- Post Doctoral
MIT Unit Affiliation:
- Electrical Engineering & Computer Science
- Health Sciences and Technology
Post Doc Sponsor / Advisor:
Date PhD Completed:
Top 3 Areas of Expertise:
Biomedical engineer driven by applied research with a focus in imaging technologies. I have led international, multidisciplinar projects with applications in cancer care, cardiovascular pathologies, meningitis diagnosis and developmental biology. Currently involved in an exciting venture, the M+Vision program, devoted to translate biomedical imaging innovation into clinically-applicable products at the crossroads of engineering, business and medicine.
Expected End Date of Post Doctoral Position:
- "Home-based neutrophil blood testing to tailor chemotherapy regimens to personal toxicity limits". Madrid-MIT M+Visión Consortium (Massachusetts Institute of Technology & Madri+d Foundation), NIH-CFTCC, Coulter Foundation. PI: Carlos Castro-Gonzalez. 01/01/2014 - 06/30/2016.
- "Energy-based technologies to reduce central-line infections in hemodialysis patients". Madrid-MIT M+Visión Consortium (Massachusetts Institute of Technology & Madri+d Foundation). PI: Aurelien Bourquard & Carlos Castro-Gonzalez. 01/01/2014 - 12/31/2014.
- "A medical device to measure noninvasively bulk properties of the cerebrospinal fluid". Madrid-MIT M+Visión Consortium (Massachusetts Institute of Technology & Madri+d Foundation). PI: Javier Jimeneze. 01/01/2013 - 12/31/2014.
- "Real-time multimodal medical imaging for complex treatment schemes". Spanish Ministry of Science. PI: Andres Santos. 01/01/2011 - 12/31/2013.
- "Evalution about the feasibility and usability of a tool for planning and 3D ultrasound guiding in liver metastasis surgery". Spanish Ministry of Science. PI: Maria J Ledesma. 01/01/2010 - 12/31/2012.
- "Advance Techniques for the Visualization and Processing of cardiac imaging to analyze ventricular deformation and asynchrony". Spanish Ministry of Science. PI: Maria J Ledesma. 10/01/2007 - 09/31/2011.
- "Consortium for the development of advanced technologies for medicine". Spanish Ministry of Industry. PI: Andres Santos. 01/12/2006 - 01/11/2010.
- "Genomics and Technologies for Health". European Molecular Imaging Laboratories. PI: Andres Santos. 01/01/2004 - 12/31/2009.
- "BioEmergences: 'In what' and 'how much' are individuals similar and different? Towards the measurement of the individual susceptibility to diseases or response to treatments". European Union Frame Program 6 (FP6-NEST). PI: Paul Bourgine. 06/01/2008 - 05/31/2009.
- "MorphoNet: Reconstructing Genetic and Cellular Dynamics in Early Zebrafish Embryogenesis". Integrated Action Spain-France (HF2007-0074). PI: Nadine Peyrieras. 01/01/2008 - 12/31/2009.
The creation of atlases, or digital models where information from different subjects can be combined, is a field of increasing interest in biomedical imaging. When a single image does not contain enough information to appropriately describe the organism under study, it is then necessary to acquire images of several individuals, each of them containing complementary data with respect to the rest of the components in the cohort. This approach allows creating digital prototypes, ranging from anatomical atlases of human patients and organs, obtained for instance from Magnetic Resonance Imaging, to gene expression cartographies of embryo development, typically achieved from Light Microscopy.
Within such context, in this PhD Thesis we propose, develop and validate new dedicated image processing methodologies that, based on image registration techniques, bring information from multiple individuals into alignment within a single digital atlas model. We also elaborate a dedicated software visualization platform to explore the resulting wealth of multi-dimensional data and novel analysis algorithms to automatically mine the generated resource in search of biological insights.
