Twenty-five pitfalls in the analysis of diffusion MRI data†
Corresponding Author
Derek K. Jones
CUBRIC, Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff, UK
CUBRIC, School of Psychology, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.Search for more papers by this authorMara Cercignani
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy
Search for more papers by this authorCorresponding Author
Derek K. Jones
CUBRIC, Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff, UK
CUBRIC, School of Psychology, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.Search for more papers by this authorMara Cercignani
Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy
Search for more papers by this authorThis article is published in NMR in Biomedicine as a special issue on Progress in Diffusion-Weighted Imaging: Concepts, Techniques, and Applications to the Central Nervous System, edited by Jens H. Jensen and Joseph A. Helpern, Center for Biomedical Imaging, Department of Radiology, NYU School of Medicine, New York, NY, USA.
Abstract
Obtaining reliable data and drawing meaningful and robust inferences from diffusion MRI can be challenging and is subject to many pitfalls. The process of quantifying diffusion indices and eventually comparing them between groups of subjects and/or correlating them with other parameters starts at the acquisition of the raw data, followed by a long pipeline of image processing steps. Each one of these steps is susceptible to sources of bias, which may not only limit the accuracy and precision, but can lead to substantial errors. This article provides a detailed review of the steps along the analysis pipeline and their associated pitfalls. These are grouped into 1 pre-processing of data; 2 estimation of the tensor; 3 derivation of voxelwise quantitative parameters; 4 strategies for extracting quantitative parameters; and finally 5 intra-subject and inter-subject comparison, including region of interest, histogram, tract-specific and voxel-based analyses. The article covers important aspects of diffusion MRI analysis, such as motion correction, susceptibility and eddy current distortion correction, model fitting, region of interest placement, histogram and voxel-based analysis. We have assembled 25 pitfalls (several previously unreported) into a single article, which should serve as a useful reference for those embarking on new diffusion MRI-based studies, and as a check for those who may already be running studies but may have overlooked some important confounds. While some of these problems are well known to diffusion experts, they might not be to other researchers wishing to undertake a clinical study based on diffusion MRI. Copyright © 2010 John Wiley & Sons, Ltd.
REFERENCES
- 1 Le Bihan D, Breton E. Imagerie de diffusion in vivo par résonance magnétique nucléaire. C.R. Acad. Sc: Paris, 1985; T.301, Série II, 1109–1112.
- 2 Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval Jeantet M. MR Imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology. 1986; 161: 401–407.
- 3 Basser PJ, Mattiello J, Le Bihan D. MR diffusion tensor spectroscopy and imaging. Biophys. J. 1994; 66: 259–267.
- 4 Basser PJ, Mattiello J, Le Bihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J. Magn. Reson. 1994; 103: 247–254.
- 5 Jones DK. Studying connections in the living human brain with diffusion MRI. Cortex. 2008; 44: 936–952.
- 6 Sodickson DK, Manning WJ. Simultaneous acquisition of spatial harmonics (SMASH): fast imaging with radiofrequency coil arrays Magn. Reson. Med. 1997; 38: 591–603.
- 7
Pruessmann KP,
Weiger M,
Scheidegger MB.
Boesiger P SENSE: sensitivity encoding for fast MRI.
Magn. Reson. Med.
1999;
42:
952–962.
10.1002/(SICI)1522-2594(199911)42:5<952::AID-MRM16>3.0.CO;2-S CASPubMedWeb of Science®Google Scholar
- 8 Griswold MA, Jakob PM, Heidemann RM, Nittka M, Jellus V, Wang J, Kiefer B, Haase A. 135. Generalized autocalibrating partially parallel acquisitions (GRAPPA). Magn. Reson. Med. 2002; 47: 1202–1210.
- 9 Reese TG, Heid O, Weisskoff RM, Wedeen VJ. Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magn. Reson. Med. 2003; 49: 177–182.
- 10 Jezzard P, Balaban RS. Correction for geometric distortion in echo planar images from B0 field variations. Magn. Reson. Med. 1995; 34: 65–73.
- 11 Chang H, Fitzpatrick JM. A technique for accurate magnetic resonance imaging in the presence of field inhomogeneities. IEEE Transact. Medic.Imaging. 1992; 11: 319–329.
- 12 Reber PJ, Wong EC, Buxton RB, Frank LR. Correction of off resonance-related distortion in echo-planar imaging using EPI-based field maps. Magn. Reson. Med. 1998; 39: 328–330.
- 13 Morgan PS, Bowtell RW, McIntyre DJ, Worthington BS. Correction of spatial distortion in EPI due to inhomogeneous static magnetic fields using the reversed gradient method. J. Magn. Reson. Imaging. 2004; 19: 499–507.
