Quantifying the optical properties and chromophore concentrations of turbid media by chemometric analysis of hyperspectral diffuse reflectance data collected using a fourier interferometric imaging system

A non-contact Fourier transform interferometric imaging system was used to collect hyperspectral images of the steady-state diffuse reflectance from a point source in turbid media for the spectral range of 550-850 nm. Steady-state diffuse reflectance profiles were generated from the hyperspectral images, and partial least-squares (PLS) regression was performed on the diffuse reflectance profiles to quantify absorption (mu (alpha)) and reduced scattering (mu (s)') properties of turbid media. The feasibility of using PLS regression to predict optical properties was examined for two different sets of spatially-resolved diffuse reflectance data. One set of data was collected from 40 turbid phantoms, while the second set was generated by convolving Monte Carlo simulations with the instrument response of the imaging system. Study results show that PLS prediction of mu (alpha) and mu (s)' was accurate to within +/-8% and +/-5%, respectively, when the model was trained on turbid phantom data. Moreover, PLS prediction of optical properties was considerably faster and more efficient than direct least-squares fitting of spatially-resolved profiles. When the PLS model was trained on Monte Carlo simulated data and subsequently used to predict mu (alpha) and mu (s)' from the diffuse reflectance of turbid phantom, the percent accuracies degraded to +/-12% and +/-5%, respectively. These accuracy values are applicable to homogenous, semi-infinite turbid phantoms with optical property ranges comparable to tissues

Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m-THPC

Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEG-m-THPC at dosages of 0.3, 3.0 and 30 mg kg−1 body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm−1 diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg−1 body weight and an optical dose of 900 J cm−1 diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose–response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg−1 and 11 mm using 3 mg kg−1 photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm−1 diffuser-length for 30 mg kg−1 and between 300 and 500 J cm−1 for 3 mg kg−1 PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg−1 photosensitizer was activated with optical doses of 700 J cm−1 or more. In the survival study, all treated animals survived PDT for at least 2 weeks and the intestinal and urinary tract remained functional. No clinical signs of blood vessel or nerve injury were observed. Mean overall survival of untreated tumour-bearing rats was 25.0 ± 4.5 days compared to 38.4 ± 3.8 days and 40.0 ± 3.6 days for rats treated with 3 mg kg−1 or 9 mg kg−1 PEG-m-THPC mediated PDT respectively (P < 0.05). We conclude that PEG-m-THPC mediated PDT has a favourable therapeutic window and that this minimally-invasive procedure can reduce pelvic cancer bulks effectively and selectively. © 1999 Cancer Research Campaig

Towards an understanding of isospin violation in pion-nucleon scattering

We investigate isospin breaking in low-energy pion-nucleon scattering in the framework of chiral perturbation theory. This work extends the systematic analysis of [1] to the energy range above threshold. Various relations, which identically vanish in the limit of isospin symmetry, are used to quantify isospin breaking effects. We study the energy dependence of the S- and P-wave projections of these ratios and find dramatic effects in the S-waves of those two relations which are given in terms of isoscalar quantities only. This effect drops rather quickly with growing center-of-mass energy.Comment: 12 pp, REVTeX, 8 figs, FZJ-IKP(TH)-2000-2

Laser speckle imaging in the spatial frequency domain

Laser Speckle Imaging (LSI) images interference patterns produced by coherent addition of scattered laser light to map subsurface tissue perfusion. However, the effect of longer path length photons is typically unknown and poses a limitation towards absolute quantification. In this work, LSI is integrated with spatial frequency domain imaging (SFDI) to suppress multiple scattering and absorption effects. First, depth sensitive speckle contrast is shown in phantoms by separating a deep source (4 mm) from a shallow source (2 mm) of speckle contrast by using a high spatial frequency of illumination (0.24 mm−1). We develop an SFD adapted correlation diffusion model and show that with high frequency (0.24 mm−1) illumination, doubling of absorption contrast results in only a 1% change in speckle contrast versus 25% change using a planar unmodulated (0 mm−1) illumination. Similar absorption change is mimicked in vivo imaging a finger occlusion and the relative speckle contrast change from baseline is 10% at 0.26 mm−1 versus 60% at 0 mm−1 during a finger occlusion. These results underscore the importance of path length and optical properties in determining speckle contrast. They provide an integrated approach for simultaneous mapping of blood flow (speckle contrast) and oxygenation (optical properties) which can be used to inform tissue metabolism

Spatial Frequency Domain Imaging of Intrinsic Optical Property Contrast in a Mouse Model of Alzheimer’s Disease

Extensive changes in neural tissue structure and function accompanying Alzheimer’s disease (AD) suggest that intrinsic signal optical imaging can provide new contrast mechanisms and insight for assessing AD appearance and progression. In this work, we report the development of a wide-field spatial frequency domain imaging (SFDI) method for non-contact, quantitative in vivo optical imaging of brain tissue composition and function in a triple transgenic mouse AD model (3xTg). SFDI was used to generate optical absorption and scattering maps at up to 17 wavelengths from 650 to 970 nm in 20-month-old 3xTg mice (n = 4) and age-matched controls (n = 6). Wavelength-dependent optical properties were used to form images of tissue hemoglobin (oxy-, deoxy-, and total), oxygen saturation, and water. Significant baseline contrast was observed with 13–26% higher average scattering values and elevated water content (52 ± 2% vs. 31 ± 1%); reduced total tissue hemoglobin content (127 ± 9 μM vs. 174 ± 6 μM); and lower tissue oxygen saturation (57 ± 2% vs. 69 ± 3%) in AD vs. control mice. Oxygen inhalation challenges (100% oxygen) resulted in increased levels of tissue oxy-hemoglobin (ctO2Hb) and commensurate reductions in deoxy-hemoglobin (ctHHb), with ~60–70% slower response times and ~7 μM vs. ~14 μM overall changes for 3xTg vs. controls, respectively. Our results show that SFDI is capable of revealing quantitative functional contrast in an AD model and may be a useful method for studying dynamic alterations in AD neural tissue composition and physiology

Multifrequency synthesis and extraction using square wave projection patterns for quantitative tissue imaging

We present a method for spatial frequency domain data acquisition utilizing a multifrequency synthesis and extraction (MSE) method and binary square wave projection patterns. By illuminating a sample with square wave patterns, multiple spatial frequency components are simultaneously attenuated and can be extracted to determine optical property and depth information. Additionally, binary patterns are projected faster than sinusoids typically used in spatial frequency domain imaging (SFDI), allowing for short (millisecond or less) camera exposure times, and data acquisition speeds an order of magnitude or more greater than conventional SFDI. In cases where sensitivity to superficial layers or scattering is important, the fundamental component from higher frequency square wave patterns can be used. When probing deeper layers, the fundamental and harmonic components from lower frequency square wave patterns can be used. We compared optical property and depth penetration results extracted using square waves to those obtained using sinusoidal patterns on an in vivo human forearm and absorbing tube phantom, respectively. Absorption and reduced scattering coefficient values agree with conventional SFDI to within 1% using both high frequency (fundamental) and low frequency (fundamental and harmonic) spatial frequencies. Depth penetration reflectance values also agree to within 1% of conventional SFDI

ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment.

Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune microenvironment to promote continued growth

Quantitative near-infrared spectroscopy of cervical dysplasia in vivo

The aims of this study were: (i) to quantify near-infrared optical properties of normal cervical tissues and high-grade squamous intra-epithelial lesions (H-SIL); (ii) to assess the feasibility of differentiating normal cervical tissues from H-SIL on the basis of these properties; and (iii) to determine how cervical tissue optical properties change following photodynamic therapy (PDT) of H-SIL in vivo. Using the frequency domain photon migration technique, non-invasive measurements of normal and dysplastic ecto-cervical tissue optical properties, i.e. absorption (μa) and effective scattering coefficients, and physiological parameters, i.e. tissue water and haemoglobin concentration, percentage oxygen saturation (%SO2), were performed on 10 patients scheduled for PDT of histologically-proven H-SIL. Cervix absorption and effective scattering parameters were up to 15% lower in H-SIL sites compared with normal cervical tissue for all wavelengths studied (674, 811, 849, 956 nm). Following PDT, all μa values increased significantly, due to elevated tissue blood and water content associated with PDT-induced hyperaemia and oedema. Tissue total haemoglobin concentration ([TotHb]) and arterio-venous oxygen saturation measured in H-SIL sites were lower than normal sites ([TotHb]: 88.6 ± 35.8 μmol/l versus 124.7 ± 22.6 μmol/l; %SO2: 76.5 ± 14.7% versus 84.9 ± 3.4%