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.
This content will become publicly available on June 1, 2024
- Award ID(s):
- 2129617
- NSF-PAR ID:
- 10482357
- Publisher / Repository:
- Biophysical Reports
- Date Published:
- Journal Name:
- Biophysical Reports
- Volume:
- 3
- Issue:
- 2
- ISSN:
- 2667-0747
- Page Range / eLocation ID:
- 100107
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Background There is growing interest in detecting cerebro‐cerebellar circuits, which requires adequate blood oxygenation level dependent contrast and signal‐to‐noise ratio (SNR) throughout the brain. Although 7T scanners offer increased SNR, coverage of commercial head coils is currently limited to the cerebrum.
Purpose To improve cerebellar functional MRI (fMRI) at 7T with high permittivity material (HPM) pads extending the sensitivity of a commercial coil.
Study Type Simulations were used to determine HPM pad configuration and assess radiofrequency (RF) safety. In vivo experiments were performed to evaluate RF field distributions and SNR and assess improvements of cerebellar fMRI.
Subjects Eight healthy volunteers enrolled in a prospective motor fMRI study with and without HPM.
Field Strength/Sequence Gradient echo (GRE) echo planar imaging for fMRI, turbo FLASH for flip angle mapping, GRE sequence for SNR maps, and T1‐weighted MPRAGE were acquired with and without HPM pads at 7T.
Assessment Field maps, SNR maps, and anatomical images were evaluated for coverage. Simulation results were used to assess SAR levels of the experiment. Activation data from fMRI experiments were compared with and without HPM pads.
Statistical Tests fMRI data were analyzed using FEAT FSL for each subject followed by group level analysis using paired t‐test of acquisitions with and without HPM.
Results Simulations showed 52% improvement in transmit efficiency in cerebellum with HPM and SAR levels well below recommended limits. Experiments showed 27% improvement in SNR in cerebellum and improvement in coverage on T1‐weighted images. fMRI showed greater cerebellar activation in individual subjects with the HPM pad present (Z > = 4), especially in inferior slices of cerebellum, with 59% average increase in number of activated voxels in the cerebellum. Group‐level analysis showed improved functional activation (Z > = 2.3) in cerebellar regions with HPM pads without loss of measured activation elsewhere.
Data Conclusion HPM pads can improve cerebellar fMRI at 7T with a commonly‐used head coil without compromising RF safety.
Level of Evidence : 2Technical Efficacy : Stage 1J. MAGN. RESON. IMAGING 2018;48:431–440.
