Faculty Bibliography

BACKGROUND: Obesity is frequently associated with respiratory symptoms despite normal large airway function as assessed by spirometry. However, reduced functional residual capacity and expiratory reserve volume are common and might reflect distal airway dysfunction. Impulse oscillometry (IOS) might identify distal airway abnormalities not detected using routine spirometry screening. Our objective was to test the hypothesis that excess body weight will result in distal airway dysfunction detected by IOS that reverses after bariatric surgery. The setting was a university hospital. METHODS: A total of 342 subjects underwent spirometry, plethysmography, and IOS before bariatric surgery. Of these patients, 75 repeated the testing after the loss of 20% of the total body weight. The data from 47 subjects with normal baseline spirometry and complete pre- and postoperative data were analyzed. RESULTS: IOS detected preoperative distal airway dysfunction despite normal spirometry findings by an abnormal airway resistance at an oscillation frequency of 20 Hz (4.75 +/- 1.2 cm H(2)O/L/s), frequency dependence of resistance from 5 to 20 Hz (2.20 +/- 1.6 cm H(2)O/L/s), and reactance at 5 Hz (-3.47 +/- 2.1 cm H(2)O/L/s). Postoperatively, the subjects demonstrated 57% +/- 15% excess weight loss. The body mass index decreased (from 44 +/- 6 to 32 +/- 5 kg/m(2), P < .001). Improvements in functional residual capacity (from 59% +/- 11% to 75% +/- 20% predicted, P < .001) and expiratory reserve volume (from 41% +/- 20% to 75% +/- 20% predicted, P < .001) were demonstrated. Distal airway function also improved: airway resistance at an oscillation frequency of 20 Hz (3.91 +/- .9, P < .001), frequency dependence of resistance from 5 to 20 Hz (1.17 +/- .9, P < .001), and reactance at 5 Hz (-1.85 +/- .9, P < .001). CONCLUSION: The present study detected significant distal airway dysfunction despite normal preoperative spirometry findings. The effect of increased body weight was likely the main mechanism for these abnormalities. However, the inflammatory state of obesity or associated respiratory disease could also be invoked. These abnormalities improved significantly toward normal after weight loss. The results of the present study highlight the importance of bariatric surgery as an effective intervention in reversing these respiratory abnormalities.

Dairy cream is shown to be a simple, inexpensive, isotropic phantom useful for testing diffusional kurtosis imaging data acquisition and postprocessing. The MR-visible protons of cream exhibit slow and fast diffusion components, attributed to the fat and water protons, respectively, which give rise to a diffusion coefficient of 1.1 mum(2) /ms and a diffusional kurtosis of 1.2. These parameter values are similar to those observed in vivo for human brain. Heating the cream is found to increase the T(2) -relaxation time of the fat protons, which facilitates the evaluation of typical diffusional kurtosis imaging protocols used in clinical settings. The diffusion coefficient and diffusional kurtosis can both be measured directly and predicted based on the corresponding diffusion parameters of the individual water and fat components, which are independently measurable due to chemical shift misregistration, thus providing an important consistency check. This phantom is proposed as a convenient calibration standard for multicenter diffusional kurtosis imaging studies. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc

Approximately half of head and neck carcinomas arise from the oral cavity. Imaging plays an essential role in the preoperative evaluation of oral cavity carcinomas. MR imaging is particularly advantageous in the evaluation of the oral cavity, with better depiction of the anatomy in this region and reduction of dental artifacts compared with CT. MR is also the preferred imaging modality for the evaluation of bone marrow invasion and perineural tumor spread, which are findings critical for treatment planning. Advanced MR imaging techniques may potentially better delineate true tumor extent, determine lymph node metastases, and predict treatment response.

