Review Article | Published:

Light in diagnosis, therapy and surgery

Nature Biomedical Engineering volume 1, Article number: 0008 (2017) | Download Citation

Light and optical techniques have made profound impacts on modern medicine, with numerous lasers and optical devices currently being used in clinical practice to assess health and treat disease. Recent advances in biomedical optics have enabled increasingly sophisticated technologies — in particular, those that integrate photonics with nanotechnology, biomaterials and genetic engineering. In this Review, we revisit the fundamentals of light–matter interactions, describe the applications of light in imaging, diagnosis, therapy and surgery, overview their clinical use, and discuss the promise of emerging light-based technologies.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Ocular lesions produced by an optical maser (laser). Science 134, 1525–1526 (1961).

  2. 2.

    & Treatment of basal cell epithelioma by laser radiation. JAMA 189, 773–775 (1964).

  3. 3.

    , & Laser eye surgery for refractive errors. Lancet 367, 1432–1447 (2006).

  4. 4.

    , , & Long-term healing of the central cornea after photorefractive keratectomy using an exicmer laser. Opthalmology 95, 1411–1421 (1988).

  5. 5.

    et al. LASIK world literature review: quality of life and patient satisfaction. Ophthalmology 116, 691–701 (2009).

  6. 6.

    et al. Femtosecond laser-assisted cataract surgery with integrated optical coherence tomography. Sci. Transl. Med. 2, 58ra85 (2010).

  7. 7.

    Retinal tears and rhegmatogenous retinal detachment after intravitreal injections: its prevalence and case reports. Digit. J. Ophthalmol. 21, 8–10 (2015).

  8. 8.

    Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Arch. Ophthalmol. 109, 1242–1257 (1991).

  9. 9.

    , & Lasers in dermatology: four decades of progress. J. Am. Acad. Dermatol. 49, 1–34 (2003).

  10. 10.

    & Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science 220, 524–527 (1983).

  11. 11.

    & Microvasculature can be selectively damaged using dye lasers: a basic theory and experimental evidence in human skin. Lasers Surg. Med. 1, 263–276 (1981).

  12. 12.

    et al. Dynamic epidermal cooling during pulsed laser treatment of port-wine stain. A new methodology with preliminary clinical evaluation. Arch. Dermatol. 131, 695–700 (1995).

  13. 13.

    , , & Pulsed carbon dioxide laser resurfacing of photo-aged facial skin. Arch. Dermatol. 132, 395–402 (1996).

  14. 14.

    , , , & Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg. Med. 34, 426–438 (2004).

  15. 15.

    et al. Consensus recommendations on the use of an erbium-doped 1,550-nm fractionated laser and its applications in dermatologic laser surgery. Dermatologic Surg. 36, 461–469 (2010).

  16. 16.

    , , & Rapid fibrin plug formation within cutaneous ablative fractional CO2 laser lesions. Lasers Surg. Med. 48, 125–132 (2016).

  17. 17.

    & Clinical use of the Q-switched ruby and the Q-switched Nd:YAG (1064 nm and 532 nm) lasers for treatment of tattoos. J. Dermatol. Surg. Oncol. 19, 330–338 (1993).

  18. 18.

    et al. Successful and rapid treatment of blue and green tattoo pigment with a novel picosecond laser. Arch. Dermatol. 148, 820–823 (2012).

  19. 19.

    , , , & Damage to hair follicles by normal-mode ruby laser pulses. J. Am. Acad. Dermatol. 35, 889–894 (1996).

  20. 20.

    & Home-use laser and light devices for the skin: an update. Semin. Cutan. Med. Surg. 30, 144–147 (2011).

  21. 21.

    Towards high-power mid-infrared emission from a fibre laser. Nat. Photon. 6, 423–431 (2012).

  22. 22.

    , , & Holmium laser resection of the prostate: preliminary results of a new method for the treatment of benign prostatic hyperplasia. Urology 47, 48–51 (1996).

  23. 23.

    , & High-power potassium-titanyl-phosphate (KTP/532) laser vaporization prostatectomy: 24 hours later. Urology 51, 254–256 (1998).

  24. 24.

    et al. Holmium:YAG laser lithotripsy for upper urinary tract calculi in 598 patients. J. Urol. 167, 31–34 (2002).

