THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

A fast-Fourier-transform method of topography and interferometry is proposed. By computer processing of a noncontour type of fringe pattern, automatic discrimination is achieved between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour-generation techniques. The method has advantages over moire topography and conventional fringe-contour interferometry in both accuracy and sensitivity. Unlike fringe-scanning techniques, the method is easy to apply because it uses no moving components.

Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry

1.1 Photodynamic Therapy and Imaging
The purpose of this review is to present the current state of the role of imaging in photodynamic therapy (PDT). In order for the reader to fully appreciate the context of the discussions embodied in this article we begin with an overview of the PDT process, starting with a brief historical perspective followed by detailed discussions of specific applications of imaging in PDT. Each section starts with an overview of the specific topic and, where appropriate, ends with summary and future directions. The review closes with the authors’ perspective of the areas of future emphasis and promise. The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies.

PDT is a photochemistry-based approach that uses a light-activatable chemical, termed a photosensitizer (PS), and light of an appropriate wavelength, to impart cytotoxicity via the generation of reactive molecular species (Figure 1a). In clinical settings, the PS is typically administered intravenously or topically, followed by illumination using a light delivery system suitable for the anatomical site being treated (Figure 1b). The time delay, often referred to as drug-light interval, between PS administration and the start of illumination with currently used PSs varies from 5 minutes to 24 hours or more depending on the specific PS and the target disease. Strictly speaking, this should be referred to as the PS-light interval, as at the concentrations typically used the PS is not a drug, but the drug-light interval terminology seems to be used fairly frequently. Typically, the useful range of wavelengths for therapeutic activation of the PS is 600 to 800 nm, to avoid interference by endogenous chromophores within the body, and yet maintain the energetics necessary for the generation of cytotoxic species (as discussed below) such as singlet oxygen (1O2). However, it is important to note that photosensitizers can also serve as fluorescence imaging agents for which activation with light in the 400nm range is often used and has been extremely useful in diagnostic imaging applications as described extensively in Section 2 of this review. The obvious limitation of short wavelength excitation is the lack of tissue penetration so that the volumes that are probed under these conditions are relatively shallow.






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Figure 1


(A) A schematic representation of PDT where PS is a photoactivatable multifunctional agent, which, upon light activation can serve as both an imaging agent and a therapeutic agent. (B) A schematic representation of the sequence of administration, localization and light activation of the PS for PDT or fluorescence imaging. Typically the PS is delivered systemically and allowed to circulate for an appropriate time interval (the “drug-light interval”), during which the PS accumulates preferentially in the target lesion(s) prior to light activation. In the idealized depiction here the PS is accumulation is shown to be entirely in the target tissue, however, even if this is not the case, light delivery confers a second layer of selectivity so that the cytotoxic effect will be generated only in regions where both drug and light are present. Upon localization of the PS, light activation will result in fluorescence emission which can be implemented for imaging applications, as well as generation cytotoxic species for therapy. In the former case light activation is achieved with a low fluence rate to generate fluorescence emission with little or no cytotoxic effect, while in the latter case a high fluence rate is used to generate a sufficient concentration of cytotoxic species to achieve biological effects.

/pdf/imaging-and-photodynamic-therapy-mechanisms-monitoring-and-76rc7acuq5.pdf

Imaging and photodynamic therapy: mechanisms, monitoring, and optimization.

There have been three basic approaches to optical tomography since the early 1980s: diffraction tomography, diffuse optical tomography and optical coherence tomography (OCT). Optical techniques are of particular importance in the medical field, because these techniques promise to be safe and cheap and, in addition, offer a therapeutic potential. Advances in OCT technology have made it possible to apply OCT in a wide variety of applications but medical applications are still dominating. Specific advantages of OCT are its high depth and transversal resolution, the fact, that its depth resolution is decoupled from transverse resolution, high probing depth in scattering media, contact-free and non-invasive operation, and the possibility to create various function dependent image contrasting methods. This report presents the principles of OCT and the state of important OCT applications. OCT synthesises cross-sectional images from a series of laterally adjacent depth-scans. At present OCT is used in three different fields of optical imaging, in macroscopic imaging of structures which can be seen by the naked eye or using weak magnifications, in microscopic imaging using magnifications up to the classical limit of microscopic resolution and in endoscopic imaging, using low and medium magnification. First, OCT techniques, like the reflectometry technique and the dual beam technique were based on time-domain low coherence interferometry depth-scans. Later, Fourier-domain techniques have been developed and led to new imaging schemes. Recently developed parallel OCT schemes eliminate the need for lateral scanning and, therefore, dramatically increase the imaging rate. These schemes use CCD cameras and CMOS detector arrays as photodetectors. Video-rate three-dimensional OCT pictures have been obtained. Modifying interference microscopy techniques has led to high-resolution optical coherence microscopy that achieved sub-micrometre resolution. This report is concluded with a short presentation of important OCT applications. Ophthalmology is, due to the transparent ocular structures, still the main field of OCT application. The first commercial instrument too has been introduced for ophthalmic diagnostics (Carl Zeiss Meditec AG). Advances in using near-infrared light, however, opened the path for OCT imaging in strongly scattering tissues. Today, optical in vivo biopsy is one of the most challenging fields of OCT application. High resolution, high penetration depth, and its potential for functional imaging attribute to OCT an optical biopsy quality, which can be used to assess tissue and cell function and morphology in situ. OCT can already clarify the relevant architectural tissue morphology. For many diseases, however, including cancer in its early stages, higher resolution is necessary. New broad-bandwidth light sources, like photonic crystal fibres and superfluorescent fibre sources, and new contrasting techniques, give access to new sample properties and unmatched sensitivity and resolution.

