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G-EXJ-1030713 May 2012 CARDIAC MRI Diagnostic Backgrounder NOTE: These slides are for use in educational oral presentations only. If any published figures/tables.

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Presentation on theme: "G-EXJ-1030713 May 2012 CARDIAC MRI Diagnostic Backgrounder NOTE: These slides are for use in educational oral presentations only. If any published figures/tables."— Presentation transcript:

1 G-EXJ May 2012 CARDIAC MRI Diagnostic Backgrounder NOTE: These slides are for use in educational oral presentations only. If any published figures/tables from these slides are to be used for another purpose (e.g. in printed materials), it is the individual’s responsibility to apply for the relevant permission. Specific local use requires local approval

2 2 G-EXJ May 2012 Outline ● Introduction to iron overload ● Assessing cardiac iron loading –echocardiography –cardiac MRI ● Cardiac MRI in practice –preparation of the patient –acquisition of the image –analysis of the data Excel spreadsheet ThalassaemiaTools (CMRtools) cmr4 2 FerriScan MRmap MATLAB ● Summary MRI = magnetic resonance imaging.

3 G-EXJ May 2012 Introduction to iron overload

4 4 G-EXJ May 2012 Introduction to iron overload ● Iron overload is common in patients who require intermittent or regular blood transfusions to treat anaemia and associated conditions –it may be exacerbated in some conditions by excess gastrointestinal absorption of iron ● Iron overload can lead to considerable morbidity and mortality 1 ● Excess iron is deposited in major organs, resulting in organ damage –the organs that are at risk of damage due to iron overload include the liver, heart, pancreas, thyroid, pituitary gland, and other endocrine organs 2,3 1 Ladis V, et al. Ann NY Acad Sci. 2005;1054: Gabutti V, Piga A. Acta Haematol. 1996;95: Olivieri NF. N Engl J Med. 1999;341:

5 5 G-EXJ May 2012 Importance of analysing cardiac iron ● In β-thalassaemia major, cardiac failure and arrhythmia are risk factors for mortality 1 –signs of myocardial damage due to iron overload: arrhythmia, cardiomegaly, heart failure, and pericarditis 2 –heart failure has been a major cause of death in β-thalassaemia patients in the past (50–70%) 1,3 ● In MDS, the results of studies are less comprehensible –the reported proportion of MDS patients with cardiac iron overload is inconsistent; from high to only a small proportion of MDS patients 4–7 –cardiac iron overload occurs later than does liver iron overload 4,7,8 –however, cardiac iron overload can have serious clinical consequences in MDS patients 1 Borgna-Pignatti C, et al. Haematologica. 2004;89: Gabutti V, Piga A. Acta Haematol. 1996;95: Modell B, et al. Lancet. 2000;355: Jensen PD, et al. Blood. 2003;101: Chacko J, et al. Br J Haematol. 2007;138: Konen E, et al. Am J Hematol. 2007;82: Di Tucci AA, et al. Haematologica. 2008;93: Buja LM, Roberts WC. Am J Med. 1971;51:

6 6 G-EXJ May 2012 Baseline Latest follow-up p < cT2* ≤ 20 ms cT2* < 10 ms Patients (%) cT2* = cardiac T2*. 1 Thomas AS, et al. Blood. 2010;116:[abstract 1011]. 2 Modell B, et al. Lancet. 2000;355: Importance of analysing cardiac iron (cont.) ● In 2010, the overall mortality rate of β-thalassaemia major patients in the UK was substantially lower than a decade ago (1.65 vs 4.3 per 1,000 patient years) 1,2 –due to improved monitoring and management of iron overload over the last decade, 77% of patients have normal cardiac T2* 1 –cardiac iron overload is no longer the leading cause of death in this population

7 7 G-EXJ May 2012 Cardiac T2*: Overview of correlations with other measurements 1 Wood JC, et al. Blood. 2004;103: Anderson LJ, et al. Eur Heart J. 2001;22: Tanner MA, et al. J Cardiovasc Magn Reson. 2006;8: Kirk P, et al. Circulation. 2009;120: Westwood MA, et al. J Magn Reson Imaging. 2005;22: † For thalassaemia, but not sickle cell. APFR = atrial peak filling rate; EPFR = early peak filling rate; LIC = liver iron concentration; SF = serum ferritin. Weak or no correlation Transfusion duration † ↑ 1 Ventricular dysfunction ↑ 1-3 Arrhythmia and heart failure ↑ 4 APFR↓ EPFR:APFR↑ 5 Need for cardiac medication↑ 1-2 T2*↓ SF and LIC 1-3

