Computer-Aided, Multi-Modal, and Compression Diffuse Optical Studies of Breast Tissue

Diffuse Optical Tomography and Spectroscopy permit measurement of important physiological parameters non-invasively through ~10 cm of tissue. I have applied these techniques in measurements of human breast and breast cancer. My thesis integrates three loosely connected themes in this context: multi-modal breast cancer imaging, automated data analysis of breast cancer images, and microvascular hemodynamics of breast under compression. As per the first theme, I describe construction, testing, and the initial clinical usage of two generations of imaging systems for simultaneous diffuse optical and magnetic resonance imaging. The second project develops a statistical analysis of optical breast data from many spatial locations in a population of cancers to derive a novel optical signature of malignancy; I then apply this data-derived signature for localization of cancer in additional subjects. Finally, I construct and deploy diffuse optical instrumentation to measure blood content and blood flow during breast compression; besides optics, this research has implications for any method employing breast compression, e.g., mammography

The WAY theorem and the quantum resource theory of asymmetry

The WAY theorem establishes an important constraint that conservation laws impose on quantum mechanical measurements. We formulate the WAY theorem in the broader context of resource theories, where one is constrained to a subset of quantum mechanical operations described by a symmetry group. Establishing connections with the theory of quantum state discrimination we obtain optimal unitaries describing the measurement of arbitrary observables, explain how prior information can permit perfect measurements that circumvent the WAY constraint, and provide a framework that establishes a natural ordering on measurement apparatuses through a decomposition into asymmetry and charge subsystems.Comment: 11 pages, 3 figure

Decentralised Learning MACs for Collision-free Access in WLANs

By combining the features of CSMA and TDMA, fully decentralised WLAN MAC schemes have recently been proposed that converge to collision-free schedules. In this paper we describe a MAC with optimal long-run throughput that is almost decentralised. We then design two \changed{schemes} that are practically realisable, decentralised approximations of this optimal scheme and operate with different amounts of sensing information. We achieve this by (1) introducing learning algorithms that can substantially speed up convergence to collision free operation; (2) developing a decentralised schedule length adaptation scheme that provides long-run fair (uniform) access to the medium while maintaining collision-free access for arbitrary numbers of stations

A low-cost, compact device for monitoring tissue oxygen consumption using speckle contrast optical spectroscopy

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Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease

Autorregulació cerebral; Malaltia cerebrovascular; Òptica difusaAutorregulación cerebral; Enfermedad cerebrovascular; Óptica difusaCerebral autoregulation; Cerebrovascular disease; Diffuse opticsBackground The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. Methods Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. Results After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [− 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). Conclusions The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.The funders did not have any role in study design, execution and data interpretation. This work was funded by Redes Temáticas de Investigación Cooperativa (RETICS-INVICTUS RD012/0014 and RD16/0019/0010), Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad/FEDER (PHOTODEMENTIA, PHOTOMETABO, DPI2015–64358-C2–1-R, PRE2018-085082), Instituto de Salud Carlos III/FEDER (FIS PI09/0557, MEDPHOTAGE, DTS16/00087), the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra Social “la Caixa” Foundation (LlumMedBcn), Institució “Centres de Recerca de Catalunya”, “Agència de Gestió d’Ajuts Universitaris i de Recerca”-Generalitat (2017SGR-1380), LASERLAB-EUROPE IV (EU-H2020 654148), Whitaker International Program of the Institute for International Education, T32 HL007954 Multidisciplinary training in cardiovascular biology, Marie Curie initial training network (OILTEBIA 317526), Marie Sklowdowska-Curie-COFUND (H2020, ICFOstepstone 2, 71329), “Fundació La Marató TV3” (201709.30, 201709.31), São Paulo Research Foundation (FAPESP) through 2012/02500–8 and National Institutes of Health (R01-NS060653, K24-NS058386, R24-HD050836, P41-EB015893, DP2-HD101400, U54-HD086984)

Interaction in motion: designing truly mobile interaction

The use of technology while being mobile now takes place in many areas of people’s lives in a wide range of scenarios, for example users cycle, climb, run and even swim while interacting with devices. Conflict between locomotion and system use can reduce interaction performance and also the ability to safely move. We discuss the risks of such “interaction in motion”, which we argue make it desirable to design with locomotion in mind. To aid such design we present a taxonomy and framework based on two key dimensions: relation of interaction task to locomotion task, and the amount that a locomotion activity inhibits use of input and output interfaces. We accompany this with four strategies for interaction in motion. With this work, we ultimately aim to enhance our understanding of what being “mobile” actually means for interaction, and help practitioners design truly mobile interactions

Type-Decomposition of a Pseudo-Effect Algebra

The theory of direct decomposition of a centrally orthocomplete effect algebra into direct summands of various types utilizes the notion of a type-determining (TD) set. A pseudo-effect algebra (PEA) is a (possibly) noncommutative version of an effect algebra. In this article we develop the basic theory of centrally orthocomplete PEAs, generalize the notion of a TD set to PEAs, and show that TD sets induce decompositions of centrally orthocomplete PEAs into direct summands.Comment: 18 page

A role for an Hsp70 nucleotide exchange factor in the regulation of synaptic vesicle endocytosis

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 33 (2013): 8009-8021, doi:10.1523/JNEUROSCI.4505-12.2013.Neurotransmission requires a continuously available pool of synaptic vesicles (SVs) that can fuse with the plasma membrane and release their neurotransmitter contents upon stimulation. After fusion, SV membranes and membrane proteins are retrieved from the presynaptic plasma membrane by clathrin-mediated endocytosis. After the internalization of a clathrin-coated vesicle, the vesicle must uncoat to replenish the pool of SVs. Clathrin-coated vesicle uncoating requires ATP and is mediated by the ubiquitous molecular chaperone Hsc70. In vitro, depolymerized clathrin forms a stable complex with Hsc70*ADP. This complex can be dissociated by nucleotide exchange factors (NEFs) that release ADP from Hsc70, allowing ATP to bind and induce disruption of the clathrin:Hsc70 association. Whether NEFs generally play similar roles in vesicle trafficking in vivo and whether they play such roles in SV endocytosis in particular is unknown. To address this question, we used information from recent structural and mechanistic studies of Hsp70:NEF and Hsp70:co-chaperone interactions to design a NEF inhibitor. Using acute perturbations at giant reticulospinal synapses of the sea lamprey (Petromyzon marinus), we found that this NEF inhibitor inhibited SV endocytosis. When this inhibitor was mutated so that it could no longer bind and inhibit Hsp110 (a NEF that we find to be highly abundant in brain cytosol), its ability to inhibit SV endocytosis was eliminated. These observations indicate that the action of a NEF, most likely Hsp110, is normally required during SV trafficking to release clathrin from Hsc70 and make it available for additional rounds of endocytosis.This work was supported by the National Institutes of Health (Grant #NS029051 to E.M.L. and Grant #NS078165 to J.R.M.).2013-11-0

Hybrid time-domain and continuous-wave diffuse optical tomography instrument with concurrent, clinical magnetic resonance imaging for breast cancer imaging

Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system’s ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology