Characterization of Pediatric Brain Tumors and Treatment Effect using Magnetic Resonance Fingerprinting:  Initial Experience
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.

Figures

Figure 1: Regions of interest demonstrated on a T2 relaxation time map in a child with thalamic tumor

Figure 2: Relaxometry values for (A&B) tumor, peritumor and contralateral white matter (CWM) and (C&D) high vs low grade tumors

Figure 3: Longitudinal T1 values in children treated (A) and untreated (B) for primary brain tumors



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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