Validation of a Standardized Normalization Template for Statistical Parametric Mapping Analysis of 123I-FP-CIT Images

123I-FP-CIT (123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) is a SPECT dopamine transporter (DAT) tracer that probes dopaminergic cell loss in Parkinson's disease (PD). Quantification of 123I-FP-CIT images is performed at equilibrium using a ratio (BR) of specific (striatal) to nonspecific (occipital) uptake with values obtained from regions of interest drawn manually over these structures. Statistical parametric mapping (SPM) is a fully automated voxel-based statistical approach that has great potential in the context of DAT imaging. However, the accuracy of the spatial normalization provided by SPM has not been validated for 123I-FP-CIT images. Our first aim was to create an 123I-FP-CIT template that does not require the acquisition of patient-specific MRI and to validate the spatial normalization procedure. Next, we hypothesized that this customized template could be used by different SPECT centers without affecting the outcomes of imaging analyses. Methods: The spatial normalization to the customized template created with SPM (template A1) was validated using 123I-FP-CIT images obtained from 6 subjects with essential tremor (ET) with normal DAT status and 6 PD patients. Variability in BR values due to the normalization was evaluated using striatal volume of interest (VOI). To determine whether different SPECT centers could use a unique 123I-FP-CIT template, we generated 3 other 123I-FP-CIT templates using different subjects and image-processing schemes. The interchangeability of these templates was assessed using (a) putamen BR values analyzed with the intraclass correlation coefficient (ICC) and the Bland–Altman graphical analysis, and (b) SPM analysis comparing the results of group comparisons—that is, ET versus PD, obtained after normalization to each of the 4 templates. Results: There was no significant difference between pre- and postnormalization striatal BR values in our study. The mean variability calculated with putamen VOI values after normalization to each template was <10%, with the lowest ICC of 98%. Intergroup analyses performed with VOI and SPM approaches provided similar results independently of the template used. Conclusion: SPM normalization was accurate even in subjects with low striatal 123I-FP-CIT uptake, making it a promising approach for automatic analysis of 123I-FP-CIT images using a single customized template at different centers.

[1]  Willibald Gerschlager,et al.  Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: A longitudinal β‐CIT SPECT study , 2002, Movement disorders : official journal of the Movement Disorder Society.

[2]  N. Alpert,et al.  Comparison of 4 methods for quantification of dopamine transporters by SPECT with [123I]IACFT. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  V. Dhawan,et al.  Parametric mapping of [18F]FPCIT binding in early stage Parkinson's disease: A PET study , 2002, Synapse.

[4]  R. Felix,et al.  Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients , 2005, Journal of Neural Transmission.

[5]  Vesna Sossi,et al.  PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation. , 2005, Brain : a journal of neurology.

[6]  Jan Booij,et al.  The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism , 2001, European Journal of Nuclear Medicine.

[7]  J. C. Stoof,et al.  Iodine-123-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iod ophenyl)tropane SPECT in healthy controls and early-stage, drug-naive Parkinson's disease. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  Jan Booij,et al.  Iodine-123-N-ω-Fluoropropyl-2β-Carbomethoxy-3β-(4-Iodophenyl)Tropane SPECT in Healthy Controls and Early-Stage, Drug-Naive Parkinson's Disease , 1998 .

[9]  Karl J. Friston,et al.  Rapid Assessment of Regional Cerebral Metabolic Abnormalities in Single Subjects with Quantitative and Nonquantitative [18F]FDG PET: A Clinical Validation of Statistical Parametric Mapping , 1999, NeuroImage.

[10]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[11]  Marc Laruelle,et al.  Methyl 3β‐(4‐[125I]Iodophenyl)Tropane‐2β‐Carboxylate In Vitro Binding to Dopamine and Serotonin Transporters Under “Physiological” Conditions , 1994 .

[12]  M. Kaufman,et al.  Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's‐diseased striatum , 1991, Synapse.

[13]  Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. , 2002, JAMA.

[14]  P. Remy,et al.  Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT‐PD) , 1999, Movement disorders : official journal of the Movement Disorder Society.

[15]  M Laruelle,et al.  Methyl 3 beta-(4-[125I]iodophenyl)tropane-2 beta-carboxylate in vitro binding to dopamine and serotonin transporters under "physiological" conditions. , 1994, Journal of neurochemistry.

[16]  Ralph Myers,et al.  Assessment of Spatial Normalization of PET Ligand Images Using Ligand-Specific Templates , 1999, NeuroImage.

[17]  O. Pogarell,et al.  Striatal dopamine transporter binding in early to moderately advanced Parkinson's disease: monitoring of disease progression over 2 years , 2001, Nuclear medicine communications.

[18]  J D Speelman,et al.  One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [123I]FPCIT SPECT. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  Akinori Nakamura,et al.  Cognitive- and motor-related regions in Parkinson's disease: FDOPA and FDG PET studies , 2004, NeuroImage.

[20]  J. Seibyl,et al.  Do dopamine agonists or levodopa modify Parkinson's disease progression? , 2002, European journal of neurology.

[21]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[22]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[23]  André Aurengo,et al.  Scatter and cross-talk corrections in simultaneous Tc-99m/I-123 brain SPECT using constrained factor analysis and artificial neural networks , 2000 .

[24]  J. Seibyl,et al.  [123I]β-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression , 2001, Neurology.

[25]  D J Wyper,et al.  Correlation of Parkinson's disease severity and duration with 123I‐FP‐CIT SPECT striatal uptake , 2000, Movement disorders : official journal of the Movement Disorder Society.

[26]  S J Kish,et al.  [11C]RTI‐32 PET studies of the dopamine transporter in early dopa‐naive Parkinson's disease , 1997, Neurology.

[27]  J. Booij,et al.  [123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease , 2001, Journal of Neural Transmission.

[28]  D. Altman,et al.  Statistics Notes: Measurement error and correlation coefficients , 1996, BMJ.

[29]  K. Ishii,et al.  Statistical brain mapping of 18F-FDG PET in Alzheimer's disease: validation of anatomic standardization for atrophied brains. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  J. Ashburner,et al.  Nonlinear spatial normalization using basis functions , 1999, Human brain mapping.

[31]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[32]  V J Cunningham,et al.  11C-Diprenorphine Binding in Huntington's Disease: A Comparison of Region of Interest Analysis with Statistical Parametric Mapping , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[33]  Chris Rorden,et al.  Spatial Normalization of Brain Images with Focal Lesions Using Cost Function Masking , 2001, NeuroImage.

[34]  P B Hoffer,et al.  SPECT imaging of dopamine transporters in human brain with iodine-123-fluoroalkyl analogs of beta-CIT. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[35]  P. Seeman,et al.  The Dopamine Transporter Is Absent in Parkinsonian Putamen and Reduced in the Caudate Nucleus , 1991, Journal of neurochemistry.

[36]  Karl J. Friston,et al.  Statistical parametric mapping , 2013 .

[37]  Manuel Desco,et al.  Influence of the normalization template on the outcome of statistical parametric mapping of PET scans , 2003, NeuroImage.