Skip to main content

Abstract

Image-guided therapy (IGT) aims to use imaging to improve the localization and targeting of diseased tissue and to monitor and control treatments. During the past decade, image-guided surgeries and image-guided minimally invasive interventions have emerged as advances that can change traditional more invasive approaches. Advanced imaging technologies like magnetic resonance imaging (MRI), computed tomography (CT), and even positron emission tomography (PET) entered into operating rooms and interventional suites to complement already available routine imaging devices like ultrasound (US) and x-ray. At the same time, navigational tools, computer-assisted surgery devices, and image-guided robots also became part of the revolution in interventional radiology suites and the operating room. Perhaps more than any other clinical tools, these technologies required and continue to require collaboration among a team of physicians, engineers, and computer scientists; in fact, the “team approach” is characteristic to the development and clinical use of new so-called therapy delivery systems in which the three components of image-guided therapies (imaging, guidance, and therapy devices) are closely integrated.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Jolesz FA, Shtern F. The operating room of the future. Report of the national cancer institute workshop. Imaging-guided stereotactic tumor diagnosis and treatment. Invest Radiol. 1992;27(4):326–8.

    Article  CAS  PubMed  Google Scholar 

  2. Jolesz FA. Image-guided procedures and the operating room of the future.1996 RSNA Eugene P. Pendergrass new horizons lecture. Radiology. 1997;204(3):601–12.

    CAS  PubMed  Google Scholar 

  3. Warfield SK, Haker SJ, Talos IF, Kemper CA, Weisenfeld N, Mewes AU, Goldberg-Zimring D, Zou KH, Westin CF, Wells WM, Tempany CM, Golby A, Black PM, Jolesz FA, Kikinis R. Capturing intraoperative deformations: research experience at Brigham and Women’s hospital. Med Image Anal. 2005;9(2):145–62.

    Article  PubMed  Google Scholar 

  4. Haker S, Mulkern RV, Roebuck JR, Barnes AS, Dimaio SP, Hata N, Tempany CM. Magnetic resonance-guided prostate interventions. Top Magn Reson Imaging. 2005;16(5):355–68.

    Article  PubMed  Google Scholar 

  5. Chan I, Wells 3rd W, Mulkern RV, Haker S, Zhang J, Zou KH, Maier SE, Tempany CM. Detection of prostate cancer by integration of line-scan diffusion, T2-mapping and T2-weighted magnetic resonance imaging; a multichannel statistical classifier. Med Phys. 2003;30(9):2390–8.

    Article  PubMed  Google Scholar 

  6. Artan Y, Yetik I. Prostate cancer localization using multiparametric MRI based on semi-supervised techniques with automated seed initialization. IEEE Trans Inf Technol Biomed. 2012. http://www.ncbi.nlm.nih.gov/pubmed/22665512.

  7. Haker S, Angenent S, Tannenbaum A, Kikinis R. Nondistorting flattening maps and the 3-D visualization of colon CT images. IEEE Trans Med Imaging. 2000;19(7):665–70. Erratum in: IEEE Trans Med Imaging 2000;19(12):1267.

    Article  CAS  PubMed  Google Scholar 

  8. Angenent S, Haker S, Tannenbaum A, Kikinis R. On the Laplace-Beltrami operator and brain surface flattening. IEEE Trans Med Imaging. 1999;18(8):700–11.

    Article  CAS  PubMed  Google Scholar 

  9. Wells WM, Grimson WEL, Kikinis R, Jolesz FA. Adaptive segmentation of MRI data. IEEE Trans Med Imaging. 1996;15:429–42.

    Article  CAS  PubMed  Google Scholar 

  10. Pohl KM, Fisher J, Levitt JJ, Shenton ME, Kikinis R, Grimson WE, Wells WM. A unifying approach to registration, segmentation, and intensity correction. Med Image Comput Comput Assist Interv. 2005;8(Pt 1):310–8.

    PubMed Central  PubMed  Google Scholar 

  11. Wells 3rd WM, Viola P, Atsumi H, Nakajima S, Kikinis R. Multi-modal volume registration by maximization of mutual information. Med Image Anal. 1996;1(1):35–51.

    Article  PubMed  Google Scholar 

  12. Pohl KM, Fisher J, Grimson WE, Kikinis R, Wells WM. A Bayesian model for joint segmentation and registration. Neuroimage. 2006;31(1):228–39.

    Article  PubMed  Google Scholar 

  13. Pohl KM, Fisher J, Bouix S, Shenton M, McCarley RW, Grimson WE, Kikinis R, Wells WM. Using the logarithm of odds to define a vector space on probabilistic atlases. Med Image Anal. 2007;11(5):465–77.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Warfield S, et al. Intraoperative segmentation and nonrigid registration for image guided therapy. Med Image Comput Comput Assist Interv. 2000;176–185:2000.

