Alternative intraoperative optical imaging modalities for fluorescence angiography in gastrointestinal surgery: spectral imaging and imaging photoplethysmography.

INTRODUCTION: Intraoperative near-infrared fluorescence angiography with indocyanine green (ICG-FA) is a well-established modality in gastrointestinal surgery. Its main drawback is the application of a fluorescent agent with possible side effects for patients. The goal of this review paper is the presentation of alternative, non-invasive optical imaging methods and their comparison with ICG-FA. MATERIAL AND METHODS: The principles of ICG-FA, spectral imaging, imaging photoplethysmography (iPPG), and their applications in gastrointestinal surgery are described based on selected published works. RESULTS: The main applications of the three modalities are the evaluation of tissue perfusion, the identification of risk structures, and tissue segmentation or classification. While the ICG-FA images are mainly evaluated visually, leading to subjective interpretations, quantitative physiological parameters and tissue segmentation are provided in spectral imaging and iPPG. The combination of ICG-FA and spectral imaging is a promising method. CONCLUSIONS: Non-invasive spectral imaging and iPPG have shown promising results in gastrointestinal surgery. They can overcome the main drawbacks of ICG-FA, i.e. the use of contrast agents, the lack of quantitative analysis, repeatability, and a difficult standardization of the acquisition. Further technical improvements and clinical evaluations are necessary to establish them in daily clinical routine.

MRI-guided lumbar spinal injections with body-mounted robotic system: cadaver studies.

INTRODUCTION: This paper reports the system integration and cadaveric assessment of a body-mounted robotic system for MRI-guided lumbar spine injections. The system is developed to enable MR-guided interventions in closed bore magnet and avoid problems due to patient movement during cannula guidance. MATERIAL AND METHODS: The robot is comprised by a lightweight and compact structure so that it can be mounted directly onto the lower back of a patient using straps. Therefore, it can minimize the influence of patient movement by moving with the patient. The MR-Conditional robot is integrated with an image-guided surgical planning workstation. A dedicated clinical workflow is created for the robot-assisted procedure to improve the conventional freehand MRI-guided procedure. RESULTS: Cadaver studies were performed with both freehand and robot-assisted approaches to validate the feasibility of the clinical workflow and to assess the positioning accuracy of the robotic system. The experiment results demonstrate that the root mean square (RMS) error of the target position to be 2.57 ± 1.09 mm and of the insertion angle to be 2.17 ± 0.89°. CONCLUSION: The robot-assisted approach is able to provide more accurate and reproducible cannula placements than the freehand procedure, as well as to reduce the number of insertion attempts.

Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage.

PURPOSE: High-intensity focused ultrasound (HIFU/FUS) has expanded as a noninvasive quantifiable option for hyperthermia (HT). HT in a temperature range of 40-47 °C (thermal dose CEM43 ≥ 25) could work as a sensitizer to radiation therapy (RT). Here, we attempted to understand the tumor radiosensitization effect at the cellular level after a combination treatment of FUS+RT. METHODS: An in vitro FUS system was developed to induce HT at frequencies of 1.147 and 1.467 MHz. Human head and neck cancer (FaDU), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS in ultrasound-penetrable 96-well plates followed by single-dose X­ray irradiation (10 Gy). Radiosensitizing effects of FUS were investigated by cell metabolic activity (WST­1 assay), apoptosis (annexin V assay, sub-G1 assay), cell cycle phases (propidium iodide staining), and DNA double-strand breaks (γH2A.X assay). RESULTS: The FUS intensities of 213 (1.147 MHz) and 225 W/cm2 (1.467 MHz) induced HT for 30 min at mean temperatures of 45.20 ± 2.29 °C (CEM43 = 436 ± 88) and 45.59 ± 1.65 °C (CEM43 = 447 ± 79), respectively. FUS improves the effect of RT significantly by reducing metabolic activity in T98G cells 48 h (RT: 96.47 ± 8.29%; FUS+RT: 79.38 ± 14.93%; p = 0.012) and in PC-3 cells 72 h (54.20 ± 10.85%; 41.01 ± 11.17%; p = 0.016) after therapy, but not in FaDu cells. Mechanistically, FUS+RT leads to increased apoptosis and enhancement of DNA double-strand breaks compared to RT alone in T98G and PC-3 cells. CONCLUSION: Our in vitro findings demonstrate that FUS has good potential to sensitize glioblastoma and prostate cancer cells to RT by mainly enhancing DNA damage.

