Brain perfusion SPECT in the mouse: normal pattern according to gender and age.
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Brain perfusion SPECT in the mouse: normal pattern according to gender and age. normal pattern according to gender and age. / Apostolova, Ivayla; Wunder, Andreas; Dirnagl, Ulrich; Michel, Roger; Stemmer, Nina; Lukas, Mathias; Derlin, Thorsten; Gregor-Mamoudou, Betina; Goldschmidt, Jürgen; Brenner, Winfried; Buchert, Ralph.
in: NEUROIMAGE, Jahrgang 63, Nr. 4, 4, 12.2012, S. 1807-1817.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Brain perfusion SPECT in the mouse: normal pattern according to gender and age.
T2 - normal pattern according to gender and age
AU - Apostolova, Ivayla
AU - Wunder, Andreas
AU - Dirnagl, Ulrich
AU - Michel, Roger
AU - Stemmer, Nina
AU - Lukas, Mathias
AU - Derlin, Thorsten
AU - Gregor-Mamoudou, Betina
AU - Goldschmidt, Jürgen
AU - Brenner, Winfried
AU - Buchert, Ralph
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/12
Y1 - 2012/12
N2 - Regional cerebral blood flow (rCBF) is a useful surrogate marker of neuronal activity and a parameter of primary interest in the diagnosis of many diseases. The increasing use of mouse models spawns the demand for in vivo measurement of rCBF in the mouse. Small animal SPECT provides excellent spatial resolution at adequate sensitivity and is therefore a promising tool for imaging the mouse brain. This study evaluates the feasibility of mouse brain perfusion SPECT and assesses the regional pattern of normal Tc-99m-HMPAO uptake and the impact of age and gender. Whole-brain kinetics was compared between Tc-99m-HMPAO and Tc-99m-ECD using rapid dynamic planar scans in 10 mice. Assessment of the regional uptake pattern was restricted to the more suitable tracer, HMPAO. Two HMPAO SPECTs were performed in 18 juvenile mice aged 7.5 ± 1.5weeks, and in the same animals at young adulthood, 19.1 ± 4.0 weeks (nanoSPECT/CTplus, general purpose mouse apertures: 1.2kcps/MBq, 0.7mm FWHM). The 3-D MRI Digital Atlas Database of an adult C57BL/6J mouse brain was used for region-of-interest (ROI) analysis. SPECT images were stereotactically normalized using SPM8 and a custom made, left-right symmetric HMPAO template in atlas space. For testing lateral asymmetry, each SPECT was left-right flipped prior to stereotactical normalization. Flipped and unflipped SPECTs were compared by paired testing. Peak brain uptake was similar for ECD and HMPAO: 1.8 ± 0.2 and 2.1 ± 0.6 %ID (p=0.357). Washout after the peak was much faster for ECD than for HMPAO: 24 ± 7min vs. 4.6 ± 1.7h (p=0.001). The general linear model for repeated measures with gender as an intersubject factor revealed an increase in relative HMPAO uptake with age in the neocortex (p=0.018) and the hippocampus (p=0.012). A decrease was detected in the midbrain (p=0.025). Lateral asymmetry, with HMPAO uptake larger in the left hemisphere, was detected primarily in the neocortex, both at juvenile age (asymmetry index AI=2.7 ± 1.7%, p=0.000) and at young adult age (AI=2.4 ± 1.7%, p=0.000). Gender had no effect on asymmetry. Voxel-wise testing confirmed the ROI-based findings. In conclusion, high-resolution HMPAO SPECT is a promising technique for measuring rCBF in preclinical research. It indicates lateral asymmetry of rCBF in the mouse brain as well as age-related changes during late maturation. ECD is not suitable as tracer for brain SPECT in the mouse because of its fast clearance from tissue indicating an interspecies difference in esterase activity between mice and humans.