  25. 25.

    , , , & Laser lithotripsy of common bile duct stones. Gut 29, 746–751 (1988).

  26. 26.

    et al. Lead extraction in the contemporary setting: the LExICon study: an observational retrospective study of consecutive laser lead extractions. J. Am. Coll. Cardiol. 55, 579–586 (2010).

  27. 27.

    et al. Pacemaker lead extraction with the laser sheath: results of the pacing lead extraction with the excimer sheath (PLEXES) trial. J. Am. Coll. Cardiol. 33, 1671–1676 (1999).

  28. 28.

    et al. Laser ablation of human atherosclerotic plaque without adjacent tissue injury. J. Am. Coll. Cardiol. 5, 929–933 (1985).

  29. 29.

    , & Endovenous laser treatment of saphenous vein reflux: long-term results. J. Vasc. Interv. Radiol. 14, 991–996 (2003).

  30. 30.

    , & Reduced recanalization rates of the great saphenous vein after endovenous laser treatment with increased energy dosing: definition of a threshold for the endovenous fluence equivalent. J. Vasc. Surg. 44, 834–839 (2006).

  31. 31.

    , & Laser treatment of superficial leg veins. Dermatologic Surg. 37, 729–741 (2011).

  32. 32.

    & Experimental studies of the application of the Er:YAG laser on dental hard substances: I. Measurement of the ablation rate. Lasers Surg. Med. 9, 338–344 (1989).

  33. 33.

    et al. Lasers in dentistry. Lasers Surg. Med. 16, 103–133 (1995).

  34. 34.

    & Laser surgery in the larynx. Early clinical experience with continuous CO2 laser. Ann. Otol. Rhinol. Laryngol. 81, 792–798 (1972).

  35. 35.

    et al. Hepatic metastases: interstitial laser photocoagulation with real-time US monitoring and dynamic CT evaluation of treatment. Radiology 187, 339–347 (1993).

  36. 36.

    & Endoscopic laser therapy for malignancies affecting the esophagus and gastroesophageal junction: analysis of technical and functional efficacy. Arch. Intern. Med. 145, 1443–1446 (1985).

  37. 37.

    , & State of the art: interventional pulmonology. Chest 131, 261–274 (2007).

  38. 38.

    & Phototherapy for neonatal jaundice. N. Engl. J. Med. 358, 920–928 (2008).

  39. 39.

    & Milestones in photoimmunology. J. Invest. Dermatol. 133, E7–E10 (2013).

  40. 40.

    et al. UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo. J. Allergy Clin. Immunol. 123, 1117–1123 (2009).

  41. 41.

    et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 1770–1773 (2006).

  42. 42.

    Antigenicity of murine skin tumors induced by ultraviolet light. J. Natl Cancer Inst. 53, 1333–1336 (1974).

  43. 43.

    , , & The alternative complement pathway seems to be a UVA sensor that leads to systemic immunosuppression. J. Invest. Dermatol. 129, 2694–2701 (2009).

  44. 44.

    et al. Phototherapy in dermatology: a call for action. J. Am. Acad. Dermatol. 72, 1078–1080 (2015).

  45. 45.

    et al. Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. J. Invest. Dermatol. 130, 2654–2663 (2010).

  46. 46.

    Psoralen and ultraviolet A light therapy for psoriasis. N. Engl. J. Med. 357, 682–690 (2007).

  47. 47.

    & The consequences of UV-induced immunosuppression for human health. Photochem. Photobiol. 87, 965–977 (2011).

  48. 48.

    , , & UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production. Proc. Natl Acad. Sci. USA 107, 6418–6423 (2010).

  49. 49.

    et al. Ultraviolet radiation suppresses obesity and symptoms of metabolic syndrome independently of vitamin D in mice fed a high-fat diet. Diabetes 63, 3759–3769 (2014).

  50. 50.

    et al. A randomized trial of phototherapy with filtered sunlight in African neonates. N. Engl. J. Med. 373, 1115–1124 (2015).

  51. 51.

    , , , & Lux vs. wavelength in light treatment of seasonal affective disorder. Acta Psychiatr. Scand. 120, 203–212 (2009).

  52. 52.