Practical setting and potential applications of interventions guided by PET/MRI.

Multimodality imaging has emerged from a vision thirty years ago to routine clinical use today. Positron emission tomography (PET)/magnetic resonance imaging (MRI) is still relatively new in this arena and particularly suitable for clinical research and technical development. PET/MRI-guidance for interventions opens up opportunities for novel treatments but at the same time demands certain technical and organizational requirements to be fulfilled. In this work, we aimed to demonstrate a practical setting and potential application of PET/MRI guidance of interventional procedures. The superior quantitative physiologic information of PET, the various unique imaging characteristics of MRI, and the reduced radiation exposure are the most relevant advantages of this technique. As a noninvasive interventional tool, focused ultrasound (FUS) ablation of tumor cells would benefit from PET/MRI for diagnostics, treatment planning and intervention. Yet, technical limitations might impeed preclinical research, given that PET/MRI sites are per se not designed as interventional suites. Nonetheless, several approaches have been offered in the past years to upgrade MRI suites for interventional purposes. Taking advantage of state of the art and easy-to-use technology it is possible to create a supporting infrastructure that is suitable for broad preclinical adaption. Several aspects are to be addressed, including remote control of the imaging system, display of the imaging results, communication technology, and implementation of additional devices such as a FUS platform and an MR-compatible robotic system for positioning of the FUS equipment. Feasibility could be demostrated with an examplary experimental setup for interventional PET/MRI. Most PET/MRI sites could allow for interventions with just a few add-ons and modifications, such as comunication, in room image display and sytems control. By unlocking this feature, and driving preclinical research in interventional PET/MRI, translation of the protocol and methodology into clinical settings seems feasible.

MR-guided focused ultrasound application for moving target tumor ablation in abdominal area: coil selection.

BACKGROUND: Magnetic Resonance Imaging (MRI)-guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive thermal ablation method utilizing high-intensity focused ultrasound (HI-FU) energy for tissue ablation under MRI with real-time thermal mapping. Ablating to a dynamic target as in the liver is very challenging, requiring approval. A novel quality-assured liver tumor ablation system has been proposed for clinics. The paper reports the evaluation of conventional and new MR-receiving coils. PURPOSE: To evaluate the suitability of MR coils as part of the MRgFUS treatment system for liver, while simulating breathing motion in pre-clinical settings. MATERIAL AND METHODS: The novel software communicates with the MR scanner and the transducer. To monitor the temperature via proton resonance frequency (PRF) methodology echo planar imaging (EPI) sequence was used while the algorithms of static, static and dynamic tracking were tested with sonications of 100 W for 30 s on tissue-mimicking phantoms. Different coil sets were used to assess the performance of the system for fitness for dynamic thermometry. Finally, in vivo experiments were performed over a porcine model. RESULTS: Single-loop four-channel Duoflex and Gem coils provided adequate signal-to-noise ratio and contrast with consistent thermal readings. Body array coils showed severe loss of signal in dynamic cases since the integration of tracking algorithm causes low efficiency. CONCLUSION: Body array coils are unsuitable for MRgFUS of the liver due to signal loss. The dedicated coil set with a single loop around the FUS transducer combined with four-channel arrays might be the best option for liver treatment using dynamic MRgFUS applications.

Patient-Specific 3-Dimensional Model for High-Intensity Focused Ultrasound Treatment Through the Rib Cage: A Preliminary Study.