8 8 G-EXJ May 2012 LVEF (%) Cardiac T2* (ms) Cardiac T2* value of 37 ms in a normal heart Cardiac T2* value of 4 ms in a significantly iron-overloaded heart LVEF = left-ventricular ejection fraction. Anderson LJ, et al. Eur Heart J. 2001;22: Normal T2* range Normal LVEF range Cardiac T2*: Relationship with LVEF Myocardial T2* values < 20 ms are associated with a progressive and significant decline in LVEF

9 9 G-EXJ May Cardiac T2*: Relationship with cardiac failure and arrhythmia Kirk P, et al. Circulation. 2009;120: T2* < 10 ms: relative risk 159 (p < 0.001) T2* < 6 ms: relative risk 268 (p < 0.001) Cardiac failure Proportion of patients developing cardiac failure Follow-up time (days) < 6 ms 6–8 ms 8–10 ms > 10 ms Arrhythmia < 10 ms 10–20 ms > 20 ms T2* < 20 ms: relative risk 4.6 (p < 0.001) T2* < 6 ms: relative risk 8.65 (p < 0.001) Follow-up time (days) Proportion of patients with arrhythmia Low myocardial T2* predicts a high risk of developing cardiac failure and arrhythmia

10 G-EXJ May 2012 Assessing cardiac iron overload

11 11 G-EXJ May 2012 Assessing cardiac iron loading: Agenda ● Echocardiography ● Cardiac MRI –advantages and disadvantages of cardiac MRI –MRI: a non-invasive diagnostic tool –T2* is the standard method for analysing cardiac iron

12 G-EXJ May 2012 Echocardiography

13 13 G-EXJ May 2012 Assessing cardiac iron loading: Echocardiography EF = ejection fraction. 1 Leonardi B, et al. JACC Cardiovasc Imaging. 2008;1: Hoffbrand AV. Eur Heart J. 2001;22: ProsCons Readily available 1 Relatively inexpensive 1 Does not detect early damage 2 Echocardiographic diastolic function parameters correlate poorly with LVEF and T2* 1 Cannot directly or indirectly quantify cardiac iron levels

14 G-EXJ May 2012 Cardiac MRI

15 15 G-EXJ May 2012 MRI: A non-invasive diagnostic tool ● Indirectly measures levels of iron in the heart ● MRI measures longitudinal (T1) and transverse (T2) relaxation times of the protons –iron deposition disrupts the homogeneous magnetic field and shortens T1 and T2 times in a concentration-dependent manner RF = radio-frequency. 1 Wood JC, Ghugre N. Hemoglobin. 2008;32: Wood JC, et al. Circulation. 2005;112: Wang ZJ, et al. Radiology. 2005;234: Ghugre NR, et al. Magn Reson Med. 2006;56: Protons Magnetic field RF/spin echo/gradient echo Echo signal → T1, T2 Signal processing Iron

16 16 G-EXJ May 2012 MRI: A non-invasive diagnostic tool (cont.) ● If a spin-echo sequence is used, the relaxation time is T2 ● If a gradient-echo sequence is used, it is T2* ● Cardiac MRI methods –gradient-echo T2* MRI: most used in clinical practice –spin-echo T2 MRI: less useful (motion artefacts common due to characteristics of the heart) TE = echo time. Adapted from Wood JC, Ghugre N. Hemoglobin. 2008;32: Protons Magnetic field Most used in clinical practice: Gradient echo Image acquired at different TEs Excel or software T2* [ms} R2* [Hz]= 1,000/T2* Spin echo Image acquired at different TEs Excel or software T2* [ms} R2* [Hz]= 1,000/T2*

