skip to main content


Title: Optical simulations for determining efficacy of new light source designs for excitation-scanning high-speed hyperspectral imaging systems
Positive outcomes for colorectal cancer treatment have been linked to early detection. The difficulty in detecting early lesions is the limited contrast with surrounding mucosa and minimal definitive markers to distinguish between hyperplastic and carcinoma lesions. Colorectal cancer is the 3rd leading cancer for incidence and mortality rates which is potentially linked to missed early lesions which allow for increased growth and metastatic potential. One potential technology for early-stage lesion detection is hyperspectral imaging. Traditionally, hyperspectral imaging uses reflectance spectroscopic data to provide a component analysis, per pixel, of an image in fields such as remote sensing, agriculture, food processing and archaeology. This work aims to acquire higher signal-to-noise fluorescence spectroscopic data, harnessing the autofluorescence of tissue, adding a hyperspectral contrast to colorectal cancer detection while maintaining spatial resolution at video-rate speeds. We have previously designed a multi-furcated LED-based spectral light source to prove this concept. Our results demonstrated that the technique is feasible, but the initial prototype has a high light transmission loss (~98%) minimizing spatial resolution and slowing video acquisition. Here, we present updated results in developing an optical ray-tracing model of light source geometries to maximize irradiance throughput for excitation-scanning hyperspectral imaging. Results show combining solid light guide branches have a compounding light loss effect, however, there is potential to minimize light loss through the use of optical claddings. This simulation data will provide the necessary metrics to verify and validate future physical optical components within the hyperspectral endoscopic system for detecting colorectal cancer.  more » « less
Award ID(s):
1725937
NSF-PAR ID:
10185269
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Proc. SPIE 11216, Multiscale Imaging and Spectroscopy
Volume:
11216
Page Range / eLocation ID:
112160W
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Colorectal cancer is the 3rdleading cancer for incidence and mortality rates. Positive treatment outcomes have been associated with early detection; however, early stage lesions have limited contrast to surrounding mucosa. A potential technology to enhance early stagise detection is hyperspectral imaging (HSI). While HSI technologies have been previously utilized to detect colorectal cancerex vivoor post-operation, they have been difficult to employ in real-time endoscopy scenarios. Here, we describe an LED-based multifurcated light guide and spectral light source that can provide illumination for spectral imaging at frame rates necessary for video-rate endoscopy. We also present an updated light source optical ray-tracing model that resulted in further optimization and provided a ∼10X light transmission increase compared to the initial prototype. Future work will iterate simulation and benchtop testing of the hyperspectral endoscopic system to achieve the goal of video-rate spectral endoscopy.

     
    more » « less
  2. Hyperspectral imaging (HSI) is a technology used in remote sensing, food processing and documentation recovery. Recently, this approach has been applied in the medical field to spectrally interrogate regions of interest within respective substrates. In spectral imaging, a two (spatial) dimensional image is collected, at many different (spectral) wavelengths, to sample spectral signatures from different regions and/or components within a sample. Here, we report on the use of hyperspectral imaging for endoscopic applications. Colorectal cancer is the 3rd leading cancer for incidences and deaths in the US. One factor of severity is the miss rate of precancerous/flat lesions (~65% accuracy). Integrating HSI into colonoscopy procedures could minimize misdiagnosis and unnecessary resections. We have previously reported a working prototype light source with 16 high-powered light emitting diodes (LEDs) capable of high speed cycling and imaging. In recent testing, we have found our current prototype is limited by transmission loss (~99%) through the multi-furcated solid light guide (lightpipe) and the desired framerate (20-30 fps) could not be achieved. Here, we report on a series of experimental and modeling studies to better optimize the lightpipe and the spectral endoscopy system as a whole. The lightpipe was experimentally evaluated using an integrating sphere and spectrometer (Ocean Optics). Modeling the lightpipe was performed using Monte Carlo optical ray tracing in TracePro (Lambda Research Corp.). Results of these optimization studies will aid in manufacturing a revised prototype with the newly designed light guide and increased sensitivity. Once the desired optical output (5-10 mW) is achieved then the HIS endoscope system will be able to be implemented without adding onto the procedure time. 
    more » « less
  3. Hyperspectral imaging (HSI) is a spectroscopic technique which captures images at a high contrast over a wide range of wavelengths to show pixel specific composition. Traditional uses of HSI include: satellite imagery, food distribution quality control and digital archaeological reconstruction. Our lab has focused on developing applications of HSI fluorescence imaging systems to study molecule-specific detection for rapid cell signaling events or real-time endoscopic screening. Previously, we have developed a prototype spectral light source, using our modified imaging technique, excitationscanning hyperspectral imaging (HIFEX), coupled to a commercial colonoscope for feasibility testing. The 16 wavelength LED array was combined, using a multi-branched solid light guide, to couple to the scope’s optical input. The prototype acquired a spectral scan at near video-rate speeds (~8 fps). The prototype could operate at very rapid wavelength switch speeds, limited to the on/off rates of the LEDs (~10 μs), but imaging speed was limited due to optical transmission losses (~98%) through the solid light guide. Here we present a continuation of our previous work in performing an in-depth analysis of the solid light guide to optimize the optical intensity throughput. The parameters evaluated include: LED intensity input, geometry (branch curvature and combination) and light propagation using outer claddings. Simulations were conducted using a Monte Carlo ray tracing software (TracePro). Results show that transmission within the branched light guide may be optimized through LED focusing lenses, bend radii and smooth tangential branch merges. Future work will test a new fabricated light guide from the optimized model framework. 
    more » « less
  4. Abstract

    In the field of optical imaging, the ability to image tumors at depth with high selectivity and specificity remains a challenge. Surface enhanced resonance Raman scattering (SERRS) nanoparticles (NPs) can be employed as image contrast agents to specifically target cells in vivo; however, this technique typically requires time-intensive point-by-point acquisition of Raman spectra. Here, we combine the use of “spatially offset Raman spectroscopy” (SORS) with that of SERRS in a technique known as “surface enhanced spatially offset resonance Raman spectroscopy” (SESORRS) to image deep-seated tumors in vivo. Additionally, by accounting for the laser spot size, we report an experimental approach for detecting both the bulk tumor, subsequent delineation of tumor margins at high speed, and the identification of a deeper secondary region of interest with fewer measurements than are typically applied. To enhance light collection efficiency, four modifications were made to a previously described custom-built SORS system. Specifically, the following parameters were increased: (i) the numerical aperture (NA) of the lens, from 0.2 to 0.34; (ii) the working distance of the probe, from 9 mm to 40 mm; (iii) the NA of the fiber, from 0.2 to 0.34; and (iv) the fiber diameter, from 100 µm to 400 µm. To calculate the sampling frequency, which refers to the number of data point spectra obtained for each image, we considered the laser spot size of the elliptical beam (6 × 4 mm). Using SERRS contrast agents, we performed in vivo SESORRS imaging on a GL261-Luc mouse model of glioblastoma at four distinct sampling frequencies: par-sampling frequency (12 data points collected), and over-frequency sampling by factors of 2 (35 data points collected), 5 (176 data points collected), and 10 (651 data points collected). In comparison to the previously reported SORS system, the modified SORS instrument showed a 300% improvement in signal-to-noise ratios (SNR). The results demonstrate the ability to acquire distinct Raman spectra from deep-seated glioblastomas in mice through the skull using a low power density (6.5 mW/mm2) and 30-times shorter integration times than a previous report (0.5 s versus 15 s). The ability to map the whole head of the mouse and determine a specific region of interest using as few as 12 spectra (6 s total acquisition time) is achieved. Subsequent use of a higher sampling frequency demonstrates it is possible to delineate the tumor margins in the region of interest with greater certainty. In addition, SESORRS images indicate the emergence of a secondary tumor region deeper within the brain in agreement with MRI and H&E staining. In comparison to traditional Raman imaging approaches, this approach enables improvements in the detection of deep-seated tumors in vivo through depths of several millimeters due to improvements in SNR, spectral resolution, and depth acquisition. This approach offers an opportunity to navigate larger areas of tissues in shorter time frames than previously reported, identify regions of interest, and then image the same area with greater resolution using a higher sampling frequency. Moreover, using a SESORRS approach, we demonstrate that it is possible to detect secondary, deeper-seated lesions through the intact skull.

     
    more » « less
  5. Optical projection tomography (OPT) is a powerful imaging modality for attaining high resolution absorption and fluorescence imaging in tissue samples and embryos with a diameter of roughly 1 mm. Moving past this 1 mm limit, scattered light becomes the dominant fraction detected, adding significant “blur” to OPT. Time-domain OPT has been used to select out early-arriving photons that have taken a more direct route through the tissue to reduce detection of scattered photons in these larger samples, which are the cause of image domain blur1. In addition, it was recently demonstrated by our group that detection of scattered photons could be further depressed by running in a “deadtime” regime where laser repetition rates are selected such that the deadtime incurred by early-arriving photons acts as a shutter to later-arriving scattered photons2. By running in this deadtime regime, far greater early photon count rates are achievable than with standard early photon OPT. In this work, another advantage of this enhanced early photon collection approach is demonstrated: specifically, a significant improvement in signal-to-noise ratio. In single photon counting detectors, the main source of noise is “afterpulsing,” which is essentially leftover charge from a detected photon that spuriously results in a second photon count. When the arrival of the photons are time-stamped by the time correlated single photon counting (TCSPC) module , the rate constant governing afterpusling is slow compared to the time-scale of the light pulse detected so it is observed as a background signal with very little time-correlation. This signal is present in all time-gates and so adds noise to the detection of early photons. However, since the afterpusling signal is proportional to the total rate of photon detection, our enhanced early photon approach is uniquely able to have increased early photon counts with no appreciable increase in the afterpulsing since overall count-rate does not change. This is because as the rate of early photon detection goes up, the rate of late-photon detection reduces commensurately, yielding no net change in the overall rate of photons detected. This hypothesis was tested on a 4 mm diameter tissue-mimicking phantom (μa = 0.02 mm-1, μs’ = 1 mm-1) by ranging the power of a 10 MHz pulse 780-nm laser with pulse spread of < 100 fs (Calmar, USA) and an avalanche photodiode (MPD, Picoquant, Germany) and TCSPC module (HydraHarp, Picoquant, Germany) for light detection. Details of the results are in Fig. 1a, but of note is that we observed more than a 60-times improvement in SNR compared to conventional early photon detection that would have taken 1000-times longer to achieve the same early photon count. A demonstration of the type of resolution possible is in Fig 1b with an image of a 4-mm-thick human breast cancer biopsy where tumor spiculations of less than 100 μm diameter are observable. 1Fieramonti, L. et al. PloS one (2012). 2Sinha, L., et al. Optics letters (2016). 
    more » « less