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(a) Schematic of clinical instrumentation. ND = neutral density filter, L = lens, LP = long pass filter, APD = avalanche photodiode, ICCD = intensified charge coupled device.
Source publication
A photon-tissue interaction (PTI) model was developed and employed to analyze 96 pairs of reflectance and fluorescence spectra from freshly excised human pancreatic tissues. For each pair of spectra, the PTI model extracted a cellular nuclear size parameter from the measured reflectance, and the relative contributions of extracellular and intracell...
Contexts in source publication
Context 1
... the University of Michigan (U of M), a prototype Reflectance and Fluorescence Lifetime Spectrometer (RFLS), described previously [13,16], was developed to measure reflectance and fluorescence from human pancreatic tissue samples (Fig. 1). Briefly, the RFLS consisted of two light sources: a tungsten halogen lamp (HL 2000FHSA, Ocean Optics, Dunedin, FL) for CW reflectance, and a 355 nm pulsed laser with a 1 KHz repetition rate and a 500 ps pulse width (PNV001525-140, JDS Uniphase, San Jose, CA) for fluorescence excitation. Light from these two sources was directed onto ...Context 2
... of reflectance and fluorescence, the rest of the detected photons were sent to a spectrograph (MS 125, Oriel Instruments, Stratford, CT) coupled intensified charge coupled device (ICCD) camera (ICCD 2063, Andor Technology, Belfast, Northern Ireland). The detection range of the ICCD was constrained to 340-800 nm by the long-pass filter (shown in Fig. 1) and the spectral grating on the ICCD. Reflectance data from 400 to 700 nm and fluorescence data from 400 to 638 nm were used in the analysis. At each tissue site, fluorescence and reflectance measurements were made in sequence by using shutters to block the other light source. Each fluorescence (reflectance) measurement had an ...Similar publications
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Citations
... At the tissue surface, only a small part of the incident light is reflected, depending on the incidence angle and the refractive index. Whereas inside the tissue, there is an interaction between the incident light and the outlying electrons of the molecules, resulting in scattering or absorption [10]. In a turbid medium such as biological tissue, scattering is always over absorption [11]. ...
Accurate determination of the optical absorption and scattering properties of biological tissues is a vital issue in many clinical and biomedical applications. These properties assist in planning and monitoring therapeutic protocols in addition to understanding many diagnostic measurements. Diffuse optical diagnosis is a non-invasive technique to monitor tissue physiological changes using light in the red to near infrared range. In the typical procedure, light is recorded after passing through thick tissue and the optical properties are spatially reconstructed using suitable mathematical models. Tissue diffuse reflectance and transmittance are experimentally measured
using two common techniques; integrating sphere and distant-detector. These two methods are widely used for tissue diffusion measurements in the biomedical field for ex-vivo and noninvasive
investigations. In the present study, these two experimental methods have been implemented and compared under verification with Monte-Carlo simulation giving 0.0245 and 0.009 absolute errors at 808-nm laser radiation for integrating sphere and distant-detector methods respectively. Although, integrating sphere shows more accurate results, the distant-detector based method is non-invasive and gives more specific information which helps in tissue differentiation process.
... Optical biopsy via light-based spectroscopy has been proposed as a complementary tool to EUS-FNA for minimally invasive, quantitative assessment. A multimodal approach combining diffuse reflectance and steady-state fluorescence spectroscopy has accurately distinguished malignant tissues from benign tissues in studies on freshly excised pancreatic tissues using histopathologic analysis as the gold standard (6)(7)(8). Furthermore, in a pilot study examining intact pancreas in vivo during pancreatic surgery (9), our group demonstrated a good agreement between in vivo and ex vivo measurements. ...
... The single sensing unit consists of one phototransistor, as well as one 460-nm LED and one 650-nm LED, each located ~660 m away from the phototransistor at each side. This distance is the same source-detection separation with our previous fiber optic-based reflectance spectroscopy system (6)(7)(8), maintaining the same penetration depth (about a few hundred micrometers in a superficial layer) for the purpose of validation. A microfabricated PCB provides a base for microsized OE chip assembly via the deposited eutectic alloy and electrical interconnections. ...
