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Biomedical subjects

J Driller

Publications and source records attributed to J Driller.

At least 19 recordsLinked to original sources

Assessment of dental caries with Digital Imaging Fiber-Optic TransIllumination (DIFOTI): in vitro study.

This paper describes Digital Imaging Fiber-Optic TransIllumination (DIFOTI-TM), a new method for the reliable detection of dental caries. Images of teeth obtained through visible-light, fiber-optic transillumination (FOTI) are acquired with a digital CCD camera, and sent to a computer for analysis with dedicated algorithms. The algorithms were developed to facilitate the location and diagnosis of carious lesions by the operator in real time, and provide quantitative characterization for monitoring of the lesions. The DIFOTI method has been tested by imaging teeth in vitro. The results suggest the superior sensitivity of DIFOTI for detection of approximal, occlusal and smooth-surface caries vis-à-vis radiological imaging.

Dental Caries↗

Diagnostic ultrasound in dermatology: current uses and future potential.

Although ultrasound has been used for many years for a variety of medical diagnostic purposes, only recently have systems been designed that allow for its application to skin. High-resolution ultrasound systems now permit accurate, quantitative, noninvasive assessment of skin and cutaneous diseases. This technique will assist in the management of both inflammatory and neoplastic processes. Scans of skin obtained with a prototype high-resolution ultrasound system are presented. The computer-assisted creation of three-dimensional images from sequential B-mode scans is described.

Humans↗

Three-dimensional imaging for diagnostic ultrasound in dermatology.

BACKGROUND: Visual examination and cutaneous biopsies, two major tools in dermatologic diagnosis, do not provide structural information regarding the entire tissue volume. OBJECTIVE: Our purpose was to develop a high-resolution ultrasound system that quickly, with minimal operator interaction, displays structural data on the entire tissue volume. METHODS: A prototype ultrasound B-scan system was developed and operated at nominal center frequencies between 35 and 50 MHz, with computer processing of data to produce three-dimensional images. These images displayed as three-dimensional "blocks" can be sectioned to provide multiple images of internal structure (i.e., "acoustic biopsies"). RESULTS: B-scans and associated three-dimensional images were obtained from assorted skin sites in selected patients. CONCLUSION: This technique provides a valuable diagnostic tool that is now being further evaluated.

Adult↗

Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro.

Raf-1 is a serine/threonine kinase which is essential in cell growth and differentiation. Tyrosine kinase oncogenes and receptors and p21ras can activate Raf-1, and recent studies have suggested that Raf-1 functions upstream of MEK (MAP/ERK kinase), which phosphorylates and activates ERK. To determine whether or not Raf-1 directly activates MEK, we developed an in vitro assay with purified recombinant proteins. Epitope-tagged versions of Raf-1 and MEK and kinase-inactive mutants of each protein were expressed in Sf9 cells, and ERK1 was purified as a glutathione S-transferase fusion protein from bacteria. Raf-1 purified from Sf9 cells which had been coinfected with v-src or v-ras was able to phosphorylate kinase-active and kinase-inactive MEK. A kinase-inactive version of Raf-1 purified from cells that had been coinfected with v-src or v-ras was not able to phosphorylate MEK. Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1. We conclude that MEK is a direct substrate of Raf-1 and that the activation of MEK by Raf-1 is due to phosphorylation by Raf-1, which is sufficient for MEK activation. We also tested the ability of protein kinase C to activate Raf-1 and found that, although protein kinase C phosphorylation of Raf-1 was able to stimulate its autokinase activity, it did not stimulate its ability to phosphorylate MEK.

Animals↗

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.

Body Temperature↗

Computer simulations of ultrasonic heating for ocular therapy.

Computer simulations are being performed to model the temperature patterns produced during ultrasonically induced hyperthermia of ocular tumours. The software package for these simulations incorporates operator interaction and uses tissue geometry obtained from B-mode data. Previous studies used geometric approximations for the incident beams used for hyperthermia. In the current study, these beams were computed using diffraction analysis to obtain more realistic simulations of clinical exposures.

Body Temperature↗

Histologic effects of contact ultrasound for the treatment of glaucoma.

The histologic effects of a contact ultrasound applicator were compared with those of the immersion applicator that is currently used clinically for the treatment of glaucoma. The applicator coupling cone uses a distensible rubber membrane that can be inflated to control stand-off distance relative to the surface of the eye. This feature allows the focal point of the therapeutic beam to be placed at selective depths. Histologic comparisons of lesions in rabbit and pig eyes showed lesions in the sclera and ciliary body that were similar to those produced by the immersion transducer when the same focal position was used. Moving the focal point to a greater depth resulted in less superficial damage, yet still produced ciliodestruction. Damage to the blood supply of the ciliary body, as found in human cadaver eyes, may be an additional mechanism of action of therapeutic ultrasound, and perhaps of other transscleral high-energy modalities.

Animals↗

Production of corneal lesions using high-intensity focused ultrasound.

