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Kullervo Hynynen

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
Despite decades of advances in the pathology, genetics and imaging of Alzheimer's disease (AD), there remain no effective treatments that significantly alter its natural history. Several late phase clinical trials, focused largely on amyloid beta metabolism and clearance, have unfortunately demonstrated no significant benefit in early AD patients. Recent work investigating blood-brain barrier opening using focused ultrasound in transgenic animal models has shown that repeated ultrasound administration coupled with microbubble-containing contrast can reduce plaque burden and reverse memory deficits...
April 10, 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)...
January 22, 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
Meaghan A O'Reilly, Ryan M Jones, Gabriel Birman, Kullervo Hynynen
PURPOSE: Transcranial focused ultrasound (FUS) shows great promise for a range of therapeutic applications in the brain. Current clinical investigations rely on the use of magnetic resonance imaging (MRI) to monitor treatments and for the registration of preoperative computed tomography (CT)-data to the MR images at the time of treatment to correct the sound aberrations caused by the skull. For some applications, MRI is not an appropriate choice for therapy monitoring and its cost may limit the accessibility of these treatments...
September 2016: Medical Physics
W Jeffrey Elias, Nir Lipsman, William G Ondo, Pejman Ghanouni, Young G Kim, Wonhee Lee, Michael Schwartz, Kullervo Hynynen, Andres M Lozano, Binit B Shah, Diane Huss, Robert F Dallapiazza, Ryder Gwinn, Jennifer Witt, Susie Ro, Howard M Eisenberg, Paul S Fishman, Dheeraj Gandhi, Casey H Halpern, Rosalind Chuang, Kim Butts Pauly, Travis S Tierney, Michael T Hayes, G Rees Cosgrove, Toshio Yamaguchi, Keiichi Abe, Takaomi Taira, Jin W Chang
BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months...
August 25, 2016: New England Journal of Medicine
Kullervo Hynynen, Ryan M Jones
Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects...
September 7, 2016: Physics in Medicine and Biology
Skyler J Mooney, Kairavi Shah, Sharon Yeung, Alison Burgess, Isabelle Aubert, Kullervo Hynynen
Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis...
2016: PloS One
Yuexi Huang, Ryan Alkins, Michael L Schwartz, Kullervo Hynynen
Purpose To develop and test a protocol in preparation for a clinical trial on opening the blood-brain barrier (BBB) with magnetic resonance (MR) imaging-guided focused ultrasound for the delivery of chemotherapy drugs to brain tumors. Materials and Methods The procedures were approved by the institutional animal care committee. A trans-human skull porcine model was designed for the preclinical testing. Wide craniotomies were applied in 11 pigs (weight, approximately 15 kg). A partial human skull was positioned over the animal's brain...
January 2017: Radiology
William Chu, Robert M Staruch, Samuel Pichardo, Matti Tillander, Max O Köhler, Yuexi Huang, Mika Ylihautala, Merrylee McGuffin, Gregory Czarnota, Kullervo Hynynen
PURPOSE: To evaluate the feasibility of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU...
July 15, 2016: International Journal of Radiation Oncology, Biology, Physics
Justin Lee, Georges Farha, Ian Poon, Irene Karam, Kevin Higgins, Samuel Pichardo, Kullervo Hynynen, Danny Enepekides
BACKGROUND: Radiotherapy is a critical component of the multidisciplinary management of cancers of the head and neck. It may comprise the primary curative treatment modality or is used in an adjuvant setting to improve local control and survival by preventing seeding and reseeding of distant metastases from persistent reservoirs of locoregional disease. Although considerable advances have been made recently in the fields of radiotherapy, systemic treatment and surgery for head and neck tumours, locoregional recurrence rates remain high and treatment side effects may have severe impact on patients' quality of life...
2016: Journal of Therapeutic Ultrasound
Charissa Poon, Dallan McMahon, Kullervo Hynynen
The range of therapeutic treatment options for central nervous system (CNS) diseases is greatly limited by the blood-brain barrier (BBB). While a variety of strategies to circumvent the blood-brain barrier for drug delivery have been investigated, little clinical success has been achieved. Focused ultrasound (FUS) is a unique approach whereby the transcranial application of acoustic energy to targeted brain areas causes a noninvasive, safe, transient, and targeted opening of the BBB, providing an avenue for the delivery of therapeutic agents from the systemic circulation into the brain...
February 18, 2016: Neuropharmacology
Ryan Alkins, Alison Burgess, Robert Kerbel, Winfried S Wels, Kullervo Hynynen
BACKGROUND: Malignant brain tumors have a dismal prognosis, with residual tumor remaining after surgery necessitating adjuvant chemoradiotherapy. The blood-brain barrier hinders many chemotherapeutic agents, resulting in modest treatment efficacy. We previously demonstrated that targeted natural killer (NK)-92 cells could be delivered to desired regions of the brain using MRI-guided focused ultrasound and Definity microbubbles. Targeted NK-92 cells have advantages over many systemic therapies including their specific cytotoxicity to malignant cells (particularly those expressing the target antigen), ability to spare healthy cells, and being unaffected by efflux channels...
July 2016: Neuro-oncology
Ryan M Jones, Kullervo Hynynen
Computed tomography (CT)-based aberration corrections are employed in transcranial ultrasound both for therapy and imaging. In this study, analytical and numerical approaches for calculating aberration corrections based on CT data were compared, with a particular focus on their application to transcranial passive imaging. Two models were investigated: a three-dimensional full-wave numerical model (Connor and Hynynen 2004 IEEE Trans. Biomed. Eng. 51 1693-706) based on the Westervelt equation, and an analytical method (Clement and Hynynen 2002 Ultrasound Med...
January 7, 2016: Physics in Medicine and Biology
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