In vivo and ex vivo epi-mode pump-probe imaging of melanin and microvasculature

Matthews, Thomas E.; Wilson, Jesse W.; Degan, Simone; Simpson, Mary Jane; Jin, Jiashun; Zhang, Jennifer; Warren, Warren S.

doi:10.1364/boe.2.001576

Cited by 63 publications

(52 citation statements)

References 26 publications

(28 reference statements)

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“…The experimental results and the theoretical simulations at τ = 0 for Φ' (solid red curves in Figs. [3][4] are in excellent agreement, where both show the same concavity (up or down) and slight asymmetry in the parabolic shape for each sample. These results can be understood by using the approximation provided in section 3 (and appendix): Specifically, the difference in concavity between the two samples results from the fact that the OKE response of CS 2 peaks at a later time compared to water, which causes the second derivatives to have opposite signs at τ = 0.…”

Section: Resultsmentioning

confidence: 61%

“…Specifically, the output of a mode-locked Ti:Sapphire laser (Tsunami, Spectra Physics, 80 MHz), with a centered wavelength of 808 nm, is split into two beams: The first beam pumps an optical parametric oscillator (Mira OPO, Coherent) that is tuned to 720 nm and serves as the pump beam. These wavelengths are chosen since they are routinely used for biological imaging with pump-probe microscopy [1][2][3][4]. The second beam from the Ti:Sapph laser is further split into two using a Michelson interferometer to provide a probe field and a reference field, separated by a constant time T = 1.25 mm/c = 4.16 ps, where c is the speed of light in vacuum.…”

Section: Experimental System and Methodsmentioning

confidence: 99%

“…For example, pump-probe microscopy measures the transient, excited state dynamic properties of pigmented samples resulting from interactions such as excited state absorption, ground state depletion, and stimulated emission; consequently the acquired signals exhibit unique structures that enable differentiation of many molecular species. This method has had a significant impact on both biomedical applications [1,2], particularly quantitative melanoma detection [3,4], and art conservation [5]. On the other hand, various techniques have been developed to provide contrast from nonpigmented samples by using nonlinear phase changes (e.g., self/cross phase modulation), which provide greater detail of a sample's morphology [6][7][8][9], but for the most part, lack molecular specificity.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pump-probe nonlinear phase dispersion spectroscopy

Robles¹,

Samineni²,

Wilson³

et al. 2013

Opt. Express

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Pump-probe microscopy is an imaging technique that delivers molecular contrast of pigmented samples. Here, we introduce pump-probe nonlinear phase dispersion spectroscopy (PP-NLDS), a method that leverages pump-probe microscopy and spectral-domain interferometry to ascertain information from dispersive and resonant nonlinear effects. PP-NLDS extends the information content to four dimensions (phase, amplitude, wavelength, and pump-probe time-delay) that yield unique insight into a wider range of nonlinear interactions compared to conventional methods. This results in the ability to provide highly specific molecular contrast of pigmented and non-pigmented samples. A theoretical framework is described, and experimental results and simulations illustrate the potential of this method. Implications for biomedical imaging are discussed.

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Section: Resultsmentioning

confidence: 61%

Section: Experimental System and Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pump-probe nonlinear phase dispersion spectroscopy

Robles¹,

Samineni²,

Wilson³

et al. 2013

Opt. Express

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“…Previously [14,23,24], we assumed that the pump-probe signals resulted solely from a linear combination of eu-and pheo-melanin (based on similarities to sepia eumelanin and synthetic pheomelanin), which permits quantification of the transient signals using an inverse approach. More recent work, however, has generated a richer picture: pump-probe imaging is sensitive to many more properties of melanin, including type (eu-and pheo-melanin), oxidation, aggregate size, and metal content [20].…”

Section: Pigment Type Quantification: Geometrical Pca Description Of mentioning

confidence: 99%

Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential

Robles

Deb

Wilson

et al. 2015

Biomed. Opt. Express

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Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pumpprobe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct "dusty" quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas.

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“…7,8 Optical imaging techniques, such as confocal fluorescence microscopy and two-photon microscopy, are other powerful tools for both structural and functional brain imaging. [9][10][11][12] Various bio-molecules, such as hemoglobin, cytochrome, melanin, and lipid, [13][14][15] possess different optical properties, which provide contrast for structural brain imaging. Using endogenous and exogenous contrasts, light can also be used to monitor functional dynamics, such as hemodynamics and neuron activities.…”

Section: Introductionmentioning

confidence: 99%

Label-free photoacoustic tomography of whole mouse brain structures ex vivo

Xia

et al. 2016

Neurophoton.

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Abstract. Capitalizing on endogenous hemoglobin contrast, photoacoustic-computed tomography (PACT), a deep-tissue high-resolution imaging modality, has drawn increasing interest in neuroimaging. However, most existing studies are limited to functional imaging on the cortical surface and the deep brain structural imaging capability of PACT has never been demonstrated. Here, we explicitly studied the limiting factors of deep brain PACT imaging. We found that the skull distorted the acoustic signal and blood suppressed the structural contrast from other chromophores. When the two effects are mitigated, PACT can potentially provide high-resolution label-free imaging of structures in the entire mouse brain. With 100-μm in-plane resolution, we can clearly identify major structures of the brain, which complements magnetic resonance microscopy for imaging small-animal brain structures. Spectral PACT studies indicate that structural contrasts mainly originate from cytochrome distribution and that the presence of lipid sharpens the image contrast; brain histology results provide further validation. The feasibility of imaging the structure of the brain in vivo is also discussed. Our results demonstrate that PACT is a promising modality for both structural and functional brain imaging.

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In vivo and ex vivo epi-mode pump-probe imaging of melanin and microvasculature

Cited by 63 publications

References 26 publications

Pump-probe nonlinear phase dispersion spectroscopy

Pump-probe nonlinear phase dispersion spectroscopy

Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential

Label-free photoacoustic tomography of whole mouse brain structures ex vivo

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