Objective.-The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG as an indicator of function in patients with episodic migraine (EM) between attacks and patients with chronic daily headache (CDH) during headache. High-resolution magnetic resonance techniques were used to map the transverse relaxation rates R2, R2*, and R2 Ј in the PAG, red nucleus (RN), and substantia nigra (SN). R2 Ј is a measure of non-heme iron in tissues.Methods.-Seventeen patients diagnosed with EM with and without aura, 17 patients diagnosed with CDH and medication overuse, and 17 normal adults (N) were imaged with a 3.0-tesla magnetic resonance imaging system. For each subject, mean values of the relaxation rates, R2 (1/T2), R2* (1/T2*), and R2 Ј (R2* Ϫ R2) were obtained for the PAG, RN, and SN. R2, R2*, and R2 Ј values of the EM, CDH, and N groups were compared using analysis of variance, Student t test, and correlation analysis.Results.-In the PAG, there was a significant increase in mean R2 Ј and R2* values in both the EM and CDH groups ( P Ͻ .05) compared with the N group, but no significant difference in these values was demonstrated between the EM and CDH groups, or between those with migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2 Ј in the EM and CDH groups. A decrease in mean R2 Ј and R2* values also was observed in the RN and SN of the CDH group compared with the N and EM groups ( P Ͻ .05), explained best by flow activation due to head pain.Conclusions.-Iron homeostasis in the PAG was selectively, persistently, and progressively impaired in the EM and CDH groups, possibly caused by repeated migraine attacks. These results support and emphasize the role of the PAG as a possible "generator" of migraine attacks, potentially by dysfunctional control of the trigeminovascular nociceptive system. Key words: periaqueductal gray matter, iron, transverse relaxation rates Abbreviations: PAG periaqueductal gray matter, MWOA migraine without aura, DRN dorsal raphe nucleus, LC locus ceruleus, R2, R2*, R2 Ј transverse relaxation rates, RN red nucleus, SN substantia nigra, EM episodic migraine, CDH chronic daily headache, MWA migraine with aura, N healthy normal adults, GESFIDE gradient-echo sampling of free induction delay and echo, RF radiofrequency, ISODATA Iterative Self-organizing Data Analysis Technique ( Headache 2001;41:629-637) The midbrain periaqueductal gray matter (PAG) is an anatomically heterogeneous, functionally diverse region of densely layered neurons surrounding the aqueduct of Sylvius.1 Receiving input from the frontal cortex and hypothalamus and projecting to the rostral ventromedial medulla and from there to the medullary and spinal dorsal horn, the PAG is the center of a powerful descending antinociceptive neuronal network.2 Further, the PAG can be consideredFrom the

The small iron-independent component R2', as compared with that of R2, is consistent with the hypothesis that R2' has higher iron-related specificity.

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ABSTRACT. Background. Intraventricular hemorrhage (IVH) is the most common brain injury among premature infants. Neonates with IVH are at greater risk of impaired neurodevelopmental outcomes, compared with those without IVH. IVH causes destruction of the germinal matrix and glial precursor cells, with possible effects on cortical development.Objective. To investigate cortical development after uncomplicated IVH (with no parenchymal involvement and no posthemorrhagic hydrocephalus). We hypothesized that uncomplicated IVH would be followed by reduced cortical volume among premature infants at near-term age.Methods. A prospective cohort study was conducted, with preset selection criteria. Infants with small-for-gestational age birth weight, congenital abnormalities or brain malformations, metabolic disorders, recurrent sepsis, or necrotizing enterocolitis were excluded. Also, infants with posthemorrhagic hydrocephalus, parenchymal involvement of hemorrhage, cystic periventricular leukomalacia, or persistent ventriculomegaly were excluded, on the basis of routine serial ultrasonographic assessments. Three-dimensional images were acquired for 23 infants at near-term age, with 3-T magnetic resonance imaging and a magnetization-prepared rapid gradient echo sequence. Image analysis and segmentation of the cerebrum in different tissue types were based on signal contrast and anatomic localization. The cortical gray matter (CGM), subcortical gray matter, white matter, and intraventricular cerebrospinal fluid volumes of 12 infants with uncomplicated IVH were compared with those of 11 infants without IVH, using multivariate analysis of variance.Results. The multivariate analysis of variance for the regional brain volumes in the 2 groups indicated significance (Wilks' ‫؍‬ 0.546). The CGM volume was significantly reduced in the IVH group (no-IVH group: 122 ؎ 12.9 mL; IVH group: 102 ؎ 14.6 mL; F ‫؍‬ 13.218). This finding remained significant after testing for possible confounding factors and adjustment for size differences between the infants (F ‫؍‬ 9.415). There was no difference in the volumes of subcortical gray matter, white matter, and cerebrospinal fluid.Conclusions. This is the first study to document impaired cortical development after uncomplicated IVH. ABBREVIATIONS. IVH, intraventricular hemorrhage; CSF, cerebrospinal fluid; CGM, cortical gray matter; SGM, subcortical gray matter; WM, white matter; MRI, magnetic resonance imaging; CI, confidence interval. I ntraventricular hemorrhage (IVH) is the most common brain injury among premature infants and is the most common type of neonatal intracranial hemorrhage. 1,2 The incidence is directly correlated with the degree of prematurity. As the survival rates for premature infants continue to increase, IVH will continue to be a major problem in modern neonatal intensive care units. 1,2 It is known that IVH with associated ventriculomegaly or parenchymal involvement is associated with neurodevelopmental handicaps and disabilities. 3-5 Furthermore, studies have indicated that ...

We compared overexpression of the magnetotactic bacterial gene MagA with the modified mammalian ferritin genes HF + LF, in which both heavy and light subunits lack iron response elements. Whereas both expression systems have been proposed for use in non-invasive, magnetic resonance (MR) reporter gene expression, limited information is available regarding their relative potential for providing gene-based contrast. Measurements of MR relaxation rates in these expression systems are important for optimizing cell detection and specificity, for developing quantification methods, and for refinement of gene-based iron contrast using magnetosome associated genes. We measured the total transverse relaxation rate (R2*), its irreversible and reversible components (R2 and R2′, respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells. Clonal lines overexpressing MagA and HF + LF were cultured in the presence and absence of iron supplementation, and mounted in a spherical phantom for relaxation mapping at 3 Tesla. In addition to MR measures, cellular changes in iron and zinc were evaluated by inductively coupled plasma mass spectrometry, in ATP by luciferase bioluminescence and in transferrin receptor by Western blot. Only transverse relaxation rates were significantly higher in iron-supplemented, MagA- and HF + LF-expressing cells compared to non-supplemented cells and the parental control. R2* provided the greatest absolute difference and R2′ showed the greatest relative difference, consistent with the notion that R2′ may be a more specific indicator of iron-based contrast than R2, as observed in brain tissue. Iron supplementation of MagA- and HF + LF-expressing cells increased the iron/zinc ratio approximately 20-fold, while transferrin receptor expression decreased approximately 10-fold. Level of ATP was similar across all cell types and culture conditions. These results highlight the potential of magnetotactic bacterial gene expression for improving MR contrast.

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