Browsing by Author "Dincer, Alp"
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Item Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection(RADIOLOGICAL SOC NORTH AMERICA, 2020-01-01) Kandemirli, Sedat G.; Dogan, Lerzan; Sarikaya, Zeynep T.; Kara, Simay; Akinci, Canan; Kaya, Dilaver; Kaya, Yildiz; Yildirim, Duzgun; Tuzuner, Filiz; Yildirim, Mustafa S.; Ozluk, Enes; Gucyetmez, Bulent; Karaarslan, Ercan; Koyluoglu, Isil; Kaya, Hande S. Demirel; Mammadov, Orkhan; Ozdemir, Ilkay Kisa; Afsar, Nazire; Yalcinkaya, Beyza Citci; Rasimoglu, Sevdinaz; Guduk, Duygu E.; Jima, Ararso Kedir; Ilksoz, Aylin; Ersoz, Vildan; Eren, Meltem Yonca; Celtik, Nilufer; Arslan, Serdar; Korkmazer, Bora; Dincer, Saban S.; Gulek, Elif; Dikmen, Ibrahim; Yazici, Murathan; Unsal, Serkan; Ljama, Taner; Demirel, Ismail; Ayyildiz, Aykut; Kesimci, Isil; Deveci, Sahika Bolsoy; Tutuncu, Melih; Kizilkilic, Osman; Telci, Lutfi; Zengin, Rehile; Dincer, Alp; Akinci, Ibrahim O.; Kocer, NaciItem Clinical Proton MR Spectroscopy in Central Nervous System Disorders(RADIOLOGICAL SOC NORTH AMERICA, 2014-01-01) Gulin, O. Z.; Alger, Jeffry R.; Barker, Peter B.; Bartha, Robert; Bizzi, Alberto; Boesch, Chris; Bolan, Patrick J.; Brindle, Kevin M.; Cudalbu, Cristina; Dincer, Alp; Dydak, Ulrike; Emir, Uzay E.; Frahm, Jens; Gonzalez, Ramon Gilberto; Gruber, Stephan; Gruetter, Rolf; Gupta, Rakesh K.; Heerschap, Arend; Henning, Anke; Hetherington, Hoby P.; Howe, Franklyn A.; Hueppi, Petra S.; Hurd, Ralph E.; Kantarci, Kejal; Klomp, Dennis W. J.; Kreis, Roland; Kruiskamp, Marijn J.; Leach, Martin O.; Lin, Alexander P.; Luijten, Peter R.; Marjanska, Malgorzata; Maudsley, Andrew A.; Meyerhoff, Dieter J.; Mountford, Carolyn E.; Nelson, Sarah J.; Pamir, M. Necmettin; Pan, Jullie W.; Peet, Andrew C.; Poptani, Harish; Posse, Stefan; Pouwels, Petra J. W.; Ratai, Eva-Maria; Ross, Brian D.; Scheenen, Tom W. J.; Schuster, Christian; Smith, Ian C. P.; Soher, Brian J.; Tkac, Ivan; Vigneron, Daniel B.; Kauppinen, Risto A.; Grp, M.R.S. ConsensusA large body of published work shows that proton (hydrogen 1 {[}H-1]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of 1H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of 1H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which 1H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. (c) RSNA, 2014Item Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system(AMER ASSOC NEUROLOGICAL SURGEONS, 2022-01-01) Ulgen, Ege; Aras, Fuat Kaan; Cosgun, Erdal; Ersen-Danyeli, Ayca; Dincer, Alp; Usseli, M. Imre; Ozduman, Koray; Pamir, M. NecmettinOBJECTIVE Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort. METHODS Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21-71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters). RESULTS The tumors involved the anterior insula (98.3\%), posterior insula (67.8\%), temporal operculum (47.5\%), amygdala (42.4\%), frontal operculum (40.7\%), temporal pole (39\%), parolfactory area (35.6\%), hypothalamus (23.7\%), hippocampus (16.9\%), thalamus (6.8\%), striatum (5.1\%), and cingulate gyrus (3.4\%). A mean 4.2 +/- 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular {[}11.9\%], olfactocentric {[}15.3\%], olfactoopercular {[}33.9\%], operculoinsular {[}15.3\%], striatoinsular {[}3.4\%], translimbic {[}11.9\%], and multifocal {[}8.5\%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator. CONCLUSIONS The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.Item In Vivo Renal Lipid Quantification by Accelerated Magnetic Resonance Spectroscopic Imaging at 3T: Feasibility and Reliability Study(MDPI, 2022-01-01) Alhulail, Ahmad A.; Servati, Mahsa; Ooms, Nathan; Akin, Oguz; Dincer, Alp; Thomas, M. Albert; Dydak, Ulrike; Emir, Uzay E.A reliable and practical renal-lipid quantification and imaging method is needed. Here, the feasibility of an accelerated MRSI method to map renal fat fractions (FF) at 3T and its repeatability were investigated. A 2D density-weighted concentric-ring-trajectory MRSI was used for accelerating the acquisition of 48 x 48 voxels (each of 0.25 mL spatial resolution) without respiratory navigation implementations. The data were collected over 512 complex-FID timepoints with a 1250 Hz spectral bandwidth. The MRSI sequence was designed with a metabolite-cycling technique for lipid-water separation. The in vivo repeatability performance of the sequence was assessed by conducting a test-reposition-retest study within healthy subjects. The coefficient of variation (CV) in the estimated FF from the test-retest measurements showed a high degree of repeatability of