Gage J. Greening's research while affiliated with University of Arkansas and other places

Publications (26)

Article
Full-text available
Background Immunotherapy in colorectal cancer (CRC) regulates specific immune checkpoints and, when used in combination with chemotherapy, can improve patient prognosis. One specific immune checkpoint is the recruitment of circulating monocytes that differentiate into tumor-associated macrophages (TAMs) and promote tumor angiogenesis. Changes in va...
Article
Full-text available
Significance: Many studies in colorectal cancer (CRC) use murine ectopic tumor models to determine response to treatment. However, these models do not replicate the tumor microenvironment of CRC. Physiological information of treatment response derived via diffuse reflectance spectroscopy (DRS) from murine primary CRC tumors provide a better unders...
Conference Paper
A densely-packed, custom multi-pixel photodetector probe permits spatially resolved diffuse reflectance (SRDR) measurements of phantoms of varying thicknesses, showing high signal contrast between thin phantoms and high depth sensitivity.
Article
Full-text available
Colorectal cancer (CRC) is the fourth most common cancer type and is the second leading cause of cancer deaths annually in the United States. Conventional treatment options include postoperative (adjuvant) and preoperative (neoadjuvant) chemotherapy and radiotherapy. Although these treatment modalities have shown to decrease tumor burden, a major l...
Article
Diffuse reflectance spectroscopy (DRS) is a probe-based spectral biopsy technique used in cancer studies to quantify tissue reduced scattering (μs') and absorption (μa) coefficients and vary in source-detector separation (SDS) to fine-tune sampling depth. In subcutaneous murine tumor allografts or xenografts, a key design requirement is ensuring th...
Article
Spatial frequency domain imaging (SFDI) is a widefield, noncontact, and label-free imaging modality that is currently being explored as a new tool for longitudinal tracking of cancer therapies in the preclinical setting. We describe a two-layer look-up-table (LUT) inversion algorithm for SFDI that better accounts for the skin (top layer) and tumor...
Article
Diffuse reflectance spectroscopy (DRS) has been used in murine studies to quantify tumor perfusion and therapeutic response. These studies frequently use inhaled isoflurane anesthesia, which depresses the respiration rate and results in the desaturation of arterial oxygen saturation, potentially affecting tissue physiological parameters. However, t...
Article
Recent fiber-bundle microendoscopy techniques enable non-invasive analysis of in vivo tissue using either imaging techniques or a combination of spectroscopy techniques. Combining imaging and spectroscopy techniques into a single optical probe may provide a more complete analysis of tissue health. In this article, two dissimilar modalities are comb...
Article
Full-text available
Intraepithelial dysplasia of the oral mucosa typically originates in the proliferative cell layer at the basement membrane and extends to the upper epithelial layers as the disease progresses. Detection of malignancies typically occurs upon visual inspection by non-specialists at a late-stage. In this manuscript, we validate a quantitative hybrid i...
Conference Paper
Spatially–resolved diffuse reflectance (SRDR) measurements provide photon path information, and enable layered tissue analysis. This paper presents experimental SRDR measurements on two-layer PDMS skin tissue-mimicking phantoms of varying top layer thicknesses, and bulk phantoms of varying optical properties using concentric multi-pixel photodiode...
Conference Paper
Two-photon excitation of label-free tissue is of increasing interest, as advances have been made in endoscopic clinical application of multiphoton microscopy, such as second harmonic generation (SHG) scanning endoscopy used to monitor cervical collagen in mice¹. We used C57BL mice as a model to investigate the progression of gastrointestinal struct...
Conference Paper
In the non-keratinized epithelia, dysplasia typically arises near the basement membrane and proliferates into the upper epithelial layers over time. We present a non-invasive, multimodal technique combining high-resolution fluorescence imaging and broadband sub-diffuse reflectance spectroscopy (sDRS) to monitor health at various tissue layers. This...
Article
Early detection of structural or functional changes in dysplastic epithelia may be crucial for improving long-term patient care. Recent work has explored myriad non-invasive or minimally invasive "optical biopsy" techniques for diagnosing early dysplasia, such as high-resolution microendoscopy, a method to resolve sub-cellular features of apical ep...
Conference Paper
Many cases of epithelial cancer originate in basal layers of tissue and are initially undetected by conventional microendoscopy techniques. We present a bench-top, fiber-bundle microendoscope capable of providing high resolution images of surface cell morphology. Additionally, the microendoscope has the capability to interrogate deeper into materia...
Article
Optical phantoms are used in the development of various imaging systems. For certain applications, the development of thin phantoms that simulate the physical size and optical properties of tissue is important. Here, we demonstrate a method for producing thin phantom layers with tunable optical properties using poly(dimethylsiloxane) (PDMS) as a su...
Conference Paper
A method for producing thin film PDMS optical phantoms using a spin coater can be used to simulate epithelial tissues. These PDMS phantoms may be used to evaluate the performance and depth sensitivity of optical imaging systems.