    Google Scholar 

  15. Pohl KM, Bouix S, Shenton ME, Grimson WE, Kikinis R. Automatic segmentation using non-rigid registration. Med Image Comput Comput Assist Interv. 2007;26(9):1201–12.

    PubMed Central  PubMed  Google Scholar 

  16. Warfield SK, Kaus M, Jolesz FA, Kikinis R. Adaptive, template moderated, spatially varying statistical classification. Med Image Anal. 2000;4(1):43–55.

    Article  CAS  PubMed  Google Scholar 

  17. Held K, Rota Kops E, Krause BJ, Wells 3rd WM, Kikinis R, Müller-Gärtner HW. Markov random field segmentation of brain MR images. IEEE Trans Med Imaging. 1997;16(6):878–86.

    Article  CAS  PubMed  Google Scholar 

  18. Ross JC, San Jose Estepar R, Diaz A, Westin C-F, Kikinis R, Silverman EK, Washko GR. Lung extraction, lobe segmentation and hierarchical region assessment for quantitative analysis on high resolution computed tomography images. Med Image Comput Comput Assist Interv. 2009;12(Pt 2):690–8. PMID: 20426172.

    PubMed Central  PubMed  Google Scholar 

  19. Bharatha A, Hirose M, Hata N, Warfield SK, Ferrant M, Zou KH, Suarez-Santana E, Ruiz-Alzola J, D’Amico A, Cormack RA, Kikinis R, Jolesz FA, Tempany CM. Evaluation of three-dimensional finite element-based deformable registration of pre- and intraoperative prostate imaging. Med Phys. 2001;28(12):2551–60.

    Article  CAS  PubMed  Google Scholar 

  20. Wittek A, Miller K, Kikinis R, Warfield SK. Patient-specific model of brain deformation: application to medical image registration. J Biomech. 2007;40(4):919–29.

    Article  PubMed  Google Scholar 

  21. Clatz O, Delingette H, Talos IF, Golby AJ, Kikinis R, Jolesz FA, Ayache N, Warfield SK. Hybrid formulation of the model-based non-rigid registration problem to improve accuracy and robustness. Med Image Comput Comput Assist Interv. 2005;8(Pt 2):295–302.

    PubMed  Google Scholar 

  22. Oguro S, Tokuda J, Elhawary H, Haker S, Kikinis R, Tempany CM, Hata N. MRI signal intensity based B-spline nonrigid registration for pre- and intraoperative imaging during prostate brachytherapy. J Magn Reson Imaging. 2009;30(5):1052–8.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Ferrant M, Nabavi A, Macq B, Jolesz FA, Kikinis R, Warfield SK. Registration of 3-D intraoperative MR images of the brain using a finite-element biomechanical model. IEEE Trans Med Imaging. 2001;20(12):1384–97.

    Article  CAS  PubMed  Google Scholar 

  24. Archip N, Tatli S, Morrison P, Jolesz F, Warfield SK, Silverman S. Non-rigid registration of pre-procedural MR images with intra-procedural unenhanced CT images for improved targeting of tumors during liver radiofrequency ablations. Med Image Comput Comput Assist Interv. 2007;10(Pt 2):969–77.

    CAS  PubMed  Google Scholar 

  25. Archip N, Clatz O, Whalen S, Kacher D, Fedorov A, Kot A, Chrisochoides N, Jolesz F, Golby A, Black PM, Warfield SK. Non-rigid alignment of pre-operative MRI, fMRI, and DT-MRI with intra-operative MRI for enhanced visualization and navigation in image-guided neurosurgery. Neuroimage. 2007;35(2):609–24.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Fedorov A, Tuncali K, Fennessy FM, Tokuda J, Hata N, Wells WM, Kikinis R, Tempany CM. Image registration for targeted MRI-guided transperineal prostate biopsy. J Magn Reson Imaging. 2012;36(4):987–92.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Young GS, Silverman SG, Kettenbach J, Hata N, Golland P, Jolesz FA, Loughlin KR, Kikinis R. Three-dimensional computed tomography for planning urologic surgery. Urol Clin North Am. 1998;25(1):103–11.

    Article  CAS  PubMed  Google Scholar 

  28. Lorensen WE, Cline HE. Marching cubes: a high resolution 3D surface construction algorithm. Comput Graph. 1987;21(4):163–9.