    , & Light as a central modulator of circadian rhythms, sleep and affect. Nat. Rev. Neurosci. 15, 443–454 (2014).

  53. 53.

    et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am. J. Psychiatry 162, 656–662 (2005).

  54. 54.

    , & High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. J. Clin. Endocrinol. Metab. 88, 4502–4505 (2003).

  55. 55.

    et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder. JAMA Psychiatry 73, 56–63 (2015).

  56. 56.

    et al. Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action. Antimicrob. Agents Chemother. 57, 1238–1245 (2013).

  57. 57.

    et al. Blue light for infectious diseases: Propionibacterium acnes, Helicobacter pylori, and beyond?. Drug Resist. Updates 15, 233–236 (2012).

  58. 58.

    , , , & Outdoor activity during class recess reduces myopia onset and progression in school children. Ophthalmology 120, 1080–1085 (2013).

  59. 59.

    , & Protective effects of high ambient lighting on the development of form-deprivation myopia in rhesus monkeys. Investig. Ophthalmol. Vis. Sci. 53, 421–428 (2012).

  60. 60.

    , & Effective and lesion-free cutaneous influenza vaccination. Proc. Natl Acad. Sci. USA 112, 5005–5010 (2015).

  61. 61.

    , , , & Low-level laser (light) therapy (LLLT) for treatment of hair loss. Lasers Surg. Med. Surg. Med. 46, 144–151 (2014).

  62. 62.

    et al. The nuts and bolts of low-level laser (light) therapy. Ann. Biomed. Eng. 40, 516–533 (2012).

  63. 63.

    , , & Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet 374, 1897–1908 (2009).

  64. 64.

    et al. Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study. J. Neurotrauma 31, 1008–1017 (2014).

  65. 65.

    et al. Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration. Sci. Transl. Med. 6, 238ra69 (2014).

  66. 66.

    , , , & Infrared light excites cells by changing their electrical capacitance. Nat. Commun. 3, 736 (2012).

  67. 67.

    et al. Optical pacing of the embryonic heart. Nat. Photon. 4, 623–626 (2010).

  68. 68.

    , , , & Optical stimulation of the facial nerve: a new monitoring technique?. Laryngoscope 117, 1641–1647 (2007).

  69. 69.

    , & Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J. Cataract Refract. Surg. 29, 1780–1785 (2003).

  70. 70.

    et al. A blood-resistant surgical glue for minimally invasive repair of vessels and heart defects. Sci. Transl. Med. 6, 218ra6 (2014).

  71. 71.

    et al. A light-reflecting balloon catheter for atraumatic tissue defect repair. Sci. Transl. Med. 7, 306ra149 (2015).

  72. 72.

    , , & Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs. Proc. Natl Acad. Sci. USA 105, 9522–9527 (2008).

  73. 73.

    et al. Photoactivated composite biomaterial for soft tissue restoration in rodents and in humans. Sci. Transl. Med. 3, 93ra67 (2011).

  74. 74.

    , & Photodynamic therapy and anti-tumour immunity. Nat. Rev. Cancer 6, 535–545 (2006).

  75. 75.

    et al. Photodynamic therapy of cancer: an update. CA Cancer J.Clin. 61, 250–281 (2011).

  76. 76.

    , , & The role of photodynamic therapy in overcoming cancer drug resistance. Photochem. Photobiol. Sci. 14, 1476–1491 (2015).

  77. 77.

    & Current evidence and applications of photodynamic therapy in dermatology. Clin. Cosmet. Investig. Dermatol. 7, 145–163 (2014).

  78. 78.

    , & Plasma treated with methylene blue and light: clinical efficacy and safety profile. Transfus. Med. Rev. 27, 235–240 (2013).

  79. 79.

    et al. Thienopyrrole-expanded BODIPY as a potential NIR photosensitizer for photodynamic therapy. Chem. Commun. 49, 3940–3942 (2013).

  80. 80.

    et al. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat. Med. 18, 1580–1585 (2012).

  81. 81.

    et al. Bioluminescence-activated deep-tissue photodynamic therapy of cancer. Theranostics 5, 805–817 (2015).

  82. 82.

    The cellular and molecular basis of hyperthermia. Crit. Rev. Oncol. Hematol. 43, 33–56 (2002).

  83. 83.

    , , & Ablation of hypoxic tumors with dose-equivalent photothermal, but not photodynamic, therapy using a nanostructured porphyrin assembly. ACS Nano 7, 2541–2550 (2013).

  84. 84.

    , , & Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J. Am. Chem. Soc. 128, 2115–2120 (2006).

  85. 85.

    , , & Organic stealth nanoparticles for highly effective in vivo near-infrared photothermal therapy of cancer. ACS Nano 6, 5605–5613 (2012).

  86. 86.

    et al. Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. Nat. Mater. 10, 324–332 (2011).

  87. 87.

    , , , & Diagnosing otitis media — otoscopy and cerumen removal. N. Engl. J. Med. 362, e62 (2010).

  88. 88.

    , , , & Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 379, 2459–2464 (2012).

  89. 89.

    , , & Twenty years of functional near-infrared spectroscopy: introduction for the special issue. Neuroimage 85, 1–5 (2014).

  90. 90.

    et al. Noninvasive evaluation of oral lesions using depth-sensitive optical spectroscopy. Cancer 115, 1669–1679 (2009).

  91. 91.

    , , & Relevance of laser doppler and laser speckle techniques for assessing vascular function: state of the art and future trends. IEEE Trans. Biomed. Eng. 60, 659–666 (2013).

  92. 92.

    et al. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat. Med. 8, 136–142 (2002).

  93. 93.

    & Point-of-care and point-of-procedure optical imaging technologies for primary care and global health. Sci. Transl. Med. 6, 253rv2 (2014).

  94. 94.

    et al. Wide-field computational imaging of pathology slides using lens-free on-chip microscopy. Sci. Transl. Med. 6, 267ra175 (2014).

  95. 95.

    , & Point-of-care colorimetric detection with a smartphone. Lab Chip 12, 4240–4243 (2012).

  96. 96.

    et al. Integrated quantum dot barcode smartphone optical device for wireless multiplexed diagnosis of infected patients. ACS Nano 9, 3060–3074 (2015).

  97. 97.

    et al. Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope. Sci. Transl. Med. 7, 286re4 (2015).

  98. 98.

    & A colloidal quantum dot spectrometer. Nature 523, 67–70 (2013).

  99. 99.

    et al. Optical coherence tomography for advanced screening in the primary care office. J. Biophotonics 7, 525–533 (2014).

  100. 100.

    & Plasmonic ELISA for the ultrasensitive detection of disease biomarkers with the naked eye. Nat. Nanotech. 8, 1759–1764 (2012).

  101. 101.

    et al. Protein microarrays with carbon nanotubes as multicolor Raman labels. Nat. Biotechnol. 26, 1285–1292 (2008).

  102. 102.

    , , , & Detection with optical microcavities. Science 317, 783–787 (2007).

  103. 103.

    & The potential of optofluidic biolasers. Nat. Methods 11, 141–147 (2014).

  104. 104.

    , & Spatially resolved transcriptomics and beyond. Nat. Rev. Genet. 16, 57–66 (2015).

  105. 105.

    , , & Precision medicine for cancer with next-generation functional diagnostics. Nat. Rev. Cancer 15, 747–756 (2015).

  106. 106.

    , , & Optimizing early upper gastrointestinal cancer detection at endoscopy. Nat. Rev. Gastroenterol. Hepatol. 12, 660–667 (2015).

  107. 107.

    et al. Incremental diagnostic yield of chromoendoscopy and outcomes in inflammatory bowel disease patients with a history of colorectal dysplasia on white-light endoscopy. Gastrointest. Endosc. 83, 1005–1012 (2016).

  108. 108.

    , , & Wireless capsule endoscopy. Nature 405, 417 (2000).

  109. 109.

    , , & Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. Gastrointest. Endosc. 71, 280–286 (2010).

  110. 110.

    & State-of-the-art retinal optical coherence tomography. Prog. Retin. Eye Res. 27, 45–88 (2008).

  111. 111.

    et al. Optical coherence tomography. Science 254, 1178–1181 (1991).

  112. 112.

    et al. Comprehensive volumetric optical microscopy in vivo. Nat. Med. 12, 1429–1433 (2006).

