Probing volar side fingertip capillary beds with 830 nm light produces remission spectra containing Rayleigh and Raman scattered light, and fluorescence, allowing continuous monitoring of intravascular plasma volume and hematocrit using the FRD-PVOH algorithm. During dialysis, Raman emission by polyatomic electrolytes i.e., phosphate tracks with fluid removal i.e., the change in intravascular plasma volume and in agreement with simultaneous hematocrit measurement of extracorporeal blood in the dialysis unit using the FDA approved CritLine. The variation of Raman features associated with urea in interstitial fluid and plasma suggests urea is involved in chemistry in the skin compartment i.e., in the extravascular space causing its clearance to lag the removal of electrolytes and water. Consistent with known skin conditions induced by chronic kidney disease and dialysis, we speculate that routine excess urea in the interstitial fluid destabilizes hydrogen bonding networks associated with keratin bundles in both viable keratinocytes and stratum corneum, exposing disulfide linkages, making them vulnerable to reduction by other species in the interstitial fluid. Oral administration of furosemide removes more water than electrolytes relative to the proportions removed by dialysis leading to solubility stress and striking variations of the Raman spectra. These results reinforce the notion that the various compartments in the human body do not drain at equal rates during dialysis and that real time Raman and FRD-PVOH monitoring-based feedback during hemodialysis could reduce the frequency of adverse events and thus improve outcomes.
KEYWORDS: Tumors, Breast, Digital breast tomosynthesis, Biomedical optics, Mammography, Tissues, Hemodynamics, Chemotherapy, Breast cancer, Magnetic resonance imaging
SignificanceAchieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes.AimWe aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT.ApproachTwenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers.ResultsNormalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles (p=0.042). In addition, the change in normalized tumor StO2 upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle (p=0.038). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI.ConclusionsThese findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.
Multimodal x-ray mammography and optical imaging data were acquired on six breast cancer patients who underwent neoadjuvant chemotherapy (NACT) but reponded differently to their treatment. Changes in tumor contrast quantified by total hemoglobin concentration (HbT) between baseline and pre-cycle 3 are distinctive across various levels of pathological outcomes. While decreases in lesion size have been observed in all cases regardless of pathological outcomes, optical contrast shows more distinctive response characteristics that could potentially be used to differentiate complete responders from partial responders.
Breast cancer is a highly heterogeneous disease comprising a variety of genotypes and phenotypes of varying levels of aggressiveness. This presents significant challenges to clinical management of early-stage cancers. In this paper, we describe the use of multimodal optical technologies including near-infrared (NIR) spectroscopy, diffuse correlation spectroscopy (DCS) and indocyanine green (ICG) fluorescence imaging to evaluate the aggressiveness and progression of two patient-derived xenograft models of human breast cancer. Optical markers reveal distinctive features between low- and high-aggressiveness tumors that could potentially be translated for clinical use.
In this paper, we describe a deep convolutional neural network (DNN) model trained with simulated breast diffuse optical tomography data with realistic noise characteristics to solve the inverse problem in a fast single-pass feed forward reconstruction. In addition to an AUTOMAP-inspired network structure, our DNN model, a.k.a. FDU-Net, is also comprised of a U-Net to further improve the image quality. We demonstrate that our FDU-Net model can successfully recover nearly the full contrast of inclusions with accurate localization at millisecond-scale speed, outperforming the conventional finite element-based (FEM) methods. Trained with cases with a single spherical inclusion, the FDU-Net model can also recover multi-inclusions and irregular-shaped cases, demonstrating advantages of generalization.
Non-invasive monitoring of cerebral blood flow at the bedside using diffuse correlation spectroscopy is being investigated as a potential tool to improve brain health outcomes after surgery. In this work we characterize the performance of diffuse correlation spectroscopy measurements in assessing cerebral blood flow in the presence of systemic physiology interference through measurements on several healthy volunteers during CO2 inhalation. We report group averaged responses and the role of multi-layer models in increasing the accuracy of CBF estimates. We compare optical blood flow recordings with transcranial Doppler ultrasound and MRI ASL data.
