Brain perfusion SPECT in the mouse: Normal pattern according to gender and age

Apostolova, Ivayla; Wunder, Andreas; Dirnagl, Ulrich; Roger, Michel; Stemmer, Nina; Lukas, Mathias; Derlin, Thorsten; Gregor-Mamoudou, Betina; Goldschmidt, Jürgen; Brenner, Winfried; Buchert, Ralph

doi:10.1016/j.neuroimage.2012.08.038

Cited by 25 publications

(31 citation statements)

References 43 publications

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“…In concordance to other imaging modalities an MTF of 10% was chosen to define the spatial resolution in the imaging plane. Spatial resolution was about 0.7 mm full-width at half-maximum (FWHM) matching those of a previous study with the same scannertype and a whole body mouse 1 mm multipinhole aperture (Apostolova et al, 2012).…”

Section: Intravenous Injection Of 99m Tc-hmpaosupporting

confidence: 69%

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SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice

et al. 2014

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Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography.

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Section: Intravenous Injection Of 99m Tc-hmpaosupporting

confidence: 69%

“…Both tracers can be injected in the awake state and the stable brain tracer-distributions after stimulation can be mapped in the anesthetized state. Thus far, however, 99m Tc-HMPAO-SPECT has only been used in restrained rats (Wyckhuys et al, 2010(Wyckhuys et al, , 2013 or anesthetized mice (Apostolova et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice

et al. 2014

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“…The ROI used in the analysis was bilateral, i.e., included the amygdala in both hemispheres, and, therefore, does not allow detection of possible laterality. We tested the amygdala effect for hemispheric laterality as described in our previous work 26 and found no indication of left-right asymmetry, neither in ROI-nor in the voxelbased analyses (results not shown). This suggests that the observed relative hyperperfusion in the amygdala of juvenile NF1+/ − mice is a symmetric effect affecting both hemispheres more or less equally.…”

Section: Discussionmentioning

confidence: 82%

Perfusion Single Photon Emission Computed Tomography in a Mouse Model of Neurofibromatosis Type 1: Towards a Biomarker of Neurologic Deficits

Apostolova

Niedzielska

Derlin

et al. 2015

J Cereb Blood Flow Metab

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Neurofibromatosis type 1 (NF1) is a single-gene disorder affecting neurologic function in humans. The NF1+/- mouse model with germline mutation of the NF1 gene presents with deficits in learning, attention, and motor coordination, very similar to NF1 patients. The present study performed brain perfusion single-photon emission computed tomography (SPECT) in NF1+/- mice to identify possible perfusion differences as surrogate marker for altered cerebral activity in NF1. Cerebral perfusion was measured with hexamethyl-propyleneamine oxime (HMPAO) SPECT in NF1+/- mice and their wild-type littermates longitudinally at juvenile age and at young adulthood. Histology and immunohistochemistry were performed to test for structural changes. There was increased HMPAO uptake in NF1 mice in the amygdala at juvenile age, which reduced to normal levels at young adulthood. There was no genotype effect on thalamic HMPAO uptake, which was confirmed by ex vivo measurements of F-18-fluorodeoxyglucose uptake in the thalamus. Morphologic analyses showed no major structural abnormalities. However, there was some evidence of increased density of microglial somata in the amygdala of NF1-deficient mice. In conclusion, there is evidence of increased perfusion and increased density of microglia in juvenile NF1 mice specifically in the amygdala, both of which might be associated with altered synaptic plasticity and, therefore, with cognitive deficits in NF1.

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“…They are lipophilic agents, which ensures their passage through the blood brain barrier, that accumulate in the intracellular environment proportionally to the blood flow. (23) Differently from HMPAO- 99m Tc, ECD- 99m Tc is not retained in the brains of rats or rabbits, (24,25) which justifies our choice for HMPAO- 99m Tc in this experiment. Its excretion occurs through the hepatobiliary and renal systems.…”

Section: Methodsmentioning

confidence: 86%

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals

Mejía

Miranda

Durante

et al. 2016

Einstein (São Paulo)

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Objective:To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images.Methods:An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times.Results:Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO).Conclusion:This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

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Brain perfusion SPECT in the mouse: Normal pattern according to gender and age

Cited by 25 publications

References 43 publications

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice

Perfusion Single Photon Emission Computed Tomography in a Mouse Model of Neurofibromatosis Type 1: Towards a Biomarker of Neurologic Deficits

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals

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