Non-invasive imaging through dynamic scattering media via mutual coherence function transmission

Near-infrared fluorescence imaging with fluorescently labeled albumin: A novel method for non-invasive optical imaging of blood–brain barrier impairment after focal cerebral ischemia in mice

Noninvasive tomographic imaging methods including positron emission tomography (PET) and single photon emission computed tomography (SPECT) are extremely sensitive and are capable of measuring biochemical processes that occur at concentrations in the nanomolar range. Inherent to neurodegenerative processes is neuronal loss. Thus, PET or SPECT monitoring of biochemical processes altered by neuronal loss (changes in neurotransmitter turnover, alterations in receptor, transporter or enzyme concentrations) can provide unique information not attainable by other methods. Such imaging techniques can also be used to longtitudinally monitor the effects of neuroprotective treatments. This review highlights current imaging probes used to evaluate patients with specific neurodegenerative disorders (e.g., Alzheimer's Disease, Parkinson's Disease, Huntington's Chorea), including those that image receptors of the dopaminergic, cholinergic and glutamatergic systems. Areas of future research focus are also defined. It is clear that monitoring the progression of neurodegenerative disorders and the impact of neuroprotective treatments are two different but related goals for which noninvasive imaging via PET and SPECT methods plays a powerful and unique role.

This thesis consists of two parts. The first one is "Scattering of Waves in a Random Medium," and the second one is "Radiative Transfer in a Sphere Illuminated by a Parallel Beam: An Integral Equation Approach." In the first part, a new formalism tor partially coherent wave scattering in a random medium is developed. In this formalism the coherent wave is the solution of a phenomenological wave equation, and the mutual coherence function of the wave field satisfies a simple integral equation. Using this formalism, the Peierls equation can be readily derived. Also, an improved version of the Peierls equation is derived in which the intensity of the wave field and the first order derivative of the mutual coherence function are calculated at the same time. A simple problem is solved to find the mutual coherence function produced by a laser beam in the atmosphere. The similarity between the mutual coherence function and the density matrix or quantum mechanics is explored and a measure of the randomness is defined for the partially coherent wave field. In the second part of this work, the problem of multiple scattering of non-polarized light in a planetary body of arbitrary shape illuminated by a parallel beam is formulated using the integral equation approach. There exists a simple functional whose stationarity condition is equivalent to solving the equation of radiative transfer and whose value at the stationary point is proportional to the differential cross section. Our analysis reveals a direct relation between the microscopic symmetry of the. Phase function for each scattering event and the macroscopic symmetry of the differential cross section for the entire planetary body, and the intimate connection between these symmetry relations and the variational principle. The case of a homogeneous sphere containing isotropic scatterers is investigated in detail. It is shown that the solution can be expanded in a multipole series such that the general spherical problem is reduced to solving a set of decoupled integral equations in one dimension. Computations have been performed for a range of parameters of interest, and illustrative examples of applications to planetary problems are provided.

Rosacea assessment and therapy monitoring can be challenging to standardize, as most clinical evaluation systems are prone to interobserver variability and not always validated. Therefore, objective, reliable and preferably noninvasive measurement tools are needed. To give insight into available noninvasive imaging techniques and biophysical methods in rosacea by performing a systematic review. PubMed, Embase, Cochrane and Web of Science databases were searched until 1 September 2018 in accordance with PRISMA guidelines, to identify studies providing original data about objective noninvasive imaging and/or biophysical skin measurement techniques for diagnosis, assessing severity or therapy monitoring of adult patients with cutaneous facial rosacea. Risk of bias of included articles was assessed with the Cochrane Risk of Bias tool, Quality in Prognosis Studies tool, and the Newcastle-Ottawa Scale. A total of 78 studies were included, describing 14 imaging and biophysical methods. Widespread information about (sub)surface cutaneous morphology and functionality was obtained. Methodological study quality was relatively low and interstudy outcome variability was large. Several tools show promising value in research settings: for treatment follow-up Demodex mites are countable with reflectance confocal microscopy, spectrometry can quantify erythema, and rosacea severity could be objectified with skin hydration- and transepidermal water loss measurements. This systematic review describes the spectrum of noninvasive imaging and biophysical methods in rosacea assessment, giving multifaceted information about structure and properties of rosacea skin, especially useful for research purposes. Larger studies with good methodological quality are needed to create validated protocols for further implementation into research. What's already known about this topic? Rosacea is a chronic inflammatory skin disease with a variety of clinical manifestations. Most clinical evaluation systems are subjective, not always validated, and subsurface skin processes remain unnoticed. Currently, different types of noninvasive measurement tools are available for rosacea assessment and therapy monitoring, but a comprehensive overview is lacking. What does this study add? Seventy-eight publications were included, describing 14 imaging and biophysical tools, providing a wide range of information about rosacea skin morphology and functionality. Reflectance confocal microscopy and spectrometry are especially promising in therapy monitoring and skin barrier measurements for rosacea severity assessment. Larger studies with better methodological quality are needed to create validated protocols for implementation into research.

Photoacoustic (PA) imaging may be advantageous as a safe, non-invasive imaging modality to image the carotid artery. However, calcification that accompanies atherosclerotic plaque is difficult to detect with PA due to the non-distinct optical absorption spectrum of hydroxyapatite. We propose reflection-mode all-optical laser-ultrasound (LUS) imaging to obtain high-resolution, non-contact, non-ionizing images of the carotid artery wall and calcification. All-optical LUS allows for flexible acquisition geometry and user-dependent data acquisition for high repeatability. We apply all-optical techniques to image an excised human carotid artery. Internal layers of the artery wall, enlargement of the vessel, and calcification are observed with higher resolution and reduced artifacts with nonconfocal LUS compared to confocal LUS. Validation with histology and X-ray computed tomography (CT) demonstrates the potential for LUS as a method for non-invasive imaging in the carotid artery.

Background: Psoriasis is one of the most commonly recognized dermatological diseases, characterized by distinct structural changes, hyperproliferation and inflammation. The aim of the study was quantitative comparisons of psoriatic skin with skin without psoriatic lesions by non-invasive imaging methods. Methods: 71 patients diagnosed with psoriasis vulgaris underwent non-invasive imaging of skin at the site of the psoriatic lesion and at the site without such lesion. Skin density, epidermis thickness and subepidermal low-echogenic band (SLEB) thickness were measured by high-resolution ultrasound (HFU). Blood perfusion was assessed using laser speckle contrast analysis (LASCA) and skin temperature was measured by thermal imaging camera. Hyperspectral camera was used to obtain spectral reflectance profiles in psoriatic lesion and skin without psoriatic changes. Results: The greatest differences in skin density and epidermal thickness between psoriatic and unchanged skin were observed on the forearms. The skin covered with psoriatic plaques was 80% less dense, and the epidermis in this area was 121% thicker. The greatest thickness of SLEB was observed in the knee area (Me = 0.389 mm). Skin with psoriatic lesions is characterized by a higher temperature (Me = 33.6 vs. Me = 31) and blood perfusion than skin without psoriasis (Me = 98.76 vs. Me = 50.65). Skin without psoriasis shows lower reflectance than psoriatic lesion from 623 nm to 1000 nm; below this value, skin without psoriatic lesion shows higher reflectance. Conclusions: Skin density and epidermis thickness, skin blood perfusion, temperature and reflectance can be useful parameters for monitoring the course of psoriasis and its treatment, especially since the examination of psoriatic skin with proposed methods is non-invasive, quantitative and easy to perform in clinical conditions.

This paper presents an analytical expression of MIMO propagation matrix in a random medium. We first extend the SVD (singular value decomposition) to include the propagation channels in the random medium in terms of the stochastic Green’s functions. The eigenvalues and eigenfunctions are obtained from the transfer matrix 〈T〉=〈H’H〉. The elements of 〈T〉 can be expressed analytically using the coherent Green’s function and the mutual coherence function. Examples are shown for the propagation channel consisting of a random distribution of scatterers. Included in this analysis are the effects of number density, scatterer sizes, scattering pattern, and scatterer locations.

The Markov approximation significantly simplifies formulations for the statistical moments of a wave propagating in a random medium. For the phase fluctuations, the Markov approximation is expected to be valid if the propagation range is much greater than the scale of largest inhomogeneities in a medium. In the atmospheric boundary layer, this scale can be several hundred meters, indicating that the Markov approximation might be inapplicable for relatively small ranges. In this paper, using geometrical acoustics, the correlation function and variance of the phase fluctuations of a plane sound wave are calculated without the Markov approximation and compared to previous results based on this approximation. The mean sound field and the spatial mutual coherence function (MCF) are also analyzed by expressing them in terms of the phase fluctuations. It is shown that for ranges smaller than the scale of largest inhomogeneities, the variance of the phase fluctuations is significantly smaller than that found with the Markov approximation. For large ranges, the relative difference between the two results tends to zero, while the absolute difference remains constant and can be much greater than unity. For the MCF, the Markov approximation is valid for both small and large ranges.