MRSI-FF (CV = 4.3 +/- 2.5\%). Additionally, the matching level of the spectral signature within the same anatomical region was also investigated, and their intrasubject repeatability was also high, with a small standard deviation (8.1 +/- 6.4\%). The MRSI acquisition duration was similar to 3 min only. The proposed MRSI technique can be a reliable technique to quantify and map renal metabolites within a clinically acceptable scan time at 3T that supports the future application of this technique for the non-invasive characterization of heterogeneous renal diseases and tumors.Item Increased Prostate Imaging-Reporting and Data System Scores in Multiparametric Magnetic Resonance Imaging May Predict More Extensive Disease in Radical Prostatectomy Specimens(GALENOS YAYINCILIK, 2021-01-01) Karsiyakali, Nejdet; Ozgen, Mahir Bulent; Ozveren, Bora; Akbal, Cem; Dincer, Alp; Durak, Haydar; Turkeri, LeventObjective: This study aimed to investigate the correlation between index lesion prostate imaging-reporting and data system (PI-RADS) version-2 score and histopathological outcomes of prostatectomy specimens. Materials and Methods: A total of 78 male patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy between August 2015 and June 2020 were included in this study. In this cohort, suspicious lesions on multiparametric magnetic resonance imaging (mpMRI) were scored according to PI-RADS version-2 criteria. MpMRI-targeted prostate biopsy was performed for all suspicious lesions with a PI-RADS score of >= 3 followed by systematic prostate biopsy. The relationship between index lesion PI-RADS score and histopathological outcomes of prostatectomy specimens were evaluated statistically. Results: The mean age of the patients was 65.0 +/- 7.0 years. The distribution of PI-RADS scores of 3, 4, and 5 of the index lesions were 6 (7.7\%), 29 (37.2\%), and 43 (55.1\%), respectively. Lower tumor volume and tumor volume ratio were observed in patients with a PI-RADS score of 3 when they were compared with patients with PI-RADS scores of 4 and PI-RADS-5 (p<0.001, for each). No significant correlation was found between index lesion PI-RADS score in mpMRI and clinically significant PCa in prostatectomy specimens (r<0.200, p>0.05). However, a significant correlation was observed between index lesion PI-RADS score and extracapsular extension (ECE), as well as seminal vesicle invasion (SVI) and pT stage (r=0.327, p=0.004Item Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020-01-01) Dogan, Lerzan; Kaya, Dilaver; Sarikaya, Tugce; Zengin, Rehile; Dincer, Alp; Akinci, Ibrahim Ozkan; Afsar, NazireSevere SARS-CoV-2 (COVID-19) infection has the potential for a high mortality rate. In this paper, we report the results of plasmapheresis treatment in a series of severely ill patients with COVID-19-related autoimmune meningoencephalitis in the Intensive Care Unit (ICU).Item Recessive LAMC3 mutations cause malformations of occipital cortical development(NATURE PUBLISHING GROUP, 2011-01-01) Barak, Tanyeri; Kwan, Kenneth Y.; Louvi, Angeliki; Demirbilek, Veysi; Saygi, Serap; Tuysuz, Beyhan; Choi, Murim; Boyaci, Huseyin; Doerschner, Katja; Zhu, Ying; Kaymakcalan, Hande; Yilmaz, Saliha; Bakircioglu, Mehmet; Caglayan, Ahmet Okay; Oeztuerk, Ali Kemal; Yasuno, Katsuhito; Brunken, William J.; Atalar, Ergin; Yalcinkaya, Cengiz; Dincer, Alp; Bronen, Richard A.; Mane, Shrikant; Ozcelik, Tayfun; Lifton, Richard P.; Sestan, Nenad; Bilguevar, Kaya; Guenel, MuratThe biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin. 3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations.Item Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration(NATL ACAD SCIENCES, 2013-01-01) Bilguvar, Kaya; Tyagi, Navneet K.; Ozkara, Cigdem; Tuysuz, Beyhan; Bakircioglu, Mehmet; Choi, Murim; Delil, Sakir; Caglayan, Ahmet O.; Baranoski, Jacob F.; Erturk, Ozdem; Yalcinkaya, Cengiz; Karacorlu, Murat; Dincer, Alp; Johnson, Michele H.; Mane, Shrikant; Chandra, Sreeganga S.; Louvi, Angeliki; Boggon, Titus J.; Lifton, Richard P.; Horwich, Arthur L.; Gunel, MuratUbiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific deubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1(GLU7ALA).), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1(GLU7ALA), compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1(GLU7ALA) relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system.Item The effect of tumor shape irregularity on Gamma Knife treatment plan quality and treatment outcome: an analysis of 234 vestibular schwannomas(NATURE PORTFOLIO, 