Mayu Iida1,2, Junichi Hata2,3,4, Yawara Haga1,4, Akiko Uematsu4,5, Fumiko Seki2,4, Daisuke Yoshimaru2,3,4, Kei Hagiya4, Hirotaka James Okano3,4, Hideyuki Okano4, and Takako Shirakawa1
1Department of Radiological Sciences, Human Health Sciences, Tokyo Metropolitan University Graduate School, Tokyo, Japan, 2Live Imaging Center, Central Institute for Experimental Animals, Kanagawa, Japan, 3Division of Regenerative Medicine, Jikei University School of Medicine, Tokyo, Japan, 4Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Saitama, Japan, 5Center of Evolutionary Cognitive Sciences, Tokyo University Graduate School, Tokyo, Japan
Synopsis
MRI
data of 204 large common marmoset colonies were obtained and analyzed regarding
brain volume. Marmosets have a brain structure and nerve paths are similar to
those in humans compared to other experimental animals. The volume from puberty
to old age in six regions (gray matter, deep gray matter, white matter,
brainstem, cerebellum, and CSF) could be evaluated. From the viewpoint of
volume and variability when performing brain image analysis, it was suggested
that marmosets are experimental animals that can evaluate the effects of individual
differences at the same level as humans or with slightly less variation than
humans.
Introduction
Non-human primates,
such as common marmosets, have a brain structure and nerve paths are similar to
those in humans compared to other experimental animals. They are therefore an
experimental animal that is attracting attention in brain neuroscience
research. However,
it is not certain when marmosets become adults and when they have reached old
age. In addition, the dispersion of their individual brain morphology compared
to rodents when used as experimental animals needs to be determined. How is it
compared to humans? There are many things that need to be clarified. Also, the number
of individuals used in marmoset research is very small compared to human
research. There
are many studies that have targeted dozens of individuals. As with humans and
other experimental animals, it is very important to evaluate a larger number of
individuals in marmoset studies for statistical analysis of brain images.
Within this context, in this study, MRI data of 200 large marmoset colonies
were obtained and analyzed regarding brain volume. The
purpose of this study was to evaluate the variations of individual marmosets in
brain morphology, to understand individual differences in marmoset brains and
to compare the results with humans and other experiment animals.Methods
All data were acquired with
9.4T MRI (Biospec 94/30) using a transmit and receiver coil and a conventional
birdcage circuit, 86 mm (Bruker BioSpin, Ettlingen, Germany). The imaging
parameters used in this study were Rapid Acquisition with Relaxation
Enhancement (RARE), Contrast; T2WI (TR/TE : 4000/22 ms, FOV : 48 mm×48 mm, Image
size : 128×128, Rare factor : 4, Pixel Resolution : 270μm, scan time : 7 min 24
sec). The subjects were 204 healthy common marmosets who were 0.8–11
years old (male 111, female 93). The segmentation was created using in the ANTS
software package. This image was skull stripped, then segmented to produce
template specific tissue priors. Specifically, the template was segmented into
5 tissue priors: gray matter (GM), deep gray matter (deepGM), white matter (WM),
brainstem and cerebellum. The images were then processed using the
antsCorticalThickness pipeline (ANTS), which extracts the brain, warps the
tissue priors and segments the subject images into the five tissue images in
subject space. ThresholdImage was used to calculate the amount of cerebrospinal
fluid (CSF). Using ITK-SNAP (www.itksnap.org), volume measurements
were made in the whole brain and six brain regions. The volume and dispersion
of each brain region were compared and evaluated. This study was approved by
the Animal Experiment Committees in RIKEN Brain Science Institute (BSI), and
was conducted in accordance with the Guidelines for Conducting Animal
Experiments of RIKEN BSI.Results
The
whole brain volume showed a gradual decrease with age. The GM showed a clear
volume reduction. The deepGM showed a gradual decrease that was similar to that
of GM. There was no significant change in the WM. On the other hand, relative
to the whole brain, it can be said that WM increases with age. The brainstem
showed a slight increase, and there was no significant change in the cerebellum
and CSF. The correlation between body weight and brain volume was also
obtained.Discussion
In this study, from the acquired data, the volume from puberty to old
age in the whole brain and six regions could be obtained and compared with
previous research with a volume transition of marmosets and humans focusing on
the stage of development. The peak volume in the GM was observed at the age of
5.3 months and subsequently declined by 20% by the age of 30 months. It is estimated
that the decrease continues after this. The WM peak volume was observed at the age of 9.9
months, and the volume did not decline, but rather remained stable after
reaching a peak plateau.1 From previous research results, we found that there
is no contradiction, as we found a decrease in GM from the age of 1 in this study
data and continuity with WM without a significant change. This suggested that common marmosets have little
sex differences in brain volume between regions. It was suggested that marmosets
are experimental animals that can evaluate the effects of individual
differences with slightly less variation. The
brainstem, cerebellum and CSF have not been calculated in common marmoset
studies so far. In humans, GM volume decreases linearly between the ages of 20 and 70. The ratio of WM tends to consistently increase from
youth (the age of 1–2 for marmosets) to old age.2,3 The volume of WM peaks in the 50s and then
decreases slowly. The decrease in GM volume at a young age
is due to pruning and myelination with development, but the decrease in GM after
age 50 seems to reflect a decrease in neurons.Conclusion
In
this study, we analyzed brain volume using large-scale MRI brain data of common
marmosets. From
these data, the volume from puberty to old age in six regions (GM, deepGM, WM,
brainstem, cerebellum, and CSF)
could
be obtained and evaluated. From the viewpoint of volume and variability when
performing brain image analysis, it was suggested that marmosets are
experimental animals that can evaluate the effects of individual differences at
the same level as humans or with slightly less variation than humans.
Acknowledgements
This
research is partially supported by the program for Brain Mapping by Integrated
Neurotechnologies for Disease Studies (Brain/MINDS) from Japan Agency for
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