Application of resting state functional connectivity magnetic resonance imaging (fcMRI) to the study of prematurely born infants enables assessment of the earliest forms of cerebral connectivity and characterization of its early development in the human brain. We obtained 90 longitudinal fcMRI data sets from a cohort of preterm infants aged from 26 weeks postmenstrual age (PMA) through term equivalent age at PMA-specific time points. Utilizing seed-based correlation analysis, we identified resting state networks involving varied cortical regions, the thalamus, and cerebellum. Identified networks demonstrated a regionally variable age-specific pattern of development, with more mature forms consisting of localized interhemispheric connections between homotopic counterparts. Anatomical distance was found to play a critical role in the rate of connection development. Prominent differences were noted between networks identified in term control versus premature infants at term equivalent, including in the thalamocortical connections critical for neurodevelopment. Putative precursors of the default mode network were detected in term control infants but were not identified in preterm infants, including those at term equivalent. Identified patterns of network maturation reflect the intricate relationship of structural and functional processes present throughout this important developmental period and are consistent with prior investigations of neurodevelopment in this population.

SUMMARY: PTC is a clinical entity of uncertain etiology characterized by intracranial hypertension. The syndrome classically manifests with headaches and visual changes in women with obesity. Traditionally, imaging ruled out secondary causes of elevated CSF pressure but now may reveal findings frequently seen in patients with PTC, including the following: flattening of the globe, an empty sella, an enlarged ONS, protrusion and enhancement of the optic nerve head, and increased tortuosity of the optic nerve. Novel imaging methods, including MR venography, have additionally identified sinovenous stenosis as a potential indicator of PTC.ABBREVIATIONS: BMI ϭ body-mass index; CN ϭ cranial nerve; HIV ϭ human immunodeficiency virus; ICP ϭ intracranial pressure; IIH ϭ idiopathic intracranial hypertension; ISF ϭ interstitial fluid; MRI ϭ MR imaging; ONS ϭ optic nerve sheath; ONSF ϭ optic nerve sheath fenestration; IOP ϭ intraocular pressure; PCOS ϭ polycystic ovary syndrome; PTC ϭ pseudotumor cerebri syndrome

SUMMARY: Papilledema, defined as swelling of the optic disc, frequently occurs in the setting of increased ICP and in a variety of medical conditions, including pseudotumor cerebri, sinus thrombosis, intracerebral hemorrhage, frontal lobe neoplasms, and Chiari malformation. Noninvasive imaging of the ON is possible by using MR imaging, with a variety of findings occurring in the setting of papilledema, including flattening of the posterior sclera, protrusion of the optic disc, widening of the ONS, and tortuosity of the ON. Early recognition of papilledema and elevated ICP is of paramount importance for ensuring restoration of vision. Newer advanced MR imaging techniques such as fMRI and DTI may prove useful in the future to assess the potential effects of papilledema on retinal and visual pathway integrity.ABBREVIATIONS: ICP ϭ intracranial pressure; IIH ϭ idiopathic intracranial hypertension; ON ϭ optic nerve; ONS ϭoptic nerve sheath; SAS ϭ subarachnoid space

Rationale: Sepsis-related mortality results in part from immunodeficiency secondary to profound lymphoid apoptosis. The biological mechanisms responsible are not understood.Objectives: Because recent evidence shows that platelets are involved in microvascular inflammation and that they accumulate in lymphoid microvasculature in sepsis, we hypothesized a direct role for platelets in sepsis-related lymphoid apoptosis. Methods: We studied megakaryocytes and platelets from a murineinduced sepsis model, with validation in septic children, which showed induction of the cytotoxic serine protease granzyme B. Measurements and Main Results: Platelets from septic mice induced marked apoptosis of healthy splenocytes ex vivo. Platelets from septic granzyme B null (2/2) mice showed no lymphotoxicity. Conclusions: Our findings establish a conceptual advance in sepsis: Septic megakaryocytes produce platelets with acutely altered mRNA profiles, and these platelets mediate lymphotoxicity via granzyme B. Given the contribution of lymphoid apoptosis to sepsis-related mortality, modulation of platelet granzyme B becomes an important new target for investigation and therapy.

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ObjectiveIntraplaque hemorrhage is an increasingly recognized contributor to plaque instability. Neovascularization of plaque is believed to facilitate the entry of inflammatory and red blood cells (RBC). Under physiological conditions, neovessels are subject to mechanical loading from the deformation of atherosclerotic plaque by blood pressure and flow. Local mechanical environments around neovessels and their relevant pathophysiologic significance have not yet been examined.Methods and resultsFour carotid plaque samples removed at endarcterectomy were collected for histopathological examination. Neovessels and other components were manually segmented to build numerical models for mechanical analysis. Each component was assumed to be non-linear isotropic, piecewise homogeneous and incompressible. The results indicated that local maximum principal stress and stretch and their variations during one cardiac cycle were greatest around neovessels. Neovessels surrounded by RBC underwent a much larger stretch during systole than those without RBCs present nearby (median [inter quartile range]; 1.089 [1.056, 1.131] vs. 1.034 [1.020, 1.067]; p < 0.0001) and much larger stress (5.3 kPa [3.4, 8.3] vs. 3.1 kPa [1.6, 5.5]; p < 0.0001) and stretch (0.0282 [0.0190, 0.0427] vs. 0.0087 [0.0045, 0.0185]; p < 0.0001) variations during the cardiac cycle.ConclusionsLocal critical mechanical conditions may lead to the rupture of neovessels resulting in the formation and expansion of intraplaque hemorrhage.

SUMMARY: GABA serves as a major neurotransmitter of the brain and functions mainly to inhibit neural excitatory activity. Disruption of the GABAergic processes appears to occur in various neurologic and psychiatric conditions, including epilepsy, mood disorders, motor disorders such as focal dystonia and stiff-person syndrome, sleep disorders, neuroplasticity, and drug and alcohol dependence. These concentration differences may be ascertained by using MR spectroscopy to provide information on the concentration of different metabolites. This review briefly discusses advances in MR spectroscopy methods and explores the application of this technique to detect changes in GABA due to disease processes and medication-induced effects.ABBREVIATIONS: AED ϭ antiepileptic drug; GABA ϭ ␥-aminobutyric acid; GABA A R ϭ ␥-amino butyric acid A receptor; GABA B R ϭ ␥-amino butyric acid B receptor;

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