New Imaging Concepts in Central Nervous System Neoplasms Maarten Lequin Department of Pediatric Radiology Wilhelmina Children s Hospital/University Medical Center Utrecht
New Imaging Concepts in Central Nervous System Neoplasms What are the new concepts? How will it change our radiological thinking? Diagnosis, imaging protocols, treatment strategies When to use? Conventional and additional advanced MR sequences
New Imaging Concepts in Central Nervous System Neoplasms What are the new concepts? Transcriptional profiling new brain tumor subtypes
New Imaging Concepts in Central Nervous System Neoplasms What are the new concepts? Transcriptional profiling new brain tumor subtypes Subtyping better understanding of tumor behaviour
New Imaging Concepts in Central Nervous System Neoplasms What are the new concepts? Transcriptional profiling new brain tumor subtypes Subtyping better understanding of tumor behaviour Subtyping predict better outcome and may influence treatment strategy choices
New Imaging Concepts in Central Nervous System Neoplasms What are the new concepts? Transcriptional profiling new brain tumor subtypes Subtyping better understanding of tumor behaviour Subtyping predict better outcome and may influence treatment strategy choices Subtyping new concept of radiological thinking
New Imaging Concepts in Central Nervous System Neoplasms What are the new concepts? Transcriptional profiling new brain tumor subtypes Subtyping better understanding of tumor behaviour Subtyping predict better outcome and may influence treatment strategy choices Subtyping new concept of radiological thicking Predict subtype better assess outcome and treatment strategy choices
Molecular tumor subtypes MR image characteristics Molecular markers Targeted treatment Prognosis
Molecular subtypes in Brain tumors
From 2007 to 2016 WHO Classification of CNS tumors some major changes Formulating concept of how CNS tumor diagnoses are structured in the molecular era Major restructuring of diffuse gliomas, with incorporation of genetically defined entities Major restructuring of medulloblastomas, with incorporation of genetically defined entities Incorporation of a genetically defined ependymoma variant Major restructuring of other embryonal tumors, with incorporation of genetically defined entities and removal of the term primitive neuroectodermal tumor Novel approach distinguishing pediatric look-alikes, including designation of novel, genetically defined entity Courtesy of Dr. David Louis
(A) Unsupervised hierarchical clustering of human 1.0 exon array expression data from 103 primary medulloblastomas using 1,450 high standard deviation (SD) genes. Paul A. Northcott et al. JCO 2011;29:1408-1414 2011 by American Society of Clinical Oncology
Putative points of origins of WNT-subgroup medulloblastoma in sagittal, transverse, and coronal planes. 69% 31% 75% 19% Z. Patay et al. AJNR Am J Neuroradiol 2015;36:2386-2393 2015 by American Society of Neuroradiology
New Imaging Concepts in Central Nervous System Neoplasms What could be potential radiological biomarkers besides age and location? T1, T2, T1 after Gd, DWI, MRS? Or should we go for newer imaging modalities? ASL, APT, DKI?
Medulloblastoma subgroups and MR Spectroscopy
Medulloblastoma subgroups and MR Spectroscopy
4y old male. Diagnosis?
3y old girl Diagnosis?
16m old boy Diagnosis?
1y old boy Diagnosis?
New Imaging Concepts in Central Nervous System Neoplasms When to use? Conventional and additional advanced MR sequences
New Imaging Concepts in Central Nervous System Neoplasms Best differential diagnosis
New Imaging Concepts in Central Nervous System Neoplasms Best differential diagnosis Location, age and imaging sequences
New Imaging Concepts in Central Nervous System Neoplasms Best differential diagnosis Location, age and imaging sequences Posterior fossa DWI for differentiation
New Imaging Concepts in Central Nervous System Neoplasms Best differential diagnosis Location, age and imaging sequences Posterior fossa DWI for differentiation ASL in combination with Gd enhancement (ratio) characterise brain tumors infra- and supratentorial
New Imaging Concepts in Central Nervous System Neoplasms Best differential diagnosis Location, age and imaging sequences Posterior fossa DWI for differentiation ASL in combination with Gd enhancement (ratio) characterise brain tumors infra- and supratentorial Medulloblastoma, use MRS to differentiate between the subgroups
6y old boy Diagnosis?
New Imaging Concepts in Central Nervous System Neoplasms Supratentorial brain tumors are less easy to characterise using conventional and advanced sequences DWI and MRS are no good predictors for tumor grading in glial tumors Still a lot of research has to be done to look for new radiological biomarkers in other common brain tumors like glial tumors
Another possible New Imaging Concept in Central Nervous System Neoplasms To abandon the use of Gd in neuro-oncology imaging: Recently multiple papers focus on the cumulation of Gd in the brain and their possible side effects In the future we have to look for alternative sequences which may give the same information Follow-up imaging without T1 after Gd? Arterial spin labeling (ASL) Amide Proton Transfer (APT) imaging could be an alternative? Diffusion kurtosis imaging (DKI)?
New Imaging Concepts in Central Nervous System Neoplasms
New Non-contrast Imaging Concepts in Central Nervous System Neoplasms Arterial spin labeling (ASL) No Gd contrast, measures CBF Three methods, continues, pulsed and pseudocontinues Pediatric brain tumor imaging Ratio with contrast enhancement may predict tumor grading No tumor subtyping
New Non-contrast Imaging Concepts in Central Nervous System Neoplasms Amide Proton Transfer (APT) imaging Type of chemical exchange dependent saturation transfer (CEST) magnetic resonance imaging (MRI), in which amide protons of endogenous mobile proteins and peptides in tissue are detected Especially useful in high grade brain tumors APT shows better diagnostic performance than diffusion- and perfusion-weighted imaging in nonenhancing gliomas Park KJ et al. Eur Radiol. 2016 Feb 16. Added value of amide proton transfer imaging to conventional and perfusion MR imaging for evaluating the treatment response of newly diagnosed glioblastoma.
New Non-contrast Imaging Concepts in Central Nervous System Neoplasms Diffusion kurtosis imaging (DKI) Diffusion weighted method with 2 non-zero b-values More sensitive for brain tumor imaging May differentiate between low and high grade tumors
Courtesy to Susan Palasis Diffusion kurtosis imaging (DKI) in a 7 year old with resected large cell anaplastic medulloblastoma 2 nd post-op study 2 weeks later
Normalized kmean map to MNI space superimposed on T1 C+ kmean in right ROI is 0.9841 kmean in left ROI is 0.7342 Findings show definite tumor around 4 th ventricle and foramen of Luschka. Concern for tumor infiltration of right cerebellar hemisphere.
Summary Challenge: balancing desires and needs Stay connected Most accurate diagnosis Provide the best possible diagnosis Utilize the most accurate, cuttingedge techniques Fine-tune imaging protocol (D,FU) Incorporate the latest molecular signatures Do not disrupt current clinical diagnosis and patient management Weigh the availability and cost of novel diagnostic techniques Preserve the ability for longterm clinical, experimental and etiological correlations Courtesy of Dr. David Louis
New Imaging Concepts in Central Nervous System Neoplasms What are the new concepts? Molecular biology, Non Gd imaging How will it change our radiological thinking? Dedicated imaging protocols When to use? Depends on brain tumor subtyping
New Imaging Concepts in Central Nervous System Neoplasms Acknowledgements: Pieter Wesseling Zoltan Patay Susan Palasis Arthur Adams Jeroen Hendrikse Dik Rutgers