Optical Biopsy an Application in Endoscopy, Colonoscopy and Ductoscopy

Here we use signals with OAM and other signals (i.e. spatial Bessel, Laguerre-Gaussian, Hermite-Gaussian waves) for cancer detection.  We also use signals with multiple and different frequencies for cancer detection. We can use fluorescence emission with structured photons for cancer detection.  We can also use TDM for multiple probing together with video light for illumination, real-time detection and ablation of unwanted tissues.

We have identified specific tissue signatures from ratios of two frequency scattered spectrums when the tissue is hit by 2 frequency probes. We also have identified specific tissue signatures from angular momentum spectrums when the tissue is hit by a probe helical beam. Certain tissues show specific signatures with fluorescent properties when hit by a probe beam at a specific frequency. We have seen specific signatures from electromagnetic tags or biological markers when hit by a structured beam. There are distinct signatures when the sample is hit with a structured beam: a) The circular intensity pattern changes its eccentricity (in 3D) and becomes a 3D ellipsoid and the measure of this change is a signature b) The ellipsoid center of intensity is spatially shifted and the measure of this shift is a signature c) The ellipsoid major axis rotates by a specific angle and the measure of this rotation is a signature. Specific frequencies of the beam can magnify the signature. This means that we can develop an “optical biopsy” approach to Digestive (esophageal, stomach, pancreas, liver, colon, rectal, anal, …etc.), urinary (kidney, bladder, testis, prostate), Tumors (carcinoid, nasopharyngeal, retroperitoneal sarcomas), oral (Mouth and dental), gynecological (Ovarian, Choriocarcinoma…etc.), ductoscopy for breast cancer detection, soft tissues, skin, eye, glands (exocrine and endocrine), any organs that can be illuminated by fiber (invasive or non-invasive).


Fractional OAM and Applications in Biosciences 

The orbital angular momentum of light beams is a consequence of their azimuthal phase structure. Light beams have a phase factor exp(imφ), where m is an integer and φ is the azimuthal angle and they carry orbital angular momentum (OAM) of mћ per photon along the beam axis. These light beams can be generated in the laboratory by optical devices, such as spiral phase plates or holograms, which manipulate the phase of the beam. In cases where such a device generates a light beam with an integer value of m, the resulting phase structure has the form of |m| intertwined helicities of equal phase. For integer values of m, the chosen height of the phase step generated by the optical device is equal to the mean value of the OAM in the resulting beam. Spiral phase steps with fractional step height as well as spatial holograms can be used to generate light beams with fractional OAM states. In these implementations, the generating optical device imposes a phase change of exp(iMφ) where M is not restricted to integer values. The phase structure of such beams shows a far more complex pattern. A series of optical vortices with alternating charge is created in a dark line across the direction of the phase discontinuity imprinted by the optical device. In order to obtain the mean value of the orbital angular momentum of these beams, one must average over the vortex pattern. This mean value coincides with the phase step only for the integer and half integer values.  

Molecular spectroscopy using OAM twisted beams can leverage Fractional OAM states as a molecular signature along with other intensity signatures (i.e. change of eccentricity, shift of center of mass, and rotation of the elliptical intensity) as well as phase signature (i.e. changes in the phase of the scattered beam) and specific formation of helicity distributed spectrum.

Other spectroscopy techniques include the pump-probe magneto-orbital approach. Here Laguerre-Gauss optical pump pulses impart OAM to the electronic states of a material and subsequent dynamics can be studied with femto second time resolution. The excitation uses vortex modes that distribute angular momentum over a macroscopic area determined by the spot size, and the optical probe studies the chiral imbalance of vortex modes reflected off the sample. There will be transients that evolve on time scales distinctly different from population and spin relaxation, but with large lifetimes. The method of optical orientation of electronic spin by circularly polarized photons has been used to study spin angular momentum in solid state materials. The process relies on spin-orbit coupling to transfer angular momentum from the spin of photons to the spin of electrons. This can impact the spintronics industry. What is proposed here is a spectroscopy technique that focuses instead on delocalized OAM in solids. Specifically, one can distinguish between delocalized OAM associated with the envelope wavefunction, which may be macroscopic in spatial extent, and local OAM associated with atomic sites, which is incorporated into the effective spin and electronic states. The first type of angular momentum is of fundamental interest to orbital coherent systems like quantum Hall layers, superconductors, and topological insulators.

