Brief Biography

Dr. Brian Nieman is currently a scientist at the Mouse Imaging Centre (MICe) at The Hospital for Sick Children and a new investigator with the Ontario Institute for Cancer Research. His current research focuses on the development of imaging methods for evaluation of cellular movements and distribution during disease progression, with particular application to cancer in the brain.

Nieman received his PhD in 2006 from the Department of Medical Biophysics at the University of Toronto. His thesis described the development of magnetic resonance imaging (MRI) methods for the analysis of mouse models of human disease. This work included advances in imaging methods and image processing, including development of high-throughput MRI methods, evaluation and specification of mouse MRI hardware, and automated detection of anatomical phenotypes. 

From 2006 to 2009, Brian was a post-doctoral fellow with Dr. Daniel H. Turnbull at the New York University School of Medicine. His post-doctoral work featured development of MR imaging methods for study of mouse development—including in utero imaging of late stage embryos—and cellular imaging for study of neural progenitor cell migrations during homeostasis and disease in the brain.

Research Interests

• development of new imaging technologies for 3D, cell-specific imaging
• phenotyping in murine disease models
• study of cellular involvement during brain tumour development

My research program focuses on characterization of disease or development processes both spatially and temporally in relevant mouse models. Noninvasive imaging methods incorporating cellular or genetic specificity are a priority, especially as related to cancer, multiple sclerosis and development. Examples include:

The cellular MRI of glioma development
Brain tumours are made of a heterogeneous cell population, and appreciation of the roles of different cell types will lead to a better understanding of tumour development. We are adapting cellular MRI methods for study of glioma progression, evaluating both the patterns of tumour growth and the response of normal stem cell niches. Current methods permit tracking of cells labeled with particular iron-oxide contrast agents.

Development of genetically-expressible MR markers
Technologies permitting the visualization of specific cell types or gene expression patterns are critical to biomedical research, but are generally limited in the information they can provide in vivo. To date, in vivo methods enabling genetic specificity cannot also provide high-resolution images through the entire body. It is attractive to consider that MRI might be adapted for this purpose, as it already provides excellent anatomical context at high-resolution. We are investigating protein-metal and peptide-metal complexes for their ability to generate hyperintense contrast in MR images in the aim of identifying candidate transgenes providing MR readouts of gene expression.

Three-dimensional study of tumour “micro-anatomy”
It seems only a subset of tumour cells perpetuate tumour growth indefinitely. These cells—sometimes called cancer stem cells (CSCs)—reside amongst larger populations of normal and tumour cells, and intercellular interactions affect tumour development. CSCs may prefer particular cellular environments, such as adjacent to blood vessels, similar to normal neural stem cells. How such “niches” become established and how they evolve during tumour progression is best studied with three-dimensional imaging methods. We are developing optical projection tomography methods in the brain as a form of “3D histology” for imaging of specimens at near cellular resolution (~3µm) using many of the fluorescent antibodies available for immunohistochemistry.

For more information, visit the Mouse Imaging Centre (MICe)

Publications

Berrios-Otero CA, Wadghiri YZ,  Nieman BJ, Joyner AL, Turnbull DH.  Three-dimensional micro-MRI analysis of cerebral artery development in mouse embryos.  Magn. Reson. Med 2009; 62(6):1431-1439. DOI 10.1002/mrm.22113

Nieman BJ, Szulc KU, Turnbull DH. Three-dimensional, in vivo MRI with self-gating and image coregistration in the mouse. Magn Reson Med 2009; 61(5):1148-1157.  DOI 10.1002/mrm.21945

Nieman BJ, Lerch JP, Bock NA, Chen XJ, Sled JG, Henkelman RM. Mouse behavioral mutants have neuroimaging abnormalities. Hum Brain Mapp 2007; 28:567-575.  DOI 10.1002/hbm.20408

Nieman BJ, Bishop J, Dazai J, Bock NA, Lerch JP, Feintuch A, Chen XJ, Sled JG, Henkelman RM. MR technology for biological studies in mice. NMR Biomed 2007; 20:291-303.  DOI 10.1002/nbm.1142

Mori AD, Zhu Y, Vahora I, Nieman B, Koshiba-Takeuchi K, Davidson L, Pizard A, Seidman JG, Seidman CE, Chen XJ, Henkelman RM, Bruneau BG. Tbx5-dependent rheostatic control of cardiac gene expression and morphogenesis. Dev Biol 2006; 297:566-586.  DOI 10.1016/j.ydbio.2006.05.023

Bishop J, Feintuch A, Bock NA, Nieman B, Dazai J, Davidson L, Henkelman RM. Retrospective gating for mouse cardiac MRI. Magn Reson Med 2006; 55:472-477.  DOI 10.1002/mrm.20794

Nieman BJ, Flenniken AM, Adamson SL, Henkelman RM, Sled JG. Anatomical phenotyping in the brain and skull of a mutant mouse by magnetic resonance imaging and computed tomography. Physiol Genomics 2006; 24:154-162.  DOI 10.1152/physiolgenomics.00217.2005