CARDIAC MRI Diagnostic Backgrounder G-EXJ-1030713 May 2012 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 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) • cmr42 • FerriScan • MRmap • MATLAB Summary 2 G-EXJ-1030713 May 2012 MRI = magnetic resonance imaging. Introduction to iron overload G-EXJ-1030713 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 mortality1 ● 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 organs2,3 4 G-EXJ-1030713 May 2012 1Ladis V, et al. Ann NY Acad Sci. 2005;1054:445-50. 2Gabutti V, Piga A. Acta Haematol. 1996;95:26-36. NF. N Engl J Med. 1999;341:99-109. 3Olivieri Importance of analysing cardiac iron ● ● In β-thalassaemia major, cardiac failure and arrhythmia are risk factors for mortality1 – signs of myocardial damage due to iron overload: arrhythmia, cardiomegaly, heart failure, and pericarditis2 – 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 patients4–7 – cardiac iron overload occurs later than does liver iron overload4,7,8 – however, cardiac iron overload can have serious clinical consequences in MDS patients 5 G-EXJ-1030713 May 2012 1Borgna-Pignatti C, et al. Haematologica. 2004;89:1187-93. 2Gabutti V, Piga A. Acta Haematol. 1996;95:26-36. 3. Modell B, et al. Lancet. 2000;355:2051-2. 4Jensen PD, et al. Blood. 2003;101:4632-9. 5Chacko J, et al. Br J Haematol. 2007;138:587-93. 6Konen E, et al. Am J Hematol. 2007;82:1013-6. 7Di Tucci AA, et al. Haematologica. 2008;93:1385-8. 8Buja LM, Roberts WC. Am J Med. 1971;51:209-21. 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 population1 70 Patients (%) 60 60 Baseline Latest follow-up 50 40 30 p < 0.001 23 20 17 p < 0.001 10 7 0 6 G-EXJ-1030713 May 2012 cT2* = cardiac T2*. 1Thomas cT2* ≤ 20 ms cT2* < 10 ms AS, et al. Blood. 2010;116:[abstract 1011]. 2Modell B, et al. Lancet. 2000;355:2051-2. Cardiac T2*: Overview of correlations with other measurements Transfusion duration† ↑1 Ventricular dysfunction ↑1-3 Arrhythmia and heart failure ↑4 T2*↓ Need for cardiac medication↑1-2 APFR↓ EPFR:APFR↑5 SF and LIC1-3 Weak or no correlation †For thalassaemia, but not sickle cell. APFR = atrial peak filling rate; EPFR = early peak filling rate; LIC = liver iron concentration; SF = serum ferritin. 7 G-EXJ-1030713 May 2012 1Wood JC, et al. Blood. 2004;103:1934-6. 2Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 3Tanner MA, et al. J Cardiovasc Magn Reson. 2006;8:543-7. 4Kirk P, et al. Circulation. 2009;120:1961-8. 5Westwood MA, et al. J Magn Reson Imaging. 2005;22:229-33. Cardiac T2*: Relationship with LVEF 90 Normal T2* range 80 Normal LVEF range LVEF (%) 70 60 Cardiac T2* value of 37 ms in a normal heart 50 40 30 20 10 0 0 10 20 30 40 50 60 70 80 90 100 Cardiac T2* (ms) Myocardial T2* values < 20 ms are associated with a progressive and significant decline in LVEF 8 G-EXJ-1030713 May 2012 LVEF = left-ventricular ejection fraction. Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. Cardiac T2* value of 4 ms in a significantly iron-overloaded heart Cardiac T2*: Relationship with cardiac failure and arrhythmia Arrhythmia 0.6 < 6 ms 0.5 0.4 6–8 ms 0.3 0.2 8–10 ms 0.1 > 10 ms 0 0 60 120 180 240 300 Follow-up time (days) T2* < 10 ms: relative risk 159 (p < 0.001) T2* < 6 ms: relative risk 268 (p < 0.001) 360 Proportion of patients with arrhythmia Proportion of patients developing cardiac failure Cardiac failure 0.30 0.25 < 10 ms 0.20 0.15 0.10 10–20 ms 0.05 > 20 ms 0 0 60 120 Kirk P, et al. Circulation. 2009;120:1961-8. 