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New Technologies to Image Tumors

  • George McNamara
  • Justin Lucas
  • John F. Beeler
  • Ajay Basavanhally
  • George Lee
  • Cyrus V. Hedvat
  • Vipul A. Baxi
  • Darren Locke
  • Alexander Borowsky
  • Richard LevensonEmail author
Chapter
  • 61 Downloads
Part of the Cancer Treatment and Research book series (CTAR, volume 180)

Abstract

The premise of this book is the importance of the tumor microenvironment (TME). Until recently, most research on and clinical attention to cancer biology, diagnosis, and prognosis were focused on the malignant (or premalignant) cellular compartment that could be readily appreciated using standard morphology-based imaging.

References

  1. 1.
    Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H et al (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14(5):518–527 Epub 2008/04/29CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C et al (2014) Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 232(2):199–209 Epub 2013/10/15CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Beck AH, Sangoi AR, Leung S, Marinelli RJ, Nielsen TO, van de Vijver MJ et al (2011) Systematic analysis of breast cancer morphology uncovers stromal features associated with survival. Sci Transl Med 3(108):108ra13. Epub 2011/11/11Google Scholar
  4. 4.
    Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M et al (2014) Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 94(1):107–116 Epub 2013/11/13CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL et al (2017) Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Mod Pathol 30(3):340–349 Epub 2016/11/12CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Keren L, Bosse M, Marquez D, Angoshtari R, Jain S, Varma S et al (2018) A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174(6):1373–1387 e19. Epub 2018/09/08Google Scholar
  7. 7.
    Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K et al (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 ihc assay comparison project. J Thorac Oncol. 12(2):208–222 Epub 2016/12/04CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Perez-Medina C, Tang J, Abdel-Atti D, Hogstad B, Merad M, Fisher EA et al (2015) PET imaging of tumor-associated macrophages with 89Zr-labeled high-density lipoprotein nanoparticles. J Nucl Med Off Publ, Soc Nucl Med 56(8):1272–1277 Epub 2015/06/27Google Scholar
  9. 9.
    Tavare R, McCracken MN, Zettlitz KA, Knowles SM, Salazar FB, Olafsen T et al (2014) Engineered antibody fragments for immuno-PET imaging of endogenous CD8+ T cells in vivo. Proc Natl Acad Sci U S A 111(3):1108–1113 Epub 2014/01/07CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Seo JW, Tavare R, Mahakian LM, Silvestrini MT, Tam S, Ingham ES et al (2018) CD8(+) T-cell density imaging with (64)Cu-labeled cys-diabody informs immunotherapy protocols. Clin Cancer Res 24(20):4976–4987 Epub 2018/07/04PubMedPubMedCentralGoogle Scholar
  11. 11.
    McConnell HL, Schwartz DL, Richardson BE, Woltjer RL, Muldoon LL, Neuwelt EA (2016) Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific. Nanomed-Nanotechnol 12(6):1535–1542CrossRefGoogle Scholar
  12. 12.
    Shu CJ, Guo S, Kim YJ, Shelly SM, Nijagal A, Ray P et al (2005) Visualization of a primary anti-tumor immune response by positron emission tomography. Proc Natl Acad Sci USA 102(48):17412–17417 Epub 2005/11/19CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Vakoc BJ, Fukumura D, Jain RK, Bouma BE (2012) Cancer imaging by optical coherence tomography: preclinical progress and clinical potential. Nat Rev Cancer 12(5):363–368 Epub 2012/04/06CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lin R, Chen J, Wang H, Yan M, Zheng W, Song L (2015) Longitudinal label-free optical-resolution photoacoustic microscopy of tumor angiogenesis in vivo. Quant Imaging Med Surg 5(1):23–29 Epub 2015/02/20PubMedPubMedCentralGoogle Scholar
  15. 15.
    Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E et al (2007) Mammographic density and the risk and detection of breast cancer. N Engl J Med 356(3):227–236 Epub 2007/01/19CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Jones EF, Sinha SP, Newitt DC, Klifa C, Kornak J, Park CC et al (2013) MRI enhancement in stromal tissue surrounding breast tumors: association with recurrence free survival following neoadjuvant chemotherapy. PLoS One 8(5):e61969. Epub 2013/05/15Google Scholar
  17. 17.
    Carstens JL, Correa de Sampaio P, Yang D, Barua S, Wang H, Rao A et al (2017) Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer. Nat Commun 8:15095. Epub 2017/04/28Google Scholar
  18. 18.
