High‐resolution MR imaging of mouse brain microvasculature using the relaxation rate shift index Q

Magnetic resonance imaging (MRI) is a powerful method for in vivo quantification of tissue properties. It has been previously proposed that the index Q ≡ δR2/(δR  2* )2/3, where ΔR2 and δR  2* are the spin echo and gradient echo relaxation rate shifts caused by the injection of an intravascular contrast agent, may be useful for characterizing microvasculature. In particular, Q is expected to correlate well with the density of microvessels. This study presents high‐resolution in vivo Q‐maps of normal mouse brain obtained with a superparamagnetic iron oxide contrast agent at a field of level of 9.4 T. Normative Q values are derived for several regions of interest and significant interregional variations are observed. Microvessel densities estimated from the Q‐maps are found to be in reasonable accord with histologically determined values. A possible application of Q‐maps is the assessment of angiogenic activity in tumors. Copyright © 2004 John Wiley & Sons, Ltd.

[1]  M Hoehn-Berlage,et al.  Regional and directional anisotropy of apparent diffusion coefficient in rat brain , 1999, NMR in biomedicine.

[2]  M. Décorps,et al.  Vessel size imaging , 2001, Magnetic resonance in medicine.

[3]  H. Weiss,et al.  Quantitative Regional Determination of Morphometric Indices of the Total and Perfused Capillary Network in the Rat Brain , 1982, Circulation research.

[4]  Ralph Weissleder,et al.  Long-circulating iron oxides for MR imaging , 1995 .

[5]  Y Usson,et al.  In vivo assessment of tumoral angiogenesis , 2004, Magnetic resonance in medicine.

[6]  G. Yancopoulos,et al.  Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. , 1999, Science.

[7]  R. Chandra,et al.  MR imaging of microvasculature , 2000, Magnetic resonance in medicine.

[8]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[9]  B R Rosen,et al.  NMR imaging of changes in vascular morphology due to tumor angiogenesis , 1998, Magnetic resonance in medicine.

[10]  G Le Duc,et al.  Use of T2‐weighted susceptibility contrast MRI for mapping the blood volume in the glioma‐bearing rat brain , 1999, Magnetic resonance in medicine.

[11]  G. D. del Zoppo,et al.  Cerebral Microvessel Responses to Focal Ischemia , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  W. Kuschinsky,et al.  Interdependency of local capillary density, blood flow, and metabolism in rat brains. , 1986, The American journal of physiology.

[13]  Julie Morris,et al.  Assessment of Vascularity in Histological Sections: Effects of Methodology and Value as an Index of Angiogenesis in Breast Tumours , 1998, The Histochemical Journal.

[14]  G. Jayson,et al.  Intra-tumoural microvessel density in human solid tumours , 2002, British Journal of Cancer.

[15]  C. Batzios,et al.  Vascular network of the rat hippocampus is not homogeneous along the septotemporal axis , 2003, Brain Research.

[16]  H. Inoue,et al.  Three-dimensional observations on microvascular growth in rat glioma using a vascular casting method , 2005, Journal of Cancer Research and Clinical Oncology.

[17]  E. Haacke,et al.  High‐resolution BOLD venographic imaging: a window into brain function , 2001, NMR in biomedicine.

[18]  A P Pathak,et al.  Utility of simultaneously acquired gradient‐echo and spin‐echo cerebral blood volume and morphology maps in brain tumor patients , 2000, Magnetic resonance in medicine.

[19]  P. Luiten,et al.  Cerebral microvascular pathology in aging and Alzheimer's disease , 2001, Progress in Neurobiology.

[20]  F. Howe,et al.  Tumor vascular architecture and function evaluated by non‐invasive susceptibility MRI methods and immunohistochemistry , 2003, Journal of magnetic resonance imaging : JMRI.

[21]  Glyn Johnson,et al.  Dynamic, contrast‐enhanced perfusion MRI in mouse gliomas: Correlation with histopathology , 2003, Magnetic resonance in medicine.

[22]  A P Pathak,et al.  MR‐derived cerebral blood volume maps: Issues regarding histological validation and assessment of tumor angiogenesis , 2001, Magnetic resonance in medicine.

[23]  D M Shames,et al.  Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density. , 1996, Radiology.

[24]  E F Halpern,et al.  Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. , 1994, Radiology.

[25]  K. Ho,et al.  Multicenter phase-II trial of safety and efficacy of NC100150 for steady-state contrast-enhanced peripheral magnetic resonance angiography , 2003, European Radiology.

[26]  J. Murgo,et al.  Microsphere and dilution techniques for the determination of blood flows and volumes in conscious mice. , 1992, The American journal of physiology.

[27]  M. Menger,et al.  Vascular Microenvironment in Gliomas , 2000, Journal of Neuro-Oncology.

[28]  H. M. Swartz,et al.  The effects of ketamine–xylazine anesthesia on cerebral blood flow and oxygenation observed using nuclear magnetic resonance perfusion imaging and electron paramagnetic resonance oximetry , 2001, Brain Research.

[29]  M. Graves,et al.  Magnetic resonance angiography. , 1997, The British journal of radiology.

[30]  E. Wu,et al.  High‐resolution in vivo CBV mapping with MRI in wild‐type mice , 2003, Magnetic resonance in medicine.

[31]  J. Griffiths,et al.  Effects of overexpression of dimethylarginine dimethylaminohydrolase on tumor angiogenesis assessed by susceptibility magnetic resonance imaging. , 2003, Cancer research.