Assessing disease severity in late infantile neuronal ceroid lipofuscinosis using quantitative MR diffusion-weighted imaging.
OBJECTIVE
Late infantile neuronal ceroid lipofuscinosis (LINCL), a form of Batten disease, is a fatal neurodegenerative genetic disorder, diagnosed via DNA testing, that affects approximately 200 children in the United States at any one time. This study was conducted to evaluate whether quantitative data derived by diffusion-weighted MR imaging (DWI) techniques can supplement clinical disability scale information to provide a quantitative estimate of neurodegeneration, as well as disease progression and severity.


METHODS
This study prospectively analyzed 32 DWI examinations from 18 patients having confirmed LINCL at various stages of disease. A whole-brain apparent diffusion coefficient (ADC) histogram was fitted with a dual Gaussian function combined with a function designed to model voxels containing a partial volume fraction of brain parenchyma versus CSF. Previously published whole-brain ADC values of age-matched control subjects were compared with those of the LINCL patients. Correlations were tested between the peak ADC of the fitted histogram and patient age, disease severity, and a CNS disability scale adapted for LINCL.


RESULTS
ADC values assigned to brain parenchyma were higher than published ADC values for age-matched control subjects. ADC values between patients and control subjects began to differ at 5 years of age based on 95% confidence intervals. ADC values had a nearly equal correlation with patient age (R2=0.71) and disease duration (R2=0.68), whereas the correlation with the central nervous system disability scale (R2=0.27) was much weaker.


CONCLUSIONS
This study indicates that brain ADC values acquired using DWI may be used as an independent measure of disease severity and duration in LINCL.
Dyke
J P
JP
Citigroup Biomedical Imaging Center, Department of Radiology, Weill Medical College of Cornell University, New York, NY 10021, USA. jpd2001@med.cornell.edu
Voss
H U
HU
Sondhi
D
D
Hackett
N R
NR
Worgall
S
S
Heier
L A
LA
Kosofsky
B E
BE
Uluğ
A M
AM
Shungu
D C
DC
Mao
X
X
Crystal
R G
RG
Ballon
D
D
D000293:Adolescent; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D009472:Neuronal Ceroid-Lipofuscinoses / Q000145:classification / Q000175:diagnosis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
AJNR Am J Neuroradiol. 1998 Aug;19(7):1373-7
9726485
Am J Med Genet. 1995 Jun 5;57(2):137-41
7668317
Expert Rev Neurother. 2005 Sep;5(5):663-70
16162090
J Neurol Neurosurg Psychiatry. 2001 Mar;70(3):318-22
11181852
AJNR Am J Neuroradiol. 2003 May;24(5):850-4
12748084
BMC Bioinformatics. 2003 Jul 31;4:31
12892571
Acta Neuropathol. 2006 Feb;111(2):168-77
16465529
Neuropediatrics. 2004 Feb;35(1):27-35
15002049
Eur Radiol. 2004 Mar;14(3):425-30
14618363
IEEE Trans Med Imaging. 1998 Feb;17(1):74-86
9617909
Hum Gene Ther. 2004 Nov;15(11):1131-54
15610613
Curr Opin Neurol. 2005 Aug;18(4):370-5
16003111
Neurology. 2002 Sep 24;59(6):938-40
12297586
Arch Neurol. 2001 Nov;58(11):1793-8
11708986
AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1078-83
10871018
Am J Med Genet. 2002 Nov 1;112(4):347-54
12376936
Radiology. 2004 Sep;232(3):867-73
15215553
Neuroradiology. 1997 May;39(5):371-7
9189886
Neuroimaging Clin N Am. 2006 Feb;16(1):19-43, vii
16543084
Eur J Paediatr Neurol. 2001;5 Suppl A:157-61
11588989
Acta Paediatr Scand. 1981 Nov;70(6):857-60
7324937