- 14 Embleton KV, Haroon HA, Morris DM, Ralph MA, Parker GJ. Distortion correction for diffusion-weighted MRI tractography and fMRI in the temporal lobes. Hum Brain Mapp. 2010 Feb 8.
- 15 Bammer R, Auer M, Keeling SL, Augustin M, Stables LA, Prokesch RW, Stollberger R, Moseley ME, Fazekas F. Diffusion tensor imaging using single-shot SENSE-EPI. Magn. Reson. Med. 2002; 48: 128–36.
- 16 Andersson JL, Skare S. A model-based method for retrospective correction of geometric distortions in diffusion-weighted EPI. NeuroImage. 2002; 16: 177–199.
- 17 Andersson JL, Richter M, Richter W, Skare S, Nunes RG, Robson MD, Behrens TE. Effects of susceptibility distortions on tractography. Proceedings of the 12th Annual Meeting ISMRM, Kyoto, Japan, 2004; 87.
- 18 Lee J, Lazar M, Lee J, Holden J, Terasawa-Grilley E, Alexander AL. Correction of Bo EPI Distortions in Diffusion Tensor Imaging and White Matter Tractography. Proceedings of the 12th Annual Meeting ISMRM, Kyoto, Japan, 2004; 2172.
- 19 Haselgrove JC, Moore JR. Correction for distortion of echo-planar images used to calculate the apparent diffusion coefficient. Magn. Reson. Med. 1996; 36: 960–964.
- 20 Bastin ME. Correction of eddy current-induced artefacts in diffusion tensor imaging using iterative cross-correlation. Magn. Reson. Imaging. 1999; 17: 1011–1024.
- 21 Rohde GK, Barnett AS, Basser PJ, Marenco S, Pierpaoli C. Comprehensive approach for correction of motion and distortion in diffusion-weighted MRI. Magn. Reson. Med. 2004; 51: 103–114.
- 22 Horsfield MA. Mapping eddy current induced fields for the correction of diffusion-weighted echo planar images. Magn. Reson. Imaging. 1999; 17: 1335–1345.
- 23
Jones DK,
Horsfield MA,
Simmons A.
Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging.
Magn. Reson. Med.
1999;
42:
515–525.
10.1002/(SICI)1522-2594(199909)42:3<515::AID-MRM14>3.0.CO;2-Q CASPubMedWeb of Science®Google Scholar
- 24 Jones DK. The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: A Monte Carlo study. Magn. Reson. Med. 2004; 51: 807–815.
- 25 Leemans A, Jones DK. The B-matrix must be rotated when motion correcting diffusion tensor imaging data. Magn. Reson. Med. 2009; 61: 1336–1349.
- 26 Press WH, Teukolsky SA, Vetterling WT, Flannery BP. Numerical Recipes in C: The Art of Scientific Computing, 2nd edition. Cambridge University Press: New York, 1994; 183.
- 27 Davis TL, Wedeen VJ, Weisskoff Rosen BR. White matter tract visualization by echo-planar MRI. In Book of Abstracts: Twelfth Annual Meeting of the Society of Magnetic Resonance in Medicine. ISMRM: Berkeley, CA, 1993; p. 289.
- 28 Bevington PR, Robinson DK. Data Reduction and Error Analysis for the Physical Sciences, 2nd edition. McGraw-Hill: New York, 1992.
- 29 Papadakis NG, Xing D, Houston GC, Smith JM, Smith MI, James MF, Parsons AA, Huang CL, Hall LD, Carpenter TA. A study of rotationally invariant and symmetric indices of diffusion anisotropy. Magn. Reson. Imaging. 1999; 17: 881–892.
- 30 Hasan KM, Alexander AL, Narayana PA. Does fractional anisotropy have better noise immunity characteristics than relative anisotropy in diffusion tensor MRI? An analytical approach. Magn. Reson. Med. 2004; 51: 413–417.
- 31 Shimony JS, McKinstry RC, Akbudak E, Aronovitz JA, Snyder AZ, Lori NF, Cull TS, Conturo TE. Quantitative diffusion-tensor anisotropy brain MR imaging: normative human data and anatomic analysis. Radiology. 1999; 212: 770–784.
- 32 Lee CE, Danielian LE, Thomasson D, Baker EH. Normal regional fractional anisotropy and apparent diffusion coefficient of the brain measured on a 3 T MR scanner. Neuroradiol. 2009; 51: 3–9.
- 33 Yasmin H, Aoki S, Abe O, Nakata Y, Hayashi N, Masutani Y, Goto M, Ohtomo K. Tract-specific analysis of white matter pathways in healthy subjects: a pilot study using diffusion tensor MRI. Neuroradiol. 2009; 51: 831–840.