Pancreatic cancer is one of the deadliest cancers, with a 5-year survival rate of <10%. The current approach to confirming a tissue diagnosis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), requires a time-consuming, qualitative cytology analysis and may be limited because of sampling error. We designed and engineered a miniaturized optoelectronic sensor to assist in situ, real-time, and objective evaluation of human pancreatic tissues during EUS-FNA. A proof-of-concept prototype sensor, compatible with a 19-gauge hollow-needle commercially available for EUS-FNA, was constructed using microsized optoelectronic chips and microfabrication techniques to perform multisite tissue optical sensing. In our bench-top verification and pilot validation during surgery on freshly excised human pancreatic tissues (four patients), the fabricated sensors showed a comparable performance to our previous fiber-based system. The flexibility in source-detector configuration using microsized chips potentially allows for various light-based sensing techniques inside a confined channel such as a hollow needle or endoscopy.
... Future work will employ a modified model of light-tissue interaction in order to extract more physical measures of structural changes, such as changes in scattering coefficients. Quantitative approaches [12] would allow estimation of optical scatterer size and distribution and overcome some of the limitations of the assumptions described in Section II. Our MSI camera uses visible wavelengths, which is convenient for using standard clinical light sources but limits penetration depth to approximately 2 mm. ...
Induction of thermal damage to tissue through delivery of microwave energy is frequently applied in surgery to destroy diseased tissue such as cancer cells. Minimization of unwanted harm to healthy tissue is still achieved subjectively, and the surgeon has few tools at their disposal to monitor the spread of the induced damage. This work describes the use of optical methods to monitor the time course of changes to the tissue during delivery of microwave energy in the porcine liver. Multispectral imaging and diffuse reflectance spectroscopy are used to monitor temporal changes in optical properties in parallel with thermal imaging. The results demonstrate the ability to monitor the spatial extent of thermal damage on a whole organ, including possible secondary effects due to vascular damage. Future applications of this type of imaging may see the multispectral data used as a feedback mechanism to avoid collateral damage to critical healthy structures and to potentially verify sufficient application of energy to the diseased tissue.
... Future work will employ a modified model of light-tissue interaction in order to extract more physical measures of structural changes, such as changes in scattering coefficients. Quantitative approaches [12] would allow estimation of optical scatterer size and distribution and overcome some of the limitations of the assumptions described in Section II. Our MSI camera uses visible wavelengths, which is convenient for using standard clinical light sources but limits penetration depth to approximately 2 mm. ...
Induction of thermal damage to tissue through delivery of microwave energy is frequently applied in surgery to destroy diseased tissue such as cancer cells. Minimization of unwanted harm to healthy tissue is still achieved subjectively, and the surgeon has few tools at their disposal to monitor the spread of the induced damage. This work describes the use of optical methods to monitor the time course of changes to the tissue during delivery of microwave energy in the porcine liver. Multispectral imaging and diffuse reflectance spectroscopy are used to monitor temporal changes in optical properties in parallel with thermal imaging. The results demonstrate the ability to monitor the spatial extent of thermal damage on a whole organ, including possible secondary effects due to vascular damage. Future applications of this type of imaging may see the multispectral data used as a feedback mechanism to avoid collateral damage to critical healthy structures and to potentially verify sufficient application of energy to the diseased tissue.
... They also developed novel computational codes to model time-resolved excitation and fluorescent light propagation in multifluorophore biological tissues. The system presented by Chandra was later improved by Wilson et al. in [15] to make a photon-tissue interaction (PTI) model to analyze a number of 96 pairs of reflectance and fluorescence spectra from freshly excised human pancreatic tissues. For each pair of spectra, the PTI model extracted a cellular nuclear size parameter from the measured reflectance and the relative contributions of extracellular and intracellular fluorophores to the intrinsic fluorescence. ...
Optical differentiation is a promising tool in biomedical diagnosis mainly because of its safety. The optical parameters' values of biological tissues differ according to the histopathology of the tissue and hence could be used for differentiation. The optical fluence rate distribution on tissue boundaries depends on the optical parameters. So, providing image displays of such distributions can provide a visual means of biomedical diagnosis. In this work, an experimental setup was implemented to measure the spatially-resolved steady state diffuse reflectance and transmittance of native and coagulated chicken liver and native and boiled breast chicken skin at 635 and 808 nm wavelengths laser irradiation. With the measured values, the optical parameters of the samples were calculated in vitro using a combination of modified Kubelka-Munk model and Bouguer-Beer-Lambert law. The estimated optical parameters values were substituted in the diffusion equation to simulate the fluence rate at the tissue surface using the finite element method. Results were verified with Monte-Carlo simulation. The results obtained showed that the diffuse reflectance curves and fluence rate distribution images can provide discrimination tools between different tissue types and hence can be used for biomedical diagnosis.