17 17 G-EXJ May 2012 Assessing cardiac iron loading: Cardiac MRI Advantages of MRIDisadvantages of MRI Non- invasive Rapidly assesses iron content in the septum of the heart Relative iron burden can be reproducibly estimated Functional parameters can be examined concurrently (e.g. LVEF) Iron status of liver and heart can be assessed in parallel Allows longitudinal follow-up Good correlation with morbidity and mortality outcomes Indirect measurement of cardiac iron Requires MRI imager with dedicated imaging method Relatively expensive and varied availability

18 18 G-EXJ May 2012 What are sequences? Sequences are a set of radio-frequency and gradient pulses (slight tilts in the magnetization curves of the scanner) generated repeatedly during the scan, which produce echoes with varied amplitudes and shapes that will define the MR image What is gradient echo? A gradient-echo sequence is obtained after 2 gradient impulses are applied to the body, resulting in a signal echo that is read by the coils. In these sequences, the spins are not refocused and, therefore, are subject to local inhomogeneities, with a more rapid decay curve. For gradient-echo pulse sequences, the T2* relaxation times (which reflect these inhomogeneities) on the signal are more significant 1 Image from Ridgway JP. J Cardiovasc Magn Reson. 2010;12:71. FAQ: Cardiac MRI

19 19 G-EXJ May 2012 Gradient relaxometry (T2*, R2*) is the method for analysing cardiac iron levels 1 Guo H, et al. J Magn Reson Imaging. 2009;30: Anderson LJ, et al. Eur Heart J. 2001;22: Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202: Wood JC, Ghugre N. Hemoglobin. 2008;32: Westwood M, et al. J Magn Reson Imaging. 2003;18: Hoffbrand AV. Eur Heart J. 2001;22: He T, et al. Magn Reson Med. 2008;60: T2* (gradient echo)T2 (spin echo) ProsGreater sensitivity to iron deposition 2 Shorter acquisition time 1 Less affected by motion artefacts 3 More readily available 3 Easier to perform 4 Good reproducibility 5 Less affected by susceptibility artefacts 1, due to metal implants, air–tissue interfaces, proximity to cardiac veins ConsMore sensitive to static magnetic field inhomogeneity 1 Noise, motion, and blood artefacts can complicate analysis (particularly in heavily iron-loaded hearts) 7 Lack of sensitivity 6 Motion artefacts 6 Poor signal-to-background noise ratios at longer TEs 6 Longer acquisition time 1

20 20 G-EXJ May 2012 HIC = hepatic iron concentration Carpenter JP, et al. J Cardiovasc Magn Reson. 2009;11 Suppl 1:P224. Hankins et al Blood. 2009;113: Liver R2* (Hz) HIC (mg Fe/g of dry weight liver) Hankins, et al. Wood, et al. Anderson, et al. [Fe] (mg/g dry wt) Cardiac R2* (Hz) R 2 = Liver MRI Cardiac MRI Gradient relaxometry (T2*, R2*) can conveniently measure cardiac and liver iron Cardiac and liver iron can be assessed together conveniently by gradient echo during the a single MRI measurement.

21 21 G-EXJ May 2012 Cardiac T2* MRI is usually measured in the septum of the heart Heart with normal iron levels Heart with severe iron overload Images courtesy of Dr J. de Lara Fernandes. T2* = 22.8 ms or R2* = 43.9 Hz T2* = 5.2 ms or R2* = 192 Hz

22 22 G-EXJ May 2012 Conversion from T2* to R2* is a simple mathematical calculation: R2* = 1,000/T2* Level of cardiac iron overloadT2*, msR2*, Hz Normal  20 1 < 50 Mild, moderate10– –100 Severe< 10 2 > Anderson LJ, et al. Eur Heart J. 2001;22: Kirk P, et al. Circulation. 2009;120: These values are only applicable to 1.5 T scanners 1 What is R2*?

23 23 G-EXJ May 2012 Why should the data be presented as R2* and not T2*? ● Seven whole hearts from patients with transfusion-dependent anaemias were assessed by histology and cardiac MRI [Fe] (mg/g dry wt) Cardiac T2* (ms) [Fe] (mg/g dry wt) R 2 = Cardiac R2* (Hz) R 2 = Carpenter JP, et al. J Cardiovasc Magn Reson. 2009;11 Suppl 1:P224. R2* has a linear relationship with tissue iron concentration, which simplifies the interpretation of data and allows comparison of changes over time

24 24 G-EXJ May 2012 Anderson LJ, et al. Eur Heart J. 2001;22: Hockey stick effect?Or a more gradual relationship? The relationship between cardiac T2*/R2* and LVEF Heart T2* (ms) LVEF (%) R2* (s –1 ) LVEF (%) Why should the data be presented as R2* and not T2*? (cont.) R2* allows demonstration of cardiac risk in a more gradual way

25 25 G-EXJ May 2012 Transform to R2* Standard errors on a single measurement are approximately constant with R2*, but are non-uniform with T2* Westwood M, et al. J Magn Reson Imaging. 2003;18: T2* second measurement (ms) T2* first measurement (ms) R2* second measurement (s –1 ) R2* first measurement (s –1 ) Why should the data be presented as R2* and not T2*? (cont.) R2* has a constant standard error that makes assessment of the significance of changes easier

26 G-EXJ May 2012 Cardiac T2* MRI in practice

27 27 G-EXJ May 2012 MRI scanners ● Manufacturers –Siemens Healthcare (Erlangen, Germany; –GE Healthcare (Milwaukee, WI, USA; –Philips Healthcare (Best, the Netherlands; ● Magnetic field –T2* varies with magnetic field strength 1 –need 1.5 T for cutoff levels of 20 ms (iron overload) and 10 ms (severe iron overload) 1,2 ● Cardiac package –needs to be acquired separately from the manufacturers. The cost is about USD 40,000. However, in most centres, this is available since MRI is frequently used in non-iron-related cardiovascular imaging –includes all necessary for acquisition of the image –sequences are included in Siemens and Philips Healthcare cardiac packages, but for GE Healthcare they need to be acquired separately (note: variations may exist between countries) 1 Anderson LJ, et al. Eur Heart J. 2001;22: Kirk P, et al. Circulation. 2009;120:

28 28 G-EXJ May 2012 Cardiac T2* MRI in practice: The process T2*, R2* *Time to manually calculate T2*/R2* values in an Excel spreadsheet depends on the experience of the physician. 1. Patient preparation (5 min) 2. Acquisition of the MRI image (approx min) 3. Analysis of MRI data (time depends on experience*)

29 29 G-EXJ May 2012 Cardiac T2* MRI in practice: The process (cont.) ● Preparation of the patient ● Acquisition of the image ● Analysis of the data (post-processing) Excel spreadsheet ThalassaemiaTools, CMRtools cmr 42 FerriScan MRmap MATLAB

30 G-EXJ May 2012 Preparation of the patient

31 31 G-EXJ May 2012 Preparation of the patient ● Standard precautions need to be taken ● There is no need for peripheral vein access since no contrast agent is required ● Special care –remove all infusion/medication pumps (e.g. with insulin, pain-relieving drugs) –stop continuous i.v. application of ICT during the measurement –ECG signal should be positioned according to scanner specifications ECG = electrocardiography.

32 32 G-EXJ May 2012 Cardiac T2* MRI in practice: The process (cont.) ● Preparation of the patient ● Acquisition of the image ● Analysis of the data (post-processing) Excel spreadsheet ThalassaemiaTools, CMRtools cmr 42 FerriScan MRmap MATLAB

33 G-EXJ May 2012 Acquisition of the image

34 34 G-EXJ May 2012 Acquisition of the image: MRI pulse sequences ● Pulse sequences –are a preselected set of defined radio-frequency and gradient pulses –are computer programs that control all hardware aspects of the scan –determine the order, spacing, and type of radio-frequency pulses that produce magnetic resonance images according to changes in the gradients of the magnetic field ● Several different pulse sequences exist 1 –a gradient-echo sequence generates T2* 1 Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96.

