Topical MMP beacon enabled fluorescence-guided resection of oral carcinoma

PubMed Central

Burgess, Laura; Chen, Juan; Wolter, Nikolaus E.; Wilson, Brian; Zheng, Gang

2016-01-01

Each year almost 300,000 individuals worldwide are diagnosed with oral cancer, more than 90% of these being oral carcinoma [N. Engl. J. Med. 328, 184 19938417385]. Surgical resection is the standard of care, but accurate delineation of the tumor boundaries is challenging, resulting in either under-resection with risk of local recurrence or over-resection with increased functional loss and negative impact on quality of life. This study evaluates, in two pre-clinical in vivo tumor models, the potential of fluorescence-guided resection using molecular beacons activated by metalloproteinases, which are frequently upregulated in human oral cancer. In both models there was rapid (<15 min) beacon activation upon local application, allowing clear fluoresecence imaging in vivo and confirmed by ex vivo fluorescence microscopy and HPLC, with minimal activation in normal oral tissues. Although the tissue penetration was limited using topical application, these findings support further development of this approach towards translation to first-in-human trials. PMID:27231609

Fluorescence-Guided Surgery

PubMed Central

Nagaya, Tadanobu; Nakamura, Yu A.; Choyke, Peter L.; Kobayashi, Hisataka

2017-01-01

Surgical resection of cancer remains an important treatment modality. Despite advances in preoperative imaging, surgery itself is primarily guided by the surgeon’s ability to locate pathology with conventional white light imaging. Fluorescence-guided surgery (FGS) can be used to define tumor location and margins during the procedure. Intraoperative visualization of tumors may not only allow more complete resections but also improve safety by avoiding unnecessary damage to normal tissue which can also reduce operative time and decrease the need for second-look surgeries. A number of new FGS imaging probes have recently been developed, complementing a small but useful number of existing probes. In this review, we describe current and new fluorescent probes that may assist FGS. PMID:29312886

Delineating Normal from Diseased Brain by Aminolevulinic Acid-Induced Fluorescence

NASA Astrophysics Data System (ADS)

Stepp, Herbert; Stummer, Walter

5-Aminolevulinic acid (5-ALA) as a precursor of protoporphyrin IX (PpIX) has been established as an orally applied drug to guide surgical resection of malignant brain tumors by exciting the red fluorescence of PpIX. The accumulation of PpIX in glioblastoma multiforme (GBM) is highly selective and provides excellent contrast to normal brain when using surgical microscopes with appropriately filtered light sources and cameras. The positive predictive value of fluorescent tissue is very high, enabling safe gross total resection of GBM and other brain tumors and improving prognosis of patients. Compared to other intraoperative techniques that have been developed with the aim of increasing the rate of safe gross total resections of malignant gliomas, PpIX fluorescence is considerably simpler, more cost effective, and comparably reliable. We present the basics of 5-ALA-based fluorescence-guided resection, and discuss the clinical results obtained for GBM and the experience with the fluorescence staining of other primary brain tumors and metastases as well as the results for spinal cord tumors. The phototoxicity of PpIX, increasingly used for photodynamic therapy of brain tumors, is mentioned briefly in this chapter.

P12.105-ALA GUIDED REMOVAL AND COMBINED TREATMENT IN MALIGNANT GLIOMA

PubMed Central

Oppido, P.A.; Carapella, C.M.; Pompili, A.; Vidiri, A.; Pace, A.; Villani, V.

2014-01-01

INTRODUCTION: Malignant gliomas are the most unfavourable brain tumours. Recent evidence suggests that extensive tumour removal is associated with better survival. The current treatment is complete as possible resection of the contrast-enhancing tumour tissue, followed by adjuvant treatment with radiotherapy and chemotherapy. As it appears difficult to distinguish between infiltration tumour and normal tissue, specially in recurrent tumours, the radical removal becomes harmful. Techniques to visualize the borderline tumour intraoperatively are helpful. More recently, fluorescence guidance has taken advantage of intrinsic metabolic and structural changes that occur within malignant glioma by exploiting the eme biosynthetic pathway and a natural biochemical in that pathway, 5-aminolevulinic acid (5-ALA). METHODS: Since the end of 2009, in our Institute 54 patients were operated on using fluorescence guided tumour resection. Preoperatively, all enrolled patients had MRI showing contrast enhancing lesions. MRI within 72 hours after surgery and thereafter at 3-month interval was performed. 32 patients were newly diagnosed tumour, 22 were recurrent malignant glioma. An oral dose of 20 mg 5-ALA /kg body weight was administered to each patient. By a NC4 OPMI Pentero operating microscope (Zeiss), enabled switching from xenon light to violet-blue light for visualizing fluorescence, the surgical resection was performed. Histology was in 48 glioblastoma (1 gliosarcoma), in 4 anaplastic oligodendroglioma, in 1 oligodendroglioma I WHO and in 1 pleomorphic xanthoastrocytoma. All the patients, as first line treatment, were submitted to radiotherapy and chemotherapy; in recurrent tumours second and in some cases third line treatments were administered. The follow-up ranged from 2 years to 8 months. RESULTS: In all cases the yellow fluorescence due to 5-ALA in cortical vessels was seen. In 47 glioblastoma, 4 anaplastic oligodendroglioma and 1 xanthoastrocytoma the tumour tissue showed intraoperative red fluorescence. Specially in recurrent tumours, the fluorescence-guided surgery was helpful to identify, inside the gliotic tissue, some areas with active tumour from perilesional “healthy” brain. Furthermore, after surgery no relevant neurological deficit caused by 5-ALA guided resection were observed. Early postoperative MRI confirmed gross total resection without contrast enhancment in 80 % of patients. At the follow-up 24 patients are still alive. CONCLUSIONS: The 5-ALA was helpful to localize the tumour on the cortex and extended resection of infiltrating tumour, specially in recurrence. Patients affected by glioblastoma are elctive for this technique. Extended resections by 5-ALA fluorescence guide does not impair neurological functions and can impact on the overall survival of patients affected by malignant glioma.

Fluorescence-guided resection with 5-aminolevulinic Acid of subependymomas of the fourth ventricle: report of 2 cases: technical case report.

PubMed

Bernal García, Luis Miguel; Cabezudo Artero, José Manuel; Marcelo Zamorano, María Bella; Gilete Tejero, Ignacio

2015-06-01

The usefulness of 5-aminolevulinic acid (5-ALA) for resection of malignant astrocytomas has been established in recent years. In addition to these tumors, it has been reported that 5-ALA fluorescence could be elicited in other tumors such as intracranial and spinal meningiomas or posterior fossa and spinal cord ependymomas, resulting in improved resections. Here, we present 2 cases of subependymomas of the fourth ventricle that showed intense fluorescence after 5-ALA administration. To the best of our knowledge, these are the first reported cases of subependymomas in this location in which 5-ALA elicited useful fluorescence. Case 1 was a 61-year-old woman with a history of headaches accompanied by vomiting in the last month. Magnetic resonance imaging (MRI) revealed a tumor occupying the fourth ventricle with slight irregular enhancement. She was operated on after administration of 5-ALA. The tumor emitted intense red fluorescence when illuminated with blue light. An MRI performed 48 hours after surgery confirmed complete resection of the tumor. The pathological diagnosis was subependymoma. Case 2 was a 35-year-old man with a history of several months of headaches and vomiting. An MRI revealed a tumor occupying the caudal part of the fourth ventricle with moderate and irregular enhancement. He was operated on after administration of 5-ALA. The tumor showed intense fluorescence. An MRI performed 48 hours after surgery confirmed a complete resection of the tumor. The pathological diagnosis was subependymoma. Fluorescence-guided resection with 5-ALA may be useful for resection of subependymomas of the fourth ventricle. However, further studies are needed.

mTHPC-mediated photodynamic detection for fluorescence-guided resection of brain tumors

NASA Astrophysics Data System (ADS)

Kostron, Herwig; Zimmermann, Andreas; Obwegeser, Alois

1998-06-01

A most radical resection is of great importance in the treatment of brain tumors, however they can hardly be differentiated from normal brain parenchyma by the naked eye of the neurosurgeon. Photosensitizers are highly selective taken up into malignant tissues, therefore the fluorescence properties of photosensitizers could be utilized for optical differentiation of normal and malignant tissue. Ten patients presenting with brain malignancies were sensitized for photodynamic diagnosis (PDD) and photodynamic treatment (PDT) with 0.15 mg/kg b.w. m-THPC. On day 4 intraoperative PDD and fluorescence guided tumor resection (FGR) was performed, followed by intraoperative PDT. The fluorescence was induced by a xenon lamp at an excitation wavelength ranging from 370 to 440 nm. A sensitive CCD camera was employed for imaging, equipped with a long pass filter to shut off the excitation wavelength and to improve the signal to noise ratio. The pictures are converted digitally by a standard frame grabber and processed in real time and calculated for the tissue auto fluorescence in the emission band of m-THPC at 652 nm. Out of 10 0bservations, two were false negative and 2 were false positive. Our preliminary results indicate that fluorescence guided surgery is feasible and proved to be of significant help in delineating tumor margins and in resection of residual tumor that could not be detected by the surgeon, however the sensitivity and specificity needs to be further improved.

Near-infrared (NIR) fluorescence imaging of head and neck squamous cell carcinoma for fluorescence-guided surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Moore, Lindsay; Warram, Jason M.; de Boer, Esther; Carroll, William R.; Morlandt, Anthony; Withrow, Kirk P.; Rosenthal, Eben L.

2016-03-01

During fluorescence-guided surgery, a cancer-specific optical probe is injected and visualized using a compatible device intraoperatively to provide visual contrast between diseased and normal tissues to maximize resection of cancer and minimize the resection of precious adjacent normal tissues. Six patients with squamous cell carcinomas of the head and neck region (oral cavity (n=4) or cutaneous (n=2)) were injected with an EGFR-targeting antibody (Cetuximab) conjugated to a near-infrared (NIR) fluorescent dye (IRDye800) 3, 4, or 7 days prior to surgical resection of the cancer. Each patient's tumor was then imaged using a commercially available, open-field NIR fluorescence imaging device each day prior to surgery, intraoperatively, and post-operatively. The mean fluorescence intensity (MFI) of the tumor was calculated for each specimen at each imaging time point. Adjacent normal tissue served as an internal anatomic control for each patient to establish a patient-matched "background" fluorescence. Resected tissues were also imaged using a closed-field NIR imaging device. Tumor to background ratios (TBRs) were calculated for each patient using both devices. Fluorescence histology was correlated with traditional pathology assessment to verify the specificity of antibody-dye conjugate binding. Peak TBRs using the open-field device ranged from 2.2 to 11.3, with an average TBR of 4.9. Peak TBRs were achieved between days 1 and 4. This study demonstrated that a commercially available NIR imaging device suited for intraoperative and clinical use can successfully be used with a fluorescently-labeled dye to delineate between diseased and normal tissue in this single cohort human study, illuminated the potential for its use in fluoresence-guided surgery.

5-Aminolevulinic Acid-Induced Fluorescence in Cerebellar Primary Central Nervous System Lymphoma: A Case Report and Literature Review.

PubMed

Yamamoto, Junkoh; Kitagawa, Takehiro; Akiba, Daisuke; Nishizawa, Shigeru

2015-01-01

5-Aminolevulinic acid (5-ALA)-induced fluorescence-guided resection is a widely used procedure for patients with malignant gliomas. However, the clinical application of 5-ALA for surgery in primary central nervous system lymphoma (PCNSL) is uncommon. Here, we present a case of PCNSL treated using 5-ALA-induced fluorescence-guided resective surgery. A 70-year-old woman presented with cerebellar ataxia, and magnetic resonance imaging revealed an irregularly shaped and homogenously enhanced mass with surrounding brain edema in the vermis that extended to the right hemisphere of the cerebellum. Under the preoperative diagnosis of a malignant glioma in the cerebellum, the patient underwent 5-ALA-induced fluorescence-guided surgery. Under blue light illumination, the tumor revealed strong 5-ALA-induced fluorescence. The tumor was identified as a diffuse large B-cell lymphoma. After partial resection, the patient received adjuvant chemotherapy and radiotherapy. Importantly, the neurological deficit of the patient improved, and recurrence of the tumor was not observed 21 months post-surgery. Together with previous reports, this case study emphasizes the efficacy of the surgical application of 5-ALA for PCNSL.

Protoporphyrin-IX fluorescence guided surgical resection in high-grade gliomas: The potential impact of human colour perception.

PubMed

Petterssen, Max; Eljamel, Sarah; Eljamel, Sam

2014-09-01

Protoporphyrin-IX (Pp-IX) fluorescence had been used frequently in recent years to guide microsurgical resection of high-grade gliomas (HGG), particularly following the publication of a randomized controlled trial demonstrating its advantages. However, Pp-IX fluorescence is dependent upon the surgeons' eyes' perception of red fluorescent colour. This study was designed to evaluate human eye fluorescence perception and establish a fluorescence scale. 20 of 108 pre-recorded images from intraoperative fluorescence of HGG were used to construct an 8-panel visual analogue fluorescence scale. The scale was validated by testing 56 participants with normal colour vision and three red-green colour-blind participants. For intra-rater agreement ten participants were tested twice and for inter-observer reliability the whole cohort were tested. The intra- and inter-observer reliability of the scale in normal colour vision participants was excellent. The scale was less reliable in the violet-blue panels of the scale. Colour-blind participants were not able to distinguish between red fluorescence and blue-violet colours. The 8-panel fluorescence scale is valid in differentiating red, pink and blue colours in a fluorescence surgical field among participants with normal colour perception and potentially useful to standardize fluorescence-guided surgery. However, colourblind surgeons should not use fluorescence-guided surgery. Copyright © 2014 Elsevier B.V. All rights reserved.

Image-Guided Surgery using Invisible Near-Infrared Light: Fundamentals of Clinical Translation

PubMed Central

Gioux, Sylvain; Choi, Hak Soo; Frangioni, John V.

2011-01-01

The field of biomedical optics has matured rapidly over the last decade and is poised to make a significant impact on patient care. In particular, wide-field (typically > 5 cm), planar, near-infrared (NIR) fluorescence imaging has the potential to revolutionize human surgery by providing real-time image guidance to surgeons for tissue that needs to be resected, such as tumors, and tissue that needs to be avoided, such as blood vessels and nerves. However, to become a clinical reality, optimized imaging systems and NIR fluorescent contrast agents will be needed. In this review, we introduce the principles of NIR fluorescence imaging, analyze existing NIR fluorescence imaging systems, and discuss the key parameters that guide contrast agent development. We also introduce the complexities surrounding clinical translation using our experience with the Fluorescence-Assisted Resection and Exploration (FLARE™) imaging system as an example. Finally, we introduce state-of-the-art optical imaging techniques that might someday improve image-guided surgery even further. PMID:20868625

5-Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Surgery of High-Grade Gliomas: A Systematic Review.

PubMed

Guyotat, Jacques; Pallud, Johan; Armoiry, Xavier; Pavlov, Vladislav; Metellus, Philippe

2016-01-01

The current first-line treatment of malignant gliomas consists in surgical resection (if possible) as large as possible. The existing tools don't permit to identify the limits of tumor infiltration, which goes beyond the zone of contrast enhancement on MRI. The fluorescence-guided malignant gliomas surgery was started 15 years ago and had become a standard of care in many countries. The technique is based on fluorescent molecule revelation using the filters, positioned within the surgical microscope. The fluorophore, protoporphyrin IX (PpIX), is converted in tumoral cells from 5-aminolevulinic acid (5-ALA), given orally before surgery. Many studies have shown that the ratio of gross total resections was higher if the fluorescence technique was used. The fluorescence signal intensity is correlated to the cell density and the PpIX concentration. The current method has a very high specificity but still lower sensibility, particularly regarding the zones with poor tumoral infiltration. This book reviews the principles of the technique and the results (extent of resection and survival).

Color-coded Imaging Enables Fluorescence-guided Surgery to Resect the Tumor Along with the Tumor Microenvironment in a Syngeneic Mouse Model of EL-4 Lymphoma.

PubMed

Hasegawa, Kosuke; Suetsugu, Atsushi; Nakamura, Miki; Matsumoto, Takuro; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

2016-09-01

Fluorescence-guided surgery (FGS) of cancer is an emerging technology. We have previously shown the importance of resecting both the tumor and the tumor microenvironment (TME) for curative FGS. We also previously developed a syngeneic model using the mouse lymphoma cell line EL-4, expressing red fluorescent protein (EL-4-RFP), growing in green fluorescent protein (GFP) transgenic mice, which we have used in the present report to develop FGS of the tumor microenvironment. EL-4-RFP lymphoma cells were injected subcutaneously in C57/BL6 GFP transgenic mice. EL-4-RFP cells subsequently formed tumors by 35 days after cell transplantation. Using the portable hand-held Dino-Lite digital imaging system, subcutaneous tumors were resected by FGS. Resected tumor tissues were visualized with the Olympus FV1000 confocal microscope. Using the Dino-Lite, subcutaneous tumors and the tumor microenvironment were clearly visualized and resected. In the resected tumor, host stromal cells, including adipocyte-like cells and blood vessels with lymphocytes, were observed by confocal microscopy in addition to cancer cells by color-coded confocal imaging. The cancer cells and stromal cells in the TME were deeply intermingled in a highly-complex pattern. Color-coded FGS is an effective method to completely resect cancer cells along with the stromal cells in the TME which interact in a highly-complex pattern. Microscopically, cancer cells invade the TME and vice versa. To prevent tumor recurrence, it is necessary to resect the TME along with the tumor. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence.

PubMed

Widhalm, Georg

2014-01-01

Precise histopathological diagnosis of brain tumors is essential for the correct patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intra-operative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intra-operative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated pre-operative imaging data such as CSI declines during resections due to intra-operative brainshift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intra-operative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intra-operative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brainshift. Consequently, this new technique might become a novel standard in brain tumor surgery that optimizes the patient management and improves the patient prognosis by maximizing the extent of tumor resection and enabling a precise histopathological tumor diagnosis.

δ-aminolevulinic acid–induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy

PubMed Central

Valdés, Pablo A.; Kim, Anthony; Brantsch, Marco; Niu, Carolyn; Moses, Ziev B.; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2011-01-01

Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery. PMID:21798847

Fluorescein-Guided Resection of Intramedullary Spinal Cord Tumors: Results from a Preliminary, Multicentric, Retrospective Study.

PubMed

Acerbi, Francesco; Cavallo, Claudio; Schebesch, Karl-Michael; Akçakaya, Mehmet Osman; de Laurentis, Camilla; Hamamcioglu, Mustafa Kemal; Broggi, Morgan; Brawanski, Alexander; Falco, Jacopo; Cordella, Roberto; Ferroli, Paolo; Kiris, Talat; Höhne, Julius

2017-12-01

Intramedullary spinal cord tumors (IMSCTs) are rare, heterogenous lesions that are usually enhanced on preoperative magnetic resonance imaging (MRI) because of a damaged blood-brain barrier. Sodium fluorescein is a dye that accumulates in areas of the central nervous system with a damaged BBB. Given the pattern of MRI contrast enhancement of the majority of IMSCTs, the use of this fluorescent tracer could improve tumor visualization and quality of resection. In this article, we present the first experience with the application of fluorescein-guided technique for surgical removal of IMSCTs. Eleven patients (6 men, 5 women; mean age, 50.1 years), harboring 5 ependymomas, 3 hemangioblastomas, 1 astrocytoma, 1 pilocytic astrocytoma, and 1 glioneuronal tumor forming rosettes were included. Sodium fluorescein (5 mg/kg) was injected immediately after patient intubation. Tumors were removed with microsurgical technique and standard neurophysiological monitoring, under YELLOW 560 filter (Pentero 900) visualization. Surgical reports were reviewed regarding usefulness and grade of fluorescein staining. Postoperative MRI was performed within 72 hours after surgery, and postoperative clinical outcome was registered. No adverse events were registered. Fluorescent staining was reported in 9 of 11 cases (82%), all of them enhancing on preoperative MRI (100% of ependymomas, 100% of pilocytic astrocytomas, 100% of hemangioblastomas). No fluorescence was reported in 1 astrocytoma and 1 glioneuronal tumor-forming rosette. Intraoperative fluorescence was considered helpful for tumor resection in 9 of 11 cases (82%). Gross total resection was obtained in 8 of 11 cases (72.7%). Our results suggest that fluorescein-guided surgery is a safe and effective technique that can be used during the surgical resection of IMSCTs presenting with contrast-enhancement on preoperative MRI. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of near-infrared fluorescence imaging in the resection of metastatic lymph nodes in an optimized orthotopic animal model of HNSCC.

PubMed

Atallah, I; Milet, C; Quatre, R; Henry, M; Reyt, E; Coll, J-L; Hurbin, A; Righini, C A

2015-12-01

To study the role of near-infrared fluorescence imaging in the detection and resection of metastatic cervical lymph nodes in head and neck cancer. CAL33 head and neck cancer cells of human origin were implanted in the oral cavity of nude mice. The mice were followed up after tumor resection to detect the development of lymph node metastases. A specific fluorescent tracer for αvβ3 integrin expressed by CAL33 cells was injected intravenously in the surviving mice between the second and the fourth month following tumor resection. A near-infrared fluorescence-imaging camera was used to detect tracer uptake in metastatic cervical lymph nodes, to guide of lymph-node resection for histological analysis. Lymph node metastases were observed in 42.8% of surviving mice between the second and the fourth month following orthotopic tumor resection. Near-infrared fluorescence imaging provided real-time intraoperative detection of clinical and subclinical lymph node metastases. These results were confirmed histologically. Near infrared fluorescence imaging provides real-time contrast between normal and malignant tissue, allowing intraoperative detection of metastatic lymph nodes. This preclinical stage is essential before testing the technique in humans. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance.

PubMed

Neira, Justin A; Ung, Timothy H; Sims, Jennifer S; Malone, Hani R; Chow, Daniel S; Samanamud, Jorge L; Zanazzi, George J; Guo, Xiaotao; Bowden, Stephen G; Zhao, Binsheng; Sheth, Sameer A; McKhann, Guy M; Sisti, Michael B; Canoll, Peter; D'Amico, Randy S; Bruce, Jeffrey N

2017-07-01

OBJECTIVE Extent of resection is an important prognostic factor in patients undergoing surgery for glioblastoma (GBM). Recent evidence suggests that intravenously administered fluorescein sodium associates with tumor tissue, facilitating safe maximal resection of GBM. In this study, the authors evaluate the safety and utility of intraoperative fluorescein guidance for the prediction of histopathological alteration both in the contrast-enhancing (CE) regions, where this relationship has been established, and into the non-CE (NCE), diffusely infiltrated margins. METHODS Thirty-two patients received fluorescein sodium (3 mg/kg) intravenously prior to resection. Fluorescence was intraoperatively visualized using a Zeiss Pentero surgical microscope equipped with a YELLOW 560 filter. Stereotactically localized biopsy specimens were acquired from CE and NCE regions based on preoperative MRI in conjunction with neuronavigation. The fluorescence intensity of these specimens was subjectively classified in real time with subsequent quantitative image analysis, histopathological evaluation of localized biopsy specimens, and radiological volumetric assessment of the extent of resection. RESULTS Bright fluorescence was observed in all GBMs and localized to the CE regions and portions of the NCE margins of the tumors, thus serving as a visual guide during resection. Gross-total resection (GTR) was achieved in 84% of the patients with an average resected volume of 95%, and this rate was higher among patients for whom GTR was the surgical goal (GTR achieved in 93.1% of patients, average resected volume of 99.7%). Intraoperative fluorescein staining correlated with histopathological alteration in both CE and NCE regions, with positive predictive values by subjective fluorescence evaluation greater than 96% in NCE regions. CONCLUSIONS Intraoperative administration of fluorescein provides an easily visualized marker for glioma pathology in both CE and NCE regions of GBM. These findings support the use of fluorescein as a microsurgical adjunct for guiding GBM resection to facilitate safe maximal removal.

Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model

PubMed Central

Li, Yuan; Jin, Zhengyu; Xue, Huadan; Wan, Yihong; Tian, Jie

2017-01-01

An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model. Fluorescence molecular imaging was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging was performed to monitor tumor growth and evaluate postsurgical tumor residuals, recurrences, and metastases. The PD-1-IRDye800CW exhibited a specific signal at the tumor region compared with the IgG control. Furthermore, PD-1-IRDye800CW-guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases and thus improved survival rate. Our study demonstrates the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from tumor residuals. PMID:29200846

Conditions for NIR fluorescence-guided tumor resectioning in preclinical lung cancer model (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kim, Minji; Quan, Yuhua; Choi, Byeong Hyun; Choi, Yeonho; Kim, Hyun Koo; Kim, Beop-Min

2016-03-01

Pulmonary nodule could be identified by intraoperative fluorescence imaging system from systemic injection of indocyanine green (ICG) which achieves enhanced permeability and retention (EPR) effects. This study was performed to evaluate optimal injection time of ICG for detecting cancer during surgery in rabbit lung cancer model. VX2 carcinoma cell was injected in rabbit lung under fluoroscopic computed tomography-guidance. Solitary lung cancer was confirmed on positron emitting tomography with CT (PET/CT) 2 weeks after inoculation. ICG was administered intravenously and fluorescent intensity of lung tumor was measured using the custom-built intraoperative color and fluorescence merged imaging system (ICFIS) for 15 hours. Solitary lung cancer was resected through thoracoscopic version of ICFIS. ICG was observed in all animals. Because Lung has fast blood pulmonary circulation, Fluorescent signal showed maximum intensity earlier than previous studies in other organs. Fluorescent intensity showed maximum intensity within 6-9 hours in rabbit lung cancer. Overall, Fluorescent intensity decreased with increasing time, however, all tumors were detectable using fluorescent images until 12 hours. In conclusion, while there had been studies in other organs showed that optimal injection time was at least 24 hours before operation, this study showed shorter optimal injection time at lung cancer. Since fluorescent signal showed the maximum intensity within 6-9 hours, cancer resection could be performed during this time. This data informed us that optimal injection time of ICG should be evaluated in each different solid organ tumor for fluorescent image guided surgery.

First-in-human study of PET and optical dual-modality image-guided surgery in glioblastoma using 68Ga-IRDye800CW-BBN.

PubMed

Li, Deling; Zhang, Jingjing; Chi, Chongwei; Xiao, Xiong; Wang, Junmei; Lang, Lixin; Ali, Iqbal; Niu, Gang; Zhang, Liwei; Tian, Jie; Ji, Nan; Zhu, Zhaohui; Chen, Xiaoyuan

2018-01-01

Purpose : Despite the use of fluorescence-guided surgery (FGS), maximum safe resection of glioblastoma multiforme (GBM) remains a major challenge. It has restricted surgeons between preoperative diagnosis and intraoperative treatment. Currently, an integrated approach combining preoperative assessment with intraoperative guidance would be a significant step in this direction. Experimental design : We developed a novel 68 Ga-IRDye800CW-BBN PET/near-infrared fluorescence (NIRF) dual-modality imaging probe targeting gastrin-releasing peptide receptor (GRPR) in GBM. The preclinical in vivo tumor imaging and FGS were first evaluated using an orthotopic U87MG glioma xenograft model. Subsequently, the first-in-human prospective cohort study (NCT 02910804) of GBM patients were conducted with preoperative PET assessment and intraoperative FGS. Results : The orthotopic tumors in mice could be precisely resected using the near-infrared intraoperative system. Translational cohort research in 14 GBM patients demonstrated an excellent correlation between preoperative positive PET uptake and intraoperative NIRF signal. The tumor fluorescence signals were significantly higher than those from adjacent brain tissue in vivo and ex vivo (p < 0.0001). Compared with pathology, the sensitivity and specificity of fluorescence using 42 loci of fluorescence-guided sampling were 93.9% (95% CI 79.8%-99.3%) and 100% (95% CI 66.4%-100%), respectively. The tracer was safe and the extent of resection was satisfactory without newly developed neurologic deficits. Progression-free survival (PFS) at 6 months was 80% and two newly diagnosed patients achieved long PFS. Conclusions: This initial study has demonstrated that the novel dual-modality imaging technique is feasible for integrated pre- and intraoperative targeted imaging via the same molecular receptor and improved intraoperative GBM visualization and maximum safe resection.

Near-infrared fluorescence goggle system with complementary metal–oxide–semiconductor imaging sensor and see-through display

PubMed Central

Liu, Yang; Njuguna, Raphael; Matthews, Thomas; Akers, Walter J.; Sudlow, Gail P.; Mondal, Suman; Tang, Rui

2013-01-01

Abstract. We have developed a near-infrared (NIR) fluorescence goggle system based on the complementary metal–oxide–semiconductor active pixel sensor imaging and see-through display technologies. The fluorescence goggle system is a compact wearable intraoperative fluorescence imaging and display system that can guide surgery in real time. The goggle is capable of detecting fluorescence of indocyanine green solution in the picomolar range. Aided by NIR quantum dots, we successfully used the fluorescence goggle to guide sentinel lymph node mapping in a rat model. We further demonstrated the feasibility of using the fluorescence goggle in guiding surgical resection of breast cancer metastases in the liver in conjunction with NIR fluorescent probes. These results illustrate the diverse potential use of the goggle system in surgical procedures. PMID:23728180

Quantitative spatial frequency fluorescence imaging in the sub-diffusive domain for image-guided glioma resection

PubMed Central

Sibai, Mira; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Wilson, Brian C.

2015-01-01

Intraoperative 5- aminolevulinic acid induced-Protoporphyrin IX (PpIX) fluorescence guidance enables maximum safe resection of glioblastomas by providing surgeons with real-time tumor optical contrast. However, visual assessment of PpIX fluorescence is subjective and limited by the distorting effects of light attenuation and tissue autofluorescence. We have previously shown that non-invasive point measurements of absolute PpIX concentration identifies residual tumor that is otherwise non-detectable. Here, we extend this approach to wide-field quantitative fluorescence imaging by implementing spatial frequency domain imaging to recover tissue optical properties across the field-of-view in phantoms and ex vivo tissue. PMID:26713206

Development of tumor-targeted near infrared probes for fluorescence guided surgery.

PubMed

Kelderhouse, Lindsay E; Chelvam, Venkatesh; Wayua, Charity; Mahalingam, Sakkarapalayam; Poh, Scott; Kularatne, Sumith A; Low, Philip S

2013-06-19

Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.

Fluorescence Imaging/Agents in Tumor Resection.

PubMed

Stummer, Walter; Suero Molina, Eric

2017-10-01

Intraoperative fluorescence imaging allows real-time identification of diseased tissue during surgery without being influenced by brain shift and surgery interruption. 5-Aminolevulinic acid, useful for malignant gliomas and other tumors, is the most broadly explored compound approved for fluorescence-guided resection. Intravenous fluorescein sodium has recently received attention, highlighting tumor tissue based on extravasation at the blood-brain barrier (defective in many brain tumors). Fluorescein in perfused brain, unselective extravasation in brain perturbed by surgery, and propagation with edema are concerns. Fluorescein is not approved but targeted fluorochromes with affinity to brain tumor cells, in development, may offer future advantages. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Blood interference in fiber-optical based fluorescence guided resection of glioma using 5-aminolevulinic acid

NASA Astrophysics Data System (ADS)

Haj-Hosseini, Neda; Lowndes, Shannely; Salerud, Göran; Wårdell, Karin

2011-03-01

Fluorescence guidance in brain tumor resection is performed intra-operatively where bleeding is included. When using fiber-optical probes, the transmission of light to and from the tissue is totally or partially blocked if a small amount of blood appears in front of the probe. Sometimes even after rinsing with saline, the remnant blood cells on the optical probe head, disturb the measurements. In such a case, the corresponding spectrum cannot be reliably quantified and is therefore discarded. The optimal case would be to calculate and take out the blood effect systematically from the collected signals. However, the first step is to study the pattern of blood interference in the fluorescence spectrum. In this study, a fiber-optical based fluorescence spectroscopy system with a laser excitation light of 405 nm (1.4 J/cm2) was used during fluorescence guided brain tumor resection using 5-aminolevulinic acid (5-ALA). The blood interference pattern in the fluorescence spectrum collected from the brain was studied in two patients. The operation situation was modeled in the laboratory by placing blood drops from the finger tip on the skin of forearm and the data was compared to the brain in vivo measurements. Additionally, a theoretical model was developed to simulate the blood interference pattern on the skin autofluorescence. The blood affects the collected fluorescence intensity and leaves traces of oxy and deoxy-hemoglobin absorption peaks. According to the developed theoretical model, the autofluorescence signal is considered to be totally blocked by an approximately 500 μm thick blood layer.

Localization of pulmonary nodules using navigation bronchoscope and a near-infrared fluorescence thoracoscope.

PubMed

Anayama, Takashi; Qiu, Jimmy; Chan, Harley; Nakajima, Takahiro; Weersink, Robert; Daly, Michael; McConnell, Judy; Waddell, Thomas; Keshavjee, Shaf; Jaffray, David; Irish, Jonathan C; Hirohashi, Kentaro; Wada, Hironobu; Orihashi, Kazumasa; Yasufuku, Kazuhiro

2015-01-01

Video-assisted thoracoscopic wedge resection of multiple small, non-visible, and nonpalpable pulmonary nodules is a clinical challenge. We propose an ultra-minimally invasive technique for localization of pulmonary nodules using the electromagnetic navigation bronchoscope (ENB)-guided transbronchial indocyanine green (ICG) injection and intraoperative fluorescence detection with a near-infrared (NIR) fluorescence thoracoscope. Fluorescence properties of ICG topically injected into the lung parenchyma were determined using a resected porcine lung. The combination of ENB-guided ICG injection and NIR fluorescence detection was tested using a live porcine model. An electromagnetic sensor integrated flexible bronchoscope was geometrically registered to the three-dimensional chest computed tomographic image data by way of a real-time electromagnetic tracking system. The ICG mixed with iopamidol was injected into the pulmonary nodules by ENB guidance; ICG fluorescence was visualized by a near-infrared (NIR) thoracoscope. The ICG existing under 24-mm depth of inflated lung was detectable by the NIR fluorescence thoracoscope. The size of the fluorescence spot made by 0.1 mL of ICG was 10.4 ± 2.2 mm. An ICG or iopamidol spot remained at the injected point of the lung for more than 6 hours in vivo. The ICG fluorescence spot injected into the pulmonary nodule with ENB guidance was identified at the pulmonary nodule with the NIR thoracoscope. The ENB-guided transbronchial ICG injection and intraoperative NIR thoracoscopic detection is a feasible method to localize multiple pulmonary nodules. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

PubMed

Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

2014-04-01

The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

Near-infrared dye marking for thoracoscopic resection of small-sized pulmonary nodules: comparison of percutaneous and bronchoscopic injection techniques.

PubMed

Anayama, Takashi; Hirohashi, Kentaro; Miyazaki, Ryohei; Okada, Hironobu; Kawamoto, Nobutaka; Yamamoto, Marino; Sato, Takayuki; Orihashi, Kazumasa

2018-01-12

Minimally invasive video-assisted thoracoscopic surgery for small-sized pulmonary nodules is challenging, and image-guided preoperative localisation is required. Near-infrared indocyanine green fluorescence is capable of deep tissue penetration and can be distinguished regardless of the background colour of the lung; thus, indocyanine green has great potential for use as a near-infrared fluorescent marker in video-assisted thoracoscopic surgery. Thirty-seven patients with small-sized pulmonary nodules, who were scheduled to undergo video-assisted thoracoscopic wedge resection, were enrolled in this study. A mixture of diluted indocyanine green and iopamidol was injected into the lung parenchyma as a marker, using either computed tomography-guided percutaneous or bronchoscopic injection techniques. Indications and limitations of the percutaneous and bronchoscopic injection techniques for marking nodules with indocyanine green fluorescence were examined and compared. In the computed tomography-guided percutaneous injection group (n = 15), indocyanine green fluorescence was detected in 15/15 (100%) patients by near-infrared thoracoscopy. A small pneumothorax occurred in 3/15 (20.0%) patients, and subsequent marking was unsuccessful after a pneumothorax occurred. In the bronchoscopic injection group (n = 22), indocyanine green fluorescence was detected in 21/22 (95.5%) patients. In 6 patients who underwent injection marking at 2 different lesion sites, 5/6 (83.3%) markers were successfully detected. Either computed tomography-guided percutaneous or bronchoscopic injection techniques can be used to mark pulmonary nodules with indocyanine green fluorescence. Indocyanine green is a safe and easily detectable fluorescent marker for video-assisted thoracoscopic surgery. Furthermore, the bronchoscopic injection approach enables surgeons to mark multiple lesion areas with less risk of causing a pneumothorax. UMIN-CTR R000027833 accepted by ICMJE. Registered 5 January 2013.

Image-guided surgery using near-infrared fluorescent light: from bench to bedside

NASA Astrophysics Data System (ADS)

Boogerd, Leonora S. F.; Handgraaf, Henricus J. M.; van de Velde, Cornelis J. H.; Vahrmeijer, Alexander L.

2015-03-01

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). Until now, most clinical trials have focused on suboptimal, non-targeted dyes. Although successful, a new era in image-guided surgery has begun by the introduction of tumor-targeted agents. In this paper, we will describe how tumor-targeted NIR fluorescent imaging can be applied in a clinical setting.

Fluorescence Behavior and Dural Infiltration of Meningioma Analyzed by 5-Aminolevulinic Acid-Based Fluorescence: Operating Microscope Versus Mini-Spectrometer.

PubMed

Knipps, Johannes; Beseoglu, Kerim; Kamp, Marcel; Fischer, Igor; Felsberg, Joerg; Neumann, Lisa M; Steiger, Hans-Jakob; Cornelius, Jan F

2017-12-01

To compare fluorescence intensity of tumor specimens, as measured by a fluorescence-guided surgery microscope and a spectrometer, to evaluate tumor infiltration of dura mater around meningiomas with help of these 2 different 5-aminolevulinic acid (5-ALA)-based fluorescence tools, and to correlate fluorescence intensity with histopathologic data. In a clinical series, meningiomas were resected by 5-ALA fluorescence-guided surgery. Fluorescence intensity was semiquantitatively rated by the surgeon at predefined points. Biopsies were harvested and fluorescence intensity measured by a spectrometer and histopathologically analyzed. Sampling was realized at the level of the dura in a centrifugal direction. A total of 104 biopsies (n = 13 tumors) were analyzed. Specificity and sensitivity of the microscope were 0.96 and 0.53 and of the spectrometer 0.95 and 0.93, respectively. Fluorescence intensity as measured by the spectrometer was correlated to histologically confirmed tumor burden. In a centrifugal direction, tumor burden and fluorescence intensity continuously decreased (along the dural tail). Below a threshold value of 639 arbitrary units no tumor was histologically detectable. At the level of the dura the spectrometer was highly sensitive for detection of meningioma cells. The surgical microscope showed false negative results and missed residual tumor cells in more than one half of the cases. The complementary use of both fluorescence tools may improve resection quality. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Bates, Brent D.; Tselepidakis, Niki N.; DSouza, Alisha V.; Gunn, Jason R.; Ramkumar, Dipak B.; Paulsen, Keith D.; Pogue, Brian W.; Henderson, Eric R.

2017-12-01

Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ˜1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ˜1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE.

Design of Protease Activated Optical Contrast Agents That Exploit a Latent Lysosomotropic Effect for Use in Fluorescence-Guided Surgery

PubMed Central

2015-01-01

There is a need for new molecular-guided contrast agents to enhance surgical procedures such as tumor resection that require a high degree of precision. Cysteine cathepsins are highly up-regulated in a wide variety of cancers, both in tumor cells and in the tumor-supporting cells of the surrounding stroma. Therefore, tools that can be used to dynamically monitor their activity in vivo could be used as imaging contrast agents for intraoperative fluorescence image guided surgery (FGS). Although multiple classes of cathepsin-targeted substrate probes have been reported, most suffer from overall fast clearance from sites of protease activation, leading to reduced signal intensity and duration in vivo. Here we describe the design and synthesis of a series of near-infrared fluorogenic probes that exploit a latent cationic lysosomotropic effect (LLE) to promote cellular retention upon protease activation. These probes show tumor-specific retention, fast activation kinetics, and rapid systemic distribution. We demonstrate that they are suitable for detection of diverse cancer types including breast, colon and lung tumors. Most importantly, the agents are compatible with the existing, FDA approved, da Vinci surgical system for fluorescence guided tumor resection. Therefore, our data suggest that the probes reported here can be used with existing clinical instrumentation to detect tumors and potentially other types of inflammatory lesions to guide surgical decision making in real time. PMID:26039341

ALA-induced PpIX fluorescence in epileptogenic tissue

NASA Astrophysics Data System (ADS)

Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

2011-03-01

Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

Fluorescence-guided tumor visualization using a custom designed NIR attachment to a surgical microscope for high sensitivity imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kittle, David S.; Patil, Chirag G.; Mamelak, Adam; Hansen, Stacey; Perry, Jeff; Ishak, Laura; Black, Keith L.; Butte, Pramod V.

2016-03-01

Current surgical microscopes are limited in sensitivity for NIR fluorescence. Recent developments in tumor markers attached with NIR dyes require newer, more sensitive imaging systems with high resolution to guide surgical resection. We report on a small, single camera solution enabling advanced image processing opportunities previously unavailable for ultra-high sensitivity imaging of these agents. The system captures both visible reflectance and NIR fluorescence at 300 fps while displaying full HD resolution video at 60 fps. The camera head has been designed to easily mount onto the Zeiss Pentero microscope head for seamless integration into surgical procedures.

Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children--a technical report.

PubMed

Beez, Thomas; Sarikaya-Seiwert, Sevgi; Steiger, Hans-Jakob; Hänggi, Daniel

2014-03-01

5-aminolevulinic acid (5-ALA) can be used as an adjunct for the surgery of adult malignant glioma and improves the rate of gross total resection and patient survival. So far, only three casuistic reports of fluorescence-guided surgery used in children have been published. We report our pilot series of 16 pediatric brain tumors treated with 5-ALA. Sixteen patients (mean age 9 years, range 1-16 years) received a standardized 5-ALA dose according to the published protocol after informed parental consent. The fluorescence status (positive versus negative) in correlation with histology as well as blood samples and adverse clinical symptoms were recorded. Histology revealed pilocytic astrocytoma (n = 7), classical medulloblastoma (n = 4), anaplastic astrocytoma (n = 1), glioblastoma (n = 3) and anaplastic ependymoma (n = 1). Positive fluorescence was observed in cases of anaplastic astrocytoma, glioblastoma, and medulloblastoma, respectively. Significant increases were registered for alanine aminotransferase (14.92 ± 1.106 U/l vs. 37.70 ± 3.795 U/l, P = 0.0020) and gamma glutamyl transpeptidase (12.69 ± 1.638 U/l vs. 39.29 ± 6.342 U/l, P = 0.0156), correlated with young age. No further adverse reactions were evident. Positive fluorescence was observed in two high-grade gliomas and one medulloblastoma after oral administration of 5-ALA. Thus, 5-ALA appears capable of inducing fluorescence in pediatric high-grade tumors. Adverse reactions observed in children were similar to those reported for adults, although very young children might be at increased risk. Further studies are required to elucidate pharmacokinetic and pharmacodynamic properties of 5-ALA in children and to assess its prognostic role in the resection of pediatric brain tumors.

Blood-Brain Barrier Disruption, Sodium Fluorescein, And Fluorescence-Guided Surgery Of Gliomas.

PubMed

Xiang, Yan; Zhu, Xiao-Peng; Zhao, Jian-Nong; Huang, Guo-Hao; Tang, Jun-Hai; Chen, Huan-Ran; Du, Lei; Zhang, Dong; Tang, Xue-Feng; Yang, Hui; Lv, Sheng-Qing

2018-01-22

Sodium fluorescein (SF) is an ideal dye for intraoperative guided-resection of high-grade gliomas (HGGs). However, it is not well understood whether the SF-guided technique is suitable for different grades of gliomas, and the correlation between fluorescence and pathology is also not yet clear. In this study, we investigated 28 patients, including 23 patients with HGG and 5 patients with low-grade glioma (LGG). All patients were treated using the SF-guided technique on a Pentero 900 microscope (Carl Zeiss, Oberkochen, Germany). Claudin-5 immunohistochemical (IHC) staining for the tumours and peritumour tissues was analyzed. Intraoperative yellow fluorescence was noted in all the HGGs but not in the LGGs. Claudin-5 expression in the blood brain barrier endothelial cells was downregulated and disconnected in the HGGs (p < 0.05), but had no difference or slightly decreased in the LGGs (p > 0.05). The SF-guided technique is suitable for HGG surgery but not for LGG surgery. Downregulation of claudin-5 expression may contribute to the presence of yellow fluorescence in the glioma in SF-guided surgery.

A Fluorescence-Guided Laser Ablation System for Removal of Residual Cancer in a Mouse Model of Soft Tissue Sarcoma.

PubMed

Lazarides, Alexander L; Whitley, Melodi J; Strasfeld, David B; Cardona, Diana M; Ferrer, Jorge M; Mueller, Jenna L; Fu, Henry L; Bartholf DeWitt, Suzanne; Brigman, Brian E; Ramanujam, Nimmi; Kirsch, David G; Eward, William C

2016-01-01

The treatment of soft tissue sarcoma (STS) generally involves tumor excision with a wide margin. Although advances in fluorescence imaging make real-time detection of cancer possible, removal is limited by the precision of the human eye and hand. Here, we describe a novel pulsed Nd:YAG laser ablation system that, when used in conjunction with a previously described molecular imaging system, can identify and ablate cancer in vivo. Mice with primary STS were injected with the protease-activatable probe LUM015 to label tumors. Resected tissues from the mice were then imaged and treated with the laser using the paired fluorescence-imaging/ laser ablation device, generating ablation clefts with sub-millimeter precision and minimal underlying tissue damage. Laser ablation was guided by fluorescence to target tumor tissues, avoiding normal structures. The selective ablation of tumor implants in vivo improved recurrence-free survival after tumor resection in a cohort of 14 mice compared to 12 mice that received no ablative therapy. This prototype system has the potential to be modified so that it can be used during surgery to improve recurrence-free survival in patients with cancer.

Development of a novel combined fluorescence and reflectance spectroscopy system for guiding high-grade glioma resections: confirmation of capability in lab experiments

NASA Astrophysics Data System (ADS)

Mousavi, Monirehalsadat; Xie, Haiyan; Xie, Zhiyuan; Brydegaard, Mikkel; Axelsson, Johan; Andersson-Engels, Stefan

2013-11-01

Total resection of glioblastoma multiform (GBM), the most common and aggressive malignant brain tumor, is challenging among other things due to difficulty in intraoperative discrimination between normal and residual tumor cells. This project demonstrates the potential of a system based on a combination of autofluorescence and diffuse reflectance spectroscopy to be useful as an intraoperative guiding tool. In this context, a system based on 5 LEDs coupled to optical fibers was employed to deliver UV/visible light to the sample sequentially. Remitted light from the tissue; including diffuse reflected and fluorescence of endogenous and exogenous fluorophores, as well as its photobleaching product, is transmitted to one photodiode and four avalanche photodiodes. This instrument has been evaluated with very promising results by performing various tissue-equivalent phantom laboratory and clinical studies on skin lesions.

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision.

PubMed

Samkoe, Kimberley S; Bates, Brent D; Tselepidakis, Niki N; DSouza, Alisha V; Gunn, Jason R; Ramkumar, Dipak B; Paulsen, Keith D; Pogue, Brian W; Henderson, Eric R

2017-12-01

Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ∼1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ∼1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Use of near infrared fluorescence during robot-assisted laparoscopic partial nephrectomy.

PubMed

Cornejo-Dávila, V; Nazmy, M; Kella, N; Palmeros-Rodríguez, M A; Morales-Montor, J G; Pacheco-Gahbler, C

2016-04-01

Partial nephrectomy is the treatment of choice for T1a tumours. The open approach is still the standard method. Robot-assisted laparoscopic surgery offers advantages that are applicable to partial nephrectomy, such as the use of the Firefly® system with near-infrared fluorescence. To demonstrate the implementation of fluorescence in nephron-sparing surgery. This case concerned a 37-year-old female smoker, with obesity. The patient had a right kidney tumour measuring 31 mm, which was found using tomography. She therefore underwent robot-assisted laparoscopic partial nephrectomy, with a warm ischaemia time of 22 minutes and the use of fluorescence with the Firefly® system to guide the resection. There were no complications. The tumour was a pT1aN0M0 renal cell carcinoma, with negative margins. Robot-assisted renal laparoscopic surgery is employed for nephron-sparing surgery, with good oncological and functional results. The combination of the Firefly® technology and intraoperative ultrasound can more accurately delimit the extent of the lesion, increase the negative margins and decrease the ischaemia time. Near-infrared fluorescence in robot-assisted partial nephrectomy is useful for guiding the tumour resection and can potentially improve the oncological and functional results. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

PubMed

Acerbi, Francesco; Broggi, Morgan; Eoli, Marica; Anghileri, Elena; Cavallo, Claudio; Boffano, Carlo; Cordella, Roberto; Cuppini, Lucia; Pollo, Bianca; Schiariti, Marco; Visintini, Sergio; Orsi, Chiara; La Corte, Emanuele; Broggi, Giovanni; Ferroli, Paolo

2014-02-01

Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

Evaluation of intraoperative fluorescence imaging-guided surgery in cancer-bearing dogs: a prospective proof-of-concept phase II study in 9 cases.

PubMed

Cabon, Quentin; Sayag, David; Texier, Isabelle; Navarro, Fabrice; Boisgard, Raphaël; Virieux-Watrelot, Dorothée; Ponce, Frédérique; Carozzo, Claude

2016-04-01

The objective was to prospectively evaluate the application of intraoperative fluorescence imaging (IOFI) in the surgical excision of malignant masses in dogs, using a novel lipid nanoparticle contrast agent. Dogs presenting with spontaneous soft-tissue sarcoma or subcutaneous tumors were prospectively enrolled. Clinical staging and whole-body computed tomography (CT) were performed. All the dogs received an intravenous injection of dye-loaded lipid nanoparticles, LipImage 815. Wide or radical resection was realized after CT examination. Real-time IOFI was performed before skin incision and after tumor excision. In cases of radical resection, the lymph nodes (LNs) were imaged. The margin/healthy tissues fluorescence ratio or LN/healthy tissues fluorescence ratio was measured and compared with the histologic margins or LN status. Nine dogs were included. Limb amputation was performed in 3 dogs, and wide resection in 6. No adverse effect was noted. Fluorescence was observed in all 9 of the tumors. The margins were clean in 5 of 6 dogs after wide surgical resection, and the margin/healthy tissues fluorescence ratio was close to 1.0 in all these dogs. Infiltrated margins were observed in 1 case, with a margin/healthy tissues fluorescence ratio of 3.2. Metastasis was confirmed in 2 of 3 LNs, associated with LN/healthy tissues fluorescence ratios of 2.1 and 4.2, whereas nonmetastatic LN was associated with a ratio of 1.0. LipImage 815 used as a contrast agent during IOFI seemed to allow for good discrimination between tumoral and healthy tissues. Future studies are scheduled to evaluate the sensitivity and specificity of IOFI using LipImage 815 as a tracer. Copyright © 2016 Elsevier Inc. All rights reserved.

Pulsed-light imaging for fluorescence guided surgery under normal room lighting.

PubMed

Sexton, Kristian; Davis, Scott C; McClatchy, David; Valdes, Pablo A; Kanick, Stephen C; Paulsen, Keith D; Roberts, David W; Pogue, Brian W

2013-09-01

Fluorescence guided surgery (FGS) is an emerging technology that has demonstrated improved surgical outcomes. However, dim lighting conditions required by current FGS systems are disruptive to standard surgical workflow. We present a novel FGS system capable of imaging fluorescence under normal room light by using pulsed excitation and gated acquisition. Images from tissue-simulating phantoms confirm visual detection down to 0.25 μM of protoporphyrin IX under 125 μW/cm2 of ambient light, more than an order of magnitude lower than that measured with the Zeiss Pentero in the dark. Resection of orthotopic brain tumors in mice also suggests that the pulsed-light system provides superior sensitivity in vivo.

Pulsed-light imaging for fluorescence guided surgery under normal room lighting

PubMed Central

Sexton, Kristian; Davis, Scott C.; McClatchy, David; Valdes, Pablo A.; Kanick, Stephen C.; Paulsen, Keith D.; Roberts, David W.; Pogue, Brian W.

2013-01-01

Fluorescence guided surgery (FGS) is an emerging technology that has demonstrated improved surgical outcomes. However, dim lighting conditions required bycurrent FGS systems are disruptive to standard surgical workflow. We present a novel FGS system capable of imaging fluorescence under normal room lightby using pulsed excitation and gated acquisition. Images from tissue-simulating phantoms confirm visual detection down to 0.25 μM of protopor-phyrin IX under 125 μW/cm2 of ambient light, more than an order of magnitude lower than that measured with the Zeiss Pentero in the dark. Resection of orthotopic brain tumors in mice also suggests that the pulsed-light system provides superior sensitivity in vivo. PMID:23988926

Fluorescein sodium-guided resection of cerebral metastases-an update.

PubMed

Höhne, Julius; Hohenberger, Christoph; Proescholdt, Martin; Riemenschneider, Markus J; Wendl, Christina; Brawanski, Alexander; Schebesch, Karl-Michael

2017-02-01

Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identification of tumor tissue. In 2012, we started evaluating fluorescein (FL) with the dedicated microscope filter in cerebral metastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients. Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25-85 years); 5 mg/kg bodyweight of FL was intravenously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events. Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL staining. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course. FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

Early Re-Do Surgery for Glioblastoma Is a Feasible and Safe Strategy to Achieve Complete Resection of Enhancing Tumor

PubMed Central

Schucht, Philippe; Murek, Michael; Jilch, Astrid; Seidel, Kathleen; Hewer, Ekkehard; Wiest, Roland; Raabe, Andreas; Beck, Jürgen

2013-01-01

Background Complete resection of enhancing tumor as assessed by early (<72 hours) postoperative MRI is regarded as the optimal result in glioblastoma surgery. As yet, there is no consensus on standard procedure if post-operative imaging reveals unintended tumor remnants. Objective The current study evaluated the feasibility and safety of an early re-do surgery aimed at completing resections with the aid of 5-ALA fluorescence and neuronavigation after detection of enhancing tumor remnants on post-operative MRI. Methods From October 2008 to October 2012 a single center institutional protocol offered a second surgery within one week to patients with unintentional incomplete glioblastoma resection. We report on the feasibility of the use 5-ALA fluorescence guidance, the extent of resection (EOR) rates and complications of early re-do surgery. Results Nine of 151 patients (6%) with glioblastoma resections had an unintentional tumor remnant with a volume >0.175 cm3. 5-ALA guided re-do surgery completed the resection (CRET) in all patients without causing neurological deficits, infections or other complications. Patients who underwent a re-do surgery remained hospitalized between surgeries, resulting in a mean length of hospital stay of 11 days (range 7-15), compared to 9 days for single surgery (range 3-23; p=0.147). Conclusion Our early re-do protocol led to complete resection of all enhancing tumor in all cases without any new neurological deficits and thus provides a similar oncological result as intraoperative MRI (iMRI). The repeated use of 5-ALA induced fluorescence, used for identification of small remnants, remains highly sensitive and specific in the setting of re-do surgery. Early re-do surgery is a feasible and safe strategy to complete unintended subtotal resections. PMID:24348904

A projective surgical navigation system for cancer resection

NASA Astrophysics Data System (ADS)

Gan, Qi; Shao, Pengfei; Wang, Dong; Ye, Jian; Zhang, Zeshu; Wang, Xinrui; Xu, Ronald

2016-03-01

Near infrared (NIR) fluorescence imaging technique can provide precise and real-time information about tumor location during a cancer resection surgery. However, many intraoperative fluorescence imaging systems are based on wearable devices or stand-alone displays, leading to distraction of the surgeons and suboptimal outcome. To overcome these limitations, we design a projective fluorescence imaging system for surgical navigation. The system consists of a LED excitation light source, a monochromatic CCD camera, a host computer, a mini projector and a CMOS camera. A software program is written by C++ to call OpenCV functions for calibrating and correcting fluorescence images captured by the CCD camera upon excitation illumination of the LED source. The images are projected back to the surgical field by the mini projector. Imaging performance of this projective navigation system is characterized in a tumor simulating phantom. Image-guided surgical resection is demonstrated in an ex-vivo chicken tissue model. In all the experiments, the projected images by the projector match well with the locations of fluorescence emission. Our experimental results indicate that the proposed projective navigation system can be a powerful tool for pre-operative surgical planning, intraoperative surgical guidance, and postoperative assessment of surgical outcome. We have integrated the optoelectronic elements into a compact and miniaturized system in preparation for further clinical validation.

Combination of hand-held probe and microscopy for fluorescence guided surgery in the brain tumor marginal zone.

PubMed

Richter, Johan C O; Haj-Hosseini, Neda; Hallbeck, Martin; Wårdell, Karin

2017-06-01

Visualization of the tumor is crucial for differentiating malignant tissue from healthy brain during surgery, especially in the tumor marginal zone. The aim of the study was to introduce a fluorescence spectroscopy-based hand-held probe (HHF-probe) for tumor identification in combination with the fluorescence guided resection surgical microscope (FGR-microscope), and evaluate them in terms of diagnostic performance and practical aspects of fluorescence detection. Eighteen operations were performed on 16 patients with suspected high-grade glioma. The HHF-probe and the FGR-microscope were used for detection of protoporphyrin (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) and evaluated against histopathological analysis and visual grading done through the FGR-microscope by the surgeon. A ratio of PpIX fluorescence intensity to the autofluorescence intensity (fluorescence ratio) was used to quantify the spectra detected by the probe. Fluorescence ratio medians (range 0 - 40) measured by the probe were related to the intensity of the fluorescence in the FGR-microscope, categorized as "none" (0.3, n=131), "weak" (1.6, n=34) and "strong" (5.4, n=28). Of 131 "none" points in the FGR-microscope, 88 (67%) exhibited fluorescence with the HHF-probe. For the tumor marginal zone, the area under the receiver operator characteristics (ROC) curve was 0.49 for the FGR-microscope and 0.65 for the HHF-probe. The probe was integrated in the established routine of tumor resection using the FGR-microscope. The HHF-probe was superior to the FGR-microscope in sensitivity; it detected tumor remnants after debulking under the FGR-microscope. The combination of the HHF-probe and the FGR-microscope was beneficial especially in the tumor marginal zone. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo.

PubMed

Valdes, Pablo A; Bekelis, Kimon; Harris, Brent T; Wilson, Brian C; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E; Erkmen, Kadir; Paulsen, Keith D; Roberts, David W

2014-03-01

The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

PubMed Central

Valdes, Pablo A.; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

2014-01-01

BACKGROUND The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intra-operative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (CPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher CPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature. PMID:23887194

Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors.

PubMed

Colby, Aaron H; Berry, Samantha M; Moran, Ann M; Pasion, Kristine Amber; Liu, Rong; Colson, Yolonda L; Ruiz-Opazo, Nelson; Grinstaff, Mark W; Herrera, Victoria L M

2017-02-28

A current challenge in the treatment of peritoneal carcinomatosis is the inability to detect, visualize, and resect small or microscopic tumors of pancreatic, ovarian, or mesothelial origin. In these diseases, the completeness of primary tumor resection is directly correlated with patient survival, and hence, identifying small sub-millimeter tumors (i.e., disseminated disease) is critical. Thus, new imaging techniques and probes are needed to improve cytoreductive surgery and patient outcomes. Highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) are described for use as a visual aid during cytoreductive surgery of pancreatic carcinomatosis. The covalent incorporation of rhodamine into ∼30 nm eNPs increases the fluorescent signal compared to free rhodamine, thereby affording a brighter and more effective probe than would be achieved by a single rhodamine molecule. Using the intraperitoneal route of administration, HFR-eNPs localize to regions of large (∼1 cm), sub-centimeter, and sub-millimeter intraperitoneal tumor in three different animal models, including pancreatic, mesothelioma, and ovarian carcinoma. Tumoral localization of the HFR-eNPs depends on both the material property (i.e., eNP polymer) as well as the surface chemistry (anionic surfactant vs PEGylated noncharged surfactant). In a rat model of pancreatic carcinomatosis, HFR-eNP identification of tumor is validated against gold-standard histopathological analysis to reveal that HFR-eNPs possess high specificity (99%) and sensitivity (92%) for tumors, in particular, sub-centimeter and microscopic sub-millimeter tumors, with an overall accuracy of 95%. Finally, as a proof-of-concept, HFR-eNPs are used to guide the resection of pancreatic tumors in a rat model of peritoneal carcinomatosis.

A Google Glass navigation system for ultrasound and fluorescence dual-mode image-guided surgery

NASA Astrophysics Data System (ADS)

Zhang, Zeshu; Pei, Jing; Wang, Dong; Hu, Chuanzhen; Ye, Jian; Gan, Qi; Liu, Peng; Yue, Jian; Wang, Benzhong; Shao, Pengfei; Povoski, Stephen P.; Martin, Edward W.; Yilmaz, Alper; Tweedle, Michael F.; Xu, Ronald X.

2016-03-01

Surgical resection remains the primary curative intervention for cancer treatment. However, the occurrence of a residual tumor after resection is very common, leading to the recurrence of the disease and the need for re-resection. We develop a surgical Google Glass navigation system that combines near infrared fluorescent imaging and ultrasonography for intraoperative detection of sites of tumor and assessment of surgical resection boundaries, well as for guiding sentinel lymph node (SLN) mapping and biopsy. The system consists of a monochromatic CCD camera, a computer, a Google Glass wearable headset, an ultrasonic machine and an array of LED light sources. All the above components, except the Google Glass, are connected to a host computer by a USB or HDMI port. Wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A control program is written in C++ to call OpenCV functions for image calibration, processing and display. The technical feasibility of the system is tested in both tumor simulating phantoms and in a human subject. When the system is used for simulated phantom resection tasks, the tumor boundaries, invisible to the naked eye, can be clearly visualized with the surgical Google Glass navigation system. This system has also been used in an IRB approved protocol in a single patient during SLN mapping and biopsy in the First Affiliated Hospital of Anhui Medical University, demonstrating the ability to successfully localize and resect all apparent SLNs. In summary, our tumor simulating phantom and human subject studies have demonstrated the technical feasibility of successfully using the proposed goggle navigation system during cancer surgery.

Open-air multispectral fluorescence-guided surgery platform for intraoperative detection of malignant tissue under ambient lighting conditions

NASA Astrophysics Data System (ADS)

Behrooz, Ali; Vasquez, Kristine O.; Waterman, Peter; Meganck, Jeff; Peterson, Jeffrey D.; Miller, Peter; Kempner, Joshua

2017-02-01

Intraoperative resection of tumors currently relies upon the surgeon's ability to visually locate and palpate tumor nodules. Undetected residual malignant tissue often results in the need for additional treatment or surgical intervention. The Solaris platform is a multispectral open-air fluorescence imaging system designed for translational fluorescence-guided surgery. Solaris supports video-rate imaging in four fixed fluorescence channels ranging from visible to near infrared, and a multispectral channel equipped with a liquid crystal tunable filter (LCTF) for multispectral image acquisition (520-620 nm). Identification of tumor margins using reagents emitting in the visible spectrum (400-650 nm), such as fluorescein isothiocyanate (FITC), present challenges considering the presence of auto-fluorescence from tissue and food in the gastrointestinal (GI) tract. To overcome this, Solaris acquires LCTF-based multispectral images, and by applying an automated spectral unmixing algorithm to the data, separates reagent fluorescence from tissue and food auto-fluorescence. The unmixing algorithm uses vertex component analysis to automatically extract the primary pure spectra, and resolves the reagent fluorescent signal using non-negative least squares. For validation, intraoperative in vivo studies were carried out in tumor-bearing rodents injected with FITC-dextran reagent that is primarily residing in malignant tissue 24 hours post injection. In the absence of unmixing, fluorescence from tumors is not distinguishable from that of surrounding tissue. Upon spectral unmixing, the FITC-labeled malignant regions become well defined and detectable. The results of these studies substantiate the multispectral power of Solaris in resolving FITC-based agent signal in deep tumor masses, under ambient and surgical light, and enhancing the ability to surgically resect them.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

PubMed

Stummer, Walter; Rodrigues, Floriano; Schucht, Philippe; Preuss, Matthias; Wiewrodt, Dorothee; Nestler, Ulf; Stein, Marco; Artero, José Manuel Cabezudo; Platania, Nunzio; Skjøth-Rasmussen, Jane; Della Puppa, Alessandro; Caird, John; Cortnum, Søren; Eljamel, Sam; Ewald, Christian; González-García, Laura; Martin, Andrew J; Melada, Ante; Peraud, Aurelia; Brentrup, Angela; Santarius, Thomas; Steiner, Hans Herbert

2014-12-01

Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children. Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence. Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %). Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

NASA Astrophysics Data System (ADS)

Sibai, Mira; Fisher, Carl; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Roberts, David W.; Wilson, Brian C.

2017-07-01

5-Aminolevelunic acid-induced protoporphyrin IX (PpIX) fluorescence-guided resection (FGR) enables maximum safe resection of glioma by providing real-time tumor contrast. However, the subjective visual assessment and the variable intrinsic optical attenuation of tissue limit this technique to reliably delineating only high-grade tumors that display strong fluorescence. We have previously shown, using a fiber-optic probe, that quantitative assessment using noninvasive point spectroscopic measurements of the absolute PpIX concentration in tissue further improves the accuracy of FGR, extending it to surgically curable low-grade glioma. More recently, we have shown that implementing spatial frequency domain imaging with a fluorescent-light transport model enables recovery of two-dimensional images of [PpIX], alleviating the need for time-consuming point sampling of the brain surface. We present first results of this technique modified for in vivo imaging on an RG2 rat brain tumor model. Despite the moderate errors in retrieving the absorption and reduced scattering coefficients in the subdiffusive regime of 14% and 19%, respectively, the recovered [PpIX] maps agree within 10% of the point [PpIX] values measured by the fiber-optic probe, validating its potential as an extension or an alternative to point sampling during glioma resection.

A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery.

PubMed

Warram, Jason M; de Boer, Esther; Moore, Lindsay S; Schmalbach, Cecelia E; Withrow, Kirk P; Carroll, William R; Richman, Joshua S; Morlandt, Anthony B; Brandwein-Gensler, Margaret; Rosenthal, Eben L

2015-07-01

Fluorescence-guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However, a standardized method for quantitative assessment of disease-specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi-quantitatively delineate tumor from normal tissue. Open-field and a closed-field imaging devices were used to quantify fluorescence in punch biopsy tissues sampled from primary tumors collected during a phase 1 trial evaluating the safety of cetuximab-IRDye800 in patients (n = 11) undergoing surgical intervention for head and neck cancer. Fluorescence ratios were calculated using mean fluorescence intensity (MFI) from punch biopsy normalized by MFI of patient-matched tissues. Ratios were compared to pathological assessment and a ratiometric threshold was established to predict presence of cancer. During open-field imaging using an intraoperative device, the threshold for muscle normalized tumor fluorescence was found to be 2.7, which produced a sensitivity of 90.5% and specificity of 78.6% for delineating disease tissue. The skin-normalized threshold generated greater sensitivity (92.9%) and specificity (81.0%). Successful implementation of a semi-quantitative threshold can provide a scientific methodology for delineating disease from normal tissue during fluorescence-guided resection of cancer. © 2015 Wiley Periodicals, Inc.

Fluorescently labeled therapeutic antibodies for detection of microscopic melanoma

PubMed Central

Day, Kristine E.; Beck, Lauren N.; Deep, Nicholas L.; Kovar, Joy; Zinn, Kurt R; Rosenthal, Eben L.

2013-01-01

Objective Detection of microscopic disease during surgical resection of melanoma remains a significant challenge. To assess real-time optical imaging for visualization of microscopic cancer, we evaluated three FDA-approved therapeutic monoclonal antibodies. Study Design Prospective, basic science Methods Melanoma cell lines (A375 and SKMEL5) were xenografted into the ears of immunodeficient mice. Bevacizumab, panitumumab, tocilizumab, or a non-specific IgG were covalently linked to a near-infrared (NIR) fluorescent probe (IRDye800CW) and systemically injected. Primary tumors were imaged and then resected under fluorescent guidance using the SPY, an NIR imaging system used in plastic and reconstructive surgeries to evaluate perfusion. Mice were also imaged with the Pearl Impulse small animal imager, an NIR imaging system designed for use with IRDye800CW. Post-resection, small tissue fragments were fluorescently imaged and presence of tumor subsequently confirmed by correlation with histology. Results All fluorescently-labeled therapeutic monoclonal antibodies could adequately delineate tumor from normal tissue based on tumor-to-background ratios (TBR) compared to IgG-IRDye800CW. On serial imaging, panitumumab achieved the highest TBRs with both SPY and Pearl (3.8 and 6.6). When used to guide resections, the antibody-dye conjugates generated TBRs in the range of 1.3-2.2 (average=1.6) using the SPY and 1.9-6.3 (average=2.7) using the Pearl. There was no significant difference amongst the antibodies with either imaging modality or cell line (one-way ANOVA). Conclusion Our data suggests that FDA approved antibodies may be suitable targeting agents for the intraoperative fluorescent detection of melanoma. Level of Evidence N/A PMID:23616260

Quantitative fluorescence using 5-aminolevulinic acid–induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

PubMed Central

Valdés, Pablo A.; Jacobs, Valerie; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Paulsen, Keith D.; Roberts, David W.

2015-01-01

OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively. CONCLUSIONS The authors’ initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors’ initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs. PMID:26140489

[Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant gliomas--a new treatment modality].

PubMed

Cortnum, Søren; Laursen, Rene

2013-02-25

5-aminolevulinic acid (ALA) is a precursor of haemoglobin which leads to the synthesis of porphyrins in malignant gliomas which then appears with red fluorescence under blue light. In the literature we see that there is class Ib evidence that 5-ALA guided surgery significantly increases the radicalism of surgery and gives rise to a marked improvement in 6-month progression-free survival and that there is now class II evidence confirming the value of maximal cytoreductive surgery. Furthermore, existing class II evidence indicates that there is a synergistic effect between aggressive cytoreductive surgery and radiochemotherapy.

Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery

PubMed Central

Yano, Shuya; Hiroshima, Yukihiko; Maawy, Ali; Kishimoto, Hiroyuki; Suetsugu, Atsushi; Miwa, Shinji; Toneri, Makoto; Yamamoto, Mako; Katz, Matthew H.G.; Fleming, Jason B.; Urata, Yasuo; Tazawa, Hiroshi; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2015-01-01

Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. In order to achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP) containing adenovirus OBP401 was used to label the cancer cells of the pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery (BLS) or single color could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant cancer. PMID:26088297

5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature.

PubMed

Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Rossetto, Marta; Gerardi, Alessandra; Lombardi, Giuseppe; Manara, Renzo; Munari, Marina; Saladini, Marina; Scienza, Renato

2013-06-01

Only few data are available on the specific topic of 5-aminolevulinic acid (5-ALA) guided surgery of high-grade gliomas (HGG) located in eloquent areas. Studies focusing specifically on the post-operative clinical outcome of such patients are yet not available, and it has not been so far explored whether such approach could be more suitable for some particular subgroups of patients. Patients affected by HGG in eloquent areas who underwent surgery assisted by 5-ALA fluorescence and intra-operative monitoring were prospectively recruited in our Department between June 2011 and August 2012. Resection rate was reported as complete resection of enhancing tumor (CRET), gross total resection (GTR) >98 % and GTR > 90 %. Clinical outcome was evaluated at 7, 30, and 90 days after surgery. Thirty-one patients were enrolled. Resection was complete (CRET) in 74 % of patients. Tumor removal was stopped to avoid neurological impairment in 26 % of cases. GTR > 98 % and GTR > 90 % was achieved in 93 % and 100 % of cases, respectively. First surgery and awake surgery had a CRET rate of 80 % and 83 %, respectively. Even though at the first-week assessment 64 % of patients presented neurological impairment, there was a 3 % rate of severe morbidity at the 90th day assessment. Newly diagnosed patients had a significantly lower morbidity (0 %) and post-operative higher median KPS. Both pre-operative neurological condition and improvement after corticosteroids resulted significantly predictive of post-operative functional outcome. 5-ALA surgery assisted by functional mapping makes high HGG resection in eloquent areas feasible , through a reasonable rate of late morbidity. This emerges even more remarkably for selected patients.

Toward real-time tumor margin identification in image-guided robotic brain tumor resection

NASA Astrophysics Data System (ADS)

Hu, Danying; Jiang, Yang; Belykh, Evgenii; Gong, Yuanzheng; Preul, Mark C.; Hannaford, Blake; Seibel, Eric J.

2017-03-01

For patients with malignant brain tumors (glioblastomas), a safe maximal resection of tumor is critical for an increased survival rate. However, complete resection of the cancer is hard to achieve due to the invasive nature of these tumors, where the margins of the tumors become blurred from frank tumor to more normal brain tissue, but in which single cells or clusters of malignant cells may have invaded. Recent developments in fluorescence imaging techniques have shown great potential for improved surgical outcomes by providing surgeons intraoperative contrast-enhanced visual information of tumor in neurosurgery. The current near-infrared (NIR) fluorophores, such as indocyanine green (ICG), cyanine5.5 (Cy5.5), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), are showing clinical potential to be useful in targeting and guiding resections of such tumors. Real-time tumor margin identification in NIR imaging could be helpful to both surgeons and patients by reducing the operation time and space required by other imaging modalities such as intraoperative MRI, and has the potential to integrate with robotically assisted surgery. In this paper, a segmentation method based on the Chan-Vese model was developed for identifying the tumor boundaries in an ex-vivo mouse brain from relatively noisy fluorescence images acquired by a multimodal scanning fiber endoscope (mmSFE). Tumor contours were achieved iteratively by minimizing an energy function formed by a level set function and the segmentation model. Quantitative segmentation metrics based on tumor-to-background (T/B) ratio were evaluated. Results demonstrated feasibility in detecting the brain tumor margins at quasi-real-time and has the potential to yield improved precision brain tumor resection techniques or even robotic interventions in the future.

Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery.

PubMed

Hoogstins, Charlotte; Burggraaf, Jan Jaap; Koller, Marjory; Handgraaf, Henricus; Boogerd, Leonora; van Dam, Gooitzen; Vahrmeijer, Alexander; Burggraaf, Jacobus

2018-05-29

Intraoperative fluorescence imaging (FI) is a promising technique that could potentially guide oncologic surgeons toward more radical resections and thus improve clinical outcome. Despite the increase in the number of clinical trials, fluorescent agents and imaging systems for intraoperative FI, a standardized approach for imaging system performance assessment and post-acquisition image analysis is currently unavailable. We conducted a systematic, controlled comparison between two commercially available imaging systems using a novel calibration device for FI systems and various fluorescent agents. In addition, we analyzed fluorescence images from previous studies to evaluate signal-to-background ratio (SBR) and determinants of SBR. Using the calibration device, imaging system performance could be quantified and compared, exposing relevant differences in sensitivity. Image analysis demonstrated a profound influence of background noise and the selection of the background on SBR. In this article, we suggest clear approaches for the quantification of imaging system performance assessment and post-acquisition image analysis, attempting to set new standards in the field of FI.

A Ratiometric Threshold for Determining Presence of Cancer During Fluorescence-guided Surgery

PubMed Central

Warram, Jason M; de Boer, Esther; Moore, Lindsay S.; Schmalbach, Cecelia E; Withrow, Kirk P; Carroll, William R; Richman, Joshua S; Morlandt, Anthony B; Brandwein-Gensler, Margaret; Rosenthal, Eben L

2015-01-01

Background&Objective Fluorescence-guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However a standardized method for quantitative assessment of disease-specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi-quantitatively delineate tumor from normal tissue. Methods Open-field and a closed-field imaging devices were used to quantify fluorescence in punch biopsy tissues sampled from primary tumors collected during a phase 1 trial evaluating the safety of cetuximab-IRDye800 in patients (n=11) undergoing surgical intervention for head and neck cancer. Fluorescence ratios were calculated using mean fluorescence intensity (MFI) from punch biopsy normalized by MFI of patient-matched tissues. Ratios were compared to pathological assessment and a ratiometric threshold was established to predict presence of cancer. Results During open-field imaging using an intraoperative device, the threshold for muscle normalized tumor fluorescence was found to be 2.7, which produced a sensitivity of 90.5% and specificity of 78.6% for delineating disease tissue. The skin-normalized threshold generated greater sensitivity (92.9%) and specificity (81.0%). Conclusion Successful implementation of a semi-quantitative threshold can provide a scientific methodology for delineating disease from normal tissue during fluorescence-guided resection of cancer. PMID:26074273

Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between δ-aminolevulinic acid–induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters

PubMed Central

Roberts, David W.; Valdés, Pablo A.; Harris, Brent T.; Fontaine, Kathryn M.; Hartov, Alexander; Fan, Xiaoyao; Ji, Songbai; Lollis, S. Scott; Pogue, Brian W.; Leblond, Frederic; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.

2010-01-01

Object The aim of this study was to investigate the relationships between intraoperative fluorescence, features on MR imaging, and neuropathological parameters in 11 cases of newly diagnosed glioblastoma multiforme (GBM) treated using protoporphyrin IX (PpIX) fluorescence-guided resection. Methods In 11 patients with a newly diagnosed GBM, δ-aminolevulinic acid (ALA) was administered to enhance endogenous synthesis of the fluorophore PpIX. The patients then underwent fluorescence-guided resection, coregistered with conventional neuronavigational image guidance. Biopsy specimens were collected at different times during surgery and assigned a fluorescence level of 0–3 (0, no fluorescence; 1, low fluorescence; 2, moderate fluorescence; or 3, high fluorescence). Contrast enhancement on MR imaging was quantified using two image metrics: 1) Gd-enhanced signal intensity (GdE) on T1-weighted subtraction MR image volumes, and 2) normalized contrast ratios (nCRs) in T1-weighted, postGd-injection MR image volumes for each biopsy specimen, using the biopsy-specific image-space coordinate transformation provided by the navigation system. Subsequently, each GdE and nCR value was grouped into one of two fluorescence categories, defined by its corresponding biopsy specimen fluorescence assessment as negative fluorescence (fluorescence level 0) or positive fluorescence (fluorescence level 1, 2, or 3). A single neuropathologist analyzed the H & E–stained tissue slides of each biopsy specimen and measured three neuropathological parameters: 1) histopathological score (0–IV); 2) tumor burden score (0–III); and 3) necrotic burden score (0–III). Results Mixed-model analyses with random effects for individuals show a highly statistically significant difference between fluorescing and nonfluorescing tissue in GdE (mean difference 8.33, p = 0.018) and nCRs (mean difference 5.15, p < 0.001). An analysis of association demonstrated a significant relationship between the levels of intraoperative fluorescence and histopathological score (χ2 = 58.8, p < 0.001), between fluorescence levels and tumor burden (χ2 = 42.7, p < 0.001), and between fluorescence levels and necrotic burden (χ2 = 30.9, p < 0.001). The corresponding Spearman rank correlation coefficients were 0.51 (p < 0.001) for fluorescence and histopathological score, and 0.49 (p < 0.001) for fluorescence and tumor burden, suggesting a strongly positive relationship for each of these variables. Conclusions These results demonstrate a significant relationship between contrast enhancement on preoperative MR imaging and observable intraoperative PpIX fluorescence. The finding that preoperative MR image signatures are predictive of intraoperative PpIX fluorescence is of practical importance for identifying candidates for the procedure. Furthermore, this study provides evidence that a strong relationship exists between tumor aggressiveness and the degree of tissue fluorescence that is observable intraoperatively, and that observable fluorescence has an excellent positive predictive value but a low negative predictive value. PMID:20380535

A Dual Reporter Iodinated Labeling Reagent for Cancer Positron Emission Tomography Imaging and Fluorescence-Guided Surgery

PubMed Central

2018-01-01

The combination of early diagnosis and complete surgical resection offers the greatest prospect of curative cancer treatment. An iodine-124/fluorescein-based dual-modality labeling reagent, 124I-Green, constitutes a generic tool for one-step installation of a positron emission tomography (PET) and a fluorescent reporter to any cancer-specific antibody. The resulting antibody conjugate would allow both cancer PET imaging and intraoperative fluorescence-guided surgery. 124I-Green was synthesized in excellent radiochemical yields of 92 ± 5% (n = 4) determined by HPLC with an improved one-pot three-component radioiodination reaction. The A5B7 carcinoembryonic antigen (CEA)-specific antibody was conjugated to 124I-Green. High tumor uptake of the dual-labeled A5B7 of 20.21 ± 2.70, 13.31 ± 0.73, and 10.64 ± 1.86%ID/g was observed in CEA-expressing SW1222 xenograft mouse model (n = 3) at 24, 48, and 72 h post intravenous injection, respectively. The xenografts were clearly visualized by both PET/CT and ex vivo fluorescence imaging. These encouraging results warrant the further translational development of 124I-Green for cancer PET imaging and fluorescence-guided surgery. PMID:29388770

Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature

PubMed Central

Francaviglia, Natale; Iacopino, Domenico Gerardo; Costantino, Gabriele; Villa, Alessandro; Impallaria, Pietro; Meli, Francesco; Maugeri, Rosario

2017-01-01

Background: The importance of a complete resection of high-grade gliomas (HGGs) has been highlighted in scientific literature, in order to limit tumor recurrence and above all to improve disease-free survival rates. Several fluorescent biomarkers have been tested to improve intraoperative identification of residual tumor; 5-aminolevulinic acid (5-ALA) and fluorescein sodium (FS) are now starting to play a central role in glioma surgery. We performed a retrospective analysis on 47 patients operated for HGGs. Here we report our preliminary data. Methods: Data of 47 consecutive patients with HGG have been collected in our study (25 males, 22 females; mean age: 60.3 years, range: 27–86 years). Fluorescein (5 mg/kg of body weight) was injected intravenously right after the induction of general anesthesia. A YELLOW 560 filter was used on an OPMI Pentero 900 microscope (Carl Zeiss Meditec, Oberkochen, Germany) to complete a microsurgical tumor removal. Glioma resection and quality of life were evaluated preoperative and postoperatively. Results: Gross total resection (GTR) was achieved in 53.2% (n = 25) of patients. A subtotal resection (STR) (>95%) was achieved in 29.8% (n = 14), while a partial resection (PR) (<95%) was obtained in 17% (n = 8) of patients. Overall, in 83% (n = 39) of patients who underwent fluorescence-guided surgery the resection rate achieved was >95%. No adverse effects correlated to fluorescein have been recorded. Conclusion: Fluorescein seems to be safe and effective in the resection of HGGs, allowing a high rate of gross total removal of contrast enhanced areas. PMID:28781922

Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature.

PubMed

Francaviglia, Natale; Iacopino, Domenico Gerardo; Costantino, Gabriele; Villa, Alessandro; Impallaria, Pietro; Meli, Francesco; Maugeri, Rosario

2017-01-01

The importance of a complete resection of high-grade gliomas (HGGs) has been highlighted in scientific literature, in order to limit tumor recurrence and above all to improve disease-free survival rates. Several fluorescent biomarkers have been tested to improve intraoperative identification of residual tumor; 5-aminolevulinic acid (5-ALA) and fluorescein sodium (FS) are now starting to play a central role in glioma surgery. We performed a retrospective analysis on 47 patients operated for HGGs. Here we report our preliminary data. Data of 47 consecutive patients with HGG have been collected in our study (25 males, 22 females; mean age: 60.3 years, range: 27-86 years). Fluorescein (5 mg/kg of body weight) was injected intravenously right after the induction of general anesthesia. A YELLOW 560 filter was used on an OPMI Pentero 900 microscope (Carl Zeiss Meditec, Oberkochen, Germany) to complete a microsurgical tumor removal. Glioma resection and quality of life were evaluated preoperative and postoperatively. Gross total resection (GTR) was achieved in 53.2% ( n = 25) of patients. A subtotal resection (STR) (>95%) was achieved in 29.8% ( n = 14), while a partial resection (PR) (<95%) was obtained in 17% ( n = 8) of patients. Overall, in 83% ( n = 39) of patients who underwent fluorescence-guided surgery the resection rate achieved was >95%. No adverse effects correlated to fluorescein have been recorded. Fluorescein seems to be safe and effective in the resection of HGGs, allowing a high rate of gross total removal of contrast enhanced areas.

Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

PubMed Central

Valdés, Pablo A.; Leblond, Frederic; Kim, Anthony; Harris, Brent T.; Wilson, Brian C.; Fan, Xiaoyao; Tosteson, Tor D.; Hartov, Alex; Ji, Songbai; Erkmen, Kadir; Simmons, Nathan E.; Paulsen, Keith D.; Roberts, David W.

2011-01-01

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors. PMID:21438658

Comparing high-resolution microscopy techniques for potential intraoperative use in guiding low-grade glioma resections.

PubMed

Meza, Daphne; Wang, Danni; Wang, Yu; Borwege, Sabine; Sanai, Nader; Liu, Jonathan T C

2015-04-01

Fluorescence image-guided surgery (FIGS), with contrast provided by 5-ALA-induced PpIX, has been shown to enable a higher extent of resection of high-grade gliomas. However, conventional FIGS with low-power microscopy lacks the sensitivity to aid in low-grade glioma (LGG) resection because PpIX signal is weak and sparse in such tissues. Intraoperative high-resolution microscopy of PpIX fluorescence has been proposed as a method to guide LGG resection, where sub-cellular resolution allows for the visualization of sparse and punctate mitochondrial PpIX production in tumor cells. Here, we assess the performance of three potentially portable high-resolution microscopy techniques that may be used for the intraoperative imaging of human LGG tissue samples with PpIX contrast: high-resolution fiber-optic microscopy (HRFM), high-resolution wide-field microscopy (WFM), and dual-axis confocal (DAC) microscopy. Thick unsectioned human LGG tissue samples (n = 7) with 5-ALA-induced PpIX contrast were imaged using three imaging techniques (HRFM, WFM, DAC). The average signal-to-background ratio (SBR) was then calculated for each imaging modality (5 images per tissue, per modality). HRFM provides the ease of use and portability of a flexible fiber bundle, and is simple and inexpensive to build. However, in most cases (6/7), HRFM is not capable of detecting PpIX signal from LGGs due to high autofluorescence, generated by the fiber bundle under laser illumination at 405 nm, which overwhelms the PpIX signal and impedes its visualization. WFM is a camera-based method possessing high lateral resolution but poor axial resolution, resulting in sub-optimal image contrast. Consistent successful detection of PpIX signal throughout our human LGG tissue samples (n = 7), with an acceptable image contrast (SBR >2), was only achieved using DAC microscopy, which offers superior image resolution and contrast that is comparable to histology, but requires a laser-scanning mechanism to achieve optical sectioning. © 2015 Wiley Periodicals, Inc.

Clinical application of indocyanine green (ICG) fluorescent imaging of hepatoblastoma.

PubMed

Yamamichi, Taku; Oue, Takaharu; Yonekura, Takeo; Owari, Mitsugu; Nakahata, Kengo; Umeda, Satoshi; Nara, Keigo; Ueno, Takehisa; Uehara, Shuichiro; Usui, Noriaki

2015-05-01

Although the usefulness of intraoperative indocyanine green (ICG) fluorescent imaging for the resection of hepatocellular carcinoma has been reported, its usefulness for the resection of hepatoblastoma remains unclear. This study clarifies the feasibility of intraoperative ICG fluorescent imaging for the resection of hepatoblastoma. In three hepatoblastoma patients, a primary tumor, recurrent tumor, and lung metastatic lesions were intraoperatively examined using a near-infrared fluorescence imaging system after the preoperative administration of ICG. ICG fluorescent imaging was useful for the surgical navigation in hepatoblastoma patients. In the first case, the primary hepatoblastoma exhibited intense fluorescence during right hepatectomy, but no fluorescence was detected in the residual liver. In the second case, a recurrent tumor exhibited fluorescence between the residual liver and diaphragm. A complete resection of the residual liver, with a partial resection of the diaphragm, followed by liver transplantation was performed. In the third case with multiple lung metastases, each metastatic lesion showed positive fluorescence, and all were completely resected. These fluorescence-positive lesions were pathologically proven to be viable hepatoblastoma cells. Intraoperative ICG fluorescence imaging for patients with hepatoblastoma was feasible and useful for identifying small viable lesions and confirming that no remnant tumor remained after resection. Copyright © 2015 Elsevier Inc. All rights reserved.

Improved sensitivity to fluorescence for cancer detection in wide-field image-guided neurosurgery

PubMed Central

Jermyn, Michael; Gosselin, Yoann; Valdes, Pablo A.; Sibai, Mira; Kolste, Kolbein; Mercier, Jeanne; Angulo, Leticia; Roberts, David W.; Paulsen, Keith D.; Petrecca, Kevin; Daigle, Olivier; Wilson, Brian C.; Leblond, Frederic

2015-01-01

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX sensitivity in wide-field fluorescence imaging may improve the residual tumor detection during surgery with consequent impact on survival. PMID:26713218

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.

PubMed

Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

2017-01-01

The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood-brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma.

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

PubMed Central

Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

2017-01-01

The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood–brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma. PMID:28579776

Dual-modality optical biopsy of glioblastomas multiforme with diffuse reflectance and fluorescence: ex vivo retrieval of optical properties

NASA Astrophysics Data System (ADS)

Du Le, Vinh Nguyen; Provias, John; Murty, Naresh; Patterson, Michael S.; Nie, Zhaojun; Hayward, Joseph E.; Farrell, Thomas J.; McMillan, William; Zhang, Wenbin; Fang, Qiyin

2017-02-01

Glioma itself accounts for 80% of all malignant primary brain tumors, and glioblastoma multiforme (GBM) accounts for 55% of such tumors. Diffuse reflectance and fluorescence spectroscopy have the potential to discriminate healthy tissues from abnormal tissues and therefore are promising noninvasive methods for improving the accuracy of brain tissue resection. Optical properties were retrieved using an experimentally evaluated inverse solution. On average, the scattering coefficient is 2.4 times higher in GBM than in low grade glioma (LGG), and the absorption coefficient is 48% higher. In addition, the ratio of fluorescence to diffuse reflectance at the emission peak of 460 nm is 2.6 times higher for LGG while reflectance at 650 nm is 2.7 times higher for GBM. The results reported also show that the combination of diffuse reflectance and fluorescence spectroscopy could achieve sensitivity of 100% and specificity of 90% in discriminating GBM from LGG during ex vivo measurements of 22 sites from seven glioma specimens. Therefore, the current technique might be a promising tool for aiding neurosurgeons in determining the extent of surgical resection of glioma and, thus, improving intraoperative tumor identification for guiding surgical intervention.

Dual-modality optical biopsy of glioblastomas multiforme with diffuse reflectance and fluorescence: ex vivo retrieval of optical properties.

PubMed

Du Le, Vinh Nguyen; Provias, John; Murty, Naresh; Patterson, Michael S; Nie, Zhaojun; Hayward, Joseph E; Farrell, Thomas J; McMillan, William; Zhang, Wenbin; Fang, Qiyin

2017-02-01

Glioma itself accounts for 80% of all malignant primary brain tumors, and glioblastoma multiforme (GBM) accounts for 55% of such tumors. Diffuse reflectance and fluorescence spectroscopy have the potential to discriminate healthy tissues from abnormal tissues and therefore are promising noninvasive methods for improving the accuracy of brain tissue resection. Optical properties were retrieved using an experimentally evaluated inverse solution. On average, the scattering coefficient is 2.4 times higher in GBM than in low grade glioma (LGG), and the absorption coefficient is 48% higher. In addition, the ratio of fluorescence to diffuse reflectance at the emission peak of 460 nm is 2.6 times higher for LGG while reflectance at 650 nm is 2.7 times higher for GBM. The results reported also show that the combination of diffuse reflectance and fluorescence spectroscopy could achieve sensitivity of 100% and specificity of 90% in discriminating GBM from LGG during ex vivo measurements of 22 sites from seven glioma specimens. Therefore, the current technique might be a promising tool for aiding neurosurgeons in determining the extent of surgical resection of glioma and, thus, improving intraoperative tumor identification for guiding surgical intervention.

Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article.

PubMed

Stummer, Walter; Tonn, Jörg-Christian; Mehdorn, Hubertus Maximilian; Nestler, Ulf; Franz, Kea; Goetz, Claudia; Bink, Andrea; Pichlmeier, Uwe

2011-03-01

Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA-induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery. Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function. More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm(3), p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0.0036). Extended resections performed using a tool such as 5-ALA-derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.

Optical-sectioning microscopy of protoporphyrin IX fluorescence in human gliomas: standardization and quantitative comparison with histology

NASA Astrophysics Data System (ADS)

Wei, Linpeng; Chen, Ye; Yin, Chengbo; Borwege, Sabine; Sanai, Nader; Liu, Jonathan T. C.

2017-04-01

Systemic delivery of 5-aminolevulinic acid leads to enhanced fluorescence image contrast in many tumors due to the increased accumulation of protoporphyrin IX (PpIX), a fluorescent porphyrin that is associated with tumor burden and proliferation. The value of PpIX-guided resection of malignant gliomas has been demonstrated in prospective randomized clinical studies in which a twofold greater extent of resection and improved progression-free survival have been observed. In low-grade gliomas and at the diffuse infiltrative margins of all gliomas, PpIX fluorescence is often too weak to be detected with current low-resolution surgical microscopes that are used in operating rooms. However, it has been demonstrated that high-resolution optical-sectioning microscopes are capable of detecting the sparse and punctate accumulations of PpIX that are undetectable via conventional low-power surgical fluorescence microscopes. To standardize the performance of high-resolution optical-sectioning devices for future clinical use, we have developed an imaging phantom and methods to ensure that the imaging of PpIX-expressing brain tissues can be performed reproducibly. Ex vivo imaging studies with a dual-axis confocal microscope demonstrate that these methods enable the acquisition of images from unsectioned human brain tissues that quantitatively and consistently correlate with images of histologically processed tissue sections.

Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

PubMed Central

Kaneko, Sadahiro

2016-01-01

Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

A palm-sized high-sensitivity near-infrared fluorescence imager for laparotomy surgery.

