Journal of Innovative Optical Health Sciences最新文献

Pre-operative X-ray mammography and intraoperative X-ray specimen radiography are routinely used to identify breast cancer pathology. Recent advances in optical coherence tomography (OCT) have enabled its use for the intraoperative assessment of surgical margins during breast cancer surgery. While each modality offers distinct contrast of normal and pathological features, there is an essential need to correlate image-based features between the two modalities to take advantage of the diagnostic capabilities of each technique. We compare OCT to X-ray images of resected human breast tissue and correlate different tissue features between modalities for future use in real-time intraoperative OCT imaging. X-ray imaging (specimen radiography) is currently used during surgical breast cancer procedures to verify tumor margins, but cannot image tissue in situ. OCT has the potential to solve this problem by providing intraoperative imaging of the resected specimen as well as the in situ tumor cavity. OCT and micro-CT (X-ray) images are automatically segmented using different computational approaches, and quantitatively compared to determine the ability of these algorithms to automatically differentiate regions of adipose tissue from tumor. Furthermore, two-dimensional (2D) and three-dimensional (3D) results are compared. These correlations, combined with real-time intraoperative OCT, have the potential to identify possible regions of tumor within breast tissue which correlate to tumor regions identified previously on X-ray imaging (mammography or specimen radiography).

We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and survival. The redox state can be imaged by the redox scanner that collects the fluorescence signals from both the oxidized-flavoproteins (Fp) and the reduced form of nicotinamide adenine dinucleotide (NADH) in snap-frozen tissues and has been previously employed to study tumor aggressiveness and treatment responses. Here, with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large B-cell lymphoma cell line (DLCL2). The mice were treated with CHOP therapy, i.e., cyclophosphamide (C) + hydroxydoxorubicin (H) + Oncovin (O) + prednisone (P) with CHO administration on day 1 and prednisone administration on days 1-5. The Fp content of the treated group was significantly decreased (p = 0.033) on day 5, and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group (p = 0.048). The decrease of the Fp heterogeneity (measured by the mean standard deviation) had a border-line statistical significance (p = 0.071). The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOP therapy.

We have developed a noninvasive imaging method to quantify in vivo drug delivery pharmacokinetics without the need for blood or tissue collection to determine drug concentration. By combining the techniques of hyperspectral imaging and a dorsal skinfold window chamber, this method enabled the real-time monitoring of vascular transport and tissue deposition of nanoparticles labeled with near-infrared (NIR) dye. Using this imaging method, we quantified the delivery pharmacokinetics of the native high-density lipoprotein (HDL) and epidermal growth factor receptor (EGFR)-targeted HDL nanoparticles and demonstrated these HDLs had long circulation time in blood stream (half-life >12 h). These HDL nanoparticles could efficiently carry cargo DiR-BOA to extravasate from blood vessels, diffuse through extracellular matrix, and penetrate and be retained in the tumor site. The EGFR targeting specificity of EGFR-targeted HDL (EGFR-specific peptide conjugated HDL) was also visualized in vivo by competitive inhibition with excess EGFR-specific peptide. In summary, this imaging technology may help point the way toward the development of novel imaging-based pharmacokinetic assays for preclinical drugs and evaluation of drug delivery efficiency, providing a dynamic window into the development and application of novel drug delivery systems.

Multifocal multiphoton microscopy (MMM) has recently become an important tool in biomedicine for performing three-dimensional fast fluorescence imaging. Using various beamsplitting techniques, MMM splits the near-infrared laser beam into multiple beamlets and produces a multifocal array on the sample for parallel multiphoton excitation and then records fluorescence signal from all foci simultaneously with an area array detector, which significantly improves the imaging speed of multiphoton microscopy and allows for high efficiency in use of the excitation light. In this paper, we discuss the features of several MMM setups using different beamsplitting devices, including a Nipkow spinning disk, a microlens array, a set of beamsplitting mirrors, or a diffractive optical element (DOE). In particular, we present our recent work on the development of an MMM using a spatial light modulator (SLM).

Treatment-induced apoptosis of cancer cells is one goal of cancer therapy. Interestingly, more heat is generated by mitochondria during apoptosis, especially the uncoupled apoptotic state,(1,2) compared to the resting state. In this case study, we explore these thermal effects by longitudinally measuring temperature variations in a breast lesion of a pathological complete responder during neadjuvant chemotherapy (NAC). Diffuse Optical Spectroscopic Imaging (DOSI) was employed to derive absolute deep tissue temperature using subtle spectral features of the water peak at 975 nm.3 A significant temperature increase was observed in time windows during the anthracycline and cyclophosphamide (AC) regimen but in not paclitaxel and bevacizumab regimen. Hemoglobin concentration changes generally did not follow temperature, suggesting that the measured temperature increases were likely due to mitochondrial uncoupling rather than a direct vascular effect. A simultaneous increase of tissue oxygen saturation with temperature was also observed, suggesting that oxidative stress also contributes to apoptosis. Although preliminary, this study indicates that longitudinal DOSI tissue temperature monitoring provides information that can improve our understanding of the mechanisms of tissue response during NAC.

Redox state mediates embryonic stem cell (ESC) differentiation and thus offers an important complementary approach to understanding the pluripotency of stem cells. NADH redox ratio (NADH/(Fp + NADH)), where NADH is the reduced form of nicotinamide adenine dinucleotide and Fp is the oxidized flavoproteins, has been established as a sensitive indicator of mitochondrial redox state. In this paper, we report our redox imaging data on the mitochondrial redox state of mouse ESC (mESC) colonies and the implications thereof. The low-temperature NADH/Fp redox scanner was employed to image mESC colonies grown on a feeder layer of gamma-irradiated mouse embryonic fibroblasts (MEFs) on glass cover slips. The result showed significant heterogeneity in the mitochondrial redox state within individual mESC colonies (size: ∼200-440 μm), exhibiting a core with a more reduced state than the periphery. This more reduced state positively correlates with the expression pattern of Oct4, a well-established marker of pluripotency. Our observation is the first to show the heterogeneity in the mitochondrial redox state within a mESC colony, suggesting that mitochondrial redox state should be further investigated as a potential new biomarker for the stemness of embryonic stem cells.

Two-photon excited fluorescence (TPEF) spectroscopy and imaging were used to investigate the effects of gamma-irradiation on neural stem and precursor cells (NSPCs). While the observed signal from reduced nicotinamide adenine dinucleotide (NADH) was localized to the mitochondria, the signal typically associated with oxidized flavoproteins (Fp) was distributed diffusely throughout the cell. The measured TPEF emission and excitation spectra were similar to the established spectra of NAD(P)H and Fp. Fp fluorescence intensity was markedly increased by addition of the electron transport chain (ETC) modulator menadione to the medium, along with a concomitant decrease in the NAD(P)H signal. Three-dimensional (3D) neurospheres were imaged to obtain the cellular metabolic index (CMI), calculated as the ratio of Fp to NAD(P)H fluorescence intensity. Radiation effects were found to differ between low-dose (≤ 50 cGy) and high-dose (≥ 50 cGy) exposures. Low-dose irradiation caused a marked drop in CMI values accompanied by increased cellular proliferation. At higher doses, both NAD(P)H and Fp signals increased, leading to an overall elevation in CMI values. These findings underscore the complex relationship between radiation dose, metabolic state, and proliferation status in NSPCs and highlight the ability of TPEF spectroscopy and imaging to characterize metabolism in 3D spheroids.

Hemodynamic low-frequency (~0.1 Hz) spontaneous oscillations as detected in the brain by near-infrared spectroscopy have potential applications in the study of brain activation, cerebral autoregulation, and functional connectivity. In this work, we have investigated the phase lag between oscillations of cerebral deoxy- and oxy-hemoglobin concentrations in the frequency range 0.05-0.10 Hz in a human subject during a mental workload task. We have obtained a measure of such phase lag using two different methods: (1) phase synchronization analysis as used in the theory of chaotic oscillators and (2) a novel cross-correlation phasor approach. The two methods yielded comparable initial results of a larger phase lag between low-frequency oscillations of deoxy- and oxy-hemoglobin concentrations during mental workload with respect to a control, rest condition.

With the development of optical coherence tomography, the application optical coherence elastography (OCE) has gained more and more attention in biomechanics for its unique features including micron-scale resolution, real-time processing, and non-invasive imaging. In this review, one group of OCE techniques, namely dynamic OCE, are introduced and discussed including external dynamic OCE mapping and imaging of ex vivo breast tumor, external dynamic OCE measurement of in vivo human skin, and internal dynamic OCE including acoustomotive OCE and magnetomotive OCE. These techniques overcame some of the major drawbacks of traditional static OCE, and broadened the OCE application fields. Driven by scientific needs to engineer new quantitative methods that utilize the high micron-scale resolution achievable with optics, results of biomechanical properties were obtained from biological tissues. The results suggest potential diagnostic and therapeutic clinical applications. Results from these studies also help our understanding of the relationship between biomechanical variations and functional tissue changes in biological systems.

Diabetic neuropathy (DN) is, at least in part, associated with the functional attenuation of vasa nervorum, the microvascular structure of peripheral nerves. Microvascular imaging options for vasa nervorum still remain limited. In this work, Optical micro-angiography (OMAG), a volumetric, label-free imaging technique is utilized for characterizing, with high resolution, blood perfusion of peripheral nerve in diabetic mice. We demonstrate that OMAG is able to visualize the structure of microvasculature and to quantify the changes of dynamic blood flow and vessel diameters during administration of vessel stimulator in both diabetic and normal mice. The results indicate the potential of OMAG to assess the blood supply of nerve involved in the pathology and treatment of DN.