Principal Investigators

Kullervo Hynynen, PhD

Senior Scientist
Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room A3 33
Toronto, ON
M4N 3M5


• B.Sc., 1976, physics, University of Kuopio, Finland

• M.Sc., 1977, physics, University of Kuopio, Finland

• PhD, 1982, biomedical physics and biomedical engineering, University of Aberdeen, UK

Appointments and Affiliations:

Vice-president, research and innovation, Sunnybrook Health Sciences Centre
Vice-president, research and innovation, Sunnybrook Research Institute
Senior scientist, Physical Sciences, Odette Cancer Research Program, Sunnybrook Research Institute
Professor, department of medical biophysics, University of Toronto
Canada Research Chair in Imaging Systems and Image-Guided Therapy, Tier 1

Research Foci:

• Focused ultrasound for noninvasive surgery
•  Vascular surgery
•  Targeted drug delivery and gene therapy
•  Ultrasound imaging and monitoring
•  MRI thermometry

Dr. Hynynen’s research has focused on studying the effects of ultrasound beams on tissue and their utilization in therapy. He is investigating the use of focused ultrasound for noninvasive surgery, vascular surgery, targeted drug delivery and gene therapy. He has developed theoretical models to help understand treatment parameters and to allow optimization of treatment devices. He has conducted in vivo experiments to investigate the various biological end points that can be induced by controlling the sonication parameters.

His research on ultrasound transducers has been used to design and develop new phased array applicators and better ways to deliver therapy. He is also looking at the use of magnetic resonance imaging to detect and quantify noninvasive ultrasound exposure in vivo. He has developed several systems that are being tested clinically. Dr. Hynynen is currently exploring new ways to utilize ultrasound for imaging with the aim of using the methods for controlling delivery of therapy and aid in tumour diagnosis.




  1. Adams C, Jones RM, Yang SD, Kan WM, Leung K, Zhou Y, Lee KU, Huang Y, Hynynen K. Implementation of a Skull-Conformal Phased Array for Transcranial Focused Ultrasound Therapy. IEEE Trans Biomed Eng. 2021 May 5;PP. doi: 10.1109/TBME.2021.3077802.  PMID: 33950835.
  2. McMahon D, O’Reilly MA, Hynynen K. Therapeutic Agent Delivery Across the Blood-Brain Barrier Using Focused Ultrasound. Annu Rev Biomed Eng. 2021 Mar 22. doi: 10.1146/annurev-bioeng-062117-121238.  PMID: 33752471.
  3. Lea-Banks H, Meng Y, Wu SK, Belhadjhamida R, Hamani C, Hynynen K. Ultrasound-sensitive nanodroplets achieve targeted neuromodulation. J Control Release. 2021 Apr 10;332:30-39. doi: 10.1016/j.jconrel.2021.02.010. Epub 2021 Feb 16. PMID: 33600879; PMCID: PMC8089063.
  4. Weber-Adrian D, Kofoed RH, Silburt J, Noroozian Z, Shah K, Burgess A, Rideout S, Kügler S, Hynynen K, Aubert I. Systemic AAV6-synapsin-GFP administration results in lower liver biodistribution, compared to AAV1&2 and AAV9, with neuronal expression following ultrasound-mediated brain delivery. Sci Rep. 2021 Jan 21;11(1):1934. doi: 10.1038/s41598-021-81046-5. PMID: 33479314; PMCID: PMC7820310.
  5. Wan H, Brathwaite S, Ai J, Hynynen K, Macdonald RL. Role of perivascular and meningeal macrophages in outcome following experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2021 Jan 14:271678X20980296. doi: 10.1177/0271678X20980296.  PMID: 33444089.
  6. Poon C, Pellow C, Hynynen K. Neutrophil recruitment and leukocyte response following focused ultrasound and microbubble mediated blood-brain barrier treatments. Theranostics. 2021 Jan 1;11(4):1655-1671. doi: 10.7150/thno.52710. PMID: 33408773; PMCID: PMC7778596.