    Giraldo NA, Nguyen P, Engle EL, Kaunitz GJ, Cottrell TR, Berry S et al (2018) Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab. J Immunother Cancer 6Google Scholar
  19. 19.
    Feng Z (2014) Utilizing quantitative immunohistochemistry for relationship analysis of tumor microenvironment of head and neck cancer patients. J Immunother Cancer 2(3)Google Scholar
  20. 20.
    Parra ER, Francisco-Cruz A, Wistuba II (2019) State-of-the-art of profiling immune contexture in the era of multiplexed staining and digital analysis to study paraffin tumor tissues. Cancers (Basel). 11(2). Epub 2019/02/23Google Scholar
  21. 21.
    Parra ER (2018) Novel platforms of multiplexed immunofluorescence for study of paraffin tumor tissues. J Cancer Treat Diagn 2(1):43–53Google Scholar
  22. 22.
    Mao Y, Keller ET, Garfield DH, Shen K, Wang J (2013) Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev 32(1–2):303–315 Epub 2012/11/02CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Whiteside TL (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27(45):5904–5912 Epub 2008/10/07CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Baker MJ, Trevisan J, Bassan P, Bhargava R, Butler HJ, Dorling KM et al (2014) Using Fourier transform IR spectroscopy to analyze biological materials. Nat Protoc 9(8):1771–1791CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bhargava R (2007) Towards a practical Fourier transform infrared chemical imaging protocol for cancer histopathology. Anal Bioanal Chem 389(4):1155–1169CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bhargava R, Levin IW (2001) Fourier transform infrared imaging: Theory and practice. Anal Chem 73(21):5157–5167CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Bhargava R, Levin IW (2005) Spectrochemical analysis using infrared multichannel detectors preface. Sheff Analy Chem 2005:Xv–XviGoogle Scholar
  28. 28.
    Leslie LS, Wrobel TP, Mayerich D, Bindra S, Emmadi R, Bhargava R (2015) High definition infrared spectroscopic imaging for lymph node histopathology. PLoS One 10(6):e0127238. Epub 2015/06/04Google Scholar
  29. 29.
    Mittal S, Yeh K, Leslie LS, Kenkel S, Kajdacsy-Balla A, Bhargava R (2018) Simultaneous cancer and tumor microenvironment subtyping using confocal infrared microscopy for all-digital molecular histopathology. P Natl Acad Sci USA 115(25):E5651–E5660CrossRefGoogle Scholar
  30. 30.
    Goormaghtigh E (2016) Infrared imaging in histopathology: is a unified approach possible? Biomed Spectrosc Imag 5(4):325–346CrossRefGoogle Scholar
  31. 31.
    Dravid UA, Mazumder N (2018) Types of advanced optical microscopy techniques for breast cancer research: a review. Lasers Med Sci 33(9):1849–1858 Epub 2018/10/13CrossRefGoogle Scholar
  32. 32.
    Min W, Freudiger CW, Lu S, Xie XS (2011) Coherent nonlinear optical imaging: beyond fluorescence microscopy. Annu Rev Phys Chem 62:507–530 Epub 2011/04/02CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cicerone MT, Camp CH (2017) Histological coherent Raman imaging: a prognostic review. The Analyst 143(1):33–59 Epub 2017/11/04CrossRefGoogle Scholar
  34. 34.
    Kirsch R, Messenger DE, Riddell RH, Pollett A, Cook M, Al-Haddad S et al (2013) Venous invasion in colorectal cancer: impact of an elastin stain on detection and interobserver agreement among gastrointestinal and nongastrointestinal pathologists. Am J Surg Pathol 37(2):200–210 Epub 2012/10/31CrossRefGoogle Scholar
  35. 35.
    Natal RA, Vassallo J, Paiva GR, Pelegati VB, Barbosa GO, Mendonca GR et al (2018) Collagen analysis by second-harmonic generation microscopy predicts outcome of luminal breast cancer. Tumour Biol 40(4):1010428318770953. Epub 2018/04/18Google Scholar
  36. 36.
    Chen X, Nadiarynkh O, Plotnikov S, Campagnola PJ (2012) Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure. Nat Protoc 7(4):654–669 Epub 2012/03/10CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Shribak M (2015) Polychromatic polarization microscope: bringing colors to a colorless world. Sci Rep 5:17340 Epub 2015/11/28CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Cohen IJ, Blasberg R (2017) Impact of the tumor microenvironment on tumor-infiltrating lymphocytes: focus on breast cancer. Breast Cancer (Auckl) 11:1178223417731565 Epub 2017/10/06Google Scholar
  39. 39.
