Time-gated Imaging System Research Articles

Protoporphyrin IX delayed fluorescence imaging: a modality for hypoxia-based surgical guidance.

.SignificanceHypoxia imaging for surgical guidance has never been possible, yet it is well known that most tumors have microregional chronic and/or cycling hypoxia present as well as chaotic blood flow. The ability to image oxygen partial pressure () is therefore a unique control of tissue metabolism and can be used in a range of disease applications to understand the complex biochemistry of oxygen supply and consumption.AimDelayed fluorescence (DF) from the endogenous molecule protoporphyrin IX (PpIX) has been shown to be a truly unique reporter of the local oxygen partial pressure in tissue. PpIX is endogenously synthesized by mitochondria in most tissues, and the particular property of DF emission is directly related to low microenvironmental oxygen concentration. Here, it is shown that PpIX has a unique emission in hypoxic tumor tissue regions, which is measured as a DF signal in the red to near-infrared spectrum.ApproachA time-gated imaging system was used for PpIX DF for wide field direct mapping of changes. Acquiring both prompt and DF in a rapid sequential cycle allowed for imaging oxygenation in a way that was insensitive to the PpIX concentration. By choosing adequate parameters, the video rate acquisition of images could be achieved, providing real-time tissue metabolic information.ResultsIn this report, we show the first demonstration of imaging hypoxia signals from PpIX in a pancreatic cancer model, exhibiting contrast relative to surrounding normal oxygenated tissues. Additionally, tissue palpation amplifies the signal and provides intuitive temporal contrast based upon neoangiogenic blood flow differences.ConclusionsPpIX DF provides a mechanism for tumor contrast that could easily be translated to human use as an intrinsic contrast mechanism for oncologic surgical guidance.

Improving the performance of rapid lifetime determination for wide-field time-gated imaging in live cells.

In biological research, rapid wide-field fluorescence lifetime imaging has become an important imaging tool. However, the biological samples with weak fluorescence signals and lower sensitivity often suffer from very low precision in lifetime determinations which restricts its widespread utilization in many bioimaging applications. To address this issue, a method is presented in this paper to substantially enhance the precision of rapid lifetime determination (RLD). It expedites the discrimination of fluorescence lifetimes, even for the weak signals coming from the cells, stained with long-lived biocompatible AIS/ZnS QDs. The proposed method works in two phases. The first phase deals with the systematic noise analysis based on the signal and contrast of the images in a time-gated imaging system, wherein acquiring the high-quality imaging data through optimization of hardware parameters improves the overall system performance. In the second phase, the chosen images are treated using total variation denoising method combined with the Max/Min filtering method for extracting the region of interest to reconstruct the intensity images for RLD. We performed several experiments on live cells to demonstrate the improvements in imaging performance by the systematic optimizations and data treatment. Obtained results demonstrated a great enhancement in signal-to-noise and contrast-to-noise ratios beside witnessing an obvious improvement in RLD for weak signals. This approach can be used not only to improve the quality of time-gated imaging data but also for efficient fluorescence lifetime imaging of live biological samples without compromising imaging speed and light exposure.

Real-Time Imaging of Short-Wave Infrared Luminescence Lifetimes for Anti-counterfeiting Applications.

Rare-earth doped nanoparticles (RENPs) have been widely used for anti-counterfeiting and security applications due to their light frequency conversion features: they are excited at one wavelength, and they display spectrally narrow and distinguished luminescence peaks either at shorter wavelengths (i.e., frequency/energy upconversion) or at longer wavelengths (frequency/energy downconversion). RENPs with a downconversion (DC) photoluminescence (PL) in short-wave infrared (SWIR) spectral range (~1,000–1,700 nm) have recently been introduced to anti-counterfeiting applications, allowing for multilevel protection based on PL imaging through opaque layers, due to a lesser scattering of SWIR PL emission. However, as the number and spectral positions of the discrete PL bands exhibited by rare-earth ions are well-known, it is feasible to replicate luminescence spectra from RENPs, which results in a limited anti-counterfeiting security. Alternatively, lifetime of PL from RENPs can be used for encoding, as it can be finely tuned in broad temporal range (i.e., from microseconds to milliseconds) by varying type of dopants and their content in RENPs, along with the nanoparticle morphology and size. Nevertheless, the current approach to decoding and imaging the RENP luminescence lifetimes requires multiple steps and is highly time-consuming, precluding practical applications of PL lifetime encoding for anti-counterfeiting. Herein, we report the use of a rapid lifetime determination (RLD) technique to overcome this issue and introduce real-time imaging of SWIR PL lifetime for anti-counterfeiting applications. NaYF4:20% Yb, x% Er (x = 0, 2, 20, 80)@NaYF4 core@shell RENPs were synthesized and characterized, revealing DC PL in SWIR region, with maximum at ~1,530 nm and PL lifetimes ranging from 3.2 to 6 ms. Imaging of the nanoparticles with different lifetimes was performed by the developed time-gated imaging system engaging RLD method and the precise manipulation of the delay between the excitation pulses and camera gating windows. Moreover, it is shown that imaging and decrypting can be performed at a high rate (3–4 fps) in a cyclic manner, thus allowing for real-time temporal decoding. We believe that the demonstrated RLD-based fast PL lifetime imaging approach can be employed in other applications of photoluminescent RENPs.

Plastic fiber scintillator response to fast neutrons.

