Aaryani Tipirneni-Sajja1, Eric M. Kercher1, Ralf B. Loeffler1, Ruitian Song1, Matthew D. Robson2, M. Beth McCarville1, Jane S. Hankins3, and Claudia M. Hillenbrand1
1Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, United States, 2Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom, 3Hematology, St. Jude Children's Research Hospital, Memphis, TN, United States
Synopsis
Hepatic iron content
(HIC) is linearly correlated with R2*. Currently, there is little data on in
vivo human liver iron assessment via longitudinal relaxation T1 (or R1)
although an animal study previously suggested linear association, too. This
study investigates hepatic T1 quantification in a breathhold by using
ShMOLLI. T1 and T2* liver mapping were performed in 124 iron loaded
patients. We found linear association between R1 and R2*/HIC values for
mild-moderate HIC at 1.5T and 3T. No association between T1 and T2* was found for
high HIC, which is most likely due to technical limits of ShMOLLI for short
T2*.
Introduction
Assessment of hepatic
iron content (HIC) by R2*-MRI has been increasingly used as a non-invasive
alternative to liver biopsy. R2* (=1/T2*) is typically measured by quantifying
the signal decay of a breath-hold multi-echo gradient echo (mGRE) sequence. R2*
and HIC by biopsy are linearly related and R2*-based HIC is calculated using
published calibration curves.1-3
However, previous R2*-HIC biopsy studies have shown that their precision is limited
for high HIC (>20 mg Fe/g) and might even fail for massive HIC (>25 mg
Fe/g) because of the rapid signal decay associated with standard mGRE imaging.
In this study, we investigate the impact of hepatic iron overload on T1 (=1/R1)
relaxation times and if T1 values may have the potential to increase our
confidence in the assessment of HIC in a large patient cohort with
transfusional iron overload. Methods
This prospective study
was approved by the Institutional Review Board. 124 subjects with a history of ≥
12 blood transfusions underwent MRI at 1.5T to assess HIC. Of these 124 subjects,
62 also had a 3T exam. All images were acquired axially at the location of the main
portal vein in the central part of the liver. Quantitative T1 imaging and mapping was accomplished
by using the ShMOLLI sequence (TE/TI/TIincrement=1.05/105/80ms,
α=35°, FOV=323-400mm, matrix:384x312, slice-thickness=10 mm) and respective
post-processing algorithm.4 For T2* analysis, subjects also underwent multi-echo
gradient-echo (mGRE) imaging5 (TR/TE1/ΔTE=200/1.07/0.86ms, 20
echoes, α=35°, FOV= 250–400mm, matrix: 128x104, slice thickness=10 mm).
Quantitative T2*/R2* maps were calculated using a nonlinear least-squares fit
method in MATLAB.6, 7 Region of interest (ROI) analysis of T1 and T2* quantitative maps were
performed offline using a custom-written program in MATLAB.8 Two ROI analysis techniques were used: small
ROIs were drawn in a homogeneous area in the right hepatic lobe that approximately
matches the area of liver biopsy resections. Hepatic T1 and T2* values were
also extracted using whole liver ROI and histogram analysis that excluded signal from hepatic blood vessels.8 R2*-based HIC values were calculated using the R2*
values obtained at 1.5T and a previously published calibration curve.3,8 As the presence of
fat affects T1 and T2* measurements, all patients were tested for hepatic
steatosis10 and were excluded if the fat fraction ≥ 5%. Results & Discussion
Patient demographics
were summarized in Table 1. Four patients were excluded due to failed T1 or T2*
fits at 1.5T and 8 at 3T. Further, 5 patients were excluded due to the presence
of fat at 1.5T and 2 at 3T. Figure 1A compares the T1 results between the small
ROI and whole liver ROI techniques. A strong linear correlation was found at 1.5T
(slope = 1.03, R2 = 0.95) and at 3T (slope = 0.96, R2 =
0.91) between both ROI techniques. This suggests that T1 times (and thus iron)
are homogeneously distributed throughout the liver in our patient cohort.