... Simple and transparent analytical approaches that adequately model spatially resolved diffuse reflectance at the quasi-diffusive regime, i.e., the source-detector separation (SDS) is 1 order less than the mean transport free path (l 0 t ), when irradiated by a pencil beam are of significant practical interest, regarding real-time forward computation for quantitative biopsy sensing [1] or depth-sampled endoscopic imaging [2]. While the radiative transport equation is accurate for all regimes of photon migration and any values of scattering albedo, it is sophisticated to implement [3,4] and is thus out of reach to most end users of forward computation. ...
We present an empirical master–slave dual-source configuration within the diffusion approximation that enhances modeling of spatially resolved diffuse reflectance at short-path and with low scattering from a semi-infinite homogeneous medium when irradiated by a pencil beam. An isotropic virtual source positioned at a depth of 1/(reduced scattering coefficient) is used as the master source. A second isotropic virtual source whose depth and intensity depend upon those of the master source and tissue property according to a set of simple empirical formulas is added as the slave source. When tested for a semi-infinite homogeneous medium, this master–slave dual-source model consistently produces the aggressive peaking of the diffuse reflectance toward the point of entry, which is significantly underestimated by the model prediction that involves only the master source. Monte Carlo simulations have shown the effectiveness of this empirical model at a short source–detector separation of 1/100 of 1/(reduced scattering coefficient) and an absorption to reduced scattering ratio as strong as 1, with an error within 20% in the near field (1/10 of 1/(reduced scattering coefficient)).
... Optical spectroscopy has shown potential to assist with clinical (pre-) cancer diagnostics in many organs and tissues (5,6), including needle-based in vivo diagnostics (7,8). The feasibility of tissue optical spectroscopy for characterizing human pancreatic disease has been demonstrated in ex vivo pilot studies (9)(10)(11)(12)(13). Pancreatic tissue histology ( Fig. 1) illustrates some of the key morphological and biochemical changes that are typically associated with pancreatic cancer and chronic pancreatitis, relative to normal pancreas. ...
... Reflectance spectra for which the detected signal at 550 nm divided by the detected signal at 650 nm (R 550 /R 650 ) was less than 0.2 were removed from the data set because these spectra were dominated by absorption from blood. It is important to note that the presence of blood is not considered problematic in tissue-optics studies because blood can be avoided by repositioning the tip of the probe (8), removed by suctioning the region of interest (7), or accounted for mathematically (12,13). Fluorescence spectra with a signal-to-noise ratio (SNR) of less than 30 were also removed, because these spectra were considered too noisy to properly analyze. ...
... In Fig. 3(B), the first fluorescence principal component contains a spectral feature near the peak emission wavelength (~400 nm) of collagen fluorescence, which has been shown to distinguish between these tissue types in our previous work (13) . Fig. 3(A) shows that the second and third reflectance principal components display spectral features similar to those of hemoglobin absorption, which has a distinctive Soret peak near 420 nm and secondary peaks near 545 nm and 575 nm. ...
Objectives:
Current pancreatic cancer diagnostics cannot reliably detect early disease or distinguish it from chronic pancreatitis. We test the hypothesis that optical spectroscopy can accurately differentiate cancer from chronic pancreatitis and normal pancreas. We developed and tested clinically compatible multimodal optical spectroscopy technology to measure reflectance and endogenous fluorescence from human pancreatic tissues.
Methods:
Freshly excised pancreatic tissue specimens (39 normal, 34 chronic pancreatitis, 32 adenocarcinoma) from 18 patients were optically interrogated, with site-specific histopathology representing the criterion standard. A multinomial logistic model using principal component analysis and generalized estimating equations provided statistically rigorous tissue classification.
Results:
Optical spectroscopy distinguished pancreatic cancer from normal pancreas and chronic pancreatitis (sensitivity, 91%; specificity, 82%; positive predictive value, 69%; negative predictive value, 95%; area under receiver operating characteristic curve, 0.89). Reflectance alone provided essentially the same classification accuracy as reflectance and fluorescence combined, suggesting that a rapid, low-cost, reduced-footprint, reflectance-based device could be deployed without notable loss of diagnostic power.
Conclusions:
Our novel, clinically compatible, label-free optical diagnostic technology accurately characterizes pancreatic tissues. These data provide the scientific foundation demonstrating that optical spectroscopy can potentially improve diagnosis of pancreatic cancer and chronic pancreatitis.