Techniques to study non-equilibrium delocalized OAM in these and other systems would create opportunities to improve our understanding of scattering and quantum coherence of chiral electronic states, with potential implications for a material discovery. We have been studying the interaction of LG light with Glucose and Beta Amyloid and these experiments are the initial spectroscopy applications of OAM, but we have also studied the transfer of OAM between photonic modes in an optical fiber, the generation of Raman sidebands carrying OAM,  and can extend the study to OAM using a plasmonic lens, the study of optically coherent OAM in excitons using four-wave mixing, and application of linearly polarized light to create a 2D plasmonic analog to OAM light in a patterned thin metallic film. There is also the possibility of OAM light producing spin polarized photoelectrons for efficient semiconductors.

For integer OAM values, a theoretical description may exist which provides the way to treat the angle itself as quantum mechanical Hermitian operator. The description can provide the underlying theory for an uncertainty relation for angle and angular momentum.


Non-invasive Detection of Early Alzheimer By Optical Scanning of the Eye

Orbital angular momentum (OAM) beams are observed to exhibit unique topological evolution upon interacting with chiral solutions (beta-amyloid). Given these unique topological features one can detect the beta-amyloid of a given solution with specific signatures in both the amplitude and in phase measurements. When a twisted beam is incident upon the sample of beta-amyloid, the scattered intensity will have three distinct signatures including a change in eccentricity,  a shift or translation in center of gravity, and a rotation in three general directions (α,β,γ) of the ellipsoidal intensity output. These three distinct signatures will appear in varying degrees when the beta-amyloid molecule is detected. OAM is not typically carried by naturally scattered photons which makes the use of twisted beams more accurate when identifying helicities of chiral molecules because it does not have ambient light scattering (noise) in detection. Detection of the buildup of the beta-amyloid molecule in the eye, a protein associated with Alzheimer's, can be applied to a non-invasive eye examination. Twisted beams are generated by sending plane waves through a spatial light modulator (SLM), an amplitude mask or a phase mask. Those beams are then sent through a solution and a camera detects the beams after the solution to calculate its distinct topological features. Measurements of ellipticity are performed to identify the specific signatures.

Modal Crosstalk Using Structured Beams for Spectroscopy Applications

The Fluorescence ratio at the two different wavelengths appears like quantitative biomarker. It is < 1 in normal and ≥ 1 in Glycated Hb. Using the fluorescence measurement at two different wavelengths on a sample material with orthogonal signals in HG, LG, or IG to create two matrices A and B with each mode and its crosstalk. Using matrix A and B to perform Singular Value Decomposition (SVD) on C which is the product of matrix A and the inverse of matrix B (C=AB-1) to obtain a diagonal matrix D that is the signature of the sample material under test. We use the diagonal 'signature' matrix to detect glycated human Hemoglobin to act as investigative biomarkers for chronic hyperglycemic conditions such as Diabetes Mellitus Type 1 and 2. Singular Value Decomposition on the matrix C (C= AB-1) yields three matrices (UDV) and the D matrix is the signature of the molecule with only sigma values along its diagonal. Matrices A and B are the intensity matrices of the glycated sample at two different wavelengths and the alpha values that are not along the diagonal are crosstalk from other modes which are much smaller values. Emission at ≈360 nm and 325 nm is seen in both samples, higher intensity at 325 in Glycated samples. When observing absorption, Soret band ≈410 nm is altered. Also, α band at ≈570 and β band at ≈534 nm shows significant differences. Fermi doublets of tyrosine at 830, 850 cm-1 intensities indicate altered Hydrogen bonding states in Glycated Hb. The ratio of Tryptophan Fermi doublet modes at 1340 and 1360 indicate less hydrophobicity in Glycated Hb suggesting loss Hydrophobic bonding and increased unfolding of protein. Changes in the fluorescence life times of native fluorophores differ in glycated and normal proteins. Florescence stokes Δ λ (excitation – emission) differences of the native fluorophores like tryptophan differ in glycated and normal proteins

Changes in Raman vibrational modes of Amide 1 and 3 Bands related to protein structure differ in glycated and normal proteins. Changes in Raman vibrational modes of amino acid residues due to altered molecular orientation and symmetry of the bond vibrations, and chemistry differ in glycated and normal proteins. Emission wavelengths of UV fluorescence of HbA1 is due to Tryptophan get altered either by Amadori reaction or due to Hb structural changes. Glycation causes loss of globular structure of Hb due to unfolding of its α Helical segments. The non-enzymatic glycosylation of hemoglobin that results from sustained elevated blood sugar levels changes the chemistry of its native chromophore and fluorophore moieties as a result its tertiary structure gets altered significantly. Post translational molecular modifications would induce changes in optical properties like absorption, fluorescence emissions, fluorescence lifetimes and Raman fingerprints.



