Real-time Raman system for in vivo disease diagnosis

Motz, Jason T.; Gandhi, Saumil; Scepanovic, Obrad R.; Haka, Abigail S.; Kramer, John; Dasari, Ramachandra R.; Feld, Michael S.

doi:10.1117/1.1920247

Cited by 134 publications

(112 citation statements)

References 26 publications

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“…The depth of field determined by the full-width at half-maximum (FWHM) value was 520 and 280 μm, for the high-volume and confocal Raman probes, respectively. The depth of field estimated for the highvolume Raman probe is comparable to the sampling depths of typical Raman probes that report a collection depth in the range of 500 μm [22][23][24]. Evidently, these values refer to the depth of field in this (reflective) substrate whereas the presence of multiple or diffuse scattering, inherent in biological samples, is prone to increasing the aforementioned dimensions.…”

Section: Raman Instrumentationmentioning

confidence: 58%

“…The light was delivered to a spot of ca. 1 mm 2 area (where the power at the sample was approximately 60 mW) and collected from the tissue using a Raman probe, whose design is identical to the Motz probe described in detail elsewhere [22,23]. Briefly, the collection component of our probe consisted of ten tightly packed low-OH 200 μm core optical fibers (Thorlabs Inc.), for Raman signal collection where the low-OH content of the fiber reduces the generation of the large fluorescence signal.…”

Section: Raman Instrumentationmentioning

confidence: 99%

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Selective sampling using confocal Raman spectroscopy provides enhanced specificity for urinary bladder cancer diagnosis

et al. 2012

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In recent years, Raman spectroscopy has shown substantive promise in diagnosing bladder cancer, especially due to its exquisite molecular specificity. The ability to reduce false detection rates in comparison to existing diagnostic tools such as photodynamic diagnosis makes Raman spectroscopy particularly attractive as a complementary diagnostic tool for real-time guidance of transurethral resection of bladder tumor (TURBT). Nevertheless, the state-ofthe-art high-volume Raman spectroscopic probes have not reached the expected levels of specificity thereby impeding their clinical translation. To address this issue, we propose the use of a confocal Raman probe for bladder cancer diagnosis that can boost the specificity of the diagnostic algorithm based on its suppression of the out-of-focus nonanalyte-specific signals emanating from the neighboring normal tissue. In this article, we engineer and apply such a probe, having depth of field of approximately 280 μm, for Raman spectral acquisition from ex vivo normal and cancerous TURBT samples. Using this clinical dataset, a diagnostic algorithm based on principal component analysis and logistic regression is developed. We demonstrate that this approach results in comparable sensitivity but significantly higher specificity in relation to high-volume Raman spectral data. The application of only two principal components is sufficient for the discrimination of the samples underlining the robustness of the algorithm. Further, no discordance between replicate spectra is observed emphasizing the reproducible nature of the current diagnostic assessment. The high levels of sensitivity and specificity achieved in this proof-of-concept study opens substantive avenues for application of a confocal Raman probe during endoscopic procedures related to diagnosis and treatment of bladder cancer.

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Section: Raman Instrumentationmentioning

confidence: 58%

Section: Raman Instrumentationmentioning

confidence: 99%

Selective sampling using confocal Raman spectroscopy provides enhanced specificity for urinary bladder cancer diagnosis

et al. 2012

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“…The recent development of a highly efficient Raman optical fiber probe has now bridged the gap between Raman spectroscopy and the clinical setting. The optical fiber probe has successfully demonstrated its usefulness in assessing human tissue models for disease and thus has great potential as a clinically practical technique (28,29). In particular, this Raman optical fiber probe has the potential of being an extremely useful tool in an intraoperative setting, for instance in surgical debulking of cancers.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive molecular imaging of small living subjects using Raman spectroscopy

