Person: Savadjiev, Peter
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Savadjiev
First Name
Peter
Name
Savadjiev, Peter
9 results
Search Results
Now showing 1 - 9 of 9
Publication T201. THE STUDY OF WHITE MATTER MATURATION IN THREE POPULATIONS OF GENETIC HIGH RISK FOR SCHIZOPHRENIA INDIVIDUALS SPANNING THE DEVELOPMENTAL TIMELINE(Oxford University Press, 2018) Lyall, Amanda; Somes, Nathaniel; Zhang, Fan; Robertson, James; O’Donnell, Lauren J; Rathi, Yogesh; Pasternak, Ofer; Savadjiev, Peter; Styner, Martin; Fitzgerald, Zachary; Mesholam-Gately, Raquelle; Thermenos, Heidi; Whitfield-Gabrieli, Susan; Keshavan, Matcheri; DeLisi, Lynn; Gilmore, John; Seidman, Larry J; Kubicki, MarekAbstract Background: While the etiology of schizophrenia (SZ) is still unclear, it has been characterized as a neurodevelopmental disorder because patients exhibit deviations from normal maturational trajectories that are evident prior to the onset of psychotic symptoms. White matter (WM) has been purported to play a central role in the development of SZ, however, the timing and nature of WM changes in SZ is still poorly understood. This study uses diffusion imaging from three independent Genetic High Risk (GHR) populations spanning the developmental timeline from infancy to young adulthood. The aim of this study is to understand the extent and the time-course of WM maturational pathologies as a function of age and genetic risk for psychosis. Methods: Two datasets of 3T diffusion-weighted images of children aged 7 to 12 (24 HC and 16 at GHR) and young adults aged 19 to 29 (26 HC and 43 GHR) were collected at the Massachusetts Institute of Technology. The third dataset of 3T images of infants aged 2 years (35 HC and 18 GHR) was collected at the University of North Carolina – Chapel Hill. Whole brain two-tensor tractography was performed and 4 bilateral WM tracts (arcuate fasciculus (AF); inferior longitudinal fasciculus (ILF); cingulum bundle (CB); superior longitudinal fasciculus-ii (SLF-ii)), were extracted utilizing an atlas-guided fiber clustering algorithm. The fractional anisotropy of the tissue (FA-t) was obtained. We carried out group comparisons of FA-t between GHR and HCs utilizing Mann-Whitney-U tests and Cohen’s d effect sizes for each WM tract. Results: Preliminary analyses reveal significant reductions in FAt between GHR and HC in the right CB (p = 0.013) in the child GHR population. This is mirrored by medium to large effect sizes in the bilateral CB in GHR children (CB-left, d = 0.51; CB-right, d = 0.79). Reductions in FAt in the adult GHR population within the right CB was the largest effect observed in the adult analysis (CB-right, d = 0.46). Effect sizes in the bilateral CB were minimal in the infant GHR population (CB-left, d = 0.14, CB-right, d = 0.11). Significant decreases were also seen in the right SLF-ii in the adult GHR population (p = 0.012), but not in the infant or child GHR populations, though the reductions in FAt in the child GHR population exhibited a small effect (d = 0.35). All other white matter tracts in the adult analysis showed minor effects ranging from d = 0.033 (ILF-right) to 0.28 (ILF-left). The children and infant population also exhibited small effect sizes for all other tracts, with the child GHR dataset ranging from 0.036 (ILF-left) to 0.41 (ILF-right) and the infant GHR dataset ranging from d = 0.038 (SLF-left) to 0.34 (ILF-left). Discussion Our preliminary results suggest that abnormal WM maturation may occur in the right CB and right SLF-ii in individuals with increased genetic risk for SZ, specifically after early childhood (7 to 12 years) and into adulthood (19 to 29 years). The CB and SLF-ii are highly implicated in working memory performance, an ability that retrospective studies have shown begins to decline during the peripubertal period in those that develop SZ (~7 to 9 years). The lack of structural findings in GHR infants, may suggest that WM alterations are more likely to arise later in development, thereby possibly identifying childhood as a vulnerable period. Taken together, the preliminary results of this study provide possible evidence of subtle divergences from a healthy WM maturational trajectory in the