A registration based approach for 4D cardiac micro-CT using combined prospective and retrospective gating

Recent advances in murine cardiac studies with three-dimensional cone beam micro-computed tomography (CT) have used either prospective or retrospective gating technique. While prospective gating ensures the best image quality and the highest resolution, it involves longer sampling times and higher radiation dose. Sampling is faster and the radiation dose can be reduced with retrospective gating but the image quality is affected by the limited number of projections with an irregular angular distribution which complicate the reconstruction process, causing significant streaking artifacts. This work involves both prospective and retrospective gating in sampling. Deformable registration is used between a high quality image set acquired with prospective gating with the multiple data sets during the cardiac cycle obtained using retrospective gating. Tests were conducted on a four-dimensional (4D) cardiac mouse phantom and after optimization, the method was applied to in vivo cardiac micro-CT data. Results indicate that, by using our method, the sampling time can be reduced by a factor of 2.5 and the radiation dose can be reduced 35% compared to the prospective sampling while the image quality can be maintained. In conclusion, we proposed a novel solution to 4D cine cardiac micro-CT based on a combined prospective with retrospective gating in sampling and deformable registration post reconstruction that mixed the advantages of both strategies.     

Optical CT scanner for in-air readout of gels for external radiation beam 3D dosimetry

Optical CT scanners for a 3D readout of externally irradiated radiosensitive hydrogels currently require the use of a refractive index (RI) matching liquid bath to obtain suitable optical ray paths through the gel sample to the detector. The requirement for a RI matching liquid bath has been negated by the design of a plastic cylindrical gel container that provides parallel beam geometry through the gel sample for the majority of the projection. The design method can be used for various hydrogels. Preliminary test results for the prototype laser beam scanner with ferrous xylenol-orange gel show geometric distortion of 0.2?mm maximum, spatial resolution limited to beam spot size of about 0.4?mm and 0.8% noise (1 SD) for a uniform irradiation. Reconstruction of a star pattern irradiated through the cylinder walls demonstrates the suitability for external beam applications. The extremely simple and cost-effective construction of this optical CT scanner, together with the simplicity of scanning gel samples without RI matching fluid increases the feasibility of using 3D gel dosimetry for clinical external beam dose verifications.     

An improved analytical model for CT dose simulation with a new look at the theory of CT dose

Gagne [Med. Phys. 16, 29-37 (1989)] has previously described a model for predicting the sensitivity and dose profiles in the slice-width (z) direction for CT scanners. The model, developed prior to the advent of multidetector CT scanners, is still widely used; however, it does not account for the effect of anode tilt on the penumbra or include the heel effect, both of which are increasingly important for the wider beams (up to 40 mm) of contemporary, multidetector scanners. Additionally, it applied only on (or near) the axis of rotation, and did not incorporate the photon energy spectrum. The improved model described herein transcends all of the aforementioned limitations of the Gagne model, including extension to the peripheral phantom axes. Comparison of simulated and measured dose data provides experimental validation of the model, including verification of the superior match to the penumbra provided by the tilted-anode model, as well as the observable effects on the cumulative dose distribution. The initial motivation for the model was to simulate the quasiperiodic dose distribution on the peripheral, phantom axes resulting from a helical scan series in order to facilitate the implementation of an improved method of CT dose measurement utilizing a short ion chamber, as proposed by Dixon [Med. Phys. 30, 1272-1280 (2003)]. A more detailed set of guidelines for implementing such measurements is also presented in this paper. In addition, some fundamental principles governing CT dose which have not previously been clearly enunciated follow from the model, and a fundamental (energy-based) quantity dubbed "CTDI-aperture" is introduced.     

Extraction of the respiratory signal from small-animal CT projections for a retrospective gating method

We propose a retrospective respiratory gating algorithm to generate dynamic CT studies. To this end, we compared three different methods of extracting the respiratory signal from the projections of small-animal cone-beam computed tomography (CBCT) scanners. Given a set of frames acquired from a certain axial angle, subtraction of their average image from each individual frame produces a set of difference images. Pixels in these images have positive or negative values (according to the respiratory phase) in those areas where there is lung movement. The respiratory signals were extracted by analysing the shape of the histogram of these difference images: we calculated the first four central and non-central moments. However, only odd-order moments produced the desired breathing signal, as the even-order moments lacked information about the phase. Each of these curves was compared to a reference signal recorded by means of a pneumatic pillow. Given the similar correlation coefficients yielded by all of them, we selected the mean to implement our retrospective protocol. Respiratory phase bins were separated, reconstructed independently and included in a dynamic sequence, suitable for cine playback. We validated our method in five adult rat studies by comparing profiles drawn across the diaphragm dome, with and without retrospective respiratory gating. Results showed a sharper transition in the gated reconstruction, with an average slope improvement of 60.7%.     

