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Kullervo Hynynen

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https://www.readbyqxmd.com/read/27913323/a-tikhonov-regularization-scheme-for-focus-rotations-with-focused-ultrasound-phased-arrays
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
July 15, 2016: Radiology
https://www.readbyqxmd.com/read/27209510/magnetic-resonance-guided-high-intensity-focused-ultrasound-hyperthermia-for-recurrent-rectal-cancer-mr-thermometry-evaluation-and-preclinical-validation
#9
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
https://www.readbyqxmd.com/read/27042308/magnetic-resonance-guided-high-intensity-focused-ultrasound-combined-with-radiotherapy-for-palliation-of-head-and-neck-cancer-a-pilot-study
#10
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
https://www.readbyqxmd.com/read/26907805/noninvasive-and-targeted-delivery-of-therapeutics-to-the-brain-using-focused-ultrasound
#11
REVIEW
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
https://www.readbyqxmd.com/read/26819443/early-treatment-of-her2-amplified-brain-tumors-with-targeted-nk-92-cells-and-focused-ultrasound-improves-survival
#12
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
https://www.readbyqxmd.com/read/26605827/comparison-of-analytical-and-numerical-approaches-for-ct-based-aberration-correction-in-transcranial-passive-acoustic-imaging
#13
COMPARATIVE STUDY
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
https://www.readbyqxmd.com/read/26486344/microbubble-assisted-ultrasound-for-drug-delivery-in-the-brain-and-central-nervous-system
#14
REVIEW
Alison Burgess, Kullervo Hynynen
The blood-brain barrier is a serious impediment to the delivery of pharmaceutical treatments for brain diseases, including cancer, neurodegenerative and neuropsychatric diseases. Focused ultrasound, when combined with microbubbles, has emerged as an effective method to transiently and locally open the blood-brain barrier to promote drug delivery to the brain. Focused ultrasound has been used to successfully deliver a wide variety of therapeutic agents to pre-clinical disease models. The requirement for clinical translation of focused ultrasound technology is considered...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/26431798/combined-therapeutic-and-monitoring-ultrasonic-catheter-for%C3%A2-cardiac-ablation-therapies
#15
Mathew Carias, Kullervo Hynynen
This study evaluated the feasibility of a combined therapeutic and diagnostic ultrasonic catheter for cardiac ablation therapies. Ultrasound can be used to determine when diseased cardiac tissues have become fully coagulated through a method known as local harmonic motion imaging (LHMI). LHMI is an imaging modality for treatment monitoring that uses acoustic radiation force, displacement tracking and the different mechanical properties of viable and ablated tissues. In this study, we developed catheters that are capable of LHMI measurements...
January 2016: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/26233216/frequency-considerations-for-deep-ablation-with-high-intensity-focused-ultrasound-a-simulation-study
#16
Nicholas Ellens, Kullervo Hynynen
PURPOSE: The objective of this study was to explore frequency considerations for large-volume, deep thermal ablations with focused ultrasound. Though focal patterns, focal steering rate, and the size of focal clusters have all been explored in this context, frequency studies have generally explored shallower depths and hyperthermia applications. This study examines both treatment efficiency and near-field heating rate as functions of frequency and depth. METHODS: Flat, 150 mm transducer arrays were simulated to operate at frequencies of 250, 500, 750, 1000, 1250, and 1500 kHz...
August 2015: Medical Physics
https://www.readbyqxmd.com/read/26133635/experimental-demonstration-of-passive-acoustic-imaging-in-the-human-skull-cavity-using-ct-based-aberration-corrections
#17
Ryan M Jones, Meaghan A O'Reilly, Kullervo Hynynen
PURPOSE: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)]. METHODS: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0...
July 2015: Medical Physics
https://www.readbyqxmd.com/read/26053102/quantitative-mri-in-a-non-surgical-model-of-cervical-spinal-cord-injury
#18
Wendy Oakden, Jacek M Kwiecien, Meaghan A O'Reilly, Wojciech Dabrowski, Cari Whyne, Joel Finkelstein, Kullervo Hynynen, Greg J Stanisz
Quantitative T2 (qT2), diffusion tensor imaging (DTI), and histology were used to investigate a cervical model of spinal cord injury (SCI) in the rat. While quantitative MRI can significantly increase the specificity in the presence of pathology, it must be validated for each type of injury or disease. In the case of traumatic SCI most models are difficult to image, either due to the location of the injury, or as a result of damage to surrounding tissues resulting from invasive surgical procedures. In this study a non-surgical cervical model of SCI, produced using a combination of focused ultrasound and microbubbles, was used to produce pathology similar to that seen in models of contusive and compressive injuries...
August 2015: NMR in Biomedicine
https://www.readbyqxmd.com/read/25936845/focused-ultrasound-mediated-drug-delivery-through-the-blood-brain-barrier
#19
REVIEW
Alison Burgess, Kairavi Shah, Olivia Hough, Kullervo Hynynen
Despite recent advances in blood-brain barrier (BBB) research, it remains a significant hurdle for the pharmaceutical treatment of brain diseases. Focused ultrasound (FUS) is one method to transiently increase permeability of the BBB to promote drug delivery to specific brain regions. An introduction to the BBB and a brief overview of the methods, which can be used to circumvent the BBB to promote drug delivery, is provided. In particular, we discuss the advantages and limitations of FUS technology and the efficacy of FUS-mediated drug delivery in models of disease...
May 2015: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/25792225/emerging-non-cancer-applications-of-therapeutic-ultrasound
#20
REVIEW
Meaghan A O'Reilly, Kullervo Hynynen
Ultrasound therapy has been investigated for over half a century. Ultrasound can act on tissue through a variety of mechanisms, including thermal, shockwave and cavitation mechanisms, and through these can elicit different responses. Ultrasound therapy can provide a non-invasive or minimally invasive treatment option, and ultrasound technology has advanced to the point where devices can be developed to investigate a wide range of applications. This review focuses on non-cancer clinical applications of therapeutic ultrasound, with an emphasis on treatments that have recently reached clinical investigations, and preclinical research programmes that have great potential to impact patient care...
May 2015: International Journal of Hyperthermia
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