This PDF file contains the editorial “Special Section Guest Editorial: Biomedical Optics and Women’s Health” for JBO Vol. 9 Issue 03

We propose a new nonlinear matching measure for automatic analysis of the on-off type DNA microarray images in which the hybridized spots are detected by a template-matching method. The proposed measure is obtained by binary thresholding over the entire template region and taking the number of white pixels inside the spotted area. This measure is compared with the normalized covariance method in terms of classifying the ability to successfully locate markers. The proposed measure was evaluated for scanned images of human papillomavirus (HPV) DNA microarrays where locating markers is a critical issue because of the small number of spots. The targeting spots of HPV DNA chips are designed for genotyping twenty-two types of the human papillomavirus. The proposed measure is proven to give a more discriminative response, reducing the missed cases of successful marker location. The locating accuracy of the proposed method is also shown to have the same performance as that of the normalized covariance.

We describe the use of a biochip based on complementary metal oxide semiconductor (CMOS) technology for detection of specific genetic sequences using molecular beacons (MB) immobilized on solid surfaces as probes. The applicability of this miniature detection system for screening for the BRCA1 gene is evaluated using MB probes, designed especially for the BRCA1 gene. MB probes are immobilized on a zeta-probe membrane by biotin-streptavidin immobilization. Two immobilization strategies are investigated to obtain optimal assay sensitivity. The MB is immobilized by manual spotting on zeta-probe membrane surfaces with the use of a custom-made stamping system. The detection of the BRCA1 gene using an MB probe is successfully demonstrated and expands the use of the CMOS biochip for medical applications.

Real-time three-dimensional (3-D) reconstruction of epithelial structures in human mammary gland tissue blocks mapped with selected markers would be an extremely helpful tool for diagnosing breast cancer and planning treatment. Besides its clear clinical application, this tool could also shed a great deal of light on the molecular basis of the initiation and progression of breast cancer. We present a framework for real-time segmentation of epithelial structures in two-dimensional (2-D) images of sections of normal and neoplastic mammary gland tissue blocks. Complete 3-D rendering of the tissue can then be done by surface rendering of the structures detected in consecutive sections of the blocks. Paraffin-embedded or frozen tissue blocks are first sliced and sections are stained with hematoxylin and eosin. The sections are then imaged using conventional bright-field microscopy and their background corrected using a phantom image. We then use the fast-marching algorithm to roughly extract the contours of the different morphological structures in the images. The result is then refined with the level-set method, which converges to an accurate (subpixel) solution for the segmentation problem. Finally, our system stacks together the 2-D results obtained in order to reconstruct a 3-D representation of the entire tissue block under study. Our method is illustrated with results from the segmentation of human and mouse mammary gland tissue samples.

We present a real-time data-processing and display unit based on a custom-designed digital signal processor (DSP) module for imaging tissue structure and Doppler blood flow. The DSP module is incorporated into a conventional optical coherence tomography system. We also demonstrate the flexibility of embedding advanced Doppler processing algorithms in the DSP module. Two advanced velocity estimation algorithms previously introduced by us are incorporated in this DSP module. Experiments on Intralipid flow demonstrate that a pulsatile flow of several hundred pulses per minute can be faithfully captured in M-scan mode by this DSP system. In vivo imaging of a rat's abdominal blood flow is also presented.

The first time-resolved optical mammograph operating beyond 900 nm (683, 785, 913, and 975 nm) is presently being used in a clinical trial to test the diagnostic potential of the technique in detecting and characterizing breast lesions. Between November 2001 and October 2002, 101 patients with malignant and benign lesions were analyzed retrospectively. Scattering plots, as derived from a homogeneous model, and late gated intensity images, to monitor spatial changes in the absorption properties, are routinely used. The intensity images available at four wavelengths provide sensitivity to the main tissue constituents (oxy- and deoxyhemoglobin, water, and lipids), in agreement with expected tissue composition and physiology, while the scattering plots mirror structural changes. Briefly, tumors are usually identified due to the strong blood absorption at short wavelengths, cysts to the low scattering, and fibroadenomas to low absorption at 913 nm and high at 975 nm, even though the optical features of fibroadenomas seem not to be uniquely defined. The effectiveness of the technique in localizing and discriminating different lesion types is analyzed as a function of various parameters (lesion size, compressed breast thickness, and breast parenchymal pattern).

In vivo absorption and reduced scattering spectra of the human calcaneous from 650 to 1000 nm were assessed using a laboratory system for time-resolved transmittance spectroscopy. Measurements were performed on the calcaneous of seven female volunteers ranging from 26 to 82 years of age. The analysis of the absorption spectra, using a linear combination of the key tissue absorbers (bone mineral, water, lipids, oxy- and deoxyhemoglobin), revealed a general decrease in bone mineral content and an increase in lipids with age, which is in agreement with the aging transformations that occur in bone tissues. The scattering spectra were less effective in detecting such changes in older subjects, showing only a minor decrease in the coefficient for these subjects. The capability to noninvasively quantify bone tissue composition suggests a possible use of optical biopsy for the diagnosis of bone pathologies such as osteoporosis, which are characterized by a progressive reduction and transformation of the mineral in the bone matrix.

Breast cancer diagnosis may be improved by optical fluorescence imaging techniques in the near-infrared wavelength range. We have shown that the recently proposed space-space MUSIC (multiple signal classification) algorithm allows the 3-D localization of focal fluorophore-tagged lesions in a turbid medium from 2-D fluorescence data obtained from laser excitations at different positions. The data are assumed to be measured with two parallel planar sensor arrays on the top and bottom of the medium. The laser sources are integrated at different positions in one of the planes. The space-space data are arranged into an M×N matrix (M, number of sensors; N, number of excitation sources). A singular-value decomposition (SVD) of this matrix yields the detectable number of spot regions with linearly independent behavior with respect to the laser excitation positions and thus allows definition of a signal subspace. Matches between this signal subspace and data from model spots are tested at scanned points in a model medium viewed as the breast region under study. The locations of best matches are then considered the centers of gravity of focal lesions. The optical model used was unbounded and optically homogeneous. Nevertheless, simulated spots in bounded, inhomogeneous media modeling the breast could be localized accurately.

Molecular targeting with exogenous near-infrared excitable fluorescent agents using time-dependent imaging techniques may enable diagnostic imaging of breast cancer and prognostic imaging of sentinel lymph nodes within the breast. However, prior to the administration of unproven contrast agents, phantom studies on clinically relevant volumes are essential to assess the benefits of fluorescence-enhanced optical imaging in humans. Diagnostic 3-D fluorescence-enhanced optical tomography is demonstrated using 0.5 to 1 cm³ single and multiple targets differentiated from their surroundings by indocyanine green (micromolar) in a breast-shaped phantom (10-cm diameter). Fluorescence measurements of referenced ac intensity and phase shift were acquired in response to point illumination measurement geometry using a homodyned intensified charge-coupled device system modulated at 100 MHz. Bayesian reconstructions show artifact-free 3-D images (3857 unknowns) from 3-D boundary surface measurements (126 to 439). In a reflectance geometry appropriate for prognostic imaging of lymph node involvement, fluorescence measurements were likewise acquired from the surface of a semi-infinite phantom (8×8×8 cm³) in response to area illumination (12 cm²) by excitation light. Tomographic 3-D reconstructions (24,123 unknowns) were recovered from 2-D boundary surface measurements (3194) using the modified truncated Newton's method. These studies represent the first 3-D tomographic images from physiologically relevant geometries for breast imaging.

Emission and absorption properties of indocyanine green (ICG) in Intralipid solution have been investigated. The study is focused on relatively low ICG concentration at a range of 0 to 20 μM. A diffusion model was used to analyze the emission properties of ICG solution at different concentrations. In the low-concentration region, the emission strength increases with the concentration of ICG, while in the high-concentration region, the emission decreases with the concentration. In general, a maximum of emission strength exists and its position (concentration) depends on the wavelength of the excitation light, the distance between the source and the detector, and the sample geometry and size. A so-called "inner-cell-effect" and re-absorption of emission photons are found to contribute to the decay of emission strength. Also, in the concentration range of 0 to 2 μM, ICG solution always has a higher absorption coefficient at wavelength 830 nm than that at 660 nm, which is quite different from the ICG in water case.

We present a frequency-domain near-infrared optical tomography system designed for breast cancer detection, in conjunction with conventional ultrasound. It features fast optical switching, three-wavelength excitations, and avalanche photodiode as detectors. Laser diodes at 660, 780, and 830 nm are used as light sources and their outputs are distributed sequentially to one of nine source fibers. An equivalent 130-dB isolation between electrical signals from different source channels is achieved with the optical switches of very low crosstalk. Ten detection channels, each of which includes a silicon avalanche photodiode, detect diffusive photon density waves simultaneously. The dynamic range of an avalanche photodiode is about 20 to 30 dB higher than that of a photomultiplier tube, thus eliminating the need for multistep system gain control. The entire system is compact in size (<0.051 m³) and fast in data acquisition (less than 2 sec for a complete scan). Calibration and the clinical experiment results are presented in the paper.

Fluorescence spectroscopy has shown promise for the detection of precancerous changes in vivo. The epithelial and stromal layers of tissue have very different optical properties; the albedo is relatively low in the epithelium and approaches one in the stroma. As precancer develops, the optical properties of the epithelium and stroma are altered in markedly different ways: epithelial scattering and fluorescence increase, and stromal scattering and fluorescence decrease. We present an analytical model of the fluorescence spectrum of a two-layer medium such as epithelial tissue. Our hypothesis is that accounting for the two different tissue layers will provide increased diagnostic information when used to analyze tissue fluorescence spectra measured in vivo. The Beer-Lambert law is used to describe light propagation in the epithelial layer, while light propagation in the highly scattering stromal layer is described with diffusion theory. Predictions of the analytical model are compared to results from Monte Carlo simulations of light propagation under a range of optical properties reported for normal and precancerous epithelial tissue. In all cases, the mean square error between the Monte Carlo simulations and the analytical model are within 15%. Finally, model predictions are compared to fluorescence spectra of normal and precancerous cervical tissue measured in vivo; the lineshape of fluorescence agrees well in both cases, and the decrease in fluorescence intensity from normal to precancerous tissue is correctly predicted to within 5%. Future work will explore the use of this model to extract information about changes in epithelial and stromal optical properties from clinical measurements and the diagnostic value of these parameters.

Fluorescence spectroscopy is a promising technology for detection of epithelial precancers and cancers. While age and menopausal status influence measurements in the cervix, other variables do not significantly affect the diagnosis. In this study we examine probe pressure as a variable. A fiber optic probe to measure fluorescence spectra at different calibrated levels of pressure was designed and tested. A pilot study was conducted measuring fluorescence excitation emission matrices in 20 patients at light, medium, and firm pressure. Spectroscopic data were pre-processed and analyzed to compare mean peak intensities as a function of pressure. Further statistical analyses tested for differences in intensities at each excitation/emission wavelength pair. Four providers made measurements from 41 sites; 33 yielded good quality spectroscopic data (22 squamous normal, 7 squamous abnormal, 3 columnar normal, 1 transformation zone) from 17 of 20 patients. At all pressure levels, abnormal tissue showed less fluorescence intensity than normal tissue, and post-menopausal patients showed higher fluorescence intensity than premenopausal patients, consistent with previous analyses. A permutation analysis suggests that pressure does not significantly affect fluorescence intensity or lineshape. While other studies are needed to confirm these findings, this study suggests that fluorescence spectroscopy is a robust technology likely not influenced by fiber optic probe pressure.

Near-infrared (NIR) diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration (FDPM) instrument. Wavelength-dependent absorption and reduced scattering parameters (μ_a and μ_s', respectively) were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy-(HbO2) and deoxy-(Hb-R) hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal (PRE) women (20 to 30 μM) is approximately two-fold higher than for postmenopausal (POST) subjects at all positions. POST women have approximately 50% higher lipid content (50 to 60%) than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects (30 to 40%) than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration (THC), 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale (3 cm) changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for μ_a and 5 to 12% for μ_s'. Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering (674 nm) within an individual.

Near-infrared imaging was used to quantify typical values of hemoglobin concentration, oxygen saturation, water fraction, scattering power, and scattering amplitude within the breast tissue of volunteer subjects. A systematic study of the menstrual variations in these parameters was carried out by measuring a group of seven premenopausal normal women (aged 41 to 47 years) in the follicular (days 7 to 14 of the cycle) and secretory phases (days 21 to 28) of the cycle, for two complete menstrual cycles. An average increase in hemoglobin concentration of 2.6 μM or 13% of the background breast values was observed in the secretory phase relative to the follicular phase (p<0.0001), but no other average near-infrared parameter changes were significant. While repeatable and systematic changes were observed in all parameters for individual subjects, large intersubject variations were present in all parameters. In a survey of thirty-nine normal subjects, the total hemoglobin varied from 9 to 45 μM, with a systematic correlation observed between total hemoglobin concentration and breast radiographic density. Scattering power and scattering amplitude were also correlated with radiographic density, but oxygen saturation and water fraction were not. Images of breast lesions indicate that total hemoglobin-based contrast can be up to 200% relative to the background in the same breast. Yet, since the background hemoglobin values vary considerably among breasts, the maximum hemoglobin concentrations observed in cancer tumors may vary considerably as well. In light of these observations, it may be important to use hemoglobin contrast values relative to the background for a given breast, rather than absolute hemoglobin contrast when trying to compare the features of breast lesions among subjects.

The robustness of a dual-beam, optical null, Fourier-transform near-infrared (FTNIR) spectrometer was investigated by means of online, near-infrared measurements and predictions of urea concentrations in spent dialysate during hemodialysis treatment. Simple multivariate calibration using a few factors based on a small number of prepared samples provided stable and accurate predictions over a period of 1 month. The calibration was robust when faced with adjustment of reference cell intensity and did not require a daily measured reference spectrum. The root-mean-square error of prediction of urea was 0.4 mM based on a two-factor partial least-squares regression model.

The early diagnosis and proper identification of cervical squamous intraepithelial lesions plays an important role in a good prognosis for the patient. However, the present practice of screening based on PAP (Papanicolaou) smear and histopathology makes it tedious and prone to human errors. We assess the validity of FTIR microspectroscopy (FTIR-MSP) of biopsies as a method to properly assign the correct stage of premalignancy in patients with symptoms of cervical intraepithelial neoplasia. For the first time we evaluate the biopsies based on the FTIR spectra for different grades of neoplasia in tandem with probabilistic neural networks (PNNs) and histopathology. The results show that the grading of neoplasia based on FTIR-MSP and a PNN differentiates the normal from premalignant with a high level of accuracy. The false positive identification of the normal as cervical intraepithelial neoplasia 1 (CIN1), CIN2, and CIN3 patients is 9.04, 0.01, and 0.01%, respectively. The false negative identification of CIN2 patients as normal and CIN1 patients is 0.01 and 4.4%, respectively. Similarly, the false negative identification of CIN3 patients as normal, CIN1, and CIN2 is 0.14, 6.99, and 9.61%, respectively. The small errors encountered in the grading are comparable to current methods, encouraging advanced studies for the development of mechanized equipment for the diagnosis and grading of premalignant cervical neoplasia.

This study was performed to examine the usefulness of medical endoscopic imaging utilizing narrow-band illumination. The contrast between the vascular pattern and the adjacent mucosa of the underside of the human tongue was measured using five narrow-band illuminations and three broadband illuminations. The results demonstrate that the pathological features of a vascular pattern are dependent on the center wavelength and the bandwidth of illumination. By utilizing narrow-band illumination of 415±30 nm, the contrast of the capillary pattern in the superficial layer was markedly improved. This is an important benefit that is difficult to obtain with ordinary broadband illumination. The appearances of capillary patterns on color images were evaluated for three sets of filters. The narrow, band imaging (NBI) filter set (415±30 nm, 445±30 nm, 500±30 nm) was selected to achieve the preferred appearance of the vascular patterns for clinical tests. The results of clinical tests in colonoscopy and esophagoscopy indicated that NBI will be useful as a supporting method for observation of the endoscopic findings of early cancer.

We have recently demonstrated that Renilla luciferase (Rluc) is a promising bioluminescence reporter gene that can be used for noninvasive optical imaging of reporter gene expression in living mice, with the aid of a cooled charged couple device (CCD) camera. In the current study, we explore the expression of a novel synthetic Renilla luciferase reporter gene (hRluc) in living mice, which has previously been reported to be a more sensitive reporter than native Rluc in mammalian cells. We explore the strategies of simultaneous imaging of both Renilla luciferase enzyme (RL) and synthetic Renilla luciferase enzyme (hRL):coelenterazine (substrate for RL/hRL) in the same living mouse. We also demonstrate that hRL:coelenterazine can yield a higher signal when compared to Firefly luciferase enzyme (FL): D-Luciferin, both in cell culture studies and when imaged from cells at the surface and from lungs of living mice. These studies demonstrate that hRluc should be a useful primary reporter gene with high sensitivity when used alone or in conjunction with other bioluminescence reporter genes for imaging in living rodents.

