Thomas Ryan

Experimental brain hyperthermia: Techniques for heat delivery and thermometry☆

An experimental canine brain model was developed to assess the effects of hyperthermia for a range of time and temperature endpoints, delivered within a specified distance of an interstitial microwave antenna in normal brain. The target temperature location was defined radially at 5.0 or 7.5 mm from the microwave source at the longitudinal location of maximum heating along the antenna in the left cerebral cortex. Temperatures were measured with fiberoptic probes in a coronal plane at this location in an orthogonal catheter at 1.0 mm intervals. Six antennas were evaluated, including dipole, modified dipole, and four shorted helical antennas with coil lengths from 0.5 to 3.9 cm. Antenna performance evaluated in tissue equivalent phantom by adjusting frequency at a fixed insertion depth of 7.8 cm or adjusting insertion depth at 915 MHz showed dipoles to be much more sensitive to insertion depth and frequency change than helical antennas. Specific absorption rate (SAR) was measured in a brain/skull phantom and isoSAR contours were plotted. In vivo temperature studies were also used to evaluate antenna performance in large and small canine brain tissues. A helical antenna with a 2.0 cm coil length driven at 915 MHz was chosen for the beagle experiments because of tip heating characteristics, well-localized heating along the coil length, and heating pattern appropriate to the smaller beagle cranial vault. Verification of lesion dimensions in 3-D was obtained by orthogonal MRI scans and histology to document the desired heat effect, which was to obtain an imagable lesion with well-defined blood-brain-barrier breakdown and necrotic zones. The desired lesion size was between 1.5 to 2.5 cm diameter radially, in the coronal plane with the greatest diameter.

Absorbed power deposition for various insertion depths for 915 MHZ interstitial dipole antenna arrays: Experiment versus theory

Dipole antennas are commonly used in interstitial clinical hyperthermia treatments because of their compatibility with brachytherapy techniques and their good power deposition patterns when used in arrays. For accurate treatment planning, however, there must be a comprehensive knowledge base to predict the power deposition patterns when insertion depth is a non-resonant length. This is especially true for insertion depths that result in significant power deposition outside of the antenna junction plane and presumably outside of the tumor volume. A computer controlled measurement system was used with a muscle equivalent phantom to make measurements of specific absorption rate (SAR) or absorbed power per unit mass of tissue at 598 points in a plane. The diagonal plane was the measurement plane of choice because it characterized the SAR profiles at the array center as well as areas in the proximity of the antennas. Dartmouth dipole antennas were used (0.9 mm O.D.) in brachytherapy catheters with inner catheters (2.2 mm O.D./1.2 mm I.D.). The resonant half-wavelength of this dipole antenna/catheter combination is 7.8 cm. A choke modification of the dipole was also investigated. Four antennas were used in a boxlike configuration with 2.0 cm separation. Insertion depths of 5.9, 7.8, 9.8, 12.7, 15.6 and 17.6 cm were used. The hA subsection (junction to tip) was held constant at 3.9 cm. Plots were made of the experimental SAR data normalized to the maximum SAR measured in the plane. Theoretical plots were calculated in the same plane for each of the insertion depths. SAR comparisons were also made longitudinally along the central axis of the array and through the antenna junctions in the diagonal plane for resonant half-wavelength insertion depth. Experimental results verified theoretical predictions of the existence of a secondary hot-spot in the center of the array, but outside of the antenna junction plane and approximately a quarter-wavelength from the insertion point. This secondary hot-spot appears for all insertion depths greater than 10 cm. At longer insertion depths approaching a full wavelength, however, this secondary peak is not dominant. Choke antennas demonstrated a solution to the problem of shifting SAR patterns with varying insertion depths by restricting the active length of the antenna.

Effect of phase modulation on the temperature distribution of a microwave hyperthermia antenna array in vivo.

Perfused, canine skeletal muscle and the brain tumour of a cancer patient were heated with an array of four parallel, interstitial antennas placed on the corners of a 2-cm square and driven at 915 MHz. The temperature distributions along the axial and diagonal catheters were measured with equal-phase driving of the antennas and with several time-varying schemes of driving phase differences among the antennas. When equal-phase driving was replaced by a rotating scheme of 90 degrees driving phase differences, the tissue area in the junction plane heated above a normalized index temperature of 0.6 increased by a factor of about 1.25. With a rotating phase of 135 degrees, the same area increased by a factor of about 1.6. The axial temperature distribution was not affected significantly by driving phase.

Techniques for intraoperative hyperthermia with ultrasound: the Dartmouth experience with 19 patients

Over the course of 3 years, tumours of 19 patients were heated with ultrasound in the operating room during surgical resection. Immediately following intraoperative radiation therapy, thermocouples were inserted into tumour and adjacent normal structures. Patients were then given a 60-min heat treatment with ultrasound after a 10-15-min heatup period. Temperatures were measured at a total of 133 fixed locations for the 19 patient series. Temperature mapping was done in the tumour volume when logistically feasible. Treatment sites included colorectal (n = 3), portahepatus (n = 1), pancreas (n = 7), liver (n = 1), pelvis (n = 3), sacrum (n = 2), and abdomen (n = 2). A sterile, constant-volume water circulating system was utilized to control surface temperatures. Three generations of completely immersible transducers were designed over the course of this study with a 4-cm height specification. Since the ultrasound transducer was assembled on the sterile field during surgery, a 1, 2 or 3 MHz ceramic element was placed in either a 6, 8 or 10 cm diameter aluminium housing to conform the acoustic field to the tumour size. Average of the maximum temperatures attained was 46.6 degrees C. Temperature with which 90% of all measured points equalled or exceeded (T90) was 39.2 degrees C. The T50 was 42.9 degrees C. This compared favourably with T90 and T50 of 38.8 and 41.9 degrees C, respectively, in our outpatient clinic series, in which superficial tumours were treated with a similar external applicator, and patient tolerance was often a treatment limitation.

Iridium-192 Brachytherapy in Combination with Interstitial Microwave-Induced Hyperthermia for Malignant Glioma

A phase I clinical trial assessing the feasibility and safety of hyperthermia in combination with 192Ir brachytherapy (60 Gy) for the treatment of malignant glioma now includes 14 patients. Hyperthermia (42-43 degrees C at tumor margin for 60 min) has been induced using stereotactically implanted afterloading catheters and a microwave (915 or 2,450 MHz) antenna array. Thermometry recorded along each catheter confirms the general ability of the technique to heat such volumes, but thermal heterogeneities are documented. Transient or permanent worsening of previous neurologic deficit, seen in 7 patients, has been the most common morbidity.

THREE-DIMENSIONAL THEORETICAL TEMPERATURE DISTRIBUTIONS PRODUCED BY 915 MHz DIPOLE ANTENNA ARRAYS WITH VARYING INSERTION DEPTHS IN MUSCLE TISSUE

Interstitial microwave antenna array hyperthermia (IMAAH) systems are currently being used in the treatment of cancer. The insertion depth of an interstitial microwave antenna, defined as the length of the antenna from the tip to the point of insertion in tissue, affects its ability to produce uniform power deposition patterns in tumor volumes. The effect of varying insertion depths on the ability of an IMAAH system to heat two theoretical tumor models was examined. Four dipole microwave antennas were implanted in a 2 x 2 cm array and driven at 915 MHz in muscle tissue. The explicit power deposition patterns were calculated for each insertion depth using known theory. The bioheat transfer equation was solved for the 3-dimensional steady-state temperature distributions in cylindrical and ellipsoidal tumor models using a finite element method. Homogeneous and nonhomogeneous blood flow models were considered. As a basis of comparison of the various temperature distributions, the volume of tumor heated to greater than or equal to 43 degrees C was calculated. Under the conditions of this study, the insertion depth was shown to have a significant effect on the ability of an IMAAH system to heat the tumor volumes. A sharp decrease in the percentage of tumor volume heated to greater than or equal to 43 degrees C was seen for insertion depths between 7.8 and 14.6 cm. At an insertion depth of 11.7 cm (3/4 lambda) there was virtually no heating of the tumor. Regions of elevated power occurred outside of the desired treatment volume, stressing the importance of adequate thermometry techniques and demonstrating the need for hyperthermia treatment planning prior to implantation of an antenna array. Plots of the power deposition patterns and the corresponding temperatures produced in the diagonal plane of the antenna arrays are present.

Interstitial microwave hyperthermia and brachytherapy for malignancies of the vulva and vagina I: Design and testing of a modified intracavitary obturator

A vaginal obturator was fabricated to be used in combination with implanted catheters to provide microwave hyperthermia and brachytherapy to the vulva and vaginal wall. This site is difficult to heat or irradiate solely with interstitial techniques. The obturator was modified to provide grooves for the mounting of interstitial catheters into the outer wall and was matched with a template for circumferential implants. Power deposition tests were done using arrays of three microwave antenna designs: dipole (hA = hB = 3.9 cm), helical (3.9 cm coil, shorted), and modified dipole (1.0 cm helix on dipole tip) to test the performance of the obturator. The obturator and four non-obturator catheters were positioned in muscle-equivalent phantom. Two obturator catheters along with two free-standing catheters formed the obturator array. Four freestanding catheters formed the non-obturator array. Power deposition or specific absorption rate (SAR) measurements were made along the central axis, bisect, and diagonal transect of each array. SAR results showed that antennas in the obturator wall radiated as dipole theory predicts, although with less power density when compared to antennas in the same catheters spaced 1.8 cm from the obturator. This could be compensated for by increasing the power to the antennas in the obturator by 42%. Adjacent pairs of antennas were placed 90 degrees out of phase for 0.25 sec and rotated around the array. Phase rotation demonstrated that the central array SAR peaks could be lowered from 100% to 50% SAR, with dipole antennas thus resulting in lowered peak temperatures and the ability to heat larger volumes by improving the distribution of power. With helical antennas, there was 50% SAR at the array center when operated coherently without phase rotation. Three patients were treated with the obturator and a custom-made template using dipole antennas, and temperatures were measured in five obturator catheters. Therapeutic heating was measured in the catheters on the obturator between antennas in contact with the vaginal mucosa.

IS THE USE OF DRUG-ELUTING STENTS RELATED TO THE RISK OF TARGET VESSEL REVASCULARIZATION

The benefit of drug-eluding stents (DES) in reducing target vessel revascularization (TVR) is greatest in patients at high risk of restenosis with bare metal stents (BMS). Lowering the risk of TVR with DES must be weighed against the potential increased risks of stent thrombosis and of bleeding from