatment (A) and post temazolamide treatment (B)
reveal a new enhancing focus in the right trigone (white arrow). There is no increase in
perfusion at this site. A follow up study (C) shows regression of the enhancing component in
keeping with pseudoprogresion.
Case 3 - Pseudoprogression
A
B
B
Figure 17) 34 yr old male with a temporal
anaplastic astrocytoma (WHO grade III). Treated
with chemoradiotherapy. Initial pre-treatment axial
post-contrast T1 W MRI (A) shows oedema and
mass effect in the left temporal lobe with an
irregular enhancing lesion. First follow-up postcontrast T1 W MRI following chemoradiotherapy
shows increase in the size of the enhancing
component (B).
C
D
Figure 17) Second follow-up axial post contrast T1
W MRI (C) shows a rim of enhancement in the
lesion corresponding to the site of increased activity
on the NM study (see next slide). A contrast
enhanced axial T1 W MRI 4 months later shows
that the size of the enhancing component has
decreased (D).
Figure 18A) Nuclear medicine brain PET
FDG shows increased metabolic activity in
the left temporal lobe (suspicious for
residual tumour) with a background of
reduced metabolism (in keeping with postradiotherapy gliotic change).
Figure 18B) The follow up Brain PET
FDG at 4 months (E) shows complete
absence of metabolic activity in the left
medial temporal lobe. The appearances
confirm the findings of the MR studies
indicating pseudoprogression
Case 3 Continued

1.
2.
3.
4.
Signs of recurrence on imaging:
New areas of irregular enhancement adjacent to the
resection site
Progressive enlargement of the enhancing component with
increasing mass effect over serial studies
Involvement of the corpus callosum or septum pellucidum
Spreading wavefront enhancement pattern
Differentiation of Residual or
Recurrent Tumour from PostTreatment Changes
Case 1- True Progression
A
B
C
D
Figure 19) 58 year old male with a known GBM. Treated with chemoradiotherapy and temazolamide. Axial postcontrast T1 W study (A) reveals a heterogeneously enhancing tumor in the left suprasylvian parietal cortex.
Follow-up post contrast T1 W MRI (B) performed 22 days later reveals an increase in the size of the solid
enhancing component of the lesion. MR spectroscopy (C) demonstrates a high choline peak in keeping with
high grade tumour. The MRI perfusion study (D) shows increased perfusion at the periphery of the tumour.
Pseudoresponse Following
Anti-angiogenic Therapy
A
B
C
A
B
Figure 20) Patient with recurrent GBM. Treated previously with surgery and chemoradiotherapy. Axial T2
W and post-contrast T1 W studies before treatment (A), 4 weeks following treatment (B) and 12 weeks
after treatment (C) with bevazicumab and irinotecan. There is a reduction in the degree of enhancement,
but creeping increase in T2 signal change. The oedema decreased between the first and second scans
due to steroid treatment.
C
Imaging Appearances of
Chemotherapy Wafer Implants

65 male with a
recurrent GBM treated
with surgical debulking
and carmustine
chemotherapy wafer
implants. T2 weighted
axial MRI sequences
pre and post debulking
show outline of the
wafers (black arrows)
A
B
Figure 21) Axial T2 W (A) and Flair (B)
MRI sequences.
• Ommaya reservoirs
are commonly used
to manage and treat
leptomeningeal
metastases in cases
of intracranial
malignancy.
• The reservoirs can
be used to
administer
chemotherapy
agents into the
intracranial
compartment.
A
Figure 22) 50 yr old male
presenting with a partially solid and
partially cystic GBM in the left
temporal lobe. The cystic portion
demonstrates peripheral
enhancement.
B
Figure 22) Left temporal
craniotomy and insertion of an
ommaya reservoir.
Ommaya Reservoirs
Summary



The post-treatment imaging appearances of intracranial gliomas
create diagnostic challenges for the multidisciplinary team of
radiologists, neurosurgeons and oncologists.
An understanding of the variable imaging findings following
medical, surgical and oncological treatment will improve
diagnostic confidence and help to streamline further patient
management.
Multi-modality assessment with nuclear medicine, pre-operative,
intra-operative and post-operative MRI techniques can
differentiate between true progression and pseudoprogression of
disease in these complex cases.
References
1)
2)
3)
4)
Sinclair S, Scoffings D. (2010) Imaging of the Post-Operative
Cranium. Radiographics 30: 461-482.
Belden C, Valdes P, Cong Ran BS, Pastel MD, Harris B, Fadul C,
Isreal M, Paulsen K, Roberts D. (2011) Genetics of Glioblastoma: A
Window into Its Imaging and Histopathologic Variability.
Radiographics 31: 1717-1740.
Pope W, Sayre J, Perlina A, Villablanca P, Mischel P, Cloughesy T.
(2005) MR Imaging Correlates of Survival in Patients with HighGrade Gliomas. AJNR 26: 2466-2474.
Hein P, Eskey C, Dunn J, Hug E. (2004) Diffusion-Weighted
Imaging in the Follow-up of Treated High-Grade Gliomas: Tumour
Recurrence versus Radiation Injury. AJNR 25: 201-209.
References Continued




Schneider J, Schmidt F, Dietrich J, Lieberenz S, Trantakis C, Seifert V,
Kellerman S, Schober R, Schaffranietz L, Laufer M, Kahn T. (2001)
Gross-total Surgery of Supratentorial Low-grade Gliomas under Intraoperative MR Guidance. AJNR 22: 89-98.
Shah R, Vattoth S, Jacob R, Manzil F, O’Malley J, Borghei P, Patel B,
Cure J. (2012) Radiation Necrosis in the Brain: Imaging Features and
Differentiation from Tumour Recurrence. Radiographics 32: 1343-1359.
Kim E, Soo-Kyo C, Haynie T, Chang-Guen K, Byung-Jae C, Podoloff D,
Tilbury R, Yang D, Yung W, Moser R, Ajani J. (1992) Differentiation of
Residual or Recurrent Tumours from Post-treatment Changes with F-18
FDG PET. Radiographics 12: 269-279.
Ostrom Q, Bauchet L, Davis F, Deltour I, Fisher J, Langer E, Pekmezci
M, Schwartzbaum J, Turner M, Walsh K, Wrensch M, Barnholtz-Sloan J.
(2014) The Epidemiology of Glioma in Adults: a “State of the Science”
Review. Neuro-oncology 16(7): 896-913.