A novel pulse sequence scheme is presented that allows the measurement and mapping of myocardial T 1 in vivo on a 1.5 Tesla MR system within a single breath-hold. Two major modifications of conventional Look-Locker (LL) imaging are introduced: 1) selective data acquisition, and 2) merging of data from multiple LL experiments into one data set. Each modified LL inversion recovery (MOLLI) study consisted of three successive LL inversion recovery (IR) experiments with different inversion times. We acquired images in late diastole using a single-shot steady-state free-precession (SSFP) technique, combined with sensitivity encoding to achieve a data acquisition window of <200 ms duration. We calculated T 1 using signal intensities from regions of interest and pixel by pixel. T 1 accuracy at different heart rates derived from simulated ECG signals was tested in phantoms. Key words: spin-lattice relaxation time; Look-Locker; heart; myocardium Despite recent technological advances, in vivo T 1 quantification of the myocardium with modern magnetic resonance (MR) systems remains a challenge because of severe time constraints due to cardiac and respiratory motion. While myocardial T 1 is shorter and therefore relatively easier to measure at low field strengths, it has a value of ϳ1000 ms at a field strength of 1.5 T, exceeding the duration of the cardiac cycle (ϳ600 -1200 ms) in most subjects (1,2). Since standard inversion recovery (IR) measurements require a relaxation period of four to five times T 1 to allow for full magnetization recovery after each 180°pulse (3), only four to five such single-point IR experiments can be performed within one breath-hold (ca. 20 s). To achieve accurate T 1 estimates from a three-parameter curve-fitting procedure, as is commonly employed, data from at least six to 10 time points should be available (4). The multipoint approach, as first described by Look and Locker (5), samples the relaxation curve multiple times after an initial preparation pulse (6). This technique has been shown theoretically to be highly efficient (7), and has been widely used for T 1 measurements of the brain (8 -11). It is not suitable for pixel-by-pixel T 1 mapping of the heart because data acquisition is performed continuously throughout the cardiac cycle without regard for cardiac motion, which means that T 1 values can only be derived for regions of interest (ROIs) that must be defined manually for every frame (1). The resultant T 1 values may consequently be subject to inaccuracy caused by misregistration effects.In this work we present a pulse sequence scheme that allows for accurate in vivo T 1 measurements and T 1 mapping of myocardium with high spatial resolution and within a single breath-hold. To overcome the limitations of the conventional LL approach for cardiac applications, we propose a modified LL IR scheme (MOLLI), which introduces two principles to the standard LL sequence: 1) selective data acquisition at a given time of the cardiac cycle over successive heartbeats, and (2) merging of image sets...

BackgroundT1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting.MethodsHealthy subjects (n = 102; mean age 41 years (range 17–83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, λ and extracellular volume fraction (ECV) in a core lab using standardized postprocessing.ResultsIn healthy controls, mean native T1 values were 950 ± 21 msec at 1.5 T and 1052 ± 23 at 3 T. λ and ECV values were 0.44 ± 0.06 and 0.25 ± 0.04 at 1.5 T, and 0.44 ± 0.07 and 0.26 ± 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. λ and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1.ConclusionWe show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-014-0069-x) contains supplementary material, which is available to authorized users.

A prospective study approved by the local ethics committee was performed to establish the normal range and reproducibility of myocardial T1 values as assessed with single-breath-hold T1 mapping with high spatial resolution. With a 1.5-T magnetic resonance (MR) imaging system, baseline and contrast material-enhanced modified Look-Locker inversion recovery, or MOLLI, imaging was performed in 15 healthy volunteers who had given written informed consent. Image quality scores and myocardial T1 values were derived for standard short-axis segments and sections. Results were compared with those from a second MR imaging study performed on the same day (baseline only) and those from a third study performed on a different day (baseline and contrast enhanced; eight volunteers). Intra- and interobserver agreement were determined. Myocardial T1 maps were obtained rapidly in a reproducible fashion. A normal range for baseline and postcontrast myocardial T1 was established (baseline mean T1 in short-axis sections, 980 msec +/- 53 [standard deviation]; 95% confidence interval: 964, 997; number of sections, 43). This technique could enable direct quantification of changes in tissue characteristics in ischemic and inflammatory myocardial diseases.

This study demonstrates significant decreases in vitamin D status over the duration of the patient's ICU stay. Low levels of vitamin D are associated with longer time to ICU discharge alive and a trend toward increased risk of ICU-acquired infection.

The new diagnostic algorithm using native T1 can reliably discriminate between health and disease and determine the clinical disease stage in patients with a clinical diagnosis of myocarditis.

The implantation of synthetic biomaterials initiates the foreign body response (FBR), which is characterized by macrophage infiltration, foreign body giant cell formation, and fibrotic encapsulation of the implant. The FBR is orchestrated by a complex network of immune modulators, including diverse cell types, soluble mediators, and unique cell surface interactions. The specific tissue locations, expression patterns, and spatial distribution of these immune modulators around the site of implantation are not clear. This study describes a model for studying the FBR in vivo and specifically evaluates the spatial relationship of immune modulators. We modified a biomaterials implantation in vivo model that allowed for cross-sectional in situ analysis of the FBR. Immunohistochemical techniques were used to determine the localization of soluble mediators, ie, interleukin (IL)-4, IL-13, IL-10, IL-6, transforming growth factor-beta, tumor necrosis factor-alpha, interferon-gamma, and MCP-1; specific cell types, ie, macrophages, neutrophils, fibroblasts, and lymphocytes; and cell surface markers, ie, F4/80, CD11b, CD11c, and Ly-6C, at early, middle, and late stages of the FBR in subcutaneous implant sites. The cytokines IL-4, IL-13, IL-10, and transforming growth factor-beta were localized to implant-adherent cells that included macrophages and foreign body giant cells. A better understanding of the FBR in vivo will allow the development of novel strategies to enhance biomaterial implant design to achieve better performance and safety of biomedical devices at the site of implant.

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Alveolar macrophages and BDMCs undergo sequential biochemical changes during the chronic inflammatory response to chemically induced lung carcinogenesis in mice. Herein, we examine two chronic lung inflammation models-repeated exposure to BHT and infection with Mycobacterium tuberculosis-to establish whether similar macrophage phenotype changes occur in non-neoplastic pulmonary disease. Exposure to BHT or M. tuberculosis results in pulmonary inflammation characterized by an influx of macrophages, followed by systemic effects on the BM and other organs. In both models, pulmonary IFN-gamma and IL-4 production coincided with altered polarization of alveolar macrophages. Soon after BHT administration or M. tuberculosis infection, IFN-gamma content in BALF increased, and BAL macrophages became classically (M1) polarized, as characterized by increased expression of iNOS. As inflammation progressed in both models, the amount of BALF IFN-gamma content and BAL macrophage iNOS expression decreased, and BALF IL-4 content and macrophage arginase I expression rose, indicating alternative/M2 polarization. Macrophages present in M. tuberculosis-induced granulomas remained M1-polarized, implying that these two pulmonary macrophage populations, alveolar and granuloma-associated, are exposed to different activating cytokines. BDMCs from BHT-treated mice displayed polarization profiles similar to alveolar macrophages, but BDMCs in M. tuberculosis-infected mice did not become polarized. Thus, only alveolar macrophages in these two models of chronic lung disease exhibit a similar progression of polarization changes; polarization of BDMCs was specific to BHT-induced pulmonary inflammation, and polarization of granuloma macrophages was specific to the M. tuberculosis infection.