- 34 Pierpaoli C, Jezzard P, Basser PJ, Barnett AS. Diffusion tensor MR imaging of the human brain. Radiology. 1996; 201: 637–648.
- 35 Yoshiura T, Wu O, Zaheer A, Reese TG, Sorensen AG. Highly diffusion-sensitized MRI of brain: dissociation of gray and white matter. Magn. Reson. Med. 2001; 45: 734–740.
- 36 Pierpaoli C, Basser PJ. Towards a quantitative assessment of diffusion anisotropy. Magn. Reson. Med. 1996; 36: 893–906.
- 37 Gudbjartsson H, Patz S. The Rician distribution of noisy MRI data. Magn. Reson. Med. 1995; 34: 910–914.
- 38 Dietrich O, Heiland S, Sartor K. Noise correction for the exact determination of apparent diffusion coefficients at low SNR. Magn. Reson. Med. 2001; 45: 448–453.
- 39 Jones DK, Basser PJ. ‘Squashing peanuts and smashing pumpkins’: how noise distorts diffusion-weighted MR data. Magn. Reson. Med. 2004; 52: 979–993.
- 40 Jones DK. Determining and visualizing uncertainty in estimates of fiber orientation from diffusion tensor MRI. Magn. Reson. Med. 2003; 49: 7–12.
- 41 Schwartzman A, Dougherty RF, Taylor JE. Cross-subject comparison of principal diffusion direction maps. Magn. Reson. Med. 2005; 53: 1423–1431.
- 42 Whitcher B, Wisco JJ, Hadjikhani N, Tuch DS. Statistical group comparison of diffusion tensors via multivariate hypothesis testing. Magn. Reson. Med. 2007; 57: 1065–1074.
- 43 Rashid W, Hadjiprocopis A, Griffin CM, Chard DT, Davies GR, Barker GJ, Tofts PS, Thompson AJ, Miller DH. Diffusion tensor imaging of early relapsing-remitting multiple sclerosis with histogram analysis using automated segmentation and brain volume correction. Mult. Scler. 2004; 10: 9–15.
- 44 Jones DK, Catani M, Pierpaoli C, Reeves SJC, Shergill SS, O'Sullivan MO, Malley JD, McGuire P, Horsfield MA, Simmons A, Williams SCR, Howard RJ. 2005. Age effects on diffusion tensor magnetic resonance imaging tractography measures of frontal cortex connections in schizophrenia. Hum. Brain Mapp. 2005; 273: 230–238.
- 45 Shergill SS, Kanaan RAA, Chitnis XA, O'Daly O, Jones DK, Frangou S, Williams SCR, Howard RJ, Barker GJ, Murray RM, McGuire P. A diffusion tensor imaging study of fasciculi in schizophrenia. Am. J. Psychiatry. 2007; 164: 467–473.
- 46 Kanaan RA, Shergill SS, Barker GJ, Catani M, Ng VW, Howard RJ, McGuire PK, Jones DK. Tract-specific anisotropy measurements in diffusion tensor imaging. Psychiatry Res. Neuroimaging. 2006; 146: 73–82.
- 47 Jones DK, Travis AR, Eden GM, Pierpaoli C, Basser PJ. PASTA: Pointwise assessment of streamline tractography attributes. Magn. Reson. Med. 2005; 53: 1462–1467.
- 48 Liu G, van Gelderen P, Duyn J, Moonen CTW. Single-shot diffusion MRI of human brain on a conventional clinical instrument. Magn. Reson. Med. 1996; 35: 671–677.
- 49 Bhagat YA, Beaulieu C. Diffusion anisotropy in subcortical white matter and cortical gray matter: changes with aging and the role of CSF-suppression. J. Magn. Reson. Imaging. 2004; 20: 216–227.
- 50 Steens SC, Admiraal-Behloul F, Schaap JA, Hoogenraad FG, Wheeler-Kingshott CA, le Cessie S, Tofts PS, van Buchem MA. Reproducibility of brain ADC histograms. Eur. Radiol. 2004; 14: 425–430.
- 51 Concha L, Gross DW, Beaulieu C. Diffusion tensor tractography of the limbic system. AJNR Am. J. Neuroradiol. 2005; 26: 2267–2274.
- 52 Chou MC, Lin YR, Huang TY, Wang CY, Chung HW, Juan CJ, Chen CY. FLAIR diffusion-tensor MR tractography: comparison of fiber tracking with conventional imaging. AJNR Am. J. Neuroradiol. 2005; 26: 591–597.
- 53 Malykhin N, Concha L, Seres P, Beaulieu C, Coupland NJ. Diffusion tensor imaging tractography and reliability analysis for limbic and paralimbic white matter tracts. Psychiatry Res. 2008; 164: 132–142.
