Category: Image-guided Devices for Ophthalmic Care

17.12.2024

All fiber imaging probes

Dr. Karnowski developed expertise in fiber imaging probes during his postdoctoral research at the University of Western Australia. He continued this line of research through the NAWA Polish Returns project, which was integrated into the broader ICTER research initiatives.

Our team proposed an innovative design for imaging probes that strategically combines the advantages of previous probe technologies. These GRIN-Ball-lens probes (GBLP) demonstrate superior performance, particularly in terms of working distance, when compared to traditional GRIN-fiber probes (GFP) and ball-lens probes (BLP). A key breakthrough of this design is the ability to fabricate probes that are at least twice smaller in diameter without compromising optical performance.

Through meticulous research and development, we have cultivated expertise in probe fabrication that offers unprecedented flexibility. This includes creating probes with varying ball lens sizes and exploring different ball lens materials with distinct refractive indices. This versatility in probe design opens up a wide range of potential applications across multiple research domains.

The adaptability of our GRIN-Ball-lens probes suggests promising future investigations in fields such as:

  • Biomedical imaging
  • Microscopy
  • Endoscopic technologies
  • Minimally invasive diagnostic techniques

We are particularly excited about exploring these potential applications in the near future, anticipating that our novel probe design could significantly advance imaging capabilities in various scientific and medical contexts.

Text: Karol Karnowski, PhD, Acting IDoc Leader

Project team:

Karol Karnowski

Related funding: NAWA – Polish Returns, NCN – Miniatura.

References:

  1.  K. Karnowski, G. Untracht, M. Hackmann, O. Cetinkaya, D Sampson, “Superior Imaging Performance of All-Fiber, Two-Focusing-Element Microendoscopes,” IEEE Photonics Journal, 14 (5), 1-10 (2022)
  2. G. Untracht, K. Karnowski D. D. Sampson, “Imaging the small with the small: Prospects for photonics in “micro-endomicroscopy for minimally invasive cellular-resolution bioimaging,” APL Photonics, 6 (6), pp. 060901, (2021)
  3. M. J. Hackmann, A. Cairncross, J. G. Elliot, S. Mulrennan, K. Nilsen, B. R. Thompson, Q. Li, K. Karnowski, D. D. Sampson, R. A. McLaughlin, B. Cense, A. L. James, P. B. Noble, “Quantification of smooth muscle in human airways by polarization-sensitive optical coherence tomography requires correction for perichondrium,” American Journal of Physiology-Lung Cellular and Molecular Physiology, 326:3, L393-L408 (2024)
17.12.2024

Anterior segment structural and functional imaging

The anterior chamber of the eye plays a critical role in our visual mechanism, serving dual purposes of protection and optical functionality. This vital anatomical region acts not only as a protective barrier but also as a crucial optical pathway that focuses light onto the retina, enabling our visual perception of the world.

Our comprehensive research project is dedicated to developing advanced imaging methodologies for examining the structure and function of the anterior eye chamber, leveraging cutting-edge Fourier domain Optical Coherence Tomography (OCT) techniques. Our approach transcends traditional imaging methods based solely on light scattering, exploring innovative systems capable of capturing complex physiological characteristics including polarization and mechanical properties of ocular tissues.

The primary objective of our research is to develop diagnostic technologies with significant potential for early detection of anterior segment disorders and identifying retinal conditions that manifest through anterior segment changes, such as glaucoma. A notable sub-project involved designing a clinical system for multi-spot measurements of corneal deformation induced by air pulses. Through collaborative research with an ophthalmology clinic in Bydgoszcz, we conducted an extensive study involving nearly 100 patients, utilizing detailed quantitative analyses to identify and characterize corneal deformation parameters that could serve as potential biomarkers for keratoconus.

Text: Karol Karnowski, PhD, Acting IDoc Leader

Project team:

Karol Karnowski

Jadwiga Milkiewicz

Piotr Nalewajko

Related financing: IMCUSTOMEYE, IRAP (MAB) by FNP

References:

1. D. Alonso-Caneiro, K. Karnowski, B. Kaluzny, A. Kowalczyk, and M. Wojtkowski, “Assessment of corneal dynamics with high-speed swept source Optical Coherence Tomography combined with an air puff system”, Optics Express, Vol. 19, Issue 15, pp. 14188-14199 (2011)

2. S. Marcos, C. Dorronsoro, K. Karnowski, M. Wojtkowski, „Corneal biomechanics From Theory to Practice: OCT with air puff stimulus”, Kugler Publications 2016, edited by C.J. Roberts, J. Liu

3. K. Karnowski, E. Maczynska, M. Nowakowski, B. Kaluzny, I. Grulkowski, M. Wojtkowski, “Impact of diurnal IOP variations on the dynamic corneal hysteresis measured with air-puff swept-source OCT”, Photonics Letters of Poland, (2018)

4. E. Maczynska, K. Karnowski, K. Szulzycki, M. Malinowska, H. Dolezyczek, A. Cichanski, M. Wojtkowski, B. Kaluzny and I. Grulkowski, “Assessment of the influence of viscoelasticity of cornea in animal ex vivo model using air-puff optical coherence tomography and corneal hysteresis”, J Biophotonics, 2019; 12:e201800154 (2019)

5. A. Curatolo, J. S. Birkenfeld, E. Martinez-Enriquez, J. A. Germann, G. Muralidharan, J. Palací, D. Pascual, A. Eliasy, A. Abass, J. Solarski, K. Karnowski, Maciej Wojtkowski, Ahmed Elsheikh, and Susana Marcos, “Multi-meridian corneal imaging of air-puff induced deformation for improved detection of biomechanical abnormalities,” Biomed. Opt. Express 11, 6337-6355 (2020).

16.12.2024

Ultrahigh resolution OCT

Some applications require finer imaging resolution. In optical coherence tomography (OCT), the transversal resolution is determined by imaging optics (often with working distance limitations), while axial resolution depends on the effective bandwidth of the light source. We developed a dual spectrometer spectral OCT system working with a broadband femtosecond laser as a source. The system provides a voxel resolution of approximately 2 micrometers.

We utilize the system for various applications, ranging from ex vivo imaging of biological samples (e.g., cornea, bladder tissue, mouse brain) to bioprinted materials (such as porous materials or muscles). In the latter application, we collaborate with Professor Marco Constantini from IPC PAS, who is always impressed with the technology’s capabilities.

More recently, we have begun developing elastography measurements with our system. The sample is compressed (at levels not visible in structural images) between measurements, and through analysis of differential phase information, we can provide contrast that depends on tissue mechanical properties. Since our dual spectrometer system also offers polarization contrast, we aim to investigate in the future whether these two types of contrasts are equivalent or complementary to each other.

Text: Karol Karnowski, PhD, Acting IDoc Leader

Project team:

Karol Karnowski

Piotr Kasprzycki

Patricio Espinoza

Wiktor Kulesza

Related funding: NAWA – Polish Returns, FNP – IRAP (MAB)

References:

  1.  M. Marcotulli, M. C. Tirelli, M. Volpi, J. Jaroszewicz, C. Scognamiglio, P. Kasprzycki, K. Karnowski, W. Święszkowski, G. Ruocco, M. Costantini, G. Cidonio, A. Barbetta, Microfluidic 3D Printing of Emulsion Ink for Engineering Porous Functionally Graded Materials. Adv. Mater. Technol. 2023, 8, 2201244
16.12.2024

Scanning OCT system for animal model study

Our collaborative research with ICTER focuses on advancing vision restoration therapies and fundamental investigations of retinal function using animal models. The team has already established a sophisticated Full-field Optical Coherence Tomography (FF-OCT) system specifically designed for mouse model imaging, capable of capturing both structural and functional retinal characteristics with exceptional precision.

To support the critical retinal injection procedures essential for therapeutic interventions, we are developing an advanced 1060 nm swept-source OCT system. This innovative imaging platform will serve multiple crucial functions, primarily providing real-time image guidance for automated eye injections. Beyond its primary injection support role, the system offers additional versatility by functioning as a comprehensive preview and eye alignment mechanism for our Full-field OCT research studies.

The 1060 nm wavelength was carefully selected to optimize imaging penetration and resolution, ensuring clear visualization of delicate retinal structures during complex therapeutic interventions. By integrating precise image guidance directly into the injection process, we aim to enhance the accuracy, safety, and potential effectiveness of emerging vision restoration techniques.

Text: Karol Karnowski, PhD, Acting IDoc Leader

Project team:

Karol Karnowski

Wiktor Kulesza

Jadwiga Milkiewicz

Piotr Nalewajko

Project in collaboration with other ICTER’s POB and OBi groups.

Related funding: IRAP (MAB) FENG by FNP

Reference:

  1. 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, and Andrea Curatolo “In vivo volumetric analysis of retinal vascular hemodynamics in mice with spatio-temporal optical coherence tomography,” Neurophotonics 11(4), 045003 (8 October 2024). https://doi.org/10.1117/1.NPh.11.4.045003
16.12.2024

Surgery guidance and therapy administration

In this project, we address two primary challenges in ophthalmic surgeries: enhancing the accuracy and precision of surgical procedures and developing targeted drug and therapy administration methods for specific eye regions. To achieve these goals, we have developed an integrated image-guided and robotic-aided ocular microscopy platform that leverages Optical Coherence Tomography (OCT) image-guidance to improve surgical accuracy.

Our approach employs a dual cross-scan technique, with one scan recorded along the tool and the other across to the tool’s tip. This method facilitates real-time previews of the surgical area, providing depth information that are more interpretable than commonly used 3D visualizations. The 2D imaging approach offers additional advantages, being less computationally demanding and presenting potential for future cost-effective solutions.

The robotic arm, with a surgical tool mounted at the wrist, serves as a critical component of our system. It addresses several key aspects of ophthalmic surgeries: mitigating physiological tremors, supporting both surgeon assistance and fully automated operations, and providing instantaneous information about the tool’s tip position. This enables real-time locking of the OCT dual cross-scan pattern to the surgical tool position.

We are actively exploring various navigation information sources, including image-based methods from microscopes and OCT, as well as non-image-based approaches. Currently, our research focuses on developing novel retinal injection tools aimed at improving the effectiveness of vision restoration treatments.

Text: Karol Karnowski, PhD, Acting IDoc Leader

Project team:

Karol Karnowski

Krzysztof Gromada

Piotr Nalewajko

Adam Kurek

Tomasz Gawroński

Andrea Curatolo

Project in collaboration with other ICTER groups.

Related funding: IRAP (MAB) and IRAP (MAB) FENG – FNP

References:

1. Karol M. Karnowski, K. Gromada, T. Piesio, P. Ciąćka, A. Kurek, A. Curatolo „Real-Time OCT Cross-Section Display via Robotic Arm-Guided Surgical Tool,”, The Optica Biophotonics Congress: Biomedical Optic, Fort Lauderdale, USA, 09.04.2024, oral presentation

2. K. Karnowski, K. Gromada, T. Piesio, P. Ciąćka, A. Kurek, A. Curatolo, „Ophthalmic intraoperative OCT system with robotic arm-based tracking of surgical tools,” Photonics West, San Francisco, USA, 28.01.2024, oral presentation

3. K. Karnowski, K. Gromada, T. Piesio, P. Ciąćka, A. Kurek, A. Curatolo, „Robotic arm-based surgical tool tracking for real-time display of intraoperative OCT cross-sections at the surgical tool tip,” Microsimposium of the IPC PAS, 10.01.2024, oral presentation

4. K. Karnowski, K. Gromada, T. Piesio, P. Ciąćka, A. Kurek, A. Curatolo “Robotic arm-based surgical tool tracking for real-time display of intraoperative OCT cross-sections at the surgical tool tip,” The IRAP — Fostering Excellence and Innovation Conference, 12.10.2023, poster

5. K. Karnowski, K. Gromada, T. Piesio, P. Ciąćka, A. Kurek, A. Curatolo “Robotic arm-based surgical tool tracking for real-time display of intraoperative OCT cross-sections at the surgical tool tip,” Conference on Recent Advances in Translational Eye Research, 07.09.2023, poster

6. Karol Karnowski, “On imaging of structure and function

of the human cornea,” Conference on Recent Advances in Translational Eye Research, 08.09.2023, oral presentation

7. Karol Karnowski, Piotr Ciąćka, Andrea Curatolo, „Intraoperative ophthalmic OCT system tracking surgical tools at 200 Hz”, Photonics West, San Francisco, USA, 30.01.2023, oral presentation

31.10.2023

IDoc Group achievements in 3 years perspective

One of the primary initiatives within the IDoc Group focuses on the development of safer and more effective tools for eye surgery. This endeavor posed a distinct challenge for us, as it fell outside our traditional areas of expertise. Nevertheless, it is indeed a remarkable achievement that we have managed to assemble a team that, in under three years, has successfully amalgamated diverse expertise and advanced the project to its current stage. Our journey was marked by a gradual accumulation of knowledge and experience, ultimately culminating in the integration of all the components.

We are now pleased to inform you of the initial experiments where a robotic manipulator has been deployed to enhance manual ophthalmic surgical procedures. These innovations are complemented by the integration of Optical Coherence Tomography (OCT) images, meticulously aligned with the surgical tools’ tip precise position.

Another project the IDoc laboratory has been involved in goes to the very core of what the ICTER research centre aims to develop, that is methods and instrumentation to detect proper eye structure and function and their alteration in case of disease in an objective way. We did so in collaboration with the POB lab, by pioneering a technique called optoretinography. We are combining this with structural biology tools from the ISB lab for analysing the cellular machinery and its complex changes during the visual cycle in order to validate our hypotheses about what process the functional signal we measure originates from. To do so we are validating our functional imaging results with electrophysiology methods together with OBi laboratory. 

It has been a challenging and ambitious project so far, but its collaborative nature made it all the more rewarding when not long ago we observed, in a repeatable way and for the first time, reduced functional responses from mice subject to temporal inhibition of vision, compared to their response only a couple of hours before the pharmacological treatment. We were able to objectively show with optoretinography that when a central protein (from the PDE family) involved in the phototransduction is inhibited, the mouse retinal photoreceptors, when exposed to a short flash of light, do not elongate nearly as much as they do when the mouse eye is fully functional. Measuring such a small physical change on photoreceptor length in vivo, as we are talking of only few tens of nanometers, can have a huge impact on vision science and ophthalmology by providing an objective functional test of visual ability and photoreceptor health. This in turns can speed up therapy selection and efficacy studies.

We look forward to upcoming results in this field.

Authors:

Dr. Karol Karnowski & Dr. Andrea Curatolo

16.08.2023

A new paper by IDoc group researchers, international scientists and a spin-off company published in “Biomedical Optics Express”

Whole-eye optical coherence tomography (OCT) imaging is a promising tool in ocular biometry for cataract surgery planning, glaucoma diagnostics and myopia progression studies. However, conventional OCT systems are set up to perform either anterior or posterior eye segment scans and cannot easily switch between the two scan configurations without adding or exchanging optical components to account for the refraction of the eye’s optics. In this work, we present the design, optimization and experimental validation of a reconfigurable and low-cost optical beam scanner based on three electro-tunable lenses, capable of non-mechanically controlling the beam position, angle and focus. The proposed beam scanner reduces the complexity and cost of other whole-eye scanners and is well suited for 2-D ocular biometry. Additionally, with the added versatility of seamless scan reconfiguration, its use can be easily expanded to other ophthalmic applications and beyond.

Text: Dr. Andrea Curatolo – Principal Investigator in the IDoc group at ICTER.

Publication:

María Pilar Urizar, Enrique Gambra, Alberto de Castro, Álvaro de la Peña, Onur Cetinkaya, Susana Marcos, and Andrea Curatolo, “Optical beam scanner with reconfigurable non-mechanical control of beam position, angle, and focus for low-cost whole-eye OCT imaging,” Biomed. Opt. Express 14, 4468-4484 (2023)

Link: https://opg.optica.org/boe/fulltext.cfm?uri=boe-14-9-4468&id=535917

20.06.2023

Flicker Optoretinography (f-ORG)

For many years visual inspection of fundus photography [1] and examination of images acquired with optical coherence tomography (OCT) [2] have been used by ophthalmologists for eye disease diagnosis and monitoring therapy progress thanks to their ability to detect morphological changes in the retina. However, imaging the morphological manifestation of retinal diseases alone does not provide sufficient information on the loss of functionality of retinal neurons.

Over a decade ago, it was shown that optical coherence tomography (OCT) can detect small changes in the intensity of infrared light reflected from animal retinas in vitro [3,4] and in vivo [5] occurring after simultaneous stimulation with visible light. These findings laid the foundations for the development of optoretinography (ORG) [6], a method that measures photoreceptors’ response to light, thus giving a possibility for obtaining information about the functionality of retinal neurons.

At ICTER, we work on both ORG with a single pulse and flicker stimulation of the retina [7]. To acquire the ORG data, we use a Spatio-Temporal Optical Coherence-Tomography (STOC-T) [8] that records 3-D volumetric retina images within a few milliseconds each. After data processing, we extract the ORG signals by tracking subtle changes in the retina occurring between inner and outer photoreceptor junction (IS/OS) and the cone outer segment tips (COST). Fig. (a). presents the source of the ORG signal on an exemplary tomographic image of a human retina.

Exemplary results showing dark-adapted retinas’ responses to single pulse light stimulus are shown in Fig. (b) and (c). The (b) presents a spatially averaged ORG signal in function of time for uniformly distributed stimulus. The (c) shows the maximum amplitude of the ORG signal across imaged part of the retina surface in response to a projected pattern (letter E).

In the f-ORG experiments, which are the main subject of our works, a flickering light is used to stimulate the retina. First, such a study was performed by Schmoll et al. and measured photoreceptors’ response to a 5 Hz flicker [9], while, more recently, the group from Lübeck measured the response to different flicker frequencies (between 1 Hz and 6.6 Hz) [10].

Our f-ORG methodology allows for measuring retinas’ responses in a broader range of frequencies and mapping the photoreceptors’ response to a flickering light across the retinas’ surfaces. Exemplary results of measured frequency characteristics of the responses in four healthy human subjects are presented in Fig. (d). While an example of a spatially detected retina’s response to a DMD patterned stimulus with strips of light flickering at different frequencies is presented in Fig. (e).

Text: Sławomir Tomczewski, PhD, e-mail: stomczewski@ichf.edu.pl.

Team:

Sławomir Tomczewski, PhD

Piotr Węgrzyn, MSc

Dawid Borycki, PhD habil.

Egidijus Auksorius, PhD

Maciej Wielgo, MSc

Prof. Maciej Wojtkowski

Andrea Curatolo, PhD

Keywords: Optical Coherence Tomography, STOC-T, OCT, Optoretinography, Flicker ORG.

Publications:

  1. V. J. Srinivasan, M. Wojtkowski, J. G. Fujimoto, and J. S. Duker, “In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography,” Opt. Lett. 31, 2308 (2006).
  2. S. Tomczewski, P. Węgrzyn, D. Borycki, E. Auksorius, M. Wojtkowski, and A. Curatolo, “Light-adapted flicker optoretinograms captured with a spatio-temporal optical coherence-tomography (STOC-T) system,” Biomed. Opt. Express 13, 2186 (2022).
  3. E. Auksorius, D. Borycki, P. Wegrzyn, B. L. Sikorski, K. Lizewski, I. Zickiene, M. Rapolu, K. Adomavicius, S. Tomczewski, and M. Wojtkowski, “Spatio-Temporal Optical Coherence Tomography provides full thickness imaging of the chorioretinal complex,” iScience 25, 105513 (2022).