Cardiac CT perfusion imaging of pericoronary adipose tissue (PCAT) highlights potential confounds in coronary CTA

Features of pericoronary adipose tissue (PCAT) assessed from coronary computed tomography angiography (CCTA) are associated with inflammation and cardiovascular risk. As PCAT is vascularly connected with coronary vasculature, the presence of iodine is a potential confounding factor on PCAT HU and textures that has not been adequately investigated. Use dynamic cardiac CT perfusion (CCTP) to inform contrast determinants of PCAT assessment. From CCTP, we analyzed HU dynamics of territory-specific PCAT, myocardium, and other adipose depots in patients with coronary artery disease. HU, blood flow, and radiomics were assessed over time. Changes from peak aorta time, Pa, chosen to model the time of CCTA, were obtained. HU in PCAT increased more than in other adipose depots. The estimated blood flow in PCAT was ~23% of that in the contiguous myocardium. Comparing PCAT distal and proximal to a significant stenosis, we found less enhancement and longer time-to-peak distally. Two-second offsets [before, after] Pa resulted in [ 4-HU, 3-HU] differences in PCAT. Due to changes in HU, the apparent PCAT volume reduced ~15% from the first scan (P1) to Pa using a conventional fat window. Comparing radiomic features over time, 78% of features changed >10% relative to P1. CCTP elucidates blood flow in PCAT and enables analysis of PCAT features over time. PCAT assessments (HU, apparent volume, and radiomics) are sensitive to acquisition timing and the presence of obstructive stenosis, which may confound the interpretation of PCAT in CCTA images. Data normalization may be in order.Comment: 13 pages, 8 figure

Quantitative Poly-energetic Reconstruction Schemes for Single Spectrum CT Scanners

<p>X-ray computed tomography (CT) is a non-destructive medical imaging technique for assessing the cross-sectional images of an object in terms of attenuation. As it is designed based on the physical processes involved in the x-ray and matter interactions, faithfully modeling the physics in the reconstruction procedure can yield accurate attenuation distribution of the scanned object. Otherwise, unrealistic physical assumptions can result in unwanted artifacts in reconstructed images. For example, the current reconstruction algorithms assume the photons emitted by the x-ray source are mono-energetic. This oversimplified physical model neglects the poly-energetic properties of the x-ray source and the nonlinear attenuations of the scanned materials, and results in the well-known beam-hardening artifacts (BHAs). The purpose of this work was to incorporate the poly-energetic nature of the x-ray spectrum and then to eliminate BHAs. By accomplishing this, I can improve the image quality, enable the quantitative reconstruction ability of the single-spectrum CT scanner, and potentially reduce unnecessary radiation dose to patients.</p><p>In this thesis, in order to obtain accurate spectrum for poly-energetic reconstruction, I first presented a novel spectral estimation technique, with which spectra across a large range of angular trajectories of the imaging field of view can be estimated with a single phantom and a single axial acquisition. The experimental results with a 16 cm diameter cylindrical phantom (composition: ultra-high-molecular-weight polyethylene [UHMWPE]) on a clinical scanner showed that the averaged absolute mean energy differences and the normalized root mean square differences with respect to the actual spectra across kVp settings (i.e., 80, 100, 120, 140) and angular trajectories were less than 0.61 keV and 3.41%, respectively</p><p>With the previous estimation of the x-ray spectra, three poly-energetic reconstruction algorithms are proposed for different clinical applications. The first algorithm (i.e., poly-energetic iterative FBP [piFBP]) can be applied to routine clinical CT exams, as the spectra of the x-ray source and the nonlinear attenuations of diverse body tissues and metal implant materials are incorporated to eliminate BHAs and to reduce metal artifacts. The simulation results showed that the variation range of the relative errors of various tissues across different phantom sizes (i.e., 16, 24, 32, and 40 cm in diameter) and kVp settings (80, 100, 120, 140) were reduced from [-7.5%, 17.5%] for conventional FBP to [-0.1%, 0.1%] for piFBP, while the noise was maintained at the same low level (about [0.3%, 1.7%]).</p><p>When iodinated contrast agents are involved and patient motions are not readily correctable (e.g., in myocardial perfusion exam), a second algorithm (i.e., poly-energetic simultaneous algebraic reconstruction technique [pSART]) can be applied to eliminate BHAs and to quantitatively determine the iodine concentrations of blood-iodine mixtures with our new technique. The phantom experiment on a clinical CT scanner indicated that the maximum absolute relative error across material inserts was reduced from 4.1% for conventional simultaneous algebraic reconstruction technique [SART] to 0.4% for pSART.</p><p>Extending the work beyond minimizing BHAs, if patient motions are correctable or negligible, a third algorithm (i.e., poly-energetic dynamic perfusion algorithm [pDP]) is developed to retrieve iodine maps of any iodine-tissue mixtures in any perfusion exams, such as breast, lung, or brain perfusion exams. The quantitative results of the simulations with a dynamic anthropomorphic thorax phantom indicated that the maximum error of iodine concentrations can be reduced from 1.1 mg/cc for conventional FBP to less than 0.1 mg/cc for pDP.</p><p>Two invention disclosure forms based on the work presented in this thesis have been submitted to Office of Licensing & Ventures of Duke University.</p>Dissertatio