    Article  Google Scholar 

  29. Wittek A, Kikinis R, Warfield SK, Miller K. Brain shift computation using a fully nonlinear biomechanical model. Med Image Comput Comput Assist Interv. 2005;8(Pt 2):583–90.

    PubMed  Google Scholar 

  30. Jolesz FA, Lorensen WE, Shinmoto H, Atsumi H, Nakajima S, Kavanaugh P, Saiviroonporn P, Seltzer SE, Silverman SG, Phillips M, Kikinis R. Interactive virtual endoscopy. AJR Am J Roentgenol. 1997;169(5):1229–35.

    Article  CAS  PubMed  Google Scholar 

  31. Gering D, Nabavi A, Kikinis R, Hata N, O’Donnell L, Eric W, Grimson L, Jolesz F, Black P, Wells III W. An integrated visualization system for surgical planning and guidance using image fusion and an open MR. J Magn Reson Imaging. 2001;13:967–75.

    Article  CAS  PubMed  Google Scholar 

  32. Gering DT, Nabavi A, Kikinis R, Grimson WEL, Hata N, Everett P, Jolesz FA, Wells III WM. An integrated visualization system for surgical planning and guidance using image fusion and interventional imaging. Med Image Comput Comput Assist Interv. 1999;2:809–19.

    Google Scholar 

  33. Hata N, Piper S, Jolesz FA, Tempany CM, Black PM, Morikawa S, Iseki H, Hashizume M, Kikinis R. Application of open source image guided therapy software in MR-guided therapies. Med Image Comput Comput Assist Interv. 2007;10(Pt 1):491–8.

    PubMed  Google Scholar 

  34. Nakajima S, Kikinis R, Atsumi H, Leventon M, Hata N, Metcalf D, Moriarty T, Alexander E, Black P, Jolesz F. Image-guided neurosurgery at Brigham and Women’s Hospital. In: Tamaki N and Ehara K (eds) Computer-Assisted Neurosurgery. Tokyo: Springer-Verlag; 1997;144–62.

    Chapter  Google Scholar 

  35. Gleason PL, Kikinis R, Altobelli D, Wells W, Alexander 3rd E, Black PM, Jolesz F. Video registration virtual reality for nonlinkage stereotactic surgery. Stereotact Funct Neurosurg. 1994;63(1–4):139–43.

    Article  CAS  PubMed  Google Scholar 

  36. Silverman SG, Collick BD, Figueira MR, Khorasani R, Adams DF, Newman RW, Topulos GP, Jolesz FA. Interactive MR-guided biopsy in an open-configuration MR imaging system. Radiology. 1995;197(1):175–81.

    CAS  PubMed  Google Scholar 

  37. Nabavi A, Gering DT, Kacher DF, Talos IF, Wells WM, Kikinis R, Black PM, Jolesz FA. Surgical navigation in the open MRI. Acta Neurochir Suppl. 2003;85:121–5.

    Article  CAS  PubMed  Google Scholar 

  38. Schenck JF, Jolesz FA, Roemer PB, Cline HE, Lorensen WE, Kikinis R, Silverman SG, Hardy CJ, Barber WD, Laskaris ET. Superconducting open-configuration MR imaging system for image-guided therapy. Radiology. 1995;195(3):805–14.

    CAS  PubMed  Google Scholar 

  39. Nabavi A, Black PM, Gering DT, Westin CF, Mehta V, Pergolizzi Jr RS, Ferrant M, Warfield SK, Hata N, Schwartz RB, Wells 3rd WM, Kikinis R, Jolesz FA. Serial intraoperative magnetic resonance imaging of brain shift. Neurosurgery. 2001;48(4):787–97; discussion 797–8.

    CAS  PubMed  Google Scholar 

  40. Clatz O, Bondiau P-Y, Delingette H, Malandain G, Sermesant M, Warfield SK, Ayache N. In silico tumor growth: application to glioblastomas. Int Conf Med Image Comput Comput Assist Interv. 2004;7(Pt 2):337–45.

    Google Scholar 

  41. Jolesz FA, Nabavi A, Kikinis R. Integration of interventional MRI with computer-assisted surgery. J Magn Reson Imaging. 2001;13(1):69–77.

    Article  CAS  PubMed  Google Scholar 

  42. Jolesz FA, Talos IF, Schwartz RB, Mamata H, Kacher DF, Hynynen K, McDannold N, Saivironporn P, Zhao L. Intraoperative magnetic resonance imaging and magnetic resonance imaging-guided therapy for brain tumors. Neuroimaging Clin N Am. 2002;12(4):665–83.

    Article  PubMed  Google Scholar 

  43. Colen RR, Kekhia H, Jolesz FA. Multimodality intraoperative MRI for brain tumor surgery. Expert Rev Neurother. 2010;10(10):1545–58.

