Laser based devices with ability to heat sub-surface zones at certain depths within skin have several potential
applications. Methods to achieve such heating at different depths have been explored in this work. Monte Carlo
modeling and heat transfer calculations were performed to calculate fluence distribution, temperature distribution, and
thermal damage for various laser wavelengths in the range of 1,200-1,800 nm with various pulse durations. The
treatment consisted of laser irradiation combined with contact cooling. Cooling leads to preservation of the top layer
leading to a zone of thermally damaged tissue under the top layer. The results indicated that the thickness and mean
depth of the thermally damaged sub-surface zone can be controlled by choice of laser wavelength and cooling and
irradiation times. Thermally damaged zone was deeper with lower absorbing wavelengths and/or with longer pulse
durations. Histological evaluation of <i>ex vivo </i>pig skin immediately after treatment was done to determine thermal damage
band depth and thickness for various wavelengths and pulse durations. Histological evaluation supported the modeling
results. Thus, variable depth heating can be achieved through selection of the wavelength and/or laser pulse duration.
With a chosen wavelength device, a variable depth heating device can be constructed by varying the cooling and laser
Compared to traditional CO<SUB>2</SUB> or Er:YAG laser resurfacing, sub-surface thermal injury to stimulate skin remodeling for the removal of wrinkles is attractive due to the lower morbidity associated with epidermal preservation. We have developed a technique that thermally damages dermal collagen while preserving the epidermis by a combination of infra-red laser irradiation and dynamic cooling of skin. Wound healing response to the thermal denaturation of collagen may trigger synthesis of fresh collagen and result in restoration of a more youthful appearance. The laser wavelength is chosen so as to thermally injure dermis in a narrow band at depths of 150 to 500 microns from the surface of the skin. The epidermis is preserved by a Candela dynamic cooling device (DCD<SUP>TM</SUP>) cryogen spray. Three-dimensional Monte Carlo calculations have been done to calculate the light distribution within tissue while taking into account light absorption and scattering. This light distribution has been used to calculate heat generation within tissue. Heat transfer calculations have been done while taking into consideration the cryogen cooling. The resulting temperature profiles have been used to suggest heating and cooling parameters. Freshly excised ex vivo pig skin was irradiated with laser and DCD at these heating and cooling parameters. Histological evaluation of the biopsies has shown that it is possible to spare the epidermis while thermally denaturing the dermal collagen. The modeling and histology results are discussed.
The feasibility of employing fluorescent agents to perform optical imaging in tissues and other scattering media has been examined through experimental and computational studies. Fluorescence lifetime and yield can give crucial information about local metabolite concentration or environmental conditions within tissues. This information can be employed towards disease detection, diagnosis, and treatment if non-invasively quantitated from re-emitted optical signals. However, the inverse problem for image reconstruction of fluorescence yield and lifetime is complicated due to the highly scattering nature of the tissue. In this work, a light propagation model employing the diffusion equation is used to account for the scattering of both the excitation and fluorescent light. Simulated measurements of frequency-domain parameters of fluorescent modulated AC amplitude and phase-lag are used as inputs to an inverse image reconstruction algorithm which employs the diffusion model to predict frequency-domain measurements resulting from a modulated input at the phantom periphery. In the inverse image reconstruction algorithm, we employ a Newton-Raphson technique combined with Marquardt algorithm to converge upon the fluorescent properties within the medium. The successful reconstruction of both the fluorescence yield and lifetime in the case of heterogeneous fluorophore distribution within a scattering medium has been demonstrated without a priori information or without the necessity of obtaining `absence' images.
The progression of disease is certainly accompanied by biochemical changes. Since early detection promises a greater efficacy for therapeutic intervention, non-invasive biomedical optics may offer the opportunity for detecting biochemical changes thereby improving prognosis by providing early diagnosis. Magnetic resonance imaging (MRI) is an example of a modality that has successfully monitored the relaxation of spin states of paramagnetic nuclei in order to provide biomedical imaging and biochemical spectroscopy of tissues. In this paper, we discuss an optical analog of MRI, called fluorescence lifetime imaging. instead of monitoring the relaxation of a spin state, lifetime imaging depends upon monitoring the relaxation of an electronically activated state which is brought about by the absorption of a photon. Figure 1 is the Jablonski diagram outlining the electronic transitions which occur following the absorption of light. Relaxation from the activated state to the ground state can occur via either non-radiative or fluorescent decay, depending upon the local environment. The mean time between the events of the absorption of an excitation photon and the radiative relaxation process which produces a fluorescent photon is known as the lifetime, (tau) , of the activated state. Typically, endogenous fluorophores have lifetimes on the order of nanoseconds while exogenous compounds have lifetimes ranging from sub nanosecond to tens of nanoseconds. If the spin state of the electron in the activated state is 'flipped' (referred to as a 'intersystem crossing') then radiative relaxation requires extra time since paired electrons of the same spin are forbidden. Consequently, the resulting phosphorescence lifetime is on the order of milliseconds. The lifetime of the activated probe is dependent on its environment much the same as the time for relaxation of the spin states of paramagnetic nuclei in MRI and NMR depends upon local environment. There are two mechanisms responsible for reducing the lifetime of an activated probe: (1) energy transfer from the activated state to a donor molecule(s), and (2) collisional quenching of the activated state. For an activated probe experiencing collisional quenching, the measured lifetime, (tau) , can be used to determine metabolite or quencher concentration [Q], from the empirical Stern-Volmer relationship. Consequently, a map of lifetime provides a map of metabolite or quencher concentration. In this paper, we report computational experiments which point to the feasibility of the optical analog to MRI: fluorescence lifetime imaging in tissues and other scattering media.
The opportunity to monitor the onset and progression of disease may be enabled by the smart implementation of biomedical optical engineering approaches to monitor tissue biochemistry. Uncorrected, these biochemical disturbances manifest themselves in microscopic structural changes which lead to gross pathophysiology and symptoms by which the disease is outwardly identified. Biomedical optical engineering techniques offer the opportunity to detect these biochemical changes and provide diagnostic information at earlier stages in the disease process, enabling greater efficacy of therapeutic intervention. In this paper, we concentrate on the fluorescence and phosphorescence lifetime spectroscopy due to advantages these techniques have to offer in tissues. The development of fluorescent and phosphorescent dyes which excite and re-emit in the near-infrared wavelength region promises the capacity for non- invasive biochemical sensing in tissues. Fluorescence intensity and fluorescence lifetime spectroscopies are established methods by which a fluorophore can provide sensing in dilute, non-scattering samples. However, fluorescence intensity or fluorescence lifetime spectroscopy in tissues or other scattering media is a complex problem. In order to extract the intrinsic fluorescence intensity for identification of the fluorophore concentration and yield, a priori information about tissue absorption and scattering must be obtained or assumed. Yet in tissues, the optical properties of absorption and scattering are highly variable. Nonetheless when successful, fluorescence intensity spectroscopy enables determination of the product of fluorescent yield and fluorophore concentration. In contrast to fluorescence intensity spectroscopy, fluorescence-lifetime tissue spectroscopy offers the ability to directly determine metabolite concentration independently of the concentration of fluorophore, whether it is endogenous or exogenous. Instead of monitoring the fluorescent intensity due to the re- emission process, the 'lifetime' or stability of the photon-activated fluorophore is measured. The lifetime of the activated state is defined as the mean time between absorption of the excitation photon and re-emission of a fluorescent photon. Typically, endogenous fluorophores have lifetimes on the order of nanoseconds while exogenous compounds have lifetimes ranging from sub nanosecond to milliseconds.