PubMed

Dorval, Paul; Mangeret, Norman; Guillermet, Stephanie; Atallah, Ihab; Righini, Christian; Barabino, Gabriele; Coll, Jean-Luc; Rizo, Philippe; Poulet, Patrick

2016-01-01

In laparotomy surgery guided by near-infrared fluorescence imaging, the access to the field of operation is limited by the illumination and/or the imaging field. The side of cavities or organs such as the liver or the heart cannot be examined with the systems available on the market, which are too large and too heavy. In this article, we describe and evaluate a palm sized probe, whose properties, weight, size and sensitivity are adapted for guiding laparotomy surgery. Different experiments have been performed to determine its main characteristics, both on the illumination and imaging sides. The device has been tested for fluorescent molecular probe imaging in preclinical procedures, to prove its ability to be used in cancer nodule detection during surgery. This system is now CE certified for clinical procedures and Indocyanine Green imaging has been performed during clinical investigations: lymphedema and surgical resection of liver metastases of colorectal cancers. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients

PubMed Central

Cordova, James S.; Shu, Hui-Kuo G.; Liang, Zhongxing; Gurbani, Saumya S.; Cooper, Lee A. D.; Holder, Chad A.; Olson, Jeffrey J.; Kairdolf, Brad; Schreibmann, Eduard; Neill, Stewart G.; Hadjipanayis, Constantinos G.; Shim, Hyunsuk

2016-01-01

Background The standard of care for glioblastoma (GBM) is maximal safe resection followed by radiation therapy with chemotherapy. Currently, contrast-enhanced MRI is used to define primary treatment volumes for surgery and radiation therapy. However, enhancement does not identify the tumor entirely, resulting in limited local control. Proton spectroscopic MRI (sMRI), a method reporting endogenous metabolism, may better define the tumor margin. Here, we develop a whole-brain sMRI pipeline and validate sMRI metrics with quantitative measures of tumor infiltration. Methods Whole-brain sMRI metabolite maps were coregistered with surgical planning MRI and imported into a neuronavigation system to guide tissue sampling in GBM patients receiving 5-aminolevulinic acid fluorescence-guided surgery. Samples were collected from regions with metabolic abnormalities in a biopsy-like fashion before bulk resection. Tissue fluorescence was measured ex vivo using a hand-held spectrometer. Tissue samples were immunostained for Sox2 and analyzed to quantify the density of staining cells using a novel digital pathology image analysis tool. Correlations among sMRI markers, Sox2 density, and ex vivo fluorescence were evaluated. Results Spectroscopic MRI biomarkers exhibit significant correlations with Sox2-positive cell density and ex vivo fluorescence. The choline to N-acetylaspartate ratio showed significant associations with each quantitative marker (Pearson's ρ = 0.82, P < .001 and ρ = 0.36, P < .0001, respectively). Clinically, sMRI metabolic abnormalities predated contrast enhancement at sites of tumor recurrence and exhibited an inverse relationship with progression-free survival. Conclusions As it identifies tumor infiltration and regions at high risk for recurrence, sMRI could complement conventional MRI to improve local control in GBM patients. PMID:26984746

Intraoperative imaging using intravascular contrast agent

NASA Astrophysics Data System (ADS)

Watson, Jeffrey R.; Martirosyan, Nikolay; Garland, Summer; Lemole, G. Michael; Romanowski, Marek

2016-03-01

Near-infrared (NIR) contrast agents are becoming more frequently studied in medical imaging due to their advantageous characteristics, most notably the ability to capture near-infrared signal across the tissue and the safety of the technique. This produces a need for imaging technology that can be specific for both the NIR dye and medical application. Indocyanine green (ICG) is currently the primary NIR dye used in neurosurgery. Here we report on using the augmented microscope we described previously for image guidance in a rat glioma resection. Luc-C6 cells were implanted in a rat in the left-frontal lobe and grown for 22 days. Surgical resection was performed by a neurosurgeon using augmented microscopy guidance with ICG contrast. Videos and images were acquired to evaluate image quality and resection margins. ICG accumulated in the tumor tissue due to enhanced permeation and retention from the compromised bloodbrain- barrier. The augmented microscope was capable of guiding the rat glioma resection and intraoperatively highlighted tumor tissue regions via ICG fluorescence under normal illumination of the surgical field.

Multispectral open-air intraoperative fluorescence imaging.

PubMed

Behrooz, Ali; Waterman, Peter; Vasquez, Kristine O; Meganck, Jeff; Peterson, Jeffrey D; Faqir, Ilias; Kempner, Joshua

2017-08-01

Intraoperative fluorescence imaging informs decisions regarding surgical margins by detecting and localizing signals from fluorescent reporters, labeling targets such as malignant tissues. This guidance reduces the likelihood of undetected malignant tissue remaining after resection, eliminating the need for additional treatment or surgery. The primary challenges in performing open-air intraoperative fluorescence imaging come from the weak intensity of the fluorescence signal in the presence of strong surgical and ambient illumination, and the auto-fluorescence of non-target components, such as tissue, especially in the visible spectral window (400-650 nm). In this work, a multispectral open-air fluorescence imaging system is presented for translational image-guided intraoperative applications, which overcomes these challenges. The system is capable of imaging weak fluorescence signals with nanomolar sensitivity in the presence of surgical illumination. This is done using synchronized fluorescence excitation and image acquisition with real-time background subtraction. Additionally, the system uses a liquid crystal tunable filter for acquisition of multispectral images that are used to spectrally unmix target fluorescence from non-target auto-fluorescence. Results are validated by preclinical studies on murine models and translational canine oncology models.

Evaluation of a Centyrin-Based Near-Infrared Probe for Fluorescence-Guided Surgery of Epidermal Growth Factor Receptor Positive Tumors.

PubMed

Mahalingam, Sakkarapalayam M; Dudkin, Vadim Y; Goldberg, Shalom; Klein, Donna; Yi, Fang; Singhal, Sunil; O'Neil, Karyn T; Low, Philip S

2017-11-15

Tumor-targeted near-infrared fluorescent dyes have the potential to improve cancer surgery by enabling surgeons to locate and resect more malignant lesions where good visualization tools are required to ensure complete removal of malignant tissue. Although the tumor-targeted fluorescent dyes used in humans to date have been either small organic molecules or high molecular weight antibodies, low molecular weight protein scaffolds have attracted significant attention because they penetrate solid tumors almost as efficiently as small molecules, but can be infinitely mutated to bind almost any antigen. Here we describe the use of a 10 kDa protein scaffold, a Centyrin, to target a near-infrared fluorescent dye to tumors that overexpress the epidermal growth factor receptor (EGFR) for fluorescence-guided surgery (FGS). We have developed and optimized the dose and time required for imaging small tumor burdens with minimal background fluorescence in real-time fluorescence-guided surgery of EGFR-expressing tumor xenografts in murine models. We demonstrate that the Centyrin-near-infrared dye conjugate (CNDC) binds selectively to human EGFR + cancer cells with an EC 50 of 2 nM, localizes to EGFR + tumor xenografts in athymic nude mice and that uptake of the dye in xenografts is significantly reduced when EGFR are blocked by preinjection of excess unlabeled Centyrin. Taken together, these data suggest that CNDCs can be used for intraoperative identification and surgical removal of EGFR-expressing lesions and that Centyrins targeted to other tumor-specific antigens should prove similarly useful in fluorescence guided surgery of cancer. In addition, we demonstrate that the CNDC is detected in the NIR region of the spectrum and can be utilized for fluorescence-guided surgery (FGS). In addition, we propose that with its eventual complete clearance from EGFR-negative tissues and its quantitative retention in the tumor mass for >24 h, a Centyrin-targeted NIR dye should provide excellent tumor contrast when injected at least 6-8 h before initiation of cancer surgery in human patients.

NI-16INTRA-OPERATIVE USE OF FLUORESCEIN FOR MALIGNANT GLIOMA RESECTION DIFFERENTIATES TUMOR FROM NORMAL BRAIN TISSUE BASED ON HISTOPATHOLOGIC ANALYSIS

PubMed Central

Decker, Matthew; Kresak, Jesse; Yachnis, Anthony; Bova, Frank; Rahman, Maryam

2014-01-01

OBJECTIVES: To determine whether the use of IV fluorescein during surgery for malignant glioma can reliably be used to differentiate between infiltrative tumor and normal brain tissue. BACKGROUND: Fluorescein sodium is a molecular compound with fluorescent capabilities between light wavelengths of 520-530nm, appearing yellow-green (1). Neurosurgical application of fluorescein has been studied primarily for increasing intra-operative visibility of malignant gliomas (1). The mechanism of action has been hypothesized to involve disruption of the blood brain barrier (BBB) (2). Cells in areas with disrupted BBB take up fluorescein with a sensitivity of 94% and specificity of 89% for high-grade gliomas (2). We performed histopathologic analysis on tissue obtained during fluorescein-guided tumor resections to evaluate the differences between fluorescent and non-fluorescent tissue. METHODS: Two adult patients with suspected high-grade gliomas underwent surgical resection. Prior to opening of the dura 3mg/kg of IV fluorescein was given. A Zeiss OPMI Pentero microscope (Carl Zeiss Meditech Inc.) with a yellow 560nm filter was used to visualize the tumor. At the tumor margins, tissue was identified as "bright" and "dark" and sent as separate specimens for histopathological analysis. RESULTS: Histological sections of specimens labeled "bright" contained infiltrating glioma with focal microvascular proliferation. Histological sections of specimens labeled "dark" contained gray matter and focal subcortical white matter with no high-grade glioma identified. Final grading for both patients was WHO Grade IV, glioblastoma. CONCLUSION: Intra-operative use of fluorescein in surgical resection of malignant gliomas can help to distinguish between infiltrating tumor and normal brain tissue based on histopathological analysis. Further evaluation of the utility of flurorescein during high and low-grade glioma surgery is necessary.

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

PubMed Central

Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2016-01-01

We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model. PMID:27689331

EGFR-directed Affibody for fluorescence-guided glioma surgery: time-dose analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ribeiro de Souza, Ana Luiza; Marra, Kayla; Gunn, Jason R.; Elliott, Jonathan T.; Samkoe, Kimberley S.; Paulsen, Keith D.; Draney, Daniel R.; Feldwisch, Joachim

2016-03-01

The key to fluorescence guided surgical oncology is the ability to create specific contrast between normal and glioma tissue. The blood brain barrier that limits the delivery of substances to the normal brain is broken in tumors, allowing accumulation of agents in the tumor interior. However, for a clinical success, imaging agents should be in the infiltrative edges to minimize the resection of normal brain while enable the removal of tumor. The aberrant overexpression and/or activation of EGFR is associated with many types of cancers, including glioblastoma and the injection of a fluorescent molecule targeted to these receptors would improve tumor contrast during fluorescence guided surgery. Affibody molecules have intentional medium affinity and high potential specificity, which are the desirable features of a good surgical imaging agent. The aim of this study was evaluate the brain/glioma uptake of ABY029 labeled with near-infrared dye IRDye800CW after intravenous injection. Rats were either inoculated with orthotopic implantations of U251 human glioma cell line or PBS (shams control) in the brain. The tumors were allowed to grow for 2-3 weeks before carrying out fluorescent tracer experiments. Fluorescent imaging of ex vivo brain slices from rats was acquired at different time points after infection of fluorescently labeled EGFR-specific affibody to verify which time provided maximal contrast tumor to normal brain. Although the tumor was most clearly visualized after 1h of IRDye800CW-labeled ABY029 injection, the tumor location could be identified from the background after 48h. These results suggest that the NIR-labeled affibody examined shows excellent potential to increase surgical visualization for confirmed EGFR positive tumors.

5-Aminolevulinic Acid Accumulation in a Cerebral Infarction Mimicking High-Grade Glioma.

PubMed

Behling, Felix; Hennersdorf, Florian; Bornemann, Antje; Tatagiba, Marcos; Skardelly, Marco

2016-08-01

5-Aminolevulinic acid (5-ALA) has become an integral part in the neurosurgical treatment of malignant glioma. Over time, several other tumor entities have been identified to metabolize 5-ALA and show a similar fluorescence pattern during surgical resection. This case report is the first description of 5-ALA accumulation in postischemic cerebral tissue. This evidence questions the assumption that 5-ALA accumulation in glioma is exclusively attributed to tumor infiltration. Instead, 5-ALA accumulation can also occur beyond the tumor borders and may be partially ascribed to inflammatory changes in the surrounding brain tissue. A 64-year old woman presented with episodes of apraxia and a ring-enhancing lesion in postcontrast T1-weighted magnetic resonance sequences suggestive of high grade glioma. Strong fluorescence was observed during 5-ALA-guided resection. However, although the frozen section was inconclusive, the final histopathologic examination revealed a stage II cerebral infarction. 5-ALA accumulation in postischemic cerebral tissue should be considered for intended supramarginal resections near eloquent brain regions. Therefore, sufficient preoperative imaging should regularly include magnetic resonance imaging spectroscopy and perfusion sequences to ascertain the proper diagnosis. Moreover, further research is warranted to determine the role of 5-ALA accumulation in postischemic and inflammatory brain tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

PubMed

Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

2012-10-01

Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: a single-centre feasibility study.

PubMed

Harlaar, Niels J; Koller, Marjory; de Jongh, Steven J; van Leeuwen, Barbara L; Hemmer, Patrick H; Kruijff, Schelto; van Ginkel, Robert J; Been, Lukas B; de Jong, Johannes S; Kats-Ugurlu, Gursah; Linssen, Matthijs D; Jorritsma-Smit, Annelies; van Oosten, Marleen; Nagengast, Wouter B; Ntziachristos, Vasilis; van Dam, Gooitzen M

2016-12-01

Optimum cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is essential for the curative treatment of peritoneal carcinomatosis of colorectal origin. At present, surgeons depend on visual inspection and palpation for tumour detection. Improved detection of tumour tissue using molecular fluorescence-guided surgery could not only help attain a complete cytoreduction of metastatic lesions, but might also prevent overtreatment by avoiding resection of benign lesions. For this non-randomised, single-centre feasibility study, we enrolled patients with colorectal peritoneal metastases scheduled for cytoreductive surgery and HIPEC. 2 days before surgery, 4·5 mg of the near-infrared fluorescent tracer bevacizumab-IRDye800CW was administered intravenously. The primary objectives were to determine the safety and feasibility of molecular fluorescence-guided surgery using bevacizumab-IRDye800CW. Molecular fluorescence-guided surgery was deemed safe if no allergic or anaphylactic reactions were recorded and no serious adverse events were attributed to bevacizumab-IRDye800CW. The technique was deemed feasible if bevacizumab-IRDye800CW enabled detection of fluorescence signals intraoperatively. Secondary objectives were correlation of fluorescence with histopathology by back-table imaging of the fresh surgical specimen and semi-quantitative ex-vivo analyses of formalin-fixed paraffin embedded (FFPE) tissue on all peritoneal lesions. Additionally, VEGF-α staining and fluorescence microscopy was done. This study is registered with the Netherlands Trial Registry, number NTR4632. Between July 3, 2014, and March 2, 2015, seven patients were enrolled in the study. One patient developed an abdominal sepsis 5 days postoperatively and another died from an asystole 4 days postoperatively, most probably due to a cardiovascular thromboembolic event. However, both serious adverse events were attributed to the surgical cytoreductive surgery and HIPEC procedure. No serious adverse events related to bevacizumab-IRDye800CW occurred in any of the patients. Intraoperatively, fluorescence was seen in all patients. In two patients, additional tumour tissue was detected by molecular fluorescence-guided surgery that was initially missed by the surgeons. During back-table imaging of fresh surgical specimens, a total of 80 areas were imaged, marked, and analysed. All of the 29 non-fluorescent areas were found to contain only benign tissue, whereas tumour tissue was detected in 27 of 51 fluorescent areas (53%). Ex-vivo semi-quantification of 79 FFPE peritoneal lesions showed a tumour-to-normal ratio of 6·92 (SD 2·47). Molecular fluorescence-guided surgery using the near-infrared fluorescent tracer bevacizumab-IRDye800CW is safe and feasible. This technique might be of added value for the treatment of patients with colorectal peritoneal metastases through improved patient selection and optimisation of cytoreductive surgery. A subsequent multicentre phase 2 trial is needed to make a definitive assessment of the diagnostic accuracy and the effect on clinical decision making of molecular fluorescence-guided surgery. FP-7 Framework Programme BetaCure and SurgVision BV. Copyright © 2016 Elsevier Ltd. All rights reserved.

An intraoperative spectroscopic imaging system for quantification of Protoporphyrin IX during glioma surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Angulo-Rodríguez, Leticia M.; Laurence, Audrey; Jermyn, Michael; Sheehy, Guillaume; Sibai, Mira; Petrecca, Kevin; Roberts, David W.; Paulsen, Keith D.; Wilson, Brian C.; Leblond, Frédéric

2016-03-01

Cancer tissue often remains after brain tumor resection due to the inability to detect the full extent of cancer during surgery, particularly near tumor boundaries. Commercial systems are available for intra-operative real-time aminolevulenic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence imaging. These are standard white-light neurosurgical microscopes adapted with optical components for fluorescence excitation and detection. However, these instruments lack sensitivity and specificity, which limits the ability to detect low levels of PpIX and distinguish it from tissue auto-fluorescence. Current systems also cannot provide repeatable and un-biased quantitative fluorophore concentration values because of the unknown and highly variable light attenuation by tissue. We present a highly sensitive spectroscopic fluorescence imaging system that is seamlessly integrated onto a neurosurgical microscope. Hardware and software were developed to achieve through-microscope spatially-modulated illumination for 3D profilometry and to use this information to extract tissue optical properties to correct for the effects of tissue light attenuation. This gives pixel-by-pixel quantified fluorescence values and improves detection of low PpIX concentrations. This is achieved using a high-sensitivity Electron Multiplying Charge Coupled Device (EMCCD) with a Liquid Crystal Tunable Filter (LCTF) whereby spectral bands are acquired sequentially; and a snapshot camera system with simultaneous acquisition of all bands is used for profilometry and optical property recovery. Sensitivity and specificity to PpIX is demonstrated using brain tissue phantoms and intraoperative human data acquired in an on-going clinical study using PpIX fluorescence to guide glioma resection.

New chemical probe technologies: applications to imaging and drug discovery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bogyo, Matthew

2017-02-01

Proteases are enzymes that play pathogenic roles in many common human diseases such as cancer, asthma, arthritis, atherosclerosis and infection by pathogens. Tools to dynamically monitor their activity can be used as diagnostic agents, as imaging contrast agents for intra-operative image guidance and for the identification of novel classes of protease-targeted drugs. I will describe our efforts to design and synthesize small molecule probes that produce a fluorescent signal upon binding to a protease target. We have identified probes that show tumor-specific retention, fast activation kinetics, and rapid systemic distribution making them useful for real-time fluorescence guided tumor resection and other diagnostic imaging applications.

Designing a wearable navigation system for image-guided cancer resection surgery

PubMed Central

Shao, Pengfei; Ding, Houzhu; Wang, Jinkun; Liu, Peng; Ling, Qiang; Chen, Jiayu; Xu, Junbin; Zhang, Shiwu; Xu, Ronald

2015-01-01

A wearable surgical navigation system is developed for intraoperative imaging of surgical margin in cancer resection surgery. The system consists of an excitation light source, a monochromatic CCD camera, a host computer, and a wearable headset unit in either of the following two modes: head-mounted display (HMD) and Google glass. In the HMD mode, a CMOS camera is installed on a personal cinema system to capture the surgical scene in real-time and transmit the image to the host computer through a USB port. In the Google glass mode, a wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A software program is written in Python to call OpenCV functions for image calibration, co-registration, fusion, and display with augmented reality. The imaging performance of the surgical navigation system is characterized in a tumor simulating phantom. Image-guided surgical resection is demonstrated in an ex vivo tissue model. Surgical margins identified by the wearable navigation system are co-incident with those acquired by a standard small animal imaging system, indicating the technical feasibility for intraoperative surgical margin detection. The proposed surgical navigation system combines the sensitivity and specificity of a fluorescence imaging system and the mobility of a wearable goggle. It can be potentially used by a surgeon to identify the residual tumor foci and reduce the risk of recurrent diseases without interfering with the regular resection procedure. PMID:24980159

Designing a wearable navigation system for image-guided cancer resection surgery.

PubMed

Shao, Pengfei; Ding, Houzhu; Wang, Jinkun; Liu, Peng; Ling, Qiang; Chen, Jiayu; Xu, Junbin; Zhang, Shiwu; Xu, Ronald

2014-11-01

A wearable surgical navigation system is developed for intraoperative imaging of surgical margin in cancer resection surgery. The system consists of an excitation light source, a monochromatic CCD camera, a host computer, and a wearable headset unit in either of the following two modes: head-mounted display (HMD) and Google glass. In the HMD mode, a CMOS camera is installed on a personal cinema system to capture the surgical scene in real-time and transmit the image to the host computer through a USB port. In the Google glass mode, a wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A software program is written in Python to call OpenCV functions for image calibration, co-registration, fusion, and display with augmented reality. The imaging performance of the surgical navigation system is characterized in a tumor simulating phantom. Image-guided surgical resection is demonstrated in an ex vivo tissue model. Surgical margins identified by the wearable navigation system are co-incident with those acquired by a standard small animal imaging system, indicating the technical feasibility for intraoperative surgical margin detection. The proposed surgical navigation system combines the sensitivity and specificity of a fluorescence imaging system and the mobility of a wearable goggle. It can be potentially used by a surgeon to identify the residual tumor foci and reduce the risk of recurrent diseases without interfering with the regular resection procedure.

Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping

NASA Astrophysics Data System (ADS)

B. Mondal, Suman; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P.; Liang, Kexian; Som, Avik; Akers, Walter J.; Fields, Ryan C.; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

2015-07-01

The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging.

Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery.

PubMed

Ashitate, Yoshitomo; Hyun, Hoon; Kim, Soon Hee; Lee, Jeong Heon; Henary, Maged; Frangioni, John V; Choi, Hak Soo

2014-01-01

The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We developed near-infrared fluorophores, which have fluorescence emission maxima either at 700 nm or at 800 nm. One was injected intravenously for identification of all regional lymph nodes in a basin, and the other was injected locally for identification of the SLN. Using the dual-channel FLARE intraoperative imaging system, we could identify and resect all PLNs and SLNs simultaneously. The technology we describe enables simultaneous, real-time visualization of both PLNs and SLNs in the same subject.

Indocyanine green fluorescence-guided surgery after IV injection in metastatic colorectal cancer: A systematic review.

PubMed

Liberale, G; Bourgeois, P; Larsimont, D; Moreau, M; Donckier, V; Ishizawa, T

2017-09-01

Indocyanine green fluorescence-guided surgery (ICG-FGS) has emerged as a potential new imaging modality for improving the detection of hepatic, lymph node (LN), and peritoneal metastases in colorectal cancer (CRC) patients. The aim of this paper is to review the available literature in the clinical setting of ICG-FGS for tumoral detection in various fields of metastatic colorectal disease. PubMed and Medline literature databases were searched for original articles on the use of ICG in the setting of clinical studies on colorectal cancer. The search terms used were "near-infrared fluorescence", "intraoperative imaging", "indocyanine green", "human" and "colorectal cancer". ICG fluorescence imaging (ICG-FI) is clearly supported as an intraoperative technique that allows the detection of additional superficial hepatic metastases of CRC. Data on the role of ICG-FI in the intraoperative detection of peritoneal metastases and LN metastases are scarce but encouraging and ICG-FI could potentially improve the staging and treatment of these patients. ICG-FI is a promising imaging technique in the detection of small infraclinic LN, hepatic, and peritoneal metastatic deposits that may allow better staging and more complete surgical resection with a potential prognostic benefit for patients. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Fluorescein-guided surgery for grade IV gliomas with a dedicated filter on the surgical microscope: preliminary results in 12 cases.

PubMed

Acerbi, Francesco; Broggi, Morgan; Eoli, Marica; Anghileri, Elena; Cuppini, Lucia; Pollo, Bianca; Schiariti, Marco; Visintini, Sergio; Orsi, Chiara; Franzini, Angelo; Broggi, Giovanni; Ferroli, Paolo

2013-07-01

Fluorescein is widely used as a fluorescent tracer for many applications. Its capability to accumulate in cerebral areas with blood-brain barrier damage makes it an ideal dye for intraoperative visualization of malignant gliomas (MG). We report our preliminary experience in fluorescein-guided removal of grade IV gliomas using a dedicated filter on the surgical microscope. In September 2011 we started a prospective phase II trial (FLUOGLIO) to evaluate the safety and obtain initial indications about the efficacy of fluorescein-guided surgery for MG. Patients with suspected MG amenable to complete resection of contrast-enhancing areas were eligible to participate in this study. This report is based on a preliminary analysis of the results of 12 patients with grade IV gliomas out of 15 consecutive cases (age range 48-72 years) enrolled since September 2011. Fluorescein was injected intravenously (i.v.) after intubation (5-10 mg/kg). The tumor was removed using a microsurgical technique and fluorescence visualization by BLU 400 or YELLOW 560 filters on a Pentero microscope (Carl Zeiss, Germany). The study was approved by our ethics committee and registered on the European Regulatory Authorities website (EudraCT no. 2011-002527-18). Histological analysis confirmed grade IV gliomas in 12/15 cases. Median preoperative tumor volume was 33.15 cm(3) (9.6-87.8 cm(3)). No adverse reaction related to the administration of fluorescein was registered. Contrast-enhanced tumor was completely removed in 75 % of the patients. This preliminary analysis suggested that the use of intravenous fluorescein during surgery on grade IV gliomas is safe and allows a high rate of complete resection of contrast-enhanced tumor at the early postoperative MRI.

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

PubMed Central

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-01-01

Abstract. There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here. PMID:27533438

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-08-01

There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here.

In vivo fluorescence imaging of hepatocellular carcinoma xenograft using near-infrared labeled epidermal growth factor receptor (EGFR) peptide

PubMed Central

Li, Z.; Zhou, Q.; Zhou, J.; Duan, X.; Zhu, J.; Wang, T. D.

2016-01-01

Minimally-invasive surgery of hepatocellular carcinoma (HCC) can be limited by poor tumor visualization with white light. We demonstrate systemic administration of a Cy5.5-labeled peptide specific for epidermal growth factor receptor (EGFR) to target HCC in vivo in a mouse xenograft model. We attached a compact imaging module to the proximal end of a medical laparoscope to collect near-infrared fluorescence and reflectance images concurrently at 15 frames/sec. We measured a mean target-to-background ratio of 2.99 ± 0.22 from 13 surgically exposed subcutaneous human HCC tumors in vivo in 5 mice. This integrated imaging methodology is promising to guide laparoscopic resection of HCC. PMID:27699089

Liver tumor boundaries identified intraoperatively using real-time indocyanine green fluorescence imaging.

PubMed

Zhang, Ya-Min; Shi, Rui; Hou, Jian-Cun; Liu, Zi-Rong; Cui, Zi-Lin; Li, Yang; Wu, Di; Shi, Yuan; Shen, Zhong-Yang

2017-01-01

Clear delineation between tumors and normal tissues is ideal for real-time surgical navigation imaging. We investigated applying indocyanine green (ICG) fluorescence imaging navigation using an intraoperative administration method in liver resection. Fifty patients who underwent liver resection were divided into two groups based on clinical situation and operative purpose. In group I, sizes of superficial liver tumors were determined; tiny tumors were identified. In group II, the liver resection margin was determined; real-time navigation was performed. ICG was injected intravenously at the beginning of the operation; the liver surface was observed with a photodynamic eye (PDE). Liver resection margins were determined using PDE. Fluorescence contrast between normal liver and tumor tissues was obvious in 32 of 35 patients. A boundary for half the liver or specific liver segments was determined in nine patients by examining the portal vein anatomy after ICG injection. Eight small tumors not observed preoperatively were detected; the smallest was 2 mm. ICG fluorescence imaging navigation is a promising, simple, and safe tool for routine real-time intraoperative imaging during hepatic resection and clinical exploration in hepatocellular carcinoma, enabling high sensibility for identifying liver resection margins and detecting tiny superficial tumors.

O5.05FLUORESCEIN-GUIDED REMOVAL OF HIGH-GRADE GLIOMAS WITH A DEDICATED FILTER ON THE SURGICAL MICROSCOPE: PRELIMINARY RESULTS OF THE FLUOGLIO STUDY

PubMed Central

Acerbi, F.; Broggi, M.; Cavallo, C.; Anghileri, E.; Eoli, M.; Schiariti, M.; Corte, E. La; Pollo, B.; Boffano, C.; Ferroli, P.

2014-01-01

BACKGROUND: Fluorescein is a fluorescent tracer that can be used for many applications. It is able to accumulate in brain areas with blood-brain barrier disruption, and thus it can be considered an ideal dye for intraoperative visualization of high-grade gliomas (HGG). We report the preliminary results of a phase II trail (FLUOGLIO) on a new fluorescein-guided technique to remove HHG with a dedicated filter on the surgical microscope. METHODS: In September 2011 we started a prospective phase II-trial (FLUOGLIO) to evaluated safety and obtain initial indications about efficacy of fluorescein-guided surgery for HGG. Patients with suspected HGG amenable to complete resection of contrast-enhancing area were eligible to participate in this study. This report is based on the analysis of the short- and long-term results in 28 consecutive patients with HGG (age range 45-74 years), enrolled since September 2011. Fluorescein was intravenous (i.v.) injected after intubation (5-10 mg/Kg). Tumor was removed with microsurgical technique and fluorescence visualization by BLU400 or YELLOW560 filters on Pentero microscope (Carl Zeiss, Germany). The study was approved by our Ethical Committee and registered on the European Regulatory Authorities website (EudraCT No. 2011-002527-18). RESULTS: Median pre-operative tumor volume was 33.1 cm3 (2.4-87.8 cm3). We found no adverse reaction to fluorescein administration. Tumor was completely removed in 80% of the patients. Median follow-up was 10 months. 6 months Progression-free Survival (PFS) and median survival were respectively 71.4 % and 11 months. CONCLUSION: Our analysis suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows high-rate of complete resection of contrast-enhanced tumor at the early post-operative MRI.

Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas.

PubMed

Sanai, Nader; Snyder, Laura A; Honea, Norissa J; Coons, Stephen W; Eschbacher, Jennifer M; Smith, Kris A; Spetzler, Robert F

2011-10-01

Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5-ALA)-induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection. Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence. Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses. Intraoperative confocal microscopy can visualize cellular 5-ALA-induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors' institution.

Indocyanine Green Fluorescence Navigation Thoracoscopic Metastasectomy for Pulmonary Metastasis of Hepatocellular Carcinoma.

PubMed

Kawakita, Naoya; Takizawa, Hiromitsu; Kondo, Kazuya; Sakiyama, Shoji; Tangoku, Akira

2016-12-20

Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment. We performed wide wedge resection using the fluorescence image for navigation to confirm the surgical margins. The specimen was histologically confirmed as a pulmonary metastasis of HCC. In conclusion, thoracoscopic indocyanine green near-infrared fluorescence imaging for pulmonary metastases of HCC is useful in identifying tumor locations and ensuring resection margins.

An initial report on the intraoperative use of indocyanine green fluorescence imaging in the surgical management of liver tumorss.

PubMed

Takahashi, Hideo; Zaidi, Nisar; Berber, Eren

2016-10-01

There has been a recent interest in the use of Indocyanine green (ICG) imaging. The aim of this study is to review our initial experience in liver surgery. ICG fluorescent imaging was used in 15 patients undergoing surgical treatment of their liver tumors between 2015 and 2016. ICG imaging was initially performed, followed by intraoperative ultrasound (IOUS). Findings on fluorescence were compared with preoperative cross-sectional imaging and IOUS. Sixty-two lesions were identified, with 34 located superficially and 28 deeply in the liver. While 13 patients underwent surgery for malignant liver metastases, two patients had operations for benign liver diseases. Seven patients underwent open or robotic liver resections, five laparoscopic microwave liver ablation, and three diagnostic laparoscopy. ICG identified all of the superficial lesions. IOUS identified 98% of all lesions. The most benefit of ICG was in showing the margins of the superficial lesions in real-time and guiding surgical treatment, which was limited by IOUS. This is the first North American study to evaluate the potential utility of ICG during liver surgery. Its major benefit seems to be in providing real-time feedback to the surgeon about the margins of superficial tumors for resection or ablation. J. Surg. Oncol. 2016;114:625-629. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Interventional fluorescence spectroscopy: preliminary results to detect tumor margins during glioma resection with two fluorescence spectra of PpIX

NASA Astrophysics Data System (ADS)

Alston, L. M.; Guyotat, J.; Mahieu-Williame, L.; Hebert, M.; Kantapareddy, P.; Meyronet, D.; Rousseau, D.; Montcel, B.

2017-07-01

We show the feasibility of using an intraoperative spectroscopic device to identify tumors margins during glioma resection. The collected fluorescence spectra is fitted with two reference spectra of PpIX and the contribution of each spectrum enables to overcome the sensitivity of current techniques by seeing tumor margins and low grade gliomas.

3D-printed guiding templates for improved osteosarcoma resection

NASA Astrophysics Data System (ADS)

Ma, Limin; Zhou, Ye; Zhu, Ye; Lin, Zefeng; Wang, Yingjun; Zhang, Yu; Xia, Hong; Mao, Chuanbin

2016-03-01

Osteosarcoma resection is challenging due to the variable location of tumors and their proximity with surrounding tissues. It also carries a high risk of postoperative complications. To overcome the challenge in precise osteosarcoma resection, computer-aided design (CAD) was used to design patient-specific guiding templates for osteosarcoma resection on the basis of the computer tomography (CT) scan and magnetic resonance imaging (MRI) of the osteosarcoma of human patients. Then 3D printing technique was used to fabricate the guiding templates. The guiding templates were used to guide the osteosarcoma surgery, leading to more precise resection of the tumorous bone and the implantation of the bone implants, less blood loss, shorter operation time and reduced radiation exposure during the operation. Follow-up studies show that the patients recovered well to reach a mean Musculoskeletal Tumor Society score of 27.125.

Fluorophore-conjugated antibodies for imaging and resection of GI tumors

NASA Astrophysics Data System (ADS)

Bouvet, Michael; Hoffman, Robert M.

2016-03-01

Negative surgical margins are critical to prevent recurrence in cancer surgery. This is because with current technology in many cases negative margins are impossible due the inability of the surgeon to detect the margin. Our laboratory has developed fluorophore-labeled monoclonal antibodies to aid in cancer visualization in orthotopic nude mouse models of human gastrointestinal (GI) cancer in order to achieve negative margins in fluorescence-guided surgery (FGS). The technologies described herein have the potential to change the paradigm of surgical oncology to engender significantly improved outcomes.

Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping

PubMed Central

B. Mondal, Suman; Gao, Shengkui; Zhu, Nan; Sudlow, Gail P.; Liang, Kexian; Som, Avik; Akers, Walter J.; Fields, Ryan C.; Margenthaler, Julie; Liang, Rongguang; Gruev, Viktor; Achilefu, Samuel

2015-01-01

The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging. PMID:26179014

Fluorescence lifetime technique for surgical imaging, guidance and augmented reality (Conference Presentation)

NASA Astrophysics Data System (ADS)

Marcu, Laura

2017-02-01

The surgeon's limited ability to accurately delineate the tumor margin during surgical interventions is one key challenge in clinical management of cancer. New methods for guiding tumor resection decisions are needed. Numerous studies have shown that tissue autofluorescence properties have the potential to asses biochemical features associates with distinct pathologies in tissue and to distinguish various cancers from normal tissues. However, despite these promising reports, autofluorescence techniques were sparsely adopted in clinical settings. Moreover, when adopted they were primarily used for pre-operative diagnosis rather than guiding interventions. To address this need, we have researched and engineered instrumentation that utilizes label-free fluorescence lifetime contrast to characterize tissue biochemical features in vivo in patients and methodologies conducive to real-time (few seconds) diagnosis of tissue pathologies during surgical procedures. This presentation overviews clinically-compatible multispectral fluorescence lifetime imaging techniques developed in our laboratory and their ability to operate as stand-alone tools, integrated in a biopsy needle and in conjunction with the da Vinci surgical robot. We present pre-clinical and clinical studies in patients that demonstrate the potential of these techniques for intraoperative assessment of brain tumors and head and neck cancer. Current results demonstrate that intrinsic fluorescence signals can provide useful contrast for delineation distinct types of tissues including tumors intraoperatively. Challenges and solutions in the clinical implementation of these techniques are discussed.

Fluorescence-based enhanced reality (FLER) for real-time estimation of bowel perfusion in minimally invasive surgery

NASA Astrophysics Data System (ADS)

Diana, Michele

2016-03-01

Pre-anastomotic bowel perfusion is a key factor for a successful healing process. Clinical judgment has limited accuracy to evaluate intestinal microperfusion. Fluorescence videography is a promising tool for image-guided intraoperative assessment of the bowel perfusion at the future anastomotic site in the setting of minimally invasive procedures. The standard configuration for fluorescence videography includes a Near-Infrared endoscope able to detect the signal emitted by a fluorescent dye, more frequently Indocyanine Green (ICG), which is administered by intravenous injection. Fluorescence intensity is proportional to the amount of fluorescent dye diffusing in the tissue and consequently is a surrogate marker of tissue perfusion. However, fluorescence intensity alone remains a subjective approach and an integrated computer-based analysis of the over-time evolution of the fluorescence signal is required to obtain quantitative data. We have developed a solution integrating computer-based analysis for intra-operative evaluation of the optimal resection site, based on the bowel perfusion as determined by the dynamic fluorescence intensity. The software can generate a "virtual perfusion cartography", based on the "fluorescence time-to-peak". The virtual perfusion cartography can be overlapped onto real-time laparoscopic images to obtain the Enhanced Reality effect. We have defined this approach FLuorescence-based Enhanced Reality (FLER). This manuscript describes the stepwise development of the FLER concept.

Intraoperative spatial frequency domain diffuse optical tomography with indo-cyanine green (ICG) fluorescence contrast (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chong, Sang Hoon; Parthasarathy, Ashwin B.; Kavuri, Venkaiah C.; Moscatelli, Frank A.; Singhal, Sunil; Yodh, Arjun G.

2017-02-01

Surgical resection is the most effective treatment strategy for solid tumors, but complete removal of the tumor is critical for post-surgical recovery/long-term survival and is dependent on correct identification of the tumor margin and accurate excision of microscopic residual tumor in the surgical field. Fluorescence image guided surgery is an emerging technique that has shown promise for intraoperative location of tumors and tumor margins. Current versions of such intraoperative fluorescence imaging, however, are generally limited to 2D near-surface images, i.e., without information about tumor depth. Here we present an intraoperative fluorescence imaging system for 3D volumetric imaging of tumors; the system uses spatial frequency domain diffuse optical tomography with an analytic inversion reconstruction method. The new instrument can derive depth-sensitive 3D tumor images at depths up to 1 cm, and it employs compact epi-imaging and illumination suitable for the operating room, with quasi-real-time image reconstruction for surgical visualization. We present experimental results with FDA-approved Indocynanine Green using an extensive array of tissue phantoms and in a pilot in-vivo study.

Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

2015-03-01

Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

Intraoperative imaging technology to maximise extent of resection for glioma.

PubMed

Jenkinson, Michael D; Barone, Damiano Giuseppe; Bryant, Andrew; Vale, Luke; Bulbeck, Helen; Lawrie, Theresa A; Hart, Michael G; Watts, Colin

2018-01-22

Extent of resection is considered to be a prognostic factor in neuro-oncology. Intraoperative imaging technologies are designed to help achieve this goal. It is not clear whether any of these sometimes very expensive tools (or their combination) should be recommended as standard care for people with brain tumours. We set out to determine if intraoperative imaging technology offers any advantage in terms of extent of resection over standard surgery and if any one technology was more effective than another. To establish the overall effectiveness and safety of intraoperative imaging technology in resection of glioma. To supplement this review of effects, we also wished to identify cost analyses and economic evaluations as part of a Brief Economic Commentary (BEC). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7, 2017), MEDLINE (1946 to June, week 4, 2017), and Embase (1980 to 2017, week 27). We searched the reference lists of all identified studies. We handsearched two journals, the Journal of Neuro-Oncology and Neuro-oncology, from 1991 to 2017, including all conference abstracts. We contacted neuro-oncologists, trial authors, and manufacturers regarding ongoing and unpublished trials. Randomised controlled trials evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included intraoperative MRI (iMRI), fluorescence-guided surgery, ultrasound, and neuronavigation (with or without additional image processing, e.g. tractography). Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. We identified four randomised controlled trials, using different intraoperative imaging technologies: iMRI (2 trials including 58 and 14 participants, respectively); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around autumn 2018. We identified no trials for ultrasound.Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies. All studies included people with high-grade glioma only.Extent of resection was increased in one trial of iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI) 0.02 to 0.96; 1 study, 49 participants; very low-quality evidence) and in the trial of 5-ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study, 270 participants; low-quality evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants, therefore the trial provides very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection.Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-quality evidence). Overall, reported events were low in most trials. There was no clear evidence of improvement in overall survival with 5-ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270 participants; low-quality evidence). Progression-free survival data were not available in an appropriate format for analysis. Data for quality of life were only available for one study and suffered from significant attrition bias (very low-quality evidence). Intra-operative imaging technologies, specifically iMRI and 5-ALA, may be of benefit in maximising extent of resection in participants with high grade glioma. However, this is based on low to very low quality evidence, and is therefore very uncertain. The short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly. Further research, including studies of ultrasound-guided surgery, is needed.

Real-Time Intraoperative Detection of Breast Cancer using Near-infrared Fluorescence Imaging and Methylene Blue

PubMed Central

Tummers, Quirijn R.J.G.; Verbeek, Floris P.R.; Schaafsma, Boudewijn E.; Boonstra, Martin C.; van der Vorst, Joost R.; Liefers, Gerrit-Jan; van de Velde, Cornelis J.H.; Frangioni, John V.; Vahrmeijer, Alexander L.

2014-01-01

Background Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast-conserving surgery. Based on certain physicochemical similarities between Technetium(99mTc)-sestamibi (MIBI), a SPECT radiodiagnostic with a sensitivity of 83–90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging. Methods Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy. Results 20/24 (83%) of breast tumors (carcinoma in N=21 and ductal carcinoma in situ in N=3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue. Conclusions This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management. PMID:24862545

Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue.

PubMed

Tummers, Q R J G; Verbeek, F P R; Schaafsma, B E; Boonstra, M C; van der Vorst, J R; Liefers, G-J; van de Velde, C J H; Frangioni, J V; Vahrmeijer, A L

2014-07-01

Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast conserving surgery. Based on certain physicochemical similarities between Technetium((99m)Tc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83-90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging. Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy. 20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue. This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hippocampography Guides Consistent Mesial Resections in Neocortical Temporal Lobe Epilepsy

PubMed Central

Kilbride, Ronan; Simon, Mirela; Eskandar, Emad

2016-01-01

Background. The optimal surgery in lesional neocortical temporal lobe epilepsy is unknown. Hippocampal electrocorticography maximizes seizure freedom by identifying normal-appearing epileptogenic tissue for resection and minimizes neuropsychological deficit by limiting resection to demonstrably epileptogenic tissue. We examined whether standardized hippocampal electrocorticography (hippocampography) guides resection for more consistent hippocampectomy than unguided resection in conventional electrocorticography focused on the lesion. Methods. Retrospective chart reviews any kind of electrocorticography (including hippocampography) as part of combined lesionectomy, anterolateral temporal lobectomy, and hippocampectomy over 8 years . Patients were divided into mesial (i.e., hippocampography) and lateral electrocorticography groups. Primary outcome was deviation from mean hippocampectomy length. Results. Of 26 patients, fourteen underwent hippocampography-guided mesial temporal resection. Hippocampography was associated with 2.6 times more consistent resection. The range of hippocampal resection was 0.7 cm in the mesial group and 1.8 cm in the lateral group (p = 0.01). 86% of mesial group versus 42% of lateral group patients achieved seizure freedom (p = 0.02). Conclusions. By rationally tailoring excision to demonstrably epileptogenic tissue, hippocampography significantly reduces resection variability for more consistent hippocampectomy than unguided resection in conventional electrocorticography. More consistent hippocampal resection may avoid overresection, which poses greater neuropsychological risk, and underresection, which jeopardizes postoperative seizure freedom. PMID:27703809

A portable fluorescence microscopic imaging system for cholecystectomy

NASA Astrophysics Data System (ADS)

Ye, Jian; Yang, Chaoyu; Gan, Qi; Ma, Rong; Zhang, Zeshu; Chang, Shufang; Shao, Pengfei; Zhang, Shiwu; Liu, Chenhai; Xu, Ronald

2016-03-01

In this paper we proposed a portable fluorescence microscopic imaging system to prevent iatrogenic biliary injuries from occurring during cholecystectomy due to misidentification of the cystic structures. The system consisted of a light source module, a CMOS camera, a Raspberry Pi computer and a 5 inch HDMI LCD. Specifically, the light source module was composed of 690 nm and 850 nm LEDs, allowing the CMOS camera to simultaneously acquire both fluorescence and background images. The system was controlled by Raspberry Pi using Python programming with the OpenCV library under Linux. We chose Indocyanine green(ICG) as a fluorescent contrast agent and then tested fluorescence intensities of the ICG aqueous solution at different concentration levels by our fluorescence microscopic system compared with the commercial Xenogen IVIS system. The spatial resolution of the proposed fluorescence microscopic imaging system was measured by a 1951 USAF resolution target and the dynamic response was evaluated quantitatively with an automatic displacement platform. Finally, we verified the technical feasibility of the proposed system in mouse models of bile duct, performing both correct and incorrect gallbladder resection. Our experiments showed that the proposed system can provide clear visualization of the confluence between the cystic duct and common bile duct or common hepatic duct, suggesting that this is a potential method for guiding cholecystectomy. The proposed portable system only cost a total of $300, potentially promoting its use in resource-limited settings.

Accurate three-dimensional virtual reconstruction of surgical field using calibrated trajectories of an image-guided medical robot

PubMed Central

Gong, Yuanzheng; Hu, Danying; Hannaford, Blake; Seibel, Eric J.

2014-01-01

Abstract. Brain tumor margin removal is challenging because diseased tissue is often visually indistinguishable from healthy tissue. Leaving residual tumor leads to decreased survival, and removing normal tissue causes life-long neurological deficits. Thus, a surgical robotics system with a high degree of dexterity, accurate navigation, and highly precise resection is an ideal candidate for image-guided removal of fluorescently labeled brain tumor cells. To image, we developed a scanning fiber endoscope (SFE) which acquires concurrent reflectance and fluorescence wide-field images at a high resolution. This miniature flexible endoscope was affixed to the arm of a RAVEN II surgical robot providing programmable motion with feedback control using stereo-pair surveillance cameras. To verify the accuracy of the three-dimensional (3-D) reconstructed surgical field, a multimodal physical-sized model of debulked brain tumor was used to obtain the 3-D locations of residual tumor for robotic path planning to remove fluorescent cells. Such reconstruction is repeated intraoperatively during margin clean-up so the algorithm efficiency and accuracy are important to the robotically assisted surgery. Experimental results indicate that the time for creating this 3-D surface can be reduced to one-third by using known trajectories of a robot arm, and the error from the reconstructed phantom is within 0.67 mm in average compared to the model design. PMID:26158071

Quantitative Tumor Segmentation for Evaluation of Extent of Glioblastoma Resection to Facilitate Multisite Clinical Trials12

PubMed Central

Cordova, James S; Schreibmann, Eduard; Hadjipanayis, Costas G; Guo, Ying; Shu, Hui-Kuo G; Shim, Hyunsuk; Holder, Chad A

2014-01-01

Standard-of-care therapy for glioblastomas, the most common and aggressive primary adult brain neoplasm, is maximal safe resection, followed by radiation and chemotherapy. Because maximizing resection may be beneficial for these patients, improving tumor extent of resection (EOR) with methods such as intraoperative 5-aminolevulinic acid fluorescence-guided surgery (FGS) is currently under evaluation. However, it is difficult to reproducibly judge EOR in these studies due to the lack of reliable tumor segmentation methods, especially for postoperative magnetic resonance imaging (MRI) scans. Therefore, a reliable, easily distributable segmentation method is needed to permit valid comparison, especially across multiple sites. We report a segmentation method that combines versatile region-of-interest blob generation with automated clustering methods. We applied this to glioblastoma cases undergoing FGS and matched controls to illustrate the method's reliability and accuracy. Agreement and interrater variability between segmentations were assessed using the concordance correlation coefficient, and spatial accuracy was determined using the Dice similarity index and mean Euclidean distance. Fuzzy C-means clustering with three classes was the best performing method, generating volumes with high agreement with manual contouring and high interrater agreement preoperatively and postoperatively. The proposed segmentation method allows tumor volume measurements of contrast-enhanced T1-weighted images in the unbiased, reproducible fashion necessary for quantifying EOR in multicenter trials. PMID:24772206

Ultrasound-guided breast-sparing surgery to improve cosmetic outcomes and quality of life. A prospective multicentre randomised controlled clinical trial comparing ultrasound-guided surgery to traditional palpation-guided surgery (COBALT trial)

PubMed Central

2011-01-01

Background Breast-conserving surgery for breast cancer was developed as a method to preserve healthy breast tissue, thereby improving cosmetic outcomes. Thus far, the primary aim of breast-conserving surgery has been the achievement of tumour-free resection margins and prevention of local recurrence, whereas the cosmetic outcome has been considered less important. Large studies have reported poor cosmetic outcomes in 20-40% of patients after breast-conserving surgery, with the volume of the resected breast tissue being the major determinant. There is clear evidence for the efficacy of ultrasonography in the resection of nonpalpable tumours. Surgical resection of palpable breast cancer is performed with guidance by intra-operative palpation. These palpation-guided excisions often result in an unnecessarily wide resection of adjacent healthy breast tissue, while the rate of tumour-involved resection margins is still high. It is hypothesised that the use of intra-operative ultrasonography in the excision of palpable breast cancer will improve the ability to spare healthy breast tissue while maintaining or even improving the oncological margin status. The aim of this study is to compare ultrasound-guided surgery for palpable tumours with the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumour-free margins, cosmetic outcomes and quality of life. Methods/design In this prospective multicentre randomised controlled clinical trial, 120 women who have been diagnosed with palpable early-stage (T1-2N0-1) primary invasive breast cancer and deemed suitable for breast-conserving surgery will be randomised between ultrasound-guided surgery and palpation-guided surgery. With this sample size, an expected 20% reduction of resected breast tissue and an 18% difference in tumour-free margins can be detected with a power of 80%. Secondary endpoints include cosmetic outcomes and quality of life. The rationale, study design and planned analyses are described. Conclusion The COBALT trial is a prospective, multicentre, randomised controlled study to assess the efficacy of ultrasound-guided breast-conserving surgery in patients with palpable early-stage primary invasive breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life. Trial Registration Number Netherlands Trial Register (NTR): NTR2579 PMID:21410949

Imaging of Lymph Flow in Breast Cancer Patients after Microdose Administration of a Near-Infrared Fluorophore: Feasibility Study1

PubMed Central

Sevick-Muraca, Eva M.; Sharma, Ruchi; Rasmussen, John C.; Marshall, Milton V.; Wendt, Juliet A.; Pham, Hoang Q.; Bonefas, Elizabeth; Houston, Jessica P.; Sampath, Lakshmi; Adams, Kristen E.; Blanchard, Darlene Kay; Fisher, Ronald E.; Chiang, Stephen B.; Elledge, Richard; Mawad, Michel E.

