Edward A. Gardner

Contrast agent imaging with destruction pulses in diagnostic medical ultrasound

The invention is directed to improvements in diagnostic medical ultrasound contrast agent imaging. In a preferred embodiment, high pulse repetition frequency (HPRF) destruction pulses are fired at a rate higher than necessary for receiving returning echoes. Pulse parameters can also be changed between the plurality of contrast agent-destroying pulses. Other preferred embodiments of the invention are directed to simultaneous transmission of multiple beams of destruction pulses. Destruction frames that consist of a plurality of destruction pulses can be triggered and swept over the entire region of tissue being imaged and at a variety of focal depths from the transmitter. The destruction frames are fired at some time triggered from a timer or some fixed part of a physiological signal, such as an ECG signal. Other preferred embodiments of the invention are directed to continuous low power imaging pulses alternating with destruction pulses triggered at a fixed point of a physiological signal, and a comparison of the received signals from imaging pulses fired before and after the destruction pulses. Alternatively, destruction pulses are triggered at a fixed point on a physiological signal different from the fixed point of a physiological signal used to trigger imaging pulses. In another embodiment, triggered destruction frames are used to enable a comparison of imaging frames in order to determine physiological functions, such as perfusion of blood in cardiac tissue. Finally, in another embodiment, destruction pulses are combined with subharmonic imaging.

Medical diagnostic ultrasound-aided drug delivery system and method

A method and system is provided for delivering drugs carried by microspheres. A medical diagnostic ultrasound system destroys microspheres in a specific localized area or at a specific time. A region of interest that is a subset of an imaged area is identified for destroying drug-carrying microspheres. The transmit beamformer is configured to transmit acoustic energy for destroying microspheres within that area while minimizing the destruction of microspheres outside of the region of interest. A multidimensional transducer array may provide focusing in three-dimensions for accurately destroying microspheres in the specific region while minimizing the destruction of microspheres outside that region. A trigger responsive to a heart or breathing cycle may control when microspheres are destroyed, providing delivery of drugs at the most opportune time in the cycle.

A sensitive ultrasonic imaging method for targeted contrast microbubble detection

We have recently developed a targeted imaging technique for selective and sensitive ultrasound molecular imaging by taking advantage of wideband transient high frequency acoustic emission from ultrasound contrast agents. The imaging modality makes use of a novel multi-frequency co-linear array (two outer 1.4MHz and one center 5.3MHz arrays) transducer integrated with the Siemens AntaresSystem. The imaging sequence includes a B-mode imaging pulse sequence in which a short pulse is transmitted with the outer low frequency arrays and received with the inner high frequency array (TLRH: transmit at low frequency and receive at high frequency), followed by a long radiation force pulse to induce immediate bubble adhesion using the center array, and a second B-mode imaging pulse sequence. The RF data obtained from the second B-mode pulse sequence are averaged and then subtracted from the first B-mode sequence. The imaging technique was tested in a targeted imaging phantom, where lipid-shelled biotin microbubbles flow within an avidin coated-cellulose. Results showed that tissue signals were suppressed up to 33 dB and a targeted bubble contrast-to-free bubble signal ratio of up to 23 dB was obtained from the composite sequence imaging.

Stereotactic Ablative Radiotherapy for the Treatment of Refractory Cardiac Ventricular Arrhythmia