/pdf/optical-coherence-tomography-principles-and-applications-17y32cabbm.pdf

Optical coherence tomography - principles and applications

Label-Free Optical Micro-Angiography for Functional Imaging of Microcirculations within Tissue Beds In Vivo

Tissue stiffness can be measured from the propagation speed of shear waves. Acoustic radiation force (ARF) can generate shear waves by focusing ultrasound in tissue for ~100 μs. Safety considerations and electronics abilities limit ultrasound pressures. We previously presented shear wave elastography combining ARF and phase-sensitive optical coherence tomography (PhS-OCT) [1]. Here, we use amplitude-modulated ARF to enhance shear wave signal-to-noise ratio (SNR) at low pressures. Experiments were performed on tissue-mimicking phantoms. ARF was applied using a single-element transducer, driven by a 7.5 MHz, 3-ms, sine wave modulated in amplitude by a linear-swept frequency (1 to 7 kHz). Pressures between 1 to 3 MPa were tested. Displacements were tracked using PhS-OCT and numerically compressed using pulse compression methods detailed in previous work [2]. SNR was compared to that of 200-μs bursts. Stiffness maps were reconstructed using time-of-flight computations. 200-μs bursts give barely detectable displacements at 1 MPa (3.7 dB SNR). Pulse compression gives 36.2 dB at 1.5 MPa. In all cases with detectable displacements, shear wave speeds were determined in 5%-gelatin and 10%-gelatin phantoms and compared to literature values. Applicability to ocular tissues (cornea, intraocular lens) is under investigation.

Amplitude-modulated ultrasound radiation force combined with phase-sensitive optical coherence tomography for shear wave elastography

Peripapillary Retinal Nerve Fiber Layer (RNFL) Vascular Microcirculation in Glaucomatous Eyes with Asymmetric Hemifield Visual Field (VF) Loss

In our previous report, we have presented the possibility of optical coherence tomography (OCT) to monitor the redox state of mitochondria enzyme Cytochrome oxidase (CytOx) in bone tissue. The previous results showed that reduction of the enzyme in periosteal tissue leads to a change in attenuation coefficient of 1.68 +/- 0.67mm -1 by OCT measurements. The new results from cultured cells fixed in 300 (mu) l agarose plug showed the difference in attenuation coefficient is 0.26+-0.10 mm -1 (n = 9) for 7x10 6 astrocytoma cells and 0.28+-0.13 mm -1 (n = 7) for 20x10 6 astrocytoma cells in agarose plug, respectively between cells with oxidised and reduced enzyme at 820nm. A decrease in attenuation coefficient of 0.35+-0.09 mm -1 (n = 4) for 10 million SKMES cells in agarose was also observed with the redox shift of CytOx. The absorption coefficient of the oxidized-reduced form of CytOx is measured approximately 8.4+-1.5x10 -3 /mm (n=3) and 8.2+-1.0x10 -3 /mm (n=3) at 820nm for astrocytoma cells and rat periosteum respectively by means of a biochemical assay. Thereby it can be seen that the change in attenuation coefficient of cultured cells with redox shift of CytOx mainly results from the scattering change.

Does light scattering affect the OCT quantitation of redox state of cytochrome oxidase in bone tissue

In this paper, we demonstrate for the first time utilizing a super continuum light source to achieve ultra high
sensitive Optical Micro-Angiography (UHS-OMAG) system. The broad band light with central wavelength around
800nm, emitted from the super continuum light source, could provide a ~2μm coherence gate for the system. Based
on a fast CMOS camera, we could successfully develop a high speed (~70 kHz line rate) Fourier Domain Optical
coherence tomography system. Applying the ultra high sensitive OMAG algorithm onto the system, we could
visualize blood vessel networks buried within the tissue bed in a high resolution and high sensitivity mode. The
modality is performed on imaging the human finger nail fold and the mouse pinna to obtain both high resolution
structure image and detailed blood perfusion map. The excellent performance shows a great potential of our system
in future biological imaging application.

Ruikang K. Wang

Papers

Label-Free Optical Micro-Angiography for Functional Imaging of Microcirculations within Tissue Beds In Vivo

Amplitude-modulated ultrasound radiation force combined with phase-sensitive optical coherence tomography for shear wave elastography

Peripapillary Retinal Nerve Fiber Layer (RNFL) Vascular Microcirculation in Glaucomatous Eyes with Asymmetric Hemifield Visual Field (VF) Loss

Does light scattering affect the OCT quantitation of redox state of cytochrome oxidase in bone tissue

Ultra high resolution ultra high sensitive optical micro-angiography based on super continuum light source