2011-01-01

Purpose To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods Informed consent was obtained from 24 women (age range, 30–85 years) who received intradermal subcutaneous injections of 0.31–100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between “packets” of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. Conclusion NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs. PMID:18223125

A Novel Imaging System Distinguishes Neoplastic from Normal Tissue During Resection of Soft Tissue Sarcomas and Mast Cell Tumors in Dogs.

PubMed

Bartholf DeWitt, Suzanne; Eward, William C; Eward, Cindy A; Lazarides, Alexander L; Whitley, Melodi Javid; Ferrer, Jorge M; Brigman, Brian E; Kirsch, David G; Berg, John

2016-08-01

To assess the ability of a novel imaging system designed for intraoperative detection of residual cancer in tumor beds to distinguish neoplastic from normal tissue in dogs undergoing resection of soft tissue sarcoma (STS) and mast cell tumor (MCT). Non-randomized prospective clinical trial. 12 dogs with STS and 7 dogs with MCT. A fluorescent imaging agent that is activated by proteases in vivo was administered to the dogs 4-6 or 24-26 hours before tumor resection. During surgery, a handheld imaging device was used to measure fluorescence intensity within the cancerous portion of the resected specimen and determine an intensity threshold for subsequent identification of cancer. Selected areas within the resected specimen and tumor bed were then imaged, and biopsies (n=101) were obtained from areas that did or did not have a fluorescence intensity exceeding the threshold. Results of intraoperative fluorescence and histology were compared. The imaging system correctly distinguished cancer from normal tissue in 93/101 biopsies (92%). Using histology as the reference, the sensitivity and specificity of the imaging system for identification of cancer in biopsies were 92% and 92%, respectively. There were 10/19 (53%) dogs which exhibited transient facial erythema soon after injection of the imaging agent which responded to but was not consistently prevented by intravenous diphenhydramine. A fluorescence-based imaging system designed for intraoperative use can distinguish canine soft tissue sarcoma (STS) and mast cell tumor (MCT) tissue from normal tissue with a high degree of accuracy. The system has potential to assist surgeons in assessing the adequacy of tumor resections during surgery, potentially reducing the risk of local tumor recurrence. Although responsive to antihistamines, the risk of hypersensitivity needs to be considered in light of the potential benefits of this imaging system in dogs. © Copyright 2016 by The American College of Veterinary Surgeons.

Review of the potential of optical technologies for cancer diagnosis in neurosurgery: a step toward intraoperative neurophotonics

PubMed Central

Vasefi, Fartash; MacKinnon, Nicholas; Farkas, Daniel L.; Kateb, Babak

2016-01-01

Abstract. Advances in image-guided therapy enable physicians to obtain real-time information on neurological disorders such as brain tumors to improve resection accuracy. Image guidance data include the location, size, shape, type, and extent of tumors. Recent technological advances in neurophotonic engineering have enabled the development of techniques for minimally invasive neurosurgery. Incorporation of these methods in intraoperative imaging decreases surgical procedure time and allows neurosurgeons to find remaining or hidden tumor or epileptic lesions. This facilitates more complete resection and improved topology information for postsurgical therapy (i.e., radiation). We review the clinical application of recent advances in neurophotonic technologies including Raman spectroscopy, thermal imaging, optical coherence tomography, and fluorescence spectroscopy, highlighting the importance of these technologies in live intraoperative tissue mapping during neurosurgery. While these technologies need further validation in larger clinical trials, they show remarkable promise in their ability to help surgeons to better visualize the areas of abnormality and enable safe and successful removal of malignancies. PMID:28042588

Paired-agent imaging for resection during surgery (PAIRS) of head and neck squamous cell carcinomas (Conference Presentation)

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Tichauer, Kenneth M.; Chen, Eunice; Gunn, Jason R.; Hoopes, P. Jack; Wells, Wendy A.; Hasan, Tayyaba; Pogue, Brian W.

2016-03-01

Ninety percent of patients with head and neck squamous cell carcinomas (HNSCC) have overexpression of epidermal growth factor receptor (EGFR), which is correlated with poor prognosis. Complete surgical resection of HNSCC tumors has a large impact on patient survival, where detection of tumor at or close to surgical margins increases the risk of death at 5-years by 90%. In addition, large surgical margins can greatly increase the morbidity experienced by the patient due to functional and cosmetic damage of oral and facial structures. Single fluorescence targeting agents are often used for tumor detection in in vivo pre-clinical imaging; however, the arising signal is qualitative at best because it is a complex mixture of vascular perfusion, vascular leakage, inhibited lymphatic clearance, and receptor binding. In vivo ratiometric receptor concentration imaging (RCI) allows quantification of receptor expression (hence identification of cancerous tissue) by utilizing co-administered paired-agents consisting of a targeted agent and non-targeted perfusion agent to reference the plasma delivery and leakage. A panel of HNSCC tumors with varying levels of EGFR expression (SCC-15 >SCC-25 > SCC-09) have been imaged using ABY-029, a clinically relevant anti-EGFR affibody labeled with IRDye 800CW, and affibody control imaging agent labeled with IRDye 680RD. RCI maps of in vivo tissue have been created and are spatially correlated with EGFR and CD31 immunohistochemistry and basic H and E staining. The RCI threshold parameters for distinguishing tumor from normal tissues (skin and muscle) and the accuracy of margin detection in these tumors will be presented. RCI surgical resection will be further developed using a novel multi-channel, gated fluorescence-guided surgery (FGS) imaging system that is capable of performing RCI in normal room light.

Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance.

PubMed

Boogerd, Leonora S F; Handgraaf, Henricus J M; Lam, Hwai-Ding; Huurman, Volkert A L; Farina-Sarasqueta, Arantza; Frangioni, John V; van de Velde, Cornelis J H; Braat, Andries E; Vahrmeijer, Alexander L

2017-02-01

Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver. Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard of care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered 1 day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard. Twenty-two patients suspected of having hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 2) or liver metastases from colorectal carcinoma (n = 12), uveal melanoma (n = 2), and breast cancer (n = 2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80 % (CT), 84 % (MRI), 62 % (inspection), 86 % (LUS), and 92 % (FI), respectively. Three metastases (12 %) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100 % sensitivity). This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance.

Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities

PubMed Central

Zehri, Aqib H.; Ramey, Wyatt; Georges, Joseph F.; Mooney, Michael A.; Martirosyan, Nikolay L.; Preul, Mark C.; Nakaji, Peter

2014-01-01

Background: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. Methods: A comprehensive literature search was performed utilizing PubMed and key words: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. Results: Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. Conclusion: In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery. PMID:24872922

Randomized trial for superiority of high field strength intra-operative magnetic resonance imaging guided resection in pituitary surgery.

PubMed

Tandon, Vivek; Raheja, Amol; Suri, Ashish; Chandra, P Sarat; Kale, Shashank S; Kumar, Rajinder; Garg, Ajay; Kalaivani, Mani; Pandey, Ravindra M; Sharma, Bhawani S

2017-03-01

Till date there are no randomized trials to suggest the superiority of intra-operative magnetic resonance imaging (IOMRI) guided trans-sphenoidal pituitary resection over two dimensional fluoroscopic (2D-F) guided resections. We conducted this trial to establish the superiority of IOMRI in pituitary surgery. Primary objective was to compare extent of tumor resection between the two study arms. It was a prospective, randomized, outcome assessor and statistician blinded, two arm (A: IOMRI, n=25 and B: 2D-F, n=25), parallel group clinical trial. 4 patients from IOMRI group cross-over to 2D-F group and were consequently analyzed in latter group, based on modified intent to treat method. A total of 50 patients were enrolled till completion of trial (n=25 in each study arm). Demographic profile and baseline parameters were comparable among the two arms (p>0.05) except for higher number of endoscopic procedures and experienced neurosurgeons (>10years) in arm B (p=0.02, 0.002 respectively). Extent of resection was similar in both study arms (A, 94.9% vs B, 93.6%; p=0.78), despite adjusting for experience of operating surgeon and use of microscope/endoscope for surgical resection. We observed that use of IOMRI helped optimize the extent of resection in 5/20 patients (25%) for pituitary tumor resection in-group A. Present study failed to observe superiorty of IOMRI over conventional 2D-F guided resection in pituitary macroadenoma surgery. By use of this technology, younger surgeons could validate their results intra-operatively and hence could increase EOR without causing any increase in complications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Current perspectives in the use of molecular imaging to target surgical treatments for genitourinary cancers.

PubMed

Greco, Francesco; Cadeddu, Jeffrey A; Gill, Inderbir S; Kaouk, Jihad H; Remzi, Mesut; Thompson, R Houston; van Leeuwen, Fijs W B; van der Poel, Henk G; Fornara, Paolo; Rassweiler, Jens

2014-05-01

Molecular imaging (MI) entails the visualisation, characterisation, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. Translating this technology to interventions in real-time enables interventional MI/image-guided surgery, for example, by providing better detection of tumours and their dimensions. To summarise and critically analyse the available evidence on image-guided surgery for genitourinary (GU) oncologic diseases. A comprehensive literature review was performed using PubMed and the Thomson Reuters Web of Science. In the free-text protocol, the following terms were applied: molecular imaging, genitourinary oncologic surgery, surgical navigation, image-guided surgery, and augmented reality. Review articles, editorials, commentaries, and letters to the editor were included if deemed to contain relevant information. We selected 79 articles according to the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL method. MI techniques included optical imaging and fluorescent techniques, the augmented reality (AR) navigation system, magnetic resonance imaging spectroscopy, positron emission tomography, and single-photon emission computed tomography. Experimental studies on the AR navigation system were restricted to the detection and therapy of adrenal and renal malignancies and in the relatively infrequent cases of prostate cancer, whereas fluorescence techniques and optical imaging presented a wide application of intraoperative GU oncologic surgery. In most cases, image-guided surgery was shown to improve the surgical resectability of tumours. Based on the evidence to date, image-guided surgery has promise in the near future for multiple GU malignancies. Further optimisation of targeted imaging agents, along with the integration of imaging modalities, is necessary to further enhance intraoperative GU oncologic surgery. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Intraoperative efficiency of fluorescence imaging by Visually Enhanced Lesion Scope (VELscope) in patients with bisphosphonate related osteonecrosis of the jaw (BRONJ).

PubMed

Assaf, Alexandre T; Zrnc, Tomislav A; Riecke, Björn; Wikner, Johannes; Zustin, Jozef; Friedrich, Reinhard E; Heiland, Max; Smeets, Ralf; Gröbe, Alexander

2014-07-01

The purpose of this study was to determine the potential of tissue fluorescence imaging by using Visually Enhanced Lesion Scope (VELscope) for the detection of osteonecrosis of the jaw induced by bisphosphonates (BRONJ). We investigated 20 patients (11 females and 9 males; mean age 74 years, standard deviation ± 6.4 years), over a period of 18 month with the diagnosis of BRONJ in this prospective cohort study. All patients received doxycycline as a fluorescending marker for osseous structures. VELscope has been used intraoperatively using the loss of fluorescence to detect presence of osteonecrosis. Osseous biopsies were taken to confirm definite histopathological diagnosis of BRONJ in each case. Diagnosis of BRONJ was confirmed for every patient. In all patients except one, VELscope was sufficient to differentiate between healthy and necrotic bone by visual fluorescence retention (VFR) and visual fluorescence loss (VFL). 19 cases out of a total of 20 showed no signs of recurrence of BRONJ during follow-up (mean 12 months, range 4-18 months). VELscope examination is a suitable tool to visualize necrotic areas of the bone in patients with bisphosphonate related osteonecrosis of the jaw. Loss of fluorescence in necrotic bone areas is useful intraoperatively as a tool for fluorescence-guided bone resection with relevant clinical interpretation. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Use of monoclonal antibody-IRDye800CW bioconjugates in the resection of breast cancer

PubMed Central

Korb, Melissa L.; Hartman, Yolanda E.; Kovar, Joy; Zinn, Kurt R.; Bland, Kirby I.; Rosenthal, Eben L.

2015-01-01

Background Complete surgical resection of breast cancer is a powerful determinant of patient outcome, and failure to achieve negative margins results in reoperation in between 30% and 60% of patients. We hypothesize that repurposing Food and Drug Administration approved antibodies as tumor-targeting diagnostic molecules can function as optical contrast agents to identify the boundaries of malignant tissue intraoperatively. Materials and methods The monoclonal antibodies bevacizumab, cetuximab, panitumumab, trastuzumab, and tocilizumab were covalently linked to a near-infrared fluorescence probe (IRDye800CW) and in vitro binding assays were performed to confirm ligand-specific binding. Nude mice bearing human breast cancer flank tumors were intravenously injected with the antibody-IRDye800 bioconjugates and imaged over time. Tumor resections were performed using the SPY and Pearl Impulse systems, and the presence or absence of tumor was confirmed by conventional and fluorescence histology. Results Tumor was distinguishable from normal tissue using both SPY and Pearl systems, with both platforms being able to detect tumor as small as 0.5 mg. Serial surgical resections demonstrated that real-time fluorescence can differentiate subclinical segments of disease. Pathologic examination of samples by conventional and optical histology using the Odyssey scanner confirmed that the bioconjugates were specific for tumor cells and allowed accurate differentiation of malignant areas from normal tissue. Conclusions Human breast cancer tumors can be imaged in vivo with multiple optical imaging platforms using near-infrared fluorescently labeled antibodies. These data support additional preclinical investigations for improving the surgical resection of malignancies with the goal of eventual clinical translation. PMID:24360117

Intraoperative fluorescence-based enhanced reality laparoscopic real-time imaging to assess bowel perfusion at the anastomotic site in an experimental model.

PubMed

Diana, M; Agnus, V; Halvax, P; Liu, Y-Y; Dallemagne, B; Schlagowski, A-I; Geny, B; Diemunsch, P; Lindner, V; Marescaux, J

2015-01-01

Fluorescence videography is a promising technique for assessing bowel perfusion. Fluorescence-based enhanced reality (FLER) is a novel concept, in which a dynamic perfusion cartogram, generated by computer analysis, is superimposed on to real-time laparoscopic images. The aim of this experimental study was to assess the accuracy of FLER in detecting differences in perfusion in a small bowel resection-anastomosis model. A small bowel ischaemic segment was created laparoscopically in 13 pigs. Animals were allocated to having anastomoses performed at either low perfusion (25 per cent; n = 7) or high perfusion (75 per cent; n = 6), as determined by FLER analysis. Capillary lactate levels were measured in blood samples obtained by serosal puncturing in the ischaemic area, resection lines and vascularized areas. Pathological inflammation scoring of the anastomosis was carried out. Lactate levels in the ischaemic area (mean(s.d.) 5·6(2·8) mmol/l) were higher than those in resection lines at 25 per cent perfusion (3·7(1·7) mmol/l; P = 0·010) and 75 per cent perfusion (2·9(1·3) mmol/l; P < 0·001), and higher than levels in vascular zones (2·5(1·0) mmol/l; P < 0·001). Lactate levels in resection lines with 75 per cent perfusion were lower than those in lines with 25 per cent perfusion (P < 0·001), and similar to those in vascular zones (P = 0·188). Levels at resection lines with 25 per cent perfusion were higher than those in vascular zones (P = 0·001). Mean(s.d.) global inflammation scores were higher in the 25 per cent perfusion group compared with the 75 per cent perfusion group for mucosa/submucosa (2·1(0·4) versus 1·2(0·4); P = 0·003) and serosa (1·8(0·4) versus 0·8(0·8); P = 0·014). A ratio of preanastomotic lactate levels in the ischaemic area relative to the resection lines of 2 or less was predictive of a more severe inflammation score. In an experimental model, FLER appeared accurate in discriminating bowel perfusion levels. Surgical relevance Clinical assessment has limited accuracy in evaluating bowel perfusion before anastomosis. Fluorescence videography estimates intestinal perfusion based on the fluorescence intensity of injected fluorophores, which is proportional to bowel vascularization. However, evaluation of fluorescence intensity remains a static and subjective measure. Fluorescence-based enhanced reality (FLER) is a dynamic fluorescence videography technique integrating near-infrared endoscopy and specific software. The software generates a virtual perfusion cartogram based on time to peak fluorescence, which can be superimposed on to real-time laparoscopic images. This experimental study demonstrates the accuracy of FLER in detecting differences in bowel perfusion in a survival model of laparoscopic small bowel resection-anastomosis, based on biochemical and histopathological data. It is concluded that real-time imaging of bowel perfusion is easy to use and accurate, and should be translated into clinical use. © 2015 BJS Society Ltd. Published by John Wiley & Sons Ltd.

A novel endoscopic fluorescent band ligation method for tumor localization.

PubMed

Hyun, Jong Hee; Kim, Seok-Ki; Kim, Kwang Gi; Kim, Hong Rae; Lee, Hyun Min; Park, Sunup; Kim, Sung Chun; Choi, Yongdoo; Sohn, Dae Kyung

2016-10-01

Accurate tumor localization is essential for minimally invasive surgery. This study describes the development of a novel endoscopic fluorescent band ligation method for the rapid and accurate identification of tumor sites during surgery. The method utilized a fluorescent rubber band, made of indocyanine green (ICG) and a liquid rubber solution mixture, as well as a near-infrared fluorescence laparoscopic system with a dual light source using a high-powered light-emitting diode (LED) and a 785-nm laser diode. The fluorescent rubber bands were endoscopically placed on the mucosae of porcine stomachs and colons. During subsequent conventional laparoscopic stomach and colon surgery, the fluorescent bands were assayed using the near-infrared fluorescence laparoscopy system. The locations of the fluorescent clips were clearly identified on the fluorescence images in real time. The system was able to distinguish the two or three bands marked on the mucosal surfaces of the stomach and colon. Resection margins around the fluorescent bands were sufficient in the resected specimens obtained during stomach and colon surgery. These novel endoscopic fluorescent bands could be rapidly and accurately localized during stomach and colon surgery. Use of these bands may make possible the excision of exact target sites during minimally invasive gastrointestinal surgery.

Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

NASA Astrophysics Data System (ADS)

Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

2014-11-01

Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

Fluorescence detection of malignant liver tumors using 5-aminolevulinic acid-mediated photodynamic diagnosis: principles, technique, and clinical experience.

PubMed

Inoue, Yoshihiro; Tanaka, Ryo; Komeda, Koji; Hirokawa, Fumitoshi; Hayashi, Michihiro; Uchiyama, Kazuhisa

2014-07-01

Photoactive drugs selectively accumulate in malignant tissue specimens and cause drug-induced fluorescence. Photodynamic diagnosis (PDD) and fluorescence can distinguish normal from malignant tissue. From May 2012 to September 2013, a total of 70 patients underwent hepatic resections using 5-ALA-mediated PDD for liver tumors at our hospital. 5-ALA fluorescence was detected in all hepatocellular carcinoma cases with serosa invasion. In liver metastasis from colorectal cancer cases with serosa invasion, 18 patients (85.7 %) were detected, and three patients (14.2 %) whose tumors showed complete response to neoadjuvant chemotherapy showed no fluorescence. Both superficial and deep malignant liver tumors were detected with 92.5 % sensitivity. Using 5-ALA-mediated PDD, tumors remaining at the cut surface and postoperative bile leakage were less frequent than in our previous hepatic resections using conventional white-light observation. Moreover, all malignant liver tumors were completely removed with a clear microscopic margin using 5-ALA, with a significant difference in resection margin width between 5-ALA-mediated PDD (6.7 ± 6.9 mm) and white-light observation (9.2 ± 7.0 mm; p = 0.0083). With the detection of malignant liver tumors, residual tumor and bile leakage at the cut surface of the remnant liver were improved by PDD with 5-ALA. This procedure may provide greater sensitivity than the conventional procedure. Furthermore, 5-ALA-mediated PDD can ensure histological clearance regardless of the resection margin and preserve as much liver parenchyma as possible in patients with impaired liver function.

Hybrid radioguided occult lesion localization (hybrid ROLL) of (18)F-FDG-avid lesions using the hybrid tracer indocyanine green-(99m)Tc-nanocolloid.

PubMed

KleinJan, G H; Brouwer, O R; Mathéron, H M; Rietbergen, D D D; Valdés Olmos, R A; Wouters, M W; van den Berg, N S; van Leeuwen, F W B

2016-01-01

To assess if combined fluorescence- and radio-guided occult lesion localization (hybrid ROLL) is feasible in patients scheduled for surgical resection of non-palpable (18)F-FDG-avid lesions on PET/CT. Four patients with (18)F-FDG-avid lesions on follow-up PET/CT that were not palpable during physical examination but were suspected to harbor metastasis were enrolled. Guided by ultrasound, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was injected centrally in the target lesion. SPECT/CT imaging was used to confirm tracer deposition. Intraoperatively, lesions were localized using a hand-held gamma ray detection probe, a portable gamma camera, and a fluorescence camera. After excision, the gamma camera was used to check the wound bed for residual activity. A total of six (18)F-FDG-avid lymph nodes were identified and scheduled for hybrid ROLL. Comparison of the PET/CT images with the acquired SPECT/CT after hybrid tracer injection confirmed accurate tracer deposition. No side effects were observed. Combined radio- and fluorescence-guidance enabled localization and excision of the target lesion in all patients. Five of the six excised lesions proved tumor-positive at histopathology. The hybrid ROLL approach appears to be feasible and can facilitate the intraoperative localization and excision of non-palpable lesions suspected to harbor tumor metastases. In addition to the initial radioguided detection, the fluorescence component of the hybrid tracer enables high-resolution intraoperative visualization of the target lesion. The procedure needs further evaluation in a larger cohort and wider range of malignancies to substantiate these preliminary findings. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

2014-03-01

Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

Fluorescence intensity and bright spot analyses using a confocal microscope for photodynamic diagnosis of brain tumors.

PubMed

Yoneyama, Takeshi; Watanabe, Tetsuyo; Kagawa, Hiroyuki; Hayashi, Yutaka; Nakada, Mitsutoshi

2017-03-01

In photodynamic diagnosis using 5-aminolevulinic acid (5-ALA), discrimination between the tumor and normal tissue is very important for a precise resection. However, it is difficult to distinguish between infiltrating tumor and normal regions in the boundary area. In this study, fluorescent intensity and bright spot analyses using a confocal microscope is proposed for the precise discrimination between infiltrating tumor and normal regions. From the 5-ALA-resected brain tumor tissue, the red fluorescent and marginal regions were sliced for observation under a confocal microscope. Hematoxylin and eosin (H&E) staining were performed on serial slices of the same tissue. According to the pathological inspection of the H&E slides, the tumor and infiltrating and normal regions on confocal microscopy images were investigated. From the fluorescent intensity of the image pixels, a histogram of pixel number with the same fluorescent intensity was obtained. The fluorescent bright spot sizes and total number were compared between the marginal and normal regions. The fluorescence intensity distribution and average intensity in the tumor were different from those in the normal region. The probability of a difference from the dark enhanced the difference between the tumor and the normal region. The bright spot size and number in the infiltrating tumor were different from those in the normal region. Fluorescence intensity analysis is useful to distinguish a tumor region, and a bright spot analysis is useful to distinguish between infiltrating tumor and normal regions. These methods will be important for the precise resection or photodynamic therapy of brain tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

Flexible omnidirectional carbon dioxide laser as an effective tool for resection of brainstem, supratentorial, and intramedullary cavernous malformations.

PubMed

Choudhri, Omar; Karamchandani, Jason; Gooderham, Peter; Steinberg, Gary K

2014-03-01

Lasers have a long history in neurosurgery, yet bulky designs and difficult ergonomics limit their use. With its ease of manipulation and multiple applications, the OmniGuide CO2 laser has reintroduced laser technology to the microsurgical resection of brain and spine lesions. This laser, delivered through a hollow-core fiber lined with a unidirectional mirror, minimizes energy loss and allows precise targeting. To analyze resections performed by the senior author from April 2009 to March 2013 of 58 cavernous malformations (CMs) in the brain and spine with the use of the OmniGuide CO2 laser, to reflect on lessons learned from laser use in eloquent areas, and to share data on comparisons of laser power calibration and histopathology. Data were collected from electronic medical records, radiology reports, operative room records, OmniGuide CO2 laser case logs, and pathology records. Of 58 CMs, approximately 50% were in the brainstem (30) and the rest were in supratentorial (26) and intramedullary spinal locations (2). Fifty-seven, ranging from 5 to 45 mm, were resected, with a subtotal resection in 1. Laser power ranged from 2 to 10 W. Pathology specimens showed minimal thermal damage compared with traditionally resected specimens with bipolar coagulation. The OmniGuide CO2 laser is safe and has excellent precision for the resection of supratentorial, brainstem, and spinal intramedullary CMs. No laser-associated complications occurred, and very low energy was used to dissect malformations from their surrounding hemosiderin-stained parenchymas. The authors recommend its use for deep-seated and critically located CMs, along with traditional tools.

Intraoperative Identification of a Normal Pituitary Gland and an Adenoma Using Near-Infrared Fluorescence Imaging and Low-Dose Indocyanine Green.

PubMed

Verstegen, Marco J T; Tummers, Quirijn R J G; Schutte, Pieter J; Pereira, Alberto M; van Furth, Wouter R; van de Velde, Cornelis J H; Malessy, Martijn J A; Vahrmeijer, Alexander L

2016-09-01

The intraoperative distinction between normal and abnormal pituitary tissue is crucial during pituitary adenoma surgery to obtain a complete tumor resection while preserving endocrine function. Near-infrared (NIR) fluorescence imaging is a technique to intraoperatively visualize tumors by using indocyanine green (ICG), a contrast agent allowing visualization of differences in tissue vascularization. Although NIR fluorescence imaging has been described in pituitary surgery, it has, in contrast to other surgical areas, never become widely used. To evaluate NIR fluorescence imaging in pituitary surgery, both qualitatively and quantitatively, and to assess the additional value of resecting adenoma tissue under NIR fluorescence guidance. We included 10 patients planned to undergo transnasal transsphenoidal selective adenomectomy. Patients received multiple intravenous administrations of 5 mg ICG, up to a maximum of 15 mg per patient. Endoscopic NIR fluorescence imaging was performed at multiple points in time. The NIR fluorescent signal in both the adenoma and pituitary gland was obtained, and the fluorescence contrast ratio was assessed. Four patients had Cushing disease, 1 had acromegaly, and 1 had a prolactinoma. Four patients had a nonfunctioning macroadenoma. In 9 of 10 patients with a histologically proven pituitary adenoma, the normal pituitary gland showed a stronger fluorescent signal than the adenoma. A fluorescence contrast ratio of normal pituitary gland to adenoma of 1.5 ± 0.2 was obtained. In 2 patients; adenoma resection was actually performed under NIR fluorescence guidance instead of under white light. NIR fluorescence imaging can easily and safely be implemented in pituitary surgery. The timing of ICG administration is important for optimal results and warrants further study. It appears that injection of ICG can best be postponed until some part of the normal pituitary gland is identified. Subsequent repeated low-dose ICG administrations improved the distinction between adenoma and gland.

The application of 3D printed surgical guides in resection and reconstruction of malignant bone tumor.

PubMed

Wang, Fengping; Zhu, Jun; Peng, Xuejun; Su, Jing

2017-10-01

The clinical value of 3D printed surgical guides in resection and reconstruction of malignant bone tumor around the knee joint were studied. For this purpose, a sample of 66 patients from October 2013 to October 2015 were randomly selected and further divided into control group and observation group, each group consisted of 33 cases. The control group was treated by conventional tumor resection whereas, in the observation group, the tumor was resected with 3D printed surgical guide. However, reconstruction of tumor-type hinge prosthesis was performed in both groups and then the clinical effect was compared. Results show that there was no significant difference in the operation time between the two groups (p>0.05). However, the blood loss, resection length and complication rate were found significantly lower in the observation group than in the control group (p<0.05). The rate of negative margin and the recurrence rate in the 12-month follow-up (p>0.05) between two groups were statistically the same (p>0.05), whereas the Musculoskeletal Tumor Society (MSTS) score of the knee joint in the observation group was significantly better than that of the control group (p<0.05) after 1, 3, 6 and 12 months of the operation. Consequently, the 3D printed surgical guides can significantly improve the postoperative joint function after resection and reconstruction of malignant bone tumor around the knee joint and can reduce the incidence of complications.

A multiplanar complex resection of a low-grade chondrosarcoma of the distal femur guided by K-wires previously inserted under CT-guide: a case report.

PubMed

Zoccali, Carmine; Rossi, Barbara; Ferraresi, Virginia; Anelli, Vincenzo; Rita, Alessandro

2014-08-13

In muscular skeletal oncology aiming to achieve wide surgical margin is one of the main factors influencing patient prognosis. In cases where lesions are either meta or epiphyseal, surgery most often compromises joint integrity and stability because muscles, tendons and ligaments are involved in wide resection. When lesions are well circumscribed they can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. We describe a case of low-grade chondrosarcoma of the distal femur where a simple but effective technique was useful to perform complex multiplanar osteotomies. No similar techniques are reported in the literature. A 57 year-old Caucasian female was referred to our department for the presence of a distal femur chondrosarcoma. A resection with the presenting technique was scheduled. The first step consists of inserting several K-wires under CT-scan control to delimitate the tumor; the second step consists of tumor removal: in operative theatre, following surgical access, k-wires are used as guide positioning; scalpels are externally placed to k-wires to perform a safe osteotomy. Computed assisted resections can be considered the most advantageous method to reach the best surgical outcome; unfortunately navigation systems are only available in specialized centres. The present technique allows for a multiplanar complex resection when navigation systems are not available. This technique can be applied in low-grade tumours where a minimal wide margin can be considered sufficient.

Development and characterisation of a brain tumour mimicking protoporphyrin IX fluorescence phantom (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xie, Yijing; Tisca, Cristiana; Peveler, William; Noimark, Sacha; Desjardins, Adrien E.; Parkin, Ivan P.; Ourselin, Sebastien; Vercauteren, Tom

2017-02-01

5-ALA-PpIX fluorescence-guided brain tumour resection can increase the accuracy at which cancerous tissue is removed and thereby improve patient outcomes, as compared with standard white light imaging. Novel optical devices that aim to increase the specificity and sensitivity of PpIX detection are typically assessed by measurements in tissue-mimicking optical phantoms of which all optical properties are defined. Current existing optical phantoms specified for PpIX lack consistency in their optical properties, and stability with respect to photobleaching, thus yielding an unstable correspondence between PpIX concentration and the fluorescence intensity. In this study, we developed a set of aqueous-based phantoms with different compositions, using deionised water or PBS buffer as background medium, intralipid as scattering material, bovine haemoglobin as background absorber, and either PpIX dissolved in DMSO or a novel nanoparticle with similar absorption and emission spectrum to PpIX as the fluorophore. We investigated the phantom stability in terms of aggregation and photobleaching by comparing with different background medium and fluorophores, respectively. We characterised the fluorescence intensity of the fluorescent nanoparticle in different concentration of intralipid and haemoglobin and its time-dependent stability, as compared to the PpIX-induced fluorescence. We corroborated that the background medium was essential to prepare a stable aqueous phantom. The novel fluorescent nanoparticle used as surrogate fluorophore of PpIX presented an improved temporal stability and a reliable correspondence between concentration and emission intensity. We proposed an optimised phantom composition and recipe to produce reliable and repeatable phantom for validation of imaging device.

Feasibility of Real-Time Near-Infrared Fluorescence Tracer Imaging in Sentinel Node Biopsy for Oral Cavity Cancer Patients.

PubMed

Christensen, Anders; Juhl, Karina; Charabi, Birgitte; Mortensen, Jann; Kiss, Katalin; Kjær, Andreas; von Buchwald, Christian

2016-02-01

Sentinel node biopsy (SNB) is an established method in oral squamous cell carcinoma (OSCC) for staging the cN0 neck and to select patients who will benefit from a neck dissection. Near-infrared fluorescence (NIRF) imaging has the potential to improve the SNB procedure by facilitating intraoperative visual identification of the sentinel lymph node (SN). The purpose of this study was to evaluate the feasibility of fluorescence tracer imaging for SN detection in conjunction with conventional radio-guided technique. Prospective study of patients with primary OSCC planned for tumor resection and SNB. Thirty patients were injected peritumorally with a bimodal tracer (ICG-99mTc-Nanocoll) followed by lymphoscintigraphy and SPECT/CT to define the SNs and their anatomic allocation preoperatively. SNs were detected intraoperatively with a hand-held gamma-probe and a hand-held NIRF camera. In 29 of 30 subjects (97%), all preoperatively defined SNs could be identified intraoperatively using a combination of radioactive and fluorescence guidance. A total of 94 SNs (mean 3, range 1-5) that were both radioactive and fluorescent ex vivo were harvested. Eleven of 94 SNs (12%) could only be identified in vivo using NIRF imaging, and the majority of those were located in level 1 close to the primary tumor. A combined fluorescent and radioactive tracer for SNB is feasible, and the additional use of NIRF imaging may improve the accuracy of SN identification in oral cancer patients. Intraoperative fluorescence guidance seems of particular value when SNs are located in close proximity to the injection site.

Pre-operative localization of solitary pulmonary nodules with computed tomography-guided hook wire: report of 181 patients.

PubMed

Hanauer, Matthieu; Perentes, Jean Yannis; Krueger, Thorsten; Ris, Hans-Beat; Bize, Pierre; Schmidt, Sabine; Gonzalez, Michel

2016-01-16

Video-assisted thoracic surgery (VATS) is currently performed to diagnose and treat solitary pulmonary nodules (SPN). However, the intra-operative identification of deep nodules can be challenging with VATS as the lung is difficult to palpate. The aim of the study was to report the utility and the results of pre-operative computed tomography (CT)-guided hook wire localization of SPN. All records of the patients undergoing CT-guided hook wire localization prior to VATS resection for SPN between 2002 and 2013 were reviewed. The efficacy in localizing the nodule, hook wire complications, necessity to convert VATS to thoracotomy and the histology of SPN are reported. One hundred eighty-one patients (90 females, mean age 63 y, range 28-82 y) underwent 187 pulmonary resections after CT-guided hook wire localization. The mean SPN diameter was 10.3 mm (range: 4-29 mm). The mean distance of the lesion from the pleural surface was 11.6 mm (range: 0-45 mm). The mean time interval from hook wire insertion to VATS resection was 224 min (range 54-622 min). Hook wire complications included pneumothorax requiring chest tube drainage in 4 patients (2.1%) and mild parenchymal haemorrhage in 11 (5.9%) patients. Migration of the hook wire occurred in 7 patients (3.7%) although it did not affect the success of VATS resection (nodule location guided by the lung puncture site). Three patients underwent additional wedge resection by VATS during the same procedure because no lesion was identified in the surgical specimen. Conversion thoracotomy was required in 13 patients (7 %) for centrally localized lesions (6 patients) and pleural adhesions (7 patients). The mean operative time was 60 min (range 18-135 min). Pathological examination revealed a malignant lesion in 107 patients (59 %). The diagnostic yield was 98.3 %. VATS resection for SPN after CT-guided hook wire localization for SPN is safe and allows for proper diagnosis with a low thoracotomy conversion rate.

Electromagnetic Navigational Bronchoscopy Reduces the Time Required for Localization and Resection of Lung Nodules.

PubMed

Bolton, William David; Cochran, Thomas; Ben-Or, Sharon; Stephenson, James E; Ellis, William; Hale, Allyson L; Binks, Andrew P

The aims of the study were to evaluate electromagnetic navigational bronchoscopy (ENB) and computed tomography-guided placement as localization techniques for minimally invasive resection of small pulmonary nodules and determine whether electromagnetic navigational bronchoscopy is a safer and more effective method than computed tomography-guided localization. We performed a retrospective review of our thoracic surgery database to identify patients who underwent minimally invasive resection for a pulmonary mass and used either electromagnetic navigational bronchoscopy or computed tomography-guided localization techniques between July 2011 and May 2015. Three hundred eighty-three patients had a minimally invasive resection during our study period, 117 of whom underwent electromagnetic navigational bronchoscopy or computed tomography localization (electromagnetic navigational bronchoscopy = 81; computed tomography = 36). There was no significant difference between computed tomography and electromagnetic navigational bronchoscopy patient groups with regard to age, sex, race, pathology, nodule size, or location. Both computed tomography and electromagnetic navigational bronchoscopy were 100% successful at localizing the mass, and there was no difference in the type of definitive surgical resection (wedge, segmentectomy, or lobectomy) (P = 0.320). Postoperative complications occurred in 36% of all patients, but there were no complications related to the localization procedures. In terms of localization time and surgical time, there was no difference between groups. However, the down/wait time between localization and resection was significant (computed tomography = 189 minutes; electromagnetic navigational bronchoscopy = 27 minutes); this explains why the difference in total time (sum of localization, down, and surgery) was significant (P < 0.001). We found electromagnetic navigational bronchoscopy to be as safe and effective as computed tomography-guided wire placement and to provide a significantly decreased down time between localization and surgical resection.

Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells.

PubMed

Lawrence, Johnathan E; Steele, Christopher J; Rovin, Richard A; Belton, Robert J; Winn, Robert J

2016-03-01

Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma.

PubMed

Belykh, Evgenii; Miller, Eric J; Hu, Danying; Martirosyan, Nikolay L; Woolf, Eric C; Scheck, Adrienne C; Byvaltsev, Vadim A; Nakaji, Peter; Nelson, Leonard Y; Seibel, Eric J; Preul, Mark C

2018-05-01

Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM). 5-Aminolevulinic acid-induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared. SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6×) before tumor-to-background contrast was diminished because of photobleaching. SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Toward image guided robotic surgery: system validation.

PubMed

Herrell, Stanley D; Kwartowitz, David Morgan; Milhoua, Paul M; Galloway, Robert L

2009-02-01

Navigation for current robotic assisted surgical techniques is primarily accomplished through a stereo pair of laparoscopic camera images. These images provide standard optical visualization of the surface but provide no subsurface information. Image guidance methods allow the visualization of subsurface information to determine the current position in relationship to that of tracked tools. A robotic image guided surgical system was designed and implemented based on our previous laboratory studies. A series of experiments using tissue mimicking phantoms with injected target lesions was performed. The surgeon was asked to resect "tumor" tissue with and without the augmentation of image guidance using the da Vinci robotic surgical system. Resections were performed and compared to an ideal resection based on the radius of the tumor measured from preoperative computerized tomography. A quantity called the resection ratio, that is the ratio of resected tissue compared to the ideal resection, was calculated for each of 13 trials and compared. The mean +/- SD resection ratio of procedures augmented with image guidance was smaller than that of procedures without image guidance (3.26 +/- 1.38 vs 9.01 +/- 1.81, p <0.01). Additionally, procedures using image guidance were shorter (average 8 vs 13 minutes). It was demonstrated that there is a benefit from the augmentation of laparoscopic video with updated preoperative images. Incorporating our image guided system into the da Vinci robotic system improved overall tissue resection, as measured by our metric. Adding image guidance to the da Vinci robotic surgery system may result in the potential for improvements such as the decreased removal of benign tissue while maintaining an appropriate surgical margin.

Effectiveness of navigation-guided cyst aspiration before resection of large cystic brain tumors: a proof of concept for more radical surgery.

PubMed

Roh, Tae Hoon; Sung, Kyoung Su; Kang, Seok-Gu; Moon, Ju Hyung; Kim, Eui Hyun; Kim, Sun Ho; Chang, Jong Hee

2017-10-01

Resection of tumors close to the corticospinal tract (CST) carries a high risk of damage to the CST. For cystic tumors, aspirating the cyst before resection may reduce the risk of damage to vital structures. This study evaluated the effectiveness of cyst aspiration, by comparing the results before and after aspiration of diffusion tensor image (DTI) tractography. This study enrolled 23 patients with large cystic brain tumors (>20 cm 3 ) between 2012 and 2016. All underwent magnetic resonance imaging (MRI), including DTI tractography, followed by navigation-guided aspiration of the cyst and subsequent tumor resection via craniotomy. Distances between the tumor margin and CST before and after cyst aspiration, volume reduction, and postoperative outcomes were assessed. Median tumor volume decreased from 88 cm 3 (range, 25-153) to 29 cm 3 (range, 20-80) and distances between tumor margins and the CST increased from 5.7 mm (range, 0.6-22.0) to 14.8 mm (range, 0.6-41.4) after aspiration. Neurological symptoms of patients immediately improved after cyst aspiration. All patients, except for one with a secondary glioblastoma, underwent gross total resection of the tumor. No neurological deterioration was observed after tumor resection. Navigation-guided cyst aspiration followed by resection is a useful and safe procedure for brain tumors with large cystic components. Cyst aspiration resulted in expansion of the compressed brain tissue between the tumor margins and vital structures, making maximal safe resection possible.

A multiplanar complex resection of a low-grade chondrosarcoma of the distal femur guided by K-wires previously inserted under CT-guide: a case report

PubMed Central

2014-01-01

Background In muscular skeletal oncology aiming to achieve wide surgical margin is one of the main factors influencing patient prognosis. In cases where lesions are either meta or epiphyseal, surgery most often compromises joint integrity and stability because muscles, tendons and ligaments are involved in wide resection. When lesions are well circumscribed they can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. We describe a case of low-grade chondrosarcoma of the distal femur where a simple but effective technique was useful to perform complex multiplanar osteotomies. No similar techniques are reported in the literature. Case presentation A 57 year-old Caucasian female was referred to our department for the presence of a distal femur chondrosarcoma. A resection with the presenting technique was scheduled. The first step consists of inserting several K-wires under CT-scan control to delimitate the tumor; the second step consists of tumor removal: in operative theatre, following surgical access, k-wires are used as guide positioning; scalpels are externally placed to k-wires to perform a safe osteotomy. Conclusions Computed assisted resections can be considered the most advantageous method to reach the best surgical outcome; unfortunately navigation systems are only available in specialized centres. The present technique allows for a multiplanar complex resection when navigation systems are not available. This technique can be applied in low-grade tumours where a minimal wide margin can be considered sufficient. PMID:25123066

Utilizing neuronavigation for virtual electrode representation and safe resection following SEEG; a technical report.

PubMed

Brandmeir, Nicholas; Sather, Michael

2018-02-20

One of the most effective treatments for epilepsy is resection, but it remains underutilized. Efforts must be made to increase the ease, safety, and efficacy of epilepsy resection to improve utilization. Studies have shown an improved risk profile of stereoelectroencephalography (SEEG) over subdural grids (SDG) for invasive monitoring. One limitation to increased adoption of SEEG at epilepsy centers is the theoretical difficulty of planning a delayed resection once electrodes are removed. Our objective was to develop and present a technique using readily available neuronavigation technology to guide a cortical, non-lesional epilepsy resection with co-registration of imaging during invasive monitoring to imaging in an explanted patient, allowing for virtual visualization of electrodes. An example case taking advantage of the technique described above as an adjunct for an anatomically guided resection is presented with technical details and images. Intraoperative neuronavigation was successfully used to virtually represent previously removed SEEG electrodes and accuracy could be easily verified by examining scars on the scalp, bone, dura and pia. The simple technique presented can be a useful adjunct to resection following SEEG. This may help increase the adoption of SEEG, even when resection is planned.

Advancing molecular-guided surgery through probe development and testing in a moderate cost evaluation pipeline

NASA Astrophysics Data System (ADS)

Pogue, Brian W.; Paulsen, Keith D.; Hull, Sally M.; Samkoe, Kimberley S.; Gunn, Jason; Hoopes, Jack; Roberts, David W.; Strong, Theresa V.; Draney, Daniel; Feldwisch, Joachim

2015-03-01

Molecular guided oncology surgery has the potential to transform the way decisions about resection are done, and can be critically important in areas such as neurosurgery where the margins of tumor relative to critical normal tissues are not readily apparent from visual or palpable guidance. Yet there are major financial barriers to advancing agents into clinical trials with commercial backing. We observe that development of these agents in the standard biological therapeutic paradigm is not viable, due to the high up front financial investment needed and the limitations in the revenue models of contrast agents for imaging. The hypothesized solution to this problem is to develop small molecular biologicals tagged with an established fluorescent reporter, through the chemical agent approval pathway, targeting a phase 0 trials initially, such that the initial startup phase can be completely funded by a single NIH grant. In this way, fast trials can be completed to de-risk the development pipeline, and advance the idea of fluorescence-guided surgery (FGS) reporters into human testing. As with biological therapies the potential successes of each agent are still moderate, but this process will allow the field to advance in a more stable and productive manner, rather than relying upon isolated molecules developed at high cost and risk. The pathway proposed and tested here uses peptide synthesis of an epidermal growth factor receptor (EGFR)-binding Affibody molecules, uniquely conjugated to IRDye 800CW, developed and tested in academic and industrial laboratories with well-established records for GMP production, fill and finish, toxicity testing, and early phase clinical trials with image guidance.

Awake Craniotomy with Noninvasive Brain Mapping by 3-Tesla Functional Magnetic Resonance Imaging for Excision of Low-grade Glioma: A Case of a Young Patient from Pakistan.

PubMed

Aleem Bhatti, Atta Ul; Jakhrani, Nasir Khan; Parekh, Maria Adnan

2018-01-01

The past few years have seen increasing support for gross total resection in the management of low-grade gliomas (LGGs), with a greater extent of resection correlated with better overall survival, progression-free survival, and time to malignant transformation. There is consistent evidence in literature supporting extent of safe resection as a good prognostic indicator as well as positively affecting seizure control, symptomatic relief in pressure symptoms, and longer progression-free and total survival. The operative goal in most LGG cases is to maximize the extent of resection for these benefits while avoiding postoperative neurologic deficits. Several advanced invasive and noninvasive surgical techniques such as intraoperative magnetic resonance imaging (MRI), fluorescence-guided surgery, intraoperative functional pathway mapping, and neuronavigation have been developed in an attempt to better achieve maximal safe resection. We present a case of LGG in a young patient with a 5-year history of refractory seizures and gradual onset walking difficulty. Serial MRI brain scans revealed a progressive increase in right frontal tumor size with substantial edema and parafalcine herniation. Noninvasive brain mapping by functional MRI (fMRI) and sleep-awake-sleep type of anesthesia with endotracheal tube insertion was utilized during an awake craniotomy. Histopathology confirmed a Grade II oligodendroglioma, and genetic analysis revealed no codeletion at 1p/19q. Neurological improvement was remarkable in terms of immediate motor improvement, and the patient remained completely seizure free on a single antiepileptic drug. There is no radiologic or clinical evidence of recurrence 6 months postoperatively. This is the first published report of an awake craniotomy for LGG in Pakistan. The contemporary concept of supratotal resection in LGGs advocates generous functional resection even beyond MRI findings rather than mere excision of oncological boundaries. This relatively aggressive approach is only possible with an awake craniotomy, which ensures preservation of functional status and thus less postoperative morbidity and better outcomes. Noninvasive mapping for intracranial space-occupying lesions, including fMRI and blood-oxygen-level dependent (BOLD) imaging modality, is an essential tool in a resource-limited setting such as Pakistan.

