Stress-Induced Sensitization of Insula Activation Predicts Alcohol Craving and Alcohol Use in Alcohol Use Disorder.

BACKGROUND: Stress and alcohol cues trigger alcohol consumption and relapse in alcohol use disorder. However, the neurobiological processes underlying their interaction are not well understood. Thus, we conducted a randomized, controlled neuroimaging study to investigate the effects of psychosocial stress on neural cue reactivity and addictive behaviors. METHODS: Neural alcohol cue reactivity was assessed in 91 individuals with alcohol use disorder using a validated functional magnetic resonance imaging (fMRI) task. Activation patterns were measured twice, at baseline and during a second fMRI session, prior to which participants were assigned to psychosocial stress (experimental condition) or a matched control condition or physical exercise (control conditions). Together with fMRI data, alcohol craving and cortisol levels were assessed, and alcohol use data were collected during a 12-month follow-up. Analyses tested the effects of psychosocial stress on neural cue reactivity and associations with cortisol levels, craving, and alcohol use. RESULTS: Compared with both control conditions, psychosocial stress elicited higher alcohol cue-induced activation in the left anterior insula (familywise error-corrected p < .05) and a stress- and cue-specific dynamic increase in insula activation over time (F22,968 = 2.143, p = .007), which was predicted by higher cortisol levels during the experimental intervention (r = 0.310, false discovery rate-corrected p = .016). Cue-induced insula activation was positively correlated with alcohol craving during fMRI (r = 0.262, false discovery rate-corrected p = .032) and alcohol use during follow-up (r = 0.218, false discovery rate-corrected p = .046). CONCLUSIONS: Results indicate a stress-induced sensitization of cue-induced activation in the left insula as a neurobiological correlate of the effects of psychosocial stress on alcohol craving and alcohol use in alcohol use disorder, which likely reflects changes in salience attribution and goal-directed behavior.

Robotic-assisted versus manual Uro Dyna-CT-guided puncture in an ex-vivo kidney phantom.

INTRODUCTION AND OBJECTIVES: Challenging percutaneous renal punctures to gain access to the kidney requiring guidance by cross-sectional imaging. To test the feasibility of robotic-assisted CT-guided punctures (RP) and compare them with manual laser-guided punctures (MP) with Uro Dyna-CT (Siemens Healthcare Solutions, Erlangen, Germany). MATERIAL AND METHODS: The silicon kidney phantom contained target lesions of three sizes. RP were performed using a robotic assistance system (guidoo, BEC GmbH, Pfullingen, Germany) with a robotic arm (LBR med R800, KUKA AG, Augsburg, Germany) and a navigation software with a cone-beam-CT Artis zeego (Siemens Healthcare GmbH, Erlangen, Germany). MP were performed using the syngo iGuide Uro-Dyna Artis Zee Ceiling CT (Siemens Healthcare Solutions). Three urologists with varying experience performed 20 punctures each. Success rate, puncture accuracy, puncture planning time (PPT), and needle placement time (NPT) were measured and compared with ANOVA and Chi-Square Test. RESULTS: One hundred eighteen punctures with a success rate of 100% for RP and 78% for MP were included. Puncture accuracy was significantly higher for RP. PPT (RP: 238 ± 90s, MP: 104 ± 21s) and NPT (RP: 128 ± 40s, MP: 81 ± 18s) were significantly longer for RP. The outcome variables did not differ significantly with regard to levels of investigators' experience. CONCLUSION: The accuracy of RP was superior to that of MP. This study paves the way for first in-human application of this robotic puncture system.

[Development and evaluation of ultrasound navigation for free-hand biopsies of small masses in the head and neck area]. / Entwicklung und Evaluation einer Ultraschallnavigation für Freihandbiopsien kleiner Raumforderungen im Kopf-Hals-Bereich.

