PURPOSE: To provide further quantitative studies concerning the relationship with age between regional brain iron and T2 shortening. METHODS: a) Quantitative T2 calculations of eight anatomic regions (red nucleus, substantia nigra, dentate nucleus, corpus callosum, caudate, putamen, temporal lobe white matter, and frontal lobe white matter) from T2-weighted spin-echo images were performed in 60 patients aged newborn to 35 years. b) Quantitative brain iron concentrations were obtained in six of the eight anatomic regions (red nucleus, substantia nigra, dentate nucleus, corpus callosum, cauda, and putamen) using 13 autopsied brains (newborn to 78 years). Brain tissue from these six regions was digested with 0.6 N HCl-2.5% wt/vol KMnO4 for 2 hours at 60 degrees C. After centrifugation, 0.1 mL of an iron-chelating reagent (2 mol/L ascorbic acid, 5 mol/L ammonium acetate, 6.5 nmol/L ferrozine, 13.1 mmol/L neocuprine) was added and the absorbance was measured at 562 nm/L and compared with a standard curve with ferric chloride. c) The in vivo iron concentrations in tissue that were obtained were reproduced in four test tube phantom studies with ferric ammonium sulfate or ferrous ammonium sulfate dissolved in either deionized water or 5% agarose. T2 calculations of the phantoms were made with a single-section multiple repetition time, multiple echo time acquisition. RESULTS: a) Clinical T2 calculations--all eight anatomic regions showed a decrease with age in T2 value, beginning shortly after birth. During the first three decades, the T2 shortening was most significant in the region of substantia nigra. b) Quantitative brain iron--five anatomic regions but not the corpus callosum demonstrated an age-related increase in brain iron (1449.6 nmol/g for the red nucleus versus 261.8 nmol/g for the corpus callosum). c) T2 effect of iron in vitro--both the ferric and ferrous iron phantoms showed a decreased T2 value in the in vivo concentration range of iron obtained from the postmortem studies. The T2 shortening was most marked for the ferric phantoms. CONCLUSION: There is an age-related accumulation of iron in five regions of the brain, correlating with an associated decrease in T2 value that can be demonstrated in iron phantoms. Brain iron appears to contribute to the progressive decrease of T2 signal that occurs with aging.
PURPOSE: To provide further quantitative studies concerning the relationship with age between regional brain iron and T2 shortening. METHODS: a) Quantitative T2 calculations of eight anatomic regions (red nucleus, substantia nigra, dentate nucleus, corpus callosum, caudate, putamen, temporal lobe white matter, and frontal lobe white matter) from T2-weighted spin-echo images were performed in 60 patients aged newborn to 35 years. b) Quantitative brain iron concentrations were obtained in six of the eight anatomic regions (red nucleus, substantia nigra, dentate nucleus, corpus callosum, cauda, and putamen) using 13 autopsied brains (newborn to 78 years). Brain tissue from these six regions was digested with 0.6 N HCl-2.5% wt/vol KMnO4 for 2 hours at 60 degrees C. After centrifugation, 0.1 mL of an iron-chelating reagent (2 mol/L ascorbic acid, 5 mol/L ammonium acetate, 6.5 nmol/L ferrozine, 13.1 mmol/L neocuprine) was added and the absorbance was measured at 562 nm/L and compared with a standard curve with ferric chloride. c) The in vivo iron concentrations in tissue that were obtained were reproduced in four test tube phantom studies with ferric ammonium sulfate or ferrous ammonium sulfate dissolved in either deionized water or 5% agarose. T2 calculations of the phantoms were made with a single-section multiple repetition time, multiple echo time acquisition. RESULTS: a) Clinical T2 calculations--all eight anatomic regions showed a decrease with age in T2 value, beginning shortly after birth. During the first three decades, the T2 shortening was most significant in the region of substantia nigra. b) Quantitative brain iron--five anatomic regions but not the corpus callosum demonstrated an age-related increase in brain iron (1449.6 nmol/g for the red nucleus versus 261.8 nmol/g for the corpus callosum). c) T2 effect of iron in vitro--both the ferric and ferrousiron phantoms showed a decreased T2 value in the in vivo concentration range of iron obtained from the postmortem studies. The T2 shortening was most marked for the ferric phantoms. CONCLUSION: There is an age-related accumulation of iron in five regions of the brain, correlating with an associated decrease in T2 value that can be demonstrated in iron phantoms. Brain iron appears to contribute to the progressive decrease of T2 signal that occurs with aging.
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