Why measure heart iron?

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2 Why measure heart iron? It predicts impending cardiac dysfunction. It predicts noncardiac complications It cannot be inferred by measurements of liver iron Heart iron loading occurs occultly in patients otherwise doing well It is really hard to get iron out of the heart once present It dramatically affects the type and intensity of iron chelation

3 Which Heart Technique? T2 T1 QSM T2* Septum only 1.5 Tesla White Blood 3.0 Tesla Black Blood Reduced R2 Segmental Approach Signal Intensity Ratios Susceptibility Mapping

4 Why T2*? Interexam/Interreader Reliability Anderson et al, Eur Heart J, 22(23)2171-9, 2001 Westwood et al, Int J Card Im 21(5):531-8, 2005 Kirk et al, JMRI 32(2): , 2010 Picker to Siemens Westwood et al, JMRI 18(5):616-20, 2003 Multi BH to single BH Westwood et al, JMRI 18(1):33-9, 2003 White Blood to Black Blood Smith et al, JCMR 13(21):21, 2011 Single breathhold, COV 5.9% Fast Easy Widely available Large dynamic range Robust 49 patients Kirk et al, JMRI 32(2): , 2010 Single Center to Multicenter Westwood et al, Int J Card Im 21(5):531-8, 2005 Kirk et al, JMRI 32(2): , 2010

5 LIC (mg/g) & T2* (ms) LIC (mg/g) & T2* (ms) Black blood versus white blood LIC T2* Time (Months) LIC T2* Time (Months) Edge detection easier with black blood. Better result stability in the normal range. Either is suitable for clinical trials and clinical practice.

6 Cardiac T2* at 3T Storey et al, JMRI 25: (2007)

7 Cardiac T2* at 3T Storey et al, JMRI 25: (2007)

8 Multislice, multiple ROI approach All segments normal Some segments abnormal, T2* > 2 Some segments abnormal, T2* < 2 All segments abnormal Pepe et al, JMRI 23:662-8, 2006 Eur Heart J, Cardiovasc Imaging 16, , 2015 Meloni et al, JMRI 64: , 2010

9 Correcting for susceptibility variations Positiano et al, NMR in Biomedicine, 20: , Background correction has not been validated in an independent non-iron loaded cohort. Susceptibility effects are not linear. Positiano et al, NMR in Biomedicine, 22: , 200

10 Cardiac T2 Similar principle to T2* but using a spin-echo instead of a gradient echo. More robust to magnetic field inhomogeneities (like portacaths). Has been validated against autopsy. Smaller dynamic range than R2*. Is more sensitive to smaller iron deposits than R2*.

11 Comparing T2 and T2* Liver Ferritin Hemosiderin Heart Liver He T et al, MRM 61(3):501-6, 2009 Feng et al, JMRI, 38: (2013)

12 Cardiac T1 and heart iron T1 is just another MRI relaxation parameter It is sensitive to iron, although not as sensitive as T2 and T2*. It used to be hard to measure in heart because of motion. The change in cardiac T1 can also be used to measure fibrosis. Doubling iron-> 12%T1 Sado et al, JMRI COV 41: is ~3-4%. (2015) Wood et al, MRM 60(1):82-89,2008

13 T1 is proportional to T2 T1 and T2 vary linearly with one another. T2* 20 ms Relationship trends even with T2* in normal range. Some argue the T1 and T2 are more reproducible than T2*. Feng Y et al, JMRI 38(3):588-93, 2013 However, validation are lacking.

14 Early warning system? Low T1 may indicate early cardiac iron loading. Sado et al, JMRI 41: (2015)

15 Comparison of T1 methods Slice to slice reproducibilty Interstudy reproducibilty

16 T1 mapping? Advantages Some scanners output a T1 map automatically. May be more sensitive to low iron. Can be used, with contrast, to assess fibrosis. Disadvantages Numbers vary with technique. Interscanner reproducibility has not been proven. Motion artifacts with high heart rate. T1 changes are not specific. Not clinically validated.

17 LIC (mg/g) & T2* (ms) LIC (mg/g) & T2* (ms) Do we really need T1, T2, to track iron? LIC T2* Time (Months) LIC T2* Panc Iron Time (Months) Trends in T2* are highly robust. Pancreas T2* also offers insights into response.

18 Summary for Cardiac Iron T1, T2, and T2* all reflect cardiac iron. T2* is robust across imaging platforms and is well calibrated to cardiac risk; Black blood is a good idea but not a game changer. Cardiac T2* at 3T is feasible and calibrated. T2* between is abnormal and ms is borderline. Multi-slice, multi-segment T2* assessment does not offer clinical advantages to good septal T2* assessment. T2 and T1 could potentially help identify early cardiac iron deposition. T1 mapping assessment of ECV is potentially a powerful tool to probe the prevalence and etiology of fibrosis in iron overload disorders.

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20 Reduced R2 11 um 0.9 um Cheung et al, JMRI, 33: (2011)

21 Detecting ferritin pool Baseline MRI Hold Chelation 7 Days Repeat MRI Restore Chelation 7 Days Final MRI Cheung et al, JMRI, 33: (2011)