Brain Tumor Imaging Caribbean Medical Providers Practicing Abroad June 13, 2015 Asante M. Dickson, MD CAQ Neuroradiology Washington Adventist Hospital Takoma Park, MD

Role of Imaging Diagnosis Grade Guide Biopsy Monitor treatment response and prognosis Post-operative base-line

Imaging Modalities Available CT MRI PET

Pediatric Supratentorial Infratentorial JPA juvenile pilocytic astrocytoma, Ganglioglioma, PXA pleomorphic xanthoastrocytoma, PNET primitive neuroectodermal tumor, DNT dysembroplastic neuroepithelial tumor Infratentorial JPA, Medulloblastoma, ATRT, Ependymoma, Diffuse pontine glioma (Not usually intra-axial but don’t forget about LCH and Neuroblastoma)

Hoag - Medulloblastoma

Medulloblastoma

4 year old Brainstem glioma

Brainstem Glioma Brainstem glioma

26 yo M

Craniopharyngioma

56 yo M T2 FLAIR

DWI ADC

Intravascular Lymphoma Post Gad

Okay, it’s a brain tumor – But then what ? WHO divides CNS neoplasms into 9 primary groups and mets Neuroepithelial tumours (astrocytic, oligo, astroblastoma, ependymal, choroid plexus) Neuronal, mixed glial-neuronal and neurocytic Pineal parenchymal tumors Embryonal tumors (PNET, medullo, ATRT) Peripheral neuroblastic tumors (neuroblastoma) Tumors of cranial, spinal or peripheral nerves Meningeal tumors (meningioma, chondrosarcoma, hemangioblastoma) Lymphoma, hematopoietic tumors (leukemia, plasmacytoma) Germ Cell Tumors Metastases

The Approach to Differential Diagnosis Where is it? Intra-axial Vs Extra-axial Cortical, white matter or deep grey matter, Intraventricular Supra-tentorial or Infra-tentorial Solitary or Multiple How old is the patient? Child, Young Adult, Older Adult, Ready to die of other causes Primary vs Secondary Is the patient immunocompromised? Other clinical history... E.g. Lymphoma Imaging features – T2, DWI, PWI, MRS, Gad

Gamuts Tumors in children <2yo Cortically based tumors Astrocytoma, CPP, Teratoma, Embryonal tumors Cortically based tumors DNET, Ganglioglioma, Oligo, PXA(pleomorphic xanthoastrocytoma) Intraventricular tumors Pineal Region tumors Dural Based tumors Intracranial extension from extracranial Chordoma, paraganglioma, carcinomas (NPCA), sarcomas (rhabdo) Cyst + Nodule Pilocytic, Craniopharyngioma, Ganglioglioma, Hemangioblastoma

Intra-axial vs Extra-axial Features Surrounded by white matter Expands cortex May destroy GM/WM jx Effaces CSF cisterns Internal vascular supply Extra-axial CSF Cleft Widening of CSF cisterns Buckling of grey matter GM/WM junction preserved Continuity with bone or falx Bony changes External vascular supply

12yoM – Intra or Extra-axial? Cavernous Hemangioma with Intra-osseous hemangioma

Differential Diagnosis – Extra-axial Skull-base/calvarium Dural Sellar/Parasellar/Optic chiasm Perineural Intra-ventricular Central neurocytoma, ependymoma, subependymoma, oligo, pilocytic astro, meningioma, choroid plexus tumour, epidermoid, subependymal giant cell astrocytoma, colloid cyst, arachnoid cyst Pineal Region CP Angle

Pre T1 Post T1 Post T1 Post T1 Post T1 Post T1 Myxoid chondrosarcoma

56 yo M Primary CNS Lymphoma

Primary CNS Lymphoma

Diagnosis – Is it neoplastic? Mass Lesions – The standard Ddx (Congenital) Infectious Inflammatory Neoplastic Vascular – Ischemic, Hemorrhagic (Toxic, Metabolic) (Traumatic) (Degenerative)

56year old male history of lung CA Abscesses DWI ADC FSE T2 Abscesses Post-Gad

19 yo Male, Previously well, presents with new onset of seizures x 3

MRI Same Day ADC GRE DWI Katz Demyelination Post-Gad

5 Days Later Now Enhances FSE T2 Post-Gad Pre-Gad

10 days after presentation FSE T2 DWI ADC Post Gad Perfusion

15 days after presentation GRE FLAIR Hemorrhagic acute demyelination; Patient received multiple antibiotics and steroids; Radiology DDx – Encephalitis vs Demyelination Post-Gad