Developments in PET-MRI for Radiotherapy Planning Applications

The hybridization of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides the benefit of soft-tissue contrast and specific molecular information in a simultaneous acquisition. The applications of PET-MRI in radiotherapy are only starting to be realised. However, quantitative accuracy of PET relies on accurate attenuation correction (AC) of, not only the patient anatomy but also MRI hardware and current methods, which are prone to artefacts caused by dense materials. Quantitative accuracy of PET also relies on full characterization of patient motion during the scan. The simultaneity of PET-MRI makes it especially suited for motion correction. However, quality assurance (QA) procedures for such corrections are lacking. Therefore, a dynamic phantom that is PET and MR compatible is required. Additionally, respiratory motion characterization is needed for conformal radiotherapy of lung. 4D-CT can provide 3D motion characterization but suffers from poor soft-tissue contrast. In this thesis, I examine these problems, and present solutions in the form of improved MR-hardware AC techniques, a PET/MRI/CT-compatible tumour respiratory motion phantom for QA measurements, and a retrospective 4D-PET-MRI technique to characterise respiratory motion. Chapter 2 presents two techniques to improve upon current AC methods that use a standard helical CT scan for MRI hardware in PET-MRI. One technique uses a dual-energy computed tomography (DECT) scan to construct virtual monoenergetic image volumes and the other uses a tomotherapy linear accelerator to create CT images at megavoltage energies (1.0 MV) of the RF coil. The DECT-based technique reduced artefacts in the images translating to improved μ-maps. The MVCT-based technique provided further improvements in artefact reduction, resulting in artefact free μ-maps. This led to more AC of the breast coil. In chapter 3, I present a PET-MR-CT motion phantom for QA of motion-correction protocols. This phantom is used to evaluate a clinically available real-time dynamic MR images and a respiratory-triggered PET-MRI protocol. The results show the protocol to perform well under motion conditions. Additionally, the phantom provided a good model for performing QA of respiratory-triggered PET-MRI. Chapter 4 presents a 4D-PET/MRI technique, using MR sequences and PET acquisition methods currently available on hybrid PET/MRI systems. This technique is validated using the motion phantom presented in chapter 3 with three motion profiles. I conclude that our 4D-PET-MRI technique provides information to characterise tumour respiratory motion while using a clinically available pulse sequence and PET acquisition method

Improving Attenuation Correction in Hybrid Positron Emission Tomography

Hybrid positron emission tomography imaging techniques such as PET/CT and PET/MR have undergone significant developments over the last two decades and have played increasingly more important roles both in research and in the clinic. A unique advantage PET has over other clinical imaging modalities is its capability of accurate quantification. However, as the most critical component of PET quantification, attenuation correction in hybrid PET systems is challenged in several different aspects, including the spatial- temporal mismatch between the PET emission images and the associated attenuation images provided by the complementary modality, and the difficulty in bone identification in the MR-based attenuation correction approaches. These problems, if left unaddressed, can limit the potential of the hybrid PET systems. This research developed solutions to overcome the spatial-temporal mismatch in PET/CT and PET/MR, and established the requirements for bone identification in PET/MR. An automatic registration algorithm based on a modified fuzzy c-means clustering method and gradient correlation was developed and validated to perform automatic registration in cardiac PET/CT data of different breathing protocols. A free- breathing MR protocol and post-process algorithm were developed to provide MR-based attenuation images that also match the temporal resolution of PET and were evaluated in a feasibility study. The relationship between the sensitivity of bone identification in attenuation images and PET quantification of bone lesions uptake was evaluated in a simulated study using data from 18F-sodium fluoride PET/CT exams

