Saving Oneself

Co-taught with Antoine Jerusalem and Lili Zhang

IEB MR4 Tues. 2-4pm

Synopsis

Technology is emerging that makes it possible to fix, section, and scan brain tissue at very high resolution – high enough to resolve even synaptic strengths. This brings whole new meaning to the idea of saving oneself. See The Brain Preservation Foundation for additional clarification and inspiration.

Design Brief

Your task will be to design hardware, a facility, and set of computational processes that make it possible to process, scan, and upload, process (extracting neuronal connections and strength) and save an entire human brain for possible future reanimation for amortized cost of no more than 50k GBP per person. Design elements can realistically be expected to include high-volume electron or other microscopes, precision cutters, software infrastructure, computing infrastructure, process optimisations, and archival mechanisms.

Challenge Problem

The human brain is a phenomenally complex organ with meaningful structure requiring nanometer-resolution scans to even possibly be able to reanimate in the future. Besides the challenges of sourcing or building microscopes capable of processing the required volume, designing automation machinery, processes, and the like; naïve data capture would require staggering amounts of storage. As a result powerful machine learning systems and processes also will need to be designed.

Course Design

Beyond the usual 3YP organization involving log books, group work, presentations, and writing, we expect several of the leading researchers in this area to be able to join us either in person or via Skype to answer questions.

Course Organization

All groups will follow the same rough design trajectory with the course time being divided roughly equally into four areas of particular consideration. I: in weeks 1-4 (MT) we will consider and read about data gathering technology. II: in weeks 5-8 (MT) we will examine mechanical, chemical, and process considerations. III: in weeks 1-4 (HT) we will consider data management challenges and IV: 5-8 (HT) data processing. Recommended reading and starting-point reference materials are provided as a bibliography below.

Requirements

Version control for collaborative writing

You must use git via bitbucket for version control of your reports and presentations. Each group must create a repository and add “fwood” as a collaborator with read permission. You may wish to read online resources like this blog and this tutorial to help acquaint yourself with this essential technology. And remember, practice makes perfect. In addition to other metrics for judging relative contributions, your git behaviour will be used to evaluate your relative contribution. Also, version control systems, in addition to writing in laboratory notebooks, can help to establish IP precedence. Working from examples example.tex and refs.bib can help get you started.
LaTeX for writing

You must use latex and bibtex to write your final report and the report must be versioned in the aforementioned git repository. You may wish to read online resources like this blog to get started.
Beamer for presentations

You must use beamer for presentations (i.e. not powerpoint, keynote, etc.). All presentations must be version controlled as well. The beamer source file for the introductory lecture to this course is a reasonable starting point from which you might start. Note that that the images, videos, and references for this presentation also must be downloaded or commented out in order for the presentation to compile to pdf.

Groups

Group 1

1 Suleyman Abdi
2 Anatoly Smirnov
3 Billy Smith
4 Ben Shillito

Group 2

5 Andrew Cloke
6 Andrew Warrington
7 Dongjin Kim
8 Mu Chen

Group 3

9 Piotr Czaban
10 Stephen Lilico
11 Siyi Xiong
12 Rob Wight

Schedule

Michaelmas

Week	Date	Due	Activity
1.	14/10		Intro Lecture (Wood)
2.	21/10	Groups	Design Lecture (Jerusalem)
3.	28/10	Talks (1, 5, and 9)
4.	04/11	Talks (2 ,6, and 10) & Log books
5.	11/11		Guest Lecture Lichtman
6.	18/11	Talks (3, 7, and 11)
7.	25/11	Talks (4,8, and 12), Log books
8.	02/12		Guest Lecture Hayworth

Hilary

Week	Date	Due	Activity
1.	20/01		Guest Lecture Kasthuri
2.	27/01	Talks (2, 6, and 10)
3.	03/02	Talks (3, 7, and 11)
4.	10/02	Log books	Guest Lecture Roncal/Vogelstein
5.	17/02	Walk through of projects as they stand
6.	24/02	Talks (4, 8, 12)
7.	03/03	Log books	Talks (1, 5, 9)
8.	10/03		Guest Lecture