    Veitch NC (2004) Horseradish peroxidase: a modern view of a classic enzyme. Phytochemistry 65(3):249–259CrossRefGoogle Scholar
  40. 40.
    Sato S, Nakamura K, Nakamura H (2015) Tyrosine-specific chemical modification with in situ hemin-activated luminol derivatives. ACS Chem Biol 10(11):2633–2640CrossRefGoogle Scholar
  41. 41.
    Sato S, Nakamura K, Nakamura H (2017) Horseradish-peroxidase-catalyzed tyrosine click reaction. Chembiochem: a Eur J Chem Biol 18(5):475–478 Epub 2016/12/23CrossRefGoogle Scholar
  42. 42.
    Beyzavi K, Hampton S, Kwasowski P, Fickling S, Marks V, Clift R (1987) Comparison of horseradish peroxidase and alkaline phosphatase-labelled antibodies in enzyme immunoassays. Ann Clin Biochem 24(Pt 2):145–152 Epub 1987/03/01CrossRefGoogle Scholar
  43. 43.
    Schwenecke H, Benzidine MD, Benzidine Derivatives (2005) Ullmann’s encyclopedia of industrial chemistry, 7th edn. Wiley, Inc., New York, p 18Google Scholar
  44. 44.
    Nakane PK, Pierce GB Jr (1966) Enzyme-labeled antibodies: preparation and application for the localization of antigens. J Histochem Cytochem 14(12):929–931 Epub 1966/12/01CrossRefGoogle Scholar
  45. 45.
    Mason DY, Sammons R (1978) Alkaline-phosphatase and peroxidase for double immunoenzymatic labeling of cellular constituents. J Clin Pathol 31(5):454–460CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    van der Loos CM (2010) Chromogens in multiple immunohistochemical staining used for visual assessment and spectral imaging: the colorful future. J Histotechnol 33(1):31–40CrossRefGoogle Scholar
  47. 47.
    Day WA, Lefever MR, Ochs RL, Pedata A, Behman LJ, Ashworth-Sharpe J et al (2017) Covalently deposited dyes: a new chromogen paradigm that facilitates analysis of multiple biomarkers in situ. Lab Invest 97(1):104–113CrossRefGoogle Scholar
  48. 48.
    Bogoslovsky T, Bernstock JD, Bull G, Gouty S, Cox BM, Hallenbeck JM et al (2018) Development of a systems-based in situ multiplex biomarker screening approach for the assessment of immunopathology and neural tissue plasticity in male rats after traumatic brain injury. J Neurosci Res 96(4):487–500 Epub 2017/05/04CrossRefGoogle Scholar
  49. 49.
    McNamara G, Difilippantonio M, Ried T, Bieber FR (2017) Microscopy and image analysis. Curr Protoc Hum Genet 94:4 1–4 89. Epub 2017/07/12Google Scholar
  50. 50.
  51. 51.
    McNamara G (2019) 18plex flow cytometry from Brilliants—when will fluorescence microscopes catch up? 2018. https://www.linkedin.com/pulse/18plex-flow-cytometry-from-brilliants-when-catch-up-george-mcnamara/
  52. 52.
    McNamara G (2019) “Resolution Blues” meets 21plex salute fluorescence microscopy for immuno-oncology and basic biomedical research 2017. https://www.linkedin.com/pulse/resolution-blues-meets-21plex-salute-fluorescence-basic-mcnamara
  53. 53.
    Kerstens HM, Poddighe PJ, Hanselaar AG (1995) A novel in situ hybridization signal amplification method based on the deposition of biotinylated tyramine. J Histochem Cytochem 43(4):347–352 Epub 1995/04/01CrossRefGoogle Scholar
  54. 54.
    vanGijlswijk RPM, Zijlmans HJMAA, Wiegant J, Bobrow MN, Erickson TJ, Adler KE et al (1997) Fluorochrome-labeled tyramides: use in immunocytochemistry and fluorescence in situ hybridization. J Histochem Cytochem 45(3):375–82Google Scholar
  55. 55.
    Peterson VM, Zhang KX, Kumar N, Wong J, Li L, Wilson DC et al (2017) Multiplexed quantification of proteins and transcripts in single cells. Nat Biotechnol 35(10):936–939 Epub 2017/08/31CrossRefGoogle Scholar
  56. 56.
    Rodgers JR, Rich RR (2013) Antigens and antigen presentation. In: Clinical immunology, 4th edn, pp 77–89Google Scholar
  57. 57.
