We report coregistration of near-infrared diffuse optical spectroscopy (DOS) and magnetic resonance imaging (MRI) for the study of animal model tumors. A combined broadband steady-state and ...frequency-domain apparatus was used to determine tissue oxyhemoglobin, deoxyhemoglobin, and water concentration locally in tumors. Simultaneous MRI coregistration provided structural (T2-weighted) and contrast-enhanced images of the tumor that were correlated with the optical measurements. By use of Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, showing precisely which tissue structure was probed optically. DOS and MRI coregistration measurements were performed on seven rats over 20 days and were separated into three tumor tissue classifications: viable, edematous, and necrotic. A ratio of water concentration to total hemoglobin concentration, as measured optically, was performed for each tissue type and showed values for edematous tissue to be greater than viable tissue (1.2 +/- 0.49 M/microM versus 0.48 +/- 0.15 M/microM). Tissue hemoglobin oxygen saturation (StO2) also showed a large variation between tissue types: viable tissue had an optically measured StO2 value of 61 +/- 5%, whereas StO2 determined for necrotic tissue was 43 +/- 6%.
We present a combined near-infrared diffuse optical spectroscopy (DOS) and Magnetic Resonance Imaging (MRI) system for the study of animal model tumors. Acombined broadband steady-state and frequency ...domain optical spectroscopy apparatus was integrated with the MRI. The physiological properties of tissue rendered by MRI, including vascular volume fraction and water, were compared with chromophore concentrations as determined from the parameters obtained by optical measurements. DOS measurements provided oxyhemoglobin, deoxy-hemoglobin, and water concentration locally in tumors. A method for coregistration of the information obtained by both modalities was developed. Using Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, illustrating which tissue structure was probed optically. Finally, two optical contrast agents, indocyanine green (ICG) and methylene blue (MB), were employed and their kinetics were measured by DOS system from different locations on the tumor and compared with Gd-DTPA enhancement maps obtained from MRI.
Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, February 2010.
Vita. Cataloged from PDF version of thesis.
Includes bibliographical references.
In addition to cancer cells, ...solid tumors consist of a variety of cell types and tissues defining a complex microenvironment that influences disease progression and response to therapy. To fully characterize and probe the tumor microenvironment, new tools are needed to quantitatively assess microanatomical and physiological changes during tumor growth and treatment. Particularly important, is the metabolic microenvironment defined in tumors by hypoxia (low p02) and acidity (low pH). These parameters have been shown to influence response to radiation therapy and chemotherapy. However, very little is known about spatio-temporal changes in p02 and pH during tumor progression and therapy. By modifying the technique of intravital multiphoton microscopy (MPM) to perform phosphorescence quenching microscopy, I developed a non-invasive method to quantify oxygen tension (p02) in living tissue at high three-dimensional resolution. To probe functional changes in the metabolic microenvironment, I measured in vivo P02 during tumor growth and antiangiogenic (vascular targeted) treatment in preclinical tumor models. Nanotechnology is rapidly emerging as an important source of biocompatible tools that may shape the future of medical practice. Fluorescent semiconductor nanocrystals (NCs), also known as quantum dots, are a powerful tool for biological imaging, cellular targeting and molecular sensing.
(cont.) I adapted novel fluorescence resonance energy transfer (FRET) -based nanocrystal (NC) biosensors for use with MPM to qualitatively measure in vivo extracellular pH in tumors at high-resolution. While intravital multiphoton microscopy demonstrates utility and adaptability in the study of cancer and response to therapy, the requisite high numerical aperture and exogenous contrast agents result in a limited capacity to investigate substantial tissue volumes or probe dynamic changes repeatedly over prolonged periods. By applying optical frequency domain imaging (OFDI) as an intravital microscopic tool, the technical limitations of multiphoton microscopy can be circumvented providing unprecedented access to previously unexplored, critically important aspects of tumor biology. Using entirely intrinsic mechanisms of contrast within murine tumor models, OFDI is able to simultaneously, rapidly, and repeatedly probe the microvasculature, lymphatic vessels, and tissue microstructure and composition over large volumes. Using OFDI-based techniques, measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy were demonstrated, thereby highlighting the potential of OFDI to facilitate the exploration of pathophysiological processes and the evaluation of treatment strategies.
by Ryan M. Lanning.
Ph.D.
Frequency-domain photon migration (FDPM) is a non-invasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick ...tissues. Optical properties (absorption,
µ
a
, and scattering,
µ
s
′, parameters) derived from FDPM measurements can be used to construct low-resolution (0.5 to 1 cm) functional images of tissue hemoglobin (total, oxy-, and deoxyforms), oxygen saturation, blood volume fraction, water content, fat content and cellular structure. Unlike conventional NIR transillumination, FDPM enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by FDPM makes it well-suited to characterizing tumors in thick tissues. In order to test the sensitivity of FDPM for cancer diagnosis, we have initiated clinical studies to quantitatively determine normal and malignant breast tissue optical and physiological properties in human subjects. Measurements are performed using a non-invasive, multi-wavelength, diode-laser FDPM device optimized for clinical studies. Results show that ductal carcinomas (invasive and
in situ
) and benign fibroadenomas exhibit 1.25 to 3-fold higher absorption than normal breast tissue. Within this group, absorption is greatest for measurements obtained from sites of invasive cancer. Optical scattering is approximately 20% greater in pre-menopausal versus post-menopausal subjects due to differences in gland/cell proliferation and collagen/fat content. Spatial variations in tissue scattering reveal the loss of differentiation associated with breast disease progression. Overall, the metabolic demands of hormonal stimulation and tumor growth are detectable using photon migration techniques. Measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development.