In particular, this work focuses on gene expression data from developing zebrafish embryos imaged at the cellular resolution level with Two-Photon Laser Scanning Microscopy. Disposing of quantitative measurements relating multiple gene expressions to cell position and their evolution in time is a fundamental prerequisite to understand embryogenesis multi-scale processes. However, the number of gene expressions that can be simultaneously stained in one acquisition is limited due to optical and labeling constraints. These limitations motivate the implementation of atlasing strategies that can recreate a virtual gene expression multiplex.
The developed computational tools have been tested in two different scenarios. The first one is the early zebrafish embryogenesis where the resulting atlas constitutes a link between the phenotype and the genotype at the cellular level. The second one is the late zebrafish brain where the resulting atlas allows studies relating gene expression to brain regionalization and neurogenesis.
The proposed computational frameworks have been adapted to the requirements of both scenarios, such as the integration of partial views of the embryo into a whole embryo model with cellular resolution or the registration of anatomical traits with deformable transformation models non-dependent on any specific labeling.
The software implementation of the atlas generation tool (Match-IT) and the visualization platform (Atlas-IT) together with the gene expression atlas resources developed in this Thesis are to be made freely available to the scientific community.
Lastly, a novel proof-of-concept experiment integrates for the first time 3D gene expression atlas resources with cell lineages extracted from live embryos, opening up the door to correlate genetic and cellular spatio-temporal dynamics.
Top 5 Awards and honors (name of award, date received):
5 Recent Papers:
X. Jimenez , S.K. Shukla, I. Ortega, F.J. Illana, C. Castro-González, B. Marti-Fuster, I. Butterworth, Arroyo M., B. Anthony, L. Elvira. (2016) "Quantification Of Very Low Concentrations Of Leukocyte Suspensions In Vitro By High-Frequency Ultrasound". Ultrasounds in Medicine and Biology, in press.
Castro-González, C., Luengo-Oroz, M.A., Duloquin, L., Savy, T., Rizzi, B., Desnoulez, S., Doursat, R., Kergosien, Y.L., Ledesma-Carbayo, M.J., Bourgine, P., Peyriéras, N., Santos, A. (2014) "A Digital Framework to Build, Visualize and Analyze a Gene Expression Atlas with Cellular Resolution in Zebrafish Early Embryogenesis". PLoS Computational Biology, 10(6):e1003670. (doi:10.1371/journal.pcbi.1003670).
Luengo-Oroz, M.A., Pastor-Escuredo, D., Castro-Gonzalez, C., Faure, E., Savy, T., Lombardot, B., Rubio-Guivernau, J.L., Duloquin, L., Ledesma-Carbayo, M.J., Bourgine, P., Peyrieras, N., Santos, A. (2012) "3D+t Morphological Processing: Applications to Embryogenesis Image Analysis". IEEE Transaction in Image Processing, 21(8):3518-3530. (doi: 10.1109/TIP.2012.2197007).
Castro-González, C., Ledesma-Carbayo, M.J., Peyriéras, N., Santos, A. (2012). "Assembling Models of Embryo Development: Image Analysis and the Construction of Digital Atlases". Birth Defects Research Part C-Embryo Today, 96(2):109-120. (doi: 10.1002/bdrc.21012).
Schaap, M., Metz, C.T., van Walsum, T., van der Giessen, A.G., Weustink, A.C., Mollet, N.R., Bauer, C., Bogunović, H., Castro, C., Deng, X., Dikici, E., O’Donnell, T., Frenay, M., Friman, O., Hernández Hoyos, M., Kitslaar, P.H., Krissian, K., Kühnel, C., Luengo-Oroz, M.A., Orkisz, M., Smedby, Ö., Styner, M., Szymczak, A., Tek, H., Wang, C., Warfield, S.K., Zambal, S., Zhang, Y., Krestin, G.P., Niessen, W.J. (2009) "Standardized Evaluation Methodology and Reference Database for Evaluating Coronary Artery Centerline Extraction Algorithms", Medical Image Analysis, 13(5):701-714. (doi: 10.1016/j.media.2009.06.003).