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Kullervo Hynynen

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https://www.readbyqxmd.com/read/28912896/investigation-of-the-safety-of-focused-ultrasound-induced-blood-brain-barrier-opening-in-a-natural-canine-model-of-aging
#1
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
https://www.readbyqxmd.com/read/28819458/focused-ultrasound-hyperthermia-mediated-drug-delivery-using-thermosensitive-liposomes-and-visualized-with-in-vivo-two-photon-microscopy
#2
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
https://www.readbyqxmd.com/read/28783716/a-viscoelastic-model-for-the-prediction-of-transcranial-ultrasound-propagation-application-for-the-estimation-of-shear-acoustic-properties-in-the-human-skull
#3
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
https://www.readbyqxmd.com/read/28665289/design-of-patient-specific-focused-ultrasound-arrays-for-non-invasive-brain-therapy-with-increased-trans-skull-transmission-and-steering-range
#4
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
https://www.readbyqxmd.com/read/28486218/design-of-a-hifu-array-for-the-treatment-of-deep-venous-thrombosis-a-simulation-study
#5
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
https://www.readbyqxmd.com/read/28412948/a-computerized-tablet-system-for-evaluating-treatment-of-essential-tremor-by-magnetic-resonance-guided-focused-ultrasound
#6
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
https://www.readbyqxmd.com/read/28395123/focused-ultrasound-as-a-novel-strategy-for-alzheimer-disease-therapeutics
#7
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
https://www.readbyqxmd.com/read/28374753/acute-effects-of-focused-ultrasound-induced-increases-in-blood-brain-barrier-permeability-on-rat-microvascular-transcriptome
#8
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
https://www.readbyqxmd.com/read/28209068/urinary-cytokines-chemokines-after-magnetic-resonance-guided-high-intensity-focused-ultrasound-for-palliative-treatment-of-painful-bone-metastases
#9
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
https://www.readbyqxmd.com/read/28122204/to-heat-or-not-to-heat-challenges-with-clinical-translation-of-thermosensitive-liposomes
#10
REVIEW
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
https://www.readbyqxmd.com/read/28113366/a-tikhonov-regularization-scheme-for-focus-rotations-with-focused-ultrasound-phased-arrays
#11
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
https://www.readbyqxmd.com/read/28108988/blood-brain-barrier-closure-time-after-controlled-ultrasound-induced-opening-is-independent-of-opening-volume
#12
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
https://www.readbyqxmd.com/read/27913323/a-tikhonov-regularization-scheme-for-focus-rotations-with-focused-ultrasound-phased-arrays
#13
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
https://www.readbyqxmd.com/read/27845920/a-multi-frequency-sparse-hemispherical-ultrasound-phased-array-for-microbubble-mediated-transcranial-therapy-and-simultaneous-cavitation-mapping
#14
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
https://www.readbyqxmd.com/read/27779134/a-numerical-study-on-the-oblique-focus-in-mr-guided-transcranial-focused-ultrasound
#15
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
https://www.readbyqxmd.com/read/27587036/registration-of-human-skull-computed-tomography-data-to-an-ultrasound-treatment-space-using-a-sparse-high-frequency-ultrasound-hemispherical-array
#16
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
https://www.readbyqxmd.com/read/27557301/a-randomized-trial-of-focused-ultrasound-thalamotomy-for-essential-tremor
#17
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/27494561/image-guided-ultrasound-phased-arrays-are-a-disruptive-technology-for-non-invasive-therapy
#18
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
https://www.readbyqxmd.com/read/27459643/focused-ultrasound-induced-neurogenesis-requires-an-increase-in-blood-brain-barrier-permeability
#19
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
https://www.readbyqxmd.com/read/27420647/opening-the-blood-brain-barrier-with-mr-imaging-guided-focused-ultrasound-preclinical-testing-on-a-trans-human-skull-porcine-model
#20
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
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