Adults with limited health literacy have difficulty managing chronic conditions, higher hospitalization rates, and more healthcare expenditures. Simple screening tools have been developed, but ...limited work has evaluated instruments among low-income populations. This study assessed health literacy among primary care patients of a federally qualified health center, and compared a single screening question about perceived difficulty completing medical forms.A cross-sectional survey was administered to English-speaking patients ≥40 years. Both the Newest Vital Sign (NVS), a 6-item questionnaire, and a single-item screening question about perceived difficulty with completing medical forms, assessed health literacy. Logistic regression was used to identify predictors of inadequate health literacy and receiver operator curves compared the NVS and single-item question.Participants (n = 406) were, on average, aged 58.5 years (±11.3), 72.2% female, and identified as Hispanic/Latino (19.2%), non-Hispanic white (31.0%), non-Hispanic black (40.9%), or other (8.9%). Of the 406 participants, 335 (82.5%) completed the NVS. Patients who declined NVS were more likely to be older (P < .001) and male (P = .01). Only 13.7% had adequate health literacy. Older adults, Hispanic and non-Hispanic black patients, patients with missed office visits, and those reporting less confidence completing medical forms were significantly more likely to have inadequate health literacy. Perceived confidence completing medical forms demonstrated low sensitivity but high specificity at multiple thresholds.This is the first investigation to compare the NVS and confidence completing medical forms question. Many patients declined health literacy assessments, but health literacy screening may identify patients who need additional health education and resources.
Objectives
We evaluate the association between food insecurity (FI) and clinical depression, and the modifying effects of seasonality on this association.
Methods
Food insecurity is assessed from 175 ...post-partum women in the rural Ntcheu District of central Malawi using the USAID’s Household Food Insecurity Access Scale (HFIAS). Clinical depression is measured using a validated Chichewa version of the Self-Reporting Questionnaire (SRQ). Interviews were conducted from October 2016 to June 2017 and spanned 5 months of the dry season (April–November) and the 4 months of rainy season (December–March).
Results
After adjusting for age and parity, participants who reported high FI (HFIAS score ≥ 9) had 4.6 (95%CI 1.8–11.4) times the odds of meeting the cut-off for clinical depression (SRQ score ≥ 8). The effect was greater during the dry season (OR 9.9; 95%CI 2.0–48.6), than in the rainy season (OR 2.6; 95%CI 0.8–8.3) though the interaction term was not statistically significant (p = 0.18)
Conclusions for Practice
High FI is associated with diagnostic markers of clinical depression.
Loop is an open-source automated insulin dosing system that allows users unrivaled control over system settings that affect future glucose prediction. Thousands use Loop, but little is known about ...those who discontinue.
In a large observational study, 874 Loop participants completed surveys and provided glycemic data, 46 (5.3%) of those self-identified as discontinuing Loop use during the observation window, 45 completed a discontinued use survey, 22 provided system settings data, and 19 participated in semistructured interviews about their discontinuation. Qualitative data were transcribed, coded, and analyzed.
Older age and not trusting Loop were associated with discontinued use, although no other demographic or clinical characteristics were significant correlates. The most endorsed reasons were "I decided to try something else" (27.8%) followed by "It just didn't help as much as I thought it would" (22.2%). Qualitative analyses revealed prominent themes centered upon mental and emotional burden and adjusting settings. Other reasons for discontinued use included fear of disapproval of Loop use from diabetes provider, barriers to acquiring component devices, a desire to try new/different technologies, concerns that Loop could not accommodate specific exercise or low insulin dose regimens, and worry about Loop use during pregnancy. It was noted that burdens might be alleviated by enhanced technical assistance and expert guidance.
Although the majority of individuals in the Loop observational study continued use, those who discontinued reported similar challenges. Technical support and education specific to setting calculations could expand Loop benefits, alleviate burden, and support sustained use among new Loop users. Clinical Trial Registration: clinicaltrials.gov (NCT03838900).
We compare the contents of Fox and MSNBC weekday evening telecasts using natural language analysis with Linguistic Inventory Word Count (LIWC) and sociopolitical dictionaries tapping into moral ...foundations, values, grievances, and personality. Across time, the two networks differed substantially across many constructs, particularly those from LIWC. The core of the difference between the networks was captured by a four‐component measure which we labeled Personalizing versus Formal speech. Scores on this measure were particularly volatile during 2019 and 2020, a period which included Trump's first impeachment, the beginning of the COVID pandemic, and the 2020 presidential campaign. In comparison with prior presidential election years, only MSNBC showed a drop in positive emotions in 2020, while both networks increased in the use of communal and analytic language. Contrary to our expectations, the language style of the two networks did not demonstrate increasing divergence over time.
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