scholarly journals Fast holographic scattering compensation for deep tissue biological imaging

2021 ◽  
Author(s):  
Molly A. May ◽  
Nicolas Barré ◽  
Kai Kummer ◽  
Micheala Kress ◽  
Monika Ritsch-Marte ◽  
...  
Keyword(s):  
Single Point ◽  
Biological Tissues ◽  
Rapid Improvement ◽  
Major Barrier ◽  
Non Invasive ◽  
Phase Stepping ◽  
Order Of Magnitude ◽  
Previous State ◽  
Two Photon Fluorescence

Scattering in biological tissues is a major barrier for in vivo optical imaging of all but the most superficial structures. Progress toward overcoming the distortions caused by scattering in turbid media has been made by shaping the excitation wavefront to redirect power into a single point in the imaging plane. However, fast, non-invasive determination of the required wavefront compensation remains challenging. Here, we introduce a quickly converging algorithm for non-invasive scattering compensation, termed DASH, in which holographic phase stepping interferometry enables new phase information to be updated after each measurement. This leads to rapid improvement of the wavefront correction, forming a focus after just one measurement iteration and achieving an order of magnitude higher signal enhancement at this stage than the previous state-of-the-art. Using DASH, we demonstrate two-photon fluorescence imaging of microglia cells in highly turbid mouse hippocampal tissue down to a depth of 530 μm.

scholarly journals Fast holographic scattering compensation for deep tissue biological imaging

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Molly A. May ◽  
Nicolas Barré ◽  
Kai K. Kummer ◽  
Michaela Kress ◽  
Monika Ritsch-Marte ◽  
...  
Keyword(s):  
Single Point ◽  
Biological Tissues ◽  
Rapid Improvement ◽  
Major Barrier ◽  
Non Invasive ◽  
Phase Stepping ◽  
Order Of Magnitude ◽  
Previous State ◽  
Two Photon Fluorescence

AbstractScattering in biological tissues is a major barrier for in vivo optical imaging of all but the most superficial structures. Progress toward overcoming the distortions caused by scattering in turbid media has been made by shaping the excitation wavefront to redirect power into a single point in the imaging plane. However, fast, non-invasive determination of the required wavefront compensation remains challenging. Here, we introduce a quickly converging algorithm for non-invasive scattering compensation, termed DASH, in which holographic phase stepping interferometry enables new phase information to be updated after each measurement. This leads to rapid improvement of the wavefront correction, forming a focus after just one measurement iteration and achieving an order of magnitude higher signal enhancement at this stage than the previous state-of-the-art. Using DASH, we demonstrate two-photon fluorescence imaging of microglia cells in highly turbid mouse hippocampal tissue down to a depth of 530 μm.

scholarly journals Targeting Cancer Cell Tight Junctions Enhances PLGA-Based Photothermal Sensitizers’ Performance In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 43
Author(s):  
Victoria O. Shipunova ◽  
Vera L. Kovalenko ◽  
Polina A. Kotelnikova ◽  
Anna S. Sogomonyan ◽  
Olga N. Shilova ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
3D Culture ◽  
Intercellular Junctions ◽  
Cell Junctions ◽  
Multicellular Spheroids ◽  
Mesenchymal Transition ◽  
Non Invasive ◽  
Order Of Magnitude

The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions. In this work, we synthesized 200 nm nanoparticles from the biocompatible copolymer of lactic and glycolic acid, PLGA, loaded with magnesium phthalocyanine, PLGA/Pht-Mg. The PLGA/Pht-Mg particles under the irradiation with NIR light (808 nm), heat the surrounding solution by 40 °C. The effectiveness of using such particles for cancer cells elimination was demonstrated in 2D culture in vitro and in our original 3D model with multicellular spheroids possessing tight cell contacts. It was shown that the mean inhibitory concentration of such nanoparticles upon light irradiation for 15 min worsens by more than an order of magnitude: IC50 increases from 3 µg/mL for 2D culture vs. 117 µg/mL for 3D culture. However, when using the JO-4 intercellular junction opener protein, which causes a short epithelial–mesenchymal transition and transiently opens intercellular junctions in epithelial cells, the efficiency of nanoparticles in 3D culture was comparable or even outperforming that for 2D (IC50 = 1.9 µg/mL with JO-4). Synergy in the co-administration of PTT nanosensitizers and JO-4 protein was found to retain in vivo using orthotopic tumors of BALB/c mice: we demonstrated that the efficiency in the delivery of such nanoparticles to the tumor is 2.5 times increased when PLGA/Pht-Mg nanoparticles are administered together with JO-4. Thus the targeting the tumor cell junctions can significantly increase the performance of PTT nanosensitizers.