- 54 Pierpaoli C, Jones DK. Removing CSF Contamination in Brain DT-MRIs by Using a Two-Compartment Tensor Model. In Proceedings of the 12th Annual Meeting ISMRM, Kyoto, 2004; 1215.
- 55 Pasternak O, Sochen N, Gur Y, Intrator N, Assaf Y. Free water elimination and mapping from diffusion MRI. Magn. Reson. Med. 2009; 62: 717–730.
- 56 Ashburner J, Friston KJ. Voxel-based morphometry—the methods. NeuroImage. 2000; 11: 805–821.
- 57 Bookstein FL. ‘Voxel-based morphometry’ should not be used with imperfectly registered images. NeuroImage. 2001; 14: 1454–1462.
- 58 Ashburner J, Friston KJ. Why voxel-based morphometry should be used. Neuroimage. 2001; 14: 1238–1243.
- 59 Davatzikos C. Why voxel-based morphometric analysis should be used with great caution when characterizing group differences. NeuroImage. 2004; 23: 17–20.
- 60 Park HJ, Kubicki M, Shenton ME, Guimond A, McCarley RW, Maier SE, Kikinis R, Jolesz FA, Westin CF. Spatial normalization of diffusion tensor MRI using multiple channels. NeuroImage. 2003; 20: 1995–2009.
- 61 Guimond A, Guttmann CRG. Deformable registration of DT-MRI data based on transformation invariant tensor characteristics. Proceedings of the IEEE International Symposium on Biomedical Imaging (ISBI'02), Washington, DC. USA, 2002.
- 62 Alexander DC, Pierpaoli C, Basser PJ, Gee JC. Spatial transformations of diffusion tensor magnetic resonance images. IEEE Trans. Med. Imaging. 2001; 20: 1131–1139.
- 63 Kawashima T, Nakamura M, Bouix S, Kubicki M, Salisbury DF, Westin CF, McCarley RW, Shenton ME. Uncinate fasciculus abnormalities in recent onset schizophrenia and affective psychosis: a diffusion tensor imaging study. Schizophr. Res. 2009; 110: 119–126.
- 64 Fujiwara H, Namiki C, Hirao K, Miyata J, Shimizu M, Fukuyama H, Sawamoto N, Hayashi T, Murai T. Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: a diffusion tensor imaging study. Schizophr. Res. 2007; 95: 215–222.
- 65 Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC. A unified statistical approach for determining significant signals in images of cerebral activation, Hum. Brain Mapp. 1996; 4: 58–73.
- 66 Friston KJ, Holmes AP, Worsley KJ, Poline J-B, Frith CD, Frackowiak RSJ. Statistical parametric maps in functional imaging: a general linear approach, Hum. Brain Mapp. 1995; 2: 189–210.
- 67 Rosenfeld A, Kak AC. Digital Picture Processing 2. Academic Press: Orlando, FL, 1982; 42.
- 68 Jones DK, Symms MR, Cercignani M, Howard RJ. 2005. The effect of filter size on the outcome of VBM analyses of DT-MRI data. NeuroImage. 2005; 26: 546–554.
- 69 Lilliefors H. On the Kolmogorov–Smirnov test for normality with mean and variance unknown. J. Am. Statistic. Assoc. 1967; 62: 399–402.
- 70 Worsley KJ, Evans AC, Marrett S, Neelin P. A three-dimensional statistical analysis for CBF activation studies in human brain. J. Cereb. Blood Flow Metab. 1992; 12: 900–918.
- 71 Genovese CR, Lazar NA, Nichols T. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage. 2002; 15: 870–878.
- 72 Nichols TE, Holmes AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum. Brain Mapp. 2002; 15: 1–25.
- 73 Jones DK, Chitnis XA, Job D, Khong PL, Leung LT, Marenco S, Smith SM, Symms MR. (ehat happens when nine different groups analyze the same DT-MRI data set using voxel-based methods?). In Proceedings of the 15th Annual Meeting ISMRM. Berlin, 2007; 74.
- 74 Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ. Matthews PM and others. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 2006; 31: 1487–1450.
- 75 Smith SM, Johansen-Berg H, Jenkinson M, Rueckert D, Nichols TE, Miller KL, Robson MD, Jones DK, Klein JC, Bartsch AJ, Behrens TEJ. 2007. A protocol for acquisition and voxelwise analysis of multi-subject diffusion data with tract-based spatial statistics. Nature Protocol. 2007; 2: 499–503.
- 76 Jones DK. The challenges and limitations of using diffusion MRI to quantify brain connectivity in vivo. Imaging in Medicine (under review), 2010.