Chris J. Diederich

Ultrasound technology for hyperthermia

Hyperthermia (HT) is used in the clinical management of cancer and benign disease. Numerous biological and clinical investigations have demonstrated that HT in the 41-45 degrees C range can significantly enhance clinical responses to radiation therapy, and has potential for enhancing other therapies, such as chemotherapy, immunotherapy and gene therapy. Furthermore, high-temperature hyperthermia (greater than 50 degrees C) alone is being used for selective tissue destruction as an alternative to conventional invasive surgery. The degree of thermal enhancement of these therapies is strongly dependent on the ability to localize and maintain therapeutic temperature elevations. Due to the often heterogeneous and dynamic properties of tissues, most notably blood perfusion and the presence of thermally significant blood vessels, therapeutic temperature elevations are difficult to spatially and temporally control during these forms of HT therapy. However, ultrasound technology has significant advantages that allow for a higher degree of spatial and dynamic control of the heating compared to other commonly utilized heating modalities. These advantages include a favorable range of energy penetration characteristics in soft tissue and the ability to shape the energy deposition patterns. Thus, heating systems have been developed for interstitial, intracavitary, or external approaches that utilize properties such as multiple transducer arrays, phased arrays, focused beams, mechanical and/or electrical scanning, dynamic frequency control and transducers of various shapes and sizes. This article provides a general review of a selection of ultrasound hyperthermia systems that are either in clinical use or currently under development, that utilize these advantages as a means to better localize and control HT for the aforementioned therapies.

Thermal ablation and high-temperature thermal therapy: Overview of technology and clinical implementation

High-temperature hyperthermia or thermal therapy is being applied for destruction of cancerous tissue, eradication or reduction of benign tumours and targeted tissue modification and remodelling. Many of these high-temperature technologies provide a minimally-invasive alternative with lower morbidities compared to the traditional surgical procedures. The effects of high-temperature thermal exposure on tissues, examples of heating technology and procedures of clinical practice related to high-temperature thermal therapy are reviewed. This brief review encompasses interstitial, endocavity, intraluminal and external applications of RF, microwave, ultrasound, laser and thermal conduction energy sources. The technology is prevalent and in various levels of advancement, with the move toward more spatially-accurate and controllable heating systems combined with image-guidance and treatment verification warranted, especially for the treatment of cancer.

Acute biomechanical and histological effects of intradiscal electrothermal therapy on human lumbar discs

Study Design. Human cadaver lumbar spines were used to assess the acute effects of intradiscal electrothermal therapy in vitro. Objective. To determine whether intradiscal electrothermal therapy produces acute changes in disc histology and motion segment stability. Summary of Background Data. Intradiscal electrothermal therapy has been introduced as an alternative for the treatment of discogenic low back pain. Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested including shrinkage of the nucleus or sealing of the anulus fibrosus by contraction of collagen fibers, and thermal ablation of sensitive nerve fibers in the outer anulus. Methods. Intradiscal electrothermal therapy was performed with the Spinecath by Oratec on 19 fresh, frozen human lumbar cadaver specimens. In a separate study, eight specimens were tested biomechanically and instrumented to map the thermal distribution, whereas five specimens were tested only biomechanically, both before and after intradiscal electrothermal therapy. Six additional specimens were heated with intradiscal electrothermal therapy, and the resulting canal was backfilled with a silicone rubber compound to allow colocalization of the catheter and anular architecture. Results. A consistent pattern of increased motion and decreased stiffness was observed. For the specimens in which only biomechanical measurements were taken, a 10% increase in the motion, on the average, at 5 Nm torque was observed after intradiscal electrothermal therapy. No apparent alteration of the anular architecture was observed around the catheter site in the intradiscal electrothermal therapy–treated discs. Conclusion. The data from this study suggest that the temperatures developed during intradiscal electrothermal therapy are insufficient to alter collagen architecture or stiffen the treated motion segment acutely.