    Lemus R, Karol MH (2008) Conjugation of haptens. Methods Mol Med 138:167–182 Epub 2008/07/10CrossRefGoogle Scholar
  58. 58.
    Levin M, Lingen M, Schwartz D, Snyder H (2017) Multiplex immunofluorescence profiling of tumor infiltrating immune subsets in HNSCC biopsies provides a powerful tool when combined with patient outcome data. Cancer Res 77Google Scholar
  59. 59.
    Joerger RD, Truby TM, Hendrickson ER, Young RM, Ebersole RC (1995) Analyte detection with DNA-labeled antibodies and polymerase chain-reaction. Clin Chem 41(9):1371–1377CrossRefGoogle Scholar
  60. 60.
    Schubert W, Bonnekoh B, Pommer AJ, Philipsen L, Bockelmann R, Malykh Y et al (2006) Analyzing proteome topology and function by automated multidimensional fluorescence microscopy. Nat Biotechnol 24(10):1270–1278 Epub 2006/10/03CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Friedenberger M, Bode M, Krusche A, Schubert W (2007) Fluorescence detection of protein clusters in individual cells and tissue sections by using toponome imaging system: sample preparation and measuring procedures. Nat Protoc 2(9):2285–2294CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Schubert W, Gieseler A, Krusche A, Serocka P, Hillert R (2012) Next-generation biomarkers based on 100-parameter functional super-resolution microscopy TIS. New Biotechnol 29(5):599–610 Epub 2012/01/03CrossRefGoogle Scholar
  63. 63.
    Schubert W (2015) Advances in toponomics drug discovery: Imaging cycler microscopy correctly predicts a therapy method of amyotrophic lateral sclerosis. Cytom Part A J Int Soc Anal Cytol 87(8):696–703 Epub 2015/04/15CrossRefGoogle Scholar
  64. 64.
    Glass G, Papin JA, Mandell JW (2009) SIMPLE: a sequential immunoperoxidase labeling and erasing method. J Histochem Cytochem 58(10):899–939Google Scholar
  65. 65.
    Gerdes MJ, Sevinsky CJ, Sood A, Adak S, Bello MO, Bordwell A et al (2013) Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue. P Natl Acad Sci USA 110(29):11982–11987CrossRefGoogle Scholar
  66. 66.
    Hollman-Hewgley D, Lazare M, Bordwell A, Zebadua E, Tripathi P, Ross AS et al (2014) A single slide multiplex assay for the evaluation of classical hodgkin lymphoma. Am J Surg Pathol 38(9):1193–1202CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Goltsev Y, Samusik N, Kennedy-Darling J, Bhate S, Hale M, Vazquez G et al (2018) Deep profiling of mouse splenic architecture with CODEX multiplexed imaging. Cell 174(4):968–981 e15. Epub 2018/08/07Google Scholar
  68. 68.
    Lin JR, Izar B, Wang S, Yapp C, Mei SL, Shah PM et al (2018) Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes. eLife 7Google Scholar
  69. 69.
    Matros A, Mock HP (2013) Mass spectrometry based imaging techniques for spatially resolved analysis of molecules. Front Plant Sci 4:89 Epub 2013/04/30CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Bendall SC, Simonds EF, Qiu P, el Amir AD, Krutzik PO, Finck R et al (2011) Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332(6030):687–696 Epub 2011/05/10CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Dempsey LA (2017) CyTOF analysis of anti-tumor responses. Nat Immunol 18(3):254. Epub 2017/02/16Google Scholar
  72. 72.
    Singh M, Chaudhry P, Gerdtsson E, Maoz A, Cozen W, Hicks J et al (2017) Highly multiplexed imaging mass cytometry allows visualization of tumor and immune cell interactions of the tumor microenvironment in FFPE tissue sections. Blood 130Google Scholar
  73. 73.
    Schulz D, Zanotelli VRT, Fischer JR, Schapiro D, Engler S, Lun XK et al (2018) Simultaneous multiplexed imaging of mRNA and proteins with subcellular resolution in breast cancer tissue samples by mass cytometry. Cell Syst 6(4):531. Epub 2018/04/27Google Scholar
  74. 74.
    Angelo M, Bendall SC, Finck R, Hale MB, Hitzman C, Borowsky AD et al (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20(4):436–442 Epub 2014/03/04CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Li ZY, Theile CS, Chen GY, Bilate AM, Duarte JN, Avalos AM et al (2015) Fluorophore-conjugated holliday junctions for generating super-bright antibodies and antibody fragments. Angew Chem Int Ed 54(40):11706–11710CrossRefGoogle Scholar
  76. 76.
