Real-time X-ray-based 4D image guidance of minimally invasive interventions.

OBJECTIVE: A new technology is introduced that enables real-time 4D (three spatial dimensions plus time) X-ray guidance for vascular catheter interventions with acceptable levels of ionising radiation. METHODS: The enabling technology is a combination of low-dose tomographic data acquisition with novel compressed sensing reconstruction and use of prior image information. It was implemented in a prototype set-up consisting of a gantry-based flat detector system. In pigs (n = 5) angiographic interventions were simulated. Radiation dosage on a per time base was compared with the "gold standard" of X-ray projection imaging. RESULTS: Contrary to current image guidance methods that lack permanent 4D updates, the spatial position of interventional instruments could be resolved in continuous, spatial 4D guidance; the movement of the guide wire as well as the expansion of stents could be precisely tracked in 3D angiographic road maps. Dose rate was 23.8 µGy/s, similar to biplane standard angiographic fluoroscopy, which has a dose rate of 20.6 µGy/s. CONCLUSION: Real-time 4D X-ray image-guidance with acceptable levels of radiation has great potential to significantly influence the field of minimally invasive medicine by allowing faster and safer interventions and by enabling novel, much more complex procedures for vascular and oncological minimally invasive therapy. KEY POINTS: • Real-time 4D (three spatial dimensions plus time) angiographic intervention guidance is realistic. • Low-dose tomographic data acquisition with special compressed sensing-based algorithms is enabled. • Compared with 4D CT fluoroscopy, this method reduces radiation to acceptable levels. • Once implemented, vascular interventions may become safer and faster. • More complex intervention approaches may be developed.

Dual-contrast photon-counting micro-CT using iodine and a novel bismuth-based contrast agent.

Objectives.To characterize for the first timein vivoa novel bismuth-based nanoparticular contrast agent developed for preclinical applications. Then, to design and testin vivoa multi-contrast protocol for functional cardiac imaging using the new bismuth nanoparticles and a well-established iodine-based contrast agent.Approach.A micro-computed tomography scanner was assembled and equipped with a photon-counting detector. Five mice were administered with the bismuth-based contrast agent and systematically scanned over 5 h to quantify the contrast enhancement in relevant organs of interest. Subsequently, the multi-contrast agent protocol was tested on three mice. Material decomposition was performed on the acquired spectral data to quantify the concentration of bismuth and iodine in multiple structures, e.g. the myocardium and vasculature.Main results.In the vasculature, the bismuth agent provides a peak enhancement of 1100 HU and a half-life of about 260 min. After the injection, it accumulates in the liver, spleen and intestinal wall reaching a CT value of 440 HU about 5 h post injection. Phantom measurements showed that the bismuth provides more contrast enhancement than iodine for a variety of tube voltages. The multi-contrast protocol for cardiac imaging successfully allowed the simultaneous decomposition of the vasculature, the brown adipose tissue and the myocardium.Significance.The new bismuth-based contrast agent was proven to have a long circulation time suitable for preclinical applications and to provide more contrast than iodine agents. The proposed multi-contrast protocol resulted in a new tool for cardiac functional imaging. Furthermore, thanks to the contrast enhancement provided in the intestinal wall, the novel contrast agent may be used to develop further multi contrast agent protocols for abdominal and oncological imaging.

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.

Gating in small-animal cardio-thoracic CT.

Gating is necessary in cardio-thoracic small-animal imaging because of the physiological motions that are present during scanning. In small-animal computed tomography (CT), gating is mainly performed on a projection base because full scans take much longer than the motion cycle. This paper presents and discusses various gating concepts of small-animal CT, and provides examples of concrete implementation. Since a wide variety of small-animal CT scanner systems exist, scanner systems are discussed with respect to the most suitable gating methods. Furthermore, an overview is given of cardio-thoracic imaging and gating applications. The necessary contrast media are discussed as well as gating limitations. Gating in small-animal imaging requires the acquisition of a gating signal during scanning. This can be done extrinsically (additional hardware, e.g. electrocardiogram) or intrinsically from the projection data itself. The gating signal is used retrospectively during CT reconstruction, or prospectively to trigger parts of the scan. Gating can be performed with respect to the phase or the amplitude of the gating signal, providing different advantages and challenges. Gating methods should be optimized with respect to the diagnostic question, scanner system, animal model, type of narcosis and actual setup. The software-based intrinsic gating approaches increasingly employed give the researcher independence from difficult and expensive hardware changes.

