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Radiation damage studies are used to optimize radiotherapy treatment techniques. Although biological indicators of damage are the best assays of effect, they are highly variable due to biological heterogeneity. The free radical radiochemistry can be assayed with optical reporters, allowing for high precision titration of techniques.
Aim
We examine the optical reporters of radiochemistry to highlight those with the best potential for translational use in vivo, as surrogates for biological damage assays, to inform on mechanisms.
Approach
A survey of the radical chemistry effects from reactive oxygen species (ROS) and oxygen itself was completed to link to DNA or biological damage. Optical reporters of ROS include fluorescent, phosphorescent, and bioluminescent molecules that have a variety of activation pathways, and each was reviewed for its in vivo translation potential.
Results
There are molecular reporters of ROS having potential to report within living systems, including derivatives of luminol, 2′7′-dichlorofluorescein diacetate, Amplex Red, and fluorescein. None have unique specificity to singular ROS species. Macromolecular engineered reporters unique to specific ROS are emerging. The ability to directly measure oxygen via reporters, such as Oxyphor and protoporphyrin IX, is an opportunity to quantify the consumption of oxygen during ROS generation, and this translates from in vitro to in vivo use. Emerging techniques, such as ion particle beams, spatial fractionation, and ultra-high dose rate FLASH radiotherapy, provide the motivation for these studies.
Conclusions
In vivo optical reporters of radiochemistry are quantitatively useful for comparing radiotherapy techniques, although their use comes at the cost of the unknown connection to the mechanisms of radiobiological damage. Still their lower measurement uncertainty, compared with biological response assay, makes them an invaluable tool. Linkage to DNA damage and biological damage is needed, and measures such as oxygen consumption serve as useful surrogate measures that translate to in vivo use.
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Cervical cancer is one of the major causes of death in females worldwide. HPV infection is the key cause of uncontrolled cell growth leading to cervical cancer. About 90% of cervical cancer is preventable because of the slow progression of the disease, giving a window of about 10 years for the precancerous lesion to be recognized and treated.
Aim
The present challenges for cervical cancer diagnosis are interobserver variation in clinicians’ interpretation of visual inspection with acetic acid/visual inspection with Lugol’s iodine, cost of cytology-based screening, and lack of skilled clinicians. The optical modalities can assist in qualitatively and quantitatively analyzing the tissue to differentiate between cancerous and surrounding normal tissues.
Approach
This work is on the recent advances in optical techniques for cervical cancer diagnosis, which promise to overcome the above-listed challenges faced by present screening techniques.
Results
The optical modalities provide substantial measurable information in addition to the conventional colposcopy and Pap smear test to clinically aid the diagnosis.
Conclusions
Recent optical modalities on fluorescence, multispectral imaging, polarization-sensitive imaging, microendoscopy, Raman spectroscopy, especially with the portable design and assisted by artificial intelligence, have a significant scope in the diagnosis of premalignant cervical cancer in future.
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Photoacoustic tomography has emerged as a prominent medical imaging technique that leverages its hybrid nature to provide deep penetration, high resolution, and exceptional optical contrast with notable applications in early cancer detection, functional brain imaging, drug delivery monitoring, and guiding interventional procedures. Test phantoms are pivotal in accelerating technology development and commercialization, specifically in photoacoustic (PA) imaging, and can be optimized to achieve significant advancements in PA imaging capabilities.
Aim
The analysis of material properties, structural characteristics, and manufacturing methodologies of test phantoms from existing imaging technologies provides valuable insights into their applicability to PA imaging. This investigation enables a deeper understanding of how phantoms can be effectively employed in the context of PA imaging.
Approach
Three primary categories of test phantoms (simple, intermediate, and advanced) have been developed to differentiate complexity and manufacturing requirements. In addition, four sub-categories (tube/channel, block, test target, and naturally occurring phantoms) have been identified to encompass the structural variations within these categories, resulting in a comprehensive classification system for test phantoms.