right CB and right SLF-ii in early to late childhood that may persist into adulthood and these deviations may contribute to cognitive phenotypes described in other studies.Publication Localized abnormalities in the cingulum bundle in patients with schizophrenia: A Diffusion Tensor tractography study(Elsevier, 2014) Whitford, T; Lee, Sun Woo; Oh, Jungsu S.; de Luis-Garcia, Rodrigo; Savadjiev, Peter; Alvarado, Jorge L.; Westin, Carl-Fredrik; Niznikiewicz, Margaret; Nestor, Paul; McCarley, Robert William; Kubicki, Marek; Shenton, MarthaThe cingulum bundle (CB) connects gray matter structures of the limbic system and as such has been implicated in the etiology of schizophrenia. There is growing evidence to suggest that the CB is actually comprised of a conglomeration of discrete sub-connections. The present study aimed to use Diffusion Tensor tractography to subdivide the CB into its constituent sub-connections, and to investigate the structural integrity of these sub-connections in patients with schizophrenia and matched healthy controls. Diffusion Tensor Imaging scans were acquired from 24 patients diagnosed with chronic schizophrenia and 26 matched healthy controls. Deterministic tractography was used in conjunction with FreeSurfer-based regions-of-interest to subdivide the CB into 5 sub-connections (I1 to I5). The patients with schizophrenia exhibited subnormal levels of FA in two cingulum sub-connections, specifically the fibers connecting the rostral and caudal anterior cingulate gyrus (I1) and the fibers connecting the isthmus of the cingulate with the parahippocampal cortex (I4). Furthermore, while FA in the I1 sub-connection was correlated with the severity of patients' positive symptoms (specifically hallucinations and delusions), FA in the I4 sub-connection was correlated with the severity of patients' negative symptoms (specifically affective flattening and anhedonia/asociality). These results support the notion that the CB is a conglomeration of structurally interconnected yet functionally distinct sub-connections, of which only a subset are abnormal in patients with schizophrenia. Furthermore, while acknowledging the fact that the present study only investigated the CB, these results suggest that the positive and negative symptoms of schizophrenia may have distinct neurobiological underpinnings.Publication Beyond Crossing Fibers: Bootstrap Probabilistic Tractography Using Complex Subvoxel Fiber Geometries(Frontiers Media S.A., 2014) Campbell, Jennifer S. W.; MomayyezSiahkal, Parya; Savadjiev, Peter; Leppert, Ilana R.; Siddiqi, Kaleem; Pike, G. BruceDiffusion magnetic resonance imaging fiber tractography is a powerful tool for investigating human white matter connectivity in vivo. However, it is prone to false positive and false negative results, making interpretation of the tractography result difficult. Optimal tractography must begin with an accurate description of the subvoxel white matter fiber structure, includes quantification of the uncertainty in the fiber directions obtained, and quantifies the confidence in each reconstructed fiber tract. This paper presents a novel and comprehensive pipeline for fiber tractography that meets the above requirements. The subvoxel fiber geometry is described in detail using a technique that allows not only for straight crossing fibers but for fibers that curve and splay. This technique is repeatedly performed within a residual bootstrap statistical process in order to efficiently quantify the uncertainty in the subvoxel geometries obtained. A robust connectivity index is defined to quantify the confidence in the reconstructed connections. The tractography pipeline is demonstrated in the human brain.Publication Hockey Concussion Education Project, Part 3. White matter microstructure in ice hockey players with a history of concussion: a diffusion tensor imaging study(Journal of Neurosurgery Publishing Group (JNSPG), 2014) Sasaki, Takeshi; Pasternak, Ofer; Mayinger, Michael; Muehlmann, Marc; Savadjiev, Peter; Bouix, Sylvain; Kubicki, Marek; Fredman, Eli; Dahlben, Brian; Helmer, Karl; Johnson, Andrew M.; Holmes, Jeffrey D.; Forwell, Lorie A.; Skopelja, Elaine N.; Shenton, Martha; Echlin, Paul