Trinity

Week	Date	Due
0.	28/05	Draft of report
1.	05/05	A possible date for final presentation. (to be scheduled)
2.	05/12	A possible date for final presentation. (to be scheduled)
4.	12.00 on Wednesday of Week 4	Reports

Essential Reading

Recording technology

Denk, W., & Horstmann, H. (2004). Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure. PLoS biology, 2(11), e329. BIB

@article{denk2004serial,
  title = {Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure},
  author = {Denk, Winfried and Horstmann, Heinz},
  journal = {PLoS biology},
  volume = {2},
  number = {11},
  pages = {e329},
  year = {2004},
  publisher = {Public Library of Science}
}

Knott, G., Marchman, H., Wall, D., & Lich, B. (2008). Serial section scanning electron microscopy of adult brain tissue using focused ion beam milling. The Journal of Neuroscience, 28(12), 2959–2964. BIB

@article{knott2008serial,
  title = {Serial section scanning electron microscopy of adult brain tissue using focused ion beam milling},
  author = {Knott, Graham and Marchman, Herschel and Wall, David and Lich, Ben},
  journal = {The Journal of Neuroscience},
  volume = {28},
  number = {12},
  pages = {2959--2964},
  year = {2008},
  publisher = {Soc Neuroscience}
}

Lichtman, J. W., Livet, J., & Sanes, J. R. (2008). A technicolour approach to the connectome. Nature Reviews Neuroscience, 9(6), 417–422. BIB

@article{lichtman2008technicolour,
  title = {A technicolour approach to the connectome},
  author = {Lichtman, Jeff W and Livet, Jean and Sanes, Joshua R},
  journal = {Nature Reviews Neuroscience},
  volume = {9},
  number = {6},
  pages = {417--422},
  year = {2008},
  publisher = {Nature Publishing Group}
}

Dani, A., & Huang, B. (2010). New resolving power for light microscopy: applications to neurobiology. Current opinion in neurobiology, 20(5), 648–652. BIB

@article{dani2010new,
  title = {New resolving power for light microscopy: applications to neurobiology},
  author = {Dani, Adish and Huang, Bo},
  journal = {Current opinion in neurobiology},
  volume = {20},
  number = {5},
  pages = {648--652},
  year = {2010},
  publisher = {Elsevier}
}

Denk, W., Strickler, J. H., Webb, W. W., & others. (1990). Two-photon laser scanning fluorescence microscopy. Science, 248(4951), 73–76. BIB

@article{denk1990two,
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}

Kralj, J. M., Douglass, A. D., Hochbaum, D. R., Maclaurin, D., & Cohen, A. E. (2012). Optical recording of action potentials in mammalian neurons using a microbial rhodopsin. Nature methods, 9(1), 90–95. BIB

@article{kralj2012optical,
  title = {Optical recording of action potentials in mammalian neurons using a microbial rhodopsin},
  author = {Kralj, Joel M and Douglass, Adam D and Hochbaum, Daniel R and Maclaurin, Dougal and Cohen, Adam E},
  journal = {Nature methods},
  volume = {9},
  number = {1},
  pages = {90--95},
  year = {2012},
  publisher = {Nature Publishing Group}
}

Leighton, S. B. (1980). SEM images of block faces, cut by a miniature microtome within the SEM-a technical note. Scanning electron microscopy, (Pt 2), 73–76. BIB

@article{leighton1980sem,
  title = {SEM images of block faces, cut by a miniature microtome within the SEM-a technical note.},
  author = {Leighton, Stephen B},
  journal = {Scanning electron microscopy},
  number = {Pt 2},
  pages = {73--76},
  year = {1980}
}

Logothetis, N. K. (2008). What we can do and what we cannot do with fMRI. Nature, 453(7197), 869-878. Retrieved from http://dx.doi.org/10.1038/nature06976 BIB