Results
Based on a thorough examination of literature and studies on phantoms in various imaging modalities, proposals have been put forth for the development of multiple PA-capable phantoms, encompassing considerations related to the material composition, structural design, and specific applications within each sub-category.
Conclusions
The advancement of novel and sophisticated test phantoms within each sub-category is poised to foster substantial progress in both the commercialization and development of PA imaging. Moreover, the continued refinement of test phantoms will enable the exploration of new applications and use cases for PA imaging.
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Special Section on Seeing Inside Tissue with Optical Molecular Probes
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This first-in-kind, perfused, and amputated human limb model allows for the collection of human data in preclinical selection of lead fluorescent agents. The model facilitates more accurate selection and testing of fluorophores with human-specific physiology, such as differential uptake and signal in fat between animal and human models with zero risk to human patients. Preclinical testing using this approach may also allow for the determination of tissue toxicity, clearance time of fluorophores, and the production of harmful metabolites.
Aim
This study was conducted to determine the fluorescence intensity values and tissue specificity of a preclinical, nerve tissue targeted fluorophore, as well as the capacity of this first-in-kind model to be used for lead fluorescent agent selection in the future.
Approach
Freshly amputated human limbs were perfused for 30 min prior to in situ and ex vivo imaging of nerves with both open-field and closed-field commercial fluorescence imaging systems.
Results
In situ, open-field imaging demonstrated a signal-to-background ratio (SBR) of 4.7 when comparing the nerve with adjacent muscle tissue. Closed-field imaging demonstrated an SBR of 3.8 when the nerve was compared with adipose tissue and 4.8 when the nerve was compared with muscle.
Conclusions
This model demonstrates an opportunity for preclinical testing, evaluation, and selection of fluorophores for use in clinical trials as well as an opportunity to study peripheral pathologies in a controlled environment.
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X-ray imaging is frequently used for gastrointestinal imaging. Photoacoustic imaging (PAI) of the gastrointestinal tract is an emerging approach that has been demonstrated for preclinical imaging of small animals. A contrast agent active in both modalities could be useful for imaging applications.
Aim
We aimed to develop a dual-modality contrast agent comprising an admixture of barium sulfate with pigments that absorb light in the second near-infrared region (NIR-II), for preclinical imaging with both x-ray and PAI modalities.
Approach
Eleven different NIR-II dyes were evaluated after admixture with a 40% w/v barium sulfate mixture. The resulting NIR-II absorption in the soluble fraction and in the total mixture was characterized. Proof-of-principle imaging studies in mice were carried out.
Results
Pigments that produced more uniform suspensions were assessed further for photoacoustic contrast signal at a wavelength of 1064 nm that corresponds to the output of the Nd:YAG laser used. Phantom imaging studies demonstrated that the pigment-barium sulfate mixture generated imaging contrast in both x-ray and PAI modalities. The optimal pigment selected for further study was a cyanine tetrafluoroborate salt. Ex-vivo and whole-body mouse imaging demonstrated that photoacoustic and x-ray contrast signals co-localized in the intestines for both imaging modalities.
Conclusion
These data demonstrate that commercially-available NIR-II pigments can simply be admixed with barium sulfate to generate a dual-modality contrast agent appropriate for small animal gastrointestinal imaging.
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TOPICS: Photoacoustic spectroscopy, Photoacoustic tomography, Acquisition tracking and pointing, Switching, Signal detection, Tissues, Color, Temperature metrology, In vivo imaging, Absorption
Based on acoustic detection of optical absorption, photoacoustic tomography (PAT) allows functional and molecular imaging beyond the optical diffusion limit with high spatial resolution. However, multispectral functional and molecular PAT is often limited by decreased spectroscopic accuracy and reduced detection sensitivity in deep tissues, mainly due to wavelength-dependent optical attenuation and inaccurate acoustic inversion.
Aim
Previous work has demonstrated that reversible color-shifting can drastically improve the detection sensitivity of PAT by suppressing nonswitching background signals. We aim to develop a new color switching-based PAT method using reversibly switchable thermochromics (ReST).
