Near-infrared Signals Research Articles

Simultaneous quantification of polymeric and surface active stabilizers of nanosuspensions by using near-infrared spectroscopy

Nanosuspension technology is an attractive approach for the formulation and solubility enhancement of poorly water-soluble drug compounds. The technology requires adequate excipients for stabilizing the suspensions during nanogrinding and storage. This study aimed at establishing a near-infrared (NIR) method for assaying simultaneously the two nanoparticle stabilizers, sodium dodecyl sulphate (SDS) and hydroxypropylcellulose (HPC), in miconazole nanosuspensions. Second derivative of NIR signals was used to establish calibration curves in concentration ranges of interest of SDS (0.03–0.3%) and HPC (0.75–7.5%). The suitability and applicability of the NIR method was verified by evaluating the linearity, accuracy, precision, and specificity of the obtained data. The method was then used to quantify indirectly the amount of SDS and HPC adsorbed onto miconazole nanoparticles. Within the concentration range of interest, SDS adsorption increased up to 122 µg/m2 (4.2 × 10−7 mol/m2) with increasing SDS concentration, and HPC adsorption was in the range of 800–1000 µg/m2 (21–27 × 10−7 mol/m2) for nanosuspensions containing nominally 5% HPC and 12.5% or 20% miconazole. Interestingly, some of the adsorbed HPC was displaced upon increase of SDS concentration and adsorption. The data were also confirmed by surface tension measurements of aqueous solutions of SDS and HPC and nanosuspension supernatants. The availability of a fast and nondestructive method for quantifying simultaneously the adsorption of two stabilizers onto nanoground particles may not only speed up nanosuspension development, but also provide insight into the mechanisms of nanoparticle stabilization regarding competitive adsorption and electrostatic versus steric stabilization.

Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy

Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64±0.14 and 4.50±0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88±0.04 and 0.81±0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions.

Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson's disease.

BackgroundWe have previously shown that human mesenchymal stem cells (hMSCs) can reduce toxin-induced neurodegeneration in a well characterized rodent model of Parkinson’s disease. However, the precise mechanisms, optimal cell concentration required for neuroprotection, and detailed cell tracking need to be defined. We exploited a near-infrared imaging platform to perform noninvasive tracing following transplantation of tagged hMSCs in live parkinsonian rats.MethodshMSCs were labeled both with a membrane intercalating dye, emitting in the near- infrared 815 nm spectrum, and the nuclear counterstain, Hoechst 33258. Effects of near-infrared dye on cell metabolism and proliferation were extensively evaluated in vitro. Tagged hMSCs were then administered to parkinsonian rats bearing a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, via two alternative routes, ie, intrastriatal or intranasal, and the cells were tracked in vivo and ex vivo using near-infrared technology.ResultsIn vitro, NIR815 staining was stable in long-term hMSC cultures and did not interfere with cell metabolism or proliferation. A significant near-infrared signal was detectable in vivo, confined around the injection site for up to 14 days after intrastriatal transplantation. Conversely, following intranasal delivery, a strong near-infrared signal was immediately visible, but rapidly faded and was completely lost within 1 hour. After sacrifice, imaging data were confirmed by presence/absence of the Hoechst signal ex vivo in coronal brain sections. Semiquantitative analysis and precise localization of transplanted hMSCs were further performed ex vivo using near-infrared imaging.ConclusionNear-infrared technology allowed longitudinal detection of fluorescent-tagged cells in living animals giving immediate information on how different delivery routes affect cell distribution in the brain. Near-infrared imaging represents a valuable tool to evaluate multiple outcomes of transplanted cells, including their survival, localization, and migration over time within the host brain. This procedure considerably reduces the number of animal experiments needed, as well as interindividual variability, and may favor the development of efficient therapeutic strategies promptly applicable to patients.

