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Background and Purpose: A novel quantitative susceptibility mapping (QSM) processing technology has been developed to map tissue susceptibility property without blooming artifacts. We hypothesize that hematoma volume measurement on QSM is independent of imaging parameters, eliminating its echo time dependence on gradient echo MRI., Methods: Gradient echo MRI of 16 patients with intracerebral hemorrhage was processed with susceptibility-weighted imaging, R2* (=1/T2*) mapping, and QSM at various echo times. Hematoma volumes were measured from these images., Results: Linear regression of hematoma volume versus echo time showed substantial slopes for gradient echo magnitude (0.45±0.31 L/s), susceptibility-weighted imaging (0.52±0.46), and R2* (0.39±0.30) but nearly zero slope for QSM (0.01±0.05). At echo time=20 ms, hematoma volume on QSM was 0.80× that on gradient echo magnitude image (R2=0.99)., Conclusions: QSM can provide reliable measurement of hematoma volume, which can be performed rapidly and accurately using a semiautomated segmentation tool.

Objective: Preterm infants often show intolerance to the first enteral feeds, and the structural and functional basis of this intolerance remains unclear. We hypothesized that preterm and term neonates show similar gut trophic responses to feeding but different expression of intestinal functional proteins, thus helping to explain why preterm neonates are more susceptible to feeding-induced disorders such as necrotizing enterocolitis (NEC)., Methods: Incidence of feeding-induced NEC, intestinal mass, and brush border enzyme activities, and the intestinal proteome in preterm cesarean-delivered pigs were compared with the corresponding values in pigs delivered spontaneously at term., Results: For both preterm and term pigs, mucosal mass and maltase activity increased (50%-100%), whereas lactase decreased (-50%), relative to values at birth. Only preterm pigs were highly NEC sensitive (30% vs 0% in term pigs, P < 0.05). By gel-based proteomics, 36 identified proteins differed in expression, with most proteins showing downregulation in preterm pigs, including proteins related to intestinal structure and actin filaments, stress response, protein processing, and nutrient metabolism., Conclusions: Despite that enteral feeding induces rapid gut tropic response in both term and preterm neonates, the expression level of cellular proteins related to mucosal integrity, metabolism, and stress response differed markedly (including complement 3, prohibitin, ornithine carbamoyltransferase, and arginosuccinate synthetase). These proteins may play a role in the development of functional gut disorders and NEC in preterm neonates.

Background: The anthracycline doxorubicin is an effective chemotherapeutic agent used to treat pediatric cancers but is associated with cardiotoxicity that can manifest many years after the initial exposure. To date, very little is known about the mechanism of this late-onset cardiotoxicity., Methods and Results: To understand this problem, we developed a pediatric model of late-onset doxorubicin-induced cardiotoxicity in which juvenile mice were exposed to doxorubicin, using a cumulative dose that did not induce acute cardiotoxicity. These mice developed normally and had no obvious cardiac abnormalities as adults. However, evaluation of the vasculature revealed that juvenile doxorubicin exposure impaired vascular development, resulting in abnormal vascular architecture in the hearts with less branching and decreased capillary density. Both physiological and pathological stress induced late-onset cardiotoxicity in the adult doxorubicin-treated mice. Moreover, adult mice subjected to myocardial infarction developed rapid heart failure, which correlated with a failure to increase capillary density in the injured area. Progenitor cells participate in regeneration and blood vessel formation after a myocardial infarction, but doxorubicin-treated mice had fewer progenitor cells in the infarct border zone. Interestingly, doxorubicin treatment reduced proliferation and differentiation of the progenitor cells into cells of cardiac lineages., Conclusions: Our data suggest that anthracycline treatment impairs vascular development as well as progenitor cell function in the young heart, resulting in an adult heart that is more susceptible to stress.

Rationale: Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis., Objective: Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis., Methods and Results: Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-alpha, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation., Conclusions: Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease.

