A. Naber, M. Reiß, and W. Nahm. Transit Time Measurement in Indicator Dilution Curves: Overcoming the Missing Ground Truth and Quantifying the Error. In Frontiers in Physiology, vol. 12, pp. 1-16, 2021
The vascular function of a vessel can be qualitatively and intraoperatively checked by recording the blood dynamics inside the vessel via fluorescence angiography (FA). Although FA is the state of the art in proving the existence of blood flow during interventions such as bypass surgery, it still lacks a quantitative blood flow measurement that could decrease the recurrence rate and postsurgical mortality. Previous approaches show that the measured flow has a significant deviation compared to the gold standard reference (ultrasonic flow meter). In order to systematically address the possible sources of error, we investigated the error in transit time measurement of an indicator. Obtaining in vivo indicator dilution curves with a known ground truth is complex and often not possible. Further, the error in transit time measurement should be quantified and reduced. To tackle both issues, we first computed many diverse indicator dilution curves using an in silico simulation of the indicator’s flow. Second, we post-processed these curves to mimic measured signals. Finally, we fitted mathematical models (parabola, gamma variate, local density random walk, and mono-exponential model) to re-continualize the obtained discrete indicator dilution curves and calculate the time delay of two analytical functions. This re-continualization showed an increase in the temporal accuracy up to a sub-sample accuracy. Thereby, the Local Density Random Walk (LDRW) model performed best using the cross-correlation of the first derivative of both indicator curves with a cutting of the data at 40% of the peak intensity. The error in frames depends on the noise level and is for a signal-to-noise ratio (SNR) of 20dB and a sampling rate of fs = 60 Hz at f−1 · 0.25(±0.18), so this error is smaller than the distance between two consecutive s samples. The accurate determination of the transit time and the quantification of the error allow the calculation of the error propagation onto the flow measurement. Both can assist surgeons as an intraoperative quality check and thereby reduce the recurrence rate and post-surgical mortality.
A. Naber, D. Berwanger, and W. Nahm. Geodesic Length Measurement in Medical Images: Effect of the Discretization by the Camera Chip and Quantitative Assessment of Error Reduction Methods. In Photonics, vol. 7(3) , pp. 1-16, 2020
Afterinterventionssuchasbypasssurgeriesthevascularfunctionischeckedqualitatively and remotely by observing the blood dynamics inside the vessel via Fluorescence Angiography. This state-of-the-art method has to be improved by introducing a quantitatively measured blood flow. Previous approaches show that the measured blood flow cannot be easily calibrated against a gold standard reference. In order to systematically address the possible sources of error, we investigated the error in geodesic length measurement caused by spatial discretization on the camera chip. We used an in-silico vessel segmentation model based on mathematical functions as a ground truth for the length of vessel-like anatomical structures in the continuous space. Discretization errors for the chosen models were determined in a typical magnitude of 6%. Since this length error would propagate to an unacceptable error in blood flow measurement, counteractions need to be developed. Therefore, different methods for the centerline extraction and spatial interpolation have been tested and compared against their performance in reducing the discretization error in length measurement by re-continualization. In conclusion, the discretization error is reduced by the re-continualization of the centerline to an acceptable range. The discretization error is dependent on the complexity of the centerline and this dependency is also reduced. Thereby the centerline extraction by erosion in combination with the piecewise Bézier curve fitting performs best by reducing the error to 2.7% with an acceptable computational time.
The vascular function after interventions as revascularization surgeries is checked intraoperatively and qualita- tively by observing the blood flow dynamic in the vessel via Indocyanine Green (ICG) Fluorescence Angiography. This state-of-the-art technique does not provide the surgeon with objective information whether the revascu- larization is sufficient and should be improved by obtaining a quantitative intraoperative optical blood flow measurement. Previous approaches using ICG Fluorescence Angiography show that the blood flow measure- ment does not match the reference and overestimates the flow. The experiments indicate that the amount of overestimation is linked to the vessels diameter. We have, in previous work, quantified the propagated error on the flow calculation resulting from the error in the measurement of the vessels diameter and length and realized that they cannot be accounted solely for this deviation. The influence of the transit time error is not revealed yet. We propose a model combining the penetration depth of diffusely reflected photons and the flow velocity profile to estimate the error in transit time measurement. The flow is assumed to be laminar. The photons path is obtained from a Monte Carlo simulation. This is used to determine the maximum penetration depth of each diffusely reflected photon and therefore state how the recorded signal is composed of the signals originating from different depths to check the hypothesis that the error is systematically linked to the vessels diameter. A simplified geometry is set as a homogeneous layer structure of vessel wall, blood and vessel wall. The total thickness ranges from 1 mm to 5 mm. The probability density of the depth distribution of the diffusely reflected photons and the parabolic flow profile are convolved to obtain a weighted average of the flow velocity, which is set into relation with the mean flow velocity. The results show a clear dependency of the error in transit time measurement on the vessels diameter which complies qualitatively with literature and confirms the hypothesis.
