Jack Driller

Therapeutic Ultrasound in the Treatment of Glaucoma: II. Clinical Applications

Focused, high-intensity therapeutic ultrasound was used to treat 69 selected patients with uncontrollably elevated intraocular pressure (IOP). This new technique selectively thins scleral collagen, and produces focal damage to the ciliary epithelium. These tissue modifications provide a reduction in IOP pressure to 25 mmHg or less in 83% of patients with a minimum three-month follow-up period.

Therapeutic Ultrasound in the Treatment of Glaucoma: I. Experimental Model

Controlled ultrasonic energy was used to treat a series of laboratory animals in which glaucoma had been induced experimentally. Insonification successfully reduced elevated intraocular pressure in the majority (86%) of test animals. Histopathologic review of globes examined at varying time intervals following treatment showed localized thinning of the sclera with intact conjunctiva, allowing filtration and focal disruption of ciliary epithelium. This technique of treating elevated intraocular pressure in a noninvasive manner offers potential for clinical application in humans.

Ultrasonic hyperthermia and radiation in the management of intraocular malignant melanoma

Hyperthermia and radiation were used in combination to treat four patients with choroidal malignant melanoma. This technique uses ultrasonically induced hyperthermia synergistically with radiation to destroy tumor cells. The lower levels of radiation used should avoid the late vascular and inflammatory complications seen in conventional radiation therapy. Tumors were scanned by a computerized diagnostic ultrasound system before treatment and assigned an acoustic tissue type on the basis of a statistical comparison of their ultrasound backscatter spectrum with spectra of tumors of known pathologic status. During the follow-up period, the longest of which was 15 months, all tumors demonstrated regression patterns consistent with choroidal tumors of the same acoustic tissue types treated with conventional radiation therapy.

Treatment of Glaucoma with High-Intensity Focused Ultrasound

This report is a summary of results for 170 eyes of patients with refractory glaucoma treated with high-intensity focused ultrasound. The results are analyzed in terms of the effectiveness of various treatment regimens, complications, and classifications of the patient population according to such factors as age and etiology. The mean pretreatment intraocular pressure (IOP) for the ensemble of patients treated with optimal intensity levels was 38.6 mmHg. Whereas only 10% of these patients had an IOP of 25 mmHg or less prior to treatment, 90% had an IOP of 25 mmHg or less within 3 months of treatment. At 1 year after a single treatment, 65% of patients still maintained intraocular pressures of 25 mmHg or less, and 56% had pressures of 22 mmHg or less. The effectiveness of retreatment of failed or unresponsive cases was also investigated and found to have a degree of success comparable to that of initial treatments.

Ultrasonic Hyperthermia for Ophthalmic Therapy

Absfrucct-A theoretical model was developed to compute the spatiotemporal features of temperature rises induced in ocular tissue during exposure to high-intensity focused ultrasound. The model incorporates damage integral evaluation to predict the Occurrence and dimensions of thermally induced lesions. Experimental data confirmed the accuracy of computed lesion dimensions for scleral and chorioretinal lesions. Computed results also are in agreement with measured threshold exposure levels needed to produce minimal chorioretinal lesions. The model is being improved to account for blood-flow cooling effects during longterm hyperthermia. Data were collected using this long-term mode on Greene’s melanoma implanted in the rabbit choroid, and these data indicate that tumor regression can be achieved at levels that are consistent with damage integral predictions.

Effects of pulsed ultrasound on ocular tissue

Abstract Focused ultrasound at a center frequency of 9.8 MHz was used to create lesions of the retina and choroid in the proptosed eye of the anesthetized albino rabbit. Pulsed ultrasound was employed and results were compared to those obtained under continuous-wave (CW) exposures. Short pulses (e.g. 100 μsec) delivered at high repetition frequencies (e.g. 3 KHz) produced the same average intensity threshold values as those found for CW conditions. Longer pulses (e.g. 0.1 sec) delivered at low repetition frequencies (e.g. 2 Hz) produced lesions at lower temporally averaged intensities. The lowered thresholds are related to cyclical blanching occurring in insonified choroidal blood vessels. All lesion-producing intensities (approximately 100 W/cm2) were orders of magnitude larger than diagnostic levels.

Computer model of ultrasonic hyperthermia and ablation for ocular tumors using b-mode data

Computer simulations have been conducted to examine hyperthermia and ablation for treating ocular tumors. An interactive software package has been implemented that permits relevant tissue dimensions to be determined from B-mode data. This package also permits interactive beam positioning, and it provides image displays depicting computed absorbed doses and temperature rises. Results are presented showing how hyperthermia temperature patterns are influenced by beam position, beam geometry and frequency. Images showing ablative temperature rises at various time intervals are also presented. For hyperthermia, geometric models of beam profiles showed that a non-uniform beam pattern (with a central low-intensity region) can produce more uniform heating of small ocular tumors than a beam with a uniform intensity profile. For a given tumor, the uniformity of hyperthermia temperatures was found to be a function of frequency, with 4.75 MHz providing reasonably uniform results for typical tumor heights (near 7 mm). For ablation, diffraction computations were employed to calculate beam intensity profiles; results show an initially rapid rise in temperature levels with subsequent, slower heating beyond the -3-dB limits of the focal volume. The model is now being refined, and additional phenomena, including nonlinear propagation, will be incorporated.

DIAGNOSTIC HIGH-RESOLUTION ULTRASOUND IN DERMATOLOGY

During the past two decades., diagnostic ultrasound, which has gained an important place in many areas of medicine, has been extended to dermatology. The advantages of employing ultrasound for diagnosis in dermatology are clear. Dermatologists rely primarily on visual examination or on biopsy for assessment of skin. Biopsy, while more exact, has attendant pain and scarring. Ultrasound affords the possibility of non-invasive assessment of multiple areas of skin. In addition, ultrasound may appreciate aspects of skin that would not otherwise be recorded by visual observation or by histologic examination.In this paper, we will briefly review the technology that has made ultrasound applicable to dermatology, describe some specific applications of ultrasound to dermatology, and discuss potential future uses of ultrasound for assessment of skin.

ULTRASONIC TISSUE CHARACTERIZATION AND HISTOPATHOLOGY IN TUMOR XENOGRAFTS FOLLOWING ULTRASONICALLY INDUCED HYPERTHERMIA

Cells derived from human skin malignant melanoma were implanted subcutaneously in athymic nude mice. Tumors which developed at the implant site were treated with ultrasonically induced hyperthermia at 49 degrees C for 30 min. Tumors were scanned with a computerized diagnostic ultrasound system before and after treatment. Light (LM) and electron (EM) micrographs of tumors were obtained after scanning. Changes in ultrasonic tissue characterization parameters following treatment were well correlated with histopathologic changes observed in tumors. The results are significant in terms of clinical application of ultrasonically induced hyperthermia for treatment of intraocular tumors and the noninvasive monitoring of tumors by use of diagnostic ultrasound.

THERMAL MODEL FOR ULTRASONIC TREATMENT OF GLAUCOMA

Focused ultrasound, at a frequency of 4.6 MHz, was used to create lesions of the sclera in the proptosed glaucomatous eye of the anesthetized albino rabbit, with the result that elevated intra-ocular pressures were reduced to normal levels. Initial trials on carefully selected glaucoma patients have also shown that pressure reductions can be produced with high-intensity ultrasound. A theoretical model was developed to compute the spatio-temporal features of temperature rises induced in the sclera during these treatments. Experimental data confirmed the accuracy of the model.