2022-01-01) Sumer, Esra; Tek, Ece; Ture, O. Artunc; Sengoz, Meric; Dincer, Alp; Ozcan, Alpay; Pamir, M. Necmettin; Ozduman, Koray; Ozturk-Isik, EsinThe primary aim of Gamma Knife (GK) radiosurgery is to deliver high-dose radiation precisely to a target while conforming to the target shape. In this study, the effects of tumor shape irregularity (TSI) on GK dose-plan quality and treatment outcomes were analyzed in 234 vestibular schwannomas. TSI was quantified using seven different metrics including volumetric index of sphericity (VioS). GK treatment plans were created on a single GK-Perfexion/ICON platform. The plan quality was measured using selectivity index (SI), gradient index (GI), Paddick's conformity index (PCI), and efficiency index (EI). Correlation and linear regression analyses were conducted between shape irregularity features and dose plan indices. Machine learning was employed to identify the shape feature that predicted dose plan quality most effectively. The treatment outcome analysis including tumor growth control and serviceable hearing preservation at 2 years, were conducted using Cox regression analyses. All TSI features correlated significantly with the dose plan indices (P < 0.0012). With increasing tumor volume, vestibular schwannomas became more spherical (P < 0.05) and the dose plan indices varied significantly between tumor volume subgroups (P < 0.001 and P < 0.01). VioS was the most effective predictor of GK indices (P < 0.001) and we obtained 89.36\% accuracy (79.17\% sensitivity and 100\% specificity) for predicting PCI. Our results indicated that TSI had significant effects on the plan quality however did not adversely affect treatment outcomes.Item The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis(CELL PRESS, 2011-01-01) Bakircioglu, Mehmet; Carvalho, Ofelia P.; Khurshid, Maryam; Cox, James J.; Tuysuz, Beyhan; Barak, Tanyeri; Yilmaz, Saliha; Caglayan, Okay; Dincer, Alp; Nicholas, Adeline K.; Quarrell, Oliver; Springell, Kelly; Karbani, Gulshan; Malik, Saghira; Gannon, Caroline; Sheridan, Eamonn; Crosier, Moira; Lisgo, Steve N.; Lindsay, Susan; Bilguvar, Kaya; Gergely, Fanni; Gunel, Murat; Woods, C. GeoffreyWe investigated three families whose offspring had extreme microcephaly at birth and profound mental retardation. Brain scans and postmortem data showed that affected individuals had brains less than 10\% of expected size (<= 10 standard deviation) and that in addition to a massive reduction in neuron production they displayed partially deficient cortical lamination tinicrolissencephaly). Other body systems were apparently unaffected and overall growth was normal. We found two distinct homozygous mutations of NDE1, c.83+1G>T (p.Ala29GlnfsX114) in a Turkish family and c.684\_685del (p.Pro229TrpfsX85) in two families of Pakistani origin. Using patient cells, we found that c.83+1G>T led to the use of a novel splice site and to a frameshift after NDE1 exon 2. Transfection of tagged NDE1 constructs showed that the c.684\_685del mutation resulted in a NDE1 that was unable to localize to the centrosome. By staining a patient-derived cell line that carried the c.83+1G>T mutation, we found that this endogeneously expressed mutated protein equally failed to localize to the centrosome. By examining human and mouse embryonic brains, we determined that NDE1 is highly expressed in neuroepithelial cells of the developing cerebral cortex, particularly at the centrosome. We show that NDE1 accumulates on the mitotic spindle of apical neural precursors in early neurogenesis. Thus, NDE1 deficiency causes both a severe failure of neurogenesis and a deficiency in cortical lamination. Our data further highlight the importance of the centrosome in multiple aspects of neurodevelopment.Item Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations(NATURE PUBLISHING GROUP, 2010-01-01) Bilguvar, Kaya; Ozturk, Ali Kemal; Louvi, Angeliki; Kwan, Kenneth Y.; Choi, Murim; Tatli, Burak; Yalnizoglu, Dilek; Tuysuz, Beyhan; Caglayan, Ahmet Okay; Gokben, Sarenur; Kaymakcalan, Hande; Barak, Tanyeri; Bakircioglu, Mehmet; Yasuno, Katsuhito; Ho, Winson; Sanders, Stephan; Zhu, Ying; Yilmaz, Sanem; Dincer, Alp; Johnson, Michele H.; Bronen, Richard A.; Kocer, Naci; Per, Hueseyin; Mane, Shrikant; Pamir, Mehmet Necmettin; Yalcinkaya, Cengiz; Kumandas, Sefer; Topcu, Meral; Ozmen, Meral; Sestan, Nenad; Lifton, Richard P.; State, Matthew W.; Gunel, MuratThe development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers(1,2). An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development(3-6). Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.