Intraoperative MRI-guided resection of focal cortical dysplasia in pediatric patients: technique and outcomes.

PubMed

Sacino, Matthew F; Ho, Cheng-Ying; Murnick, Jonathan; Tsuchida, Tammy; Magge, Suresh N; Keating, Robert F; Gaillard, William D; Oluigbo, Chima O

2016-06-01

OBJECTIVE Previous meta-analysis has demonstrated that the most important factor in seizure freedom following surgery for focal cortical dysplasia (FCD) is completeness of resection. However, intraoperative detection of epileptogenic dysplastic cortical tissue remains a challenge, potentially leading to a partial resection and the need for reoperation. The objective of this study was to determine the role of intraoperative MRI (iMRI) in the intraoperative detection and localization of FCD as well as its impact on surgical decision making, completeness of resection, and seizure control outcomes. METHODS The authors retrospectively reviewed the medical records of pediatric patients who underwent iMRI-assisted resection of FCD at the Children's National Health System between January 2014 and April 2015. Data reviewed included demographics, length of surgery, details of iMRI acquisition, postoperative seizure freedom, and complications. Postsurgical seizure outcome was assessed utilizing the Engel Epilepsy Surgery Outcome Scale. RESULTS Twelve consecutive pediatric patients (8 females and 4 males) underwent iMRI-guided resection of FCD lesions. The mean age at the time of surgery was 8.8 years ± 1.6 years (range 0.7 to 18.8 years), and the mean duration of follow up was 3.5 months ± 1.0 month. The mean age at seizure onset was 2.8 years ± 1.0 year (range birth to 9.0 years). Two patients had Type 1 FCD, 5 patients had Type 2A FCD, 2 patients had Type 2B FCD, and 3 patients had FCD of undetermined classification. iMRI findings impacted intraoperative surgical decision making in 5 (42%) of the 12 patients, who then underwent further exploration of the resection cavity. At the time of the last postoperative follow-up, 11 (92%) of the 12 patients were seizure free (Engel Class I). No patients underwent reoperation following iMRI-guided surgery. CONCLUSIONS iMRI-guided resection of FCD in pediatric patients precluded the need for repeat surgery. Furthermore, it resulted in the achievement of complete resection in all the patients, leading to a high rate of postoperative seizure freedom.

Accidental entrapment of an endo-bronchial blocker tip by a surgical stapler during selective ventilation for lung lobectomy in a dog.

PubMed

Levionnois, Olivier L; Bergadano, Alessandra; Schatzmann, Urs

2006-01-01

To describe the use of an endobronchial blocker (EBB) and to perform selective ventilation during pulmonary lobe resection via thoracotomy in a dog and report its accidental stapling in the resection site. Clinical case report. One female dog with a suspected abscess or neoplasia of the right caudal pulmonary lobe. One-lung ventilation was performed using a wire-guided EBB to seal the contaminated parenchyma and facilitate surgical access. The affected lung parenchyma was resected and the resection site was closed with staples. Lobar resection was performed successfully, but the loop of the EBB guide wire was inadvertently entrapped in the staple line of the lobectomy. Staples were removed to release the wire loop, and the resulting air leak caused loss of ventilation control until the parenchyma was re-sealed. We recommend removing the wire guide associate with the EBB after successful lung separation to avoid accidents that could have life-threatening consequences if not recognized. One-lung ventilation is useful to isolate healthy parenchyma from diseased parenchyma during lobectomy. Anesthesiologists and surgeons need to be aware of the potential complications associated with use of EBB.

A pilot cost-effectiveness analysis of treatments in newly diagnosed high-grade gliomas: the example of 5-aminolevulinic Acid compared with white-light surgery.

PubMed

Esteves, Susana; Alves, Marta; Castel-Branco, Marta; Stummer, Walter

2015-05-01

High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratios are below &OV0556;10 000 in all evaluated outcomes, being around &OV0556;9100 per quality-adjusted life-year gained, &OV0556;6700 per life-year gained, and &OV0556;8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of &OV0556;20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data.

Gadolinium and 5-Aminolevulinic Acid-induced Protoporphyrin IX Levels in Human Gliomas: An Ex Vivo Quantitative Study to Correlate Protoporphyrin IX Levels and Blood-Brain Barrier Breakdown

PubMed Central

Valdés, Pablo A.; Moses, Ziev B.; Kim, Anthony; Belden, Clifford J.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2012-01-01

In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence guidance has been used as a surgical adjunct to improve the extent of resection of gliomas. Exogenous administration of ALA prior to surgery leads to the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can visualize and thereby discriminate between normal and tumor tissue. Selective accumulation of PpIX has been linked to numerous factors, of which blood-brain barrier (BBB) breakdown has been suggested to be a key factor. To test the hypothesis that PpIX concentration (CPpIX) positively correlates with gadolinium (Gd) concentrations (CGd), we performed ex vivo measurements of PpIX and of Gd using Inductively-Coupled Plasma Mass Spectrometry (ICP-MS) the latter as a quantitative biomarker of BBB breakdown; this was corroborated with immunohistochemistry of microvascular density in surgical biopsies of patients undergoing fluorescence guided surgery for glioma .We found positive correlations between CPpIX and CGd (r = 0.58, p < 0.0001), and between CPpIX and microvascular density (r = 0.55, p < 0.0001), suggesting a significant, yet limited association between BBB breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first time that Gd measurements by ICP-MS have been used in human gliomas. PMID:22878664

Fluorescence endoscopic imaging study of anastomotic recurrence of Crohn's disease after right ileocolonic resection

NASA Astrophysics Data System (ADS)

Mordon, Serge R.; Maunoury, Vincent; Klein, Olivier; Colombel, Jean-Frederic

1995-12-01

Crohn's disease is an inflammatory bowel disease of unknown etiology. Vasculitis is hypothesized but it was never demonstrated in vivo. This study aimed to evaluate the vascular mucosa perfusion using fluorescence imaging in 13 patients who had previously undergone eileocolonic resection and who agreed to participate in a prospective endoscopic study of anastomotic recurrence. This anastomotic recurrence rate is known to be high (73% after 1 year follow-up) and is characterized by ulcerations. The fluorescence study was started with an I.V. bolus injection of sodium fluorescein. The pre-anastomotic mucosa was endoscopically examined with blue light that stimulates fluorescein fluorescence. Fluorescence emission was recorded with an ultra-high-sensitivity camera connected to the endoscope via an interference filter (520 - 560 nm). A uniform fluorescence was observed a few seconds after the injection and lasted for 15 min in healthy subjects. In case of recurrence, the centers of the ulcerations displayed a very low fluorescence indicating localized ischemia. In contrast, the rims of the ulcers revealed brighter fluorescent images than those of normal mucosa. The anastomotic ulcerations of Crohn's disease recurrence exhibit a high fluorescence intensity at their margins indicating an increased mucosal blood flow and/or enhanced transcapillary diffusion. These findings support the hypothesis of a primary vasculitis in Crohn's disease.

Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology.

PubMed

Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

2014-01-01

Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.

Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology

PubMed Central

Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

2014-01-01

Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery. PMID:25250092

Navigated total knee arthroplasty: is it error-free?

PubMed

Chua, Kerk Hsiang Zackary; Chen, Yongsheng; Lingaraj, Krishna

2014-03-01

The aim of this study was to determine whether errors do occur in navigated total knee arthroplasty (TKAs) and to study whether errors in bone resection or implantation contribute to these errors. A series of 20 TKAs was studied using computer navigation. The coronal and sagittal alignments of the femoral and tibial cutting guides, the coronal and sagittal alignments of the final tibial implant and the coronal alignment of the final femoral implant were compared with that of the respective bone resections. To determine the post-implantation mechanical alignment of the limb, the coronal alignment of the femoral and tibial implants was combined. The median deviation between the femoral cutting guide and bone resection was 0° (range -0.5° to +0.5°) in the coronal plane and 1.0° (range -2.0° to +1.0°) in the sagittal plane. The median deviation between the tibial cutting guide and bone resection was 0.5° (range -1.0° to +1.5°) in the coronal plane and 1.0° (range -1.0° to +3.5°) in the sagittal plane. The median deviation between the femoral bone resection and the final implant was 0.25° (range -2.0° to 3.0°) in the coronal plane. The median deviation between the tibial bone resection and the final implant was 0.75° (range -3.0° to +1.5°) in the coronal plane and 1.75° (range -4.0° to +2.0°) in the sagittal plane. The median post-implantation mechanical alignment of the limb was 0.25° (range -3.0° to +2.0°). When navigation is used only to guide the positioning of the cutting jig, errors may arise in the manual, non-navigated steps of the procedure. Our study showed increased cutting errors in the sagittal plane for both the femur and the tibia, and following implantation, the greatest error was seen in the sagittal alignment of the tibial component. Computer navigation should be used not only to guide the positioning of the cutting jig, but also to check the bone resection and implant position during TKA. IV.

Simple Improvisation to Enhance Utility of Fluorescein Sodium in Resection of Intracranial Lesions at Routine Neurosurgical Centers.

PubMed

Gollapudi, Prakash Rao; Mohammed, Imran; Pittala, Sandeep R; Kotha, Arjun Reddy; Reddycherla, Naga Raju; Ginjupally, Dhanunjaya Rao

2018-04-01

Fluorescein sodium is one of the fluorophores that is used in the resection of intracranial lesions. It is commonly used along with a customized microscope, which is expensive and not available universally. In this study, we describe a simple, inexpensive method for better visualization of intracranial and spinal cord lesions with fluorescein. After a test dose, 20 mg/kg of fluorescein sodium was administered intravenously at the time of intubation. A blue light source was used before resection for precise localization of the intracranial lesions after durotomy. Most of the resection was done under the white light, while the blue light was used intermittently to delineate the pathologic tissue from the normal tissue and to ensure safe maximal resection. The intensity of fluorescein staining under white light and blue light was noted. The study comprised 40 cases of gliomas, meningiomas, abscesses, spinal cord tumors, and cerebellopontine angle lesions. Thirty-five lesions showed good fluorescence under the blue light, which helped us achieve better resection of the pathologic lesions. Fluorescein sodium is a safe dye; it can be used to aid in precise localization and safe maximal resection of the pathologic tissue with the help of a blue light source at any center with challenged resources. The blue light enhances the fluorescence and visualization of the pathologic tissue, and this technique can be adopted by any surgeon without much difficulty even with a basic neurosurgical setup. Copyright © 2018 Elsevier Inc. All rights reserved.

Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience

PubMed Central

Verbeek, Floris P.R.; Troyan, Susan L.; Mieog, J. Sven D.; Liefers, Gerrit-Jan; Moffitt, Lorissa A.; Rosenberg, Mireille; Hirshfield-Bartek, Judith; Gioux, Sylvain; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.; Frangioni, John V.

2014-01-01

NIR fluorescence imaging using indocyanine green (ICG) has the potential to improve the SLN procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 ml of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of near-infrared (NIR) fluorescence for sentinel lymph node (SLN) mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using 99Technetium-colloid in all subjects and patent blue in 27 (28%) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99%) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean = 1.9, range = 1–5) were resected: 100% NIR fluorescent, 88% radioactive, and 78% (of 40 nodes) blue. In 2 of 95 subjects (2.1%), SLNs containing macrometastases were found only by NIR fluorescence, and in 1 patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies. PMID:24337507

Photodynamic therapy: a review of applications in neurooncology and neuropathology

NASA Astrophysics Data System (ADS)

Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

2015-06-01

Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

ALA-mediated fluorescence-guided resection (FGR) and PDT of glioma

NASA Astrophysics Data System (ADS)

Johansson, Ann; Stepp, Herbert; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Meinel, Thomas; Stummer, Walter; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian; Baumgartner, Reinhold

2009-06-01

A summary of clinical trials employing photodynamic diagnosis (PDD) and photodynamic therapy (PDT) for the diagnosis and treatment of brain malignancies is presented. Intra-cavity PDT has been performed within the surgical cavity following FGR, employing oral administration of 5-aminolevulinic acid (5-ALA), either targeting fluorescing tissue regions that were not removed during FGR due to safety reasons (referred to as focal PDT, n=20) or illuminating the entire resection cavity (referred to as integral PDT, n=9). Both approaches proved technically feasible and safe. Spectroscopic measurements performed pre-, during and post-PDT revealed Protoporphyrin IX (PpIX)-photobleaching of more than 95% after the delivery of 200 J/cm2. This light dose did not induce any side effects. Furthermore, interstitial PDT (iPDT) has been employed within one feasibility trial (n=10) and one Phase I/II trial (n=15). Here, three to six cylindrical light diffusors (20-30 mm length, 200 mW/cm, 720 J/cm) were positioned within the target tissue under stereotactic guidance. Pre-treatment planning was performed with the intent to target the entire tumour volume with a sufficient light dose while also minimising the risk of any light-induced temperature increase. For the feasibility trial patients with small, recurrent gliomas were included, resulting in a median survival of 15 months as well as some unexpected longterm survivals (up to 5 years). The Phase I/II trial employed the same clinical procedures. Here, the 12-month survival was 35% and the median progression-free survival was 6 months. In summary, stereotactic iPDT in combination with treatment-planning could be shown to be a safe and feasible treatment modality. These trials are presently being extended to also include on-line monitoring of PpIX fluorescence and photobleaching kinetics. Preliminary data has revealed dramatically different PpIX levels and photobleaching kinetics. Such data could possibly be employed for realtime treatment monitoring and as an early prognostic marker for the PDT response.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

PubMed Central

Lee, John Y-K.; Thawani, Jayesh P.; Pierce, John; Zeh, Ryan; Martinez-Lage, Maria; Chanin, Michelle; Venegas, Ollin; Nims, Sarah; Learned, Kim; Keating, Jane; Singhal, Sunil

2016-01-01

Background Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. Objective To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Methods Fifteen patients were identified and administered an FDA-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) prior to surgical resection. An NIR camera was utilized to localize the tumor prior to resection and to visualize surgical margins following resection. Neuropathology and MR imaging data were used to assess the accuracy and precision of NIR-fluorescence in identifying tumor tissue. Results NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12/15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with SBR (P = .03). Non-enhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). Conclusion Using Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. PMID:27741220

Intestinal blood flow assessment by indocyanine green fluorescence imaging in a patient with the incarcerated umbilical hernia: Report of a case.

PubMed

Ryu, Shunjin; Yoshida, Masashi; Ohdaira, Hironori; Tsutsui, Nobuhiro; Suzuki, Norihiko; Ito, Eisaku; Nakajima, Keigo; Yanagisawa, Satoru; Kitajima, Masaki; Suzuki, Yutaka

2016-06-01

After reduction of the incarceration during surgery for incarcerated hernia, intestinal blood flow (IBF) and the need for bowel resection must be evaluated. We report the case of a patient with incarcerated umbilical hernia in whom the bowel was preserved after evaluating IBF using indocyanine green (ICG) fluorescence. A woman in her 40s with a chief complaint of abdominal pain visited our hospital, was diagnosed with incarcerated umbilical hernia and underwent surgery. Laparotomy was performed to reduce bowel incarceration. After reducing the incarceration, IBF was observed using ICG fluorescence detected using a brightfield full-color fluorescence camera. The small bowel that had been incarcerated showed deep-red discoloration on gross evaluation, but intravenous injection of ICG revealed uniform fluorescence of the mesentery and bowel wall. This indicated an absence of irreversible ischemic changes of the bowel, so no resection was performed. The patient showed a good postoperative course, including resumption of eating on day 4 and discharge on day 11. In surgery for incarcerated hernia, ICG fluorescence may offer a useful method to evaluate IBF after reducing the incarceration. This case implied that PINPOINT could be used in open conventional surgery.

Should spikes on post-resection ECoG guide pediatric epilepsy surgery?

PubMed

Greiner, Hansel M; Horn, Paul S; Tenney, Jeffrey R; Arya, Ravindra; Jain, Sejal V; Holland, Katherine D; Leach, James L; Miles, Lili; Rose, Douglas F; Fujiwara, Hisako; Mangano, Francesco T

2016-05-01

There is wide variation in clinical practice regarding the role of electrocorticography immediately after resection (post-resection ECoG) for pediatric epilepsy surgery. Results can guide further resection of potentially epileptogenic tissue. We hypothesized that post-resection ECoG spiking represents a biomarker of the epileptogenic zone and predicts seizure outcome in children undergoing epilepsy surgery. We retrospectively identified 124 children with post-resection ECoG performed on the margins of resection. ECoG records were scored in a blinded fashion based on presence of frequent spiking. For patients identified as having additional resection based on clinical post-resection ECoG interpretation, these "second-look" ECoG results were re-reviewed for ongoing discharges or completeness of resection. Frequent spike populations were grouped using a standard scoring system into three ranges: 0.1-0.5Hz, 0.5-1Hz, >1Hz. Seizure outcomes were determined at minimum 12-month followup. Of 124 patients who met inclusion criteria, 60 (48%) had an identified spike population on post-resection ECoG. Thirty (50%) of these had further resection based on clinical interpretation. Overall, good outcome (ILAE 1) was seen in 56/124 (45%). Completeness of resection of spiking (absence of spiking on initial post-resection ECoG or resolution of spiking after further resection) showed a trend toward good outcome (OR 2.03, p=0.099). Patients with completeness of resection had good outcome in 41/80 (51%) of cases; patients with continued spikes had good outcome in 15/44 (35%) of cases. Post-resection ECoG identifies residual epileptogenic tissue in a significant number of children. Lower frequency or absence of discharges on initial recording showed a trend toward good outcome. Completeness of resection demonstrated on final ECoG recording did not show a significant difference in outcome. This suggests that post-resection discharges represent a prognostic marker rather than a remediable biomarker of the epileptogenic zone in all patients. Resecting residual spike-generating cortex may be beneficial in selected patients, including children with tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluorescence-guided surgery for cancer patients: a proof of concept study on human xenografts in mice and spontaneous tumors in pets

PubMed Central

Mery, Eliane; Golzio, Muriel; Guillermet, Stephanie; Lanore, Didier; Naour, Augustin Le; Thibault, Benoît; Tilkin-Mariamé, Anne Françoise; Bellard, Elizabeth; Delord, Jean Pierre; Querleu, Denis; Ferron, Gwenael; Couderc, Bettina

2017-01-01

Surgery is often the first treatment option for patients with cancer. Patient survival essentially depends on the completeness of tumor resection. This is a major challenge, particularly in cases of peritoneal carcinomatosis, where tumors are widely disseminated in the large peritoneal cavity. Any development to help surgeons visualize these residual cells would improve the completeness of the surgery. For non-disseminated tumors, imaging could be used to ensure that the tumor margins and the draining lymph nodes are free of tumor deposits. Near-infrared fluorescence imaging has been shown to be one of the most convenient imaging modalities. Our aim was to evaluate the efficacy of a near-infrared fluorescent probe targeting the αvβ3 integrins (Angiostamp™) for intraoperative detection of tumors using the Fluobeam® device. We determined whether different human tumor nodules from various origins could be detected in xenograft mouse models using both cancer cell lines and patient-derived tumor cells. We found that xenografts could be imaged by fluorescent staining irrespective of their integrin expression levels. This suggests imaging of the associated angiogenesis of the tumor and a broader potential utilization of Angiostamp™. We therefore performed a veterinary clinical trial in cats and dogs with local tumors or with spontaneous disseminated peritoneal carcinomatosis. Our results demonstrate that the probe can specifically visualize both breast and ovarian nodules, and suggest that Angiostamp™ is a powerful fluorescent contrast agent that could be used in both human and veterinary clinical trials for intraoperative detection of tumors. PMID:29312629

Thick tissue diffusion model with binding to optimize topical staining in fluorescence breast cancer margin imaging

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Kang, Soyoung; Navarro-Comes, Eric; Wang, Yu; Liu, Jonathan T. C.; Tichauer, Kenneth M.

2018-03-01

Intraoperative tumor/surgical margin assessment is required to achieve higher tumor resection rate in breast-conserving surgery. Though current histology provides incomparable accuracy in margin assessment, thin tissue sectioning and the limited field of view of microscopy makes histology too time-consuming for intraoperative applications. If thick tissue, wide-field imaging can provide an acceptable assessment of tumor cells at the surface of resected tissues, an intraoperative protocol can be developed to guide the surgery and provide immediate feedback for surgeons. Topical staining of margins with cancer-targeted molecular imaging agents has the potential to provide the sensitivity needed to see microscopic cancer on a wide-field image; however, diffusion and nonspecific retention of imaging agents in thick tissue can significantly diminish tumor contrast with conventional methods. Here, we present a mathematical model to accurately simulate nonspecific retention, binding, and diffusion of imaging agents in thick tissue topical staining to guide and optimize future thick tissue staining and imaging protocol. In order to verify the accuracy and applicability of the model, diffusion profiles of cancer targeted and untargeted (control) nanoparticles at different staining times in A431 tumor xenografts were acquired for model comparison and tuning. The initial findings suggest the existence of nonspecific retention in the tissue, especially at the tissue surface. The simulator can be used to compare the effect of nonspecific retention, receptor binding and diffusion under various conditions (tissue type, imaging agent) and provides optimal staining and imaging protocols for targeted and control imaging agent.

Benchtop and Animal Validation of a Projective Imaging System for Potential Use in Intraoperative Surgical Guidance

PubMed Central

Gan, Qi; Wang, Dong; Ye, Jian; Zhang, Zeshu; Wang, Xinrui; Hu, Chuanzhen; Shao, Pengfei; Xu, Ronald X.

2016-01-01

We propose a projective navigation system for fluorescence imaging and image display in a natural mode of visual perception. The system consists of an excitation light source, a monochromatic charge coupled device (CCD) camera, a host computer, a projector, a proximity sensor and a Complementary metal–oxide–semiconductor (CMOS) camera. With perspective transformation and calibration, our surgical navigation system is able to achieve an overall imaging speed higher than 60 frames per second, with a latency of 330 ms, a spatial sensitivity better than 0.5 mm in both vertical and horizontal directions, and a projection bias less than 1 mm. The technical feasibility of image-guided surgery is demonstrated in both agar-agar gel phantoms and an ex vivo chicken breast model embedding Indocyanine Green (ICG). The biological utility of the system is demonstrated in vivo in a classic model of ICG hepatic metabolism. Our benchtop, ex vivo and in vivo experiments demonstrate the clinical potential for intraoperative delineation of disease margin and image-guided resection surgery. PMID:27391764

Portal vein territory identification using indocyanine green fluorescence imaging: Technical details and short-term outcomes.

PubMed

Kobayashi, Yuta; Kawaguchi, Yoshikuni; Kobayashi, Kosuke; Mori, Kazuhiro; Arita, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

2017-12-01

Portal vein (PV) territory identification during liver resection may be performed using indocyanine green (ICG) fluorescence imaging technique. However, the technical details of the fluorescence staining technique have not been fully elucidated. This study was performed to demonstrate the technical details of PV territory identification using fluorescence imaging and evaluates the short-term outcomes. From 2011 to 2015, 105 underwent liver resection at the University of Tokyo Hospital with one of the following fluorescence staining techniques by transhepatic PV injection or intravenous injection of ICG: single staining (n = 36), multiple staining (n = 31), counterstaining (n = 22), negative staining (n = 13), or paradoxical negative staining (n = 3). The PV territory was identified as a region with fluorescence or a defect of fluorescence using one of the five staining techniques. ICG was administered by transhepatic PV injection in all but the negative staining technique, which employed intravenous injection. No adverse events associated with the ICG administration occurred. The mortality, postoperative total morbidity, and the major complication (Clavien-Dindo grade ≥III) rates were 0.0%, 14.3%, and 7.6%. We have demonstrated the technical details of five types of fluorescence staining techniques. These techniques are safe to perform and facilitate clear visualization of the PV territory in real time, enhancing the efficacy of anatomical removal of such territories. © 2017 Wiley Periodicals, Inc.

Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma.

PubMed

Ishizawa, Takeaki; Masuda, Koichi; Urano, Yasuteru; Kawaguchi, Yoshikuni; Satou, Shouichi; Kaneko, Junichi; Hasegawa, Kiyoshi; Shibahara, Junji; Fukayama, Masashi; Tsuji, Shingo; Midorikawa, Yutaka; Aburatani, Hiroyuki; Kokudo, Norihiro

2014-02-01

Although clinical applications of intraoperative fluorescence imaging of liver cancer using indocyanine green (ICG) have begun, the mechanistic background of ICG accumulation in the cancerous tissues remains unclear. In 170 patients with hepatocellular carcinoma cells (HCC), the liver surfaces and resected specimens were intraoperatively examined by using a near-infrared fluorescence imaging system after preoperative administration of ICG (0.5 mg/kg i.v.). Microscopic examinations, gene expression profile analysis, and immunohistochemical staining were performed for HCCs, which showed ICG fluorescence in the cancerous tissues (cancerous-type fluorescence), and HCCs showed fluorescence only in the surrounding non-cancerous liver parenchyma (rim-type fluorescence). ICG fluorescence imaging enabled identification of 273 of 276 (99%) HCCs in the resected specimens. HCCs showed that cancerous-type fluorescence was associated with higher cancer cell differentiation as compared with rim-type HCCs (P < 0.001). Fluorescence microscopy identified the presence of ICG in the canalicular side of the cancer cell cytoplasm, and pseudoglands of the HCCs showed a cancerous-type fluorescence pattern. The ratio of the gene and protein expression levels in the cancerous to non-cancerous tissues for Na(+)/taurocholate cotransporting polypeptide (NTCP) and organic anion-transporting polypeptide 8 (OATP8), which are associated with portal uptake of ICG by hepatocytes that tended to be higher in the HCCs that showed cancerous-type fluorescence than in those that showed rim-type fluorescence. Preserved portal uptake of ICG in differentiated HCC cells by NTCP and OATP8 with concomitant biliary excretion disorders causes accumulation of ICG in the cancerous tissues after preoperative intravenous administration. This enables highly sensitive identification of HCC by intraoperative ICG fluorescence imaging.

Toward integrated image guided liver surgery

NASA Astrophysics Data System (ADS)

Jarnagin, W. R.; Simpson, Amber L.; Miga, M. I.

2017-03-01

While clinical neurosurgery has benefited from the advent of frameless image guidance for over three decades, the translation of image guided technologies to abdominal surgery, and more specifically liver resection, has been far more limited. Fundamentally, the workflow, complexity, and presentation have confounded development. With the first real efforts in translation beginning at the turn of the millennia, the work in developing novel augmented technologies to enhance screening, planning, and surgery has come to realization for the field. In this paper, we will review several examples from our own work that demonstrate the impact of image-guided procedure methods in eight clinical studies that speak to: (1) the accuracy in planning for liver resection, (2) enhanced surgical planning with portal vein embolization impact, (3) linking splenic volume changes to post-hepatectomy complications, (4) enhanced intraoperative localization in surgically occult lesions, (5) validation of deformation correction, and a (6) a novel blinded study focused at the value of deformation correction. All six of these studies were achieved in human systems and show the potential impact image guided methodologies could make on liver tissue resection procedures.

[The application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional areas].

PubMed

Ren, X H; Yang, X C; Huang, W; Yang, K Y; Liu, L; Qiao, H; Guo, L J; Cui, Y; Lin, S

2018-03-06

Objective: This study aimed to analyze the application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional area, and to illustrate the minimal safe threshold by ROC method. Methods: Fifty-seven patients with gliomas in the functional areas were enrolled in the study at Beijing Tiantan Hospital from 2015 to 2017. Anesthesia was maintained intravenously with propofol 10% and remifentanil. Throughout the resection process, cortical or subcortical stimulation threshold was determined along tumor border using monopolar or bipolar electrodes. The motor pathway was identified and protected from resection according to the stimulation threshold and transcranial MEPs. Minimal threshold in each case was recorded. Results: Total resection was achieved in 32 cases(56.1%), sub-total resection in 22 cases(38.6%), and partial resection in 3 cases(5.3%). Pre-operative motor disability was found in 9 cases. Compared with pre-operative motor scores, 19 exhibited impaired motor functions on day 1 after surgery, 5 had quick recovery by day 7 after surgery, and 7 had late recovery by 3 months after surgery. At 3 months, 7 still had impaired motor function. The frequency of intraoperative seizure was 1.8%(1/57). No other side effect was found during electronic monitoring in the operation. The ROC curve revealed that the minimal safe monopolar subcortical threshold was 5.70 mA for strength deterioration on day 1 and day 7 after surgery. Univariate analysis revealed that decreased transcranial MEPs and minimal subcortical threshold ≤5.7 mA were correlated with postoperative strength deterioration. Conclusions: Cortical and subcortical stimulation threshold has its merit in identifying the motor pathway and guiding the resection for tumors within the functional areas. 5.7 mA can be used as the minimal safe threshold to protect the motor pathway from injury.

Comparison of auto-fluorescence and tetracycline fluorescence for guided bone surgery of medication-related osteonecrosis of the jaw: a randomized controlled feasibility study.

PubMed

Ristow, O; Otto, S; Geiß, C; Kehl, V; Berger, M; Troeltzsch, M; Koerdt, S; Hohlweg-Majert, B; Freudlsperger, C; Pautke, C

2017-02-01

Recent studies have indicated that bone shows auto-fluorescence under an appropriate fluorescence lamp. The aim of this preliminary study was to compare the success rates of the established tetracycline fluorescence-guided bone surgery with auto-fluorescence-guided bone surgery in the treatment of medication-related osteonecrosis of the jaw (MRONJ). Forty patients suffering from MRONJ were referred for surgical treatment and were divided randomly into two groups: auto-fluorescence (n=20) or tetracycline fluorescence (n=20) guided bone surgery. The primary endpoint was treatment success, defined as the absence of exposed bone at 8 weeks after surgery. Secondary outcomes assessed were mucosal integrity, signs of infection, pain, and loss of sensitivity; these were evaluated descriptively at 10 days, 8 weeks, 6 months, and 1 year after surgery. At 8 weeks postoperative, 18/20 patients (90%) in the auto-fluorescence group and 17/20 patients (85%) in the tetracycline fluorescence group showed mucosal integrity (P>0.05). At the last follow-up, 94% in the auto-fluorescence group and 89% in the tetracycline fluorescence group presented complete mucosal coverage with no exposed bone, infection, or pain (P>0.05). There was no significant difference between the two techniques for any of the secondary outcomes (P>0.05). The results of this preliminary study show that auto-fluorescence-guided bone surgery has comparable success rates to the established tetracycline fluorescence-guided bone surgery. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Purposeful creation of a pneumothorax and chest tube placement to facilitate CT-guided coil localization of lung nodules before video-assisted thoracoscopic surgical wedge resection.

PubMed

Iqbal, Shams I; Molgaard, Christopher; Williamson, Christina; Flacke, Sebastian

2014-07-01

To evaluate the feasibility and efficacy of pneumothorax creation and chest tube insertion before computed tomography (CT)-guided coil localization of small peripheral lung nodules for video-assisted thoracoscopic surgical (VATS) wedge resection. From May 2011 to October 2013, 21 consecutive patients (seven men; mean age, 62 y; range, 42-76 y) scheduled for VATS wedge resection required CT-guided coil localization for small, likely nonpalpable peripheral lung lesions at a single institution. Outcomes were evaluated retrospectively for technical success and complications. There were 12 nodules and nine ground-glass opacities. Mean lesion distance from the pleural surface was 15 mm (range, 5-35 mm), and average size was 13 mm (range, 7-30 mm). A pneumothorax was successfully created in all patients with a Veress needle, and a chest tube was inserted. All target lesions were marked successfully, leaving one end of the coil within/beyond the lesion and the other end of the coil in the pleural space. The inserted chest tube was used to insufflate air to widen the pleural space during coil positioning and to aspirate any residual air before transfer of the patient to the operating room holding area. Intraparenchymal hemorrhages smaller than 7 cm in diameter developed in two patients during coil placement. All lesions were successfully resected with VATS. Histologic examinaiton revealed 13 primary adenocarcinomas, four metastases, and four benign lesions. Pneumothorax creation and chest tube placement before CT-guided coil localization of peripheral lung nodules for VATS wedge resection facilitates the deployment of the peripheral end of the coil in the pleural space and provides effective management of procedure-related pneumothorax until surgery. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Safety and Tumor-specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer

PubMed Central

Rosenthal, Eben L; Warram, Jason M; de Boer, Esther; Chung, Thomas K; Korb, Melissa L; Brandwein-Gensler, Margie; Strong, Theresa V; Schmalbach, Cecelia E; Morlandt, Anthony B; Agarwal, Garima; Hartman, Yolanda E; Carroll, William R; Richman, Joshua S; Clemons, Lisa K; Nabell, Lisle M; Zinn, Kurt R

2016-01-01

Purpose Positive margins dominate clinical outcomes after surgical resections in most solid cancer types including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that epidermal growth factor receptor (EGFR) can be targeted for safe and specific real-time localization of cancer. Experimental design A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n=12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days post-infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology. Results There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathological analysis of tissues ex-vivo. Fluorescence levels positively correlated with EGFR levels. Conclusion We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology. PMID:25904751

Laser-induced fluorescence in the detection of esophageal carcinoma

NASA Astrophysics Data System (ADS)

Wang, Kenneth K.; Gutta, Kumar; Laukka, Mark A.; Densmore, John

1995-01-01

Laser induced fluorescence (LIF) is a technique which can perform an 'optical biopsy' of gastrointestinal mucosa. LIF was performed in resected specimens using a pulsed N2-laser coupled fiberoptically to a probe. Fluorescence was measured using a 0.2 meter spectroscope with an intensified photodiode array. Measurements were made on fresh (<30 minutes after resection) esophageal specimens containing normal mucosa, Barrett's esophagus, and adenocarcinoma. Each tissue section was examined using an optical probe consisting of a central fiber for delivering the excitation energy and a 6 fiber bundle surrounding the central fiber for detection of the fluorescence. An excitation wavelength of 337 nm was used which generated 3-ns pulses while fluorescence intensities were acquired from 300-800 nm. Spectra were obtained from each section in a standardized fashion and background spectra subtracted. Fluorescence readings were taken from 54 normal esophageal sections and 32 sections of adenocarcinoma. A fluorescence index obtained from the tumor sections was 0.68+/- 0.01 compared with 0.51+/- 0.01 for the normal sections (p<0.001). Using a discriminant value of 0.65, this technique had a sensitivity of 81% and a specificity of 100% for detection of malignant tissue. The positive predictive value was 100% and the negative predictive value was 90% for an overall accuracy of 93%. LIF is a promising technique which has the capability of distinguishing normal versus malignant tissue in the esophagus with good accuracy.

The use of fluorescein sodium in the biopsy and gross-total resection of a tectal plate glioma.

PubMed

Ung, Timothy H; Kellner, Christopher; Neira, Justin A; Wang, Shih-Hsiu J; D'Amico, Randy; Faust, Phyllis L; Canoll, Peter; Feldstein, Neil A; Bruce, Jeffrey N

2015-12-01

Intravenous administration of fluorescein sodium fluoresces glioma burden tissue and can be visualized using the surgical microscope with a specialized filter. Intraoperative guidance afforded through the use of fluorescein may enhance the fidelity of tissue sampling, and increase the ability to accomplish complete resection of tectal lesions. In this report the authors present the case of a 19-year-old man with a tectal anaplastic pilocytic astrocytoma in which the use of fluorescein sodium and a Zeiss Pentero surgical microscope equipped with a yellow 560 filter enabled safe complete resection. In conjunction with neurosurgical navigation, added intraoperative guidance provided by fluorescein may be beneficial in the resection of brainstem gliomas.

Near-infrared intraoperative imaging during resection of an anterior mediastinal soft tissue sarcoma.

PubMed

Predina, Jarrod D; Newton, Andrew D; Desphande, Charuhas; Singhal, Sunil

2018-01-01

Sarcomas are rare malignancies that are generally treated with multimodal therapy protocols incorporating complete local resection, chemotherapy and radiation. Unfortunately, even with this aggressive approach, local recurrences are common. Near-infrared intraoperative imaging is a novel technology that provides real-time visual feedback that can improve identification of disease during resection. The presented study describes utilization of a near-infrared agent (indocyanine green) during resection of an anterior mediastinal sarcoma. Real-time fluorescent feedback provided visual information that helped the surgeon during tumor localization, margin assessment and dissection from mediastinal structures. This rapidly evolving technology may prove useful in patients with primary sarcomas arising from other locations or with other mediastinal neoplasms.

Pleural Dye Marking Using Radial Endobronchial Ultrasound and Virtual Bronchoscopy before Sublobar Pulmonary Resection for Small Peripheral Nodules.

PubMed

Lachkar, Samy; Baste, Jean-Marc; Thiberville, Luc; Peillon, Christophe; Rinieri, Philippe; Piton, Nicolas; Guisier, Florian; Salaun, Mathieu

2018-01-01

Minimally invasive surgery of pulmonary nodules allows suboptimal palpation of the lung compared to open thoracotomy. The objective of this study was to assess endoscopic pleural dye marking using radial endobronchial ultrasound (r-EBUS) and virtual bronchoscopy to localize small peripheral lung nodules immediately before minimally invasive resection. The endoscopic procedure was performed without fluoroscopy, under general anesthesia in the operating room immediately before minimally invasive surgery. Then, 1 mL of methylene blue (0.5%) was instilled into the guide sheath, wedged in the subpleural space. Wedge resection or segmentectomy were guided by visualization of the dye on the pleural surface. Contribution of dye marking to the surgical procedure was rated by the surgeon. Twenty-five nodules, including 6 ground glass opacities, were resected in 22 patients by video-assisted thoracoscopic wedge resection (n = 11) or robotic-assisted thoracoscopic surgery (10 segmentectomies and 1 wedge resection). The median greatest diameter of nodules was 8 mm. No conversion to open thoracotomy was needed. The endoscopic procedure added an average 10 min to surgical resection. The dye was visible on the pleural surface in 24 cases. Histological diagnosis and free margin resection were obtained in all cases. Median skin-to-skin operating time was 90 min for robotic segmentectomy and 40 min for video-assisted wedge resection. The same operative precision was considered impossible by the surgeon without dye marking in 21 cases. Dye marking using r-EBUS and virtual bronchoscopy can be easily and safely performed to localize small pulmonary nodules immediately before minimally invasive resection. © 2018 S. Karger AG, Basel.

A Pilot Cost-Effectiveness Analysis of Treatments in Newly Diagnosed High-Grade Gliomas: The Example of 5-Aminolevulinic Acid Compared With White-Light Surgery

PubMed Central

Alves, Marta; Castel-Branco, Marta; Stummer, Walter

2015-01-01

BACKGROUND: High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). OBJECTIVE: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. METHODS: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratios are below €10 000 in all evaluated outcomes, being around €9100 per quality-adjusted life-year gained, €6700 per life-year gained, and €8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of €20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. CONCLUSION: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data. ABBREVIATIONS: 5-ALA, 5-aminolevulinic acid ICER, incremental cost-effectiveness ratio LY, life-year PFLY, progression-free life-year QALY, quality-adjusted life-year PMID:25714513

[Evaluation of green indocyanine interest compared to Technetium in sentinel lymph node detection in breast cancer].

PubMed

Guenane, Y; Gorj, M; Nguyen, V; Revol, M; Mazouz-Dorval, S

2016-12-01

Axillary sentinel lymph node (SN) biopsy by using indocyanine green (ICG) fluorescence for breast cancer is a recent technique. However, compared to Technetium-99m (Tc), which is the reference technique, its efficiency has received little testing. Between December 2013 and January 2014, 40 patients with node-negative breast cancer underwent SN biopsy by injecting sub areolar Tc in preoperative stage and injecting sub areolar ICG in intraoperative stage. SN were previously identified and resected by using ICG coupled with infrared camera. After resection of fluorescent SN, we check its radioactivity with a gamma probe (isotopic method). In case of residual radioactive labeling in the axillary crease, we remove the remaining SN. We have retrospectively analyzed the SN detection concordance rates of these two methods. In total we resected 53 SN, among which 48 (90.6%) were indocyanine green positive and 53 (100%) Tc positive. The remaining 5 SN were all ICG negative and Tc positive. Using ICG has not caused any side effect. SN detection for breast cancer by using ICG fluorescence is a promising, reliable technique which nonetheless requires a degree of expertise before reaching similar results as the Tc technique. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Optimizing fluorescently tethered Hsp90 inhibitor dose for maximal specific uptake by breast tumors

NASA Astrophysics Data System (ADS)

Crouch, Brian T.; Duer, Joy; Wang, Roujia; Gallagher, Jennifer; Hall, Allison; Soo, Mary Scott; Hughes, Philip; Haystead, Timothy A. J.; Ramanujam, Nirmala

2018-03-01

Despite improvements in surgical resection, 20-40% of patients undergoing breast conserving surgery require at least one additional re-excision. Leveraging the unique surface expression of heat shock protein 90 (Hsp90), a chaperone protein involved in several key hallmarks of cancer, in breast cancer provides an exciting opportunity to identify residual disease during surgery. We developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens using a fluorescence microendoscope with a field of view of 750 μm and subcellular resolution of 4 μm. HS-27 consists of an FDA approved Hsp90 inhibitor tethered to fluorescein isothiocyanate (EX 488nm, EM 525nm). Here, we optimized ex vivo HS-27 administration in pre-clinical breast cancer models and validated our approach on 21 patients undergoing standard of care ultrasound guided core needle biopsy. HS-27 administration time was fixed at 1- minute to minimize imaging impact on clinical workflow. HS-27 and HS-217 (non-specific control) doses were modulated from 1 μM up to 100 μM to identify the dose maximizing the ratio of specific uptake (HS-27 fluorescence) to non-specific uptake (HS-217 fluorescence). The specificity ratio was maximized at 100 μM and was significantly greater than all other doses (p<0.05). We applied our optimized imaging protocol to clinical samples and demonstrated significantly greater uptake of HS-27 by tumor than non-tumor tissue (p<0.05). The ubiquitous nature of HS-27 binding to all subtypes of breast cancer makes this technology attractive for assessing tumor margins, as one agent can be used for all subtypes.

Multimodal Approach for Radical Excision of Focal Cortical Dysplasia by Combining Advanced Magnetic Resonance Imaging Data to Intraoperative Ultrasound, Electrocorticography, and Cortical Stimulation: A Preliminary Experience.

PubMed

Tringali, Giovanni; Bono, Beatrice; Dones, Ivano; Cordella, Roberto; Didato, Giuseppe; Villani, Flavio; Prada, Francesco

2018-05-01

Type II focal cortical dysplasia is the most common malformation of cortical development associated with drug resistant epilepsy and susceptible to surgical resection. Although, at present, advanced imaging modalities are capable of detecting most cortical disorders, it is still a challenge for the surgeon to visualize them intraoperatively. The lack of direct identification between normal brain and subtle dysplastic tissue may explain the poor results in terms of being seizure-free versus other forms of epilepsy. The aim of this study is to compare magnetic resonance imaging (MRI) and intraoperative ultrasound-guided neuronavigation, along with cortical stimulation and acute electrocorticography, as a multimodal surgical approach to cortical dysplasia's tailored resection. Six consecutive patients with type II cortical dysplasia underwent epilepsy surgery by means of MRI/intraoperative ultrasound-guided neuronavigation. Intraoperative cortical stimulation of sensory/motor cortex was performed to localize cortical eloquent areas. Acute electrocorticography was used to identify epileptogenic tissue. These findings were correlated to real-time ultrasound imaging to establish the extent of the resection. Intraoperative ultrasound depicted cortical dysplasias at a higher resolution and accuracy than MRI. Therefore it maximized the extent of the resection. Both postoperative MRIs and pathology documented the extent of the resection in all patients. Seizure-freedom was achieved in 5 cases (Engel class IA), and in 1 patient it was classified as Engel class IB. No postoperative neurological deficits were observed. These results strongly suggest feasibility of ultrasound-guided resection of focal cortical dysplasia. Providing high resolution and accuracy, it allows an easy, real-time discrimination between normal and dysplastic brain. Copyright © 2018 Elsevier Inc. All rights reserved.

Habilitation of facial nerve dysfunction after resection of a vestibular schwannoma.

PubMed

Rudman, Kelli L; Rhee, John S

2012-04-01

Facial nerve dysfunction after resection of a vestibular schwannoma is one of the most common indications for facial nerve habilitation. This article presents an overview of common and emerging management options for facial habilitation following resection of a vestibular schwannoma. Immediate and delayed nerve repair options, as well as adjunctive surgical, medical, and physical therapies for facial nerve dysfunction, are discussed. Two algorithms are provided as guides for the assessment and treatment of facial nerve paralysis after resection of vestibular schwannoma. Copyright © 2012 Elsevier Inc. All rights reserved.

[Use of four kinds of three-dimensional printing guide plate in bone tumor resection and reconstruction operation].

PubMed

Fu, Jun; Guo, Zheng; Wang, Zhen; Li, Xiangdong; Fan, Hongbin; Li, Jing; Pei, Yanjun; Pei, Guoxian; Li, Dan

2014-03-01

To explore the effectiveness of excision and reconstruction of bone tumor by using operation guide plate made by variety of three-dimensional (3-D) printing techniques, and to compare the advantages and disadvantages of different 3-D printing techniques in the manufacture and application of operation guide plate. Between September 2012 and January 2014, 31 patients with bone tumor underwent excision and reconstruction of bone tumor by using operation guide plate. There were 19 males and 12 females, aged 6-67 years (median, 23 years). The disease duration ranged from 15 days to 12 months (median, 2 months). There were 13 cases of malignant tumor and 18 cases of benign tumor. The tumor located in the femur (9 cases), the spine (7 cases), the tibia (6 cases), the pelvis (5 cases), the humerus (3 cases), and the fibula (1 case). Four kinds of 3-D printing technique were used in processing operation guide plate: fused deposition modeling (FDM) in 9 cases, stereo lithography appearance (SLA) in 14 cases, 3-D printing technique in 5 cases, and selective laser sintering (SLS) in 3 cases; the materials included ABS resin, photosensitive resin, plaster, and aluminum alloy, respectively. Before operation, all patients underwent thin layer CT scanning (0.625 mm) in addition to conventional imaging. The data were collected for tumor resection design, and operation guide plate was designed on the basis of excision plan. Preoperatively, the operation guide plates were made by 3-D printing equipment. After sterilization, the guide plates were used for excision and reconstruction of bone tumor. The time of plates processing cycle was recorded to analyse the efficiency of 4 kinds of 3-D printing techniques. The time for design and operation and intraoperative fluoroscopy frequency were recorded. Twenty-eight patients underwent similar operations during the same period as the control group. The processing time of operation guide plate was (19.3 +/- 6.5) hours in FDM, (5.2 +/- 1.3) hours in SLA, (8.6 +/- 1.9) hours in 3-D printing technique, and (51.7 +/- 12.9) hours in SLS. The preoperative design and operation guide plate were successfully made, which was used for excision and reconstruction of bone tumor in 31 cases. Except 3 failures (operation guide plate fracture), the resection and reconstruction operations followed the preoperative design in the other 28 cases. The patients had longer design time, shorter operation time, and less fluoroscopy frequency than the patients of the control group, showing significant differences (P < 0.05). The follow-up time was 1-12 months (mean, 3.7 months). Postoperative X-ray and CT showed complete tumor resection and stable reconstruction. 3-D printing operation guide plates are well adapted to the requirements of individual operation for bone tumor resection and reconstruction. The 4 kinds of 3-D printing techniques have their own advantages and should be chosen according to the need of operation.

A handheld MEMS-based line-scanned dual-axis confocal microscope for early cancer detection and surgical guidance (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chen, Ye; Yin, Chengbo; Wei, Linpeng; Glaser, Adam K.; Abeytunge, Sanjee; Peterson, Gary; Mandella, Michael J.; Sanai, Nader; Rajadhyaksha, Milind; Liu, Jonathan T.

