Contribution of speckle noise in near-infrared spectroscopy measurements

Near-infrared spectroscopy (NIRS) is widely used in biomedical optics with applications ranging from basic science, such as in functional neuroimaging, to clinical, as in pulse oximetry. Despite the relatively low absorption of tissue in the near-infrared, there is still a significant amount of optical attenuation produced by the highly scattering nature of tissue. Because of this, designers of NIRS systems have to balance source optical power and source–detector separation to maximize the signal-to-noise ratio (SNR). However, theoretical estimations of SNR neglect the effects of speckle. Speckle manifests as fluctuations of the optical power received at the detector. These fluctuations are caused by interference of the multiple random paths taken by photons in tissue. We present a model for the NIRS SNR that includes the effects of speckle. We performed experimental validations with a NIRS system to show that it agrees with our model. Additionally, we performed computer simulations based on the model to estimate the contribution of speckle noise for different collection areas and source–detector separations. We show that at short source–detector separation, speckle contributes most of the noise when using long coherence length sources. Considering this additional noise is especially important for hybrid applications that use NIRS and speckle contrast simultaneously, such as in diffuse correlation spectroscopy.R01 EB025145 - NIBIB NIH HHS; R24 NS104096 - NINDS NIH HHSPublished versio

Experimental Evidence of the Role of Compound Counting Processes in Random Walk Approaches to Fractional Dynamics

We present dielectric spectroscopy data obtained for gallium-doped Cd$_{0.99}$Mn$_{0.01}$Te:Ga mixed crystals which exhibit a very special case of the two-power-law relaxation pattern with the high-frequency power-law exponent equal to 1. We explain this behavior, which cannot be fitted by none of the well-known empirical relaxation functions, in a subordinated diffusive framework. We propose diffusion scenario based on a renormalized clustering of random number of spatio-temporal steps in the continuous time random walk. Such a construction substitutes the renewal counting process, used in the classical continuous time random walk methodology, by a compound counting one. As a result, we obtain a novel relaxation function governing the observed non-standard pattern, and we show the importance of the compound counting processes in studying fractional dynamics of complex systems.Comment: 6 pages, 5 figures; corrected versio

Anomalous transport in the crowded world of biological cells

A ubiquitous observation in cell biology is that diffusion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarising their densely packed and heterogeneous structures. The most familiar phenomenon is a power-law increase of the MSD, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations, non-gaussian distributions of the displacements, heterogeneous diffusion, and immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarise some widely used theoretical models: gaussian models like FBM and Langevin equations for visco-elastic media, the CTRW model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Emphasis is put on the spatio-temporal properties of the transport in terms of 2-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even for identical MSDs. Then, we review the theory underlying common experimental techniques in the presence of anomalous transport: single-particle tracking, FCS, and FRAP. We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where model systems mimic physiological crowding conditions. Finally, computer simulations play an important role in testing the theoretical models and corroborating the experimental findings. The review is completed by a synthesis of the theoretical and experimental progress identifying open questions for future investigation.Comment: review article, to appear in Rep. Prog. Phy

Deducing effective light transport parameters in optically thin systems

We present an extensive Monte Carlo study on light transport in optically thin slabs, addressing both axial and transverse propagation. We completely characterize the so-called ballistic-to-diffusive transition, notably in terms of the spatial variance of the transmitted/reflected profile. We test the validity of the prediction cast by diffusion theory, that the spatial variance should grow independently of absorption and, to a first approximation, of the sample thickness and refractive index contrast. Based on a large set of simulated data, we build a freely available look-up table routine allowing reliable and precise determination of the microscopic transport parameters starting from robust observables which are independent of absolute intensity measurements. We also present the Monte Carlo software package that was developed for the purpose of this study

Axon diameters and myelin content modulate microscopic fractional anisotropy at short diffusion times in fixed rat spinal cord

Mapping tissue microstructure accurately and noninvasively is one of the frontiers of biomedical imaging. Diffusion Magnetic Resonance Imaging (MRI) is at the forefront of such efforts, as it is capable of reporting on microscopic structures orders of magnitude smaller than the voxel size by probing restricted diffusion. Double Diffusion Encoding (DDE) and Double Oscillating Diffusion Encoding (DODE) in particular, are highly promising for their ability to report on microscopic fractional anisotropy ({\mu}FA), a measure of the pore anisotropy in its own eigenframe, irrespective of orientation distribution. However, the underlying correlates of {\mu}FA have insofar not been studied. Here, we extract {\mu}FA from DDE and DODE measurements at ultrahigh magnetic field of 16.4T in the aim to probe fixed rat spinal cord microstructure. We further endeavor to correlate {\mu}FA with Myelin Water Fraction (MWF) derived from multiexponential T2 relaxometry, as well as with literature-based spatially varying axonal diameters. In addition, a simple new method is presented for extracting unbiased {\mu}FA from three measurements at different b-values. Our findings reveal strong anticorrelations between {\mu}FA (derived from DODE) and axon diameter in the distinct spinal cord tracts; a moderate correlation was also observed between {\mu}FA derived from DODE and MWF. These findings suggest that axonal membranes strongly modulate {\mu}FA, which - owing to its robustness towards orientation dispersion effects - reflects axon diameter much better than its typical FA counterpart. The {\mu}FA exhibited modulations when measured via oscillating or blocked gradients, suggesting selective probing of different parallel path lengths and providing insight into how those modulate {\mu}FA metrics. Our findings thus shed light into the underlying microstructural correlates of {\mu}FA and are (...

Two-Dimensional Electronic Spectroscopy of Chlorophyll a: Solvent Dependent Spectral Evolution

The interaction of the monomeric chlorophyll Q-band electronic transition with solvents of differing physical-chemical properties is investigated through two-dimensional electronic spectroscopy (2DES). Chlorophyll constitutes the key chromophore molecule in light harvesting complexes. It is well-known that the surrounding protein in the light harvesting complex fine-tunes chlorophyll electronic transitions to optimize energy transfer. Therefore, an understanding of the influence of the environment on the monomeric chlorophyll electronic transitions is important. The Q-band 2DES is inhomogeneous at early times, particularly in hydrogen bonding polar solvents, but also in nonpolar solvents like cyclohexane. Interestingly this inhomogeneity persists for long times, even up to the nanosecond time scale in some solvents. The reshaping of the 2DES occurs over multiple time scales and was assigned mainly to spectral diffusion. At early times the reshaping is Gaussian-like, hinting at a strong solvent reorganization effect. The temporal evolution of the 2DES response was analyzed in terms of a Brownian oscillator model. The spectral densities underpinning the Brownian oscillator fitting were recovered for the different solvents. The absorption spectra and Stokes shift were also properly described by this model. The extent and nature of inhomogeneous broadening was a strong function of solvent, being larger in H-bonding and viscous media and smaller in nonpolar solvents. The fastest spectral reshaping components were assigned to solvent dynamics, modified by interactions with the solute