Peter de Blank1,2, Dan Ma2, Chaitra Badve2, Shivani Pahwa2, Sara Dastmalchian3, Duncan Stearns1,2, Deborah Rukin Gold2,4, Krystal Tomei2,5, Jill S Barnholtz-Sloan2, Andrew Sloan2,5, Vikas Gulani2,6, and Mark Griswold2
1Pediatrics, University Hospitals, Cleveland, OH, United States, 2Case Western Reserve University, Cleveland, OH, United States, 3University Hospitals, Cleveland, OH, United States, 4Neurology, University Hospitals, Cleveland, OH, United States, 5Surgery, University Hospitals, Cleveland, OH, United States, 6Radiology, University Hospitals, Cleveland, OH, United States
Synopsis
This study uses magnetic resonance
fingerprinting to investigate relaxometry values in pediatric and young adult primary
brain tumors. Six children with primary
brain tumors were scanned: 3 with
low-grade tumors and 3 with high-grade tumors.
T1 and T2 values of tumor were significantly different from
contralateral white matter. T1, T2
quantification of tumor were also significantly different between high- and
low-grade tumors. Three subjects
underwent serial observations: 2 received therapy and 1 did not. Subjects that underwent surgical
decompression and chemotherapy appeared to have larger changes in T1 values
than those that were only observed.Purpose
Traditional MR methods for staging, pre-operative planning
and post-therapy surveillance of brain tumors rely largely on qualitative
comparisons, limiting accuracy in diagnosis and the measurement of longitudinal
changes. Magnetic resonance
fingerprinting (MRF) allows rapid, simultaneous mapping of multiple tissue properties, including relaxation times (T1 and T2) and proton density.[1] MRF
has been shown to distinguish pathology and tumor grade in adults with primary
and metastatic brain tumors.[2] However, brain tumors in children and young
adults are often pathologically distinct and frequently rely on non-surgical
treatments to forestall growth.[3] A
fast, quantitative method to identify tumor pathology and measure the effect of
treatment would be an important diagnostic and therapeutic tool. We examined children and young adults with
primary brain tumors to determine whether MRF can measure differences in histologic
grade and measure treatment effects.
Methods
Subjects with primary brain tumors were scanned
on a 3T scanner (Siemens, Skyra) using a 20 channel head coil in an
IRB-approved study. A FISP based MRF
sequence [4] was used to create T1 and T2 maps for 7-10 slices acquired in each
subject. Longitudinal surveillance scans
with or without chemotherapy were performed.
Scan parameters included field of view 300x300 mm2,
resolution 1.17x1.17 mm2, slice thickness 5 mm, flip angle 0 to 74
degrees, TR 12 to 15 ms, sinc pulse with duration of 2000 ms, and
time-bandwidth product of 8. Total acquisition time was 41 seconds/slice. Regions
of interest included tumor tissue, the peritumor region 1cm adjacent to tumor, and contralateral white matter (CWM) (Figure 1). In the absence of enhancement, T2
hyperintensity with mass effect was used to define the extent
of tumor. Diagnosis was based on clinical presentation and MR spectroscopy when
pathology was impractical (eg, for optic pathway gliomas). Wilcoxon tests were
used to compare paired mean relaxometry values between tumor and CWM; Mann-Whitney
tests were used to compare parameter distributions between histologic groups.
Results
6 subjects (3 male, 5 children (1-14years) and 1
young adult (34years)) underwent a total of 11 scans. Tumors included 3 low-grade
tumors (2 optic pathway glioma, 1 thalamic glioma) and 3 high-grade tumors (primitive
neuroectodermal tumor, atypical teratoid/rhabdoid tumor, anaplastic astrocytoma). Mean (±SEM) T1 and T2 for tumors differed significantly
from CWM: T1 1586(±167)ms vs. 980(±76)ms (p=0.028) and T2 67.6(±10.2)ms, vs. 45.3(±3.2)ms
( p=0.046). T1 and T2 of peritumor regions also differed from
CWM: T1 1669(±180)ms vs. 980(±76)ms
(p=0.043) and T2 76.9(±17.2)ms vs. 45.3(±3.2)ms (p=0.043). T1 and T2 relaxation
times were significantly different between histologic grade (high- vs low-): T1 2340 (±309)ms vs. 1255(±115)ms (p=0.049) and
T2 156.0(±80.4)ms vs. 48.3(±1.8)ms (p=0.049) (Figure 2). 3 tumors (2 treated, 1 untreated) were
followed longitudinally over time. Treatments included surgical decompression
and chemotherapy. T1 in treated tumors changed
14% and 17% but only 6% in untreated tumors, similar to treatment effects shown
in previous preclinical tumor models (Figure 3). [5,6]
Discussion
This study describes the first use of MRF in
pediatric patients and the first description of treatment effects using MRF.
Despite the small cohort, MRF-derived relaxation times distinguished tumor from
CWM and differentiated tumor grade. Treated
tumors appeared to have larger changes in T1 values than untreated tumors. Therapy-related changes in low- and high-grade tumors were in opposite directions, which may be related to treatment modality and will be further explored as subject accrual continues. MRF
may be an important tool for the characterization of pediatric brain tumors and
the evaluation of treatment effects. Future
studies will determine whether treatment effect correlates with clinical
outcome. This study continues to accrue
pediatric, adolescent and young adult subjects and follow current subjects to
expand our cohort and develop our longitudinal data.
Conclusion
MRF was able to characterize pediatric and young
adult brain tumors and measure the effect of treatment on tumor tissue. MRF may be an important tool in the early
evaluation of treatment efficacy.
Acknowledgements
PdB received support from the Francis S. Collins Scholarship
and the St. Baldrick’s Foundation.References
1. Ma D, et
al. Nature. (2013) 187-192. 2. Badve C et
al. Proc ISMRM 22 (2014) p. 3234. 3.
Ostrom QT et al. Neuro Oncol (2015) 16
(suppl 10): x1-x36. 4. Jiang Y, et al,
(2014) MRM. 5. McSheehy et al. Clin
Cancer Research (2010): p.212. 6. Weidensteiner et al. BMC Cancer
(2014): p. 88.