Approach
We developed a family of ReST with excellent water dispersion, biostability, and temperature-controlled color changes by surface modification of commercial thermochromic microcapsules with the hydrophilic polysaccharide alginate.
Results
The optical absorbance of the ReST was switched on and off repeatedly by modulating the surrounding temperature, allowing differential photoacoustic detection that effectively suppressed the nonswitching background signal and substantially improved image contrast and detection sensitivity. We demonstrate reversible thermal-switching imaging of ReST in vitro and in vivo using three PAT modes at different length scales.
Conclusions
ReST-enabled PAT is a promising technology for high-sensitivity deep tissue imaging of molecular activity in temperature-related biomedical applications, such as cancer thermotherapy.
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Corticosteroids—commonly prescribed medications for skin diseases—inhibit the secretion of vasodilators, such as prostaglandin, thereby exerting anti-inflammatory action by constricting capillaries in the dermis. The effectiveness of corticosteroids is determined by the degree of vasoconstriction followed by skin whitening, namely, the blanching effect. However, the current method of observing the blanching effect indirectly evaluates the effects of corticosteroids.
Aim
In this study, we employed optical-resolution photoacoustic (PA) microscopy (OR-PAM) to directly visualize the blood vessels and quantitatively evaluate vasoconstriction.
Approach
Using OR-PAM, the vascular density in mice skin was monitored for 60 min after performing each experimental procedure for four groups, and the vasoconstriction was quantified. Volumetric PA data were segmented into the papillary dermis, reticular dermis, and hypodermis based on the vascular characteristics obtained through OR-PAM. The vasoconstrictive effect of each skin layer was quantified according to the dermatological treatment method.
Results
In the case of corticosteroid topical application, vasoconstriction was observed in the papillary (56.4 ± 10.9 % ) and reticular (45.1 ± 4.71 % ) dermis. For corticosteroid subcutaneous injection, constriction was observed solely in the reticular (49.5 ± 9.35 % ) dermis. In contrast, no vasoconstrictions were observed with nonsteroidal topical application.
Conclusions
Our results indicate that OR-PAM can quantitatively monitor the vasoconstriction induced by corticosteroids, thereby validating OR-PAMs potential as a practical evaluation tool for predicting the effectiveness of corticosteroids in dermatology.
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Positive margin status due to incomplete removal of tumor tissue during radical prostatectomy for high-risk localized prostate cancer requires reoperation or adjuvant therapy, which increases morbidity and mortality. Adverse effects of prostate cancer treatments commonly include erectile dysfunction, urinary incontinence, and bowel dysfunction, making successful initial curative prostatectomy imperative.
Aim
Current intraoperative tumor margin assessment is largely limited to frozen section analysis, which is a lengthy, labor-intensive process that is obtrusive to the clinical workflow within the operating room (OR). Therefore, a rapid method for prostate cancer margin assessment in the OR could improve outcomes for patients.
Approach
Dual probe difference specimen imaging (DDSI), which uses paired antibody-based probes that are labeled with spectrally distinct fluorophores, was shown herein for prostate cancer margin assessment. The paired antibody-based probes consisted of a targeted probe to prostate-specific membrane antigen (PSMA) and an untargeted probe, which were used as a cocktail to stain resected murine tissue specimens including prostate tumor, adipose, muscle, and normal prostate. Ratiometric images (i.e., DDSI) of the difference between targeted and untargeted probe uptake were calculated and evaluated for accuracy using receiver operator characteristic curve analysis with area under the curve values used to evaluate the utility of the DDSI method to detect PSMA positive prostate cancer.
Results
Targeted and untargeted probe uptake was similar between the high and low PSMA expressing tumor due to nonspecific probe uptake after topical administration. The ratiometric DDSI approach showed substantial contrast difference between the PSMA positive tumors and their respective normal tissues (prostate, adipose, muscle). Furthermore, DDSI showed substantial contrast difference between the high PSMA expressing tumors and the minimally PSMA expressing tumors due to the ratiometric correction for the nonspecific uptake patterns in resected tissues.
