ITVT-04. Management of intraoperative technological advances [intraoperative MRI, neuronavigation system using PET, and 5-aminolevulinic acid (5-ALA)–induced fluorescence image-guided surgery] for glioblastoma

Abstract OBJECTIVE The maximum resection of Glioblastoma (GBM) is the standard therapy and is expected to improve prognosis. Image-guided surgery using a neuronavigation system is the standard technique for glioma. However, due to the brain shift during surgery, intraoperative technologies, such as 5-ALA fluorescence and intraoperative MRI (IoMRI), are employed. Radiotracers are used during positron emission tomography (PET) for metabolic imaging and assist the evaluation of glioma metabolism. We compared the effectiveness of these intraoperative technologies. METHODS Between January 2016 and May 2021, 52 patients with gliomas underwent IoMRI. 21 patients were selected for 5-ALA fluorescence-guided resection of GBM and underwent multiple PET studies (MET, FLT, and FMISO). We graded fluorescence level as strong, vague, or none. Following tumor resection, we identified the fluorescence level and evaluated the residual volume of gadolinium-enhanced T1WI (T1-Gd) on IoMRI and at each PET study. After calculating the extent of resection (EOR) for T1-Gd, we compared the residual volume on T1-Gd for IoMRI and each PET study, between EOR ≥ 93% and EOR < 93%. RESULTS We detected strong 5-ALA fluorescence during induction and before tumor resection in all 21 (100%) patients with a newly-diagnosed and histopathologically-confirmed GBM. Following tumor resection, we noted an EOR ≥ 93% for T1-Gd in 12 cases (vague, 4; none, 8) and an EOR < 93% for T1-Gd in 9 cases (vague, 5; none, 4). The compared median residual volume (mL) with no fluorescence between EOR ≥ 93% and EOR < 93% for T1-Gd were T1-Gd (0.22, 0.74), MET (0.29, 3.31), FLT (0.24, 1.77), and FMISO (0.22, 1.02). CONCLUSIONS GBM cells are difficult to distinguish in cases without 5-ALA fluorescence. For cases without 5-ALA fluorescence, we were able to maximize the resection of GBM by extracting the area of MET accumulation.

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Radiopharmaceutical and Eu3+ doped gadolinium oxide nanoparticles mediated triple-excited fluorescence imaging and image-guided surgery

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00920-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiaojing Shi ◽

Caiguang Cao ◽

Zeyu Zhang ◽

Jie Tian ◽

Zhenhua Hu

Keyword(s):

Fluorescent Probes ◽

Signal Intensity ◽

Tumor Imaging ◽

Tumor Resection ◽

Optical Signal ◽

Gadolinium Oxide ◽

Image Guided Surgery ◽

Guided Surgery ◽

Image Guided ◽

The Impact

AbstractCerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various radionuclides and radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various fluorescent probes have been combined with radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it’s interaction with fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+ doped gadolinium oxide (Gd2O3:Eu) was synthesized and combined with radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and radiopharmaceutical were investigated using 18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and 18F-FDG reached 369 times as high as that of CLI using 18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative tumor imaging. Compared with 18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and 18F-FDG combination achieved a much higher tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24 vs. 1.87 ± 0.73, P = 0.0030). The use of Gd2O3:Eu@PVA and 18F-FDG also assisted intraoperative detection of tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of image-guided surgery demonstrated feasibility of image-guided tumor resection using Gd2O3:Eu@PVA and 18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with 18F-FDG in intraoperative tumor imaging and image-guided tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of tumor and intraoperatively guide tumor resection.

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Neurosurgery and brain shift: review of the state of the art and main contributions of robotics

TecnoLógicas ◽

10.22430/22565337.719 ◽

2017 ◽

Vol 20 (40) ◽

pp. 125-138

Author(s):

Karin Correa-Arana ◽

Oscar A. Vivas-Albán ◽

José M. Sabater-Navarro

Keyword(s):

Brain Tumor ◽

State Of The Art ◽

Image Guided Surgery ◽

Medical Procedures ◽

Brain Shift ◽

Future Perspectives ◽

Guided Surgery ◽

Image Guided ◽

Neuronavigation System ◽

Minimal Invasion

This paper presents a review about neurosurgery, robotic assistants in this type of procedure, and the approach to the problem of brain tissue displacement, including techniques for obtaining medical images. It is especially focused on the phenomenon of brain displacement, commonly known as brain shift, which causes a loss of reference between the preoperative images and the volumes to be treated during image-guided surgery. Hypothetically, with brain shift prediction and correction for the neuronavigation system, minimal invasion trajectories could be planned and shortened. This would reduce damage to functional tissues and possibly lower the morbidity and mortality in delicate and demanding medical procedures such as the removal of a brain tumor. This paper also mentions other issues associated with neurosurgery and shows the way robotized systems have helped solve these problems. Finally, it highlights the future perspectives of neurosurgery, a branch of medicine that seeks to treat the ailments of the main organ of the human body from the perspective of many disciplines.

