International Tomography Center

The use of artificial intelligence (AI) technologies in clinical trials (CT) of medicines has led to a significant reduction in time and financial costs for the development of new medicines. However, their widespread adoption faces a number of unresolved issues related to data quality, regulation, ethics, and security. The purpose of this study was to assess the current state of AI application in CT and identify key issues hindering its widespread adoption. Results and discussion . The key applications of AI in CT are analyzed: the use of large language models (TrialGPT, Elsa) for data analysis, the creation of digital patient counterparts and synthetic controls for CT modeling, as well as predictive analytics to optimize research design and risk assessment. It has been shown that these methods can improve the efficiency of patient selection, predict outcomes with a high area under ROC score (up to 92.7 %), and accelerate drug development. However, serious limitations have been identified: the dependence of the quality of models on the representativeness of data, the risks associated with imperfect algorithms, as well as the lack of specialized regulatory regulation and standards, including in the Russian Federation. The problems of data confidentiality, obtaining informed consent, and determining responsibility for harm caused by the use of AI are highlighted. Conclusions. The widespread use of AI to increase the efficiency and personalization of CT, its scaling requires solving complex regulatory, legal and ethical challenges.

Objective. To evaluate structural retinal changes in patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) over time and to analyze their association with the progression of neurological impairment. Material and methods . Clinical data (EDSS, T25FW, 9-HPT, SDMT) and optical coherence tomography (OCT) results (average thickness of the ganglion cell and inner plexiform layer [avgGCL+IPL]; average thickness of the peripapillary retinal nerve fiber layer [avgRNFL]) were analyzed in patients with RRMS and SPMS (42 women, 19 men; age 46.20 ± 9.49 years) over a follow-up period of 12.87 ± 1.25 months. Comparisons were performed between groups stratified by disability level (Group 1: EDSS 0–2.0, Group 2: EDSS 2.5–3.5, Group 3: EDSS≥4.0), as well as by the presence of at least one sign of progression (increase in EDSS by 0.5–1.0, ≥20 % worsening in T25FW/9HPT, or ≥4-point/10 % decrease in SDMT). Results and discussion . EDSS did not change significantly during follow-up (p = 0.451); however, 45.2 % of patients demonstrated signs of progression according to T25FW/9HPT/sDMT. T25FW performance worsened more markedly in Groups 2 and 3 (p < 0.001), while no significant differences were observed between groups in other measures. Statistically significant differences in avgGCL+IPL and avgRNFL were found between Groups 1 and 3 (p = 0.007 and p = 0.016, respectively). Annual avgGCL+IPL change was −0.58 [−1.00; −0.17] μm in Group 1 vs. −3.00 [−3.33; −1.25] μm in Group 3; annual avgRNFL change was −0.62 [−1.75; 0.75] μm in Group 1 vs. −2.38 [−3.25; −1.88] μm in Group 3. Moreover, annual reductions in avgGCL+IPL and avgRNFL were greater in patients with progression (−1.54 [−3.00; −0.46] and −2.31 [−4.69; −1.25] μm, respectively) compared with stable patients (−0.83 [−1.50; −0.25] and −0.75 [−1.88; 0.50] μm, respectively), with statistically significant differences (p = 0.018 and p = 0.003, respectively). Progression was predicted by avgGCL+IPL loss >1.17 μm/year (sensitivity 64.3%; specificity 66.7 %) and avgRNFL loss >1.125 μm/year (78.6 and 63.6 %, respectively). Conclusions. Accumulation of neurological deficits occurs even in the absence of EDSS changes, while the neurodegenerative process is more active in patients with greater disability and longer disease duration. Annual thinning of avgGCL+IPL and avgRNFL on OCT may serve as a predictor of MS progression.

Arterial spin labeling (ASL) perfusion MRI represents a modern non-invasive approach to assessing tissue perfusion that is gaining increasing importance in clinical and research practice. Unlike traditional contrast-enhanced methods, ASL enables quantitative blood flow evaluation without the need for contrast agents, which is particularly valuable in certain clinical scenarios and for longitudinal patient monitoring. This review synthesizes current data on ASL perfusion applications, including key clinical uses and future development prospects. The topic’s relevance stems from growing interest in functional imaging techniques and the need for ASL protocol standardization to facilitate widespread clinical adoption. Purpose: To evaluate the diagnostic capabilities of ASL perfusion MRI by analyzing current applications and future development trends based on contemporary scientific evidence. Material and methods . A retrospective review of randomized clinical trials and cross-sectional studies was performed from PubMed, EMBASE, LILACS, Scopus, and eLibrary databases (2015–2025) using search terms: «arterial spin labeling,» «pulsed ASL,» «continuous ASL,» «pseudo-continuous ASL,» «diffusion-prepared ASL,» «artificial intelligence ASL,» and their Russian equivalents. Results. From 132 screened publications, 81 were selected for analysis. The review examined ASL technique variations, clinical applications, and emerging trends in the field. Conclusions. ASL perfusion is a promising non-invasive method for tissue blood flow assessment with demonstrated diagnostic utility across multiple pathologies. Future development potential lies in methodological optimization, artificial intelligence integration for data processing, and protocol standardization for routine clinical implementation.

Ternary transition metal borides exhibit a wide variety of crystal structures and, as a consequence, a wide range of functional properties. This work investigates ternary phases formed via the interaction of zirconium diboride with iridium. The analysis of powder XRD, SEM, and WDS indicates the formation of three known ternary boride phases (Zr2Ir6B, ZrIr3B4, and Zr2Ir5B2) and two novel phases (ZrIr7B2 and ZrIr2B). In the wide range of reagents' mixture compositions, the main products are Zr2Ir5B2 and ZrIr2B; in the 4-fold excess of iridium, the composition of products changes to a mixture of Zr2Ir6B and ZrIr7B2. The structure of the novel phase, ZrIr7B2, was studied with single-crystal X-ray diffraction and powder time-of-flight neutron diffraction, which showed that it crystallizes in a new structure type with a layered hexagonal structure P6̅2m: a = 5.5683(7) Å, c = 5.6058(7) Å. The structure consists of Kagomé net layers formed by [BIr6] trigonal prisms, with Zr atoms in the free space of each layer and Ir atoms in the interlayer space. Additionally, the Vickers microhardness of the ternary borides was measured; all ternary compounds display microhardness in the range of 15-19 GPa.

Hyperpolarized acetoacetate is a promising probe for detection of redox status inside mitochondria using 13C MRI. In this pilot study we used parahydrogen-induced polarization by means of side arm hydrogenation (PHIP-SAH) approach for hyperpolarization of [1,3-13C2]acetoacetate. The propargyl [1,3-13C2]acetoacetate precursor was synthesized and subjected to homogeneous hydrogenation with parahydrogen. After optimization, the observed 1H polarization was 25.5% while achieving 100% chemical conversion of propargyl moiety and 80% selectivity to allyl [1,3-13C2]acetoacetate product. After hydrogenation, linear magnetic field sweep was performed for 1H-to-13C polarization transfer in allyl [1,3-13C2]acetoacetate with maximum observed 13C polarizations: P(13C-1) = 4.1% and P(13C-3) = 2.7%. Next, we analyzed the products of allyl [1,3-13C2]acetoacetate hydrolysis under different conditions. Alkaline hydrolysis results in the formation of stereoisomeric enolates of allyl [1,3-13C2]acetoacetate, which can then be converted into hyperpolarized [1,3-13C2]acetoacetate under harsh alkaline conditions with subsequent decomposition to hyperpolarized [2-13C]acetone and [13C]carbonate. These results represent a step toward expanding the PHIP-SAH agent portfolio beyond pyruvate, here specifically towards establishing acetoacetate as a promising candidate for future redox and ROS-sensitive 13C MRI studies.

Light-responsive molecules that can release drugs upon light absorption have attracted significant interest in chemistry and biology. BODIPY-based photoremovable protecting groups, or photocages, have recently emerged as especially promising tools in this respect. However, the exact photorelease mechanism is still not fully understood. We study the photochemical decomposition of meso-Methyl-BODIPY-conjugated epinephrine using 1H nuclear magnetic resonance and chemically induced dynamic nuclear polarization (CIDNP) techniques. After irradiation, epinephrine was detected only in trace amounts, whereas its oxidation product, adrenochrome, was the predominant product. Surprisingly, the CIDNP study has shown that the electron transfer (ET) in this reaction does not proceed from epinephrine to the BODIPY moiety, but rather occurs between two BODIPY cores. To validate this hypothesis, we applied the CIDNP method to detect photoinduced ET between two model BODIPY molecules in solution. In addition, the radical cation of BODIPY has been detected for the first time by CIDNP under photolysis in the presence of the electron acceptor-chloranil. The hyperfine interaction (HFI) constants of the BODIPY radical cation were estimated from the CIDNP spectrum, and they are in agreement with the HFI constant predicted by density functional theory calculations. Due to high enhancement coefficients, the CIDNP technique allows for to detection of polarized BODIPY products at very low concentrations.

A novel nitronyl nitroxide organocopper derivative has been reported─a unique reagent for cross-coupling reactions of aryl and heteroaryl halides. The innovative protocol involves a copper complex supported by a sterically hindered NHC ligand, specifically SIPrCuNN, and a Pd(0)-catalytic system resulting from Pd2dba3·CHCl3 and the phosphine ligand MeCgPPh. The designed method is compatible with various aromatic and heteroaromatic iodides, therefore increasing new applications for creating functionalized nitronyl nitroxide paramagnet and open-shell compounds.

Hyperpolarization techniques provide a dramatic enhancement of the sensitivity of magnetic resonance spectroscopy and imaging. Signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) is an efficient technique for hyperpolarization of 13C and 15N nuclei in various biologically relevant compounds. Nitroimidazole antibiotics are prone to reduction under anaerobic conditions, making them prospective molecular contrast agents for the visualization of hypoxic tumors. In this work, we systematically studied 15N SABRE-SHEATH hyperpolarization of the ornidazole antibiotic at natural abundance (n.a.) of the 15N isotope and in the isotopically 15N3-labeled form. Optimization of such experimental conditions as polarization transfer magnetic field, temperature, parahydrogen pressure, and flow rate resulted in average 15N polarization levels of 9.3 ± 0.5% for n.a. ornidazole and 5.3 ± 0.2% for [15N3]ornidazole. T1 polarization decay time of 7.4 min was achieved for the 15NO2 group of [15N3]ornidazole at a clinically relevant 1.4 T magnetic field, allowing for the detection of the 15N NMR signal more than 20 min after hyperpolarization. DFT calculations of 15N chemical shifts for ornidazole and plausible intermediates and products of its reduction under hypoxic conditions showed that it should be feasible to discriminate these compounds by using 15N NMR.

Bistability in molecule-based magnets is crucial for their applications in functional devices, and thermally induced excited spin state trapping (TIESST) represents a promising route to maintain two distinct spin states for a significant period of time. Heterospin compounds based on Cu(II) and nitroxide radicals demonstrate highly tunable non-classical spin transitions, nevertheless they did not reveal TIESST effects up to date. Here, we report the first Cu(II)-nitroxide complex that exhibits TIESST-driven bistability up to 116K. The TIESST temperature is close to temperatures of the spin transition, which is accompanied by a hysteresis of 30K (T1/2↑ = 144K, T1/2↓ = 114K). The trapped excited state features a very slow relaxation that exceeds 9h at 95K. Fast switching is also feasible for this complex: almost complete conversion from the ground to excited state occurs in a single THz pulse within 50ms. The slow relaxation and preservation of the crystal quality enabled us to perform an XRD study and demonstrate that the trapped and stable phases coexist during the transition. It was demonstrated, that relaxation of excited state proceeds via an autocatalytic mechanism, previously unreported for spin-crossover systems, which introduces a new paradigm in spin relaxation dynamics.