An accurate tumor delineation in neurosurgery is still a very challenging problem which we are addressing with optical coherence elastography (OCE). Because of the highly viscoelastic properties of brain tissue, we developed a new Air-Jet based tissue excitation source and evaluated the tissue stiffness with a 3.2 MHz swept-source Optical Coherence Tomography (OCT) system with a line scan rate of 2.45 kHz. The phase based displacement per pixel is measured and stiffness maps are calculated for brain tumor samples. However, certain features in the stiffness maps are seemingly not correlatable to the tissue features in the histological sections. Therefore, the structural properties of the histological sections e.g. fiber orientation, cell nuclei concentration and the “onion structure” with their rotational direction for meningioma were given greater consideration. The structural information are extracted from the histological sections via color deconvolution and structural tensor analysis. First results show that the stiffness transitions correlate with some structures of the histological sections. In summary, the Air-Jet OCE seems to be capable of measuring the stiffness as well as the structural composition of the sample. The long-term aim of this project is to establish OCE to support tumor delineation in the field of neurosurgery.
Microscope integrated real time 4D MHz-OCT operating at high scanning densities are capable of capturing additional visual contrast resolving depth and tissue. Even within a plain C-scan en-face projection structures are recognizable, that are not visible in a white light camera image. With advanced post processing methods, such as absorption coefficient mapping, and morphological classifiers more information is extracted. Presentation to the user in an intuitive way poses practical challenges that go beyond the implementation of a mere overlay display. We present our microscope integrated high speed 4D OCT imaging system, its clinical study use for in-vivo brain tissue imaging, and user feedback on the presentation methods we developed. In neurosurgery the de-facto standard contrast agents used for visibly highlighting brain tumors are Fluorescin and ALA, both of which come with certain caveats. As part of a clinical study we developed a microscope integrated real time 4D MHz-OCT system, operating as high scanning densities, with the intent of creating visual tissue contrast without the use of such contrast agents. Advanced post processing methods to classify tissue can be derived from static properties such as light absorption and morphology, and from dynamic properties, such as perfusion and elastography. However we also noticed that even in a plain C-scan en-face projection structures of interest could be recognized, that were not visible in the corresponding white light camera image. As part of a clinical study so far we collected data from 20 patients, used it for machine learning based classifiers and developing data presentation modalities for eventual use in a surgical environment. We present the challenges in implementing our microscope integrated high speed 4D OCT imaging system, a selection of the imaging data we collected so far during brain tumor surgeries, and the avenues toward presenting processed data to the surgeon.
Optical coherence elastography represents mechanical characteristics of biological tissue in so-called mechanical contrast maps. In addition to the standard intensity image, the contrast map illustrates numerous mechanical tissue features that would otherwise be undetectable. This is of great interest as abnormal physiological changes influence the mechanical behavior of the tissue. We demonstrate an advanced mechanical contrast approach based on the phase signal of our 3.2 MHz optical coherence tomography system. The robustness and performance of this contrast approach is evaluated and discussed based on preliminary results.
Neuro-surgery is challenged by the difficulties of determining brain tumor boundaries during excisions. Optical coherence tomography is investigated as an imaging modality for providing a viable contrast channel. Our MHz-OCT technology enables rapid volumetric imaging, suitable for surgical workflows. We present a surgical microscope integrated MHz-OCT imaging system, which is used for the collection of in-vivo images of human brains, with the purpose of being used in machine learning systems that shall be trained to identify and classify tumorous tissue.
The long-term aim of this project is to establish optical coherence elastography for tumor delineation in the field of neurosurgery. Because of the challenging highly viscoelastic properties of brain tissue, we developed a new Air-Jet based excitation source. With pulse duration of up to 700 ms and real time force measurement, this novel system allows the sample to reach a semi-steady state. In parallel with a 3.2 MHz swept-source optical coherence tomography system over 800 line scans are acquired over the whole sample excitation process. The phase data is extracted, unwrapped and the displacement per pixel is calculated. This system enables the measurement of mechanical properties like stiffness and Young’s modulus, similar to the standard indentation measurement. As well as viscoelastic properties i.e. relaxation times, in non-contact. The first processing step is to split the excitation progression into three main time ranges: the high dynamic, the steady state, and the viscoelastic range. In each range typical features of the displacement curve are extracted for every pixel in the B-scan. For those features, various mechanical parameters are calculated mainly, the stiffness and Young’s modulus and stored as feature matrices. The results are processed, visualized and overlaid with either the OCT intensity image or the histological sections. Strain stress curves are generated for some selected positions in the B-scan leading to a specific viscoelastic hysteresis. The feature matrices will be utilized as a fingerprint for each tissue, and are the first step for an AI based classification of the tissue.