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5-aminolevulinic acid as a potential contrast agent for image-guided surgery in pancreatic cancer

17th International Photodynamic Association World Congress ◽

10.1117/12.2525084 ◽

2019 ◽

Author(s):

Peter L. Labib ◽

Elnaz Yaghini ◽

Brian R. Davidson ◽

Alexander J. MacRobert ◽

Stephen P. Pereira

Keyword(s):

Pancreatic Cancer ◽

Contrast Agent ◽

Aminolevulinic Acid ◽

Image Guided Surgery ◽

Guided Surgery ◽

Image Guided

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Image-guided resection of aggressive sacral tumors

Neurosurgical FOCUS ◽

10.3171/2016.6.focus16125 ◽

2017 ◽

Vol 42 (1) ◽

pp. E15 ◽

Cited By ~ 4

Author(s):

Doniel Drazin ◽

Neil Bhamb ◽

Lutfi T. Al-Khouja ◽

Ari D. Kappel ◽

Terrence T. Kim ◽

...

Keyword(s):

Tumor Resection ◽

Case Series ◽

Benign Tumors ◽

Image Guided Surgery ◽

Tumor Type ◽

Retrospective Case ◽

Giant Cell Tumors ◽

Guided Surgery ◽

Image Guided ◽

Sacral Tumors

OBJECTIVE The aim of this study was to identify and discuss operative nuances utilizing image guidance in the surgical management of aggressive sacral tumors. METHODS The authors report on their single-institution, multi-surgeon, retrospective case series involving patients with pathology-proven aggressive sacral tumors treated between 2009 and 2016. They also reviewed the literature to identify articles related to aggressive sacral tumors, their diagnosis, and their surgical treatment and discuss the results together with their own experience. Information, including background, imaging, treatment, and surgical pearls, is organized by tumor type. RESULTS Review of the institutional records identified 6 patients with sacral tumors who underwent surgery between 2009 and 2016. All 6 patients were treated with image-guided surgery using cone-beam CT technology (O-arm). The surgical technique used is described in detail, and 2 illustrative cases are presented. From the literature, the authors compiled information about chordomas, chondrosarcomas, giant cell tumors, and osteosarcomas and organized it by tumor type, providing a detailed discussion of background, imaging, and treatment as well as surgical pearls for each tumor type. CONCLUSIONS Aggressive sacral tumors can be an extremely difficult challenge for both the patient and the treating physician. The selected surgical intervention varies depending on the type of tumor, size, and location. Surgery can have profound risks including neural compression, lumbopelvic instability, and suboptimal oncological resection. Focusing on the operative nuances for each type can help prevent many of these complications. Anecdotal evidence is provided that utilization of image-guided surgery to aid in tumor resection at our institution has helped reduce blood loss and the local recurrence rate while preserving function in both malignant and aggressive benign tumors affecting the sacrum.

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The Emerging Role of CD24 in Cancer Theranostics—A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond

Journal of Personalized Medicine ◽

10.3390/jpm10040255 ◽

2020 ◽

Vol 10 (4) ◽

pp. 255

Author(s):

Katrin Kleinmanns ◽

Vibeke Fosse ◽

Line Bjørge ◽

Emmet McCormack

Keyword(s):

Ovarian Cancer ◽

Fluorescence Imaging ◽

Tumor Resection ◽

Cell Surface Receptor ◽

Image Guided Surgery ◽

Fluorescence Image ◽

Guided Surgery ◽

Image Guided ◽

Surface Receptor ◽

Novel Target

Complete cytoreductive surgery is the cornerstone of the treatment of epithelial ovarian cancer (EOC). The application of fluorescence image-guided surgery (FIGS) allows for the increased intraoperative visualization and delineation of malignant lesions by using fluorescently labeled targeting biomarkers, thereby improving intraoperative guidance. CD24, a small glycophosphatidylinositol-anchored cell surface receptor, is overexpressed in approximately 70% of solid cancers, and has been proposed as a prognostic and therapeutic tumor-specific biomarker for EOC. Recently, preclinical studies have demonstrated the benefit of CD24-targeted contrast agents for non-invasive fluorescence imaging, as well as improved tumor resection by employing CD24-targeted FIGS in orthotopic patient-derived xenograft models of EOC. The successful detection of miniscule metastases denotes CD24 as a promising biomarker for the application of fluorescence-guided surgery in EOC patients. The aim of this review is to present the clinical and preclinically evaluated biomarkers for ovarian cancer FIGS, highlight the strengths of CD24, and propose a future bimodal approach combining CD24-targeted fluorescence imaging with radionuclide detection and targeted therapy.

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Multimodal image-guided surgery of HER2-positive breast cancer using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast tumor model

EJNMMI Research ◽

10.1186/s13550-019-0564-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Marion M. Deken ◽

Desirée L. Bos ◽

Willemieke S. F. J. Tummers ◽

Taryn L. March ◽

Cornelis J. H. van de Velde ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Tissue ◽

Tumor Resection ◽

Image Guided Surgery ◽

Cancer Model ◽

Her2 Positive ◽

Guided Surgery ◽

Image Guided ◽

Breast Cancer Model ◽

Positive Breast Cancer

Abstract Background Combining modalities using dual-labeled antibodies may allow preoperative and intraoperative tumor localization and could be used in image-guided surgery to improve complete tumor resection. Trastuzumab is a monoclonal antibody against the human epidermal growth factor-2 (HER2) receptor and dual-labeled trastuzumab with both a fluorophore (IRDye800CW) and a radioactive label (111In) can be used for multimodal imaging of HER2-positive breast cancer. The aim of this study was to demonstrate the feasibility of HER2-targeted multimodal imaging using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast cancer model. Methods Trastuzumab was conjugated with p-isothiocyanatobenzyl (ITC)-diethylenetriaminepentaacetic acid (DTPA) and IRDye800CW-NHS ester and subsequently labeled with 111In. In a dose escalation study, the biodistribution of 10, 30, and 100 μg [111In]In-DTPA-trastuzumab-IRDye800CW was determined 48 h after injection in BALB/c nude mice with orthotopic high HER2-expressing tumors. Also, a biodistribution study was performed in a low HER2-expressing breast cancer model. In addition, multimodal image-guided surgery was performed in each group. Autoradiography, fluorescence microscopy, and immunohistochemically stained slices of the tumors were compared for co-localization of tumor tissue, HER2 expression, fluorescence, and radiosignal. Results Based on the biodistribution data, a 30 μg dose of dual-labeled trastuzumab (tumor-to-blood ratio 13 ± 2) was chosen for all subsequent studies. [111In]In-DTPA-trastuzumab-IRDye800CW specifically accumulated in orthotopic HER2-positive BT474 tumors (101 ± 7 %IA/g), whereas uptake in orthotopic low HER2-expressing MCF7 tumor was significantly lower (1.2 ± 0.2 %IA/g, p = 0.007). BT474 tumors could clearly be visualized with both micro-SPECT/CT, fluorescence imaging and subsequently, image-guided resection was performed. Immunohistochemical analyses of BT474 tumors demonstrated correspondence in fluorescence, radiosignal, and high HER2 expression. Conclusions Dual-labeled trastuzumab showed specific accumulation in orthotopic HER2-positive BT474 breast tumors with micro-SPECT/CT and fluorescence imaging and enabled image-guided tumor resection. In the clinical setting, [111In]In-DTPA-trastuzumab-IRDye800CW could be valuable for preoperative detection of (metastatic) tumors by SPECT/CT imaging, and intraoperative localization by using a gamma probe and fluorescence image-guided surgery to improve radical resection of tumor tissue in patients with HER2-positive tumors.

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Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery

Cancers ◽

10.3390/cancers12040987 ◽

2020 ◽

Vol 12 (4) ◽

pp. 987

Author(s):

Fortuné M.K. Elekonawo ◽

Jan Marie de Gooyer ◽

Desirée L. Bos ◽

David M. Goldenberg ◽

Otto C. Boerman ◽

...

Keyword(s):

Tumor Targeting ◽

Near Infrared ◽

Ex Vivo ◽

Tumor Resection ◽

Human Tumor ◽

Image Guided Surgery ◽

Radioactive Label ◽

Near Infrared Fluorescence ◽

Guided Surgery ◽

Image Guided

Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

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