Significance: Contamination of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow (CBF) due to systemic physiology remains a significant challenge in the clinical translation of DCS for neuromonitoring. Tunable, multi-layer Monte Carlo-based (MC) light transport models have the potential to remove extracerebral flow cross-talk in cerebral blood flow index (CBFi) estimates.
Aim: We explore the effectiveness of MC DCS models in recovering accurate CBFi changes in the presence of strong systemic physiology variations during a hypercapnia maneuver.
Approach: Multi-layer slab and head-like realistic (curved) geometries were used to run MC simulations of photon propagation through the head. The simulation data were post-processed into models with variable extracerebral thicknesses and used to fit DCS multi-distance intensity autocorrelation measurements to estimate CBFi timecourses. The results of the MC CBFi values from a set of human subject hypercapnia sessions were compared with CBFi values estimated using a semi-infinite analytical model, as commonly used in the field.
Results: Group averages indicate a gradual systemic increase in blood flow following a different temporal profile versus the expected rapid CBF response. Optimized MC models, guided by several intrinsic criteria and a pressure modulation maneuver, were able to more effectively separate CBFi changes from scalp blood flow influence than the analytical fitting, which assumed a homogeneous medium. Three-layer models performed better than two-layer ones; slab and curved models achieved largely similar results, though curved geometries were closer to physiological layer thicknesses.
Conclusion: Three-layer, adjustable MC models can be useful in separating distinct changes in scalp and brain blood flow. Pressure modulation, along with reasonable estimates of physiological parameters, can help direct the choice of appropriate layer thicknesses in MC models.
The initial biological response to spinal cord injury is initiated by intra- and extracellular chemical signals. We compare Raman spectra of injured spinal cord obtained minutes after injury to those of uninjured spinal cord to obtain chemical information that precedes the biological response. We studied 29 rats including both Injured and Control using Raman spectra of spinal cords in vivo. Principal Component Analysis (PCA) indicates that <99% of the variation of these spectra across both Injured and Control groups is accounted for with 3 components. The first component does not vary significantly representing structural materials. The second and third components reflect the variation in the chemistry of the cerebrospinal fluid. We demonstrate the first noninvasive in vivo measurement of pH in the CSF using only Raman spectra. We hypothesize that the earliest inflammatory response to mild contusive injury reflects the chemistry of inorganic phosphate present at abnormally high concentrations, likely due to physical disruption of the blood-brain barrier in the choroid plexus and/or mitochondrial release of phosphate, reacting with CSF water.
Thermoregulation is a mammalian physiological function fulfilled in large part by autonomic control of blood flow. We demonstrate the variation in hematocrit (Hct) and intravascular volume (VV) in the peripheral circulation when the external means of maintaining the initial thermal disequilibrium is removed using a PV[O]H device capable of noninvasively measuring both Hct and VV with unprecedented sensitivity, accuracy and precision on a 3 second timescale. Calibrated using an FDA approved device now in standard use for monitoring Hct during dialysis, the PV[O]H detection limit for measuring Hct variation is ±0.03 where 45% is normal. Observing the return to thermal equilibrium at 2 separate anatomic locations, we observe the return to normal homeostasis in a matter of a few minutes. Heat induced vasodilation results in an antecedent increase in plasma volume in greater proportion than for red blood cells into the dilated capillaries. At equilibrium homeostasis i.e. when there is no externally maintained thermal gradient we observe periodic fluctuations in the peripheral Hct and VV on a roughly 15 second to 1.5 minute timescale.
We previously reported a new algorithm “PV[O]H” for continuous, noninvasive, in vivo monitoring of hematocrit changes in blood and have since shown its utility for monitoring in humans during 1) hemodialysis, 2) orthostatic perturbations and 3) during blood loss and fluid replacement in a rat model. We now show that the algorithm is sensitive to changes in hemoglobin oxygen saturation. We document the phenomenology of the effect and explain the effect using new results obtained from humans and rat models. The oxygen sensitivity derives from the differential absorption of autofluorescence originating in the static tissues by oxy and deoxy hemoglobin. Using this approach we show how to perform simultaneous, noninvasive, in vivo, continuous monitoring of hematocrit, vascular volume, hemoglobin oxygen saturation, pulse rate and breathing rate in mammals using a single light source. We suspect that monitoring of changes in this suite of vital signs can be provided with improved time response, sensitivity and precision compared to existing methodologies. Initial results also offer a more detailed glimpse into the systemic oxygen transport in the circulatory system of humans.