A. Naber, D. Berwanger, G. K. Steinberg, and W. Nahm. Spatial gradient based segmentation of vessels and quantitative measurement of the inner diameter and wall thickness from ICG fluorescence angiographies. In SPIE Photonics West, vol. 11229 1122916-2, 2020
During neurovascular surgery the vascular function can be checked intraoperatively and qualitatively by observing the blood dynamics inside the vessel via Indocyanine Green (ICG) Fluorescence Angiography. This state-of-the- art method provides the surgeon with valuable semi-quantitative information but needs to be improved towards a quantitative assessment of vascular volume flow. The precise measurement of volume flow rely on the assumption that both the inner geometry of the blood vessel and the blood flow velocity can be precisely obtained from Fluorescence Angiography. The correct reconstruction of the inner diameter of the vessel is essential in order to minimize the propagated error in the flow calculation. Although ICG binds specifically on blood plasma proteins the fluorescence light radiates also from outside the inner vessel volume due to multiple scattering in the vessel wall, causing a fading edge intensity contrast. A spatial gradient based segmentation method is proposed to reliably estimate the inner diameter of cerebral vessels from intraoperative Fluorescence Angiography images. As result the minimum of the second deviation of the intensity values perpendicular to the vessels edge was identified as the best feature to assess the inner diameter of artificial vessel phantoms. This method has been applied to cerebrovascular vessel images and the results, since no ground truth is available, comply with literature values.
A. Naber, L. Meyer-Hilberg, and W. Nahm. Design of a Flow Phantom for the Evaluation of Quantitative ICG Fluorescence Angiography. In Current Directions in Biomedical Engineering, vol. 5(1) , 2019
Fluorescence video angiography is used in neurosurgery to intraoperatively monitor the vascular func-tion, namely the blood flow. This is done by injecting the dye Indocyanine green (ICG) intravenously. After excitation by a near-infrared light source, the fluorescence signal is captured by a camera system. The recorded signal is used to qualitatively assess the vascular function during the intervention. This provides the surgeon with an immediate feedback of the quality of his surgery. Nevertheless, this qualitative assessment needs to be extended and a quantitative value should be calculated to assist the surgical staff. This step requires a standardized and validated test setup mimicking cerebral vessels for studies, such as measurement of the flow and flow profile. This includes the confirmation of the suita-bility of the investigation site in the phantom. Therefore, a flow phantom is designed according to the requirements and set up. The requirements include a variable diameter of the vessel mimicking tubes, variable flow range within the clinical relevant range, a handy and precise injection system with an ini-tial ICG concentration which minimizes quenching effects, a non-toxic and low cost blood analogue with similar viscosity as human blood and finally a last requirement which need more explanation. Re-al blood should not be used due to the contamination of the pump, so water is used as flow media. But the ICG is dissolved in a protein solution and should be surrounded by a protein solution to ensure mixing and diffusion into the same solution media, so the ICG should not get into touch with the flow media water. The investigation sites are given in the ranges which are confirmed to be suitable. The flow phantom provides a consistent testing environment and will be used to conduct studies analyzing the suitability of different methods to assess the flow by fluorescence imaging.
A. Naber, D. Berwanger, and W. Nahm. In Silico Modelling of Blood Vessel Segmentations for Estimation of Discretization Error in Spatial Measurement and its Impact on Quantitative Fluorescence Angiography. In 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 4787-4790, 2019
Today the vascular function after interventions as Bypass surgeries are checked qualitatively by observing the blood dynamics inside the vessel via Indocyanine Green (ICG) Fluorescence Angiography. This state-of-the-art should be upgraded and has to be improved and converted towards a quantitatively measured blood flow. Previous approaches show that the blood flow measured from fluorescence angiography cannot be easily calibrated to a gold standard reference. In order to systematically address the possible source of error we investigate as a first step the discretization error in a camera-based measurement of the vessel’s geometry. In order to generate an error-free ground truth, a vessel model has been developed based on mathematical functions. This database is then used to determine the error in discretizing the centerline of the structure and estimate its effects on the accuracy of the flow calculation. As result the model is implemented according to the conditions which are set up to ensure transferability on camera-based segmentations of vessels. In this paper the relative discretization error for estimating the centerline length of segmented vessels could be calculated in the range of 6.3%. This would reveal significant error propagated to the estimation of the blood flow value derived by camera-based angiography.
A. Naber, and W. Nahm. Bi - Domain Intraoperative Registration of Vessels. In Current Directions in Biomedical Engineering, vol. 4(1) , pp. 25-28, 2018
The segmentation and registration of structures are gaining importance due to the increasing demand of auto- mated image enhancement and understanding. Especially in medicine and life science, assistance systems could have a large impact on diagnosis, treatment and quality control. Dye driven procedures, such as uorescence imaging with Indocya- nine green (ICG), are nowadays indispensable because they enhance contrast, reveal structures and deliver the operator with important information. The contact free ICG angiography is providing the surgeon spatial and temporal information on blood ow w ithin a v essel. T he p rocessing o f t hose informa- tion is done manually or semi automated but is very helpful for the surgeon. Extending the degree of automatism, the amount of information processed and even augment or transfer it into another domain could deliver the operator useful support and improve surgical work ow. Using, analyzing and transferring those information from ICG-IR domain into the RGB domain is the focus of this project. We are introducing a vessel regis- tration method in the RGB domain driven by the spatial u- orescence behavior of the vessel in the ICG-IR domain. The method includes Superpixel based segmentation of the vessel in the ICG-IR domain, the spatial gradient based transfer and registration in the RGB domain and the continuous segmen- tation of the vessel in a RGB video. This paper show a proof of concept of the method. The results show an successful in- ter domain information transfer and registration of the vessel. Further tracking of the vessel over all frames is possible. Nev- ertheless limitations are revealed and discussed.
A. Naber, and W. Nahm. Video magnification for intraoperative assessment of vascular function. In Current Directions in Biomedical Engineering, vol. 3(2) , pp. 175-178, 2017
In neurovascular surgery the intraoperative fluorescence angiography has been proven to be a reliable contact-free optical imaging technique to visualize vascular blood-flow. This angiography is obtained by injecting a fluorescence dye e.g. indocyanine green and using an infrared camera system to visualize the fluorescence inside the vessel. Obviously this requires a medical approved dye and an additional camera setup and therefore generating risks and costs. Hence, the aim of our research is to develop a comparable technique for assessing the vascular function. This approach would not require dye nor an additional infrared camera setup. It is achieved by first preprocessing the video data of a camera that records only the visible spectrum and then filter it spatially as well as temporally. The prepared data is again processed to extract information about the vascular function and visualize it. This method would provide an option to compute and visualize the vascular function using the data recorded in the visible spectrum by the surgical microscopes. Given this contact-free optical imaging system, physiological information can be easily provided to the surgeon without an additional setup. In the case of comparable results with the state-of-the-art, this technique provides a straightforward optical intraoperative angiography. Further no drug approval is needed since no dye is injected.
M. Reiß, A. Naber, and W. Nahm. Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves. In Current Directions in Biomedical Engineering, vol. 6(3) , pp. 268-271, 2020
Transit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The tran- sit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt can- not be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measure- ments. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while be- ing accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over differ- ent cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measure- ments. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions re- garding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.
K. Sieler, A. Naber, and W. Nahm. An Evaluation of Image Feature Detectors Based on Spatial Density and Temporal Robustness in Microsurgical Image Processing. In Current Directions in Biomedical Engineering, vol. 5(1) , pp. 273-276, 2019
Optical image processing is part of many applications used for brain surgeries. Microscope camera, or patient movement, like brain-movement through the pulse or a change in the liquor, can cause the image processing to fail. One option to compensate movement is feature detection and spatial allocation. This allocation is based on image features. The frame wise matched features are used to calculate the transformation matrix. The goal of this project was to evaluate different feature detectors based on spatial density and temporal robustness to reveal the most appropriate feature. The feature detectors included corner-, and blob-detectors and were applied on nine videos. These videos were taken during brain surgery with surgical microscopes and include the RGB channels. The evaluation showed that each detector detected up to 10 features for nine frames. The feature detector KAZE resulted in being the best feature detector in both density and robustness.