Hyperspectral near Infrared Image Analysis of a Phenol Formaldehyde Resin Curing Reaction

In the production of sandpaper, a phenol formaldehyde polymer bonds the abrasive material to a backing material made of paper or a textile. The reaction takes place at elevated temperatures (90–120°C) for a long time (at least eight hours) and is thereby a very energy-demanding process step. A possible future application would be to use near infrared (NIR) hyperspectral imaging (1000–2498 nm) for (1) monitoring the curing reaction and determining an end point for it and (2) for identifying in homogeneous regions with low adhesion in the final product. A feasibility study was carried out on four series of resin-coated backing materials without abrasives. These were imaged at half hour intervals for eight hours of curing using a NIR line scan imager. In order to analyse the influence of the backing material on the net NIR signal from resin-coated samples, spectra of the backing material (paper, textile) were also collected using a moving grating NIR spectrometer (1100–2498 nm). Results from principal components analysis of the hyperspectral images indicated that the reaction was stabilised after five to six hours, although it continued slowly for at least 16 more hours. A relevant question was when to finish the heating (curing) and still obtain a final product of high quality. Partial least squares regression models for predicting the curing time were thus also evaluated. A calibration made on image mean spectra was used for predicting the curing time of each pixel in the full set of hyperspectral images. The predicted images showed the curing progress, in homogeneous regions where the reaction had progressed to a slower extent and other physical abnormalities (for example air bubbles). Pixel prediction distribution analysis of the images was found useful for determining the significant number of components of the proposed regression models.

Phase-Matching and Parametric Conversion for the Mid-Infrared in As<sub>2</sub>S<sub>3</sub> Waveguides

We illustrate two As2S3 waveguide designs for four-wave mixing, which can generate 3.03 μm mid-infrared light from a 1.55 μm near-infrared signal source and a 2.05 μm pump source. Through simulations, we verify that four-wave mixing phase-matching efficiencies up to 100% can be achieved using dispersion engineering to maintain the dispersion at 2.05 μm near to zero. The best conversion efficiency is –10 dB. When the waveguide length is 1 cm, the parametric conversion bandwidth is 1525 nm. We also evaluated the shift of 100% phase-matching efficiency wavelengths based upon fabrication tolerances.

High-power, fiber-laser-pumped, picosecond optical parametric oscillator based on MgO:sPPLT

We report a stable, high-power, mid-infrared synchronously-pumped optical parametric oscillator (SPOPO) based on MgO:sPPLT, pumped by a 1064 nm, picosecond Yb-fiber laser operating at a repetition rate of 81.1 MHz. The singly resonant SPOPO is tunable over 1531-1642 nm (111 nm) in the near-infrared signal and 3022-3488 nm (466 nm) in the mid-infrared idler, providing a total tuning range of 577 nm. Careful optimization of output coupling results in a signal output power as high as 4.3 W at 1593 nm and a mid-infrared idler power of 2 W at 3204 nm for 13.4 W of pump power at a total extraction efficiency of 47%. The SPOPO can be operated near room temperature, down to 30 °C, and exhibits passive peak-to-peak power stability better than 8.6% at 1568 nm (signal) and 8.2% at 3310 nm (idler) over 13 hours at full power. The output signal pulses have duration of 17.5 ps, with a FWHM spectral bandwidth of 1.4 nm centered at 1568 nm.

Do earthworms and roots cooperate to build soil macroaggregates? A microcosm experiment

Soil ecosystem engineers are major actors of soil macroaggregation, a process that drives the production of ecosystem services by soils. However, our inability to identify the origins of different types of macroaggregates found in soils is an obstacle to describing and modeling their dynamics and associated processes (C sequestration; hydraulic properties). This laboratory study investigated mechanisms of biological soil macroaggregation by two different earthworm species ( Apporectodea caliginosa (Savigny) and Allolobophora chlorotica (Savigny) and two plant species ( Trifolium pratense, Plantago lanceolata L.), in isolation and in all possible combinations. Near infrared (NIR) spectral analysis significantly discriminated macroaggregates according to the organisms that created them since each organism produced macroaggregates with distinct NIR signals (p < 0.001). The largest departure from the control signal was observed with T. pratense whereas earthworms and P. lanceolata specific signals were less contrasted. Macroaggregates formed in the presence of more than one ecosystem engineers had mixed signals showing that several actors had participated in their construction. This means that roots and earthworms did not produce macroaggregates in isolation and rather added their effects in building structures of mixed origins. Further studies based on the present methodology will tell us more on below ground behaviors of ecosystem engineers and their interactive building of soil habitats.