Diffuse optical tomography (DOT) is emerging as a noninvasive functional imaging method for breast cancer diagnosis and neoadjuvant chemotherapy monitoring. In particular, the multimodal approach of combining DOT with x-ray digital breast tomosynthesis (DBT) is especially synergistic as DBT prior information can be used to enhance the DOT reconstruction. DOT, in turn, provides a functional information overlay onto the mammographic images, increasing sensitivity and specificity to cancer pathology. We describe a dynamic DOT apparatus designed for tight integration with commercial DBT scanners and providing a fast (up to 1 Hz) image acquisition rate to enable tracking hemodynamic changes induced by the mammographic breast compression. The system integrates 96 continuous-wave and 24 frequency-domain source locations as well as 32 continuous wave and 20 frequency-domain detection locations into low-profile plastic plates that can easily mate to the DBT compression paddle and x-ray detector cover, respectively. We demonstrate system performance using static and dynamic tissue-like phantoms as well as in vivo images acquired from the pool of patients recalled for breast biopsies at the Massachusetts General Hospital Breast Imaging Division.
A new device incorporating a new algorithm and measurement process allows simultaneous noninvasive in vivo monitoring of intravascular plasma volume and red blood cell volume. The purely optical technique involves probing fingertip skin with near infrared laser light and collecting the wavelength shifted light, that is, the inelastic emission (IE) which includes the unresolved Raman and fluorescence, and the un-shifted emission, that is, the elastic emission (EE) which includes both the Rayleigh and Mie scattered light. Our excitation and detection geometry is designed so that from these two simultaneous measurements we can calculate two parameters within the single scattering regime using radiation transfer theory, the intravascular plasma volume fraction and the red blood cell volume fraction. Previously calibrated against a gold standard FDA approved device, 2 hour monitoring sessions on three separate occasions over a three week span for a specific, motionless, and mostly sleeping individual produced 3 records containing a total of 5706 paired measurements of hematocrit and plasma volume. The average over the three runs, relative to the initial plasma volume taken as 100%, of the plasma volume±1σ was 97.56±0.55 or 0.56%.For the same three runs, the average relative hematocrit (Hct), referenced to an assumed initial value of 28.35 was 29.37±0.12 or stable to ±0.4%.We observe local deterministic circulation effects apparently associated with the pressure applied by the finger probe as well as longer timescale behavior due to normal ebb and flow of internal fluids due to posture changes and tilt table induced gravity gradients.
To enable tissue function-based tumor diagnosis over the large number of existing digital mammography systems worldwide, we propose a cost-effective and robust approach to incorporate tomographic optical tissue characterization with separately acquired digital mammograms. Using a flexible contour-based registration algorithm, we were able to incorporate an independently measured two-dimensional x-ray mammogram as structural priors in a joint optical/x-ray image reconstruction, resulting in improved spatial details in the optical images and robust optical property estimation. We validated this approach with a retrospective clinical study of 67 patients, including 30 malignant and 37 benign cases, and demonstrated that the proposed approach can help to distinguish malignant from solid benign lesions and fibroglandular tissues, with a performance comparable to the approach using spatially coregistered optical/x-ray measurements.
