Retrospective Cardiac Gating with A Prototype Small-Animal X-ray Computed Tomograph

Summary

We provide a comprehensive description of the intrinsic retrospective cardiac gating method of the CrumpCAT, a prototype small-animal X-ray computed tomography (CT) scanner designed and constructed at our research institution.

Abstract

The CrumpCAT is a prototype small-animal X-ray computed tomography (CT) scanner developed at our research institution. The CMOS detector with a maximum frame rate of 29 Hz and similar Tungsten X-ray sources with energies ranging from 50 kVp to 80 kVp are widely used across commercially available preclinical X-ray CT instruments. This makes the described work highly relevant to other institutions, despite the generally perceived wisdom that these detectors are not suitable for gating the high heart rates of mice (~600 beats/min). The scanner features medium- (200 µm) and high- (125 µm) resolution imaging, fluoroscopy, retrospective respiratory gating, and retrospective cardiac gating, with iterative or filtered-back projection image reconstruction. Among these features, cardiac gating is the most useful feature for studying cardiac functions in vivo, as it effectively eliminates image blurring caused by respiratory and cardiac motion.

Here, we describe our method for preclinical intrinsic retrospective cardiac-gated CT imaging, aimed at advancing research on in vivo cardiac function and structure analysis. The cardiac-gating method acquires a large number of projections at the shortest practical exposure time (~20 ms) and then retrospectively extracts respiratory and cardiac signals from temporal changes in raw projection sequences. These signals are used to reject projections belonging to the high motion rate inspiration phase of the respiratory cycle and to divide the remaining projections into 12 groups, each corresponding to one phase of the cardiac cycle. Each group is reconstructed independently using an iterative method to produce a volumetric image for each cardiac phase, resulting in a four-dimensional (4D) dataset.

These phase images can be analyzed either collectively or individually, allowing for detailed assessment of cardiac function. We demonstrated the effectiveness of both approaches of the prototype scanner's cardiac-gating feature through representative in vivo imaging results.

Introduction

Small-animal research often employs a combination of non-invasive imaging modalities, with X-ray computed tomography (CT), being a prominent choice due to its maturity, cost-effectiveness, speed^1,2, and ability to provide complementary information alongside other modalities such as positron emission tomography (PET)^2,3 and single-photon emission computed tomography (SPECT)^2,4. However, like other imaging techniques, CT is susceptible to physiological motion artifacts caused by the beating heart....

Protocol

Animal experimental protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the University of California, Los Angeles (UCLA). C57BL/6J mice (8 weeks old, male, 24-26 g) were used in this protocol. The CT scanner used in this study is the CrumpCAT (Figure 2), a prototype developed at our research institution for preclinical research, providing us with the control and flexibility needed to optimize acquisition and reconstruction protocols. The method assumes that anesthetized mice will have a heart rate no greater than 600 beats/min and a respiration rate between 20 and 180 breaths/min^15<....

Discussion

The specific hardware implementation described here is a custom-made X-ray CT system unique to our institute, but the specific detector is widely used across commercially available preclinical X-ray CT instruments, making the described work relevant to other institutions. This system is functionally the prototype for two commercially available and widely used in vivo X-ray microCT subsystems embedded
in preclinical PET/CT scanners. These microCT scanners share the detector architecture and performance.......

Materials

Name	Company	Catalog Number	Comments
C57BL/6J mice	Jackson Laboratory	664	Male, 8 weeks old, 24-26 g
Dexela camera	Varex	1512	Detector, 20 ms exposure, 74.8/149.6 µm pixel
VivoVist	Nanoprobes	1301-5X0.25ML	CT Contrast agent
X-ray source	Moxtek	TUB00082	50 kV peak, 200 µA, 1.0 mm-thick Al filter