  113. 113.

    et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J. Am. Coll. Cardiol. 59, 1058–1072 (2012).

  114. 114.

    et al. Expert review document part 2: methodology, terminology and clinical applications of optical coherence tomography for the assessment of interventional procedures. Eur. Heart J. 33, 2513–2520 (2012).

  115. 115.

    , , & High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography. Gastrointest. Endosc. 51, 467–474 (2000).

  116. 116.

    et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Nat. Med. 17, 1010–1014 (2011).

  117. 117.

    et al. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat. Med. 17, 1680–1684 (2011).

  118. 118.

    et al. Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment. Proc. Natl Acad. Sci. USA 108, 14626–14631 (2011).

  119. 119.

    et al. Optical mammography using diffuse optical spectroscopy for monitoring tumor response to neoadjuvant chemotherapy in women with locally advanced breast cancer. Clin. Cancer Res. 21, 577–584 (2015).

  120. 120.

    et al. Predicting breast tumor response to neoadjuvant chemotherapy with diffuse optical spectroscopic tomography prior to treatment. Clin. Cancer Res. 20, 6006–6015 (2014).

  121. 121.

    et al. Combined optical and X-ray tomosynthesis breast imaging. Radiology 258, 89–97 (2011).

  122. 122.

    et al. Mapping distributed brain function and networks with diffuse optical tomography. Nat. Photon. 8, 448–454 (2014).

  123. 123.

    , , , & Bedside optical imaging of occipital resting-state functional connectivity in neonates. Neuroimage 59, 2529–2538 (2012).

  124. 124.

    et al. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 127, 706–713 (2004).

  125. 125.

    et al. Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology 138, 834–842 (2010).

  126. 126.

    et al. Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo. Gut 60, 26–33 (2011).

  127. 127.

    et al. Optical biopsy of human bladder neoplasia with in vivo confocal laser endomicroscopy. J. Urol. 182, 1299–1305 (2009).

  128. 128.

    et al. Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy. Nat. Med. 14, 454–458 (2008).

  129. 129.

    et al. Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: first-in-human results. Sci. Transl. Med. 5, 184ra61 (2013).

  130. 130.

    et al. Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus. Nat. Med. 18, 315–321 (2012).

  131. 131.

    et al. Endoscopic molecular imaging of human bladder cancer using a CD47 antibody. Sci. Transl. Med. 6, 260ra148 (2014).

  132. 132.

    et al. Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nat. Med. 21, 955–961 (2015).

  133. 133.

    Assessing the potential impact of fluorescence angiography in preventing limb loss. Pod. Today 29, (2016).

  134. 134.

    , & In vivo fluorescence microscopy: lessons from observing cell behavior in their native environment. Physiology 30, 40–49 (2015).

  135. 135.

    et al. Sensitivity and specificity of multiphoton laser tomography for in vivo and ex vivo diagnosis of malignant melanoma. J. Invest. Dermatol. 129, 1752–1758 (2009).

  136. 136.

    et al. Noninvasive two-photon microscopy imaging of mouse retina and retinal pigment epithelium through the pupil of the eye. Nat. Med. 20, 785–789 (2014).

  137. 137.

    et al. Video-rate molecular imaging in vivo with stimulated Raman scattering. Science 330, 1368–1370 (2010).

  138. 138.

    et al. Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy. Sci. Transl. Med. 7, 309ra163 (2015).

  139. 139.

    et al. High-speed label-free functional photoacoustic microscopy of mouse brain in action. Nat. Methods 12, 407–410 (2015).

  140. 140.

    et al. Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo. Nat. Med. 18, 1297–1302 (2012).

  141. 141.

    et al. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat. Nanotech. 4, 855–860 (2009).

  142. 142.

    et al. Laser optoacoustic imaging system for detection of breast cancer. J. Biomed. Opt. 14, 24007 (2009).

  143. 143.

    et al. Photoacoustic mammography: initial clinical results. Breast Cancer 21, 146–153 (2014).

  144. 144.

    et al. In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins. Br. J. Dermatol. 163, 1218–1228 (2010).

  145. 145.

    et al. In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases. J. Invest. Dermatol. 132, 2386–2394 (2012).

  146. 146.

