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Kullervo Hynynen

Daniel Coluccia, Carlyn A Figueiredo, Megan YiJun Wu, Alexandra N Riemenschneider, Roberto Diaz, Amanda Luck, Christian Smith, Sunit Das, Cameron Ackerley, Meaghan O'Reilly, Kullervo Hynynen, James T Rutka
Glioblastoma (GBM) is the most common and aggressive primary brain tumor resulting in high rates of morbidity and mortality. A strategy to increase the efficacy of available drugs and enhance the delivery of chemotherapeutics through the blood brain barrier (BBB) is desperately needed. We investigated the potential of Cisplatin conjugated gold nanoparticles (GNP-UP-Cis) in combination with MR-guided Focused Ultrasound (MRgFUS) to intensify GBM treatment. Viability assays demonstrated that GNP-UP-Cis greatly inhibits the growth of GBM cells compared to free cisplatin and shows marked synergy with radiation therapy...
February 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Skyler J Mooney, José N Nobrega, Anthony J Levitt, Kullervo Hynynen
In many cases, hippocampal neurogenesis appears to be a hallmark of antidepressant treatments. One novel technique for inducing this type of neurogenesis is using focused ultrasound waves, in conjunction with circulating microbubbles, to open the blood-brain-barrier. The present experiment aimed to test whether this technique has antidepressant effects in a rodent model. Rats were subjected to 1, 2 or 3 weekly treatments of magnetic resonance-guided focused ultrasound in order to open the blood-brain-barrier in the hippocampal region...
January 8, 2018: Behavioural Brain Research
Ying Meng, Yuexi Huang, Benjamin Solomon, Kullervo Hynynen, Nadia Scantlebury, Michael L Schwartz, Nir Lipsman
Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment...
December 13, 2017: Journal of Visualized Experiments: JoVE
Dallan McMahon, Kullervo Hynynen
Rationale: Focused ultrasound (FUS), in conjunction with circulating microbubbles (MBs), can be used to transiently increase the permeability of the blood-brain barrier (BBB) in a targeted manner, allowing therapeutic agents to enter the brain from systemic circulation. While promising preclinical work has paved the way for the initiation of 3 human trials, there remains concern regarding neuroinflammation following treatment. The aim of this study was to assess the magnitude of this response following sonication and explore the influence of MB dose...
2017: Theranostics
Mingzhe Liu, Stefan Jevtic, Kelly Markham-Coultes, Nicholas P K Ellens, Meaghan A O'Reilly, Kullervo Hynynen, Isabelle Aubert, JoAnne McLaurin
Amyloid-beta peptide (Aβ) plays a critical role in the pathogenesis of Alzheimer's disease (AD). Here, we explored the use of a combination treatment to reduce amyloid load through microglial phagocytosis in a mouse model of AD. We hypothesized that using an initial treatment of magnetic resonance image guided focused ultrasound (MRIgFUS) to transiently increase the blood-brain barrier (BBB) permeability and enhance the delivery of an Aβ-antibody (BAM-10), followed by scyllo-inositol treatment would result in accelerated clearance...
January 1, 2018: Brain Research
Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony Schwab, Elizabeth Head, Kullervo Hynynen
Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits...
2017: Theranostics
Marc A Santos, David E Goertz, Kullervo Hynynen
The future of nanomedicines in oncology requires leveraging more than just the passive drug accumulation in tumors through the enhanced permeability and retention effect. Promising results combining mild hyperthermia (HT) with lyso-thermosensitive liposomal doxorubicin (LTSL-DOX) has led to improved drug delivery and potent antitumor effects in pre-clinical studies. The ultimate patient benefit from these treatments can only be realized when robust methods of HT can be achieved clinically. One of the most promising methods of non-invasive HT is the use of focused ultrasound (FUS) with MRI thermometry for anatomical targeting and feedback...
2017: Theranostics
Samuel Pichardo, Carlos Moreno-Hernández, Robert Andrew Drainville, Vivian Sin, Laura Curiel, Kullervo Hynynen
A better understanding of ultrasound transmission through the human skull is fundamental to develop optimal imaging and therapeutic applications. In this study, we present global attenuation values and functions that correlate apparent density calculated from computed tomography scans to shear speed of sound. For this purpose, we used a model for sound propagation based on the viscoelastic wave equation (VWE) assuming isotropic conditions. The model was validated using a series of measurements with plates of different plastic materials and angles of incidence of 0°, 15° and 50°...
August 7, 2017: Physics in Medicine and Biology
Alec Hughes, Kullervo Hynynen
The use of a phased array of ultrasound transducer elements to sonicate through the skull has opened the way for new treatments and the delivery of therapeutics beyond the blood-brain barrier. The limited steering range of current clinical devices, particularly at higher frequencies, limits the regions of the brain that are considered treatable by ultrasound. A new array design is introduced that allows for high levels of beam steering and increased transmission throughout the brain. These improvements are achieved using concave transducers normal to the outer-skull surface in a patient-specific configuration to target within the skull, so that the far-field of each beam is within the brain...
