Alex D. Leow, MD Ph.D

I am currently with Neuropsychiatric hospital at UCLA (psychiatry is my practice). However, my main ongoing research activities are through Laboratory of NeuroImaging.

My research

My research mainly consists of two branches: application and theory. Though practicing medicine, I do consider myself more of a theoretically/mathematically inclined person. On the theory front, my main research interests, at this moment, are the following:

· The statistical analyses of group deformation fields as well as their applications to brain imaging in neuropsychiatric diseases such as, but not limited to, Alzheimer's disease, schizophrenia, autism, and bipolar disorder (please refer to list of publications for recent papers).

· The development of novel non-linear registration frameworks incorporating mathematical techniques in continuum mechanics, differential geometry, as well as information theory.

· The quantification of diffusion tensor images, both within subject and across groups. This would help visualize the configuration of white matter myelination, both longitudinally and cross-sectionally, leading to better understandings of the human brain. Our most recent work is called the “Tensor Distribution Function”, a very powerful tool that we believe is advantageous to other HARDI techniques.

In short and lay person term, I am trying to figure out how one we judge different non-linear registration methods. Mostly recently, I have been developing a novel framework, based on information theory, which would provide a statistically correct framework for analyzing Jacobian maps ( Unbiased Large-Deformation Non-linear Image Registration; refer to IPMI 05, the MICCAI workshop paper below, and 07 IEEE TMI paper. For a short description of this idea, refer to UCLA CAM report 06-64 that can be found here http://www.math.ucla.edu/applied/cam/).

Another new field that I have worked on is diffusion tensor imaging (DTI), q-ball imaging, and HARDI, an exciting field. In particular, I have looked into multi-tensor estimation, and developed new methodology -the computation of Tensor Distribution Function- to directly estimate the particle displacement function. Orientation diffusion tensor, and dominant fiber tract directions can be easily derived from TDF through analytic relations (see http://www.math.ucla.edu/applied/cam/ for a technical report on the concept of Tensor Distribution Function).

I have been a regular reviewer, for IEEE Transactions on Medical Imaging, IEEE Transactions on Image Processing, NeuroImage, as well as other journals. I also served as a reviewer for various conferences/workshops including the 2007 ISBI (International Symposium on Biomedical Imaging), and the MICCAI 2007 workshop on statistical registration: pair-wise and group-wise alignment and atlas formation (http://www.miccai2007.org/workshops/)

My Main collaborators

I work extensively with Prof. Paul Thompson, as well as some of the most amazing graduate students/research assistants in our group: Agatha Lee, Allen Lu, Andrea Klunder, and Kiralee Hayashi (I am eternally grateful to these people). I consider them the nicest, smartest, most mature, and most efficient people in the world. As far as mathematical theory/algorithm design goes, I also work with Dr. Ming-Chang Chiang, who I think is the hardest-working person I've ever met.

Most recently, I have also mentored Igor Yanovsky, at the Mathematics department of UCLA, on fine-tuning algorithm implementation as well as testing of the proposed Unbiased registration framework. The goal is to vigorously establish and test theories leading to unbiased statistics when making inference of Jacobian operators resulting from deformation maps. For some of our work on the Unbiased Large Deformation Registration, please see his website here: http://www.math.ucla.edu/~yanovsky/.

Here are some images from our most recent work, showing that ULDIR outperforms regular fluid registration, even on a visual level. The images in this figure are part of the Alzheimer’s Disease Neuroimaging Initiative, where normal elderly subjects were scanned twice within a two-week time period. As a result, these images are used for calibration purposes (i.e., no structural changes are present)

Image1.jpg

Image2.jpg

This figure examines the inverse consistency of two different deformation models in tensor-based morphometry. Products of Jacobian maps generated using fluid registration and ULDIR for forward direction (time 1 to time 2) and backward direction (time 2 to time 1) are shown. Both the fluid and ULDIR registrations are driven by L² intensity matching functional. Jacobian maps are superimposed on the deformed volumes. Rows depict slices in axial, sagittal, and coronal planes. For the ULDIR method, the visualization of the product of Jacobian maps is less noisy, with values closer to 1, showing better inverse consistency.

Hobbies

PIANO- a hobby shared by both Paul and I. Although the similarity ends here!! Paul likes piano music with extreme technical difficulties (Rachmaninoff, some Chopin, and Liszt), while I prefer intimate music, like some other Chopin (mutually exclusive!!), Ravel, Mozart (mainly piano concertos).

