Abstract
The need for algorithms that capture subject-specific abnormalities (SSA) in neuroimaging data is increasingly recognized across many neuropsychiatric disorders. However, the effects of initial distributional properties (e.g., normal versus non-normally distributed data), sample size, and typical preprocessing steps (spatial normalization, blurring kernel and minimal cluster requirements) on SSA remain poorly understood. The current study evaluated the performance of several commonly used z-transform algorithms [leave-one-out (LOO); independent sample (IDS); Enhanced Z-score Microstructural Assessment of Pathology (EZ-MAP); distribution-corrected z-scores (DisCo-Z); and robust z-scores (ROB-Z)] for identifying SSA using simulated and diffusion tensor imaging data from healthy controls (N = 50). Results indicated that all methods (LOO, IDS, EZ-MAP and DisCo-Z) with the exception of the ROB-Z eliminated spurious differences that are present across artificially created groups following a standard z-transform. However, LOO and IDS consistently overestimated the true number of extrema (i.e., SSA) across all sample sizes and distributions. The EZ-MAP and DisCo-Z algorithms more accurately estimated extrema across most distributions and sample sizes, with the exception of skewed distributions. DTI results indicated that registration algorithm (linear versus non-linear) and blurring kernel size differentially affected the number of extrema in positive versus negative tails. Increasing the blurring kernel size increased the number of extrema, although this effect was much more prominent when a minimum cluster volume was applied to the data. In summary, current results highlight the need to statistically compare the frequency of SSA in control samples or to develop appropriate confidence intervals for patient data.
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References
Bigler, E. D., Abildskov, T. J., Petrie, J., Farrer, T. J., Dennis, M., Simic, N., et al. (2013). Heterogeneity of brain lesions in pediatric traumatic brain injury. Neuropsychology, 27(4), 438–451.
Birmingham, A., Selfors, L. M., Forster, T., Wrobel, D., Kennedy, C. J., Shanks, E., et al. (2009). Statistical methods for analysis of high-throughput RNA interference screens. Nature Methods, 6(8), 569–575.
Booth, B. G., Miller, S. P., Brown, C. J., Poskitt, K. J., Chau, V., Grunau, R. E., et al. (2016). STEAM — Statistical template estimation for abnormality mapping: A personalized DTI analysis technique with applications to the screening of preterm infants. NeuroImage, 125, 705–723.
Bouix, S., Pasternak, O., Rathi, Y., Pelavin, P. E., Zafonte, R., & Shenton, M. E. (2013). Increased gray matter diffusion anisotropy in patients with persistent post-concussive symptoms following mild traumatic brain injury. PloS One, 8(6), e66205.
Ceritoglu, C., Oishi, K., Li, X., Chou, M. C., Younes, L., Albert, M., et al. (2009). Multi-contrast large deformation diffeomorphic metric mapping for diffusion tensor imaging. NeuroImage, 47(2), 618–627.
Commowick, O. & Stamm, A. (2012). Non-local robust detection of DTI white matter differences with small databases. In International Conference on Medical Image Computing and Computer-Assisted Intervention (pp. 476–484). Berlin Heidelburg: Springer.
Commowick, O., Fillard, P., Clatz, O., & Warfield, S. K. (2008). Detection of DTI white matter abnormalities in multiple sclerosis patients. Medical Image Computer Assist Interventions, 11(Pt 1), 975–982.
Cox, R., & Glen, D. (2006). Efficient, robust, nonlinear, and guaranteed positive definite diffusion tensor estimation. In Seattle: Proceedings of the International Society for Magnetic Resonance and Medicine, 14th Scientific Meeting.
Ding, Z., Gore, J. C., & Anderson, A. W. (2005). Reduction of noise in diffusion tensor images using anisotropic smoothing. Magnetic Resonance in Medicine, 53(2), 485–490.
Eklund, A., Nichols, T., Andersson, M., & Knutsson, H. (2015). Empirically investigating the statistical validity of SPM, FSL and AFNI for single subject fMRI analysis. In (pp. 1376–1380). IEEE 12th International Symposium on Biomedical Imaging (ISBI).
Eklund, A., Nichols, T. E., & Knutsson, H. (2016). Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences of the United States of America, 113(28), 7900–7905.
Friston, K. J., Holmes, A., Poline, J. B., Price, C. J., & Frith, C. D. (1996). Detecting activations in PET and fMRI: Levels of inference and power. NeuroImage, 4(3 Pt 1), 223–235.
Ge, Y., Law, M., & Grossman, R. I. (2005). Applications of diffusion tensor MR imaging in multiple sclerosis. Annals of the New York Academy of Sciences, 1064, 202–219.
Gebhard, T., Koerte, I., & Bouix, S. (2015). Sample size estimation for outlier detection. In N. Navab, J. Hornegger, W. M. Wells, & A. F. Frangi (Eds.), Medical image computing and computer-assisted intervention - MICCAI 2015 (pp. 743–750). Switzerland: Springer International Publishing.
Hayasaka, S., Phan, K. L., Liberzon, I., Worsley, K. J., & Nichols, T. E. (2004). Nonstationary cluster-size inference with random field and permutation methods. NeuroImage, 22(2), 676–687.