Coronary micro-computed tomography angiography in mice.

Coronary computed tomography angiography is an established technique in clinical practice and a valuable tool in the diagnosis of coronary artery disease in humans. Imaging of coronaries in preclinical research, i.e. in small animals, is very difficult due to the high demands on spatial and temporal resolution. Mice exhibit heart rates of up to 600 beats per minute motivating the need for highest detector framerates while the coronaries show diameters below 100 µm indicating the requirement for highest spatial resolution. We herein use a custom built micro-CT equipped with dedicated reconstruction algorithms to illustrate that coronary imaging in mice is possible. The scanner provides a spatial and temporal resolution sufficient for imaging of smallest, moving anatomical structures and the dedicated reconstruction algorithms reduced radiation dose to less than 1 Gy but do not yet allow for longitudinal studies. Imaging studies were performed in ten mice administered with a blood-pool contrast agent. Results show that the course of the left coronary artery can be visualized in all mice and all major branches can be identified for the first time using micro-CT. This reduces the gap in cardiac imaging between clinical practice and preclinical research.

Technical Note: Intrinsic raw data-based CT misalignment correction without redundant data.

PURPOSE: CT image reconstruction requires accurate knowledge of the used geometry or image quality might be degraded by misalignment artifacts. To overcome this issue, an intrinsic method, that is, a method not requiring a dedicated calibration phantom, to perform a raw data-based misalignment correction for CT is proposed herein that does not require redundant data and hence is applicable to measurements with less than 180 ∘ plus fan-angle of data. METHODS: The forward projection of a volume reconstructed from a misaligned geometry resembles the acquired raw data if no redundant data are used, that is, if less than 180 ∘ plus fan-angle are used for image reconstruction. Hence, geometric parameters cannot be deduced from such data by an optimization of the geometry-dependent raw data fidelity. We propose to use a nonlinear transform applied to the reconstructed volume to introduce inconsistencies in the raw data that can be employed to estimate geometric parameters using less than 180 ∘ plus fan-angle of data. The proposed method is evaluated using simulations of the FORBILD head phantom and using actual measurements of a contrast-enhanced scan of a mouse acquired using a micro-CT. RESULTS: Noisy simulations and actual measurements demonstrate that the proposed method is capable of correcting for artifacts arising from a misaligned geometry without redundant data while ensuring raw data fidelity. CONCLUSIONS: The proposed method extends intrinsic raw data-based misalignment correction methods to an angular range of 180 ∘ or less and is thus applicable to systems with a limited scan range.

Real-time scatter estimation for medical CT using the deep scatter estimation: Method and robustness analysis with respect to different anatomies, dose levels, tube voltages, and data truncation.

PURPOSE: X-ray scattering leads to CT images with a reduced contrast, inaccurate CT values as well as streak and cupping artifacts. Therefore, scatter correction is crucial to maintain the diagnostic value of CT and CBCT examinations. However, existing approaches are not able to combine both high accuracy and high computational performance. Therefore, we propose the deep scatter estimation (DSE): a deep convolutional neural network to derive highly accurate scatter estimates in real time. METHODS: Gold standard scatter estimation approaches rely on dedicated Monte Carlo (MC) photon transport codes. However, being computationally expensive, MC methods cannot be used routinely. To enable real-time scatter correction with similar accuracy, DSE uses a deep convolutional neural network that is trained to predict MC scatter estimates based on the acquired projection data. Here, the potential of DSE is demonstrated using simulations of CBCT head, thorax, and abdomen scans as well as measurements at an experimental table-top CBCT. Two conventional computationally efficient scatter estimation approaches were implemented as reference: a kernel-based scatter estimation (KSE) and the hybrid scatter estimation (HSE). RESULTS: The simulation study demonstrates that DSE generalizes well to varying tube voltages, varying noise levels as well as varying anatomical regions as long as they are appropriately represented within the training data. In any case the deviation of the scatter estimates from the ground truth MC scatter distribution is less than 1.8% while it is between 6.2% and 293.3% for HSE and between 11.2% and 20.5% for KSE. To evaluate the performance for real data, measurements of an anthropomorphic head phantom were performed. Errors were quantified by a comparison to a slit scan reconstruction. Here, the deviation is 278 HU (no correction), 123 HU (KSE), 65 HU (HSE), and 6 HU (DSE), respectively. CONCLUSIONS: The DSE clearly outperforms conventional scatter estimation approaches in terms of accuracy. DSE is nearly as accurate as Monte Carlo simulations but is superior in terms of speed (≈10 ms/projection) by orders of magnitude.

