Stephen Thomas Flock

Thermally induced shrinkage of joint capsule.

Thermal shrinkage of collagen currently is being used in orthopaedic surgery to treat ligamentous laxity. Understanding the kinetics of collagen shrinkage is key to revealing the events that take place during application of thermal energy. To elucidate the thermokinetic properties of collagen, punch biopsies of bovine joint capsule were immersed in a heated saline bath at temperatures between 20° and 90°C for periods up to 60 minutes. The resulting tissue thermal shrinkage was measured by the change in the cross-sectional area of the specimens. Only a small amount of shrinkage occurred at temperatures below 63°C, and increasing amounts and rates of shrinkage were seen at temperatures between 63° and 72°C. The denaturation kinetics of bovine knee collagen, which could be described by a first order reaction rate, had an activation energy of 2.3 × 105 kJ/mol.

Q-switched neodymium:yttrium-aluminum-garnet laser treatment of lentigo maligna☆☆☆

Lentigo maligna is a premalignant lesion of atypical melanocytes that typically arises on the head and neck of elderly patients. It is considered a melanoma in situ with a significant risk for transformation to invasive lentigo maligna melanoma. Surgery is the preferred method of treatment; however, because of the advanced age of the typical patient with lentigo maligna, the frequency of complicating medical problems, and the cosmetic or functional aspects of treatment, surgical excision is not always feasible. The purpose of this pilot study was to evaluate the efficacy and safety of Q-switched neodymium:yttrium-aluminum-garnet laser treatment of lentigo maligna. Eight patients were treated with 532 and/or 1064 nm wavelengths from the laser. All patients showed a response to laser therapy, and 2 patients treated with 1 treatment from each wavelength had complete eradication of the LM, with no evidence of recurrence in 42 months. Further study is warranted, but Q-switched neodymium:yttrium-aluminum-garnet laser is a promising alternative treatment for lentigo maligna.

Thermal damage of blood vessels in a rat skin-flap window chamber using indocyanine green and a pulsed alexandrite laser: A feasibility study

The design criteria and feasibility of specifically targeting blood vessels for thermal damage by using a pulsed alexandrite infra-red laser to heat an intravascularly injected infra-redabsorbing dye, namely indocyanine green (ICG), is demonstrated. Theoretical calculations map the distribution of light and heat in and around the subcutaneous blood vessels in a rat skin-flap window chamber as functions of dye concentration, vessel size, and vessel depth. Theoretical calculations showed that an injected dose of 6–24 mgkg−1 of ICG and a 120-μs, 1-J cm−2 alexandrite laser pulse at a wavelength of 785 nm would be sufficient to achieve selective vascular damage to a depth of at least 0.15 cm. Feasibility experiments were performed which illustrated that an irradiation of 1.27 J cm−2 of skin flaps in uninjected control rats showed no evidence of vascular damage while vascular damage was seen in skin flaps using an experimental protocol of 12 mg kg−1 i.v. of ICG and an energy fluence of 0.76 J cm−2. This procedure could conceivably prove useful in the treatment of vascular lesions or cancer.

Quantifying the effects on blood of irradiation with four different vascular-lesion lasers

We have done a study addressing the effects of blood of irradiation with different vascular- lesion lasers. Irradiation of dilute whole blood with light (577 - 585 nm) produced by an argon-dye laser, copper-vapor laser, flashlamp-pumped dye laser or Q-switched frequency- doubled Nd:YAG dye laser causes the release of hemoglobin from the red blood cells. The magnitude of this release is shown to be proportional to the magnitude of thermal insult. With this experimental technique, we compare the efficacy of each laser for producing thermal damage, using clinically realistic irradiation parameters. We have determined that an equivalent energy fluence from these lasers produced comparable amounts of thermal damage in whole blood, except in the experiments where the flashlamp-pumped dye laser was used. The flashlamp-pumped dye laser produced much greater damage than the other lasers at equivalent irradiance levels. This was felt to be due to the flashlamp-pumped dye lasers relatively large spot size. Measurable differences in thermal damage elicited by irradiation of red blood cells with the argon-dye laser and copper-vapor laser emphasized the fact that the latter is a pulsed laser, while former is a continuous-wave laser. All of the experimental results show that laser induced thermal damage is a function of not only the energy fluence, but also of the energy fluence rate and geometry of the irradiation.

Construction of a vein-pouch aneurysm at a surgically created carotid bifurcation in the rat.

Currently available animal models for the study of treatment of aneurysms are either expensive or yield unreliable results. An animal series was devised to address both of these problems by creating a new animal model. Twelve Sprague‐Dawley rats were used to demonstrate that a vein‐pouch aneurysm could be constructed at a surgically created carotid bifurcation. Patency rates, growth dynamics, and histologic morphology were studied at three time intervals. A 100% patency rate at the aneurysm orifice was achieved with one‐third of the aneurysms showing varying degrees of partial apical thrombosis. A growth pattern was established over the study period. Magnetic resonance angiography and digital subtraction angiography were successfully employed to study a small number of additional aneurysms. Our conclusion is that a bifurcation aneurysm can be constructed in the rat with high patency rates and predictable saccular morphology which resembles most human intracranial aneurysms. This inexpensive animal model can be used to study novel modalities for the treatment of aneurysms.