Pulmonary hypertension (PH) is defined as resting mean pulmonary arterial pressure (mPAP) ≥25 millimeters of mercury (mmHg) via right heart (RH) catheterization (RHC), where increased afterload in the pulmonary arterial vasculature leads to alterations in RH structure and function. Mortality rates have remained high despite therapy, however non-invasive imaging holds the potential to expedite diagnosis and lead to earlier initiation of treatment, with the hope of improving prognosis. While historically the right ventricle (RV) had been considered a passive chamber with minimal role in the overall function of the heart, in recent years in the evaluation of PH and RH failure the anatomical and functional assessment of the RV has received increased attention regarding its performance and its relationship to other structures in the RH-pulmonary circulation. Today, the RV is the key determinant of patient survival. This review provides an overview and summary of non-invasive imaging methods to assess RV structure, function, flow, and tissue characterization in the setting of imaging's contribution to the diagnostic, severity stratification, prognostic risk, response of treatment management, and disease surveillance implications of PH's impact on RH dysfunction and clinical RH failure.

The earthquake source duration is short; however, the apparent duration time of observed seismogram increases with travel distance. The amplitude excitation is observed even on the transverse component for P waves, on the longitudinal component for S waves. These phenomena are well explained by scattering due to random velocity inhomogeneities around the global seismic ray. We directly synthesize vector‐wave envelopes in 3‐D random elastic media statistically characterized by a nonisotropic Gaussian autocorrelation function (ACF). The method uses the Markov approximation in the case that the wavelength is shorter than the correlation distance and the ray direction is parallel to one of the principal axes of the ACF. A spherical outgoing vector wavelet radiated from a point source in the random elastic media is used as a basic model for high‐frequency seismogram envelopes from micro‐earthquakes in the inhomogeneous lithosphere. The stochastic master equation for the two‐frequency mutual coherence function (TFMCF) of the potential field is analytically solved. The Fourier transform of TFMCF gives mean square (MS) envelopes of band‐pass filtered vector‐wave traces. If the ACF is axially symmetric around the ray direction, MS envelopes of vector components are analytically solved. The aspect ratio of the correlation distance in the longitudinal direction to that in the transverse direction is the key parameter for the envelope broadening and the excitation in the orthogonal component. Envelope broadening becomes longer and the transverse (longitudinal) component amplitude increases for a P wavelet (for an S wavelet) when the correlation distance in the transverse plane becomes smaller. When the vertical correlation distance is shorter than the horizontal one as seen in the real Earth, the envelope broadening is larger for horizontal raypaths compared with vertical raypaths.

We present a method for noninvasive three-dimensional imaging through scattering media by using a three-dimensional memory effect in scattering phenomena. In the proposed method, an object in a scattering medium is reconstructed from a three-dimensional autocorrelation of speckle images captured by axially scanning an image sensor, based on a three-dimensional phase retrieval algorithm. We experimentally demonstrated our method with a lensless setup by using a three-dimensionally printed object between diffusers.

Objective. Compression-induced solid stress (SSc) and fluid pressure (FPc) during ultrasound poroelastography (USPE) experiments are correlated with two markers of cancer growth and treatment effectiveness: growth-induced solid stress (SSg) and interstitial fluid pressure (IFP). The spatio-temporal distributions of SSg and IFP are determined by the transport properties of the vessels and interstitium in the tumor microenvironment. Approach. We propose a new USPE method for the non-invasive imaging of the local cancer mechanical parameters and dynamics of fluid flow. When performing poroelastography experiments, it may be difficult to implement a typical creep compression protocol, which requires to maintain a constant normally applied force. In this paper, we investigate the use of a stress relaxation protocol, which might be a more convenient choice for clinical poroelastography applications. Main results. Based on our finite element and ultrasound simulations study, we demonstrate that the SSc, FPc and their spatio-temporal distribution related parameters, interstitial permeability and vascular permeability, can be determined from stress relaxation experiments with errors below 10% as compared to the ground truth and accuracy similar to that of corresponding creep tests, respectively. We also demonstrate the feasibility of the new methodology for in vivo experiments using a small animal cancer model. Significance. The proposed non-invasive USPE imaging methods may become an effective tool to assess local tumor pressure and mechanopathological parameters in cancers.

BackgroundGene therapy continues to hold great potential for treating many different types of disease and dysfunction. Safe and efficient techniques for gene transfer and expression in vivo are needed to enable gene therapeutic strategies to be effective in patients. Currently, the most commonly used methods employ replication-defective viral vectors for gene transfer, while physical gene transfer methods such as biolistic-mediated ("gene-gun") delivery to target tissues have not been as extensively explored. In the present study, we evaluated the efficacy of biolistic gene transfer techniques in vivo using non-invasive bioluminescent imaging (BLI) methods.ResultsPlasmid DNA carrying the firefly luciferase (LUC) reporter gene under the control of the human Cytomegalovirus (CMV) promoter/enhancer was transfected into mouse skin and liver using biolistic methods. The plasmids were coupled to gold microspheres (1 μm diameter) using different DNA Loading Ratios (DLRs), and "shot" into target tissues using a helium-driven gene gun. The optimal DLR was found to be in the range of 4-10. Bioluminescence was measured using an In Vivo Imaging System (IVIS-50) at various time-points following transfer. Biolistic gene transfer to mouse skin produced peak reporter gene expression one day after transfer. Expression remained detectable through four days, but declined to undetectable levels by six days following gene transfer. Maximum depth of tissue penetration following biolistic transfer to abdominal skin was 200-300 μm. Similarly, biolistic gene transfer to mouse liver in vivo also produced peak early expression followed by a decline over time. In contrast to skin, however, liver expression of the reporter gene was relatively stable 4-8 days post-biolistic gene transfer, and remained detectable for nearly two weeks.ConclusionsThe use of bioluminescence imaging techniques enabled efficient evaluation of reporter gene expression in vivo. Our results demonstrate that different tissues show different expression kinetics following gene transfer of the same reporter plasmid to different mouse tissues in vivo. We evaluated superficial (skin) and abdominal organ (liver) targets, and found that reporter gene expression peaked within the first two days post-transfer in each case, but declined most rapidly in the skin (3-4 days) compared to liver (10-14 days). This information is essential for designing effective gene therapy strategies in different target tissues.

Recently, new non-invasive imaging methods have been developed and applied to cellular and animal mammary models that have enabled breast cancer researchers to track key players and events in mammary metastasis. Noninvasive nonlinear optical methods such as multiphoton laser scanning microscopy (MPLSM), Fluorescence Lifetime Microscopy (FLIM) and second harmonic generation (SHG) imaging provide an unrivaled ability for obtaining high-resolution images from deep within tissue that can be exploited in the quest to understand breast cancer progression. These optical methods can add greatly to our knowledge of cancer progression by allowing key processes to be non-invasively imaged such as metabolism (on the basis of free and bound NADH detection via FLIM) and interactions with the extracellular matrix (SHG imaging of collagen). In this short application note we present a survey of our latest optical and computational efforts to study intrinsic fluorescence in breast cancer models. In particular we present the latest development in our SLIM Plotter application, an open source visualization program for interactive visualization and inspection of combined spectral lifetime (SLIM) data.

Islet transplantation is a promising treatment for type 1 diabetic patients. However, there is acute as well as chronic loss of islets after transplantation. A noninvasive imaging method that could monitor islet mass might help to improve transplantation outcomes. In this study, islets were visualized after transplantation in a rat model with a dedicated small-animal SPECT scanner by targeting the glucagonlike peptide-1 receptor (GLP-1R), specifically expressed on β-cells, with (111)In-labeled exendin-3. Targeting of (111)In-exendin-3 to GLP-1R was tested in vitro on isolated islets of WAG/Rij rats. For in vivo evaluation, 400 or 800 islets were transplanted into the calf muscle of WAG/Rij rats (6-8 wk old). Four weeks after transplantation, SPECT/CT images were acquired 1 h after injection of (111)In-labeled exendin-3. After SPECT acquisition, the muscles containing the transplant were analyzed immunohistochemically and autoradiographically. The binding assay, performed on isolated islets, showed a linear correlation between the number of islets and (111)In-exendin-3 accumulation (Pearson r = 0.98). In vivo, a 1.70 ± 0.44-fold difference in tracer uptake between 400 and 800 transplanted islets was observed. Ex vivo analysis of the islet transplant showed colocalization of tracer accumulation on autoradiography, with insulin-positive cells and GLP-1R expression on immunohistochemistry. (111)In-exendin-3 accumulates specifically in the β-cells after islet transplantation and is a promising tracer for noninvasive monitoring of the islet mass.