Dr. Alexei A. Bogdanov Profile

Dr. Alexei A. Bogdanov

at Univ of Massachusetts Chan Medical School

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Publications (8)

Proceedings Article | 17 March 2023 Presentation

In vivo imaging of CRISPRi-attenuated receptor expression by using a miniaturized near-infrared anti-EGFR probe (Conference Presentation)

Alexei Bogdanov, Suresh Gupta, Anand Kumar, Rahul Pal, Eric Schmidt

Proceedings Volume PC12398, PC123980E (2023) https://doi.org/10.1117/12.2648483

KEYWORDS: Tumors, In vivo imaging, Receptors, Cancer, Near infrared, Luminescence, Tumor growth modeling, Tissues, Optical imaging, Image registration

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Proceedings Article | 7 March 2023 Presentation + Paper

Clinical MRI contrast agent improves fluorescent imaging of red fluorescent protein expression in-vivo due to the effect of tissue optical clearing

Alexei Bogdanov, Valery Tuchin, Natalia Kazachkina, Victoria Zherdeva, Lilya Maloshenok, Daria Tuchina, Irina Meerovich, Ilya Solovyev, Alexander Savitsky

Proceedings Volume 12378, 1237806 (2023) https://doi.org/10.1117/12.2648493

KEYWORDS: Tumors, Magnetic resonance imaging, Tissues, Skin, In vivo imaging, Mixtures, Body composition, Contrast agents, Signal to noise ratio, Refractive index, Optical clearing

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The use of multimodality approaches may benefit from simultaneous or sequential optical and magnetic resonance (MR) imaging applied to the same tissue volume. Previously observed in vivo optical clearing (OC) effect of MRI contrast agent was investigated with a goal of quantifying the effect of gadobutrol (GB) and biocompatible compositions containing GB as means of improving fluorescence intensity imaging (FI) in a rodent model of cancer. MRI was also explored as a technique enabling localization of the tumor volumes affected by intravenous administration of GB performed for the purpose of achieving an OC effect. Xenografting of cells expressing a red fluorescent marker TagRFP in athymic mice resulted in subcutaneous tumors that were subjected to 1H MRI at 1T by applying T1w-3D gradient-echo (GRE) pulse sequences. MRI allowed to measure the longitudinal changes in MR signal intensity that were sufficient for ROI analysis after manual or automated image segmentation. By performing topical application of an OC compositions, which contained 1.0 M or 0.7 M GB mixed with water and dimethyl sulfoxide (DMSO) onto the skin similar tumor MRI signal enhancement by 30–40% within the first 15 min was achieved. Over time, the effect of GB-mediated OC on FI and tumor/background ratio decreased. The application of 0.7 M GB OC mixture in contrast, to concentrated 1.0 M GB resulted in a continuous increase of both tumor red fluorescence as well as of the tumor/background ratio within 15 min and 1 h post cutaneous application. By applying T1w-3D GRE MR it was determined that concentrated 1.0 M GB resulted in MR signal loss measured in the skin due to high magnetic susceptibility. However, the MR signal loss was colocalized with the OC effect in tumor tissue. Intravenous injection of GB at a dose of 0.3 mmol/kg resulted in a rapid and temporary increase of FI by 40%. In conclusion, low-field MRI proved to be useful for performing in vivo imaging of GB-containing OC compositions behavior after local and systemic applications in cancer models and supported the observation of FI longitudinal changes in vivo.

Proceedings Article | 9 March 2021 Presentation + Paper

Optical clearing and multimodality fluorescence and magnetic resonance imaging in cancer models

Alexei Bogdanov, Natalia Kazachkina, Victoria Zherdeva, Irina Meerovich, Daria Tuchina, Ilya Solovyev, Alexander Savitsky, Valery Tuchin

Proceedings Volume 11641, 116410C (2021) https://doi.org/10.1117/12.2586113

KEYWORDS: Optical clearing, Luminescence, Tumor growth modeling, Cancer, Tumors, Tissues, In vivo imaging, Tissue optics, Skin, Magnetic resonance imaging

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Proceedings Article | 8 April 2020 Presentation

In vivo application of magnetic resonance imaging contrast agents for tissue optical clearing (Conference Presentation)

Daria Tuchina, Olga Sindeeva, Alexander Savitsky, Alexei Bogdanov, Valery Tuchin

Proceedings Volume 11363, 1136327 (2020) https://doi.org/10.1117/12.2557365

KEYWORDS: Magnetic resonance imaging, Skin, Optical clearing, Tissue optics, In vivo imaging, Tissues, Optical coherence tomography, Light scattering, Scattering, Medicine

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Solving the problem of limited depth penetration of light in vivo remains important due to the innate high scattering of light in the tissues. One way to reduce tissue scattering is to apply immersion optical clearing using chemical agents. This reversible process is based on partial replacement of tissue intercellular fluid with clearing agents, which leads to matching of refractive indices between tissue components as well as tissue dehydration and consequently to more regular packing of tissue structural elements. Earlier we discovered that low molecular weight MRI contrast agents have the ability of optical clearing [1]. This was shown for the first time in the case of mouse skin samples ex vivo. The next logical step included an in vivo study. The expected advantages of using MRI contrast agent compositions as optical clearing agents are: 1) their biocompatibility; 2) the possibility of combining the areas of enhanced contrast of MRI and optical images in time and space. The effect of optical clearing was obtained when MRI contrast agents were applied to the surface of mouse skin in vivo. We used the following MRI contrast agents: Gadavist (Bayer HealthCare Pharmaceuticals, Germany), Magnevist (Bayer HealthCare Pharmaceuticals, Germany) and Dotarem (Guerbet, France). The Spectral Radar OCT System OCP930SR 022 (Thorlabs Inc., United States) with a wavelength of 930 nm was used to quantify the change in the optical properties of the skin. After hair removal from the mouse skin, a B-scan of the intact skin region with OCT was recorded. Then, the selected MRI agent was applied topically to the target skin area. Skin OCT scans were recorded every 5-10 min during the exposure of the skin area to an MRI agent. The solution was removed each time before scanning and applied again after scanning. OCT showed an increase in the penetration depth of the light beam into the tissue and resulted in more contrast images of the skin by reducing skin scattering for each of the used MRI agents. OCT data were processed to quantify the diffusion coefficients of MRI agents in the skin and the effectiveness of optical clearing of skin using these agents. The obtained results show the possibility of not only improving the quality of optical imaging, but also open the way for the implementation of a new approach to multimodality, when synchronization in time and space of regions with increased contrast of both the optical image and MRI image is automatically ensured since the same agent enables both effects simultaneously.

Proceedings Article | 6 April 2020 Presentation

Optical clearing effects in subcutaneous red-fluorescent tumors monitored by fluorescence and magnetic resonance imaging in vivo (Conference Presentation)

Alexei Bogdanov, Irina Meerovich, Natalia Kazachkina, Victoria Zherdeva, Ilya Solovyev, Daria Tuchina, Alexander Savitsky, Valery Tuchin

Proceedings Volume 11363, 113630S (2020) https://doi.org/10.1117/12.2560186

KEYWORDS: Tumors, Magnetic resonance imaging, Luminescence, In vivo imaging, Optical clearing, Skin, Tissues, Proteins, Magnetism, Confocal microscopy

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The goal of this study was in investigating potential correlation of the effects induced by optical clearing (OC) of the skin and the underlying peripheral tissues with the changes in T2-weighted (T2w) magnetic resonance (MR) signal measured over the matched area in vivo. OC/MRI experiments were performed in athymic nu/nu mice carrying subcutaneous HEp2 tumor xenografts expressing Tag-RFP marker protein at 2-3 weeks after tumor inoculation. Initially, to investigate the effect of OC induced by a mixture of 70% glycerol, 5% DMSO, 25% water, we performed measurements of Tag-RFP fluorescence intensity (FI) and lifetime (FL) before and after OC using a macroscopic confocal scanning system equipped with a supercontinuum laser with the acousto-optic tunable filter and a photon-counting detector. The OC effect was achieved by applying the OC mixture onto the skin over the tumor area for 10 min followed by mixture removal from the skin. Subsequently we performed MRI at 1T using T2w fast spin-echo (FSE) MR pulse sequences before and after OC mixture application in the same animals on two non-consecutive days. Time-correlated single photon counting experiments showed that after OC application FL of Tag-RFP was higher with median difference of 51 ps (P<0.05, Wilcoxon matched-pairs test). Average FI increased by 33% after OC resulting in the higher frequency of fluorescence intensity increase observations (n=19 vs. n=3 with FI decreasing) measured over multiple ROI in 3 animals. The analysis of obtained T2w FSE MR images showed significant quantitative differences (p=0.03) between Gaussian noise-normalized MR signal intensities of the 0.7mm-thick axial peripheral tissue/skin slices before and after OC mixture applications in 2 animals, though in one animal those differences were statistically insignificant. The comparison of T2w MR signal intensities measured in OC mixture phantoms prepared at various dilutions and pure water showed that at chosen FSE MRI parameters the observed differences in MR signal intensity were not due to the application of OC mixture alone and must have been a consequence of OC mixture interaction with the skin and peripheral tumor tissue components. The obtained results point to the potential mechanism of OC clearing as it relates to: 1) a transient change of the peripheral tumoral microenvironment affecting the layer of Tag-RFP expressing cells and resulting in FL increase and T2w MR hypointensity increase caused by shortening of mean proton relaxation times within the voxels of subcutaneous tumors; 2) potential microviscosity increase due to skin permeability for the OC components resulting in the shortening of tissue water proton transverse relaxation times. The phantom experiments suggest that the effect of the OC mixture on MR signal is indirect rather than direct consequence of either OC/water magnetic relaxation properties, or additional chemical shift artifact. Therefore, T2w 1T MRI showed promise as a technique suitable for detecting small longitudinal changes of the MR signal in the subcutaneous tissue under the conditions of OC, which resulted in an increase of FI/FL of a red fluorescent marker protein. The latter effects are expected to benefit in vivo imaging of marker protein expression in animal tumor models.

Proceedings Article | 21 February 2020 Presentation + Paper

Towards registration of optical and MR signal changes in subcutaneous tumor volume in vivo after optical skin clearing

Alexei Bogdanov, Valery Tuchin, Irina Meerovich, Natalia Kazachkina, Viktoria Zherdeva, Ilya Solovyev, Daria Tuchina, Alexander Savitsky

Proceedings Volume 11239, 112390N (2020) https://doi.org/10.1117/12.2545312

KEYWORDS: Tumors, Tissues, Skin, Magnetic resonance imaging, Luminescence, Tissue optics, In vivo imaging, Water, Optical clearing, Optical imaging

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Proceedings Article | 1 March 2019 Open Access

Near-infrared oligonucleotide duplex sensors for imaging rapidly activated transcription factors in vitro and in situ

Alexei Bogdanov, Valeriy Metelev, Toloo Taghian, Ilya Solovyev, Anand T. Kumar, Surong Zhang, Alexander Savitsky

Proceedings Volume 10877, 1087702 (2019) https://doi.org/10.1117/12.2511124

KEYWORDS: Luminescence, Near infrared, Proteins, Molecules, In vivo imaging, Sensors, In vitro testing, Pancreas, Inflammation, Tissues

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SPIE Journal Paper | 20 April 2012 Open Access

In vivo fluorescence lifetime detection of an activatable probe in infarcted myocardium

Craig Goergen, Anand Kumar, Howard Chen, Alexei Bogdanov, David Sosnovik

JBO, Vol. 17, Issue 5, 056001, (April 2012) https://doi.org/10.1117/12.10.1117/1.JBO.17.5.056001

KEYWORDS: Luminescence, In vivo imaging, Liver, Heart, Fluorescence spectroscopy, Tissues, Signal detection, Biomedical optics, Continuous wave operation

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