David Goertz - Academia.edu (original) (raw)

Papers by David Goertz

Cancer research, Jan 15, 2002

The effect of antivascular therapy on blood flow in superficial tumors was monitored using novel ... more The effect of antivascular therapy on blood flow in superficial tumors was monitored using novel high frequency Doppler (HFD) ultrasound techniques. Human melanoma cells (MeWo) were injected orthotopically into the skin of athymic nude mice. Volumetric HFD imaging of established melanomas detected a significant reduction in blood flow 4 h after injection of the tumor vascular targeting agent ZD6126 followed by a recovery of flow by 24 h after injection. Measurements of tumor perfusion in situ by Hoechst 33342 staining correlated with the ultrasound results. This study demonstrates the feasibility of HFD as a noninvasive, quantitative tool for following longitudinally the effects of antivascular therapy on blood flow in superficial tumors.

European Journal of Echocardiography, 2007

GEOPHYSICS, 1998

Laboratory measurements of drying rates and elastic wave velocities are made on limestone, dolomi... more Laboratory measurements of drying rates and elastic wave velocities are made on limestone, dolomite, and sandstone samples during evaporative drying. The drying rate data are very similar in form. There is a constant rate period at higher saturations and a falling rate period below saturation levels of approximately 0.2. The falling rate period marks the transition in the sample from hydraulically connected to disconnected water. There is a strong link between elastic wave velocities and the drying process because different pore geometries drain at different stages in drying. The drainage of these different geometries results in specific changes in the moduli and velocities. Simple models of the pore geometries and the drying process are used to model the velocity data. The velocity‐saturation relationship for each of the three samples is very different in form because of differences in pore‐space microgeometry. Of particular interest is the velocity response during the falling rate...

An exciting recent development in ultrasound microbubble contrast agent technology is their exten... more An exciting recent development in ultrasound microbubble contrast agent technology is their extension from non-specific diagnostic tools to targeted and therapeutic agents. This process involves the addition of large molecules such as ligands or DNA segments to the microbubbles. The aim of this work was to evaluate the effects of these additional components on the acoustic properties and the stability of microbubbles. Novel encapsulated microbubbles were produced in our laboratory with shell materials containing albumin or phospholipid. In each case both targeted, conjugated bubbles and simple unconjugated versions were manufactured. Laboratory made microbubbles were compared to similar commercially produced microbubbles. The attenuation coefficient was measured with a broadband single element transducer using a substitution approach and the backscatter was measured with a Toshiba PowerVisionr 8000. Samples of each bubble type were sized from photographs taken through a standard lig...

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 2006

Antonius F.W. van der Steen1,2*, Radj A. Baldewsing1, F. Levent Degertekin3, Stanislav Emelianov4... more Antonius F.W. van der Steen1,2*, Radj A. Baldewsing1, F. Levent Degertekin3, Stanislav Emelianov4, Martijn. E. Frijlink1, Yuji Furukawa5, Dave Goertz1,2, Mustafa Karaman6, Pierre T. Khuri-Yakub7, Kang Kim8, Frits Mastik1, T. Moriya9, Ömer Oralkan7, Yoshifumi Saijo10, Johannes A Schaar1, Patrick W Serruys1, Shriram Sethuraman4, Akira Tanaka11, Hendrik. J. Vos1,12, Russell Witte8, Matthew O’Donnell8

Netherlands Heart Journal, 2007

IEEE Ultrasonics Symposium, 2004

We have investigated surface vibrations generated by ultrasound excitation of individual unencaps... more We have investigated surface vibrations generated by ultrasound excitation of individual unencapsulated micron-sized bubbles. In addition, we present surface modes (n = 2 and 3) observed for phospholipid-coated ultrasound contrast agents excited through excitation of radial modes at frequencies between 1 and 4 MHz. Even higher modes of vibration (up to mode 5) are observed for coated microbubbles at insonation frequencies of 10 and 19 MHz. The potential relevance of surface modes for medical ultrasound is discussed, including the possible implications for current theoretical models of ultrasound contrast agents.

The Journal of the Acoustical Society of America, 2006

An ultrasonically driven air bubble can become shape-unstable through a parametric instability. H... more An ultrasonically driven air bubble can become shape-unstable through a parametric instability. Here, we report time-resolved optical observations of shape oscillations (mode n=2 to 6) of micron-sized single air bubbles for a range of acoustic pressures. The observed mode number n was found to be linearly related to the resting radius of the bubble. Above the critical driving pressure threshold for shape oscillations, which as expected is minimum at the resonance of the volumetric radial mode, the observed mode number n is independent of the forcing pressure amplitude. The microbubble shape oscillations were also analyzed numerically by introducing a small, nonspherical linear perturbation into a Rayleigh-Plesset-type equation model which includes a physical thermal damping mechanism describing heat and mass transport in the thin boundary layer at the bubble-to-water interface. Indeed, a parametric instability is responsible for the shape oscillations, and the Rayleigh-Plesset-type ...

