Papers by George Themelis
PubMed, Jul 7, 2000
Photodynamic therapy (PDT) with topical d-aminolevulinic acid (ALA) has become a therapeutic opti... more Photodynamic therapy (PDT) with topical d-aminolevulinic acid (ALA) has become a therapeutic option of growing interest for superficial non-melanoma precancerous and malignant lesions. After application of ALA, in situ conversion to endogenous porphyrins is accomplished in a gradual manner. Therefore, the determination of fluorescence kinetics and spatial distribution in vivo versus time is a crucial point for the success of ALA-PDT. Seventeen basal cell carcinomas (BCC) and 20 actinic keratoses (AK) were enrolled in this study. In 5 BCC and 4 AK, in vivo fluorescence kinetics were performed over 24 hrs and for the remaining lesions between 2 and 7 hrs after ALA application. In vivo spatial and quantitative detection of the fluorescence intensity versus time showed considerable variations among tumors of the same type, so light irradiation was performed according to patient individualities. Both BCC and AK showed maximal median fluorescence intensity at 4-6.5 hrs post-application. In the present study, a high cure rate was proven after topical ALA-PDT (70.6% in BCC and 85% in AK). The results of fluorescence studies suggest that optimum irradiation time for BCC is approximately 3.5-5 hrs and for AK 5 hrs after ALA application, when relative maximal fluorescence intensity in correlation with fluorescence selectivity on the lesion, is obtained.
The Journal of Nuclear Medicine, Feb 18, 2014
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable... more Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials of α v β 3 integrin-targeted molecular imaging technologies for detection of PDAC using genetically engineered mouse models. Methods: Immunohistochemistry and Western blot were used for characterization of α v β 3 expression in murine and human PDAC. We applied IntegriSense 680 fluorescence molecular tomography, intraoperative fluorescence imaging, and 68 Ga-NODAGA-RGD PET for α v β 3 integrin molecular in vivo imaging of spontaneous PDAC occurring in Ptf1a 1/Cre ;Kras 1/LSL-G12D ;p53 LoxP/LoxP mice. (NODAGA is 1,4,7-triazacyclononane-1,4-bis[acetic acid]-7-[2-glutaric acid] and RGD is arginine-glycine-aspartic acid.) Results: α v β 3 integrin is expressed in tumor cells of human and murine PDAC. IntegriSense fluorescence molecular tomography and 68 Ga-NODAGA-RGD PET enabled faithful visualization of PDAC. Furthermore, intraoperative optical imaging with IntegriSense 680 allowed good delineation of tumor borders. Conclusion: Imaging approaches targeting α v β 3 integrin expand the potential of molecular imaging for identification of α v β 3-positive PDAC with potential implications in early detection, fluorescenceguided surgery, and therapy monitoring.
Radiotherapy and Oncology, Jun 1, 2011
Gynecologic Oncology, Feb 1, 2011
INTRODUCTION: Intraoperative identification of tumors can be challenging. Near-infrared (NIR) flu... more INTRODUCTION: Intraoperative identification of tumors can be challenging. Near-infrared (NIR) fluorescence imaging is an innovative technique that can assist in intraoperative identification of tumors, which may otherwise be undetectable. PRESENTATION OF CASE: A 19-year-old patient with symptoms, normetanephrine levels and radiological findings suspicious for a paraganglioma, a rare tumor arising from extra-adrenal chromaffin cells within the sympathetic nervous system, is presented. Intraoperative NIR fluorescence imaging using intravenous administration of methylene blue (MB) assisted in intraoperative detection of the tumor, and even identified a smaller second lesion, which was not identified during surgery by visual inspection. DISCUSSION: Although the exact mechanism of MB accumulation in neuroendocrine tumors is unclear, it is described in both preclinical and clinical studies. CONCLUSION: In this report, we describe the first case of intraoperative NIR fluorescence imaging of a paraganglioma using MB, which identified an otherwise undetectable lesion.
Hawaii, USA, 2001
We present a novel Hyper-Spectral Imaging (HySI) System capable of acquiring and real time displa... more We present a novel Hyper-Spectral Imaging (HySI) System capable of acquiring and real time displaying of 5nm specrtal images, with 2nm tuning step, in the range of 400nm-1000nm. Synchronized spectral scanning and image storing enables the collection of a stack of calibrated spectral images, from which a fully resolved spectrum per image pixel can be calculated and displayed. We also present results from a pilot use of the developed HySI system as a research tool, in an attempt to develop novel, non-invasive diagnostic ...
Zeitschrift für Gastroenterologie, 2012
Πανεπιστήμιο Κρήτης. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής. Τομέας Ακτινολογίας, Aug 26, 2021
Cervical cancer is the commonest form of cancer in females under 35 years of age and the second m... more Cervical cancer is the commonest form of cancer in females under 35 years of age and the second most common in females of all ages. Limitations of the existing diagnostic methods have led to the development of new diagnostic approaches. Acetic acid is a marker used for more than 70 years in gynecology for the detection of abnormal lesions. Local application of acetic acid causes a temporal whiting to abnormal areas (acetowhite) while normal areas are not affected. Extensive clinical trials have shown that the visual assessment of acetowhitening exhibits similar diagnostic performance to other methods such as Test Pap. The diagnostic method proposed in this project is based on the quantitative and objective assessment of the acetic acid-tissue interaction by means of an Imaging Spectroscopy System. For the purpose of this study a new Imaging Spectroscopy system has been designed and developed. The method was used for the in vivo detection of dysplasias in the cervix and the results, from measurements of 181 women, indicated that there is a strong correlation between the histological condition of the tissue and the kinetics of the acetowhitening development. The best fit of the time course measurements of acetowhitening was achieved by the triple exponential function. Statistical analysis of several parameters that characterize the acetowhitening kinetics, have indicated that the combined evaluation of the parameters that express the duration (t5) and the intensity of acetowhitening (EDRmax) differentiates sufficiently all the examined histological conditions. Estimation of the sensitivity and the specificity of this method indicates that its diagnostic performance is comparable or better than that of the existing methods. In order to explain the experimental results, a model for the acetic acid-tissue interaction is proposed. According to this model the tissue-pH alterations induced by the application of acetic acid can be simulated with a 3-compartment model (the intracellular, the extracellular and the blood sink compartments). The solution of the model has shown that, after the application of acetic acid, the intracellular pH exhibits the same kinetics with the acetowhitening. The alterations of the intracellular pH cause increment in the relative refractive index of the nuclear proteins, and consequently increase the light scattering by the nuclei. Furthermore, this model correlates qualitatively the kinetics of the acetowhitening with some structural, compositional and functional features of the epithelial tissue and successfully interprets the experimental results. In particular, epithelial tissue features such as the nuclear size and inhomogeneity, the epithelium thickness, the cellular energy reserves (e.g. glycogen), the density of cell-packing, the cellular metabolism, and the efficiency of the vascularity determine the acetowhitening kinetics.
The prognosis in virtually all solid tumors depends on the presence or absence of lymph node meta... more The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases. 1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema. 4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor. 6 In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix. 7 The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one...
Purpose: Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising techni... more Purpose: 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. Procedures: In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system. Results: Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases. Concl...
The prognosis in virtually all solid tumors depends on the presence or absence of lymph node meta... more The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema.4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor.6 In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix.7 The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day...
Laser Focus World, 2008
A new and highly potent technique allows concurrent capture of application-defined spectral bands... more A new and highly potent technique allows concurrent capture of application-defined spectral bands using standard color CCD cameras.
Purpose: Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising techni... more Purpose: 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. Procedures: In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system. Results: Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases. Concl...
Otolaryngol Head Neck Surg, 1999
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Papers by George Themelis