Plum pudding random medium model of biological tissue toward remote microscopy from spectroscopic light scattering

Biological tissue has a complex structure and exhibits rich spectroscopic behavior. There is \emph{no} tissue model up to now able to account for the observed spectroscopy of tissue light scattering and its anisotropy. Here we present, \emph{for the first time}, a plum pudding random medium (PPRM) model for biological tissue which succinctly describes tissue as a superposition of distinctive scattering structures (plum) embedded inside a fractal continuous medium of background refractive index fluctuation (pudding). PPRM faithfully reproduces the wavelength dependence of tissue light scattering and attributes the "anomalous" trend in the anisotropy to the plum and the powerlaw dependence of the reduced scattering coefficient to the fractal scattering pudding. Most importantly, PPRM opens up a novel venue of quantifying the tissue architecture and microscopic structures on average from macroscopic probing of the bulk with scattered light alone without tissue excision. We demonstrate this potential by visualizing the fine microscopic structural alterations in breast tissue (adipose, glandular, fibrocystic, fibroadenoma, and ductal carcinoma) deduced from noncontact spectroscopic measurement

Validation data of lysosphingolipids measurement in plasma.

<p>Validation data of lysosphingolipids measurement in plasma.</p

Skillings-Mack and Wilcoxon signed-rank test (with Bonferroni adjustment) for FOXP3 data (see Table 2).

<p>Skillings-Mack and Wilcoxon signed-rank test (with Bonferroni adjustment) for FOXP3 data (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039368#pone-0039368-t002" target="_blank">Table 2</a>).</p

Chromatogram of lysosphingolipids standard solutions and internal standards (IS) in positive mode, standard concentrations, calibration curves, correlation coefficient (R²) and relative standard deviation (RSD) of the calibration points.

<p>1: LysoSM d17 (IS); 2: GlyLysoGb₃ (IS); 3: LysoGb₃; 4: LysoSM; 5: LysoGlcCer; 6: LysoGlcCer d5 (IS).</p

T cells expressing FOXP3.

<p>(<b>A</b>) Example of plots showing gate settings. (<b>B</b>) The frequency of FOXP3⁺ T cells at different time points, gating on CD3⁺ T cells. (<b>C</b>) Inverse correlation between the frequencies of FOXP3⁺ Treg and CEF-specific TNFα/IFNγ dual functional T cells.</p

Lysohexosylceramide (LysoHexCer) data in amniotic fluid (AF) supernatant from non-immune hydrops fetalis (NIHF) pregnancies including Gaucher disease, and controls.

<p>*** <i>p</i> < 0.001.</p

Chromatogram of lysosphingolipids standard solution and internal standard (IS) in negative mode, standard concentrations, calibration curve, correlation coefficient (R²) and relative standard deviation (RSD) of the calibration points.

<p>1: LysoGM1; 2: S1P d17 (IS).</p

Lysosphingolipids concentrations (nmol/L) in amniotic fluid (AF) supernatant from non-immune hydrops fetalis (NIHF) pregnancies (including Gaucher disease), and controls.

<p>Lysosphingolipids concentrations (nmol/L) in amniotic fluid (AF) supernatant from non-immune hydrops fetalis (NIHF) pregnancies (including Gaucher disease), and controls.</p

Gating strategy and example of ICS data.

<p>(<b>A</b>) Lymphocytes were gated based on FSC and SSC, followed by a CD3⁺ViViD⁻ viable T cell gate. (<b>B</b>) Example of data from PT#3, depicting typical positive (6×CTL, core antigen) and negative (E1E2 antigen) responses following DC infusion compared to baseline. (<b>C</b>) These plots are derived from the same data as the core antigen response at week 2 (W2), depicting the cellular source of the cytokines. The 1^st plot (left) shows cytokine positive cells (red) within viable CD3 T cells (grey), the 2^nd plot shows the position of the CD4⁺ and CD8⁺ T cell gates, and the 3^rd and 4^th plots depict the cytokine staining profiles of CD4⁺ T cells and CD8⁺ T cells respectively.</p

Lysosphingolipids concentrations (nmol/L) in plasma from controls, sphingolipidoses, Niemann-Pick type C disease and other inborn error of metabolism.

<p>Statistical significance is indicated as follows: * <i>p</i> < 0.05; ** <i>p</i> < 0.01; *** <i>p</i> < 0.001. LALD: Lysosomal Acid Lipase Deficiency; LSDs: lysosomal storage diseases.</p