Clinical Implementation of In-House Developed MR-Based Patient-Specific 3D Models of Liver Anatomy.

Knowledge of patient-specific liver anatomy is key to patient safety during major hepatobiliary surgery. Three-dimensional (3D) models of patient-specific liver anatomy based on diagnostic MRI images can provide essential vascular and biliary anatomical insight during surgery. However, a method for generating these is not yet publicly available. This paper describes how these 3D models of the liver can be generated using open source software, and then subsequently integrated into a sterile surgical environment. The most common image quality aspects that degrade the quality of the 3D models as well possible ways of eliminating these are also discussed. Per patient, a single diagnostic multiphase MRI scan with hepatospecific contrast agent was used for automated segmentation of liver contour, arterial, portal, and venous anatomy, and the biliary tree. Subsequently, lesions were delineated manually. The resulting interactive 3D model could be accessed during surgery on a sterile covered tablet. Up to now, such models have been used in 335 surgical procedures. Their use simplified the surgical treatment of patients with a high number of liver metastases and contributed to the localization of vanished lesions in cases of a radiological complete response to neoadjuvant treatment. They facilitated perioperative verification of the relationship of tumors and the surrounding vascular and biliary anatomy, and eased decision-making before and during surgery.

Prospective study on image-guided navigation surgery for pelvic malignancies.

BACKGROUND AND OBJECTIVES: Surgery of advanced tumors and lymph nodes in the pelvis can be challenging due to the narrow pelvic space and vital surrounding structures. This study explores the application of a novel electromagnetic navigation system to guide pelvic surgery. METHODS: This was a prospective study on surgery for malignancies in the pelvis. Preoperatively obtained imaging was used to create a patient-specific three-dimensional (3D) roadmap. In the operating room, the 3D roadmap was registered to an intraoperative computed tomography scan. A tracked pointer was used during surgery for guidance. Primary endpoint was safety and feasibility, secondary endpoints were accuracy and usability. RESULTS: Twenty-eight colorectal, four liposarcomas, and one gynecological patient were included. There were no safety issues. Navigation was feasible in 31 patients. The mean target registration errors of 4.0 and 6.3 mm were achieved for straight and French position, respectively. In seven of seven patients with a locally advanced rectal tumor and in seven of eight patients with recurrences, negative margins were achieved. Thirty-three of 36 target lymph nodes were successfully removed. Surgeons using the system indicated faster localization of the tumor and improved decisiveness. CONCLUSION: This novel surgical navigation system was safe and feasible during pelvic surgery and can facilitate its users.

SPECT/CT Imaging of Pluronic Nanocarriers with Varying Poly(ethylene oxide) Block Length and Aggregation State.

Optimal biodistribution and prolonged circulation of nanocarriers improve diagnostic and therapeutic effects of enhanced permeability and retention-based nanomedicines. Despite extensive use of Pluronics in polymer-based pharmaceuticals, the influence of different poly(ethylene oxide) (PEO) block length and aggregation state on the biodistribution of the carriers is rather unexplored. In this work, we studied these effects by evaluating the biodistribution of Pluronic unimers and cross-linked micelles with different PEO block size. In vivo biodistribution of (111)In-radiolabeled Pluronic nanocarriers was investigated in healthy mice using single photon emission computed tomography. All carriers show fast uptake in the organs from the reticuloendothelial system followed by a steady elimination through the hepatobiliary tract and renal filtration. The PEO block length affects the initial renal clearance of the compounds and the overall liver uptake. The aggregation state influences the long-term accumulation of the nanocarriers in the liver. We showed that the circulation time and elimination pathways can be tuned by varying the physicochemical properties of Pluronic copolymers. Our results can be beneficial for the design of future Pluronic-based nanomedicines.

Quarter-millimeter-resolution molecular mouse imaging with U-SPECT⁺.

Limited spatial resolution of preclinical positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has slowed down applications of molecular imaging in small animals. Here we present the latest-generation U-SPECT system (U-SPECT⁺, MILabs, Utrecht, the Netherlands) enabling radionuclide imaging of mice with quarter-millimeter resolution. The system was equipped with the newest high-resolution collimator with 0.25 mm diameter circular pinholes. It was calibrated with technetium-99 m point source measurements from which the system matrix was calculated. Images were reconstructed using pixel-based ordered subset expectation maximization (OSEM). Various phantoms and mouse SPECT scans were acquired. The reconstructed spatial resolution (the smallest visible capillary diameter in a hot-rod resolution phantom) was 0.25 mm. Knee joint images show tiny structures such as the femur epicondyle sulcus, as well as a clear separation between cortical and trabecular bone structures. In addition, time-activity curves of the lumbar spine illustrated that tracer dynamics in tiny tissue amounts could be measured. U-SPECT⁺ allows discrimination between molecular concentrations in adjacent volumes of as small as 0.015 µL, which is significantly better than can be imaged by any existing SPECT or PET system. This increase in the level of detail makes it more and more attractive to replace ex vivo methods and allows monitoring biological processes in tiny parts of organs in vivo.

Time-Activity data fitting in molecular Radiotherapy: Methodology and pitfalls.

Absorbed radiation doses are essential in assessing the effects, e.g. safety and efficacy, of radiopharmaceutical therapy (RPT). Patient-specific absorbed dose calculations in the target or the organ at risk require multiple inputs. These include the number of disintegrations in the organ, i.e. the time-integrated activities (TIAs) of the organs, as well as other parameters describing the process of radiation energy deposition in the target tissue (i.e. mean energy per disintegration, radiation dose constants, etc). TIAs are then estimated by incorporating the area under the radiopharmaceutical's time-activity curve (TAC), which can be obtained by quantitative measurements of the biokinetics in the patient (typically based on imaging data such as planar scintigraphy, SPECT/CT, PET/CT, or blood and urine samples). The process of TAC determination/calculation for RPT generally depends on the user, e.g., the chosen number and schedule of measured time points, the selection of the fit function, the error model for the data and the fit algorithm. These decisions can strongly affect the final TIA values and thus the accuracy of calculated absorbed doses. Despite the high clinical importance of the TIA values, there is currently no consensus on processing time-activity data or even a clear understanding of the influence of uncertainties and variations in personalised RPT dosimetry related to user-dependent TAC calculation. As a first step towards minimising site-dependent variability in RPT dosimetry, this work provides an overview of quality assurance and uncertainty management considerations of the TIA estimation.

Implementation of dosimetry for molecular radiotherapy; results from a European survey.

PURPOSE: The use of molecular radiotherapy (MRT) has been rapidly evolving over the last years. The aim of this study was to assess the current implementation of dosimetry for MRTs in Europe. METHODS: A web-based questionnaire was open for treating centres between April and June 2022, and focused on 2020-2022. Questions addressed the application of 16 different MRTs, the availability and involvement of medical physicists, software used, quality assurance, as well as the target regions for dosimetry, whether treatment planning and/or verification were performed, and the dosimetric methods used. RESULTS: A total of 173 responses suitable for analysis was received from centres performing MRT, geographically distributed over 27 European countries. Of these, 146 centres (84 %) indicated to perform some form of dosimetry, and 97 % of these centres had a medical physicist available and almost always involved in dosimetry. The most common MRTs were 131I-based treatments for thyroid diseases and thyroid cancer, and [223Ra]RaCl2 for bone metastases. The implementation of dosimetry varied widely between therapies, from almost all centres performing dosimetry-based planning for microsphere treatments to none for some of the less common treatments (like 32P sodium-phosphate for myeloproliferative disease and [89Sr]SrCl2 for bone metastases). CONCLUSIONS: Over the last years, implementation of dosimetry, both for pre-therapeutic treatment planning and post-therapy absorbed dose verification, increased for several treatments, especially for microsphere treatments. For other treatments that have moved from research to clinical routine, the use of dosimetry decreased in recent years. However, there are still large differences both across and within countries.

