aprzybylo-jozefowicz@ichf.edu.pl, Author at ICTER

05.12.2024

How do we use STOC-T to assess ocular microcirculation? – new paper in Neurophotonics by 3 ICTER research groups

aprzybylo-jozefowicz@ichf.edu.pl

Like a complex network of highways, the retinal microcirculation is a hidden system that powers the life of the eye – delivering oxygen, nourishing tissues, and allowing cells to function without disruption. New research conducted by ICTER (International Centre for Translational Eye Research) scientists will enable us to track every “movement” on these microscopic roads using the STOC-T (Spatio-Temporal Optical Coherence Tomography) technique. This offers the opportunity to understand the mechanisms of retinal function and discover how microcirculation disorders herald the onset of neurological and ophthalmological diseases.

Retinal microcirculation and hemodynamics provide valuable information on neurovascular diseases, as many diseases of the central nervous system (CNS) can manifest themselves through changes in the retina. Given that about 80% of external information is processed through visual perception, understanding the structure and function of the retina, vascular hemodynamics, and neurovascular coupling (NVC) is of paramount importance.

Now, ICTER scientists have used spatio-temporal optical coherence tomography (STOC-T) to assess retinal microcirculation. It turns out that the STOC-T technique, which uses fast near-infrared tomographic imaging, offers the possibility of visualizing even the smallest capillaries in real-time. Unlike other techniques, such as ocular angiography (angio-OCT) or Doppler tomography, STOC-T allows for obtaining 3D images of the entire structure of the retina and choroid with high temporal precision. Additionally, the use of digital aberration correction and a specially designed optical system allows for obtaining images unaffected by refractive errors, which is particularly important for imaging small structures, such as the mouse retina. The results were published in the journal Neurophotonics in a paper entitled “In vivo volumetric analysis of retinal vascular hemodynamics in mice with spatiotemporal optical coherence tomography.”

What connects STOC-T and ocular microcirculation?

Spatio-temporal optical coherence tomography (STOC-T) is an advanced optical tomography method that allows for obtaining three-dimensional images of tissue microstructures in real time with high temporal resolution. In turn, ocular microcirculation is, broadly speaking, a network of small blood vessels supplying the retina and choroid, allowing for the proper functioning of photoreceptors. Adequate blood flow is essential for the delivery of oxygen and nutrients and the removal of metabolic products.

Retinal microcirculation research is becoming particularly important in the context of the increasing number of neurodegenerative and ophthalmological diseases. Disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, as well as eye diseases such as glaucoma or diabetic retinopathy, are often associated with microcirculation disorders that can be visible at the retinal level even before neurological symptoms appear. The use of STOC-T allows precise monitoring of hemodynamic changes in the retina, which can help in the early detection of pathologies and the development of new therapeutic methods.Retinal blood flow can be quantitatively monitored in vivo using laser speckle flowgraphy (LSFG), a technique that generates angiographic contrast from speckle variance, enabling full-field (arbitrary units) blood flow measurements with high temporal resolution. Alternatively, laser Doppler flowmetry (LDF) can measure blood flow and mean velocity in relative units, and its extension, laser Doppler holography (LDH), can estimate pulsatile retinal flow in the lateral field of view (FOV) with millisecond resolution. These techniques cannot perform deep slices, making the influence of choroidal flow unclear. It would be beneficial to analyze choroidal hemodynamics separately from the internal retinal hemodynamics and with high temporal resolution, which is what STOC-T allows.

Groundbreaking observations and a chance for new therapeutic options

The study aimed to implement the STOC-T technique, previously developed by ICTER scientists, for monitoring retinal microcirculation and neurovascular coupling (NVC). Now, it was possible to obtain detailed images of different layers of the mouse retina, such as the neurofibrous layer (NFL), the inner plexiform layer (IPL), the inner and outer photoreceptor segments (IS/OS) and the choroid. These images allow for the observation of both larger blood vessels on the surface and the more complex network of capillaries in deeper layers, such as the IPL.

Analysis of the STOC-T signal amplitude allowed for the differentiation of arterial and venous pulsations in the mouse retina. In particular it was found that the pulsation in the venous vessels is delayed by an average of 29 milliseconds about the arteries, which allows for the identification of phase differences between these vessels. This pulsation time delay between arteries and veins is crucial for understanding the different roles these vessels play in microcirculation. STOC-T allows tracking of tissue displacements induced by the pulse wave as it travels through the retinal layers. These micromovements are measured in nanometers and observed mainly around arteries and veins, with modulation amplitudes ranging from 100 to 150 nanometers.

Measurement of the blood pulse wave velocity (0.35 mm/s) in the capillaries of the outer plexiform layer (OPL) and tissue displacements induced by vessel pulsation (up to 150 nm) provided data on the biomechanical properties of the different retinal layers. This analysis revealed differences in the biomechanical response to pulsation between layers, which is particularly valuable for NVC studies. Although the system is limited in recording pulse wave velocity in larger vessels due to the field of view and pulse wavelength, it remains highly effective in analyzing blood flow in capillaries.

Mapping of tissue shifts in time caused by vascular pulsation revealed that retinal layers exhibit periodic expansion and contraction synchronized with vascular pulsation. These observations, with an amplitude of 100-150 nm, provide important information on tissue elasticity and biomechanical properties of the retina, enabling further studies on neurodegenerative diseases in which the preservation of microcirculation and vascular elasticity may be impaired.

New quality in imaging of ocular hemodynamics

Studies conducted using the STOC-T technique provided detailed data on the hemodynamics and biomechanics of the mouse retina, which opens new diagnostic and therapeutic perspectives. The possibility of noninvasive monitoring of retinal blood flow and precise analysis of phase differences between venous and arterial pulsations may be crucial in the detection and treatment of many neurological and ophthalmological diseases. Ocular microcirculation, being a hidden highway supplying the retina with oxygen and nutrients, is crucial not only for the health of the eyes but also for the condition of the entire nervous system.

This publication is the result of the fruitful cooperation of three ICTER groups: POB, IDoc, and OBi, which emphasizes its interdisciplinary nature. These teams, combining their unique experiences and expertise, created the foundations for innovative solutions described in the publication. Such a combination of knowledge from different research areas is a key element in the search for innovative answers to contemporary challenges, which is one of the pillars of ICTER.

Authors of the paper “In vivo volumetric analysis of retinal vascular hemodynamics in mice with spatio-temporal optical coherence tomography”: Piotr Węgrzyn, Wiktor Kulesza, Maciej Wielgo, Sławomir Tomczewski, Anna Galińska, Bartłomiej Bałamut, Katarzyna Kordecka, Onur Cetinkaya, Andrzej Foik, Robert J. Zawadzki, Dawid Borycki, Maciej Wojtkowski, Andrea Curatolo.

Press note author: Scientific Editor Marcin Powęska.

The pictures portray the first author of the paper: Piotr Węgrzyn. Photos by Dr. Karol Karnowski.

18.11.2024

Strategic guidance and future directions: ICTER’s 2024 International Scientific Committee Meeting

aprzybylo-jozefowicz@ichf.edu.pl

On November 8, 2024, ICTER hosted its International Scientific Committee (ISC) meeting at its Warsaw headquarters. Chaired by Prof. Olaf Strauss from Charité from Universitätsmedizin Berlin, the meeting convened ISC members whose strategic insights support the shaping of ICTER’s research directions. Attendees included Deputy Chair Prof. Francesca Fanelli (Università degli Studi di Modena e Reggio Emilia), Prof. Arie Lev Gruzman (Bar-Ilan University), Prof. Karl-Wilhelm Koch (Carl von Ossietzky University of Oldenburg), Prof. Pablo Artal (Universidad de Murcia), Prof. James Bainbridge (UCL Institute of Ophthalmology), Prof. Majlinda Lako (Newcastle University), Dr. Georgios Skretas (BSRC Alexander Fleming), and Dr. Henri Leinonen (University of Eastern Finland), each bringing valuable expertise to guide ICTER’s research priorities. Prof. Maciej Wojtkowski, ICTER Chair, formally welcomed new ISC members with nominations for the 2024–2028 term.

The agenda covered key topics, with Managing Director Anna Pawlus outlining ICTER’s organizational structure and ISC responsibilities, followed by presentations on ICTER’s development as a centre of excellence under the Teaming for Excellence project by Prof. Christophe Gorecki and updates on ICTER’s new building at the Institute of Physical Chemistry, Polish Academy of Sciences campus by its Director, Dr. hab. Adam Kubas. Next, Dr. Anna Przybyło-Józefowicz, Deputy Chair for International Cooperation, highlighted upcoming events and conferences in 2025, including the 25th Anniversary of the SdOCT technology, and the CRATER 2.0 edition.

Throughout the day, an observer from the Foundation for Polish Science, Dr. Anna Skarżyńska, was present, ensuring a transparent and collaborative approach.

The second stage of recruitment for the Group Leader position within the Integrated Structural Biology (ISB) Group took place in the afternoon, with ISC members conducting in-depth candidate interviews. Following these evaluations, Prof. Strauss presented the committee’s recommendations, providing ICTER with essential guidance on the selection of new leadership for this pivotal research area. Next, ISC members expressed their opinion on ICTER’s latest grant, evaluating its alignment with the research agenda.

After concluding remarks, ISC members toured ICTER’s laboratories, guided by Group Leaders and researchers: Katarzyna Komar, Stefania Robakiewicz, Natalia Ochocka, Lidia Wolińska-Nizioł, Anna Posłuszny, Jadwiga Milkiewicz, Anna Galińska, Karolina Saran, Milena Gumkowska, Bartłomiej Bałamut, Piotr Kasprzycki, Adam Kurek, Piotr Nalewajko, Tomasz Gawroński and Krzysztof Gromada. The tour provided ISC members with an in-depth look at ongoing projects and advancements within ICTER’s facilities. The hands-on engagement allowed the committee to directly observe the innovative work driving ICTER’s impact on eye research, vision sciences and ophthalmology.

Photos: Patricio Espinoza and Anna Pawlus.

18.11.2024

ICTER Centre of Scientific Excellence: agreement signed with the European Commission

aprzybylo-jozefowicz@ichf.edu.pl

How can technology be developed to help patients gain faster access to specialized ophthalmological care? Polish researchers from the ICTER scientific centre, who are exploring this question, will officially join forces with their French and British counterparts on January 1, 2025. Adam Kubas, Director of the Institute of Physical Chemistry of the Polish Academy of Sciences (IChF), signed a grant agreement with the European Commission for the “Teaming for Excellence” project. This achievement reflects months of dedicated efforts by the ICTER team, which operates within the IChF.

“This project marks a significant milestone in establishing ICTER as a centre of scientific and research excellence. It will empower us to validate and bring our cutting-edge technologies to market, boost our visibility, and reinforce both international and local partnerships. Through these advancements, ICTER is poised to make a lasting impact on innovation in ophthalmology in Poland and beyond,” said Professor Maciej Wojtkowski, head of the ICTER scientific centre.

A prestigious grant under the “Teaming for Excellence” programme within Horizon Europe has secured the researchers a total of €30 million in funding, with €15 million from the European Commission and an additional matching contribution from the Foundation for Polish Science and the Ministry of Science and Higher Education.

Theory Meets Practice

Today, ICTER scientists integrate knowledge from physics, biology, chemistry, engineering, and medicine. Thanks to the collaboration with the Institute of Ophthalmology at University College London and the Institut de la Vision at Sorbonne Université, researchers will not only enhance the exchange of knowledge and experience between leading eye research centres but also gain better opportunities to test new solutions. The Warsaw-based ICTER Centre of Scientific Excellence will be a place where science meets practice, transforming research into tangible medical solutions.

ICTER and its partners have already begun building the project’s visibility, both within the scientific community and among organizations that supported the team during the grant application phase. These activities mark the first step in creating a network of organizations and individuals dedicated to fighting for patients’ eye health. This network will accelerate the implementation of new technologies and ensure that research teams stay closely aligned with the needs of ophthalmologists. As a result, ICTER can be confident that the technologies it develops will effectively support medical professionals.

Technology to the Aid of Ophthalmologists

These approaches form the foundation of scientists’ work. Researchers analyze issues that hinder the progress of ophthalmology and determine whether current technological solutions can address these challenges. Their devices utilize advanced eye illumination methods, cameras capable of recording up to 60,000 frames per second, and artificial intelligence solutions that allow for rapid analysis of eye function.

One of the technologies now emerging from ICTER’s laboratories is STOC-T. This equipment will facilitate faster and more accurate diagnosis of diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Early diagnosis is critical because, in Poland, each ophthalmologist serves approximately 10,000 patients. According to the National Health Fund, by the end of the second quarter of 2024, over 470,000 Poles were waiting for ophthalmological consultations—a number equivalent to the entire population of Gdańsk.

23.10.2024

Key to the invisible world found. ICTER scientists decipher two-photon vision

aprzybylo-jozefowicz@ichf.edu.pl

Two-photon vision is a novel method with great potential for the future of ophthalmic diagnostics. Although it has many advantages, it requires improvement in key areas. ICTER scientists have taken a step forward by improving this technology and opening up new perspectives in ocular medicine.

Imagine that instead of viewing an image through a lens, you look through a kaleidoscope that focuses invisible light to obtain a new range of colors. The photon, this ephemeral messenger of light, usually appears alone, but here it appears in a duet, which is the basis of two-photon vision. This extraordinary phenomenon in which the human eye, instead of perceiving traditional light, receives pulses of infrared lasers, the gateway to the invisible world.

However, the key to them is measuring the brightness of two-photon stimuli, which until now was only possible for visible light. ICTER scientists have made a breakthrough and determined the luminance value for infrared using photometric units (cd/m²). Thanks to this approach, it was possible to link the luminance of two-photon stimuli to a new physical quantity related to perceived brightness: the two-photon retinal illumination.

Research conducted by scientists from the International Centre for Eye Research (ICTER) with the participation of PhD student Oliwia Kaczkoś, PhD Eng. Katarzyna Komar and Prof. Maciej Wojtkowski have shown that the luminance of a two-photon stimulus can reach almost 670 cd/m² in the safe range of laser power for the eye. The result is the paper entitled “Method for the determination of the luminance of two-photon vision stimuli,” published in the journal Biomedical Optics Express.

From left: Oliwia Kaczkoś and Dr. Katarzyna Komar. Photo by Dr. Karol Karnowski.

Seeing the Invisible World

The human eye can receive stimuli from the surrounding world in the form of electromagnetic waves in the range of about 380 nm to 780 nm (from violet to red). Waves outside this range, such as infrared (above 780 nm) and ultraviolet (below 380 nm), are invisible to us without special devices, although they can affect the senses in other ways.

Every vision process follows the same path when a photon of visible light is absorbed by the visual pigment of the photoreceptor in the retina (the light-sensitive part of the eye). This event initiates a series of chemical reactions, as a result of which a quantum of light is converted into an electrical signal, processed in the brain.

Two-photon vision is a phenomenon in which the human eye can perceive ultrashort pulses of infrared lasers with a wavelength in the range of 800-1300 nm by absorbing two photons. This process causes isomerization of visual pigments, which leads to the perception of light with a wavelength corresponding to half the infrared wavelength. Although these lasers are outside the visible range of the spectrum, their effect on visual pigments allows infrared light to be recorded as different colors.

Two-photon vision differs from single-photon vision primarily in the way light is absorbed. In single-photon vision, each photon with a specific energy is absorbed by molecules in the eye, which allows light to be perceived in the visible range. In two-photon vision, on the other hand, two photons with half the energy are simultaneously absorbed by visual pigments, which leads to the perception of light with half the wavelength, which theoretically should not be visible.

Furthermore, the brightness of the two-photon stimulus varies with the square of the power of optical radiation, so light scattered in the eye will not be perceived. Brightness also depends on the focus of the beam on the observer’s retina – the received stimuli are sharper and have better contrast than in the case of “normal,” single-photon vision.

ICTER scientists have long been studying the phenomenon of two-photon vision, were the first in the world to describe it, and now they have made another groundbreaking discovery.

On the picture: Oliwia Kaczkoś. Photo by Dr. Karol Karnowski.

A novel method for determining the brightness of two-photon stimuli

Two-photon vision shows potential in two key areas: medical diagnostics and virtual/augmented reality (VR/AR). It can be used for advanced diagnostic tests, especially in neurology and ophthalmology, where infrared pulses allow for safe monitoring of visual functions without the need to use visible light. On the other hand, this phenomenon allows the creation of new, realistic visual experiences by manipulating light stimuli from the infrared range, opening up new possibilities in interaction with virtual images (VR/AR).

All future applications of this phenomenon require knowledge of the luminance of two-photon stimuli, but the luminous efficiency function V(λ) outside the visible range is unknown. A non-standard approach to quantifying the luminance of two-photon stimuli is necessary, e.g., using infrared – which is what ICTER scientists did.

The method presented in the paper allowed the expression of the brightness of two-photon stimuli in photometric units. Thanks to the measurements performed, the scientists were able to demonstrate the relationship between the power of the infrared beam and the power of the visible beam, which was subjectively adjusted so that both were perceived as having the same luminance. Using the relationship between the power density of the VIS laser and the luminance of the projected stimuli, it was possible to determine the subjective luminance of the infrared stimuli using photometric units (cd/m²). These results emphasize the nonlinear nature of two-photon vision, which is in agreement with previous studies.

“The study aimed to develop a repeatable method for determining the brightness of stimuli for two-photon vision. Standard methods do not allow this to be done outside the visible spectrum of light, but our research opens the door to achieving this goal, which is necessary for further research and development of applications of this phenomenon in medical diagnostics and augmented reality (AR) and virtual reality (VR) technologies. The new approach will also enable comparison of the brightness of two-photon stimuli with traditional displays based on standard, single-photon vision”. – says Oliwia Kaczkoś, ICTER PhD student and optometrist, lead author of the study.

From left: Dr. Katarzyna Komar and Oliwia Kaczkoś. Photo by Dr. Karol Karnowski.

A platform for further discoveries

The result of the research is the proposal of a completely new physical quantity, called two-photon retinal illumination, which is sufficient to describe systems emitting two-photon stimuli. This relationship allowed the prediction of the luminance values of two-photon stimuli, which could reach 670 cd/m² in the safe laser power range of the human eye without adaptive optics (AO) correction.

Moreover, ICTER scientists documented twice the repeatability for measurements made on a background with a luminance of 10 cd/m². This is crucial for the development of future technologies, such as two-photon retinal displays, which could be used in augmented reality (AR) glasses or in advanced diagnostic tools such as two-photon microperimetry.

Authors of the paper “Method for determination of luminance of two-photon vision stimuli”: Oliwia Kaczkoś, Agnieszka Zielińska, Jacek Pniewski, Maciej Wojtkowski, and Katarzyna Komar.

Author of the press release: Marcin Powęska.

Photos: Dr. Karol Karnowski.

ICTER, or the International Centre for Translational Eye Research, is a research, development and innovation centre at the Institute of Physical Chemistry of the Polish Academy of Sciences (IChF), located in Warsaw, Poland. ICTER was established in 2019 to develop cutting-edge technologies to support the diagnosis and therapy of eye diseases, based on funding from the International Research Agendas Programme of the Foundation for Polish Science, co-financed by the European Union – European Regional Development Fund. The centre is currently implementing the MAB FENG grant of the Foundation for Polish Science. In 2024, IChF has won a prestigious grant under the Teaming for Excellence / WIDERA program of Horizon Europe, which will enable ICTER unit to develop into a European centre of excellence. The centre’s website is: www.icter.pl.

25.06.2024

A new way to monitor eye microcirculation. Multiwavelength laser Doppler holography (MLDH) in time-frequency optical tomography OCT (STOC-T)

aprzybylo-jozefowicz@ichf.edu.pl

For the eyes to function properly, they must be adequately supplied with blood, and abnormalities in the microcirculation may indicate dysfunctions in other arteries, which are difficult to examine. For the first time, scientists from the International Centre from Translational Eye Research (ICTER), operating within the Institute of Physical Chemistry of the Polish Academy of Sciences, used multiwavelength laser Doppler holography to assess blood flow in various layers of the human retina in vivo, which may impact the diagnosis of circulatory disorders.

Spatio-temporal optical coherence tomography (STOC-T) is a novel method for fast and aberration-free three-dimensional retinal imaging in vivo. In previous research, ICTER scientists used a multimode optical fiber, i.e. one that at its end emits several hundred non-repeating spatial patterns in the cross-section of the beam (so-called transverse modes) to obtain hundreds of OCT images which, when added together, reduce undesirable effects, including: speckle noise.

It turns out that the data set obtained during the STOC-T study can be processed in such a way as to reveal blood flow in the human retina. Classically, visualization of blood vessels requires at least two volumes. Subtracting them from each other allows you to determine voxels whose intensity changed during the measurement. From there images of blood vessels are generated. However, this approach requires very fast repetition times, which are not available in STOC-T. To solve this problem, ICTER scientists have developed a new method, called multiwavelength laser Doppler holography (MLDH), which allows the generation flow images from one volume, which may revolutionize the way of monitoring not only the microcirculation of the eye but also the condition of the entire body.

The research was carried out by Dawid Borycki, Egidijus Auksorius, Piotr Węgrzyn, Kamil Liżewski, Sławomir Tomczewski, Karol Karnowski and Maciej Wojtkowski from ICTER, and the results were published in the journal Biocybernetics and Biomedical Engineering in a paper titled “Multiwavelength laser Doppler holography (MLDH) in spatiotemporal optical coherence tomography (STOC-T)“.

What is microcirculation?

Microcirculation is the part of the cardiovascular system located between the arterial and venous systems. Microcirculation consists of vessels with a diameter of less than 150 μm, called capillaries. Arterial and venous elements are connected by “bridges” called metarterioles, from which some of the capillaries branch off. They contain the so-called precapillary sphincters, which regulate blood flow through the capillaries. The task of microcirculation is to deliver nutrients, exchange gases and metabolites, as well as regulate thermal and humoral processes.

Due to their unique accessibility, retinal arteries enable easy assessment of early vascular changes in vivo. Changes in retinal microcirculation mean global changes in the circulatory system, and therefore potential cardiac disorders. Additionally, pathological changes detected during the assessment of retinal microcirculation are one of the first signs of organ damage, which may precede, for example, proteinuria.

The retina is vascularized by two vascular systems: the choroid, which primarily supplies cones and rods; and the central retinal artery, mainly feeding the nervous tissue in the inner layers. The two systems differ in the amount of blood flow, which is much higher in the choroid than in the retinal vessels. Moreover, in the choroid, there are also significantly lower differences in blood oxygenation between arterial and venous vessels. When assessing retinal microcirculation, it is very important to precisely determine the measurement site.

Since the invention of the first ophthalmoscope in 1851 by Helmholtz, the fundus of the eye has been assessed. Even though this test was not very accurate, it allowed a small extent to assess the damage to the retinal microcirculation in the course of various diseases. In 1939, a 4-stage classification of hypertensive angiopathy and the relationship between subsequent stages of retinal vessels and an increased risk of a cardiovascular event were presented.

The study of retinal vessels has undergone a huge revolution, especially noticeable in the last 30 years. Currently, there are many tools available to assess the diameter of the vessel, the thickness of its wall, or the speed of blood flow based on the assessment of flowing erythrocytes or leukocytes. Another one just appeared.

Laser Doppler flowmetry and its modifications

One of the first non-invasive methods for assessing retinal microcirculation was laser Doppler flowmetry (LDF). In the early 1980s, it began to be more widely used in the study of flows in tissues and organs. This method uses a helium-neon laser with a wavelength of 632,8 nm.

Light is reflected from red blood cells moving in the vessels and from the solid, motionless surface of the skin. LDF results are presented as erythrocyte flow values expressed in arbitrary perfusion units (PU), as it is not possible to calibrate the measurement to physiological units. This is not an ideal method because it assumes that the examined area should remain completely still, otherwise, artifacts will be created that affect the result.

An extension of LDF is scanning laser Doppler flowmetry (SLDF), which allows not only the assessment of retinal microcirculation parameters but also the morphology of the arterioles themselves. In turn, bidirectional laser Doppler flowmetry (BLDV) involves a complete assessment of the flow velocity of erythrocytes in the retina.

The Doppler spectrum of the laser can be decomposed to obtain the velocity distribution of moving cells. Recently, a similar approach was used to visualize in vivo velocity-resolved images of human retinal blood flow. For this purpose, laser Doppler holography (LDH) was introduced and used, in which the shifted Doppler optical field, backscattered from the retina, is detected using a holographic or interferometric full-field optical system.

A new technique for imaging eye microcirculation

Both LDF and LDH use light with a fixed wavelength. For this reason, both techniques in their original implementation do not provide detailed information about blood flow encoded in the optical field, which changes over time due to movement. A very interesting approach is the combination of dual-beam Doppler with optical tomography (OCT), which enables imaging and assessment of retinal layers. This, in turn, allows for simultaneous assessment of blood velocity and blood flow in the retinal vessels.

ICTER scientists recently demonstrated that by spatially modulating the phase of incident light, the laser’s spatial coherence can be reduced. Using a technique called spatio-temporal optical coherence tomography (STOC-T), it is possible to obtain many different OCT images, which, when averaged, allow for the removal of noise and distortions. This approach allows for in vivo imaging of the choroid with high spatial resolution.

It turns out that the same dataset can also be used to extract dynamic images of blood flow in the human retina. Individual two-dimensional STOC-T images, after appropriate digital correction, can be used to increase time resolution and obtain flow images. Now, a team led by Dr. Dawid Borycki has developed and tested an innovative method using STOC-T tomography to improve the visualization of blood flow in the human retina in vivo using the so-called multiwavelength laser Doppler holography (MLDH). It combines laser flowmetry with holographic multiwavelength detection, allowing non-invasive visualization and quantification of blood flow in various layers of the retina. This is possible at high blood cell flow rates and with high resolution. This combined approach enables effective assessment of eye microcirculation and, ultimately, extrapolation of the obtained results to the entire circulatory system.

Our method enables the acquisition of two-dimensional images of blood flow en face from a stack of interferometric images with different wavelengths recorded in ~8.5 ms. This time is comparable to the time needed in the case of conventional optical OCT (assuming a scanning frequency of 100 kHz) to register a pair of repeated cross-sectional scans, from which a one-dimensional image of blood flow can be obtained – says Dr. Dawid Borycki from ICTER, one of the authors of the newly published work.

It is worth adding that the implementation of MLDH does not require any modification of the standard STOC-T tomography protocol because this method uses blood flow information from the same data set. Therefore, MLDH can be considered a valuable extension of STOC-T tomography, which gives a complete picture of what is happening in our retina.

Author: Scientific Editor Marcin Powęska.

Publication:

“Multiwavelength laser doppler holography (MLDH) in spatiotemporal optical coherence tomography (STOC-T)” authors: Dr. Dawid Borycki, Dr. Egidijus Auksorius, Piotr Węgrzyn, Dr. Eng. Kamil Liżewski, Dr. Eng. Sławomir Tomczewski, Dr. Karol Karnowski, Prof. Maciej Wojtkowski.

Photo description: Nature repeats patterns in the most unexpected yet ordinary places. Just like the intricate network of blood vessels in the human eye, the tree branches in a park create mesmerizing patterns. In this photo, Dawid, the first author of our latest paper on retinal blood vessel imaging, admires the natural beauty of the trees nearby.

Photos: Dr. Karol Karnowski.

24.06.2024

ICTER is changing into a Centre of Excellence! “Teaming for Excellence” competition within Horizon Europe resolved

aprzybylo-jozefowicz@ichf.edu.pl

The International Centre for Eye Research (ICTER) is one of the winners of the prestigious “Teaming for Excellence” competition within Horizon Europe (HE). The funding will allow the establishment of a Centre of Excellence. ICTER’s current mission – creating modern ophthalmic diagnostic tools and combating eye diseases affecting over 250 million people worldwide – will be implemented on an even larger scale.

The Institute of Physical Chemistry of the Polish Academy of Sciences (IChF), under the Translational Research and Innovation in Ophthalmology Vision – Centre of Excellence (TRIO-VI CoE), will elevate the existing sub-unit, the International Centre for Translational Eye Research (ICTER), to a Centre of Scientific Excellence. The new Centre for Scientific Excellence will operate in Warsaw and will be established in cooperation with strategic partners: the Institute of Ophthalmology from University College London and the Institut de la Vision at Sorbonne Université. ICTER CoE will continue the Centre’s mission to date, which is to advance new technologies leading to the development of new eye treatment methods in the fields of minimally invasive surgery, biochemical control of protein machinery, genetic repair of inherited diseases, and tissue engineering; and also, the advancement of optical imaging technology and state-of-the-art robotics to assist in eye surgery and drug delivery.

The project leader is Prof. Maciej Wojtkowski, who almost 25 years ago built the first laboratory system for examining the retina and changed the paradigm of eye imaging.

ICTER CoE is a milestone aimed at unleashing the full scientific and commercialization potential of ICTER and intensifying its impact on society, science, education, and health by accelerating the introduction of therapies and new solutions in eye protection. The project is a response to the growing global health problem associated with eye diseases – lack of early diagnosis for many diseases, lack of effective therapies slowing down the progression of the disease, and – most importantly – lack of effective methods of restoring vision. The ambitious goal of ICTER CoE is to contribute to overcoming each of the above barriers, improving patients’ quality of life, and reducing the burden on national healthcare systems.

The main scientific goal of the ICTER CoE is to thoroughly investigate the dynamics and plasticity of the human eye, which will translate into the development of new therapies and diagnostic tools. The most important challenges facing the ICTER CoE include:

• creating modern methods of optical eye imaging and diagnostic tools for ophthalmological practice;

• deciphering the mechanisms of eye diseases – both rare and common;

• developing gene therapies and alternative methods of treating existing vision disorders;

• educating and training young scientists and doctors;

• creating a virtual eye clinic;

Centres of Excellence are a way to develop the best research institutes

Creating new or improving existing Centres of Excellence is an effective instrument for including Polish scientific and research institutions in the world elite. In our country, there are currently 4 projects implemented as part of the “Teaming for Excellence” programme, and three more are now joining. In addition to ICTER, the Astronomical Center named after Nicolaus Copernicus Polish Academy of Sciences (Astrocent Plus) and Łukasiewicz Research Network – PORT Polish Center for Technology Development (P4Health). Poland is the only country that received funding for three projects in this prestigious competition.

Each project will last six years and will receive a grant from the Horizon Europe Framework Program in the amount of 15 million euros. The funds from the European Commission will be supplemented by the Foundation for Polish Science under the MAB FENG program (8 million euros) and by the Ministry of Science and Higher Education (7 million euros).

We congratulate the other winners of the competition and look forward to the success of the Centres of Excellence being created.

Author: Scientific Editor Marcin Powęska.

06.06.2024

The f-ORG technique will detect the smallest changes in human photoreceptors – new paper in Optics Letters

aprzybylo-jozefowicz@ichf.edu.pl

Photoreceptors are the fundamental component of the entire vision process. These specialized cells that absorb light and trigger a specific physiological reaction in the body come in two varieties: cones (responsible for sharp color vision) and rods (responsible for black-and-white vision in low light, e.g. after dark). To properly receive visual stimuli and perceive the world around us, we need both in large quantities.

Flicker electroretinography (f-ERG) is a valuable tool that has been used for decades to study the physiological functions of the retina. Scientists from the International Centre for Translational Eye Research – ICTER, operating within the Institute of Physical Chemistry, Polish Academy of Sciences, have made great progress in developing a technique that is its optical equivalent – flicker optoretinography (f-ORG) – which may be applied in diagnosing certain visual disorders.

A team of scientists consisting of Sławomir Tomczewski, Piotr Węgrzyn, Maciej Wojtkowski and Andrea Curatolo developed a method that allows for quick measurement of the frequency characteristics of photoreceptors’ response to flicker stimulation. The work “Chirped flicker optoretinography for in vivo characterization of human photoreceptors’ frequency response to light” was published in the journal Optics Letters.

Optoretinography is a step ahead of electroretinography

Many eye diseases have a complex structure-function relationship, and photoreceptor abnormalities often manifest themselves on various levels, including their appearance and operation. The time interval between functional deficits and the perceived pathological changes in the eye is variable and difficult to determine, and in ophthalmological practice, psychophysical methods (e.g. microperimetry, tests of sensitivity to flickering light) and electrophysical methods (e.g. electroretinography) are used.

Electroretinography (ERG) is an objective, slightly invasive method capable of measuring electrical potentials from retinal neurons in response to light stimulation. This technique has proven effective in the early detection of retinitis pigmentosa, X-linked retinal detachment, and diabetic retinopathy. In recent years, it has been shown that optical coherence tomography (OCT) allows the detection of small changes in the structure of the retina occurring in response to a light stimulus. This was the basis for developing optoretinography (ORG) – the optical and non-invasive equivalent of ERG.

Professor Maciej Wojtkowski’s team focuses on the use of flickering light to stimulate the retina (f-ORG method). In 2022, in their previous publication on f-ORG, the ICTER team showed that it is possible to perform f-ORG measurements in a largefrequency range (up to 50 Hz). In their latest work, the ICTER research team proposed a new approach to f-ORG measurements allowing for quick determination of the frequency characteristics of photoreceptors.

“A flicker protocol with variable instantaneous frequency combined with appropriate light adaptation has two advantages. On the one hand, it enables rapid measurement of the frequency response characteristics of photoreceptors; on the other hand, it also allows you to shorten the time between measurements by avoiding several minutes of adaptation to darkness.” – says Dr. Sławomir Tomczewski from ICTER.

Important findings regarding f-ORG

In the standard f-ORG approach, obtaining a full frequency response of the human eye’s photoreceptors to flicker requires a large number of measurements at separate stimulus frequencies and time-consuming data processing for each of these sets.

Implementing variable frequency flicker into f-ORG significantly decreases the number of measurements needed to characterize the frequency response of photoreceptors, drastically reducing the time required to conduct experiments and analyze data. ICTER scientists have shown that there are no significant differences between results obtained using this new, fast approach and a separatefrequency flicker ORG.

Taking into account the limited number of objects and measurements, the research carried out is preliminary and requires further development. Work is currently underway to explain the mechanism of the phenomenon used in ORG and its relationship with the vision process. Ultimately, the new tool developed at ICTER may deliver a new frequency response-based biomarker for early detection of retinal diseases and therapy monitoring.

Author of the press note: Marcin Powęska.

ICTER at the Ursynów Science Festival in Warsaw on May 23 – invitation to optical and eye model design workshops

aprzybylo-jozefowicz@ichf.edu.pl

We kindly invite the public to visit our stands and participate in the workshops that we have prepared for young people and adults at the Ursynów Science Festival in Warsaw this Thursday. Please see below for details.

📅 Date: Thursday, May 23, 2024
🕒 Time: 12:00-18:00
📍 Location: Ursynów Cultural Center “Alternatywy”, 9 Indira Gandhi Street, Warsaw, Poland
🚇 Public transport by metro: M1, Imielin stop
🎫 Free admission, youth and adults welcome

𝗠𝗮𝗶𝗻 𝗵𝗮𝗹𝗹, first floor of Ursynów Cultural Center “Alternatywy”

𝗜𝘀𝗮𝗱𝗼𝗿𝗮 𝗜𝗜 Room:
Workshop – Designing the eye model
12:15-12:45 p.m.
13:00-13:30

Workshop – Optical illusions
14:00-14:30 hrs.
14:45-15:15 hrs

𝗠𝗮𝘁𝗲𝗷𝗸𝗼 Room:
Optical workshop
17:00-17:30

𝗣𝗮𝗿𝗸𝗶𝗻𝗴 at Ursynów Cultural Center “Alternatywy”

Stand/Workshop:
Sight – the most important of the senses:

Visual acuity test, vision test
Poster on retinal diseases and OCT method
Information on research being developed at ICTER
Stereoscopic and color vision

The idea of the festival is to popularize science among young, but also older residents of Ursynów and Warsaw. The festival is organized by LXIII Lajos Kossuth High School in Warsaw together with the Ursynów District of the City of Warsaw.

More information and schedule of the event: https://ursynow.um.warszawa.pl/-/ursynowski-festiwal-nauki-3.

We look forward to welcoming the public to this activity.