    Krieg R, Halbhuber KJ (2010) Detection of endogenous and immuno-bound peroxidase—the status Quo in histochemistry. Prog Histochem Cytochem 45(2):81–139CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Kotani N, Gu J, Isaji T, Udaka K, Taniguchi N, Honke K (2008) Biochemical visualization of cell surface molecular clustering in living cells. Proc Natl Acad Sci USA 105(21):7405–7409 Epub 2008/05/23CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Ou HD, Phan S, Deerinck TJ, Thor A, Ellisman MH, O’Shea CC (2017) ChromEMT: visualizing 3D chromatin structure and compaction in interphase and mitotic cells. Sci. 357(6349). Epub 2017/07/29Google Scholar
  79. 79.
    Ryan BJ, Carolan N, O’Fagain C (2006) Horseradish and soybean peroxidases: comparable tools for alternative niches? Trends Biotechnol 24(8):355–363CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Han Y, Branon TC, Martell JD, Boassa D, Shechner D, Ellisman MH et al (2019) Directed evolution of split APEX2 peroxidase. ACS Chem Biol 14(4):619–635 Epub 2019/03/09CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Kaewsapsak P, Shechner DM, Mallard W, Rinn JL, Ting AY (2017) Live-cell mapping of organelle-associated RNAs via proximity biotinylation combined with protein-RNA crosslinking. eLife 6. Epub 2017/12/15Google Scholar
  82. 82.
    Martell JD, Deerinck TJ, Lam SS, Ellisman MH, Ting AY (2017) Electron microscopy using the genetically encoded APEX2 tag in cultured mammalian cells. Nat Protoc 12(9):1792–1816 Epub 2017/08/11CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Hung V, Lam SS, Udeshi ND, Svinkina T, Guzman G, Mootha VK et al (2017) Proteomic mapping of cytosol-facing outer mitochondrial and ER membranes in living human cells by proximity biotinylation. eLife 6. Epub 2017/04/26Google Scholar
  84. 84.
    Hung V, Udeshi ND, Lam SS, Loh KH, Cox KJ, Pedram K et al (2016) Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. Nat Protoc 11(3):456–475 Epub 2016/02/13CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Han S, Udeshi ND, Deerinck TJ, Svinkina T, Ellisman MH, Carr SA et al (2017) Proximity biotinylation as a method for mapping proteins associated with mtDNA in living cells. Cell Chem Biol 24(3):404–414 Epub 2017/02/28CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Lam SS, Martell JD, Kamer KJ, Deerinck TJ, Ellisman MH, Mootha VK et al (2015) Directed evolution of APEX2 for electron microscopy and proximity labeling. Nat Methods 12(1):51–54 Epub 2014/11/25CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Krieg R, Halbhuber KJ (2004) Novel oxidative self-anchoring fluorescent substrates for the histochemical localization of endogenous and immunobound peroxidase activity. J Mol Histol 35(5):471–487CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Bobrow MN, Harris TD, Shaughnessy KJ, Litt GJ (1989) Catalyzed reporter deposition, a novel method of signal amplification application to immunoassays. J Immunol Methods 125(1–2):279–285 Epub 1989/12/20CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Bobrow MN, Litt GJ, Shaughnessy KJ, Mayer PC, Conlon J (1992) The use of catalyzed reporter deposition as a means of signal amplification in a variety of formats. J Immunol Methods 150(1–2):145–149CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Buchwalow IB, Böcker W (2010) Immunostaining enhancement in Immunohistochemistry. In: Basica and methods. Springer, New York, pp 47–59Google Scholar
  91. 91.
    Hopman AHN, Ramaekers FCS, Speel EJM (1998) Rapid synthesis of biotin-, digoxigenin-, trinitrophenyl-, and fluorochrome-labeled tyramides and their application for in situ hybridization using CARD amplification. J Histochem Cytochem 46(6):771–777CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Kaplan D (2003) Enzymatic amplification staining for single cell analysis: applied to in situ hybridization. J Immunol Methods 283(1–2):1–7 Epub 2003/12/09CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Kaplan D, Meyerson H, Lewandowska K (2001) High resolution immunophenotypic analysis of chronic lymphocytic leukemic cells by enzymatic amplification staining. Am J Clin Pathol 116(3):429–436 Epub 2001/09/14CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Kaplan D, Smith D (2000) Enzymatic amplification staining for flow cytometric analysis of cell surface molecules. Cytometry 40(1):81–85 Epub 2000/04/08CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Takahashi H, Ruiz P, Ricordi C, Delacruz V, Miki A, Mita A et al (2012) Quantitative in situ analysis of FoxP3+ T regulatory cells on transplant tissue using laser scanning cytometry. Cell Transplant 21(1):113–125 Epub 2011/09/21CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Xing Y, Chaudry Q, Shen C, Kong KY, Zhau HE, WChung L et al (2007) Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry. Nat Protoc 2(5):1152–1165Google Scholar
  97. 97.
