Neuroimaging reveals distinct brain glucose metabolism patterns associated with morphine consumption in Lewis and Fischer 344 rat strains.

Vulnerability to addiction may be given by the individual's risk of developing an addiction during their lifetime. A challenge in the neurobiology of drug addiction is understanding why some people become addicted to drugs. Here, we used positron emission tomography (PET) and statistical parametric mapping (SPM) to evaluate changes in brain glucose metabolism in response to chronic morphine self-administration (MSA) in two rat strains with different vulnerability to drug abuse, Lewis (LEW) and Fischer 344 (F344). Four groups of animals were trained to self-administer morphine or saline for 15 days. 2-deoxy-2-[18F]-fluoro-D-glucose (FDG)-PET studies were performed on the last day of MSA (acquisition phase) and after 15 days of withdrawal. PET data were analyzed using SPM12. LEW-animals self-administered more morphine injections per session than F344-animals. We found significant brain metabolic differences between LEW and F344 strains in the cortex, hypothalamus, brainstem, and cerebellum. In addition, the different brain metabolic patterns observed after the MSA study between these rat strains indicate differences in the efficiency of neural substrates to translate the drug effects, which could explain the differences in predisposition to morphine abuse between one individual and another. These findings have important implications for the use of these rat strains in translational morphine and opiate research.

Radiation-Free Thoracic Endovascular Aneurysm Repair with Fiberoptic and Electromagnetic Guidance: A Phantom Study.

PURPOSE: To evaluate the feasibility and accuracy of a radiation-free implantation of a thoracic aortic stent graft employing fiberoptic and electromagnetic tracking in an anthropomorphic phantom. MATERIALS AND METHODS: An anthropomorphic phantom was manufactured based on computed tomography (CT) angiography data from a patient. An aortic stent graft application system was equipped with a fiber Bragg gratings and 3 electromagnetic sensors. The stent graft was navigated in the phantom by 3 interventionalists using the tracking data generated by both technologies. One implantation procedure was performed. The technical success of the procedure was evaluated using digital subtraction angiography and CT angiography (before and after the intervention). Tracking accuracy was determined at various anatomical landmarks based on separately acquired fluoroscopic images. The mean/maximum errors were measured for the stent graft application system and the tip/end of the stent graft. RESULTS: The procedure resulted in technical success with a mean error below 3 mm for the entire application system and <2 mm for the position of the tip of the stent graft. Navigation/implantation and handling of the device were rated sufficiently accurate and on par with comparable, routinely used stent graft application systems. CONCLUSIONS: The study demonstrates successful stent graft implantation during a thoracic endovascular aortic repair procedure employing advanced guidance techniques and avoiding fluoroscopic imaging. This is an essential step in facilitating the implantation of stent grafts and reducing the health risks associated with ionizing radiation during endovascular procedures.

Instrument localisation for endovascular aneurysm repair: Comparison of two methods based on tracking systems or using imaging.

BACKGROUND: In endovascular aneuysm repair (EVAR) procedures, medical instruments are currently navigated with a two-dimensional imaging based guidance requiring X-rays and contrast agent. METHODS: Novel approaches for obtaining the three-dimensional instrument positions are introduced. Firstly, a method based on fibre optical shape sensing, one electromagnetic sensor and a preoperative computed tomography (CT) scan is described. Secondly, an approach based on image processing using one 2D fluoroscopic image and a preoperative CT scan is introduced. RESULTS: For the tracking based method, average errors from 1.81 to 3.13 mm and maximum errors from 3.21 to 5.46 mm were measured. For the image-based approach, average errors from 3.07 to 6.02 mm and maximum errors from 8.05 to 15.75 mm were measured. CONCLUSION: The tracking based method is promising for usage in EVAR procedures. For the image-based approach are applications in smaller vessels more suitable, since its errors increase with the vessel diameter.

Medical Robotics for Ultrasound Imaging: Current Systems and Future Trends.

