Comparison of manual and automatic techniques for substriatal segmentation in C-11-raclopride high-resolution PET studies

Background: The striatum is the primary target in regional C-11-raclopride-PET studies, and despite its small volume, it contains several functional and anatomical subregions. The outcome of the quantitative dopamine receptor study using C-11-raclopride-PET depends heavily on the quality of the region-of-interest (ROI) definition of these subregions. The aim of this study was to evaluate subregional analysis techniques because new approaches have emerged, but have not yet been compared directly.Materials and methods: In this paper, we compared manual ROI delineation with several automatic methods. The automatic methods used either direct clustering of the PET image or individualization of chosen brain atlases on the basis of MRI or PET image normalization. State-of-the-art normalization methods and atlases were applied, including those provided in the FreeSurfer, Statistical Parametric Mapping8, and FSL software packages. Evaluation of the automatic methods was based on voxel-wise congruity with the manual delineations and the test-retest variability and reliability of the outcome measures using data from seven healthy male participants who were scanned twice with C-11-raclopride-PET on the same day.Results: The results show that both manual and automatic methods can be used to define striatal subregions. Although most of the methods performed well with respect to the test-retest variability and reliability of binding potential, the smallest average test-retest variability and SEM were obtained using a connectivity-based atlas and PET normalization (test-retest variability=4.5%, SEM=0.17).Conclusion: The current state-of-the-art automatic ROI methods can be considered good alternatives for subjective and laborious manual segmentation in C-11-raclopride-PET studies.Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.</div

Noninvasive Neuromodulation: Modeling and Analysis of Transcranial Brain Stimulation with Applications to Electric and Magnetic Seizure Therapy

Bridging the fields of engineering and psychiatry, this dissertation proposes a novel framework for the rational dosing of electric and magnetic seizure therapy, including electroconvulsive therapy (ECT) and magnetic seizure therapy (MST), for the treatment of psychiatric disorders such as medication resistant major depression and schizophrenia. The objective of this dissertation is to develop computational modeling tools that allow ECT and MST stimulation paradigms to be biophysically optimized ex vivo, prior to testing safety and efficacy in preclinical and clinical trials. Despite therapeutic advances, treatment resistant depression (TRD) remains a largely unmet clinical need. ECT is highly effective for TRD, but its side effects limit its real-world clinical utility. Modifications of treatment technique (e.g., electrode placement, stimulus parameters, novel paradigms such as MST) significantly improve the tolerability of convulsive therapy. However, we know relatively little about the distribution of the electric field (E-field) induced in the brain to inform spatial targeting of ECT and MST. Lacking an understanding of biophysical and physiological mechanisms, refinements in ECT/MST technique rely exclusively on time-consuming and costly clinical trials. Consequently, key questions remain unanswered about how to position the ECT electrodes or MST coil for targeted brain stimulation. Addressing this knowledge gap, this dissertation proposes a new platform that will inform an improved spatial targeting of ECT and MST through state-of-the-art computer simulations of the E-field distribution in human and nonhuman primate (NHP) brain. Part I of this dissertation aims to develop anatomically realistic finite element models of transcranial electric and magnetic stimulation in human and NHPs incorporating tissue heterogeneity and anisotropy derived from structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data. The NHP models of ECT and MST are created alongside the human model since NHPs are used in preclinical studies on the mechanisms of seizure therapy. Part II of this dissertation aims to apply the model developed in Part I to electric and magnetic seizure therapy. We compute the strength and spatial distributions of the E-field induced in the brain by various ECT and MST paradigms. The relative E-field strength among various regions of interest (ROIs) is examined to select electrode/coil configurations that produce most focal stimulation of target ROIs that are considered to mediate the therapeutic action of ECT and MST. Since E-field alone is insufficient to account for individual differences in neurophysiological response, we calibrate the E-field maps relative to the neural activation threshold via in vivo measurements of the corticospinal tract response to single pulses (motor threshold, MT). We derive an empirical estimate of the neural activation threshold by coupling simulated E-field strength with individually measured MT. The E-field strength relative to an empirical neural activation threshold and corresponding volume of suprathreshold stimulation (focality) is examined to inform the selection of ECT and MST stimulus pulse amplitude that will result in focal ROI stimulation. We contrast the ECT/MST stimulation strength and focality with conventional fixed and individually titrated pulse amplitude necessary to induce a seizure (seizure threshold, ST) to study pulse amplitude adjustment as a novel means of controlling stimulation strength and focality. This work provides a basis for rational dosing of seizure therapies that could help improve their risk/benefit ratio and guide the development of safer alternatives for patients with severe psychiatric disorders

