Diffuse optical spectroscopy (DOS) of breast tissue provides quantitative, functional information based on optical absorption and scattering properties that cannot be obtained with other radiographic methods. DOS-measured absorption spectra are used to determine the tissue concentrations of deoxyhemoglobin (Hb-R), oxyhemoglobin (Hb-O2), lipid, and water (H2O), as well as to provide an index of tissue hemoglobin oxygen saturation (StO2). Tissue-scattering spectra provide insight into epithelial, collagen, and lipid contributions to breast density. Clinical studies of women with malignant tumors show that DOS is sensitive to processes such as increased tissue vascularization, hypoxia, and edema. In studies of healthy women, DOS detects variations in breast physiology associated with menopausal status, menstrual cycle changes, and hormone replacement. Current research involves using DOS to monitor tumor response to therapy and the co-registration of DOS with magnetic resonance imaging. By correlating DOS-derived parameters with lesion pathology and specific molecular markers, we anticipate that composite &#x201c;tissue optical indices&#x201d; can be developed that non-invasively characterize both tumor and normal breast-tissue function.

Natasha Shah

Albert E. Cerussi

Dorota Jakubowski

David Hsiang

John Butler

Bruce J. Tromberg

The Role of Diffuse Optical Spectroscopy in the Clinical Management of Breast Cancer

The atomic force microscope (AFM) is emerging as a powerful tool in cell biology. Originally developed for high-resolution imaging purposes, the AFM also has unique capabilities as a nano-indenter to probe the dynamic viscoelastic material properties of living cells in culture. In particular, AFM elastography combines imaging and indentation modalities to map the spatial distribution of cell mechanical properties, which in turn reflect the structure and function of the underlying cytoskeleton. Such measurements have contributed to our understanding of cell mechanics and cell biology and appear to be sensitive to the presence of disease in individual cells. This chapter provides a background on the principles and practice of AFM elastography and reviews the literature comparing cell mechanics in normal and diseased states, making a case for the use of such measurements as disease markers. Emphasis is placed on the need for more comprehensive and detailed quantification of cell biomechanical properties beyond the current standard methods of analysis. A number of technical and practical hurdles have yet to be overcome before the method can be of clinical use. However, the future holds great promise for AFM elastography of living cells to provide novel biomechanical markers that will enhance the detection, diagnosis, and treatment of disease.

Kevin D. Costa

Single-Cell Elastography: Probing for Disease with the Atomic Force Microscope

This article reviews two types of ultrasound-mediated biophotonic imaging&#x2013;acousto-optical tomography (AOT, also called ultrasound-modulated optical tomography) and photo-acoustic tomography (PAT, also called opto-acoustic or thermo-acoustic tomography)&#x2013;both of which are based on non-ionizing optical and ultrasonic waves. The goal of these technologies is to combine the contrast advantage of the optical properties and the resolution advantage of ultrasound. In these two technologies, the imaging contrast is based primarily on the optical properties of biological tissues, and the imaging resolution is based primarily on the ultrasonic waves that either are provided externally or produced internally, within the biological tissues. In fact, ultrasonic mediation overcomes both the resolution disadvantage of pure optical imaging in thick tissues and the contrast and speckle disadvantages of pure ultrasonic imaging. In our discussion of AOT, the relationship between modulation depth and acoustic amplitude is clarified. Potential clinical applications of ultrasound-mediated biophotonic imaging include early cancer detection, functional imaging, and molecular imaging.

Lihong V. Wang

Ultrasound-Mediated Biophotonic Imaging: A Review of Acousto-Optical Tomography and Photo-Acoustic Tomography

The advent of recent advances in near-infrared laser diodes and fast electro-optic detection has spawned a new research field of diagnostic spectroscopy and imaging based on targeting and reporting exogenous fluorescent agents. This review seeks to concisely address the physics, instrumentation, advancements in tomography, and near-infrared fluorescent contrast agent development that promises selective and specific molecular targeting of diseased tissues. As an example of one area of the field, recent work focusing on pharmacokinetic analysis of fluorophores targeting the epidermal growth factor receptor (EGFR) is presented in a human breast cancer xenograft mouse model to demonstrate specificity of molecularly targeted contrast agents. Finally, a critical evaluation of the limitations and the opportunities for future translation of fluorescence-enhanced optical imaging of deep tissues is presented.