S.; Koerte, IngaObject—The aim of this study was to examine the brain’s white matter microstructure using magnetic resonance diffusion tensor imaging (DTI) in ice hockey players with a history of clinically symptomatic concussion compared to those players without a history of concussion. Methods—Sixteen players with a history of concussion (Concussed Group; mean age: 21.7 ± 1.5 years; 6 female) and eighteen players without a history of concussion (Non-Concussed Group; mean age: 21.3 ± 1.8 years, 10 female) underwent 3T DTI at the end of the Canadian Interuniversity Sports ice hockey season 2011–2012. Tract-based spatial statistics (TBSS) was used to test for group differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and trace. Cognitive evaluation was performed using the Immediate PostConcussion Assessment and Cognitive Test (ImPACT) and the Sport Concussion Assessment Tool-2 (SCAT2). Results—TBSS revealed a significant increase in FA and AD, and a significant decrease in RD and trace in several brain regions in the Concussed group, compared with the Non-concussed group (p < 0.05). The regions with increased FA and decreased RD and trace included the right posterior limb of the internal capsule, the right corona radiata, and the right temporal lobe. Increased AD was observed in a small area in the left corona radiata. DTI measures neither correlated with the ImPACT nor SCAT2. Conclusion—The results of the current study indicate that a history of concussion may result in alterations of the brain’s white matter microstructure in ice hockey players. Increased FA based on decreased RD may reflect neuroinflammatory or neuroplastic processes of the brain responding to brain trauma. Future studies are needed that include a longitudinal analysis of the brain’s structure and function following a concussion in order to elucidate further the complex time course of DTI changes and their clinical meaning.Publication Insights into the Brain: Neuroimaging of Brain Development and Maturation(2017) Lyall, Amanda; Savadjiev, Peter; Shenton, Martha; Kubicki, MarekThe study of how the human brain develops has always been a challenge and an interest to the scientific community. In recent years, new evidence has suggested that many neuropsychiatric disorders may originate from aberrations early in development. This discovery necessitates the application of methodologies that make possible the investigation of human brain development in vivo and across the lifespan. In this commentary, we present evidence that the advent of structural neuroimaging has specifically and significantly contributed critical information about the developmental trajectories of postnatal human brain development that would otherwise not have been possible. We believe that this is particularly relevant to present day research as it has become increasingly clear that growth trajectories within the brain might serve as an endophenotype for a number of factors, ranging from IQ to psychiatric illness. We highlight seminal early works that helped to jumpstart the field of developmental neuroimaging and which inspired incredible new advances in neuroimaging methodologies that are being developed and applied in the field today.Publication Fiber geometry in the corpus callosum in schizophrenia: Evidence for transcallosal misconnection(Elsevier BV, 2011) Whitford, T; Savadjiev, Peter; Kubicki, Marek; O, Lauren J.; Terry, Douglas P.; Bouix, Sylvain; Westin, Carl-Fredrik; Schneiderman, Jason S.; Bobrow, Laurel; Rausch, Andrew C.; Niznikiewicz, Margaret; Nestor, Paul; Pantelis, Christos; Wood, Stephen J.; McCarley, Robert William; Shenton, MarthaBackground—Structural abnormalities in the callosal fibers connecting the heteromodal association areas of the prefrontal and temporoparietal cortices bilaterally have been suggested to play a role in the etiology of schizophrenia. Aims—To investigate for geometric abnormalities in these callosal fibers in schizophrenia patients using a novel Diffusion-Tensor Imaging (DTI) metric of fiber geometry named ShapeNormalized Dispersion (SHD). Methods—DTIs (3T, 51 gradient directions, 1.7 mm isotropic voxels) were acquired from 26 schizophrenia patients and 23 matched healthy