scholarly journals A Robust Method for Adjustment of Laser Speckle Contrast Imaging during Transcranial Mouse Brain Visualization

Photonics ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 80 ◽  
Author(s):  
Vyacheslav Kalchenko ◽  
Anton Sdobnov ◽  
Igor Meglinski ◽  
Yuri Kuznetsov ◽  
Guillaume Molodij ◽  
...  
Keyword(s):  
Biological Tissues ◽  
Laser Speckle ◽  
Robust Method ◽  
Scattering Media ◽  
Contrast Imaging ◽  
Speckle Contrast ◽  
Non Invasive ◽  
Sagittal Sinus ◽  
Brain Vasculature

Laser speckle imaging (LSI) is a well-known and useful approach for the non-invasive visualization of flows and microcirculation localized in turbid scattering media, including biological tissues (such as brain vasculature, skin capillaries etc.). Despite an extensive use of LSI for brain imaging, the LSI technique has several critical limitations. One of them is associated with inability to resolve a functionality of vessels. This limitation also leads to the systematic error in the quantitative interpretation of values of speckle contrast obtained for different vessel types, such as sagittal sinus, arteries, and veins. Here, utilizing a combined use of LSI and fluorescent intravital microscopy (FIM), we present a simple and robust method to overcome the limitations mentioned above for the LSI approach. The proposed technique provides more relevant, abundant, and valuable information regarding perfusion rate ration between different types of vessels that makes this method highly useful for in vivo brain surgical operations.

scholarly journals Cooperative Binding of Heat Shock Factor to the Yeast HSP82 Promoter In Vivo and In Vitro

1999 ◽  
Vol 19 (3) ◽  
pp. 1627-1639 ◽  
Author(s):  
Alexander M. Erkine ◽  
Serena F. Magrogan ◽  
Edward A. Sekinger ◽  
David S. Gross
Keyword(s):  
Heat Shock ◽  
Single Point ◽  
Heat Shock Factor ◽  
Single Point Mutation ◽  
Heat Shock Element ◽  
Cooperative Interactions ◽  
Before And After ◽  
Order Of Magnitude

ABSTRACT Previous work has shown that heat shock factor (HSF) plays a central role in remodeling the chromatin structure of the yeastHSP82 promoter via constitutive interactions with its high-affinity binding site, heat shock element 1 (HSE1). The HSF-HSE1 interaction is also critical for stimulating both basal (noninduced) and induced transcription. By contrast, the function of the adjacent, inducibly occupied HSE2 and -3 is unknown. In this study, we examined the consequences of mutations in HSE1, HSE2, and HSE3 on HSF binding and transactivation. We provide evidence that in vivo, HSF binds to these three sites cooperatively. This cooperativity is seen both before and after heat shock, is required for full inducibility, and can be recapitulated in vitro on both linear and supercoiled templates. Quantitative in vitro footprinting reveals that occupancy of HSE2 and -3 by Saccharomyces cerevisiae HSF (ScHSF) is enhanced ∼100-fold through cooperative interactions with the HSF-HSE1 complex. HSE1 point mutants, whose basal transcription is virtually abolished, are functionally compensated by cooperative interactions with HSE2 and -3 following heat shock, resulting in robust inducibility. Using a competition binding assay, we show that the affinity of recombinant HSF for the full-length HSP82promoter is reduced nearly an order of magnitude by a single-point mutation within HSE1, paralleling the effect of these mutations on noninduced transcript levels. We propose that the remodeled chromatin phenotype previously shown for HSE1 point mutants (and lost in HSE1 deletion mutants) stems from the retention of productive, cooperative interactions between HSF and its target binding sites.

scholarly journals Detection of Age-Related Changes in Tendon Molecular Composition by Raman Spectroscopy—Potential for Rapid, Non-Invasive Assessment of Susceptibility to Injury