We report a new algorithm and measurement system that permits simultaneous monitoring of the hematocrit and
plasma volume fraction of blood within the intravascular space of an optically probed volume of skin. The system
involves probing with a near infrared laser and simultaneously collecting the Rayleigh and Mie scattered light as one
raw signal and the undifferentiated Raman and fluorescence emission as the second raw signal. Those two
physically independent raw signals and six parameters that can be obtained by either direct calculation or empirical
calibration permit monitoring of the blood in rat paws. We tested a device based on the algorithm in the context of
improving detection of blood loss for people with an early undiagnosed internal hemorrhage via real-time
monitoring of signal changes with direct correlation to hematocrit. We performed experiments monitoring rat paw
skin in vivo while removing blood, centrally or peripherally, and then adding replacement fluids such as Normocarb and blood. Blood removal itself elicits a predictable and consistent response, decreasing hematocrit and increasing relative plasma volume, that depends on the rate and location of removal, the total amount of blood removed, the location of monitoring, and possibly other factors as yet unknown. Similarly, replacing the blood with whole blood vs. saline consistently produces a rational range of responses. Calibration across subjects and the measurement of absolute hematocrit will also be discussed.
We report a new device and algorithm that allows simultaneous monitoring of the hematocrit and plasma volume
fraction of blood within the intravascular space of an optically probed volume of skin. Skin is probed with a near
infrared (NIR) laser and simultaneously collecting the Rayleigh and Mie scattered light as one raw signal and the
undifferentiated Raman and fluorescence emission as the second raw signal. These signals are combined using six
parameters that can be obtained by either direct calculation or empirical calibration to permit monitoring of the
blood in human skin (e.g. fingertips). We tested a device based on the algorithm that might be useful in allowing the
early detection of blood loss for people who have no external injury but may be hemorrhaging internally. IRB
allowed experiments monitoring blood in human fingertip skin in vivo during routine hemodialysis demonstrated
good agreement between the experimental device and the CRIT-LINE®, an FDA approved device that is built into
the dialysis machine and applies the Twersky algorithm to blood in the dialysis machine (i.e. in vitro). Based on
observation of 9 different test subjects, as dialysis removes fluid from the intravascular space causing an increase in
hematocrit and a decrease in plasma volume, the CRIT-LINE response is closely emulated (typical per session linear
correlation r2=0.78, N=87, p<0.0001) with the new device. Calibration across subjects, the measurement of absolute
hematocrit, and potential confounding factors will also be discussed.
Nonenzymatic glycation and oxidation of ubiquitous proteins in vivo leads to irreversible formation of advanced
glycation end products (AGEs). Due to their relatively long half life and low clearance rate AGEs tend to accumulate
within static tissues and the circulatory system. Spectra obtained using 830 nm near-infrared (NIR) excitation suggest
that the so-called "autofluorescence" from all tissues has a finite number of sources but the fact that senior and diabetic
subjects produce more than other members of the general population suggests that a significant portion of the total
autofluorescence from all sources originates from AGEs. Using pentosidine generated in a reaction mixture as described
by Monnier as representative, an in vitro study unveiled very similar fluorescence and photobleaching pattern as
observed for autofluorescence in vivo. A series of oxygen, air and argon purging experiments on the pentosidine-generating
reaction mixture suggests that pentosidine is a singlet oxygen sensitizer and secondary reactions between the
pentosidine itself and/or other fluorophores and the photosensitized singlet oxygen explain the observed photobleaching.
Ab initio Gaussian calculations on pentosidine reveal the existence of low-lying triplet excited states required for the
sensitization of ground state oxygen. A commercially available product known as singlet oxygen sensor green (SOSG)
that specifically serves as a singlet oxygen detection reagent confirms the generation of singlet oxygen from NIR
irradiated pentosidine trimixture. This study provides one definite chemical mechanism for understanding in vivo human
skin autofluorescence and photobleaching.
