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In JoVE (1)
Other Publications (12)
- Gynecologic Oncology
- Journal of Biomedical Optics
- Pediatric Research
- Optics Letters
- Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
- Journal of Biomedical Optics
- Nature Medicine
- Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging
- Journal of Cellular and Molecular Medicine
- Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging
- Annals of Surgical Oncology
- Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
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Articles by George Themelis in JoVE
JoVE Clinical and Translational Medicine
Multispectrale Real-time Fluorescentie Imaging voor intra-operatief detectie van de schildwachtklier in gynaecologische oncologie
1Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, 2Helmholtz Zentrum, Technical University Munich, 3Department of Obstetrics and Gynaecology, University Medical Center Groningen
Fluorescentie beeldvorming is een veelbelovende innovatieve modaliteit voor beeld-geleide operatie in de chirurgische oncologie. In deze video beschrijven we de technische procedure voor de detectie van de schildwachtklier met behulp van fluorescentie beeldvorming als tentoongesteld in gynaecologische oncologicy. Een multispectrale fluorescentie camera-systeem, in combinatie met de fluorescerende stof groene Indocyanine, wordt toegepast.
Other articles by George Themelis on PubMed
A Clinical Study of Optical Biopsy of the Uterine Cervix Using a Multispectral Imaging System
To present the clinical application of the multispectral imaging colposcopic system (MIS colposcopy).
Near-infrared Spectroscopy Measurement of the Pulsatile Component of Cerebral Blood Flow and Volume from Arterial Oscillations
We describe a near-infrared spectroscopy (NIRS) method to noninvasively measure relative changes in the pulsate components of cerebral blood flow (pCBF) and volume (pCBV) from the shape of heartbeat oscillations. We present a model that is used and data to show the feasibility of the method. We use a continuous-wave NIRS system to measure the arterial oscillations originating in the brains of piglets. Changes in the animals' CBF are induced by adding CO(2) to the breathing gas. To study the influence of scalp on our measurements, comparative, invasive measurements are performed on one side of the head simultaneously with noninvasive measurements on the other side. We also did comparative measurements of CBF using a laser Doppler system to validate the results of our method. The results indicate that for sufficient source-detector separation, the signal contribution of the scalp is minimal and the measurements are representative of the cerebral hemodynamics. Moreover, good correlation between the results of the laser Doppler system and the NIRS system indicate that the presented method is capable of measuring relative changes in CBF. Preliminary results show the potential of this NIRS method to measure pCBF and pCBV relative changes in neonatal pigs.
Assessment of Infant Brain Development with Frequency-domain Near-infrared Spectroscopy
This is the first report to demonstrate quantitative monitoring of infant brain development with frequency-domain near-infrared spectroscopy (FD-NIRS). Regionally specific increases in blood volume and oxygen consumption were measured in healthy infants during their first year. The results agree with prior PET and SPECT reports; but, unlike these methods, FD-NIRS is portable and uses nonionizing radiation. Further, new information includes the relatively constant tissue oxygenation with age and location, suggesting a tight control between local oxygen delivery and consumption in healthy infants during brain development. FD-NIRS could become the preferred clinical tool for quantitatively assessing infant brain development.
Multispectral Imaging Using Multiple-bandpass Filters
We present a method for multispectral imaging. This method uses color CCD cameras with a multiple-bandpass filter, which modifies the spectral response of the cameras used and enables concurrent acquisition of multiple images at defined spectral bands. We experimentally demonstrate methodological feasibility using two color CCD cameras and a polychroic mirror to simultaneously capture eight spectral bands. We discuss how the method developed is well suited for multispectral applications of transient phenomena or for real-time measurements.
Increased Cerebral Blood Volume and Oxygen Consumption in Neonatal Brain Injury
With the increasing interest in treatments for neonatal brain injury, bedside methods for detecting and assessing injury status and evolution are needed. We aimed to determine whether cerebral tissue oxygenation (StO(2)), cerebral blood volume (CBV), and estimates of relative cerebral oxygen consumption (rCMRO(2)) determined by bedside frequency-domain near-infrared spectroscopy (FD-NIRS) have the potential to distinguish neonates with brain injury from those with non-brain issues and healthy controls. We recruited 43 neonates < or =15 days old and >33 weeks gestational age (GA): 14 with imaging evidence of brain injury, 29 without suspicion of brain injury (4 unstable, 6 stable, and 19 healthy). A multivariate analysis of variance with Newman-Keuls post hoc comparisons confirmed group similarity for GA and age at measurement. StO(2) was significantly higher in brain injured compared with unstable neonates, but not statistically different from stable or healthy neonates. Brain-injured neonates were distinguished from all others by significant increases in CBV and rCMRO(2). In conclusion, although NIRS measures of StO(2) alone may be insensitive to evolving brain injury, increased CBV and rCMRO(2) seem to be useful for detecting neonatal brain injury and suggest increased neuronal activity and metabolism occurs acutely in evolving brain injury.
Real-time Intraoperative Fluorescence Imaging System Using Light-absorption Correction
We present a novel fluorescence imaging system developed for real-time interventional imaging applications. The system implements a correction scheme that improves the accuracy of epi-illumination fluorescence images for light intensity variation in tissues. The implementation is based on the use of three cameras operating in parallel, utilizing a common lens, which allows for the concurrent collection of color, fluorescence, and light attenuation images at the excitation wavelength from the same field of view. The correction is based on a ratio approach of fluorescence over light attenuation images. Color images and video is used for surgical guidance and for registration with the corrected fluorescence images. We showcase the performance metrics of this system on phantoms and animals, and discuss the advantages over conventional epi-illumination systems developed for real-time applications and the limits of validity of corrected epi-illumination fluorescence imaging.
Intraoperative Tumor-specific Fluorescence Imaging in Ovarian Cancer by Folate Receptor-α Targeting: First In-human Results
The prognosis in advanced-stage ovarian cancer remains poor. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and thereby improve prognosis. The overexpression of folate receptor-α (FR-α) in 90-95% of epithelial ovarian cancers prompted the investigation of intraoperative tumor-specific fluorescence imaging in ovarian cancer surgery using an FR-α-targeted fluorescent agent. In patients with ovarian cancer, intraoperative tumor-specific fluorescence imaging with an FR-α-targeted fluorescent agent showcased the potential applications in patients with ovarian cancer for improved intraoperative staging and more radical cytoreductive surgery.
Imaging the Bio-distribution of Fluorescent Probes Using Multispectral Epi-illumination Cryoslicing Imaging
The increasing availability of fluorescent probes for in vivo optical imaging enables the interrogation of complex biological processes in small animals serving as models for human-like tissue function and disease. However, the validation of probe bio-distribution during their development or the study of different disease models, in support of in vivo imaging studies, is not straightforward.
In Vivo Imaging of CT26 Mouse Tumours by Using CmHsp70.1 Monoclonal Antibody
The major stress-inducible heat shock protein 70 (Hsp70) is frequently present on the cell surface of human tumours, but not on normal cells. Herein, the binding characteristics of the cmHsp70.1 mouse monoclonal antibody (mAb) were evaluated in vitro and in a syngeneic tumour mouse model. More than 50% of the CT26 mouse colon carcinoma cells express Hsp70 on their cell surface at 4°C. After a temperature shift to 37°C, the cmHsp70.1-fluorescein isothiocyanate mAb translocates into early endosomes and lysosomes. Intraoperative and near-infrared fluorescence imaging revealed an enrichment of Cy5.5-conjugated mAb cmHsp70.1, but not an identically labelled IgG1 isotype-matched control, in i.p. and s.c. located CT26 tumours, as soon as 30 min. after i.v. injection into the tail vein. Due to the rapid turnover rate of membrane-bound Hsp70, the fluorescence-labelled cmHsp70.1 mAb became endocytosed and accumulated in the tumour, reaching a maximum after 24 hrs and remained detectable at least up to 96 hrs after a single i.v. injection. The tumour-selective internalization of mAb cmHsp70.1 at the physiological temperature of 37°C might enable a targeted uptake of toxins or radionuclides into Hsp70 membrane-positive tumours. The anti-tumoral activity of the cmHsp70.1 mAb is further supported by its capacity to mediate antibody-dependent cytotoxicity.
Intraoperative Multispectral Fluorescence Imaging for the Detection of the Sentinel Lymph Node in Cervical Cancer: a Novel Concept
Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising technique for lymphatic mapping and sentinel lymph node (SLN) detection. The purpose of this technical feasibility pilot study was to evaluate the applicability of NIRF imaging with indocyanin green (ICG) for the detection of the SLN in cervical cancer.
Enhancing Surgical Vision by Using Real-time Imaging of αvβ3-integrin Targeted Near-infrared Fluorescent Agent
This study was designed to improve the surgical procedure and outcome of cancer surgery by means of real-time molecular imaging feedback of tumor spread and margin delineation using targeted near-infrared fluorescent probes with specificity to tumor biomarkers. Surgical excision of cancer often is confronted with difficulties in the identification of cancer spread and the accurate delineation of tumor margins. Currently, the assessment of tumor borders is afforded by postoperative pathology or, less reliably, intraoperative frozen sectioning. Fluorescence imaging is a natural modality for intraoperative use by directly relating to the surgeon's vision and offers highly attractive characteristics, such as high-resolution, sensitivity, and portability. Via the use of targeted probes it also becomes highly tumor-specific and can lead to significant improvements in surgical procedures and outcome.
Detection of Irradiation-induced, Membrane Heat Shock Protein 70 (Hsp70) in Mouse Tumors Using Hsp70 Fab Fragment
The major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in highly aggressive tumors, and elevated intracellular Hsp70 levels mediate protection against apoptosis. Following therapeutic intervention, such as ionizing irradiation, translocation of cytosolic Hsp70 to the plasma membrane is selectively increased in tumor cells and therefore, membrane Hsp70 might serve as a therapy-inducible, tumor-specific target structure.