2017-02-01

Considerable efforts have been recently undertaken to develop miniature optical-sectioning microscopes for in vivo microendoscopy and point-of-care pathology. These devices enable in vivo interrogation of disease as a real-time and noninvasive alternative to gold-standard histopathology, and therefore could have a transformative impact for the early detection of cancer as well as for guiding tumor-resection procedures. Regardless of the specific modality, various trade-offs in size, speed, field of view, resolution, contrast, and sensitivity are necessary to optimize a device for a particular application. Here, a miniature MEMS-based line-scanned dual-axis confocal (LS-DAC) microscope, with a 12-mm diameter distal tip, has been developed for point-of-care pathology. The dual-axis architecture has demonstrated superior rejection of out-of-focus and multiply scattered photons compared to a conventional single-axis confocal configuration. The use of line scanning enables fast frame rates (≥15 frames/sec), which mitigates motion artifacts of a handheld device during clinical use. We have developed a method to actively align the illumination and collection beams in this miniature LS-DAC microscope through the use of a pair of rotatable alignment mirrors. Incorporation of a custom objective lens, with a small form factor for in vivo application, enables the device to achieve an axial and lateral resolution of 2.0 and 1.1 microns, respectively. Validation measurements with reflective targets, as well as in vivo and ex vivo images of tissues, demonstrate that this high-speed LS-DAC microscope can achieve high-contrast imaging of fluorescently labeled tissues with sufficient sensitivity for applications such as oral cancer detection and guiding brain-tumor resections.

Radio-guided thoracoscopic surgery (RGTS) of small pulmonary nodules.

PubMed

Ambrogi, Marcello Carlo; Melfi, Franca; Zirafa, Carmelina; Lucchi, Marco; De Liperi, Annalisa; Mariani, Giuliano; Fanucchi, Olivia; Mussi, Alfredo

2012-04-01

The demand for adequate tissue sampling to determine individual tumor behavior is increasing the number of lung nodule resections, even when the diagnosis is already recognized. Video-assisted thoracic surgery (VATS) is the procedure of choice for diagnosis and treatment of small pulmonary nodules. Difficulties in localizing smaller and deeper nodules have been approached with different techniques. Herein we report our 13-years' experience with radio-guided thoracoscopic resection. Patients with pulmonary nodules smaller than 1 cm and/or deeper than 1 cm, below the visceral pleura, underwent computed tomography (CT)-guided injection of a solution, composed of 0.2 ml (99)Tc-labeled human serum albumin microspheres and 0.1 ml nonionic contrast, into the nodule. During the VATS procedure, an 11-mm-diameter collimated probe connected to a gamma ray detector was introduced to scan the lung surface. The area of major radioactivity, which matched with the area of the nodule, was resected. From 1997 to 2009, 573 patients underwent thoracoscopic resection of small pulmonary nodules, 211 with the radio-guided technique. There were 159 men and 52 women, with an average age of 60.6 years (range = 12-83). The mean duration of the surgical procedure was 41 min (range = 20-100). The procedure was successful in 208/211 cases. Three patients (0.5%) required conversion to a minithoracotomy. The mean length of pleural drainage and hospital stay was 2.3 and 3.7 days, respectively. Histological examination showed 98 benign lesions and 113 malignant lesions (61 metastases and 52 primary lung cancers). This study confirms that radio-guided localization of small pulmonary nodules is a feasible, safe, and quick procedure, with a high rate of success. The spread of the sentinel lymph node technique has increased the availability of technology required for RGTS.

Osteoid osteoma: CT-guided percutaneous resection and follow-up in 38 patients.

PubMed

Sans, N; Galy-Fourcade, D; Assoun, J; Jarlaud, T; Chiavassa, H; Bonnevialle, P; Railhac, N; Giron, J; Morera-Maupomé, H; Railhac, J J

1999-09-01

To reevaluate at medium term the results of computed tomography (CT)-guided percutaneous resection of osteoid osteomas. Thirty-eight patients who had undergone treatment by means of this technique were reexamined with a mean follow-up of 3.7 years. The short- and medium-term clinical course and histologic features of the resection specimens were analyzed. The bone fragment could be analyzed in all cases, and the diagnosis of osteoid osteoma was confirmed in 28 patients (74%). A different diagnosis was made in six patients: mucoid cyst, subchondral arthritic geode, fibrous dysplastic lesion, focal osteochondritis, or focal chronic osteomyelitis. Cure was obtained in 32 patients (84%), whatever the cause. Complications, generally minor and transient, were observed in nine patients (24%). The most severe complications were two femoral fractures and one focal chronic osteomyelitis due to Staphylococcus aureus infection. The results of this study confirm the efficacy of percutaneous resection of osteoid osteomas and the possibility of using this method for successful treatment of other small bone lesions.

Non-invasive, photonics-based diagnostic, imaging, monitoring, and light delivery techniques for the recognition, quantification and treatment of malignant and chronic inflammatory conditions

NASA Astrophysics Data System (ADS)

Davies, N.; Davies-Shaw, D.; Shaw, J. D.

2007-02-01

We report firsthand on innovative developments in non-invasive, biophotonic techniques for a wide range of diagnostic, imaging and treatment options, including the recognition and quantification of cancerous, pre-cancerous cells and chronic inflammatory conditions. These techniques have benefited from the ability to target the affected site by both monochromatic light and broad multiple wavelength spectra. The employment of such wavelength or color-specific properties embraces the fluorescence stimulation of various photosensitizing drugs, and the instigation and detection of identified fluorescence signatures attendant upon laser induced fluorescence (LIF) phenomena as transmitted and propagated by precancerous, cancerous and normal tissue. In terms of tumor imaging and therapeutic and treatment options, we have exploited the abilities of various wavelengths to penetrate to different depths, through different types of tissues, and have explored quantifiable absorption and reflection characteristics upon which diagnostic assumptions can be reliably based and formulated. These biophotonic-based diagnostic, sensing and imaging techniques have also benefited from, and have been further enhanced by, the integrated ability to provide various power levels to be employed at various stages in the procedure. Applications are myriad, including non-invasive, non destructive diagnosis of in vivo cell characteristics and functions; light-based tissue analysis; real-time monitoring and mapping of brain function and of tumor growth; real time monitoring of the surgical completeness of tumor removal during laser-imaged/guided brain resection; diagnostic procedures based on fluorescence life-time monitoring, the monitoring of chronic inflammatory conditions (including rheumatoid arthritis), and continuous blood glucose monitoring in the control of diabetes.

Recommendations for fluorescence instrument qualification: the new ASTM Standard Guide.

PubMed

DeRose, Paul C; Resch-Genger, Ute

2010-03-01

Aimed at improving quality assurance and quantitation for modern fluorescence techniques, ASTM International (ASTM) is about to release a Standard Guide for Fluorescence, reviewed here. The guide's main focus is on steady state fluorometry, for which available standards and instrument characterization procedures are discussed along with their purpose, suitability, and general instructions for use. These include the most relevant instrument properties needing qualification, such as linearity and spectral responsivity of the detection system, spectral irradiance reaching the sample, wavelength accuracy, sensitivity or limit of detection for an analyte, and day-to-day performance verification. With proper consideration of method-inherent requirements and limitations, many of these procedures and standards can be adapted to other fluorescence techniques. In addition, procedures for the determination of other relevant fluorometric quantities including fluorescence quantum yields and fluorescence lifetimes are briefly introduced. The guide is a clear and concise reference geared for users of fluorescence instrumentation at all levels of experience and is intended to aid in the ongoing standardization of fluorescence measurements.

Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome.

PubMed

Schucht, Philippe; Seidel, Kathleen; Beck, Jürgen; Murek, Michael; Jilch, Astrid; Wiest, Roland; Fung, Christian; Raabe, Andreas

2014-12-01

Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.

PubMed

Roberts, David W; Olson, Jonathan D; Evans, Linton T; Kolste, Kolbein K; Kanick, Stephen C; Fan, Xiaoyao; Bravo, Jaime J; Wilson, Brian C; Leblond, Frederic; Marois, Mikael; Paulsen, Keith D

2018-06-01

OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis. RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery. CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional blue-light excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov).

Real-time endoscopic guidance using near-infrared fluorescent light for thoracic surgery

NASA Astrophysics Data System (ADS)

Venugopal, Vivek; Stockdale, Alan; Neacsu, Florin; Kettenring, Frank; Frangioni, John V.; Gangadharan, Sidharta P.; Gioux, Sylvain

2013-03-01

Lung cancer is the leading cause of cancer death in the United States, accounting for 28% of all cancer deaths. Standard of care for potentially curable lung cancer involves preoperative radiographic or invasive staging, followed by surgical resection. With recent adjuvant chemotherapy and radiation studies showing a survival advantage in nodepositive patients, it is crucial to accurately stage these patients surgically in order to identify those who may benefit. However, lymphadenectomy in lung cancer is currently performed without guidance, mainly due to the lack of tools permitting real-time, intraoperative identification of lymph nodes. In this study we report the design and validation of a novel, clinically compatible near-infrared (NIR) fluorescence thoracoscope for real-time intraoperative guidance during lymphadenectomy. A novel, NIR-compatible, clinical rigid endoscope has been designed and fabricated, and coupled to a custom source and a dual channel camera to provide simultaneous color and NIR fluorescence information to the surgeon. The device has been successfully used in conjunction with a safe, FDA-approved fluorescent tracer to detect and resect mediastinal lymph nodes during thoracic surgery on Yorkshire pigs. Taken together, this study lays the foundation for the clinical translation of endoscopic NIR fluorescence intraoperative guidance and has the potential to profoundly impact the management of lung cancer patients.

Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds

NASA Astrophysics Data System (ADS)

Holt, David; Parthasarathy, Ashwin B.; Okusanya, Olugbenga; Keating, Jane; Venegas, Ollin; Deshpande, Charuhas; Karakousis, Giorgos; Madajewski, Brian; Durham, Amy; Nie, Shuming; Yodh, Arjun G.; Singhal, Sunil

2015-07-01

Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ˜16. Ten animals showed no residual tumor cells in the wound bed (mean SBR<2, P<0.001). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15, and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations.

Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds

PubMed Central

Holt, David; Parthasarathy, Ashwin B.; Okusanya, Olugbenga; Keating, Jane; Venegas, Ollin; Deshpande, Charuhas; Karakousis, Giorgos; Madajewski, Brian; Durham, Amy; Nie, Shuming; Yodh, Arjun G.; Singhal, Sunil

2015-01-01

Abstract. Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ∼16. Ten animals showed no residual tumor cells in the wound bed (mean SBR<2, P<0.001). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15, and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations. PMID:26160347

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

PubMed Central

Keating, Jane J.; Okusanya, Olugbenga T.; De Jesus, Elizabeth; Judy, Ryan; Jiang, Jack; Deshpande, Charuhas; Nie, Shuming; Low, Philip; Singhal, Sunil

2017-01-01

Purpose During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection. Procedures Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in 3 humans with lung adenocarcinoma. Results The peak tumor-to background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 hours and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (P<0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5. Conclusions Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection. PMID:26228697

An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas

PubMed Central

Predina, Jarrod D.; Newton, Andrew D.; Xia, Leilei; Corbett, Christopher; Connolly, Courtney; Shin, Michael; Sulyok, Lydia Frezel; Litzky, Leslie; Deshpande, Charuhas; Nie, Shuming; Kularatne, Sumith A.; Low, Philip S.; Singhal, Sunil

2018-01-01

Background Clinical applicability of folate receptor-targeted intraoperative molecular imaging (FR-IMI) has been established for surgically resectable pulmonary adenocarcinoma. A role for FR-IMI in other lung cancer histologies has not been studied. In this study, we evaluate feasibility of FR-IMI in patients undergoing pulmonary resection for squamous cell carcinomas (SCCs). Methods In a human clinical trial (NCT02602119), twelve subjects with pulmonary SCCs underwent FR-IMI with a near-infrared contrast agent that targets the folate receptor-α (FRα), OTL38. Near-infrared signal from tumors and benign lung was quantified to calculate tumor-to-background ratios (TBR). Folate receptor-alpha expression was characterized, and histopathologic correlative analyses were performed to evaluate patterns of OTL38 accumulation. An exploratory analysis was performed to determine patient and histopathologic variables that predict tumor fluorescence. Results 9 of 13 SCCs (in 9 of 12 of subjects) displayed intraoperative fluorescence upon NIR evaluation (median TBR, 3.9). OTL38 accumulated within SCCs in a FRα-dependent manner. FR-IMI was reliable in localizing nodules as small as 1.1 cm, and prevented conversion to thoracotomy for nodule localization in three subjects. Upon evaluation of patient and histopathologic variables, in situ fluorescence was associated with distance from the pleural surface, and was independent of alternative variables including tumor size and metabolic activity. Conclusions This work demonstrates that FR-IMI is potentially feasible in 70% of SCC patients, and that molecular imaging can improve localization during minimally invasive pulmonary resection. These findings complement previous data demonstrating that ∼98% of pulmonary adenocarcinomas are localized during FR-IMI and suggest broad applicability for NSCLC patients undergoing resection. PMID:29568374

Indocyanine green fluorescence angiography during laparoscopic low anterior resection: results of a case-matched study.

PubMed

Boni, Luigi; Fingerhut, Abe; Marzorati, Alessandro; Rausei, Stefano; Dionigi, Gianlorenzo; Cassinotti, Elisa

2017-04-01

Colorectal anastomoses after anterior resection for cancer carry a high risk of leakage. Different factors might influence the correct healing of anastomosis, but adequate perfusion of the bowel is highlighted as one of the most important elements. Fluorescence angiography (FA) is a new technique that allows the surgeon to perform real-time intraoperative angiography to evaluate the perfusion of the anastomosis and hence, potentially, reduce leak rate. The aim of this study was to evaluate the impact of FA of the bowel on postoperative complications and anastomotic leakage after laparoscopic anterior resection with total mesorectal excision (TME). FA was performed in all patients undergoing laparoscopic anterior resection with TME for cancer followed by colorectal or coloanal anastomosis. Results were compared to a historical controls group of 38 patients previously operated by the same surgeon for the same indication but without the use of FA. From October 2014 to November 2015, 42 patients underwent laparoscopic anterior resection with TME and FA of the bowel. The surgeon subjectively decided to change the planned anastomotic level of the descending colon due to hypoperfused distal segment in two out of 42 patients in the FA group (4.7 %). Anastomotic leakage, confirmed by postoperative CT scan and water-soluble contrast enema, was found in two cases of a historical controls group and none in the FA group. No adverse events (side effects or allergic reaction) related to FA were recorded. All the other postoperative complications were comparable between the two groups. In our experience, ICG FA was safe and effective in low rectal cancer resection, possibly leading to a reduction in the anastomotic leakage rate after TME.

Transoesophageal Doppler compared to central venous pressure for perioperative hemodynamic monitoring and fluid guidance in liver resection.

PubMed

El Sharkawy, Osama A; Refaat, Emad K; Ibraheem, Abdel Elmoniem M; Mahdy, Wafiya R; Fayed, Nirmeen A; Mourad, Wesam S; Abd Elhafez, Hanaa S; Yassen, Khaled A

2013-10-01

Major hepatic resections may result in hemodynamic changes. Aim is to study transesophageal Doppler (TED) monitoring and fluid management in comparison to central venous pressure (CVP) monitoring. A follow-up comparative hospital based study. 59 consecutive cirrhotic patients (CHILD A) undergoing major hepatotomy. CVP monitoring only (CVP group), (n=30) and TED (Doppler group), (n=29) with CVP transduced but not available on the monitor. Exclusion criteria include contra-indication for Doppler probe insertion or bleeding tendency. An attempt to reduce CVP during the resection in both groups with colloid restriction, but crystalloids infusion of 6 ml/kg/h was allowed to replace insensible loss. Post-resection colloids infusion were CVP guided in CVP group (5-10 mmHg) and corrected flow time (FTc) aortic guided in Doppler group (>0.4 s) blood products given according to the laboratory data. Using the FTc to guide Hydroxyethyl starch 130/0.4 significantly decreased intake in TED versus CVP (1.03 [0.49] versus 1.74 [0.41] Liter; P<0.05). Nausea, vomiting, and chest infection were less in TED with a shorter hospital stay (P<0.05). No correlation between FTc and CVP (r=0.24, P > 0.05). Cardiac index and stroke volume of TED increased post-resection compared to baseline, 3.0 (0.9) versus 3.6 (0.9) L/min/m(2), P<0.05; 67.1 (14.5) versus 76 (13.2) ml, P<0.05, respectively, associated with a decrease in systemic vascular resistance (SVR) 1142.7 (511) versus 835.4 (190.9) dynes.s/cm(5), P<0.05. No significant difference in arterial pressure and CVP between groups at any stage. CVP during resection in TED 6.4 (3.06) mmHg versus 6.1 (1.4) in CVP group, P=0.6. TED placement consumed less time than CVP (7.3 [1.5] min versus 13.2 [2.9], P<0.05). TED in comparison to the CVP monitoring was able to reduced colloids administration post-resection, lower morbidity and shorten hospital stay. TED consumed less time to insert and was also able to present significant hemodynamic changes. Advanced surgical techniques of resection play a key role in reducing blood loss despite CVP more than 5 cm H2O. TED fluid management protocols during resection need to be developed.

Role of 5-ALA in improving extent of tumour resection in patients with Glioblastoma Multiforme.

PubMed

Waqas, Muhammad; Khan, Inamullah; Shamim, Muhammad Shahzad

2017-10-01

Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use of 5- ALA in improving the extent of resection when compared to white light microscopy. A systematic review on the topic had a similar conclusion. Few studies have also hinted on a high false negative rate with the use of this technique..

Real-time quantitative fluorescence imaging using a single snapshot optical properties technique for neurosurgical guidance

NASA Astrophysics Data System (ADS)

Valdes, Pablo A.; Angelo, Joseph; Gioux, Sylvain

2015-03-01

Fluorescence imaging has shown promise as an adjunct to improve the extent of resection in neurosurgery and oncologic surgery. Nevertheless, current fluorescence imaging techniques do not account for the heterogeneous attenuation effects of tissue optical properties. In this work, we present a novel imaging system that performs real time quantitative fluorescence imaging using Single Snapshot Optical Properties (SSOP) imaging. We developed the technique and performed initial phantom studies to validate the quantitative capabilities of the system for intraoperative feasibility. Overall, this work introduces a novel real-time quantitative fluorescence imaging method capable of being used intraoperatively for neurosurgical guidance.

99mTechnetium and methylene blue guided pulmonary nodules resections: preliminary British experience.

PubMed

Nardini, Marco; Bilancia, Rocco; Paul, Ian; Jayakumar, Shruti; Papoulidis, Pavlos; ElSaegh, Mohamed; Hartley, Richard; Richardson, Mark; Misra, Pankash; Migliore, Marcello; Dunning, Joel

2018-02-01

Subcentimetre pulmonary nodules can be challenging to locate either during video-assisted thoracoscopic surgery (VATS) or by open techniques. In an era of increasing computed tomography scan availability the number of nodules that are identified that are suspicious for malignancy is rising, and thoracic surgeons require a reliable method to locate these nodules intraoperatively. Our aim was to evaluate, for the first time in the UK, resection of pulmonary nodules using radioactive dye labelling. Local research ethics approval was obtained and the study was submitted to the Integrated Research Application System (IRAS). All data were prospectively collected in our dedicated thoracic surgical database and analyzed at the conclusion of the study. This represents a consecutive series of patients, from January 2016 and until April 2017, who underwent this procedure at our institution: James Cook University Hospital, Middlesbrough, United Kingdom. The primary outcome measured was successful resection rate of the target nodules. Twenty-three patients underwent radiolabeled excision of pulmonary nodules, their average age was 61 years (range, 28-79 years), 13 women and 10 men. The average maximum diameter of the nodule was 8 mm (range, 3-16 mm). All patients underwent successful excision of the target lesion (success rate 100%). One patient (4.3%) sustained pneumothorax following the CT-guided injection of the radio-labelled dye and this required chest drainage prior to general anesthesia. We conclude that technetium guided pulmonary nodule resection is a very reliable method for localization and resection of subcentimetre nodules which may be otherwise be difficult to identify.

99mTechnetium and methylene blue guided pulmonary nodules resections: preliminary British experience

PubMed Central

Bilancia, Rocco; Paul, Ian; Jayakumar, Shruti; Papoulidis, Pavlos; ElSaegh, Mohamed; Hartley, Richard; Richardson, Mark; Misra, Pankash; Migliore, Marcello; Dunning, Joel

2018-01-01

Background Subcentimetre pulmonary nodules can be challenging to locate either during video-assisted thoracoscopic surgery (VATS) or by open techniques. In an era of increasing computed tomography scan availability the number of nodules that are identified that are suspicious for malignancy is rising, and thoracic surgeons require a reliable method to locate these nodules intraoperatively. Methods Our aim was to evaluate, for the first time in the UK, resection of pulmonary nodules using radioactive dye labelling. Local research ethics approval was obtained and the study was submitted to the Integrated Research Application System (IRAS). All data were prospectively collected in our dedicated thoracic surgical database and analyzed at the conclusion of the study. This represents a consecutive series of patients, from January 2016 and until April 2017, who underwent this procedure at our institution: James Cook University Hospital, Middlesbrough, United Kingdom. The primary outcome measured was successful resection rate of the target nodules. Results Twenty-three patients underwent radiolabeled excision of pulmonary nodules, their average age was 61 years (range, 28–79 years), 13 women and 10 men. The average maximum diameter of the nodule was 8 mm (range, 3–16 mm). All patients underwent successful excision of the target lesion (success rate 100%). One patient (4.3%) sustained pneumothorax following the CT-guided injection of the radio-labelled dye and this required chest drainage prior to general anesthesia. Conclusions We conclude that technetium guided pulmonary nodule resection is a very reliable method for localization and resection of subcentimetre nodules which may be otherwise be difficult to identify. PMID:29607175

First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800.

PubMed

Miller, Sarah E; Tummers, Willemieke S; Teraphongphom, Nutte; van den Berg, Nynke S; Hasan, Alifia; Ertsey, Robert D; Nagpal, Seema; Recht, Lawrence D; Plowey, Edward D; Vogel, Hannes; Harsh, Griffith R; Grant, Gerald A; Li, Gordon H; Rosenthal, Eben L

2018-04-06

Maximizing extent of surgical resection with the least morbidity remains critical for survival in glioblastoma patients, and we hypothesize that it can be improved by enhancements in intraoperative tumor detection. In a clinical study, we determined if therapeutic antibodies could be repurposed for intraoperative imaging during resection. Fluorescently labeled cetuximab-IRDye800 was systemically administered to three patients 2 days prior to surgery. Near-infrared fluorescence imaging of tumor and histologically negative peri-tumoral tissue was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratios (TBRs) were calculated by comparing MFIs of tumor and histologically uninvolved tissue. The mean TBR was significantly higher in tumor tissue of contrast-enhancing (CE) tumors on preoperative imaging (4.0 ± 0.5) compared to non-CE tumors (1.2 ± 0.3; p = 0.02). The TBR was higher at a 100 mg dose than at 50 mg (4.3 vs. 3.6). The smallest detectable tumor volume in a closed-field setting was 70 mg with 50 mg of dye and 10 mg with 100 mg. On sections of paraffin embedded tissues, fluorescence positively correlated with histological evidence of tumor. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (73.0% for 50 mg dose, 98.2% for 100 mg dose) and specific (66.3% for 50 mg dose, 69.8% for 100 mg dose) for viable tumor tissue in CE tumors while normal peri-tumoral tissue showed minimal fluorescence. This first-in-human study demonstrates the feasibility and safety of antibody based imaging for CE glioblastomas.

Cryo-Assisted Resection En Bloc, and Cryoablation In Situ, of Primary Breast Cancer Coupled With Intraoperative Ultrasound-Guided Tracer Injection: A Preliminary Clinical Study.

PubMed

Korpan, Nikolai N; Xu, Kecheng; Schwarzinger, Philipp; Watanabe, Masashi; Breitenecker, Gerhard; Patrick, Le Pivert

2018-01-01

The aim of the study was to perform cryosurgery on a primary breast tumor, coupled with simultaneous peritumoral and intratumoral tracer injection of a blue dye, to evaluate lymphatic mapping. We explored the ability of our strategy to prevent tumor cells, but not that of injected tracers, to migrate to the lymphovascular drainage during conventional resection of frozen breast malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]), presenting primary breast cancer with stage I to IV, were randomly selected and treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study. Under intraoperative ultrasound, 14 patients underwent curative cryo-assisted tumor resection en bloc, coupled with peritumoral tracer injection, which consisted of complete tumor freezing and concomitant peritumor injection with a blue dye, before resection and sentinel lymph node dissection (group A). Group B consists of 3 patients previously refused any standard therapy and had palliative tumor cryoablation in situ combined with intratumoral tracer injection. The intraoperative ultrasound facilitated needle positioning and dye injection timing. In group A, the frozen site extruded the dye that was distributed through the unfrozen tumor, the breast tissue, and the resection cavity for 12 patients. One to 4 lymph nodes were stained for 10 of 14 patients. The resection margin was evaluable. Our intraoperative ultrasound-guided performance revealed the injection and migration of a blue dye during the frozen resection en bloc and cryoablation in situ of primary breast tumors. Sentinel lymph node mapping, pathological determination of the tumor, and resection margins were achievable. The study paves the way for intraoperative cryo-assisted therapeutic strategies for breast cancer.

The effectiveness and cost-effectiveness of intraoperative imaging in high-grade glioma resection; a comparative review of intraoperative ALA, fluorescein, ultrasound and MRI.

PubMed

Eljamel, M Sam; Mahboob, Syed Osama

2016-12-01

Surgical resection of high-grade gliomas (HGG) is standard therapy because it imparts significant progression free (PFS) and overall survival (OS). However, HGG-tumor margins are indistinguishable from normal brain during surgery. Hence intraoperative technology such as fluorescence (ALA, fluorescein) and intraoperative ultrasound (IoUS) and MRI (IoMRI) has been deployed. This study compares the effectiveness and cost-effectiveness of these technologies. Critical literature review and meta-analyses, using MEDLINE/PubMed service. The list of references in each article was double-checked for any missing references. We included all studies that reported the use of ALA, fluorescein (FLCN), IoUS or IoMRI to guide HGG-surgery. The meta-analyses were conducted according to statistical heterogeneity between studies. If there was no heterogeneity, fixed effects model was used; otherwise, a random effects model was used. Statistical heterogeneity was explored by χ 2 and inconsistency (I 2 ) statistics. To assess cost-effectiveness, we calculated the incremental cost per quality-adjusted life-year (QALY). Gross total resection (GTR) after ALA, FLCN, IoUS and IoMRI was 69.1%, 84.4%, 73.4% and 70% respectively. The differences were not statistically significant. All four techniques led to significant prolongation of PFS and tended to prolong OS. However none of these technologies led to significant prolongation of OS compared to controls. The cost/QALY was $16,218, $3181, $6049 and $32,954 for ALA, FLCN, IoUS and IoMRI respectively. ALA, FLCN, IoUS and IoMRI significantly improve GTR and PFS of HGG. Their incremental cost was below the threshold for cost-effectiveness of HGG-therapy, denoting that each intraoperative technology was cost-effective on its own. Copyright © 2016 Elsevier B.V. All rights reserved.

Indocyanine green videoangiography (ICGV)-guided surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS).

PubMed

d'Avella, Elena; Volpin, Francesco; Manara, Renzo; Scienza, Renato; Della Puppa, Alessandro

2013-03-01

Maximal safe resection is the goal of correct surgical treatment of parasagittal meningiomas, and it is intimately related to the venous anatomy both near and directly involved by the tumor. Indocyanine green videoangiography (ICGV) has already been advocated as an intra-operative resourceful technique in brain tumor surgery for the identification of vessels. The aim of this study was to investigate the role of ICGV in surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS). In this study, we prospectively analyzed clinical, radiological and intra-operative findings of patients affected by parasagittal meningioma occluding the SSS, who underwent ICGV assisted-surgery. Radiological diagnosis of complete SSS occlusion was pre-operatively established in all cases. ICGV was performed before dural opening, before and during tumor resection, at the end of the procedure. Five patients were included in our study. In all cases, ICGV guided dural opening, tumor resection, and venous management. The venous collateral pathway was easily identified and preserved in all cases. Radical resection was achieved in four cases. Surgery was uneventful in all cases. Despite the small number of patients, our study shows that ICG videoangiography could play a crucial role in guiding surgery of parasagittal meningioma occluding the SSS. Further studies are needed to define the role of this technique on functional and oncological outcome of these patients.

Endoscopic Ultrasound-guided drainage of an abdominal fluid collection following Whipple’s resection

PubMed Central

Jah, Asif; Jamieson, Neville; Huguet, Emmanuel; Griffiths, William; Carroll, Nicholas; Praseedom, Raaj

2008-01-01

Percutaneous aspiration and drainage of post-operative abdominal fluid collections is a well established standard technique. However, some fluid collections are not amenable to percutaneous drainage either due to location or the presence of surrounding visceral structures. Endoscopic Ultrasound (EUS) has been widely used for the drainage of pancreatitis-related abdominal fluid collections. However, there are no reports on the use of this technique in the post-operative setting. We report a case where the EUS-guided technique was used to drain a percutaneously inaccessible post-operative collection which had developed after Whipple’s resection. PMID:19058316

Intraoperative navigation-guided resection of anomalous transverse processes in patients with Bertolotti's syndrome

PubMed Central

Babu, Harish; Lagman, Carlito; Kim, Terrence T.; Grode, Marshall; Johnson, J. Patrick; Drazin, Doniel

2017-01-01

Background: Bertolotti's syndrome is characterized by enlargement of the transverse process at the most caudal lumbar vertebra with a pseudoarticulation between the transverse process and sacral ala. Here, we describe the use of intraoperative three-dimensional image-guided navigation in the resection of anomalous transverse processes in two patients with Bertolotti's syndrome. Case Descriptions: Two patients diagnosed with Bertolotti's syndrome who had undergone the above-mentioned procedure were identified. The patients were 17- and 38-years-old, and presented with severe, chronic low back pain that was resistant to conservative treatment. Imaging revealed lumbosacral transitional vertebrae at the level of L5-S1, which was consistent with Bertolotti's syndrome. Injections of the pseudoarticulations resulted in only temporary symptomatic relief. Thus, the patients subsequently underwent O-arm neuronavigational resection of the bony defects. Both patients experienced immediate pain resolution (documented on the postoperative notes) and remained asymptomatic 1 year later. Conclusion: Intraoperative three-dimensional imaging and navigation guidance facilitated the resection of anomalous transverse processes in two patients with Bertolotti's syndrome. Excellent outcomes were achieved in both patients. PMID:29026672

Intraoperative navigation-guided resection of anomalous transverse processes in patients with Bertolotti's syndrome.

PubMed

Babu, Harish; Lagman, Carlito; Kim, Terrence T; Grode, Marshall; Johnson, J Patrick; Drazin, Doniel

2017-01-01

Bertolotti's syndrome is characterized by enlargement of the transverse process at the most caudal lumbar vertebra with a pseudoarticulation between the transverse process and sacral ala. Here, we describe the use of intraoperative three-dimensional image-guided navigation in the resection of anomalous transverse processes in two patients with Bertolotti's syndrome. Two patients diagnosed with Bertolotti's syndrome who had undergone the above-mentioned procedure were identified. The patients were 17- and 38-years-old, and presented with severe, chronic low back pain that was resistant to conservative treatment. Imaging revealed lumbosacral transitional vertebrae at the level of L5-S1, which was consistent with Bertolotti's syndrome. Injections of the pseudoarticulations resulted in only temporary symptomatic relief. Thus, the patients subsequently underwent O-arm neuronavigational resection of the bony defects. Both patients experienced immediate pain resolution (documented on the postoperative notes) and remained asymptomatic 1 year later. Intraoperative three-dimensional imaging and navigation guidance facilitated the resection of anomalous transverse processes in two patients with Bertolotti's syndrome. Excellent outcomes were achieved in both patients.

Image-guided sphenoid wing meningioma resection and simultaneous computer-assisted cranio-orbital reconstruction: technical case report.

PubMed

Westendorff, Carsten; Kaminsky, Jan; Ernemann, Ulrike; Reinert, Siegmar; Hoffmann, Jürgen

2007-02-01

Resection of large intraosseous sphenoid wing meningiomas is traditionally associated with significant morbidity. Rapid prototyping techniques have become widely used for treatment planning. Yet, the transfer of a treatment plan into the intraoperative situs strongly depends on the experience of the individual surgeon. Extensive resection with orbital decompression was planned and performed on the basis of rapid prototyping and surgical navigation techniques in a 44-year-old woman presenting with a large sphenoid wing meningioma on the right infiltrating the orbit. Tumor resection was simulated on a stereolithography model of the patient's head. The stereolithography model was scanned using computed tomography (CT) and the defect geometry was used to create a custom-made titanium implant. The implant consisted of a solid titanium core and a spot-welded titanium mesh surrounding the core, allowing for minor intraoperative adjustments of the implant size by reducing the mesh size. The stereolithography model with the incorporated implant was CT scanned again and the CT data were fused with the patient's original CT data. The implant borders indicating the resection borders were marked within the patient's CT data set. This treatment plan was transferred to an optical navigation system. Intraoperatively, tumor resection was performed using surgical navigation. In the presented case report, the combination of computer-assisted planning using rapid prototyping techniques and image-guided surgery allowed for an extensive tumor resection precisely according to a preoperative treatment plan in a patient presenting with a large intraosseous sphenoid wing meningioma. A larger clinical series with a long-term follow-up period will be needed to determine the reproducibility.

qF-SSOP: real-time optical property corrected fluorescence imaging

PubMed Central

Valdes, Pablo A.; Angelo, Joseph P.; Choi, Hak Soo; Gioux, Sylvain

2017-01-01

Fluorescence imaging is well suited to provide image guidance during resections in oncologic and vascular surgery. However, the distorting effects of tissue optical properties on the emitted fluorescence are poorly compensated for on even the most advanced fluorescence image guidance systems, leading to subjective and inaccurate estimates of tissue fluorophore concentrations. Here we present a novel fluorescence imaging technique that performs real-time (i.e., video rate) optical property corrected fluorescence imaging. We perform full field of view simultaneous imaging of tissue optical properties using Single Snapshot of Optical Properties (SSOP) and fluorescence detection. The estimated optical properties are used to correct the emitted fluorescence with a quantitative fluorescence model to provide quantitative fluorescence-Single Snapshot of Optical Properties (qF-SSOP) images with less than 5% error. The technique is rigorous, fast, and quantitative, enabling ease of integration into the surgical workflow with the potential to improve molecular guidance intraoperatively. PMID:28856038

Ultrasound-stimulated drug delivery for treatment of residual disease after incomplete resection of head and neck cancer.

PubMed

Sorace, Anna G; Korb, Melissa; Warram, Jason M; Umphrey, Heidi; Zinn, Kurt R; Rosenthal, Eben; Hoyt, Kenneth

2014-04-01

Microbubbles triggered with localized ultrasound (US) can improve tumor drug delivery and retention. Termed US-stimulated drug delivery, this strategy was applied to head and neck cancer (HNC) in a post-surgical tumor resection model. Luciferase-positive HNC squamous cell carcinoma (SCC) was implanted in the flanks of nude athymic mice (N = 24) that underwent various degrees of surgical tumor resection (0%, 50% or 100%). After surgery, animals received adjuvant therapy with cetuximab-IRDye alone, or cetuximab-IRDye in combination with US-stimulated drug delivery or saline injections (control) on days 4, 7 and 10. Tumor drug delivery was assessed on days 0, 4, 7, 10, 14 and 17 with an in vivo fluorescence imaging system, and tumor viability was evaluated at the same times with in vivo bioluminescence imaging. Tumor caliper measurements occurred two times per week for 24 d. Optical imaging revealed that in the 50% tumor resection group, US-stimulated drug delivery resulted in a significant increase in cetuximab delivery compared with administration of drug alone on day 10 (day of peak fluorescence) (p = 0.03). Tumor viability decreased in all groups that received cetuximab-IRDye in combination with US-stimulated drug delivery, compared with the group that received only the drug. After various degrees of surgical resection, this novel study reports positive improvements in drug uptake in the residual cancer cells when drug delivery is stimulated with US. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Eder Puestow dilatation of benign rectal stricture following anterior resection.

PubMed

Woodward, A; Tydeman, G; Lewis, M H

1990-01-01

Benign anastomotic stricture following anterior resection can be difficult to manage when the stricture is proximal. The acceptable surgical options are either a redo low resection with its accompanying hazards or, alternatively, the formation of a permanent colostomy. Although dilatation of such strictures is possible by blind passage of metal bougies, the authors believe that this technique must be regarded as hazardous. A technique of dilatation is described that is usually reserved for esophageal stricture, namely, Eder Puestow dilatation over a guide wire inserted under direct vision. Although this technique may not be without risk, this readily available equipment may be valuable in making a further resection unnecessary.

The utilization of fluorescein in brain tumor surgery: a systematic review.

PubMed

Cavallo, Claudio; De Laurentis, Camilla; Vetrano, Ignazio G; Falco, Jacopo; Broggi, Morgan; Schiariti, Marco; Ferroli, Paolo; Acerbi, Francesco

2018-05-22

Sodium Fluorescein (SF) is a green, water-soluble dye with the capacity to accumulate in cerebral areas as a result of damaged blood-brain barrier (BBB); this property allows SF to concentrate specifically at the tumor site of various types of brain neoplasms, making the tumor tissue more clearly visible. A literature search (1947-2018) was conducted with the keywords "fluorescein neurosurgery", "YELLOW neurosurgery", "fluorescein brain tumor", "YELLOW brain tumor". We included clinical studies, clinical trials, observational studies, only conducted on humans and concerning surgery; in addition, we have included 3 articles derived from the analysis of the references of other papers. Ultimately, 57 articles were included for further analysis. Fluorescein as a fluorescent tracer in neuro-oncology is gaining a wider acceptance in the neurosurgical literature: until February 1st, 2018, at least 1099 neuro-oncological patients have been operated through fluorescein-assistance, mostly only after 2012. The most important application remains the aim to improve tumor visualization and extent of resection for high-grade gliomas (HGG), but the nonspecific mechanism of action is the theoretical base for its use also for tumors different from HGG. Nevertheless, no homogenous protocol of fluorescein utilization in neurosurgical oncology can be found in literature. Fluorescein-guided surgery is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration, with a growing evidence-based background.

Design and validation of a diffuse reflectance and spectroscopic microendoscope with poly(dimethylsioxane)-based phantoms

PubMed Central

Greening, Gage J.; Powless, Amy J.; Hutcheson, Joshua A.; Prieto, Sandra P.; Majid, Aneeka A.; Muldoon, Timothy J.

2015-01-01

Many cases of epithelial cancer originate in basal layers of tissue and are initially undetected by conventional microendoscopy techniques. We present a bench-top, fiber-bundle microendoscope capable of providing high resolution images of surface cell morphology. Additionally, the microendoscope has the capability to interrogate deeper into material by using diffuse reflectance and broadband diffuse reflectance spectroscopy. The purpose of this multimodal technique was to overcome the limitation of microendoscopy techniques that are limited to only visualizing morphology at the tissue or cellular level. Using a custom fiber optic probe, high resolution surface images were acquired using topical proflavine to fluorescently stain non-keratinized epithelia. A 635 nm laser coupled to a 200 μm multimode fiber delivers light to the sample and the diffuse reflectance signal was captured by a 1 mm image guide fiber. Finally, a tungsten-halogen lamp coupled to a 200 μm multimode fiber delivers broadband light to the sample to acquire spectra at source-detector separations of 374, 729, and 1051 μm. To test the instrumentation, a high resolution proflavine-induced fluorescent image of resected healthy mouse colon was acquired. Additionally, five monolayer poly(dimethylsiloxane)-based optical phantoms with varying absorption and scattering properties were created to acquire diffuse reflectance profiles and broadband spectra. PMID:25983372

Design and validation of a diffuse reflectance and spectroscopic microendoscope with poly(dimethylsiloxane)-based phantoms

NASA Astrophysics Data System (ADS)

Greening, Gage J.; Powless, Amy J.; Hutcheson, Joshua A.; Prieto, Sandra P.; Majid, Aneeka A.; Muldoon, Timothy J.

2015-03-01

Many cases of epithelial cancer originate in basal layers of tissue and are initially undetected by conventional microendoscopy techniques. We present a bench-top, fiber-bundle microendoscope capable of providing high resolution images of surface cell morphology. Additionally, the microendoscope has the capability to interrogate deeper into material by using diffuse reflectance and broadband diffuse reflectance spectroscopy. The purpose of this multimodal technique was to overcome the limitation of microendoscopy techniques that are limited to only visualizing morphology at the tissue or cellular level. Using a custom fiber optic probe, high resolution surface images were acquired using topical proflavine to fluorescently stain non-keratinized epithelia. A 635 nm laser coupled to a 200 μm multimode fiber delivers light to the sample and the diffuse reflectance signal was captured by a 1 mm image guide fiber. Finally, a tungsten-halogen lamp coupled to a 200 μm multimode fiber delivers broadband light to the sample to acquire spectra at source-detector separations of 374, 729, and 1051 μm. To test the instrumentation, a high resolution proflavine-induced fluorescent image of resected healthy mouse colon was acquired. Additionally, five monolayer poly(dimethylsiloxane)-based optical phantoms with varying absorption and scattering properties were created to acquire diffuse reflectance profiles and broadband spectra.

Multimodal fiber-probe spectroscopy as a clinical tool for diagnosing and classifying biological tissues

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Anand, Suresh; Fantechi, Riccardo; Giordano, Flavio; Gacci, Mauro; Conti, Valerio; Nesi, Gabriella; Buccoliero, Anna Maria; Carini, Marco; Guerrini, Renzo; Pavone, Francesco Saverio

2017-07-01

An optical fiber probe for multimodal spectroscopy was designed, developed and used for tissue diagnostics. The probe, based on a fiber bundle with optical fibers of various size and properties, allows performing spectroscopic measurements with different techniques, including fluorescence, Raman, and diffuse reflectance, using the same probe. Two visible laser diodes were used for fluorescence spectroscopy, a laser diode emitting in the NIR was used for Raman spectroscopy, and a fiber-coupled halogen lamp for diffuse reflectance. The developed probe was successfully employed for diagnostic purposes on various tissues, including brain and bladder. In particular, the device allowed discriminating healthy tissue from both tumor and dysplastic tissue as well as to perform tumor grading. The diagnostic capabilities of the method, determined using a cross-validation method with a leave-one-out approach, demonstrated high sensitivity and specificity for all the examined samples, as well as a good agreement with histopathological examination performed on the same samples. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities with respect to what can be obtained from individual techniques. The experimental setup presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used clinically for guiding surgical resection in the near future.

Image-derived arterial input function for quantitative fluorescence imaging of receptor-drug binding in vivo

PubMed Central

Elliott, Jonathan T.; Samkoe, Kimberley S.; Davis, Scott C.; Gunn, Jason R.; Paulsen, Keith D.; Roberts, David W.; Pogue, Brian W.

2017-01-01

Receptor concentration imaging (RCI) with targeted-untargeted optical dye pairs has enabled in vivo immunohistochemistry analysis in preclinical subcutaneous tumors. Successful application of RCI to fluorescence guided resection (FGR), so that quantitative molecular imaging of tumor-specific receptors could be performed in situ, would have a high impact. However, assumptions of pharmacokinetics, permeability and retention, as well as the lack of a suitable reference region limit the potential for RCI in human neurosurgery. In this study, an arterial input graphic analysis (AIGA) method is presented which is enabled by independent component analysis (ICA). The percent difference in arterial concentration between the image-derived arterial input function (AIFICA) and that obtained by an invasive method (ICACAR) was 2.0 ± 2.7% during the first hour of circulation of a targeted-untargeted dye pair in mice. Estimates of distribution volume and receptor concentration in tumor bearing mice (n = 5) recovered using the AIGA technique did not differ significantly from values obtained using invasive AIF measurements (p=0.12). The AIGA method, enabled by the subject-specific AIFICA, was also applied in a rat orthotopic model of U-251 glioblastoma to obtain the first reported receptor concentration and distribution volume maps during open craniotomy. PMID:26349671

The utility of high-resolution intraoperative MRI in endoscopic transsphenoidal surgery for pituitary macroadenomas: early experience in the Advanced Multimodality Image Guided Operating suite.

PubMed

Zaidi, Hasan A; De Los Reyes, Kenneth; Barkhoudarian, Garni; Litvack, Zachary N; Bi, Wenya Linda; Rincon-Torroella, Jordina; Mukundan, Srinivasan; Dunn, Ian F; Laws, Edward R

2016-03-01

Endoscopic skull base surgery has become increasingly popular among the skull base surgery community, with improved illumination and angled visualization potentially improving tumor resection rates. Intraoperative MRI (iMRI) is used to detect residual disease during the course of the resection. This study is an investigation of the utility of 3-T iMRI in combination with transnasal endoscopy with regard to gross-total resection (GTR) of pituitary macroadenomas. The authors retrospectively reviewed all endoscopic transsphenoidal operations performed in the Advanced Multimodality Image Guided Operating (AMIGO) suite from November 2011 to December 2014. Inclusion criteria were patients harboring presumed pituitary macroadenomas with optic nerve or chiasmal compression and visual loss, operated on by a single surgeon. Of the 27 patients who underwent transsphenoidal resection in the AMIGO suite, 20 patients met the inclusion criteria. The endoscope alone, without the use of iMRI, would have correctly predicted extent of resection in 13 (65%) of 20 cases. Gross-total resection was achieved in 12 patients (60%) prior to MRI. Intraoperative MRI helped convert 1 STR and 4 NTRs to GTRs, increasing the number of GTRs from 12 (60%) to 16 (80%). Despite advances in visualization provided by the endoscope, the incidence of residual disease can potentially place the patient at risk for additional surgery. The authors found that iMRI can be useful in detecting unexpected residual tumor. The cost-effectiveness of this tool is yet to be determined.

With a Little Help from My Friends: The Role of Intraoperative Fluorescent Dyes in the Surgical Management of High-Grade Gliomas

PubMed Central

Maugeri, Rosario; Villa, Alessandro; Pino, Mariangela; Imperato, Alessia; Costantino, Gabriele; Graziano, Francesca; Gulì, Carlo; Meli, Francesco; Francaviglia, Natale; Iacopino, Domenico Gerardo

2018-01-01

High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA) is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX) is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS), on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB) areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO) but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients. PMID:29414911

The use of intraoperative near-infrared indocyanine green videoangiography in the microscopic resection of hemangioblastomas.

PubMed

Tamura, Yoji; Hirota, Yuki; Miyata, Shiro; Yamada, Yoshitaka; Tucker, Adam; Kuroiwa, Toshihiko

2012-08-01

The authors assessed the usefulness of intraoperative near-infrared indocyanine green videoangiography (ICG-VA) in the microscopic resection of hemangioblastomas. From January 2009 to February 2012, nine consecutive patients (seven men, two women) who underwent surgery for hemangioblastomas using intraoperative ICG-VA were included in this study. Surgery was performed on four cystic cerebellar lesions with mural nodules, two solid tumors (one in the cerebellar hemisphere and one in the medulla oblongata), one spinal tumor and multiple tumors in two patients with von Hippel-Lindau disease. Of the nine patients, three were treated for recurrent tumor. The ICG-induced fluorescence images of hemangioblastomas with variable presentation were evaluated. All tumors could be completely removed en bloc. Blood flow in the tumor and tumor-related vessels at the brain surface were clearly detected by ICG-VA in all cases, except one recurrent tumor where postoperative adhesive scar tissue obstructed ICG-induced fluorescence resulting in poor delineation of the blood flow patterns and tumor margins. ICG-VA was also helpful for detecting the multiple small mural nodules within the cyst or the tumors buried under thin gliotic neural tissue despite reduced fluorescence. Intraoperative ICG-VA is a safe and easy modality for confirming the vascular flow patterns in hemangioblastomas. In addition, ICG-VA provided useful information for intracystic small lesions or lesions concealed under thin brain tissue in order to accomplish total resection of these tumors.

