preliminary clinical evaluation of the ASTRA4D algorithm

Objectives. To propose and evaluate a four-dimensional (4D) algorithm for joint motion elimination and spatiotemporal noise reduction in low-dose dynamic myocardial computed tomography perfusion (CTP). Methods. Thirty patients with suspected or confirmed coronary artery disease were prospectively included und underwent dynamic contrast-enhanced 320-row CTP. The presented deformable image registration method ASTRA4D identifies a low-dimensional linear model of contrast propagation (by principal component analysis, PCA) of the ex-ante temporally smoothed time-intensity curves (by local polynomial regression). Quantitative (standard deviation, signal-to-noise ratio (SNR), temporal variation, volumetric deformation) and qualitative (motion, contrast, contour sharpness; 1, poor; 5, excellent) measures of CTP quality were assessed for the original and motion-compensated volumes (without and with temporal filtering, PCA/ASTRA4D). Following visual myocardial perfusion deficit detection by two readers, diagnostic accuracy was evaluated using 1.5T magnetic resonance (MR) myocardial perfusion imaging as the reference standard in 15 patients. Results. Registration using ASTRA4D was successful in all 30 patients and resulted in comparison with the benchmark PCA in significantly (p<0.001) reduced noise over time (-83%, 178.5 vs 29.9) and spatially (-34%, 21.4 vs 14.1) as well as improved SNR (+47%, 3.6 vs 5.3) and subjective image quality (motion, contrast, contour sharpness: +1.0, +1.0, +0.5). ASTRA4D resulted in significantly improved per-segment sensitivity of 91% (58/64) and similar specificity of 96% (429/446) compared with PCA (52%, 33/64; 98%, 435/446; p=0.011) and the original sequence (45%, 29/64; 98%, 438/446; p=0.003) in the visual detection of perfusion deficits. Conclusions. The proposed functional approach to temporal denoising and morphologic alignment was shown to improve quality metrics and sensitivity of 4D CTP in the detection of myocardial ischemia.Zielsetzung. Die Entwicklung und Bewertung einer Methode zur simultanen Rauschreduktion und Bewegungskorrektur für niedrig dosierte dynamische CT Myokardperfusion. Methoden. Dreißig prospektiv eingeschlossene Patienten mit vermuteter oder bestätigter koronarer Herzkrankheit wurden einer dynamischen CT Myokardperfusionsuntersuchung unterzogen. Die präsentierte Registrierungsmethode ASTRA4D ermittelt ein niedrigdimensionales Modell des Kontrastmittelflusses (mittels einer Hauptkomponentenanalyse, PCA) der vorab zeitlich geglätteten Intensitätskurven (mittels lokaler polynomialer Regression). Quantitative (Standardabweichung, Signal-Rausch-Verhältnis (SNR), zeitliche Schwankung, räumliche Verformung) und qualitative (Bewegung, Kontrast, Kantenschärfe; 1, schlecht; 5, ausgezeichnet) Kennzahlen der unbearbeiteten und bewegungskorrigierten Perfusionsdatensätze (ohne und mit zeitlicher Glättung PCA/ASTRA4D) wurden ermittelt. Nach visueller Beurteilung von myokardialen Perfusionsdefiziten durch zwei Radiologen wurde die diagnostische Genauigkeit im Verhältnis zu 1.5T Magnetresonanztomographie in 15 Patienten ermittelt. Resultate. Bewegungskorrektur mit ASTRA4D war in allen 30 Patienten erfolgreich und resultierte im Vergleich mit der PCA Methode in signifikant (p<0.001) verringerter zeitlicher Schwankung (-83%, 178.5 gegenüber 29.9) und räumlichem Rauschen (-34%, 21.4 gegenüber 14.1) sowie verbesserter SNR (+47%, 3.6 gegenüber 5.3) und subjektiven Qualitätskriterien (Bewegung, Kontrast, Kantenschärfe: +1.0, +1.0, +0.5). ASTRA4D resultierte in signifikant verbesserter segmentweiser Sensitivität 91% (58/64) und ähnlicher Spezifizität 96% (429/446) verglichen mit der PCA Methode (52%, 33/64; 98%, 435/446; p=0.011) und dem unbearbeiteten Perfusionsdatensatz (45%, 29/64; 98%, 438/446; p=0.003) in der visuellen Beurteilung von myokardialen Perfusionsdefiziten. Schlussfolgerungen. Der vorgeschlagene funktionale Ansatz zur simultanen Rauschreduktion und Bewegungskorrektur verbesserte Qualitätskriterien und Sensitivität von dynamischer CT Perfusion in der visuellen Erkennung von Myokardischämie