  1. Wu SK, Tsai CL, Huang Y, Hynynen K. Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor. Pharmaceutics. Pharmaceutics. 2020 Dec 24;13(1):15. doi: 10.3390/pharmaceutics13010015. PMID: 33374205; PMCID: PMC7823947.
  2. Meng Y, Jones RM, Davidson B, Huang Y, Pople CB, Surendrakumar S, Hamani C, Hynynen K, Lipsman N. Technical Principles and Clinical Workflow of Transcranial MR-Guided Focused Ultrasound. Stereotact Funct Neurosurg. 2020 Dec 10:1-14. doi: 10.1159/000512111. PMID: 33302282.
  3. McMahon D, Lassus A, Gaud E, Jeannot V, Hynynen K. Microbubble formulation influences inflammatory response to focused ultrasound exposure in the brain. Sci Rep. 2020 Dec 9;10(1):21534. doi: 10.1038/s41598-020-78657-9. PMID: 33299094; PMCID: PMC7725832.
  4. McMahon D, Deng L, Hynynen K. Comparing rapid short-pulse to tone burst sonication sequences for focused ultrasound and microbubble-mediated blood-brain barrier permeability enhancement.  J Control Release. 2021 Jan 10;329:696-705. doi: 10.1016/j.jconrel.2020.10.004. Epub 2020 Oct 3. PMID: 33022327.’
  5. Santos MA, Wu SK, Regenold M, Allen C, Goertz DE, Hynynen K. Novel fractionated ultrashort thermal exposures with MRI-guided focused ultrasound for treating tumors with thermosensitive drugs. Sci Adv. 2020 Sep 2;6(36):eaba5684. doi: 10.1126/sciadv.aba5684. PMID: 32917589; PMCID: PMC7467687.
  6. Rahimi S, Jones RM, Hynynen K. A High-Frequency Phased Array System for Transcranial Ultrasound Delivery in Small Animals. IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Jan;68(1):127-135. doi: 10.1109/TUFFC.2020.3012868. Epub 2020 Dec 23. PMID: 32746231; PMCID: PMC7863589.
  7. Kooiman K, Roovers S, Langeveld SAG, Kleven RT, Dewitte H, O’Reilly MA,Escoffre JM, Bouakaz A, Verweij MD, Hynynen K, Lentacker I, Stride E, Holland CK. Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery. Ultrasound Med Biol. 2020 Jun;46(6):1296-1325. doi: 10.1016/j.ultrasmedbio.2020.01.002. Epub 2020 Mar 10. Review. PubMed PMID: 32165014.
  8. Drost L, Hynynen K, Huang Y, Lucht B, Wong E, Czarnota G, Yee C, Wan BA, Ganesh V, Chow E, David E. Ultrasound-Guided Focused Ultrasound Treatment for Painful Bone Metastases: A Pilot Study. Ultrasound Med Biol. 2020 Jun;46(6):1455-1463. doi: 10.1016/j.ultrasmedbio.2020.01.032. Epub 2020 Mar 4. PubMed PMID: 32146008.
  9. McMahon D, Oakden W, Hynynen K. Investigating the effects of dexamethasone on blood-brain barrier permeability and inflammatory response following focused ultrasound and microbubble exposure. Theranostics. 2020 Jan 1;10(4):1604-1618. doi: 10.7150/thno.40908. eCollection 2020. PubMed PMID: 32042325; PubMed Central PMCID: PMC6993222.
  10. Deng L, Hughes A, Hynynen K. A Noninvasive Ultrasound Resonance Method for Detecting Skull Induced Aberrations May Provide a Signal for Adaptive Focusing. IEEE Trans Biomed Eng. 2020 Jan 16. doi: 10.1109/TBME.2020.2967033. PubMed PMID: 31976875.