The Neutron Imaging System at NIF uses an array of plastic scintillator fibers in conjunction with a time-gated imaging system to form an image of the neutron emission from the imploded capsule. By gating on neutrons that have scattered from the 14.1 MeV DT energy to lower energy ranges, an image of the dense, cold fuel around the hotspot is also obtained. An unmoderated spallation neutron beamline at the Weapons Neutron Research facility at Los Alamos was used in conjunction with a time-gated imaging system to measure the yield of a scintillating fiber array over several energy bands ranging from 1 to 15 MeV. The results and comparison to simulation are presented.

SU-E-T-11: LINAC Dose Profiling Using Cherenkov Emission Imaging.

To demonstrate the potential for fast 3D dose profile imaging of a LINAC beam using images of the induced Cherenkov radiation in a water tank. A specialized time-gated imaging system was developed as a prototype to quantify and compare with Monte Carlo, to illustrate the concept. Images were acquired from a water tank during irradiation from a 6 MV Varian-2100C linear accelerator beam using a time-gated CCD-based imaging system. The camera was placed normal to the tank wall to minimize parallax reflections, and resultant images were produced by evaluating the median of each pixel in a stack of 2000 images taken at a rate of 60 Hz with an exposure time of 10 ms. Experimental data was compared to images obtained from GEANT4 simulations of the optical setup. Examination of the scored quantities for dose and generated Cherenkov photons indicates that there is a strong similarity, which can be explained by considering the electron energy losses per unit path length. However, due to the complex convolution of the Cherenkov emission directionality and camera lens angular field of view, this relationship is distorted. These errors can be calibrated using the GEANT4 simulations to more accurately reflect the intrinsic dose in the water volume. This work demonstrates dose profiling using the induced Cherenkov radiation signal for the first time. These preliminary results serve as a proof of concept of imaging at one azimuthal angle. Analogous to SPECT, the technique could easily be translated to multiple angles yielding full dose reconstructions following filtered back projection. Further refinement of this technology could be the first step in a paradigm shift towards an alternative method for fast radiation field analysis. Advantages would include increased speed, as well as the ability to profile dynamic beam shapes within transparent solid anthropomorphic phantoms. This work has been financially supported by NIH grant R01CA109558.

The use of chloroaluminium phthalocyanine tetrasulfonate (AlPcTS) for time-delayed fluorescence imaging

Phthalocyanine derivatives are currently under investigation for use in photodynamic therapy, which is a promising cancer treatment. These materials, which display preferential uptake in cancerous cells, also exhibit high fluorescence yields and can be used for tumour detection. Problems with steady-state fluorescence techniques such as excitation scatter and background autofluorescence can be eliminated by using time-resolved imaging techniques without the need for filters. A tissue phantom was assembled to test a constructed time-gated imaging system by drilling 36 wells of varying diameter and depth (10 mm to 1 mm) into a block of polymethyl methacrylate (PMMA). The system was used to record images of chloroaluminium phthalocyanine tetrasulfonate (AlPcTS) at differing concentrations in neat aqueous solvent and cell suspensions within the wells. A mixture of Intralipid (to mimic tissue scatter) and Evan's blue (to mimic tissue absorption) of depths ranging from 1 mm to 10 mm was placed on top of the PMMA block. The ensuing images were analysed using signal-to-noise ratios and contrast–detail curves. The results indicate that the time-gated imaging system can prevent background excitation scatter from distorting the fluorescence signal from a longer-lived photosensitizer without the need for filters.

Determination of the modulation transfer function for a time-gated fluorescence imaging system

The use of fluorescence for cancer detection is currently under investigation. Presently, steady-state fluorescence detection methods are in use, but have limitations due to poor contrast between the fluorescence of the tumor and background autofluorescence. Improved contrast can be obtained with time-resolved techniques because of the differing lifetimes between autofluorescence and exogenous photosensitizers that selectively accumulate within tumor tissue. An imaging system is constructed using a fast-gated (200-ps) charge-coupled device (CCD) camera and a pulsed 635-nm laser diode. To characterize the ability of the system to transfer object contrast to an image, the modulation transfer function (MTF) of the system is acquired by employing an extended knife-edge technique. A knife-edge target is assembled by drilling a rectangular well into a block of polymethyl methacrylate (PMMA). The imaging system records images of the photosensitizer, chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), within the well. AlPcTS was chosen to test the system because of its strong absorption of 635-nm, high fluorescence yield, and relatively long fluorescence lifetime (approximately 7.5 ns). The results show that the system is capable of resolving 10(-4) M AlPcTS fluorescence as small as 1 mm. The findings of this study contribute to the development of a time-gated imaging system using fluorescence lifetimes.

Time-gated imaging system for tumor diagnosis

novel approach is proposed for fluorescence imaging of biological substrates. Discrimination among the contributions of different fluorophores is achieved in the time domain, taking advantage of the differences in decay times of exogenous versus endogenous fluorescences. The experimental setup relies on an intensified video camera and on a subnanosecond dye laser used for the excitation. The video camera has an electronic shutter that provides exposure times as short as 5 ns. A detailed description of the apparatus is reported with an analysis of performances. The time-gated technique is especially attractive for tumor detection in combination with photosensitizing drugs. Experiments performed on a murine tumor have shown interesting results that make this technique promising for a future application in the clinical diagnosis.