Assessment of Disease Severity in Late Infantile Neuronal Ceroid Lipofuscinosis Using Multiparametric Magnetic Resonance Imaging
| Autor: | Dyke, J. P., Sondhi, D., Voss, H. U., Shungu, D. C., Mao, X., Yohay, K., Worgall, S., Hackett, N. R., Hollmann, C., Yeotsas, M. E., Jeong, A.L., Van de Graaf, B., Cao, I., Kaminsky, S. M., Heier, L. A., Rudser, K.D., Souweidane, M. M., Kaplitt, M.G., Kosofsky, B., Crystal, R. G., Ballon, D. |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Databases Factual Tripeptidyl-Peptidase 1 Age Factors Brain Aminopeptidases Magnetic Resonance Imaging Severity of Illness Index Article Neuronal Ceroid-Lipofuscinoses Child Preschool Disease Progression Humans Female Serine Proteases Artifacts Child Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Biomarkers |
| Popis: | 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.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.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).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. |
| Databáze: | OpenAIRE |
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