Search

Vulnerable plaques constitute a risk for serious heart problems, and are difficult to identify using existing methods. Hyperspectral imaging combines spectral- and spatial information, providing new possibilities for precise optical characterization of atherosclerotic lesions. Hyperspectral data were collected from excised aorta samples (n = 11) using both white-light and ultraviolet illumination. Single lesions (n = 42) were chosen for further investigation, and classified according to histological findings. The corresponding hyperspectral images were characterized using statistical image analysis tools (minimum noise fraction, K-means clustering, principal component analysis) and evaluation of reflectance/fluorescence spectra. Image analysis combined with histology revealed the complexity and heterogeneity of aortic plaques. Plaque features such as lipids and calcifications could be identified from the hyperspectral images. Most of the advanced lesions had a central region surrounded by an outer rim or shoulder-region of the plaque, which is considered a weak spot in vulnerable lesions. These features could be identified in both the white-light and fluorescence data. Hyperspectral imaging was shown to be a promising tool for detection and characterization of advanced atherosclerotic plaques in vitro. Hyperspectral imaging provides more diagnostic information about the heterogeneity of the lesions than conventional single point spectroscopic measurements. © (2011) Society of Photo-Optical Instrumentation Engineers (SPIE)

Cardiovascular disease is the primary cause of death in the United States; the majority of these deaths are caused by the rupture of vulnerable plaques. An important feature of vulnerable plaques is the thickness of the fibrous cap that covers the necrotic core. A thickness of less than 65 microm has been proposed as a value that renders the plaque prone to rupture. This work shows that multiphoton microscopy (MPM) can image the plaque with microm resolution to a depth deeper than 65 microm. The fibrous cap emits primarily second harmonic generation due to collagen, in contrast to the necrotic core and healthy artery, which emits primarily two-photon excited fluorescence from elastin. This gives a good demarcation of the fibrous cap from underlying layers, facilitating the measurement of the fibrous cap thickness. Based on a measure of the collagen/elastin ratio, plaques were detected with a sensitivity of 65% and specificity of 81%. Furthermore, the technique gives detailed information on the structure of the collagen network in the fibrous cap. This network ultimately determines the mechanical strength of the plaque. A mechanical model based on this information could yield a measure of the propensity of the plaque to rupture.

We present functional imaging of the concentration of a photodynamic therapy (PDT)-related dye in scattering tissue phantoms based on spatially resolved measurements of optical properties through spectroscopic optical coherence tomography (OCT). Expressions for the OCT signal are developed, enabling estimation of depth-resolved sample optical properties. Based on these expressions, we discuss speckle statistics and speckle correlations of the OCT signal. Speckle noise reduction is performed by spatial filtering and is used to improve accuracy in the estimated optical properties at the expense of spatial resolution. An analytic expression for the precision in the estimated optical properties is derived. This expression shows that axial filtering, and thereby a reduction of axial resolution, gives a larger improvement in precision compared to the same filtering and reduction in the transversal resolution. It also shows that imaging with a shorter coherence length, or a larger numerical aperture, improves precision when the filter length determines the spatial resolution. Good agreement is obtained between experimentally determined and theoretically predicted variance in the estimated attenuation coefficients and dye concentration. Finally, we present guidelines for spectroscopic OCT systems for concentration imaging and discuss application of the method to more realistic phantoms and tissue.

The physical basis for optimization of wavelength, pulse duration, and cooling for laser-induced selective photothermolysis of hair follicles in human skin is discussed. The results indicate that the most important optimization parameter is the cooling efficiency of the technique utilized for epidermal protection. The optical penetration is approximately the same for lasers at 694, 755, and 800 nm. The penetration of radiation from Nd:yttrium-aluminum-garnet lasers at 1064 nm is, however, somewhat larger. Photothermal damage to the follicle is shown to be almost independent of laser pulse duration up to 100 ms. The results reveal that epidermal cooling by a 30-80-ms-long cryogen spurt immediately before laser exposure is the only efficient technique for laser pulse durations less than 10 ms. For longer pulse durations in the 30-100 ms range, protection can be done efficiently by skin cooling during laser exposure. For laser pulses of 100 ms, an extended precooling period, e.g., by bringing a cold object into good thermal contact with the skin for about 1 s, can be of value. Thermal quenching of laser induced epidermal temperature rise after pulsed exposure can most efficiently be done with a 20 ms cryogen spurt applied immediately after irradiation.

