neuro - intraaxial neoplasms - smirniotopoulos (rsna 2005)

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1 The WHO 2000 Astrocytoma Classification James G. Smirniotopoulos, M.D. Uniformed Services University of the Health Sciences Bethesda, MD Visit us at: http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way Features of Glioma Site of Origin Character of lesion Signal intensity (MR) Attenuation (CT) Blood-brain-barrier (Gd or I) Chemistry (MRS) Metabolism (Th 201, FDG-PET) Vascularity (PWI) Mode of Spread DTI Traditional Tumor Grading PATHOLOGIST LOW GRADE HIGH GRADE RADIOLOGIST NON-ENHANCING ENHANCING NEUROSURGEON “SUCKABLE” “NON-SUCKABLE” Kernohan-Sayre (AFIP) Grading System: GRADE I- “BENIGN” or “Low-Grade” GRADE II - “ GRADE III - ANAPLASTIC cellular atypia, etc. GRADE IV- MALIGNANT NECROSIS, Vascularity, Mitoses GLIOBLASTOMA MULTIFORME NOTE: Numerous modifications exist, most into three grades, e.g..: Low Grade (Benign), Anaplastic, and GBM (w/ NECROSIS). Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way Pathologic – Radiologic Correlation T2 SI, DWI & ADC Cellularity T1 and T2 SI, DTI Infiltration MRS, Th 201 and FDG Labeling Indices T1 and T2 SI Hemorrhage Ring Lesion, MRS, DWI & ADC Necrosis Enhancement, PWI, and Permeability Imaging Endothelial proliferation and Vascularity Radiology Pathology ASTROCYTOMA Five Year Survival 0 20 40 60 80 100 Percent Survival Glioblastoma (IV) Anaplastic (III) Astrocytoma (I-II) Pilocytic

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Neuro - Intraaxial Neoplasms - Smirniotopoulos (RSNA 2005)

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Page 1: Neuro - Intraaxial Neoplasms - Smirniotopoulos (RSNA 2005)

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The WHO 2000 Astrocytoma Classification

James G. Smirniotopoulos, M.D.Uniformed Services University

of the Health SciencesBethesda, MD

Visit us at: http://rad.usuhs.mil

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Features of Glioma• Site of Origin• Character of lesion

– Signal intensity (MR)– Attenuation (CT)– Blood-brain-barrier (Gd or I)– Chemistry (MRS)– Metabolism (Th 201, FDG-PET)– Vascularity (PWI)

• Mode of Spread– DTI

Traditional Tumor Grading

• PATHOLOGIST– LOW GRADE– HIGH GRADE

• RADIOLOGIST– NON-ENHANCING– ENHANCING

• NEUROSURGEON– “SUCKABLE”– “NON-SUCKABLE”

Kernohan-Sayre (AFIP)Grading System:

• GRADE I- “BENIGN” or “Low-Grade”• GRADE II - “ “• GRADE III - ANAPLASTIC

– cellular atypia, etc.• GRADE IV- MALIGNANT

– NECROSIS, Vascularity, Mitoses– GLIOBLASTOMA MULTIFORME

• NOTE: Numerous modifications exist, most into three grades, e.g..: Low Grade (Benign), Anaplastic, and GBM (w/ NECROSIS).

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Correlation

T2 SI, DWI & ADCCellularity

T1 and T2 SI, DTIInfiltration

MRS, Th 201 and FDGLabeling Indices

T1 and T2 SIHemorrhage

Ring Lesion, MRS, DWI & ADC

Necrosis

Enhancement, PWI, and Permeability Imaging

Endothelial proliferation and Vascularity

RadiologyPathology

ASTROCYTOMAFive Year Survival

0 20 40 60 80 100

Percent Survival

Glioblastoma (IV)

Anaplastic (III)

Astrocytoma (I-II)

Pilocytic

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GRADING SYSTEMSSem Rad Onc (1991); 1: 2-9

