skip to main content

Explore Research Products in the NSF-PAR

  • NSF Public Access
  • Search Results
  • In vivo imaging using surface enhanced spatially offset raman spectroscopy (SESORS): balancing sampling frequency to improve overall image acquisition
Title: In vivo imaging using surface enhanced spatially offset raman spectroscopy (SESORS): balancing sampling frequency to improve overall image acquisition
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
NSF-PAR ID:
10498791
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
Nature Publishing Group
Date Published:
Journal Name:
npj Imaging
Volume:
2
Issue:
1
ISSN:
2948-197X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ( , Applied Spectroscopy)
    null (Ed.)
    A new hyperspectral Raman imaging technique is described using a spatial heterodyne Raman spectrometer (SHRS) and a microlens array (MLA). The new technique enables the simultaneous acquisition of Raman spectra over a wide spectral range at spatially isolated locations within two spatial dimensions ( x, y) using a single exposure on a charge-coupled device (CCD) or other detector types such as a complementary metal-oxide semiconductor (CMOS) detector. In the SHRS system described here, a 4 × 4 mm MLA with 1600, 100 µm diameter lenslets is used to image the sample, with each lenslet illuminating a different region of the SHRS diffraction gratings and forming independent fringe images on the CCD. The fringe images from each lenslet contain the fully encoded Raman spectrum of the region of the sample “seen” by the lenslet. Since the SHRS requires no moving parts, all fringe images can be measured simultaneously with a single detector exposure, and in principle using a single laser shot, in the case of a pulsed laser. In this proof of concept paper, hyperspectral Raman spectra of a wide variety of heterogeneous samples are used to characterize the technique in terms of spatial and spectral resolution tradeoffs. It is shown that the spatial resolution is a function of the diameter of the MLA lenslets, while the number of spatial elements that can be resolved is equal to the number of MLA lenslets that can be imaged onto the SHRS detector. The spectral resolution depends on the spatial resolution desired, and the number of grooves illuminated on both diffraction gratings by each lenslet, or combination of lenslets in cases where they are grouped. 
    more » « less
  2. ; ; ; ; ; ; ; ( , Advanced Functional Materials)
    Abstract

    Gold‐based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near‐infrared (NIR‐II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR‐II gold nanostructures, a particular liposome template‐guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR‐II region, affording their capacity of NIR‐II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44‐overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4‐aminothiophenol (4‐ATP) onto AuNFs yields a surface‐enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA‐4‐ATP‐AuNFs‐DOX on tumor‐bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR‐II under PA–Raman dual image‐guided photo‐chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.

     
    more » « less
  3. ; ; ( , Sensors)

    A compact and planar imaging system was developed using a flexible polymer substrate that can distinguish subcutaneous tissue abnormalities, such as breast tumors, based on electromagnetic-wave interactions in materials where permittivity variations affect wave reflection. The sensing element is a tuned loop resonator operating in the industrial, scientific, and medical (ISM) band at 2.423 GHz, providing a localized high-intensity electric field that penetrates into tissues with sufficient spatial and spectral resolutions. The resonant frequency shifts and magnitudes of the reflection coefficients indicate the boundaries of abnormal tissues under the skin due to their high contrasts to normal tissues. The sensor was tuned to the desired resonant frequency with a reflection coefficient of −68.8 dB for a radius of 5.7 mm, with a tuning pad. Quality factors of 173.1 and 34.4 were achieved in simulations and measurements in phantoms. An image-processing method was introduced to fuse raster-scanned 9 × 9 images of resonant frequencies and reflection coefficients for image-contrast enhancement. The results showed a clear indication of the tumor’s location at a depth of 15 mm and the capability to identify two tumors both at the depth of 10 mm. The sensing element can be expanded to a four-element phased array for deeper field penetration. Field analysis showed the depths of −20 dB attenuation were improved from 19 to 42 mm, giving wider coverage in tissues at resonance. Results showed that a quality factor of 152.5 was achieved and a tumor could be identified at a depth of up to 50 mm. In this work, simulations and measurements were conducted to validate the concept, showing great potential for subcutaneous imaging in medical applications in a noninvasive, efficient, and lower-cost way.

     
    more » « less
  4. ; ; ; ( , Biomedical Optics Express)

    Ultrasound-switchable fluorescence (USF) is a novel imaging technique that provides high spatial resolution fluorescence images in centimeter-deep biological tissue. Recently, we successfully demonstrated the feasibility ofin vivoUSF imaging using a frequency-domain photomultiplier tube-based system. In this work, for the first time we carried outin vivoUSF imaging via a camera-based USF imaging system. The system acquires a USF signal on a two-dimensional (2D) plane, which facilitates the image acquisition because the USF scanning area can be planned based on the 2D image and provides high USF photon collection efficiency. We demonstratedin vivoUSF imaging in the mouse’s glioblastoma tumor with multiple targets via local injection. In addition, we designed the USF contrast agents with different particle sizes (70 nm and 330 nm) so that they could bio-distribute to various organs (spleen, liver, and kidney) via intravenous (IV) injections. The results showed that the contrast agents retained stable USF properties in tumors and some organs (spleen and liver). We successfully achievedin vivoUSF imaging of the mouse’s spleen and liver via IV injections. The USF imaging results were compared with the images acquired from a commercial X-ray micro computed tomography (micro-CT) system.

     
    more » « less
  5. ; ; ; ; ; ; ; ; ; ; et al ( , Advanced Science)
    Abstract The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high spatial resolution, low background signal, and deep tissue penetration properties, but NIR‐II dyes with adequate in vivo performance and safety profiles are scarce. A novel NIR‐II fluorophore, XW‐03‐66, with a fluorescence quantum yield (QY) of 6.0% in aqueous media is reported. XW‐03‐66 self‐assembles into nanoparticles (≈80 nm) and has a systemic circulation half‐life ( t 1/2 ) of 11.3 h. In mouse models of human papillomavirus (HPV)+ and HPV‐ OSCC, XW‐03‐66 outperformed indocyanine green (ICG), a clinically available NIR dye, and enabled intraoperative NIR‐II image‐guided resection of the tumor and adjacent draining lymph node with negative margins. In vitro and in vivo toxicity assessments revealed minimal safety concerns for in vivo applications. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email