Publications by authors named "Daniel M Sforza"

12 Publications

  • Page 1 of 1

Hemodynamics in growing and stable cerebral aneurysms.

J Neurointerv Surg 2016 Apr 4;8(4):407-12. Epub 2015 Feb 4.

Center for Computational Fluid Dynamics, College of Sciences, George Mason University, Fairfax, Virginia, USA.

Objective: The detailed mechanisms of cerebral aneurysm evolution are poorly understood but are important for objective aneurysm evaluation and improved patient management. The purpose of this study was to identify hemodynamic conditions that may predispose aneurysms to growth.

Methods: A total of 33 intracranial unruptured aneurysms longitudinally followed with three-dimensional imaging were studied. Patient-specific computational fluid dynamics models were constructed and used to quantitatively characterize the hemodynamic environments of these aneurysms. Hemodynamic characteristics of growing (n=16) and stable (n=17) aneurysms were compared. Logistic regression statistical models were constructed to test the predictability of aneurysm growth by hemodynamic features.

Results: Growing aneurysms had significantly smaller shear rate ratios (p=0.01), higher concentration of wall shear stress (p=0.03), smaller vorticity ratios (p=0.01), and smaller viscous dissipation ratios (p=0.01) than stable aneurysms. They also tended to have larger areas under low wall shear stress (p=0.06) and larger aspect ratios (p=0.18), but these trends were not significant. Mean wall shear stress was not significantly different between growing and stable aneurysms. Logistic regression models based on hemodynamic variables were able to discriminate between growing and stable aneurysms with a high degree of accuracy (94-100%).

Conclusions: Growing aneurysms tend to have complex intrasaccular flow patterns that induce non-uniform wall shear stress distributions with areas of concentrated high wall shear stress and large areas of low wall shear stress. Statistical models based on hemodynamic features seem capable of discriminating between growing and stable aneurysms.
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http://dx.doi.org/10.1136/neurintsurg-2014-011339DOI Listing
April 2016

Analysis of hemodynamics and wall mechanics at sites of cerebral aneurysm rupture.

J Neurointerv Surg 2015 Jul 14;7(7):530-6. Epub 2014 May 14.

Department of Interventional Neuroradiology, Inova Fairfax Hospital, Falls Church, Virginia, USA.

Background: It is thought that aneurysms evolve as the result of progressive degradation of the wall in response to abnormal hemodynamics characterized by either high or low wall shear stress (WSS).

Objective: To investigate the effects of these two different hemodynamic pathways in a series of cerebral aneurysms with known rupture sites.

Methods: Nine aneurysms in which the rupture site could be identified in three-dimensional images were analyzed. The WSS distribution was obtained from computational fluid dynamics (CFD) simulations. Internal wall stresses were computed using structural wall models under hemodynamic loads determined by the CFD models. Wall properties (thickness and stiffness) were modulated with the WSS distribution (increased or decreased in regions of high or low WSS) to test possible wall degradation pathways. Rupture probability indices (RPI) were calculated to compare different wall models.

Results: Most rupture sites aligned with the intrasaccular flow stream and downstream of the primary impaction zone. The model that best explained the rupture site (produced higher RPI) in eight of the nine aneurysms (89%) had thinner and stiffer walls in regions of abnormally high WSS. The remaining case (11%) was best explained by a model with thinner and stiffer walls in regions of abnormally low WSS.

Conclusions: Aneurysm rupture seems to be caused by localized degradation and weakening of the wall in response to abnormal hemodynamics. Image-based computational models assuming wall thinning and stiffening in regions of abnormally high WSS were able to explain most of the observed rupture sites.
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http://dx.doi.org/10.1136/neurintsurg-2014-011247DOI Listing
July 2015

Computational fluid dynamics in brain aneurysms.

Int J Numer Method Biomed Eng 2012 Jun-Jul;28(6-7):801-8. Epub 2011 Nov 28.

Center for Computational Fluid Dynamics, School of Physics, Astronomy and Computational Sciences, George Mason University, 4400 University Drive, MSN 6A2, Fairfax, VA 22030, USA.

Because of its ability to deal with any geometry, image-based computational fluid dynamics (CFD) has been progressively used to investigate the role of hemodynamics in the underlying mechanisms governing the natural history of cerebral aneurysms. Despite great progress in methodological developments and many studies using patient-specific data, there are still significant controversies about the precise governing processes and divergent conclusions from apparently contradictory results. Sorting out these issues requires a global vision of the state of the art and a unified approach to solving this important scientific problem. Towards this end, this paper reviews the contributions made using patient-specific CFD models to further the understanding of these mechanisms, and highlights the great potential of patient-specific computational models for clinical use in the assessment of aneurysm rupture risk and patient management.
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http://dx.doi.org/10.1002/cnm.1481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221804PMC
July 2015

Hemodynamic Analysis of Intracranial Aneurysms with Moving Parent Arteries: Basilar Tip Aneurysms.

Int J Numer Method Biomed Eng 2010 Oct;26(10):1219-1227

The effects of parent artery motion on the hemodynamics of basilar tip saccular aneurysms and its potential effect on aneurysm rupture were studied.The aneurysm and parent artery motions in two patients were determined from cine loops of dynamic angiographies. The oscillatory motion amplitude was quantified by registering the frames. Patient-specific computational fluid dynamics (CFD) models of both aneurysms were constructed from 3D rotational angiography images. Two CFD calculations were performed for each patient, corresponding to static and moving models. The motion estimated from the dynamic images was used to move the surface grid points in the moving model. Visualizations from the simulations were compared for wall shear stress (WSS), velocity profiles, and streamlines.In both patients a rigid oscillation of the aneurysm and basilar artery in the anterio-posterior direction was observed and measured. The distribution of WSS was nearly identical between the models of each patient, as well as major intra-aneurysmal flow structures, inflow jets, and regions of impingement.The motion observed in pulsating intracranial vasculature does not have a major impact on intra-aneurysmal hemodynamic variables. Parent artery motion is unlikely to be a risk factor for increased risk of aneurysmal rupture.
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http://dx.doi.org/10.1002/cnm.1385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990194PMC
October 2010

Hemodynamics of Cerebral Aneurysms.

Annu Rev Fluid Mech 2009 Jan;41:91-107

Center for Computational Fluid Dynamics, George Mason University, Fairfax, Virginia 22030.

The initiation and progression of cerebral aneurysms are degenerative processes of the arterial wall driven by a complex interaction of biological and hemodynamic factors. Endothelial cells on the artery wall respond physiologically to blood-flow patterns. In normal conditions, these responses are associated with nonpathological tissue remodeling and adaptation. The combination of abnormal blood patterns and genetics predisposition could lead to the pathological formation of aneurysms. Here, we review recent progress on the basic mechanisms of aneurysm formation and evolution, with a focus on the role of hemodynamic patterns.
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http://dx.doi.org/10.1146/annurev.fluid.40.111406.102126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750901PMC
January 2009

Mitochondrial dysfunction, oxidative stress, and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson's disease.

J Proteome Res 2008 Feb;7(2):666-77

Department of Molecular and Medical Pharmacology, Human Genetics, Laboratory of NeuroImaging, Department of Neurology, and Surgery, David Geffen School of Medicine at University of California-Los Angeles (UCLA), Los Angeles, California 90095, USA.

The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson's disease (PD) are not completely understood. Here, we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 86 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA, following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response, and apoptosis. These results constitute one of the largest descriptive data sets integrating protein and transcript changes for these neurotoxin models with many similar end point phenotypes but distinct mechanisms.
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http://dx.doi.org/10.1021/pr070546lDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319057PMC
February 2008

Genetic program of neuronal differentiation and growth induced by specific activation of NMDA receptors.

Neurochem Res 2007 Feb 27;32(2):363-76. Epub 2006 Dec 27.

Mental Retardation Research Center, Jane and Terry Semel Institute for Neuroscience and Human Behaviour, Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.

Glutamate and its receptors are expressed very early during development and may play important roles in neurogenesis, synapse formation and brain wiring. The levels of glutamate and activity of its receptors can be influenced by exogenous factors, leading to neurodevelopmental disorders. To investigate the role of NMDA receptors on gene regulation in a neuronal model, we used primary neuronal cultures developed from embryonic rat cerebri in serum-free medium. Using Affymetrix Gene Arrays, we found that genes known to be involved in neuronal plasticity were differentially expressed 24 h after a brief activation of NMDA receptors. The upregulation of these genes was accompanied by a sustained induction of CREB phosphorylation, and an increase in synaptophysin immunoreactivity. We conclude that NMDA receptor activation elicits expression of genes whose downstream products are involved in the regulation of early phases of the process leading to synaptogenesis and its consolidation, at least in part through sustained CREB phosphorylation.
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http://dx.doi.org/10.1007/s11064-006-9213-9DOI Listing
February 2007

Gene expression is differentially regulated by neurotransmitters in embryonic neuronal cortical culture.

J Neurochem 2006 Apr;97 Suppl 1:35-43

Mental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7332, USA.

