Orbital neoplasms in adults may be categorized on the basis of location and histologic type. Imaging features of these lesions often reflect their tissue composition. Cavernous malformations (also known as cavernous hemangiomas), although not true neoplasms, are the most common benign adult orbital tumor. They typically appear as a well-circumscribed, ovoid intraconal mass on cross-sectional images. Lymphoma, which may be primary or secondary to systemic disease, is the most prevalent orbital neoplasm in older adults (≥60 years of age). Choroidal melanoma is the most common primary adult ocular malignancy. Melanin has intrinsic T1 and T2 shortening effects, classically manifesting with hyperintense signal on T1-weighted magnetic resonance (MR) images and with hypointense signal on T2-weighted images. However, amelanotic or mildly pigmented lesions of melanoma do not demonstrate these characteristic MR imaging features. Breast cancer is the most common malignancy to metastasize to the orbit, followed by prostate cancer, melanoma, and lung cancer. In women with bilateral enophthalmos, metastatic scirrhous breast cancer should be considered in the differential diagnosis. Neoplasms that arise from the optic nerve or its sheath include glioma and meningioma. At imaging, gliomas often cause fusiform expansion of the optic nerve, in which the nerve itself cannot be delineated from the lesion. In contrast, meningiomas classically have a "tram-track" configuration, whereby the contrast-enhancing tumor is seen alongside the optic nerve. Neoplasms that derive from peripheral nerves include schwannoma and neurofibroma, the latter of which is associated with neurofibromatosis type 1. MR imaging is particularly valuable for evaluation of orbital neoplasms, as it provides critical anatomic information about ocular structures involved, perineural spread, and intracranial extension.

Summary Albright hereditary osteodystrophy is a monogenic obesity disorder due to heterozygous mutations of Gsα, the G protein which mediates receptor-stimulated cAMP generation, in which obesity only develops when the mutation is on the maternal allele. Likewise, mice with maternal (but not paternal) germline Gsα mutation develop obesity, insulin resistance, and diabetes. These parent-of-origin effects are due to Gsα imprinting with preferential expression from the maternal allele in some tissues. As Gsα is ubiquitously expressed, the tissue involved in this metabolic imprinting effect is unknown. Using brain-specific Gsα knockout mice we show that Gsα imprinting within the central nervous system underlies these effects and that Gsα is imprinted in the paraventricular nucleus of the hypothalamus. Maternal Gsα mutation impaired melanocortin stimulation of energy expenditure but did not affect melanocortin's effect on food intake, suggesting that melanocortins may regulate energy balance in the central nervous system through both Gsα-dependent and -independent pathways.

PurposeTo investigate optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique.DesignCross-sectional, observational study.SubjectsTwenty-eight normal, 30 POAG, and 31 NTG subjects.MethodsOne eye from each subject was scanned with a 68 kHz Cirrus HD-OCT 5,000-based OMAG prototype system centered at the optic nerve head (ONH) (Carl Zeiss Meditec Inc, Dublin, CA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program.Main Outcome MeasuresOptic disc perfusion, quantified as flux, vessel area density, and normalized flux (flux normalized by the vessel area) within the ONH.ResultsGlaucomatous eyes had significantly lower optic disc perfusion in preLC in all three perfusion metrics (p<0.0001) compared to normal eyes. The visual field (VF) mean deviation (MD) and pattern standard deviation (PSD) were similar between the POAG and NTG groups, and no differences in optic disc perfusion were observed between POAG and NTG. Univariate analysis revealed significant correlation between optic disc perfusion and VF MD, VF PSD, and rim area in both POAG and NTG groups (p≤0.0288). However, normalized optic disc perfusion was correlated with some structural measures (retinal nerve fiber layer thickness and ONH cup/disc ratio) only in POAG eyes.ConclusionsOptic disc perfusion detected with OMAG was significantly reduced in POAG and NTG groups compared to normal controls, but no difference was seen between POAG and NTG groups with similar levels of VF damage. Disc perfusion was significantly correlated with VF MD, VF PSD, and rim area in glaucomatous eyes. Vascular changes at the optic disc as measured using OMAG may provide useful information for diagnosis and monitoring of glaucoma.

The ubiquitously expressed G protein alpha-subunit G(s)alpha is required for receptor-stimulated intracellular cAMP responses and is an important regulator of energy and glucose metabolism. We have generated skeletal muscle-specific G(s)alpha-knockout (KO) mice (MGsKO) by mating G(s)alpha-floxed mice with muscle creatine kinase-cre transgenic mice. MGsKO mice had normal body weight and composition, and their serum glucose, insulin, free fatty acid, and triglyceride levels were similar to that of controls. However, MGsKO mice were glucose intolerant despite the fact that insulin sensitivity and glucose-stimulated insulin secretion were normal, suggesting an insulin-independent mechanism. Isolated muscles from MGsKO mice had increased basal glucose uptake and normal responses to a stimulator of AMP-activated protein kinase (AMPK), which indicates that AMPK and its downstream pathways are intact. Compared with control mice, MGsKO mice had reduced muscle mass with decreased cross-sectional area and force production. In addition, adult MGsKO mice showed an increased proportion of type I (slow-twitch, oxidative) fibers based on kinetic properties and myosin heavy chain isoforms, despite the fact that these muscles had reduced expression of peroxisome proliferator-activated receptor coactivator protein-1alpha (PGC-1alpha) and reduced mitochondrial content and oxidative capacity. Therefore G(s)alpha deficiency led to fast-to-slow fiber-type switching, which appeared to be dissociated from the expected change in oxidative capacity. MGsKO mice are a valuable model for future studies of the role of G(s)alpha signaling pathways in skeletal muscle adaptation and their effects on whole body metabolism.