Regularized 4D-CT reconstruction from a single dataset with a spatio-temporal prior

X-ray Computerized Tomography (CT) reconstructions can be severely impaired by the patient’s respiratory motion and cardiac beating. Motion must thus be recovered in addition to the 3D reconstruction problem. The approach generally followed to reconstruct dynamic volumes consists of largely increasing the number of projections so that independent reconstructions be possible using only subsets of projections from the same phase of the cyclic movement. Apart from this major trend, motion compensation (MC) aims at recovering the object of interest and its motion by accurately modeling its deformation over time, allowing to use the whole dataset for 4D reconstruction in a coherent way.We consider a different approach for dynamic reconstruction based on inverse problems, without any additional measurements, nor explicit knowledge of the motion. The dynamic sequence is reconstructed out of a single data set, only assuming the motion’s continuity and periodicity. This inverse problem is solved by the minimization of the sum of a data-fidelity term, consistent with the dynamic nature of the data, and a regularization term which implements an efficient spatio-temporal version of the total variation (TV). We demonstrate the potential of this approach and its practical feasibility on 2D and 3D+t reconstructions of a mechanical phantom and patient data

Segmentation, tracking, and kinematics of lung parenchyma and lung tumors from 4D CT with application to radiation treatment planning.

This thesis is concerned with development of techniques for efficient computerized analysis of 4-D CT data. The goal is to have a highly automated approach to segmentation of the lung boundary and lung nodules inside the lung. The determination of exact lung tumor location over space and time by image segmentation is an essential step to track thoracic malignancies. Accurate image segmentation helps clinical experts examine the anatomy and structure and determine the disease progress. Since 4-D CT provides structural and anatomical information during tidal breathing, we use the same data to also measure mechanical properties related to deformation of the lung tissue including Jacobian and strain at high resolutions and as a function of time. Radiation Treatment of patients with lung cancer can benefit from knowledge of these measures of regional ventilation. Graph-cuts techniques have been popular for image segmentation since they are able to treat highly textured data via robust global optimization, avoiding local minima in graph based optimization. The graph-cuts methods have been used to extract globally optimal boundaries from images by s/t cut, with energy function based on model-specific visual cues, and useful topological constraints. The method makes N-dimensional globally optimal segmentation possible with good computational efficiency. Even though the graph-cuts method can extract objects where there is a clear intensity difference, segmentation of organs or tumors pose a challenge. For organ segmentation, many segmentation methods using a shape prior have been proposed. However, in the case of lung tumors, the shape varies from patient to patient, and with location. In this thesis, we use a shape prior for tumors through a training step and PCA analysis based on the Active Shape Model (ASM). The method has been tested on real patient data from the Brown Cancer Center at the University of Louisville. We performed temporal B-spline deformable registration of the 4-D CT data - this yielded 3-D deformation fields between successive respiratory phases from which measures of regional lung function were determined. During the respiratory cycle, the lung volume changes and five different lobes of the lung (two in the left and three in the right lung) show different deformation yielding different strain and Jacobian maps. In this thesis, we determine the regional lung mechanics in the Lagrangian frame of reference through different respiratory phases, for example, Phase10 to 20, Phase10 to 30, Phase10 to 40, and Phase10 to 50. Single photon emission computed tomography (SPECT) lung imaging using radioactive tracers with SPECT ventilation and SPECT perfusion imaging also provides functional information. As part of an IRB-approved study therefore, we registered the max-inhale CT volume to both VSPECT and QSPECT data sets using the Demon\u27s non-rigid registration algorithm in patient subjects. Subsequently, statistical correlation between CT ventilation images (Jacobian and strain values), with both VSPECT and QSPECT was undertaken. Through statistical analysis with the Spearman\u27s rank correlation coefficient, we found that Jacobian values have the highest correlation with both VSPECT and QSPECT

Virtual clinical trials in medical imaging: a review

The accelerating complexity and variety of medical imaging devices and methods have outpaced the ability to evaluate and optimize their design and clinical use. This is a significant and increasing challenge for both scientific investigations and clinical applications. Evaluations would ideally be done using clinical imaging trials. These experiments, however, are often not practical due to ethical limitations, expense, time requirements, or lack of ground truth. Virtual clinical trials (VCTs) (also known as in silico imaging trials or virtual imaging trials) offer an alternative means to efficiently evaluate medical imaging technologies virtually. They do so by simulating the patients, imaging systems, and interpreters. The field of VCTs has been constantly advanced over the past decades in multiple areas. We summarize the major developments and current status of the field of VCTs in medical imaging. We review the core components of a VCT: computational phantoms, simulators of different imaging modalities, and interpretation models. We also highlight some of the applications of VCTs across various imaging modalities