@article{Logothetis2008,
  author = {Logothetis, Nikos K.},
  title = {What we can do and what we cannot do with fMRI},
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  url = {http://dx.doi.org/10.1038/nature06976}
}

D., C. (1968). Magnetoencephalography: evidence of magnetic fields produced by alpha-rhythm currents. Science, 161, 784-786. Retrieved from http://www.sciencemag.org/content/161/3843/784.long BIB

@article{Cohen1968,
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  title = {Magnetoencephalography: evidence of magnetic fields produced by alpha-rhythm currents},
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}

Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., Sanes, J. R., & Lichtman, J. W. (2007). Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature, 450(7166), 56-62. Retrieved from http://dx.doi.org/10.1038/nature06293 BIB

@article{Livet2007,
  author = {Livet, Jean and Weissman, Tamily A. and Kang, Hyuno and Draft, Ryan W. and Lu, Ju and Bennis, Robyn A. and Sanes, Joshua R. and Lichtman, Jeff W.},
  title = {Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system},
  journal = {Nature},
  volume = {450},
  number = {7166},
  pages = {56-62},
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  url = {http://dx.doi.org/10.1038/nature06293}
}

Lichtman, J. W., Livet, J., & Sanes, J. R. (2008). A technicolour approach to the connectome. Nat Rev Neurosci, 9(6), 417-422. Retrieved from http://dx.doi.org/10.1038/nrn2391 BIB

@article{Lichtman,
  author = {Lichtman, Jeff W. and Livet, Jean and Sanes, Joshua R.},
  title = {A technicolour approach to the connectome},
  journal = {Nat Rev Neurosci},
  volume = {9},
  number = {6},
  pages = {417-422},
  year = {2008},
  url = {http://dx.doi.org/10.1038/nrn2391}
}

Smith, K. C. A., & Oatley, C. W. (1955). The scanning electron microscope and its fields of application. British Journal of Applied Physics, 6, 391-399. Retrieved from http://stacks.iop.org/0508-3443/6/i=11/a=304 BIB

@article{1955BJAP,
  author = {{Smith}, K. C. A. and {Oatley}, C. W.},
  title = {{The scanning electron microscope and its fields of application}},
  journal = {British Journal of Applied Physics},
  year = {1955},
  month = {nov},
  volume = {6},
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}

MAYERICH, D., ABBOTT, L., & McCORMICK, B. (2008). Knife-edge scanning microscopy for imaging and reconstruction of three-dimensional anatomical structures of the mouse brain. Journal of Microscopy, 231(1), 134-143. Retrieved from http://dx.doi.org/10.1111/j.1365-2818.2008.02024.x BIB

@article{JMI2024,
  author = {MAYERICH, D. and ABBOTT, L. and McCORMICK, B.},
  title = {Knife-edge scanning microscopy for imaging and reconstruction of three-dimensional anatomical structures of the mouse brain},
  journal = {Journal of Microscopy},
  volume = {231},
  number = {1},
  publisher = {Blackwell Publishing Ltd},
  pages = {134-143},
  year = {2008},
  url = {http://dx.doi.org/10.1111/j.1365-2818.2008.02024.x}
}

W, D., & H, H. (2004). Serial Block-Face Scanning Electron Microscopy to Reconstruct Three-Dimensional Tissue Nanostructure. PLoS Biol, 2(11), 1900-1909. Retrieved from http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020329 BIB

@article{Denk2004,
  author = {W, Denk and H, Horstmann},
  title = {Serial Block-Face Scanning Electron Microscopy to Reconstruct Three-Dimensional Tissue Nanostructure},
  journal = {PLoS Biol},
  volume = {2},
  number = {11},
  pages = {1900-1909},
  year = {2004},
  url = {http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020329}
}

Helmstaedter, M., Briggman, K. L., & Denk, W. (2008). 3D structural imaging of the brain with photons and electrons. Current Opinion in Neurobiology , 18(6), 633 - 641. Retrieved from http://www.sciencedirect.com/science/article/pii/S0959438809000130 BIB