Wobbled splatting--a fast perspective volume rendering method for simulation of x-ray images from CT

3D/2D registration, the automatic assignment of a global rigid-body transformation matching the coordinate systems of patient and preoperative volume scan using projection images, is an important topic in image-guided therapy and radiation oncology. A crucial part of most 3D/2D registration algorithms is the fast computation of digitally rendered radiographs (DRRs) to be compared iteratively to radiographs or portal images. Since registration is an iterative process, fast generation of DRRs-which are perspective summed voxel renderings-is desired. In this note, we present a simple and rapid method for generation of DRRs based on splat rendering. As opposed to conventional splatting, antialiasing of the resulting images is not achieved by means of computing a discrete point spread function (a so-called footprint), but by stochastic distortion of either the voxel positions in the volume scan or by the simulation of a focal spot of the x-ray tube with non-zero diameter. Our method generates slightly blurred DRRs suitable for registration purposes at framerates of approximately 10 Hz when rendering volume images with a size of 30 MB.     

Deposition of (90)YPO(4) and (144)CePO(4) radioisotopes on polymer surfaces for radiation delivery devices

Intravascular irradiation with beta emitters inhibits restenosis in arteries after balloon angioplasty or stent implantation. Yttrium-90 ((90)Y, T(1/2)=64 h) and cerium-144 ((144)Ce, T(1/2)=286 d) emit beta particles (E(max)=2.28--3.50 MeV) having an ideal energy range for brachytherapy delivery system. In this article, a previously reported method for depositing (32)P on poly(ethylene terephtalate) (PET) surfaces is generalized and modifications that allow deposition of other beta-emitting radioisotopes, such as (90)Y and (144)Ce, are demonstrated. PET films were first coated with chitosan hydrogel and then adsorbed different amounts of phosphoric acid (PA) in aqueous solutions. Yttrium was deposited onto the surface as YPO(4) after the films were immersed in YCl(3) solutions. 1 muCi (90)YCl(3) (2 x 10(-9) g) was used in each sample as a tracer for measuring the deposition efficiency, which is defined as the percentage of YCl(3) deposited on the surface compared to the amount of YCl(3) in solutions before the deposition. In order to improve the safety of brachytherapy treatments, polyurethanes were used to seal the deposited radioisotopes on the surface to minimize the leakage of the isotopes into the patients. The generality of this method presented here for a wide variety of particular radioisotopic components allows design of a broad range of versatile radioisotope sources.     

An optical flow based method for improved reconstruction of 4D CT data sets acquired during free breathing

Respiratory motion degrades anatomic position reproducibility and leads to issues affecting image acquisition, treatment planning, and radiation delivery. Four-dimensional (4D) computer tomography (CT) image acquisition can be used to measure the impact of organ motion and to explicitly account for respiratory motion during treatment planning and radiation delivery. Modern CT scanners can only scan a limited region of the body simultaneously and patients have to be scanned in segments consisting of multiple slices. A respiratory signal (spirometer signal or surface tracking) is used to reconstruct a 4D data set by sorting the CT scans according to the couch position and signal coherence with predefined respiratory phases. But artifacts can occur if there are no acquired data segments for exactly the same respiratory state for all couch positions. These artifacts are caused by device-dependent limitations of gantry rotation, image reconstruction times and by the variability of the patient's respiratory pattern. In this paper an optical flow based method for improved reconstruction of 4D CT data sets from multislice CT scans is presented. The optical flow between scans at neighboring respiratory states is estimated by a non-linear registration method. The calculated velocity field is then used to reconstruct a 4D CT data set by interpolating data at exactly the predefined respiratory phase. Our reconstruction method is compared with the usually used reconstruction based on amplitude sorting. The procedures described were applied to reconstruct 4D CT data sets for four cancer patients and a qualitative and quantitative evaluation of the optical flow based reconstruction method was performed. Evaluation results show a relevant reduction of reconstruction artifacts by our technique. The reconstructed 4D data sets were used to quantify organ displacements and to visualize the abdominothoracic organ motion.     