    , , , & In vivo biomechanical mapping of normal and keratoconus corneas. JAMA Ophthalmol. 133, 480–482 (2015).

  147. 147.

    , & Minimally invasive surgery: national trends in adoption and future directions for hospital strategy. Surg. Endosc. Other Interv. Tech. 27, 2253–2257 (2013).

  148. 148.

    et al. Acute gastric volvulus associated with wandering spleen in an adult treated laparoscopically after endoscopic reduction: a case report. Surg. Case Reports 2, 47 (2016).

  149. 149.

    et al. Stereoscopic vision provides a significant advantage for precision robotic laparoscopy. Br. J. Surg. 91, 879–885 (2004).

  150. 150.

    , , , & Image-guided cancer surgery using near-infrared fluorescence. Nat. Rev. Clin. Oncol. 10, 507–518 (2013).

  151. 151.

    & Fluorescence-guided surgery with live molecular navigation—a new cutting edge. Nat. Rev. Cancer 13, 653–662 (2013).

  152. 152.

    et al. 5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement. PLoS ONE 8, e76988 (2013).

  153. 153.

    et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 7, 392–401 (2006).

  154. 154.

    et al. Targeted zwitterionic near-infrared fluorophores for improved optical imaging. Nat. Biotechnol. 31, 148–153 (2013).

  155. 155.

    et al. Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging. Nat. Med. 21, 192–197 (2015).

  156. 156.

    et al. Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience. Breast Cancer Res. Treat. 143, 333–342 (2014).

  157. 157.

    et al. Near-infrared fluorescence-guided resection of colorectal liver metastases. Cancer 119, 3411–3418 (2013).

  158. 158.

    et al. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat. Med. 17, 1315–1319 (2011).

  159. 159.

    et al. Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Ann. Surg. Oncol. 22, 2082–2087 (2014).

  160. 160.

    et al. Fluorescent peptides highlight peripheral nerves during surgery in mice. Nat. Biotechnol. 29, 352–356 (2011).

  161. 161.

    , , & In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat. Biotechnol. 17, 375–378 (1999).

  162. 162.

    et al. A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer. Sci. Transl. Med. 8, 320ra4 (2016).

  163. 163.

    et al. The prospective intraoperative and perioperative ophthalmic imaging with optical coherence tomography (PIONEER) study: 2-year results. Am. J. Ophthalmol. 158, 999–1007 (2014).

  164. 164.

    et al. Angiography alone versus angiography plus optical coherence tomography to guide decision-making during percutaneous coronary intervention: the Centro per la Lotta contro l’Infarto-Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) study. EuroIntervention 8, 823–829 (2012).

  165. 165.

    et al. Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography. Sci. Transl. Med. 7, 292ra100 (2015).

  166. 166.

    et al. Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy. Sci. Transl. Med. 5, 201ra119 (2013).

  167. 167.

    et al. Intraoperative brain cancer detection with Raman spectroscopy in humans. Sci. Transl. Med. 7, 274ra19 (2015).

  168. 168.

    et al. Imaging and photodynamic therapy: mechanisms, monitoring, and optimization. Chem. Rev. 110, 2795–2838 (2010).

  169. 169.

    , , & A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative Photofrin-photodynamic therapy of brain tumors. Lasers Surg. Med. 32, 224–232 (2003).

  170. 170.

    et al. Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate. Proc. Natl. Acad. Sci. USA 101, 12294–12299 (2004).

  171. 171.

    et al. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease. Nat. Med. 20, 313–318 (2014).

  172. 172.

    et al. Real-time in vivo Cherenkoscopy imaging during external beam radiation therapy. J. Biomed. Opt. 18, 110504 (2013).

  173. 173.

    et al. Diffraction-unlimited all-optical imaging and writing with a photochromic GFP. Nature 478, 204–208 (2011).

  174. 174.

    et al. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346, 1257998 (2014).

  175. 175.

    et al. Single-cell phenotyping within transparent intact tissue through whole-body clearing. Cell 158, 945–958 (2014).

  176. 176.

    , , & Controlling waves in space and time for imaging and focusing in complex media. Nat. Photon. 6, 283–292 (2012).

  177. 177.

    & The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy. Chem. Soc. Rev. 41, 2885–2911 (2012).

  178. 178.