Jones, D. K., & Cercignani, M. (2010). Twenty five pitfalls in the analysis of diffusion MRI data. NMR in Biomedicine, 23(7), 803–820.
Kim, N., Branch, C. A., Kim, M., & Lipton, M. L. (2013). Whole brain approaches for identification of microstructural abnormalities in individual patients: Comparison of techniques applied to mild traumatic brain injury. PloS One, 8(3), e59382.
Klein, A., Andersson, J., Ardekani, B. A., Ashburner, J., Avants, B., Chiang, M. C., et al. (2009). Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration. NeuroImage, 46(3), 786–802.
Landman, B. A., Yang, X., & Kang, H. (2012). Do we really need robust and alternative inference methods for brain MRI? In (pp. 77–93). Springer.
Lindquist, M. A. (2008). The statistical analysis of fMRI data. Statistical Science, 23(4), 439–464.
Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H. (2000). Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Annals of Neurology, 47(6), 707–717.
Mac Donald, C. L., Dikranian, K., Bayly, P., Holtzman, D., & Brody, D. (2007). Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. The Journal of Neuroscience, 27(44), 11869–11876.
Mayer, A. R., Bedrick, E. J., Ling, J. M., Toulouse, T., & Dodd, A. (2014). Methods for identifying subject-specific abnormalities in neuroimaging data. Human Brain Mapping, 35(11), 5457–5470.
Mori, S., & van Zijl, P. C. (2007). Human white matter atlas. The American Journal of Psychiatry, 164(7), 1005.
Nichols, T., & Hayasaka, S. (2003). Controlling the familywise error rate in functional neuroimaging: A comparative review. Statistical Methods in Medical Research, 12(5), 419–446.
Nichols, T. E., & Holmes, A. P. (2002). Nonparametric permutation tests for functional neuroimaging: A primer with examples. Human Brain Mapping, 15(1), 1–25.
Parrish, T. B., Gitelman, D. R., LaBar, K. S., & Mesulam, M. M. (2000). Impact of signal-to-noise on functional MRI. Magnetic Resonance in Medicine, 44(6), 925–932.
Pasternak, O., Koerte, I. K., Bouix, S., Fredman, E., Sasaki, T., Mayinger, M., et al. (2014). Hockey concussion education project, part 2. Microstructural white matter alterations in acutely concussed ice hockey players: A longitudinal free-water MRI study. Journal of Neurosurgery, 120(4), 873–881.
Rosenberg, G. A. (2012). Neurological diseases in relation to the blood-brain barrier. Journal of Cerebral Blood Flow and Metabolism, 32(7), 1139–1151.
Saad, Z. S., Glen, D. R., Chen, G., Beauchamp, M. S., Desai, R., & Cox, R. W. (2009). A new method for improving functional-to-structural MRI alignment using local Pearson correlation. NeuroImage, 44(3), 839–848.
Schwarz, C. G., Reid, R. I., Gunter, J. L., Senjem, M. L., Przybelski, S. A., Zuk, S. M., et al. (2014). Improved DTI registration allows voxel-based analysis that outperforms tract-based spatial statistics. NeuroImage, 94, 65–78.
Shaker, M., Erdogmus, D., Dy, J., & Bouix, S. (2017). Subject-specific abnormal region detection in traumatic brain injury using sparse model selection on high dimensional diffusion data. Medical Image Analysis.
Smith, S. M., & Nichols, T. E. (2009). Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage, 44(1), 83–98.
Suri, A. K., Fleysher, R., & Lipton, M. L. (2015). Subject based registration for individualized analysis of diffusion tensor MRI. PloS One, 10(11), e0142288.
Watts, R., Thomas, A., Filippi, C. G., Nickerson, J. P., & Freeman, K. (2014). Potholes and molehills: Bias in the diagnostic performance of diffusion-tensor imaging in concussion. Radiology, 272(1), 217–223.
White, T., Schmidt, M., & Karatekin, C. (2009). White matter ‘potholes’ in early-onset schizophrenia: A new approach to evaluate white matter microstructure using diffusion tensor imaging. Psychiatry Research, 174(2), 110–115.
Woo, C. W., Krishnan, A., & Wager, T. D. (2014). Cluster-extent based thresholding in fMRI analyses: Pitfalls and recommendations. NeuroImage, 91, 412–419.
Acknowledgements
This work was supported by the National Institutes of Health (grant numbers 1R01MH101512-01A1 and 1R01NS098494-01A1 to A.M.). The funding agencies had no involvement in the study design, data collection, analyses, writing of the manuscript, or decisions related to submission for publication. We would also like to thank Diana South and Catherine Smith for their assistance with data collection.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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Mayer, A.R., Dodd, A.B., Ling, J.M. et al. An evaluation of Z-transform algorithms for identifying subject-specific abnormalities in neuroimaging data. Brain Imaging and Behavior 12, 437–448 (2018). https://doi.org/10.1007/s11682-017-9702-2
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DOI: https://doi.org/10.1007/s11682-017-9702-2