    Article  PubMed  Google Scholar 

  44. Nabavi A, Mamisch CT, Gering DT, Kacher DF, Pergolizzi RS, Wells 3rd WM, Kikinis R, Black PM, Jolesz FA. Image-guided therapy and intraoperative MRI in neurosurgery. Minim Invasive Ther Allied Technol. 2000;9(3–4):277–86.

    CAS  PubMed  Google Scholar 

  45. Jolesz FA. Neurosurgical suite of the future. II. Neuroimaging Clin N Am. 2001;11(4):581–9.

    CAS  PubMed  Google Scholar 

  46. Jolesz FA. Intraoperative imaging in neurosurgery: where will the future take us? Acta Neurochir Suppl. 2011;109:21–5.

    Article  PubMed  Google Scholar 

  47. Dimaio SP, Archip N, Hata N, Talos IF, Warfield SK, Majumdar A, Mcdannold N, Hynynen K, Morrison PR, Wells 3rd WM, Kacher DF, Ellis RE, Golby AJ, Black PM, Jolesz FA, Kikinis R. Image-guided neurosurgery at Brigham and Women’s Hospital. IEEE Eng Med Biol Mag. 2006;25(5):67–73.

    Article  PubMed  Google Scholar 

  48. Claus EB, Horlacher A, Hsu L, Schwartz RB, Dello-Iacono D, Talos F, Jolesz FA, Black PM. Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance. Cancer. 2005;103(6):1227–33.

    Article  PubMed  Google Scholar 

  49. Talos IF, Zou KH, Ohno-Machado L, Bhagwat JG, Kikinis R, Black PM, Jolesz FA. Supratentorial low-grade glioma resectability: statistical predictive analysis based on anatomic MR features and tumor characteristics. Radiology. 2006;239(2):506–13.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Agar NY, Golby AJ, Ligon KL, Norton I, Mohan V, Wiseman JM, Tannenbaum A, Jolesz FA. Development of stereotactic mass spectrometry for brain tumor surgery. Neurosurgery. 2011;68(2):280–9; discussion 290.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Gholami B, Agar NY, Jolesz FA, Haddad WM, Tannenbaum AR. A compressive sensing approach for glioma margin delineation using mass spectrometry. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:5682–5.

    PubMed Central  PubMed  Google Scholar 

  52. Keall PJ, Sawant A, Cho B, Ruan D, Wu J, Poulsen P, Petersen J, Newell LJ, Cattel H, Korreman S. Electromagnetic-guided dynamic multileaf collimator tracking enables motion management for intensity-modulated arc therapy. Int J Radiat Oncol Biol Phys. 2011;79(1):312–20.

    Article  PubMed Central  PubMed  Google Scholar 

  53. D’Amico AV, Cormack R, Tempany CM, Kumar S, Topulos G, Kooy HM, Coleman CN. Real-time magnetic resonance image-guided interstitial brachytherapy in the treatment of select patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 1998;42(3):507–15.

    Article  PubMed  Google Scholar 

  54. Viswanathan AN, Cormack R, Holloway CL, Tanaka C, O’Farrell D, Devlin PM, Tempany C. Magnetic resonance-guided interstitial therapy for vaginal recurrence of endometrial cancer. Int J Radiat Oncol Biol Phys. 2006;66(1):91–9.

    Article  PubMed  Google Scholar 

  55. Song SE, Cho NB, Fischer G, Hata N, Tempany C, Fichtinger G, Iordachita I. Development of a pneumatic robot for MRI-guided transperineal prostate biopsy and brachytherapy: new approaches. IEEE Int Conf Robot Autom. 2010;2010:2580–5.

    PubMed Central  PubMed  Google Scholar 

  56. McDannold NJ, Jolesz FA. Magnetic resonance image-guided thermal ablations. Top Magn Reson Imaging. 2000;11(3):191–202.

    Article  CAS  PubMed  Google Scholar 

  57. Kettenbach J, Silverman SG, Hata N, Kuroda K, Saiviroonporn P, Zientara GP, Morrison PR, Hushek SG, Black PM, Kikinis R, Jolesz FA. Monitoring and visualization techniques for MR-guided laser ablations in an open MR system. J Magn Reson Imaging. 1998;8(4):933–43.

