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Great Expectations: Great Expectations: The Multi-modal Intracranial The Multi-modal Intracranial

Imaging Appearances in Post-Imaging Appearances in Post-treatment Gliomastreatment Gliomas

Topple JATopple JA11, Francies O, Francies O11, Krishnan A, Krishnan A1,21,2, , Evanson JEvanson J11

11Barts Health Trust, London, United KingdomBarts Health Trust, London, United Kingdom22The National Hospital for Neurology and Neurosurgery, The National Hospital for Neurology and Neurosurgery, London, United KingdomLondon, United Kingdom

Abstract number: eEdE 71Sub number: 993

DisclosuresDisclosures

The authors have no The authors have no disclosuresdisclosures

Figure 1) Royal London Hospital, Whitechapel, London, United Kingdom

““Take nothing on its looks;Take nothing on its looks;take everything on evidence. take everything on evidence.

There’s no better rule.”There’s no better rule.”

Charles Dickens, Charles Dickens, Great ExpectationsGreat Expectations

Epidemiology:Epidemiology:Gliomas are the most commonly diagnosed primary Gliomas are the most commonly diagnosed primary malignant intracranial neoplasm in adultsmalignant intracranial neoplasm in adultsIncidence of all gliomas is 4.67-5.73 per 100,000 Incidence of all gliomas is 4.67-5.73 per 100,000 populationpopulationPeak age for high grade tumours is 75-84Peak age for high grade tumours is 75-84Low grade tumours are more common in younger Low grade tumours are more common in younger adults aged 35-44adults aged 35-44Males are affected more frequentlyMales are affected more frequently

BackgroundBackground

(Ostrom et al 2014)

Epidemiology continued:Epidemiology continued:The incidence of high grade glioblastoma (GBM) is The incidence of high grade glioblastoma (GBM) is 0.59-3.69 per 100,0000.59-3.69 per 100,000The survival rate of patients with GBM is poor (0.05-The survival rate of patients with GBM is poor (0.05-4.7% at 5yrs)4.7% at 5yrs)Risk factors include exposure to ionising radiationRisk factors include exposure to ionising radiationEarly complete surgical resection is associated with Early complete surgical resection is associated with improved survivalimproved survival

BackgroundBackground

(Ostrom et al 2014)

Histological Tumour Type Tumour Grade

Astrocytoma Grades I-IV

Oligodendroglioma Grades II-III

Oligoastrocytoma Grades II-III

Glioblastoma multiforme Grade IV

World Health Organisation World Health Organisation (WHO) Tumour Grading(WHO) Tumour Grading

Medical Surgical Oncological

Steroid therapy Biopsy (Confirm histological diagnosis)

Radiotherapy

Debulking (seizure control and reduction of mass effect)

Intravascular chemotherapy

Complete resection (improves patient survival and potential for complete cure)

Combined chemoradiotherapy

Chemotherapeutic wafer implants

Ommaya reservoirs

Anti-angiogenic therapies

Current TreatmentsCurrent Treatments

Computed tomography (CT)Computed tomography (CT)

Magnetic resonance imaging (MRI)Magnetic resonance imaging (MRI)

Brain FDG Positron Emission Tomography Brain FDG Positron Emission Tomography (PET)(PET)

Imaging MethodsImaging Methods

The Macdonald Criteria:The Macdonald Criteria:- Guideline for assessing response in high grade Guideline for assessing response in high grade

gliomasgliomas- Two dimensional measurements on MRI of tumour Two dimensional measurements on MRI of tumour

sizesize- Tumour progression on follow-up imaging requires Tumour progression on follow-up imaging requires

>25% increase in the size of the enhancing >25% increase in the size of the enhancing componentcomponent

Measuring Degree of Progression Measuring Degree of Progression

To review the post medical, surgical To review the post medical, surgical and oncological treatment imaging and oncological treatment imaging appearances in patients with appearances in patients with intracranial gliomasintracranial gliomas

To showcase the diagnostic pearls and To showcase the diagnostic pearls and pitfalls of these complex casespitfalls of these complex cases

Purpose of ExhibitPurpose of Exhibit

Retrospective review of patients with Retrospective review of patients with histologically confirmed glioma chosen from a histologically confirmed glioma chosen from a prospectively collected surgical database over prospectively collected surgical database over a 7 year period at a tertiary neurosurgical a 7 year period at a tertiary neurosurgical referral centrereferral centre

