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White N.S.,University of California at San Diego | White N.S.,Multimodal Imaging Laboratory | Dale A.M.,University of California at San Diego
Magnetic Resonance in Medicine | Year: 2014

Purpose: While many recent studies have demonstrated improved detection and characterization of malignant lesions using high b-value diffusion imaging techniques, little is known about the underlying physical characteristics of tumor cells that modulate the restricted water signal at high b on clinical scanners.Methods: Monte Carlo simulations of diffusion in a synthetic tumor cell environment were used to study the specific effects of tumor cell diameter and nuclear volume fraction (m) on high b diffusion contrast.Results: Results indicate that clinical pulsed-gradient spinecho diffusion-weighted signals measured at high b (Δ4000 s/ mm2), long diffusion time (Δ ∼40-60 ms), and long echo time (TE ∼60-140 ms) are generally insensitive to tumor cell diameter, but increase exponentially with m. Moreover, these results are predicted by a simple analytic expression for the intracellular restricted water signal with elevated T2 for the intranuclear versus cytosolic compartment.Conclusion: Nuclear volume fraction is an important characteristic of cancer cells that modulates the apparent restriction of water at high b on clinical scanners. This model offers a possible explanation for the apparent unreliable correlation between tumor cell density (cellularity) and traditional ADC. © 2013 Wiley Periodicals, Inc. Source


McDonald C.R.,Multimodal Imaging Laboratory | McDonald C.R.,University of California at San Diego | Hagler D.J.,University of California at San Diego | Girard H.M.,University of California at San Diego | And 9 more authors.
Neurology | Year: 2010

Objective: To investigate postoperative changes in fiber tract integrity in patients with temporal lobe epilepsy (TLE) following anterior temporal lobectomy (ATL) and to determine whether postoperative changes are 1) stable vs progressive and 2) related to visual field defects. Methods: Diffusion tensor imaging (DTI) was obtained in 7 patients with TLE before, 2 months after, and 1 year after ATL. Changes in fractional anisotropy (FA) were evaluated in a whole-brain voxel-wise analysis, as well within specific fiber tracts. Repeated-measures analysis of variance was performed to examine the time course of FA changes within ipsilateral and contralateral fiber tracts. Quantitative visual field analysis was performed to determine whether decreases in regional FA were related to the extent or location of visual field defects. Results: Patients showed decreased FA 2 months post-ATL in ipsilateral fiber tracts transected during surgery (parahippocampal cingulum, uncinate fasciculus, inferior longitudinal fasciculus, and fornix), as well as in fiber tracts not directly transected (inferior fronto-occipital fasciculus and corpus callosum). Additional decreases in FA were not observed from 2 months to 1 year post-ATL. Visual field defects in most patients were characterized by incomplete quadrantanopsias. However, FA reductions in one patient extended into temporo-occipital cortex and the splenium of the corpus callosum and were associated with a complete hemianopia. Conclusions: Wallerian degeneration is apparent 2 months following unilateral ATLs in ipsilateral fibers directly and indirectly affected during surgery. These changes do not appear to progress over the course of a year, but may correlate with the nature and extent of postoperative visual field defects. Copyright © 2010 by AAN Enterprises, Inc. All rights reserved. Source


Chan A.M.,Medical Engineering and Medical Physics | Dykstra A.R.,Harvard-MIT Division of Health Sciences and Technology | Jayaram V.,Harvard University | Leonard M.K.,Multimodal Imaging Laboratory | And 5 more authors.
Cerebral cortex (New York, N.Y. : 1991) | Year: 2014

How the brain extracts words from auditory signals is an unanswered question. We recorded approximately 150 single and multi-units from the left anterior superior temporal gyrus of a patient during multiple auditory experiments. Against low background activity, 45% of units robustly fired to particular spoken words with little or no response to pure tones, noise-vocoded speech, or environmental sounds. Many units were tuned to complex but specific sets of phonemes, which were influenced by local context but invariant to speaker, and suppressed during self-produced speech. The firing of several units to specific visual letters was correlated with their response to the corresponding auditory phonemes, providing the first direct neural evidence for phonological recoding during reading. Maximal decoding of individual phonemes and words identities was attained using firing rates from approximately 5 neurons within 200 ms after word onset. Thus, neurons in human superior temporal gyrus use sparse spatially organized population encoding of complex acoustic-phonetic features to help recognize auditory and visual words. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. Source


Andreassen O.A.,University of Oslo | McEvoy L.K.,Multimodal Imaging Laboratory | McEvoy L.K.,University of California at San Diego | Wang Y.,University of Oslo | And 15 more authors.
Hypertension | Year: 2014

Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affected by environmental factors, but has a strong heritable component. Despite recent large genome-wide association studies, few genetic risk factors for blood pressure have been identified. Epidemiological studies suggest associations between blood pressure and several diseases and traits, which may partly arise from a shared genetic basis (genetic pleiotropy). Using genome-wide association studies summary statistics and a genetic pleiotropy-informed conditional false discovery rate method, we systematically investigated genetic overlap between systolic blood pressure (SBP) and 12 comorbid traits and diseases. We found significant enrichment of single nucleotide polymorphisms associated with SBP as a function of their association with body mass index, low-density lipoprotein, waist/hip ratio, schizophrenia, bone mineral density, type 1 diabetes mellitus, and celiac disease. In contrast, the magnitude of enrichment due to shared polygenic effects was smaller with the other phenotypes (triglycerides, high-density lipoproteins, type 2 diabetes mellitus, rheumatoid arthritis, and height). Applying the conditional false discovery rate method to the enriched phenotypes, we identified 62 loci associated with SBP (false discovery rate <0.01), including 42 novel loci. The observed polygenic overlap between SBP and several related disorders indicates that the epidemiological associations are not mediated solely via lifestyle factors but also reflect an etiologic relation that warrants further investigation. The new gene loci identified implicate novel genetic mechanisms related to lipid biology and the immune system in SBP. © 2014 American Heart Association, Inc. Source


Ferjan Ramirez N.,Multimodal Imaging Laboratory | Leonard M.K.,Multimodal Imaging Laboratory | Torres C.,Multimodal Imaging Laboratory | Halgren E.,University of California at San Diego
Cerebral cortex (New York, N.Y. : 1991) | Year: 2014

The relation between the timing of language input and development of neural organization for language processing in adulthood has been difficult to tease apart because language is ubiquitous in the environment of nearly all infants. However, within the congenitally deaf population are individuals who do not experience language until after early childhood. Here, we investigated the neural underpinnings of American Sign Language (ASL) in 2 adolescents who had no sustained language input until they were approximately 14 years old. Using anatomically constrained magnetoencephalography, we found that recently learned signed words mainly activated right superior parietal, anterior occipital, and dorsolateral prefrontal areas in these 2 individuals. This spatiotemporal activity pattern was significantly different from the left fronto-temporal pattern observed in young deaf adults who acquired ASL from birth, and from that of hearing young adults learning ASL as a second language for a similar length of time as the cases. These results provide direct evidence that the timing of language experience over human development affects the organization of neural language processing. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. Source

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