@article{Helmstaedter2008,
  title = {3D structural imaging of the brain with photons and electrons},
  journal = {Current Opinion in Neurobiology },
  volume = {18},
  number = {6},
  pages = {633 - 641},
  year = {2008},
  author = {Helmstaedter, Moritz and Briggman, Kevin L and Denk, Winfried},
  url = {http://www.sciencedirect.com/science/article/pii/S0959438809000130}
}

Knott, G., Rosset, S., & Cantoni, M. (2011). Focussed Ion Beam Milling and Scanning Electron Microscopy of Brain Tissue. J. Vis. Exp., 53, e2588. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196160/ BIB

@article{Knott2011,
  title = {Focussed Ion Beam Milling and Scanning Electron Microscopy of Brain Tissue},
  journal = {J. Vis. Exp.},
  volume = {53},
  number = {},
  pages = {e2588},
  year = {2011},
  author = {Knott, G. and Rosset, S. and Cantoni, M.},
  url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196160/}
}

CreweA.~V., Isaacson, M., & Johnson, D. (1969). A Simple Scanning Electron Microscope. Review of Scientific Instruments, 40, 241-246. Retrieved from http://adsabs.harvard.edu/abs/1969RScI...40..241C BIB

@article{1969RScI,
  author = {{Crewe}, A.~V. and {Isaacson}, M. and {Johnson}, D.},
  title = {{A Simple Scanning Electron Microscope}},
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  year = {1969},
  volume = {40},
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  url = {http://adsabs.harvard.edu/abs/1969RScI...40..241C}
}

Knott, G., Marchman, H., Wall, D., & Lich, B. (2008). Serial Section Scanning Electron Microscopy of Adult Brain Tissue Using Focused Ion Beam Milling. The Journal of Neuroscience, 28(12), 2959-2964. Retrieved from http://www.jneurosci.org/content/28/12/2959.full BIB

@article{Knott2008,
  author = {Knott, Graham and Marchman, Herschel and Wall, David and Lich, Ben},
  title = {Serial Section Scanning Electron Microscopy of Adult Brain Tissue Using Focused Ion Beam Milling},
  volume = {28},
  number = {12},
  pages = {2959-2964},
  year = {2008},
  journal = {The Journal of Neuroscience},
  url = {http://www.jneurosci.org/content/28/12/2959.full}
}

Susaki, E. A., Tainaka, K., Perrin, D., Kishino, F., Tawara, T., Watanabe, T. M., Yokoyama, C., Onoe, H., Eguchi, M., Yamaguchi, S., Abe, T., Kiyonari, H., Shimizu, Y., Miyawaki, A., Yokota, H., & Ueda, H. R. (2014). Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis. Cell, 157(3), 726-739. Retrieved from http://www.cell.com/cell/abstract/S0092-8674(14)00418-8 BIB

@article{Susaki2014,
  author = {Susaki, Etsuo A. and Tainaka, Kazuki and Perrin, Dimitri and Kishino, Fumiaki and Tawara, Takehiro and Watanabe, Tomonobu M. and Yokoyama, Chihiro and Onoe, Hirotaka and Eguchi, Megumi and Yamaguchi, Shun and Abe, Takaya and Kiyonari, Hiroshi and Shimizu, Yoshihiro and Miyawaki, Atsushi and Yokota, Hideo and Ueda, Hiroki R.},
  title = {Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis},
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}

Stender, A. S., Marchuk, K., Liu, C., Sander, S., Meyer, M. W., Smith, E. A., Neupane, B., Wang, G., Li, J., Cheng, J.-X., Huang, B., & Fang, N. (2013). Single Cell Optical Imaging and Spectroscopy. Chemical Reviews, 113(4), 2469-2527. Retrieved from http://dx.doi.org/10.1021/cr300336e BIB