In order to study the potential use of ultrasound as a noninvasive system for altering corneal curvature, we used high-density focused ultrasound at a frequency of 4.8 MHz and 7.9 MHz to produce corneal lesions in the rabbit eye. Intensity and duration threshold exposure conditions were determined for the production of minimally visible lesions. Threshold lesions were initially apparent as discrete white opacities resulting from stromal edema and disruption. Light and scanning electron microscopy of higher-energy, suprathreshold lesions revealed more extensive disruption, including the formation of a superficial stromal depression and a larger zone of edema and disorganization surrounding each lesion. Posterior stromal lamellae, endothelium, and Descemet's membrane were intact. Healing and reepithelialization resulted in a smooth corneal surface with no residual opacification. Threshold determinations predict safe exposure levels to the cornea during insonification of other ocular structures. Selective heating of the peripheral cornea using focused ultrasound may be a useful technique for correcting astigmatism.

Animals↗

Ultrasonically induced disruption and hemolysis of vitreous hemorrhages.

High-intensity focused ultrasound was used to insonify simulated vitreous hemorrhages in two in vitro models and one in vivo animal model. Histopathologic evaluation of the treatment effect was performed with light and electron microscopy. Ultrasonic parameters resulting in histopathologically proven disruption and hemolysis of intravitreal blood were investigated. Most important in obtaining this effect were the temporal average acoustic power and pulse repetition rate of the applied ultrasonic beam. Accurate positioning of the therapeutic beam and visualization of internal spatio-temporal response patterns in the blood during insonification were monitored via simultaneous diagnostic B-mode imaging. Results suggested that high-intensity focused ultrasound might facilitate the two major mechanisms involved in the natural resorption process of vitreous hemorrhages namely hemolysis and surface-dependent phagocytosis.

Animals↗

Histopathologic effects of ultrasonically induced hyperthermia in intraocular malignant melanoma.

Four cases of human intraocular malignant melanoma were treated with ultrasonically induced hyperthermia immediately before enucleation. Tumors were treated in two regimens: 30 minutes at 43 degrees to 45 degrees C and 5 minutes at greater than 50 degrees C. Temperatures were estimated from applied power levels, based on empirical data and mathematical models. Histopathologic changes observed in human tumors were compared with changes seen in malignant melanoma xenografts in athymic nude mice which were treated with ultrasonically induced hyperthermia for 30 minutes at 42 degrees to 46 degrees C. The effects of treatment were similar to changes seen in the animal model treated under analogous conditions: increased intercellular spacing, cytoplasmic vacuole formation, clumping of chromatin, breaks in cell membranes, and swelling and collapse of cells. Perivascular and peripheral zones sometimes showed decreased damage levels. The high temperature (greater than 50 degrees C) technique is presently being used as a means of "sterilizing" tumors before planned enucleation. The moderate temperature (43 degrees-45 degrees C) technique has been used in combination with radiotherapy to treat tumors when vision can be salvaged.

Animals↗

Histologic changes in porcine eyes treated with high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) has recently been described in the treatment of patients with glaucoma. However, despite previous studies in animal and mathematical models, the mechanisms of action are not completely understood. We therefore undertook a histologic study of 15 porcine eyes to evaluate the effect of HIFU and, in particular, the changes seen after sequential insonification on previously treated areas of sclera. We demonstrated initial scleral swelling that was followed by scleral thinning. The scleral thinning could be maximized by a second superimposed course of HIFU. The most consistent change in the ciliary body was necrosis of the pars plana. Some treated animals developed a hemorrhagic retinal detachment that we believe to be due to the presence of a circumferential blood vessel, which runs in the ora serrata of the pig but which is not present in humans. Based on our observations, possible mechanisms of action of this treatment are discussed.

Animals↗

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.

Aged↗

Therapeutic ultrasound.

Currently the most widely applied use of therapeutic ultrasound in ophthalmology is for the treatment of refractory glaucoma. This new technique is described, histologic changes in experimental animals discussed, and mode of action postulated. The intraocular pressure (IOP) results obtained after treatment of 187 patient eyes are presented, with a review of complications and visual acuity changes. This study demonstrates that 70% of patients treated had an IOP reduction to 25 mm Hg or less one year after ultrasound therapy.

Adult↗

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.

Animals↗

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.

Choroid↗

Proton beam irradiation and hyperthermia. Effects on experimental choroidal melanoma.

Ultrasonically induced hyperthermia (4.75 MHz) and proton irradiation (160 meV) were evaluated alone and combined to treat experimental choroidal melanoma in 58 rabbit eyes. Threshold tumoricidal doses were established for each modality. Therapy was performed combining subthreshold doses of heat and radiation. Focused ultrasonic energy via an external beam was found to deliver well-localized heat to an intraocular tumor. Ectopic temperature elevations due to soft-tissue-bone interfaces were alleviated by modifying beam alignment. The results indicate that hyperthermia (43 degrees C for one hour) potentiated the tumoricidal effects of radiation, while sparing normal ocular structures. Therefore, we believe that experimental hyperthermia is suitable as an adjuvant treatment modality. This shows that ultrasound hyperthermia has the potential to increase the efficacy of proton irradiation by lowering radiation doses and thus decreasing posttreatment ocular morbidity in human intraocular malignancies.

Animals↗

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.

Ciliary Body↗