Synopsis

This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MR) for structural/metabolic abnormality in infantile spasms. We evaluated both the morphology and parameters of PET/MR images by qualitative and quantitative assessment. Our results showed quantitative analysis of PET/MR images could improve the diagnosis of etiologic abnormality. Furthermore, the classification of etiology using PET/MR can indicate the efficacy of adrenocorticotropic hormone (ACTH) treatment and provide valuable information for surgery plan.

Introduction

Infantile spasms（IS）is an age-dependent epileptic encephalopathy that occurs in infancy. It can be etiologically classified into structure/metabolic abnormality，genetic and unknown etiology groups. The medication with adrenocorticotropic hormone (ACTH) is the first choice for IS. However，the long-term prognosis of each etiologic group is quite heterogeneous and the side effect could not be ignored [1]. Furthermore, some cases with diagnosis of unknown etiology in the early days were found to evolve with structural/metabolic abnormality in the follow-up imaging [2]. Accurate diagnosis with etiology during the early stage of IS is beneficial for optimal clinical strategy.

The purpose of this study was to investigate the diagnostic performance of PET/MR in IS using both qualitative and quantitative assessment of morphology and metabolism, as well as to estimate the efficacy of ACTH therapy in different etiology groups classified by PET/MR.

Materials and methods

According to the diagnostic guideline of the International League against Epilepsy (ILAE) 2014, patients with IS were included. The patients who were diagnosed or suspected with genetic, immune or infectious etiology or could not cooperate during PET/MR examination were excluded.

All patients were scanned on a whole-body PET/MR scanner (Biograph mMR, Siemens Healthcare, Erlangen, Germany). The PET/MR sequences include: (1) 18F-FDG PET; (2) an ultrashort echo sequence for PET attenuation correction; b. Transversal and coronal T2 fluid-attenuated inversion recovery; c. Sagittal T1-weighted (T1w) imaging with three-dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE).

Qualitative morphology analysis of PET/MR images was implemented in a double-blind method. The abnormal spot localized with both MR and PET images were considered as the epileptic foci. These detected cases were included into the structural/metabolic group.

For the remaining cases, quantitative analysis was performed using an in-house developed software, BrainQuan, based on the UNC Infant 0-1-2 Atlases [3]. For the automated segmented brain ROIs, the volume and corresponding mean value of standardized uptake value (SUVmean) were calculated to detect slight abnormality in the new structural/metabolic cases. Asymmetry index（AI）were calculated for ROIs volume and corresponding SUVmean in bilateral sides: AI=[(R-L)/(R+L)]×100%×2. The absolute value of AI >15% was defined to be asymmetric [4], and the corresponding cases were considered with the structural/metabolic abnormality.

The patients with no positive findings from PET and MR images were assigned to unknown etiology group.

All patients were scheduled to complete the entire ACTH treatment within 4 weeks of the PET/MR examination and were classified into ACTH treatment effective and ineffective group according to the evaluation with both EEG and symptoms. The efficacy of ACTH treatment among different groups was analyzed using significance difference test (t-test and Chi-square test).

Results

73 children with IS were enrolled in the study and divided into two groups with/without obvious structural and metabolic abnormalities according to qualitative morphological analysis of PET/MR images. According to the significance difference test, there was no significant difference in gender and age of onset between the two groups. EEG result had a statistically different distribution between different etiological groups. As shown in Table 1, 39 cases were consistently identified as abnormal with PET/MR images, considering obvious focal cortical/white matter dysplasia，gray matter ectopic and schizencephaly. A typical case is shown in Figure 1. The other 34 subjects had no obvious abnormalities and were further analyzed quantitatively. Among them, 22 cases were newly found with statistical differences between bilateral brain regions in both PET and T1w images. A newly detected case is shown in Figure 2. The abnormalities of the remaining 12 cases still could not be identified and thus classified as unknown etiology. The whole flow chart of the PET/MR analysis results is shown in Figure 3.

As shown in Figure 4, the effective rates of qualitatively abnormal, quantitatively abnormal and unknown etiology groups were 23.1% (9/39), 40.9% (9/22) and 58.3% (7/12). According to the Chi-square test with multiple comparison correction, the efficacy with ACTH treatment among different groups of diagnostic results was statistically significant (χ2 = 11.31，p<0.01).

Discussion and Conclusion

Acknowledgements

References

【1】 Song, J. M., Hahn, J., Kim, S. H., & Chang, M. J. (2017). Efficacy of treatments for infantile spasms: a systematic review. Clinical neuropharmacology, 40(2), 63-84.

【2】 Gaillard WD, Chiron C, Cross JH, et al. Guidelines for imaging infants and children with recent-onset epilepsy. Epilepsia. 2009; 50:2147-2153.

【3】 Shi F, Yap P-T, Wu G, et al. Infant Brain Atlases from Neonates to 1- and 2-Year-Olds. PLOS ONE 2011, 6(4): e18746.

【4】 Wu HB, Wang QS, Wang MF, et al．The localization of epileptic foci in 18 F- FDG PET imaging and its use in surgical therapy. [J].Chin J N ucl Med.2006, 26(2):69- 72．