Silicon-on-Insulator Platform for Integration of 3-D Nanoplasmonic Devices

We experimentally demonstrate a compact platform to convert near-infrared signals between nanoplasmonic and nanophotonic domains. In particular, we utilize a pair of adiabatic nanoplasmonic tapers to assist direct-coupling and shrink the plasmonic guiding area to a deep-subwavelength scale as small as 50-nm-by-80-nm with a propagation loss of 2.28 dB/μm. The integrated plasmonic devices developed on a silicon-on-insulator (SOI) substrate could build up a solid platform for plasmonic gauges of ultrafast communications and optical sensing.

Polymeric Micelles for Neoadjuvant Cancer Therapy and Tumor-Primed Optical Imaging

Poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) micelles act as a 3-in-1 nanocontainer for three poorly water-soluble drugs-paclitaxel, 17-allylamino-17-demethoxygeldanamycin, and rapamycin (PTX/17-AAG/RAPA)-for cancer therapy. In a LS180 human colon xenograft model, a single intravenous (IV) injection of 3-in-1 PEG-b-PLA micelles reduced tumor volume by 1.6-fold with <10% body weight change. In a second step, IV injection of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles carrying a carbocyanine dye (1,1'-dioctadecyl tetramethyl indotricarbocyanine iodide (DiR)) after 48 h resulted in a 2.1-fold higher near-infrared (NIR) optical signal from excised solid tumors versus a negative control, presumably due to a reduction in tumor cell density and interstitial tumor pressure. Thus, a tandem of 3-in-1 PEG-b-PLA and PEG-b-PCL micelles could potentially be used for neoadjuvant cancer therapy and tumor-primed NIR optical imaging for intraoperative surgical guidance in oncology, offering a promising multimodal strategy for cancer therapy and imaging.

CMOS silicon avalanche photodiodes for NIR light detection: a survey

This paper surveys recent research on CMOS silicon avalanche photodiodes (SiAPD) and presents the design of a SiAPD based photoreceiver dedicated to near-infrared spectroscopy (NIRS) application. Near-infrared spectroscopy provides an inexpensive, non-invasive, and portable means to image brain function, and is one of the most efficient diagnostic techniques of different neurological diseases. In NIRS system, brain tissue is penetrated by near-infrared (NIR) radiation and the reflected signal is captured by a photodiode. Since the reflected NIR signal has very low amplitude, SiAPD is a better choice than regular photodiode for NIR signal detection due to SiAPD`s ability to amplify the photo generated signal by avalanche multiplication. Design requirements of using CMOS SiAPDs for NIR light detection are discussed, and the challenges of fabricating SiAPDs using standard CMOS process are addressed. Performances of state-of-the-art CMOS SiAPDs with different device structures are summarized and compared. The efficacy of the proposed SiAPD based photoreceiver is confirmed by post layout simulation. Finally, the SiAPD and its associated circuits has been implemented in one chip using 0.35 μm standard CMOS technology for an integrated NIRS system.

Quantum Dots-Based All-Optical-Readout Middle-Far-Infrared Imaging

A quantum dot (QD) middle-far-infrared (MFIR) detection and imaging approach based on all-optical-readout (AORO) is proposed. Using the intersubband (ISB) optical transition to change the interband (IB) absorption, it converts the ISB MFIR signal into the IB near-infrared signal. It might overcome the problems in the electrical readout infrared detection and imaging, such as dark current, low-temperature operation, low resolution, and vulnerability to the high radiation intensity. Based on the In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.5</sub> Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.5</sub> As/GaAs lens-shaped QD structure, our calculation shows the potential of this AORO approach for the MFIR detection and high-resolution imaging, the potential for room-temperature operation, and the ability for frequency selectivity and spectrum scanning.

Spectrally resolving and scattering-compensated x-ray luminescence∕fluorescence computed tomography

The nanophosphors, or other similar materials, emit near-infrared (NIR) light upon x-ray excitation. They were designed as optical probes for in vivo visualization and analysis of molecular and cellular targets, pathways, and responses. Based on the previous work on x-ray fluorescence computed tomography (XFCT) and x-ray luminescence computed tomography (XLCT), here we propose a spectrally-resolving and scattering-compensated x-ray luminescence/fluorescence computed tomography (SXLCT or SXFCT) approach to quantify a spatial distribution of nanophosphors (other similar materials or chemical elements) within a biological object. In this paper, the x-ray scattering is taken into account in the reconstruction algorithm. The NIR scattering is described in the diffusion approximation model. Then, x-ray excitations are applied with different spectra, and NIR signals are measured in a spectrally resolving fashion. Finally, a linear relationship is established between the nanophosphor distribution and measured NIR data using the finite element method and inverted using the compressive sensing technique. The numerical simulation results demonstrate the feasibility and merits of the proposed approach.

