title: Assessment of disease severity in late infantile neuronal ceroid lipofuscinosis using multiparametric MR imaging.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, New York 10021, USA. jpd2001@med.cornell.edu
authors.forename: J P
authors.initials: JP
authors.lastname: Dyke
authors.forename: D
authors.initials: D
authors.lastname: Sondhi
authors.forename: H U
authors.initials: HU
authors.lastname: Voss
authors.forename: D C
authors.initials: DC
authors.lastname: Shungu
authors.forename: X
authors.initials: X
authors.lastname: Mao
authors.forename: K
authors.initials: K
authors.lastname: Yohay
authors.forename: S
authors.initials: S
authors.lastname: Worgall
authors.forename: N R
authors.initials: NR
authors.lastname: Hackett
authors.forename: C
authors.initials: C
authors.lastname: Hollmann
authors.forename: M E
authors.initials: ME
authors.lastname: Yeotsas
authors.forename: A L
authors.initials: AL
authors.lastname: Jeong
authors.forename: B
authors.initials: B
authors.lastname: Van de Graaf
authors.forename: I
authors.initials: I
authors.lastname: Cao
authors.forename: S M
authors.initials: SM
authors.lastname: Kaminsky
authors.forename: L A
authors.initials: LA
authors.lastname: Heier
authors.forename: K D
authors.initials: KD
authors.lastname: Rudser
authors.forename: M M
authors.initials: MM
authors.lastname: Souweidane
authors.forename: M G
authors.initials: MG
authors.lastname: Kaplitt
authors.forename: B
authors.initials: B
authors.lastname: Kosofsky
authors.forename: R G
authors.initials: RG
authors.lastname: Crystal
authors.forename: D
authors.initials: D
authors.lastname: Ballon
mesh_terms: D000367:Age Factors; D000626:Aminopeptidases / Q000235:genetics; D016477:Artifacts; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000473:pathology*; D057057:Serine Proteases / Q000235:genetics; D012720:Severity of Illness Index; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D015415:Biomarkers; D000091346:Tripeptidyl-Peptidase 1; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human