Transurethral ultrasound applicators with directional heating patterns for prostate thermal therapy: In vivo evaluation using magnetic resonance thermometry

A catheter-based transurethral ultrasound applicator with angularly directional heating patterns has been designed for prostate thermal therapy and evaluated in canine prostate in vivo using MRI to monitor and assess performance. The ultrasound transducer array (3.5 mm diameter tubular transducers, 180 degrees active sectors, approximately 7.5 MHz) was integrated to a flexible delivery catheter (4 mm OD), and encapsulated within an expandable balloon (35 mm x 10 mm OD, 80 ml min(-1) ambient water) for coupling and cooling of the prostatic urethra. These devices were used to thermally coagulate targeted portions of the canine prostate (n = 2) while using MR thermal imaging (MRTI) to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. MRTI was based upon the complex phase-difference mapping technique using an interleaved gradient echo-planar imaging sequence with lipid suppression. MRTI derived temperature distributions, thermal dose exposures, T1-contrast enhanced MR images, and histology of sectioned prostates were used to define destroyed tissue zones and characterize the three-dimensional heating patterns. The ultrasound applicators produced approximately 180 degrees directed zones of thermal coagulation within targeted tissue which extended 15-20 mm radially to the outer boundary of the prostate within 15 min. Transducer activation lengths of 17 mm and 24 mm produced contiguous zones of coagulation extending axially approximately 18 mm and approximately 25 mm from base to apex, respectively. Peak temperatures around 90 degrees C were measured, with approximately 50 degrees C-52 degrees C corresponding to outer boundary t43 = 240 min at approximately 15 min treatment time. These devices are MRI compatible, and when coupled with multiplanar MRTI provide a means for selectively controlling the length and sector angle of therapeutic thermal treatment in the prostate.

MRI-guided thermal therapy of transplanted tumors in the canine prostate using a directional transurethral ultrasound applicator

To evaluate MRI‐based techniques for visual guidance, thermal monitoring, and assessment during transurethral ultrasound thermal therapy of implanted tumors in an in vivo canine prostate model.

Transurethral ultrasound array for prostate thermal therapy: initial studies

This study presents the initial evaluation of an applicator designed for transurethral ultrasound thermotherapy (TUST) of prostate tissue in the treatment of benign prostatic hyperplasia (BPH) and cancer. A tubular multitransducer applicator, consisting of four piezoceramic tubes (2.5 mm diameter, 6 mm long, 6.8 MHz) under separate power control, was designed to fit within a semiflexible water-cooled temperature-regulated delivery catheter to be placed within the prostatic urethra during therapy. Sonication patterns were tailored to produce power depositions which avoid nontargeted tissues, such as the rectum. Computer simulations have demonstrated that 1.4-2.0 cm radial therapeutic zones (temperatures /spl ges/50-55/spl deg/C, thermal doses >300 EM/sub 43/) with concurrent sparing of the urethral mucosa can be produced within prostate tissue having blood perfusion as high as 10 kg m/sup -3/ s/sup -1/ within 15-30 min. Acoustic distributions and power output measurements of a prototype applicator have demonstrated acoustic power levels approaching 10 W per each sectored transducer segment are attainable, with beam profiles collimated within the transducer length and with desired circumferential distributions. In vivo thermal dosimetry characterizations of these transurethral applicators have indicated that therapeutic temperatures between 50 and 90/spl deg/C are attainable, controllable in the longitudinal and circumferential directions, and have effective radial heating. These results clearly indicate that transurethral ultrasound applicators have potential to provide improved spatial localization and control of the heating distribution over existing transurethral thermal therapy techniques for both hyperthermia and thermal coagulative therapy of the prostate.

Ultrasound applicators with integrated catheter-cooling for interstitial hyperthermia: theory and preliminary experiments.

Theoretical and experimental methods were used to evaluate a design of ultrasound applicators for interstitial hyperthermia. The basic schema consists of a multielement array of tubular piezoceramic radiators (1.5-1.6 mm diameter), each 5-10 mm long with separate power control, designed to be inserted within a 13-14 gauge closed-end brachytherapy implant catheter. Channels for circulating temperature-regulated water are integrated within the applicator to provide control of the catheter/tissue interface temperature. A quantitative theoretical analysis was undertaken to determine heating performance as a function of applicator spacing, blood perfusion, catheter material, frequency and required acoustic power output. Prototype multielement applicators were constructed and characterized in terms of acoustic pressure-squared distributions and acoustic power output capabilities. This study demonstrated distinct advantages of these catheter-cooled multielement ultrasound applicators within an implant, including higher T90s achievable within highly perfused tissues, dynamic control of the longitudinal power deposition, and no interaction between adjacent applicators or elements or sensitivity to applicator alignment. Preliminary measurements of prototype devices have indicated that implementation of these interstitial ultrasound applicators with integrated catheter-cooling is practicable, yet further development and in vivo verification of performance is warranted.

Magnetic resonance-guided high-intensity ultrasound ablation of the prostate.

