Pathologic Basis of Diseaseby Stanley L. Robbins is really the fourth edition of hisPathology. Appropriate updating and addition enhance the otherwise identical format, sequence, writing, and illustrations. So many medical students have benefited from this source that it may be the best known general book in the field. I recommend it even more now. Like his former texts, this will be enjoyed for its readability. He clearly lays out a great deal of information. When he includes minutiae, the reasons are clear and one feels that all the material is pertinent. Robbins keeps the whole field in perspective—that is, he does not dwell so long or so heavily on pathologic anatomy or pathogenesis as to tempt the reader to overlook clinical presentation or prognosis. A great strength of the subject of pathology is that it bonds strongly with many other medical sciences and specialties and thus occupies the

Pathologic Basis of Disease

Diffuse optical imaging DOI may be a beneficial diagnos- tic method for women with mammographically dense breast tissue. In order to evaluate the utility of DOI, we are developing broadband diffuse optical spectroscopy DOS to characterize the functional ori- gins of optical signals in breast cancer patients. Broadband DOS com- bines multifrequency intensity-modulated and continuous-wave near- infrared light to quantify tissue absorption and scattering spectra from 650 to 1000 nm. Values of intrinsic physiological properties oxy- and deoxy-hemoglobin, water, lipid, and scatter power derived from absorption and scattering spectra provide detailed information on breast physiology. We present the results of clinical studies of 58 stage II/III malignant breast tumors using a noninvasive, handheld, broad- band DOS probe. On average, eight positions were scanned over tumor and contralateral normal breast for each subject. Intrinsic physiological properties were statistically significantly different for malignant vs. normal tissues for all subjects, without patient age or tumor size/type stratification. Breast tissues containing malignant tu- mors displayed reduced lipid content 20% and increased water, deoxy-, and oxy-hemoglobin 50% each compared to normal breast tissues. Functional perturbations by the tumor were signifi- cantly larger than functional variations in normal tissues. A tissue op- tical index TOI derived from intrinsic physiological properties yielded an average two-fold contrast difference between malignant tumors and intrinsic tissue properties. Our results demonstrate that intrinsic optical signals can be influenced by functional perturbations characteristic of malignant transformation; cellular metabolism, extra- cellular matrix composition, and angiogenesis. Our findings further underscore the importance of broadband measurements and patient age stratification in breast cancer DOI. © 2006 Society of Photo-Optical Instru-

http://www.bli.uci.edu/profiles/editor/userfiles/acerussi/cerussi.jbo06.pdf

In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy

Early identification of high-risk disease could greatly reduce both mortality and morbidity due to oral cancer. We describe a simple handheld device that facili- tates the direct visualization of oral-cavity fluorescence for the detection of high-risk precancerous and early cancer- ous lesions. Blue excitation light 400 to 460 nm is em- ployed to excite green-red fluorescence from fluorophores in the oral tissues. Tissue fluorescence is viewed directly along an optical axis collinear with the axis of excitation to reduce inter- and intraoperator variability. This robust, field-of-view device enables the direct visualization of fluorescence in the context of surrounding normal tissue. Results from a pilot study of 44 patients are presented. Using histology as the gold standard, the device achieves a sensitivity of 98% and specificity of 100% when dis- criminating normal mucosa from severe dysplasia/ carcinoma in situ CIS or invasive carcinoma. We envis- age this device as a suitable adjunct for oral cancer screening, biopsy guidance, and margin delineation.

/pdf/simple-device-for-the-direct-visualization-of-oral-cavity-1teqg1x78b.pdf

Simple device for the direct visualization of oral-cavity tissue fluorescence

A thorough understanding of optical properties of biological tissues is critical to effective treatment planning for therapies such as photodynamic therapy (PDT). In the last two decades, new technologies, such as broadband diffuse spectroscopy, have been developed to obtain in vivo data in humans that was not possible before. We found that the in vivo optical properties generally vary in the ranges μ(a) = 0.03-1.6 cm⁻¹ and μ'(s) = 1.2-40 cm⁻¹, although the actual range is tissue-type dependent. We have also examined the overall trend of the absorption spectra (for μ(a) and μ'(s)) as a function of wavelength within a 95% confidence interval for various tissues in vivo. The impact of optical properties on light fluence rate is also discussed for various light application geometries including superficial, interstitial, and within a cavity.

