Evidence map›Paper›PMID 27903865›Full record

ArticleScience translational medicine2016

Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis.

Dimitra Pouli, Mihaela Balu, Carlo A Alonzo, Zhiyi Liu, Kyle P Quinn, Francisca Rius-Diaz, Ronald M Harris, Kristen M Kelly, Bruce J Tromberg, Irene Georgakoudi

Abstract read
In one paragraph

Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed.

  1. Article
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  5. Advanced Microscopy Techniques.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026
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  16. Review
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  19. Label-Free Optical Metabolic Imaging in Cells and Tissues.Annual review of biomedical engineering · 2023
    Review
  20. Review

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Dimitra PouliDepartment of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Mihaela BaluLaser Microbeam and Medical Program, Beckman Laser Institute, University of California, Irvine, Irvine, CA 92612, USA.
Carlo A AlonzoDepartment of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Zhiyi LiuDepartment of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Kyle P QuinnDepartment of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Francisca Rius-DiazDepartment of Preventive Medicine and Public Health, Faculty of Medicine, University of Malaga, 32 Louis Pasteur Boulevard, 29071 Málaga, Spain.
Ronald M HarrisDepartment of Dermatology, University of California, Irvine, 1 Medical Plaza Drive, Irvine, CA 92697, USA.
Kristen M KellyDepartment of Dermatology, University of California, Irvine, 1 Medical Plaza Drive, Irvine, CA 92697, USA.
Bruce J TrombergLaser Microbeam and Medical Program, Beckman Laser Institute, University of California, Irvine, Irvine, CA 92612, USA.
Irene GeorgakoudiDepartment of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA. irene.georgakoudi@tufts.edu.

Funding

Virtual Photonocs TechnologiesP41EB015890 · NIBIB · UNIVERSITY OF CALIFORNIA-IRVINE · PI DURKIN, ANTHONY · 2012 to 2017
$7.0M
Quantitative multiphoton microscopy for non-invasive diagnosis of melanomaR01CA195466 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BALU, MIHAELA, KELLY, KRISTEN M · 2016 to 2018
$825k
NCI NIH HHS R01 CA195466NIBIB NIH HHS P41 EB015890
6 · The paper itself

Abstract

Active changes in mitochondrial structure and organization facilitate cellular homeostasis. Because aberrant mitochondrial dynamics are implicated in a variety of human diseases, their assessment is potentially useful for diagnosis, therapy, and disease monitoring. Because current techniques for evaluating mitochondrial morphology are invasive or necessitate mitochondria-specific dyes, their clinical translation is limited. We report that mitochondrial dynamics can be monitored in vivo, within intact human skin by relying entirely on endogenous two-photon-excited fluorescence from the reduced metabolic coenzyme nicotinamide adenine dinucleotide (NADH). We established the sensitivity of this approach with in vivo, fast temporal studies of arterial occlusion-reperfusion, which revealed acute changes in the mitochondrial metabolism and dynamics of the lower human epidermal layers. In vitro hypoxic-reperfusion studies validated that the in vivo outcomes were a result of NADH fluorescence changes. To demonstrate the diagnostic potential of this approach, we evaluated healthy and cancerous human skin epithelia. Healthy tissues displayed consistent, depth-dependent morphological and mitochondrial organization patterns that varied with histological stratification and intraepithelial mitochondrial protein expression. In contrast, these consistent patterns were absent in cancerous skin lesions. We exploited these differences to successfully differentiate healthy from cancerous tissues using a predictive classification approach. Collectively, these results demonstrate that our label-free, automated, near real-time assessments of mitochondrial organization-relying solely on endogenous contrast-could be useful for accurate, noninvasive in vivo diagnosis.

Indexed as

Basal Cell CarcinomaBiomarkersEpidermisHomeostasisHumansHypoxiaKeratinocytesMelanomaMicroscopy, Fluorescence, MultiphotonMitochondriaMitochondrial DynamicsNADOxygenPhotonsSkinBiomarkersNADOxygen

Identifiers

PMID27903865
PMCPMC5176339

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.