Regularized Image Reconstruction Algorithms for Dual-Isotope Myocardial Perfusion SPECT (MPS) Imaging Using a Cross-Tracer Prior

In simultaneous dual-isotope myocardial perfusion SPECT (MPS) imaging, data are simultaneously acquired to determine the distributions of two radioactive isotopes. The goal of this work was to develop penalized maximum likelihood (PML) algorithms for a novel cross-tracer prior that exploits the fact that the two images reconstructed from simultaneous dual-isotope MPS projection data are perfectly registered in space. We first formulated the simultaneous dual-isotope MPS reconstruction problem as a joint estimation problem. A cross-tracer prior that couples voxel values on both images was then proposed. We developed an iterative algorithm to reconstruct the MPS images that converges to the maximum a posteriori solution for this prior based on separable surrogate functions. To accelerate the convergence, we developed a fast algorithm for the cross-tracer prior based on the complete data OS-EM (COSEM) framework. The proposed algorithm was compared qualitatively and quantitatively to a single-tracer version of the prior that did not include the cross-tracer term. Quantitative evaluations included comparisons of mean and standard deviation images as well as assessment of image fidelity using the mean square error. We also evaluated the cross tracer prior using a three-class observer study with respect to the three-class MPS diagnostic task, i.e., classifying patients as having either no defect, reversible defect, or fixed defects. For this study, a comparison with conventional ordered subsets-expectation maximization (OS-EM) reconstruction with postfiltering was performed. The comparisons to the single-tracer prior demonstrated similar resolution for areas of the image with large intensity changes and reduced noise in uniform regions. The cross-tracer prior was also superior to the single-tracer version in terms of restoring image fidelity. Results of the three-class observer study showed that the proposed cross-tracer prior and the convergent algorithms improved the ima- - ge quality of dual-isotope MPS images compared to OS-EM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85873/1/Fessler3.pd

TOWARDS FURTHER OPTIMIZATION OF RECONSTRUCTION METHODS FOR DUAL-RADIONUCLIDE MYOCARDIAL PERFUSION SPECT

Coronary artery disease (CAD) is the most prevalent type of heart disease and a leading cause of death both in the United States and worldwide. Myocardial perfusion SPECT (MPS) is a well-established and widely-used non-invasive imaging technique to diagnose CAD. MPS images the distribution of radioactive perfusion agent in the myocardium to assess the myocardial perfusion status at rest and stress state and allow diagnosis of CAD and allow differentiation of CAD and previous myocardial infarctions. The overall goal of this dissertation was to optimize the image reconstruction methods for MPS by patient-specific optimization of two advanced iterative reconstruction methods based on simulations of realistic patients population modeling existing hardware and previously optimized dual-isotope simultaneous-acquisition imaging protocols. After optimization, the two algorithms were compared to determine the optimal reconstruction methods for MPS. First, we developed a model observer strategy to evaluate image quality and allow optimization of the reconstruction methods using a population of phantoms modeling the variability seen in human populations. The Hotelling Observer (HO) is widely used to evaluate image quality, often in conjunction with anthropomorphic channels to model human observer performance. However, applying the HO to non- multivariate-normally (MVN) distributed, such as the output from a channel model applied to images with variable signals and background, is not optimal. In this work, we proposed a novel model observer strategy to evaluate the image quality of such data. First, the entire data ensemble is divided into sub-ensembles that are exactly or approximately MVN and homoscedastic. Next, the Linear Discriminant (LD) is applied to estimate test statistics for each sub-ensemble, and a single area under the receiver operating characteristics curve (AUC) is calculated using the pooled test statistics from all the sub-ensembles. The AUC serves as the figure of merit for performance on the defect detection task. The proposed multi-template LD was compared to other model observer strategies and was shown to be a practical, theoretically justified, and produced higher AUC values for non-MVN data such as that arising from the clinically-realistic SKS task used in the remainder of this work. We then optimized two regularized statistical reconstruction algorithms. One is the widely used post-filtered ordered subsets-expectation maximization (OS-EM) algorithm. The other is a maximum a posteriori (MAP) algorithm with dual-tracer prior (DTMAP) that was proposed for dual-isotope MPS study and was expected to outperform the post-filtered OS-EM algorithm. Of importance, we proposed to investigate patient-specific optimization of the reconstruction parameters. To accomplish this, the phantom population was divided into three anatomy groups based on metrics that expected to affect image noise and resolution and thus the optimal reconstruction parameters. In particular, these metrics were the distance from the center of the heart to the face of the collimator, which is directly related to image resolution, heart size, and counts from the myocardium, which is expected to determine image noise. Reconstruction parameters were optimized for each of these groups using the proposed model observer strategy. Parameters for the rest and stress images were optimized separately, and the parameters that achieve the highest AUC were deemed optimal. The results showed that the proposed group-wise optimization method offered slightly better task performance than using a single set of parameters for all the phantoms. For DTMAP, we also applied the group-wise optimization approach. The extra challenges for DTMAP optimization are that it has three parameters to be optimized simultaneously, and it is substantially more computationally expensive than OS-EM. Thus, we adopted optimization strategies to reduce the size of the parameter search space. In particular, we searched in two parameter ranges expected to give result in good image quality. We also reduced the computation burden by exploiting limiting behavior of the penalty function to reduce the number of parameters that need to be optimized. Despite this effort, the optimized DTMAP had poorer task performance compared to the optimized OS-EM algorithm. As a result, we studied the limitations of the DTMAP algorithm and suggest reasons of its worse performance for the task investigated. The results of this study indicate that there is benefit from patient-specific optimization. The methods and optimal patient-specific parameters may be applicable to clinical MPS studies. In addition, the model observer strategy and the group-wise optimization approach may also be applicable both to future work in MPS and to other relevant fields