Objectives: This paper describes our work in developing techniques and devices for magnetic resonance (MR)-guided high-intensity ultrasound ablation of the prostate and includes review of relevant literature. Methods: Catheter-based high-intensity ultrasound applicators, in interstitial and transurethral configurations, were developed to be used under MR guidance. Magnetic resonance thermometry and the relevant characteristics and artifacts were evaluated during in vivo thermal ablation of the prostate in 10 animals. Contrast-enhanced MR imaging (MRI) and diffusion-weighted MRI were used to assess tissue damage and compared with histology. Results: During evaluation of these applicators, MR thermometry was used to monitor the temperature distributions in the prostate in real time. Magnetic resonance-derived maximum temperature thresholds of 52°C and thermal dose thresholds of 240 minutes were used to control the extent of treatment and qualitatively correlated well with posttreatment imaging studies and histology. The directional transurethral devices are selective in their ability to target well-defined regions of the prostate gland and can be rotated in discrete steps to conform treatment to prescribed boundaries. The curvilinear applicator is the most precise of these directional techniques. Multisectored transurethral applicators, with dynamic angular control of heating and no rotation requirements, offer a fast and less complex means of treatment with less selective contouring. Conclusions: The catheter-based ultrasound devices can produce spatially selective regions of thermal destruction in prostate. The MR thermal imaging and thermal dose maps, obtained in multiple slices through the target volume, are useful for controlling therapy delivery (rotation, power levels, duration). Contrast-enhanced T1-weighted MRI and diffusion-weighted imaging are useful tools for assessing treatment.

MR‐guided focused ultrasound surgery, present and future

MR-guided focused ultrasound surgery (MRgFUS) is a quickly developing technology with potential applications across a spectrum of indications traditionally within the domain of radiation oncology. Especially for applications where focal treatment is the preferred technique (for example, radiosurgery), MRgFUS has the potential to be a disruptive technology that could shift traditional patterns of care. While currently cleared in the United States for the noninvasive treatment of uterine fibroids and bone metastases, a wide range of clinical trials are currently underway, and the number of publications describing advances in MRgFUS is increasing. However, for MRgFUS to make the transition from a research curiosity to a clinical standard of care, a variety of challenges, technical, financial, clinical, and practical, must be overcome. This installment of the Vision 20∕20 series examines the current status of MRgFUS, focusing on the hurdles the technology faces before it can cross over from a research technique to a standard fixture in the clinic. It then reviews current and near-term technical developments which may overcome these hurdles and allow MRgFUS to break through into clinical practice.

Evaluation of multielement catheter-cooled interstitial ultrasound applicators for high-temperature thermal therapy

Catheter-cooled (CC) interstitial ultrasound applicators were evaluated for their use in high-temperature coagulative thermal therapy of tissue. Studies in ex vivo beef muscle were conducted to determine the influences of applied electrical power levels (5-20 W per element), catheter flow rate (20-60 ml min(-1)), circulating water temperature (7-40 degrees C), and frequency (7-9 MHz) on temperature distribution and thermal lesion geometry. The feasibility of using multiple interstitial applicators to thermally coagulate a predetermined volume of tissue was also investigated. Results of these studies revealed that the directional shape of the thermal lesions is maintained with increasing time and power. Radial depths of the thermal lesions ranged from 10.7 +/- 0.7 mm after heating for 4 min with an applied power level of 5 W, to 16.2 +/- 1.4 mm with 20 W. The axial length of the thermal lesions is controlled tightly by the number of active transducers. A catheter flow rate of 20 to 40 ml min(-1) (52.2 +/- 5.5 kPa at 40 ml min(-1)) with 22 degrees C water was determined to provide sufficient cooling of the transducers for power levels used in this study. In vivo temperatures measured in the center of a 3-cm-diam peripheral implant of four applicators in pig thigh muscle reached 89.3 degrees C after 4 min of heating, with boundaries of coagulation clearly defined by applicator position and directivity. Conformability of heating in a clinically relevant model was demonstrated by inserting two directional CC applicators with a 2 cm separation within an in vivo canine prostate, and generating a thermal lesion measuring 3.8 cm x 2.2 cm in cross section while directing energy away from, and protecting the rectum. Maximum measured temperatures at midgland exceeded 90 degrees C within 20 min of heating. The results of this study demonstrate the utility of single or multiple CC applicators for conformal thermal coagulation and high temperature thermal therapy, with potential for clinical applications in sites such as prostate, liver, breast, or uterus.