Vizualna utemeljena teorija: metodološki nacrt i primjeri iz empirijskog rada

Grounded theory has not usually been associated with the extensive use of visual data. The author of the paper wants to present a basic introduction to methodological concepts and procedures, which allow researchers to incorporate visual data in their analyses while designing their research projects within the framework of grounded theory. The author also discusses the different approaches of visual data analysis that use the name of grounded theory but do not in fact perform the analysis according to its basic principles. At the outset, the author describes some inspirations that have come from a few researchers who have used the visual data in constructing theories in the grounded theory methodology style of analysis. The status of visual data and a methodological model of visual data analysis in grounded theory (multislice imagining) is also described. The multislice imagining is a grammar of visual narrations analysis that accents the following stages: a) an act of creating pictures and images (analysis of context of creation); b) participation in demonstrating/communicating visual images; c) the visual product, its content and stylistic structure; d) the reception of an “image” and visual aspects of presenting/representing something. Next, procedures of analyzing the visual data to generate categories on visual processes (transcription, open coding and memo writing) are presented. The presentation is based on examples from the author’s two research projects on a visualization of yoga practice and on a visualization of homelessness. The author also presents a selective coding of visual cases and empirical materials together with theoretical memo examples and comparative analysis. The last described procedure is a theoretical sampling indicating how and where to look for visual data to generate the properties of the category. The paper will end with conclusions and some remarks on future prospects of visual grounded theory.Utemeljenu se teoriju obično ne povezuje s opsežnom upotrebom vizualnih podataka. Autor ovog članka želi podastrijeti elementaran uvod u metodološke pojmove i procedure koji istraživačima omogućuju uključivanje vizualnih podataka u analizu dok osmišljavaju nacrte istraživačkih projekata u okviru utemeljene teorije. Autor također raspravlja o različitim pristupima analizi vizualnih podataka koji se služe imenom utemeljene teorije, ali zapravo ne izvode analizu u skladu s njezinim temeljnim načelima. Na početku autor opisuje neka nadahnuća koja potječu od malobrojnih istraživača koji su upotrijebili vizualne podatke pri konstruiranju teorija u stilu analize metodologije utemeljene teorije. Također se opisuje status vizualnih podataka i metodološki model analize vizualnih podataka u utemeljenoj teoriji (stvaranje slikovnih predodžbi u više isječaka). Stvaranje slikovnih predodžbi u više isječaka jest gramatika analize vizualnih pripovijesti koja naglašava sljedeće faze: a) čin stvaranja slika i slikovnih predodžbi (analiza konteksta stvaranja); b) sudjelovanje u prikazivanju/komuniciranju vizualnih slikovnih predodžbi; c) vizualni proizvod, njegov sadržaj i stilska struktura; d) recepcija »slikovne predodžbe« i vizualnih aspekata predstavljanja/predočavanja nečega. Nadalje, predstavljaju se procedure analiziranja vizualnih podataka u svrhu generiranja kategorija o vizualnim procesima (transkripcija, otvoreno kodiranje i pisanje bilježaka). Predstavljanje se zasniva na primjerima iz dvaju autorovih istraživačkih projekata o vizualizaciji prakse joge i vizualizaciji beskućništva. Autor također predstavlja selektivno kodiranje vizualnih slučajeva i empirijskih materijala zajedno s primjerima teorijskih bilježaka i usporedne analize. Posljednja od opisanih procedura jest teorijsko uzorkovanje koje upućuje na to kako i gdje tražiti vizualne podatke u svrhu generiranja svojstava kategorije. Članak završava zaključcima i napomenama o budućim izgledima vizualne utemeljene teorije

Towards an epistemology of medical imaging

Tese de doutoramento (co-tutela), História e Filosofia das Ciências (Filosofia), Faculdade de Ciências da Universidade de Lisboa, Università degli Studi di Milano, 201