Objectives: Human thymus can be infected by HIV-1 with potential consequences on immune regeneration and homeostasis. We previously showed that CD4 thymocytes preferentially replicate CXCR4 tropic (X4) HIV-1 dependently on interleukin (IL)-7. Here we addressed the susceptibility of thymic dendritic cells (DC) to HIV-1 infection., Methods: We investigated the replication ability of CXCR4 or CCR5 (R5) tropic HIV-1 in thymic micro-explants as well as in isolated thymic CD11clowCD14- DC, CD11chighCD14+ DC and plasmacytoid DC subsets., Results: Thymic tissue was productively infected by both X4 and R5 viruses. However, X4 but not R5 HIV-1 replication was enhanced by IL-7 in thymic micro-explants, suggesting that R5 virus replication occurred in cells other than thymocytes. Indeed, we found that R5 HIV-1 replicated efficiently in DC isolated from thymic tissue. The replicative capacity of X4 and R5 viruses differed according to the different DC subsets. R5 but not X4 HIV-1 efficiently replicated in CD11chighCD14+ DC. In contrast, no HIV-1 replication was detected in CD11clowCD14- DC. Both X4 and R5 viruses efficiently replicated in plasmacytoid DC, which secreted interferon-alpha upon HIV-1 exposure. Productive HIV-1 infection also caused DC loss, consistent with different permissivity of each DC subset., Conclusions: Thymic DC sustain high levels of HIV-1 replication. DC might thus be the first target for R5 HIV-1 infection of thymus, acting as a Trojan horse for HIV-1 spread to thymocytes. Furthermore, DC death induced by HIV-1 infection may affect thymopoiesis.

Background: Several sources have attributed the vulnerability of the abducens nerve to its long intracranial course. However, other anatomic factors likely contribute to the apparent vulnerability of the abducens nerve to mass lesions and trauma., Methods: The authors performed a two-part anatomic study of the abducens nerve. In the first part of the study, they compared the length of the abducens with another cranial nerve, the trochlear, at the autopsy of 26 pediatric patients. In the second part of the study, the authors used an endoscopic exposure of these two cranial nerves in a preserved human cadaver head., Results: The abducens nerve was consistently approximately one-third the length of the trochlear nerve at all ages that they studied. The endoscopic views revealed the structural and vascular relationships of the abducens nerve in situ., Conclusions: The authors conclude from these findings and the literature that abducens nerve vulnerability results from factors other than its intracranial length.

Study Design: In Study 1 the authors measured the vertical and sagittal dimensions of the intervertebral foramen in dried lumbar vertebrae. In Study 2 the dimensions of the intervertebral foramen were measured in fresh cadaveric spines in which the soft tissues forming the foraminal walls were preserved., Objectives: To investigate whether disc narrowing, or other factors related to the morphometry of lumbar vertebrae, may predispose to foraminal stenosis., Summary of Background Data: Predisposing factors to foraminal stenosis have been little investigated. Previous studies suggested that narrowing of the disc space might cause a reduction in the foraminal dimensions; however, it is not clear whether such a reduction is to such an extent as to compress the nerve root within the foramen., Methods: In Study 1 the vertical and sagittal dimensions of 160 intervertebral foramens were measured on dried white spines. Measurements were performed in the presence of a normal height of the disc space, obtained using a silicone rubber disc, and repeated in the same specimen after disc removal. Foraminal dimensions were then related to the sagittal diameter of the spinal canal and the pedicle length. In Study 2, the authors evaluated the dimensions of 50 intervertebral foramens of fresh cadaveric spines, in which the soft tissues forming the foraminal walls and the nerve root were preserved. In specimens showing normal or slightly decreased disc height, the foraminal dimensions were measured before and after disc excision., Results: In Study 1 the reduction in the foraminal height after disc removal was, on average, 6.5 mm (P < 0.0001). In both Studies 1 and 2 the sagittal dimensions of the foramen were not significantly reduced after disc removal. No significant difference was found in Study 1 in the sagittal dimensions of the foramen between specimens showing normal or degenerated facet joints. In Study 2 a compression of the nerve root within the foramen was found in one specimen, showing a concomitant central stenosis at multiple levels. A significant correlation was found between the sagittal diameters of the foramen and the sagittal diameter of the spinal canal and the pedicle length., Conclusions: Narrowing of the disc space significantly reduces the vertical diameter of the foramen but has no significant effects on its sagittal dimensions. In contrast, the sagittal dimensions of the foramen are strictly related to the sagittal diameter of the spinal canal and the pedicle length. These results suggest that in patients with developmental or combined stenosis of the central spinal canal, a concomitant foraminal stenosis is likely to be present, or at least should be suspected.