    Zrazhevskiy P, True LD, Gao X (2013) Multicolor multicycle molecular profiling with quantum dots for single-cell analysis. Nat Protoc 8(10):1852–1869 Epub 2013/09/07CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Liu B, Jiang B, Zheng ZP, Liu TC (2019) Semiconductor quantum dots in tumor research. J Lumin 209:61–68CrossRefGoogle Scholar
  99. 99.
    Gao X, Cui Y, Levenson RM, Chung LW, Nie S (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22(8):969–976 Epub 2004/07/20CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Levenson RM, Mansfield JR (2006) Multispectral imaging in biology and medicine: slices of life. Cytometry Part A J Int Soc Anal Cytol 69(8):748–758 Epub 2006/09/14CrossRefGoogle Scholar
  101. 101.
    Gonda K, Watanabe M, Tada H, Miyashita M, Takahashi-Aoyama Y, Kamei T et al (2017) Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness. Sci Rep 7(1):7509. Epub 2017/08/10Google Scholar
  102. 102.
    Mansfield JR, Hoyt C, Levenson RM (2008) Visualization of microscopy-based spectral imaging data from multi-label tissue sections. Curr Protoc Mol Biol Chapter 14:Unit 14 9. Epub 2008/10/31Google Scholar
  103. 103.
    Walker RA (2006) Quantification of immunohistochemistry–issues concerning methods, utility and semiquantitative assessment I. Histopathology 49(4):406–410 Epub 2006/09/19CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Taylor CR, Levenson RM (2006) Quantification of immunohistochemistry–issues concerning methods, utility and semiquantitative assessment II. Histopathology 49(4):411–424 Epub 2006/09/19CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Rimm DL (2006) What brown cannot do for you. Nat Biotechnol 24(8):914–916CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Oliveira VC, Carrara RC, Simoes DL, Saggioro FP, Carlotti CG Jr, Covas DT et al (2010) Sudan Black B treatment reduces autofluorescence and improves resolution of in situ hybridization specific fluorescent signals of brain sections. Histol Histopathol 25(8):1017–1024 Epub 2010/06/17PubMedPubMedCentralGoogle Scholar
  107. 107.
    Mansfield JR (2010) Distinguished photons: a review of in vivo spectral fluorescence imaging in small animals. Curr Pharm Biotechnol 11(6):628–638 Epub 2010/05/26CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Dickinson ME, Bearman G, Tille S, Lansford R, Fraser SE (2001) Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy. Biotechniques 31(6):1272, 4–6, 8. Epub 2002/01/05Google Scholar
  109. 109.
    Megjhani M, Correa de Sampaio P, Leigh Carstens J, Kalluri R, Roysam B (2017) Morphologically constrained spectral unmixing by dictionary learning for multiplex fluorescence microscopy. Bioinformatics 33(14):2182–2190. Epub 2017/03/24Google Scholar
  110. 110.
    Bordeaux J, Welsh A, Agarwal S, Killiam E, Baquero M, Hanna J et al (2010) Antibody validation. Biotechniques 48(3):197–209 Epub 2010/04/03CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Moran L (2007) Basic concepts: the central dogma of molecular biology. https://sandwalk.blogspot.com/2007/01/central-dogma-of-molecular-biology.html
  112. 112.
    Li JJ, Bickel PJ, Biggin MD (2014) System wide analyses have underestimated protein abundances and the importance of transcription in mammals. PeerJ 2Google Scholar
  113. 113.
    Li JJ, Biggin MD (2015) Statistics requantitates the central dogma. Science 347(6226):1066–1067CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Battle A, Khan Z, Wang SH, Mitrano A, Ford MJ, Pritchard JK et al (2015) Genomic variation. Impact of regulatory variation from RNA to protein. Science 347(6222):664–667. Epub 2015/02/07Google Scholar
  115. 115.
    Jovanovic M, Rooney MS, Mertins P, Przybylski D, Chevrier N, Satija R et al (2015) Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens. Sci 347(6226):1259038. Epub 2015/03/07Google Scholar
  116. 116.
