Multimodal analyses of vitiligo skin identifies tissue characteristics of stable disease

Shiu, Jessica; Zhang, Lihua; Lentsch, Griffin; Flesher, Jessica L.; Jin, Suoqin; Polleys, Christopher; Jo, Seong Jin; Mizzoni, Craig; Mobasher, Pezhman; Kwan, Jasmine; Rius-Díaz, Francisca; Tromberg, Bruce J.; Georgakoudi, Irene; Nie, Qing; Balu, Mihaela; Ganesan, Anand K.

doi:10.1172/jci.insight.154585

Cited by 24 publications

(19 citation statements)

References 66 publications

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“…Label-free schemes are promising for clinical translation. Label-free, 2PM provides powerful insights into diseased tissue based on the detection of morphological and functional metrics of metabolic activity [5][6][7][8][9] . Clinical translation of 2PM from benchtop systems necessitates mitigation of motion artifacts and reduced illumination power.…”

Section: Discussionmentioning

confidence: 99%

“…At the onset of disease, metabolic activity in cells is perturbed due to the reprogramming of cellular metabolism 6 . 2PM has previously been applied for in vivo clinical detection of human dermatological conditions 5,8,9 . Recent work by our group has demonstrated ex vivo detection of cervical pre-cancer with high sensitivity (93.3%) and specificity (83.3%) using 2PM 6 .…”

Section: Introductionmentioning

confidence: 99%

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Denoising of depth-resolved, label-free, two-photon images using deep-learning-based algorithms

Vora

Polleys

Sakellariou

et al. 2023

Label-Free Biomedical Imaging and Sensing (LBIS) 2023

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The potential to differentiate between diseased and healthy tissue has been demonstrated through the extraction of morphological and functional metrics from label-free, two-photon images. Acquiring such images as fast as possible without compromising their diagnostic and functional content is critical for clinical translation of two-photon imaging. Computational restoration methods have demonstrated impressive recovery of image quality and important biological information. However, access to large clinical datasets has hampered advancement of denoising algorithms. Here, we seek to demonstrate the application of denoising algorithms on depth-resolved two-photon excited fluorescence (TPEF) images with specific focus on recovery of functional metabolic metrics. Datasets were generated through the collection of images of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavoproteins from freshly excised rat cheek epithelium. Image datasets were patched across depth, generating 1012, 256-by-256 patches. A well-known Unet architecture was trained on 6628 low-signal-to-noise-ratio (SNR) patches from a previously collected large dataset and later retrained on a smaller 620 low-SNR patches dataset before being validated and evaluated on 88 and 304 low-SNR patches, respectively, using a structural similarity index measure (SSIM) loss function. We demonstrate models trained on larger datasets of human cervical tissue could be used to successfully restore metabolic metrics with an improvement in image quality when applied to rat cheek epithelium images. These results motivate further exploration of weight transfer for denoising of small clinical two-photon microscopy datasets.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Denoising of depth-resolved, label-free, two-photon images using deep-learning-based algorithms

Vora

Polleys

Sakellariou

et al. 2023

Label-Free Biomedical Imaging and Sensing (LBIS) 2023

Self Cite

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“…In a study of metabolic processes in vitiligo lesioned skin, researchers quantitatively assessed enriched metabolic pathways using gene scoring analysis. They found that Oxidative phosphorylation (OXPHOS) and glycolysis showed the most significant differences between stressed keratinocytes and the other, respectively ( 86 ). Therefore, abnormal glucose metabolism in vitiligo patients may result from an imbalance in the secretion of pro-inflammatory factors, low oxidative stress, or impaired G6PD levels.…”

Section: Abnormalities Of Glucose Metabolism Implicated In Vitiligomentioning

confidence: 99%

“…In addition, Shiu et al. implies that combining therapies that reverse defects in keratinocytes’ metabolism with JAK inhibitors could be a novel approach to treating vitiligo ( 86 ).…”

Section: New Therapeutic Strategies In Vitiligo Immunometabolismmentioning

confidence: 99%

Immunometabolism in the pathogenesis of vitiligo

Lyu

Sun

2022

Front. Immunol.

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Vitiligo is a common depigmenting skin disorder characterized by the selective loss of melanocytes. Autoimmunity, genetic, environmental, and biochemical etiology have been proposed in vitiligo pathogenesis. However, the exact molecular mechanisms of vitiligo development and progression are unclear, particularly for immunometabolism. Sporadic studies have suggested mitochondrial dysfunction, enhanced oxidative stress, and specific defects in other metabolic pathways can promote dysregulation of innate and adaptive immune responses in vitiligo. These abnormalities appear to be driven by genetic and epigenetic factors modulated by stochastic events. In addition, glucose and lipid abnormalities in metabolism have been associated with vitiligo. Specific skin cell populations are also involved in the critical role of dysregulation of metabolic pathways, including melanocytes, keratinocytes, and tissue-resident memory T cells in vitiligo pathogenesis. Novel therapeutic treatments are also raised based on the abnormalities of immunometabolism. This review summarizes the current knowledge on immunometabolism reprogramming in the pathogenesis of vitiligo and novel treatment options.

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“…Applications of human in vivo label-free, 2P metabolic imaging are limited to dermatologic applications 1,2 . Recent advances in the field of 2P fiber endoscopy indicate that clinical translation to human internal organ imaging is feasible 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Two-photon imaging of endogenous biomolecules in freshly excised human cervical tissue biopsies captures pre-cancer induced changes in tissue metabolism and morphology

Polleys

Thieu²,

Genega³

et al. 2023

Multiscale Imaging and Spectroscopy IV

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Fiber endoscopes capable of making two-photon (2P) autofluorescence measurements, time-resolved fluorescence decay measurements, and collagen second harmonic generation (SHG) measurements have been applied to animal models. Clinical translation of such devices to internal human organs has the potential to overhaul conventional methods of disease diagnosis and monitoring. Previous work by our lab has established the potential to diagnose high-grade cervical precancers using 2P autofluorescence measurements. Other groups have demonstrated that 2P-based fluorescence lifetime imaging microscopy (FLIM) measurements of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and collagen SHG measurements have the potential to discriminate between cancerous and benign tissues. In this work, we demonstrate the potential to discern high-grade cervical precancerous lesions (HSILs) from benign tissues using fluorescence intensity measurements of NAD(P)H and oxidized flavoproteins, FLIM NAD(P)H measurements, and collagen SHG measurements. Consistent with previous results, benign tissues demonstrated increased depth-dependent heterogeneity in mitochondrial clustering, and increased overall and intrafield heterogeneity of oxido-reductive state relative to HSILs. FLIM phasor analysis demonstrated a relative decrease in NAD(P)H short and long lifetime, and a relative increase in NAD(P)H bound fraction for benign tissues compared to HSILs. Collagen SHG intensity in benign tissues was greater than that of HSIL tissues, along with overall intrafield variations in collagen fiber orientation. This work motivates the functionalization of a clinical 2P fiber endoscope capable of making SHG, autofluorescence intensity and lifetime measurements of metabolic coenzymes in the human cervix.

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Multimodal analyses of vitiligo skin identifies tissue characteristics of stable disease

Cited by 24 publications

References 66 publications

Denoising of depth-resolved, label-free, two-photon images using deep-learning-based algorithms

Denoising of depth-resolved, label-free, two-photon images using deep-learning-based algorithms

Immunometabolism in the pathogenesis of vitiligo

Two-photon imaging of endogenous biomolecules in freshly excised human cervical tissue biopsies captures pre-cancer induced changes in tissue metabolism and morphology

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