PURPOSE OF REVIEW: This review provides an overview of the most recent robotic ultrasound systems that have contemporary emerged over the past five years, highlighting their status and future directions. The systems are categorized based on their level of robot autonomy (LORA). RECENT FINDINGS: Teleoperating systems show the highest level of technical maturity. Collaborative assisting and autonomous systems are still in the research phase, with a focus on ultrasound image processing and force adaptation strategies. However, missing key factors are clinical studies and appropriate safety strategies. Future research will likely focus on artificial intelligence and virtual/augmented reality to improve image understanding and ergonomics. SUMMARY: A review on robotic ultrasound systems is presented in which first technical specifications are outlined. Hereafter, the literature of the past five years is subdivided into teleoperation, collaborative assistance, or autonomous systems based on LORA. Finally, future trends for robotic ultrasound systems are reviewed with a focus on artificial intelligence and virtual/augmented reality.

Three-dimensional guidance including shape sensing of a stentgraft system for endovascular aneurysm repair.

PURPOSE: During endovascular aneurysm repair (EVAR) procedures, medical instruments are guided with two-dimensional (2D) fluoroscopy and conventional digital subtraction angiography. However, this requires X-ray exposure and contrast agent is used, and the depth information is missing. To overcome these drawbacks, a three-dimensional (3D) guidance approach based on tracking systems is introduced and evaluated. METHODS: A multicore fiber with fiber Bragg gratings for shape sensing and three electromagnetic (EM) sensors for locating the shape were integrated into a stentgraft system. A model for obtaining the located shape of the first 38 cm of the stentgraft system with two EM sensors is introduced and compared with a method based on three EM sensors. Both methods were evaluated with a vessel phantom containing a 3D-printed vessel made of silicone and agar-agar simulating the surrounding tissue. RESULTS: The evaluation of the guidance methods resulted in average errors from 1.35 to 2.43 mm and maximum errors from 3.04 to 6.30 mm using three EM sensors, and average errors from 1.57 to 2.64 mm and maximum errors from 2.79 to 6.27 mm using two EM sensors. Moreover, the videos made from the continuous measurements showed that a real-time guidance is possible with both approaches. CONCLUSION: The results showed that an accurate real-time guidance with two and three EM sensors is possible and that two EM sensors are already sufficient. Thus, the introduced 3D guidance method is promising to use it as navigation tool in EVAR procedures. Future work will focus on developing a method with less EM sensors and a detailed latency evaluation of the guidance method.

Intraoperative computed tomography imaging for dose calculation in intraoperative electron radiation therapy: Initial clinical observations.

In intraoperative electron radiation therapy (IOERT) the energy of the electron beam is selected under the conventional assumption of water-equivalent tissues at the applicator end. However, the treatment field can deviate from the theoretic flat irradiation surface, thus altering dose profiles. This patient-based study explored the feasibility of acquiring intraoperative computed tomography (CT) studies for calculating three-dimensional dose distributions with two factors not included in the conventional assumption, namely the air gap from the applicator end to the irradiation surface and tissue heterogeneity. In addition, dose distributions under the conventional assumption and from preoperative CT studies (both also updated with intraoperative data) were calculated to explore whether there are other alternatives to intraoperative CT studies that can provide similar dose distributions. The IOERT protocol was modified to incorporate the acquisition of intraoperative CT studies before radiation delivery in six patients. Three studies were not valid to calculate dose distributions due to the presence of metal artefacts. For the remaining three cases, the average gamma pass rates between the doses calculated from intraoperative CT studies and those obtained assuming water-equivalent tissues or from preoperative CT studies were 73.4% and 74.0% respectively. The agreement increased when the air gap was included in the conventional assumption (98.1%) or in the preoperative CT images (98.4%). Therefore, this factor was the one mostly influencing the dose distributions of this study. Our experience has shown that intraoperative CT studies are not recommended when the procedure includes the use of shielding discs or surgical retractors unless metal artefacts are removed. IOERT dose distributions calculated under the conventional assumption or from preoperative CT studies may be inaccurate unless the air gap (which depends on the surface irregularities of the irradiated volume and on the applicator pose) is included in the calculations.

