Diffusion tensor imaging reveals early dissemination of pediatric diffuse intrinsic

pontine gliomasMatthias W. Wagner¹, Joyce Mhlanga¹, Thangamadhan Bosemani¹,

Kathryn A. Carson2,3, Kenneth J. Cohen⁴, Andrea Poretti¹, Thierry A. G. M. Huisman¹

¹ Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of

Medicine, 2 Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, ³ Division of General Internal Medicine, Department of Medicine , and ⁴ Division of Pediatric

Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

EP-131

ASNR 53rd Annual Meeting, Chicago, April 25-30, 2015

DisclosureK.A. Carson is supported by the National

Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (Grant Number 1UL1TR001079)

Diffuse intrinsic pontine glioma (DIPG)

10% of all brain tumors in children Tumor dissemination in 26%

within the first 7 months after initial presentation

Role of neuroimaging: 1. DIPG typically diagnosed by imaging

characteristics 2. Tumor involves >50-70% of the pons 3. T1w hypo, T2w hyper

T2w

T1w

Diffusion Tensor Imaging (DTI)

Advanced MR technique for in vivo evaluation of the microstructure and integrity of white matter tracts

DTI Scalars: Fractional anisotropy (FA)Mean diffusivity (MD)Axial diffusivity (AD)Radial diffusivity (RD)

λ1

λ2

λ3

Purpose

Comparison of the microstructural integrity of supratentorial WM tracts at initial presentation using DTI

Hypotheses:

1.DIPG: Tumor dissemination along the corticospinal tract (CST)

2.Low-grade brain stem glioma (LGBG):No tumor dissemination

3.Controls: No tumor dissemination

Changes in DTI scalars

No changes in DTI scalars

Inclusion criteria

A. Diagnosis of DIPG or LGBG based on neuroimaging and/or histology

B. Absence of macroscopic tumor dissemination at diagnosis as assessed by conventional MRI

C. Availability of pre-treatment DTI data

D. Age at MRI <18 years

E. Controls with normal brain anatomy + absence of neurological disorders

Methods: DTI analysis

ROI based analysis of DIPG, LGBG, controls

FA+MD+AD+RDBilateral posterior centrum

semiovale (PCSO, A)Bilateral posterior limb of

internal capsule (PLIC, B)

Statistical analysis / Histology

Two-sample t-tests: age difference DIPG ↔ controls, LGBG ↔ controls, DIPG ↔ LGBG

Wilcoxon rank sum tests: DTI scalars DIPG ↔ controls, LGBG ↔ controls

Linear regression model: DTI scalars DIPG ↔ LGBG All tests: 2-sided, significance if p<0.05, no adjustment

for multiple comparisons Histology available for bilateral PLIC and PCSO in one

DIPG patient

Results: Patients / Controls

DIPG: n = 8 (5 males), mean age at MRI = 5.74±1.28 25 age-matched controls (p>0.99)

LGBG: n = 8 (3 males), mean age at MRI = 8.82±3.23 years 25 age-matched controls (p>0.99)

Results: DTI DIPG ↔ controls

* indicates significance, p<0.05

No significant differences

Results: DTI LGBG ↔ controls

Results: DTI DIPG ↔ LGBG

* indicates significance, p<0.05

Results: HistologyA, B: Sections from main tumor bulk in the pons show hypercellularity with diffuse infiltration of hyperchromatic, atypical astrocytes (arrow)

C, D: Sections of the left PLIC showed infiltrating astrocytoma and increased mitotic activity (arrow)

E, F: Infiltrating tumor not observed in the right PLIC

Conclusion

1. Conventional MRI fails to demonstrate early tumor dissemination/migration in pediatric DIPG

2. Quantitative DTI analysis may detect early dissemination/migration of tumor cells along the CST in DIPG

3. In pediatric DIPG, DTI may help to:1. Understand tumor biology2. Monitor disease progression3. Guide treatment options