High-Speed Nonlinear Interferometric Vibrational Imaging of Biological Tissue With Comparison to Raman Microscopy

Benalcazar, Wladimir A.; Chowdary, Praveen D.; Jiang, Zhi; Marks, Dan; Chaney, Eric J.; Gruebele, Martin; Boppart, Stephen A.

doi:10.1109/jstqe.2009.2035537

Cited by 18 publications

(16 citation statements)

References 41 publications

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“…Thus, significant progress has been made in near-infrared spectroscopic imaging of tissues. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] On the other hand, light scattering methods operate on the assumption that subtle tissue morphological modifications induced by cancer onset and development are accompanied by changes in the scattering properties and, thus, offer a noninvasive window into pathology. [19][20][21][22][23][24][25][26][27] Despite these promising efforts, light scattering-based techniques currently have limited use in the clinic.…”

Section: Introductionmentioning

confidence: 99%

Tissue refractive index as marker of disease

et al. 2011

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Abstract. The gold standard in histopathology relies on manual investigation of stained tissue biopsies. A sensitive and quantitative method for in situ tissue specimen inspection is highly desirable, as it would allow early disease diagnosis and automatic screening. Here we demonstrate that quantitative phase imaging of entire unstained biopsies has the potential to fulfill this requirement. Our data indicates that the refractive index distribution of histopathology slides, which contains information about the molecular scale organization of tissue, reveals prostate tumors and breast calcifications. These optical maps report on subtle, nanoscale morphological properties of tissues and cells that cannot be recovered by common stains, including hematoxylin and eosin. We found that cancer progression significantly alters the tissue organization, as exhibited by consistently higher refractive index variance in prostate tumors versus normal regions. Furthermore, using the quantitative phase information, we obtained the spatially resolved scattering mean free path and anisotropy factor g for entire biopsies and demonstrated their direct correlation with tumor presence. In essence, our results show that the tissue refractive index reports on the nanoscale tissue architecture and, in principle, can be used as an intrinsic marker for cancer diagnosis. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Section: Introductionmentioning

confidence: 99%

Tissue refractive index as marker of disease

et al. 2011

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“…157 On the other hand, the combination of SRS with other modalities has not yet been reported to our knowledge, as the measurement scheme of SRS is based on temporal modulation, which makes it less ideal for combination with other methods employing constant intensity. Linear and nonlinear Raman spectroscopy have been compared in several reports, 158,159 but due to the large di®erence in measurement principle, and that both modalities probe similar vibrations, no simultaneous measurements were performed. Additionally, most applications employ CARS as an imaging technique, while until recently, Raman was nearly always implemented as a nonimaging spectroscopy technique measured at one point.…”

Section: Nonlinear Spectroscopy Multimodal Implementationsmentioning

confidence: 99%

Multimodal label-free microscopy

Pavillon

Fujita

Smith

2014

J. Innov. Opt. Health Sci.

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This paper reviews the di®erent multimodal applications based on a large extent of label-free imaging modalities, ranging from linear to nonlinear optics, while also including spectroscopic measurements. We put speci¯c emphasis on multimodal measurements going across the usual boundaries between imaging modalities, whereas most multimodal platforms combine techniques based on similar light interactions or similar hardware implementations. In this review, we limit the scope to focus on applications for biology such as live cells or tissues, since by their nature of being alive or fragile, we are often not free to take liberties with the image acquisition times and are forced to gather the maximum amount of information possible at one time. For such samples, imaging by a given label-free method usually presents a challenge in obtaining su±cient optical signal or is limited in terms of the types of observable targets. Multimodal imaging is then particularly attractive for these samples in order to maximize the amount of measured information. While multimodal imaging is always useful in the sense of acquiring additional information from additional modes, at times it is possible to attain information that could not be discovered using any single mode alone, which is the essence of the progress that is possible using a multimodal approach.

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“…The reconstructed CARS spectra of biomolecules are equivalent to the corresponding Raman spectra, but can be acquired at least 1000 times faster than Raman micro-spectroscopy for a comparable signal-to-noise ratio [52]. In a study using a preclinical breast cancer rat tumor model [53], this scheme was used to differentiate mammary tumors from normal mammary tissue with a >99% confidence interval, and resolve the “molecular” tumor margin within 100 mm [Figure 3(b)].…”

Section: Representative Schemesmentioning

confidence: 99%

Coherent anti‐Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation

Boppart

2013

Journal of Biophotonics

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Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring. An optimal scheme of clinical CARS micro-spectroscopy for thin ex vivo tissues.

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High-Speed Nonlinear Interferometric Vibrational Imaging of Biological Tissue With Comparison to Raman Microscopy

Cited by 18 publications

References 41 publications

Tissue refractive index as marker of disease

Tissue refractive index as marker of disease

Multimodal label-free microscopy

Coherent anti‐Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation

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