Automatic hepatic tumor segmentation in intra-operative ultrasound: a supervised deep-learning approach.

Purpose: Training and evaluation of the performance of a supervised deep-learning model for the segmentation of hepatic tumors from intraoperative US (iUS) images, with the purpose of improving the accuracy of tumor margin assessment during liver surgeries and the detection of lesions during colorectal surgeries. Approach: In this retrospective study, a U-Net network was trained with the nnU-Net framework in different configurations for the segmentation of CRLM from iUS. The model was trained on B-mode intraoperative hepatic US images, hand-labeled by an expert clinician. The model was tested on an independent set of similar images. The average age of the study population was 61.9 ± 9.9 years. Ground truth for the test set was provided by a radiologist, and three extra delineation sets were used for the computation of inter-observer variability. Results: The presented model achieved a DSC of 0.84 (p=0.0037), which is comparable to the expert human raters scores. The model segmented hypoechoic and mixed lesions more accurately (DSC of 0.89 and 0.88, respectively) than hyper- and isoechoic ones (DSC of 0.70 and 0.60, respectively) only missing isoechoic or >20 mm in diameter (8% of the tumors) lesions. The inclusion of extra margins of probable tumor tissue around the lesions in the training ground truth resulted in lower DSCs of 0.75 (p=0.0022). Conclusion: The model can accurately segment hepatic tumors from iUS images and has the potential to speed up the resection margin definition during surgeries and the detection of lesion in screenings by automating iUS assessment.

Ultrasound-based navigation for open liver surgery using active liver tracking.

PURPOSE: Despite extensive preoperative imaging, intraoperative localization of liver lesions after systemic treatment can be challenging. Therefore, an image-guided navigation setup is explored that links preoperative diagnostic scans and 3D models to intraoperative ultrasound (US), enabling overlay of detailed diagnostic images on intraoperative US. Aim of this study is to assess the workflow and accuracy of such a navigation system which compensates for liver motion. METHODS: Electromagnetic (EM) tracking was used for organ tracking and movement of the transducer. After laparotomy, a sensor was attached to the liver surface while the EM-tracked US transducer enabled image acquisition and landmark digitization. Landmarks surrounding the lesion were selected during patient-specific preoperative 3D planning and identified for registration during surgery. Endpoints were accuracy and additional times of the investigative steps. Accuracy was computed at the center of the target lesion. RESULTS: In total, 22 navigated procedures were performed. Navigation provided useful visualization of preoperative 3D models and their overlay on US imaging. Landmark-based registration resulted in a mean fiducial registration error of 10.3 ± 4.3 mm, and a mean target registration error of 8.5 ± 4.2 mm. Navigation was available after an average of 12.7 min. CONCLUSION: We developed a navigation method combining ultrasound with active liver tracking for organ motion compensation, with an accuracy below 10 mm. Fixation of the liver sensor near the target lesion compensates for local movement and contributes to improved reliability during navigation. This represents an important step forward in providing surgical navigation throughout the procedure. TRIAL REGISTRATION: This study is registered in the Netherlands Trial Register (number NL7951).

Artificial intelligence in the medical physics community: An international survey.

PURPOSE: To assess current perceptions, practices and education needs pertaining to artificial intelligence (AI) in the medical physics field. METHODS: A web-based survey was distributed to the European Federation of Organizations for Medical Physics (EFOMP) through social media and email membership list. The survey included questions about education, personal knowledge, needs, research and professionalism around AI in medical physics. Demographics information were also collected. Responses were stratified and analysed by gender, type of institution and years of experience in medical physics. Statistical significance (p<0.05) was assessed using paired t-test. RESULTS: 219 people from 31 countries took part in the survey. 81% (n = 177) of participants agreed that AI will improve the daily work of Medical Physics Experts (MPEs) and 88% (n = 193) of respondents expressed the need for MPEs of specific training on AI. The average level of AI knowledge among participants was 2.3 ± 1.0 (mean ± standard deviation) in a 1-to-5 scale and 96% (n = 210) of participants showed interest in improving their AI skills. A significantly lower AI knowledge was observed for female participants (2.0 ± 1.0), compared to male responders (2.4 ± 1.0). 64% of participants indicated that they are not involved in AI projects. The percentage of female leading AI projects was significantly lower than the male counterparts (3% vs 19%). CONCLUSIONS: AI was perceived as a positive resource to support MPEs in their daily tasks. Participants demonstrated a strong interest in improving their current AI-related skills, enhancing the need for dedicated training for MPEs.