    Hausser J, Mayo A, Keren L, Alon U (2019) Central dogma rates and the trade-off between precision and economy in gene expression. Nat Commun 10Google Scholar
  117. 117.
    Symmons O, Chang M, Mellis IA, Kalish JM, Park J, Susztak K et al (2019) Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting. Plos Genet 15(1)Google Scholar
  118. 118.
    Caveney PM, Norred SE, Chin CW, Boreyko JB, Razooky BS, Retterer ST et al (2017) Resource sharing controls gene expression bursting. ACS Synth Biol 6(2):334–343 Epub 2016/10/04CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Li JJ, Bickel PJ, Biggin MD (2014) System wide analyses have underestimated protein abundances and the importance of transcription in mammals. PeerJ 2:e270 Epub 2014/04/02CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Eraslan B, Wang D, Gusic M, Prokisch H, Hallstrom BM, Uhlen M et al (2019) Quantification and discovery of sequence determinants of protein-per-mRNA amount in 29 human tissues. Molecular systems biology. 15(2):e8513. Epub 2019/02/20Google Scholar
  121. 121.
    Wang F, Flanagan J, Su N, Wang LC, Bui S, Nielson A et al (2012) RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J Mol Diagn: JMD 14(1):22–29 Epub 2011/12/15CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Gall JG, Pardue ML (1969) Formation and detection of Rna-DNA hybrid molecules in cytological preparations. P Natl Acad Sci USA 63(2):378Google Scholar
  123. 123.
    Pardue ML, Gall JG (1969) Molecular hybridization of radioactive DNA to the DNA of cytological preparations. Proc Natl Acad Sci USA 64(2):600–604 Epub 1969/10/01CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Pardue ML, Gall JG (1970) Chromosomal localization of mouse satellite DNA. Science 168(3937):1356–1358 Epub 1970/06/12CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Femino AM, Fay FS, Fogarty K, Singer RH (1998) Visualization of single RNA transcripts in situ. Science 280(5363):585–590 Epub 1998/05/09CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Vargas DY, Raj A, Marras SAE, Kramer FR, Tyagi S (2005) Mechanism of mRNA transport in the nucleus. P Natl Acad Sci USA 102(47):17008–17013CrossRefGoogle Scholar
  127. 127.
    Raj A, Peskin CS, Tranchina D, Vargas DY, Tyagi S (2006) Stochastic mRNA synthesis in mammalian cells. PLoS Biol 4(10):1707–1719CrossRefGoogle Scholar
  128. 128.
    Raj A, van den Bogaard P, Rifkin SA, van Oudenaarden A, Tyagi S (2008) Imaging individual mRNA molecules using multiple singly labeled probes. Nat Methods 5(10):877–879CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Raj A, Tyagi S (2010) Detection of individual endogenous Rna transcripts in situ using multiple singly labeled probes. In: Methods in enzymology, vol 472: Single Molecule Tools, Pt A: Fluorescence Based Approaches 472:365–386Google Scholar
  130. 130.
    Batish M, Raj A, Tyagi S (2011) Single molecule imaging of RNA in situ. Methods Mol Biol 714:3–13 Epub 2011/03/25CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Shaffer SM, Wu MT, Levesque MJ, Raj A (2013) Turbo FISH: a method for rapid single molecule RNA FISH. PLoS One. 8(9):e75120. Epub 2013/09/26Google Scholar
  132. 132.
    Levesque MJ, Raj A (2013) Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation. Nat Methods 10(3):246–248CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Levesque MJ, Ginart P, Wei YC, Raj A (2013) Visualizing SNVs to quantify allele-specific expression in single cells. Nat Methods 10(9):865Google Scholar
  134. 134.
    Player AN, Shen LP, Kenny D, Antao VP, Kolberg JA (2001) Single-copy gene detection using branched DNA (bDNA) in situ hybridization. J Histochem Cytochem 49(5):603–611CrossRefGoogle Scholar
  135. 135.
    Choi HMT, Schwarzkopf M, Fornace ME, Acharya A, Artavanis G, Stegmaier J et al (2018) Third-generation in situ hybridization chain reaction: multiplexed, quantitative, sensitive, versatile, robust. Development 145(12). Epub 2018/06/28Google Scholar
  136. 136.
    Schweller RM, Zimak J, Duose DY, Qutub AA, Hittelman WN, Diehl MR (2012) Multiplexed in situ immunofluorescence using dynamic DNA complexes. Angew Chem Int Ed Engl 51(37):9292–9296 Epub 2012/08/16CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Zimak J, Schweller RM, Duose DY, Hittelman WN, Diehl MR (2012) Programming in situ immunofluorescence intensities through interchangeable reactions of dynamic DNA complexes. Chembiochem: A Eur J Chem Biol 13(18):2722–2728 Epub 2012/11/21CrossRefGoogle Scholar
  138. 138.
