Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Panic attacks induced by doxapram

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30965/1/0000638.pd

Helping Business Schools Engage with Real Problems: The Contribution of Critical Realism and Systems Thinking

The world faces major problems, not least climate change and the financial crisis, and business schools have been criticised for their failure to help address these issues and, in the case of the financial meltdown, for being causally implicated in it. In this paper we begin by describing the extent of what has been called the rigour/relevance debate. We then diagnose the nature of the problem in terms of historical, structural and contextual mechanisms that initiated and now sustain an inability of business schools to engage with real-world issues. We then propose a combination of measures, which mutually reinforce each other, that are necessary to break into this vicious circle – critical realism as an underpinning philosophy that supports and embodies the next points; holism and transdisciplinarity; multimethodology (mixed-methods research); and a critical and ethical-committed stance. OR and management science have much to contribute in terms of both powerful analytical methods and problem structuring methods

Comparison of 3 T and 1.5 T for T2* magnetic resonance of tissue iron.

BACKGROUND: T2* magnetic resonance of tissue iron concentration has improved the outcome of transfusion dependant anaemia patients. Clinical evaluation is performed at 1.5 T but scanners operating at 3 T are increasing in numbers. There is a paucity of data on the relative merits of iron quantification at 3 T vs 1.5 T. METHODS: A total of 104 transfusion dependent anaemia patients and 20 normal volunteers were prospectively recruited to undergo cardiac and liver T2* assessment at both 1.5 T and 3 T. Intra-observer, inter-observer and inter-study reproducibility analysis were performed on 20 randomly selected patients for cardiac and liver T2*. RESULTS: Association between heart and liver T2* at 1.5 T and 3 T was non-linear with good fit (R (2) = 0.954, p < 0.001 for heart white-blood (WB) imaging; R (2) = 0.931, p < 0.001 for heart black-blood (BB) imaging; R (2) = 0.993, p < 0.001 for liver imaging). R2* approximately doubled between 1.5 T and 3 T with linear fits for both heart and liver (94, 94 and 105 % respectively). Coefficients of variation for intra- and inter-observer reproducibility, as well as inter-study reproducibility trended to be less good at 3 T (3.5 to 6.5 %) than at 1.5 T (1.4 to 5.7 %) for both heart and liver T2*. Artefact scores for the heart were significantly worse with the 3 T BB sequence (median 4, IQR 2-5) compared with the 1.5 T BB sequence (4 [3-5], p = 0.007). CONCLUSION: Heart and liver T2* and R2* at 3 T show close association with 1.5 T values, but there were more artefacts at 3 T and trends to lower reproducibility causing difficulty in quantifying low T2* values with high tissue iron. Therefore T2* imaging at 1.5 T remains the gold standard for clinical practice. However, in centres where only 3 T is available, equivalent values at 1.5 T may be approximated by halving the 3 T tissue R2* with subsequent conversion to T2*

T1 at 1.5T and 3T compared with conventional T2* at 1.5T for cardiac siderosis

Background: Myocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers. Methods: A total of 73 subjects (42 male) were recruited, comprising 20 healthy volunteers (controls) and 53 patients (thalassemia major 22, sickle cell disease 9, hereditary hemochromatosis 9, other iron overload conditions 13). Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T. Results: In healthy volunteers, median T1 was 1014 ms (full range 939–1059 ms) at 1.5T and modestly increased to 1165ms (full range 1056–1224 ms) at 3T. All patients with significant cardiac iron overload (1.5T T2* values <20 ms) had T1 values <939 ms at 1.5T, and <1056 ms at 3T. Associations between T2* and T1 were found to be moderate with y =377 · x0.282 at 1.5T (R2 = 0.717), and y =406 · x0.294 at 3T (R2 = 0.715). Measures of reproducibility of T1 appeared superior to T2*. Conclusions: T1 mapping at 1.5T and at 3T can identify individuals with significant iron loading as defined by the current gold standard T2* at 1.5T. However, there is significant scatter between results which may reflect measurement error, but it is also possible that T1 interacts with T2*, or is differentially sensitive to aspects of iron chemistry or other biology. Hurdles to clinical implementation of T1 include the lack of calibration against human myocardial iron concentration, no demonstrated relation to cardiac outcomes, and variation in absolute T1 values between scanners, which makes inter-centre comparisons difficult. The relative merits of T1 at 3T versus T2* at 3T require further consideration