Development of new devices for detection of gastric cancer on laparoscopic surgery using near-infrared light

NASA Astrophysics Data System (ADS)

Inada, Shunko A.; Fuchi, Shingo; Mori, Kensaku; Hasegawa, Junichi; Misawa, Kazunari; Nakanishi, Hayao

2015-03-01

In recent year, for the treatment of gastric cancer the laparoscopic surgery is performed, which has good benefits, such as low-burden, low-invasive and the efficacy is equivalent to the open surgery. For identify location of the tumor intraperitoneally for extirpation of the gastric cancer, several points of charcoal ink is injected around the primary tumor. However, in the time of laparoscopic operation, it is difficult to estimate specific site of primary tumor, because the injected charcoal ink diffusely spread to the area distant from the tumor in the stomach. Therefore, a broad area should be resected which results in a great stress for the patients. To overcome this problem, we focused in the near-infrared wavelength of 1000nm band which have high biological transmission. In this study, we developed a fluorescent clip which was realized with glass phosphor (Yb3+, Nd3+ doped to Bi2O3-B2O3 based glasses. λp: 976 nm, FWHM: 100 nm, size: 2x1x3 mm) and the laparoscopic fluorescent detection system for clip-derived near-infrared light. To evaluate clinical performance of a fluorescent clip and the laparoscopic fluorescent detection system, we used resected stomach (thickness: 13 mm) from the patients. Fluorescent clip was fixed on the gastric mucosa, and an excitation light (λ: 808 nm) was irradiated from outside of stomach for detection of fluorescence through stomach wall. As a result, fluorescence emission from the clip was successfully detected. Furthermore, we confirmed that detection sensitivity of the emission of fluorescence from the clip depends on the output power of the excitation light. We conformed that the fluorescent clip in combination with laparoscopic fluorescent detection system is very useful method to identify the exact location of the primary gastric cancer.

Feasibility of simultaneous sodium fluorescein and indocyanine green injection in neurosurgical procedures.

PubMed

Acerbi, F; Restelli, F; Broggi, M; Schiariti, M; Ferroli, P

2016-07-01

The objective of this study is to assess the feasibility of simultaneous Sodium Fluorescein (SF) and Indocyanine Green (ICG) injection during neurosurgical procedures. Three patients harboring a high-grade glioma (HGG) were retrospectively identified in the surgical database of the Neurosurgical Unit 2 at the Foundation IRCCS Istituto Neurologico C. Besta in Milan, by having received intraoperatively both SF for tumor resection and ICG for vasculature angiographic studies in the same surgical procedure. We identified 2 males and 1 female (age range 25-60). Lesions were located in the left temporo-polar area and hippocampus (1 case), right superior frontal gyrus (1 case), left supplementary motor area (1 case). All the three lesions showed Magnetic Resonance Imaging (MRI) characteristics of HGG and, for this reason, in all patients a fluorescein-guided tumor removal was proposed. In the same surgical procedure ICG videoangiography was considered necessary in order to study arterial and venous vasculature, given by the strict relation of the tumor with an unexpected Posterior Communicating Artery (PComA) aneurysm in one case and with cortical drainage veins complexes in the other two cases. In all cases a microscope equipped with both YELLOW560 and IR800 integrated filters (Pentero 900, Carl Zeiss, Oberkorchen, Germany) was used. Fluorescein was i.v. injected at a dose of 5mg/kg immediately after patient intubation. ICG was i.v. injected in bolus on demand of the operating surgeon at a dose of 12.5mg. No side-effects related to simultaneous injection of SF and ICG were identified. In all three cases, the use of SF allowed to better visualize the tumor areas during surgical removal, thus leading to a radical resection until no macroscopic appearance of residual tumor mass and no fluorescence was visible in the surgical cavity. ICG videoangiography confirmed the patency of branches of internal carotid artery after clipping of an unexpected small PComA aneurysm found intraoperatively during tumor removal in one case, while in patient 2 and 3 it allowed to evaluate patency and study flow pattern in cortical drainage veins that were intimately related to the tumors and the way of the surgical approach. Postoperative MRI showed a Gross Total Resection of the tumors in all cases. This study showed for the first time the feasibility of intravenous SF injection and ICG videoangiography in the same surgical procedure. The presence of different fluorescence filters on the same surgical microscope allows the surgeon to recognize and safely resect the tumor and simultaneously evaluate local brain vascularization. Copyright © 2016 Elsevier B.V. All rights reserved.

Preclinical Comparison of Near-Infrared-Labeled Cetuximab and Panitumumab for Optical Imaging of Head and Neck Squamous Cell Carcinoma

PubMed Central

Day, Kristine E.; Sweeny, Larissa; Kulbersh, Brian; Zinn, Kurt R.; Rosenthal, Eben L.

2014-01-01

Purpose: Though various targets have been proposed and evaluated, no agent has yet been investigated in a clinical setting for head and neck cancer. The present study aimed to compare two fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibodies for detection of head and neck squamous cell carcinoma (HNSCC). Procedures: Antigen specificities and in vitro imaging of the fluorescently labeled anti-EGFR antibodies were performed. Next, immunodeficient mice (n=22) bearing HNSCC (OSC-19 and SCC-1) tongue tumors received systemic injections of cetuximab-IRDye800CW, panitumumab-IRDye800CW, or IgG-IRDye800CW (a nonspecific control). Tumors were imaged and resected using two near-infrared imaging systems, SPY and Pearl. Fluorescent lymph nodes were also identified, and all resected tissues were sent for pathology. Results: Panitumumab-IRDye800CW and cetuximab-IRDye800CW had specific and high affinity binding for EGFR (KD=0.12 and 0.31 nM, respectively). Panitumumab-IRDye800CW demonstrated a 2-fold increase in fluorescence intensity compared to cetuximab-IRDye800CW in vitro. In vivo, both fluorescently labeled antibodies produced higher tumor-to-background ratios compared to IgG-IRDye800CW. However, there was no significant difference between the two in either cell line or imaging modality (OSC-19: p=0.08 SPY, p=0.48 Pearl; SCC-1: p=0.77 SPY, p=0.59 Pearl; paired t tests). Conclusions: There was no significant difference between the two fluorescently labeled anti-EGFR monoclonal antibodies in murine models of HNSCC. Both cetuximab and panitumumab can be considered suitable targeting agents for fluorescent intraoperative detection of HNSCC. PMID:23715932

Virally-directed Fluorescent Imaging (VFI) Improves Diagnostic Sensitivity in the Detection of Minimal Residual Disease Following Potentially Curative Cytoreductive Surgery

PubMed Central

Adusumilli, Prasad S.; Eisenberg, David P.; Chun, Yun Shin; Ryu, Keun-Won; Ben-Porat, Leah; Hendershott, Karen; Chan, Mei-Ki; Huq, Rumana; Riedl, Christopher; Fong, Yuman

2005-01-01

Background Completeness of cytoreduction is an independent prognostic factor following cure-intended surgery for peritoneal carcinomatosis (PC). Intraoperative detection of the minimal residual disease may aid in achieving complete cytoreduction. NV1066, a genetically-engineered herpes simplex virus carrying the transgene for green fluorescent protein (GFP), selectively infects cancer cells. NV1066-infected cancer cells express GFP that can be detected by fluorescence laparoscopy. We sought to determine the feasibility of Virally-directed Fluorescent Imaging (VFI) in the intraoperative detection of minimal residual disease following cytoreductive surgery. Methods Human cancer cell lines OCUM-2MD3 (gastric) and JMN (malignant Mesothelioma) were infected with NV1066 at MOIs (multiplicity of infection; ratio of viral particles to cancer cells) of 0.01, 0.1 and 1.0. Viral infectivity was determined by flow cytometry for GFP and cytotoxicity was determined by a colorimetric assay. PC was established in mice by injection of OCUM cells into the peritoneal cavity. Forty-eight hours following intraperitoneal injection of NV1066, two experienced surgeons resected all visible disease and identified mice free of disease. Five independent observers examined these mice by bright-field and fluorescent laparoscopy and documented residual disease as per the peritoneal cancer index. Selective expression of GFP in tumor tissue was evaluated by histology and PCR for the viral gene ICP0. Results In vitro, NV1066 infected, expressed GFP, and killed both cell lines at all MOIs. GFP signal was detected as early as 4-6 hours following infection. GFP signal intensity of infected cells was significantly higher than the autofluorescence of normal cells (230 – 670 -logs). In vivo, macroscopically undetectable tumor nodules by gross examination and conventional bright-field laparoscopy were identified by GFP fluorescence. Following resection, 8 of 13 mice thought to be free of disease were found to have residual disease as identified by green fluorescence (mean number of observations: 5 range: 1-9). Residual disease was most frequently observed in the retroperitoneum, pelvis, peritoneal surface, and liver (inter-observer agreement 99%). Specificity of NV1066 infection to tumor nodules was confirmed by immunohistochemistry and by PCR for viral gene. Conclusion We have demonstrated that virally-directed fluorescent imaging (VFI), a novel molecular imaging technology, can be used for real-time visualization of minimal residual disease following cytoreductive surgery and can improve the completeness of cure-intended resection. PMID:16269385

Low dose mTHPC photodynamic therapy for cholangiocarcinoma

NASA Astrophysics Data System (ADS)

Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

2013-06-01

Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma

PubMed Central

Day, Kristine E.; Beck, Lauren N.; Heath, C. Hope; Huang, Conway C.; Zinn, Kurt R.; Rosenthal, Eben L.

2013-01-01

Intraoperative, real-time fluorescence imaging may significantly improve tumor visualization and resection and postoperatively, in pathological assessment. To this end, we sought to determine the optimal FDA approved therapeutic monoclonal antibody for optical imaging of human cutaneous squamous cell carcinoma (cSCC). A near-infrared (NIR) fluorescent probe (IRDye800) was covalently linked to bevacizumab, panitumumab or tocilizumab and injected systemically into immunodeficient mice bearing either cutaneous tumor cell lines (SCC13) or cutaneous human tumor explants. Tumors were then imaged and resected under fluorescent guidance with the SPY, an FDA-approved intraoperative imaging system, and the Pearl Impulse small animal imaging system. All fluorescently labeled antibodies delineated normal tissue from tumor in SCC13 xenografts based on tumor-to-background (TBR) ratios. The conjugated antibodies produced TBRs of 1.2–2 using SPY and 1.6–3.6 using Pearl; in comparison, isotype control antibody IgG-IRDye produced TBRs of 1.0 (SPY) and 0.98 (Pearl). Comparison between antibodies revealed them to be roughly equivalent for imaging purposes with both the SPY and Pearl (p = 0.89 SPY, p = 0.99 Pearl; one way ANOVA). Human tumor explants were also imaged and tumor detection was highest with panitumumab-IRDye800 when using the SPY (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC. PMID:23298904

Microfluidics for rapid detection of isocitrate dehydrogenase 1 mutation for intraoperative application.

PubMed

Aibaidula, Abudumijiti; Zhao, Wang; Wu, Jin-Song; Chen, Hong; Shi, Zhi-Feng; Zheng, Lu-Lu; Mao, Ying; Zhou, Liang-Fu; Sui, Guo-Dong

2016-06-01

OBJECT Conventional methods for isocitrate dehydrogenase 1 (IDH1) detection, such as DNA sequencing and immunohistochemistry, are time- and labor-consuming and cannot be applied for intraoperative analysis. To develop a new approach for rapid analysis of IDH1 mutation from tiny tumor samples, this study used microfluidics as a method for IDH1 mutation detection. METHODS Forty-seven glioma tumor samples were used; IDH1 mutation status was investigated by immunohistochemistry and DNA sequencing. The microfluidic device was fabricated from polydimethylsiloxane following standard soft lithography. The immunoanalysis was conducted in the microfluidic chip. Fluorescence images of the on-chip microcolumn taken by the charge-coupled device camera were collected as the analytical results readout. Fluorescence signals were analyzed by NIS-Elements software to gather detailed information about the IDH1 concentration in the tissue samples. RESULTS DNA sequencing identified IDH1 R132H mutation in 33 of 47 tumor samples. The fluorescence signal for IDH1-mutant samples was 5.49 ± 1.87 compared with 3.90 ± 1.33 for wild type (p = 0.005). Thus, microfluidics was capable of distinguishing IDH1-mutant tumor samples from wild-type samples. When the cutoff value was 4.11, the sensitivity of microfluidics was 87.9% and the specificity was 64.3%. CONCLUSIONS This new approach was capable of analyzing IDH1 mutation status of tiny tissue samples within 30 minutes using intraoperative microsampling. This approach might also be applied for rapid pathological diagnosis of diffuse gliomas, thus guiding personalized resection.

A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer.

PubMed

Adumeau, Pierre; Carnazza, Kathryn E; Brand, Christian; Carlin, Sean D; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M

2016-01-01

The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89 Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans -cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64 Cu-labeled tetrazine radioligand ( 64 Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful clinical tool.

3D Navigation-guided Resection of Giant Ventral Cervical Intradural Schwannoma With 360-Degree Stabilization.

PubMed

Hussain, Ibrahim; Navarro-Ramirez, Rodrigo; Lang, Gernot; Härtl, Roger

2018-06-01

Giant schwannomas are defined as intradural extramedullary tumors that span >2 vertebral body lengths. Although uncommon, these lesions can cause significant mass effect on the spinal cord and subsequent neurologic compromise. Gross total resection is the goal of operative intervention, however, is extremely challenging in cases where the tumor occupies a ventral, midline position within the lower cervical thecal sac. Using a representative case presentation, we describe an adult male with insidious progression of upper extremity radicular pain and paresthesias, found to have a ventral, solid/cystic C5-C7 giant schwannoma. We demonstrate the step-by-step surgical technique for an anterior approach 2-level cervical corpectomy, microsurgical resection of an intradural giant schwannoma, watertight dural closure, and lastly 360-degrees instrumented stabilization of the cervicothoracic spine. In addition we incorporate the utilization of a portable intraoperative computed tomography for stereotactic localization and 3-dimensional navigation-guided screw implantation. Finally, we discuss various preoperative, perioperative, and postoperative considerations that can have profound impact on successful outcomes.

XFEM-based modeling of successive resections for preoperative image updating

NASA Astrophysics Data System (ADS)

Vigneron, Lara M.; Robe, Pierre A.; Warfield, Simon K.; Verly, Jacques G.

2006-03-01

We present a new method for modeling organ deformations due to successive resections. We use a biomechanical model of the organ, compute its volume-displacement solution based on the eXtended Finite Element Method (XFEM). The key feature of XFEM is that material discontinuities induced by every new resection can be handled without remeshing or mesh adaptation, as would be required by the conventional Finite Element Method (FEM). We focus on the application of preoperative image updating for image-guided surgery. Proof-of-concept demonstrations are shown for synthetic and real data in the context of neurosurgery.

Photodynamic application in neurosurgery: present and future

NASA Astrophysics Data System (ADS)

Kostron, Herwig

2009-06-01

Photodynamic techniques such as photodynamic diagnosis (PDD), fluorescence guided tumor resection (FGR) and photodynamic therapy (PDT) are currently undergoing intensive clinical investigations as adjunctive treatment for malignant brain tumours. This review provides an overview on the current clinical data and trials as well as on photosensitisers, technical developments and indications for photodynamic application in Neurosurgery. Furthermore new developments and clinical significance of FGR for neurosurgery will be discussed. Over 1000 patients were enrolled in various clinical phase I/II trials for PDT for malignant brain tumours. Despite various treatment protocols, variation of photosensitisers and light dose there is a clear trend towards prolonging median survival after one single PDT as compared to conventional therapeutic modalities. The median survival after PDT for primary glioblastoma multiforme WHO IV was 19 months and for recurrent GBM 9 months as compared to standard convential treatment which is 15 months and 3 months, respectively. FGR in combination with adjunctive radiation was significantly superior to standard surgical resection followed by radiation. The combination of FGR/PDD and intraoperative PDT increased significantly survival in recurrent glioblastoma patients. The combination of PDD/ FGR and PDT offers an exciting approach to the treatment of malignant brain tumours "to see and to treat." PDT was generally well tolerated and side effects consisted of occasionally increased intracranial pressure and prolonged skin sensitivity against direct sunlight. This review covers the current available data and draws the future potential of PDD and PDT for its application in neurosurgery.

Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention

PubMed Central

Paulsen, Keith D.; Samkoe, Kimberley S.; Elliott, Jonathan T.; Hasan, Tayyaba; Strong, Theresa V.; Draney, Daniel R.; Feldwisch, Joachim

2016-01-01

Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective performance criteria, and issues around calibration, validation, and interpretation need to be established before a clinical trial starts. Finally, as early phase trials become more established, the costs associated with failures can be crippling to the field, and so judicious use of phase 0 trials with microdose levels of agents is one viable paradigm to help the field advance, but this places high sensitivity requirements on the imaging systems used. Molecular-guided surgery has truly transformative potential, and several key challenges are outlined here with the goal of seeing efficient advancement with ideal choices. The focus of this vision 20/20 paper is on the technological aspects that are needed to be paired with these agents. PMID:27277060

Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention.

PubMed

Pogue, Brian W; Paulsen, Keith D; Samkoe, Kimberley S; Elliott, Jonathan T; Hasan, Tayyaba; Strong, Theresa V; Draney, Daniel R; Feldwisch, Joachim

2016-06-01

Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective performance criteria, and issues around calibration, validation, and interpretation need to be established before a clinical trial starts. Finally, as early phase trials become more established, the costs associated with failures can be crippling to the field, and so judicious use of phase 0 trials with microdose levels of agents is one viable paradigm to help the field advance, but this places high sensitivity requirements on the imaging systems used. Molecular-guided surgery has truly transformative potential, and several key challenges are outlined here with the goal of seeing efficient advancement with ideal choices. The focus of this vision 20/20 paper is on the technological aspects that are needed to be paired with these agents.

The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery

PubMed Central

Schaafsma, Boudewijn E.; Mieog, J.Sven D.; Hutteman, Merlijn; van der Vorst, Joost R.; Kuppen, Peter J.K.; Löwik, Clemens W.G.M.; Frangioni, John V.; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.

2011-01-01

Optical imaging using near-infrared (NIR) fluorescence provides new prospects for general and oncologic surgery. ICG is currently utilised in NIR fluorescence cancer-related surgery for three indications: sentinel lymph node (SLN) mapping, intraoperative identification of solid tumours, and angiography during reconstructive surgery. Therefore, understanding its advantages and limitations is of significant importance. Although non-targeted and non-conjugatable, ICG appears to be laying the foundation for more widespread use of NIR fluorescence-guided surgery. PMID:21495033

Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis

PubMed Central

Hur, H; Kim, N K; Kim, H G; Min, B S; Lee, K Y; Shin, S J; Cheon, J H; Choi, S H

2012-01-01

Background: This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis. Patients and methods: Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared. Results: Between November 2008 and October 2010, a total 63 patients were randomised to Group A (N=32) or Group B (N=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) vs 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% vs 21.9%, P=0.027). The resectability of hepatic lesion was higher in Group B (35.5% vs 12.5%, P=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B. Conclusion: This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis. PMID:22068817

Three-dimensional printing and computer navigation assisted hemipelvectomy for en bloc resection of osteochondroma

PubMed Central

Zhang, Yaqing; Wen, Lianjiang; Zhang, Jun; Yan, Guoliang; Zhou, Yue; Huang, Bo

2017-01-01

Abstract Rationale: Three-dimensional (3D) printed templates can be designed to match an individual's anatomy, allowing surgeons to refine preoperative planning. In addition, the use of computer navigation (NAV) is gaining popularity to improve surgical accuracy in the resection of pelvic tumors. However, its use in combination with 3D printing to assist complex pelvic tumor resection has not been reported. Patient concerns: A 36-year-old man presented with left-sided pelvic pain and a fast-growing mass. He also complained of a 3-month history of radiating pain and numbness in the lower left extremity. Diagnoses: A biopsy revealed an osteochondroma with malignant potential. This osteochondroma arises from the ilium and involves the sacrum and lower lumbar vertebrae. Interventions: Here, we describe a novel combined application of 3D printing and intraoperative NAV systems to guide hemipelvectomy for en-bloc resection of the osteochondroma. The 3D printed template is analyzed during surgical planning and guides the initial intraoperative bone work to improve surgical accuracy and efficiency, while a computer NAV system provides real-time imaging during the tumor removal to achieve adequate resection margins and minimize the likelihood of injury to adjacent critical structures. Outcomes: The tumor mass and the invaded spinal structures were removed en bloc. Lessons: The combined application of 3D printing and computer NAV may be useful for tumor targeting and safe osteotomies in pelvic tumor surgery. PMID:28328842

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer.

PubMed

Rosenthal, Eben L; Moore, Lindsay S; Tipirneni, Kiranya; de Boer, Esther; Stevens, Todd M; Hartman, Yolanda E; Carroll, William R; Zinn, Kurt R; Warram, Jason M

2017-08-15

Purpose: Comprehensive cervical lymphadenectomy can be associated with significant morbidity and poor quality of life. This study evaluated the sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic disease in patients with head and neck cancer. Experimental Design: Consenting patients scheduled for curative resection were enrolled in a clinical trial to evaluate the safety and specificity of cetuximab-IRDye800CW. Patients ( n = 12) received escalating doses of the study drug. Where indicated, cervical lymphadenectomy accompanied primary tumor resection, which occurred 3 to 7 days following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph nodes were imaged with a closed-field, near-infrared imaging device during gross processing of the fresh specimens. Intraoperative imaging of exposed neck levels was performed with an open-field fluorescence imaging device. Blinded assessments of the fluorescence data were compared to histopathology to calculate sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results: Of the 35 nodes diagnosed pathologically positive, 34 were correctly identified with fluorescence imaging, yielding a sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were correctly assessed using fluorescence imaging, yielding a specificity of 92.7%. The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently false-positive nodes were sectioned deeper (1 mm) into their respective blocks, metastatic cancer was found in 8.1% of the recut nodal specimens, which altered staging in two of those cases. Conclusions: Fluorescence imaging of lymph nodes after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity and was capable of identifying additional positive nodes on deep sectioning. Clin Cancer Res; 23(16); 4744-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Sonography-guided hydrostatic reduction of ileocolic intussusception in children: analysis of failure and success in consecutive patients presenting timely to the hospital.

PubMed

Menke, Jan; Kahl, Fritz

2015-03-01

In children with ileocolic intussusception sonography is increasingly being used for diagnosis, whereas fluoroscopy is frequently used for guiding non-invasive reduction. This study assessed the success rate of radiation-free sonography-guided hydrostatic reduction in children with ileocolic intussusception, using novel well-defined success rate indices. All children were evaluated who presented from 2005 to 2013 to the local university hospital with ileocolic intussusception. The patients were treated with sonography-guided hydrostatic reduction unless primary surgery was clinically indicated. The according success rate was determined by indices of Bekdash et al. They represent the ratio of persistently successful non-surgical reductions versus four different denominators, depending on including/excluding cases with primary surgery and including/excluding cases requiring bowel resection/intervention. Fifty-six consecutive patients were included (age, 3 months to 7.8 years). About 80% of the patients presented until 24 h and 20% until 48 h after the onset of symptoms. Seven patients underwent primary surgery, with bowel resection required in three cases. Hydrostatic reduction was attempted in 49 patients, being permanently successful in 41 cases (selective reduction rate 41/49 = 83.7%; crude reduction rate 41/56 = 73.2%). The remaining eight patients underwent secondary surgery, with just two patients not requiring surgical bowel resection/intervention (corrected selective reduction rate 41/43 = 95.3%). The composite reduction rate was 87.2% (successful/feasible reductions, 41/47). Radiation-free sonography-guided hydrostatic reduction has a good success rate in children with ileocolic intussusception. It may be particularly valuable in centers that are already experienced with using sonography for the diagnosis.

Effect of digital template in the assistant of a giant condylar osteochondroma resection.

PubMed

Bai, Guo; He, Dongmei; Yang, Chi; Lu, Chuan; Huang, Dong; Chen, Minjie; Yuan, Jianbing

2014-05-01

Exostosis osteochondroma is usually resected with the whole condyle even part of it is not involved. This study was to report the effect of using digital template in the assistant of resection while protecting the uninvolved condyle. We used computer-aided design technique in the assistant of making preoperative plan of a patient with giant condylar osteochondroma of exogenous type, including determining the boundary between the tumor and the articular surface of condyle, and designing the virtual tumor resection plane, surgical approach, and remove-out path of the tumor. The digital osteotomy template was made by rapid prototyping technique based on the preoperative plan. Postoperative CT scan was performed and merged with the preoperative CT by the Proplan 1.3 system to evaluate the accuracy of surgical resection with the guide of digital template. The osteotomy template was attached to the lateral surface of condyle accurately, and the tumor was removed totally by the guide of the template without injuries to adjacent nerves and vessels. Postoperative CT showed that the osteochondroma was removed completely and the unaffected articular surface of condyle was preserved well. The merging of postoperative and preoperative CT by Proplan 1.3 system showed the outcome of the operation matched with the preoperative planning quite well with an error of 0.92 mm. There was no sign of recurrence after 6 months of follow-up. The application of digital template could improve the accuracy of the giant condylar tumor resection and help to preserve the uninvolved condyle. The use of digital template could reduce injuries to the nerves and vessels as well as save time for the operation.

Endoscopic image-guided thermal therapy using targeted near infrared fluorescent gold nanorods (Conference Presentation)

NASA Astrophysics Data System (ADS)

Elson, Daniel S.

2016-09-01

We present an in vivo study of endoscopic fluorescence image-guided photothermal therapy of human oesophageal adenocarcinoma in a murine xenograft model, using intratumoural or intravenous gold nanorods functionalised with Cy5.5 and EGFR.

Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection.

PubMed

Altieri, Roberto; Zenga, Francesco; Fontanella, Marco Maria; Cofano, Fabio; Agnoletti, Alessandro; Spena, Giannantonio; Crobeddu, Emanuela; Fornaro, Riccardo; Ducati, Alessandro; Garbossa, Diego

2015-11-01

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.

Towards a successful clinical implementation of fluorescence-guided surgery.

PubMed

Snoeks, T J A; van Driel, P B A A; Keereweer, S; Aime, S; Brindle, K M; van Dam, G M; Löwik, C W G M; Ntziachristos, V; Vahrmeijer, A L

2014-04-01

During the European Molecular Imaging Meeting (EMIM) 2013, the fluorescence-guided surgery study group held its inaugural session to discuss the clinical implementation of fluorescence-guided surgery. The general aim of this study group is to discuss and identify the steps required to successfully and safely bring intraoperative fluorescence imaging to the clinics. The focus group intends to use synergies between interested groups as a tool to address regulatory and implementation hurdles in Europe and operates within the intraoperative focus group of the World Molecular Imaging Society (WMIS) that promotes the same interests at the WMIS level. The major topics on the critical path of implementation identified within the study group were quality controls and standards for ensuring accurate imaging and the ability to compare results from different studies, regulatory affairs, and strategies to increase awareness among physicians, regulators, insurance companies, and a broader audience. These hurdles, and the possible actions discussed to overcome them, are summarized in this report. Furthermore, a number of recommendations for the future shape of the fluorescence-guided study group are discussed. A main driving conclusion remains that intraoperative imaging has great clinical potential and that many of the solutions required are best addressed with the community working together to optimally promote and accelerate the clinical implementation of fluorescence imaging towards improving surgical procedures.

Endoscopic fluorescence imaging for early assessment of anastomotic recurrence of Crohn's disease

NASA Astrophysics Data System (ADS)

Mordon, Serge R.; Maunoury, Vincent; Geboes, K.; Klein, Olivier; Desreumaux, P.; Debaert, A.; Colombel, Jean-Frederic

1999-02-01

Crohn's disease is an inflammatory bowel disease of unknown etiology. The mechanism of the initial mucosal alterations is still unclear: ulcerations overlying lymphoid follicles and/or vasculitis have been proposed as the early lesions. We have developed a new and original method combining endoscopy of fluorescence angiography for identifying the early pathological lesions, occurring in the neo-terminal ileum after right ileocolonic resection. The patient population consisted of 10 subjects enrolled in a prospective protocol of endoscopic follow-up at 3 and 12 months after surgery. Fluorescence imaging showed small spots giving a bright fluorescence distributed singly in mucosa which appeared normal in routine endoscopy. Histopathological examination demonstrated that the fluorescence of small spots originated from small, usually superficial, erosive lesions. In several cases, these erosive lesions occurred over lymphoid follicles. Endoscopic fluorescence imaging provides a suitable means of investigating the initial aspect of the Crohn's disease process in displaying some correlative findings between fluorescent aspects and early pathological mucosal alterations.

Photodynamic diagnosis (PDD) of bladder cancer with intravesical 5-aminolevulinic-acid-induced fluorescence

NASA Astrophysics Data System (ADS)

Grimbergen, Matthijs C. M.; Jonges, T. G. N.; Lock, M. Tycho W.; van Swol, Christiaan F. P.; Boon, Tom A.; van Moorselaar, R. Jeroen A.

2001-05-01

Flat urothelial lesions as well as small papillary tumors are easily missed during transurethral resection (TUR). PDD is based on the detection of protoporphyrin-IX induced fluorescence after topical administration of 5- aminolevulinic acid (ALA). We report on our initial clinical results of 130 procedures in 98 patients. Two hours prior to TUR 1.5 g ALA dissolved in 50 ml 1.4% NaHCO3 solution was installed intravesically. For fluorescence excitation a blue light source (375-440 nm, Karl Storz) was used. In total 478 biopsies (2-9 per patient) were taken from fluorescent and nonfluorescent areas. Normal nonfluorescent bladder urothelium was blue, whereas cancer epithelium developed a brilliant red fluorescence. During white light cystoscopy, 143 bladder tumors were found. Sixty-three additional tumors were detected because of their positive fluorescence. The overall sensitivity of fluorescence cystoscopy (98%) was greater than that of white light cystoscopy (69%). Their specificities were 51% and 80% respectively.

Indocyanine green fluorescence imaging in the surgical management of liver cancers: current facts and future implications.

PubMed

Lim, C; Vibert, E; Azoulay, D; Salloum, C; Ishizawa, T; Yoshioka, R; Mise, Y; Sakamoto, Y; Aoki, T; Sugawara, Y; Hasegawa, K; Kokudo, N

2014-04-01

Imaging detection of liver cancers and identification of the bile ducts during surgery, based on the fluorescence properties of indocyanine green, has recently been developed in liver surgery. The principle of this imaging technique relies on the intravenous administration of indocyanine green before surgery and the illumination of the surface of the liver by an infrared camera that simultaneously induces and collects the fluorescence. Detection by fluorescence is based on the contrast between the (fluorescent) tumoral or peri-tumoral tissues and the healthy (non-fluorescent) liver. Results suggest that indocyanine green fluorescence imaging is capable of identification of new liver cancers and enables the characterization of known hepatic lesions in real time during liver resection. The purpose of this paper is to present the fundamental principles of fluorescence imaging detection, to describe successively the practical and technical aspects of its use and the appearance of hepatic lesions in fluorescence, and to expose the diagnostic and therapeutic perspectives of this innovative imaging technique in liver surgery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Clinical use of endovenous indocyanine green during rectosigmoid segmental resection for endometriosis.

PubMed

Seracchioli, Renato; Raimondo, Diego; Arena, Alessandro; Zanello, Margherita; Mabrouk, Mohamed

2018-06-01

To describe a new use of endovenous indocyanine green (ICG) to allow real-time visualization of bowel perfusion in women with recto-sigmoid endometriosis who may be candidates for segmental resection. Step-by-step explanation of this method using descriptive text and educational video. Tertiary level referral academic center. A nulliparous 36-year-old woman affected by a large rectal endometriotic nodule was referred for severe dysmenorrhea, dyspareunia, hematochezia, and dyschezia, despite progestinic therapy. An intravenous injection of 1.5 mL solution containing 3.75 mg dose of ICG for intraoperative fluorescence imaging. Evaluation of blood perfusion of bowel and rectal endometriosis nodule. Evaluation of neoanastomosis vascularization after bowel resection. The procedure of endometriosis removal was performed using the daVinciXi surgical platform (Intuitive Surgical, Sunnyvale, CA). After ovarian endometriosis removal and adhesiolysis, we identified the endometriosis nodule on the anterior surface of the rectum. Pararectal, rectovaginal, and retrorectal spaces were dissected with a nerve-sparing technique. Indocyanine green was administered through a peripheral line. A near-infrared camera head enabled vision of the colorant after latency of a few seconds. We observed the ischemic area around the rectal nodule and perfusion areas upstream and downstream from the lesion. We selected the transecting line for rectal resection, taking account of this objective evaluation, beyond the limits of macroscopic disease. After direct mechanical anastomosis, we checked the rectal vascularization with ICG. To the best of our knowledge, this is the first reported use of endovenous ICG during a bowel resection for deep endometriosis. Endovenous ICG is proposed during surgery for rectosigmoid endometriosis to assess the perfusion of the bowel and select the transecting line. With ICG fluorescence imaging, we can objectively evaluate whether blood supply to the anastomosis is adequate. Endovenous ICG for objective vascular assessment is simple and rapid to use, and no complications related to ICG use were recorded. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The utility of high-resolution intraoperative MRI in endoscopic transsphenoidal surgery for pituitary macroadenomas: early experience in the Advanced Multimodality Image Guided Operating suite

PubMed Central

Zaidi, Hasan A.; De Los Reyes, Kenneth; Barkhoudarian, Garni; Litvack, Zachary N.; Bi, Wenya Linda; Rincon-Torroella, Jordina; Mukundan, Srinivasan; Dunn, Ian F.; Laws, Edward R.

2016-01-01

Objective Endoscopic skull base surgery has become increasingly popular among the skull base surgery community, with improved illumination and angled visualization potentially improving tumor resection rates. Intraoperative MRI (iMRI) is used to detect residual disease during the course of the resection. This study is an investigation of the utility of 3-T iMRI in combination with transnasal endoscopy with regard to gross-total resection (GTR) of pituitary macroadenomas. Methods The authors retrospectively reviewed all endoscopic transsphenoidal operations performed in the Advanced Multimodality Image Guided Operating (AMIGO) suite from November 2011 to December 2014. Inclusion criteria were patients harboring presumed pituitary macroadenomas with optic nerve or chiasmal compression and visual loss, operated on by a single surgeon. Results Of the 27 patients who underwent transsphenoidal resection in the AMIGO suite, 20 patients met the inclusion criteria. The endoscope alone, without the use of iMRI, would have correctly predicted 13 (65%) of 20 cases. Gross-total resection was achieved in 12 patients (60%) prior to MRI. Intraoperative MRI helped convert 1 STR and 4 NTRs to GTRs, increasing the number of GTRs from 12 (60%) to 16 (80%). Conclusions Despite advances in visualization provided by the endoscope, the incidence of residual disease can potentially place the patient at risk for additional surgery. The authors found that iMRI can be useful in detecting unexpected residual tumor. The cost-effectiveness of this tool is yet to be determined. PMID:26926058

Magnetoencephalography-guided surgery in frontal lobe epilepsy using neuronavigation and intraoperative MR imaging.

PubMed

Sommer, Björn; Roessler, Karl; Rampp, Stefan; Hamer, Hajo M; Blumcke, Ingmar; Stefan, Hermann; Buchfelder, Michael

2016-10-01

Especially in hidden lesions causing drug-resistant frontal lobe epilepsy (FLE), the localization of the epileptic zone EZ can be a challenge. Magnetoencephalography (MEG) can raise the chances for localization of the (EZ) in combination with electroencephalography (EEG). We investigated the impact of MEG-guided epilepsy surgery with the aid of neuronavigation and intraoperative MR imaging (iopMRI) on seizure outcome of FLE patients. Twenty-eight patients (15 females, 13 males; mean age 31.0±11.1 years) underwent surgery in our department. All patients underwent presurgical MEG monitoring (two-sensor Magnes II or whole head WH3600 MEG system; 4-D Neuroimaging, San Diego, CA, USA). Of those, six patients (group 1) with MRI-negative FLE were operated on before 2002 with intraoperative electrocorticography (ECoG) and invasive EEG mapping only. Eleven patients with MRI-negative FLE (group 2) and eleven with lesional FLE (group 3) underwent surgery using 1.5T-iopMRI and neuronavigation, including intraoperative visualization of the MEG localizations in 22 and functional MR imaging (for motor and speech areas) as well as DTI fiber tracking (for language and pyramidal tracts) in 13 patients. In the first group, complete resection of the defined EZ including the MEG localization according to the latest postoperative MRI was achieved in four out of six patients. Groups two and three had complete removal of the MEG localizations in 20/22 (91%, 10 of 11 each). Intraoperative MRI revealed incomplete resection of the MEG localizations of four patients (12%; two in both groups), leading to successful re-resection. Transient and permanent neurological deficits alike occurred in 7.1%, surgery-associated complications in 11% of all patients. In the first group, excellent seizure outcome (Engel Class IA) was achieved in three (50%), in the second in 7 patients (61%) and third group in 8 patients (64%, two iopMRI-based re-resections). Mean follow-up was 70.3 months (from 12 to 284 months). In our series, MEG-guided resection using neuronavigation and iopMR imaging led to promising seizure control rates. Even in non-lesional FLE, seizure control rates and the probability of complete resection of the MEG localizations was similar to lesional FLE using multimodal navigation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Photoacoustic Tomography of Human Hepatic Malignancies Using Intraoperative Indocyanine Green Fluorescence Imaging

PubMed Central

Miyata, Akinori; Ishizawa, Takeaki; Kamiya, Mako; Shimizu, Atsushi; Kaneko, Junichi; Ijichi, Hideaki; Shibahara, Junji; Fukayama, Masashi; Midorikawa, Yutaka; Urano, Yasuteru; Kokudo, Norihiro

2014-01-01

Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed to improve the visibility of photoacoustic signals emitted from deeply-located lesions. PMID:25379674

Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.

PubMed

Miyata, Akinori; Ishizawa, Takeaki; Kamiya, Mako; Shimizu, Atsushi; Kaneko, Junichi; Ijichi, Hideaki; Shibahara, Junji; Fukayama, Masashi; Midorikawa, Yutaka; Urano, Yasuteru; Kokudo, Norihiro

2014-01-01

Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed to improve the visibility of photoacoustic signals emitted from deeply-located lesions.

MRI-guided fluorescence tomography of the breast: a phantom study

NASA Astrophysics Data System (ADS)

Davis, Scott C.; Pogue, Brian W.; Dehghani, Hamid; Paulsen, Keith D.

2009-02-01

Tissue phantoms simulating the human breast were used to demonstrate the imaging capabilities of an MRI-coupled fluorescence molecular tomography (FMT) imaging system. Specifically, phantoms with low tumor-to-normal drug contrast and complex internal structure were imaged with the MR-coupled FMT system. Images of indocyanine green (ICG) fluorescence yield were recovered using a diffusion model-based approach capable of estimating the distribution of fluorescence activity in a tissue volume from tissue-boundary measurements of transmitted light. Tissue structural information, which can be determined from standard T1 and T2 MR images, was used to guide the recovery of fluorescence activity. The study revealed that this spatial guidance is critical for recovering images of fluorescence yield in tissue with low tumor-to-normal drug contrast.

Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography

NASA Astrophysics Data System (ADS)

Pan, Y. T.; Xie, T. Q.; Du, C. W.; Bastacky, S.; Meyers, S.; Zeidel, M. L.

2003-12-01

We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.

Autofluorescence lifetime imaging during transoral robotic surgery: a clinical validation study of tumor detection (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lagarto, João. L.; Phipps, Jennifer E.; Unger, Jakob; Faller, Leta M.; Gorpas, Dimitris; Ma, Dinglong M.; Bec, Julien; Moore, Michael G.; Bewley, Arnaud F.; Yankelevich, Diego R.; Sorger, Jonathan M.; Farwell, Gregory D.; Marcu, Laura

2017-02-01

Autofluorescence lifetime spectroscopy is a promising non-invasive label-free tool for characterization of biological tissues and shows potential to report structural and biochemical alterations in tissue owing to pathological transformations. In particular, when combined with fiber-optic based instruments, autofluorescence lifetime measurements can enhance intraoperative diagnosis and provide guidance in surgical procedures. We investigate the potential of a fiber-optic based multi-spectral time-resolved fluorescence spectroscopy instrument to characterize the autofluorescence fingerprint associated with histologic, morphologic and metabolic changes in tissue that can provide real-time contrast between healthy and tumor regions in vivo and guide clinicians during resection of diseased areas during transoral robotic surgery. To provide immediate feedback to the surgeons, we employ tracking of an aiming beam that co-registers our point measurements with the robot camera images and allows visualization of the surgical area augmented with autofluorescence lifetime data in the surgeon's console in real-time. For each patient, autofluorescence lifetime measurements were acquired from normal, diseased and surgically altered tissue, both in vivo (pre- and post-resection) and ex vivo. Initial results indicate tumor and normal regions can be distinguished based on changes in lifetime parameters measured in vivo, when the tumor is located superficially. In particular, results show that autofluorescence lifetime of tumor is shorter than that of normal tissue (p < 0.05, n = 3). If clinical diagnostic efficacy is demonstrated throughout this on-going study, we believe that this method has the potential to become a valuable tool for real-time intraoperative diagnosis and guidance during transoral robot assisted cancer removal interventions.

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer.

PubMed

Inoue, Tomoo; Nishi, Toshio; Nakano, Yoshiaki; Nishimae, Ayaka; Sawai, Yuka; Yamasaki, Masaru; Inaji, Hideo

2016-03-01

There is limited information on indocyanine green (ICG) fluorescence and blue dye for detecting sentinel lymph node (SLN) in early breast cancer. A retrospective study was conducted to assess the feasibility of an SLN biopsy using the combination of ICG fluorescence and the blue dye method. Seven hundred and fourteen patients with clinically node-negative breast cancer were included in this study. They underwent SLN biopsy using a combination of ICG fluorescence and the blue dye method from March 2007 to February 2014. The ICG (a fluorescence-emitting source) and patent blue (the blue dye) were injected into the patients' subareolar region. The removed lymph nodes that had ICG fluorescence and/or blue dye uptake were defined as SLNs. The results of the SLN biopsies and follow-up results of patients who underwent SLN biopsy alone were investigated. In 711 out of 714 patients, SLNs were identified by a combination of ICG fluorescence and the blue dye method (detection rate, 99.6 %). The average number of SLNs was 2.4 (range 1-7), and the average number of resected swollen para-SLNs was 0.4 (range 0-5). Ninety-nine patients with an SLN and/or para-SLN involvement during the intraoperative pathological diagnosis underwent axillary lymph node resection (ALND). In addition, two of three patients whose SLN was not identified also underwent ALND. In 46 of 101 patients with an ALND, non-SLN involvement was not found. Follow-up results were analyzed in 464 patients with invasive carcinoma excluding those with ductal carcinoma in situ (n = 148) and those who underwent ALND (n = 101). During the follow-up period (range 4.4-87.7 months; median, 38 months), two patients (0.4 %) developed axillary lymph node recurrence. They were successfully salvaged, and to date, no further locoregional recurrence has been observed. A high rate of SLN detection and low rate of axillary lymph node recurrence were confirmed by an SLN biopsy using a combination of ICG fluorescence and the blue dye method. Therefore, it is suggested that this method may replace the combination of dye and radioisotope methods.

Postoperative seizure outcome-guided machine learning for interictal electrocorticography in neocortical epilepsy.

PubMed

Park, Seong-Cheol; Chung, Chun Kee

2018-06-01

The objective of this study was to introduce a new machine learning guided by outcome of resective epilepsy surgery defined as the presence/absence of seizures to improve data mining for interictal pathological activities in neocortical epilepsy. Electrocorticographies for 39 patients with medically intractable neocortical epilepsy were analyzed. We separately analyzed 38 frequencies from 0.9 to 800 Hz including both high-frequency activities and low-frequency activities to select bands related to seizure outcome. An automatic detector using amplitude-duration-number thresholds was used. Interictal electrocorticography data sets of 8 min for each patient were selected. In the first training data set of 20 patients, the automatic detector was optimized to best differentiate the seizure-free group from not-seizure-free-group based on ranks of resection percentages of activities detected using a genetic algorithm. The optimization was validated in a different data set of 19 patients. There were 16 (41%) seizure-free patients. The mean follow-up duration was 21 ± 11 mo (range, 13-44 mo). After validation, frequencies significantly related to seizure outcome were 5.8, 8.4-25, 30, 36, 52, and 75 among low-frequency activities and 108 and 800 Hz among high-frequency activities. Resection for 5.8, 8.4-25, 108, and 800 Hz activities consistently improved seizure outcome. Resection effects of 17-36, 52, and 75 Hz activities on seizure outcome were variable according to thresholds. We developed and validated an automated detector for monitoring interictal pathological and inhibitory/physiological activities in neocortical epilepsy using a data-driven approach through outcome-guided machine learning. NEW & NOTEWORTHY Outcome-guided machine learning based on seizure outcome was used to improve detections for interictal electrocorticographic low- and high-frequency activities. This method resulted in better separation of seizure outcome groups than others reported in the literature. The automatic detector can be trained without human intervention and no prior information. It is based only on objective seizure outcome data without relying on an expert's manual annotations. Using the method, we could find and characterize pathological and inhibitory activities.

A study of MRI-guided diffuse fluorescence molecular tomography for monitoring PDT effects in pancreas cancer

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.

2009-06-01

Over the last several decades little progress has been made in the therapy and treatment monitoring of pancreas adenocarcinoma, a devastating and aggressive form of cancer that has a 5-year patient survival rate of 3%. Currently, investigations for the use of interstitial Verteporfin photodynamic therapy (PDT) are being undertaken in both orthotopic xenograft mouse models and in human clinical trials. In the mouse models, magnetic resonance (MR) imaging has been used as a measure of surrogate response to Verteporfin PDT; however, MR imaging alone lacks the molecular information required to assess the metabolic function and growth rates of the tumor immediately after treatment. We propose the implementation of MR-guided fluorescence tomography in conjunction with a fluorescently labeled (IR-Dye 800 CW, LI-COR) epidermal growth factor (EGF) as a molecular measure of surrogate response. To demonstrate the effectiveness of MR-guided diffuse fluorescence tomography for molecular imaging, we have used the AsPC-1 (+EGFR) human pancreatic adenocarcinoma in an orthotopic mouse model. EGF IRDye 800CW was injected 48 hours prior to imaging. MR image sequences were collected simultaneously with the fluorescence data using a MR-coupled diffuse optical tomography system. Image reconstruction was performed multiple times with varying abdominal organ segmentation in order to obtain a optimal tomographic image. It is shown that diffuse fluorescence tomography of the orthotopic pancreas model is feasible, with consideration of confounding fluorescence signals from the multiple organs and tissues surrounding the pancreas. MR-guided diffuse fluorescence tomography will be used to monitor EGF response after photodynamic therapy. Additionally, it provide the opportunity to individualize subsequent therapies based on response to PDT as well as to evaluate the success of combination therapies, such as PDT with chemotherapy, antibody therapy or even radiation.

Electromagnetic Navigation Bronchoscopy-directed Pleural Tattoo to Aid Surgical Resection of Peripheral Pulmonary Lesions.

PubMed

Tay, Jun H; Wallbridge, Peter D; Larobina, Marco; Russell, Prudence A; Irving, Louis B; Steinfort, Daniel P

2016-07-01

Limited (wedge) resection of pulmonary lesions is frequently performed as a diagnostic/therapeutic procedure. Some lesions may be difficult to locate thoracoscopically with conversion to open thoracotomy or incomplete resection being potential limitations to this approach. Multiple methods have been described to aid video-assisted thoracoscopic surgical (VATS) wedge resection of pulmonary nodules, including hookwire localization, percutaneous tattoo, or intraoperative ultrasound. We report on our experience using electromagnetic navigation bronchoscopic dye marking of small subpleural lesions to aid VATS wedge resection. A retrospective cohort study of consecutive patients undergoing VATS wedge resection of peripheral lesions. Preoperative bronchoscopy with electromagnetic navigation was utilized to guide a 25 G needle to within/adjacent to the target lesion with injection of 1 mL of methylene blue or indigo carmine under fluoroscopic vision. Six patients underwent bronchoscopic marking of peripheral pulmonary lesions, navigation deemed successful in all patients, with no procedural complications. Surgery was performed within 24 hours of bronchoscopic marking. Pleural staining by dye was visible thoracoscopically in all 6 lesions either adjacent to or overlying the lesion. All lesions were fully excised with wedge resection. Pathologic examination confirmed accuracy of dye staining. Electromagnetic navigation bronchoscopic dye marking of peripheral lesions is feasible, without complications commonly associated with percutaneous marking procedures. Further experience is required but early findings suggest that this method may have utility in aiding minimally invasive resection of small subpleural lesions.