Remote identification of chemicals concealed behind clothing using near infrared spectroscopy.

Measurements are presented which demonstrate that near infrared (NIR) spectroscopy can be used to identify chemicals concealed behind clothing. This has been achieved for detector stand-off distances of 3 m. The optical properties of a range of clothing materials have been investigated, and the transmission of NIR signals found to be sufficient for spectroscopy. The study has shown that granular solid materials can be identified when hidden behind a layer of clothing. Examples of chemicals used in this study include ammonium nitrate and other ammonium salts. Details of the current measurements and results are given, together with suggestions for increasing detection sensitivity.

Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging

AimTo evaluate near-infrared (NIR) autofluorescence (AF) in patients with geographic atrophy (GA) secondary to age-related macular degeneration and to investigate the origin of the signal by in vivo and histological...

Dynamic analysis of temporal moisture profiles in heatset printing studied with near-infrared spectroscopy

Dynamic analysis of the water transfer onto coated paper, and its permeation and absorption into the porous structure were studied online in a full-scale heatset web offset printing environment. The moisture content of the paper was investigated at five different positions during the printing process. Changes in the moisture content of the paper were studied as a function of the web temperature, printing speed and silicone application in the folding unit positioned after the hot air drying oven. Additionally, the influence of fountain solution composition on the pick-up by the paper was investigated. The water content of the fountain solution transferred to the paper from the printing units was observed as changes in near-infrared absorbance. A calibration data set enabled the subsequent quantification of the dynamic moisture content of the paper at the studied locations. An increase in the printing speed reduced the water transfer to the paper and an increase in web temperature resulted in a reduction in the moisture content. An increase in the dosage level of the water–silicone mixture was observed as a re-moistening effect of the paper. Differences in the drying strategy resulted in different moisture profiles depending on the type of fountain solution used. As a conclusion, the near-infrared signal provides an effective way to characterize the moisture dynamics online at different press units.

Poly(ethylene glycol)-block-poly(d,l-lactide acid) micelles anchored with angiopep-2 for brain-targeting delivery

In this study, angiopep with high transcytosis capacity and parenchymal accumulation was used as a novel ligand for the brain-targeting delivery of poly(ethylene glycol)-block-poly(d,l-lactide acid) (PEG-PLA) micelles. Angiopep-2 was synthesized by solid-phase peptide synthesis, and then conjugated with maleimide-PEG-PLA to form angiopep-PEG-PLA. The micelles composed of methoxy-PEG-PLA (mPEG-PLA) and angiopep-PEG-PLA was prepared by film-hydration method. Near-infrared fluorescence dye, DiR was loaded into micelles to evaluate the brain-targeting ability of micelles with or without angiopep modification by near-infrared fluorescence imaging in vivo and ex vivo. Significant near-infrared (NIR) fluorescent signal was detected in the brain after angiopep-anchored micelles administration and further confirmed by imaging the whole brain and brain slices, compared with that of the micelles without modification. 125I-radiolabeled angiopep-PEG-PLA micelles after intravenous administration in mice showed high brain accumulation for up to 24 h. These results indicate that angiopep-modified PEG-PLA micelle is a promising brain-targeting nanocarrier for lipophilic drugs.