(An overview of) Synergistic reconstruction for multimodality/multichannel imaging methods

Imaging is omnipresent in modern society with imaging devices based on a zoo of physical principles, probing a specimen across different wavelengths, energies and time. Recent years have seen a change in the imaging landscape with more and more imaging devices combining that which previously was used separately. Motivated by these hardware developments, an ever increasing set of mathematical ideas is appearing regarding how data from different imaging modalities or channels can be synergistically combined in the image reconstruction process, exploiting structural and/or functional correlations between the multiple images. Here we review these developments, give pointers to important challenges and provide an outlook as to how the field may develop in the forthcoming years. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'

Development of whole-heart myocardial perfusion magnetic resonance imaging

Myocardial perfusion imaging is of huge importance for the detection of coronary artery disease (CAD), one of the leading causes of morbidity and mortality worldwide, as it can provide non-invasive detection at the early stages of the disease. Magnetic resonance imaging (MRI) can assess myocardial perfusion by capturing the rst-pass perfusion (FPP) of a gadolinium-based contrast agent (GBCA), which is now a well-established technique and compares well with other modalities. However, current MRI methods are restricted by their limited coverage of the left ventricle. Interest has therefore grown in 3D volumetric \whole-heart" FPP by MRI, although many challenges currently limit this. For this thesis, myocardial perfusion assessment in general, and 3D whole-heart FPP in particular, were reviewed in depth, alongside MRI techniques important for achieving 3D FPP. From this, a 3D `stack-of-stars' (SOS) FPP sequence was developed with the aim of addressing some current limitations. These included the breath-hold requirement during GBCA rst-pass, long 3D shot durations corrupted by cardiac motion, and a propensity for artefacts in FPP. Parallel imaging and compressed sensing were investigated for accelerating whole-heart FPP, with modi cations presented to potentially improve robustness to free-breathing. Novel sequences were developed that were capable of individually improving some current sequence limits, including spatial resolution and signal-to-noise ratio, although with some sacri ces. A nal 3D SOS FPP technique was developed and tested at stress during free-breathing examinations of CAD patients and healthy volunteers. This enabled the rst known detection of an inducible perfusion defect with a free-breathing, compressed sensing, 3D FPP sequence; however, further investigation into the diagnostic performance is required. Simulations were performed to analyse potential artefacts in 3D FPP, as well as to examine ways towards further optimisation of 3D SOS FPP. The nal chapter discusses some limitations of the work and proposes opportunities for further investigation.Open Acces