@article{Stender2013,
  author = {Stender, Anthony S. and Marchuk, Kyle and Liu, Chang and Sander, Suzanne and Meyer, Matthew W. and Smith, Emily A. and Neupane, Bhanu and Wang, Gufeng and Li, Junjie and Cheng, Ji-Xin and Huang, Bo and Fang, Ning},
  title = {Single Cell Optical Imaging and Spectroscopy},
  journal = {Chemical Reviews},
  volume = {113},
  number = {4},
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  year = {2013},
  url = {http://dx.doi.org/10.1021/cr300336e}
}

Xia, T., Li, N., & Fang, X. (2013). Single-Molecule Fluorescence Imaging in Living Cells. Annual Review of Physical Chemistry, 64(1), 459-480. Retrieved from http://dx.doi.org/10.1146/annurev-physchem-040412-110127 BIB

@article{Tie2013,
  author = {Xia, Tie and Li, Nan and Fang, Xiaohong},
  title = {Single-Molecule Fluorescence Imaging in Living Cells},
  journal = {Annual Review of Physical Chemistry},
  volume = {64},
  number = {1},
  pages = {459-480},
  year = {2013},
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}

Stosiek, C., Garaschuk, O., Holthoff, K., & Konnerth, A. (2003). In vivo two-photon calcium imaging of neuronal networks. Proceedings of the National Academy of Sciences, 100(12), 7319-7324. Retrieved from http://www.pnas.org/content/100/12/7319.abstract BIB

@article{Stosiek2003,
  author = {Stosiek, Christoph and Garaschuk, Olga and Holthoff, Knut and Konnerth, Arthur},
  title = {In vivo two-photon calcium imaging of neuronal networks},
  volume = {100},
  number = {12},
  pages = {7319-7324},
  year = {2003},
  url = {http://www.pnas.org/content/100/12/7319.abstract},
  journal = {Proceedings of the National Academy of Sciences}
}

Wang, J. W., Wong, A. M., Flores, J., Vosshall, L. B., & Axel, R. (2003). Two-Photon Calcium Imaging Reveals an Odor-Evoked Map of Activity in the Fly Brain . Cell, 112(2), 271 - 282. Retrieved from http://www.cell.com/cell/abstract/S0092-8674(03)00004-7 BIB

@article{Wang2003,
  title = {Two-Photon Calcium Imaging Reveals an Odor-Evoked Map of Activity in the Fly Brain },
  journal = {Cell},
  volume = {112},
  number = {2},
  pages = {271 - 282},
  year = {2003},
  author = {Wang, Jing W. and Wong, Allan M. and Flores, Jorge and Vosshall, Leslie B. and Axel, Richard},
  url = {http://www.cell.com/cell/abstract/S0092-8674(03)00004-7}
}

Wilson, J. M., Dombeck, D. A., Dı́az-Rı́osManuel, Harris-Warrick, R. M., & Brownstone, R. M. (2007). Two-Photon Calcium Imaging of Network Activity in XFP-Expressing Neurons in the Mouse. Journal of Neurophysiology, 97(4), 3118-3125. Retrieved from http://jn.physiology.org/content/97/4/3118.long BIB

@article{Wilson2007,
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}

Chemical, process, and other considerations

Prevost, T. P., Balakrishnan, A., Suresh, S., & Socrate, S. (2011). Biomechanics of brain tissue. Acta biomaterialia, 7(1), 83–95. BIB

@article{prevost2011biomechanics,
  title = {Biomechanics of brain tissue},
  author = {Prevost, Thibault P and Balakrishnan, Asha and Suresh, Subra and Socrate, Simona},
  journal = {Acta biomaterialia},
  volume = {7},
  number = {1},
  pages = {83--95},
  year = {2011},
  publisher = {Elsevier}
}

Mastronarde, D. N. (2005). Automated electron microscope tomography using robust prediction of specimen movements. Journal of structural biology, 152(1), 36–51. BIB

@article{mastronarde2005automated,
  title = {Automated electron microscope tomography using robust prediction of specimen movements},
  author = {Mastronarde, David N},
  journal = {Journal of structural biology},
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  number = {1},
  pages = {36--51},
  year = {2005},
  publisher = {Elsevier}
}