In neurosurgical tumor operations on the central nervous system, intraoperative haptic information often assists for discrimination between healthy and diseased tissue. Thus, it can provide the neurosurgeon with additional intraoperative source of information during resection, next to the visual information by the light microscope, fluorescent dyes and neuronavigation. One approach to obtain elastic and viscoelastic tissue characteristics non-subjectively is phase-sensitive optical coherence elastography (OCE), which is based on the principle of optical coherence tomography (OCT). While phase-sensitive OCE offers significantly higher displacement sensitivity inside a sample than commonly used intensity-based correlation methods, it requires a reliable algorithm to recover the phase signal, which is mathematically restricted in the -π to π range. This problem of phase wrapping is especially critical for inter-frame phase analysis since the time intervals between two referenced voxels is long. Here, we demonstrate a one-dimensional unwrapping algorithm capable of removing up to 4π-ambiguities between two frames in the complex phase data obtained from a 3.2 MHz-OCT system. The high sampling rate allows us to resolve large sample displacements induced by a 200 ms air pulse and acquires pixel-precise detail information. The deformation behavior of the tissue can be monitored over the entire acquisition time, offering various subsequent mechanical analysis procedures. The reliability of the algorithm and imaging concept was initially evaluated using different brain tumor mimicking phantoms. Additionally, results from human ex vivo brain tumor samples are presented and correlated with histological findings supporting the robustness of the algorithm.
Optical coherence elastography (OCE) offers the possibility of obtaining the mechanical behavior of a tissue. When also using a non-contact mechanical excitation, it mimics palpation without interobserver variability. One of the most frequently used techniques is phase-sensitive OCE. Depending on the system, depth-resolved changes in the sub-µm to nm range can be detected and visualized volumetrically. Such an approach is used in this work to investigate and detect transitions between healthy and tumorous brain tissue as well as inhomogeneities in the tumor itself to assist the operating surgeon during tumor resection in the future. We present time-resolved, phase-sensitive OCE measurements on various ex vivo brain tumor samples using an ultra-fast 3.2 MHz swept-source optical coherence tomography (SS-OCT) system with a frame rate of 2.45 kHz. 4 mm line scans are acquired which, in combination with the high imaging speed, allow monitoring and investigation of the sample's behavior in response to the mechanical load. Therefore, an air-jet system applies a 200 ms short air pulse to the sample, whose non-contact property facilitates the possibility for future in vivo measurements. Since we can temporally resolve the response of the sample over the entire acquisition time, the mechanical properties are evaluated at different time points with depth resolution. This is done by unwrapping the phase data and performing subsequent assessment. Systematic ex vivo brain tumor measurements were conducted and visualized as distribution maps. The study outcomes are supported by histological analyses and examined in detail.
A precision air puff excitation system for MHz Optical Coherence Elastography in neurosurgery was developed. It enables non-contact soft-tissue excitation down to μN, with direct, noncontact force determination via gas flow measurement.
A 1.6 MHz Fourier-domain mode-locked (FDML) optical coherence tomography (OCT) was adapted to an OR-Microscope for clinical application in neurosurgery. 3D-volume scans at video rate are envisaged with approximately 50μm lateral and 20μm axial resolution
Tumor discrimination from healthy tissue is often performed by haptically probing tissue elasticity. We demonstrate non-contact elastography using air-puff excitation and tissue indentation measurement by phase-sensitive OCT with a 3.2 MHz FDML-laser
This paper describes the further investigation into the capabilities of the already established noncontact optoacoustic method to measure temperature profiles in cell cultures during controlled heating. The technic is scalable in spatial and temporal resolution. The intra and extracellular medium is heated by a thulium laser (wavelength 1.94 μm; power up to 25W). With a second Q-switched thulium laser (2.01 μm; up to 3 mJ) the sample medium temperature is simultaneously probed in the dish (20 mm diameter) via the photoacoustic effect. The pressure waves emitted due to the thermoelastic expansion of water are measured with an ultrasonic hydrophone at the side of the dish. The amplitudes of the waves are temperature dependent and are used to calculate the temperature/time course at 10 locations. Temperatures of up to 70°C with a heating power of up to 25 W after 5 s were measured, as well as lateral temperature profiles over time. Measurements in water show temperature fluctuations likely due to thermal convection and water circulation. Since measurements in agar do not show similar temperature fluctuations, this theory seems to be confirmed. In conclusion optoacoustics can serve as a real-time non-contact technique to determine temperature changes in cell and organ cultures as well as in vivo and during hyperthermia based therapies.
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