Jesse Butler

Presurgical chemotherapy is widely used in the treatment of locally advanced breast cancer. Monitoring the response to therapy can improve survival and reduce morbidity. We employ a noninvasive, near-infrared method based on diffuse optical spectroscopy to quantitatively monitor tumor response to neoadjuvant chemotherapy. DOS was used to monitor tumor response in one patient with locally advanced breast cancer throughout the course of her therapy. Measurements were performed prior to doxorubicin-cyclophosphamide therapy and at several time points over the course of three treatment cycles. Our results show strong tumor to normal tissue contrast in total hemoglobin concentration, water fraction, tissue hemoglobin oxygen saturation, S tO 2, and lipid fraction prior to treatment. Over a 10-week period, the peak total hemoglobin and water dropped 56 and 67%, respectively. Lipid content nearly returned to baseline while S tO 2 exceeded pretreatment levels. Approximately half of the hemoglobin and water changes occurred within 5 days of treatment. These data suggest that noninvasive, quantitative optical methods that characterize tumor physiology may be useful in assessing and optimizing individual response to neoadjuvant chemotherapy. © 2004 Society of Photo-Optical Instrumentation Engineers.

Near-infrared diffuse optical spectroscopy and, diffuse optical imaging show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration instrument. Wavelength-dependent absorption and reduced scattering parameters were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy- and deoxy- hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal women is approximately two-fold higher than for postmenopausal subjects at all positions. POST women have approximately 50% higher lipid content than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration, 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for μa and 5 to 12% for μs′. Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering within an individual. © 2004 Society of Photo-Optical Instrumentation Engineers.

Near-infrared diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR techniques are based on quantitative measurements of functional contrast between healthy and diseased tissue. In this study we measured the spectral dependence of tissue absorption and reduced scattering in the breasts of 30 healthy women and one woman with a fibroadenoma using a seven-wavelength frequency-domain photon migration probe. Subjects included pre- and postmenopausal women between the ages of 18 and 64. Multi-spectral measurements were used along with a four-component fit to determine the concentrations of de-oxy and oxyhemoglobin, water and lipids in breast. The scattering spectral shape was also quantified. Our measurements demonstrate that the measured concentrations of NIR analytes correlate well with known breast physiology. Although the tissue scattering at a single wavelength was found to have little value as a functional parameter, the dependence of the scattering on wavelength provided key insights into breast composition and physiology. Lipids and scattering spectra in the breast were found to increase and decrease, respectively, with increasing body mass index. Simple calculations are also provided to demonstrate potential penalties from ignoring the contributions of water and lipids in breast measurements. Finally, water is shown to be a possible indicator for detecting a fibroadenoma, whereas the hemoglobin saturation was found to be a poor indicator. Multi-spectral measurements, compared to measurements restricted to one or two wavelengths, provide additional information that may be useful in managing breast disease. © 2002 Society of Photo-Optical Instrumentation Engineers.

Rationale and Objectives. Near-infrared diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR techniques are based on sensitive, quantitative measurements of functional contrast between healthy and diseased tissue. In this study, the authors quantified the origins of this contrast in healthy breasts. Materials and Methods. A seven-wavelength frequency-domain photon migration probe was used to perform noninvasive NIR measurements in the breasts of 28 healthy women, both pre- and postmenopausal, aged 18-64 years. A diffusive model of light transport quantified oxygenated and deoxygenated hemoglobin, water, and lipid by their absorption signatures. Changes in the measured light-scattering spectra were quantified by means of a "scatter power" parameter. Results. Substantial quantitative differences were observed in both absorption and scattering spectra of breast as a function of subject age. These physiologic changes were consistent with long-term hormone-dependent transformations that occur in breast. Instrument response was not adversely affected by subject age or menopausal status. Conclusion. These measurements provide new insight into endogenous optical absorption and scattering contrast mechanisms and have important implications for the development of optical mammography. NIR spectroscopy yields quantitative functional information that cannot be obtained with other noninvasive radiologic techniques.

In this dissertation I offer a new framework for understanding introspection, characterizing it as a multi-faceted phenomenon that has a broad range of epistemic qualities. I begin by arguing that the standard understanding of introspection as a kind of perception through which we observe our own minds is misguided as a literal account of introspection. With this established, I move on to discuss our diverse abilities to know, and fail to know, our own minds. First, I describe the uniquely first-person experiential knowledge that we have in virtue of being constituted by our own conscious mental states. Second, I illustrate how we know about our own minds through higher-order cognitive abilities, through which we represent, conceptualize, and pay attention to aspects of our own minds in much the same way that we do in understanding the world around us. Finally, I present and discuss several different ways in which language, through the phenomenon of inner speech, contributes to our ability to introspect. Throughout this project, one prominent goal is to map out the varied epistemic dimensions of introspection. Some kinds of introspection provide unique ways of knowing our own minds that are not subject to typical epistemic error, such as the experiential self-knowledge intrinsic to being in a conscious state. However, many other kinds of introspection are subject to error, such as the inherent capacity to misrepresent anything that is mediated through conceptual and representational thought and the capacity to deceive ourselves through the narratives we construct in inner speech. In addition, we can also engage in self-constitutive mental processes, such that what we know about ourselves can at times be a function of what we ourselves determine. Taking note of these diverse aspects of introspection provides a foundational framework for further empirical inquiry and conceptual analysis, whereby the broad range of introspective activities we engage in, along with the impacts they have on both our ordinary lives and our intellectual investigations into the nature of the mind, can be more accurately understood, evaluated, and utilized.

We seem to have private privileged access to our own minds through introspection, but what exactly does this involve? Do we somehow literally perceive our own minds, as the common idea of a 'mind's eye' suggests, or are there other processes at work in our ability to know our own minds? Rethinking Introspection offers a new pluralist framework for understanding the nature, scope, and limits of introspection. The book argues that, contrary to common misconceptions, introspection does not consist of a single mechanism but rather a diverse range of mental states and cognitive processes with a broad spectrum of epistemic properties. Building upon this revised conception of introspection, the book illustrates and analyzes the variety of ways in which we introspectively grasp the contents of our own minds, from the immediate phenomenal knowledge generated by conscious experience to the self-deceptive possibilities enabled by certain kinds of inner speech.

In response to Petitmengin and Bitbol's recent account of first-person methodologies in the study of consciousness, I provide a revised model of our introspective knowledge of our own conscious experience. This model, which I call the existential constitution model of phenomenal knowledge, avoids the problems that Petitmengin and Bitbol identify with standard observational models of introspection while also avoiding an underlying metaphorical misconception in their own proximity model, which misconstrues first-person knowledge of consciousness in terms of a dichotomous epistemic relationship. The end result is a clearer understanding of the unique nature and epistemic properties of our knowledge of consciousness, as well as the epistemic status of subsequent first-person reports on conscious experience