Advertisement

Abstract

Optical projection tomography (OPT) is a relatively new technology that is especially well suited to the 3D imaging of “mesoscopic” specimens (those from about 1 to 10 mm across). It is fundamentally different from optical sectioning techniques such as confocal microscopy, since it does not attempt to limit data acquisition to a narrow focused 2D plane. Instead, it is an optical equivalent of computed tomography (CT), in which projection images are captured for many angles around the specimen and the 3D results are calculated using a back-projection algorithm. Volumetric data sets can be generated from both bright-field and fluorescent images. OPT has seen the development of a wide range of applications over the last five years, especially in the field of developmental biology, and increasingly for the analysis of whole mouse organs (such as the pancreas, brain and lungs). Within these contexts, it is particularly useful for mapping gene expression patterns at both RNA and protein levels. In this chapter, both the principles of the technology and the range of applications will be introduced. A few potential directions for the future will be summarized at the end.

Keywords

Autosomal Dominant Polycystic Kidney Disease Virtual Histology Optical Projection Tomography Virtual Section Edinburgh Mouse Atlas Project 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alanentalo T, Asayesh A, Morrison H, Loren CE, Holmberg D, Sharpe J, Ahlgren U (2007) Tomo-graphic molecular imaging and 3D quantification within adult mouse organs. Nat Methods 4:31–33PubMedCrossRefGoogle Scholar
  2. Arques CG, Doohan R, Sharpe J, Torres M (2007) Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme. Development 134:3173–3722CrossRefGoogle Scholar
  3. Asayesh A, Sharpe J, Watson RP, Hecksher-Sørensen J, Hastie ND, Hill RE, Ahlgren U (2006) Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1-/- mice. Genes Dev 20:2208–2213PubMedCrossRefGoogle Scholar
  4. Baldock RA, Bard JBL, Burger A, Burton N, Christiansen J, Feng G, Hill R, Houghton D, Kaufman M, Rao J, Sharpe J, Ross A, Stevenson P, Venkataraman S, Waterhouse A, Yang Y, Davidson DR (2003) EMAP and EMAGE: a framework for understanding spatially organized data. Neuroinformatics 1:309–325PubMedCrossRefGoogle Scholar
  5. Boot M, Westerberg H, Sanz-Esquerro J, Schweitzer R, Cotterell J, Torres M, Sharpe J (2008) In vitro whole-organ imaging: Quantitative 4D analysis of growth and dynamic gene expression in mouse limb buds. Nature Methods 5:609–612PubMedCrossRefGoogle Scholar
  6. Bryson-Richardson RJ, Berger S, Schilling TF, Hall TE, Cole NJ, Gibson AJ, Sharpe J, Currie PD (2007) FishNet: an online database of zebrafish anatomy. BMC Biol 5:34PubMedCrossRefGoogle Scholar
  7. Coultas L, Chawengsaksophak K, Rossant J (2005) Endothelial cells and VEGF in vascular development. Nature 438:937–945PubMedCrossRefGoogle Scholar
  8. Davies JA, Armstrong J (2006) The anatomy of organogenesis: novel solutions to old problems. Progr Histochem Cytochem 40:165–176CrossRefGoogle Scholar
  9. DeLaurier A, Schweitzer R, Logan M (2006) Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb. Dev Biol 299:22–34PubMedCrossRefGoogle Scholar
  10. Dhenain D, Ruffins S, Jacobs RE (2001) Three-dimensional digital mouse atlas using high-resolution MRI. Dev Biol 232:458–470PubMedCrossRefGoogle Scholar
  11. Dickinson ME (2006) Multimodal imaging of mouse development: tools for the postgenomic era. Dev Dyn 235:2386–2400PubMedCrossRefGoogle Scholar
  12. Dickinson ME, Bearman G, Tilie S, Lansford R, Fraser SE (2001) Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning flourescence microscopy. Biotechniques 31:1274–1278Google Scholar
  13. Fisher ME, Clelland AK, Bain A, Baldock RA, Murphy P, Downie H, Tickle C, Davidson DR, Buckland RA (2008) Integrating technologies for comparing 3D gene expression domains in the developing chick limb. Dev Biol 317:13–23PubMedCrossRefGoogle Scholar
  14. Gibson AP, Hebden JC, Arridge SR (2005) Recent advances in diffuse optical imaging. Phys Med Biol 50:R1–R43PubMedCrossRefGoogle Scholar
  15. Hajihosseini MK, Langhe S, Lana-Elola E, Morrison H, Sparshott N, Kelly R, Sharpe J, Rice D, Bellusci S (2008a) Localization and fate of Fgf10-expressing cells in the adult mouse brain implicate Fgf10 in control of neurogenesis. Mol Cell Neurosci 37:857–868CrossRefGoogle Scholar
  16. Hajihosseini MK, Duarte R, Pegrum J, Donjacour A, Lana-Elola X, Rice D, Sharpe J, Dickson C (2008b) Evidence that Fgf10 contributes to the skeletal and visceral defects of an Apert syndrome mouse model. Dev Dyn (online publication: 4 Sep 2008)Google Scholar
  17. Hart AW, Morgan JE, Schneider J, West K, McKie L, Bhattacharya S, Jackson IJ, Cross SH (2006) Cardiac malformations and midline skeletal defects in mice lacking filamin A. Human Mol Genet 15:2457–2467CrossRefGoogle Scholar
  18. Hecksher-Sørensen J, Sharpe J (2001) 3D confocal reconstruction of gene expression in mouse. Mech Dev 100:59–63PubMedCrossRefGoogle Scholar
  19. Hecksher-Sørensen J, Watson RP, Lettice LA, Serup P, Eley L, De Angelis C, Ahlgren U, Hill RE (2004) The splanchnic mesodermal plate directs spleen and pancreatic laterality, and is regulated by Bapx1/Nkx3.2 Development 131:4665–4675PubMedCrossRefGoogle Scholar
  20. Huang D, Swanson E, Lin C, Schuman J, Stinson W, Chang W, Hee M, Flotte T, Gregory K, Puliafito C, Fujimoto J (1991) Optical coherence tomography. Science 254:1178–1181PubMedCrossRefGoogle Scholar
  21. Huisken J, Swoger J, Del Bene F, Wittbrodt J, Steltzer E (2004) Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305:1007–1009PubMedCrossRefGoogle Scholar
  22. Jenkins M, Pankti P, Huayun D, Monica MM, Michiko W, Andrew MR (2007) Phenotyp-ing transgenic embryonic murine hearts using optical coherence tomography. Appl Opt 46:1776–1781PubMedCrossRefGoogle Scholar
  23. Johnson J, Mark SH, Isabel W, Lindsey JH, Christopher RJ, Greg MJ, Mario RC, Charles K (2006) Virtual histology of transgenic mouse embryos for high-throughput phenotyping. PLoS Genet 2(4):e61PubMedCrossRefGoogle Scholar
  24. Kak AC, Slaney M (1988) Principles of computerized tomographic imaging. IEEE, New YorkGoogle Scholar
  25. Kerwin J, Scott M, Sharpe J, Puelles L, Robson S, Mart*#x00ED;nez-de-la-Torre M, Feran JL, Feng G, Baldock R, Strachan T, Davidson D, Lindsay S (2004) 3-Dimensional modelling of early human brain development using optical projection tomography. BioMedCentral Neurobiology 5:27Google Scholar
  26. Kulesa PM, Fraser SE (1998) Confocal imaging of living cells in intact embryos. In: Paddock SW (ed) Confocal microscopy: methods and protocols (Methods in Molocular Biology 122). Humana, Totowa, NJGoogle Scholar
  27. Lee K, Avondo J, Morrison H, Blot L, Stark M, Sharpe J, Bangham A, Coen E (2006) Visualizing plant development and gene expression in three dimensions using optical projection tomography. Plant Cell 18:2145–2156PubMedCrossRefGoogle Scholar
  28. Lickert H, Takeuchi JK, Von Both I, Walls JR, McAuliffe F, Adamson SL, Henkelman RM, Wrana JL, Rossant J, Bruneau BG (2004) Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432:107–112PubMedCrossRefGoogle Scholar
  29. Louie AY, Huber MM, Ahrens ET, Rothbacher U, Moats R, Jacobs RE, Fraser SE, Meade TJ (2000) In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 18:321–325PubMedCrossRefGoogle Scholar
  30. Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17:545–580PubMedCrossRefGoogle Scholar
  31. McGurk L, Morrison H, Keegan LP, Sharpe J, O'Connell MA (2007) Three-dimensional imaging of Drosophila melanogaster. PLoS ONE 2(9):e834PubMedCrossRefGoogle Scholar
  32. Ntziachristos V, Ripoll J, Wang LV, Weissleder R (2005) Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotechnol 23:313–320PubMedCrossRefGoogle Scholar
  33. Potter SM, Fraser SE, Pine J (1996) The greatly reduced photodamage of 2-photon microscopy enables extended 3-dimensional time-lapse imaging of living neurons. Scanning 18:147Google Scholar
  34. Pryce BA, Brent AE, Murchison ND, Tabin CJ, Schweitzer R (2007) Generation of transgenic tendon reporters, ScxGFP and ScxAP, utilizing regulatory elements of the Scleraxis gene. Dev Dyn 236:1677–1682PubMedCrossRefGoogle Scholar