Effect of detruncation on the accuracy of Monte Carlo-based scatter estimation in truncated CBCT.

PURPOSE: The purpose of this study is to investigate the necessity of detruncation for scatter estimation of truncated cone-beam CT (CBCT) data and to evaluate different detruncation algorithms. Scattered radiation results in some of the most severe artifacts in CT and depends strongly on the size and the shape of the scanned object. Especially in CBCT systems the large cone-angle and the small detector-to-isocenter distance lead to a large amount of scatter detected, resulting in cupping artifacts, streak artifacts, and inaccurate CT-values. If a small field of measurement (FOM) is used, as it is often the case in CBCT systems, data are truncated in longitudinal and lateral direction. Since only truncated data are available as input for the scatter estimation, the already challenging correction of scatter artifacts becomes even more difficult. METHODS: The following detruncation methods are compared and evaluated with respect to scatter estimation: constant detruncation, cosine detruncation, adaptive detruncation, and prior-based detruncation using anatomical data from a similar phantom or patient, also compared to the case where no detruncation was performed. Each of the resulting, detruncated reconstructions serve as input volume for a Monte Carlo (MC) scatter estimation and subsequent scatter correction. An evaluation is performed on a head simulation, measurements of a head phantom and a patient using a dental CBCT geometry with a FOM diameter of 11 cm. Additionally, a thorax phantom is measured to assess performance in a C-Arm geometry with a FOM of up to 20 cm. RESULTS: If scatter estimation is based on simple detruncation algorithms like a constant or a cosine detruncation scatter is estimated inaccurately, resulting in incorrect CT-values as well as streak artifacts in the corrected volume. For the dental CBCT phantom measurement CT-values for soft tissue were corrected from -204 HU (no scatter correction) to -87 HU (no detruncation), -218 HU (constant detruncation), -141 HU (cosine detruncation), -91 HU (adaptive detruncation), -34 HU (prior-based detruncation using a different prior) and -24 HU (prior-based detruncation using the identical prior) for a reference value of -26 HU measured in slit scan mode. In all cases the prior-based detruncation results in the best scatter correction, followed by the adaptive detruncation, as these algorithms provide a rather accurate model of high-density structures outside the FOM, compared to a simple constant or a cosine detruncation. CONCLUSIONS: Our contribution is twofold: first we give a comprehensive comparison of various detruncation methods for the purpose of scatter estimation. We find that the choice of the detruncation method has a significant influence on the quality of MC-based scatter correction. Simple or no detruncation is often insufficient for artifact removal and results in inaccurate CT-values. On the contrary, prior-based detruncation can achieve a high CT-value accuracy and nearly artifact-free volumes from truncated CBCT data when combined with other state-of-the-art artifact corrections. Secondly, we show that prior-based detruncation is effective even with data from a different patient or phantom. The fact that data completion does not require data from the same patient dramatically increases the applicability and usability of this scatter estimation.

Model-based sphere localization (MBSL) in x-ray projections.

