A series of bis-diimine rhenium(I) complexes Re(NN1-OMe)-Re(NN3-OMe), containing neocuproine and methyl [2-(pyridin-2-yl)quinoline-4-carboxylate (NN1), methyl [2,2 '-biquinoline]-4-carboxylate (NN2), dimethyl [2,2 '-biquinoline]-4,4 '-dicarboxylate (NN3) was synthesized and characterized. Utilization of the asymmetric NN1 and NN2 ligands affords two types of structural isomers, which were isolated and structurally studied by X-ray diffraction analysis in the solid state. 1H-1H COSY and NOESY NMR experiments confirmed preservation of the structural patterns in liquid media for the complexes under study. Alkaline hydrolysis of the ester groups in the NN# diimine ligands was performed to give the Re(NN1-OK)-Re(NN3-OK) complexes exhibiting higher water solubility that made possible to use them in biological experiments. In MeOH and aqueous media, the complexes display NIR absorption with a long wavelength band at ca. 715 nm extended up to 850 nm in the case of both forms of Re(NN3)-OX. The Re(NN3-OK) complex demonstrated stable photoacoustic signal in oxygenated blood phantoms and showed no significant toxicity with the cell viability above 80% even at concentrations of 1 mM in cell experiments with CHO-K1 cell line.

Reconstruction of biotissue optical properties from spatially resolved fiber optic diffuse reflectance spectroscopy (DRS) measurements requires a fast and accurate solution of the forward problem of light transport for a specified DRS configuration. In this study we report on comparative analysis of three analytical models of diffuse reflectance (Green’s function, a model proposed by Farrell et al (1992), and a refined model proposed by Sergeeva et al (2024)) with the Monte Carlo-simulated reflectance in extensive range of optical parameters. The refined model demonstrates the best accuracy among all three analytical models for source-detector distances (SDDs) exceeding 2 mm. A semi-analytical fit of massive MC reflectance is proposed which possesses a discrepancy of less than 2% in the entire range of considered absorption and scattering and at SDDs below 2 mm. The accuracy of chromophore concentration recovery from MC simulated spectra of reflectance for a medium mimicking dermis is evaluated for all the discussed models.

Owing to its unique ability to capture volumetric tomographic information with a single light flash, optoacoustic (OA) tomography has recently demonstrated ultrafast imaging speeds ultimately limited by the ultrasound time-of-flight. The method’s scalability and the achievable spatial resolution are yet limited by the narrow bandwidth of piezo-composite arrays currently employed for OA signal detection. Here we report on the first implementation of high-density spherical array technology based on flexible polyvinylidene difluoride films featuring ultrawideband (0.3–40 MHz) sub mm2 area elements, thus enabling real-time multi-scale volumetric imaging with 22–35 µm spatial resolution, superior image fidelity and over an order of magnitude signal-to-noise enhancement compared to piezo-composite equivalents. We further demonstrate five-dimensional (spectroscopic, time-resolved, volumetric) imaging capabilities by visualizing fast stimulus-evoked cerebral oxygenation changes in mice and performing real-time functional angiography of deep human micro-vasculature. The new technology thus leverages the true potential of OA for quantitative high-resolution visualization of rapid bio-dynamics across scales. This work reports on the first implementation of ultrawideband high density spherical detection array based on flexible polyvinylidene difluoride films for real time functional 3D optoacoustic micro-angiography

We report on the development of Monte Carlo based models of signal formation in systems of spectral and fluorescence imaging. Numerical simulations allow tracking photon trajectories providing imaging volume analysis, while parallel processor architecture allows to significantly speed up calculations.

The effects of cytotoxic chemotherapy on tumor vasculature and oxygenation are in the focus of modern investigations because vascular structure and distribution of oxygen influence tumor behavior and treatment response. The aim of our study was to monitor changes in the vascular component of colorectal tumor xenografts induced by a clinical combination of chemotherapy drugs FOLFOX in vivo using two complementary techniques: diffuse reflectance spectroscopy (DRS) and optical coherence tomography-based microangiography (OCT-MA). These techniques revealed a slower decrease in tumor blood oxygenation in treated tumors as compared to untreated ones, faster suppression of tumor vasculature perfusion and increase in water content as a result of treatment, and decrease in total hemoglobin in untreated tumors. Immunohistochemical analysis of hypoxia-inducible factor HIF-2α detected tissue hypoxia as a consequence of inappropriate oxygen supply in the treated tumors. The obtained results show the prospects for monitoring of treatment efficacy using DRS and OCT-MA.

