A feasible and automatic free tool for T1 and ECV mapping

Purpose: Cardiac magnetic resonance (CMR) is a useful non-invasive tool for characterizing tissues and detecting myocardial fibrosis and edema. Estimation of extracellular volume fraction (ECV) using T1 sequences is emerging as an accurate biomarker in cardiac diseases associated with diffuse fibrosis. In this study, automatic software for T1 and ECV map generation consisting of an executable file was developed and validated using phantom and human data. Methods: T1 mapping was performed in phantoms and 30 subjects (22 patients and 8 healthy subjects) on a 1.5T MR scanner using the modified Look-Locker inversion-recovery (MOLLI) sequence prototype before and 15 min after contrast agent administration. T1 maps were generated using a Fast Nonlinear Least Squares algorithm. Myocardial ECV maps were generated using both pre- and post-contrast T1 image registration and automatic extraction of blood relaxation rates. Results: Using our software, pre- and post-contrast T1 maps were obtained in phantoms and healthy subjects resulting in a robust and reliable quantification as compared to reference software. Coregistration of pre- and post-contrast images improved the quality of ECV maps. Mean ECV value in healthy subjects was 24.5% ± 2.5%. Conclusions: This study demonstrated that it is possible to obtain accurate T1 maps and informative ECV maps using our software. Pixel-wise ECV maps obtained with this automatic software made it possible to visualize and evaluate the extent and severity of ECV alterations

Cardiac magnetic resonance T1 and extracellular volume mapping with motion correction and co-registration based on fast elastic image registration

OBJECTIVE: Our aim was to investigate the technical feasibility of a novel motion compensation method for cardiac magntic resonance (MR) T1 and extracellular volume fraction (ECV) mapping. MATERIALS AND METHODS: Native and post-contrast T1 maps were obtained using modified look-locker inversion recovery (MOLLI) pulse sequences with acquisition scheme defined in seconds. A nonrigid, nonparametric, fast elastic registration method was applied to generate motion-corrected T1 maps and subsequently ECV maps. Qualitative rating was performed based on T1 fitting-error maps and overlay images. Local deformation vector fields were produced for quantitative assessment. Intra- and inter-observer reproducibility were compared with and without motion compensation. RESULTS: Eighty-two T1 and 39 ECV maps were obtained in 21 patients with diverse myocardial diseases. Approximately 60% demonstrated clear quality improvement after motion correction for T1 mapping, particularly for the poor-rating cases (23% before vs 2% after). Approximately 67% showed further improvement with co-registration in ECV mapping. Although T1 and ECV values were not clinically significantly different before and after motion compensation, there was improved intra- and inter-observer reproducibility after motion compensation. CONCLUSIONS: Automated motion correction and co-registration improved the qualitative assessment and reproducibility of cardiac MR T1 and ECV measurements, allowing for more reliable ECV mapping

Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions

Mapping of the longitudinal relaxation time (T1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson- Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field. Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions. Available from: https://www.researchgate.net/publication/317548806_Towards_accurate_and_precise_T1_and_extracellular_volume_mapping_in_the_myocardium_a_guide_to_current_pitfalls_and_their_solutions [accessed Jun 13, 2017]

