Reproducible Analysis of Rat Brain PET Studies Using an Additional [18F]NaF Scan and an MR-Based ROI Template

Background. An important step in the analysis of positron emission tomography (PET) studies of the brain is the definition of regions of interest (ROI). Image coregistration, ROI analysis, and quantification of brain PET data in small animals can be observer dependent. The purpose of this study was to investigate the feasibility of ROI analysis based on a standard MR template and an additional [18F]NaF scan. Methods. [18F]NaF scans of 10 Wistar rats were coregistered with a standard MR template by 3 observers and derived transformation matrices were applied to corresponding [11C]AF150(S) images. Uptake measures were derived for several brain regions delineated using the MR template. Overall agreement between the 3 observers was assessed by interclass correlation coefficients (ICC) of uptake data. In addition, [11C]AF150(S) ROI data were compared with ex vivo biodistribution data. Results. For all brain regions, ICC analysis showed excellent agreement between observers. Reproducibility, estimated by calculation of standard deviation of the between-observer differences, was demonstrated by an average of 17% expressed as coefficient of variation. Uptake of [11C]AF150(S) derived from ROI analysis closely matched ex vivo biodistribution data. Conclusions. The proposed method provides a reproducible and tracer-independent method for ROI analysis of rat brain PET data.

[1]  Johan Nuyts,et al.  Construction and evaluation of multitracer small-animal PET probabilistic atlases for voxel-based functional mapping of the rat brain. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  H. Hodge,et al.  The Adsorption of Fluorides by Enamel, Dentin, Bone and Hydroxyapatite as shown by the Radioactive Isotope. , 1940 .

[3]  Sanjiv S. Gambhir,et al.  AMIDE: A Completely Free System for Medical Imaging Data Analysis , 1994 .

[4]  J. Leysen,et al.  Radiosynthesis and biological evaluation of the M1 muscarinic acetylcholine receptor agonist ligand [11C]AF150(S) , 2012 .

[5]  P. Cumming,et al.  Pig brain stereotaxic standard space: Mapping of cerebral blood flow normative values and effect of MPTP-lesioning , 2005, Brain Research Bulletin.

[6]  Gene Robert DiResta,et al.  Measurement of brain tissue specific gravity using pycnometry , 1991, Journal of Neuroscience Methods.

[7]  W. Marsden.  I and J , 2012 .

[8]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[9]  C. Kuntner,et al.  Limitations of Small Animal PET Imaging with [18F]FDDNP and FDG for Quantitative Studies in a Transgenic Mouse Model of Alzheimer’s Disease , 2009, Molecular Imaging and Biology.

[10]  Arthur W. Toga,et al.  A Probabilistic Atlas of the Human Brain: Theory and Rationale for Its Development The International Consortium for Brain Mapping (ICBM) , 1995, NeuroImage.

[11]  Abraham Z. Snyder,et al.  Template Images for Nonhuman Primate Neuroimaging: 2. Macaque , 2001, NeuroImage.

[12]  Jean Logan,et al.  Reproducibility of 11C-raclopride binding in the rat brain measured with the microPET R4: effects of scatter correction and tracer specific activity. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[13]  D. Mash,et al.  Autoradiographic localization of M1 and M2 muscarine receptors in the rat brain , 1986, Neuroscience.

[14]  R. Stephenson.  A and V , 1962, The British journal of ophthalmology.

[15]  Ronald Boellaard,et al.  Performance evaluation of the ECAT HRRT: an LSO-LYSO double layer high resolution, high sensitivity scanner , 2007, Physics in medicine and biology.

[16]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[17]  R. Harper,et al.  X-RAY DIFFRACTION ANALYSIS OF THE EFFECT OF FLUORIDE ON HUMAN BONE APATITE. , 1963, Archives of oral biology.

[18]  J. R. Landis,et al.  The measurement of observer agreement for categorical data. , 1977, Biometrics.

[19]  Ronald Boellaard,et al.  Accuracy of 3-Dimensional Reconstruction Algorithms for the High-Resolution Research Tomograph , 2008, Journal of Nuclear Medicine.

[20]  Olaf B. Paulson,et al.  MR-based automatic delineation of volumes of interest in human brain PET images using probability maps , 2005, NeuroImage.

[21]  Vesna Sossi,et al.  Positron emission tomography kinetic modeling algorithms for small animal dopaminergic system imaging , 2010, Synapse.

[22]  L. Battistin,et al.  Uptake and life time of fluoride ion in rats by 19F-NMR. , 1993, Magnetic resonance imaging.

[23]  Adriaan A. Lammertsma,et al.  The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease , 1996, Journal of Neuroscience Methods.

[24]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[25]  Janine Doorduin,et al.  Evaluation of [11C]-DAA1106 for imaging and quantification of neuroinflammation in a rat model of herpes encephalitis. , 2010, Nuclear medicine and biology.

[26]  Masahiro Fujita,et al.  Quantification of brain phosphodiesterase 4 in rat with (R)-[11C]Rolipram-PET , 2005, NeuroImage.