BACKGROUND: Ultrasound is an important imaging method in the head and neck area. It is readily available, dynamic, inexpensive, and does not involve radiation exposure. Interventions in the complex head and neck anatomy require good orientation, which is supported by navigation systems. OBJECTIVE: This work aimed to develop a new ultrasound-controlled navigation system for taking biopsies of small target structures in the head and neck region. METHODS: A neck phantom with sonographically detectable masses (size: 8-10 mm) was constructed. These were automatically segmented using a ResNet-50-based deep neural network. The ultrasound scanner was equipped with an individually manufactured tracking tool. RESULTS: The positions of the ultrasound device, the masses, and a puncture needle were recorded in the world coordinate system. In 8 out of 10 cases, an 8­mm mass was hit. In a special evaluation phantom, the average deviation was calculated to be 2.5 mm. The tracked biopsy needle is aligned and navigated to the masses by auditory feedback. CONCLUSION: Outstanding advantages compared to conventional navigation systems include renunciation of preoperative tomographic imaging, automatic three-dimensional real-time registration that considers intraoperative tissue displacements, maintenance of the surgeon's optical axis at the surgical site without having to look at a navigation monitor, and working freely with both hands without holding the ultrasound scanner during biopsy taking. The described functional model can also be used in open head and neck surgery.

A semi-automated robotic system for percutaneous interventions.

PURPOSE: A robotic assistive device is developed for needle-based percutaneous interventions. The aim is a hybrid system using both manual and actuated robotic operation in order to obtain a device that has a large workspace but can still fit in the gantry opening of a CT scanner. This will enable physicians to perform precise and time-efficient CT-guided percutaneous interventions. The concept of the mechanics and software of the device is presented in this work. METHODS: The approach is a semi-automated robotic assistive device, which combines manual and robotic positioning to reduce the number and size of necessary motors. The system consists of a manual rough positioning unit, a robotic fine positioning unit and an optical needle tracking unit. The resulting system has eight degrees of freedom, of which four are manual, which comprise encoders to monitor the position of each axis. The remaining four axes are actuated axes for fine positioning of the needle. Cameras are attached to the mechanical structure for 3D tracking of the needle pose. The software is based on open-source software, mainly ROS2 as robotic middleware, Moveit2 for trajectory calculation and 3D Slicer for needle path planning. RESULTS: The communication between the components was successfully tested with a clinical CT scanner. In a first experiment, four needle insertions were planned and the deviation of the actual needle path from the planned path was measured. The mean deviation from the needle path to the target point was 21.9 mm, which is mainly caused both by translational deviation (15.4 mm) and angular deviation (6.8°) of the needle holder. The optical tracking system was able to detect the needle position with a mean deviation of 3.9 mm. CONCLUSION: The first validation of the system was successful which proves that the proposed concept for both the hardware and software is feasible. In a next step, an automatic position correction based on the optical tracking system will be integrated, which is expected to significantly improve the system accuracy.

Learning Needle Placement in Soft Tissue With Robot-assisted Navigation.

BACKGROUND/AIM: The aim of this phantom study was to evaluate the learning curves of novices practicing how to place a cone-beam computed tomography (CBCT)-guided needle using a novel robotic assistance system (RAS). MATERIALS AND METHODS: Ten participants performed 18 punctures each with random trajectories in a phantom setting, supported by a RAS over 3 days. Precision, duration of the total intervention, duration of the needle placement, autonomy, and confidence of the participants were measured, displaying possible learning curves. RESULTS: No statistically significant differences were observed in terms of needle tip deviation during the trial days (mean deviation day 1: 2.82 mm; day 3: 3.07 mm; p=0.7056). During the trial days, the duration of the total intervention (mean duration: day 1: 11:22 min; day 3: 07:39 min; p<0.0001) and the duration of the needle placement decreased (mean duration: day 1: 03:17 min; day 3: 02:11 min; p<0.0001). In addition, autonomy (mean percentage of achievable points: day 1: 94%; day 3: 99%; p<0.0001) and confidence of the participants (mean percentage of achievable points: day 1: 78%; day 3: 91%; p<0.0001) increased significantly during the trial days. CONCLUSION: The participants were already able to carry out the intervention precisely using the RAS on the first day of the trial. Throughout the trial, the participants' performance improved in terms of duration and confidence.

Augmented reality during parotid surgery: real-life evaluation of voice control of a head mounted display.

PURPOSE: Augmented Reality can improve surgical planning and performance in parotid surgery. For easier application we implemented a voice control manual for our augmented reality system. The aim of the study was to evaluate the feasibility of the voice control in real-life situations. METHODS: We used the HoloLens 1® (Microsoft Corporation) with a special speech recognition software for parotid surgery. The evaluation took place in a audiometry cubicle and during real surgical procedures. Voice commands were used to display various 3D structures of the patient with the HoloLens 1®. Commands had different variations (male/female, 65 dB SPL)/louder, various structures). RESULTS: In silence, 100% of commands were recognized. If the volume of the operation room (OR) background noise exceeds 42 dB, the recognition rate decreases significantly, and it drops below 40% at > 60 dB SPL. With constant speech volume at 65 dB SPL male speakers had a significant better recognition rate than female speakers (p = 0.046). Higher speech volumes can compensate this effect. The recognition rate depends on the type of background noise. Mixed OR noise (52 dB(A)) reduced the detection rate significantly compared to single suction noise at 52 dB(A) (p ≤ 0.00001). The recognition rate was significantly better in the OR than in the audio cubicle (p = 0.00013 both genders, 0.0086 female, and 0.0036 male). CONCLUSIONS: The recognition rate of voice commands can be enhanced by increasing the speech volume and by singularizing ambient noises. The detection rate depends on the loudness of the OR noise. Male voices are understood significantly better than female voices.

Development of an abdominal phantom for the validation of an oligometastatic disease diagnosis workflow.

PURPOSE: The liver is a common site for metastatic disease, which is a challenging and life-threatening condition with a grim prognosis and outcome. We propose a standardized workflow for the diagnosis of oligometastatic disease (OMD), as a gold standard workflow has not been established yet. The envisioned workflow comprises the acquisition of a multimodal image data set, novel image processing techniques, and cone beam computed tomography (CBCT)-guided biopsy for subsequent molecular subtyping. By combining morphological, molecular, and functional information about the tumor, a patient-specific treatment planning is possible. We designed and manufactured an abdominal liver phantom that we used to demonstrate multimodal image acquisition, image processing, and biopsy of the OMD diagnosis workflow. METHODS: The anthropomorphic abdominal phantom contains a rib cage, a portal vein, lungs, a liver with six lesions, and a hepatic vessel tree. This phantom incorporates three different lesion types with varying visibility under computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography CT (PET-CT), which reflects clinical reality. The phantom is puncturable and the size of the corpus and the organs is comparable to those of a real human abdomen. By using several modern additive manufacturing techniques, the manufacturing process is reproducible and allows to incorporate patient-specific anatomies. As a first step of the OMD diagnosis workflow, a preinterventional CT, MRI, and PET-CT data set of the phantom was acquired. The image information was fused using image registration and organ information was extracted via image segmentation. A CBCT-guided needle puncture experiment was performed, where all six liver lesions were punctured with coaxial biopsy needles. RESULTS: Qualitative observation of the image data and quantitative evaluation using contrast-to-noise ratio (CNR) confirms that one lesion type is visible only in MRI and not CT. The other two lesion types are visible in CT and MRI. The CBCT-guided needle placement was performed for all six lesions, including those visible only in MRI and not CBCT. This was possible by successfully merging multimodal preinterventional image data. Lungs, bones, and liver vessels serve as realistic inhibitions during needle path planning. CONCLUSIONS: We have developed a reusable abdominal phantom that has been used to validate a standardized OMD diagnosis workflow. Utilizing the phantom, we have been able to show that a multimodal imaging pipeline is advantageous for a comprehensive detection of liver lesions. In a CBCT-guided needle placement experiment we have punctured lesions that are invisible in CBCT using registered preinterventional MRI scans for needle path planning.

Robotic Assistance System for Cone-Beam Computed Tomography-Guided Percutaneous Needle Placement.

PURPOSE: The study aimed to evaluate a new robotic assistance system (RAS) for needle placement in combination with a multi-axis C-arm angiography system for cone-beam computed tomography (CBCT) in a phantom setting. MATERIALS AND METHODS: The RAS consisted of a tool holder, dedicated planning software, and a mobile platform with a lightweight robotic arm to enable image-guided needle placement in conjunction with CBCT imaging. A CBCT scan of the phantom was performed to calibrate the robotic arm in the scan volume and to plan the different needle trajectories. The trajectory data were sent to the robot, which then positioned the tool holder along the trajectory. A 19G needle was then manually inserted into the phantom. During the control CBCT scan, the exact needle position was evaluated and any possible deviation from the target lesion measured. RESULTS: In total, 16 needle insertions targeting eight in- and out-of-plane sites were performed. Mean angular deviation from planned trajectory to actual needle trajectory was 1.12°. Mean deviation from target point and actual needle tip position was 2.74 mm, and mean deviation depth from the target lesion to the actual needle tip position was 2.14 mm. Mean time for needle placement was 361 s. Only differences in time required for needle placement between in- and out-of-plane trajectories (337 s vs. 380 s) were statistically significant (p = 0.0214). CONCLUSION: Using this RAS for image-guided percutaneous needle placement with CBCT was precise and efficient in the phantom setting.