240 300 Follow-up time (days) T2* < 20 ms: relative risk 4.6 (p < 0.001) T2* < 6 ms: relative risk 8.65 (p < 0.001) Low myocardial T2* predicts a high risk of developing cardiac failure and arrhythmia 9 G-EXJ-1030713 May 2012 180 360 Assessing cardiac iron overload G-EXJ-1030713 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 11 G-EXJ-1030713 May 2012 Echocardiography G-EXJ-1030713 May 2012 Assessing cardiac iron loading: Echocardiography Pros Cons • Readily available1 • Does not detect early damage2 • Relatively inexpensive1 • Echocardiographic diastolic function parameters correlate poorly with LVEF and T2*1 • Cannot directly or indirectly quantify cardiac iron levels 13 G-EXJ-1030713 May 2012 EF = ejection fraction. 1Leonardi B, et al. JACC Cardiovasc Imaging. 2008;1:572-8. 2Hoffbrand AV. Eur Heart J. 2001;22:2140-1. Cardiac MRI G-EXJ-1030713 May 2012 MRI: A non-invasive diagnostic tool ● Indirectly measures levels of iron in the heart Protons Magnetic field ● 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 15 G-EXJ-1030713 May 2012 RF/spin echo/gradient echo Iron Echo signal → T1, T2 Signal processing RF = radio-frequency. 1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. 2Wood JC, et al. Circulation. 2005;112:535-43. 3Wang ZJ, et al. Radiology. 2005;234:749-55. 4Ghugre NR, et al. Magn Reson Med. 2006;56:681-6. MRI: A non-invasive diagnostic tool (cont.) ● If a spin-echo sequence is used, the relaxation time is T2 Protons Magnetic field ● If a gradient-echo sequence is used, it is T2* Most used in clinical practice: Gradient echo Spin echo Image acquired at different TEs Image acquired at different TEs Excel or software Excel or software T2* [ms} T2* [ms} R2* [Hz]= 1,000/T2* R2* [Hz]= 1,000/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) 16 G-EXJ-1030713 May 2012 TE = echo time. Adapted from Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. Assessing cardiac iron loading: Cardiac MRI Advantages of MRI Disadvantages 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 17 G-EXJ-1030713 May 2012 FAQ: Cardiac MRI 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 18 G-EXJ-1030713 May 2012 1Image from Ridgway JP. J Cardiovasc Magn Reson. 2010;12:71. Gradient relaxometry (T2*, R2*) is the method for analysing cardiac iron levels T2* (gradient echo) T2 (spin echo) Pros • • • • • • Greater sensitivity to iron deposition2 Shorter acquisition time1 Less affected by motion artefacts3 More readily available3 Easier to perform4 Good reproducibility5 • Less affected by susceptibility artefacts1, due to metal implants, air–tissue interfaces, proximity to cardiac veins Cons • More sensitive to static magnetic field inhomogeneity1 Noise, motion, and blood artefacts can complicate analysis (particularly in heavily iron-loaded hearts)7 • • • Lack of sensitivity6 Motion artefacts6 Poor signal-to-background noise ratios at longer TEs6 Longer acquisition time1 • 19 G-EXJ-1030713 May 2012 1Guo • H, et al. J Magn Reson Imaging. 2009;30:394-400. 2Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 3Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9.4Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. 5Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9. 6Hoffbrand AV. Eur Heart J. 2001;22:2140-1. 7He T, et al. Magn Reson Med. 2008;60:1082-9. Gradient relaxometry (T2*, R2*) can conveniently measure cardiac and liver iron Liver MRI [Fe] (mg/g dry wt) 14 12 10 8 6 4 R2 = 2 0.82540 0 0 100 200 300 400 HIC (mg Fe/g of dry weight liver) Cardiac MRI 30 Hankins, et al. 25 20 Wood, et al. 15 10 Anderson, et al. 5 0 Cardiac R2* (Hz) 0 200 400 600 800 Liver R2* (Hz) Cardiac and liver iron can be assessed together conveniently by gradient echo during the a single MRI measurement. 20 G-EXJ-1030713 May 2012 HIC = hepatic iron concentration Carpenter JP, et al. J Cardiovasc Magn Reson. 