Kullervo Hynynen

Research Synopsis

Imaging and Image-Guided Interventions

The overall goal of my research is to use technology to improve healthcare. One way this goal can be achieved is through the development of new diagnostic and therapeutic methods that can extend our ability to restore health or relive the symptoms of diseases that are not effectively treated today. To help to reach this goal, my research interests have focused on the development of noninvasive therapy and imaging systems.

Most of my current research interests are centered in utilizing focused ultrasound in medicine. Focused ultrasound can provide highly localized and controllable energy deposition deep in the tissue when it is guided by noninvasive imaging such as MRI. This high frequency pressure wave can be used to probe tissue properties and functions for diagnostic purposes or to modify tissue to provide treatment. The rapid and focal energy delivery can induce tissue temperature elevation such that the target is coagulated within a few seconds without damage to the overlying or surrounding tissues. Similarly, by modifying the pressure wave, various biological effects can be induced, including the occlusion of blood vessels, the disintegration of thrombi, and the increase of blood vessel wall and cell membrane permeability. The research so far has concentrated in harnessing this power of ultrasound for minimally or completely non-invasive interventions and imaging. These research initiatives entail considerable collaboration across disciplines, across institutions, and with industry, and they are starting to make an impact on patient care. With funding from the National Institutes of Health (NIH) and other granting agencies and collaborating with private industry, three major research initiatives have been established:

1. To develop high power, MRI-guided ultrasound phased array technology, including theoretical models, transducer arrays, deriving electronics, and controlling software for controlled and noninvasive ultrasound exposures of tissues.
2. To develop systems for ultrasound exposure of brain through the intact skull for MRI guided noninvasive tumor surgery and local drug delivery
3. To develop intracavitary applicators and image guidance methods for exposure of tissues close to body cavities.

Recent Publications

• Huber PE, Mann MJ, Melo LG, Ehsan A, Kong D, Zhang L, Rezvani M, Pescheke P, Jolesz F, Dzau V, Hynynen K. Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery. J Gene Therapy Mol Biol, 2003; 10: 1600-1607.
• Connor WC, Hynynen K. Patterns of thermal deposition in the skull during transcranial focused ultrasound surgery. IEEE Transactions on Biomed. Eng. 2004, 10(51): 1693-1706
• E. Sassaroli and K. Hynynen, On the Impact of Vessel Size on the Threshold of Bubble Collapse. Appl. Phys. Lett. 2006 ; 89: 123901
• Hynynen K, McDannold N, Vykhodtseva N, Raymond S, Weissleder R, Jolesz FA, Sheikov N. Focal disruption of the blood-brain barrier by 260 kHz ultrasound bursts - a method for molecular imaging and targeted drug delivery. J Neurosurgery, 2006;105 (3) 445-54.
• Yin X, Epstein LM, Hynynen K. Related Articles, Noninvasive transesophageal cardiac thermal ablation using a 2-D focused, ultrasound phased array: a simulation study. IEEE Trans Ultrason Ferroelectr Freq Control. 2006;53(6):1138-49.
• McDannold NJ, Vykhodtseva NI, Hynynen K. Microbubble contrast agent with focused ultrasound to create brain lesions at low power levels: MR imaging and histologic study in rabbits. Radiology. 2006; 241(1):95-106.
• 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.
• Treat LH, McDannold N, Vyhodtseva N, Zhang Y, Tam K, Hynynen K. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer. 2007:121(4): 901-7. (Cover Illustration)

Graduate Students

Mikko Hyvarinen
Yi Lin
Maryam Motmaen Dadgar
Ginni Ting