... Clinical applications of reflectance spectroscopy include analyzing malignant tissue 9 and tissue oxygenation. 10,11 Clinical applications of Raman spectroscopy include assessment of bone quality 12 and HO. 13 We have previously reported the use of Raman spectroscopy to identify changes in the extracellular matrix associated with HO 13-15 and calciphylaxis. 16 However, this technique is limited to the detection of suspicious calcification and does not focus on angiogenesis. ...
Background:
Angiogenesis, the formation of blood vessels, is a critical aspect of wound healing. Disorders of wound healing are often characterized by lack of angiogenesis, a condition frequently observed in aging and diabetic patients. Current techniques for assessing blood at injury sites are limited to contrast-imaging, including angiography. However, these techniques do not directly observe oxygenation of blood and are not amenable to serial evaluation. A multimodal noninvasive reflectance and Raman spectrometer have been proposed to help clinicians as a point-of-care tool to interrogate local angiogenesis and tissue architecture, respectively. The spectrometer system is a rapid, noninvasive, and label-free technology well-suited for the clinical environment.
Materials and methods:
To demonstrate feasibility, the spectrometer system was used to interrogate angiogenesis serially over 9 wk as a result of heterotopic ossification (HO) development in a validated murine model. End-stage HO was confirmed by micro-computed tomography.
Results:
Our preliminary results suggest that reflectance spectroscopy can be used to delineate vessel formation and that pathologic wounds may be characterized by unique spectra. In our model, HO formed at sites 1-3, whereas sites 4 and 5 did not have radiographic evidence of HO.
Conclusions:
A point-of-care system like that demonstrated here shows potential as a noninvasive tool to assess local angiogenesis and tissue architecture that may allow for timely intervention in a clinical setting.
... DRS together with different spectral analysis methods have been demonstrated in many different biomedical applications, from the obtaining of quantitative data of tissue oxygenation and blood volume [118], to the characterization of skin hemodynamics [119,120] and the measurement of collagen content [121] and lipids and water contents [122]. Besides this, DRS has been applied to the assistance in diagnosing different diseases, from gingivitis and periodontitis [123] to pancreatitis [124] and the prediction of ulcer healing [125,126] and wound [127] healing. Also, to pigmented skin lesions (including melanoma) [128,129] and breast cancer [86]. ...
... Further, optical spectroscopy is compatible with clinical EUS-FNA procedures [10]. Optical techniques investigated in pancreatic tissues include optical coherence tomography [11,12], needle-based confocal laser endomicroscopy [13], near-infrared spectroscopy [14,15], nonlinear optical imaging [16], optical field effect analysis from duodenal tissues [17,18], diffuse optical tomography [19], and our own studies employing optical spectroscopy [20][21][22][23][24]. Advantages to our optical spectroscopy technology include addressing the primary medical need: improved and minimally invasive detection of pancreatic cancer in the presence of overall tissue inflammation. ...
... In Stage 1, measurements from ex vivo human adenocarcinoma tissues were shown to correspond well to in vivo measurements from a tumor xenograft [20]. In Stage 2, accurate detection of normal, chronic pancreatitis (inflamed), and adenocarcinoma tissues was achieved [21][22][23]. Malignant tissues were distinguished from benign tissues with sensitivities and specificities of 85% and 86%, respectively [21], and with statistical significance [22] in the setting of chronic pancreatitis. In Stage 3, a PTI model was employed to detect a pancreatic cancer precursor [24]. ...
... In Stage 2, accurate detection of normal, chronic pancreatitis (inflamed), and adenocarcinoma tissues was achieved [21][22][23]. Malignant tissues were distinguished from benign tissues with sensitivities and specificities of 85% and 86%, respectively [21], and with statistical significance [22] in the setting of chronic pancreatitis. In Stage 3, a PTI model was employed to detect a pancreatic cancer precursor [24]. ...
Pancreatic adenocarcinoma has a five-year survival rate of less than 6%. This low survival rate is attributed to the lack of accurate detection methods, which limits diagnosis to late-stage disease. Here, an in vivo pilot study assesses the feasibility of optical spectroscopy to improve clinical detection of pancreatic adenocarcinoma. During surgery on 6 patients, we collected spectrally-resolved reflectance and fluorescence in vivo. Site-matched in vivo and ex vivo data agreed qualitatively and quantitatively. Quantified differences between adenocarcinoma and normal tissues in vivo were consistent with previous results from a large ex vivo data set. Thus, optical spectroscopy is a promising method for the improved diagnosis of pancreatic cancer in vivo.