AB - Regional cerebral blood flow (rCBF) is a useful surrogate marker of neuronal activity and a parameter of primary interest in the diagnosis of many diseases. The increasing use of mouse models spawns the demand for in vivo measurement of rCBF in the mouse. Small animal SPECT provides excellent spatial resolution at adequate sensitivity and is therefore a promising tool for imaging the mouse brain. This study evaluates the feasibility of mouse brain perfusion SPECT and assesses the regional pattern of normal Tc-99m-HMPAO uptake and the impact of age and gender. Whole-brain kinetics was compared between Tc-99m-HMPAO and Tc-99m-ECD using rapid dynamic planar scans in 10 mice. Assessment of the regional uptake pattern was restricted to the more suitable tracer, HMPAO. Two HMPAO SPECTs were performed in 18 juvenile mice aged 7.5 ± 1.5weeks, and in the same animals at young adulthood, 19.1 ± 4.0 weeks (nanoSPECT/CTplus, general purpose mouse apertures: 1.2kcps/MBq, 0.7mm FWHM). The 3-D MRI Digital Atlas Database of an adult C57BL/6J mouse brain was used for region-of-interest (ROI) analysis. SPECT images were stereotactically normalized using SPM8 and a custom made, left-right symmetric HMPAO template in atlas space. For testing lateral asymmetry, each SPECT was left-right flipped prior to stereotactical normalization. Flipped and unflipped SPECTs were compared by paired testing. Peak brain uptake was similar for ECD and HMPAO: 1.8 ± 0.2 and 2.1 ± 0.6 %ID (p=0.357). Washout after the peak was much faster for ECD than for HMPAO: 24 ± 7min vs. 4.6 ± 1.7h (p=0.001). The general linear model for repeated measures with gender as an intersubject factor revealed an increase in relative HMPAO uptake with age in the neocortex (p=0.018) and the hippocampus (p=0.012). A decrease was detected in the midbrain (p=0.025). Lateral asymmetry, with HMPAO uptake larger in the left hemisphere, was detected primarily in the neocortex, both at juvenile age (asymmetry index AI=2.7 ± 1.7%, p=0.000) and at young adult age (AI=2.4 ± 1.7%, p=0.000). Gender had no effect on asymmetry. Voxel-wise testing confirmed the ROI-based findings. In conclusion, high-resolution HMPAO SPECT is a promising technique for measuring rCBF in preclinical research. It indicates lateral asymmetry of rCBF in the mouse brain as well as age-related changes during late maturation. ECD is not suitable as tracer for brain SPECT in the mouse because of its fast clearance from tissue indicating an interspecies difference in esterase activity between mice and humans.
KW - Animals
KW - Male
KW - Female
KW - Mice
KW - Mice, Inbred C57BL
KW - Image Processing, Computer-Assisted
KW - Sex Characteristics
KW - Perfusion
KW - Tomography, Emission-Computed, Single-Photon
KW - Cerebrovascular Circulation/physiology
KW - Functional Laterality/physiology
KW - Aging/physiology
KW - Brain/growth & development/radionuclide imaging
KW - Cysteine/analogs & derivatives/diagnostic use/pharmacokinetics
KW - Organotechnetium Compounds/diagnostic use/pharmacokinetics
KW - Radiopharmaceuticals/diagnostic use/pharmacokinetics
KW - Technetium Tc 99m Exametazime/diagnostic use/pharmacokinetics
KW - Animals
KW - Male
KW - Female
KW - Mice
KW - Mice, Inbred C57BL
KW - Image Processing, Computer-Assisted
KW - Sex Characteristics
KW - Perfusion
KW - Tomography, Emission-Computed, Single-Photon
KW - Cerebrovascular Circulation/physiology
KW - Functional Laterality/physiology
KW - Aging/physiology
KW - Brain/growth & development/radionuclide imaging
KW - Cysteine/analogs & derivatives/diagnostic use/pharmacokinetics
KW - Organotechnetium Compounds/diagnostic use/pharmacokinetics
KW - Radiopharmaceuticals/diagnostic use/pharmacokinetics
KW - Technetium Tc 99m Exametazime/diagnostic use/pharmacokinetics
U2 - 10.1016/j.neuroimage.2012.08.038
DO - 10.1016/j.neuroimage.2012.08.038
M3 - SCORING: Journal article
C2 - 22971548
VL - 63
SP - 1807
EP - 1817
JO - NEUROIMAGE
JF - NEUROIMAGE
SN - 1053-8119
IS - 4
M1 - 4
ER -