A refined analytical model of spatially resolved diffuse reflectance with small source-detector separations (SDSs) for the in vivo skin studies is proposed. Compared to the conventional model developed by Farrell et al., it accounts for the limited acceptance angle of the detector fiber. The refined model is validated in the wide range of optical parameters by Monte Carlo simulations of skin diffuse reflectance at SDSs of units of mm. Cases of uniform dermis and two-layered epidermis-dermis structures are studied. Higher accuracy of the refined model compared to the conventional one is demonstrated in the separate, constraint-free reconstruction of absorption and reduced scattering spectra of uniform dermis from the Monte Carlo simulated data. In the case of epidermis-dermis geometry, the recovered values of reduced scattering in dermis are overestimated and the recovered values of absorption are underestimated for both analytical models. Presumably, in the presence of a thin mismatched topical layer, only the effective attenuation coefficient of the bottom layer can be accurately recovered using a diffusion theory-based analytical model while separate reconstruction of absorption and reduced scattering fails due to the inapplicability of the method of images. These findings require implementation of more sophisticated models of light transfer in inhomogeneous media in the recovery algorithms.

We report on creation of a diffuse optical spectroscopy (DOS) setup in a wide VIS-NIR spectral range with a contact fiber-optic probe using a self-calibration technique. A four measurement procedure employing two source and two collection fibers arranged symmetrically allows to calculate extinction spectrum of investigated tissue, excluding DOS instrumental characteristics and reducing the influence of absorption inhomogeneities on a tissue surface. High accuracy of a measured extinction spectra allows one to account for more tissue chromophores and precisely assess tissue physiological properties. The proposed system was applied successfully in preliminary in vivo studies.

Differences in the vessel fraction, hemoglobin content and oxygenation level of tumor xenografts are revealed by optoacoustic microscopy and diffuse optical spectroscopy.

The objective of this work was to study the dynamics and mechanisms of oxygenation changes of an experimental rat tumor Plyss lymphosarcoma in the process of its growth using diffuse optical spectroscopy (DOS). DOS in trans-illumination configuration utilizing high-frequency (140 MHz) modulation of light intensity is used to assess absorption and scattering coefficients averaged over tumor tissue at several wavelengths 684, 794, and 850 nm. Those values were used to assess concentrations of tissue oxyhemoglobin and deoxyhemoglobin and oxygen saturation. During the observation period (from the 5th to the 15th day after transplantation) the tumor volume increased up to 25 times. In the process of tumor growth, a gradual increase in the content of deoxyhemoglobin, a decrease of oxyhemoglobin level, and a decrease of blood oxygen saturation without changes in the level of total tissue hemoglobin concentration were observed. Thus, the main mechanisms of oxygen saturation decrease in the process of tumor growth are associated with two effects: the increase of oxygen consumption rate (demonstrated by the increase of deoxyhemoglobin) and the decrease of oxygen supply (demonstrated by the decrease of oxyhemoglobin).

We report on the comparative analysis of self-calibrating and single-slope diffuse reflectance spectroscopy in resistance to different measurement perturbations. We developed an experimental setup for diffuse reflectance spectroscopy (DRS) in a wide VIS-NIR range with a fiber-optic probe equipped with two source and two detection fibers capable of providing measurements employing both single- and dual-slope (self-calibrating) approaches. In order to fit the dynamic range of a spectrometer in the wavelength range of 460–1030 nm, different exposure times have been applied for short (2 mm) and long (4 mm) source-detector distances. The stability of the self-calibrating and traditional single-slope approaches to instrumental perturbations were compared in phantom and in vivo studies on human palm, including attenuations in individual channels, fiber curving, and introducing optical inhomogeneities in the probe–tissue interface. The self-calibrating approach demonstrated high resistance to instrumental perturbations introduced in the source and detection channels, while the single-slope approach showed resistance only to perturbations introduced into the source channels.

Abstract Background Breast cancer neoadjuvant chemotherapy (NACT) allows for assessing tumor sensitivity to systemic treatment, planning adjuvant treatment and follow-up. However, a sufficiently large number of patients fail to achieve the desired level of pathological tumor response while optimal early response assessment methods have not been established now. In our study, we simultaneously assessed the early chemotherapy-induced changes in the tumor volume by ultrasound (US), the tumor oxygenation by diffuse optical spectroscopy imaging (DOSI), and the state of the tumor vascular bed by Doppler US to elaborate the predictive criteria of breast tumor response to treatment. Methods A total of 133 patients with a confirmed diagnosis of invasive breast cancer stage II to III admitted to NACT following definitive breast surgery were enrolled, of those 103 were included in the final analysis. Tumor oxygenation by DOSI, tumor volume by US, and tumor vascularization by Doppler US were determined before the first and second cycle of NACT. After NACT completion, patients underwent surgery followed by pathological examination and assessment of the pathological tumor response. On the basis of these, data regression predictive models were created. Results We observed changes in all three parameters 3 weeks after the start of the treatment. However, a high predictive potential for early assessment of tumor sensitivity to NACT demonstrated only the level of oxygenation, ΔStO2, (ρ = 0.802, p ≤ 0.01). The regression model predicts the tumor response with a high probability of a correct conclusion (89.3%). The “Tumor volume” model and the “Vascularization index” model did not accurately predict the absence of a pathological tumor response to treatment (60.9% and 58.7%, respectively), while predicting a positive response to treatment was relatively better (78.9% and 75.4%, respectively). Conclusions Diffuse optical spectroscopy imaging appeared to be a robust tool for early predicting breast cancer response to chemotherapy. It may help identify patients who need additional molecular genetic study of the tumor in order to find the source of resistance to treatment, as well as to correct the treatment regimen.

The analysis of age-related changes in skin vessels based on optoacoustic angiographic images during the in vivo skin monitoring of healthy volunteers at different ages is reported. As a result of a quantitative analysis of the three-dimensional OA images, the age-associated differences in the following image parameters were revealed: image intensity, ratio of blood content at different characteristics depths, total vessel length, and number of branches. The reported approach can be effectively employed for automatic assessment and monitoring of age-related vascular changes in the skin and underlying tissues.

The research is devoted to comparison of the blood vessel structure and the oxygen state of three xenografts: SN-12C, HCT-116 and Colo320. Differences in the vessel formation and the level of oxygenation are revealed by optoacoustic (OA) microscopy and diffuse optical spectroscopy (DOS) respectively. The Colo320 tumor is characterized by the highest values of vessel size and fraction. DOS showed increased content of deoxyhemoglobin that led to reduction of saturation level for Colo320 as compared to other tumors. Immunohistochemical (IHC) analysis for CD31 demonstrates the higher number of vessels in Colo320. The IHC for hypoxia was consistent with DOS results and revealed higher values of the relative hypoxic fraction in Colo320.

The aim of the study was to investigate the dynamics of the state of allo- and autografts of skin on a wound using optical modalities: diffuse reflectance spectroscopy (DRS), optical coherence tomography (OCT), and laser Doppler flowmetry (LDF). A deep thermal burn was simulated in 24 rats covering 20% of the body surface. On day 3 after the injury, a fascial necrectomy of two 500 mm(2) areas on the left and right sides of the midline of the animal body were excised. Allografts and autografts were placed in the centers of these areas. Optical measurements of grafts were performed on the 0, 3rd, 6th, 10th, and 13th days after transplantation. The allografts demonstrated a pronounced decrease in oxygenation, blood content, and perfusion compared to autografts on the 6th day; in the following days of observation, these values returned to the average values of autografts. Water content gradually decreased from the beginning to the end of observation. In conclusion, optical diagnostics revealed changes in the morphological microstructure, the rate of restoration of blood circulation, and oxygen exchange in the early stages, specific for the allo- and autograft.

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text A. Orlova, K. Pavlova, A. Kurnikov, A. Maslennikova, D. Skamnitskiy, V. Perekatova, A. Khilov, A. Kovalchuk, I. Turchin, and P. Subochev, "Optoacoustic and Diffuse Optical Spectroscopy Monitoring of Tumor Response to Radiation Therapy," in Biophotonics Congress: Biomedical Optics 2022 (Translational, Microscopy, OCT, OTS, BRAIN), Technical Digest Series (Optica Publishing Group, 2022), paper OM2D.3. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article

The newly developed multimodal imaging system combining raster-scan optoacoustic (OA) microscopy and fluorescence (FL) wide-field imaging was used for characterizing the tumor vascular structure with 38/50 μm axial/transverse resolution and assessment of photosensitizer fluorescence kinetics during treatment with novel theranostic agents. A multifunctional photoactivatable multi-inhibitor liposomal (PMILs) nano platform was engineered here, containing a clinically approved photosensitizer, Benzoporphyrin derivative (BPD) in the bilayer, and topoisomerase I inhibitor, Irinotecan (IRI) in its inner core, for a synergetic therapeutic impact. The optimized PMIL was anionic, with the hydrodynamic diameter of 131.6 ± 2.1 nm and polydispersity index (PDI) of 0.05 ± 0.01, and the zeta potential between −14.9 ± 1.04 to −16.9 ± 0.92 mV. In the in vivo studies on BALB/c mice with CT26 tumors were performed to evaluate PMILs’ therapeutic efficacy. PMILs demonstrated the best inhibitory effect of 97% on tumor growth compared to the treatment with BPD-PC containing liposomes (PALs), 81%, or IRI containing liposomes (L-[IRI]) alone, 50%. This confirms the release of IRI within the tumor cells upon PMILs triggering by NIR light, which is additionally illustrated by FL monitoring demonstrating enhancement of drug accumulation in tumor initiated by PDT in 24 h after the treatment. OA monitoring revealed the largest alterations of the tumor vascular structure in the PMILs treated mice as compared to BPD-PC or IRI treated mice. The results were further corroborated with histological data that also showed a 5-fold higher percentage of hemorrhages in PMIL treated mice compared to the control groups. Overall, these results suggest that multifunctional PMILs simultaneously delivering PDT and chemotherapy agents along with OA and FL multi-modal imaging offers an efficient and personalized image-guided platform to improve cancer treatment outcomes.

Diffuse reflectance spectroscopy (DRS) is an optical imaging modality based on extraction of tissue structural and functional information from back-reflectance spectra. In this paper we analyze the spectral dependence of DRS probing depth for different source-detector separations (SDSs) in the range of 1.5–7.0 mm by means of Monte Carlo simulations. The simulated spectra are employed to analyze the effect of the selected spectral range on the accuracy of oxygen saturation (StO 2 ) reconstruction for different parameters of skin. It is shown that the probing depth varies in the range of 1–4 mm depending on SDS and tissue parameters, and in the hemoglobin absorption band for particular medium configuration it demonstrates a 2-fold decrease as compared to the neighboring spectral ranges. Comparison of different spectral ranges for StO 2 reconstruction from the measured spectra at different SDSs demonstrated that the range of 480–600 nm and the full range of 480–900 nm benefit over near infrared (NIR) range (700–900 nm) in the reconstruction accuracy. The 480–600 nm range provides the best reconstruction accuracy for low blood volume content, while the full range of 480–900 nm provides better accuracy for larger blood volume content. The comprehensive study of the spectral dependency of probing depth in DSR for SDSs in the range of 1.5–7.0 mm based on MC simulations for multi-layered skin model depending on skin layers properties and numerical aperture combined with analysis of StO 2 reconstruction accuracy was conducted for the first time to our knowledge.

Using OA and DOS the comparison of vascular structure and oxygenation of renal (SN-12C) and colon (Colo320, HCT116) cancer models was carried out. High vascularity was found for Colo320 and SN-12C as compared to HCT116. For Colo320 the presence of extended hemoglobin-containing structures was revealed, as well as a significantly decreased level of oxygenation.

Tumor microvascular responses may provide a sensitive readout indicative of radiation therapy efficacy, its time course and dose dependencies. However, direct high-resolution observation and longitudinal monitoring of large-scale microvascular remodeling in deep tissues remained challenging with the conventional microscopy approaches. We report on a non-invasive longitudinal study of morphological and functional neovascular responses by means of scanning optoacoustic (ОА) microangiography. In vivo imaging of CT26 tumor response to a single irradiation at varying dose (6, 12, and 18 Gy) has been performed over ten days following treatment. Tumor oxygenation levels were further estimated using diffuse optical spectroscopy (DOS) with a contact fiber probe. OA revealed the formation of extended vascular structures on the whole tumor scale during its proliferation, whereas only short fragmented vascular regions were identified following irradiation. On the first day post treatment, a decrease in the density of small (capillary-sized) and medium-sized vessels was revealed, accompanied by an increase in their fragmentation. Larger vessels exhibited an increase in their density accompanied by a decline in the number of vascular segments. Short-lasting response has been observed after 6 and 12 Gy irradiations, whereas 18 Gy treatment resulted in prolonged responses, up to the tenth day after irradiation. DOS measurements further revealed a delayed increase of tumor oxygenation levels for 18 Gy irradiations, commencing on the sixth day post treatment. The ameliorated oxygenation is attributed to diminished oxygen consumption by inhibited tumor cells but not to the elevation of oxygen supply. This work is the first to demonstrate the differential (size-dependent) nature of vascular responses to radiation treatments at varying doses in vivo. The OA approach thus facilitates the study of radiation-induced vascular changes in an unperturbed in vivo environment while enabling deep tissue high-resolution observations at the whole tumor scale.

Strong dispersion of biotissue optical properties in visible and NIR ranges determines difference in probing depths in optical diagnostics modalities thus allowing to control probing depth by the choice of the wavelength range. The paper discusses spectral dependence of the probing depth and the accuracy of oxygen saturation reconstruction in diffuse reflectance spectroscopy and reviews dual-wavelength approach in fluorescence imaging.