/pdf/a-review-of-in-vivo-optical-properties-of-human-tissues-and-4sa3qlende.pdf

A review of in-vivo optical properties of human tissues and its impact on PDT

We propose a new illumination method for a medical endoscope: narrow band imaging (NBI), in which the spectral bandwidth of the filtered light is narrowed. To confirm how the spectral specifications of the filtered light influence a reproduced image, an experiment was conducted observing the endoscopic images of the back mucosa of a human tongue. In addition, the effect of NBI on endoscopic images was investigated through preliminary clinical tests in colonoscopy and upper gastrointestinal endoscopy. It has been shown that NBI can enhance the capillary pattern and the crypt pattern on the mucosa. These patterns are useful features for diagnosing an early cancer.

Endoscopic observation of tissue by narrowband illumination

As part of our ongoing efforts to understand the fundamental nature of light scattering from cells and tissues, we present data on elastic light scattering from isolated mammalian tumor cells and nuclei. The contribution of scattering from internal structures and in particular from the nuclei was compared to scattering from whole cells. Roughly 55% of the elastic light scattering at high-angles (> 40 degrees) comes from intracellular structures. An upper limit of 40% on the fractional contribution of nuclei to scattering from cells in tissue was determined. Using cell suspensions isolated from monolayer cultures at different stages of growth, we have also found that scattering at angles greater than about 110 degrees was correlated with the DNA content of the cells. Based on model calculations and the relative size difference of nuclei from cells in different stages of growth, we argue that this difference in scattering results from changes in the internal structures of the nucleus. This interpretation is consistent with our estimate of 0.2 micron as the mean size of the scattering centers in cells. Additionally, we find that while scattering from the nucleus accounts for a majority of internal scattering, a significant portion must result from scattering off of cytoplasmic structures such as mitochondria.

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-5/issue-02/0000/Light-scattering-from-cells--the-contribution-of-the-nucleus/10.1117/1.429979.pdf

Light scattering from cells: the contribution of the nucleus and the effects of proliferative status

As part of our ongoing efforts to understand the fundamen- tal nature of light scattering from cells and tissues, we present data on elastic light scattering from isolated mammalian tumor cells and nu- clei. The contribution of scattering from internal structures and in par- ticular from the nuclei was compared to scattering from whole cells. Roughly 55% of the elastic light scattering at high-angles (>40°) comes from intracellular structures. An upper limit of 40% on the fractional contribution of nuclei to scattering from cells in tissue was determined. Using cell suspensions isolated from monolayer cultures at different stages of growth, we have also found that scattering at angles greater than about 110° was correlated with the DNA content of the cells. Based on model calculations and the relative size differ- ence of nuclei from cells in different stages of growth, we argue that this difference in scattering results from changes in the internal struc- tures of the nucleus. This interpretation is consistent with our estimate of 0.2 mm as the mean size of the scattering centers in cells. Addition- ally, we find that while scattering from the nucleus accounts for a majority of internal scattering, a significant portion must result from scattering off of cytoplasmic structures such as mitochondria. © 2000 Society of Photo-Optical Instrumentation Engineers. (S1083-3668(00)00202-1)

Tissue strongly scatters light. Therefore, virtually all techniques for probing tissue with light are dependent on the scattering interactions of light with tissue. In particular, noninvasive optical methods for determining tissue morphology are dependent on light scattering. A fundamental understanding of what cellular features scatter light and of how changes internal cellular structures affect the measurement of light transport are needed. In this work, we describe some of the recent progress made towards understanding the basic mechanisms of light scattering in tissue.

K. Stetter

Papers

Light scattering from cells: the contribution of the nucleus and the effects of proliferative status

Light scattering from cells: the contribution of the nucleus and the effects of proliferative status

Basic mechanisms of light scattering in tissue