Abstract 2257: Optical imaging guidance of tumor resection margin for head and neck cancer

Abstract Traditional methods for assessing adequacy of head and neck tumor resection rely upon intraoperative palpation or visualization. Positive margins are strongly associated with recurrence and poor patient survival. To ensure the complete tumor removal, surgeons may resect additional peritumoral tissues. During the past decade, intraoperative pathologic consultation by frozen section has become standard. Each round of consultation takes 20 minutes and the average number of such consultation is 3 − 4 per operation, which prolongs the procedure. Two additional potential problems are: (1) it is impossible to locate all cohorts of infiltrating tumor cells; (2) the final pathology may reveal a positive margin when the frozen section was negative. Currently 20 − 30% of head and neck patients that undergo surgery still leave the operating room with an incomplete resection. Thus, major opportunities exist to develop a deep tissue imaging near infrared (NIR) agent and an intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The advantage of using optical imaging over radioisotopes is that it avoids continuous exposure of operating room personnel to radioactivity. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. We exploited integrin overexpression on infiltrating cancer cells for intraoperative detection of tumor margins. We tested a new optical instrumentation in conjunction with the integrin-targeted NIR dye, RGD-IRDye800CW, for assessing malignant tumor margins in an orthotopic head and neck cancer animal model. RGD peptides have high binding specificity to integrin αvβ3. For intraoperative tumor margin detection, we developed an intraoperative wavelength-resolved NIR imaging system. This device offers real-time, portable detection of tumor margins with high stability, faster throughput, and better co-registration than other imaging methods. In our animal model, the tumors infiltrated to the mylohoid neck muscle beyond tumor boundaries and the primary tumor resection left residual infiltrating tumors and metastatic lymph nodes behind, which were easily detected by our technology. We also found NIR signal in several spots of the lungs from the same mice. Histological analysis in correlation to imaging results support that we can detect extremely small cohorts of 20 − 50 tumor cells in intraoperative settings with high specificity. Thus our technology will be ideal in detecting tumor margins intraoperatively because the average number of tumor cells in invading cohorts is 50 − 100 and NIR penetration depth is about 3 − 5 cm. Of note, we found that NIR signals from the RGD peptides were stronger at the edge (rim) of tumors than the center; therefore, the integrin-targeted imaging probe will allow us to detect the tumor margins as well as infiltrating cohorts of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2257.

Abstract 2649: Whole body vibration effects on binding kinetics and targeting of near-infrared dye conjugated bisphosphonate

Abstract A non-invasive means of targeting bisphophonate to specific skeletal sites, along with the passive binding/decay kinetics of the near-infrared bisphosphanate analog to the skeleton are determined. Bone is the third common site where breast, lung, and prostate cancer cells spread and metastasize. Debilitating pain is the major complication resulting from bone metastases in nearly 70% of the patients. The palliative bone pain management includes the bisphosphanate therapy. Bisphosphonates, a potent inhibitor of bone resorption, gives both pain relief and improves bone health. However these medications result in complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Combinations of low-risk exercise programs along with reduced drug dosage are a likely alternative to counter such drug-related side effects. Site-selective skeletal targeting of bisphosphonates, if feasible, is however ideal to overcome drug-related side effects. We utilized whole body vibration (WBV), to target NIR dye conjugate bisphosphonate to specific skeletal sites. Using near-infrared (NIR) fluorescence imaging, both the targeting and the passive binding of the bisphosphonate in vivo was determined. Vibration loading, utilizing whole body vibration (WBV) was performed on twelve mice by subjecting them to vibration frequency of 35 Hz for fifteen min (5-10 times/week) duration. Alendronate was conjugated to near-infrared tricarbocyanine, cyclic enamine-functionalized dye, and was injected intravenously after 21-day exercise regime. Yet to be reported, we show that NIR-alendronate probe bound to the lumbar L6 vertebrae, resultant of direct high-frequency WBV stimulation. This is besides several other specific targeting sites. Further, both the passive binding and the decay kinetics of the NIR signal at the skeleton was determined in a six-week non-invasive longitudinal study of mouse pups. This provides opportunity to utilize such approaches in future translational studies in assessing the role of bisphosphonates in preventing spreading of cancer cells at other secondary sites, especially bone. The targeted drug binding in response to the vibratory protocol also provides hope in the development of whole body vibration (WBV) as a bisphosphonate-therapeutic aid. Further, to develop strategies in reducing the drug dosage in treatment of other morbidity factors that stem from complications from bone metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2649.

New approach to neural dynamics of emotion: Decoding skin conductance from near-infrared spectroscopic signals

New approach to neural dynamics of emotion: Decoding skin conductance from near-infrared spectroscopic signals

Source separation of multi-channel near-infrared spectroscopic signals by time delayed decorrelation

Source separation of multi-channel near-infrared spectroscopic signals by time delayed decorrelation