This paper reviews the history of the optoelectric devices applied to biomedical sciences in 20th century. It describes history of Vacuum tubes and Spectroscopies with the author’s personal experiences, especially doublebeam spectroscopy. Further, the present developments of Near Infra Red (NIR) devices are described in translational biomedical applications. It includes particulary micro optoelectronics developments and present status of NIR breast cancer detection. Lastly, intrinsic molecular biomarkers are discussed especially NIR measurements of angiogenensis, hypermetabolism and heat production for cancer detection.

Welcome to the inaugural issue of the Journal of Innovative Optical Health Sciences. In the past decades, we have witnessed how the combination of photonics and health sciences has benefited and touched our lives. Through products and techniques such as spectroscopy, lasers, microscopy, imaging and fiber optics, the science of biomedical photonics has shown great potential in solving clinical and research problems in diverse applications. Under this consideration, the JIOHS has been founded to serve as an international forum for the publication of the latest developments in all areas of biomedical photonics.

An ultra high resolution spectral-domain optical coherence tomography (SD-OCT) together with an advanced animal restraint and positioning system was built for noninvasive non-contact in vivo three-dimensional imaging of rodent models of ocular diseases. The animal positioning system allowed the operator to rapidly locate and switch the areas of interest on the retina. This function together with the capability of precise spatial registration provided by the generated OCT fundus image allows the system to locate and compare the same lesion (retinal tumor in the current study) at different time point throughout the entire course of the disease progression. An algorithm for fully automatic segmentation of the tumor boundaries and calculation of tumor volume was developed. The system and algorithm were successfully applied to monitoring retinal tumor growth quantitatively over time in the LHBETATAG mouse model of retinoblastoma.

Terahertz technology is continually evolving and much progress has been made in recent years. Many new applications are being discovered and new ways to implement terahertz imaging investigated. In this review, we limit our discussion to biomedical applications of terahertz imaging such as cancer detection, genetic sensing and molecular spectroscopy. Our discussion of the development of new terahertz techniques is also focused on those that may accelerate the progress of terahertz imaging and spectroscopy in biomedicine.

Recent years have seen the design and implementation of many optical activatable smart probes. These probes are activatable because they change their optical properties and are smart because they can identify specific targets. This broad class of detection agents has allowed previously unperformed visualizations, facilitating the study of diverse biomolecules including enzymes, nucleic acids, ions and reactive oxygen species. Designed to be robust in an in vivo environment, these probes have been used in tissue culture cells and in live small animals. An emerging class of smart probes has been designed to harness the potency of singlet oxygen generating photosensitizers. Combining the discrimination of activatable agents with the toxicity of photosensitizers represents a new and powerful approach to disease treatment. This review highlights some applications of activatable smart probes with a focus on developments of the past decade.

Focal ischemia due to reduction of cerebral blood flow (CBF), creates 2 zones of damage: the core area, which suffers severe damage, and penumbra area, which surrounds the core and suffers intermediate levels of injury. Objectives: A novel method is introduced, which evaluates mitochondrial function in the core and in the penumbra, during focal cerebral ischemia. Methods: Wistar rats underwent focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by 60 minutes of reperfusion. Mitochondrial function was assessed by a unique Multi-Site — Multi-Parametric (MSMP) monitoring system, which measures mitochondrial NADH using fluorometric technique, and CBF using Laser Doppler Flowmetry (LDF). Results: At the onset of occlusion, CBF dropped and NADH increased significantly only in the right hemisphere. CBF levels were significantly lower and NADH significantly higher in the core than in the penumbra. After reperfusion, CBF and NADH recovered correspondingly to the intensity of ischemia. Conclusion: Application of the MSMP system can add significant information for the understanding of the cerebral metabolic state under ischemic conditions, with an emphasis on mitochondrial function.