Keren

Zavaleta

Cheng

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

558

475

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Molecular imaging of living subjects continues to rapidly evolve with bioluminescence and fluorescence strategies, in particular being frequently used for small-animal models. This article presents noninvasive deep-tissue molecular images in a living subject with the use of Raman spectroscopy. We describe a strategy for small-animal optical imaging based on Raman spectroscopy and Raman nanoparticles. Surface-enhanced Raman scattering nanoparticles and single-wall carbon nanotubes were used to demonstrate whole-body Raman imaging, nanoparticle pharmacokinetics, multiplexing, and in vivo tumor targeting, using an imaging system adapted for small-animal Raman imaging. The imaging modality reported here holds significant potential as a strategy for biomedical imaging of living subjects.nanotubes ͉ SERS nanoparticles M olecular imaging of living subjects provides the ability to study cellular and molecular processes that have the potential to impact many facets of biomedical research and clinical patient management (1-4). Imaging of small-animal models is currently possible by using positron emission tomography (PET), single photon emission computed tomography, magnetic resonance imaging, computed tomography, optical bioluminescence and fluorescence, high frequency ultrasound, and several other emerging modalities. However, no single modality currently meets the needs of high sensitivity, high spatial and temporal resolution, high multiplexing capacity, low cost, and high-throughput.Fluorescence imaging, in particular, has significant potential for in vivo studies but is limited by several factors (5, 6), including a limited number of fluorescent molecular imaging agents available in the near infra-red (NIR) window with large spectral overlap between them, which restricts the ability to interrogate multiple targets simultaneously (multiplexing). In addition, background autofluorescence emanating from superficial tissue layers restricts the sensitivity and the depth to which fluorescence imaging can be used. Moreover, rapid photobleaching of fluorescent molecules limits their useful lifetime and prevents studies of prolonged duration. Therefore, we have attempted to develop new strategies that may solve some of the limitations of fluorescence imaging in living subjects.Raman spectroscopy can differentiate the spectral fingerprint of many molecules, resulting in very high multiplexing capabilities. Narrow spectral features are easily separated from the broadband autofluorescence, because Raman is a scattering phenomenon as opposed to absorption/emission in fluorescence, and Raman active molecules are more photostable compared with fluorophores, which are rapidly photobleached. Unfortunately, the precise mechanism for photobleaching is not well understood. However, it has been linked to a transition from the excited singlet state to the excited triplet state. Photobleaching is significantly reduced for single molecules adsorbed onto metal particles because of the rapid quenching of excited electrons by the metal surface...

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“…Each spectrum was collected for a total of 1 second. The data was analyzed in real time as detailed below and a spectral-based diagnosis was displayed within 1 second (39). A range of powers, 82 to 125 mW, was used depending on the throughput of the probe used.…”

Section: Methodsmentioning

confidence: 99%

In vivo Margin Assessment during Partial Mastectomy Breast Surgery Using Raman Spectroscopy

et al. 2006

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We present the first demonstration of in vivo collection of Raman spectra of breast tissue. Raman spectroscopy, which analyzes molecular vibrations, is a promising new technique for the diagnosis of breast cancer. We have collected 31 Raman spectra from nine patients undergoing partial mastectomy procedures to show the feasibility of in vivo Raman spectroscopy for intraoperative margin assessment. The data was fit with an established model, resulting in spectral-based tissue characterization in only 1 second. Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity for distinguishing cancerous from normal and benign tissues in our small data set. Significantly, we have detected a grossly invisible cancer that, upon pathologic review, required the patient to undergo a second surgical procedure. Had Raman spectroscopy been used in a real-time fashion to guide tissue excision during the procedure, the additional reexcision surgery might have been avoided. These preliminary findings suggest that Raman spectroscopy has the potential to lessen the need for reexcision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries. (Cancer Res 2006; 66(6): 3317-22)

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Real-time Raman system for in vivo disease diagnosis

Cited by 134 publications

References 26 publications

Selective sampling using confocal Raman spectroscopy provides enhanced specificity for urinary bladder cancer diagnosis

Selective sampling using confocal Raman spectroscopy provides enhanced specificity for urinary bladder cancer diagnosis

Noninvasive molecular imaging of small living subjects using Raman spectroscopy

In vivo Margin Assessment during Partial Mastectomy Breast Surgery Using Raman Spectroscopy

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