Thesis (Ph. D. in Electrical and Medical Engineering)--Harvard-MIT Division of Health Sciences and Technology, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 121-128). / Magnetoencephalography (MEG) non-invasively offers information about neural activity in the brain by measuring its magnetic field. Estimating the cerebral sources of neural activity from MEG is an ill-posed inverse problem that presents several challenges. First, this inverse problem is high-dimensional, as the number of possible sources exceeds the number of MEG recording sensors by at least an order of magnitude. Second, even though the neural activity has a strong temporal dynamic and the MEG recordings are made at high-temporal resolution, the temporal dynamic is usually not exploited to enhance the spatial accuracy of the source localization. Third, whereas a dynamic form of the MEG source localization problem can be easily formulated as a state-space model (SSM) problem, the high dimension of the resulting state-space makes this approach computationally impractical. In this thesis we use a SSM to characterize from MEG recordings the spatiotemporal dynamics of underlying neural activity. We use the Kalman fixed-interval smoother (KS) to obtain maximum a posteriori (MAP) estimates of the hidden states, the expectation-maximization (EM) algorithm to obtain maximum-likelihood (ML) estimates of the parameters defining the SSM, and standard model-selection criteria to choose among competing SSMs. Because of the high dimensionality of the SSM, the computational requirements of these algorithms are high, and preclude the use of current frameworks for MEG analysis. We address these computational problems by developing an accelerated, distributed-memory version of the KS+EM algorithm appropriate for the analysis of high-dimensional data sets. Using the accelerated KS+EM algorithm, we introduce two SSM-based algorithms for MEG data analysis: KronEM (Kronecker Product modeling using KS+EM) and StimEM (Stimulus effect estimation using KS+EM). KronEM characterizes the spatiotemporal covariance of MEG recordings using an parameterization that efficiently describes the rhythmicity present in resting state neural activity. KronEM describes the data as a sum of components composed of a time-invariant spatial signature and a temporal second-order autorregresive process. In comparison with previous attempts at modeling resting-state activity, the KronEM algorithm estimates the number of such components using the data, and is able to identify an arbitrary number of them. We illustrate these properties on a simulation study, and then analyze MEG recordings collected from a human subject in resting state. The KronEM algorithm recovered components consistent with well-known physiological rhythmic activity. We then compare the resulting topographic maps of frequency with multi-taper based ones, and show that KronEM-based maps better localize naturally occurring rhythms. These results make the KronEM algorithm a useful single-trial frequency analysis technique. StimEM estimates neural activity using MEG recordings made in evoked-potential studies, in which the subject is repeatedly presented with a stimulus and only the stimulus effect is of interest. In contrast with other dynamic source-localization techniques, StimEM accepts arbitrary description of neural dynamics, parameterized as a weighted sum of user-defined candidates, and finds the MAP estimate of the weights. Using the estimated dynamics, StimEM generates a time-resolved ML estimate of the evoked-potential activity in the cortex. We illustrate the ability of StimEM to identify dynamics in a simulated data set of realistic dimensions, and show that the estimates improve substantially when dynamics are taken into account. We next analyze experimental MEG data from an auditory evoked-potential study and show that StimEM identifies dynamics consistent with neurophysiology and neuroanatomy and improves the localization of the evoked cortical response. In summary, we establish the feasibility of non-approximate SSM-based analysis of high-dimensional state-space models using a distributed-memory implementation of an accelerated KS+EM algorithm. We develop two novel algorithms to analyze MEG data in resting-state and evoked potential studies, and show that SSM analysis improves substantially on previous non-SSM based techniques. / by Antonio Molins Jiménez. / Ph.D.in Electrical and Medical Engineering

This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2020 / Cataloged from student-submitted PDF of thesis. / Includes bibliographical references (pages 208-242). / Contemporary technological approaches to address limb loss and neuromuscular dysfunction consist of synthetic, mechanical devices which lack an intimate bidirectional interface with nervous tissues. On the therapeutic front, the current amputation paradigm disrupts neuromuscular architecture, discards sensory organs and provides no anatomical or prosthetic replacement. This precludes the generation of afferent sensory feedback, which is critical for sensory integration, motor planning, peripheral and central neurological health, and myoelectric prosthesis control. Utilizing a paradigm of coevolution, I simultaneously engineer neuromuscular anatomy and bioelectronics to enable seamless, bidirectional neuroprosthetic interfacing. In this dissertation, I describe the design and preclinical validation of the regenerative agonist-antagonist myoneural interface (AMI) and myodermal interface (MI), which are reconstructive surgical models to restore musculotendinous and cutaneous sensory feedback, respectively. Then, through case-control studies, the functional outcomes of human subjects who have undergone below-knee and above-knee amputations incorporating native AMIs are compared to standard amputation controls. The effect of AMI amputation on sensorimotor neuroplasticity is investigated through anatomical and functional neuroimaging. These preclinical and clinical evaluations demonstrate the a) production of graded efferent and afferent signals, b) the maintenance of peripheral limb volume and central sensorimotor substrates, c) improvements in phantom sensation, phantom pain, and neuroprosthetic controllability, and d) decreased dependence on compensatory visuomotor circuitry. To address challenges with functional electrical stimulation (FES) of neuromusculature, employed for prosthetic feedback and control, I develop a closed-loop functional optogenetic stimulation system (FOS) for peripheral neuromuscular control. This system demonstrates greater accuracy, biomimetic orderly recruitment of fibers, and minimized fatigue during cyclic movements as compared to FES. Spanning from animal models to human implementation, this dissertation presents 1) a model to design new surgical techniques for afferent/efferent signaling, 2) characterize the physiology following clinical translation, and 3) recursively apply the lessons to the design of neural interfaces back at the bench. In summary, the results of this work steer a shift of the clinical amputation paradigm towards one that performs strategic rewiring of neuromuscular constructs to enable improved neurological health and neural interfacing. / Shriya Srinivasan. / Ph. D. in Medical Engineering and Medical Physics / Ph. D. in Medical Engineering and Medical Physics Harvard-MIT Program in Health Sciences and Technology

Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2018 / Cataloged from PDF version of thesis. Cataloged from PDF of thesis. / Includes bibliographical references (pages 379-400). / For persons living with lower extremity amputation, the prosthetic socket -- the cup-like interface connecting the residuum to prosthesis - is considered the most critical component. It must be custom-made and tailored to each individual user, and if not fit properly can significantly hinder quality of life. As an alternative to conventional fabrication practices that involve subjective input from a clinician, computational modeling-based socket design practices have emerged. Despite early success, its clinical implementation and potential for broad accessibility are limited since it relies on expensive imaging technologies and robotic indentation devices. Medical ultrasound imaging, a cost-effective modality that can be used at the bedside, is a promising and clinically-viable solution. In order for ultrasound to become a viable scanning method for this application, technological development was necessary that allows for three-dimensional acquisition of (1) limb geometry and (2) mechanical tissue properties. Toward this goal, we first present the design of a novel multi-modal imaging system for rapidly acquiring volumetric ultrasound imagery of human limbs. Second, we present results of two studies that evaluate the use of ultrasound indentation and shear wave elastography (SWE) to characterize tissue biomechanics: the former to investigate how SWE is affected by transducer force, and the latter presenting a novel approach for constitutive parameter identification using a combination of finite element analysis (FEA), indentation, and SWE. Finally, we demonstrate that SWE may be performed using a non-contact approach, allowing for human limb data to be collected under discrete transducer-independent loading conditions. The techniques and results presented in this thesis highlight the potential for ultrasound imaging for improved prosthesis design, as well as more broadly to quantitative musculoskeletal tissue assessment for a variety of clinical applications. Specifically, data may be directly incorporated into computational prosthetic socket design practices that are in development in the Biomechatronics Group. / Bryan James Ranger. / Ph. D. in Medical Engineering and Medical Physics / Ph. D. in Medical Engineering and Medical Physics Harvard-MIT Program in Health Sciences and Technology

No description available.

Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, February 2019 / Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references (pages 71-81). / Originally viewed as 'garbage bags' which cells release to dispose of unwanted material, extracellular vesicles (EVs) have emerged as potent messengers that package and disseminate biochemical signals. This newly recognized mode of communication between cells has brought unprecedented therapeutic opportunities; at least 8 clinical trials and 7 companies are investigating or developing EVs as therapeutic products. As the EV industry rapidly grows, there is a rising demand for strategies that facilitate EV manufacturing. In this thesis, we address several challenges in EV manufacturing. By quantifying how many EVs a cell can release before it divides, we discovered that EV output increases as cells divide more slowly, providing a new way to maximize EV output from cells. Using our mathematical description of EV output, we built a computational model to estimate costs of EV manufacturing. Selecting cells with higher EV output despite slower proliferation can drastically lower costs. Meanwhile, although ultracentrifugation is the current standard for purifying EVs, we found that ultrafiltration-specifically tangential-flow filtration-is a more economical and scalable alternative, and we experimentally determined its utility for scaling up EV purification. For quality control, we established a suite of potency assays to measure the overall inflammatory action of EVs derived from human stem cells. Significant variability in EV potency between cells of different donors was detected, substantiating the need to robustly screen for appropriate cell sources when manufacturing EVs. Towards controlling EV function, we genetically constructed a versatile, multi-domain ligand that localizes to and modifies the surface of vesicles. Integrating biological, processing, and economic aspects of EV manufacturing, this thesis recommends strategies that may accelerate commercialization and clinical translation of EV therapy. / by Kelvin S. Ng. / Ph. D. / Ph.D. Harvard-MIT Program in Health Sciences and Technology

Univ., Diss.-2006--Freiburg, 2005. / Literaturverz. S. [451] - 481.

Univ., Diss.-2004--Passau, 2003. / Literaturverz. S. 294 - 306.

Studio umschichten, an der Schnittstelle von Architektur, Kunst und Stadtentwicklung agierend, stellen eine Auswahl ihrer Projekte im Entstehungsprozess vor und erlauben einen Blick hinter die Kulissen der komplexen Vorgänge, die zur Realisierung sowie zur Nutzung ihrer temporären Gebäude geführt haben. Dabei demonstrieren sie ihre Arbeitsweise anhand von Phasen, die jedes Projekt notwendigerweise durchläuft. Beginnend von dem Schritt der Vereinbarung mit den Bauherr*innen über das Ausloten der Rahmenbedingungen und Materialfragen bis hin zum Bau- und schließlich Nutzungsprozess. Diese teils aufeinander folgenden, teils parallel verlaufenden Prozesse illustriert der Text anhand von vier beispielhaften Projekten: Weltausstellung, Berlin (zusammen mit Hebbel am Ufer HAU), Opelation, Bochum (mit Urbane Künste Ruhr), Inventur Jena (mit Theaterhaus Jena) und Performeum Wien (mit Wiener Festwochen). Handlungsleitend für alle Arbeiten sind Orts- und Kontextspezifik, die Fragen des Materialkreislaufs sowie der partizipativen inhaltlichen und funktionalen Raumprogrammierung und die Übereinkunft des Temporären als produktiven Zustand.

Proceedings from the Fab 9 Research Stream 9th International Fablab Conference, 21-27 July 2013, Yokohama. / Since 2007, Latin America has incorporated a set of emerging techniques promoted under three initiatives: a) from the experience of Master and Doctoral students who return to their home countries and promote their experience, b) from the external academic experience that goes towards the region, and c) from self-learning. These experiences are developed in an academic area, unlike Europe or the U.S., where they were promoted from and to professional practice, with varying degrees of implementation and effect. Generally speaking, the academic programs of the region lack a policy of inclusion of systematized emerging technologies, and that produces a slow uptake, especially in architecture. On one hand, if educational policies are not stable, equipment investment cannot be stable, and on the other hand, the generation gap between those who promote and those who accept blends into disruption and status quo. Each implementation in the region produces adverse and complex patterns, replicating existing models and seeking alliances with institutions in developed countries. Thus, there are self-help groups, while others incorporate academic, technical and/or commercial supervisions, in principle through the Center for Bits and Atoms (MIT Fab Lab) and McNeel Associates (Rhino Fab Lab). In this research, we evidence evolution and implementation processes in Latin America of the three types of initiatives, analyzing the case study in Peru, which together open up the possibility of moving from a phase of experimentation, trial and error to another that actually promotes local innovation and inclusion.

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology; and, (S.M.)--Massachusetts Institute of Technology, Sloan School of Management, 2005. / Includes bibliographical references (leaves 56-57). / Executive Summary: In this thesis, I examine faculty inventors' involvement in university spin-off firms formed to commercialize their inventions. In particular, I analyze the association between a faculty inventor's various roles in commercializing his/her invention and the performance of the ensuing fledging ventures. The study is based on a group of spin-off firms from MIT in the biomedical/life science sector between 1976 and 2003. Structured questionnaires were distributed to the 110 faculty inventors identified by the technology licensing office (TLO) in April 2005, yielding 31 valid responses covering 60 companies. / by Hong Hocking Cheng. / S.M.