    Chen KH, Boettiger AN, Moffitt JR, Wang S, Zhuang X (2015) RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348(6233):aaa6090. Epub 2015/04/11Google Scholar
  139. 139.
    Moor AE, Itzkovitz S (2017) Spatial transcriptomics: paving the way for tissue-level systems biology. Curr Opin Biotechnol 46:126–133 Epub 2017/03/28CrossRefGoogle Scholar
  140. 140.
    Stahl PL, Salmen F, Vickovic S, Lundmark A, Navarro JF, Magnusson J et al (2016) Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353(6294):78–82 Epub 2016/07/02CrossRefGoogle Scholar
  141. 141.
    Strell C, Hilscher MM, Laxman N, Svedlund J, Wu C, Yokota C et al (2019) Placing RNA in context and space—methods for spatially resolved transcriptomics. FEBS J 286(8):1468–1481 Epub 2018/03/16CrossRefGoogle Scholar
  142. 142.
    Burgess DJ (2019) Spatial transcriptomics coming of age. Nat Rev Genet 20(6):317. Epub 2019/04/14Google Scholar
  143. 143.
    Shalek AK, Satija R, Shuga J, Trombetta JJ, Gennert D, Lu DN et al (2014) Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. Nature 510(7505):363Google Scholar
  144. 144.
    Moor AE, Golan M, Massasa EE, Lemze D, Weizman T, Shenhav R et al (2017) Global mRNA polarization regulates translation efficiency in the intestinal epithelium. Science 357(6357):1299–1303 Epub 2017/08/12CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Moor AE, Harnik Y, Ben-Moshe S, Massasa EE, Rozenberg M, Eilam R et al (2018) Spatial Reconstruction of single enterocytes uncovers broad zonation along the intestinal villus axis. Cell 175(4):1156–1167 e15. Epub 2018/10/03Google Scholar
  146. 146.
    McKinley ET, Sui Y, Al-Kofahi Y, Millis BA, Tyska MJ, Roland JT et al (2017) Optimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneity. JCI Insight. 2(11). Epub 2017/06/02Google Scholar
  147. 147.
    Herring CA, Banerjee A, McKinley ET, Simmons AJ, Ping J, Roland JT et al (2018) Unsupervised trajectory analysis of single-cell RNA-Seq and imaging data reveals alternative tuft cell origins in the gut. Cell Syst 6(1):37Google Scholar
  148. 148.
    Li CX, Ma HT, Wang Y, Cao Z, Graves-Deal R, Powel AE et al (2014) Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. J Clin Inv 124(5):2172–2187CrossRefGoogle Scholar
  149. 149.
    Moffitt JR, Bambah-Mukku D, Eichhorn SW, Vaughn E, Shekhar K, Perez JD et al (2018) Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region. Science. 362(6416). Epub 2018/11/06Google Scholar
  150. 150.
    Eng CL, Lawson M, Zhu Q, Dries R, Koulena N, Takei Y et al (2019) Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature 568(7751):235–239 Epub 2019/03/27CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E, Vanderburg CR et al (2019) Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science 363(6434):1463Google Scholar
  152. 152.
    Lein E, Borm LE, Linnarsson S (2017) The promise of spatial transcriptomics for neuroscience in the era of molecular cell typing. Science 358(6359):64–69 Epub 2017/10/07CrossRefGoogle Scholar
  153. 153.
    Decalf J, Albert ML, Ziai J (2019) New tools for pathology: a user’s review of a highly multiplexed method for in situ analysis of protein and RNA expression in tissue. J Pathol 247(5):650–661 Epub 2018/12/21CrossRefGoogle Scholar
  154. 154.
    NanoString Technologies I. GeoMxTM digital spatial profilerGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • George McNamara
    • 1
  • Justin Lucas
    • 2
  • John F. Beeler
    • 2
  • Ajay Basavanhally
    • 2
  • George Lee
    • 2
  • Cyrus V. Hedvat
    • 2
  • Vipul A. Baxi
    • 2
  • Darren Locke
    • 2
  • Alexander Borowsky
    • 3
  • Richard Levenson
    • 3
    Email author
  1. 1.Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Bristol-Myers SquibbPrincetonUSA
  3. 3.UC Davis HealthSacramentoUSA

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