Supratentorial Neoplasms – Adults Metastases Infiltrative (Diffuse or fibrillary) astrocytic tumours Astrocytoma, anaplastic astrocytoma, GBM, gliomatosis Localized/Noninfiltrative astrocytic tumours (Pilocytic astrocytoma - peds), Pleomorphic xanthoastrocytoma, (supependymal giant cell astrocytoma) Oligodendroglioma and anaplastic oligo Neuronal and Glial-neuronal composition Gangliocytoma and ganglioglioma, (desmoplastic infantile ganglioglioma <1yo), (central neurocytoma), DNT Primary CNS Lymphoma

GBM GBM

Epithelioid Hemangioendothelioma

Metastatic Adenocarcinoma Mets from lung

Infratentorial Neoplasms - Adults Metastases Hemangioblastoma Medulloblastoma (Cerebellar astrocytoma, Ependymoma)

JPA

Proton MRS Elevated choline:Creatine ratio and reduced NAA considered “tumor spectrum” but non-specific Metabolic ratios for glioma grading remains investigational May be useful to help differentiate high vs low grade gliomas (II vs III/IV) Lactate (high and low grades, ?radioresistance) vs Mobile Lipids (high grade only) – can’t separate on standard MRS Imaging brain tumor after therapy – elevated choline (>50% contralateral oe Ch:Cr >2) – moderate to high sensitivity and high specificity for identifying active tumor (but no large series)

MRS TE 144 TE 35 Cho Cr NAA Lactate inversion

Single Voxel

67 yo M

MR Perfusion – elevated relative CBV Multivoxel MR Spectroscopy – increased choline, reduced NAA

Grading of Brain Tumors WHO grading revised in 2000 Based on histological appearance Does not take into account anatomic location and size of tumor which influence resectability Primary basis for guiding therapy, prognosis, scientific study

Diffusion Weighted Imaging and Grade Tumor grade and cellularity reflected by ADC values But most astrocytomas are too heterogeneous for ADC values to be helpful Post-operative injury Enhancement post-surgery may be subacute infarction Peritumoral edema Vasogenic edema (mets and meningiomas) vs Tumoral edema – not so helpful Integrity and Position of White Matter Tracts (DTI)

Tumor grade and cellularity Higher cellularity, reduced ADC Minimum ADC may correlate inversely with grade Limit due to tumor heterogeneity Non-glial neoplasms – Meningioma, Lymphoma

MR Perfusion Measures Degree of tumour angiogenesis and capillary permeability CBV is proportional to the area under the contrast agent concentration-time curve Contrast concentration is proportional to the change in relaxation rate (dR2*) Assumptions of negligible recirculation and contrast leakage – generally violated Measurement is relative therefore compare to contralateral white matter

MR Perfusion continued Oligo’s – high CBV regardless of grade Astrocytomas – higher CBV = high grade Choroid plexus tumours, some meningiomas, mets – may not return to baseline – contrast leakage/leaky capillaries CNS Lymphoma – high but not as high as GBM Tumefactive MS – intralesional venous enhancement, possible mild elevation of CBV

Permeability imaging (DCE steady-state T1 measurement or DSC) Endothelial permeability of vessels in brain tumors gives info about BBB integrity, vascular morphology and nature of neovascularization Quantitative estimates of microvascular permeability (Ktrans) correlate with brain tumour grade Ktrans (endothelial transfer coefficient) is a generalized measure to decribe the relationship between the time course of blood plasma Gad concentration (arterial input function) and Gad concentration changes in the voxel Affected by blood flow, blood volume, endothelial surface area, endothelial permeability

Monitoring Response to Therapy Post-operative Baseline Tumour recurrence vs radiation necrosis

48year old previously well FLAIR DWI Post-Gad

3 months later - Following one course of steroids

following more steroids 11 months after presentation 1 year following more steroids 11 months after presentation

13 months after initial presentation

MR Perfusion 13 months Perfusion 11 months Perfusion Non-Hodgkings lymphoma Lois Nakamura

FDG-18

Thank You very much ! Special thanks to Dr. Talia Vertinsky