Abstract

The pig is growing in popularity as an experimental animal because its gyrencephalic brain is similar to humans. Currently, however, there is a lack of appropriate brain templates to support functional and structural neuroimaging pipelines. The primary contribution of this work is an average volume from an iterative, non-linear registration of 70 five- to seven-month-old male Yucatan minipigs. In addition, several aspects of this study are unique, including the comparison of linear and non-linear template generation, the characterization of a large and homogeneous cohort, an analysis of effective resolution after averaging, and the evaluation of potential in-template bias as well as a comparison with a template from another minipig species using a “left-out” validation set. We found that within our highly homogeneous cohort, non-linear registration produced better templates, but only marginally so. Although our T1-weighted data were resolution limited, we preserved effective resolution across the multi-subject average, produced templates that have high gray-white matter contrast and demonstrate superior registration accuracy compared to an alternative minipig template.

Highlights

  • Across a broad spectrum of biomedical research, the pig is emerging as an important experimental animal that is more human-relevant than rodents while balancing the monetary and ethical costs associated with non-human primates

  • We examined the internal error for TL58 and the final (TL58) and (TNL58) by transforming each of the 58 subjects’ landmark coordinates to T (2)L and T (2)NL using their subject-specific transformations obtained from iteration 2 (recall that data transformed to T (2)L and T (2)NL were averaged to generate TL58 and TNL58)

  • A visual comparison demonstrates that the non-linear template has enhanced outer edge boundaries and greater anatomical detail surrounding white matter (WM), gray matter (GM), and ventricles compared to the linear template

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Summary

Introduction

Across a broad spectrum of biomedical research, the pig is emerging as an important experimental animal that is more human-relevant than rodents while balancing the monetary and ethical costs associated with non-human primates. It is not surprising that neuroimaging studies using pigs have been conducted across the full range of modalities, including PET, CT, MRI, EEG and fNIRS (Lind et al, 2007; Roura et al, 2016; Sauleau et al, 2009; Schubert et al, 2016) Despite their promise and increasing use, neuroimaging software and analysis pipelines for pigs are currently lacking compared to primates, rodents, and humans. The most data and labor intensive component of species-specific analysis pipelines, is the development of appropriate templates and atlases Though both terms are sometimes used interchangeably, we refer to a template as a reference brain that defines a standardized coordinate “brain space” and an atlas as providing the additional benefit of defined anatomical labels. Templates can provide a coordinate system to report the spatial locations of those statistics

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