35 35 G-EXJ May Anderson LJ, et al. Eur Heart J. 2001;22: Westwood M, et al. J Magn Reson Imaging. 2003;18: He T, et al. J Magn Reson Imaging. 2007;25: He T, et al. Magn Reson Med. 2008;60: Pepe A, et al. J Magn Reson Imaging. 2006;23: SequenceGroup Number of echoes per breath-hold Heart regions Pre- pulse RR intervals TR Bright blood (Anderson et al.) 1 London (Pennell) 1 (but multiple breath-holds) 1 (septum)No1Variable Novel bright blood (Westwood et al) 2 London (Pennell) Multiple1 (septum)No1Fixed Black blood (He et al) 3-4 London (Pennell) Multiple1 (septum)Yes2Fixed Multi-slice (Pepe et al) 5 Pisa (Pepe) Multiple Multi- region No1Fixed The most common commercially available T2* acquisition techniques The various techniques give clinically comparable results. 2-3, 5

36 36 G-EXJ May 2012 Acquisition of the image: TEs ● Images are taken at a minimum of 5 different TEs, normally 8 ‒ 12 1 ● The choice of minimum TE determines the smallest measurable T2 1 ideally, min TE  2 ms, max TE 17 ‒ 20 ms ● Different T2* acquisition techniques according to TE multiple breath-hold: acquire an image for each TE in separate breath-holds 2 single breath-hold multi-echo acquisition: acquire images for all TE during 1 breath-hold 3 Mean R2* compared with true value in the case of synthetic images for different minimum TEs, but same echo duration (18 ms) 4 1 Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202: Anderson LJ, et al. Eur Heart J. 2001;22: Westwood M, et al. J Magn Reson Imaging. 2003;18: Ghugre NR, et al. J Magn Reson Imaging. 2006;23: True R2* (Hz) Mean R2*: ramp, dualtone, & uniform (Hz) Shortest TE = 2 ms Shortest TE = 1 ms Shortest TE = 4 ms Shortest TE = 5.5 ms True

37 37 G-EXJ May 2012 How does the MRI data output looks like? Data visualizationMRI data output 1 Wood JC, Ghugre N. Hemoglobin. 2008;32: During a single breath hold the pulse sequence run several times at increasing echo time (TE), generating data points corresponding to decreased signal intensity 1 FrameTE (ms)Mean ST

38 38 G-EXJ May 2012 Which is recommended: single or multiple breath-hold technique? Comparison of the 2 methods, single and multiple breath-hold, showed no significant skewing between T2* values in all patients with  -thalassaemia major, regardless of their T2* value (see Bland- Altman plots) 1 However, in cardiac MRI the most recommended technique is single breath-hold, because it allows quick acquisition of the information. This is especially important to avoid movement artefacts (heart beating, breathing) and assure the good quality of the MRI image 1 Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9. Patients with T2* < 20 ms 1 Patients with T2*  20 ms 1 FAQ: Acquisition technique

39 39 G-EXJ May 2012 Acquisition of the image ● Single breath-hold multi-echo acquisition –take a short-axis slice of the ventricle (halfway between the base and the apex): orange line –image acquisition should occur immediately after the R wave –do not alter any settings that could alter TE (e.g. FOV) Image courtesy of Dr J. de Lara Fernandes.

40 40 G-EXJ May 2012 Cardiac T2* MRI in practice: The process (cont.) ● Preparation of the patient ● Acquisition of the image ● Analysis of the data (post-processing) Excel spreadsheet ThalassaemiaTools, CMRtools cmr 42 FerriScan MRmap MATLAB

41 G-EXJ May 2012 Analysis of the data (post-processing)

42 42 G-EXJ May 2012 How T2* is calculated from the MRI output? Data visualization 1 Wood JC, Ghugre N. Hemoglobin. 2008;32: Curve Fitting T2* Noise level T2* calculation is fitting a curve on the data points and calculating at what echo time no signal is left from iron (only noise) 1

43 43 G-EXJ May 2012 Analysis of the data ● The data can be analysed manually or using post-processing software ManuallyPost-processing software Excel spreadsheet ThalassaemiaTools (CMRtools) cmr 42 FerriScan MRmap MATLAB

44 44 G-EXJ May 2012 Analysis of the data (cont.) MethodProsCons Excel spreadsheetLow costTime-consuming Tedious ThalassaemiaTools (CMRtools) 1 Fast (1 min) 2 Easy to use FDA approved GBP 3,000 per year cmr 42(3) Easy to use FDA approved 3 Can generate T2*/R2* and T2/R2 maps with same software Allows different forms of analysis Generates pixel-wise fitting with colour maps 40,000 USD first year costs 12,000 USD per year after FDA = Food and Drug Administration. 1 Accessed Dec Pennell DJ. JACC Cardiovasc Imaging. 2008;1: Accessed Dec 2010.

45 45 G-EXJ May 2012 MethodProsCons FerriScan 1 Centralized analysis of locally acquired data (206 active sites across 25 countries) Easy set-up on most MRI machines EU approved Validated on GE, Philips, and Siemens scanners USD 100 per scan Patients data are sent to reference centre MRmap 2 Uses IDL runtime, which is a commercial software (less expensive than cmr 42 /CMRtools) Can quantify T1 and T2 map with the same software Purely a research tool Not intended for diagnostic or clinical use MATLAB 3 Low costAvailable only locally Physicists or engineers need to write a MATLAB program for display and T2* measurement 1 Accessed Dec mrmapengl/index.html. Accessed Dec Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202: Analysis of the data (cont.)

46 46 G-EXJ May 2012 What are the most common mistakes in analysing the data that could lead to a wrong interpretation of the T2* value? Interpreting the data from cardiac MRI is usually quite straightforward; problems may arise when analysing data from patients with severe cardiac iron overload. In this case, the signal from heavily iron-loaded muscle will decay quickly and a single exponential decay curve does not fit the data well. 1 Models exist that can help to solve this issue (see next slide): 1. the offset model (Prof Wood and colleagues) 2. truncation of the data (Prof Pennell and colleagues) Both models should give comparable results; the differences should not be clinically relevant 1 Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202: Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16. Signal decay curve from a patient with T2* ≈ 5 ms, showing that the data do not fit well 2 FAQ: Mistakes in analysing the data

47 47 G-EXJ May 2012 What is truncation? After the selection of the ROI, the signal decay can be fitted using different models. In the truncation model, the late points in the curve that form a plateau are subjectively discarded; the objective is to have a curve with an R 2 > A new single exponential curve is made by fitting the remaining signals. 1 Generally, a truncation model should be used with the bright-blood technique to obtain more reproducible and more accurate T2* measurements 1 What is an offset model? The offset model consists of a single exponential with a constant offset. Using only the exponential model can underestimate the real T2* values (at quick signal loss at short TE, there is a plateau), while inclusion of the offset model into the fitting equation can improve this. 2 Generally, the offset model is recommended to be used with the black-blood technique 1 He T, et al. Magn Reson Med. 2008;60: Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16. FAQ: Mistakes in analysing the data (cont.)

48 48 G-EXJ May 2012 How to start measuring cardiac iron loading in a hospital? What steps need to be taken? To start assessing cardiac iron loading by MRI, these steps can be followed: 1.Check MRI machine requirements 1.5 T calibrated 2.Buy cardiac package from the manufacturer. It must include all that is necessary for acquisition of the data (the sequences are included with Siemens and Philips Healthcare cardiac packages, but for GE Healthcare they need to be acquired separately) 3.Optional: buy software for analysing the data (if not, Excel spreadsheet can be used) 4.Highly recommended: training of personnel for acquisition of cardiac MR images (e.g. functional analyses) 5.Highly recommended: training of personnel on how to analyse the data with the chosen software FAQ: How to start measuring cardiac iron loading?

49 49 G-EXJ May 2012 Implementation of liver and cardiac MRI 1.5T MRI Scanner Experienced radiologist Cardiac acquisition package Routine cardiac MR exams Post-processing analysis US$ US$ US$ or US$4.000/y or in-house or outsource Yes No ½ day training 1 day training Yes No 1-2 day training 4 day training Liver Analysis Liver Analysis Heart Analysis Heart Analysis Slide presented at Global Iron Summit With the permission of Juliano de Lara Fernandes

50 G-EXJ May 2012 Summary

51 51 G-EXJ May 2012 Summary ● Iron overload is common in patients who require intermittent or regular blood transfusions to treat anaemia and associated conditions ● Analysing cardiac iron levels is important –in β-thalassaemia major, cardiac failure and arrhythmia are risk factors for mortality –in MDS, cardiac iron overload can have serious clinical consequences –due to improved monitoring and management of iron overload over the last decade, 77% of patients have normal cardiac T2* 1 ● MRI: the method to rapidly and effectively assess cardiac iron loading –T2* allows specific assessment of cardiac iron levels. The use of this convenient, non-invasive procedure has had a significant impact on outcomes in patients with cardiac iron overload 1 –R2* is a simple calculation from T2* and has a linear relationship with cardiac iron concentration 1 Thomas AS, et al. Blood. 2010;116:[abstract 1011]. 2 Modell B, et al. J Cardiovasc Magn Reson. 2008;10:42-9.

52 G-EXJ May 2012 GLOSSARY OF TERMS

53 53 G-EXJ May 2012 GLOSSARY ● AML = acute myeloid leukemia ● APFR = Atrialp peak filling rate ● BA = basilar artery ● ß-TM = Beta Thalassemia Major ● ß-TI = Beta Thalassemia Intermedia ● BM = bone marrow ● BTM = bone marrow transplantation ● BW = bandwidth ● CFU = colony-forming unit ● CMML = chronic myelomonocytic leukemia ● CT2 = cardiac T2*. ● DAPI = 4',6-diamidino-2-phenylindole

54 54 G-EXJ May 2012 GLOSSARY ● DFS = = disease-free survival. ● DysE = dyserythropoiesis ● ECG = electrocardiography ● EDV = end-diastolic velocity ● EF = ejection fraction ● EPFR = early peak filling rate ● FatSat = fat saturation ● FAQ = frequently asked questions ● FDA = Food and Drug Administration ● FISH = fluorescence in situ hybridization. ● FOV = field of view ● GBP = Currency, pound sterling (£)

55 55 G-EXJ May 2012 GLOSSARY ● Hb = hemoglobin ● HbE = hemoglobin E ● HbF = fetal hemoglobin ● HbS = sickle cell hemoglobin. ● HbSS = sickle cell anemia. ● HIC = hepatic iron concentration ● HU = hydroxyurea ● ICA = internal carotid artery. ● ICT = iron chelation therapy ● IDL = interface description language ● IPSS = International Prognostic Scoring System ● iso = isochromosome

56 56 G-EXJ May 2012 GLOSSARY ● LIC = liver iron concentration ● LVEF = left-ventricular ejection fraction ● MCA = middle cerebral artery ● MDS = Myelodysplastic syndromes ● MDS-U = myelodysplastic syndrome, unclassified ● MRA = magnetic resonance angiography ● MRI = magnetic resonance imaging ● MV = mean velocity. ● N = neutropenia ● NEX = number of excitations ● NIH = National Institute of Health ● OS = overall survival

57 57 G-EXJ May 2012 GLOSSARY ● pB = peripheral blood ● PI = pulsatility index ● PSV = peak systolic Velocity ● RA =refractory anemia ● RAEB = refractory anemia with excess blasts ● RAEB -T = refractory anemia with excess blasts in transformation ● RARS = refractory anemia with ringed sideroblasts ● RBC = red blood cells ● RF = radio-frequency ● RCMD = refractory cytopenia with multilineage dysplasia ● RCMD-RS = refractory cytopenia with multilineage dysplasia with ringed sideroblasts ● RCUD = refractory cytopenia with unilineage dysplasia

58 58 G-EXJ May 2012 GLOSSARY ● RN = refractory neutropenia ● ROI = region of interest ● RT = refractory thrombocytopenia ● SCD = sickle cell disease ● SD = standard deviation ● SI = signal intensity ● SIR = signal intensity ratio ● SF = serum ferritin ● SNP-a = single-nucleotide polymorphism ● SQUID = superconducting quantum interface device. ● STOP = = Stroke Prevention Trial in Sickle Cell Anemia ● STOP II = Optimizing Primary Stroke Prevention in Sickle Cell Anemia

59 59 G-EXJ May 2012 GLOSSARY ● T = thrombocytopenia ● TAMMV = time-averaged mean of the maximum velocity. ● TCCS = transcranial colour-coded sonography ● TCD = transcranial doppler ultrasonography ● TCDI = duplex (imaging TCD) ● TE = echo time ● TR = repetition time ● WHO = World Health Organization ● WPSS = WHO classification-based Prognostic Scoring System


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