Surface scanning for 3D dose calculation in intraoperative electron radiation therapy.

BACKGROUND: Dose calculations in intraoperative electron radiation therapy (IOERT) rely on the conventional assumption of water-equivalent tissues at the applicator end, which defines a flat irradiation surface. However, the shape of the irradiation surface modifies the dose distribution. Our study explores, for the first time, the use of surface scanning methods for three-dimensional dose calculation of IOERT. METHODS: Two different three-dimensional scanning technologies were evaluated in a simulated IOERT scenario: a tracked conoscopic holography sensor (ConoProbe) and a structured-light three-dimensional scanner (Artec). Dose distributions obtained from computed tomography studies of the surgical field (gold standard) were compared with those calculated under the conventional assumption or from pseudo-computed tomography studies based on surfaces. RESULTS: In the simulated IOERT scenario, the conventional assumption led to an average gamma pass rate of 39.9% for dose values greater than 10% (two configurations, with and without blood in the surgical field). Results improved when considering surfaces in the dose calculation (88.5% for ConoProbe and 92.9% for Artec). CONCLUSIONS: More accurate three-dimensional dose distributions were obtained when considering surfaces in the dose calculation of the simulated surgical field. The structured-light three-dimensional scanner provided the best results in terms of dose distributions. The findings obtained in this specific experimental setup warrant further research on surface scanning in the IOERT context owing to the clinical interest of improving the documentation of the actual IOERT scenario.

Navigation and visualisation with HoloLens in endovascular aortic repair.

INTRODUCTION: Endovascular aortic repair (EVAR) is a minimal-invasive technique that prevents life-threatening rupture in patients with aortic pathologies by implantation of an endoluminal stent graft. During the endovascular procedure, device navigation is currently performed by fluoroscopy in combination with digital subtraction angiography. This study presents the current iterative process of biomedical engineering within the disruptive interdisciplinary project Nav EVAR, which includes advanced navigation, image techniques and augmented reality with the aim of reducing side effects (namely radiation exposure and contrast agent administration) and optimising visualisation during EVAR procedures. This article describes the current prototype developed in this project and the experiments conducted to evaluate it. METHODS: The current approach of the Nav EVAR project is guiding EVAR interventions in real-time with an electromagnetic tracking system after attaching a sensor on the catheter tip and displaying this information on Microsoft HoloLens glasses. This augmented reality technology enables the visualisation of virtual objects superimposed on the real environment. These virtual objects include three-dimensional (3D) objects (namely 3D models of the skin and vascular structures) and two-dimensional (2D) objects [namely orthogonal views of computed tomography (CT) angiograms, 2D images of 3D vascular models, and 2D images of a new virtual angioscopy whose appearance of the vessel wall follows that shown in ex vivo and in vivo angioscopies]. Specific external markers were designed to be used as landmarks in the registration process to map the tracking data and radiological data into a common space. In addition, the use of real-time 3D ultrasound (US) is also under evaluation in the Nav EVAR project for guiding endovascular tools and updating navigation with intraoperative imaging. US volumes are streamed from the US system to HoloLens and visualised at a certain distance from the probe by tracking augmented reality markers. A human model torso that includes a 3D printed patient-specific aortic model was built to provide a realistic test environment for evaluation of technical components in the Nav EVAR project. The solutions presented in this study were tested by using an US training model and the aortic-aneurysm phantom. RESULTS: During the navigation of the catheter tip in the US training model, the 3D models of the phantom surface and vessels were visualised on HoloLens. In addition, a virtual angioscopy was also built from a CT scan of the aortic-aneurysm phantom. The external markers designed for this study were visible in the CT scan and the electromagnetically tracked pointer fitted in each marker hole. US volumes of the US training model were sent from the US system to HoloLens in order to display them, showing a latency of 259±86 ms (mean±standard deviation). CONCLUSION: The Nav EVAR project tackles the problem of radiation exposure and contrast agent administration during EVAR interventions by using a multidisciplinary approach to guide the endovascular tools. Its current state presents several limitations such as the rigid alignment between preoperative data and the simulated patient. Nevertheless, the techniques shown in this study in combination with fibre Bragg gratings and optical coherence tomography are a promising approach to overcome the problems of EVAR interventions.

