Implementation and evaluation of respiratory gating in small animal radiotherapy.

Major advance was done in preclinical radiotherapy thanks to the development of image guided micro-irradiator. Nevertheless, some applications still can benefit of improvements, such as the irradiation of mobile tumors. This preclinical radiotherapy case presents increased difficulties compared to clinical practice because of the waveform of small animals breathing cycle, its frequency and amplitude. To answer this issue, we developed a specific beam shutter and implemented respiratory gating on the X-RAD 225Cx preclinical irradiator. In the first step of this study, the shutter was accurately characterized. Opening and closing speed of 1.28 and 0.33 mm ms-1 were respectively measured, and a transmission of 0.7% of the beam was measured with the shutter fully closed. Beam-on times were also determined for various gating parameters and highlighted a difference of 57 ms between the beam delivery duration and the gate width. This discrepancy was compensated during the respiratory monitoring adjustment. In a second step, a respiratory protocol was evaluated with two vertical beams of 2.5 and 5 mm diameters, for motion amplitudes ranging from 0.5 to 4 mm. This evaluation demonstrated the effectiveness of our set up to perform motion compensation for amplitude as small as 0.5 mm despite a dose gradient of 1.47 cGy mm-1 observed with the 5 mm irradiation field, due to the shutter opening and closing durations. We also investigated the efficiency of a scintillating fiber dosimeter, adapted to small beams and providing real-time dose rate measurements. This detector showed very good performances to detect motion in small irradiation fields and would be very suitable to monitor the number of delivered gates until the planned delivered dose is achieved. This study presented a new respiratory gating set up and showed that very efficient motion compensation could be achieved in small animal radiotherapy.

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator.

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms do not incorporate respiratory gating, which is required for accurate and precise targeting in organs subject to respiration related motions that may be up to the order of 5 mm in mice. Therefore, a new treatment head assembly for the Xstrahl Small Animal Radiation Research Platform (SARRP) has been designed. This includes a fast X-ray shutter subsystem, a motorized beam hardening filter assembly, an integrated transmission ionization chamber to monitor beam delivery, a kinematically positioned removable beam collimator and a targeting laser exiting the center of the beam collimator. The X-ray shutter not only minimizes timing errors but also allows beam gating during imaging and treatment, with irradiation only taking place during the breathing cycle when tissue movement is minimal. The breathing related movement is monitored by measuring, using a synchronous detector/lock-in amplifier that processes diffuse reflectance light from a modulated light source. After thresholding of the resulting signal, delays are added around the inhalation/exhalation phases, enabling the "no movement" period to be isolated and to open the X-ray shutter. Irradiation can either be performed for a predetermined time of X-ray exposure, or through integration of a current from the transmission monitor ionization chamber (corrected locally for air density variations). The ability to successfully deliver respiratory-gated X-ray irradiations has been demonstrated by comparing movies obtained using planar X-ray imaging with and without respiratory gating, in addition to comparing dose profiles observed from a collimated beam on EBT3 radiochromic film mounted on the animal's chest. Altogether, the development of respiratory-gated irradiation facilitates improved dose delivery during animal movement and constitutes an important new tool for preclinical radiation studies. This approach is particularly well suited for irradiation of orthotopic tumors or other targets within the chest and abdomen where breathing related movement is significant.

Derivation of a respiration trigger signal in small animal list-mode PET based on respiration-induced variations of the ECG signal.

BACKGROUND: Raw PET list-mode data contains motion artifacts causing image blurring and decreased spatial resolution. Unless corrected, this leads to underestimation of the tracer uptake and overestimation of the lesion size, as well as inaccuracies with regard to left ventricular volume and ejection fraction (LVEF), especially in small animal imaging. METHODS AND RESULTS: A respiratory trigger signal from respiration-induced variations in the electro-cardiogram (ECG) was detected. Original and revised list-mode PET data were used for calculation of left ventricular function parameters using both respiratory gating techniques. For adequately triggered datasets we saw no difference in mean respiratory cycle period between the reference standard (RRS) and the ECG-based (ERS) methods (1120 ± 159 ms vs 1120 ± 159 ms; P = n.s.). While the ECG-based method showed somewhat higher signal noise (66 ± 22 ms vs 51 ± 29 ms; P < .001), both respiratory triggering techniques yielded similar estimates for EDV, ESV, LVEF (RRS: 387 ± 56 µL, 162 ± 34 µL, 59 ± 5%; ERS: 389 ± 59 µL, 163 ± 35 µL, 59 ± 4%; P = n.s.). CONCLUSIONS: This study showed that respiratory gating signals can be accurately derived from cardiac trigger information alone, without the additional requirement for dedicated measurement of the respiratory motion in rats.

Assessment of respiration-induced displacement of canine abdominal organs in dorsal and ventral recumbency using multislice computed tomography.