Citations

... At 16 weeks after the last AOM injection the size of tumors was periodically assessed using a veterinary colonoscopy system (ColoVIEW, Karl Storz) as we have previously described [27] . Briefly, mice were anesthetized using 2% isoflurane using a precision vaporizer and placed on a heating pad set at 42 • C to maintain body temperature through the procedure. ...
... Pro-tumor functions of TAMs include direct secretion of angiogenic growth factors (GFs) leading to an increase in vascular endothelial growth factor (VEGF) [10,19,24] and ECM-degrading matrix metalloproteases (MMPs) which allow for the release of ECM-sequestered angiogenic GFs [10,17]. FDA approval of anti-VEGFs, such as bevacizumab, has shown significant benefit in overall survival in breast cancer; however, it has shown no significant benefit in terms of overall survival, leading to many clinicians restricting its use and a shift in focus to modulation of cytokines [25]. CCL2-mediated TAM infiltration is linked to increased inflammation, angiogenesis, and tumorigenesis; therefore, anti-CCL2 immunotherapy has the potential to reduce tumor burden and recurrence risk [12,26]. ...
... Our group has previously used DRS in subcutaneous models of CRC, 23 demonstrating the feasibility and advantages of extracting in-vivo physiological information. However, as the diameter of a mouse colon is below 4 mm and the thickness of the colonic wall ranges between 180 and 800 μm, 6,7 the miniaturization of DRS instrumentation presents different challenges: the probe needs to be miniaturized while maintaining an adequate signal-to-noise ratio, 24 and peristalsis and subject breathing can both cause displacement between the probe and the tissue when data are collected, thereby introducing artifacts in the collected signal. ...
... At the beginning of the monitoring period, the StO 2 values of CT26 tissue were in the range of 20-30%. These values are in agreement with the results of other researchers obtained by diffuse reflectance spectroscopy using a probe with 2-4 mm sourcedetector separation [39]. In the untreated group, the level of StO 2 gradually decreased with the tumor growth from 27.5 ± 3.6% to 3.4 ± 1.5% on day 7. ...
... The two-layer model assumes optical properties of the top and bottom layers during fitting of d 1 and D B2 . Precise knowledge of the optical properties in each layer, however, can be hard to obtain for some applications [40]. To evaluate the influence of layer optical properties on the reconstruction of d 1 and D B2 , we separately varied the μ a and m 0 s in each layer by ± 20% and performed the same two-parameter fitting procedure as described previously. ...
... On the other hand, the impact of anesthesia during the in vivo imaging is also important. Greening et al. (2018) have reported that isoflurane concentrations greater than 2% can affect tissue hemoglobin (HbO 2 ) concentration, thereby requiring the use of ketamine/xylazine solutions. Another method that can be used for the measurement of sO 2 in tissue instead of PAI, diffuse reflectance spectroscopy, does not provide anatomic imaging (Awan et al. 2011;Dadgar et al. 2018). ...
... Walters et al. [14] used a lens-less holographic imaging system to achieve sample imaging at a resolution of 80 µm through fiber bundles and different wavelengths of excitation light. Greening et al. [15] combined fluorescent microscopic endoscopy with spectroscopic techniques to obtain a 4.5-µm resolution image of melanoma on human skin tissue with an imaging field of 1 × 1 mm. In addition, research has been performed in the construction of multi-modal imaging platforms, which combine the advantages of multiple imaging modes [16][17][18][19]. ...
... Then, the LUT was used as an inverse model to fit measured spectral data and extract optical properties. [18][19][20] DRS data at each SDS represent a weighted average of physiological parameters collected at increasing depths. Therefore, a one-layer inverse experimental model was chosen to quantity volume-averaged, rather than layerspecific, physiological parameters without assuming precise thickness of overlying skin layers. ...
... Subsequently, the system was validated in the clinical environment and in vivo sub-DRS data were collected from the inner lip of 13 volunteers. This hybrid system was reported to be capable of gathering information on functional and structural properties of tissue [93]. ...
... The utility of SRDRS for quantitative optical characterization of tissues has been widely recognized [18][19][20][21][22]. The increased dimensionality of the DRS data yields increased information density for the unique determination of tissue optical properties, and the illumination/detection separations of SRDRS probes may be optimized for specific tissue applications to reduce noise and target specific interrogation depths [23,24]. ...