Conclusions
Previous work has shown that ratiometic imaging has strong predictive value for breast cancer margin status using topical administration. Translation of the ratiometric DDSI methodology herein from breast to prostate cancers demonstrates it as a robust, ratiometric technique that provides a molecularly specific imaging modality for intraoperative margin detection. Using the validated DDSI protocol on resected prostate cancers permitted rapid and accurate assessment of PSMA status as a surrogate for prostate cancer margin status. Future studies will further evaluate the utility of this technology to quantitatively characterize prostate margin status using PSMA as a biomarker.
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Fatemeh Ostadhossein, Parikshit Moitra, Maha Alafeef, Dinabandhu Sar, Shannon D’Souza, Lily Benig, Michael Nelappana, Xuedong Huang, Julio Soares, Kai Zhang, Dipanjan Pan
Carbon dots (CDs) have attracted a host of research interest in recent years mainly due to their unique photoluminescence (PL) properties that make them applicable in various biomedical areas, such as imaging and image-guided therapy. However, the real mechanism underneath the PL is a subject of wide controversy and can be investigated from various angles.
Aim
Our work investigates the effect of the isomeric nitrogen position as the precursor in the synthesis of CDs by shedding light on their photophysical properties on the single particles and ensemble level.
Approach
To this end, we adopted five isomers of diaminopyridine (DAP) and urea as the precursors and obtained CDs during a hydrothermal process. The various photophysical properties were further investigated in depth by mass spectroscopy. CD molecular frontier orbital analyses aided us in justifying the fluorescence emission profile on the bulk level as well as the charge transfer processes. As a result of the varying fluorescent responses, we indicate that these particles can be utilized for machine learning (ML)-driven sensitive detection of oral microbiota. The sensing results were further supported by density functional theoretical calculations and docking studies.
Results
The generating isomers have a significant effect on the overall photophysical properties at the bulk/ensembled level. On the single-particle level, although some of the photophysical properties such as average intensity remained the same, the overall differences in brightness, photo-blinking frequency, and bleaching time between the five samples were conceived. The various photophysical properties could be explained based on the different chromophores formed during the synthesis. Overall, an array of CDs was demonstrated herein to achieve ∼100 % separation efficacy in segregating a mixed oral microbiome culture in a rapid (<0.5 h), high-throughput manner with superior accuracy.
Conclusions
We have indicated that the PL properties of CDs can be regulated by the precursors’ isomeric position of nitrogen. We emancipated this difference in a rapid method relying on ML algorithms to segregate the dental bacterial species as biosensors.
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Forces inside cells play a fundamental role in tissue growth, affecting important processes such as cancer cell migration or tissue repair after injury. Förster resonance energy transfer (FRET)-based tension sensors are a remarkable tool for studying these forces and should be made easier to use.
Aim
We prove that absolute FRET efficiency can be measured on a simple setup, an order of magnitude more cost-effective than a standard FRET microscopy setup, by applying it to vinculin tension sensors (VinTS) at the focal adhesions of live CHO-K1 cells.
Approach
Our setup located at Université Paris-Saclay acquires donor and acceptor fluorescence in parallel on two low-cost CMOS cameras and uses two LEDs for rapid switching of the excitation wavelength at a reduced cost. The calibration required to extract FRET efficiency was achieved using a single construct (TSMod). FRET efficiencies were measured for VinTS and the tail-less control VinTL, lacking the actin-binding domain of vinculin. Measurements were confirmed on the same cell type using a more standard intensity-based setup located at Rutgers University.
Results
The average FRET efficiency of VinTS (22.0 % ± 4 % ) over more than 10,000 focal adhesions is significantly lower (p < 10 − 6) than that of VinTL (30.4 % ± 5 % ), our control that is insensitive to force, in agreement with the force exerted on vinculin at focal adhesions. Attachment of the CHO-K1 cells on fibronectin decreases FRET efficiency, thus increasing the force, compared with poly-lysine. FRET efficiency for the VinTL control is consistent with all measurements currently available in the literature, confirming the validity of our measurements and hence of our simpler setup.
Conclusions
Force measurements, resolved spatially inside a cell, can be achieved using FRET-based tension sensors with a cost effective intensity-based setup. This will facilitate combining FRET with techniques for applying controlled forces such as optical tweezers.
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India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed.
Aim
Our study aimed to use a hand-held smartphone-coupled intraoral imaging device, previously investigated for autofluorescence (auto-FL) diagnostics adapted here for treatment guidance and monitoring photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence (FL).
Approach
A total of 12 patients with 14 buccal mucosal lesions having moderately/well-differentiated micro-invasive OSCC lesions (<2 cm diameter and <5 mm depth) were systemically (in oral solution) administered three doses of 20 mg / kg ALA (total 60 mg / kg). Lesion site PpIX and auto-FL were imaged using the multichannel FL and polarized white-light oral cancer imaging probe before/after ALA administration and after light delivery (fractionated, total 100 J / cm2 of 635 nm red LED light).
Results
The handheld device was conducive for access to lesion site images in the oral cavity. Segmentation of ratiometric images in which PpIX FL is mapped relative to auto-FL enabled improved demarcation of lesion boundaries relative to PpIX alone. A relative FL (R-value) threshold of 1.4 was found to segment lesion site PpIX production among the patients with mild to severe dysplasia malignancy. The segmented lesion size is well correlated with ultrasound findings. Lesions for which R-value was >1.65 at the time of treatment were associated with successful outcomes.
Conclusion
These results indicate the utility of a low-cost, handheld intraoral imaging probe for image-guided PDT and treatment monitoring while also laying the groundwork for an integrated approach, combining cancer screening and treatment with the same hardware.
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Breast conservation therapy is the preferred technique for treating primary breast cancers. However, breast tumor margins are hard to determine as tumor borders are often ill-defined. As such, there exists a need for a clinically compatible tumor margin detection system.
Aim
A combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system has been developed to determine the optical properties of breast tissue. This study aims to improve tissue classification to aid in surgical decision making.
Approach
Normal and tumor breast tissue were collected from 80 patients with invasive ductal carcinoma and measured in the optical system. Optical parameters were extracted, and the tissue underwent histopathological examination. In total, 761 adipose, 77 fibroglandular, and 347 tumor spectra were analyzed. Principal component analysis and decision tree modeling were performed using only TRF optical parameters, only DR optical parameters, and using the combined datasets.
Results
The classification modeling using TRF data alone resulted in a tumor margin detection sensitivity of 72.3% and specificity of 88.3%. Prediction modeling using DR data alone resulted in greater sensitivity and specificity of 80.4% and 94.0%, respectively. Combining both datasets resulted in the improved sensitivity and specificity of 85.6% and 95.3%, respectively. While both sensitivity and specificity improved with the combined modeling, further study of fibroglandular tissue could result in improved classification.
Conclusion
The combined TRF-DR system showed greater tissue classification capability than either technique alone. Further work studying more fibroglandular tissue and tissue of mixed composition would develop this system for intraoperative use for tumor margin detection.
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TOPICS: Signal attenuation, Optical coherence tomography, Backscatter, Tissues, Signal intensity, Monte Carlo methods, Biological samples, Scattering, Optical properties, Attenuation
Extracting optical properties of tissue [e.g., the attenuation coefficient (μ) and the backscattering fraction] from the optical coherence tomography (OCT) images is a valuable tool for parametric imaging and related diagnostic applications. Previous attenuation estimation models depend on the assumption of the uniformity of the backscattering fraction (R) within layers or whole samples, which does not accurately represent real-world conditions.
Aim
Our aim is to develop a robust and accurate model that calculates depth-wise values of attenuation and backscattering fractions simultaneously from OCT signals. Furthermore, we aim to develop an attenuation compensation model for OCT images that utilizes the optical properties we obtained to improve the visual representation of tissues.