In October of 2006, my dearest friend Dr. Clayton Bullock MD PhD (a great violinist and harpsichord-ist) and I had formally formed a group, the Duo Doctor Duo, and have since given several recitals. We are currently working very hard on our repertoire, which has included music by Handel, Mozart, Brahms, various violin transcriptions, as well as piano solo by Chopin, Bach, Rachmaninoff, Ravel. We recently did the first of the 2007 concert series at the Neuropsychiatric Hospital at UCLA. See here for full recording (finally!!) of Mozart e-minor piano/violin sonata K304 Track2.mp4, Track3.mp4. This was composed right after his mother’s death, and is arguably his most well known violin sonata, and the only one in minor key. It definitely is my favorite!! I also attach Brahms violin/piano scherzo hereTrack5.mp4

2008… latest update:

more music files here

This time they are from our 2008 January concert.

The piano is… Fazioli’s 7 footer

Chopin Mazurka Mazurka_op50_no3

Mozart violin sonata Violin_Piano_K377

Chopin scherzo Scherzo_no2

A big goal in my life is to own one grand piano from the following brands: Hamburg Steinway (the new NY Steinway’s really not so good), Fazioli (Ferarri of pianos) (for people who never heard of it, link is http://www.fazioli.com/, Bluthner (another romantic sounding instrument, link here http://www.bluthnerpiano.com/ ), Mason and Hamlin (the old company actually kind of went out of bzness, but the new ones are reported to be made using the same specs. Link here http://www.masonhamlin.com/ . Mason and Hamlin probably, to my knowledge, makes pianos with the most rich overtone, reminding me of the good old days, turn-of-the-century-ish. I highly recommend any piano lover to give it a try.), and Estonia (the most affordable in this group, though as nice an instrument). I currently play on a Yamaha C1, whose action has been totally regulated to my liking.

TENNIS- I used to be a very very avid tennis player.

Contact me at alexfeuillet@gmail.com if you have any questions or comments about my research. Thanks for visiting my homepage.

Peer-reviewed Publications (selected from over 40+ publications; submitted papers, preprints, or technical reports not included):

Journal papers

1. W. Liao, K. Lange, M. Bergsneider and S.C. Huang (2002) Optimal design in dynamic PET data acquisition: A new approach using simulated annealing and component-wise metropolis updating. IEEE Transactions on Nuclear Science, 49(5) pp. 2291-2296.

2. A.D. Leow, C.L. Yu, S.J. Lee, S.C. Huang, R.Nicolson, K.M. Hayashi, H. Protas, A.W. Toga, and P.M. Thompson (2004) Brain Structural Mapping using a Novel Hybrid Implicit/Explicit Framework based on the Level-Set Method. NeuroImage 24(3) pp. 910-927

3.N. Hattori, S.C. Huang, H.M. Wu, W. Liao, T. Glenn, P. Vespa, M. Phelps, D. Hovda, M. Bergsneider (2004) Acute changes in regional cerebral FDG kinetics in patients with traumatic brain injury. Journal of Nuclear Medicine, 2004.

4. E.F.Lee, R. Jacobs, I. Dinov, A.D. Leow, A.W. Toga (2005) standard atlas space for C57 BL/6J neonatal mouse brain. Anatomy and Embryology NOV, 210(4): 245-63, 2005

5.Leow AD, Klunder AD, Jack CR, Toga AW, Dale AM, Bernstein MA, Britson PJ, Gunter JL, Ward CP, Whitwell JL, Borowski B, Fleisher A, Fox NC, Harvey D, Kornak J, Schuff N, Studholme C, Alexander GE, Weiner MW, Thompson PM; For the ADNI Preparatory Phase Study (2005). Longitudinal Stability of MRI for Mapping Brain Change using Tensor-Based Morphometry, NeuroImage 2006; 31:627-40

6.AD Lee, AD Leow, A Lu, A. Reiss, S. Hall, M-C. Chiang, A. Toga, P. Thompson (2007) 3D pattern of brain abnormalities in fragile X syndrome visualized using tensor-based morphometry. NeuroImage, 34(3), pp 924-938.

7 AD Leow, M-C. Chiang, I. Yanovsky, AD Lee, A. Klunder, J. Becker, S. Davis, A. Toga, P. Thompson (2007) Statistical properties of Jacobian maps and the realization of unbiased large-deformation non-linear image registration. IEEE Transactions on Medical Imaging, vol. 26, no. 06, June 2007, pp 822-832.