The involvement of mitochondrial dysfunction in various pathophysiological conditions, developed in experimental and clinical situations, is widely documented. Nevertheless, real time monitoring of mitochondrial function In-vivo is very rare. The pressing question is how the mitochondria of intact tissues behave under In-vivo conditions as compared to isolated mitochondria that had been described by Chance and Williams over 50 years ago. This subject has been recently discussed in detail (Mayevsky and Rogatsky 2007). We reviewed the subject of evaluating mitochondrial function by monitoring NADH fluorescence together with microcirculatory blood flow, Hemoglobin oxygenation and tissue reflectance. These 4 parameters represent the vitality of the tissue and could be monitored in vivo, using optical spectroscopy, in animal models as well as in clinical practice. It is a well known physiological hypothesis that, under emergency conditions, the sympathetic nervous system will give preference to the most vital organs in the body, namely the brain, heart and adrenal glands. The less vital organs, such as the skin, GI-tract, and Urethral wall, will become hypoperfused and their mitochondrial activity will be inhibited. The monitoring of the less vital organs may reveal critical tissue conditions that may manifest an early phase of body deterioration. The aim of the current presentation is to review the experimental and preliminary clinical results accumulated using a new integrated medical device – the “CritiView” which enabled, for the first time, monitoring 4 parameters from the tissue using a single optical probe. The CritiView is a computerized optical device that integrates hardware and software in order to provide real time information on tissue vitality. In preliminary clinical testing, we used a 3-way Foley catheter that includes a bundle of optical fibers enabling the monitoring of the 4 parameters, representing the vitality of the urethral wall (a less vital organ).We found that the exposure of patients to metabolic imbalances in the operation room led to changes in tissue blood flow and inhibition of mitochondrial function in the urethral wall. In conclusion, the new device “CritiView” could provide reliable, real time data on mitochondrial function and tissue vitality in experimental animals as well as in patients.

An overview of three techniques developed by our group for imaging superficial tissue is presented. Firstly, a novel polarized light capillaroscope has been developed for imaging the microcirculation. The capillaroscope has been used to make in vivo measurements of sickle cell disorder sufferers with aim of monitoring the polymerization of sickled red blood cells. Secondly, hyperspectral imaging for measuring oxygen saturation is described. The accuracy of such measurements is affected by the non-linear relationship between scattering and absorption and it is demonstrated that polarization techniques can be used to make the relationship more linear, thus improving accuracy. Finally, the use of smart CMOS optical sensors for laser Doppler blood flowmetry is described. A 32×32 pixel imaging array with on-chip processing is described and the potential for full field laser Doppler blood flow imaging is demonstrated through measurement on blood flow of tissue before and after occlusion.

Raman spectroscopy is a noninvasive, nondestructive analytical method capable of determining the biochemical constituents based on molecular vibrations. It does not require sample preparation or pretreatment. However, the use of Raman spectroscopy for in vivo clinical applications will depend on the feasibility of measuring Raman spectra in a relatively short time period (a few seconds). In this work, a fast dispersive-type nearinfrared (NIR) Raman spectroscopy system and a skin Raman probe were developed to facilitate real-time, noninvasive, in vivo human skin measurements. Spectrograph image aberration was corrected by a parabolic-line fiber array, permitting complete CCD vertical binning, thereby yielding a 16-fold improvement in signal-to-noise ratio. Good quality in vivo skin NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired within one second, which greatly facilitates practical noninvasive tissue characterization and clinical diagnosis. Currently, we are conducting a large clinical study of various skin diseases in order to develop Raman spectroscopy into a useful tool for non-invasive skin cancer detection. Intermediate data analysis results are presented. Recently, we have also successfully developed a technically more challenging endoscopic Laser-Raman probe for early lung cancer detection. Preliminary in vivo results from endoscopic lung Raman measurements are discussed.

A surface plasmon resonance imaging (SPRI) system was developed for the discrimination of proteins on a gold surface. As a label-free and high-throughput technique, SPRI enables simultaneously monitoring of the biomolecular interactions at low concentrations. We used SPRI as a label-free and parallel method to detect different proteins based on protein microarray. Bovine Serum Albumin (BSA), Casein and Immunoglobulin G (IgG) were immobilized onto the Au surface of a gold-coated glass chip as spots forming a 6×6 matrix. These proteins can be discriminated directly by changing the incident angle of light. Excellent reproducibility for label-free detection of protein molecules was achieved. This SPRI platform represents a simple and robust method for performing high-sensitivity detection of protein microarray.

We generalize a previously proposed imaging scheme to situations for which the set of hidden objects embedded in the highly scattering medium can take arbitrary shapes. We compare the accuracy of images obtained from optical detection fibers with those from a ccd camera. The latter approach is more efficient and can be applied to non-contact geometries, but it requires an a priori linearization of the obtained digitized images. We discuss some details of this calibration for the camera and establish its potential as a new tool for decomposition based imaging.

This paper summarizes the recent technological development in our lab on cystoscopic optical coherence tomography (COCT) by integrating time-domain OCT (TDOCT) and spectral-domain OCT (SDOCT) with advanced MEMS-mirror technology for endoscopic laser scanning imaging. The COCT catheter can be integrated into the instrument channel of a commercial 22Fr rigid cystoscopic sheath for in vivo imaging of human bladder under the cystosocopic visual guidance; the axial/transverse resolutions of the COCT catheter are roughly 9 μm and 12μm, respectively, and 2D COCT imaging can be performed with over 110dB dynamic range at 4–8 fps. To examine the utility and potential limitations of OCT for bladder cancer diagnosis, systemic ex vivo rat bladder carcinogenesis studies were performed to follow various morphological changes induced by tumor growth and in vivo porcine study was performed to examine the feasibility of COCT for in vivo imaging. Justified by promising results of the animal studies, preliminary clinical study was conducted on patients scheduled for operating-room cystoscopy for bladder cancers. Double-blind clinical results reveal that COCT can delineate detailed bladder architectures (e.g., urothelium, lamina propria, muscularis) at high resolution and detect bladder cancers based on enhanced urothelial heterogeneity as a result of excessive growing nature of bladder cancers. The diagnostic sensitivity and specificity can be enhanced to 92% and 85%, respectively. Results also suggest that due to reduced imaging depth of COCT in cancerous lesions, staging of bladder cancers may be limited to Ta or T1 for non-outgrowing cancerous lesions.

The major cytotoxic agent with most current photosensitizers used in photodynamic therapy (PDT) is widely believed to be singlet oxygen (1O2). Determination of the 1O2 quantum yields for porphyrin-based photosensitizers, including hematoporphyrin derivative (HiPorfin), hematoporphyrin monomethyl ether (HMME) and photocarcinorin (PsD-007) in air-saturated dimethylformamide (DMF) solutions were performed by the direct measurement of their near-infrared luminescence. In addition, 1O2 quencher sodium azide was employed to confirm the 1O2 generation from the investigated photosensitizers. The maximal 1O2 luminescence occurs at about 1280 nm with full width at half maximum of 30 nm. The 1O2 quantum yields were found to be 0.61 ± 0.03, 0.60 ± 0.02 and 0.59 ± 0.03 for HiPorfin, HMME and PsD-007, respectively. These results provide that these porphyrin-based photosensitizers produce 1O2 under irradiation, which is of significance for the study of their photodynamic action in PDT.

Xiao-Ai-Ping (XAP), a traditional oriental medicinal herb isolated from the stem of Marsdenia tenacissima (Roxb.) Wight et Arn., has been shown to induce tumor cell apoptosis. In this study, we used confocal fluorescence microscopy and fluorescence resonance energy transfer (FRET) techniques to study the molecular mechanism of XAPinduced apoptosis in single living human lung adenocarcinoma (ASTC-a-1) cells. The efficacious apoptosis was observed at 6 h after of 100 μl XAP treatment. Further monitoring the dynamics of caspase-3 activation using FRET imaging in single living ASTC-a-1 cell expressing stably with SCAT3, a FRET probe, showed that XAP activated the caspase-3 at about 2 h after XAP treatment. These data suggest that caspase-3 activation was involved in the XAP-induced apoptosis in ASTC-a-1 cells.