Kernohan Berger WHO 1993 1 Pilocytic,SEGA

Benign (1) Astrocytoma2 Astrocytoma

Benign (2)Anaplastic 3 Anaplastic

Anaplastic (3)

Glioblastoma (4) Glioblastoma 4 Glioblastoma

Define the Problem:

• Some Low Grade Enhance• Some Low Grade Do Not

• Some Low Grade => GBM• Some Low Grade Do Not

WHO Classification

• Defines Histologic Subtypes• Grades Biologic Potential• Allows International Cooperation• Ascending scale of Aggression from 1-4

WHO CORRELATION

• Low Grade

– Long-Term Survival

– Stable Histology no progression

Possible Cure

WHO Grading CNS Tumors

GRADE 1 JPA SGCA GANG MENING

GRADE 2 PXA HPC

GRADE 3 PXA ANAPLASTIC HPC

GRADE 4 GBM

CNS NEOPLASM-GLIALPrognostic Factors

Location Age

Histology

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“BENIGN” ASTROCYTOMA

• Two types:– Low grade (“benign”)

Diffuse (Adults)– Low grade “special”

Circumscribed (Children)

Normal appearing white matter Normal appearing white matter …… few cell bodiesfew cell bodies

Diffuse Low Grade Astrocytoma Diffuse Low Grade Astrocytoma …… too many cells !too many cells !

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WHO Gr1 - Pilocytic Astrocytoma

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WHO Gr1 - Pilocytic Astrocytoma

Circumscribed Mass:

Cyst w/Nodule

Pushing Margin

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Circumscribed Astrocytoma

WHO Grade 1

Pilocytic

Astrocytoma

SEGA

Circumscribed Astrocytoma

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ASTROCYTOMA:Circumscribed

• “Special” Astrocytomas• Astrocytoma of Young• Various Locations• Well circumscribed (yet, no capsule)

• Do NOT spread along WM• Do NOT change grade (except PXA)

• Constellation of findings correlates w/ Histology

PILOCYTIC ASTROCYTOMA

Cystic Cerebellar Astrocytoma Juvenile Pilocytic Astrocytoma

(“PA” or “JPA”)

PILOCYTIC ASTROCYTOMA

• Synonyms: Polar Spongioblastoma, Cystic Cerebellar Astrocytoma

• Cell of Origin: Astrocyte (bi-polar, hairlike)• Associations: in ON w/ NF-1• Incidence: 3-6% of ALL Cranial, 32% of Child• Age: 5-15 (Zulch 3-7) Sex: Slight F (11/9)• Location: Cerebellum, Chiasm/Hypothal, Optic• Treatment: Surgery, patience• Prognosis: 77% at 5 yrs, 75% at 10 yrs, 75% at 15 yrs

PILOCYTIC ASTROCYTOMARadiology

• Cerebellum, Diencephalon– rare in BS or Cerebrum

• Majority have significant “cyst”– “Cyst and Mural Nodule”

• part of lining does NOT enhance– Nodule may be heterogeneous– Exceptional purely solid

• Nodule NOT hyperdense• Calcification in 5-25%

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NOT a true cyst - no lining, just gliosis

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WHO Gr1 - Pilocytic Astrocytoma

Circumscribed Mass:

Cyst w/Nodule

Pushing Margin

PATHOLOGY• Biphasic pattern

– dense pilocytic glia– Rosenthal fibers– loose microcystic areas

• No necrosis• Low grade• Abnormal capillaries

– allow enhancement– fluid production

Grading Problems in Gliomas51 Pilocytic (WHO Gr. 1)

KERNOHAN MAYO-ST.ANNE

1 26% 1 2%

2 69% 2 55%

3 6% 3 35%

4 0% 4 8%

By conventional “feature counting” most pilocytic astrocytomas were overgraded.

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Pilocytic Astrocytoma

• Variant Appearance

• Variant Location

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Pilocytic AstrocytomaA Cyst with mural nodule?

Not Always !!!

