Assessment of disease severity in late infantile neuronal ceroid lipofuscinosis using multiparametric MR imaging.
Assessment of disease severity in late infantile neuronal ceroid lipofuscinosis using multiparametric MR imaging.
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DOI：
10.3174/ajnr.a3297
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Ballon D
中科院分区：
文献类型：
--
作者：
Dyke JP;Sondhi D;Voss HU;Shungu DC;Mao X;Yohay K;Worgall S;Hackett NR;Hollmann C;Yeotsas ME;Jeong AL;Van de Graaf B;Cao I;Kaminsky SM;Heier LA;Rudser KD;Souweidane MM;Kaplitt MG;Kosofsky B;Crystal RG;Ballon D
Late infantile neuronal ceroid lipofuscinosis (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 degradation of products of cellular metabolism. With the goal of developing quantitative, non-invasive imaging biomarkers sensitive to disease progression, we evaluated a five-component magnetic resonance imaging metric, and tested its correlation with a clinically derived disease severity score. MRI parameters were measured across the brain, including quantitative measures of the apparent diffusion coefficient (ADC), diffusion fractional anisotropy (FA), nuclear spin-spin relaxation times (T2), volume percentage of cerebrospinal fluid (%CSF), and N-acetylaspartate to creatine ratios (NAA/Cr). Thirty MRI data sets were prospectively acquired from twenty three subjects with LINCL [2.5–8.4 yr, 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 magnetic resonance imaging parameters against the clinical disease severity scale yielded linear regressions with R2 ranging from 0.25 to 0.70. Combinations of the five biomarkers were evaluated using principal component analysis (PCA). The best combination included ADC, %CSF, and NAA/Cr (R2 = 0.76, p < 0.001). The multiparametric disease severity score obtained from the combination of ADC, %CSF, and NAA/Cr whole brain MRI techniques provided a robust measure of disease severity that may be useful in clinical therapeutic trials of LINCL where objective assessment of therapeutic response is desired.
