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Cristian T. Badea, PhD
Associate Professor, Radiology and Biomedical Engineering

4D Micro-CT for Anatomical and Functional Preclinical Imaging

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The complete characterization of mouse / human genomes has enabled development of a number of mouse models to study the cardiovascular system and gain insight into the pathogenesis of disease, as well as develop new treatments. Our micro-CT system provides integrated high-throughput morphological and functional imaging for small-animal cardiovascular research. Below is an overview of the instrument and the novel technological strategies we use.

microCT
Dual-source Micro-CT System

Fig.1: Our dual tube/detector micro-CT system in a rotating specimen geometry[1,2] uses:

  • 2 Varian G297 x-ray tubes (fs=0.3/0.8 mm)
  • 2 Epsilon High Frequency x-ray generators (EMD Technologies (Quebec, Canada)
  • 2 XDI-VHR CCD x-ray detectors (Photonic Science, East Sussex, UK) with a Gd2O2S phosphor and 22-micron pixel size
Sampling Protocols for Cardiac Micro-CT sampling
  Prospective Gating: Acquisition waits for the coincidence of desired respiratory and cardiac phases (Fig.2a) [3,4]
  Retrospective Gating: Acquisition occurs at a fast and constant rate, while ECG / respiratory signals are recorded (Fig.2b) [7]
  Fast Prospective Gating:

Projections of all phases are acquired at each angle before rotation, and the delays between each acquisition are computed in real time (Fig.2c) [10]

Contrast Agents - Liposomal Iodine (Lip-I) CT [5] (Fig.3)
  • Nano-size (100 nm) (remains intravascular)
  • PEG – long circulation times (t1/2 ~18 hours)
  • Concentration (133 mg I/ml)
  • Cleared via the liver and spleen (no renal toxicity)
liposomeI

Image Reconstruction Fig 4: Image reconstruction: prospective (A) and retrospective (B) gating reconstruction
Sampling strategy affects image reconstruction for 4D cardiac CT. Although slow, prospective gating (Fig.4A) creates a regular angular projection distribution with adequate reconstructions using filtered backprojection (FBP)[8]. Retrospective gating (Fig.4B) is fast, but irregular angular projection distribution creates streaking artifacts. We use either PSF deconvolution[6] or iterative CT algorithms with total variation (TV)[7] implemented on GPU (Figs. 5,6).
GPU-CPU
Fig.6: FBP (A) and TV-CT (B) using only 95 retrospectively gated projections

Fig.5: GPU/CPU reconstruction efficiency compared.

Hybrid Bilateral Filtration
hybrid deformable registration
Fig.7: Hybrid bilateral filtration[9] provides an ideal compromise between edge preservation and de-noising, making it appropriate for 4D applications.   Fig.8: Segmented structures can be transformed from first cardiac phase to all other phases based on deformable registration.
APPLICATIONS

Morphological and Functional Phenotyping

Fig.9: Micro-CT-based measurements (A) show both morphological (LV dilatation, wall thinning) and functional aspects (EF, SV, CO, FS) that separate MLPs null (B) from controls C57BL/6 (C)[11].

   

Evaluating Effects of Various Test Drugs

Fig.10: Micro-CT measurements of Dobutamine-induced cardiac stress in rats[12]. With micro-CT, we can assess cardiac output (A), ejection fraction (EF) (B), and compare systole and diastole (C).

(A) (B)
fig 10
MIDelayedHyper

Imaging Myocardial Infarction (MI) with Delayed Hyper-enhancement

Fig.11: MI mouse model by LAD ligation scanned at 5 days and 5 weeks post-MI [13]. This study's goal was to quantify MI size (A-D) and cardiac function (E-G). (H) MI in a rat model. Red arrows indicate MI regions.

 

Dual-energy CT of Atherosclerotic Plaques [14]

Fig.12:

  • APOE KO mice, fed a Western diet
  • Injected with liposomal blood pool contrast
  • Imaged pre-, 2-hr, 48-hr, and 96-hr post-contrast
  • Scanned with 40 kVp and 80 kVp, with gating

 

fig12 fig12-2

CONCLUSIONS

4D micro-CT can be used for morphological and functional cardiac imaging. <5 minutes sampling time allows high-throughput imaging. Both time and energy can be explored using dual source micro-CT. Micro-CT with nanoparticle-based contrast agents enables atherosclerotic plaque imaging, and combining temporal and spectral imaging is also possible.

Movie of beating heart

beating heart

REFERENCES  
  1. Badea C et al. Proc SPIE, 2009
  2. Johnston SM et al. Med Phys, 2008
  3. Badea C et al. Med Phys, 2004
  4. Badea C et al. Mol Img, 2005
  5. Mukundan S et al. AJR, 2005
  6. Badea C et al., Phys Med Biol, 2011
  7. Song J et al., Phys Med Biol 2007
  1. Feldcamp LA et al. JOSA, 2008
  2. Clark D et al. Proc SPIE, 2012
  3. Guo X et al. Phys Med Biol, 2012
  4. Badea C et al. Mol Img, 2007
  5. Badea C et al. J Pharma Tox Methods, 2011
  6. Narendoft M et al., AJP, 2007
  7. Bhavane R et al. Circulation, submitted 2012
 

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