PURPOSE: To compare vascularity and angiogenic activity in aggressive and nonaggressive giant cell lesions (GCLs) of the jaws. MATERIALS AND METHODS: This is a retrospective study of 14 GCLs treated at the University of California, San Francisco. Immunohistochemistry was used to determine of the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), CD34, and CD31. VEGF and bFGF expression in giant cells (GCs) and surrounding mononuclear stroma was classified into 1) high immunoreactivity (>50% staining) and 2) low immunoreactivity (<50% staining). CD31- and CD34-stained vessels were counted at 200x magnification. Clinical and radiographic records were reviewed to classify lesions as aggressive or nonaggressive. RESULTS: Of the lesions, 8 were aggressive and 6 were nonaggressive. High VEGF expression was found within the GCs in 4 of 8 aggressive lesions compared with 1 of 6 nonaggressive lesions. The stroma in both groups had low staining. High staining of the GCs for bFGF was found in 6 of 8 aggressive lesions compared with 3 of 6 nonaggressive lesions. The stroma of all aggressive cases showed high expression of bFGF compared with 3 of 6 nonaggressive cases. The aggressive group had a mean of 20.1 +/- 5.4 vessels/high-powered field (hpf) stained for CD31 compared with 11.5 +/- 5.6 vessels/hpf in the nonaggressive group. The aggressive group had 24.6 +/- 7.0 vessels/hpf stained with CD34 compared with 18.5 +/- 4.0 vessels/hpf in the nonaggressive group. CONCLUSIONS: The vascularity and level of angiogenesis within aggressive GCLs are higher than those in nonaggressive lesions.

Synchronized spontaneous firing among retinal ganglion cells (RGCs), on timescales faster than visual responses, has been reported in many studies. Two candidate mechanisms of synchronized firing include direct coupling and shared noisy inputs. In neighboring parasol cells of primate retina, which exhibit rapid synchronized firing that has been studied extensively, recent experimental work indicates that direct electrical or synaptic coupling is weak, but shared synaptic input in the absence of modulated stimuli is strong. However, previous modeling efforts have not accounted for this aspect of firing in the parasol cell population. Here we develop a new model that incorporates the effects of common noise, and apply it to analyze the light responses and synchronized firing of a large, densely-sampled network of over 250 simultaneously recorded parasol cells. We use a generalized linear model in which the spike rate in each cell is determined by the linear combination of the spatio-temporally filtered visual input, the temporally filtered prior spikes of that cell, and unobserved sources representing common noise. The model accurately captures the statistical structure of the spike trains and the encoding of the visual stimulus, without the direct coupling assumption present in previous modeling work. Finally, we examined the problem of decoding the visual stimulus from the spike train given the estimated parameters. The common-noise model produces Bayesian decoding performance as accurate as that of a model with direct coupling, but with significantly more robustness to spike timing perturbations.

The CA3 and CA1 pyramidal neurons are the major principal cell types of the hippocampus proper. The strongly recurrent collateral system of CA3 cells and the largely parallel-organized CA1 neurons suggest that these regions perform distinct computations. However, a comprehensive comparison between CA1 and CA3 pyramidal cells in terms of firing properties, network dynamics, and behavioral correlations is sparse in the intact animal. We performed large-scale recordings in the dorsal hippocampus of rats to quantify the similarities and differences between CA1 (n > 3,600) and CA3 (n > 2,200) pyramidal cells during sleep and exploration in multiple environments. CA1 and CA3 neurons differed significantly in firing rates, spike burst propensity, spike entrainment by the theta rhythm, and other aspects of spiking dynamics in a brain state-dependent manner. A smaller proportion of CA3 than CA1 cells displayed prominent place fields, but place fields of CA3 neurons were more compact, more stable, and carried more spatial information per spike than those of CA1 pyramidal cells. Several other features of the two cell types were specific to the testing environment. CA3 neurons showed less pronounced phase precession and a weaker position versus spike-phase relationship than CA1 cells. Our findings suggest that these distinct activity dynamics of CA1 and CA3 pyramidal cells support their distinct computational roles. (c) 2012 Wiley Periodicals, Inc.

Kidney stones are listed among the complications of eating disorders; however, very few cases have been reported. We present an additional case of nephrolithiasis associated with laxative abuse, including detailed results of the patient's urine metabolic profiles, in a patient with idiopathic hypercalciuria. We review the literature and provide an explanation for the paucity of cases of nephrolithiasis associated with these disorders. Despite low urine volumes resulting from extracellular fluid volume depletion and hypocitraturia resulting from hypokalemia, both of which would tend to favor the formation of kidney stones, most patients with eating disorders are likely to be protected from stone formation by the hypocalciuric effect of extracellular fluid volume depletion and increased proximal tubular sodium reabsorption. However, patients with underlying idiopathic hypercalciuria who develop eating disorders may be at increased risk of stone formation in the setting of low urine volume and therefore high supersaturation of calcium oxalate and phosphate.