The detection of spherical markers in x-ray projections is an important task in a variety of applications, e.g. geometric calibration and detector distortion correction. Therein, the projection of the sphere center on the detector is of particular interest as the used spherical beads are no ideal point-like objects. Only few methods have been proposed to estimate this respective position on the detector with sufficient accuracy and surrogate positions, e.g. the center of gravity, are used, impairing the results of subsequent algorithms. We propose to estimate the projection of the sphere center on the detector using a simulation-based method matching an artificial projection to the actual measurement. The proposed algorithm intrinsically corrects for all polychromatic effects included in the measurement and absent in the simulation by a polynomial which is estimated simultaneously. Furthermore, neither the acquisition geometry nor any object properties besides the fact that the object is of spherical shape need to be known to find the center of the bead. It is shown by simulations that the algorithm estimates the center projection with an error of less than [Formula: see text] of the detector pixel size in case of realistic noise levels and that the method is robust to the sphere material, sphere size, and acquisition parameters. A comparison to three reference methods using simulations and measurements indicates that the proposed method is an order of magnitude more accurate compared to these algorithms. The proposed method is an accurate algorithm to estimate the center of spherical markers in CT projections in the presence of polychromatic effects and noise.

In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent.

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation (R2 = 0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

The rotate-plus-shift C-arm trajectory. Part I. Complete data with less than 180° rotation.

PURPOSE: In the last decade, C-arm-based cone-beam CT became a widely used modality for intraoperative imaging. Typically a C-arm CT scan is performed using a circular or elliptical trajectory around a region of interest. Therefore, an angular range of at least 180° plus fan angle must be covered to ensure a completely sampled data set. However, mobile C-arms designed with a focus on classical 2D applications like fluoroscopy may be limited to a mechanical rotation range of less than 180° to improve handling and usability. The method proposed in this paper allows for the acquisition of a fully sampled data set with a system limited to a mechanical rotation range of at least 180° minus fan angle using a new trajectory design. This enables CT like 3D imaging with a wide range of C-arm devices which are mainly designed for 2D imaging. METHODS: The proposed trajectory extends the mechanical rotation range of the C-arm system with two additional linear shifts. Due to the divergent character of the fan-beam geometry, these two shifts lead to an additional angular range of half of the fan angle. Combining one shift at the beginning of the scan followed by a rotation and a second shift, the resulting rotate-plus-shift trajectory enables the acquisition of a completely sampled data set using only 180° minus fan angle of rotation. The shifts can be performed using, e.g., the two orthogonal positioning axes of a fully motorized C-arm system. The trajectory was evaluated in phantom and cadaver examinations using two prototype C-arm systems. RESULTS: The proposed trajectory leads to reconstructions without limited angle artifacts. Compared to the limited angle reconstructions of 180° minus fan angle, image quality increased dramatically. Details in the rotate-plus-shift reconstructions were clearly depicted, whereas they are dominated by artifacts in the limited angle scan. CONCLUSIONS: The method proposed here employs 3D imaging using C-arms with less than 180° rotation range adding full 3D functionality to a C-arm device retaining both handling comfort and the usability of 2D imaging. This method has a clear potential for clinical use especially to meet the increasing demand for an intraoperative 3D imaging.

The rotate-plus-shift C-arm trajectory. Part II. Exact reconstruction from less than 180° rotation.

PURPOSE: CT reconstruction requires an angular coverage of 180° or more for each point within the field of measurement. Thus, common trajectories use a 180° plus fan angle rotation. This is sometimes combined with a translation of the rotational isocenter in order to achieve circular trajectories with an isocenter different from the mechanical rotation center or elliptical trajectories. Rays measured redundantly are appropriately weighted. In case of an angular coverage smaller than 180°, the reconstructed images suffer from limited angle artifacts. In mechanical constructions with a rotation range limited to less than 180° plus fan angle, the angular coverage can be extended by adding one or two shifts to the rotational motion. If the missing angle is less than the fan angle, the shifts can completely compensate for the limited rotational capabilities. METHODS: The authors give weight functions that can be viewed as generalized Parker weights, which can be applied to the raw data before image reconstruction. Raw data of Forbild phantoms using the rotate-plus-shift trajectory are simulated with the geometry of a typical mobile flat detector-based C-arm system. Filtered backprojection (FBP) reconstructions using the new redundancy weight are performed and compared to FBP reconstructions of limited angle scans as well as short-scan reference trajectories using Parker weight. RESULTS: The new weighting method is exact in 2D, and for 3D Feldkamp-type reconstructions, it is exact in the mid-plane. The proposed weight shows a mathematically exact match with Parker weight for conventional short-scan trajectories. Reconstructions of rotate-plus-shift trajectories using the new weight do not suffer from limited angle artifacts, whereas scans limited to less than 180° without shift show prominent artifacts. Image noise in rotate-plus-shift scans is comparable to that of corresponding short scans. CONCLUSIONS: The new weight function enables the straightforward reconstruction using filtered backprojection of data acquired with the rotate-plus-shift C-arm trajectory and a large variety of other advanced trajectories.