CBCT-based navigation system for open liver surgery: Accurate guidance toward mobile and deformable targets with a semi-rigid organ approximation and electromagnetic tracking of the liver.

PURPOSE: The surgical navigation system that provides guidance throughout the surgery can facilitate safer and more radical liver resections, but such a system should also be able to handle organ motion. This work investigates the accuracy of intraoperative surgical guidance during open liver resection, with a semi-rigid organ approximation and electromagnetic tracking of the target area. METHODS: The suggested navigation technique incorporates a preoperative 3D liver model based on diagnostic 4D MRI scan, intraoperative contrast-enhanced CBCT imaging and electromagnetic (EM) tracking of the liver surface, as well as surgical instruments, by means of six degrees-of-freedom micro-EM sensors. RESULTS: The system was evaluated during surgeries with 35 patients and resulted in an accurate and intuitive real-time visualization of liver anatomy and tumor's location, confirmed by intraoperative checks on visible anatomical landmarks. Based on accuracy measurements verified by intraoperative CBCT, the system's average accuracy was 4.0 ± 3.0 mm, while the total surgical delay due to navigation stayed below 20 min. CONCLUSIONS: The electromagnetic navigation system for open liver surgery developed in this work allows for accurate localization of liver lesions and critical anatomical structures surrounding the resection area, even when the liver was manipulated. However, further clinically integrating the method requires shortening the guidance-related surgical delay, which can be achieved by shifting to faster intraoperative imaging like ultrasound. Our approach is adaptable to navigation on other mobile and deformable organs, and therefore may benefit various clinical applications.

A workflow for automated segmentation of the liver surface, hepatic vasculature and biliary tree anatomy from multiphase MR images.

Accurate assessment of 3D models of patient-specific anatomy of the liver, including underlying hepatic and biliary tree, is critical for preparation and safe execution of complex liver resections, especially due to high variability of biliary and hepatic artery anatomies. Dynamic MRI with hepatospecific contrast agents is currently the only type of diagnostic imaging that provides all anatomical information required for generation of such a model, yet there is no information in the literature on how the complete 3D model can be generated automatically. In this work, a new automated segmentation workflow for extraction of patient-specific 3D model of the liver, hepatovascular and biliary anatomy from a single multiphase MRI acquisition is developed and quantitatively evaluated. The workflow incorporates course 4D k-means clustering estimation and geodesic active contour refinement of the liver boundary, based on organ's characteristic uptake of gadolinium contrast agents overtime. Subsequently, hepatic vasculature and biliary ducts segmentations are performed using multiscale vesselness filters. The algorithm was evaluated using 15 test datasets of patients with liver malignancies of various histopathological types. It showed good correlation with expert manual segmentation, resulting in an average of 1.76 ± 2.44 mm Hausdorff distance for the liver boundary, and 0.58 ± 0.72 and 1.16 ± 1.98 mm between centrelines of biliary ducts and liver veins, respectively. A workflow for automatic segmentation of the liver, hepatic vasculature and biliary anatomy from a single diagnostic MRI acquisition was developed. This enables automated extraction of 3D models of patient-specific liver anatomy, and may facilitating better perception of organ's anatomy during preparation and execution of liver surgeries. Additionally, it may help to reduce the incidence of intraoperative biliary duct damage due to an unanticipated variation in the anatomy.