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Courtesy of Paul Sherman

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USU – Learning to Care for Those in Harm’s WayPILOCYTIC ASTROCYTOMA:

Locations

• CEREBELLUM

• Chiasm And Optic Nerve

• Hypothalmus/thalamus• Cerebral Hemisphere• Spinal Cord (Intramedullary)

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PILOCYTIC ASTROCYTOMA(Juvenile Pilocytic)

• Childhood, Young Adults• Benign, no mitosis/necrosis• Circumscribed - Enhancing• Cyst Formation, Mural Nodule• Cerebellum and Diencephalon

(Optic tracts, Hypothalmus)

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WHO GRADE I

• Circumscribed Astrocytoma– JPA (Pilocytic)– SGCA (Subependymal Giant Cell)

• Ganglioglioma• Meningioma

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Subependymal Giant Cell Astro

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ASTROCYTOMAS

• “SPECIAL” ASTROCYTOMAS– Circumscribed Growth:

• Pilocytic•Subependymal Giant Cell• Pleomorphic Xantho-Astrocytoma

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Circumscribed Astrocytoma

WHO Grade 1 2 3 4

PXA PXA

Circumscribed Astrocytoma

PLEOMORPHIC XANTHOASTROCYTOMA

• Rare Variant of Astrocytoma• Arises from Subpial Astrocytes• Affects Superficial Cerebral Cortex and

Meninges• Skull erosion (scalloped excavation)• Temporal > Frontal > Parietal• WHO Grade 2,3• 50% progress over time

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ASTROCYTOMAS

• “Ordinary” Astrocytoma• Diffuse Infiltration of WM by:

– Fibrillary Astrocytes– Protoplasmic Astrocytes– Gemistocytic Astrocytes

• WHO 2,3,4 (NOT 1)

• KS & Mayo Grades 1-4

Daddy,Where do Glioblastomas

come from?

Normal appearing white matter Normal appearing white matter …… few cell bodiesfew cell bodies

Diffuse Astrocytoma Diffuse Astrocytoma …… too many cells !too many cells ! KERNOHAN (KS) 1 2 3 4

ANAPLASIA 0 Min >1/2 Marked

CELLULARITY Mild Mild Inc Marked

MITOSIS 0 0 Plus Marked

ENDOTHELIAL 0 Min Min MarkedProliferation

NECROSIS Marked

TRANSITION <== Broad Sharp ==>ZONE

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Diffuse High Grade Astrocytoma Diffuse High Grade Astrocytoma …… Cells and Vessels Cells and Vessels KERNOHAN (KS) 1 2 3 4

ANAPLASIA 0 Min >1/2 Marked

CELLULARITY Mild Mild Inc Marked

MITOSIS 0 0 Plus Marked

ENDOTHELIAL 0 Min Min MarkedProliferation

NECROSIS Marked

TRANSITION <== Broad Sharp ==>ZONE

KERNOHAN (KS) 1 2 3 4

ANAPLASIA 0 Min >1/2 Marked

CELLULARITY Mild Mild Inc Marked

MITOSIS 0 0 Plus Marked

ENDOTHELIAL 0 Min Min MarkedProliferation

NECROSIS Marked

TRANSITION <== Broad Sharp ==>ZONE

ASTROCYTOMA:DIFFUSE

(Fibrillary, protoplasmic, etc.)

“Adult type” or “Hemispheric” AstrocytomaDiffusely infiltrate brain, along WM tractsContinuum, from low-grade to high-gradeGenetic Alterations 17 => 9 => 10Many Progress in Histology over time, changing from

WHO Gr. 2 => Gr. 3 => Gr. 4 (GBM)Imaging tends to correlate with histology, especially at

the ends of spectrum

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Astrocyte Mutation

• Normal Astrocyte• Neoplastic• Anaplastic• GBM

Deletions:17 p P5322q NF2

Excess production of:PDGF

Deletions:13q RB19q 10

Excess production of:CDK4

Deletions: 10 PTEN/MMAC19p P16,P15.P14

Excess production of:EGFRVEGF

WHO Gr 2 Gr 3 Gr 4 = GBMNormal

Genetically Heterogeneous

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Diffuse Astrocytoma

WHO GR 2

WHO GR 3

WHO GR 4

Normal

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WHO 4WHO 3WHO 2

AstrocytomaAnaplastic

Astrocytoma

Glioblastoma

Multiforme

A spectrum of tumors

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Dr. Eastwood:

The Good

The Bad

The Ugly

Diffuse Astrocytoma

‘Astrocytoma’

Anaplastic Astrocytoma

Glioblastoma Multiforme

ASTROCYTOMARadiologic Grading

• TYPE 1 - WHO 2, KS Grade 1-2, “Benign”– Homogeneous– No Enhancement, No Vasogenic Edema

• TYPE 2 – WHO Grade 3, Anaplastic– Variable Enhancement, Edema– 50% enhance - 50% don’t

• TYPE 3 – WHO Grade 4 Glioblastoma– Heterogeneous (Necrosis, Blood)– Ring Enhancement, Edema

“BENIGN” ASTROCYTOMA:WHO 2, KS 1-2, Mayo 1

• YOUNGER PATIENT– CHILDHOOD– Young Adults (20’s - 40’s)

• NL VESSELS (NO NEOVASCULARITY)– BBB INTACT– NO EDEMA– NO ENHANCEMENT– NO TUMOR VESSELS

Benign - Diffuse

• HOMOGENEOUS– NO NECROSIS– NO HEMORRHAGE– INCREASED WATER

• DARK and Poorly Demarcated on CT• Dark and Sharp on T1W• BRIGHT and Sharp on T2W

– MICROCYST >>> MACROCYST(macrocysts occur in JPA, etc.)

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Gr 2 Fibrillary Astrocytoma

T2PD

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Gr 2 Fibrillary Astrocytoma

T1-gadT1-non

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Gr 2 Astrocytoma: PWI

Reduced perfusionReduced perfusionADCADC PWIPWI--CBVCBV

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T1-gadT2

Gliomatosis Cerebri

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Gliomatosis Cerebri:Diffuse Astrocytoma – 2 lobes

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Spread along White Matter Tracts

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Gliomatosis Cerebri

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CHO

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NAA ?

Gliomatosis Cerebri

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Thickened Genu

Enlarged Fornix

Blurring of Gray Matter

Infiltration of peduncle

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Astrocytoma: Microcystic change

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Astrocytoma

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MODES OF SPREAD

1. Natural passages

2. Along surfaces

3. Along white matter tracts

4. Across the meninges

SPREAD ALONG TRACTS:

• Corona Radiata• Peduncles• Corpus Callosum• Anterior Commisure• Arcuate Fibres

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Astrocytes Track Along WM

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Pontine Astrocytoma

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Pontine Astrocytoma: WHO 2

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Six Weeks Later

WHO 2 … GBM

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Expanded Brain

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Expanded Brain

Anaplastic Astrocytoma Rad

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Anaplastic Astrocytoma: Overall Characteristics

• Grade III malignant glioma• Less aggressive than GBM, malignant with somewhat

better prognosis• Frequency: highest in young adults (30 – 40 years)• Recurrence: often as a higher-grade glioma• Challenge: difficult to remove completely with surgery• Median survival: 3 – 4 years

Anaplastic AstrocytomaAnaplastic Astrocytoma

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Anaplastic Astrocytoma

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Anaplastic Astrocytoma

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Anaplastic Astrocytoma( WHO 3 )

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Increased Cellularity, +/-minimal vascular changes, no necrosis , no hemorrhage

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GBM - Glioblastoma

“MALIGNANT” ASTROCYTOMA:• Older patient

– 40’s and up– exceptions (PNET)– ~ 1/2 arise from previous low grade (2-3)

• Abnormal Vessels (neovascularity)- BBB abnormality– vasogenic edema– contrast enhancement– irregular vessels, shunting, etc.

• HETEROGENEOUS– hemorrhage (old/new)– tumor necrosis– tumor itself

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Astrocytoma Gr4:

Necrosis !