Prediction of Heart Deterioration and Sudden Cardiac Arrest Via a Wearable

We show how prediction of deteriorating heart efficiency as well as sudden cardiac death is possible. We combine the techniques of Catastrophe theory, time domain, frequency domain, time-frequency, decision based neural net, back propagation neural net, wavelets, as well as topological and chaotic feature analysis to increase accuracy (AC), sensitivity (SN), specifity (SP) and precision (P). These deaths can be reduced by using medical equipment, such as defibrillators, after detection. Today a simple inspection of the ECG cannot extract proper information in the signal to predict deterioration of heart health and sudden cardiac death. However, there is a way to predict such deterioration of heart and a catastrophic sudden cardiac death with enough time for the patient to get to a hospital via a wearable device (i.e. Apple or Google Watch). To do this, we leverage two of our previous patents on Attractor Assisted AI as well as Multiple Layer Overlay Modulation. From these two patents, we can extract Time-Bandwidth and the nonlinear features, topological features and dynamical invariants from HRV of ECG signal. Finally, healthy people and people at risk of sudden cardiac death can be classified by such time-bandwidth and topological features. It seems that HRV signals have special features indicating the occurrence of SCD that can be distinguished between patients prone to sudden cardiac death and normal people. The techniques introduced here and in our previous patent can be incorporated into wearable devices such as watches with biometric sensors (i.e. Apple watch can monitor ECG signals and over 30 countries are able to use this feature today).  The most common cause of sudden cardiac death in adults over the age of 30 is coronary artery atheroma. The most common finding at postmortem examination is chronic high-grade stenosis of at least one segment of a major coronary artery, the arteries which supply the heart muscle with its blood supply. A significant number of cases also have an identifiable clot in a major coronary artery which causes transmural occlusion of that vessel. Left ventricular hypertrophy is the second leading cause of sudden cardiac death in the adult population. This is most commonly the result of longstanding high blood pressure which has caused secondary damage to the wall of the main pumping chamber of the heart, the left ventricle. Hypertrophy, as well, is associated with cardiac arrhythmias. The mechanism of death in most patients dying of sudden cardiac death is ventricular fibrillation; therefore, there may be no prodromal symptoms associated with the death. Patients may be going about their daily business and suddenly collapse, without any typical features of myocardial infarction (heart attack) like chest pain or shortness of breath. However, it may abruptly strike any person if he or she possesses of high-risk heart disease, even young person, and athlete. Besides utilizing public access defibrillation (PAD) procedure to rescue impending death patient after collapse, the better way is to prevent SCD by adopting medical aid prior to collapse. Here, we show how it is possible to make an early warning, even before crisis.  Researchers have found that the respiratory peak of the heart rate variability (HRV) in SCD patient can disappear during the nighttime one-week before death. They had observed that HRV is low in patients who experience SCD and is high in young healthy subjects. Though the relationship between short-term HRV and SCD is unknown, it seems repolarization alternans phenomena provides a safe, noninvasive marker for the risk of SCD, and has proven equally effective to an invasive and more expensive procedure - invasive electrophysiological study (EPS), which is commonly used by cardiac electrophysiologists. Analysis of heart rate variability (HRV) has provided a non-invasive method for assessing cardiac autonomic control. HRV is generally accepted as a strong and independent predictor of mortality after an acute myocardial infarction, such that a reduced HRV is associated with a higher risk for severe ventricular arrhythmia and sudden cardiac death. Although until now different Linear methods have been used for analysis of HRV signal, here we try to use a nonlinear attractor reconstruction which provides more information than Linear methods. We can use the QRS-complexes in the ECG-signal (i.e. RR, QQ, SS, RP, RT or any combination of signals) as time series for reconstructing the attractor, evaluation of time-bandwidth product and prediction.

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