Three-dimensional model-based analysis of vascular and cardiac images

This thesis is concerned with the geometrical modeling of organs to perform medical image analysis tasks. The thesis is divided in two main parts devoted to model linear vessel segments and the left ventricle of the heart, respectively. Chapters 2 to 4 present different aspects of a model-based technique for semi-automated quantification of linear vessel segments from 3-D Magnetic Resonance Angiography (MRA). Chapter 2 is concerned with a multiscale filter for the enhancement of vessels in 2-D and 3-D angiograms. Chapter 3 applies the filter developed in Chapter 2 to determine the central vessel axis in 3-D MRA images. This procedure is initialized using an efficient user interaction technique that naturally incorporates the knowledge of the operator about the vessel of interest. Also in this chapter, a linear vessel model is used to recover the position of the vessel wall in order to carry out an accurate quantitative analysis of vascular morphology. Prior knowledge is provided in two main forms: a cylindrical model introduces a shape prior while prior knowledge on the image acquisition (type of MRA technique) is used to define an appropriate vessel boundary criterion. In Chapter 4 an extensive in vitro and in vivo evaluation of the algorithm introduced in Chapter 3 is described. Chapters 5 to 7 change the focus to 3D cardiac image analysis from Magnetic Resonance Imaging. Chapter 5 presents an extensive survey, a categorization and a critical review of the field of cardiac modeling. Chapter 6 and Chapter 7 present successive refinements of a method for building statistical models of shape variability with particular emphasis on cardiac modeling. The method is based on an elastic registration method using hierarchical free-form deformations. A 3D shape model of the left and right ventricles of the heart was constructed. This model contains both the average shape of these organs as well as their shape variability. The methodology presented in the last two chapters could also be applied to other anatomical structures. This has been illustrated in Chapter 6 with examples of geometrical models of the nucleus caudate and the radius

Spatio-Temporal Nonrigid Registration for Ultrasound Cardiac Motion Estimation

We propose a new spatio-temporal elastic registration algorithm for motion reconstruction from a series of images. The specific application is to estimate displacement fields from two-dimensional ultrasound sequences of the heart. The basic idea is to find a spatio-temporal deformation field that effectively compensates for the motion by minimizing a difference with respect to a reference frame. The key feature of our method is the use of a semi-local spatio-temporal parametric model for the deformation using splines, and the reformulation of the registration task as a global optimization problem. The scale of the spline model controls the smoothness of the displacement field. Our algorithm uses a multiresolution optimization strategy to obtain a higher speed and robustness. We evaluated the accuracy of our algorithm using a synthetic sequence generated with an ultrasound simulation package, together with a realistic cardiac motion model. We compared our new global multiframe approach with a previous method based on pairwise registration of consecutive frames to demonstrate the benefits of introducing temporal consistency. Finally, we applied the algorithm to the regional analysis of the left ventricle. Displacement and strain parameters were evaluated showing significant differences between the normal and pathological segments, thereby illustrating the clinical applicability of our method

A 5D computational phantom for pharmacokinetic simulation studies in dynamic emission tomography

Introduction: Dynamic image acquisition protocols are increasingly used in emission tomography for drug development and clinical research. As such, there is a need for computational phantoms to accurately describe both the spatial and temporal distribution of radiotracers, also accounting for periodic and non-periodic physiological processes occurring during data acquisition. Methods: A new 5D anthropomorphic digital phantom was developed based on a generic simulation platform, for accurate parametric imaging simulation studies in emission tomography. The phantom is based on high spatial and temporal information derived from real 4D MR data and a detailed multi-compartmental pharmacokinetic modelling simulator. Results: The proposed phantom is comprised of three spatial and two temporal dimensions, including periodic physiological processes due to respiratory motion and non-periodic functional processes due to tracer kinetics. Example applications are shown in parametric [18F]FDG and [15O]H2O PET imaging, successfully generating realistic macro- and micro-parametric maps. Conclusions: The envisaged applications of this digital phantom include the development and evaluation of motion correction and 4D image reconstruction algorithms in PET and SPECT, development of protocols and methods for tracer and drug development as well as new pharmacokinetic parameter estimation algorithms, amongst others. Although the simulation platform is primarily developed for generating dynamic phantoms for emission tomography studies, it can easily be extended to accommodate dynamic MR and CT imaging simulation protocols