Respiratory-induced organ displacement during image acquisition can produce motion artifacts and variation in spatial localization of an organ in diagnostic computed tomography (CT) examinations. The purpose of this prospective study was to quantify respiratory-induced abdominal organ displacement in dorsal and ventral recumbency using five normal dogs. All dogs underwent CT examinations using 64 multidetector row CT (64-MDCT). A "3-dimensional (3D) apneic CT exam" of the abdomen was acquired followed by a "4-dimensional (4D) ventilated CT exam." The liver, pancreas, both kidneys, both medial iliac lymph nodes, and urinary bladder were delineated on the 3D-apneic examination and the organ outlines were compared to the maximum alteration in organ position in the 4D-ventilated examination. Displacement was measured in dorsal-to-ventral (DV), right-to-left (RL), and cranial-to-caudal (CC) directions. Respiratory-induced displacement of canine abdominal organs was not predictable and showed large variability in the three directions evaluated. For most canine abdominal organs, dorsal recumbency provided overall the least amount of displacement among all directions evaluated except for liver and urinary bladder. For liver, a large variability was found for all directions and a statistically significant difference was found only in the RL direction with ventral recumbency exhibiting less displacement (P = 0.0099). For the urinary bladder, ventral recumbency also provided less displacement but this was statistically significant only in the RL direction (P < 0.0001). Findings from this study indicated that dorsal recumbency may be preferred for minimizing respiratory motion artifacts in whole abdomen studies, but ventral recumbency may be preferred for liver and urinary bladder studies when respiration cannot be controlled.

MRI compatible small animal monitoring and trigger system for whole body scanners.

Performing magnetic resonance imaging (MRI) experiments with small animals requires continuous monitoring of vital parameters, especially the respiration rate. Clinical whole-body MR scanners represent an attractive option for preclinical imaging as dedicated animal scanners are cost-intensive in both investment and maintenance, thus limiting their availability. Even though impressive image quality is achievable with clinical MR systems in combination with special coils, their built-in physiologic monitoring and triggering units are often not suited for small animal imaging. In this work, we present a simple, MRI compatible low cost solution to monitor the respiration and heart rate of small animals in a clinical whole-body MR scanner. The recording and processing of the biosignals as well as the optimisation of the respiratory trigger generation is decribed. Additionally rat and mouse in-vivo MRI experiments are presented to illustrate the effectiveness of the monitoring and respiratory trigger system in suppressing motion artifacts.

Imaging of cardiac perfusion of free-breathing small animals using dynamic phase-correlated micro-CT.

PURPOSE: Mouse models of cardiac diseases have proven to be a valuable tool in preclinical research. The high cardiac and respiratory rates of free breathing mice prohibit conventional in vivo cardiac perfusion studies using computed tomography even if gating methods are applied. This makes a sacrification of the animals unavoidable and only allows for the application of ex vivo methods. METHODS: To overcome this issue the authors propose a low dose scan protocol and an associated reconstruction algorithm that allows for in vivo imaging of cardiac perfusion and associated processes that are retrospectively synchronized to the respiratory and cardiac motion of the animal. The scan protocol consists of repetitive injections of contrast media within several consecutive scans while the ECG, respiratory motion, and timestamp of contrast injection are recorded and synchronized to the acquired projections. The iterative reconstruction algorithm employs a six-dimensional edge-preserving filter to provide low-noise, motion artifact-free images of the animal examined using the authors' low dose scan protocol. RESULTS: The reconstructions obtained show that the complete temporal bolus evolution can be visualized and quantified in any desired combination of cardiac and respiratory phase including reperfusion phases. The proposed reconstruction method thereby keeps the administered radiation dose at a minimum and thus reduces metabolic inference to the animal allowing for longitudinal studies. CONCLUSIONS: The authors' low dose scan protocol and phase-correlated dynamic reconstruction algorithm allow for an easy and effective way to visualize phase-correlated perfusion processes in routine laboratory studies using free-breathing mice.

Fully automated intrinsic respiratory and cardiac gating for small animal CT.

A fully automated, intrinsic gating algorithm for small animal cone-beam CT is described and evaluated. A parameter representing the organ motion, derived from the raw projection images, is used for both cardiac and respiratory gating. The proposed algorithm makes it possible to reconstruct motion-corrected still images as well as to generate four-dimensional (4D) datasets representing the cardiac and pulmonary anatomy of free-breathing animals without the use of electrocardiogram (ECG) or respiratory sensors. Variation analysis of projections from several rotations is used to place a region of interest (ROI) on the diaphragm. The ROI is cranially extended to include the heart. The centre of mass (COM) variation within this ROI, the filtered frequency response and the local maxima are used to derive a binary motion-gating parameter for phase-sensitive gated reconstruction. This algorithm was implemented on a flat-panel-based cone-beam CT scanner and evaluated using a moving phantom and animal scans (seven rats and eight mice). Volumes were determined using a semiautomatic segmentation. In all cases robust gating signals could be obtained. The maximum volume error in phantom studies was less than 6%. By utilizing extrinsic gating via externally placed cardiac and respiratory sensors, the functional parameters (e.g. cardiac ejection fraction) and image quality were equivalent to this current gold standard. This algorithm obviates the necessity of both gating hardware and user interaction. The simplicity of the proposed algorithm enables adoption in a wide range of small animal cone-beam CT scanners.