Analysis using the whole liver ROI approach is preferable as it removes the
ambiguities associated with the size and placement of ROI compared to the small
ROI approach.8 Liver T1 times measured at 3T produced slopes of 1.2
and 1.4 when compared to those obtained at 3T using the whole liver and small
ROI analyses, respectively. Figure 2 shows the results of comparing T1 and R1
values with R2*-based HIC. A monotonic decrease in T1 (increase in R1) was seen
at both field strengths with increasing HIC. This trend however saturates
around T1 = 300 ms for HIC > 15 mg Fe/g (i.e., R2* > 500 s-1).
The observed ‘saturation’ of T1 times could be explained by a systematic bias
in the ShMOLLI sequence fitting algorithm. This algorithm has not been tested11 for T2* < 2 ms (R2* > 500 s-1)
[HC1] which
happens to be where our data begins to flatten out. However, there is a moderate
linear relationship (R2 = 0.5) between R1 and R2*-based HIC (Fig. 2B)
for normal to moderate iron overloaded cases (0 – 15 mg Fe/g) and the slope
obtained at 1.5T was close to that reported in
literature.Conclusion
T1 relaxation times
in the liver can be quantified with ShMOLLI in normal and moderately iron
overloaded cases. T1 values are relatively homogeneous throughout the liver. T1
values are associated with T2* values and consequently with HIC. T1 times
plateau in highly overloaded cases, which likely is due to the fact that T2* times are too short for ShMOLLI to quantify accurately. Therefore, future work should focus on testing with a fast T1 sequence (e.g., snapshotFLASH) if there is indeed a plateau or a linear association also for severe HIC.Acknowledgements
No acknowledgement found.References
1.
Anderson LJ, Holden S, Davis B, et al. Cardiovascular T2-star (T2*) magnetic
resonance for the early diagnosis of myocardial iron overload. European heart journal. 2001; 22:
2171-9.
2. Wood JC, Enriquez C, Ghugre N, et al. MRI R2 and
R2* mapping accurately estimates hepatic iron concentration in
transfusion-dependent thalassemia and sickle cell disease patients. Blood. 2005; 106: 1460-5.
3. Hankins JS, McCarville MB, Loeffler RB, et al. R2*
magnetic resonance imaging of the liver in patients with iron overload. Blood. 2009; 113: 4853-5.
4. Piechnik SK, Neubauer S and Robson MD. Shortened
Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-
mapping at 1.5 and 3 T within a 9 heartbeat breathhold. Journal of Cardiovascular Magnetic Resonance. 2010; 12.
5. Hankins JS, McCarville BM, Loeffler RB, Smeltzer
M, Wang WC and Hillenbrand CM. R2* magnetic resonance imaging of the liver in
patients with iron overload. Blood.
2009; 113: 4853-5.
6. Gudbjartsson H and Patz S. The Rician distribution
of noisy MRI data. Magn Reson Med.
1995; 34: 910-4.
7. Krafft AJ, Loeffler RB, Song R, et al. Does fat
suppression via chemically selective saturation affect R2*-MRI for
transfusional iron overload assessment? A clinical evaluation at 1.5T and 3T. Magnetic resonance in medicine. 2015.
8. McCarville BM, Hillenbrand CM and Loeffler RB.
Comparison of whole liver and small region-of-interest measurements of MRI
liver R2* in children with iron overload. Pediatric
Radiol. 2010; 40: 1360. 9. Krafft AJ, Taylor BA, Lin H, Loeffler RB and
Hillenbrand CM. A Systematic Evaluation of an Auto Regressive Moving Average
(ARMA) Model for Fat-water Quantification and Simultaneous T2* Mapping. International Society of Magnetic Resonance
in Medicine. Salt Lake City, Utah2013.
10. Banerjee R, Tunnicliffe E, Piechnik SK, Robson MD
and Neubauer S. Multiparametric magnetic resonance for the non-invasive
diagnosis of liver disease. Journal of
Hepatology. 2014; 60: 69-77.
11.
Wood JC, Nelson MD, Coates TD and Moats R. Cardiac Iron Determines Cardiac T2*,
T2, and T1 in the Gerbil Model of Iron Cardiomyopathy. Circulation. 2005; 112: 535-43.