Er:YAG laser-induced changes in skin in vivo and transdermal drug delivery

It has been shown that laser ablation of stratum corneum, in vitro, can result in an increased uptake of topically applied pharmaceuticals. We have performed measurements of drug permeation, using an in vitro model of human skin, that involves a portable Er:YAG laser used to ablate the stratum corneum. For the first time, this method of drug administration was tested in vivo in human volunteers, whereby a hydrocortisone blanching assay was used to assess the efficiency of the procedure. The results show that this is a safe and efficient way to ablate stratum corneum for the purpose of enhanced transcutaneous drug administration.

Photofrin and 5-aminolevulinic acid permeation through oral mucosa in vitro

Photofrin and 5-aminolevulinic acid are photosensitizers that show promise in the photodynamic treatment of cancer, port-wine stains, atherosclerosis and viral lesions. Photofrin is a mixture of porphyrins which, upon the absorption of light, become temporarily cytotoxic. One side-effect associated with the use of Photofrin is long-term cutaneous photosensitivity. It is possible that topical application of this photosensitizing dye will ameliorate such a side-effect. Another way to avoid the cutaneous photosensitivity in photodynamic therapy is to use 5- aminolevulinic acid, which is a porphyrin precursor that causes an increase in the synthesis and concentration of the photosensitizer protoporphyrin IX. 5-aminolevulinic acid is usually applied topically, and so minimizes cutaneous photosensitivity while maximizing the local protoporphyrin concentration. There are a host of disorders in oral mucosa that are potentially treatable by photodynamic therapy. However, since stratum corneum presents an impermeable barrier to many pharmaceuticals, it is not clear that topical application of the photosensitizer will result in a clinically relevant tissue concentration. We have therefore studied the permeation behavior of Photofrin and 5-aminolevulinic acid by applying them to the surface of ex vivo oral mucosa tissue positioned by a Franz diffusion cell. In order to increase the permeability of the photosensitizer across the stratum corneum, we studied the effects of four different drug carriers: phosphate buffered saline, dimethylsulfoxide, ethanol and Azone with isopropyl alcohol.

A semianalytical method for the design of a linac x-ray beam flattening filter

The purpose of this study was to design an improved flattening filter for a Therac 20 medical linear accelerator. Profiles of the 18-MV x-ray beam produced by this accelerator measured along the diagonal of a 40 X 40 cm field at a depth of 5 cm were measured, and it was found that there were regions near the corners of the field where the dose was 109% of the central axis dose. An iterative algorithm for designing flattening filters was developed which required, as input, precise measurements of the following data: the unflattened primary beam profile, the fraction of the beam due to contamination radiation arising from interactions of primary photons with the flattening filter and the collimator assemblies, and the attenuation of the primary photons in water and lead as a function of angle from the central axis of the beam. A new flattening filter was designed and profiles of the beam were measured at a number of depths. These measurements showed that the beam was flattened to within +/- 1% out to 24 cm along the diagonal of a 40 X 40 cm field at a depth of 5 cm.

Comparison of the treatment of vascular lesions with the copper-vapor laser and flashlamp-pumped dye laser

Vascular lesions such as port-wine stains and telangiectases are sometimes treated with carbon-dioxide lasers, argon lasers or argon-pumped dye lasers; however these lasers are non- specific in their thermal effect on tissues and as a result often cause significant scarring. Recently, evidence has accumulated that the flashlamp-pumped dye (585 nm) and copper- vapor (578 nm) lasers, which produce pulsed light that is efficiently absorbed by hemoglobin, are more selective in coagulating abnormal vascular tissue and as a result give a superior clinical result. It is not yet clear what the most important physical and biological mechanisms are during the light-tissue interaction mediated by these two lasers. The post-treatment sequence of events is different for tissue irradiated by each laser; most significantly, the flashlamp-pumped dye laser causes significant transient purpura, whereas the copper vapor laser causes blanching and eschar formation. The clinical outcome, that is regression of the lesion, is equally successful with either laser although some evidence has accumulated showing that the flashlamp-pumped dye laser is best suited to the treatment of small vessel disease while the copper-vapor laser is better for the treatment of large vessel disease. In this paper, we will discuss our observations of the treatment of vascular lesions on humans with the copper-vapor and flashlamp-pumped dye lasers using empirically derived efficacious treatment parameters. Mathematical models of light and heat propagation and in vivo experiments involving mice ears and rat skin flaps will be used to elucidate what we feel are the important underlying mechanisms of this vascular lesion laser therapy.

Laser vibrometer measurements and middle ear prostheses

One of us has developed an improved partial ossicular replacement prosthesis that is easier to implant and, based on pilot clinical measurements, results in better high-frequency hearing as compared to patients receiving one of the alternative prostheses. It is hypothesized that the primary reason for this is because of the relatively light weight (about 25 mg) and low compliance of the prosthesis, which could conceivably result in better high frequency vibrational characteristics. The purpose of our initial work was to develop an instrument suitable for objectively testing the vibrational characteristics of prostheses. We have developed a laser based device suitable for measuring the vibrational characteristics of the oval window or other structures of the middle ear. We have tested this device using a piezoelectric transducer excited at audio frequencies, as well as on the oval window in human temporal bones harvested from cadavers. The results illustrate that it is possible to non-invasively monitor the vibrational characteristics of anatomic structures with a very inexpensive photonic device.