Kolff program: Restoring organ function by means of regenerative medicine (REGENERATE), Bioadhesion, biocompatibility and infection (BIOBI)

Due to copyright restrictions, the access to the full text of this article is only available via subscription.In this paper, real-time needle tip tracking method using 2D ultrasound (US) images for robotic biopsies is presented. In this method, the needle tip is estimated with the Gabor filter based image processing algorithm, and the estimation noise is reduced with the Kalman filter. This paper also presents the needle tip tracking simulation to test accuracy of the Kalman filter under position misalignments and tissue deformations. In order to execute proposed method in real-time, the bin packing method is used and the processing time is reduced by 56%, without a GPU. The proposed method was tested in four different phantoms and water medium. The accuracy of the needle tip estimation was measured with optical tracking system, and root mean square error (RMS) of the tip position is found to be 1.17 mm. The experiments showed that the algorithm could track the needle tip in real-time.TÜBİTA

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Due to copyright restrictions, the access to the full text of this article is only available via subscription.Ultrasound (US) is one the most commonly used medical imaging techniques in percutaneous needle procedures. However, US images are inherently noisy and contain excessive number of artifacts. Hence, it is not easy to track the needle tip in the US images during the needle insertions. At this point, image based visual tracking techniques can be used for needle tip tracking. This paper presents a method for visual tracking of biopsy needles in 2D US images using sum of squared differences and sum of conditional variances. Second order Gauss-Newton optimization is used to decrease processing time and make the tracking more robust. The needle template images used in the method are updated with a strategy to prevent needle loss and detection failures during tracking. The paper also explains how to identify needle losses during tracking and how to recover the needle position without using a needle localization algorithm. We demonstrate the precision of the visual needle tip tracking method with experiments under challenging tracking conditions.TÜBİTA

Multicolor fluorescence microscopy is a powerful technique to fully visualize many biological phenomena by acquiring images from different spectrum channels. This study expands the scope of multicolor fluorescence microscopy by serial imaging of polystyrene micro-beads as surrogates for drug carriers, cancer spheroids formed using HeLa cells, and microfluidic channels. Three fluorophores with different spectral characteristics are utilized to perform multicolor microscopy. According to the spectrum analysis of the fluorophores, a multicolor widefield fluorescence microscope is developed. Spectral crosstalk is corrected by exciting the fluorophores in a round-robin manner and synchronous emitted light collection. To report the performance of the multicolor microscopy, a simplified 3D tumor model is created by placing beads and spheroids inside a channel filled with the cell culture medium is imaged at varying exposure times. As a representative case and a method for bio-hybrid drug carrier fabrication, a spheroid surface is coated with beads in a channel utilizing electrostatic forces under the guidance of multicolor microscopy. Our experiments show that multicolor fluorescence microscopy enables crosstalk-free and spectrally-different individual image acquisition of beads, spheroids, and channels with the minimum exposure time of 5.5 ms. The imaging technique has the potential to monitor drug carrier transportation to cancer cells in real-time.

In order to fabricate functional organoids and microtissues, a high cell density is generally required. As such, the placement of cell suspensions in molds or microwells to allow for cell concentration by sedimentation is the current standard for the production of organoids and microtissues. Even though molds offer some level of control over the shape of the resulting microtissue, this control is limited as microtissues tend to compact towards a sphere after sedimentation of the cells. 3D bioprinting on the other hand offers complete control over the shape of the resulting structure. Even though the printing of dense cell suspensions in the ink has been reported, extruding dense cellular suspensions is challenging and generally results in high shear stresses on the cells and a poor shape fidelity of the print. As such, additional materials such as hydrogels, are added in the bioink to limit shear stresses, and to improve shape fidelity and resolution. The maximum cell concentration that can be incorporated in a hydrogel-based ink before the ink’s rheological properties are compromised, is significantly lower than the concentration in a tissue equivalent. Additionally, the hydrogel components often interfere with cellular self-assembly processes. To circumvent these limitations, we report a simple and inexpensive xanthan bath based embedded printing method to 3D print dense functional linear tissues using dilute particle suspensions consisting of cells, spheroids, hydrogel beads, or combinations thereof. Using this method, we demonstrated the self-organization of functional cardiac tissue fibers with a layer of epicardial cells surrounding a body of cardiomyocytes.

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Percutaneous needle procedures are mostly carried out with the guidance of 2D ultrasound (US) imaging. US images are inherently noisy and their resolutions are low. Hence, target tracking can be challenging. Image based tracking methods can be used to track the needle and the target. This paper proposes visual tracking of multiple moving points, such as biopsy needles and targets, in 2D US images using normalized cross correlation and mutual information similarity functions. Both moving and deformable targets can be tracked. An affine motion model is used for small and moving target tracking and a thin plate spline motion model is used for deformable target tracking. During the tracking, needle and target template images are updated with a template update strategy. Also, tracking outputs of normalized cross correlation and mutual information are fused using the Kalman filter to reduce the tracking error. During the experiments, needle is inserted using a needle insertion robot. 2D US probe is attached to a robotic arm's end effector to servo the probe along the needle insertion path. Proposed needle and target tracking methods were tested with phantoms. Accuracies of the needle tip and moving target tracking methods were measured using an optical tracking system. Experimental results showed that the proposed tracking method could be used to simultaneously track the needle tip and the targets in real-time in 2D US guided percutaneous needle procedures.TÜBİTA

Minimally invasive surgery can benefit greatly from utilizing micro-agents. These miniaturized agents need to be clearly visualized and precisely controlled to ensure the success of the surgery. Since medical imaging modalities suffer from low acquisition rate, multi-rate sampling methods can be used to estimate the intersample states of micro-agents. Hence, the sampling rate of the controller can be virtually increased even if the position data is acquired using a slow medical imaging modality. This study presents multi-rate Luenberger and Kalman state estimators for visual tracking of microagents. The micro-agents are tracked using sum of squared differences and normalized cross correlation based visual tracking. Further, the outputs of the two methods are merged to minimize the tracking error and prevent tracking failures. During the experiments, the micro-agents with different geometrical shapes and sizes are imaged using a 2D ultrasound machine and a microscope, and manipulated using electromagnetic coils. The multi-rate state estimation accuracy is measured using a high speed camera. The precision of the tracking and multi-rate state estimation are verified experimentally under challenging conditions. For this purpose, an elliptical shaped magnetic micro-agent with a length of 48 pixels is used. Maximum absolute error in x and y axes are 2.273 and 2.432 pixels for an 8-fold increase of the sample rate (25 frames per second), respectively. During the experiments, it was observed that the micro-agents could be tracked more reliably using normalized cross correlation based visual tracking and intersample states could be estimated more accurately using Kalman state estimator. Experimental results show that the proposed method could be used to track micro-agents in medical imaging modalities and estimate system states at intermediate time instants in real-time.