The leading preventable cause of death, world-wide, civilian or military, for all people between the ages of 18-45 is
undetected internal hemorrhage. Autonomic compensation mechanisms mask changes such as e.g. hematocrit
fluctuations that could give early warning if only they could be monitored continuously with reasonable degrees of
precision and relative accuracy. Probing tissue with near infrared radiation (NIR) simultaneously produces remitted
fluorescence and Raman scattering (IE) plus Rayleigh/Mie light scattering (EE) that noninvasively give chemical
and physical information about the materials and objects within. We model tissue as a three-phase system: plasma
and red blood cell (RBC) phases that are mobile and a static tissue phase. In vivo, any volume of tissue naturally
experiences spatial and temporal fluctuations of blood plasma and RBC content. Plasma and RBC fractions may be
discriminated from each other on the basis of their physical, chemical and optical properties. Thus IE and EE from
NIR probing yield information about these fractions. Assuming there is no void volume in viable tissue, or that void
volume is constant, changes in plasma and RBC volume fractions may be calculated from simultaneous
measurements of the two observables, EE and IE. In a previously published analysis we showed the underlying
phenomenology but did not provide an algorithm for calculating volume fractions from experimental data. Here we
present a simple analysis that allows continuous monitoring of fluid fraction and hematocrit (Hct) changes by
measuring IE and EE, and apply it to some experimental in vivo measurements.
Probing tissue with near-infrared radiation (NIR) simultaneously produces remitted fluorescence and Raman scattering (IE) plus Rayleigh/Mie light scattering (EE) that noninvasively give chemical and physical information about the materials and objects within. We model tissue as a three-phase system: plasma and red blood cell (RBC) phases that are mobile and a static tissue phase. In vivo, any volume of tissue naturally experiences spatial and temporal fluctuations of blood plasma and RBC content. Plasma and RBC fractions may be discriminated from each other on the basis of their physical, chemical, and optical properties. Thus, IE and EE from NIR probing yield information about these fractions. Assuming there is no void volume in viable tissue, or that void volume is constant, changes in plasma and RBC volume fractions may be calculated from simultaneous measurements of the two observables, EE and IE. In a previously published analysis we showed the underlying phenomenology but did not provide an algorithm for calculating volume fractions from experimental data. Now, we present a simple analysis that allows monitoring of fluid fraction and hematocrit (Hct) changes by measuring IE and EE, and apply it to some experimental in vivo measurements.
KEYWORDS: Raman spectroscopy, Spinal cord, Injuries, Luminescence, Tissues, Spectroscopy, In vivo imaging, Control systems, Cell death, In vitro testing
Raman spectroscopy was used to study temporal molecular changes associated with spinal cord injury (SCI) in a rat model. Raman spectra of saline-perfused, injured, and healthy rat spinal cords were obtained and compared. Two injury models, a lateral hemisection and a moderate contusion were investigated. The net fluorescence and the Raman spectra showed clear differences between the injured and healthy spinal cords. Based on extensive histological and biochemical characterization of SCI available in the literature, these differences were hypothesized to be due to cell death, demyelination, and changes in the extracellular matrix composition, such as increased expression of proteoglycans and hyaluronic acid, at the site of injury where the glial scar forms. Further, analysis of difference spectra indicated the presence of carbonyl containing compounds, hypothesized to be products of lipid peroxidation and acid catalyzed hydrolysis of glycosaminoglycan moieties. These results compared well with in vitro experiments conducted on chondroitin sulfate sugars. Since the glial scar is thought to be a potent biochemical barrier to nerve regeneration, this observation suggests the possibility of using near infrared Raman spectroscopy to study injury progression and explore potential treatments ex vivo, and ultimately monitor potential remedial treatments within the spinal cord in vivo.
Comparative Raman spectra of ex vivo, saline-perfused, injured and healthy rat spinal cord as well as experiments using
enzymatic digestion suggest that proteoglycan over expression may be observable in injured tissue. Comparison with
authentic materials in vitro suggest the occurrence of side reactions between products of cord digestion with
chondroitinase (cABC) that produce lactones and similar species with distinct Raman features that are often not
overlapped with Raman features from other chemical species. Since the glial scar is thought to be a biochemical and
physical barrier to nerve regeneration, this observation suggests the possibility of using near infrared Raman
spectroscopy to study disease progression and explore potential treatments ex vivo and if potential treatments can be
designed, perhaps to monitor potential remedial treatments within the spinal cord in vivo.