PURPOSE: To assess a recently developed magnetic resonance imaging (MRI) technique called magnetic field correlation (MFC) imaging along with a conventional imaging method, the transverse relaxation rate (R2), for estimating age-related brain iron concentration in adolescents and adults. Brain region measures were compared with nonheme iron concentrations (C(PM) ) based on a prior postmortem study. MATERIALS AND METHODS: Asymmetric spin echo (ASE) images were acquired at 3T from 26 healthy individuals (16 adolescents, 10 adults). Regions of interest (ROIs) were placed in areas in which age-related iron content was estimated postmortem: globus pallidus (GP), putamen (PUT), caudate nucleus (CN), thalamus (THL), and frontal white matter (FWM). Regression and group analyses were conducted on ROI means. RESULTS: MFC and R2 displayed significant linear relationships to C(PM) when all regions were combined. Whereas MFC was significantly correlated with C(PM) for every individual region except FWM and detected significantly lower means in adolescents than adults for each region, R2 detected significant correlation and lower means for only PUT and CN. CONCLUSION: Our results support the hypothesis that MFC is sensitive to brain iron in GM regions and detects age-related iron increases known to occur from adolescence to adulthood. MFC may be more sensitive than R2 to iron-related changes occurring within specific brain regions. J. Magn. Reson. Imaging 2012;36:322-331. (c) 2012 Wiley Periodicals, Inc.

The network architecture of functional connectivity within the human brain connectome is poorly understood at the voxel level. Here, using resting state functional magnetic resonance imaging data from 1003 healthy adults, we investigate a broad array of network centrality measures to provide novel insights into connectivity within the whole-brain functional network (i.e., the functional connectome). We first assemble and visualize the voxel-wise (4 mm) functional connectome as a functional network. We then demonstrate that each centrality measure captures different aspects of connectivity, highlighting the importance of considering both global and local connectivity properties of the functional connectome. Beyond "detecting functional hubs," we treat centrality as measures of functional connectivity within the brain connectome and demonstrate their reliability and phenotypic correlates (i.e., age and sex). Specifically, our analyses reveal age-related decreases in degree centrality, but not eigenvector centrality, within precuneus and posterior cingulate regions. This implies that while local or (direct) connectivity decreases with age, connections with hub-like regions within the brain remain stable with age at a global level. In sum, these findings demonstrate the nonredundancy of various centrality measures and raise questions regarding their underlying physiological mechanisms that may be relevant to the study of neurodegenerative and psychiatric disorders.

BACKGROUND: Default network (DN) abnormalities have been identified in patients with chronic schizophrenia using "resting state" functional magnetic resonance imaging (R-fMRI). Here, we examined the integrity of the DN in patients experiencing their first episode of psychosis (FEP) compared with sex- and age-matched healthy controls. METHODS: We collected R-fMRI data from 19 FEP patients (mean age 24.9 +/- 4.8 yrs, 14 males) and 19 healthy controls (26.1 +/- 4.8 yrs, 14 males) at 3T. Following standard preprocessing, we examined the functional connectivity (FC) of two DN subsystems and the two DN hubs (P<0.0045, corrected). RESULTS: Patients with FEP exhibited abnormal FC that appeared largely restricted to the dorsomedial prefrontal cortex (dMPFC) DN subsystem. Relative to controls, FEP patients exhibited weaker positive FC between dMPFC and posterior cingulate cortex (PCC) and precuneus, extending laterally through the parietal lobe to the posterior angular gyrus. Patients with FEP exhibited weaker negative FC between the lateral temporal cortex and the intracalcarine cortex, bilaterally. The PCC and temporo-parietal junction also exhibited weaker negative FC with the right fusiform gyrus extending to the lingual gyrus and lateral occipital cortex, in FEP patients, compared to controls. By contrast, patients with FEP showed stronger negative FC between the temporal pole and medial motor cortex, anterior precuneus and posterior mid-cingulate cortex. CONCLUSIONS: Abnormalities in the dMPFC DN subsystem in patients with a FEP suggest that FC patterns are altered even in the early stages of psychosis.