Determination of maximum leaf velocity and acceleration of a dynamic multileaf collimator: implications for 4D radiotherapy

The dynamic multileaf collimator (MLC) can be used for four-dimensional (4D), or tumor tracking radiotherapy. However, the leaf velocity and acceleration limitations become a crucial factor as the MLC leaves need to respond in near real time to the incoming respiration signal. The aims of this paper are to measure maximum leaf velocity, acceleration, and deceleration to obtain the mechanical response times for the MLC, and determine whether the MLC is suitable for 4D radiotherapy. MLC leaf sequence files, requiring the leaves to reach maximum acceleration and velocity during motion, were written. The leaf positions were recorded every 50 ms, from which the maximum leaf velocity, acceleration, and deceleration were derived. The dependence on the velocity and acceleration of the following variables were studied: leaf banks, inner and outer leaves, MLC-MLC variations, gravity, friction, and the stability of measurements over time. Measurement results show that the two leaf banks of a MLC behave similarly, while the inner and outer leaves have significantly different maximum leaf velocities. The MLC-MLC variations and the dependence of gravity on maximum leaf velocity are statistically significant. The average maximum leaf velocity at the isocenter plane of the MLC ranged from 3.3 to 3.9 cm/s. The acceleration and deceleration at the isocenter plane of the MLC ranged from 50 to 69 cm/s2 and 46 to 52 cm/s2, respectively. Interleaf friction had a negligible effect on the results, and the MLC parameters remained stable with time. Equations of motion were derived to determine the ability of the MLC response to fluoroscopymeasured diaphragm motion. Given the present MLC mechanical characteristics, 4D radiotherapy is feasible for up to 97% of respiratory motion. For the largest respiratory motion velocities observed, beam delivery should be temporarily stopped (beam hold).     

Comparison of two respiration monitoring systems for 4D imaging with a Siemens CT using a new dynamic breathing phantom

Four-dimensional computed tomography (4D-CT) requires breathing information from the patient, and for this, several systems are available. Testing of these systems, under realistic conditions, requires a phantom with a moving target and an expandable outer contour. An anthropomorphic phantom was developed to simulate patient breathing as well as lung tumor motion. Using the phantom, an optical camera system (GateCT) and a pressure sensor (AZ-733V) were simultaneously operated, and 4D-CTs were reconstructed with a Siemens CT using the provided local-amplitude-based sorting algorithm. The comparison of the tumor trajectories of both systems revealed discrepancies up to 9.7 mm. Breathing signal differences, such as baseline drift, temporal resolution and noise level were shown not to be the reason for this. Instead, the variability of the sampling interval and the accuracy of the sampling rate value written on the header of the GateCT-signal file were identified as the cause. Interpolation to regular sampling intervals and correction of the sampling rate to the actual value removed the observed discrepancies. Consistently, the introduction of sampling interval variability and inaccurate sampling rate values into the header of the AZ-733V file distorted the tumor trajectory for this system. These results underline the importance of testing new equipment thoroughly, especially if components of different manufacturers are combined.     

A CCD-based optical CT scanner for high-resolution 3D imaging of radiation dose distributions: equipment specifications, optical simulations and preliminary results.

Methods based on magnetic resonance imaging for the measurement of three-dimensional distributions of radiation dose are highly developed. However, relatively little work has been done on optical computed tomography (OCT). This paper describes a new OCT scanner based on a broad beam light source and a two-dimensional charge-coupled device (CCD) detector. A number of key design features are discussed including the light source; the scanning tank, turntable and stepper motor control; the diffuser screen onto which images are projected and the detector. It is shown that the non-uniform pixel sensitivity of the low-cost CCD detector used and the granularity of the diffuser screen lead to a serious ring artefact in the reconstructed images. Methods are described for eliminating this. The problems arising from reflection and refraction at the walls of the gel container are explained. Optical ray-tracing simulations are presented for cylindrical containers with a variety of radii and verified experimentally. Small changes in the model parameters lead to large variations in the signal intensity observed in the projection data. The effect of imperfect containers on data quality is discussed and a method based on a 'correction scan' is shown to be successful in correcting many of the related image artefacts. The results of two tomography experiments are presented. In the first experiment, a radiochromic Fricke gel sample was exposed four times in different positions to a 100 kVp x-ray beam perpendicular to the plane of imaging. Images of absorbed dose with slice thickness of 140 microm were acquired. with 'true' in-plane resolution of 560 x 560 microm2 at the edge of the 72 mm field of view and correspondingly higher resolution at the centre. The nominal doses measured correlated well with the known exposure times. The second experiment demonstrated the well known phenomenon of diffusion in the dosemeter gels and yielded a value of (0.12 +/- 0.02) mm2 s(-1) for the diffusion coefficient of the xylenol orange/iron complex. Finally, the overall implications of the above findings for dosimetry using OCT are discussed.     