8.M.C. Chiang, A.D. Leow, R.A. Dutton, M. Barysheva, S. Rose, K.L. McMahon, G. I. de Zubicaray, A.W. Toga, and P.T. Thomspon Fluid registration of diffusion tensor images using information theory. To appear in IEEE Transactions on Medical Imaging.

9. Xue Hua, Alex D. Leow, Jennifer G. Levitt, Rochelle Caplan, Paul M. Thompson, Arthur W. Toga (2007) Detecting brain growth patterns in normal children using tensor-based morphometry. Human Brain Mapping (published online in advance of print)

10.Foland, L.C., Altshuler, L., Sugar, C.A., Leow, A.D., Townsend, J., Narr, K.L., Toga, A.W., Thompson, P.M. Increased Volume of the Amygdala and Hippocampus in Bipolar Patients Treated with Lithium. Neuroreport; in press.

11. Hua X., Leow, A.D., Lee S., Klunder A.D., Toga, A.W., et al. 3D characterization of brain atrophy in Alzheimer’s disease and mild cognitive impairment using tensor-Based morphometry. To appear in NeuroImage

12 A.D. Leow, S. Zhu, L. Zhan, K. McMahon, G.I. de Zubicaray, M. Meredith, M.J. Wright, A.W. Toga, P.M. Thompson the Tensor distribution function. To appear in Magnetic Resonance in Medicine

13. X. Hua, A.D. Leow, N. Parikshak, S. Lee, M.C. Chiang, A.W. Toga, C.R. Jack Jr, M.W. Weiner, P.M. Thompson(2008). Tensor-Based Morphometry as a Neuroimaging Biomarker for Alzheimer’s Disease: An MRI Study of 676 AD, MCI, and Normal Subjects. Epub ahead of print, Neuroimage

14. A.D. Leow et al., Alzheimer’s disease neuroimaging initiative: a one-year follow up study correlating degenerative rates, biomarkers, and cognition. Accepted to NeuroImage

Book Chapters

1. A.D. Leow, S.C. Huang, A. Geng, J. Becker, S. Davis, A. Toga, and P. Thompson (2005) Inverse consistent mapping in 3D deformable image registration: its construction and statistical properties, IPMI 2005, G.E. Christensen and M. Sonka (Eds.): Lecture Notes in Computer Science 3565, pp. 493-503, 2005

2. W. Liao, L. Vese, S.C. Huang, M. Bergsneider, and S. Osher (2003) Computational anatomy and implicit object representation: a level set approach, Lecture Notes in Computer Science, vol. 2717, pp. 40-49.

3. P.M. Thompson, E.R. Sowell, N. Gogtay, J.N. Giedd, C.N. Vidal, K.M. Hayashi, A.D. Leow, R. Nicolson, J.L. Rapoport, A.W. Toga (2005). Structural MRI and Brain Development, in: Glabus M [ed.], International Review of Neurobiology (IRN), 2005.

4. S.C. Huang, W. Liao, N. Hattori, H.M. Wu, C.L. Yu, and M. Bergsneider (2003) Strategies for reducing noise level of parametric images in emission tomography. In Modeling and Control in Biomedical Systems, Ed. David Feng and Ewart R.Carson, Elsevier, 2003, pp. 5-10.

5. Tracking Alzheimer's Disease: Paul M. Thompson, Kiralee M. Hayashi, Rebecca A. Dutton, Ming-Chang Chiang, Alex D. Leow, Elizabeth R. Sowell, Greig De Zubicaray, James T. Becker, Oscar L. Lopez, Howard J. Aizenstein, and Arthur W. Toga. Imaging and the aging brain

Conference Papers

1. I. Yanovsky, P.M. Thompson, S. Osher, X. Hua, D.W. Shattuck, A.W. toga, and A.D. Leow (2008) Validating unbiased registration on longitudinal MRI scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). In Proc. ISBI, pp. 1091-1094.

2. A.D. Leow, S. Zhu, K. McMahon, G.I. de Zubicaray, M. Meredith, M.J. Wright, P.M. Thompson (2008) the tensor distribution function. In Proc. ISBI, pp. 863-866

3. A.D. Leow, S. Zhu, K. McMahon, G.I. de Zubicaray, M. Meredith, M.J. Wright, P.M. Thompson (2008) Probabilistic multi-tensor estimation using the tensor distribution function. In Proc. CVPR 2008.

4. I. Yanovsky, P.M. Thompson, S. Osher, A.D. Leow (2008) Asymmetric and Symmetric Unbiased Image Registration: Statistical Assessment of Performance. In MMBIA (Mathematical Methods in Biomedical Image Analysis) 2008.