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

QUANTITATIVE NUCLEAR MEDICINE IMAGING USING ADVANCED IMAGE RECONSTRUCTION AND RADIOMICS

Our aim is to help put nuclear medicine at the forefront of quantitation on the path to the realization of personalized medicine. We propose and evaluate (Part I) advanced image reconstruction and (Part II) robust radiomics (large-scale data-oriented study of radiological images). The goal is to attain significantly improved diagnostic, prognostic and treatment-response assessment capabilities. Part I presents a new paradigm in point-spread function (PSF)-modeling, a partial volume correction method in PET imaging where resolution-degrading phenomena are modeled within the reconstruction framework. PSF-modeling improves resolution and enhances contrast, but significantly alters noise properties and induces edge-overshoots. Past efforts involve a dichotomy of PSF vs. no-PSF modeling; by contrast, we focus on a wide-spectrum of PSF models, including under- and over-estimation of the true PSF, for the potential of enhanced quantitation in standardized uptake values (SUVs). We show for the standard range of iterations employed in clinic (not excessive), edge enhancement due to overestimation actually lower SUV bias in small regions, while inter-voxel correlations suppress image roughness and enhance uniformity. An overestimated PSF yields improved contrast and limited edge-overshoot effects at lower iterations, enabling enhanced SUV quantitation. Overall, our framework provides an effective venue for quantitative task-based optimization. Part II proposes robust and reproducible radiomics methods. Radiomics workflows are complex, generating hundreds of features, which can lead to high variability and overfitting, and ultimately hampering performance. We developed and released a Standardized Environment for Radiomics Analysis (SERA) solution to enable robust radiomics analyses. We conduct studies on two unique imaging datasets – renal cell carcinoma SPECT and prostate cancer PET – identifying robust and reproducible radiomic features. In addition, we evaluate a novel hypothesis that radiomic features extracted from clinically normal (non-ischemic) myocardial perfusion SPECT (MPS) can predict coronary artery calcification (CAC; as extracted from CT). This has important implications, since CAC assessment is not commonly-performed nor reimbursed in wide community settings. SERA-derived radiomic features were utilized in a multi-step feature selection framework, followed by the application of machine learning to radiomic features. Our results show the potential to predict CAC from normal MPS, suggesting added usage and value for routine standard MPS

Reconstruction Methods for Free-Breathing Dynamic Contrast-Enhanced MRI

Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) is a valuable diagnostic tool due to the combination of anatomical and physiological information it provides. However, the sequential sampling of MRI presents an inherent tradeoff between spatial and temporal resolution. Compressed Sensing (CS) methods have been applied to undersampled MRI to reconstruct full-resolution images at sub-Nyquist sampling rates. In exchange for shorter data acquisition times, CS-MRI requires more computationally intensive iterative reconstruction methods. We present several model-based image reconstruction (MBIR) methods to improve the spatial and temporal resolution of MR images and/or the computational time for multi-coil MRI reconstruction. We propose efficient variable splitting (VS) methods for support-constrained MRI reconstruction, image reconstruction and denoising with non-circulant boundary conditions, and improved temporal regularization for breast DCE-MRI. These proposed VS algorithms decouple the system model and sparsity terms of the convex optimization problem. By leveraging matrix structures in the system model and sparsifying operator, we perform alternating minimization over a list of auxiliary variables, each of which can be performed efficiently. We demonstrate the computational benefits of our proposed VS algorithms compared to similar proposed methods. We also demonstrate convergence guarantees for two proposed methods, ADMM-tridiag and ADMM-FP-tridiag. With simulation experiments, we demonstrate lower error in spatial and temporal dimensions for these VS methods compared to other object models. We also propose a method for indirect motion compensation in 5D liver DCE-MRI. 5D MRI separates temporal changes due to contrast from anatomical changes due to respiratory motion into two distinct dimensions. This work applies a pre-computed motion model to perform motion-compensated regularization across the respiratory dimension and improve the conditioning of this highly sparse 5D reconstruction problem. We demonstrate a proof of concept using a digital phantom with contrast and respiratory changes, and we show preliminary results for motion model-informed regularization on in vivo patient data.PHDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/138498/1/mtle_1.pd

Accelerated Computation of Regularized Estimates in Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is a non-invasive medical imaging modality that uses magnetic fields. Accurate estimates of these fields are often used to improve the quality of MR imaging techniques. Regularized estimators for such fields are robust and can provide high quality estimates but often at a significant computational cost. In this work, we investigate several of these estimators with a focus on developing novel minimization methods that reduce their computation times. First, we explore regularized receive coil sensitivity estimation by demonstrating the improved performance of regularized methods over existing, heuristic approaches and by presenting several algorithms, based on augmented Lagrangian methods, that minimize the quadratic cost function in half the time required by a preconditioned conjugate gradient (CG) method. Second, we present a general cost function that combines the regularized estimation of the main magnetic field inhomogeneity for both multiple echo time field map estimation and chemical shift based water-fat imaging. We present two methods, both based on optimization transfer principles, that reduce the computation time of this estimator by a factor of 30 compared to the existing separable quadratic surrogates method. We also evaluate the effectiveness of edge preserving regularization for field inhomogeneity estimation near tissue interfaces. Third, we present a novel alternating minimization method that uses augmented Lagrangian methods to accelerate the computation of the compressed sensing based water-fat image reconstruction problem by at least ten times compared to the existing nonlinear CG method. The algorithms presented in this thesis may also be applicable to other MRI topics including B1+ estimation, T1 estimation from variable flip angles, and R2* corrected or parallel imaging extensions of compressed sensing based water-fat imaging.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107096/1/mjalliso_1.pd