EMIM 2018 ControlCenter

Online Program Overview Session: SpotSymp 02

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Intra-Operative Imaging - from Concept to Knife

Session chair: Sophie Hernot - Brussels, Belgium; Stephan Rogalla - Stanford, USA
 
Shortcut: SpotSymp 02
Date: Tuesday, 20 March, 2018, 2:30 PM
Room: Lecture Room 4/5 | level -1
Session type: Spotlight Symposium

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The Spotlight Symposium is supported by LICOR.

Abstract

Click on an contribution preview the abstract content.

2:30 PM SpotSymp 02-1

Where do we stand in the clinic? (#618)

A. Vahrmeijer1

1 Leiden University Medical Center, Surgery, Leiden, Netherlands

Content

Due to its relatively high tissue penetration, near-infrared (NIR; 700-900 nm) fluorescent light has the potential to visualize structures that need to be resected (e.g. tumors, lymph nodes) and structures that need to be spared (e.g. nerves, ureters, bile ducts). NIR fluorescence imaging using non-targeted fluorescent probes has been extensively studied in the last decade. Although proven feasible, tumor-specific imaging can be dramatically enhanced using tumor-specific fluorescent contrast agents. Clinical translation of these agents is challenging, and hurdles have to be overcome. In this overview we recapitulate the key regulations for first-in-human studies with fluorescent agents, provide insight in different strategies for swift clinical translation and discuss how clinical introduction of these fluorescent agents was achieved. We will review the key results from these studies and from recent clinical studies using tumor targeted contrast agents (antibody or peptide based), discuss the advantages and limitations of the technology, and suggest various imaging system and contrast agent parameters that could be optimized in future trials. Moreover, a clear roadmap for clinical translation of targeted probes will be presented.

3:00 PM SpotSymp 02-2

Real-time Quantitative Fluorescence-Guided Surgery (#610)

S. Gioux1

1 University of Strasbourg, ICube Laboratory, Strasbourg, France

Content

There is a pressing clinical need to provide image guidance during surgery. Currently, assessment of tissue that needs to be resected or avoided is performed subjectively leading to a large number of failures, patient morbidity and increased healthcare cost. Because near-infrared (NIR) light propagates deeply within living tissues and interacts with molecular constituents, it offers unparalleled capabilities for objectively identifying healthy and diseased tissue intraoperatively. These capabilities are well illustrated through the ongoing clinical translation of fluorescence imaging during oncologic surgery. In this work, we will review our efforts to provide real-time image-guidance during surgery using NIR diffuse optical imaging. We will present our latest methods and results in wide-field quantitative intraoperative imaging, with a particlar focus onto real-time quantitative fluorescence imaging.

References

1. Valdes PA, Angelo JP, Choi HS, Gioux S. qF-SSOP: real-time optical property corrected fluorescence imaging. Biomed Opt Exp 2017; 8(8): 3597-605.

2. van de Giessen M, Angelo JP, Vargas C, Gioux S. Real-time, profile-corrected single snapshot imaging of optical properties. Biomed Opt Exp 2015; 6(10): 4051-62.

3. Gioux S, Choi HS, Frangioni JV. Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation. Mol Imaging 2010; 9: 237-255.

Acknowledgement

Funding for this research was provided by European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program under grant agreement No 715737 (QuantSURG); National Institute of Health (NIH) (K01-DK-093603, F31-DK-105839, R01-EB-011523); National Science Foundation (NSF) (DGE-1247312); France Life Imaging; University of Strasbourg IdEx and ICube Laboratory.

Keywords: Image-guided surgery, fluorescence imaging, quantitative imaging
3:30 PM SpotSymp 02-3

Designing a Clinical Trial with Impact (#587)

M. Koller1

1 UMCG, Surgery, Groningen, Netherlands

Content

The impact of a clinical trial is not only related to the Impact Factor of a journal in which the paper is published. Many other factors are important that determines the impact of a clinical trial. In this lecture I would like to give an overview on these different factors, and how these factors can be translated to the design of a clinical trial. Furthermore, based on our 10 years experience in clinical trials in the field of optical imaging I will elaborate on the progress made in the field and what is needed to keep making progress in the future.

4:00 PM SpotSymp 02-4

Clinically Relevant Imaging Strategies in Endoscopy. (#578)

S. Rogalla1, 2

1 Stanford University, Radiology, Stanford, California, United States of America
2 Stanford University, Medicine, Stanford, California, United States of America

Content

Malignant neoplastic lesions account for around 600,000 deaths in the United States and is the second leading cause of death in Western Countries after cardiovascular disease. A majority of cancer types present at readily accessible surfaces offer unique detection opportunities. Effective clinical management of cancer is facilitated by early detection, when full surgical resection is possible, prior to invasion into adjacent tissue or significant intravasation into blood vessels leading to metastasis or by optimized surgical resection aiming for a R0, defined as zero tumor rest, resection without harming functional tissue. Good prognosis with long-term disease-free survival is therefore more likely following early detection when progression is limited.

At present, detection of several types of cancer largely relies on routine inspection with the naked eye (e.g. skin and oropharynx) or simple white light tools (e.g. cervix and colon). Emerging optical tools based on differential refraction, absorption, reflection, scattering or fluorescence of carcinomas relative to normal tissues enable label-free visualization of neoplasia. However, the differences in intrinsic optical properties of normal and malignant tissues can be subtle, and relying on these may lead to high miss rates. Enhanced optical contrast offered by molecularly targeted agents can be used to improve early detection, and given that optical imaging and sensing tools can be readily combined, integrated systems that image over a range of scales, or detect multiple parameters, can be developed to aid in early detection or optimized image-guided resection improving the signal to noise ratio. Moreover, diagnosis is, at present, made by histologic examination of tissue biopsies following identification of suspicious lesions. Miniature and handheld microscopic imaging tools have recently been developed, and integration of these tools with wide-field optical surveillance devices offers both rapid detection and confirmatory histologic examination at the point-of-care offering guidance for biopsy and/or resection. A wide-variety of targeted probe strategies have been described with demonstrated benefit in preclinical models and in a limited number of human studies.

Here I present an overview of integrated multimodality optical imaging strategies and sensing tools that use combinations of intrinsic and extrinsic optical contrast for early detection or margin delineation for carcinomas at epithelial surfaces and brain tumors. I will discuss these new technologies, such as fluorescence and Raman-based optical imaging and show that they have utility in detecting the most common cancer types to improve the overall-survival of patients.

Acknowledgement

Will Foundation, Kenneth Rainin Foundation, NIH

Keywords: Optical, Endoscopy, Guided Resection, Fluorescence, Raman
4:30 PM SpotSymp 02-5

BREAK

5:00 PM SpotSymp 02-6

Optoacoustic clinical imaging: current and future perspectives (#580)

C. Zakian1

1 Helmholtz Zentrum Munich, IBMI, Munich, Germany

Content

Multispectral optoacoustic imaging has emerged as a promising non-invasive clinical and pre-clinical modality suitable for vascular and microvascular structure mapping along with hemoglobin metabolism as well as lipid and water distribution in tissue.  This technique relies on intrinsic tissue chromophore light absorption followed by the emission and detection of ultrasound waves.

The current state-of-the-art optoacoustic devices, such as MSOT (multispectral optoacoustic tomography) and RSOM (raster-scanning optoacoustic mesoscopy) are based on extensive and continuous engineering progress resulting in improved laser sources, ultrasound detectors and scanning mechanisms. These advances enabled and propelled the translation of this technique into the clinics.

In this review, we present exciting new insights into the clinical applications of MSOT and RSOM in dermatology, gastroenterology, oncology, endocrinology and cardiovascular diseases .  We discuss unique clinical capabilities of these optoacoustic modalities in psoriasis assessment, skin and breast cancer detection, assessment of periphery vascular disease, muscular metabolism and thyroid imaging.

We will further highlight current challenges and future directions, with special emphasis on GI endoscopic applications, currently tackled by the EC research project ESOTRAC, an international multi-disciplinary consortiums aiming at improving early detection of esophageal cancer.

Acknowledgement

ESOTRAC has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 732720.

5:30 PM SpotSymp 02-7

Update on Targeted PhotoDynamic Therapy (#599)

M. Gotthardt1

1 Radboud university medical centre, Department of Radiology and Nuclear Medicine, Nijmegen, Gelderland, Netherlands

Content

Tracer molecules can in most cases be used for radionuclide as well as fluorescence imaging, but they also have potential for use in photodynamic therapy. Here, the development and translation of a tracer targeting the GLP-1 receptor is described starting from selection of an optimal ligand to clinical translation for radionuclide imaging of tumors, diabetes and congential hyperinsulinism. The achievement of the EU FP7 BetaCure project will be presented in respect to development of this probe for image guided surgery and photodynamic therapy. Finally, a perspective towards future clinical implementation of such multi-purpose ligands within the context of precision medicine treatment of tumours and other diseases is presented.

Keywords: image guided surgery, tracer, radionuclide imaging, photodynamic therapy
6:00 PM SpotSymp 02-8

Intra-Operative Nuclear Imaging: Current Applications, Limitations and Future Strategies (#593)

I. Alam1

1 Stanford University, Radiology Dept, Radiology, Stanford, California, United States of America

Content

Nuclear imaging modalities, single photon emission computed tomography (SPECT) and positron emission tomography (PET), are valued for their sensitive imaging of molecular processes and targets and their limitless depth of detection. They are frequently used pre-operatively for the diagnosis, localization and staging of solid tumors informing both surgical and therapeutic management.

Due to geometric constraints of SPECT and PET scanners, the real-time localization of radioactive tracers within the intraoperative setting has only been possible because of portable hand-held probes for radio-guided surgery (RGS). Typically RGS involves the use of a hand-held gamma radio-detection probe to detect SPECT isotopes such as 99mTc, injected directly into or next to suspected lesions prior to surgery and has become standard-of-care in a defined set of surgical procedures e.g. SLN biopsy in breast cancer and malignant melanoma. Despite their utility, the lack of image documentation in the use of these probes, has in recent years fueled the development of small gamma cameras for intra-operative use, which have improved surgical accuracy as demonstrated in various clinical studies. In contrast, RGS using PET tracers, is not yet well established though two classes of hand-held PET probes have been developed and evaluated to date; a dedicated PET gamma probe, designed specifically to detect the high-energy 511 keV photons and a PET positron detection probe. Often used in conjunction with 18Fluorodeoxyglucose (18F-FDG), these studies have at times yielded limited results, partly due to the limitations of the radiotracer itself. The use of more specific PET tracers as well as ongoing hardware and software development for these RGS technologies are expected to enhance spatial resolution and improve their accuracy and utility.

The current use of RGS probes and the evolution of nuclear imaging systems compatible with the intra-operative setting will be discussed as well as their advantages and limitations. In this regard, intraoperative guidance with nuclear imaging could benefit greatly from multimodal approaches, made possible due to recent advances in technology. Recent examples of such hybrid intra-operative approaches will be discussed and their exciting potential to enhance the utility of nuclear approaches in the future.

Keywords: Nuclear imaging, Radioguided Surgery, Hand-held probes, Intra-operative imaging, PET, SPECT
6:30 PM SpotSymp 02-9

BREAK

7:00 PM SpotSymp 02-10

Bimodal probes for guided interventions (#607)

M. Schottelius1

1 TU München, Chair for Pharmaceutical Radiochemistry, Garching, Bavaria, Germany

Objectives

Over the last decades, radioguided surgery has evolved as a reliable tool for the sensitive intraoperative detection and identification of tissues of interest, based on the pre- or intraoperative specific accumulation of a dedicated radiotracer in these tissues. Based on the excellent tissue penetration of gamma radiation, valuable information about the anatomical location of the diseased tissue is obtained, greatly facilitating surgical procedures and improving their outcome.

However, the inherent disadvantage of using intraoperative radioguidance alone is its limited spatial resolution. The use of hybrid tracers combining gamma emission and fluorescence in one (targeted) molecule merges the best of both modalities - by additionally providing the high spatial and temporal resolution of fluorescence imaging (far-red and near-infrared), allowing for highly sensitive real-time visualization directly correlated to the surgical field. The unquestionable utility of such a hybrid approach has initially been established by the introduction of ICG-[99mTc]nanocolloid (ICG: indocyanine green) for sentinel lymph node biopsy in different cancer types, demonstrating substantially improved sensitivity for the optical SLN detection in the hybrid setting. This finding has triggered the recent development of a broad variety of targeted hybrid nuclear/NIR-probes for different cancer types, ranging from full-size antibodies to small molecules (peptides, inhibitors).

Especially for the latter, the choice of the radiolabeling strategy and the fluorescent dye have tremendous impact on the overall performance of the hybrid tracer, including its targeting efficency, its physicochemical characteristics, in vivo stability, its tendency towards plasma protein binding and tracer pharmacokinetics.

Content

This contribution aims at providing a comprehensive overview over the different aspects of hybrid tracer development, with a certain focus on the selection criteria for the most suitable fluorescent dye for a given targeting vector and application, in combination with a given radiolabeling methodology. Our own recent data on hybrid PSMA-ligands will be presented to illustrate the complex interplay between ligand structure and tracer performance, and will be complemented by findings from other groups, highlighting selected aspects of this vibrant field of research and its potential for clinical translation.

7:30 PM SpotSymp 02-11

Defining the Cutting Edge: The use of molecular imaging for image guided surgery and tumor treatment. (#575)

J. P. Basilion1

1 Case Western Reserve University, Department of Radiology, Cleveland, United States of America

Content

A challenge for surgical removal of cancer is to maximize the removal of the cancerous tissue while minimizing removal of normal tissues.  This is critical for a number of prevalent cancers.  Several investigators have shown the utility of systemically delivered optical imaging probes to image tumors and guide surgical removal in small animal models of cancer and recently first-in-man studies have demonstrated feasibility in Europe and the USA. However, to date there are no FDA approved cancer-selective optical imaging probes that can be used to guide surgery.

The future direction of this field is to develop and translate into clinical use effective optical imaging probes for real-time assessment of surgical margins during tumor resection.  Here we demonstrate methods for imaging tumors margins during surgery that have a shorter time to clinical translation. Specifically, we will show that optical imaging probes topically applied ex vivo to resected tumor and surrounding normal tissue can rapidly differentiate between tissues. In contrast to systemic delivery of optical imaging probes which label tumors uniformly over a long period of time (i.e. hours), topical probe application results in rapid and robust probe activation that is detectable as early as 5 minutes following application.

We have also moved to implement a theranostic approach for image guided surgery. Using Prostate specific membrane antigen (PSMA), a well-established biomarker for prostate cancer, we have developed a PSMA-targeted photodynamic therapy (PDT) conjugate, PSMA-1-Pc413, which has demonstrated the ability to effectively inhibit prostate tumor growth after irradiation with 672nm laser light. Using this molecule for image guided surgery (IGS) we have exploited the PDT component to improve IGS. Our data demonstrate that mice undergoing imaged-guided surgery had less residual tumor in the surgical cavity than mice that had surgery under white light only and that IGS followed by PDT significantly improved survival. Kaplan-Meier survival curves showed that image guided surgery can improve the survival of mice (57%) compared to white light surgery followed by PDT (33%) and white light surgery without PDT (40%). PDT after image-guided surgery further improved the survival rate to 75%.

Keywords: cancer, image guided surgery