A 71-year-old man with coronary artery disease, coronary artery bypass grafting in 2000, baseline ejection fraction of 0.24, and implantation of a single chamber implanted cardioverter defibrillator (ICD) in 2009 for ventricular tachycardia (VT) presented with continuous episodes of nonsustained and sustained VT refractory to sotalol and mexiletine. Despite angioplasty and stent for coronary artery disease, VT continued for 2 years. Medical history included atrial fibrillation and oxygen-dependent chronic obstructive pulmonary disease. Baseline electrocardiogram (ECG) showed atrial fibrillation with a ventricular rate of 82 beats per minute with inferior Q waves and QRS duration of 90 ms. Twelve-lead ECG during VT showed a regular, wide-complex tachycardia at 160 beats per minute (CL 380–400 ms), with a right bundle branch block pattern, superior axis, precordial transition at V3–V4. His ICD log showed numerous VT episodes, with a single morphology seen on intracardiac ventricular electrogram, cycle length 380–411ms. Episodes were nonsustained, pace-terminated, and shock-terminated. As catheter ablation was relatively medically contraindicated, he consented to a Food and Drug Administration and Institutional Review Board–approved compassionate-use protocol of stereotactic arrhythmia radioablation (STAR), noninvasive ablation of VT substrate by stereotactic ablative radiotherapy (SABR) techniques for tumors. STAR therapy was delivered in October, 2012. Baseline echocardiogram showed a dilated left ventricle (LV), ejection fraction of 0.24, with basal inferior aneurysm, and apical and infero-posterior akinesis. Positron emission tomography–computed tomography showed extensive hypometabolic scar in the LV extending between the LV base and the apex, involving the inferior, inferoseptal, and inferolateral walls. A target for STAR was delineated using proprietary visualization and contouring software (CardioPlan™, CyberHeart™, Portola Valley, CA), outlining the target volume corresponding to what would have been the …

In vivo dose measurement using TLDs and MOSFET dosimeters for cardiac radiosurgery

In vivo measurements were made of the dose delivered to animal models in an effort to develop a method for treating cardiac arrhythmia using radiation. This treatment would replace RF energy (currently used to create cardiac scar) with ionizing radiation. In the current study, the pulmonary vein ostia of animal models were irradiated with 6 MV X‐rays in order to produce a scar that would block aberrant signals characteristic of atrial fibrillation. The CyberKnife radiosurgery system was used to deliver planned treatments of 20–35 Gy in a single fraction to four animals. The Synchrony system was used to track respiratory motion of the heart, while the contractile motion of the heart was untracked. The dose was measured on the epicardial surface near the right pulmonary vein and on the esophagus using surgically implanted TLD dosimeters, or in the coronary sinus using a MOSFET dosimeter placed using a catheter. The doses measured on the epicardium with TLDs averaged 5% less than predicted for those locations, while doses measured in the coronary sinus with the MOSFET sensor nearest the target averaged 6% less than the predicted dose. The measurements on the esophagus averaged 25% less than predicted. These results provide an indication of the accuracy with which the treatment planning methods accounted for the motion of the target, with its respiratory and cardiac components. This is the first report on the accuracy of CyberKnife dose delivery to cardiac targets. PACS numbers: 87.53.Ly, 87.53.Bn

Removing local motion from ultrasonic images using nonaffine registration for contrast quantification

A contrast quantification package has been developed to be part of a medical ultrasound system. This package provides motion compensation through nonaffine image registration. An explanation of the image registration system is given. A set of analyses made with this system is presented; they show that the registration system provides significant improvements over using images without motion correction.

Synchronization of contrast agent destruction and imaging for perfusion assessment

Modifications were made to a commercial ultrasound scanner to improve established myocardial perfusion estimation methods. These modified methods were tested in a series of animal experiments where the coronary flow was controlled. The measured flow was related to perfusion parameters determined through ultrasonic imaging.

11A-3 A Novel Sensitive Targeted Imaging Technique for Ultrasonic Molecular Imaging

We have recently developed a targeted imaging technique for selective and sensitive ultrasound molecular imaging by taking advantage of wideband transient high frequency acoustic emission from ultrasound contrast agents. The imaging modality makes use of a novel multi-frequency co-linear array (two outer 1.4 MHz and one center 5.3 MHz arrays) transducer integrated with the Siemens Antares System. The imaging sequence includes a B-mode imaging pulse sequence in which a short pulse is transmitted with the outer low frequency arrays and received with the inner high frequency array (TLRH: transmit at low frequency and receive at high frequency), followed by a long radiation force pulse to induce immediate bubble adhesion using the center array, and a second B-mode imaging pulse sequence. The RF data obtained from the second B-mode pulse sequence are averaged and then subtracted from the first B-mode sequence. The imaging technique was tested in a targeted imaging phantom, where lipid-shelled biotin microbubbles flow within an avidin coated-cellulose. Results showed that tissue signals were suppressed up to 33 dB and a targeted bubble contrast-to-free bubble signal ratio of up to 23 dB was obtained from the composite sequence imaging.

Stereotactic Arrhythmia Radioablation (STAR) of Ventricular Tachycardia: A Treatment Planning Study

Purpose The first stereotactic arrhythmia radioablation (STAR) of ventricular tachycardia (VT) was delivered at Stanford on a robotic radiosurgery system (CyberKnife® G4) in 2012. The results warranted further investigation of this treatment. Here we compare dosimetrically three possible treatment delivery platforms for STAR. Methods The anatomy and target volume of the first treated patient were used for this study. A dose of 25 Gy in one fraction was prescribed to the planning target volume (PTV). Treatment plans were created on three treatment platforms: CyberKnife® G4 system with Iris collimator (Multiplan, V. 4.6)(Plan #1), CyberKnife® M6 system with InCise 2TM multileaf collimator (Multiplan V. 5.3)(Plan #2) and Varian TrueBeamTM STx with HD 120TM MLC and 10MV flattening filter free (FFF) beam (Eclipse planning system, V.11) (Plan #3 coplanar and #4 noncoplanar VMAT plans). The four plans were compared by prescription isodose line, plan conformity index, dose gradient, as well as dose to the nearby critical structures. To assess the delivery efficiency, planned monitor units (MU) and estimated treatment time were evaluated. Results Plans #1-4 delivered 25 Gy to the PTV to the 75.0%, 83.0%, 84.3%, and 84.9% isodose lines and with conformity indices of 1.19, 1.16, 1.05, and 1.05, respectively. The dose gradients for plans #1-4 were 3.62, 3.42, 3.93, and 3.73 with the CyberKnife® MLC plan (Plan #2) the best, and the TrueBeamTM STx co-planar plan (Plan #3) the worst. The dose to nearby critical structures (lung, stomach, bowel, and esophagus) were all well within tolerance. The MUs for plans #1-4 were 27671, 16522, 6275, and 6004 for an estimated total-treatment-time/beam-delivery-time of 99/69, 65/35, 37/7, and 56/6 minutes, respectively, under the assumption of 30 minutes pretreatment setup time. For VMAT gated delivery, a 40% duty cycle, 2400MU/minute dose rate, and an extra 10 minutes per extra arc were assumed. Conclusion Clinically acceptable plans were created with all three platforms. Plans with MLC were considerably more efficient in MU. CyberKnife® M6 with InCise 2TM collimator provided the most conformal plan (steepest dose drop-off) with significantly reduced MU and treatment time. VMAT plans were most efficient in MU and delivery time. Fluoroscopic image guidance removes the need for additional fiducial marker placement; however, benefits may be moderated by worse dose gradient and more operator-dependent motion management by gated delivery.

Analysis of Dose Distribution in the Heart for Radiosurgical Ablation of Atrial Fibrillation

In a treatment planning study, radiosurgical treatment plans designed to produce lesions on the left atrium were created using two different methodologies. In one, structures in the heart (mitral valve and coronary arteries) were designated as critical structures while this was not done in the second plan. The treatment plans that were created were compared with standards for heart dose used when treating spine tumors. Although the dosage for the whole heart greatly exceeded the dose standards, when only the dose to the ventricles was considered, the plan where the mitral valve was spared was very close to the dose standards. The ventricles received a substantially higher dose in the plan where the mitral valve was not a critical structure. Although neither treatment plan was delivered, this study demonstrated the feasibility of treating the heart while minimizing dose to the ventricles.