Skip to main content

Advertisement

Log in

Comparison of Digital Subtraction Angiography, Micro-Computed Tomography Angiography and Magnetic Resonance Angiography in the Assessment of the Cerebrovascular System in Live Mice

  • Original Article
  • Published:
Clinical Neuroradiology Aims and scope Submit manuscript

Abstract

Purpose

Mice are often used as small animal models of brain ischemia, venous thrombosis, or vasospasm. This article aimed at providing an overview of the currently available methodologies for in vivo imaging of the murine cerebrovasculature and comparing the capabilities and limitations of the different methods.

Methods

Micro-computed tomography angiography (CTA) was performed during intra-arterial and intravenous administration of a contrast agent bolus. Digital subtraction angiography (DSA) was performed during intra-arterial administration of contrast agent using the micro-CT scanner. Time-of-flight (ToF) magnetic resonance (MR) angiography was performed using a small animal scanner (9.4 T) equipped with a cryogenic transceive quadrature coil. Datasets were compared for scan time, contrast-to-noise ratio (CNR), temporal and spatial resolution, radiation dose, contrast agent dose and detailed recognition of cerebrovascular structures.

Results

Highest spatial resolution was achieved using micro-CTA (16 ´ 16 ´ 16 µm) and DSA (14 ´ 14 µm). Compared to micro-CTA (20–40 s) and ToF-MRA (57 min), DSA provided highest temporal resolutions (30 fps) allowing analyses of the cerebrovascular blood flow. Highest mean CNR was reached using ToF-MRA (50.7 ± 15.0), while CNR of micro-CTA depended on the intra-arterial (19.0 ± 1.0) and intravenous (1.3 ± 0.4) use of agents. The CNR of DSA was 10.0 ± 1.8.

Conclusions

The use of dedicated small animal scanners allows cerebrovascular imaging in live animals as small as mice. As each of the methods analyzed has its advantages and limitations, choosing the best suited imaging modality for a defined question is of great importance. By this means the aforementioned methods offer a great potential for future projects in preclinical cerebrovascular research including ischemic stroke or vasospasm.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Barone FC, Knudsen DJ, Nelson AH, Feuerstein GZ, Willette RN. Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy. J Cereb Blood Flow Metab. 1993;13(4):683–92.

    Article  PubMed  CAS  Google Scholar 

  2. Zhang Z, Chopp M, Zhang RL, Goussev A. A mouse model of embolic focal cerebral ischemia. J Cereb Blood Flow Metab. 1997;17(10):1081–8. doi:10.1097/00004647-199710000-00010.

    Article  PubMed  CAS  Google Scholar 

  3. Kim DE, Schellingerhout D, Jaffer FA, Weissleder R, Tung CH. Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis. J Cereb Blood Flow Metab. 2005;25(2):226–33. doi:9600023 [pii] 10.1038/sj.jcbfm.9600023.

    Article  PubMed  Google Scholar 

  4. Nagai M, Yilmaz CE, Kirchhofer D, Esmon CT, Mackman N, Granger DN. Role of coagulation factors in cerebral venous sinus and cerebral microvascular thrombosis. Neurosurgery. 2010;66(3):560–5; discussion 5–6. doi:10.1227/01.NEU.0000365745.49583.FD.

    Article  PubMed  Google Scholar 

  5. Sabri M, Jeon H, Ai J, Tariq A, Shang X, Chen G, et al. Anterior circulation mouse model of subarachnoid hemorrhage. Brain Res. 2009;1295:179–85. doi:s0006-8993(09)01633-3 [pii] 10.1016/j.brainres.2009.08.021.

    Article  PubMed  CAS  Google Scholar 

  6. Sabri M, Ai J, Knight B, Tariq A, Jeon H, Shang X, et al. Uncoupling of endothelial nitric oxide synthase after experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2011;31(1):190–9. doi:jcbfm201076 [pii] 10.1038/jcbfm.2010.76.

    Article  PubMed  CAS  Google Scholar 

  7. Parra A, McGirt MJ, Sheng H, Laskowitz DT, Pearlstein RD, Warner DS. Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: methodological analysis. Neurol Res. 2002;264(5):510–6.

    Article  Google Scholar 

  8. Kidoguchi K, Tamaki M, Mizobe T, Koyama J, Kondoh T, Kohmura E, et al. In vivo X-ray angiography in the mouse brain using synchrotron radiation. Stroke. 2006;37(7):1856–61. doi:01.STR.0000226904.96059.a6 [pii] 10.1161/01.STR.0000226904.96059.a6.

    Article  PubMed  Google Scholar 

  9. Schambach SJ, Bag S, Steil V, Isaza C, Schilling L, Groden C, et al. Ultrafast high-resolution in vivo volume-CTA of mice cerebral vessels. Stroke. 2009;40(4):1444–50. doi:STROKEAHA.108.521740 [pii] 10.1161/STROKEAHA.108.521740.

    Article  PubMed  Google Scholar 

  10. Rosenblum WI. Effects of blood pressure and blood viscosity on fluorescein transit time in the cerebral microcirculation in the mouse. Circ Res. 1970;27(5):825–33.

    PubMed  CAS  Google Scholar 

  11. Dorr A, Sled JG, Kabani N. Three-dimensional cerebral vasculature of the CBA mouse brain: a magnetic resonance imaging and micro-computed tomography study. Neuroimage. 2007;35(4):1409–23. doi:s1053-8119(06)01204-3 [pii] 10.1016/j.neuroimage.2006.12.040.