2009;11 Suppl 1:P224. Hankins et al Blood. 2009;113:4853-4855. 1000 Cardiac T2* MRI is usually measured in the septum of the heart Heart with normal iron levels T2* = 22.8 ms or R2* = 43.9 Hz Heart with severe iron overload 21 G-EXJ-1030713 May 2012 T2* = 5.2 ms or R2* = 192 Hz Images courtesy of Dr J. de Lara Fernandes. What is R2*? Conversion from T2* to R2* is a simple mathematical calculation: R2* = 1,000/T2* Level of cardiac iron overload Normal Mild, moderate Severe T2*, ms R2*, Hz 201 < 50 10–201 50–100 < 102 > 100 These values are only applicable to 1.5 T scanners1 22 G-EXJ-1030713 May 2012 1Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 2Kirk P, et al. Circulation. 2009;120:1961-8. Why should the data be presented as R2* and not T2*? 14 14 12 12 [Fe] (mg/g dry wt) [Fe] (mg/g dry wt) ● Seven whole hearts from patients with transfusion-dependent anaemias were assessed by histology and cardiac MRI 10 8 6 4 R2 = 0.949 2 10 8 6 4 R2 = 0.82540 2 0 0 0 10 20 30 40 50 60 70 0 Cardiac T2* (ms) 100 200 Cardiac R2* (Hz) R2* has a linear relationship with tissue iron concentration, which simplifies the interpretation of data and allows comparison of changes over time 23 G-EXJ-1030713 May 2012 Carpenter JP, et al. J Cardiovasc Magn Reson. 2009;11 Suppl 1:P224. 300 400 Why should the data be presented as R2* and not T2*? (cont.) The relationship between cardiac T2*/R2* and LVEF Hockey stick effect? Or a more gradual relationship? 100 90 80 80 LVEF (%) LVEF (%) 70 60 50 40 60 40 30 20 20 10 0 0 0 10 20 30 40 50 60 70 80 Heart T2* (ms) 90 100 0 50 100 R2* (s–1) R2* allows demonstration of cardiac risk in a more gradual way 24 G-EXJ-1030713 May 2012 Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 150 200 250 Standard errors on a single measurement are approximately constant with R2*, but are non-uniform with T2* Transform to R2* 120 60 R2* first measurement (s–1) T2* first measurement (ms) Why should the data be presented as R2* and not T2*? (cont.) 50 40 30 20 10 0 0 10 20 30 40 50 60 T2* second measurement (ms) 100 80 60 40 20 0 0 Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9. 40 60 80 100 120 R2* second measurement (s–1) R2* has a constant standard error that makes assessment of the significance of changes easier 25 G-EXJ-1030713 May 2012 20 Cardiac T2* MRI in practice G-EXJ-1030713 May 2012 MRI scanners ● ● ● Manufacturers – Siemens Healthcare (Erlangen, Germany; www.siemensmedical.com) – GE Healthcare (Milwaukee, WI, USA; www.gemedicalsystems.com) – Philips Healthcare (Best, the Netherlands; www.medical.philips.com) Magnetic field – T2* varies with magnetic field strength1 – 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) 27 G-EXJ-1030713 May 2012 1Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 2Kirk P, et al. Circulation. 2009;120:1961-8. Cardiac T2* MRI in practice: The process 1. Patient preparation 2. Acquisition of the MRI image (5 min) (approx. 5-20 min) 3. Analysis of MRI data (time depends on experience*) LIVER TE Please insert the values of TE and ROI from an individual patient. ROI 1.3 2.46 3.62 4.78 5.94 7.1 8.26 9.42 10.58 11.74 134 114 99 81 70 59 49 40 35 28 160 140 y = 166.48552e-0.14925x R² = 0.99845 120 100 80 60 40 20 E 0.14925 0 T2* 2.1 ms R2* 476.1905 Hz 0 2 4 6 LIC 12.88801 mg/g LIC calculation according to: Hankins JS, et al. Blood. 