Journal of Dentistry, 2007

IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 2005

A recent study has shown the feasibility of tissue harmonic imaging (THI) using an intravascular ... more A recent study has shown the feasibility of tissue harmonic imaging (THI) using an intravascular ultrasound (IVUS) transducer. This correspondence describes the design, fabrication, and characterization of a THIoptimized piezoelectric transducer with oval aperture of 0.75 mm by 1 mm. The transducer operated at 20 MHz and 40 MHz, and was comprised of a single piezoelectric layer with additional passive layers. The Krimholtz-Leedom-Matthaei (KLM) model was used to iteratively find optimal material properties of the different layers. The transducer characterization showed ;6 dB fractional bandwidths of 30% and 25%, and two-way insertion losses of

investigate the nonspherical oscillations, or surface modes, of bubbles of radius between 10 and ... more investigate the nonspherical oscillations, or surface modes, of bubbles of radius between 10 and 60 microns within an ultrasonic field of frequency of 130 kHz. We show experimentally that a threshold in acoustic pressure is required to trigger the surface modes, that they appear only after a few cycles of ultrasons, and that the observed mode number (2 to 6) is linearly related to the resting radius of the bubble and does not depend significantly on the acoustic pressure. We relate the observations to a parametric instability: The amplitude of nonspherical oscillations is modulated by the radial dynamics. Using a simple, linear radial dynamics, we reproduce the dependence of the observed mode number with the radius. A more accurate, nonlinear radial dynamics model determined from a modified Rayleigh-Plesset equation yields excellent agreement, both for the threshold in acoustic pressure and for the mode number, in the whole parameter space. The implications of these results for the coated microbubbles widely used as ultrasound contrast agents in medical acoustics are discussed.

Ultrasound in Medicine and Biology, 2017

$Research paper thumbnail of Novel fractionated ultrashort thermal exposures with MRI-guided focused ultrasound for treating tumors with thermosensitive drugs$

Science Advances, 2020

Focused ultrasound mild heating in short durations has an antitumor effect when combined with tem... more Focused ultrasound mild heating in short durations has an antitumor effect when combined with temperature-sensitive chemotherapy.

Theranostics, 2020

Background: There has been growing interest in nanobubbles for their potential to extend bubble-m... more Background: There has been growing interest in nanobubbles for their potential to extend bubble-mediated ultrasound approaches beyond that of their larger microbubble counterparts. In particular, the smaller scale of nanobubbles may enable them to access the tumor extravascular compartment for imaging and therapy in closer proximity to cancer cells. Compelling preliminary demonstrations of the imaging and therapeutic abilities of nanobubbles have thus emerged, with emphasis on their ability to extravasate. However, studies to date rely on indirect histologic evidence that cannot confirm whether the structures remain intact beyond the vasculature-leaving their extravascular potential largely untapped. Methods: Nanobubble acoustic scattering was assessed using a recently reported ultra-stable formulation at low concentration (10 6 mL-1) and frequency (1 MHz), over a range of pressures (100-1500 kPa) in a channel phantom. The pressure-dependent response was utilized as a basis for in vivo experiments where ultrasound transmitters and receivers were integrated into a window chamber for simultaneous intravital multiphoton microscopy and acoustic monitoring in tumor-affected microcirculation. Microscopy and acoustic data were utilized to assess passive and active delivery of nanobubbles and determine whether they remained intact beyond the vasculature. Results: Nanobubbles exhibit pressure-dependent nonlinear acoustic scattering. Nanobubbles are also found to have prolonged acoustic vascular pharmacokinetics, and passively extravasate intact into tumors. Ultrasound stimulation of nanobubbles is shown to actively enhance the delivery of both intact nanobubbles and shell material, increasing their spatial bioavailability deeper into the extravascular space. A range of acute vascular effects were also observed. Conclusion: This study presents the first direct evidence that nanobubbles passively and actively extravasate intact in tumor tissue, and is the first to directly capture acute vascular events from ultrasound-stimulation of nanobubbles. The insights gained here demonstrate an important step towards unlocking the potential of nanobubbles and extending ultrasound-based applications.

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, Jan 8, 2018

Ultrasound contrast agent microbubbles were combined with magnetic resonance imaging (MRI)-guided... more Ultrasound contrast agent microbubbles were combined with magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) as a means to achieve mild hyperthermia at reduced power levels. MRgFUS hyperthermia (42°C for 20 min) was evaluated in rabbit thigh muscle or Vx2 tumors using infusions of microbubbles (Definity, 20 µL/kg) or saline (sham) administered over 5 min. The impact of treatments on drug uptake was assessed with liposomal doxorubicin (Caelyx, 2.5 mg/kg). Applied power levels before and after the injection of microbubbles or saline were compared, and drug uptake was evaluated with fluorometry of tissues harvested 24 hr post-treatment. MRgFUS hyperthermia in muscle and tumors resulted in accurate temperature control (mean =42.0°C, root mean square error (RMSE) = 0.3°C). The power dropped significantly following the injection of microbubbles in muscle and tumors compared to exposures without microbubbles (-21.9% ± 12.5% vs -5.9% ± 7.8%, p = .009 in muscle; -33.8% ± 9.9...