    Chronopharmaceutical drug delivery systems: hurdles, hype or hope?. Adv. Drug Deliv. Rev. 62, 898–903 (2010).

  179. 179.

    , & Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers. Proc. Natl Acad. Sci. USA 109, 8483–8488 (2012).

  180. 180.

    et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat. Mater. 8, 935–939 (2009).

  181. 181.

    et al. Porphyrin-phospholipid liposomes permeabilized by near-infrared light. Nat. Commun. 5, 3546 (2014).

  182. 182.

    et al. A smart and versatile theranostic nanomedicine platform based on nanoporphyrin. Nat. Commun. 5, 4712 (2014).

  183. 183.

    et al. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci. Transl. Med. 6, 260ra149 (2014).

  184. 184.

    et al. A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle. Nat. Med. 18, 829–834 (2012).

  185. 185.

    et al. Photosensitizer-loaded gold vesicles with strong plasmonic coupling effect for imaging-guided photothermal/photodynamic therapy. ACS Nano 7, 5320–5329 (2013).

  186. 186.

    et al. Bismuth sulfide nanorods as a precision nanomedicine for in vivo multimodal imaging-guided photothermal therapy of tumor. ACS Nano 9, 696–707 (2015).

  187. 187.

    et al. A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways. Nat. Nanotech. 11, 378–387 (2016).

  188. 188.

    , , & Harnessing photochemical internalization with dual degradable nanoparticles for combinatorial photo-chemotherapy. Nat. Commun. 5, 3623 (2014).

  189. 189.

    et al. On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles. Nat. Med. 20, 778–784 (2014).

  190. 190.

    et al. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 1, 16014 (2016).

  191. 191.

    & Nanomedicines targeting the tumor microenvironment. Cancer J. 21, 314–321 (2015).

  192. 192.

    , & A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).

  193. 193.

    et al. Nanoparticles that communicate in vivo to amplify tumour targeting. Nat. Mater. 10, 545–552 (2011).

  194. 194.

    et al. Programmable artificial phototactic microswimmer. Nat. Nanotech. (2016).

  195. 195.

    , , , & Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).

  196. 196.

    , , , & Optical deconstruction of parkinsonian neural circuitry. Science 324, 354–359 (2009).

  197. 197.

    , & Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology. Science 347, 659–664 (2015).

  198. 198.

    & From optogenetic technologies to neuromodulation therapies. Sci. Transl. Med. 5, 177ps6 (2013).

  199. 199.

    & Optogenetics and translational medicine. Sci. Transl. Med. 5, 177ps5 (2013).

  200. 200.

    et al. Activating positive memory engrams suppresses depression-like behaviour. Nature 522, 335–339 (2015).

  201. 201.

    et al. Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice. Nat. Biotechnol. 32, 274–278 (2014).

  202. 202.

    et al. Optogenetic control of contractile function in skeletal muscle. Nat. Commun. 6, 7153 (2015).

  203. 203.

    & Optogenetic approaches to restoring visual function in retinitis pigmentosa. Curr. Opin. Neurobiol. 21, 942–946 (2011).

  204. 204.

    , & Optogenetic approaches to retinal prosthesis. Vis. Neurosci. 31, 345–354 (2014).

  205. 205.

    , & Optogenetic pharmacology for control of native neuronal signaling proteins. Nat. Neurosci. 16, 816–823 (2013).

  206. 206.

    et al. Photochemical restoration of visual responses in blind mice. Neuron 75, 271–282 (2012).

  207. 207.

    et al. Rapid optical control of nociception with an ion-channel photoswitch. Nat. Methods 9, 396–402 (2012).

  208. 208.

    et al. Optical control of metabotropic glutamate receptors. Nat. Neurosci. 16, 507–516 (2013).

  209. 209.

    et al. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells. Proc. Natl. Acad. Sci. USA 111, E5574–E5583 (2014).

  210. 210.

    , , , & Addition of human melanopsin renders mammalian cells photoresponsive. Nature 433, 741–745 (2005).

  211. 211.

    , , & A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332, 1565–1568 (2011).

  212. 212.

    et al. Light-guiding hydrogels for cell-based sensing and optogenetic synthesis in vivo. Nat. Photon. 7, 987–994 (2013).