  1. Aslani P, Drost L, Huang Y, Lucht B, Wong E, Czarnota G, Yee C, Wan A, Ganesh V, Gunaseelan S, David E, Chow E, Hynynen K. Thermal therapy with a fully electronically steerable HIFU phased array using ultrasound guidance and local harmonic motion monitoring. IEEE Trans Biomed Eng. 2019 Oct 24. doi:10.1109/TBME.2019.2949478. [Epub ahead of print] PubMed PMID: 31647420.
  2. Meng Y, Pople CB, Lea-Banks H, Abrahao A, Davidson B, Suppiah S, Vecchio LM, Samuel N, Mahmud F, Hynynen K, Hamani C, Lipsman N. Safety and efficacy of focused ultrasound induced blood-brain barrier opening, an integrative review of animal and human studies. J Control Release. 2019 Sep 10;309:25-36. doi:10.1016/j.jconrel.2019.07.023. Epub 2019 Jul 18. Review. PubMed PMID: 31326464.
  3. Wu SK, Santos MA, Marcus SL, Hynynen K. MR-guided Focused Ultrasound Facilitates Sonodynamic Therapy with 5-Aminolevulinic Acid in a Rat Glioma Model. Sci Rep. 2019 Jul 18;9(1):10465. doi: 10.1038/s41598-019-46832-2. PubMed PMID: 31320671; PubMed Central PMCID: PMC6639400.
  4. Le Floc’h J, Lu HD, Lim TL, Démoré C, Prud’homme RK, Hynynen K, Foster FS. Transcranial Photoacoustic Detection of Blood-Brain Barrier Disruption Following Focused Ultrasound-Mediated Nanoparticle Delivery. Mol Imaging Biol. 2020 Apr;22(2):324-334. doi: 10.1007/s11307-019-01397-4. PubMed PMID: 31286352.
  5. Acconcia CN, Leung BYC, Winch G, Wang J, Hynynen K, Goertz DE. Acoustic radiation force induced accumulation and dynamics of microbubbles on compliant surfaces. Phys Med Biol. 2019 Jul 2;64(13):135003. doi: 10.1088/1361-6560/ab2163. PubMed PMID: 31082815.
  6. Hynynen K. Hyperthermia-induced drug delivery in humans. Nat Biomed Eng. 2018 Sep;2(9):637-639. doi: 10.1038/s41551-018-0297-8. PubMed PMID: 31015680.
  7. Noroozian Z, Xhima K, Huang Y, Kaspar BK, Kügler S, Hynynen K, Aubert I. MRI-Guided Focused Ultrasound for Targeted Delivery of rAAV to the Brain. Methods Mol Biol. 2019;1950:177-197. doi: 10.1007/978-1-4939-9139-6_10. PubMed PMID: 30783974; PubMed Central PMCID: PMC6546162.
  8. Mainprize T, Lipsman N, Huang Y, Meng Y, Bethune A, Ironside S, Heyn C, Alkins R, Trudeau M, Sahgal A, Perry J, Hynynen K. Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Sci Rep. 2019 Jan 23;9(1):321. doi: 10.1038/s41598-018-36340-0. PubMed PMID: 30674905; PubMed Central PMCID: PMC6344541.
  9. McMahon D, Poon C, Hynynen K. Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability. Expert Opin Drug Deliv. 2019 Feb;16(2):129-142. doi: 10.1080/17425247.2019.1567490. Epub 2019 Jan 29. Review. PubMed PMID: 30628455; PubMed Central PMCID: PMC6576291.
  10. Jones RM, Hynynen K. Advances in acoustic monitoring and control of focused ultrasound-mediated increases in blood-brain barrier permeability. Br J Radiol. 2019 Apr;92(1096):20180601. doi: 10.1259/bjr.20180601. Epub 2019 Feb 28. Review. PubMed PMID: 30507302; PubMed Central PMCID: PMC6540854.