Evaluation of pre-treatment and post-treatment Evaluation of pre-treatment and post-treatment imaging studies from our PACS systemimaging studies from our PACS system

MethodsMethods

After reviewing this presentation, the reader will be able to:After reviewing this presentation, the reader will be able to:

1.1.Recognise the post treatment multimodal imaging appearances Recognise the post treatment multimodal imaging appearances of medical, surgical and oncological therapies employed to treat of medical, surgical and oncological therapies employed to treat low and high grade intracranial gliomaslow and high grade intracranial gliomas

1.1.Describe the possible complications of surgical and oncological Describe the possible complications of surgical and oncological therapies for intracranial gliomastherapies for intracranial gliomas

1.1.Appreciate the role of intra-operative MRI to determine extent of Appreciate the role of intra-operative MRI to determine extent of residual disease prior to surgical closureresidual disease prior to surgical closure

1.1.Differentiate between true disease progression, Differentiate between true disease progression, pseudoprogression and pseudoresponsepseudoprogression and pseudoresponse

Educational ObjectivesEducational Objectives

Dexamethasone is the steroid of choiceDexamethasone is the steroid of choice Used to decrease parenchymal oedema and Used to decrease parenchymal oedema and

improve intracranial pressure prior to surgery or improve intracranial pressure prior to surgery or chemoradiotherapychemoradiotherapy

Improves white matter oedema on serial CT or Improves white matter oedema on serial CT or MRI studiesMRI studies

Steroid Treatment-related Steroid Treatment-related ChangesChanges

Steroid-related changesSteroid-related changes

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.

Post-surgical Findings: burr holesPost-surgical Findings: burr holes

Appearances of burr holes Appearances of burr holes post stereotactic brain post stereotactic brain biopsy:biopsy:

1.1. Well circumscribed defect in Well circumscribed defect in the calvariumthe calvarium

2.2. Overlying subgaleal or Overlying subgaleal or subdural fluid collectionssubdural fluid collections

3.3. PneumocephalusPneumocephalus

4.4. Enhancement of burr hole Enhancement of burr hole tract on contrast enhanced tract on contrast enhanced T1 W MRIT1 W MRI

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).

A B

Post-surgical Findings: craniotomyPost-surgical Findings: craniotomy

Surgical excision of a piece Surgical excision of a piece of the calvarium which is of the calvarium which is replaced at the end of the replaced at the end of the procedureprocedure

Reattached with stainless Reattached with stainless steel wires, screw/plate steel wires, screw/plate systems or titanium clampssystems or titanium clamps

Skin closed with Skin closed with staples/scalp clipsstaples/scalp clips

The dura mater deep to the The dura mater deep to the craniotomy site will normally craniotomy site will normally enhance on post contrast enhance on post contrast studiesstudies

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.

A B

Post-surgical Findings: craniectomyPost-surgical Findings: craniectomy Excision of a section of the Excision of a section of the

calvarium which is not calvarium which is not replaced at the end of the replaced at the end of the procedureprocedure

Unilateral or bilateralUnilateral or bilateral Used to treat medically Used to treat medically

refractory increased refractory increased intracranial pressure in intracranial pressure in glioma patientsglioma patients

Dura mater open – brain Dura mater open – brain contents herniate through contents herniate through the defect with or without the defect with or without pseudomeningocoelepseudomeningocoele

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.

Post-surgical Findings: Post-surgical Findings: haemorrhagehaemorrhage

Types of haemorrhagic Types of haemorrhagic complications post complications post biopsy include:biopsy include:

1.1. Intraparenchymal Intraparenchymal haematomahaematoma

2.2. Extradural haematomaExtradural haematoma

3.3. Subdural haematomaSubdural haematoma

4.4. Subarachnoid Subarachnoid haemorrhagehaemorrhage

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.

A B

Post-surgical Findings: infectionPost-surgical Findings: infection

Signs of Intracranial Signs of Intracranial infection on CT/MRI:infection on CT/MRI:

1.1. Leptomeningeal Leptomeningeal enhancement (meningitis)enhancement (meningitis)

2.2. Ring enhancing extra-axial Ring enhancing extra-axial fluid collection (extradural fluid collection (extradural abscess)abscess)

3.3. Ring enhancing subdural Ring enhancing subdural collection (subdural collection (subdural empyema)empyema)

4.4. Ring enhancing Ring enhancing intraparenchymal collection intraparenchymal collection (intracerebral abscess)(intracerebral abscess)

5.5. Bone flap infectionBone flap infection

6.6. Persistent pneumocephalus Persistent pneumocephalus within fluid collectionswithin fluid collections

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.

A B C

Surgical Debulking Surgical Debulking

Aim is to reduce the Aim is to reduce the symptoms due to symptoms due to mass effect by the mass effect by the tumourtumour

Not a curative Not a curative proceureproceure

Residual tumour will Residual tumour will be identified on post be identified on post surgical MRI studies surgical MRI studies as enhancing tissue as enhancing tissue at the tumour at the tumour marginsmargins

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).

A B

Complete Surgical ResectionComplete Surgical Resection

Potential for complete cure Potential for complete cure in low grade gliomas and in low grade gliomas and improved survival in high improved survival in high grade tumoursgrade tumours

A cavity will be seen at the A cavity will be seen at the resection site on initial resection site on initial follow-up imagingfollow-up imaging

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.

AB

Intra-operative MRIIntra-operative MRI

A B C 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.

D

Allows for real-time localisation of residual tumour at the Allows for real-time localisation of residual tumour at the periphery of the lesion during surgical excisionperiphery of the lesion during surgical excision

Utilises 1.5 Tesla scannerUtilises 1.5 Tesla scanner At the National Hospital for Neurology and Neurosurgery At the National Hospital for Neurology and Neurosurgery

we incorporate Pre and post contrast T1, T2 and DWI we incorporate Pre and post contrast T1, T2 and DWI axial intra-operative sequencesaxial intra-operative sequences

Has been shown to improve resection results Has been shown to improve resection results

(Schneider JP et al 2001)(Schneider JP et al 2001)

Intra-operative MRI Intra-operative MRI ContinuedContinued

Post Radiotherapy Changes – Post Radiotherapy Changes – white matter signal changewhite matter signal change

May be acute, subacute, May be acute, subacute, delayed or latedelayed or late

Imaging featuresImaging features::- Increased white matter Increased white matter

signal change within the signal change within the radiotherapy fieldradiotherapy field

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.

A B

Post Radiotherapy Changes - Post Radiotherapy Changes - microhaemorrhagesmicrohaemorrhages

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.

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.

A B

Post Radiotherapy Changes – Post Radiotherapy Changes – radiation necrosisradiation necrosis

Occurs 18-24 months Occurs 18-24 months post radiotherapy post radiotherapy treatmenttreatment

Mostly confined to white Mostly confined to white mattermatter

Deep gray matter affected Deep gray matter affected post intra-arterial post intra-arterial chemotherapy earlier at 2-chemotherapy earlier at 2-23 months23 months

Difficult to distinguish from Difficult to distinguish from progression or recurrenceprogression or recurrence

Imaging signsImaging signs: : - Loss of central Loss of central

enhancementenhancement- increased T2 signal increased T2 signal

change and enhancementchange and enhancement

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.

A B

Progressive confluent high T2 signal changes in Progressive confluent high T2 signal changes in the white matterthe white matter

Periventricular enhancing foci distant from the Periventricular enhancing foci distant from the resection cavity lying within the irradiated fieldresection cavity lying within the irradiated field

Distant enhancement away from the primary siteDistant enhancement away from the primary site Cut green pepper or soap bubble signCut green pepper or soap bubble sign

Post-radiotherapy Changes – Post-radiotherapy Changes – New EnhancementNew Enhancement

Radiation NecrosisRadiation 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.