OBJECTIVES: The purpose of this study was to develop a patient-specific 3-dimensional model for high-intensity focused ultrasound (HIFU) treatment through the rib cage using patient data. METHODS: Experimental testing to derive parameters used in defining the amount of energy and alteration needed in treatment protocols for upper abdominal disorders under the rib cage was performed. Reconstructed rib cage models based on patient data, tissue-mimicking material phantoms, and magnetic resonance imaging-guided HIFU using a multielement phased array transducer were used in the experiments. Changes in the focal temperature, acoustic power, and acoustic pressure distribution were investigated with and without the presence of the rib cage model. An ExAblate system (InSightec Ltd, Tirat Carmel, Israel) was used to sonicate phantoms by varying the target phantom or rib cage model location. RESULTS: The effect of the rib cage on the acoustic pressure distribution and acoustic power was closely related to the anatomic structures of the ribs. Thermometry revealed that heating at the focus could be controlled by changing either the power or duration of HIFU application to improve the focal temperature change. The focal temperature change was found to be related to the distance between the rib cage model and focus and the shadow area on the transducer elements covered by the rib cage model in the beam path. CONCLUSIONS: Experimental results suggest that the rib cage model is a valuable and useful tool that can provide realistic human anatomic structures and properties for evaluating the effects of the rib cage on ultrasound propagation.

Evaluation of hyperspectral imaging (HSI) for the measurement of ischemic conditioning effects of the gastric conduit during esophagectomy.

BACKGROUND: Hyperspectral imaging (HSI) is a relatively new method used in image-guided and precision surgery, which has shown promising results for characterization of tissues and assessment of physiologic tissue parameters. Previous methods used for analysis of preconditioning concepts in patients and animal models have shown several limitations of application. The aim of this study was to evaluate HSI for the measurement of ischemic conditioning effects during esophagectomy. METHODS: Intraoperative hyperspectral images of the gastric tube through the mini-thoracotomy were recorded from n = 22 patients, 14 of whom underwent laparoscopic gastrolysis and ischemic conditioning of the stomach with two-step transthoracic esophagectomy and gastric pull-up with intrathoracic anastomosis after 3-7 days. The tip of the gastric tube (later esophagogastric anastomosis) was measured with HSI. Analysis software provides a RGB image and 4 false color images representing physiologic parameters of the recorded tissue area intraoperatively. These parameters contain tissue oxygenation (StO2), perfusion-(NIR Perfusion Index), organ hemoglobin (OHI), and tissue water index (TWI). RESULTS: Intraoperative HSI of the gastric conduit was possible in all patients and did not prolong the regular operative procedure due to its quick applicability. In particular, the tissue oxygenation of the gastric conduit was significantly higher in patients who underwent ischemic conditioning ([Formula: see text] = 78%; [Formula: see text] = 66%; p = 0.03). CONCLUSIONS: HSI is suitable for contact-free, non-invasive, and intraoperative evaluation of physiological tissue parameters within gastric conduits. Therefore, HSI is a valuable method for evaluating ischemic conditioning effects and may contribute to reduce anastomotic complications. Additional studies are needed to establish normal values and thresholds of the presented parameters for the gastric conduit anastomotic site.

Reference-less MR thermometry on pre-clinical thiel human cadaver for liver surgery with MRgFUS.

PURPOSE: Reference-less MR thermometry can be a promising technique for temperature mapping during liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS), as it is more robust to breathing motion than Proton Resonance Frequency MR thermometry. However, there is a lack of a pre-clinical model for repeatable testing of reference-less thermometry. The purpose of this work was to verify the explanted Thiel embalmed human liver and whole Thiel embalmed human cadaver for application of a custom made reference-less thermometry algorithm during MRgFUS sonication. MATERIAL AND METHODS: Phase maps were generated during sonication as an input to the algorithm. A square Region-of-Interest (ROI) was designed around the heated area. The ROI was interpolated using a two-dimensional polynomial to the surrounding phase map to calculate the background phase. RESULTS: Using the phase information from the images, the temperature rise was measured. Validation of the methodology showed accordance of temperatures with actual temperatures. CONCLUSIONS: The explanted liver and the whole cadaver constitute a promising and feasible model to study reference-less techniques for thermometry during MRgFUS, before clinical trials.