August 3, 2017: Physics in Medicine and Biology
Petr Smirnov, Kullervo Hynynen
Deep Venous Thrombosis of the iliofemoral veins is a common and morbid disease, with the recommended interventional treatment carrying a high risk of hemorrhaging and complications. High Intensity Focused Ultrasound delivered with a single element transducer has been shown to successfully precipitate thrombolysis non-invasively in vitro and in vivo. However, in all previous studies damage to the veins or surrounding tissue has been observed. Using a simulation model of the human thigh, this study investigated whether a phased array device could overcome the large focal region limitations faced by single transducer treatment devices...
May 9, 2017: Physics in Medicine and Biology
Fred Tam, Yuexi Huang, Michael L Schwartz, Tom A Schweizer, Kullervo Hynynen, Simon J Graham
BACKGROUND: Transcranial magnetic resonance guided focused ultrasound is an emerging technology under evaluation for treatment of essential tremor, a prevalent movement disorder. A qualitative evaluation is performed by a clinician periodically during the procedure to maximize treatment effects and minimize adverse effects. The present work demonstrates a magnetic resonance-compatible method to enable more precise, quantitative measurement of tremor severity. METHODS: Tremor severity was measured in 12 patients pre-, post-, and intra-operatively, using a magnetic resonance-compatible tablet and a computerized adaptation of drawing tasks from the widely-used Fahn-Tolosa-Marin Tremor Rating Scale...
April 17, 2017: BMC Neurology
Ying Meng, Matthew Volpini, Sandra Black, Andres M Lozano, Kullervo Hynynen, Nir Lipsman
No abstract text is available yet for this article.
May 2017: Annals of Neurology
Dallan McMahon, Reina Bendayan, Kullervo Hynynen
Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression...
April 4, 2017: Scientific Reports
Ahmad Bushehri, Gregory Czarnota, Liying Zhang, Kullervo Hynynen, Yuexi Huang, Michael Chan, William Chu, Kristopher Dennis, Charles Mougenot, Jennifer Coccagna, Arjun Sahgal, Edward Chow, Carlo DeAngelis
BACKGROUND: Pain is experienced by 50-75% of patients with bone metastases, representing a major source of morbidity amongst cancer patients. Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is a new, non-invasive, outpatient treatment modality for painful bone metastases. The aim of this study was to analyze urinary cytokines/chemokines pattern after MRgHIFU for palliative treatment of painful bone metastases. The findings were compared to the cytokines/chemokines pattern post single 8 Gy fraction radiation from our previous study...
January 2017: Annals of Palliative Medicine
Yannan Dou, Kullervo Hynynen, Christine Allen
Thermosensitive liposomes have been put forward as a strategy to improve upon the limited tumor drug availability associated with conventional non-thermosensitive liposomes. ThermoDox® is the first and only thermosensitive liposome formulation to reach clinical development. The initial Phase III clinical trial on ThermoDox® (i.e. HEAT trial) evaluating the combination of ThermoDox® and radiofrequency ablation (RFA) in comparison to RFA alone for treatment of inoperable hepatocellular carcinoma (HCC) failed to reach its primary endpoint in progression-free survival (PFS)...
March 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Alec Hughes, Kullervo Hynynen
Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individuallydriven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency...
September 5, 2016: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
Meaghan A O'Reilly, Olivia Hough, Kullervo Hynynen
OBJECTIVES: Microbubble-mediated focused ultrasound (US) opening of the blood-brain barrier (BBB) has shown promising results for the treatment of brain tumors and conditions such as Alzheimer disease. Practical clinical implementation of focused US treatments would aim to treat a substantial portion of the brain; thus, the safety of opening large volumes must be investigated. This study investigated whether the opened volume affects the time for the BBB to be restored after treatment...
March 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
Alec Hughes, Kullervo Hynynen
Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound-phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency...
December 2016: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
Lulu Deng, Meaghan A O'Reilly, Ryan M Jones, Ran An, Kullervo Hynynen
Focused ultrasound (FUS) phased arrays show promise for non-invasive brain therapy. However, the majority of them are limited to a single transmit/receive frequency and therefore lack the versatility to expose and monitor the treatment volume. Multi-frequency arrays could offer variable transmit focal sizes under a fixed aperture, and detect different spectral content on receive for imaging purposes. Here, a three-frequency (306, 612, and 1224 kHz) sparse hemispherical ultrasound phased array (31.8 cm aperture; 128 transducer modules) was constructed and evaluated for microbubble-mediated transcranial therapy and simultaneous cavitation mapping...
December 21, 2016: Physics in Medicine and Biology
Alec Hughes, Yuexi Huang, Aki Pulkkinen, Michael L Schwartz, Andres M Lozano, Kullervo Hynynen
Recent clinical data showing thermal lesions from treatments of essential tremor using MR-guided transcranial focused ultrasound shows that in many cases the focus is oblique to the main axis of the phased array. The potential for this obliquity to extend the focus into lateral regions of the brain has led to speculation as to the cause of the oblique focus, and whether it is possible to realign the focus. Numerical simulations were performed on clinical export data to analyze the causes of the oblique focus and determine methods for its correction...
November 21, 2016: Physics in Medicine and Biology
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