Near-infrared autofluorescence imaging of tissues under long-wavelength laser excitation in the green and red spectral region complemented by cross-polarized elastic light scattering was explored for cancer detection. Various types of normal and malignant human tissue samples were utilized in this investigation. A set of images for each tissue sample was recorded that consisted of two autofluorescence images obtained under 532- and 632.8-nm excitation and light-scattering images obtained under linearly polarized illumination at 700, 850, and 1000 nm. These images were compared with the histopathology of the tissue sample. The experimental results indicated that for various tissue types, the intensity of the autofluorescence integrated over the 700 to 1000-nm spectral region was considerably different in cancer tissues than in that of the contiguous non-neoplastic tissues. This difference provided the basis for the detection of cancer and delineation of the tumor margins. Variations on the relative intensity were observed among different tissue types and excitation wavelengths.

We introduce a novel setup combining a micro-Raman spectrometer with external optical tweezers, suitable for resonance Raman studies of single functional trapped cells. The system differs from earlier setups in that two separate laser beams used for trapping and Raman excitation are combined in a double-microscope configuration. This has the advantage that the wavelength and power of the trapping and probe beam can be adjusted individually to optimize the functionality of the setup and to enable the recording of resonance Raman profiles from a single trapped cell. Trapping is achieved by tightly focusing infrared (IR) diode laser radiation (830 nm) through an inverted oil-immersion objective, and resonance Raman scattering is excited by the lines of an argon:krypton ion laser. The functionality of the system is demonstrated by measurements of trapped single functional erythrocytes using different excitation lines (488.0, 514.5, and 568.2 nm) in resonance with the heme moiety and by studying spectral evolution during illumination. We found that great care has to be taken in order to avoid photodamage caused by the visible Raman excitation, whereas the IR trapping irradiation does not seem to harm the cells or alter the hemoglobin Raman spectra. Stronger photodamage is induced by Raman excitation using 488.0- and 514.5-nm irradiation, compared with excitation with the 568.2-nm line.

We present the results of the Vicker's hardness test and the use of near-infrared Raman spectroscopy (RS) to measure in vitro the degree of conversion (DC) of a bis(phenol)-A-glycidyl-dimethacrylate-based composite resin, photoactivated by both a halogen lamp (power density = 478 mW/cm²; 8-mm diameter spot) and an argon laser (power density = 625 mW/cm²; 7-mm diameter spot). The degree of conversion was estimated by analyzing the relative intensities between the aromatic CC stretching Raman mode at 1610 cm^–1 and the methacrylate CC stretching Raman mode (1640 cm^–1) on top and bottom surfaces. For the hardness evaluation, the samples were embedded in polyester resin and three indentations with a 50-g load for 10 s were made on the top surface. The higher relative DC values achieved by the photoactivation of a composite resin by the argon laser suggest a better biocompatibility in the bottom surface. The correlation test showed that the higher Vicker's hardness number (VHN) values were associated with higher DC values. The derivative analysis showed a greater curing rate from 5 to 20 s of exposure. The comparison of VHN and DC values with both light sources at each curing time showed that a small change in conversion is related to a large change in hardness. Raman spectroscopy is more sensitive to changes in the first stages of curing reaction than later ones, and the Vicker's hardness assay is more sensitive to changes in the last stages.

We present a new detection instrument for sensor measurements based on excited-state fluorescence lifetimes. This system consists of a primary optoelectronic loop containing a resonance-type rf amplifier, a modulatable fluorescence-excitation light source, a fiber optic feedback loop (with a gap for a fluorescent sensor), and a photomultiplier tube. A secondary, phase-feedback optoelectronic circuit consists of a long-wavelength-pass optical filter, a second photomultiplier tube, a photodiode, an electronic phase detector, a dc amplifier, and an electronic phase shifter (inserted into the main loop). This phase-feedback circuit is new with respect to our previous work. Under the appropriate conditions, the main loop exhibits self-oscillations, manifesting themselves as sinusoidal rf modulation of light intensity. The phase-feedback circuit detects the modulation phase shift resulting from the finite excited-state lifetimes of a fluorophore. As the excited state lifetime changes, the phase shift from the electronic phase shifter also changes, which results in a shift in self-oscillation frequency. The detection system uses self-oscillation frequency as the detection parameter and has excellent resolution with respect to changes in excited-state lifetime (~1 ps).