Principles of focused ultrasound.

Focused ultrasound (FUS/HIFU) relies on ablation of pathological tissues by delivering a sufficiently high level of acoustic energy in situ of the human body. Magnetic Resonance guided FUS (MRgFUS/HIFU) and Ultrasound guided (USgFUS/HIFU) are image guided techniques combined with therapeutic FUS for monitoring purposes. The principles and technologies of FUS/HiFU are described in this paper including the basics of MR guidance techniques and MR temperature mapping. Clinical applications of FUS/HIFU gained CE and FDA approvals for the treatment of various benign and few malignant lesions in the last two decades. Current technical limitations of ultrasound guided and MRI guided Focused Ultrasound, as well as adverse effects for the application of this technique are outlined including challenges of ablating moving organs (liver and kidney). An outlook to possible applications is provided; exampling clinical trials discussing future options.

Acoustic characterization of Thiel liver for magnetic resonance-guided focused ultrasound treatment.

BACKGROUND: The purpose of this work was to measure the essential acoustic parameters, i.e., acoustic impedance, reflection coefficient, attenuation coefficient, of Thiel embalmed human and animal liver. The Thiel embalmed tissue can be a promising, pre-clinical model to study liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS). MATERIAL AND METHODS: Using a single-element transducer and the contact pulse-echo method, the acoustic parameters, i.e., acoustic impedance, reflection coefficient and attenuation coefficient of Thiel embalmed human and animal liver were measured. RESULTS: The Thiel embalmed livers had higher impedance, similar reflection and lower attenuation compared to the fresh tissue. CONCLUSIONS: Embalming liver with Thiel fluid affects its acoustic properties. During MRgFUS sonication of a Thiel organ, more focused ultrasound (FUS) will be backscattered by the organ, and higher acoustic powers are required to reach coagulation levels (temperatures >56 °C).

Evidence-based cross validation for acoustic power transmission for a novel treatment system.

INTRODUCTION: The novel Trans-Fusimo Treatment System (TTS) is designed to control Magnetic Resonance guided Focused Ultrasound (MRgFUS) therapy to ablate liver tumours under respiratory motion. It is crucial to deliver the acoustic power within tolerance limits for effective liver tumour treatment via MRgFUS. Before application in a clinical setting, evidence of reproducibility and reliability is a must for safe practice. MATERIALS AND METHODS: The TTS software delivers the acoustic power via ExAblate-2100 Conformal Bone System (CBS) transducer. A built-in quality assurance application was developed to measure the force values, using a novel protocol to measure the efficiency for the electrical power values of 100 and 150W for 6s of sonication. This procedure was repeated 30 times by two independent users against the clinically approved ExAblate-2100 CBS for cross-validation. RESULTS: Both systems proved to deliver the power within the accepted efficiency levels (70-90%). Two sample t-tests were used to assess the differences in force values between the ExAblate-2100 CBS and the TTS (p > 0.05). Bland-Altman plots were used to demonstrate the limits of agreement between the two systems falling within the 10% limits of agreement. Two sample t-tests indicated that TTS does not have user dependency (p > 0.05). CONCLUSIONS: The TTS software proved to deliver the acoustic power without exceeding the safety levels. Results provide evidence as a part of ISO13485 regulations for CE marking purposes. The developed methodology could be utilised as a part of quality assurance system in clinical settings; when the TTS is used in clinical practice.

Workflow optimisation for multimodal imaging procedures: a case of combined X-ray and MRI-guided TACE.