The Estimation and Correction of Rigid Motion in Helical Computed Tomography

X-ray CT is a tomographic imaging tool used in medicine and industry. Although technological developments have significantly improved the performance of CT systems, the accuracy of images produced by state-of-the-art scanners is still often limited by artefacts due to object motion. To tackle this problem, a number of motion estimation and compensation methods have been proposed. However, no methods with the demonstrated ability to correct for rigid motion in helical CT scans appear to exist. The primary aims of this thesis were to develop and evaluate effective methods for the estimation and correction of arbitrary six degree-of-freedom rigid motion in helical CT. As a first step, a method was developed to accurately estimate object motion during CT scanning with an optical tracking system, which provided sub-millimetre positional accuracy. Subsequently a motion correction method, which is analogous to a method previously developed for SPECT, was adapted to CT. The principle is to restore projection consistency by modifying the source-detector orbit in response to the measured object motion and reconstruct from the modified orbit with an iterative reconstruction algorithm. The feasibility of this method was demonstrated with a rapidly moving brain phantom, and the efficacy of correcting for a range of human head motions acquired from healthy volunteers was evaluated in simulations. The methods developed were found to provide accurate and artefact-free motion corrected images with most types of head motion likely to be encountered in clinical CT imaging, provided that the motion was accurately known. The method was also applied to CT data acquired on a hybrid PET/CT scanner demonstrating its versatility. Its clinical value may be significant by reducing the need for repeat scans (and repeat radiation doses), anesthesia and sedation in patient groups prone to motion, including young children

Evaluation of physical image quality of the preclinical scanner IRIS CT using conventional and nanoparticle-based contrast agents

Sub-millimeter Computed Tomography (micro-CT) is an essential tool to study small animal models of human diseases. Micro-CT generally provides high-resolution anatomic information, either on its own or in conjuction with functional imaging modalities such as Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT). The increasing development of new contrast agents and the advanced applications of micro-CT, make possible to provide morpho-functional information by translating preclinical models to clinical applications and pioneering new ones. The main goal in micro-CT imaging is to obtain a high spatial resolution, while reducing the long scanning time and radiation dose. In fact, the animal dose strongly depends on the scanning protocol and it should be kept at low levels in order to enable longitudinal studies avoiding radiation-related injuries. This work falls into the wide research field of molecular imaging, where collaboration between physicists, biologists, and chemists is very close. The aim of this thesis is to evaluate the performance of the CT component of a novel combined PET/CT scanner for preclinical imaging which is operating at the Institute of Clinical Physiology of the National Research Council, in Pisa. In the first part of the thesis the physical background of CT and micro- CT imaging is described. Then it focuses on IRIS CT components and the related imaging perfomances. A digression on the contrast agents available on the market for micro-CT imaging is then given, including a discussion on the difference between water-soluble contrast agents and blood-pool contrast agents. The relating properties reflecting on CT enhancement of animal studies will be also examined. In the second part, results of experimental measurements on the IRIS CT are reported. More specifically, spatial resolution and micro-CT image noise are evaluated as a function of the spatial frequency, in terms of the Modulation Transfer Function (MTF) and Noise Power Spectrum (NPS), re- spectively. As a new achievement of this work, the beam hardening artifact is analyzed and a first correction of it is provided. Then the focus shifts on stu- dies with contrast media. Phantom studies employing conventional contrast agents based on iodine are reported. They have allowed the first investigations of the IRIS CT scanner high temporal resolution protocol, specifically designed for dynamic (functional) imaging. Moreover the response to X-rays of a novel nanoparticle-based contrast agent under development at the Center for Nanotechnology Innovation@Nest, Istituto Italiano di Tecnologia, is first analyzed by means of phantom simulations. Simulations aimed to give a replication of the real imaging process in order to foresee the experimental results of phantom studies employing this novel contrast agent. The sensitivity of the IRIS CT scanner to nanoparticles was finally evaluated for all tube voltages. The results obtained from fast imaging protocols could represent the basis of further analysis aimed to optimize the contrast agent injection protocol in real dynamic acquisitions. Further investigations of these novel nanoparticle-based contrast agents are also needed in order to implement advanced preclinical applications of the IRIS CT with potential big impact on molecular imaging research, and, hopefully, potential translation to the clinical world