T. Wirth, A. Naber, and W. Nahm. Combination of Color and Focus Segmentation for Medical Images with Low Depth-of-Field. In Current Directions in Biomedical Engineering, vol. 4(1) , pp. 345-349, 2018
Image segmentation plays an increasingly important role in image processing. It allows for various applications including the analysis of an image for automatic image understanding and the integration of complementary data. During vascular surgeries, the blood flow in the vessels has to be checked constantly, which could be facilitated by a segmentation of the affected vessels. The segmentation of medical images is still done manually, which depends on the surgeon’s experience and is time-consuming. As a result, there is a growing need for automatic image segmentation methods. We propose an unsupervised method to detect the regions of no interest (RONI) in intraoperative images with low depth-of-field (DOF). The proposed method is divided into three steps. First, a color segmentation using a clustering algorithm is performed. In a second step, we assume that the regions of interest (ROI) are in focus whereas the RONI are unfocused. This allows us to segment the image using an edge-based focus measure. Finally, we combine the focused edges with the color RONI to determine the final segmentation result. When tested on different intraoperative images of aneurysm clipping surgeries, the algorithm is able to segment most of the RONI not belonging to the pulsating vessel of interest. Surgical instruments like the metallic clips can also be excluded. Although the image data for the validation of the proposed method is limited to one intraoperative video, a proof of concept is demonstrated.
A miniaturized ceramic atmospheric plasma source for the utilization in life sciences has been developed. It is manufactured in LTCC-technology (low temperature cofired ceramic). The plasma generation is based on buried electrodes which lead to a Dielectric Barrier Discharge (DBD). The employed technology allows small feature sizes (electrode width 150 μm, barrier thickness 40μm etc.) as well as precision in the μm range, resulting in a very low power consumption of the system (approx. 5 W). Thus, the maximum temperature at the point of use can be kept below 40 °C. The flexibility of the manufacturing process (layer lamination, screen printing, patterning with picosecond laser etc.) offers additional features like robust fluidic structures (channels, chambers, gas distribution etc.) as well as the direct implementation of electronic components. The technology concept as well as the design of the ceramic parts and the handhold matched to the multi-well plate format is demonstrated. The plasma of the system can be tuned depending on the assembly of the system and the electric excitation. To prove the biocompatibility and the experimental compatibility with cell cultures (low temperature at the point of use), a method for temperature measurements on the bottom of a multi-well plate was developed. First results of the impact of the plasma source on cell cultures are presented. The effects occurring in the plasma, as well as their effects on the cell cultures (ozone formation, ultraviolet radiation etc.) are separately considered. Furthermore, the cell tolerability of the treatment with the micro-plasma source is investigated with L929 fibroblast cells.
A. Naber. Intraoperative, Quantitative, and Non-Contact Blood Volume Flow Measurement via Indocyanine Green Fluorescence Angiography. Karlsruher Instituts für Technologie (KIT). Dissertation. 2021
Patients suffering from a cerebrovascular disease, which causes the hypoperfusion of the brain, can undergo revascularization surgery as treatment. It is often performed as an open surgery and its goal is to restore the vascular function, in particular the flow of blood. There- fore, an anastomosis (connection of arteries) is installed to augment flow into a hypoperfused area. Complications occur in approximately 10% of the cases, partly related to an insufficient flow augmentation. Hence, the blood flow should be checked intraoperatively to assess the intervention’s quality and intervene rapidly to prevent a negative patient outcome. The current state-of-the-art measurement device is the ultrasonic transit time flow probe. It provides a quantitative flow value but needs to be placed around the vessel. This is cumber- some and holds the risk of contamination, vessel compromise, and rupture. An alternative method is the indocyanine green (ICG) fluorescence angiography (FA), which is a camera-based method. It is the state-of-the-art method in the high resolution anatomical visualization and it is able to provide the surgeon with a qualitative functional imaging of vessels in the field of view. Approaches to quantify the blood flow via ICG FA failed to obtain trustworthy flow values so far. This thesis analyzes and improves the capability of ICG FA to provide quantitative values by 1. clarifying on how accurate the measurement can be. 2. proposing methods to improve the accuracy. 3. deriving the existence of a systemic error. 4. proposing a method to compensate for the systemic error. 5. providing an end-to-end workflow from video data input to flow value output. 6. validating the proposed methods and the workflow in an ex vivo and in vivo study. The proposed measurement in this thesis is based on the systemic mean transit time theorem for single input and single output systems. To calculate the flow, the transit time of a bolus for a certain distance and the cross sectional area of the vessel need to be obtained. Methods were developed to obtain the blood volume flow, and to identify and quantify the sources of errors in this measurement. The statistical errors in measuring the transit distance and transit time of the ICG bolus as well as the cross sectional area of the vessel are often neglected in research and thus were quantified in this thesis using in silico models. It revealed that the error is too large and requires methods to reduce it.....