Assessment of disease severity in late infantile neuronal ceroid lipofuscinosis using multiparametric MR imaging

J. P. Dyke, D. Sondhi, H. U. Voss, D. C. Shungu, X. Mao, K. Yohay, S. Worgall, N. R. Hackett, C. Hollmann, M. E. Yeotsas, A. L. Jeong, B. Van de Graaf, I. Cao, S. M. Kaminsky, L. A. Heier, K. D. Rudser, M. M. Souweidane, M. G. Kaplitt, B. Kosofsky, R. G. CrystalD. Ballon

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


BACKGROUND AND PURPOSE: LINCL is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene that encodes for tripeptidyl peptidase 1, a lysosomal enzyme necessary for the degradation of products of cellular metabolism. With the goal of developing quantitative noninvasive imaging biomarkers sensitive to disease progression, we evaluated a 5-component MR imaging metric and tested its correlation with a clinically derived disease-severity score. MATERIALS AND METHODS: MR imaging parameters were measured across the brain, including quantitative measures of the ADC, FA, nuclear spin-spin relaxation times (T2), volume percentage of CSF (%CSF), and NAA/Cr ratios. Thirty MR imaging datasets were prospectively acquired from 23 subjects with LINCL (2.5- 8.4 years of age; 8 male/15 female). Whole-brain histograms were created, and the mode and mean values of the histograms were used to characterize disease severity. RESULTS: Correlation of single MR imaging parameters against the clinical disease-severity scale yielded linear regressions with R2 ranging from 0.25 to 0.70. Combinations of the 5 biomarkers were evaluated by using PCA. The best combination included ADC, %CSF, and NAA/Cr (R2 = 0.76, P < .001). CONCLUSIONS: The multiparametric disease-severity score obtained from the combination of ADC, %CSF, and NAA/Cr whole-brain MR imaging techniques provided a robust measure of disease severity, which may be useful in clinical therapeutic trials of LINCL in which an objective assessment of therapeutic response is desired.

Original languageEnglish (US)
Pages (from-to)884-889
Number of pages6
JournalAmerican Journal of Neuroradiology
Issue number4
StatePublished - Apr 2013


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