  35. Requejo-Isidro J, McGinty J, Munro I, Elson DS, Galletly NP, Lever MJ, Neil MA, Stamp GW, French PM, Kellett PA, Hares JD, Dymoke-Bradshaw AK (2004) High-speed wide-field time-gated endoscopic fluorescence-lifetime imaging. Opt Lett 29:2249PubMedCrossRefGoogle Scholar
  36. Rinaldi A (2005) A bloodless revolution—a growing interest in artificial blood substitutes has resulted in new products that could soon improve transfusion medicine. EMBO Rep 6:705–708PubMedCrossRefGoogle Scholar
  37. Risebro CA, Smart N, Dupays L, Breckenridge R, Mohun TJ, Riley PR (2006) Hand1 regulates cardiomyocyte proliferation versus differentiation in the developing heart. Development 133:4595–4606PubMedCrossRefGoogle Scholar
  38. Ruijter JM, Soufan AT, Hagoort J, Moorman AF (2004) Molecular imaging of the embryonic heart: fables and facts on 3D imaging of gene expression patterns. Birth Defects Res C Embryo Today 72:224–240PubMedCrossRefGoogle Scholar
  39. Sakhalkar HS, Dewhirst M, Oliver T, Cao Y, Oldham M (2007) Functional imaging in bulk tissue specimens using optical emission tomography: fluorescence preservation during optical clearing. Phys Med Biol 52:2035–2054PubMedCrossRefGoogle Scholar
  40. Sarma S, Kerwin J, Puelles L, Scott M, Strachan T, Feng G, Sharpe J, Davidson D, Baldock R, Lindsay S (2005) 3D modelling, gene expression mapping and post-mapping image analysis in the developing human brain. Brain Res Bull 66:449–453PubMedCrossRefGoogle Scholar
  41. Schneider X, Böse J, Bamforth S, Gruber AD, Broadbent C, Clarke K, Neubauer S, Lengeling A, Bhattacharya S (2004) Identification of cardiac malformations in mice lacking Ptdsr using a novel high-throughput magnetic resonance imaging technique. BMC Dev Biol 4:16PubMedCrossRefGoogle Scholar
  42. Sharpe J (2003) Optical projection tomography as a new tool for studying embryo anatomy. J Anat 202:175–181PubMedCrossRefGoogle Scholar
  43. Sharpe J (2004) Optical projection tomography. Annu Rev Biomed Eng 6:209–228PubMedCrossRefGoogle Scholar
  44. Sharpe J (2005) Optical projection tomography: imaging 3D organ shapes and gene expression patterns in whole vertebrate embryos. In: Yuste X, Konnerth X (eds) Imaging in neuroscience and development. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NYGoogle Scholar
  45. Sharpe J, Ahlgren U, Perry P, Hill B, Ross A, Hecksher-Sørensen J, Baldock R, Davidson D (2002) Optical projection tomography as a tool for 3D microscopy and gene expression studies. Science 296:541–545PubMedCrossRefGoogle Scholar
  46. Summerhurst K, Stark M, Sharpe J, Davidson D, Murphy P (2008) 3D representation of Wnt and Frizzled gene expression patterns in the mouse embryo at embryonic day 11.5 (Ts19). Gene Expression Patterns 8:331–348PubMedCrossRefGoogle Scholar
  47. Tickle C (2004) The contribution of chicken embryology to the understanding of vertebrate limb development. Mechanisms Dev 121:1019–1029PubMedCrossRefGoogle Scholar
  48. Walls JR, Sled JG, Sharpe J, Henkelman RM (2005) Correction of artefacts in optical projection tomography. Phys Med Biol 50:1–21CrossRefGoogle Scholar
  49. Walls JR, Sled JG, Sharpe J, Henkelman RM (2007) Resolution improvement in emission optical projection tomography. Phys Med Biol 52:2775–2790PubMedCrossRefGoogle Scholar
  50. Walls J, Coultas L, Rossant J, Henkelman M (2008) Three-dimensional analysis of early embryonic mouse vascular development. PLoS ONE 3(8):e2853PubMedCrossRefGoogle Scholar
  51. Wilkie A, Jordan SA, Sharpe J, Price DJ, Jackson IJ (2004) Widespread tangential dispersion and extensive cell death during early neurogenesis in the mouse neocortex. Dev Biol 267:109–118PubMedCrossRefGoogle Scholar
  52. Yoder BK, Mulroy S, Eustace H, Boucher C, Sandford R (2006) Molecular pathogenesis of autosomal dominant polycystic kidney disease Expert Rev Mol Med 8:1–22PubMedCrossRefGoogle Scholar
  53. Zuniga A, Haramis AP, McMahon AP, Zeller R (1999) Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds. Nature 401:598–602PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.ICREA (Catalan Institute for Advanced Research and Education), EMBL-CRG Systems Biology UnitCentre for Genomic Regulation, UPFBarcelonaSpain

Personalised recommendations