    Article  PubMed  CAS  Google Scholar 

  12. Kerl HU, Isaza CT, Boll H, Schambach SJ, Nolte IS, Groden C, et al. Evaluation of a continuous-rotation, high-speed scanning protocol for micro-computed tomography. J Comput Assist Tomogr. 2011;35(4):517–23. doi:10.1097/RCT.0b013e31821c662b 00004728-201107000-00019 [pii].

    Article  PubMed  Google Scholar 

  13. Howles GP, Ghaghada KB, Qi Y, Mukundan S Jr., Johnson GA. High-resolution magnetic resonance angiography in the mouse using a nanoparticle blood-pool contrast agent. Magn Reson Med. 2009;62(6):1447–56. doi:10.1002/mrm.22154.

    Article  PubMed  Google Scholar 

  14. Kucinski T. Imaging in acute stroke—a personal view. Klin Neuroradiol. 2009;19(1):20–30. doi:10.1007/s00062-009-8030-3.

    Article  PubMed  Google Scholar 

  15. Salomon EJ, Barfett J, Willems PW, Geibprasert S, Bacigaluppi S, Krings T. Dynamic CT angiography and CT perfusion employing a 320-detector row CT: protocol and current clinical applications. Klin Neuroradiol. 2009;19(3):187–96. doi:10.1007/s00062-009-9019-7.

    Article  PubMed  Google Scholar 

  16. Beckmann N, Stirnimann R, Bochelen D. High-resolution magnetic resonance angiography of the mouse brain: application to murine focal cerebral ischemia models. J Magn Reson. 1999;140(2):442–50. doi:10.1006/jmre.1999.1864 s1090-7807(99)91864-5 [pii].

    Article  PubMed  CAS  Google Scholar 

  17. Brubaker LM, Bullitt E, Yin C, Van Dyke T, Lin W. Magnetic resonance angiography visualization of abnormal tumor vasculature in genetically engineered mice. Cancer Res. 2005;65(18):8218–23. doi:65/18/8218 [pii] 10.1158/0008-5472.CAN-04-4355.

    Article  PubMed  CAS  Google Scholar 

  18. Bullitt E, Wolthusen PA, Brubaker L, Lin W, Zeng D, Van Dyke T. Malignancy-associated vessel tortuosity: a computer-assisted, MR angiographic study of choroid plexus carcinoma in genetically engineered mice. AJNR Am J Neuroradiol. 2006;27(3):612–9. doi:27/3/612 [pii].

    PubMed  CAS  Google Scholar 

  19. Baltes C, Radzwill N, Bosshard S, Marek D, Rudin M. Micro MRI of the mouse brain using a novel 400 MHz cryogenic quadrature RF probe. NMR Biomed. 2009;22(8):834–42. doi:10.1002/nbm.1396.

    Article  PubMed  Google Scholar 

  20. Doblas S, He T, Saunders D, Pearson J, Hoyle J, Smith N, et al. Glioma morphology and tumor-induced vascular alterations revealed in seven rodent glioma models by in vivo magnetic resonance imaging and angiography. J Magn Reson Imaging. 2010;32(2):267–75. doi:10.1002/jmri.22263.

    Article  PubMed  Google Scholar 

  21. Kitamura N, Araya R, Kudoh M, Kishida H, Kimura T, Murayama M, et al. Beneficial effects of estrogen in a mouse model of cerebrovascular insufficiency. PLoS One. 2009;4(4):e5159. doi:10.1371/journal.pone.0005159.

    Article  PubMed  Google Scholar 

  22. Umetani K, Kidoguchi K, Morishita A, Oizumi XS, Tamaki M, Yamashita H, et al. In vivo cerebral artery microangiography in rat and mouse using synchrotron radiation imaging system. Conf Proc IEEE Eng Med Biol Soc. 2007;2007:3926–9. doi:10.1109/IEMBS.2007.4353192.

    PubMed  Google Scholar 

  23. Myojin K, Taguchi A, Umetani K, Fukushima K, Nishiura N, Matsuyama T, et al. Visualization of intracerebral arteries by synchrotron radiation microangiography. AJNR Am J Neuroradiol. 2007;28(5):953–7. doi:28/5/953 [pii].

    PubMed  CAS  Google Scholar 

  24. de Lin M, Ning L, Badea CT, Mistry NN, Qi Y, Johnson GA. A high-precision contrast injector for small animal x-ray digital subtraction angiography. IEEE Trans Biomed Eng. 2008;55(3):1082–91. doi:10.1109/TBME.2007.909541.

    Article  PubMed  Google Scholar 

  25. Badea CT, Drangova M, Holdsworth DW, Johnson GA. In vivo small-animal imaging using micro-CT and digital subtraction angiography. Phys Med Biol. 2008;53(19):R319–50. doi:s0031-9155(08)59874-5 [pii] 10.1088/0031-9155/53/19/R01.

    Article  PubMed  CAS  Google Scholar 

  26. Lin MD, Samei E, Badea CT, Yoshizumi TT, Johnson GA. Optimized radiographic spectra for small animal digital subtraction angiography. Med Phys. 2006;33(11):4249–57.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marc A. Brockmann MD, MSc.

Additional information

First Author G. Figueiredo & Second Author C. Brockmann contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Figueiredo, G., Brockmann, C., Boll, H. et al. Comparison of Digital Subtraction Angiography, Micro-Computed Tomography Angiography and Magnetic Resonance Angiography in the Assessment of the Cerebrovascular System in Live Mice. Clin Neuroradiol 22, 21–28 (2012). https://doi.org/10.1007/s00062-011-0113-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00062-011-0113-2

Keywords

Navigation