This study presents a framework for workflow optimisation of multimodal image-guided procedures (MIGP) based on discrete event simulation (DES). A case of a combined X-Ray and magnetic resonance image-guided transarterial chemoembolisation (TACE) is presented to illustrate the application of this method. We used a ranking and selection optimisation algorithm to measure the performance of a number of proposed alternatives to improve a current scenario. A DES model was implemented with detail data collected from 59 TACE procedures and durations of magnetic resonance imaging (MRI) diagnostic procedures usually performed in a common MRI suite. Fourteen alternatives were proposed and assessed to minimise the waiting times and improve workflow. Data analysis observed an average of 20.68 (7.68) min of waiting between angiography and MRI for TACE patients in 71.19% of the cases. Following the optimisation analysis, an alternative was identified to reduce waiting times in angiography suite up to 48.74%. The model helped to understand and detect 'bottlenecks' during multimodal TACE procedures, identifying a better alternative to the current workflow and reducing waiting times. Simulation-based workflow analysis provides a cost-effective way to face some of the challenges of introducing MIGP in clinical radiology, highligthed in this study.

Workflow and intervention times of MR-guided focused ultrasound - Predicting the impact of new techniques.

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has become an attractive, non-invasive treatment for benign and malignant tumours, and offers specific benefits for poorly accessible locations in the liver. However, the presence of the ribcage and the occurrence of liver motion due to respiration limit the applicability MRgFUS. Several techniques are being developed to address these issues or to decrease treatment times in other ways. However, the potential benefit of such improvements has not been quantified. In this research, the detailed workflow of current MRgFUS procedures was determined qualitatively and quantitatively by using observation studies on uterine MRgFUS interventions, and the bottlenecks in MRgFUS were identified. A validated simulation model based on discrete events simulation was developed to quantitatively predict the effect of new technological developments on the intervention duration of MRgFUS on the liver. During the observation studies, the duration and occurrence frequencies of all actions and decisions in the MRgFUS workflow were registered, as were the occurrence frequencies of motion detections and intervention halts. The observation results show that current MRgFUS uterine interventions take on average 213min. Organ motion was detected on average 2.9 times per intervention, of which on average 1.0 actually caused a need for rework. Nevertheless, these motion occurrences and the actions required to continue after their detection consumed on average 11% and up to 29% of the total intervention duration. The simulation results suggest that, depending on the motion occurrence frequency, the addition of new technology to automate currently manual MRgFUS tasks and motion compensation could potentially reduce the intervention durations by 98.4% (from 256h 5min to 4h 4min) in the case of 90% motion occurrence, and with 24% (from 5h 19min to 4h 2min) in the case of no motion. In conclusion, new tools were developed to predict how intervention durations will be affected by future workflow changes and by the introduction of new technology.

Feasibility study of pre-clinical Thiel embalmed human cadaver for MR-guided focused ultrasound of the spine.

BACKGROUND: Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive treatment option based on high acoustic absorption and minimal thermal conductivity of the bone to destroy nerves and reduce pain. There is lack of a preclinical validation tool with correct human anatomy. This work introduces usage of an ex-vivo Thiel embalmed human tissue model for preclinical verification of MRgFUS on intervertebral discs or bone metastases within the spinal body. MATERIAL AND METHODS: Thiel embalmed human cadaver was subjected to FUS sonication of the vertebra (with energies 250J, 420J, 600J) and the intervertebral disc (with energies 310J, 610J, 950J) of the lumbar spine for 20s of sonication under MR guidance. RESULTS: For the vertebra, maximum temperatures were recorded as 38 °C, 58.3 °C, 69 °C. The intervertebral disc reached maximum temperatures of 23.7 °C, 54 °C, 83 °C. The temperature measurements showed that the spinal canal and adjacent organs were not heated > 0.1 °C. CONCLUSIONS: A heating pattern that can induce thermal ablation was achieved in the vertebral body and the intervertebral disc. Adjacent structures and nerves were not heated in lethal levels. Thus, the Thiel embalmed human cadaver can be a safe and efficient model for preclinical study of application of MRgFUS on the upper lumbar spine.

Measurement of proton resonance frequency shift coefficient during MR-guided focused ultrasound on Thiel embalmed tissue.

PURPOSE: To estimate the value of proton resonance frequency (PRF) shift coefficient of explanted Thiel embalmed animal and human tissue used as a preclinical model for treatment with MR-guided focused ultrasound (FUS). METHODS: Thiel embalmed human liver, ovine liver, and porcine muscle were heated using two methods: bulk heating and FUS-induced heating. Phase-referenced PRF thermometry was applied during cooling of the tissue to obtain a series of phase difference, ΔΦ, maps. A fiber-optic thermocouple was inserted in the tissue to measure the temperature difference, ΔT. The PRF shift coefficient was calculated from the measured ΔΦ, ΔT. RESULTS: In the case of bulk heating, the mean values (±SD) of the PRF coefficient for Thiel embalmed ovine liver, porcine muscle, and human liver were: 0.017 (5 × 10-4 ) ppm/°C, 0.015 (6 × 10-4 ) ppm/°C, and 0.012 (6 × 10-4 ) ppm/°C, respectively. Similar values were found in tissues heated with FUS. CONCLUSION: The values of PRF coefficient measured for the Thiel embalmed tissue were higher than the values for fresh tissue, suggesting that embalming a tissue with Thiel fluid can affect PRF thermometry. The chemical composition of the Thiel fluid and the electrical conductivity may explain these results. Magn Reson Med 74:260-265, 2015. © 2014 Wiley Periodicals, Inc.

European Association of Endoscopic Surgeons (EAES) consensus statement on the use of robotics in general surgery.

Following an extensive literature search and a consensus conference with subject matter experts the following conclusions can be drawn: 1. Robotic surgery is still at its infancy, and there is a great potential in sophisticated electromechanical systems to perform complex surgical tasks when these systems evolve. 2. To date, in the vast majority of clinical settings, there is little or no advantage in using robotic systems in general surgery in terms of clinical outcome. Dedicated parameters should be addressed, and high quality research should focus on quality of care instead of routine parameters, where a clear advantage is not to be expected. 3. Preliminary data demonstrates that robotic system have a clinical benefit in performing complex procedures in confined spaces, especially in those that are located in unfavorable anatomical locations. 4. There is a severe lack of high quality data on robotic surgery, and there is a great need for rigorously controlled, unbiased clinical trials. These trials should be urged to address the cost-effectiveness issues as well. 5. Specific areas of research should include complex hepatobiliary surgery, surgery for gastric and esophageal cancer, revisional surgery in bariatric and upper GI surgery, surgery for large adrenal masses, and rectal surgery. All these fields show some potential for a true benefit of using current robotic systems. 6. Robotic surgery requires a specific set of skills, and needs to be trained using a dedicated, structured training program that addresses the specific knowledge, safety issues and skills essential to perform this type of surgery safely and with good outcomes. It is the responsibility of the corresponding professional organizations, not the industry, to define the training and credentialing of robotic basic skills and specific procedures. 7. Due to the special economic environment in which robotic surgery is currently employed special care should be taken in the decision making process when deciding on the purchase, use and training of robotic systems in general surgery. 8. Professional organizations in the sub-specialties of general surgery should review these statements and issue detailed, specialty-specific guidelines on the use of specific robotic surgery procedures in addition to outlining the advanced robotic surgery training required to safely perform such procedures.

An integrated model-based software for FUS in moving abdominal organs.

Focused ultrasound surgery (FUS) is a non-invasive method for tissue ablation that has the potential for complete and controlled local tumour destruction with minimal side effects. The treatment of abdominal organs such as the liver, however, requires particular technological support in order to enable a safe, efficient and effective treatment. As FUS is applied from outside the patient's body, suitable imaging methods, such as magnetic resonance imaging or diagnostic ultrasound, are needed to guide and track the procedure. To facilitate an efficient FUS procedure in the liver, the organ motion during breathing and the partial occlusion by the rib cage need to be taken into account in real time, demanding a continuous patient-specific adaptation of the treatment configuration. Modelling the patient's respiratory motion and combining this with tracking data improves the accuracy of motion predictions. Modelling and simulation of the FUS effects within the body allows the use of treatment planning and has the potential to be used within therapy to increase knowledge about the patient status. This article describes integrated model-based software for patient-specific modelling and prediction for FUS treatments of moving abdominal organs.