2020 ◽  
Vol 21 (6) ◽  
pp. 2150
Author(s):  
Nai-Hao Yin ◽  
Anthony W. Parker ◽  
Pavel Matousek ◽  
Helen L. Birch
Keyword(s):  
Raman Spectroscopy ◽  
Raman Spectra ◽  
Flexor Tendon ◽  
Biological Tissues ◽  
Ring Structure ◽  
Total N ◽  
Non Invasive ◽  
Age Related ◽  
Superficial Digital Flexor Tendon

The lack of clinical detection tools at the molecular level hinders our progression in preventing age-related tendon pathologies. Raman spectroscopy can rapidly and non-invasively detect tissue molecular compositions and has great potential for in vivo applications. In biological tissues, a highly fluorescent background masks the Raman spectral features and is usually removed during data processing, but including this background could help age differentiation since fluorescence level in tendons increases with age. Therefore, we conducted a stepwise analysis of fluorescence and Raman combined spectra for better understanding of the chemical differences between young and old tendons. Spectra were collected from random locations of vacuum-dried young and old equine tendon samples (superficial digital flexor tendon (SDFT) and deep digital flexor tendon (DDFT), total n = 15) under identical instrumental settings. The fluorescence-Raman spectra showed an increase in old tendons as expected. Normalising the fluorescence-Raman spectra further indicated a potential change in intra-tendinous fluorophores as tendon ages. After fluorescence removal, the pure Raman spectra demonstrated between-group differences in CH2 bending (1450 cm−1) and various ring-structure and carbohydrate-associated bands (1000–1100 cm−1), possibly relating to a decline in cellular numbers and an accumulation of advanced glycation end products in old tendons. These results demonstrated that Raman spectroscopy can successfully detect age-related tendon molecular differences.

scholarly journals Non-invasive chemically specific measurement of subsurface temperature in biological tissues using surface-enhanced spatially offset Raman spectroscopy

2016 ◽  
Vol 187 ◽  
pp. 329-339 ◽  
Author(s):  
Benjamin Gardner ◽  
Nicholas Stone ◽  
Pavel Matousek
Keyword(s):  
Raman Spectroscopy ◽  
High Sensitivity ◽  
Biological Tissues ◽  
Temperature Monitoring ◽  
Subsurface Temperature ◽  
Non Invasive ◽  
Wide Range ◽  
Subsurface Monitoring ◽  
Mean Square Errors

Here we demonstrate for the first time the viability of characterising non-invasively the subsurface temperature of SERS nanoparticles embedded within biological tissues using spatially offset Raman spectroscopy (SORS). The proposed analytical method (T-SESORS) is applicable in general to diffusely scattering (turbid) media and features high sensitivity and high chemical selectivity. The method relies on monitoring the Stokes and anti-Stokes bands of SERS nanoparticles in depth using SORS. The approach has been conceptually demonstrated using a SORS variant, transmission Raman spectroscopy (TRS), by measuring subsurface temperatures within a slab of porcine tissue (5 mm thick). Root-mean-square errors (RMSEs) of 0.20 °C were achieved when measuring temperatures over ranges between 25 and 44 °C. This unique capability complements the array of existing, predominantly surface-based, temperature monitoring techniques. It expands on a previously demonstrated SORS temperature monitoring capability by adding extra sensitivity stemming from SERS to low concentration analytes. The technique paves the way for a wide range of applications including subsurface, chemical-specific, non-invasive temperature analysis within turbid translucent media including: the human body, subsurface monitoring of chemical (e.g. catalytic) processes in manufacture quality and process control and research. Additionally, the method opens prospects for control of thermal treatment of cancer in vivo with direct non-invasive feedback on the temperature of mediating plasmonic nanoparticles.

scholarly journals SPETTROSCOPIA E IMAGING IN OTTICA DIFFUSA: FOCUS SUL TUMORE DELLA MAMMELLA

2020 ◽  
Author(s):  
Paola Taroni
Keyword(s):  
Breast Cancer ◽  
Near Infrared ◽  
Breast Cancer Diagnosis ◽  
Biological Tissues ◽  
Blood Parameters ◽  
Collagen Content ◽  
Diffuse Optics ◽  
Non Invasive ◽  
Ultrasound Diagnostics

Through the measurement of the optical properties (absorption and scattering), diffuse optical spectroscopy allows one to estimate non-invasively the composition of biological tissues (water, lipid and collagen content) and functional blood parameters. Further, it provides information on the microscopic tissue structure. It can therefore be effectively used in vivo as an absolutely non-invasive diagnostic tool. The Department of Physics of the Politecnico di Milano has designed and built an optical mammograph that exploits diffused optics, operating with pulsed light at 7 wavelengths in the red and near infrared spectral range (635-1060 nm). The instrument was used in a clinical study on 200 subjects, in collaboration with the European Institute of Oncology: optically derived tissue composition and in particular collagen content in tissues proved to be effective both to discriminate between malignant and benign breast lesions, and to estimate the risk of breast cancer related to the density of breast tissue, which is recognized among the most important independent risk factors. Partly based on those results, “SOLUS - Smart optical and ultrasound diagnostics of breast cancer”, a European project in the H2020 Framework Program, is now working to improve the specificity of non-invasive breast cancer diagnosis by combining diffuse optics with ultrasound imaging.

scholarly journals Non-invasive depth determination of inclusion in biological tissues using spatially offset Raman spectroscopy with external calibration

The Analyst ◽  
2020 ◽  
Vol 145 (23) ◽  
pp. 7623-7629 ◽  
Author(s):  
Sara Mosca ◽  
Priyanka Dey ◽  
Marzieh Salimi ◽  
Francesca Palombo ◽  
Nick Stone ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Biological Tissues ◽  
Disease Diagnosis ◽  
Early Disease ◽  
External Calibration ◽  
Non Invasive ◽  
Depth Determination

Spatially Offset Raman Spectroscopy (SORS) allows chemical characterisation of biological tissues at depths enabling in vivo localization of biomarkers for early disease diagnosis.

scholarly journals Ultrasound-Guided Detection and Segmentation of Photoacoustic Signals from Bone Tissue In Vivo

2020 ◽  
Vol 11 (1) ◽  
pp. 19
Author(s):  
Ting Feng ◽  
Yunhao Zhu ◽  
Chengcheng Liu ◽  
Sidan Du ◽  
Dean Ta ◽  
...  
Keyword(s):  
Trabecular Bone ◽  
Bone Tissue ◽  
Bone Health ◽  
Spatial Information ◽  
Health Assessment ◽  
Biological Tissues ◽  
Ultrasound Guided ◽  
Non Invasive ◽  
In Vivo Experiment

Photoacoustic (PA) techniques provide optical absorption contrast and spatial information at an ultrasound resolution in deep biological tissues. Among the greatest challenges encountered in the PA examination of bone is the analysis of trabecular bone, which holds key chemical and physical information required for bone health assessments. Ultrasound detection is naturally registered with PA detection; therefore, in this study, we propose ultrasound guidance for the PA detection of trabecular bone. We perform both numerical simulations and an in vivo experiment on a human subject to investigate the possibility of ultrasound-guided detection and segmentation of photoacoustic signals from bone tissue in vivo in a non-invasive manner. The results obtained from the simulation and in vivo experiment suggest that the ultrasound-guided PA method can distinguish PA signals from trabecular and cortical bones as well as from the overlying soft tissue. Considering that the PA technique is non-ionizing and non-invasive, it holds potential for clinical bone health assessment.

scholarly journals Image-guided Non-invasive Ultrasonic Thrombolysis Using Histotripsy

2018 ◽  
Author(s):  
Zhen Xu
Keyword(s):  
New Technology ◽  
Ultrasound Image ◽  
Standard Of Care ◽  
Excessive Bleeding ◽  
Vein Thrombosis ◽  
Non Invasive ◽  
Image Guided ◽  
Order Of Magnitude

Deep vein thrombosis (DVT), clot formation in the deep veins in the legs, affects two million Americans annually. Clinical DVT treatments include thrombolytic drugs and catheter-based surgical procedures. Both methods have significant drawbacks, such as excessive bleeding and invasiveness. Guided by ultrasound imaging, histotripsy is a non-invasive cavitation-based ultrasound therapy that fractionates tissue. Using our laboratory prototype, histotripsy fractionated in vitro clots into debris smaller than red blood cells at a speed an order of magnitude faster than clinical thrombolysis methods. Using an in vivo porcine DVT model, histotripsy non-invasively eradicated the thrombus in 10 of 12 cases. We have designed and constructed an integrated ultrasound image-guided histotripsy thrombolysis system based on human DVT patient data. We propose a comprehensive pre-clinical study to determine the safety and efficacy of this clinically designed histotripsy system in a porcine DVT model. The proposed study is critical to advancing the clinical translation of this new technology to improve the standard of care for DVT patients.

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