P. Liu et al., QUANTIFICATION OF CARDIAC AND TISSUE IRON BY NUCLEAR-MAGNETIC-RESONANCE RELAXOMETRY IN A NOVEL MURINE THALASSEMIA CARDIAC IRON OVERLOAD MODEL, Canadian journal of cardiology, 12(2), 1996, pp. 155-164
OBJECTIVE: To determine whether nuclear magnetic resonance (NMR) relax
ation parameters can be used to quantify iron in tissues, the relation
ship between NMR spectrometric T-2 relaxation measurements and tissue
iron concentration were verified in a novel murine cardiac iron overlo
ad model. METHODS: Congenital heterozygous thalassemic mice and contro
ls were injected with intraperitoneal iron or saline and were sacrific
ed at three weeks. Samples of liver, heart and peripheral muscle were
subjected to NMR relaxation measurements and continuous distribution a
nalysis. Tissue ferritin levels were determined with immunoadsorbance
techniques, and elemental iron was assayed by flame atomic absorption.
Tissues were analyzed pathologically with hematoxylin and eosin and P
russian blue staining to confirm the localization of iron. RESULTS: Th
is murine iron loading model was uniquely successful in loading iron i
nto the major organs, especially the heart, and produced significant r
eductions in T-1 and T-2 NMR relaxation values. There was a good corre
lation between soluble ferritin and total iron levels (r = 0.92), indi
cating that there is a constant and significant fraction of total iron
present in ferritin irrespective of absolute iron concentrations. Reg
ression analysis between total iron content and T-2 relaxivity showed
a linear relationship (r=0.92), suggesting that the T-2 relaxation par
ameter is related to tissue iron concentration. The regression relatio
nship suggested that NMR can detect iron levels as low as 0.1 mg/g of
tissue. CONCLUSIONS: Parenteral iron loading in mice produces unique i
ron overload in major organs, including the heart. Local iron depositi
on is detectable by NMR relaxometry at 0.1 mg/g or higher. There is a
linear relationship between iron concentration and T-2 relaxivity. Thu
s, NMR maybe an important and useful clinical tool to quantify iron ex
cess in various pathobiological states of human disease due to iron ov
erload, including heart disease.