Optimized Intraoperative Imaging for Stereotactic Planning with a Multiaxial Robotic C-arm System: Technical Note and Case Series.

BACKGROUND: The preoperative preparation of the planning dataset for frame-based stereotactic brain biopsy is often associated with logistical effort and burden on the patient. Intraoperative imaging modalities need to be investigated to overcome these limitations. OBJECTIVE: The objective of the study was to develop and apply a new method for the intraoperative acquisition of the planning dataset with the multiaxial robotic C-arm system Artis zeego. METHODS: An indication-customized dose-reduced protocol for Artis zeego was developed and implemented into the workflow. A sample of 14 patients who had undergone intraoperative imaging with Artis zeego was analyzed. A sample of 10 patients with conventional preoperative imaging by cranial computed tomography (CT) was used as a control group. Outcomes were compared with regard to target deviation, diagnostic value of the biopsies, complications, and procedure time. RESULTS: In all patients, a suitable intraoperative planning dataset could be acquired with Artis zeego. Total procedure time was shorter for the Artis zeego group (p = 0.01), whereas time in the operating room area was longer in the Artis zeego group (p = 0.04). Biopsy results were diagnostic in 12 patients (86%) in the Artis zeego group and in 8 patients (80%) in the control group. There were no significant differences in target size, trajectory length, or target deviation. CONCLUSION: Intraoperative imaging for frame-based stereotactic brain biopsy with Artis zeego is an easy and feasible method. Accuracy is comparable to conventional CT, whereas radiation exposure could be additionally reduced. It allows a significant reduction of the total procedure length and improves the comfort for the patient and staff.

Addiction Research Consortium: Losing and regaining control over drug intake (ReCoDe)-From trajectories to mechanisms and interventions.

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

CT and MRI compatibility of flexible 3D-printed materials for soft actuators and robots used in image-guided interventions.

PURPOSE: Three-dimensional (3D) printing allows for the fabrication of medical devices with complex geometries, such as soft actuators and robots that can be used in image-guided interventions. This study investigates flexible and rigid 3D-printing materials in terms of their impact on multimodal medical imaging. METHODS: The generation of artifacts in clinical computer tomography (CT) and magnetic resonance (MR) imaging was evaluated for six flexible and three rigid materials, each with a cubical and a cylindrical geometry, and for one exemplary flexible fluidic actuator. Additionally, CT Hounsfield units (HU) were quantified for various parameter sets iterating peak voltage, x-ray tube current, slice thickness, and convolution kernel. RESULTS: We found the image artifacts caused by the materials to be negligible in both CT and MR images. The HU values mainly depended on the elemental composition of the materials and applied peak voltage was ranging between 80 and 140 kVp. Flexible, nonsilicone-based materials were ranged between 51 and 114 HU. The voltage dependency was less than 29 HU. Flexible, silicone-based materials were ranged between 60 and 365 HU. The voltage-dependent influence was as large as 172 HU. Rigid materials ranged between -69 and 132 HU. The voltage-dependent influence was <33 HU. CONCLUSIONS: All tested materials may be employed for devices placed in the field of view during CT and MR imaging as no significant artifacts were measured. Moreover, the material selection in CT could be based on the desired visibility of the material depending on the application. Given the wide availability of the tested materials, we expect our results to have a positive impact on the development of devices and robots for image-guided interventions.

System and path planning algorithm for low-kV X-ray free-form surface irradiation.

OBJECTIVE: Intraoperative radiotherapy (IORT) after surgical resection using a low-kV-X-ray source is a proven method used in cancer treatment. However, the shape and size of the targeted surface area are limited to the size of the available applicators. This can lead to nonconformal and therefore suboptimal treatment for many patients. METHODS: A system is proposed comprising an X-ray source with an applicator for surface irradiation mounted on a robotic arm. This is controlled by an algorithm designed for planning the required continuous path, enabling irradiation of any desired shape with a controlled dose distribution. RESULTS: The system is shown to be capable of irradiating areas composed of rectangles on a flat surface with a homogeneity index of less than 7% inside the targeted area. CONCLUSION: The presented results demonstrate the potential of the proposed setup to eliminate the current limitations, leading to better treatment of patients.

Towards a Treatment of Stress Urinary Incontinence: Application of Mesenchymal Stromal Cells for Regeneration of the Sphincter Muscle.

Stress urinary incontinence is a significant social, medical, and economic problem. It is caused, at least in part, by degeneration of the sphincter muscle controlling the tightness of the urinary bladder. This muscular degeneration is characterized by a loss of muscle cells and a surplus of a fibrous connective tissue. In Western countries approximately 15% of all females and 10% of males are affected. The incidence is significantly higher among senior citizens, and more than 25% of the elderly suffer from incontinence. When other therapies, such as physical exercise, pharmacological intervention, or electrophysiological stimulation of the sphincter fail to improve the patient's conditions, a cell-based therapy may improve the function of the sphincter muscle. Here, we briefly summarize current knowledge on stem cells suitable for therapy of urinary incontinence: mesenchymal stromal cells, urine-derived stem cells, and muscle-derived satellite cells. In addition, we report on ways to improve techniques for surgical navigation, injection of cells in the sphincter muscle, sensors for evaluation of post-treatment therapeutic outcome, and perspectives derived from recent pre-clinical studies.

Multisensor data fusion in an integrated tracking system for endoscopic surgery.

Surgical planning and navigation systems are vital for minimally invasive endoscopic surgeries but it is challenging to track the position and orientation of intrabody surgical instruments in these procedures. In order to address this problem, we propose a tracking system including multiple-sensor integration and data fusion. The proposed tracking approach is free of the constraints of line-of-sight, less subject to environmental distortion, and with higher update rate. By incorporating electromagnetic and inertial sensors, the system yields continuous 6-DOF information. Based on a system dynamic model and estimation theories, a new multisensor fusion algorithm, cascade orientation and position-estimation algorithm, is proposed for the integrated tracking device. The experimental results show that the proposed algorithms achieve accurate orientation and position tracking with robustness.

Development of a wireless hybrid navigation system for laparoscopic surgery.

Navigation devices have been essential components for Image-Guided Surgeries (IGS) including laparoscopic surgery. We propose a wireless hybrid navigation device that integrates miniature inertial sensors and electromagnetic sensing units, for tracking instruments both inside and outside the human-body. The proposed system is free of the constraints of line-of-sight or entangling sensor wires. The main functional (sensor) part of the hybrid tracker is only about 15 mm by 15 mm. We identify the sensor models and develop sensor fusion algorithms for the proposed system to get optimal estimation of position and orientation (pose). The proof-of-concept experimental results show that the proposed hardware and software system can meet the defined tracking requirements, in terms of tracking accuracy, latency and robustness to environmental interferences.

Automated registration of partially defective surfaces by local landmark identification.

OBJECTIVE: In computer- and robot-assisted surgery, the term "registration" refers to the definition of the geometrical relationship between the coordinate system of a surgical planning system and that of the patient. Within the context of the development of a navigation and control system for computer- and robot-assisted surgery of the lateral skull base, it was desirable to realize an algorithm for automated registration of partially defective surfaces that is reliable and suitable for use in clinical practice. MATERIALS AND METHODS: A registration algorithm based on the use of local fingerprints for specific points on a surface (so-called "spin images") was developed. Anatomical patient landmarks were identified automatically and assigned to CT data, performing a cross-correlation analysis and an investigation of the geometrical consistency. The algorithm was evaluated within the development of the navigation and robotic control system in a laboratory setting. RESULTS: Under laboratory conditions it could be shown that partially defective surfaces (simulated by, for example, adding white noise, or reducing or smoothing the polygon data) were correctly recognized and thereby registered. In particular, the algorithm proved its excellence in interpreting partially modified topologies. CONCLUSIONS: The proposed procedure can be used to accomplish dynamic intra-operative registration of the skull bone by the generation of point relations to the CT images.