Human transdermal in vivo spectroscopic applications for tissue analysis involving near infrared (NIR) light often must
contend with broadband NIR fluorescence that, depending on what kind of spectroscopy is being employed, can degrade
signal to noise ratios and dynamic range. Such NIR fluorescence, i.e. "autofluorescence" is well known to originate in
blood tissues and various other endogenous materials associated with the static tissues. Results of recent experiments on
human volar side fingertips in vivo are beginning to provide a relative ordering of the contributions from various
sources. Preliminary results involving the variation in the bleaching effect across different individuals suggest that for
830 nm excitation well over half of the total fluorescence comes from the static tissues and remainder originates with the
blood tissues, i.e. the plasma and the hematocrit. Of the NIR fluorescence associated with the static tissue, over half
originates with products of well-known post-enzymatic glycation reactions, i.e. Maillard chemistry, in the skin involving
glucose and other carbohydrates and skin proteins like collagen and cytosol proteins.
We report simultaneous observation of elastic scattering, fluorescence, and inelastic scattering from in vivo near-infrared probing of human skin. Careful control of the mechanical force needed to obtain reliable registration of in vivo tissue with an appropriate optical system allows reproducible observation of blood flow in capillary beds of human volar side fingertips. The time dependence of the elastically scattered light is highly correlated with that of the combined fluorescence and Raman scattered light. We interpret this in terms of turbidity (the impeding effect of red blood cells on optical propagation to and from the scattering centers) and the changes in the volume percentages of the tissues in the irradiated volume with normal homeostatic processes. By fitting to a model, these measurements may be used to determine volume fractions of plasma and RBCs.
In the area of noninvasive human blood glucose concentration detecting, it has always been a critical task to extract the
glucose-specific signal from the highly overlapped and disturbed near-infrared spectrum. In this paper, the methodology
of effective glucose-specific signal extraction in complicated non-scattering sample is studied. By analyzing the impact
of water displacement upon dissolution of glucose, the relationship between glucose concentration and absorption
coefficient of the sample is deduced. Then, the reference wavelength where the absorption coefficient is insensitive to the
changes of glucose concentration is put forward theoretically. Accordingly, the validating experiments in aqueous
glucose solutions are executed. Both the theoretical and laboratorial results show that the reference wavelength of
glucose appears at 1525nm. Based on the reference wavelength, an effective method for extracting the glucose-specific
signal in complicated non-scattering samples is proposed and the corresponding validating experiments are constructed
with different glucose and albumin concentration. Two different methods, traditional and the novel reference wavelength
method are used to extract glucose signal and the corresponding root mean square error of prediction are 19.86mg/dl and
9.87mg/dl respectively. The experiment results indicate that the reference wavelength method can effectively eliminate
the influence of various noises on the glucose-specific signal extraction, and thus can remarkably improve the measuring
precision in noninvasive near-infrared glucose detecting.
We have performed transcutaneous measurement and vessel bypass measurement to obtain the skin spectra and the blood vessel spectra respectively over the 1100-1700nm in the animal trial. The aim of this study is to validate the feasibility of the near-infrared (NIR) spectroscopy as a non-invasive blood glucose monitoring method, in particular during clinically relevant fluctuation in blood glucose. Two steps are adopted to evaluate the correlation between the skin diffusion spectra and the blood vessel transmission spectra. First, the variation tendencies of the skin and the blood vessel spectra were evaluated, and the partial least square (PLS) regression was adopted to establish the calibration model between the skin spectra, the vessel spectra and the corresponding concentration respectively. Then, the correlation analysis method is used to describe the relationship between the two kinds of spectra mentioned above. The correlation between the skin and the vessel spectra will be a powerful proof to demonstrate the correlation between the skin spectra and the blood glucose concentration.
High magnifying optics is now widely used in micro-region imaging, which leads to the special image structures on the recording plane, such as continue-gray distributions, large granules and spread structures. As a result, the deformation analyses are unreliable and divergent by using the conventional speckle correlation methods and these generalized speckle patterns. A new correlation algorithm, high-order gradient digital correlation method, has been proposed in this paper to measure the displacements in a micro-region. The performance of the proposed algorithm is illustrated using the generalized speckle patterns captured from the micro-regions.
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