  1. Lea-Banks H, O’Reilly MA, Hynynen K. Ultrasound-responsive droplets for therapy: A review. J Control Release. 2019 Jan 10;293:144-154. doi: 10.1016/j.jconrel.2018.11.028. Epub 2018 Nov 29. Review. PubMed PMID: 30503398; PubMed Central PMCID: PMC6459400.
  2. Bulner S, Prodeus A, Gariepy J, Hynynen K, Goertz DE. Enhancing Checkpoint Inhibitor Therapy with Ultrasound Stimulated Microbubbles. Ultrasound Med Biol. 2019 Feb;45(2):500-512. doi: 10.1016/j.ultrasmedbio.2018.10.002. Epub 2018 Nov 15. PubMed PMID: 30447880.
  3. Santos MA, Wu SK, Li Z, Goertz DE, Hynynen K. Microbubble-assisted MRI-guided focused ultrasound for hyperthermia at reduced power levels. Int J Hyperthermia. 2018;35(1):599-611. doi: 10.1080/02656736.2018.1514468. Epub 2018 Oct 8. PubMed PMID: 30295119.
  4. Alli S, Figueiredo CA, Golbourn B, Sabha N, Wu MY, Bondoc A, Luck A, Coluccia D, Maslink C, Smith C, Wurdak H, Hynynen K, O’Reilly M, Rutka JT. Brainstem blood brain barrier disruption using focused ultrasound: A demonstration of feasibility and enhanced doxorubicin delivery. J Control Release. 2018 Jul 10;281:29-41. doi: 10.1016/j.jconrel.2018.05.005. Epub 2018 May 16. PubMed PMID: 29753957; PubMed Central PMCID: PMC6026028.
  5. McMahon D, Hynynen K. Reply to Kovacs et al.: Concerning acute inflammatory response following focused ultrasound and microbubbles in the brain. Theranostics. 2018 Mar 8;8(8):2249-2250. doi: 10.7150/thno.25468. eCollection 2018. PubMed PMID: 29722372; PubMed Central PMCID: PMC5928886.
  6. Coluccia D, Figueiredo CA, Wu MY, Riemenschneider AN, Diaz R, Luck A, Smith C, Das S, Ackerley C, O’Reilly M, Hynynen K, Rutka JT. Enhancing glioblastoma treatment using cisplatin-gold-nanoparticle conjugates and targeted delivery with magnetic resonance-guided focused ultrasound. Nanomedicine. 2018 Jun;14(4):1137-1148. doi: 10.1016/j.nano.2018.01.021. Epub 2018 Feb 20. PubMed PMID: 29471172.


  1. McMahon D, Hynynen K. Acute Inflammatory Response Following Increased Blood-Brain Barrier Permeability Induced by Focused Ultrasound is Dependent on Microbubble Dose. Theranostics. 2017 Sep 15;7(16):3989-4000. doi: 10.7150/thno.21630. eCollection 2017. PubMed PMID: 29109793; PubMed Central PMCID: PMC5667420.
  2. Santos MA, Goertz DE, Hynynen K. Focused Ultrasound Hyperthermia Mediated Drug Delivery Using Thermosensitive Liposomes and Visualized With in vivo Two-Photon Microscopy. Theranostics. 2017 Jul 7;7(10):2718-2731. doi: 10.7150/thno.19662. eCollection 2017. PubMed PMID: 28819458; PubMed Central PMCID: PMC5558564.
  3. McMahon D, Bendayan R, Hynynen K. Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome. Sci Rep. 2017 Apr 4;7:45657. doi: 10.1038/srep45657. PubMed PMID: 28374753; PubMed Central PMCID: PMC5379491.
  4. Bushehri A, Czarnota G, Zhang L, Hynynen K, Huang Y, Chan M, Chu W, Dennis K, Mougenot C, Coccagna J, Sahgal A, Chow E, DeAngelis C. Urinary cytokines/chemokines after magnetic resonance-guided high intensity focused ultrasound for palliative treatment of painful bone metastases. Ann Palliat Med. 2017 Jan;6(1):36-54. doi: 10.21037/apm.2016.12.06. PubMed PMID: 28209068.
  5. O’Reilly MA, Hough O, Hynynen K. Blood-Brain Barrier Closure Time After Controlled Ultrasound-Induced Opening Is Independent of Opening Volume. J Ultrasound Med. 2017 Mar;36(3):475-483. doi: 10.7863/ultra.16.02005. Epub 2017 Jan 21. PubMed PMID: 28108988; PubMed Central PMCID: PMC5319892.
  6. Deng L, O’Reilly MA, Jones RM, An R, Hynynen K. A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping. Phys Med Biol. 2016 Dec 21;61(24):8476-8501. Epub 2016 Nov 15. PubMed PMID: 27845920; PubMed Central PMCID: PMC5135599.