Palay, S. L., McGee-Russell, Sm., Gordon, S., & Grillo, M. A. (1962). Fixation of neural tissues for electron microscopy by perfusion with solutions of osmium tetroxide. The Journal of cell biology, 12(2), 385–410. BIB

@article{palay1962fixation,
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  author = {Palay, Sanford L and McGee-Russell, SM and Gordon, Spencer and Grillo, Mary A},
  journal = {The Journal of cell biology},
  volume = {12},
  number = {2},
  pages = {385--410},
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}

Williams, T. H., & Jew, J. Y. (1975). An improved method for perfusion fixation of neural tissues for electron microscopy. Tissue and Cell, 7(3), 407–418. BIB

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Pawley, J. (1984). Low voltage scanning electron microscopy. Journal of microscopy, 136(1), 45–68. BIB

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Data challenges

Lichtman, J. W., & Denk, W. (2011). The big and the small: challenges of imaging the brain’s circuits. Science, 334(6056), 618–623. BIB

@article{lichtman2011big,
  title = {The big and the small: challenges of imaging the brain’s circuits},
  author = {Lichtman, Jeff W and Denk, Winfried},
  journal = {Science},
  volume = {334},
  number = {6056},
  pages = {618--623},
  year = {2011},
  publisher = {American Association for the Advancement of Science}
}

Beyer, J., Al-Awami, A., Kasthuri, N., Lichtman, J. W., Pfister, H., & Hadwiger, M. (2013). ConnectomeExplorer: Query-guided visual analysis of large volumetric neuroscience data. Visualization and Computer Graphics, IEEE Transactions on, 19(12), 2868–2877. BIB

@article{beyer2013connectomeexplorer,
  title = {ConnectomeExplorer: Query-guided visual analysis of large volumetric neuroscience data},
  author = {Beyer, Johanna and Al-Awami, Ali and Kasthuri, Narayanan and Lichtman, Jeff W and Pfister, Hanspeter and Hadwiger, Markus},
  journal = {Visualization and Computer Graphics, IEEE Transactions on},
  volume = {19},
  number = {12},
  pages = {2868--2877},
  year = {2013},
  publisher = {IEEE}
}

Burns, R., Lillaney, K., Berger, D. R., Grosenick, L., Deisseroth, K., Reid, R. C., Roncal, W. G., Manavalan, P., Bock, D. D., Kasthuri, N., & others. (2013). The open connectome project data cluster: scalable analysis and vision for high-throughput neuroscience. In Proceedings of the 25th International Conference on Scientific and Statistical Database Management (27). BIB

@inproceedings{burns2013open,
  title = {The open connectome project data cluster: scalable analysis and vision for high-throughput neuroscience},
  author = {Burns, Randal and Lillaney, Kunal and Berger, Daniel R and Grosenick, Logan and Deisseroth, Karl and Reid, R Clay and Roncal, William Gray and Manavalan, Priya and Bock, Davi D and Kasthuri, Narayanan and others},
  booktitle = {Proceedings of the 25th International Conference on Scientific and Statistical Database Management},
  pages = {27},
  year = {2013},
  organization = {ACM}
}

Kleissas, D. M., Roncal, W. G., Manavalan, P., Vogelstein, J. T., Bock, D. D., Burns, R., & Vogelstein, R. J. Large-Scale Synapse Detection Using CAJAL3D. BIB

@article{kleissaslarge,
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}

Compression

Jain, V., Seung, H. S., & Turaga, S. C. (2010). Machines that learn to segment images: a crucial technology for connectomics. Current opinion in neurobiology, 20(5), 653–666. BIB

@article{jain2010machines,
  title = {Machines that learn to segment images: a crucial technology for connectomics},
  author = {Jain, Viren and Seung, H Sebastian and Turaga, Srinivas C},
  journal = {Current opinion in neurobiology},
  volume = {20},
  number = {5},
  pages = {653--666},
  year = {2010},
  publisher = {Elsevier}
}

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