controls. The prefrontal and temporoparietal fibers of the corpus callosum were extracted by means of whole-brain tractography, and their mean SHD calculated. Results—The schizophrenia patients exhibited subnormal levels of SHD in the prefrontal callosal fibers when controlling for between-group differences in Fractional Anisotropy. Reduced SHD could reflect either irregularly turbulent or inhomogeneously distributed fiber trajectories in the corpus callosum. Conclusions—The results suggest that the transcallosal misconnectivity believed to be associated with schizophrenia could arise from abnormalities in fiber geometry. These abnormalities in fiber geometry could potentially be underpinned by irregularities in the normative processes of neurodevelopment.Publication Gray matter alterations in early aging: A diffusion magnetic resonance imaging study(Wiley-Blackwell, 2013) Rathi, Yogesh; Pasternak, Ofer; Savadjiev, Peter; Michailovich, O.; Bouix, Sylvain; Kubicki, Marek; Westin, Carl-Fredrik; Makris, Nikolaos; Shenton, MarthaMany studies have observed altered neurofunctional and structural organization in the aging brain. These observations from functional neuroimaging studies show a shift in brain activity from the posterior to the anterior regions with aging (PASA model), as well as a decrease in cortical thickness, which is more pronounced in the frontal lobe followed by the parietal, occipital, and temporal lobes (retrogenesis model). However, very little work has been done using diffusion MRI (dMRI) with respect to examining the structural tissue alterations underlying these neurofunctional changes in the gray matter. Thus, for the first time, we propose to examine gray matter changes using diffusion MRI in the context of aging. In this work, we propose a novel dMRI based measure of gray matter “heterogeneity” that elucidates these functional and structural models (PASA and retrogenesis) of aging from the viewpoint of diffusion MRI. In a cohort of 85 subjects (all males, ages 15–55 years), we show very high correlation between age and “heterogeneity” (a measure of structural layout of tissue in a region-of-interest) in specific brain regions. We examine gray matter alterations by grouping brain regions into anatomical lobes as well as functional zones. Our findings from dMRI data connects the functional and structural domains and confirms the “retrogenesis” hypothesis of gray matter alterations while lending support to the neurofunctional PASA model of aging in addition to showing the preservation of paralimbic areas during healthy aging.Publication Local white matter geometry from diffusion tensor gradients(Elsevier BV, 2010) Savadjiev, Peter; Kindlmann, Gordon L.; Bouix, Sylvain; Shenton, Martha; Westin, Carl-FredrikWe introduce a mathematical framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation then makes it possible to define scalar indices (or measures) that describe the local white matter geometry directly from the diffusion tensor field and its gradient, without requiring prior tractography. We derive new scalar indices of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in vivo data. Finally, we illustrate their applicability to a group study on schizophrenia.Publication A Geometry-Based Particle Filtering Approach to White Matter Tractography(Springer Science + Business Media, 2010) Savadjiev, Peter; Rathi, Yogesh; Malcolm, James G.; Shenton, Martha; Westin, Carl-FredrikWe introduce a fibre tractography framework based on a particle filter which estimates a local geometrical model of the underlying white matter tract, formulated as a `streamline flow' using generalized helicoids. The method is not dependent on the diffusion model, and is applicable to diffusion tensor (DT) data as well as to high angular resolution reconstructions. The geometrical model allows for a robust inference of local tract geometry, which, in the context of the causal filter estimation, guides tractography through regions with partial volume effects. We validate the method on synthetic data and present results on two types in vivo data: diffusion tensors and a spherical harmonic reconstruction of the fibre orientation distribution function (fODF).