Approach
Using the stationary iteration method under suitable constraint conditions, we derived the approximated solutions of μ and R on a single scattering model. During the iteration, the estimated value of μ can be rectified by introducing the large variations of R, whereas the small ones were automatically ignored. Based on the calculation of the structure information, the OCT intensity with attenuation compensation was deduced and compared with the original OCT profiles.
Results
The preliminary validation was performed in the OCT A-line simulation and Monte Carlo modeling, and the subsequent experiment was conducted on multi-layer silicone-dye-TiO2 phantoms and ex vivo cow eyes. Our method achieved robust and precise estimation of μ and R for both simulated and experimental data. Moreover, corresponding OCT images with attenuation compensation provided an improved resolution over the entire imaging range.
Conclusions
Our proposed method was able to correct the estimation bias induced by the variations of R and provided accurate depth-resolved measurements of both μ and R simultaneously. The method does not require prior knowledge of the morphological information of tissue and represents more real-life tissues. Thus, it has the potential to help OCT imaging based disease diagnosis of complex and multi-layer biological tissue.
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Imaging photoplethysmography (iPPG) is a non-contact measuring technology for several physiological parameters reflecting personal health status without a special sensor. However, the pulse signal obtained using the iPPG usually is contaminated by various noises, and the intensity of the interesting pulse signal is relatively weak compared to the noises, emphasizing the necessity of obtaining high-quality pulse signals to measure physiological parameters correctly.
Aim
Various regions of the face harbor distinct pulse information. We propose a spatial averaging method based on adaptive weights, which can obtain high-quality pulse signals by applying different weights to facial sub-regions of interest (sub-ROIs; sROIs).
Approach
First, the facial ROI is divided into seven sROIs and the coarse heart rate (HR) is calculated from them. Next, the signal-to-noise ratio (SNR) of the raw signal obtained from each sROI is calculated using the coarse HR, and then a high-quality pulse signal is obtained by assigning positive or negative weights to each sROI based on the SNRs.
Results
We compare our method with others through the quality analysis of the obtained pulse signals using the self-collected database and the public database PURE. The comparison results show that the proposed method can provide a better pulse signal compared to other methods under various resolutions and states.
Conclusions
This proposed method can obtain the pulse signal with better quality, which is helpful to accurately measure physiological parameters, such as HR and HR variability.
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Determining the extent of gastric cancer (GC) is necessary for evaluating the gastrectomy margin for GC. Additionally, determining the extent of the GC that is not exposed to the mucosal surface remains difficult. However, near-infrared (NIR) can penetrate mucosal tissues highly efficiently.
Aim
We investigated the ability of near-infrared hyperspectral imaging (NIR-HSI) to identify GC areas, including exposed and unexposed using surgical specimens, and explored the identifiable characteristics of the GC.
Approach
Our study examined 10 patients with diagnosed GC who underwent surgery between 2020 and 2021. Specimen images were captured using NIR-HSI. For the specimens, the exposed area was defined as an area wherein the cancer was exposed on the surface, the unexposed area as an area wherein the cancer was present although the surface was covered by normal tissue, and the normal area as an area wherein the cancer was absent. We estimated the GC (including the exposed and unexposed areas) and normal areas using a support vector machine, which is a machine-learning method for classification. The prediction accuracy of the GC region in every area and normal region was evaluated. Additionally, the tumor thicknesses of the GC were pathologically measured, and their differences in identifiable and unidentifiable areas were compared using NIR-HSI.
Results
The average prediction accuracy of the GC regions combined with both areas was 77.2%; with exposed and unexposed areas was 79.7% and 68.5%, respectively; and with normal regions was 79.7%. Additionally, the areas identified as cancerous had a tumor thickness of >2 mm.
Conclusions
NIR-HSI identified the GC regions with high rates. As a feature, the exposed and unexposed areas with tumor thicknesses of >2 mm were identified using NIR-HSI.
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TOPICS: Histograms, Tumor growth modeling, Image classification, Breast cancer, Feature extraction, Breast, Data modeling, Image restoration, Deep learning, Education and training
Ultrasound (US)-guided diffuse optical tomography (DOT) has demonstrated great potential for breast cancer diagnosis in which real-time or near real-time diagnosis with high accuracy is desired.
Aim
We aim to use US-guided DOT to achieve an automated, fast, and accurate classification of breast lesions.
Approach
We propose a two-stage classification strategy with deep learning. In the first stage, US images and histograms created from DOT perturbation measurements are combined to predict benign lesions. Then the non-benign suspicious lesions are passed through to the second stage, which combine US image features, DOT histogram features, and 3D DOT reconstructed images for final diagnosis.
Results
The first stage alone identified 73.0% of benign cases without image reconstruction. In distinguishing between benign and malignant breast lesions in patient data, the two-stage classification approach achieved an area under the receiver operating characteristic curve of 0.946, outperforming the diagnoses of all single-modality models and of a single-stage classification model that combines all US images, DOT histogram, and imaging features.
Conclusions
The proposed two-stage classification strategy achieves better classification accuracy than single-modality-only models and a single-stage classification model that combines all features. It can potentially distinguish breast cancers from benign lesions in near real-time.
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The quantification of protoporphyrin IX (PpIX) in skin can be used to study photodynamic therapy (PDT) treatments, understand porphyrin mechanisms, and enhance preoperative mapping of non-melanoma skin cancers.
Aim
We aim to develop a smartphone-based imager for performing simultaneous radiometric fluorescence (FL) and white light (WL) imaging to study the baseline levels, accumulation, and photobleaching of PpIX in skin.
Approach
A smartphone-based dual FL and WL imager (sDUO) is introduced alongside new radiometric calibration methods for providing SI-units of measurements in both pre-clinical and clinical settings. These radiometric measurements and corresponding PpIX concentration estimations are applied to clinical measurements to understand mechanistic differences between PDT treatments, accumulation differences between normal tissue and actinic keratosis lesions, and the correlation of photosensitizer concentrations to treatment outcomes.
Results
The sDUO alongside the developed methods provided radiometric FL measurements (nW / cm2) with a demonstrated sub nanomolar PpIX sensitivity in 1% intralipid phantoms. Patients undergoing PDT treatment of actinic keratosis (AK) lesions were imaged, capturing the increase and subsequent decrease in FL associated with the incubation and irradiation timepoints of lamp-based PDT. Furthermore, the clinical measurements showed mechanistic differences in new daylight-based treatment modalities alongside the selective accumulation of PpIX within AK lesions. The use of the radiometric calibration enabled the reporting of detected PpIX FL in units of nW / cm2 with the use of liquid phantom measurements allowing for the estimation of in-vivo molar concentrations of skin PpIX.
Conclusions
The phantom, pre-clinical, and clinical measurements demonstrated the capability of the sDUO to provide quantitative measurements of PpIX FL. The results demonstrate the use of the sDUO for the quantification of PpIX accumulation and photobleaching in a clinical setting, with implications for improving the diagnosis and treatment of various skin conditions.
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Optical tissue phantoms serve as inanimate and stable reference materials used to calibrate, characterize, standardize, and test biomedical imaging instruments. Although various types of solid tissue phantoms have been described in the literature, current phantom models are limited in that they do not have a depth feature that can be adjusted in real-time, they cannot be adapted to other applications, and their fabrication can be laborious and costly.
Aim
Our goal was to develop an optical phantom that could assess the imaging performance of fluorescence imaging devices and be customizable for different applications.
Approach
We developed a phantom with three distinct components, each of which can be customized.
Results
We present a method for fabricating a solid optical tissue that contains (1) an adjustable depth capability using thin film phantoms, (2) a refillable chip loaded with fluorophores of the user’s choice in various desired quantities, and (3) phantom materials representative of different tissue types.
Conclusions
This article describes the development of phantom models that are customizable, adaptable, and easy to design and fabricate.