2009;113:4853-5. Normal Normal Normal >11.4 <88 <2 Light Light Light 3.8 - 11.4 88-263 2-7 Moderate Moderate Moderate 8 1.8-3.8 263-555 7-15 10 12 Severe Severe Severe 14 <1.8 >555 >15 Please insert the value from the graph, encircled green. T2*, R2* 28 G-EXJ-1030713 May 2012 *Time to manually calculate T2*/R2* values in an Excel spreadsheet depends on the experience of the physician. T2* R2* mg/g 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 • cmr42 • FerriScan • MRmap • MATLAB 29 G-EXJ-1030713 May 2012 Preparation of the patient G-EXJ-1030713 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 31 G-EXJ-1030713 May 2012 ECG = electrocardiography. 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 • cmr42 • FerriScan • MRmap • MATLAB 32 G-EXJ-1030713 May 2012 Acquisition of the image G-EXJ-1030713 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 exist1 – a gradient-echo sequence generates T2* 34 G-EXJ-1030713 May 2012 1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. The most common commercially available T2* acquisition techniques Group Number of echoes per breath-hold Heart regions Prepulse RR intervals TR Bright blood (Anderson et al.)1 London (Pennell) 1 (but multiple breath-holds) 1 (septum) No 1 Variable Novel bright blood (Westwood et al)2 London (Pennell) Multiple 1 (septum) No 1 Fixed Black blood (He et al)3-4 London (Pennell) Multiple 1 (septum) Yes 2 Fixed Multi-slice Pisa (Pepe) Multiple Multiregion No 1 Fixed Sequence (Pepe et al)5 The various techniques give clinically comparable results.2-3, 5 35 G-EXJ-1030713 May 2012 1Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 2Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9. 3He T, et al. J Magn Reson Imaging. 2007;25:1205-9. 4He T, et al. Magn Reson Med. 2008;60:1082-9. 5Pepe A, et al. J Magn Reson Imaging. 2006;23:662-8. Acquisition of the image: TEs ● The choice of minimum TE determines the smallest measurable T21 • ideally, min TE 2 ms, max TE 17‒20 ms ● Different T2* acquisition techniques according to TE • • 36 G-EXJ-1030713 May 2012 multiple breath-hold: acquire an image for each TE in separate breath-holds2 Mean R2* compared with true value in the case of synthetic images for different minimum TEs, but same echo duration (18 ms)4 Mean R2*: ramp, dualtone, & uniform (Hz) ● Images are taken at a minimum of 5 different TEs, normally 8‒121 Shortest TE = 2 ms Shortest TE = 1 ms Shortest TE = 4 ms Shortest TE = 5.5 ms True 500 450 400 350 300 250 200 150 100 50 0 0 100 200 True R2* (Hz) single breath-hold multi-echo acquisition: acquire images for all TE during 1 breath-hold3 1Wood 300 JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9. 2Anderson LJ, et al. Eur Heart J. 2001;22:2171-9. 3Westwood M, et al. J Magn Reson Imaging. 2003;18:33-9. 4Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16. 400 500 How does the MRI data output looks like? MRI data output Frame TE (ms) Mean ST 0 1.9 89.5 1 3.6 83.6 2 5.3 76.8 3 7.0 70.6 4 8.7 64.5 5 10.4 59.2 6 12.2 54.9 7 13.9 50.2 8 15.6 45.8 9 17.3 42.4 Data visualization During a single breath hold the pulse sequence run several times at increasing echo time (TE), generating data points corresponding to decreased signal intensity1 37 G-EXJ-1030713 May 2012 1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. FAQ: Acquisition technique 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 BlandAltman 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 Patients with T2* < 20 ms1 38 G-EXJ-1030713 May 2012 1Westwood Patients with T2* 20 ms 1 M, et al. J Magn Reson Imaging. 2003;18:33-9. 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) 39 G-EXJ-1030713 May 2012 Image courtesy of Dr J. de Lara Fernandes. 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 • cmr42 • FerriScan • MRmap • MATLAB 40 G-EXJ-1030713 May 2012 Analysis of the data (post-processing) G-EXJ-1030713 May 2012 How T2* is calculated from the MRI output? Data visualization 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 42 G-EXJ-1030713 May 2012 1Wood JC, Ghugre N. Hemoglobin. 2008;32:85-96. Analysis of the data ● The data can be analysed manually or using post-processing software Manually Post-processing software • • • • • • Excel spreadsheet 43 G-EXJ-1030713 May 2012 ThalassaemiaTools (CMRtools) cmr42 FerriScan MRmap MATLAB Analysis of the data (cont.) Method Pros Cons Excel spreadsheet • Low cost • Time-consuming • Tedious ThalassaemiaTools (CMRtools)1 • Fast (1 min)2 • Easy to use • FDA approved • GBP 3,000 per year cmr42(3) • Easy to use • FDA approved3 • 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 44 G-EXJ-1030713 May 2012 FDA = Food and Drug Administration. 1www.cmrtools.com/cmrweb/ThalassaemiaToolsIntroduction.htm. Accessed Dec 2010. 2Pennell DJ. JACC Cardiovasc Imaging. 2008;1:579-81.3www.circlecvi.com. Accessed Dec 2010. Analysis of the data (cont.) Method Pros Cons FerriScan1 • 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 MRmap2 • Uses IDL runtime, which is a commercial software (less expensive than cmr42/CMRtools) • Can quantify T1 and T2 map with the same software • Purely a research tool • Not intended for diagnostic or clinical use MATLAB3 • Low cost 45 G-EXJ-1030713 May 2012 1www.resonancehealth.com/resonance/ferriscan. • • Available only locally Physicists or engineers need to write a MATLAB program for display and T2* measurement Accessed Dec 2010. 2www.cmr-berlin.org/forschung/ mrmapengl/index.html. Accessed Dec 2010. 3Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9. FAQ: Mistakes in analysing the data 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 Signal decay curve from a patient with T2* ≈ 5 ms, showing that the data do not fit well2 46 G-EXJ-1030713 May 2012 1Wood JC, Noetzli L. Ann N Y Acad Sci. 2010;1202:173-9. 2Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16. FAQ: Mistakes in analysing the data (cont.) 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 > 0.995. 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* measurements1 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 47 G-EXJ-1030713 May 2012 1He T, et al. Magn Reson Med. 2008;60:1082-9. 2Ghugre NR, et al. J Magn Reson Imaging. 2006;23:9-16. FAQ: How to start measuring cardiac iron loading? 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 48 G-EXJ-1030713 May 2012 Implementation of liver and cardiac MRI 1.5T MRI Scanner US$1.000.000 Yes ½ day training Liver Analysis Experienced radiologist No 1 day training Post-processing analysis Cardiac acquisition package US$50.000 Yes US$40.000 or US$4.000/y or in-house or outsource 1-2 day training Heart Analysis Routine cardiac MR exams No 49 G-EXJ-1030713 May 2012 4 day training Slide presented at Global Iron Summit 2011 - With the permission of Juliano de Lara Fernandes Summary G-EXJ-1030713 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 overload1 – R2* is a simple calculation from T2* and has a linear relationship with cardiac iron concentration 51 G-EXJ-1030713 May 2012 1Thomas AS, et al. Blood. 2010;116:[abstract 1011]. 2Modell B, et al. J Cardiovasc Magn Reson. 2008;10:42-9. GLOSSARY OF TERMS G-EXJ-1030713 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 53 G-EXJ-1030713 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 (£) 54 G-EXJ-1030713 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 55 G-EXJ-1030713 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 56 G-EXJ-1030713 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 57 G-EXJ-1030713 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 58 G-EXJ-1030713 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 59 G-EXJ-1030713 May 2012