Neurotransmitters and their receptors have been involved in both proper brain development and neurodevelopmental disorders. The role that nicotinic receptors play in immature cortical neurons was initially investigated by gene profiling using Affymetrix DNA arrays. Both short (15 min) and prolonged (18 h) treatments with nicotine did not induce modification in gene expression, whereas a significant down-regulation of c-fos protein levels was observed after 18 h treatment. Conversely, a brief treatment with the glutamatergic agonist NMDA triggered up-regulation of immediate early genes and transcription factors, which remained unaffected by pre-treatment for 18 h with nicotine. Calcium imaging studies revealed that NMDA activated a sustained increase in intracellular calcium concentration in the majority of neurons, whereas nicotine evoked only a transient calcium increase in a smaller percentage of neurons, suggesting that the calcium signalling response was correlated with activation of gene expression. Nicotine effects on immature cortical neurons perhaps do not require gene regulation but may be still acting on signalling pathways.
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http://dx.doi.org/10.1111/j.1471-4159.2006.03713.xDOI Listing
April 2006

Development and evaluation of a micro- and nanoscale proteomic sample preparation method.

J Proteome Res 2005 Nov-Dec;4(6):2397-403

Biological Sciences Division, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.

Challenges associated with the efficient and effective preparation of micro- and nanoscale (micro- and nanogram) clinical specimens for proteomic applications include the unmitigated sample losses that occur during the processing steps. Herein, we describe a simple "single-tube" preparation protocol appropriate for small proteomic samples using the organic cosolvent, trifluoroethanol (TFE) that circumvents the loss of sample by facilitating both protein extraction and protein denaturation without requiring a separate cleanup step. The performance of the TFE-based method was initially evaluated by comparisons to traditional detergent-based methods on relatively large scale sample processing using human breast cancer cells and mouse brain tissue. The results demonstrated that the TFE-based protocol provided comparable results to the traditional detergent-based protocols for larger, conventionally sized proteomic samples (>100 microg protein content), based on both sample recovery and numbers of peptide/protein identifications. The effectiveness of this protocol for micro- and nanoscale sample processing was then evaluated for the extraction of proteins/peptides and shown effective for small mouse brain tissue samples (approximately 30 microg total protein content) and also for samples of approximately 5000 MCF-7 human breast cancer cells (approximately 500 ng total protein content), where the detergent-based methods were ineffective due to losses during cleanup and transfer steps.
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http://dx.doi.org/10.1021/pr050160fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781925PMC
February 2006

Anatomical methods for voxelation of the mammalian brain.

Neurochem Res 2004 Jun;29(6):1299-306

Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles, California 90095-1735, USA.

Voxelation allows high-throughput acquisition of three-dimensional gene expression patterns in the brain through analysis of spatially registered voxels (cubes). The method results in multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging techniques. An important issue for voxelation is the development of approaches to anchor correctly harvested voxels to the underlying anatomy. Here, we describe experiments to identify fixation and cryopreservation protocols for improved registration of harvested voxels with neuroanatomical structures. Paraformaldehyde fixation greatly reduced RNA recovery as judged by ribosomal RNA abundance. However, gene expression signals from paraformaldehyde-fixed samples were not appreciably diminished as judged by average signal-noise ratios from microarrays, highlighting the difficulties of accurate quantitation of cross-linked RNA. Additional use of cryoprotection helped to improve further RNA recovery and signal from fixed tissue. It appears that the best protocol to provide the necessary resolution of neuroanatomical information in voxelation entails a controlled dose of fixation and thorough cryoprotection, complemented by histological staining.
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http://dx.doi.org/10.1023/b:nere.0000023616.67996.00DOI Listing
June 2004

Voxelation methods for genome scale imaging of brain gene expression.

Methods Enzymol 2004 ;386:314-23

Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095, USA.

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http://dx.doi.org/10.1016/S0076-6879(04)86015-4DOI Listing
June 2004

High-resolution voxelation mapping of human and rodent brain gene expression.

J Neurosci Methods 2003 May;125(1-2):93-101

Department of Molecular and Medical Pharmacology, UCLA School of Medicine, 23-120 CHS, 90095-1735, Los Angeles, CA, USA.

Voxelation allows high-throughput acquisition of multiple volumetric images of brain gene expression, similar to those obtained from biomedical imaging systems. To obtain these images, the method employs analysis of spatially registered voxels (cubes). For creation of high-resolution maps using voxelation, relatively small voxel sizes are necessary and instruments will be required for semiautomated harvesting of such voxels. Here, we describe two devices that allow spatially registered harvesting of voxels from the human and rodent brain, giving linear resolutions of 3.3 and 1 mm, respectively. Gene expression patterns obtained using these devices showed good agreement with known expression patterns. The voxelation instruments and their future iterations represent a valuable approach to the genome scale acquisition of gene expression patterns in the human and rodent brain.
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http://dx.doi.org/10.1016/s0165-0270(03)00045-1DOI Listing
May 2003