PseudoprogressionPseudoprogression

Definition:Definition:

An increase in the contrast An increase in the contrast enhancing area after enhancing area after combined chemoradiotherapy combined chemoradiotherapy followed by subsequent followed by subsequent reduction in the enhancing reduction in the enhancing volume without further volume without further treatmenttreatment

Clinically asymptomaticClinically asymptomatic Occurs in the first 3 months Occurs in the first 3 months

post treatmentpost treatment Higher incidence in patients Higher incidence in patients

with O6-methylguanine with O6-methylguanine methyltransferase (MGMT) methyltransferase (MGMT)

MRI techniques:MRI techniques:

- DWI/ADC maps- DWI/ADC maps

- Diffusion tensor imaging (DTI)- Diffusion tensor imaging (DTI)

- Hydrogen-1 MRI spectroscopy- Hydrogen-1 MRI spectroscopy

- Perfusion MR / Cerebral blood - Perfusion MR / Cerebral blood volume studiesvolume studies

Nuclear Medicine techniques:Nuclear Medicine techniques:

- FDG-PET, FLT-PET- FDG-PET, FLT-PET

- Follow up imaging- Follow up imaging

- Re-biopsy- Re-biopsy

Pseudoprogression - Case 1Pseudoprogression - Case 1

Figure 15) 53 yr old male with a known GBM on second line chemotherapy. Initial 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 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 enhanced T1 W study (B) shows thick peripheral enhancement in the left parietal lobe with surrounding white matter oedema. Repeat follow-up imaging shows lobe with surrounding white matter oedema. Repeat follow-up imaging shows progressive decreased in the size of the enhancing lesion (C). A fused cerebral 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 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 increased perfusion at the site of the enhancing tumour. The appearances are in keeping with pseudoprogression. keeping with pseudoprogression.

A B C DA B

Differentiating True Progression Differentiating True Progression from Pseudoprogression - Case 2from Pseudoprogression - Case 2

A BC

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 - PseudoprogressionCase 3 - Pseudoprogression

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 post-contrast T1 W MRI following chemoradiotherapy shows increase in the size of the enhancing component (B).

A 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).

B

Case 3 ContinuedCase 3 Continued

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 post-radiotherapy 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

Signs of recurrence on imagingSigns of recurrence on imaging::

1.1. New areas of irregular enhancement adjacent to the New areas of irregular enhancement adjacent to the resection siteresection site

2.2. Progressive enlargement of the enhancing component with Progressive enlargement of the enhancing component with increasing mass effect over serial studiesincreasing mass effect over serial studies

3.3. Involvement of the corpus callosum or septum pellucidumInvolvement of the corpus callosum or septum pellucidum

4.4. Spreading wavefront enhancement patternSpreading wavefront enhancement pattern

Differentiation of Residual or Differentiation of Residual or Recurrent Tumour from Post-Recurrent Tumour from Post-

Treatment ChangesTreatment Changes

Case 1- True ProgressionCase 1- True Progression

Figure 19) 58 year old male with a known GBM. Treated with chemoradiotherapy and temazolamide. Axial post-contrast 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.

A BC

D

Pseudoresponse Following Pseudoresponse Following Anti-angiogenic TherapyAnti-angiogenic Therapy

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.

A B C A B C

Imaging Appearances of Imaging Appearances of Chemotherapy Wafer ImplantsChemotherapy Wafer Implants

65 male with a 65 male with a recurrent GBM treated recurrent GBM treated with surgical debulking with surgical debulking and carmustine and carmustine chemotherapy wafer chemotherapy wafer implants. T2 weighted implants. T2 weighted axial MRI sequences axial MRI sequences pre and post debulking pre and post debulking show outline of the show outline of the wafers (black arrows)wafers (black arrows) Figure 21) Axial T2 W (A) and Flair (B)

MRI sequences.

A B

Ommaya ReservoirsOmmaya Reservoirs

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.

Figure 22) Left temporal craniotomy and insertion of an ommaya reservoir.

A B

• 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.

SummarySummary The post-treatment imaging appearances of intracranial gliomas The post-treatment imaging appearances of intracranial gliomas

create diagnostic challenges for the multidisciplinary team of create diagnostic challenges for the multidisciplinary team of radiologists, neurosurgeons and oncologists. radiologists, neurosurgeons and oncologists.

An understanding of the variable imaging findings following An understanding of the variable imaging findings following medical, surgical and oncological treatment will improve medical, surgical and oncological treatment will improve diagnostic confidence and help to streamline further patient diagnostic confidence and help to streamline further patient management.management.

Multi-modality assessment with nuclear medicine, pre-operative, Multi-modality assessment with nuclear medicine, pre-operative, intra-operative and post-operative MRI techniques can intra-operative and post-operative MRI techniques can differentiate between true progression and pseudoprogression of differentiate between true progression and pseudoprogression of disease in these complex cases. disease in these complex cases.

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