Skip to main content

New Technologies to Image Tumors

  • Chapter
  • First Online:
Tumor Microenvironment

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  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 2008/04/29

    Article  CAS  PubMed  Google Scholar 

  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 2013/10/15

    Article  CAS  PubMed  Google Scholar 

  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 2011/11/11

    Google Scholar 

  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 2013/11/13

    Article  CAS  PubMed  Google Scholar 

  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 2016/11/12

    Article  CAS  PubMed  Google Scholar 

  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 2018/09/08

    Google Scholar 

  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 2016/12/04

    Article  PubMed  Google Scholar 

  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 2015/06/27

    CAS  Google Scholar 

  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 2014/01/07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2018/07/04

    CAS  PubMed  PubMed Central  Google Scholar 

  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):1535–1542

    Article  CAS  Google Scholar 

  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 2005/11/19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2012/04/06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2015/02/20

    PubMed  PubMed Central  Google Scholar 

  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 2007/01/19

    Article  CAS  PubMed  Google Scholar 

  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 2013/05/15

    Google Scholar 

  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 2017/04/28

    Google Scholar 

  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 6

    Google Scholar 

  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. 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 2019/02/23

    Google Scholar 

  21. Parra ER (2018) Novel platforms of multiplexed immunofluorescence for study of paraffin tumor tissues. J Cancer Treat Diagn 2(1):43–53

    Google Scholar 

  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 2012/11/02

    Article  PubMed  PubMed Central  Google Scholar 

  23. Whiteside TL (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27(45):5904–5912 Epub 2008/10/07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):1771–1791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bhargava R (2007) Towards a practical Fourier transform infrared chemical imaging protocol for cancer histopathology. Anal Bioanal Chem 389(4):1155–1169

    Article  CAS  PubMed  Google Scholar 

  26. Bhargava R, Levin IW (2001) Fourier transform infrared imaging: Theory and practice. Anal Chem 73(21):5157–5167

    Article  CAS  PubMed  Google Scholar 

  27. Bhargava R, Levin IW (2005) Spectrochemical analysis using infrared multichannel detectors preface. Sheff Analy Chem 2005:Xv–Xvi

    Google Scholar 

  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 2015/06/04

    Google Scholar 

  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–E5660

    Article  CAS  Google Scholar 

  30. Goormaghtigh E (2016) Infrared imaging in histopathology: is a unified approach possible? Biomed Spectrosc Imag 5(4):325–346

    Article  Google Scholar 

  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 2018/10/13

    Article  Google Scholar 

  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 2011/04/02

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cicerone MT, Camp CH (2017) Histological coherent Raman imaging: a prognostic review. The Analyst 143(1):33–59 Epub 2017/11/04

    Article  PubMed  Google Scholar 

  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 2012/10/31

    Article  PubMed  Google Scholar 

  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 2018/04/18

    Google Scholar 

  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 2012/03/10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shribak M (2015) Polychromatic polarization microscope: bringing colors to a colorless world. Sci Rep 5:17340 Epub 2015/11/28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2017/10/06

    Google Scholar 

  39. Veitch NC (2004) Horseradish peroxidase: a modern view of a classic enzyme. Phytochemistry 65(3):249–259

    Article  CAS  PubMed  Google Scholar 

  40. Sato S, Nakamura K, Nakamura H (2015) Tyrosine-specific chemical modification with in situ hemin-activated luminol derivatives. ACS Chem Biol 10(11):2633–2640

    Article  CAS  PubMed  Google Scholar 

  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 2016/12/23

    Article  CAS  Google Scholar 

  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 1987/03/01

    Article  CAS  PubMed  Google Scholar 

  43. Schwenecke H, Benzidine MD, Benzidine Derivatives (2005) Ullmann’s encyclopedia of industrial chemistry, 7th edn. Wiley, Inc., New York, p 18

    Google Scholar 

  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 1966/12/01

    Article  CAS  PubMed  Google Scholar 

  45. Mason DY, Sammons R (1978) Alkaline-phosphatase and peroxidase for double immunoenzymatic labeling of cellular constituents. J Clin Pathol 31(5):454–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):31–40

    Article  Google Scholar 

  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):104–113

    Article  CAS  PubMed  Google Scholar 

  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 2017/05/04

    Article  CAS  PubMed  Google Scholar 

  49. McNamara G, Difilippantonio M, Ried T, Bieber FR (2017) Microscopy and image analysis. Curr Protoc Hum Genet 94:4 1–4 89. Epub 2017/07/12

    Google Scholar 

  50. McNamara G (2019) Fluorescence spectra graphs. https://www.linkedin.com/pulse/fluorescence-spectra-graphs-george-mcnamara

  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. 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. 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 1995/04/01