Sliding slice: a novel approach for high accuracy and automatic 3D localization of seeds from CT scans

We present a conceptually novel principle for 3D reconstruction of prostate seed implants. Unlike existing methods for implant reconstruction, the proposed algorithm uses raw CT data (sinograms) instead of reconstructed CT slices. Using raw CT data solves several inevitable problems related to the reconstruction from CT slices. First, the sinograms are not affected by reconstruction artifacts in the presence of metallic objects and seeds in the patient body. Second, the scanning axis is not undersampled as in the case of CT slices; as a matter of fact the scanning axis is the most densely sampled and each seed is typically represented by several hundred samples. Moreover, the shape of a single seed in a sinogram can be modeled exactly, thus facilitating the detection. All this allows very accurate 3D reconstruction of both position and the orientation of the seeds. Preliminary results indicate that the seed position can be estimated with 0.15 mm accuracy (average), while the orientation estimate accuracy is within 3 deg on average. Although the main contribution of the paper is to present a new principle of reconstruction, a preliminary implementation is also presented as a proof of concept. The implemented algorithm has been tested on a phantom and the obtained results are presented to validate the proposed approach.     

基于3D深度残差全卷积网络的头颈CT放疗危及器官自动勾画

头颈部肿瘤放射治疗危及器官的准确勾画是放疗计划的关键步骤,然而头颈部放疗危及器官的精确分割挑战性很大,目前临床医生手动勾画危及器官非常繁琐、耗时且缺乏一致性。提出基于3D深度残差全卷积网络的头颈部肿瘤放疗危及器官自动分割方法,通过改进的V-Net网络分割模型,有效地结合危及器官CT影像的深层特征和浅层特征,同时根据特别设计的端到端监督学习确定危及器官分割模型参数。为了解决小器官类分布极不平衡问题,提出利用器官位置先验约束采样区域与随机采样相结合的训练样本选择策略,同时采用Dice损失函数对网络进行训练。该策略不仅可加速训练过程,提升分割性能,而且可保证小器官的分割准确率。该方法在2015年MICCAI头颈自动分割挑战赛数据集PDDCA上验证,各器官分割的Dice系数平均值分别为:颌下骨0.945、左腮腺0.884、右腮腺0.882、脑干0.863、左颌下腺0.825、右颌下腺0.842、左视神经0.807、右视神经0.847、视交叉0.583。大多数器官的95% Hausdorff距离小于3 mm,所有器官的勾画平均距离均小于1.2 mm。实验结果表明,该方法在除脑干以外的危及器官分割中性能比其他对比方法更优。     

Quantification of accuracy of the automated nonlinear image matching and anatomical labeling (ANIMAL) nonlinear registration algorithm for 4D CT images of lung

The performance of the ANIMAL (Automated Nonlinear Image Matching and Anatomical Labeling) nonlinear registration algorithm for registration of thoracic 4D CT images was investigated. The algorithm was modified to minimize the incidence of deformation vector discontinuities that occur during the registration of lung images. Registrations were performed between the inhale and exhale phases for five patients. The registration accuracy was quantified by the cross-correlation of transformed and target images and distance to agreement (DTA) measured based on anatomical landmarks and triangulated surfaces constructed from manual contours. On average, the vector DTA between transformed and target landmarks was 1.6 mm. Comparing transformed and target 3D triangulated surfaces derived from planning contours, the average target volume (GTV) center-of-mass shift was 2.0 mm and the 3D DTA was 1.6 mm. An average DTA of 1.8 mm was obtained for all planning structures. All DTA metrics were comparable to inter observer uncertainties established for landmark identification and manual contouring.     

The characteristics of asymptomatic female adolescents at high risk for depression: the baseline assessment from a prospective 8-year study

OBJECTIVES: This longitudinal 8-year study assesses potential predictors of major depressive disorder (MDD) in a cohort of healthy adolescent females at high familial risk for MDD. The objective of this study was to ascertain whether risk factors for female onset MDD would differentiate youth at high or usual risk for MDD, prior to the onset of depressive symptomology. METHODS: Subjects (ages 12-15 years) were assigned to a high (n=43) or usual (n=40) risk group according to maternal history of MDD. Depressive symptomatology (Beck Depression Inventory, Hamilton Rating Scale for Depression), pubertal development (Pubertal Developmental Staging Questionnaire), social support (Social Support Scale), and cognitive vulnerability (Depressive Experiences Questionnaire) were assessed. RESULTS: High risk and usual risk group demonstrated no significant differences in demographic variables such as age, body mass index, and grade. Significantly more youth in the high risk group (n=40, 93%) had started menstruation, compared to youth in the usual risk group (n=31, 77.5%). There were no significant differences between the groups on measures of dysphoric cognitive style, perceived overall number of social supports, or satisfaction with social support. CONCLUSIONS: Females at high familial risk for the onset of depression have significant differences in pubertal development, but not in demographics, depressive symptoms, social supports, or dysphoric cognitive style, when compared to females at usual risk for depression. These findings suggest that in prevention trials for depression in asymptomatic young women no non-biological risk factors for MDD aid in identifying females at higher risk for MDD.     

Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder

Several studies have suggested a possible association of a polymorphism at the dopamine D4 receptor gene and attention-deficit hyperactivity disorder [LaHoste et al., 1996; Rowe et al., 1998; Smalley et al., 1998; Sunohara et al., submitted; Swanson et al., 1998]. The allele reported to be associated with attention-deficit hyperactivity disorder (ADHD) is the allele with seven copies of the 48 bp repeat in the third exon. We extend our study of the dopamine D4 gene and ADHD by testing for linkage using two additional polymorphisms in the dopamine D4 receptor gene and a polymorphism in the closely linked gene, tyrosine hydroxylase. We also searched for two previously reported deletions, a 13 bp and a 21 bp deletion in the first exon. We examined the haplotypes of three polymorphisms of the D4 receptor gene and observed biased transmission of two of these haplotypes. Our findings further support the role of the dopamine D4 gene in ADHD.     

An EGS4-ready tomographic computational model of a 14-year-old female torso for calculating organ doses from CT examinations.

Fifty-four consecutive CT scans have been used to construct a tomographic computational model of a 14-year-old female torso suitable for the determination of organ doses from CT. The model, known as ADELAIDE, is in the form of an input file compatible with user codes based on XYZDOS.MOR from the readily available EGS4 Monte Carlo radiation transport code. ADELAIDE's dimensions are close to the Australian averages for her age so the model is representative of a 14-year-old girl. The realistic anatomy in the model differs considerably from that in Cristy's 15-year-old mathematical computational model by having realistically shaped organs that are appropriately located within a real external contour. Average absorbed dose to organs from simulated CT examinations of the chest and abdomen have been calculated for ADELAIDE using EGS4 within a geometry specific to the General Electric Hi-Speed Advantage CT scanner and using an x-ray spectrum calculated using data from the scanner's x-ray tube. The simulations include the scanner's beam shaping filter and patient table. It is suggested that the resulting values have fewer possible sources of uncertainty than organ doses derived from dose coefficients calculated for a MIRD style model with mathematical anatomy and a spectrum that may not match that of the scanner. The organ doses were normalized using the scanner's CTDI measured free-in-air and an EGS4 simulation of the CTDI measurement. Effective dose to the torso from 26-slice chest and 24-slice abdomen examinations (at 120 kV, 200 mAs, 7 mm slices) is 4.6 +/- 0.1 mSv and 4.3 +/- 0.1 mSv respectively.     

Next generation sequencing for HLA loci in full heritage Pima Indians of Arizona,Part II: HLA-A, -B,and -C with selected non-classical loci at 4-field resolution from whole genome sequences

While the samples and data from the Pima Indians of the Gila River Indian Community have been included in many international HLA workshops and conferences and have been the focus of numerous population reports and the source of novel alleles at the classical HLA loci, they have not been studied for the non-classical loci. In order to expand our HLA-disease association studies, we typed over 300 whole genome sequences from full Pima heritage members, controlled for first degree relationship, and employed recently developed computer algorithms to resolve HLA alleles. Both classical—HLA-A, -B, and -C— and non-classical— HLA-E, -F, -G, -J, -L, -W, -Y, -DPA2, -DPB2, -DMA, -DMB, -DOA, -DRB2, -DRB9, TAP1— loci were typed at the 4-field level of resolution. We present allele and selected haplotype frequencies, test the genotype distributions for population structure, discuss the issues that are created for tests of Hardy-Weinberg equilibrium over the four sample spaces of high resolution HLA typing, and address the implications for the evolution of non-classical pseudogenes that are no longer expressed in a phenotype subject to natural selection.