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Organelle sizes, which are indicative of cellular status, have implications for drug development and immunology research. At the single cell level, such information could be used to study the heterogeneity of cell response to drugs or pathogens.
Aim
Angularly resolved elastic light scattering is known to be sensitive to changes in organelle size distribution. We developed a Mie theory-based simulation of angular scattering from single cells to quantify the effects of noise on scattering and size estimates.
Approach
We simulated randomly sampled organelle sizes (drawn from a log normal distribution), interference between different organelles’ scattering, and detector noise. We quantified each noise source’s effect upon the estimated mean and standard deviation of organelle size distributions.
Results
The results demonstrate that signal-to-noise ratio in the angular scattering increased with the number of scatterers, cell area, and exposure time and decreased with the size distribution width. The error in estimating the mean of the size distributions remained below 5% for nearly all experimental parameters tested, but the widest size distribution tested (standard deviation of 600 nm) reached 20%.
Conclusions
The simulator revealed that sparse sampling of a broad size distribution can dominate the mismatch between actual and predicted size parameters. Alternative estimation strategies could reduce the discrepancy.
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Diabetes is a prevalent disease worldwide that can cause severe health problems. Accurate blood glucose detection is crucial for diabetes management, and noninvasive methods can be more convenient and less painful than traditional finger-prick methods.
Aim
We aim to report a noncontact speckle-based blood glucose measurement system that utilizes artificial intelligence (AI) data processing to improve glucose detection accuracy. The study also explores the influence of an alternating current (AC) induced magnetic field on the sensitivity and selectivity of blood glucose detection.
Approach
The proposed blood glucose sensor consists of a digital camera, an AC-generated magnetic field source, a laser illuminating the subject’s finger, and a computer. A magnetic field is applied to the finger, and a camera records the speckle patterns generated by the laser light reflected from the finger. The acquired video data are preprocessed for machine learning (ML) and deep neural networks (DNNs) to classify blood plasma glucose levels. The standard finger-prick method is used as a reference for blood glucose level classification.
Results
The study found that the noncontact speckle-based blood glucose measurement system with AI data processing allows for the detection of blood plasma glucose levels with high accuracy. The ML approach gives better results than the tested DNNs as the proposed data preprocessing is highly selective and efficient.
Conclusions
The proposed noncontact blood glucose sensing mechanism utilizing AI data processing and a magnetic field can potentially improve glucose detection accuracy, making it more convenient and less painful for patients. The system also allows for inexpensive blood glucose sensing mechanisms and fast blood glucose screening. The results suggest that noninvasive methods can improve blood glucose detection accuracy, which can have significant implications for diabetes management. Investigations involving representative sampling data, including subjects of different ages, gender, race, and health status, could allow for further improvement.
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The vocal folds are critically important structures within the larynx which serve the essential functions of supporting the airway, preventing aspiration, and phonation. The vocal fold mucosa has a unique multilayered architecture whose layers have discrete viscoelastic properties facilitating sound production. Perturbations in these properties lead to voice loss. Currently, vocal fold pliability is inferred clinically using laryngeal videostroboscopy and no tools are available for in vivo objective assessment.
Aim
The main objective of the present study is to evaluate viability of Brillouin microspectroscopy for differentiating vocal folds’ mechanical properties against surrounding tissues.
Approach
We used Brillouin microspectroscopy as an emerging optical imaging modality capable of providing information about local viscoelastic properties of tissues in noninvasive and remote manner.
Results
Brillouin measurements of the porcine larynx vocal folds were performed. Elasticity-driven Brillouin spectral shifts were recorded and analyzed. Elastic properties, as assessed by Brillouin spectroscopy, strongly correlate with those acquired using classical elasticity measurements.
Conclusions
These results demonstrate the feasibility of Brillouin spectroscopy for vocal fold imaging. With more extensive research, this technique may provide noninvasive objective assessment of vocal fold mucosal pliability toward objective diagnoses and more targeted treatments.
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