    Article  CAS  PubMed  Google Scholar 

  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):375–82

    Google Scholar 

  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 2017/08/31

    Article  CAS  PubMed  Google Scholar 

  56. Rodgers JR, Rich RR (2013) Antigens and antigen presentation. In: Clinical immunology, 4th edn, pp 77–89

    Google Scholar 

  57. Lemus R, Karol MH (2008) Conjugation of haptens. Methods Mol Med 138:167–182 Epub 2008/07/10

    Article  CAS  PubMed  Google Scholar 

  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 77

    Google Scholar 

  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):1371–1377

    Article  CAS  PubMed  Google Scholar 

  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 2006/10/03

    Article  CAS  PubMed  Google Scholar 

  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):2285–2294

    Article  CAS  PubMed  Google Scholar 

  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 2012/01/03

    Article  CAS  Google Scholar 

  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 2015/04/15

    Article  CAS  Google Scholar 

  64. Glass G, Papin JA, Mandell JW (2009) SIMPLE: a sequential immunoperoxidase labeling and erasing method. J Histochem Cytochem 58(10):899–939

    Google Scholar 

  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):11982–11987

    Article  Google Scholar 

  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):1193–1202

    Article  PubMed  Google Scholar 

  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 2018/08/07

    Google Scholar 

  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 7

    Google Scholar 

  69. Matros A, Mock HP (2013) Mass spectrometry based imaging techniques for spatially resolved analysis of molecules. Front Plant Sci 4:89 Epub 2013/04/30

    Article  PubMed  PubMed Central  Google Scholar 

  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 2011/05/10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dempsey LA (2017) CyTOF analysis of anti-tumor responses. Nat Immunol 18(3):254. Epub 2017/02/16

    Google Scholar 

  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 130

    Google Scholar 

  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 2018/04/27

    Google Scholar 

  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 2014/03/04

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):11706–11710

    Article  CAS  Google Scholar 

  76. Krieg R, Halbhuber KJ (2010) Detection of endogenous and immuno-bound peroxidase—the status Quo in histochemistry. Prog Histochem Cytochem 45(2):81–139

    Article  PubMed  Google Scholar 

  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 2008/05/23

    Article  PubMed  PubMed Central  Google Scholar 

  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 2017/07/29

    Google Scholar 

  79. Ryan BJ, Carolan N, O’Fagain C (2006) Horseradish and soybean peroxidases: comparable tools for alternative niches? Trends Biotechnol 24(8):355–363

    Article  CAS  PubMed  Google Scholar 

  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 2019/03/09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2017/12/15

    Google Scholar 

  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 2017/08/11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2017/04/26

    Google Scholar 

  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 2016/02/13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2017/02/28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2014/11/25

    Article  CAS  PubMed  Google Scholar 

  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):471–487

    Article  CAS  PubMed  Google Scholar 

  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 1989/12/20

    Article  CAS  PubMed  Google Scholar 

  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):145–149

    Article  CAS  PubMed  Google Scholar 

  90. Buchwalow IB, Böcker W (2010) Immunostaining enhancement in Immunohistochemistry. In: Basica and methods. Springer, New York, pp 47–59

    Google Scholar 

  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):771–777

    Article  CAS  PubMed  Google Scholar 

  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 2003/12/09

    Article  CAS  PubMed  Google Scholar 

  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 2001/09/14

    Article  CAS  PubMed  Google Scholar 

  94. Kaplan D, Smith D (2000) Enzymatic amplification staining for flow cytometric analysis of cell surface molecules. Cytometry 40(1):81–85 Epub 2000/04/08

    Article  CAS  PubMed  Google Scholar 

  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 2011/09/21

    Article  PubMed  Google Scholar 

  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):1152–1165

    Google Scholar 

  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 2013/09/07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Liu B, Jiang B, Zheng ZP, Liu TC (2019) Semiconductor quantum dots in tumor research. J Lumin 209:61–68

    Article  CAS  Google Scholar 

  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 2004/07/20

    Article  CAS  PubMed  Google Scholar 

  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 2006/09/14

    Article  Google Scholar 

  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 2017/08/10

    Google Scholar 

  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 2008/10/31

    Google Scholar 

  103. Walker RA (2006) Quantification of immunohistochemistry–issues concerning methods, utility and semiquantitative assessment I. Histopathology 49(4):406–410 Epub 2006/09/19

    Article  CAS  PubMed  Google Scholar 

  104. Taylor CR, Levenson RM (2006) Quantification of immunohistochemistry–issues concerning methods, utility and semiquantitative assessment II. Histopathology 49(4):411–424 Epub 2006/09/19

    Article  CAS  PubMed  Google Scholar 

  105. Rimm DL (2006) What brown cannot do for you. Nat Biotechnol 24(8):914–916

    Article  CAS  PubMed  Google Scholar 

  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 2010/06/17

    CAS  PubMed  Google Scholar 

  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 2010/05/26

    Article  CAS  PubMed  Google Scholar 

  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 2002/01/05

    Google Scholar 

  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 2017/03/24

    Google Scholar 

  110. Bordeaux J, Welsh A, Agarwal S, Killiam E, Baquero M, Hanna J et al (2010) Antibody validation. Biotechniques 48(3):197–209 Epub 2010/04/03

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. Li JJ, Bickel PJ, Biggin MD (2014) System wide analyses have underestimated protein abundances and the importance of transcription in mammals. PeerJ 2

    Google Scholar 

  113. Li JJ, Biggin MD (2015) Statistics requantitates the central dogma. Science 347(6226):1066–1067

    Article  CAS  PubMed  Google Scholar 

  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 2015/02/07

    Google Scholar 

  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 2015/03/07

    Google Scholar 

  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 10

    Google Scholar 

  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. 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 2016/10/04

    Article  CAS  PubMed  Google Scholar 

  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 2014/04/02

    Article  PubMed  PubMed Central  Google Scholar 

  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 2019/02/20

    Google Scholar 

  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 2011/12/15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Gall JG, Pardue ML (1969) Formation and detection of Rna-DNA hybrid molecules in cytological preparations. P Natl Acad Sci USA 63(2):378

    Google Scholar 

  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 1969/10/01

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Pardue ML, Gall JG (1970) Chromosomal localization of mouse satellite DNA. Science 168(3937):1356–1358 Epub 1970/06/12

    Article  CAS  PubMed  Google Scholar 

  125. Femino AM, Fay FS, Fogarty K, Singer RH (1998) Visualization of single RNA transcripts in situ. Science 280(5363):585–590 Epub 1998/05/09

    Article  CAS  PubMed  Google Scholar 

  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):17008–17013

    Article  CAS  Google Scholar 

  127. Raj A, Peskin CS, Tranchina D, Vargas DY, Tyagi S (2006) Stochastic mRNA synthesis in mammalian cells. PLoS Biol 4(10):1707–1719

    Article  CAS  Google Scholar 

  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):877–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 472:365–386

    Google Scholar 

  130. Batish M, Raj A, Tyagi S (2011) Single molecule imaging of RNA in situ. Methods Mol Biol 714:3–13 Epub 2011/03/25

    Article  CAS  PubMed  Google Scholar 

  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 2013/09/26

    Google Scholar 

  132. Levesque MJ, Raj A (2013) Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation. Nat Methods 10(3):246–248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Levesque MJ, Ginart P, Wei YC, Raj A (2013) Visualizing SNVs to quantify allele-specific expression in single cells. Nat Methods 10(9):865

    Google Scholar 

  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):603–611

    Article  CAS  PubMed  Google Scholar 

  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 2018/06/28

    Google Scholar 

  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 2012/08/16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2012/11/21

    Article  CAS  Google Scholar 

  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 2015/04/11

    Google Scholar 

  139. Moor AE, Itzkovitz S (2017) Spatial transcriptomics: paving the way for tissue-level systems biology. Curr Opin Biotechnol 46:126–133 Epub 2017/03/28

    Article  CAS  PubMed  Google Scholar 

  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 2016/07/02

    Article  CAS  PubMed  Google Scholar 

  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 2018/03/16

    Article  CAS  PubMed  Google Scholar 

  142. Burgess DJ (2019) Spatial transcriptomics coming of age. Nat Rev Genet 20(6):317. Epub 2019/04/14

    Google Scholar 

  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):363

    Google Scholar 

  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 2017/08/12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 2018/10/03

    Google Scholar 

  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 2017/06/02

    Google Scholar 

  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):37

    Google Scholar 

  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):2172–2187

    Article  CAS  Google Scholar 

  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 2018/11/06

    Google Scholar 

  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 2019/03/27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):1463

    Google Scholar 

  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 2017/10/07

    Article  CAS  PubMed  Google Scholar 

  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 2018/12/21

    Article  PubMed  Google Scholar 

  154. NanoString Technologies I. GeoMxTM digital spatial profiler

    Google Scholar 

Internet Resources

  1. https://www.cellsignal.com/contents/resources-applications/fluorescent-multiplex-immunohistochemistry/fluoresence-mihc

  2. https://www.ultivue.com/technology/

  3. https://cellidx.com/technology/technology

  4. https://neogenomics.com/pharma-services/lab-services/multiomyx/technology/hyperplexed-immunofluorescence-assay

  5. https://www.olink.com/data-you-can-trust/technology/

  6. https://www.ionpath.com/mibi-technology/

  7. https://www.olympus-lifescience.com/en/microscope-resource/primer/techniques/fluorescence/filters/

  8. https://www.akoyabio.com/

  9. McNamara (2019). https://www.linkedin.com/pulse/fluorescence-spectra-graphs-george-mcnamara

  10. McNamara (2018). https://www.linkedin.com/pulse/18plex-flow-cytometry-from-brilliants-when-catch-up-george-mcnamara/

  11. McNamara Fluorescence Data Tables. http://www.geomcnamara.com/data

  12. McNamara (2017). https://www.linkedin.com/pulse/resolution-blues-meets-21plex-salute-fluorescence-basic-mcnamara/

  13. McNamara (2012) PubSpectra (data download site). https://works.bepress.com/gmcnamara/9

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard Levenson .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

McNamara, G. et al. (2020). New Technologies to Image Tumors. In: Lee, P., Marincola, F. (eds) Tumor Microenvironment. Cancer Treatment and Research, vol 180. Springer, Cham. https://doi.org/10.1007/978-3-030-38862-1_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-38862-1_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-38861-4

  • Online ISBN: 978-3-030-38862-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics