Andrew L Cheng^{1}, Thomas D Coates^{1}, and John C Wood^{2}

Pituitary R2 at 1.5 Tesla has been validated as a sensitive marker of pituitary siderosis and risk of clinical hypogonadism. We cross-validated pituitary R2 measurements at 3T and 1.5T in 26 patients with iron overload syndromes. Pituitary R2 scaled linearly across field strength with a relative enhancement of 42%, consistent with previous liver R2 cross-field validations. When 3T pituitary values were transformed into equivalent 1.5T R2 values, the resulting Z-score estimates were unbiased with native 1.5T R2 estimates. Thus it is not necessary to acquire normative R2 data at 3 Tesla in order to interpret 3T pituitary R2 values.

From 5/1/14 – 2/9/18, 26 patients with
transfusional siderosis (8 with sickle cell disease, 11 with thalassemia major, four
with thalassemia intermedia, one with leukemia, one with Blackfan Diamond
syndrome and one with hereditary hemochromatosis) underwent head MRI examinations
at 1.5T and 3T within one month of each other; five patients
underwent two examinations spaced more than one year apart. Study was approved by the Committee on
Clinical Investigation (CCI#2014-00034) and all patients provided informed
consent. The study population was composed of six Caucasians, six Africans,
four Chinese, two Vietnamese, two Indians, two Mediterraneans, and two subjects
of mixed race. Seven were ethnically Hispanic and 19 were non Hispanic. There
were 19 females and 7 males with ages of 22.0 ± 8.7 [range 5.3
– 46.0]. Both the 1.5 and 3.0 Tesla examinations were performed using an
8-element head coil on a Philips Achieva running system 5.1.9. Pituitary R2 was
performed using a five slice, standard mulitiple echo, spin echo examination in the sagittal
plane. Field of view was 20.8 cm, voxel size 1 x 1 x 3 mm, five slices with no gap, TR 875 ms, TE 15, 30, 45, 60, 75, 90, 105, 120 ms, bandwidth 218 Hz/pixel. Images were fit pixelwise to an exponential plus a constant as
previously described^{2,3}. Values from the central three slices were averaged. We calculated the relaxivity
enhancement(RE) between 3T and 1.5T as follows:

R2_{3T}-R2_{3Tref} = RE x (R2_{1.5T}-R2_{1.5Tref}) [1]

where R2_{3T} and R2_{1.5T}
represent the measured R2 values at the respective field strength and R2_{3Tref}
and R2_{1.5Tref} were their corresponding reference values, representing
a common point on the 3T and 1.5T calibration curves. Suitable reference points
could include the intrinsic R2 when no iron is present or population norms^{4}.
We exploited the linear relationship between R2 and age at 1.5T to set R2_{1.5Tref}
to 10.7 ms, the expected pituitary R2 value at birth^{2}. Thus equation [1] could be recast as follows:

R2_{3T} = RE x (R2_{1.5T}-10.7)
+ R2_{3Tref} [2]

where RE and R2_{3Tref} could
be interpreted as simply the slope and intercept of the regression equation
between R2_{3T }and the difference of R2_{1.5T }and 10.7 ms. To
correct for multiple measurements in five patients, we weighted each R2 value
by 0.5 in patients having two examinations. Once RE and R2_{3Tref } were estimated, R2_{3T} values
were transformed into its R2_{1.5T-}_{equivalent}, and the corresponding
Z-score, using the following relationships^{4:}

R2_{1.5Tequivalent
}= (R2_{3T}-R2_{3Tref})/RE + 10.7 Hz [3]

Z-score = (R2_{3T}-R2_{3Tref})/RE
– 0.331xAge)/0.88 [4]

1. Vogiatzi MG, Macklin EA, Trachtenberg FL, Fung EB, Cheung AM, Vichinsky E, Olivieri N, Kirby M, Kwiatkowski JL, Cunningham M, Holm IA, Fleisher M, Grady RW, Peterson CM, Giardina PJ. Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol. 2009;146(5):546-556.

2. Noetzli LJ, Panigrahy A, Mittelman SD, Hyderi A, Dongelyan A, Coates TD, Wood JC. Pituitary iron and volume predict hypogonadism in transfusional iron overload. Am J Hematol. 2012;87(2):167-171.

3. Noetzli LJ, Panigrahy A, Hyderi A, Dongelyan A, Coates TD, Wood JC. Pituitary iron and volume imaging in healthy controls. AJNR Am J Neuroradiol. 2012;33(2):259-265.

4. Ghugre NR, Doyle EK, Storey P, Wood JC. Relaxivity-iron calibration in hepatic iron overload: Predictions of a Monte Carlo model. Magn Reson Med. 2015;74(3):879-883.

Figure 1: Pituitary R2 at 3T rises linearly with the difference of the corresponding R2 at 1.5T and the 1.5T reference value (pituitary R2 of a newborn baby). One outlier (highest R2 value) was excluded because of excessive signal loss.

Figure 2: Bland Altman agreement between the pituitary Z-score predicted from 3T R2 versus 1.5T R2 measurements. 3T and 1.5T Z-scores are unbiased with one another and have 95% confidence intervals of +/- 2 Z-scores.