    Article  CAS  PubMed  Google Scholar 

  58. Morrison PR, Silverman SG, Tuncali K, Tatli S. MRI-guided cryotherapy. J Magn Reson Imaging. 2008;27(2):410–20.

    Article  PubMed  Google Scholar 

  59. Sainani NI, Shyn PB, Tatli S, Morrison PR, Tuncali K, Silverman SG. PET/CT-guided radiofrequency and cryoablation: is tumor fluorine-18 fluorodeoxyglucose activity dissipated by thermal ablation? J Vasc Interv Radiol. 2011;22(3):354–60.

    Article  PubMed  Google Scholar 

  60. Zientara GP, Saiviroonporn P, Morrison PR, Fried MP, Hushek SG, Kikinis R, Jolesz FA. MRI monitoring of laser ablation using optical flow. J Magn Reson Imaging. 1998;8(6):1306–18.

    Article  CAS  PubMed  Google Scholar 

  61. Cline HE, Hynynen K, Watkins RD, Adams WJ, Schenck JF, Ettinger RH, Freund WR, Vetro JP, Jolesz FA. Focused US system for MR imaging-guided tumor ablation. Radiology. 1995;194(3):731–7.

    CAS  PubMed  Google Scholar 

  62. Jolesz FA. MRI-guided focused ultrasound surgery. Annu Rev Med. 2009;60:417–30.

    Article  CAS  PubMed  Google Scholar 

  63. Tempany CM, McDannold NJ, Hynynen K, Jolesz FA. Focused ultrasound surgery in oncology: overview and principles. Radiology. 2011;259(1):39–56.

    Article  PubMed  Google Scholar 

  64. Shen S-H, Fennessy FM, McDannold N, Jolesz FA, Tempany CM. Image-guided thermal therapy of uterine fibroids. Semin Ultrasound CT MR. 2009;30(2):91–104.

    Article  PubMed Central  PubMed  Google Scholar 

  65. Obstein KL, Estépar RS, Jayender J, Patil VD, Spofford IS, Ryan MB, Lengyel BI, Shams R, Vosburgh KG, Thompson CC. Image Registered Gastroscopic Ultrasound (IRGUS) in human subjects: a pilot study to assess feasibility. Endoscopy. 2011;43(5):394–9.

    Article  CAS  PubMed  Google Scholar 

  66. Gergel I, Hering J, Tetzlaff R, Meinzer HP, Wegner I. An electromagnetic navigation system for transbronchial interventions with a novel approach to respiratory motion compensation. Med Phys. 2011;38(12):6742–53.

    Article  PubMed  Google Scholar 

  67. Hsu L, Fried MP, Jolesz FA. MR-guided endoscopic sinus surgery. AJNR Am J Neuroradiol. 1998;19(7):1235–40.

    CAS  PubMed  Google Scholar 

  68. Sierra R, Dimaio SP, Wada J, Hata N, Székely G, Kikinis R, Jolesz F. Patient specific simulation and navigation of ventriculoscopic interventions. Stud Health Technol Inform. 2007;125:433–5.

    CAS  PubMed  Google Scholar 

  69. Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA. Noninvasive MR imaging-guided focal opening of the blood–brain barrier in rabbits. Radiology. 2001;220(3):640–6.

    Article  CAS  PubMed  Google Scholar 

  70. Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA. Non-invasive opening of BBB by focused ultrasound. Acta Neurochir Suppl. 2003;86:555–8.

    CAS  PubMed  Google Scholar 

  71. Kinoshita M, McDannold N, Jolesz FA, Hynynen K. Targeted delivery of antibodies through the blood–brain barrier by MRI-guided focused ultrasound. Biochem Biophys Res Commun. 2006;340(4):1085–90.

    Article  CAS  PubMed  Google Scholar 

  72. Kinoshita M, McDannold N, Jolesz FA, Hynynen K. Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood–brain barrier disruption. Proc Natl Acad Sci U S A. 2006;103(31):11719–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Hynynen K, McDannold N, Vykhodtseva N, Raymond S, Weissleder R, Jolesz FA, Sheikov N. Focal disruption of the blood–brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery. J Neurosurg. 2006;105(3):445–54.

    Article  CAS  PubMed  Google Scholar 

  74. Park J, Zhang Y, Vykhodtseva N, Jolesz FA, McDannold NJ. The kinetics of blood brain barrier permeability and targeted doxorubicin delivery into brain induced by focused ultrasound. J Control Release. 2012;162(1):134–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. McDannold N, Arvanitis CD, Vykhodtseva N, Livingstone MS. Temporary disruption of the blood–brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Res. 2012;72(14):3652–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ferenc A. Jolesz MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Jolesz, F.A. (2014). Introduction. In: Jolesz, F. (eds) Intraoperative Imaging and Image-Guided Therapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7657-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7657-3_1

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-7656-6

  • Online ISBN: 978-1-4614-7657-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics