A Review on Advances in Intra-operative Imaging for Surgery and Therapy: Imagining the Operating Room of the Future

none4openZaffino, Paolo; Moccia, Sara; De Momi, Elena; Spadea, Maria FrancescaZaffino, Paolo; Moccia, Sara; De Momi, Elena; Spadea, Maria Francesc

Intraoperative Navigation Systems for Image-Guided Surgery

Recent technological advancements in medical imaging equipment have resulted in a dramatic improvement of image accuracy, now capable of providing useful information previously not available to clinicians. In the surgical context, intraoperative imaging provides a crucial value for the success of the operation. Many nontrivial scientific and technical problems need to be addressed in order to efficiently exploit the different information sources nowadays available in advanced operating rooms. In particular, it is necessary to provide: (i) accurate tracking of surgical instruments, (ii) real-time matching of images from different modalities, and (iii) reliable guidance toward the surgical target. Satisfying all of these requisites is needed to realize effective intraoperative navigation systems for image-guided surgery. Various solutions have been proposed and successfully tested in the field of image navigation systems in the last ten years; nevertheless several problems still arise in most of the applications regarding precision, usability and capabilities of the existing systems. Identifying and solving these issues represents an urgent scientific challenge. This thesis investigates the current state of the art in the field of intraoperative navigation systems, focusing in particular on the challenges related to efficient and effective usage of ultrasound imaging during surgery. The main contribution of this thesis to the state of the art are related to: Techniques for automatic motion compensation and therapy monitoring applied to a novel ultrasound-guided surgical robotic platform in the context of abdominal tumor thermoablation. Novel image-fusion based navigation systems for ultrasound-guided neurosurgery in the context of brain tumor resection, highlighting their applicability as off-line surgical training instruments. The proposed systems, which were designed and developed in the framework of two international research projects, have been tested in real or simulated surgical scenarios, showing promising results toward their application in clinical practice

Prospects for Theranostics in Neurosurgical Imaging: Empowering Confocal Laser Endomicroscopy Diagnostics via Deep Learning

Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence imaging technology that has the potential to increase intraoperative precision, extend resection, and tailor surgery for malignant invasive brain tumors because of its subcellular dimension resolution. Despite its promising diagnostic potential, interpreting the gray tone fluorescence images can be difficult for untrained users. In this review, we provide a detailed description of bioinformatical analysis methodology of CLE images that begins to assist the neurosurgeon and pathologist to rapidly connect on-the-fly intraoperative imaging, pathology, and surgical observation into a conclusionary system within the concept of theranostics. We present an overview and discuss deep learning models for automatic detection of the diagnostic CLE images and discuss various training regimes and ensemble modeling effect on the power of deep learning predictive models. Two major approaches reviewed in this paper include the models that can automatically classify CLE images into diagnostic/nondiagnostic, glioma/nonglioma, tumor/injury/normal categories and models that can localize histological features on the CLE images using weakly supervised methods. We also briefly review advances in the deep learning approaches used for CLE image analysis in other organs. Significant advances in speed and precision of automated diagnostic frame selection would augment the diagnostic potential of CLE, improve operative workflow and integration into brain tumor surgery. Such technology and bioinformatics analytics lend themselves to improved precision, personalization, and theranostics in brain tumor treatment.Comment: See the final version published in Frontiers in Oncology here: https://www.frontiersin.org/articles/10.3389/fonc.2018.00240/ful

Comparison of the Effectiveness of Two Types of Single Port Minimal Invasive Neurosurgical Robots to Ablation and Resection of Brain Tumor

Background: Using minimally invasive neurosurgical robots is one of the most desirable ablation methods and resection of brain tumors. In this study, forward kinematics and Jacobian matrix calculated for two single-port robots for comparing the effectiveness of two types of single port minimal invasive surgical robots to ablation and resection of brain tumorMethods: The motion analysis of robots type 1 and 2 has compared to each other. Ablation manipulator in robot type 1 has five degrees of freedom, but in robot type 2, three revolute degrees of freedom of this manipulator has replaced with a revolute joint perpendicular to the previous three revolute joints.Results: Results showed that for resection surgery, in the same conditions, robot type 2 damaged 58.9 mm3 more of cerebral cortex tissue than robot type 1 to resect the brain tumors. To establish a static balance, robot type 2 needs to tolerate at least 41% more internal loading than robot type 1. The maximum velocity for robot type 1 in the contact location between the end-effector and the tumor is 1.7 times more than robot type 2. The maximum end-effector force of robot type 1 to apply the tumor for ablation surgery is more than 1.8 times in robot type 2, but the maximum moment and power for ablation surgery and resection of these two robots were the same less than 1% difference.Conclusion: Despite the more straightforward mechanism, a minimum number of joints, and better kinematics range of robot type 2, robot types 1 has the possibility for transformation, establishes the static balancing, and does a better ablation surgery with less damage to the brain

SURGICAL NAVIGATION AND AUGMENTED REALITY FOR MARGINS CONTROL IN HEAD AND NECK CANCER

I tumori maligni del distretto testa-collo rappresentano un insieme di lesioni dalle diverse caratteristiche patologiche, epidemiologiche e prognostiche. Per una porzione considerevole di tali patologie, l’intervento chirurgico finalizzato all’asportazione completa del tumore rappresenta l’elemento chiave del trattamento, quand’anche esso includa altre modalità quali la radioterapia e la terapia sistemica. La qualità dell’atto chirurgico ablativo è pertanto essenziale al fine di garantire le massime chance di cura al paziente. Nell’ambito della chirurgia oncologica, la qualità delle ablazioni viene misurata attraverso l’analisi dello stato dei margini di resezione. Oltre a rappresentare un surrogato della qualità della resezione chirurgica, lo stato dei margini di resezione ha notevoli implicazioni da un punto di vista clinico e prognostico. Infatti, il coinvolgimento dei margini di resezione da parte della neoplasia rappresenta invariabilmente un fattore prognostico sfavorevole, oltre che implicare la necessità di intensificare i trattamenti postchirurgici (e.g., ponendo indicazione alla chemioradioterapia adiuvante), comportando una maggiore tossicità per il paziente. La proporzione di resezioni con margini positivi (i.e., coinvolti dalla neoplasia) nel distretto testa-collo è tra le più elevate in ambito di chirurgia oncologica. In tale contesto si pone l’obiettivo del dottorato di cui questa tesi riporta i risultati. Le due tecnologie di cui si è analizzata l’utilità in termini di ottimizzazione dello stato dei margini di resezione sono la navigazione chirurgica con rendering tridimensionale e la realtà aumentata basata sulla videoproiezione di immagini. Le sperimentazioni sono state svolte parzialmente presso l’Università degli Studi di Brescia, parzialmente presso l’Azienda Ospedale Università di Padova e parzialmente presso l’University Health Network (Toronto, Ontario, Canada). I risultati delle sperimentazioni incluse in questo elaborato dimostrano che l'impiego della navigazione chirurgica con rendering tridimensionale nel contesto di procedure oncologiche ablative cervico-cefaliche risulta associata ad un vantaggio significativo in termini di riduzione della frequenza di margini positivi. Al contrario, le tecniche di realtà aumentata basata sulla videoproiezione, nell'ambito della sperimentazione preclinica effettuata, non sono risultate associate a vantaggi sufficienti per poter considerare tale tecnologia per la traslazione clinica.Head and neck malignancies are an heterogeneous group of tumors. Surgery represents the mainstay of treatment for the large majority of head and neck cancers, with ablation being aimed at removing completely the tumor. Radiotherapy and systemic therapy have also a substantial role in the multidisciplinary management of head and neck cancers. The quality of surgical ablation is intimately related to margin status evaluated at a microscopic level. Indeed, margin involvement has a remarkably negative effect on prognosis of patients and mandates the escalation of postoperative treatment by adding concomitant chemotherapy to radiotherapy and accordingly increasing the toxicity of overall treatment. The rate of margin involvement in the head and neck is among the highest in the entire field of surgical oncology. In this context, the present PhD project was aimed at testing the utility of 2 technologies, namely surgical navigation with 3-dimensional rendering and pico projector-based augmented reality, in decreasing the rate of involved margins during oncologic surgical ablations in the craniofacial area. Experiments were performed in the University of Brescia, University of Padua, and University Health Network (Toronto, Ontario, Canada). The research activities completed in the context of this PhD course demonstrated that surgical navigation with 3-dimensional rendering confers a higher quality to oncologic ablations in the head and neck, irrespective of the open or endoscopic surgical technique. The benefits deriving from this implementation come with no relevant drawbacks from a logistical and practical standpoint, nor were major adverse events observed. Thus, implementation of this technology into the standard care is the logical proposed step forward. However, the genuine presence of a prognostic advantage needs longer and larger study to be formally addressed. On the other hand, pico projector-based augmented reality showed no sufficient advantages to encourage translation into the clinical setting. Although observing a clear practical advantage deriving from the projection of osteotomy lines onto the surgical field, no substantial benefits were measured when comparing this technology with surgical navigation with 3-dimensional rendering. Yet recognizing a potential value of this technology from an educational standpoint, the performance displayed in the preclinical setting in terms of surgical margins optimization is not in favor of a clinical translation with this specific aim

Intraoperative molecular imaging clinical trials: a review of 2020 conference proceedings

Significance: Surgery is often paramount in the management of many solid organ malignancies because optimal resection is a major factor in disease-specific survival. Cancer surgery has multiple challenges including localizing small lesions, ensuring negative surgical margins around a tumor, adequately staging patients by discriminating positive lymph nodes, and identifying potential synchronous cancers. Intraoperative molecular imaging (IMI) is an emerging potential tool proposed to address these issues. IMI is the process of injecting patients with fluorescenttargeted contrast agents that highlight cancer cells prior to surgery. Over the last 5 to 7 years, enormous progress has been achieved in tracer development, near-infrared camera approvals, and clinical trials. Therefore, a second biennial conference was organized at the University of Pennsylvania to gather surgical oncologists, scientists, and experts to discuss new investigative findings in the field. Our review summarizes the discussions from the conference and highlights findings in various clinical and scientific trials.Aim: Recent advances in IMI were presented, and the importance of each clinical trial for surgical oncology was critically assessed. A major focus was to elaborate on the clinical endpoints that were being utilized in IMI trials to advance the respective surgical subspecialties.Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's second clinical trials update on IMI were selected to discuss their clinical trials and endpoints.Results: Multiple phase III, II, and I trials were discussed during the conference. Since the approval of 5-ALA for commercial use in neurosurgical malignancies, multiple tracers and devices have been developed to address common challenges faced by cancer surgeons across numerous specialties. Discussants also presented tracers that are being developed for delineation of normal anatomic structures that can serve as an adjunct during surgical procedures.Conclusions: IMI is increasingly being recognized as an improvement to standard oncologic surgical resections and will likely advance the art of cancer surgery in the coming years. The endpoints in each individual surgical subspecialty are varied depending on how IMI helps each specialty solve their clinical challenges. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.Surgical oncolog

Multimodal optical systems for clinical oncology

This thesis presents three multimodal optical (light-based) systems designed to improve the capabilities of existing optical modalities for cancer diagnostics and theranostics. Optical diagnostic and therapeutic modalities have seen tremendous success in improving the detection, monitoring, and treatment of cancer. For example, optical spectroscopies can accurately distinguish between healthy and diseased tissues, fluorescence imaging can light up tumours for surgical guidance, and laser systems can treat many epithelial cancers. However, despite these advances, prognoses for many cancers remain poor, positive margin rates following resection remain high, and visual inspection and palpation remain crucial for tumour detection. The synergistic combination of multiple optical modalities, as presented here, offers a promising solution. The first multimodal optical system (Chapter 3) combines Raman spectroscopic diagnostics with photodynamic therapy using a custom-built multimodal optical probe. Crucially, this system demonstrates the feasibility of nanoparticle-free theranostics, which could simplify the clinical translation of cancer theranostic systems without sacrificing diagnostic or therapeutic benefit. The second system (Chapter 4) applies computer vision to Raman spectroscopic diagnostics to achieve spatial spectroscopic diagnostics. It provides an augmented reality display of the surgical field-of-view, overlaying spatially co-registered spectroscopic diagnoses onto imaging data. This enables the translation of Raman spectroscopy from a 1D technique to a 2D diagnostic modality and overcomes the trade-off between diagnostic accuracy and field-of-view that has limited optical systems to date. The final system (Chapter 5) integrates fluorescence imaging and Raman spectroscopy for fluorescence-guided spatial spectroscopic diagnostics. This facilitates macroscopic tumour identification to guide accurate spectroscopic margin delineation, enabling the spectroscopic examination of suspicious lesions across large tissue areas. Together, these multimodal optical systems demonstrate that the integration of multiple optical modalities has potential to improve patient outcomes through enhanced tumour detection and precision-targeted therapies.Open Acces

The Realm of Oncological Lung Surgery: From Past to Present and Future Perspectives

In this chapter, a historical overview as well as an overview of state of the art of the surgical techniques for the treatment of lung cancer is outlined. The chapter focuses on the introduction of open surgery, video-assisted thoracic surgery (VATS), uniportal VATS (UVATS), and robotic-assisted thoracic surgery (RATS) techniques for lung resections. A short introduction on upcoming techniques and modalities is given. The currently available tools as three-dimensional (3D) computed tomography (CT), virtual reality, and endo-bronchial surgery will be discussed. Based on the current development, this chapter attempts to delineate the horizon of oncological lung surgery. The information is generated not only from the available literature, but also from the experiences of surgeons and other physicians as well as co-workers involved in lung cancer treatment around the world. This chapter can be seen as a general introduction to several aspects of oncological lung surgery

Intraoperative Fluorescence Imaging for Personalized Brain Tumor Resection: Current State and Future Directions

abstract: Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies. Methods: Review of the literature. Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed. Conclusion: We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.View the article as published at http://journal.frontiersin.org/article/10.3389/fsurg.2016.00055/ful