Advances in Quantitative Laryngology 2006 Groningen NL 1 High Resolution MRI Microscopic Neuro-Imaging Studies and Voice Disorders K. L. Watkin 1,2, L. Ciobanu 2,5, S. London 3, P. Bajcsy 4 1 College of Applied Health Sciences, 2 Biomedical Imaging Center, Beckman Institute, 3 Institute for Genomic Biology, 4 National Center for Supercomputing Applications, University of Illinois at Urbana- Champaign, Urbana, IL, 5 Pfizer Research, Ann Arbor, Michigan

2 Advances in Quantitative Laryngology 2006 Groningen NL Voice Disorders Spasmodic dysphonia is a neurologic voice disorder. Spasmodic dysphonia is a neurologic voice disorder. Its etiology is unknown. Its etiology is unknown. Treatment methods are principally Treatment methods are principally surgical resection surgical resection longterm, low dose, periodic treatment with botulinum toxin. longterm, low dose, periodic treatment with botulinum toxin. To fully understand this disorder and to evaluate various treatment methods an animal model would be of great assistance. To fully understand this disorder and to evaluate various treatment methods an animal model would be of great assistance.

3 Advances in Quantitative Laryngology 2006 Groningen NL Background Virtually all of our healthcare advances over the last century have been made using animal models. Virtually all of our healthcare advances over the last century have been made using animal models. Our extended lifespan, treatments for heart disease, cancer, diabetes, and vaccinations all attest to the benefits of animal models in research. Our extended lifespan, treatments for heart disease, cancer, diabetes, and vaccinations all attest to the benefits of animal models in research. In the area of deafness and communication disorders we have relied heavily on animal models to our advance our understanding of In the area of deafness and communication disorders we have relied heavily on animal models to our advance our understanding of hearing, hearing, hearing mechanisms and, hearing mechanisms and, currently, new forms of gene therapy for hair cell loss. currently, new forms of gene therapy for hair cell loss. Researchers studying human sound production and their disorders typically have not relied on the use of animal models to study the motor control sound production. Researchers studying human sound production and their disorders typically have not relied on the use of animal models to study the motor control sound production. Are their animal models that may be good candidates? Are their animal models that may be good candidates?

4 Advances in Quantitative Laryngology 2006 Groningen NL One of the most relevant candidate One of the most relevant candidate songbirds is the zebra finch songbirds is the zebra finch (Taeniopygia guttata). (Taeniopygia guttata). The zebra finch is an ideal animal model since the auditory behavior, the neural pathways, the genomic profile, and the neural pathways for sound generation are similar to humans. The zebra finch is an ideal animal model since the auditory behavior, the neural pathways, the genomic profile, and the neural pathways for sound generation are similar to humans. However, for the zebra finch to be a useful research model for the study of vocal neuro-motor control, especially Spasmodic Dysphonia, non-invasive methods for visualization of the central neural pathways are needed. However, for the zebra finch to be a useful research model for the study of vocal neuro-motor control, especially Spasmodic Dysphonia, non-invasive methods for visualization of the central neural pathways are needed. One potential small animal candidate is the SONGBIRD

5 Advances in Quantitative Laryngology 2006 Groningen NL Purpose In this report we will present some of the results of our work mapping in three dimensions (3D) the vocal production circuitry of the zebra finch Tesla MRI microscopy and 3D diffusion tensor weighted fiber tracking

6 Advances in Quantitative Laryngology 2006 Groningen NL Research Plan Capture high resolution MRI images of the cadaveric ZF brain (male; female) Capture high resolution MRI images of the cadaveric ZF brain (male; female) Grayscale Grayscale Diffusion Tensor Weighted Fibertracking Diffusion Tensor Weighted Fibertracking To validate our fiber-tracking algorithms To validate our fiber-tracking algorithms Sectioning the “imaged brains” Sectioning the “imaged brains” Staining with Fast Luxor Blue myelinate nerve fibers Staining with Fast Luxor Blue myelinate nerve fibers Aligning for 3D projection and fusion Aligning for 3D projection and fusion

7 Advances in Quantitative Laryngology 2006 Groningen NL Histological Image Processing

8 Advances in Quantitative Laryngology 2006 Groningen NL MRI Microscopy FA Color Coded DTI

9 Advances in Quantitative Laryngology 2006 Groningen NL

10 Advances in Quantitative Laryngology 2006 Groningen NL Summary Zebra Finch as a model for the study of spasmodic dysphonia Zebra Finch as a model for the study of spasmodic dysphonia To fully understand this disorder and to evaluate various treatment methods To fully understand this disorder and to evaluate various treatment methods Share our recent developments on fiber trackography Share our recent developments on fiber trackography Establish a global network of voice scientists interested in exploring the use of this model Establish a global network of voice scientists interested in exploring the use of this model