Angiogenesis

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Glioblastoma Multiforme Rad

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Glioblastoma Multiforme

vascularity

necrosis

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T1-gadT2

Glioblastoma Multiforme

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(Gr 4) Glioblastoma: PWI-CBV

Increased perfusionIncreased perfusion

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Glioblastoma – WHO Grade 4

A solitary, deep, irregular, heterogenous, ring-enhancing mass with vasogenic edema.

Low NAA – High Choline/Creatine

GBM

• Center of Abnl Density/Intensity– variegated necrosis

• ENHANCING RIM– hypercellular, fleshy neoplasm– greatest neovascularity

• Corona of Abnl Density/Intensity– “edematous” white matter– areas of microscopic neoplastic infiltration

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GBM - Glioblastoma

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Pseudopalisading Necrosis

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Ring Lesion and Infiltration GLIOBLASTOMA MULTIFORME(Surrounding Zone of Infiltration)

• GBM arose from a preexisting low grade– surrounding lower grade neoplasm– may also transform over time

• GBM arose de novo– sends cells to invade the brain

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T1-gadT2

Glioblastoma Multiforme

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Courtesy of R.D. Zimmerman, NY

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GBM - Multifocal

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Multifocal GBM

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DWI of Glioblastoma (Gr 4)

Park et al., Neuroradiology 2000;42:716-721

DWIDWIT1T1--gadgad

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Ring Enhancing Mass

•Round

•Smooth

•Thin wall

•Undulating

•Irregular

•Thick wall

Benign Malignant

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Glioblastoma Multiformevs. Abscess (toxo) R

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DWI: Necrosis vs. PUS

GBM Abscess

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meningealcallosal

Glioblastomas: Growth/Spread

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T1-gadT1-gad

Glioblastoma: Ependymal spread

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GBM – Thicker on Surface

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Early Draining Veins

X-Ray Perfusion Imaging

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MR Perfusion Imaging

Courtesy of James Provenzale, Duke UniversityCourtesy of James Provenzale, Duke University

****

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GBM with increased rCBV

Courtesy Mauricio Castillo, Chapel Hill

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New Tools for Grading and Staging• Radiology

– Perfusion Imaging rCBV and rCBF

– Diffusion Imaging, ADC and DTI

– Spectroscopy– PET/SPECT– Monoclonal Ab.

• Pathology– Labeling Index– Chromosome Analysis– Histochemical– Electron Microscopy

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DTI

Loss of Anisotropy

DTI and Tumor Imaging

T2From: J. Burdette and Neeraj Chepuri, WFU

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Astrocytes Track Along WM

Anisotropy:Diffusion (ADC) is different in different directions

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Glioblastoma Multiforme

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Glioblastoma Multiforme

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Two Port Radiotherapy• Bad News

– Can’t define full extent of tumor by any current test

• Good News– 90% of tumor

recurrence within 2cm of enhancing rim

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6/15

7/22Courtesy of R.D. Zimmerman, NY

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5 weeks later

Define the Problem:

• Some Low Grade Enhance• Some Low Grade Do Not

• Some Low Grade => GBM• Some Low Grade Do Not

Define the Problem:Answers

• Some Low Grade Enhance *• Some Low Grade Do Not

• Some Low Grade => GBM• Some Low Grade Do Not *

* These are the Circumscribed AstrocytomasThe others are the Diffuse Astrocytomas

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WHO Astrocytoma Summary

Astrocytoma Anaplastic

AstrocytomaGlioblastoma

Multiforme

WHO Grade 1 2 3 4

PXA PXA

Pilocytic

Astrocytoma

SEGA

Circumscribed Astrocytoma

Diffuse

AstrocytomaA spectrum of tumors

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WHO 4WHO 3WHO 2

AstrocytomaAnaplastic

Astrocytoma

Glioblastoma

Multiforme

A spectrum of tumors

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EUXAPIΣTΩ !Mahalo !

Gracias! ObregadoMerci Beaucoup

Danke Shoen

Thank You!