Low dose tomographic fluoroscopy: 4D intervention guidance with running prior.

PURPOSE: Today's standard imaging technique in interventional radiology is the single- or biplane x-ray fluoroscopy which delivers 2D projection images as a function of time (2D+T). This state-of-the-art technology, however, suffers from its projective nature and is limited by the superposition of the patient's anatomy. Temporally resolved tomographic volumes (3D+T) would significantly improve the visualization of complex structures. A continuous tomographic data acquisition, if carried out with today's technology, would yield an excessive patient dose. Recently the authors proposed a method that enables tomographic fluoroscopy at the same dose level as projective fluoroscopy which means that if scanning time of an intervention guided by projective fluoroscopy is the same as that of an intervention guided by tomographic fluoroscopy, almost the same dose is administered to the patient. The purpose of this work is to extend authors' previous work and allow for patient motion during the intervention. METHODS: The authors propose the running prior technique for adaptation of a prior image. This adaptation is realized by a combination of registration and projection replacement. In a first step the prior is deformed to the current position via affine and deformable registration. Then the information from outdated projections is replaced by newly acquired projections using forward and backprojection steps. The thus adapted volume is the running prior. The proposed method is validated by simulated as well as measured data. To investigate motion during intervention a moving head phantom was simulated. Real in vivo data of a pig are acquired by a prototype CT system consisting of a flat detector and a continuously rotating clinical gantry. RESULTS: With the running prior technique it is possible to correct for motion without additional dose. For an application in intervention guidance both steps of the running prior technique, registration and replacement, are necessary. Reconstructed volumes based on the running prior show high image quality without introducing new artifacts and the interventional materials are displayed at the correct position. CONCLUSIONS: The running prior improves the robustness of low dose 3D+T intervention guidance toward intended or unintended patient motion.

Intrinsic gating for small-animal computed tomography: a robust ECG-less paradigm for deriving cardiac phase information and functional imaging.

BACKGROUND: A projection-based method of intrinsic cardiac gating in small-animal computed tomography imaging is presented. METHODS AND RESULTS: In this method, which operates without external ECG monitoring, the gating reference signal is derived from the raw data of the computed tomography projections. After filtering, the derived gating reference signal is used to rearrange the projection images retrospectively into data sets representing different time points in the cardiac cycle during expiration. These time-stamped projection images are then used for tomographic reconstruction of different phases of the cardiac cycle. Intrinsic gating was evaluated in mice and rats and compared with extrinsic retrospective gating. An excellent agreement was achieved between ECG-derived gating signal and self-gating signal (coverage probability for a difference between the 2 measurements to be less than 5 ms was 89.2% in mice and 85.9% in rats). Functional parameters (ventricular volumes and ejection fraction) obtained from the intrinsic and the extrinsic data sets were not significantly different. The ease of use and reliability of intrinsic gating were demonstrated via a chemical stress test on 2 mice, in which the system performed flawlessly despite an increased heart rate. Because of intrinsic gating, the image quality was improved to the extent that even the coronary arteries of mice could be visualized in vivo despite a heart rate approaching 430 bpm. Feasibility of intrinsic gating for functional imaging and assessment of cardiac wall motion abnormalities was successfully tested in a mouse model of myocardial infarction. CONCLUSIONS: Our results demonstrate that self-gating using advanced software postprocessing of projection data promises to be a valuable tool for rodent computed tomography imaging and renders ECG gating with external electrodes superfluous.