Objective quantification of epidermal melanin concentration (EMC) should be useful in laser dermatology to determine the individual maximum safe radiant exposure (IMSRE). We propose a single-wavelength remittance measurement at 390 nm as an alternative optical method to determine EMC and IMSRE. Remittance spectra (360 to 740 nm), melanin index (MI) measurements and the transient radiometric temperature increase, DeltaT(t), upon skin irradiation with an Alexandrite laser (755 nm, 3-ms pulse duration, 6 Jcm(2)) were measured on 749 skin spots (arm and calf) on 23 volunteers (skin phototypes I to IV). Due to the shallow penetration depth and independence of blood oxygen saturation (isosbestic point), remittance at 390 nm appears to provide better estimates for EMC and IMSRE than MI.

Monitoring of the tissue response to photodynamic therapy (PDT) can provide important information to help optimize treatment variables such as drug and light dose, and possibly predict treatment outcome. A urinary bladder cancer cell line (AY-27) was used to induce orthotopic transitional cell carcinomas (TCC) in female Fischer rats, and hexyl 5-aminolevulinate (HAL, 8 mM, 1 h)-induced PDT was performed on day 14 after instillation of the cancer cells (20 J/cm(2) fluence at 635 nm). In vivo optical reflectance and fluorescence spectra were recorded from bladders before and after laser treatment with a fiberoptic probe. Calculated fluorescence bleaching and oxygen saturation in the bladder wall were examined and correlated to histology results. Reflectance spectra were analyzed using a three-layer optical photon transport model. Animals with TCC treated with PDT showed a clear treatment response; decreased tissue oxygenation and protoporphyrin IX (PpIX) fluorescence photobleaching were observed. Histology demonstrated that 3 of 6 animals with treatment had no sign of the tumor 7 days after PDT treatment. The other 3 animals had significantly reduced the tumor size. The most treatment-responsive animals had the highest PpIX fluorescence prior to light irradiation. Thus, optical spectroscopy can provide useful information for PDT. The model has proved to be very suitable for bladder cancer studies.

Heart disease is the primary cause of death in the western world. Many of these deaths are caused by the rupture of vulnerable plaque. Vulnerable plaques are characterized by a large lipid core covered by a thin fibrous cap. One method for detecting these plaques is reflection spectroscopy. Several studies have investigated this method using statistical methods. A more analytic and quantita- tive study might yield more insight into the sensitivity of this detection modality. This is the approach taken in this work. Reflectance spectra in the spectral region from 400 to 1700 nm are collected from 77 measurement points from 23 human aortas. A measure of lipid con- tent in a plaque based on reflection spectra is presented. The measure of lipid content is compared with the thickness of the lipid core, de- termined from histology. Defining vulnerable plaque as having a lipid core 500 m and fibrous cap 500 m, vulnerable plaques are detected with a sensitivity of 88% and a specificity of 94%. Although the method can detect lipid content, it is not very sensitive to the thickness of the fibrous cap. Another detection modality is necessary to detect this feature. © 2006 Society of Photo-Optical Instrumentation Engineers. DOI: 10.1117/1.2186332

We demonstrate low-coherence interferometry (LCI) for dye diffusion measurements in scattering tissue phantoms. The diffusion coefficient of a phthalocyanine dye in 1.5% agar gel containing scattering Intralipid was measured using a dual-wavelength interfero-meter. One wavelength was matched to the absorption peak of the dye at 675 nm. The other, 805 nm, was not affected by the dye, and was used to correct for varying sample scattering as a function of depth, assuming a constant ratio between scattering at the two wavelengths. The same wavelength dependence of scattering is assumed for the entire sample, but no a priori knowledge about the amount of scattering is needed. The dye diffusion coefficient was estimated by fitting a mathematical model of the interferometer signal to the measured LCI envelope. We compare results obtained using both a constant-scattering and a depth-resolved-scattering approach to determine the sample scattering. The presented method provides robust estimation of the diffusion coefficient when spatial resolution in determining the depth-resolved scattering is varied. Results indicate that the method is valid for samples having continuous spatial variations in the scattering coefficient over lengths as short as the coherence length of the probing light. The method allows in situ characterization of diffusion in scattering media.

We present an initial study on applying genetic algorithms (GA) to retrieve human skin optical properties using visual reflectance spectroscopy (VRS). A three-layered skin model consisting of 13 parameters is first used to simulate skin and, through an analytical model based on optical diffusion theory, we study their independent effects on the reflectance spectra. Based on a preliminary analysis, nine skin parameters are chosen to be fitted by GA. The fitting procedure is applied first on simulated reflectance spectra with added white noise, and then on measured spectra from normal and port wine stain (PWS) human skin. A normalized residue of less than 0.005 is achieved for simulated spectra. In the case of measured spectra from human skin, the normalized residue is less than 0.01. Comparisons between applying GA and manual iteration (MI) fitting show that GA performed much better than the MI fitting method and can easily distinguish melanin concentrations for different skin types. Furthermore, the GA approach can lead to a reasonable understanding of the blood volume fraction and other skin properties, provided that the applicability of the diffusion approximation is satisfied.