Theranostics, 2017

The future of nanomedicines in oncology requires leveraging more than just the passive drug accum... more 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. MRI-guided focused ultrasound (MRgFUS) is limited by respiratory motion and large blood vessel cooling. In order to translate exciting pre-clinical results to the clinic, novel heating approaches capable of overcoming the limitations on clinical MRgFUS+HT must be tested and evaluated on their ability to locally release drug from LTSL-DOX. Methods: In this work, a new system is described to integrate focused ultrasound (FUS) into a two-photon microscopy (2PM) setting to image the release of drug from LTSL-DOX in real-time during FUS+HT in vivo. A candidate scheme for overcoming the limitations of respiratory motion and large blood vessel cooling during MRgFUS+HT involves applying FUS+HT to 42°C in short ~30s bursts. The spatiotemporal drug release pattern from LTSL-DOX as a result is quantified using 2PM and compared against continuous (3.5min and 20min at 42°C) FUS+HT schemes and unheated controls. Results: It was observed for the first time in vivo that these short duration temperature elevations could produce substantial drug release from LTSL-DOX. Ten 30s bursts of FUS+HT was able to achieve almost half of the interstitial drug concentration as 20min of continuous FUS+HT. There was no significant difference between the intravascular area under the concentration-time curve for ten 30s bursts of FUS+HT and 3.5min of continuous FUS+HT. Conclusion: We have successfully combined 2PM with FUS+HT for imaging the release of DOX from LTSL-DOX in vivo in real-time, which will permit the investigation of FUS+HT heating schemes to improve drug delivery from LTSL-DOX. We have evaluated the ability to release DOX in short 30s FUS+HT bursts to 42°C as a method to overcome limitations on clinical MRgFUS+HT and have found that such exposures are capable of releasing measurable amounts of drug. Such an exposure has the potential to overcome limitations that hamper conventional MRgFUS+HT treatments in targets that are associated with substantial tissue motion.

Physics in medicine and biology, Jan 8, 2017

It is well established that high intensity focused ultrasound can be used to disintegrate clots. ... more It is well established that high intensity focused ultrasound can be used to disintegrate clots. This approach has the potential to rapidly and noninvasively resolve clot causing occlusions in cardiovascular diseases such as deep vein thrombosis (DVT). However, lack of an appropriate treatment monitoring tool is currently a limiting factor in its widespread adoption. Here we conduct cavitation imaging with a large aperture, sparse hemispherical receiver array during sonothrombolysis with multi-cycle burst exposures (0.1 or 1 ms burst lengths) at 1.51 MHz. It was found that bubble cloud generation on imaging correlated with the locations of clot degradation, as identified with high frequency (30 MHz) ultrasound following exposures. 3D images could be formed at integration times as short as 1 µs, revealing the initiation and rapid development of cavitation clouds. Equating to megahertz frame rates, this is an order of magnitude faster than any other imaging technique available for in ...

The Journal of the Acoustical Society of America, 2016

Serial two-photon microscopy of blood clots with fluorescently tagged fibrin networks was conduct... more Serial two-photon microscopy of blood clots with fluorescently tagged fibrin networks was conducted during microbubble-mediated sonothrombolysis to examine the microscale evolution of the resulting erosion front. The development of a complex zonal erosion pattern was observed, comprised of a cell depleted layer of fibrin network overlying intact clot which then underwent progressive recession. The fibrin zone architecture was dependent on exposure conditions with 0.1 MPa causing no erosion, 0.39 MPa resulting in homogenous structure, and combination 0.39/0.96 MPa pulses forming large-scale tunnels. High speed imaging and Coulter counter data indicated the fibrin zone formation process involves the ejection of intact erythrocytes.

IEEE transactions on bio-medical engineering, Jan 23, 2014

Focused ultrasound with microbubbles is an emerging technique for blood brain barrier (BBB) openi... more Focused ultrasound with microbubbles is an emerging technique for blood brain barrier (BBB) opening. Here, a comprehensive theoretical model of a bubble-fluid-vessel system has been developed which accounts for the bubble's non-spherical oscillations inside a microvessel, and its resulting acoustic emissions. Numerical simulations of unbound and confined encapsulated bubbles were performed to evaluate the effect of the vessel wall on acoustic emissions and vessel wall stresses. Using a Marmottant shell model, the normalized second harmonic to fundamental emissions first decreased as a function of pressure (>50 kPa) until reaching a minima ("transition point") at which point they increased. The transition point of unbound compared to confined bubble populations occurred at different pressures and was associated with an accompanying increase in shear and circumferential wall stresses. As the wall stresses depend on the bubble to vessel wall distance, the stresses were...