We develop a dual-modality device that combines the anatomical imaging capabilities of optical coherence tomography (OCT) with the functional capabilities of laser-induced fluorescence (LIF) spectroscopy. OCT provides cross-sectional images of tissue structure to a depth of up to 2 mm with approximately 10-μm resolution. LIF spectroscopy provides histochemical information in the form of emission spectra from a given tissue location. The OCT subsystem utilizes a superluminescent diode with a center wavelength of 1300 nm, whereas a helium cadmium laser provides the LIF excitation source at wavelengths of 325 and 442 nm. Preliminary data are obtained on eight postmortem aorta samples, each 10 mm in length. OCT images and LIF spectra give complementary information from normal and atherosclerotic portions of aorta wall. OCT images show structures such as intima, media, internal elastic lamina, and fibrotic regions. Emission spectra ratios of 520/490 (325-nm excitation) and 595/635 (442-nm excitation) could be used to identify normal and plaque regions with 97 and 91% correct classification rates, respectively. With miniaturization of the delivery probe and improvements in system speed, this dual-modality device could provide a valuable tool for identification and characterization of atherosclerotic plaques.

An in-depth characterization of the optical properties of bovine retinal and retinal pigment epithelium-choroidal tissues has been performed. The indices of refraction of these ocular tissues were determined by applying Brewster's law. The inverse adding doubling method based on the diffusion approximation and radiative transport theory is applied to the measured values of the total diffuse transmission, total diffuse reflection, and collimated transmission to calculate the optical absorption, scattering, and scattering anisotropy coefficients of the bovine retinal and retinal pigment epithelium-choroidal tissues. The values of the optical properties obtained from the inverse adding doubling method are compared with those generated by the Monte Carlo simulation technique. Optical polarization measurements are also performed on bovine retinal tissues. Our studies show that both retina and retinal pigment epithelium-choroid possess strong polarization characteristics.

Using the δ-P₁ approximation to the Boltzmann transport equation we develop analytic solutions for the fluence rate produced by planar (1-D) and Gaussian beam (2-D) irradiation of a homogeneous, turbid, semi-infinite medium. To assess the performance of these solutions we compare the predictions for the fluence rate and two metrics of the optical penetration depth with Monte Carlo simulations. We provide results under both refractive-index matched and mismatched conditions for optical properties where the ratio of reduced scattering to absorption lies in the range 0≤(μ'_s/μ_a)≤10⁴. For planar irradiation, the δ-P₁ approximation provides fluence rate profiles accurate to ±16% for depths up to six transport mean free paths (l*) over the full range of optical properties. Metrics for optical penetration depth are predicted with an accuracy of ±4%. For Gaussian irradiation using beam radii r₀≥3l*, the accuracy of the fluence rate predictions is no worse than in the planar irradiation case. For smaller beam radii, the predictions degrade significantly. Specifically for media with (μ'_s/µ_a) = 1 irradiated with a beam radius of r₀ = l*, the error in the fluence rate approaches 100%. Nevertheless, the accuracy of the optical penetration depth predictions remains excellent for Gaussian beam irradiation, and degrades to only ±20% for r₀ = l*. These results show that for a given set of optical properties (μ'_s/µ_a), the optical penetration depth decreases with a reduction in the beam diameter. Graphs are provided to indicate the optical and geometrical conditions under which one must replace the δ-P₁ results for planar irradiation with those for Gaussian beam irradiation to maintain accurate dosimetry predictions.

Selective hyperthermia can be a feasible treatment modality for deep tissue abnormalities. It is accomplished by using a laser or ultrasound noninvasively to transfer energy to a desired target causing tissue damage. This process has two potential benefits to medical professionals: simplicity of procedure and safety to patient. However, optimizing these selective interactions is difficult due to the number of variables. We propose an optimization coefficient relating the dynamic and geometric parameters of selective hyperthermia, and proceed to measure it in an experimental setup consisting of a near-infrared laser and laser-absorbing dye. To simulate tissue, gelatin phantoms are created using a combination of water, intralipid, and gelatin. Our experiments use a 1.00-cm-diam spherical phantom that is homogeneously enhanced with an indocyanine green (ICG) solution and placed inside a nontarget phantom and irradiated by an 805-nm diode laser. Temperature measurements taken at different locations are analyzed so optimization coefficients can be calculated for different parameters. This optimization coefficient compares the difference in temperatures from inside and outside the target. Analysis of the values after thermal equilibrium provides information about the best parameter selection. Our findings indicate that the optimal ICG concentration and power combination for our tested parameters are 0.083% and 0.97 W, respectively. Based on our analysis, optimization can be obtained by using this coefficient to compare the selectivity of several parameter combinations.