Accurate surgical navigation with real-time tumor tracking in cancer surgery.

In the past decades, image-guided surgery has evolved rapidly. In procedures with a relatively fixed target area, like neurosurgery and orthopedics, this has led to improved patient outcomes. In cancer surgery, intraoperative guidance could be of great benefit to secure radical resection margins since residual disease is associated with local recurrence and poor survival. However, most tumor lesions are mobile with a constantly changing position. Here, we present an innovative technique for real-time tumor tracking in cancer surgery. In this study, we evaluated the feasibility of real-time tumor tracking during rectal cancer surgery. The application of real-time tumor tracking using an intraoperative navigation system is feasible and safe with a high median target registration accuracy of 3 mm. This technique allows oncological surgeons to obtain real-time accurate information on tumor location, as well as critical anatomical information. This study demonstrates that real-time tumor tracking is feasible and could potentially decrease positive resection margins and improve patient outcome.

High-resolution clustered pinhole (131)Iodine SPECT imaging in mice.

INTRODUCTION: High-resolution pre-clinical (131)I SPECT can facilitate development of new radioiodine therapies for cancer. To this end, it is important to limit resolution-degrading effects of pinhole edge penetration by the high-energy γ-photons of iodine. Here we introduce, optimize and validate (131)I SPECT performed with a dedicated high-energy clustered multi-pinhole collimator. METHODS: A SPECT-CT system (VECTor/CT) with stationary gamma-detectors was equipped with a tungsten collimator with clustered pinholes. Images were reconstructed with pixel-based OSEM, using a dedicated (131)I system matrix that models the distance- and energy-dependent resolution and sensitivity of each pinhole, as well as the intrinsic detector blurring and variable depth of interaction in the detector. The system performance was characterized with phantoms and in vivo static and dynamic (131)I-NaI scans of mice. RESULTS: Reconstructed image resolution reached 0.6mm, while quantitative accuracy measured with a (131)I filled syringe reaches an accuracy of +3.6±3.5% of the gold standard value. In vivo mice scans illustrated a clear shape of the thyroid and biodistribution of (131)I within the animal. Pharmacokinetics of (131)I was assessed with 15-s time frames from the sequence of dynamic images and time-activity curves of (131)I-NaI. CONCLUSIONS: High-resolution quantitative and fast dynamic (131)I SPECT in mice is possible by means of a high-energy collimator and optimized system modeling. This enables analysis of (131)I uptake even within small organs in mice, which can be highly valuable for development and optimization of targeted cancer therapies.

Ultra-high-sensitivity submillimeter mouse SPECT.

UNLABELLED: SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide range of new imaging protocols such as screening tracers with initially low yield or labeling efficiency, imaging low receptor densities, or even performing SPECT outside regular radiation laboratories. To this end we developed dedicated ultra-high-sensitivity pinhole SPECT. METHODS: A cylindric collimator with 54 focused 2.0-mm-diameter conical pinholes was manufactured and mounted in a stationary small-animal SPECT system. The system matrix for image reconstruction was calculated via a hybrid method based on both (99m)Tc point source measurements and ray-tracing analytic modeling. SPECT images were reconstructed using pixel-based ordered-subsets expectation maximization. Performance was evaluated with phantoms and low-dose bone, dynamic kidney, and cardiac mouse scans. RESULTS: The peak sensitivity reached 1.3% (13,080 cps/MBq). The reconstructed spatial resolution (rod visibility in a micro-Jaszczak phantom) was 0.85 mm. Even with only a quarter megabecquerel of activity, 30-min bone SPECT scans provided surprisingly high levels of detail. Dynamic dual-isotope kidney and (99m)Tc-sestamibi cardiac scans were acquired with a time-frame resolution down to 1 s. CONCLUSION: The high sensitivity achieved increases the range of mouse SPECT applications by enabling in vivo imaging with less than a megabecquerel of tracer activity or down to 1-s frame dynamics.