  213. 213.

    et al. Epidermal photonic devices for quantitative imaging of temperature and thermal transport characteristics of the skin. Nat. Commun. 5, 4938 (2014).

  214. 214.

    et al. Ultrathin, highly flexible and stretchable PLEDs. Nat. Photon. 7, 811–816 (2013).

  215. 215.

    et al. User-interactive electronic skin for instantaneous pressure visualization. Nat. Mater. 12, 899–904 (2013).

  216. 216.

    , , & All-organic optoelectronic sensor for pulse oximetry. Nat. Commun. 5, 5745 (2014).

  217. 217.

    et al. A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat. Sci. Transl. Med. 8, 366ra165 (2016).

  218. 218.

    et al. An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment. Nat. Commun. 6, 10059 (2015).

  219. 219.

    et al. Photovoltaic retinal prosthesis with high pixel density. Nat. Photon. 6, 391–397 (2012).

  220. 220.

    et al. Waterproof AlInGaP optoelectronics on stretchable substrates with applications in biomedicine and robotics. Nat. Mater. 9, 929–937 (2010).

  221. 221.

    et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013).

  222. 222.

    et al. Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. Nat. Methods 12, 969–974 (2015).

  223. 223.

    et al. Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nat. Biotechnol. 33, 1280–1286 (2015).

  224. 224.

    et al. Wireless optofluidic systems for programmable in vivo pharmacology and optogenetics. Cell 162, 662–674 (2015).

  225. 225.

    et al. Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant. Nat. Commun. 5, 5392 (2014).

  226. 226.

    et al. Wireless power transfer to deep-tissue microimplants. Proc. Natl Acad. Sci. USA 111, 7974–7979 (2014).

  227. 227.

    , , & Self-powered flexible inorganic electronic system. Nano Energy 14, 111–125 (2014).

  228. 228.

    et al. Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma. Biomaterials 35, 8487–8495 (2014).

  229. 229.

    , , & Step-index optical fiber made of biocompatible hydrogels. Adv. Mater. 27, 4081–4086 (2015).

  230. 230.

    et al. Bioabsorbable polymer optical waveguides for deep-tissue photomedicine. Nat. Commun. 7, 10374 (2015).

  231. 231.

    et al. Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo. Nat. Biotechnol. 33, 277–284 (2015).

  232. 232.

    & Intracellular microlasers. Nat. Photon. 9, 572–576 (2015).

  233. 233.

    , , & Laser particle stimulated emission microscopy. Phys. Rev. Lett. 117, 193902 (2016).

  234. 234.

    Some new applications of electricity and light in medicine. N. Engl. J. Med. 160, 331–333 (1909).

  235. 235.

    Optical properties of biological tissues: a review. Phys. Med. Biol. 58, R37–R61 (2013).

  236. 236.

    & Studies of thermal injury: II. The relative importance of time and surface temperature in the causation of cutaneous burns. Am. J. Pathol. 23, 695–720 (1947).

  237. 237.

    Ablation of polymers and biological tissue by ultraviolet lasers. Science 234, 559–565 (1986).

  238. 238.

    et al. ICNIRP guidelines: revision of guidelines on limits of exposure to laser radiation of wavelengths between 400 nm and 1. 4 μm. Health Phys. 79, 431–440 (2000).

  239. 239.

    Solar radiation measurement: techniques and instrumentation. Sol. Energy 18, 309–325 (1976).

Download references

Acknowledgements

This work was supported by the US National Institutes of Health Director's Pioneer Award (DP1-OD022296) and grants P41-EB015903, R01-EY025454 and R01-CA192878, and National Science Foundation grants ECCS-1505569 and CMMI-1562863.

Author information

Affiliations

  1. Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA.

    • Seok Hyun Yun
    •  & Sheldon J. J. Kwok
  2. Department of Dermatology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.

    • Seok Hyun Yun
  3. Harvard–MIT Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.

    • Seok Hyun Yun
    •  & Sheldon J. J. Kwok

Authors

  1. Search for Seok Hyun Yun in:

  2. Search for Sheldon J. J. Kwok in:

Contributions

S.H.Y. and S.J.J.K. conceived and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Seok Hyun Yun.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/s41551-016-0008

Further reading