Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies.

On T2* magnetic resonance and cardiac iron.

BACKGROUND: Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically via its reciprocal, T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans are limited. METHODS AND RESULTS: Twelve human hearts were studied from transfusion-dependent patients after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure (n=4). After cardiovascular magnetic resonance R2* measurement, tissue iron concentration was measured in multiple samples of each heart with inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean ± SD global myocardial iron causing severe heart failure in 10 patients was 5.98 ± 2.42 mg/g dry weight (range, 3.19 to 9.50 mg/g), but in 1 outlier case of heart failure was 25.9 mg/g dry weight. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] (R²=0.910, P<0.001), leading to [Fe]=45.0×(T2*)⁻¹·²² for the clinical calibration equation with [Fe] in milligrams per gram dry weight and T2* in milliseconds. Midventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron. CONCLUSIONS: These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration. The iron values are of considerable interest in terms of the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in vivo by cardiovascular magnetic resonance of the midseptum.

Laser scanning confocal ophthalmoscopy and polarimetry of human immunodeficiency virus patients without retinopathy, under antiretroviral therapy.

PURPOSE: Confocal laser scanning ophthalmoscopy (HRT; Heidelberg retinal tomograph II) and scanning laser polarimetry (GDx-variable corneal compensator [VCC]) were used to investigate whether early indicators of retinal nerve fiber layer (RNFL) thickness loss could be observed in patients infected with the human immunodeficiency virus (HIV) that had no associated retinopathy or optic neuropathy and were concomitantly receiving antiretroviral medications. METHODS: HRT and GDx-VCC parameters obtained from a group of 13 HIV-positive subjects (n=26 eyes) on antiretroviral therapy examined with HRT, with a subgroup of six subjects (n=12 eyes) examined with both HRT and GDx-VCC, were compared with those of a matched HIV-negative control cohort (13 subjects, n=26 eyes) examined with HRT, with a subgroup of five subjects (n=10 eyes) examined with both HRT and GDx-VCC. We employed generalized estimating equations for statistical analysis. RESULTS: Reduced mean values for the HRT height variation contour (p<0.045) and HRT mean RNFL thickness (p<0.023) were observed in HIV-positive subjects controlling for age, sex, and race. A significantly reduced mean value corresponding to the GDx-VCC superior maximum (p<0.014) and inferior maximum (p<0.016) were also observed for the HIV-positive cohort analyzed controlling for age, sex, and race. CONCLUSION: HRT and GDx-VCC indicators of RNFL thickness appear to be significantly reduced in HIV-positive subjects without retinopathy or optic nerve disease using antiretroviral medication, suggesting RNFL loss occurs in this population of HIV-positive patients. The lack of correlation between CD4 counts, viral load, number of antiretroviral medications used, or years from diagnosis of HIV and RNFL thinning, suggests that possibly other factors associated with HIV infection may contribute to the apparent RNFL thickness loss.