Dustin E. Kruse

Real-time beam predictions are highly desirable for the patient-specific computations required in ultrasound therapy guidance and treatment planning. To address the longstanding issue of the computational burden associated with calculating the acoustic field in large volumes, we use graphics processing unit (GPU) computing to accelerate the computation of monochromatic pressure fields for therapeutic ultrasound arrays. In our strategy, we start with acceleration of field computations for single rectangular pistons, and then we explore fast calculations for arrays of rectangular pistons. For single-piston calculations, we employ the fast near-field method (FNM) to accurately and efficiently estimate the complex near-field wave patterns for rectangular pistons in homogeneous media. The FNM is compared with the Rayleigh-Sommerfeld method (RSM) for the number of abscissas required in the respective numerical integrations to achieve 1%, 0.1%, and 0.01% accuracy in the field calculations. Next, algorithms are described for accelerated computation of beam patterns for two different ultrasound transducer arrays: regular 1-D linear arrays and regular 2-D linear arrays. For the array types considered, the algorithm is split into two parts: 1) the computation of the field from one piston, and 2) the computation of a piston-array beam pattern based on a pre-computed field from one piston. It is shown that the process of calculating an array beam pattern is equivalent to the convolution of the single-piston field with the complex weights associated with an array of pistons. Our results show that the algorithms for computing monochromatic fields from linear and regularly spaced arrays can benefit greatly from GPU computing hardware, exceeding the performance of an expensive CPU by more than 100 times using an inexpensive GPU board. For a single rectangular piston, the FNM method facilitates volumetric computations with 0.01% accuracy at rates better than 30 ns per field point. Furthermore, we demonstrate array calculation speeds of up to 11.5 × 10 ⁹ field-points per piston per second (0.087 ns per field point per piston) for a 512-piston linear array. Beam volumes containing 256 ³ field points are calculated within 1 s for 1-D and 2-D arrays containing 512 and 20 ² pistons, respectively, thus facilitating future real-time thermal dose predictions.

Gold nanoparticles (GNPs) are nontoxic, can be functionalized with ligands, and preferentially accumulate in tumors. We have developed a 13.56-MHz RF-electromagnetic field (RFEM) delivery system capable of generating high E-fleld strengths required for noninvasive, noncontact heating of GNPs. The bulk heating and specific heating rates were measured as a function of NP size and concentration. It was found that heating is both size and concentration dependent, with 5 nm particles producing a 50.6 ± 0.2°C temperature rise in 30 s for 25 μg/mL gold (125 W input). The specific heating rate was also size and concentration dependent, with 5 nm particles producing a specific heating rate of 356 ± 78 kW/g gold at 16 μg/mL (125 W input). Furthermore, we demonstrate that cancer cells incubated with GNPs are killed when exposed to 13.56 MHz RF-EM fields. Compared to cells that were not incubated with GNPs, three out of four RF-treated groups showed a significant enhancement of cell death with GNPs (p <; 0.05). GNP-enhanced cell killing appears to require temperatures above 50°C for the experimental parameters used in this study. Transmission electron micrographs show extensive vacuolization with the combination of GNPs and RF treatment.

A new system is presented for generating controlled tissue heating with a clinical ultrasound scanner, and initial in vitro and in vivo results are presented that demonstrate both transient and sustained heating in the mild-hyperthermia range of 37°C-42°C. The system consists of a Siemens Antares ultrasound scanner, a custom dual-frequency three-row transducer array and an external temperature feedback control system. The transducer has two outer rows that operate at 1.5 MHz for tissue heating and a center row that operates at 5 MHz for B-mode imaging to guide the therapy. We compare the field maps obtained using a hydrophone against calculations of the ultrasound beam based on monochromatic and linear assumptions. Using the finite-difference time-domain (FDTD) method, we compare predicted time-dependent thermal profiles to measured profiles for soy tofu as a tissue-mimicking phantom. In vitro results show differential heating of 6°C for chicken breast and tofu. In vivo tests of the system were performed on three mice bearing Met-1 tumors, which is a model of aggressive, metastatic, and highly vascular breast cancer. In superficially implanted tumors, we demonstrate controlled heating to 42°C. We show that the system is able to maintain the temperature to within 0.1°C of the desired temperature both in vitro and in vivo.

The development of transgenic reporter mice and advances in in vivo optical imaging have created unique opportunities to assess and analyze biological responses to thermal therapy directly in living tissues. Reporter mice incorporating the regulatory regions from the genes encoding the 70 kDa heat-shock proteins (Hsp70) and firefly luciferase (luc) as reporter genes can be used to non-invasively reveal gene activation in living tissues in response to thermal stress. High-intensity-focused ultrasound (HIFU) can deliver measured doses of acoustic energy to highly localized regions of tissue at intensities that are sufficient to stimulate Hsp70 expression. We report activation of Hsp70-luc expression using 1 s duration HIFU heating to stimulate gene expression in the skin of the transgenic reporter mouse. Hsp70 expression was tracked for 96 h following the application of 1.5 MHz continuous-wave ultrasound with spatial peak intensities ranging from 53 W cm(-2) up to 352 W cm(-2). The results indicated that peak Hsp70 expression is observed 6-48 h post-heating, with significant activity remaining at 96 h. Exposure durations were simulated using a finite-element model, and the predicted temperatures were found to be consistent with the observed Hsp70 expression patterns. Histological evaluation revealed that the thermal damage starts at the stratum corneum and extends deeper with increasing intensity. These results indicated that short-duration HIFU may be useful for inducing heat-shock expression, and that the period between treatments needs to be greater than 96 h due to the protective properties of Hsp70.

We present a new signal processing strategy for high frequency color flow mapping in moving tissue environments. A new application of an eigendecomposition-based clutter rejection filter is presented with modifications to deal with high blood-to-clutter ratios (BCR). Additionally, a new method for correcting blood velocity estimates with an estimated tissue motion profile is detailed. The performance of the clutter filter and velocity estimation strategies is quantified using a new swept-scan signal model. In vivo color flow images are presented to illustrate the potential of the system for mapping blood flow in the microcirculation with external tissue motion.

We present a new signal processing strategy for high frequency color flow mapping in moving tissue environments. A new application of an eigendecomposition-based clutter rejection filter is presented with modifications to deal with high blood-to-clutter ratios (BCR). Additionally, a new method for correcting blood velocity estimates with an estimated tissue motion profile is detailed. The performance of the clutter filter and velocity estimation strategies is quantified using a new swept-scan signal model. In vivo color flow images are presented to illustrate the potential of the system for mapping blood flow in the microcirculation with external tissue motion.