Doctor of Philosophy

dissertationHeart failure (HF) is a significant health care problem in the United States. Many patients advance towards end stage HF despite optimal medical therapy. For patients with end stage HF, unfortunately, therapeutic options are limited. While heart transplantation is the most proven treatment for improving survival, it is only performed in approximately 2,500 cases annually due to a shortage of donor hearts. Left ventricular assist device (LVAD) implantation is an FDA-approved therapy and is clinically indicated for two applications: (i) bridge-to-transplantation (BTT) for patients who are awaiting heart transplantation and (ii) destination therapy (DT) for patients who are ineligible for heart transplantation. Unexpectedly, patients in BTT and DT experience cardiac functional recovery after LVAD-induced unloading, which led to an investigational concept called bridge-to-recovery (BTR). For successful clinical translation, it is important to identify reliable predictors and discriminate responders from non-responders. Myocardial fibrosis, as a marker of adverse structural remodeling, is a proven predictor of poor outcomes. Cardiac magnetic resonance (CMR) is a proven and safe imaging modality for non-invasive assessment of myocardial fibrosis. Particularly, cardiac T1 mapping has been widely used for assessment of diffuse myocardial fibrosis. However, current cardiac T1 mapping techniques are unlikely to produce accurate results in LVAD candidates due to three obstacles: arrhythmia, limited breath-hold capacity, and implantable defibrillators. In response, this dissertation describes the development of new cardiac T1 mapping methods that overcome these obstacles. To overcome arrhythmia and limited breath-hold capacity, we developed a new arrhythmia-insensitive-rapid (AIR) cardiac T1 mapping pulse sequence using a robust saturation radio-frequency (RF) pulse that is inherently insensitive to arrhythmia. We also made the AIR pulse sequence rapid by acquiring only one proton-density and one T1-weighted image within a short breath-hold duration of only 2-3 heartbeats. To overcome the challenge of suppressing image artifacts induced by implantable defibrillators, we developed a new wideband AIR cardiac T1 mapping pulse sequence by incorporating a new saturation RF pulse that extends the frequency bandwidth to off-resonant spins induced by defibrillators. The AIR and wideband AIR pulse sequences are validated extensively through in vitro and in vivo experiments

Robust free-breathing SASHA T1 mapping with high-contrast image registration

Comparison of free-breathing SASHA-VFA images with navigator gating, normal image registration, and high-contrast image registration. (GIF 4289 kb

Extracellular volume quantification in Cardiac CT: a new marker of cardiovascular risk in HIV positive individuals?

Inflammation in response to infection and injury is a critical survival mechanism used by all higher vertebrates. Chronic inflammatory conditions are associated with the prolongerelease of inflammatory mediators and the activation of harmful signal transduction pathways, all of which contribute disease development and phenotypes. Extracellular Volume Fraction (ECV) may be able to detect subtle abnormalities such as diffuse inflammation acute or chronic due to infection and/or fibrosis. The validity of this technique was preliminarily evaluated in a study with 20 patients suspected to have diffuse inflammation in the myocardial tissue. Using HU (Hounsfield Unit) values before and after administration of an Extracellular Contrast Agent (ECA) allows the additional calculation of the ECV, well established in CT. In fact, the ratio of the change in blood and tissue attenuation (HU) represents the contrast agent partition coefficient. People living with HIV (PLWH) have an increase vulnerability to sub-clinical and clinical cardiovascular (CV) diseases. Purpose: PLWH are prone to develop sub-clinical Cardiovascular (sCV) disease, despite the effectiveness of combined AntiRetroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial ECV by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach. In this study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV+ individuals (45 males, median age 48 (IQR:42.5-48) years) on effective cART (CD4+ cell count: 450 cells/μL (IQR: 328-750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, median age 55 (IQR:44.5-56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly. The ECV was significantly higher in HIV+ patients than in the control group (ECV: 31% (IQR: 28%-31%) vs 27.4% (IQR: 25%-28%), p<0.001). The duration of cART (standardized=0.56 (0.33-0.95), p=0.014) and the years of exposure to HIV infection [standardized=0.53 (0.4-0.92), p<0.001], were positively and strongly associated with ECV values. Differences in ECV (p<0.001) were also observed regarding the duration of exposure to cART (<5 years, 5-10 years and >10 years). Moreover, ECV was independently associated with age of participants [standardized = 0.42 (0.33-0.89), p=0.084]. We hypothesized that quantitative assessment of tissue ECV would be clinically useful for detecting both focal and diffuse tissue abnormalities in a variety of acute and chronic infectious conditions. ECV imaging can quantitatively characterize tissue inflammation, atypical diffuse fibrosis, and subtle tissue abnormalities not clinically apparent on different method images. Therefore, ECV not only can detect tissue inflammation and/or fibrosis but also might quantify response to treatment during follow-up. HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH

Doctor of Philosophy

dissertationMedical imaging has evolved in leaps and bounds during the last century. Several medical imaging modalities such as X-rays, single photon emission computer tomography (SPECT), positron emission tomography (PET), computer tomography (CT), magnetic resonance imaging (MRI) have been developed. However, MRI has a distinct advantage over most of these imaging techniques. MRI does not use ionizing radiation, and hence, is considered a safer option for noninvasive imaging. However, every imaging modality comes with its set of limitations and challenges. Although quantitative myocardial perfusion MRI has been studied by researchers over a few decades, it has still not developed into a clinical tool. There is no consensus on the choice of imaging protocol to be used. The scientific community is still divided on the choice of pharmacokinetic model to be used for quantification of myocardial perfusion. In this dissertation, novel techniques were developed and implemented to address a few of the challenges faced by fully quantitative myocardial perfusion MRI. We strive to make it simpler and more accurate. It is with the development of such easy-to-use techniques that cardiac perfusion MRI will find increasing clinical use. These developments are a step in the transition of quantitative myocardial perfusion MRI from an "evolving tool" to an "evolved and matured tool.

Fast myocardial T(1) mapping using cardiac motion correction

PURPOSE: To improve the efficiency of native and postcontrast high-resolution cardiac T(1) mapping by utilizing cardiac motion correction. METHODS: Common cardiac T(1) mapping techniques only acquire data in a small part of the cardiac cycle, leading to inefficient data sampling. Here, we present an approach in which 80% of each cardiac cycle is used for T(1) mapping by integration of cardiac motion correction. Golden angle radial data was acquired continuously for 8 s with in-plane resolution of 1.3 × 1.3 mm(2). Cine images were reconstructed for nonrigid cardiac motion estimation. Images at different TIs were reconstructed from the same data, and motion correction was performed prior to T(1) mapping. Native T(1) mapping was evaluated in healthy subjects. Furthermore, the technique was applied for postcontrast T(1) mapping in 5 patients with suspected fibrosis. RESULTS: Cine images with high contrast were obtained, leading to robust cardiac motion estimation. Motion-corrected T(1) maps showed myocardial T(1) times similar to cardiac-triggered T(1) maps obtained from the same data (1288 ± 49 ms and 1259 ± 55 ms, respectively) but with a 34% improved precision (spatial variation: 57.0 ± 12.5 ms and 94.8 ± 15.4 ms, respectively, P < 0.0001) due to the increased amount of data. In postcontrast T(1) maps, focal fibrosis could be confirmed with late contrast-enhancement images. CONCLUSION: The proposed approach provides high-resolution T(1) maps within 8 s. Data acquisition efficiency for T(1) mapping was improved by a factor of 5 by integration of cardiac motion correction, resulting in precise T(1) maps

T1 mapping in cardiac MRI

Quantitative myocardial and blood T1 have recently achieved clinical utility in numerous pathologies, as they provide non-invasive tissue characterization with the potential to replace invasive biopsy. Native T1 time (no contrast agent), changes with myocardial extracellular water (edema, focal or diffuse fibrosis), fat, iron, and amyloid protein content. After contrast, the extracellular volume fraction (ECV) estimates the size of the extracellular space and identifies interstitial disease. Spatially resolved quantification of these biomarkers (so-called T1 mapping and ECV mapping) are steadily becoming diagnostic and prognostically useful tests for several heart muscle diseases, influencing clinical decision-making with a pending second consensus statement due mid-2017. This review outlines the physics involved in estimating T1 times and summarizes the disease-specific clinical and research impacts of T1 and ECV to date. We conclude by highlighting some of the remaining challenges such as their community-wide delivery, quality control, and standardization for clinical practice

Cardiac magnetic resonance T1 and extracellular volume mapping with motion correction and co-registration based on fast elastic image registration

10.1007/s10334-017-0668-2Magnetic Resonance Materials in Physics, Biology and Medicine311115-12