Michael Gurfinkel

Shi Ke

Xiaoxia Wen

Chun Li

Eva M. Sevick-Muraca

Near-Infrared Fluorescence Optical Imaging and Tomography

Imaging techniques are a combination of a contrast mechanism, exogenous or endogenous, and an instrument to exploit that contrast. This final chapter of these two special issues of this journal points to possible ways to improve the ability of imaging systems to exploit markers of cancer in the early detection of that disease. The aim not only is to find cancer at an earlier, more treatable stage, but to determine whether the disease discovered is dangerous and to indicate the possibilities for successful treatment. These topics are explored for each imaging system, with an emphasis on directions for future improvements.

Barbara Y. Croft

The Future of Medical Imaging in the Detection of Early Markers of Disease

Cancer cells display heterogeneous genetic characteristics, depending on the tumor dynamic microenvironment. Abnormal tumor vasculature and poor tissue oxygenation generate a fraction of hypoxic tumor cells that have selective advantages in metastasis and invasion and often resist chemo- and radiation therapies. The genetic alterations acquired by tumors modify their biochemical pathways, which results in abnormal tumor metabolism. An elevation in glycolysis known as the &#x201c;Warburg effect&#x201d; and changes in lipid synthesis and oxidation occur. Magnetic resonance spectroscopy (MRS) has been used to study tumor metabolism in preclinical animal models and in clinical research on human breast, brain, and prostate cancers. This technique can identify specific genetic and metabolic changes that occur in malignant tumors. Therefore, the metabolic markers, detectable by MRS, not only provide information on biochemical changes but also define different metabolic tumor phenotypes. When combined with the contrast-enhanced Magnetic Resonance Imaging (MRI), which has a high sensitivity for cancer diagnosis, in vivo magnetic resonance spectroscopic imaging (MRSI) improves the diagnostic specificity of malignant human cancers and is becoming an important clinical tool for cancer management and care. This article reviews the MRSI techniques as molecular imaging methods to detect and quantify metabolic changes in various tumor tissue types, especially in extracranial tumor tissues that contain high concentrations of fat. MRI/MRSI methods have been used to characterize tumor microenvironments in terms of blood volume and vessel permeability. Measurements of tissue oxygenation and glycolytic rates by MRS also are described to illustrate the capability of the MR technology in probing molecular information non-invasively in tumor tissues and its important potential for studying molecular mechanisms of human cancers in physiological conditions.

Qiuhong He

Ray Z. Xu

Pavel Shkarin

Giuseppe Pizzorno

Carol H. Lee-French

Douglas L. Rothman

Dikoma C. Shungu

Hyunsuk Shim

Magnetic Resonance Spectroscopic Imaging of Tumor Metabolic Markers for Cancer Diagnosis, Metabolic Phenotyping, and Characterization of Tumor Microenvironment

Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) has been utilized to study energy, carbohydrate, and phospholipid metabolism in vitro and in vivo in live tissues non-invasively. Despite its lack of sensitivity, its application has extended to in situ human tissues and organs since proper signal localization was devised. Follow-up of phosphocreatine in neuromuscular diseases and schizophrenia and follow-up of phospholipid-related molecules in tumors are described here to demonstrate the value of 31P-MRS as an imaging technique to determine in vivo markers of disease and in the diagnosis, prognosis, and follow-up of human diseases.

Fernando Arias-Mendoza

Truman R. Brown

In Vivo Measurement of Phosphorous Markers of Disease

Foreword

About this journal

Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

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Chief Editor Paola Gazzaniga is an Associate Professor in the Department of Molecular Medicine at Sapienza University of Rome, Italy. Her core research focuses on liquid biopsies in patients with solid tumors.

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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

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Disease Markers | Hindawi

Disease Markers

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