5th EuropEan MolEcular IMagIng MEEtIng - ESMI

5th EuropEan MolEcular IMagIng MEEtIng – EMIM2010
In-vivo imaging of a mouse traumatic brain injury model using dual-isotope quantitative
spect/ct
Máthé D. (1) , Szigeti K. (2) , Fekete K. (3) , Horváth I. (2) , Benyó Z. (3) .
(1) CROmed Ltd,
(2) Nanobiotechnology and In Vivo Imaging Centre Semmelweis University Faculty of Medicine,
(3) Semmelweis University Faculty of Medicine.
domokos.mathe@gmail.com
Introduction: Using a standardized mouse neurotrauma
model we aimed at determining the role
of high-resolution SPECT/CT in detecting and
quantifying the volumetric and functional extent of
blood-brain barrier disruption. We chose the freezing
trauma model because of its reproducibly standard
damage.
Methods: Mice were subjected to a standardized
freezing method transcranially using a cooled
needle tip. In the presented initial studies, we compared
the imaging pattern of the animals at equally 5
hours post the freezing trauma. We used a dedicated,
quantitative multiplexed multipinhole SPECT imaging
system for laboratory animals. X-ray CT of the
structures was also performed together with SPECT
data acquisition.
We correlated BBB disruption and blood perfusion
with quantitative imaging of the decrease in glial
and neuronal potassium uptake. We applied the validated
intravenous tracer 99mTc-DTPA to detect the
disruption of the BBB. Blood perfusion of the brain
was assessed using the also validated tracer 99mTc-
HMPAO. A radioactive isotopic potassium analogue,
201Tl was used to track K+ uptake changes quantitatively.
201Tl ions were passed through the BBB by
means of diethyl-dithiocarbamate (DDC) complex
that redistributes to ionic 201Tl after being taken
up in brain tissues.
Uptake volumes (in mm3) and total brain as well as
lesion radioactivity values (in kBq) were evaluated
on 3D reconstructed brain images of treated mice
(n=5 per group) and a non-treated group. Besides
imaging of single tracers (3 groups), simultaneous
multi-channel imaging was used in two other groups
of mice having received 99mTc-DTPA plus 201Tl-
DDC or, 99mTc-HMPAO plus 201Tl-DDC.
After imaging, histological control of the brain
trauma size and localization was performed in the
formaldehyde-fixed brains of all animals.
Results: The uptake of 99mTc-DTPA correlated well
with the size and localization of the lesion whereas
the cold spot of the lesion at the perfusion image
was evident in all animals having received 99mTc-
HMPAO. However the cold spot was surrounded by
an area of increased perfusion as compared to the
same area in control animals. When comparing with
201Tl-DDC images, the penumbra effect became evident,
especially in the animals imaged with 99mTc-
HMPAO and 201Tl-DDC in the same time. The
area of non-active glial and neuronal potassium uptake
was significantly larger than the non-perfused
area and the hyper-perfused area co-localized with
the edge of the disappeared neural potassium uptake
volumes in 4 animals out of 5. SPECT/CT identified
the dislocation of brain due to increased intracranial
pressure in all treated animals.
Conclusions: In vivo whole-animal imaging using
quantitative SPECT is a very promising method to
dissect different activation patterns and regulation
of different mechanisms behind the events following
neurotrauma (and consequently stroke too). Using
a unique dual-isotopic approach to detect multiple
events in the same time in the same animals, the size
and presence of a penumbral region where perfusion
is elevated but neural (both glial and neuronal) K+
utilization is decreased, could be identified.
Acknowledgement: We are grateful for Dr. Jürgen
Goldschmidt (Magdeburg) and Roberto Pasqualini
(Orsay) for valuable advice and kind hints in 201Tl-
DDC application and preparation.
References:
1. Goldschmidt et al. NeuroImage 49 (2010) 303–315
EuropEan SocIEty for MolEcular IMagIng – ESMI
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