Assessment of intraoperative 3D imaging alternatives for IOERT dose estimation.

Intraoperative electron radiation therapy (IOERT) involves irradiation of an unresected tumour or a post-resection tumour bed. The dose distribution is calculated from a preoperative computed tomography (CT) study acquired using a CT simulator. However, differences between the actual IOERT field and that calculated from the preoperative study arise as a result of patient position, surgical access, tumour resection and the IOERT set-up. Intraoperative CT imaging may then enable a more accurate estimation of dose distribution. In this study, we evaluated three kilovoltage (kV) CT scanners with the ability to acquire intraoperative images. Our findings indicate that current IOERT plans may be improved using data based on actual anatomical conditions during radiation. The systems studied were two portable systems ("O-arm", a cone-beam CT [CBCT] system, and "BodyTom", a multislice CT [MSCT] system) and one CBCT integrated in a conventional linear accelerator (LINAC) ("TrueBeam"). TrueBeam and BodyTom showed good results, as the gamma pass rates of their dose distributions compared to the gold standard (dose distributions calculated from images acquired with a CT simulator) were above 97% in most cases. The O-arm yielded a lower percentage of voxels fulfilling gamma criteria owing to its reduced field of view (which left it prone to truncation artefacts). Our results show that the images acquired using a portable CT or even a LINAC with on-board kV CBCT could be used to estimate the dose of IOERT and improve the possibility to evaluate and register the treatment administered to the patient.

ConoSurf: Open-source 3D scanning system based on a conoscopic holography device for acquiring surgical surfaces.

BACKGROUND: A difficulty in computer-assisted interventions is acquiring the patient's anatomy intraoperatively. Standard modalities have several limitations: low image quality (ultrasound), radiation exposure (computed tomography) or high costs (magnetic resonance imaging). An alternative approach uses a tracked pointer; however, the pointer causes tissue deformation and requires sterilizing. Recent proposals, utilizing a tracked conoscopic holography device, have shown promising results without the previously mentioned drawbacks. METHODS: We have developed an open-source software system that enables real-time surface scanning using a conoscopic holography device and a wide variety of tracking systems, integrated into pre-existing and well-supported software solutions. RESULTS: The mean target registration error of point measurements was 1.46 mm. For a quick guidance scan, surface reconstruction improved the surface registration error compared with point-set registration. CONCLUSIONS: We have presented a system enabling real-time surface scanning using a tracked conoscopic holography device. Results show that it can be useful for acquiring the patient's anatomy during surgery.

fMRat: an extension of SPM for a fully automatic analysis of rodent brain functional magnetic resonance series.

The purpose of this study was to develop a multi-platform automatic software tool for full processing of fMRI rodent studies. Existing tools require the usage of several different plug-ins, a significant user interaction and/or programming skills. Based on a user-friendly interface, the tool provides statistical parametric brain maps (t and Z) and percentage of signal change for user-provided regions of interest. The tool is coded in MATLAB (MathWorks(®)) and implemented as a plug-in for SPM (Statistical Parametric Mapping, the Wellcome Trust Centre for Neuroimaging). The automatic pipeline loads default parameters that are appropriate for preclinical studies and processes multiple subjects in batch mode (from images in either Nifti or raw Bruker format). In advanced mode, all processing steps can be selected or deselected and executed independently. Processing parameters and workflow were optimized for rat studies and assessed using 460 male-rat fMRI series on which we tested five smoothing kernel sizes and three different hemodynamic models. A smoothing kernel of FWHM = 1.2 mm (four times the voxel size) yielded the highest t values at the somatosensorial primary cortex, and a boxcar response function provided the lowest residual variance after fitting. fMRat offers the features of a thorough SPM-based analysis combined with the functionality of several SPM extensions in a single automatic pipeline with a user-friendly interface. The code and sample images can be downloaded from https://github.com/HGGM-LIM/fmrat .

Combination of single-photon emission computed tomography and magnetic resonance imaging to track 111in-oxine-labeled human mesenchymal stem cells in neuroblastoma-bearing mice.

Homing is an inherent, complex, multistep process performed by cells such as human bone marrow mesenchymal stem cells (hMSCs) to travel from a distant location to inflamed or damaged tissue and tumors. This ability of hMSCs has been exploited as a tumor-targeting strategy in cell-based cancer therapy. The purpose of this study was to investigate the applicability of 111In-oxine for tracking hMSCs in vivo by combining single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). 111In-labeled hMSCs (106 cells) were infused intraperitoneally in neuroblastoma-bearing mice, whereas a control group received a dose of free 111In-oxine. SPECT and MRI studies were performed 24 and 48 hours afterwards. Initially, the images showed similar activity in the abdomen in both controls and hMSC-injected animals. In general, abdominal activity decreases at 48 hours. hMSC-injected animals showed increased uptake in the tumor area at 48 hours, whereas the control group showed a low level of activity at 24 hours, which decreased at 48 hours. In conclusion, tracking 111In-labeled hMSCs combining SPECT and MRI is feasible and may be transferable to clinical research. The multimodal combination is essential to ensure appropriate interpretation of the images.

Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls.

OBJECTIVE: One of the most interesting clinical applications of 18F-FDG PET imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimer's disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls. METHODS: We evaluated the results of three spatial normalization methods in an SPM analysis by comparing patients diagnosed with MCI with a group of control subjects. We tested three methods of spatial normalization: MRI-DARTEL and MRI-SPM8, which combine structural and functional images, and FDG-SPM8, which is based on the functional images only. RESULTS: The results obtained with the three methods were consistent in terms of the main pattern of functional alterations detected; namely, a bilateral reduction in glucose metabolism in the frontal and parietal cortices in the patient group. However, MRI-SPM8 also revealed differences in the left temporal cortex, and MRI-DARTEL revealed further differences in the left temporal cortex, precuneus, and left posterior cingulate. CONCLUSIONS: The results obtained with MRI-DARTEL were the most consistent with the pattern of changes in AD. When we compared our observations with those of previous reports, MRI-SPM8 and FDG-SPM8 seemed to show an incomplete pattern. Our results suggest that basing the spatial normalization method on functional images only can considerably impair the results of SPM analysis of 18F-FDG PET studies.

Chronic cannabinoid administration to periadolescent rats modulates the metabolic response to acute cocaine in the adult brain.

PURPOSE: To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence. PROCEDURES: The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[¹8F]fluoro-D-: glucose (FDG) uptake were studied by positron emission tomography. RESULTS: The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP. CONCLUSIONS: These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated.

Regional gray matter volume deficits in adolescents with first-episode psychosis.

OBJECTIVE: The current study combined baseline voxel-based morphometry and 1-year clinical follow-up assessments to examine whether and where regional gray matter (GM) volumes differed between a control group and diagnostic subgroups of early-onset first-episode psychosis (FEP). METHOD: Magnetic resonance imaging brain scans were obtained from 70 patients with early-onset FEP, and 51 non-FEP controls. Early-onset FEP was defined as age younger than 18 years and a duration of positive symptoms of less than 6 months. The age range of the sample was 7 to 18 years. After a 1-year follow-up, patients were stratified into three subgroups: schizophrenia (n = 25), bipolar I disorder (n = 20), and other psychoses (n = 25). Regional GM volumes of each patient subgroup were compared with those of the control group. RESULTS: A follow-up diagnosis of schizophrenia was associated with GM volume deficits in the left medial and left middle frontal gyrus; bipolar I disorder was related to a GM volume deficit in the left medial frontal gyrus; and not having a follow-up diagnosis of schizophrenia or bipolar disorder was associated with smaller bilateral GM volumes in the insula and right middle occipital gyrus. CONCLUSIONS: Left medial frontal GM volume deficits were common in the groups with schizophrenia and bipolar I disorder, which may point to shared underlying pathological findings.