RT Journal Article
SR Electronic
T1 Assessment of Disease Severity in Late Infantile Neuronal Ceroid Lipofuscinosis Using Multiparametric MR Imaging
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
SP 884
OP 889
DO 10.3174/ajnr.A3297
VO 34
IS 4
A1 J.P. Dyke
A1 D. Sondhi
A1 H.U. Voss
A1 D.C. Shungu
A1 X. Mao
A1 K. Yohay
A1 S. Worgall
A1 N.R. Hackett
A1 C. Hollmann
A1 M.E. Yeotsas
A1 A.L. Jeong
A1 B. Van de Graaf
A1 I. Cao
A1 S.M. Kaminsky
A1 L.A. Heier
A1 K.D. Rudser
A1 M.M. Souweidane
A1 M.G. Kaplitt
A1 B. Kosofsky
A1 R.G. Crystal
A1 D. Ballon
YR 2013
UL http://www.ajnr.org/content/34/4/884.abstract
AB 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. FAfractional anisotropyGMgray matterLINCLlate infantile neuronal ceroid lipofuscinosisMRIDSSMR imaging disease-severity scorePCAprincipal component analysis