5. W. Liao, H. Protas, M. Bergsneider, L. Vese, S.C. Huang, and S. Osher (2003) A new framework of object warping: a semi-Lagrangian level set approach. International Conference on Image Processing, Sep. 2003.

6. A.D. Leow, P. Thompson, H. Protas, and S.C. Huang (2004) Brain warping with implicit representation. International Symposium on Biomedical Imaging, in Proc. ISBI2004.

7. A.D. Leow, M.C. Chiang, P. Thompson, and S.C. Huang (2004) Linear and non-linear geometric object matching with implicit representations. International Conference on Pattern Recognition ICPR04.

8. A.D. Leow, M.C. Chiang, S.C. Huang, A.W. Toga, and P.M. Thompson, Realizing unbiased deformation: a theoretical consideration. In Mathematical foundations of computational anatomy workshop, MICCAI 2006.

9. N. Lepore, A.D. Leow, P.M. Thompson (2006) Landmark Matching on the Sphere Using Distance Functions, IEEE International Symposium on Biomedical Imaging (ISBI2006), April 6-9 2006.

10. I Yanovsky, MC Chiang, P Thompson, A Klunder, J Becker, S Davis, A Toga, A Leow (20007) QUANTIFYING DEFORMATION USING INFORMATION THEORY: THE LOG-UNBIASED NONLINEAR REGISTRATION. Proc. ISBI 2007 pp.13-16

11. Igor Yanovsky, Stanley Osher, Paul M. Thompson, Alex D. Leow (2007) Log-Unbiased Large-Deformation Image Registration". In 2007 International Conference on Computer Vision Theory and Applications).

12. Igor Yanovsky, Paul Thompson, Stanley Osher, Alex Leow (2007) Topology Preserving Log-Unbiased Nonlinear Image Registration: Theory and Implementation. In Proc. CVPR 2007

13. Igor Yanovsky, Paul Thompson, Stanley Osher, Luminita Vese, Alex Leow (2007) Multiphase segmentation of deformation using logarithmic priors. In special workshop on image registration and fusion of CVPR 2007.

14. Igor Yanovsky, Carole le Guyader, Alex Leow, Arthur Toga, Taul Thompson, Luminita Vese (2008) Unbiased volumetric registration via nonlinear elastic regularization. Mathematical foundations of computational anatomy workshop, MICCAI 2008.

15. Alex Leow, Siwei Zhu, Katie McMahon, Greig de Zubicaray, Margie Wright, Paul Thompson (2008) A Study of Information Gain in High Angular Resolution Diffusion Imaging (HARDI). 2008 MICCAI workshop on Computational diffusion-MRI

Abstracts/Posters

Liao WH, Thompson PM, Hayashi KM, Bearden C, Nicoletti MA, Monkul SE, Brambilla P, Sassi RB, Mallinger AG, Soares JC (2005). Lithium Effects on Human Brain Structure Mapped Using Longitudinal MRI, 35th Annual Meeting of the Society for Neuroscience, Washington DC, Nov. 12-16, 200

A.D. Leow, A.D. Lee, M.C. Chiang, R.A. Dutton, K.M. Hayashi, S.C. Huang, J.T. Becker, S.W. Davis, A.W. Toga, P.M. Thompson(2005) Mapping Brain Atrophy in A Single Case of Semantic Dementia Using Serial MRI with Inverse-Consistent Non-Rigid Registration. Human Brain Mapping 2005.

A.D. Leow, S.C. Huang, J. Becker, and P. Thompson (2005) Study of tissue atrophy involvement in semantic dementia using elastic mapping. Brian 05’.

W.H. Liao, K. Lange, S.C. Huang (2001) The Use of MM algorithm for regularization of parametric images in PET. BrainPET 2001.

W.H. Liao, L. Kashida, L. Vese, M. Bergsneider, and S.C. Huang (2002) A variational approach for noise removal of parametric images in tracer kinetic modeling. Neuroimage, 16(3), 2002, S68-S69 Part 2 Suppl. S.

A.D. Leow,H. Protas, S.C. Huang, and P.M. Thompson (2004) Evaluation of a landmark curve matching technique in brain mapping based on the level set method. Human Brain Mapping, 2004.

A.D. Leow, A. Lu, A.D.Lee, N. Gogtay, J.L. Rapoport, A.W. Toga, and P.M. Thompson (2006) Tensor-Based Morphometry Reveals Significant Growth Pattern Abnormalities in Childhood-Onset Schizophrenia. To be presented in Society of biological Psychiatry, Toronto, Canada