High-intensity focused ultrasound combined with hysteroscopic resection to treat retained placenta accreta.

PubMed

Lee, Jae-Seong; Hong, Gi-Youn; Park, Byung-Joon; Hwang, Hyejin; Kim, Rayon; Kim, Tae-Eung

2016-09-01

We present a case of retained placenta accreta treated by high-intensity focused ultrasound (HIFU) ablation followed by hysteroscopic resection. The patient was diagnosed as submucosal myoma based on ultrasonography in local clinic. Pathologic examination of several pieces of tumor mass from the hysteroscopic procedure revealed necrotic chorionic villi with calcification. HIFU was performed using an ultrasound-guided HIFU tumor therapeutic system. The ultrasound machine had been used for real-time monitoring of the HIFU procedure. After HIFU treatment, no additional vaginal bleeding or complications were observed. A hysteroscopic resection was performed to remove ablated placental tissue 7 days later. No abnormal vaginal bleeding or discharge was seen after the procedure. The patient was stable postoperatively. We proposed HIFU and applied additional hysteroscopic resection for a safe and effective method for treating retained placenta accreta to prevent complications from the remaining placental tissue and to improve fertility options.

[Radiofrequency ablation of hepatocellular carcinoma].

PubMed

Widmann, Gerlig; Schullian, Peter; Bale, Reto

2013-03-01

Percutaneous radiofrequency ablation (RFA) is well established in the treatment of hepatocellular carcinoma (HCC). Due to its curative potential, it is the method of choice for non resectable BCLC (Barcelona Liver Clinic) 0 and A. RFA challenges surgical resection for small HCC and is the method of choice in bridging for transplantation and recurrence after resection or transplantation. The technical feasibility of RFA depends on the size and location of the HCC and the availability of ablation techniques (one needle techniques, multi-needle techniques). More recently, stereotactic multi-needle techniques with 3D trajectory planning and guided needle placement substantially improve the spectrum of treatable lesions including large volume tumors. Treatment success depends on the realization of ablations with large intentional margins of tumor free tissue (A0 ablation in analogy to R0 resection), which has to be documented by fusion of post- with pre-ablation images, and confirmed during follow-up imaging.

VATS intraoperative tattooing to facilitate solitary pulmonary nodule resection.

PubMed

Willekes, Lourens; Boutros, Cherif; Goldfarb, Michael A

2008-03-19

Video-assisted thoracic surgery (VATS) has become routine and widely accepted for the removal of solitary pulmonary nodules of unknown etiology. Thoracosopic techniques continue to evolve with better instruments, robotic applications, and increased patient acceptance and awareness. Several techniques have been described to localize peripheral pulmonary nodules, including pre-operative CT-guided tattooing with methylene blue, CT scan guided spiral/hook wire placement, and transthoracic ultrasound. As pulmonary surgeons well know, the lung and visceral pleura may appear featureless on top of a pulmonary nodule. This paper presents a rapid, direct and inexpensive approach to peripheral lung lesion resection by marking the lung parenchyma on top of the nodule using direct methylene blue injection. In two patients with peripherally located lung nodules (n = 3) scheduled for VATS, we used direct methylene blue injection for intraoperative localization of the pulmonary nodule. Our technique was the following: After finger palpation of the lung, a spinal 25 gauge needle was inserted through an existing port and 0.1 ml of methylene blue was used to tattoo the pleura perpendicular to the localized nodule. The methylene blue tattoo immediately marks the lung surface over the nodule. The surgeon avoids repeated finger palpation, while lining up stapler, graspers and camera, because of the visible tattoo. Our technique eliminates regrasping and repalpating the lung once again to identify a non marked lesion. Three lung nodules were resected in two patients. Once each lesion was palpated it was marked, and the area was resected with security of accurate localization. All lung nodules were resected in totality with normal lung parenchymal margins. Our technique added about one minute to the operative time. The two patients were discharged home on the second postoperative day, with no morbidity. VATS with intraoperative tattooing is a safe, easy, and accurate technique to streamline and efficiently resect solitary pulmonary nodules.

RT-06GAMMA KNIFE SURGERY AFTER NAVIGATION-GUIDED ASPIRATION FOR CYSTIC METASTATIC BRAIN TUMORS

PubMed Central

Chiba, Yasuyoshi; Mori, Kanji; Toyota, Shingo; Kumagai, Tetsuya; Yamamoto, Shota; Sugano, Hirofumi; Taki, Takuyu

2014-01-01

Metastatic brain tumors over 3 cm in diameter (volume of 14.1ml) are generally considered poor candidates for Gamma Knife surgery (GKS). We retrospectively assessed the method and efficacy of GKS for large cystic metastatic brain tumors after navigation-guided aspiration under local anesthesia. From September 2007 to April 2014, 38 cystic metastatic brain tumors in 32 patients (12 males, 20 females; mean age, 63.2 years) were treated at Kansai Rosai Hospital. The patients were performed navigation-guided cyst aspiration under local anesthesia, then at the day or the next day, were performed GKS and usually discharged on the day. The methods for preventing of leptomeningeal dissemination are following: 1) puncture from the place whose cerebral thickness is 1 cm or more; 2) avoidance of Ommaya reservoir implantation; and 3) placement of absorbable gelatin sponge to the tap tract. Tumor volume, including the cystic component, decreased from 25.4 ml (range 8.7-84.7 ml) to 11.4 ml (range 2.9-36.7 ml) following aspiration; the volume reduction was approximately 51.6%. Follow-up periods in the study population ranged from 0 to 24 months (median 3.5 months). The overall median survival was 6.7 months. There was no leptomeningeal dissemination related to the aspiration. One patient experienced radiation necrosis after GKS, one patient experienced re-aspiration by failure of aspiration, and two patients experienced surgical resections and one patient experienced re-aspiration by cyst regrowth after GKS. Long-term hospitalization is not desirable for the patients with brain metastases. In japan, Long-term hospitalization is required for surgical resection or whole brain radiation therapy, but only two days hospitalization is required for GKS after navigation-guided aspiration at our hospital. This GKS after navigation-guided aspiration is more effective and less invasive than surgical resection or whole brain radiation therapy.

Laparoscopic liver resection: Experience based guidelines

PubMed Central

Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirola; Fonseca, Gilton Marques; Araújo, Raphael Leonardo Cunha; Jeismann, Vagner Birk; Perini, Marcos Vinícius; Lupinacci, Renato Micelli; Cecconello, Ivan; Herman, Paulo

2016-01-01

Laparoscopic liver resection (LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant (both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments (1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers’ practice. Continuous surgical training, as well as new technologies should augment the application of laparoscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation. PMID:26843910

Robotic liver surgery: technical aspects and review of the literature

PubMed Central

Bianco, Francesco Maria; Daskalaki, Despoina; Gonzalez-Ciccarelli, Luis Fernando; Kim, Jihun; Benedetti, Enrico

2016-01-01

Minimally invasive surgery for liver resections has a defined role and represents an accepted alternative to open techniques for selected cases. Robotic technology can overcome some of the disadvantages of the laparoscopic technique, mainly in the most complex cases. Precise dissection and microsuturing is possible, even in narrow operative fields, allowing for a better dissection of the hepatic hilum, fine lymphadenectomy, and biliary reconstruction even with small bile ducts and easier bleeding control. This technique has the potential to allow for a greater number of major resections and difficult segmentectomies to be performed in a minimally invasive fashion. The implementation of near-infrared fluorescence with indocyanine green (ICG) also allows for a more accurate recognition of vascular and biliary anatomy. The perspectives of this kind of virtually implemented imaging are very promising and may be reflected in better outcomes. The overall data present in current literature suggests that robotic liver resections are at least comparable to both open and laparoscopic surgery in terms of perioperative and postoperative outcomes. This article provides technical details of robotic liver resections and a review of the current literature. PMID:27500143

Quantitative segmentation of fluorescence microscopy images of heterogeneous tissue: Approach for tuning algorithm parameters

NASA Astrophysics Data System (ADS)

Mueller, Jenna L.; Harmany, Zachary T.; Mito, Jeffrey K.; Kennedy, Stephanie A.; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G.; Willett, Rebecca M.; Brown, J. Quincy; Ramanujam, Nimmi

2013-02-01

The combination of fluorescent contrast agents with microscopy is a powerful technique to obtain real time images of tissue histology without the need for fixing, sectioning, and staining. The potential of this technology lies in the identification of robust methods for image segmentation and quantitation, particularly in heterogeneous tissues. Our solution is to apply sparse decomposition (SD) to monochrome images of fluorescently-stained microanatomy to segment and quantify distinct tissue types. The clinical utility of our approach is demonstrated by imaging excised margins in a cohort of mice after surgical resection of a sarcoma. Representative images of excised margins were used to optimize the formulation of SD and tune parameters associated with the algorithm. Our results demonstrate that SD is a robust solution that can advance vital fluorescence microscopy as a clinically significant technology.

Toward Intraoperative Image-Guided Transoral Robotic Surgery

PubMed Central

Liu, Wen P.; Reaugamornrat, Sureerat; Deguet, Anton; Sorger, Jonathan M.; Siewerdsen, Jeffrey H.; Richmon, Jeremy; Taylor, Russell H.

2014-01-01

This paper presents the development and evaluation of video augmentation on the stereoscopic da Vinci S system with intraoperative image guidance for base of tongue tumor resection in transoral robotic surgery (TORS). Proposed workflow for image-guided TORS begins by identifying and segmenting critical oropharyngeal structures (e.g., the tumor and adjacent arteries and nerves) from preoperative computed tomography (CT) and/or magnetic resonance (MR) imaging. These preoperative planned data can be deformably registered to the intraoperative endoscopic view using mobile C-arm cone-beam computed tomography (CBCT) [1, 2]. Augmentation of TORS endoscopic video defining surgical targets and critical structures has the potential to improve navigation, spatial orientation, and confidence in tumor resection. Experiments in animal specimens achieved statistically significant improvement in target localization error when comparing the proposed image guidance system to simulated current practice. PMID:25525474

Intraoperative β{sup -} detecting probe for radio-guided surgery in tumour resection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solfaroli Camillocci, Elena; Bellini, Fabio; Bocciy, Valerio

The development of the β{sup -} based radio-guided surgery aims to extend the technique to those tumours where surgery is the only possible treatment and the assessment of the resection would most profit from the low background around the lesion, as for brain tumours. Feasibility studies on meningioma and gliomas already estimated the potentiality of this new treatment. To validate the technique, a prototype of the intraoperative probe detecting β{sup -} decays and specific phantoms simulating tumour remnant patterns embedded in healthy tissue have been realized. The response of the probe in this simulated environment is tested with dedicated procedures.more » This document discusses the innovative aspects of the method, the status of the developed intraoperative β{sup -} detecting probe and the results of the preclinical tests. (authors)« less

Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging: Results of a Multicenter Retrospective Assessment of the German Study Group for Intraoperative Magnetic Resonance Imaging.

PubMed

Coburger, Jan; Merkel, Andreas; Scherer, Moritz; Schwartz, Felix; Gessler, Florian; Roder, Constantin; Pala, Andrej; König, Ralph; Bullinger, Lars; Nagel, Gabriele; Jungk, Christine; Bisdas, Sotirios; Nabavi, Arya; Ganslandt, Oliver; Seifert, Volker; Tatagiba, Marcos; Senft, Christian; Mehdorn, Maximilian; Unterberg, Andreas W; Rössler, Karl; Wirtz, Christian Rainer

2016-06-01

The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published. To investigate determinants for patient outcome and progression-free-survival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging. A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment. A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas "failed" GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits. GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS. EoR, extent of resectionFLAIR, fluid-attenuated inversion recoveryGTR, gross total resectionIDH1, isocitrate dehydrogenase 1iMRI, intraoperative magnetic resonance imagingLGG, low-grade gliomaMGMT, methylguanine-deoxyribonucleic acid methyltransferasenPND, new permanent neurological deficitOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization.

Image-guided surgery in resection of benign cervicothoracic spinal tumors: a report of two cases.

PubMed

Moore, Timothy; McLain, Robert F

2005-01-01

Osseous spinal tumors are an uncommon cause of persistent axial pain and muscle spasm, but even benign lesions may grow to cause deformity or neurological signs. Traditional treatment approaches to resection can be debilitating even when the tumor is benign. Emerging technologies allow surgeons to diagnose and treat osseous neoplasms while minimizing the collateral damage caused by surgical exposure and tumor excision. Technical considerations are presented through two cases of benign osseous neoplasm occurring in the cervicothoracic spine of competitive athletes, demonstrating the meth-ods used to provide effective treatment while maintaining maximal functional capacity. Stereotactic imaging and intraoperative guidance was used as an adjunct to tumor care in these patients. Used in combination with minimally invasive, microsurgical techniques,stereotactic guidance localized and verified excision margins of benign vertebral lesions, minimizing soft tissue trauma and collateral damage. Computer-assisted stereotactic localization allowed us to successfully ablate these lesions from their anatomically challenging locations, without disrupting the shoulder girdle or neck musculature, and without extensive bony resection. Image guidance can accurately localize and guide excision of benign vertebral lesions while minimizing soft tissue trauma and collateral damage, allowing patients a rapid and complete return to high-demand function.

Fluorescence-guided mapping of sentinel lymph nodes in gynecological malignancies

NASA Astrophysics Data System (ADS)

Hirsch, Ole; Szyc, Łukasz; Muallem, Mustafa Zelal; Ignat, Iulia; Chekerov, Radoslav; Macdonald, Rainer; Sehouli, Jalid; Braicu, Ioana; Grosenick, Dirk

2017-07-01

We have successfully applied a custom-made handheld fluorescence camera for intraoperative fluorescence detection of indocyanine green in a feasibility study on sentinel lymph node mapping in patients with vulvar, cervical, endometrial and ovarian cancer.

Automated fluorescent miscroscopic image analysis of PTBP1 expression in glioma

PubMed Central

Becker, Aline; Elder, Brad; Puduvalli, Vinay; Winter, Jessica; Gurcan, Metin

2017-01-01

Multiplexed immunofluorescent testing has not entered into diagnostic neuropathology due to the presence of several technical barriers, amongst which includes autofluorescence. This study presents the implementation of a methodology capable of overcoming the visual challenges of fluorescent microscopy for diagnostic neuropathology by using automated digital image analysis, with long term goal of providing unbiased quantitative analyses of multiplexed biomarkers for solid tissue neuropathology. In this study, we validated PTBP1, a putative biomarker for glioma, and tested the extent to which immunofluorescent microscopy combined with automated and unbiased image analysis would permit the utility of PTBP1 as a biomarker to distinguish diagnostically challenging surgical biopsies. As a paradigm, we utilized second resections from patients diagnosed either with reactive brain changes (pseudoprogression) and recurrent glioblastoma (true progression). Our image analysis workflow was capable of removing background autofluorescence and permitted quantification of DAPI-PTBP1 positive cells. PTBP1-positive nuclei, and the mean intensity value of PTBP1 signal in cells. Traditional pathological interpretation was unable to distinguish between groups due to unacceptably high discordance rates amongst expert neuropathologists. Our data demonstrated that recurrent glioblastoma showed more DAPI-PTBP1 positive cells and a higher mean intensity value of PTBP1 signal compared to resections from second surgeries that showed only reactive gliosis. Our work demonstrates the potential of utilizing automated image analysis to overcome the challenges of implementing fluorescent microscopy in diagnostic neuropathology. PMID:28282372

Electromagnetic Navigation Bronchoscopy for Identifying Lung Nodules for Thoracoscopic Resection.

PubMed

Marino, Katy A; Sullivan, Jennifer L; Weksler, Benny

2016-08-01

Pulmonary nodules smaller than 1 cm can be difficult to identify during minimally invasive resection, necessitating conversion to thoracotomy. We hypothesized that localizing nodules with electromagnetic navigation bronchoscopy and marking them with methylene blue would allow minimally invasive resection and reduce conversion to thoracotomy. We retrospectively identified all patients who underwent electromagnetic navigation bronchoscopy followed by minimally invasive resection of a pulmonary nodule from 2011 to 2014. Lung nodules smaller than 10 mm and nodules smaller than 20 mm that were also located more than 10 mm from the pleural surface were localized and marked with methylene blue. Immediately after marking, all patients underwent resection. Seventy patients underwent electromagnetic navigation bronchoscopy marking followed by minimally invasive resection. The majority of patients (68/70, 97%) had one nodule localized; 2 patients (2/70, 3%) had two nodules localized. The median nodule size was 8 mm (range, 4-17 mm; interquartile range, 5 mm). The median distance from the pleural surface was 6 mm (range, 1-19 mm; interquartile range, 6 mm). There were no conversions to thoracotomy. Nodule marking was successful in 70 of 72 attempts (97.2%); two nodules were identified by palpation. The nodules were most commonly metastases from other sites (31/70, 44.3%). There were no adverse events related to electromagnetic navigation bronchoscopy-guided marking or wedge resection, and minimal adverse events after resections that were more extensive. Localizing and marking small pulmonary nodules using electromagnetic navigation bronchoscopy is safe and effective for nodule identification before minimally invasive resection. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Electromagnetic navigational bronchoscopy with dye marking for identification of small peripheral lung nodules during minimally invasive surgical resection

PubMed Central

Muñoz-Largacha, Juan A.; Ebright, Michael I.; Litle, Virginia R.

2017-01-01

Background Identification of small peripheral lung nodules during minimally invasive resection can be challenging. Electromagnetic navigational bronchoscopy (ENB) with injection of dye to identify nodules can be performed by the surgeon immediately prior to resection. We evaluated the effectiveness of ENB with dye marking to aid minimally invasive resection. Methods Patients with peripheral pulmonary nodules underwent ENB before planned thoracoscopic or robotic-assisted thoracoscopic resection. Methylene blue was injected directly into the lesion for pleural-based lesions or peripherally for lesions deep to the pleural surface. Surgical resection was then immediately performed. Technical success was defined as identification of the dye marking within/close to the lesion with pathological confirmation after minimally invasive surgical resection. Results Seventeen patients (19 nodules) underwent ENB with dye marking followed by minimally invasive resection. Median lesion size was 9 mm (4–32 mm) and the median distance from the pleura was 9.5 mm (1–40 mm). Overall success rate was 79% (15/19). In two cases the dye was not visualized and in the remaining two there was extravasation of dye into the pleural space. There were trends favoring technical success for nodules that were larger or closer to the pleural surface. Five patients required adhesiolysis to visualize the target lesion and all were successful. There were no significant adverse events and a definitive diagnosis was ultimately accomplished in all patients. Conclusions ENB with dye marking is useful for guiding minimally invasive resection of small peripheral lung nodules. ENB can be undertaken immediately before performing resection in the operating room. This improves workflow and avoids the need for a separate localization procedure. PMID:28449489

Linking late cognitive outcome with glioma surgery location using resection cavity maps.

PubMed

Hendriks, Eef J; Habets, Esther J J; Taphoorn, Martin J B; Douw, Linda; Zwinderman, Aeilko H; Vandertop, W Peter; Barkhof, Frederik; Klein, Martin; De Witt Hamer, Philip C

2018-05-01

Patients with a diffuse glioma may experience cognitive decline or improvement upon resective surgery. To examine the impact of glioma location, cognitive alteration after glioma surgery was quantified and related to voxel-based resection probability maps. A total of 59 consecutive patients (range 18-67 years of age) who had resective surgery between 2006 and 2011 for a supratentorial nonenhancing diffuse glioma (grade I-III, WHO 2007) were included in this observational cohort study. Standardized neuropsychological examination and MRI were obtained before and after surgery. Intraoperative stimulation mapping guided resections towards neurological functions (language, sensorimotor function, and visual fields). Maps of resected regions were constructed in standard space. These resection cavity maps were compared between patients with and without new cognitive deficits (z-score difference >1.5 SD between baseline and one year after resection), using a voxel-wise randomization test and calculation of false discovery rates. Brain regions significantly associated with cognitive decline were classified in standard cortical and subcortical anatomy. Cognitive improvement in any domain occurred in 10 (17%) patients, cognitive decline in any domain in 25 (42%), and decline in more than one domain in 10 (17%). The most frequently affected subdomains were attention in 10 (17%) patients and information processing speed in 9 (15%). Resection regions associated with decline in more than one domain were predominantly located in the right hemisphere. For attention decline, no specific region could be identified. For decline in information speed, several regions were found, including the frontal pole and the corpus callosum. Cognitive decline after resective surgery of diffuse glioma is prevalent, in particular, in patients with a tumor located in the right hemisphere without cognitive function mapping. © The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Multicolor fluorescent intravital live microscopy (FILM) for surgical tumor resection in a mouse xenograft model.

PubMed

Thurber, Greg M; Figueiredo, Jose L; Weissleder, Ralph

2009-11-30

Complete surgical resection of neoplasia remains one of the most efficient tumor therapies. However, malignant cell clusters are often left behind during surgery due to the inability to visualize and differentiate them against host tissue. Here we establish the feasibility of multicolor fluorescent intravital live microscopy (FILM) where multiple cellular and/or unique tissue compartments are stained simultaneously and imaged in real time. Theoretical simulations of imaging probe localization were carried out for three agents with specificity for cancer cells, stromal host response, or vascular perfusion. This transport analysis gave insight into the probe pharmacokinetics and tissue distribution, facilitating the experimental design and allowing predictions to be made about the localization of the probes in other animal models and in the clinic. The imaging probes were administered systemically at optimal time points based on the simulations, and the multicolor FILM images obtained in vivo were then compared to conventional pathological sections. Our data show the feasibility of real time in vivo pathology at cellular resolution and molecular specificity with excellent agreement between intravital and traditional in vitro immunohistochemistry. Multicolor FILM is an accurate method for identifying malignant tissue and cells in vivo. The imaging probes distributed in a manner similar to predictions based on transport principles, and these models can be used to design future probes and experiments. FILM can provide critical real time feedback and should be a useful tool for more effective and complete cancer resection.

Fluorescence spectroscopy using indocyanine green for lymph node mapping

NASA Astrophysics Data System (ADS)

Haj-Hosseini, Neda; Behm, Pascal; Shabo, Ivan; Wârdell, Karin

2014-02-01

The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue.

Image-Guided Abdominal Surgery and Therapy Delivery

PubMed Central

Galloway, Robert L.; Herrell, S. Duke; Miga, Michael I.

2013-01-01

Image-Guided Surgery has become the standard of care in intracranial neurosurgery providing more exact resections while minimizing damage to healthy tissue. Moving that process to abdominal organs presents additional challenges in the form of image segmentation, image to physical space registration, organ motion and deformation. In this paper, we present methodologies and results for addressing these challenges in two specific organs: the liver and the kidney. PMID:25077012

Image navigation as a means to expand the boundaries of fluorescence-guided surgery

NASA Astrophysics Data System (ADS)

Brouwer, Oscar R.; Buckle, Tessa; Bunschoten, Anton; Kuil, Joeri; Vahrmeijer, Alexander L.; Wendler, Thomas; Valdés-Olmos, Renato A.; van der Poel, Henk G.; van Leeuwen, Fijs W. B.

2012-05-01

Hybrid tracers that are both radioactive and fluorescent help extend the use of fluorescence-guided surgery to deeper structures. Such hybrid tracers facilitate preoperative surgical planning using (3D) scintigraphic images and enable synchronous intraoperative radio- and fluorescence guidance. Nevertheless, we previously found that improved orientation during laparoscopic surgery remains desirable. Here we illustrate how intraoperative navigation based on optical tracking of a fluorescence endoscope may help further improve the accuracy of hybrid surgical guidance. After feeding SPECT/CT images with an optical fiducial as a reference target to the navigation system, optical tracking could be used to position the tip of the fluorescence endoscope relative to the preoperative 3D imaging data. This hybrid navigation approach allowed us to accurately identify marker seeds in a phantom setup. The multispectral nature of the fluorescence endoscope enabled stepwise visualization of the two clinically approved fluorescent dyes, fluorescein and indocyanine green. In addition, the approach was used to navigate toward the prostate in a patient undergoing robot-assisted prostatectomy. Navigation of the tracked fluorescence endoscope toward the target identified on SPECT/CT resulted in real-time gradual visualization of the fluorescent signal in the prostate, thus providing an intraoperative confirmation of the navigation accuracy.

Intraoperative /sup 99m/Tc bone imaging in the treatment of benign osteoblastic tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sty, J.; Simons, G.

1982-05-01

Benign bone tumors can be successfully treated by local resection with the use of intraoperative bone imaging. Intraoperative bone imaging provided accurate localization of an osteoid osteoma in a patella of a 16-year-old girl when standard radiographs failed to demonstrate the lesion. In a case of osteoblastoma of the sacrum in a 12-year old girl, intraoperative scanning was used repeatedly to guide completeness of resection. In these cases in which routine intraoperative radiographs would have failed, intraoperative scanning proved to be essential for success.

Setup for testing cameras for image guided surgery using a controlled NIR fluorescence mimicking light source and tissue phantom

NASA Astrophysics Data System (ADS)

Georgiou, Giota; Verdaasdonk, Rudolf M.; van der Veen, Albert; Klaessens, John H.

2017-02-01

In the development of new near-infrared (NIR) fluorescence dyes for image guided surgery, there is a need for new NIR sensitive camera systems that can easily be adjusted to specific wavelength ranges in contrast the present clinical systems that are only optimized for ICG. To test alternative camera systems, a setup was developed to mimic the fluorescence light in a tissue phantom to measure the sensitivity and resolution. Selected narrow band NIR LED's were used to illuminate a 6mm diameter circular diffuse plate to create uniform intensity controllable light spot (μW-mW) as target/source for NIR camera's. Layers of (artificial) tissue with controlled thickness could be placed on the spot to mimic a fluorescent `cancer' embedded in tissue. This setup was used to compare a range of NIR sensitive consumer's cameras for potential use in image guided surgery. The image of the spot obtained with the cameras was captured and analyzed using ImageJ software. Enhanced CCD night vision cameras were the most sensitive capable of showing intensities < 1 μW through 5 mm of tissue. However, there was no control over the automatic gain and hence noise level. NIR sensitive DSLR cameras proved relative less sensitive but could be fully manually controlled as to gain (ISO 25600) and exposure time and are therefore preferred for a clinical setting in combination with Wi-Fi remote control. The NIR fluorescence testing setup proved to be useful for camera testing and can be used for development and quality control of new NIR fluorescence guided surgery equipment.

[Complete Resection of Non-seminomatous Germ Cell Tumor with Plastron Approach].

PubMed

Suzuki, Jun; Oizumi, Hiroyuki; Kato, Hirohisa; Endoh, Makoto; Watarai, Hikaru; Hamada, Akira; Suzuki, Katsuyuki; Nakahashi, Kenta; Sasage, Takayuki; Sadahiro, Mitsuaki

2016-07-01

A 17-year-old man was admitted to our hospital for the abnormal chest shadow. Chest computed tomography(CT) demonstrated mediastinal tumor, measuring 13 cm in diameter with high serum level of alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG). The lesions were diagnosed as mixed germ cell tumors including a non-seminomatous malignant component by CT guided needle biopsy. After 5 courses of chemotherapy, the serum AFP and hCG were decreased almost normal level but the tumor size was not changed. Because it seemed to be difficult to get sufficient operating field with standard median sternotomy and patient wanted to treat funnel chest, we selected tumor resection with plastron approach. The tumor was completely resected with a good operation field by this procedure.

Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies.

PubMed

Delgado-López, P D; Corrales-García, E M; Martino, J; Lastra-Aras, E; Dueñas-Polo, M T

2017-08-01

The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening.

The Status of Contemporary Image-Guided Modalities in Oncologic Surgery

PubMed Central

Rosenthal, Eben L; Warram, Jason M; Bland, Kirby I; Zinn, Kurt R

2014-01-01

Surgical resection remains the cornerstone of therapy for patients with early stage solid malignancies and more than half of all cancer patients undergo surgery each year. The technical ability of the surgeon to obtain clear surgical margins at the initial resection remains crucial to improve overall survival and long-term morbidity. Current resection techniques are largely based on subjective and subtle changes associated with tissue distortion by invasive cancer. As a result, positive surgical margins occur in a significant portion of tumor resections, which is directly correlated with a poor outcome. A variety of cancer imaging techniques have been adapted or developed for intraoperative surgical guidance that have been shown to improve functional and oncologic outcomes in randomized clinical trials. There are also a large number of novel, cancer-specific contrast agents that are in early stage clinical trials and preclinical development that demonstrate significant promise to improve real-time detection of subclinical cancer in the operative setting. PMID:25599326

How 3D patient-specific instruments improve accuracy of pelvic bone tumour resection in a cadaveric study.

PubMed

Sallent, A; Vicente, M; Reverté, M M; Lopez, A; Rodríguez-Baeza, A; Pérez-Domínguez, M; Velez, R

2017-10-01

To assess the accuracy of patient-specific instruments (PSIs) versus standard manual technique and the precision of computer-assisted planning and PSI-guided osteotomies in pelvic tumour resection. CT scans were obtained from five female cadaveric pelvises. Five osteotomies were designed using Mimics software: sacroiliac, biplanar supra-acetabular, two parallel iliopubic and ischial. For cases of the left hemipelvis, PSIs were designed to guide standard oscillating saw osteotomies and later manufactured using 3D printing. Osteotomies were performed using the standard manual technique in cases of the right hemipelvis. Post-resection CT scans were quantitatively analysed. Student's t -test and Mann-Whitney U test were used. Compared with the manual technique, PSI-guided osteotomies improved accuracy by a mean 9.6 mm (p < 0.008) in the sacroiliac osteotomies, 6.2 mm (p < 0.008) and 5.8 mm (p < 0.032) in the biplanar supra-acetabular, 3 mm (p < 0.016) in the ischial and 2.2 mm (p < 0.032) and 2.6 mm (p < 0.008) in the parallel iliopubic osteotomies, with a mean linear deviation of 4.9 mm (p < 0.001) for all osteotomies. Of the manual osteotomies, 53% (n = 16) had a linear deviation > 5 mm and 27% (n = 8) were > 10 mm. In the PSI cases, deviations were 10% (n = 3) and 0 % (n = 0), respectively. For angular deviation from pre-operative plans, we observed a mean improvement of 7.06° (p < 0.001) in pitch and 2.94° (p < 0.001) in roll, comparing PSI and the standard manual technique. In an experimental study, computer-assisted planning and PSIs improved accuracy in pelvic tumour resections, bringing osteotomy results closer to the parameters set in pre-operative planning, as compared with standard manual techniques. Cite this article : A. Sallent, M. Vicente, M. M. Reverté, A. Lopez, A. Rodríguez-Baeza, M. Pérez-Domínguez, R. Velez. How 3D patient-specific instruments improve accuracy of pelvic bone tumour resection in a cadaveric study. Bone Joint Res 2017;6:577-583. DOI: 10.1302/2046-3758.610.BJR-2017-0094.R1. © 2017 Sallent et al.

Compact wearable dual-mode imaging system for real-time fluorescence image-guided surgery.

PubMed

Zhu, Nan; Huang, Chih-Yu; Mondal, Suman; Gao, Shengkui; Huang, Chongyuan; Gruev, Viktor; Achilefu, Samuel; Liang, Rongguang

2015-09-01

A wearable all-plastic imaging system for real-time fluorescence image-guided surgery is presented. The compact size of the system is especially suitable for applications in the operating room. The system consists of a dual-mode imaging system, see-through goggle, autofocusing, and auto-contrast tuning modules. The paper will discuss the system design and demonstrate the system performance.

Sprayable enzyme-activatable fluorescent probes: kinetic mapping using dynamic fluorescence imaging can help detecting tiny cancer foci (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kobayashi, Hisataka

2017-02-01

Optical fluorescence-guided imaging is increasingly used to guide surgery and endoscopic procedures. Sprayable enzyme-activatable probes are particularly useful because of high target-to-background ratios that increase sensitivity for tiny cancer foci. However, green fluorescent activatable probes suffers from interference from autofluorescence found in biological tissue. Dynamic imaging followed by the kinetic analysis could be detected local enzyme activity and used to differentiate specific fluorescence arising from an activated probe in a tumor from autofluorescence in background tissues especially when low concentrations of the dye are applied to detect tiny cancer foci. Serial fluorescence imaging was performed using various concentrations of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) which was sprayed on the peritoneal surface with tiny implants of SHIN3-dsRed ovarian cancer tumors. Temporal differences in signal between specific green fluorescence in cancer foci and non-specific autofluorescence in background tissue was measured and processed into three kinetic maps reflecting maximum fluorescence signal (MF), wash-in rate (WIR), and area under the curve (AUC), respectively. Especially at lower concentrations, kinetic maps derived from dynamic fluorescence imaging were clearly superior to unprocessed images for detection small cancer foci.

Clinical accuracy of a patient-specific femoral osteotomy guide in minimally-invasive posterior hip arthroplasty.

PubMed

Schneider, Adrian K; Pierrepont, Jim W; Hawdon, Gabrielle; McMahon, Stephen

2018-04-01

Patient specific guides can be a valuable tool in improving the precision of planned femoral neck osteotomies, especially in minimally invasive hip surgery, where bony landmarks are often inaccessible. The aim of our study was to validate the accuracy of a novel patient specific femoral osteotomy guide for THR through a minimally invasive posterior approach, the direct superior approach (DSA). As part of our routine preoperative planning 30 patients underwent low dose CT scans of their arthritic hip. 3D printed patient specific femoral neck osteotomy guides were then produced. Intraoperatively, having cleared all soft tissue from the postero-lateral neck of the enlocated hip, the guide was placed and pinned onto the posterolateral femoral neck. The osteotomy was performed using an oscillating saw and the uncemented hip components were implanted as per routine. Postoperatively, the achieved level of the osteotomy at the medial calcar was compared with the planned level of resection using a 3D/2D matching analysis (Mimics X-ray module, Materialise, Belgium). A total of 30 patients undergoing uncemented Trinity™ acetabular and TriFit TS™ femoral component arthroplasty (Corin, UK) were included in our analysis. All but one of our analysed osteotomies were found to be within 3 mm from the planned height of osteotomy. In one patient the level of osteotomy deviated 5 mm below the planned level of resection. Preoperative planning and the use of patient specific osteotomy guides provides an accurate method of performing femoral neck osteotomies in minimally invasive hip arthroplasty using the direct superior approach. IV (Case series).

Endoscopic ultrasound-guided transmural drainage of postoperative pancreatic collections.

PubMed

Tilara, Amy; Gerdes, Hans; Allen, Peter; Jarnagin, William; Kingham, Peter; Fong, Yuman; DeMatteo, Ronald; D'Angelica, Michael; Schattner, Mark

2014-01-01

Pancreatic leak is a major cause of morbidity after pancreatectomy. Traditionally, peripancreatic fluid collections have been managed by percutaneous or operative drainage. Data for endoscopic ultrasound (EUS)-guided drainage of postoperative fluid collections are limited. Here we report on the safety, efficacy, and timing of EUS-guided drainage of postoperative peripancreatic collections. This is a retrospective review of 31 patients who underwent EUS-guided drainage of fluid collections after pancreatic resection. Technical success was defined as successful transgastric deployment of at least one double pigtail plastic stent. Clinical success was defined as resolution of the fluid collection on follow-up CT scan and resolution of symptoms. Early drainage was defined as initial transmural stent placement within 30 days after surgery. Endoscopic ultrasound-guided drainage was performed effectively with a technical success rate of 100%. Clinical success was achieved in 29 of 31 patients (93%). Nineteen of the 29 patients (65%) had complete resolution of their symptoms and collection with the first endoscopic procedure. Repeat drainage procedures, including some with necrosectomy, were required in the remaining 10 patients, with eventual resolution of collection and symptoms. Two patients who did not achieve durable clinical success required percutaneous drainage by interventional radiology. Seventeen (55%) of 31 patients had successful early drainage completed within 30 days of their operation. Endoscopic ultrasound-guided drainage of fluid collections after pancreatic resection is safe and effective. Early drainage (<30 days) of postoperative pancreatic fluid collections was not associated with increased complications in this series. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Early Localization of Bronchogenic Carcinoma

PubMed Central

Macaulay, C.; Leriche, J. C.; Ikeda, N.; Palcic, B.

1994-01-01

The performance of a fluorescence imaging device was compared with conventional white-light bronchoscopy in 100 patients with lung cancer, 46 patients with resected stage I non-small cell lung cancer, 10 patients with head and neck cancer, and 67 volunteers who had smoked at least 1 pack of cigarettes per day for 25 years or more. Using differences in tissue autofluorescence between premalignant, malignant, and normal tissues, fluorescence bronchoscopy was found to detect significantly more areas with moderate/severe dysplasia or carcinoma in situ than conventional white-light bronchoscopy with a similar specificity. Multiple foci of dysplasia or cancer were found in 13–24% of these individuals. Fluorescence bronchoscopy may be an important adjunct to conventional bronchoscopic examination to improve our ability to detect and localize premalignant and early lung cancer lesions. PMID:18493345

Minimally Invasive Tubular Resection of Lumbar Synovial Cysts: Report of 40 Consecutive Cases.

PubMed

Birch, Barry D; Aoun, Rami James N; Elbert, Gregg A; Patel, Naresh P; Krishna, Chandan; Lyons, Mark K

2016-10-01

Lumbar synovial cysts are a relatively common clinical finding. Surgical treatment of symptomatic synovial cysts includes computed tomography-guided aspiration, open resection and minimally invasive tubular resection. We report our series of 40 consecutive minimally invasive microscopic tubular lumbar synovial cyst resections. Following Institutional Review Board approval, a retrospective analysis of 40 cases of minimally invasive microscopic tubular retractor synovial cyst resections at a single institution by a single surgeon (B.D.B.) was conducted. Gross total resection was performed in all cases. Patient characteristics, surgical operating time, complications, and outcomes were analyzed. Lumbar radiculopathy was the presenting symptoms in all but 1 patient, who presented with neurogenic claudication. The mean duration of symptoms was 6.5 months (range, 1-25 months), mean operating time was 58 minutes (range, 25-110 minutes), and mean blood loss was 20 mL (range, 5-50 mL). Seven patients required overnight observation. The median length of stay in the remaining 33 patients was 4 hours. There were 2 cerebrospinal fluid leaks repaired directly without sequelae. The mean follow-up duration was 80.7 months. Outcomes were good or excellent in 37 of the 40 patients, fair in 1 patient, and poor in 2 patients. Minimally invasive microscopic tubular retractor resection of lumbar synovial cysts can be done safely and with comparable outcomes and complication rates as open procedures with potentially reduced operative time, length of stay, and healthcare costs. Patient selection for microscopic tubular synovial cyst resection is based in part on the anatomy of the spine and synovial cyst and is critical when recommending minimally invasive vs. open resection to patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation between magnetoencephalography-based "clusterectomy" and postoperative seizure freedom.

PubMed

Vadera, Sumeet; Jehi, Lara; Burgess, Richard C; Shea, Katherine; Alexopoulos, Andreas V; Mosher, John; Gonzalez-Martinez, Jorge; Bingaman, William

2013-06-01

During the presurgical evaluation of patients with medically intractable focal epilepsy, a variety of noninvasive studies are performed to localize the hypothetical epileptogenic zone and guide the resection. Magnetoencephalography (MEG) is becoming increasingly used in the clinical realm for this purpose. No investigators have previously reported on coregisteration of MEG clusters with postoperative resection cavities to evaluate whether complete "clusterectomy" (resection of the area associated with MEG clusters) was performed or to compare these findings with postoperative seizure-free outcomes. The authors retrospectively reviewed the charts and imaging studies of 65 patients undergoing MEG followed by resective epilepsy surgery from 2009 until 2012 at the Cleveland Clinic. Preoperative MEG studies were fused with postoperative MRI studies to evaluate whether clusters were within the resected area. These data were then correlated with postoperative seizure freedom. Sixty-five patients were included in this study. The average duration of follow-up was 13.9 months, the mean age at surgery was 23.1 years, and the mean duration of epilepsy was 13.7 years. In 30 patients, the main cluster was located completely within the resection cavity, in 28 it was completely outside the resection cavity, and in 7 it was partially within the resection cavity. Seventy-four percent of patients were seizure free at 12 months after surgery, and this rate decreased to 60% at 24 months. Improved likelihood of seizure freedom was seen with complete clusterectomy in patients with localization outside the temporal lobe (extra-temporal lobe epilepsy) (p = 0.04). In patients with preoperative MEG studies that show clusters in surgically accessible areas outside the temporal lobe, we suggest aggressive resection to improve the chances for seizure freedom. When the cluster is found within the temporal lobe, further diagnostic testing may be required to better localize the epileptogenic zone.

Image Merge Tailored Access Resection (IMTAR) of Spinal Intradural Tumors. Technical Report of 13 Cases.

PubMed

Maduri, Rodolfo; Bobinski, Lukas; Duff, John Michael

2017-02-01

Standard translaminar approaches for intradural extramedullary (IDEM) tumors require extensive soft tissue dissection and partial facet removal. Ventral lesions may necessitate wider bone resection with subsequent possible spinal instability. Any manipulation of an already compromised spinal cord may lead to neurological injury. We describe an image-guided minimal access technique for IDEM tumor resection. Retrospective chart review of 13 consecutive patients after institutional ethics committee approval. We superimpose preoperative magnetic resonance imaging data with intraoperative 3-dimensional fluoroscopic images, allowing to simultaneously visualize osseous anatomy and the soft tissue lesion using appropriate windowing. We then plan optimal angle of trajectory to the tumor, which defines the skin incision and the transmuscular trajectory. A tubular retractor is placed to span the tumor. Microsurgical tumor resection is then carried out using this angle of approach. Thirteen patients (mean age. 57 years; male-to-female ratio, 10:3) were operated on during 28 months. Gross total resection was achieved in all patients. Neurological improvement occurred in 12 of the 13 patients. There was no neurological deficit outside of the expected sensory loss due to intentional nerve root sacrifice. No mechanical pain nor tumor recurrence were noted during the follow-up (mean, 16 months; range, 2-30 months). Image merge tailored access resection appears to be at least equivalent in terms of tumor resection, blood loss, and complications to other tubular techniques. It may reduce risks of neurological deficit and spine instability. Image merge tailored access resection is a novel application of merging intraoperative fluoroscopic images with preoperative magnetic resonance images for tailored IDEM resection. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of intraoperative indocyanine green angiography for CNS tumors: results on the first 100 cases.

PubMed

Ferroli, P; Acerbi, F; Albanese, E; Tringali, G; Broggi, M; Franzini, A; Broggi, G

2011-01-01

To investigate the application of indocyanine green (ICG) videoangiography during microsurgery for central nervous system (CNS) tumors. One hundred patients with CNS tumors who underwent microsurgical resection from December 2006 to December 2008 were retrospectively analyzed. The diagnosis was high grade glioma in 54 cases, low grade in 17 cases, meningioma in 14 cases, metastasis in 12 cases and hemangioblastoma in 3 cases. Overall, ICG was injected intraoperatively 194 times. The standard dose of 25mg of dye was injected intravenously and intravascular fluorescence from within the blood vessels was imaged through an ad hoc microscope with dedicated software (Pentero, Carl Zeiss Co., Oberkochen, Germany). Pre-resection and post-resection arterial, capillary and venous ICG videoangiographic phases were intraoperatively observed and recorded. ICG videangiography allowed for a good evaluation of blood flow in the tumoral and peritumoral exposed vessels in all cases. No side effects due to ICG were observed. ICG video-angiography is a significant method for monitoring blood flow in the exposed vessels during microsurgical removal of CNS tumors. Pre-resection videoangiography provides useful information on the tumoral circulation and the pathology-induced alteration in surrounding brain circulation. Post-resection examination allows for an immediate check of patency of those vessels that are closely related to the tumor mass and that the surgeon does not want to damage.

Functional approach using intraoperative brain mapping and neurophysiological monitoring for the surgical treatment of brain metastases in the central region.

PubMed

Sanmillan, Jose L; Fernández-Coello, Alejandro; Fernández-Conejero, Isabel; Plans, Gerard; Gabarrós, Andreu

2017-03-01

OBJECTIVE Brain metastases are the most frequent intracranial malignant tumor in adults. Surgical intervention for metastases in eloquent areas remains controversial and challenging. Even when metastases are not infiltrating intra-parenchymal tumors, eloquent areas can be affected. Therefore, this study aimed to describe the role of a functional guided approach for the resection of brain metastases in the central region. METHODS Thirty-three patients (19 men and 14 women) with perirolandic metastases who were treated at the authors' institution were reviewed. All participants underwent resection using a functional guided approach, which consisted of using intraoperative brain mapping and/or neurophysiological monitoring to aid in the resection, depending on the functionality of the brain parenchyma surrounding each metastasis. Motor and sensory functions were monitored in all patients, and supplementary motor and language area functions were assessed in 5 and 4 patients, respectively. Clinical data were analyzed at presentation, discharge, and the 6-month follow-up. RESULTS The most frequent presenting symptom was seizure, followed by paresis. Gross-total removal of the metastasis was achieved in 31 patients (93.9%). There were 6 deaths during the follow-up period. After the removal of the metastasis, 6 patients (18.2%) presented with transient neurological worsening, of whom 4 had worsening of motor function impairment and 2 had acquired new sensory disturbances. Total recovery was achieved before the 3rd month of follow-up in all cases. Excluding those patients who died due to the progression of systemic illness, 88.9% of patients had a Karnofsky Performance Scale score greater than 80% at the 6-month follow-up. The mean survival time was 24.4 months after surgery. CONCLUSIONS The implementation of intraoperative electrical brain stimulation techniques in the resection of central region metastases may improve surgical planning and resection and may spare eloquent areas. This approach also facilitates maximal resection in these and other critical functional areas, thereby helping to avoid new postoperative neurological deficits. Avoiding permanent neurological deficits is critical for a good quality of life, especially in patients with a life expectancy of over a year.

PSMA-11-Derived Dual-Labeled PSMA Inhibitors for Preoperative PET Imaging and Precise Fluorescence-Guided Surgery of Prostate Cancer.

PubMed

Baranski, Ann-Christin; Schäfer, Martin; Bauder-Wüst, Ulrike; Roscher, Mareike; Schmidt, Jana; Stenau, Esther; Simpfendörfer, Tobias; Teber, Dogu; Maier-Hein, Lena; Hadaschik, Boris; Haberkorn, Uwe; Eder, Matthias; Kopka, Klaus

2018-04-01

Resection of tumors using targeted dual-modality probes combining preoperative imaging with intraoperative guidance is of high clinical relevance and might considerably affect the outcome of prostate cancer therapy. This work aimed at the development of dual-labeled prostate-specific membrane antigen (PSMA) inhibitors derived from the established N,N' -bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine- N,N' -diacetic acid (HBED-CC)-based PET tracer 68 Ga-Glu-urea-Lys(Ahx)-HBED-CC ( 68 Ga-PSMA-11) to allow accurate intraoperative detection of PSMA-positive tumors. Methods: A series of novel PSMA-targeting fluorescent dye conjugates of Glu-urea-Lys-HBED-CC was synthesized, and their biologic properties were determined in cell-based assays and confocal microscopy. As a preclinical proof of concept, specific tumor uptake, pharmacokinetics, and feasibility for intraoperative fluorescence guidance were investigated in tumor-bearing mice and healthy pigs. Results: The designed dual-labeled PSMA inhibitors exhibited high binding affinity and PSMA-specific effective internalization. Conjugation of fluorescein isothiocyanate (10.86 ± 0.94 percentage injected dose [%ID]/g), IRDye800CW (13.66 ± 3.73 %ID/g), and DyLight800 (15.62 ± 5.52 %ID/g) resulted in a significantly increased specific tumor uptake, whereas 68 Ga-Glu-urea-Lys-HBED-CC-AlexaFluor488 (9.12 ± 5.47 %ID/g) revealed a tumor uptake similar to that of 68 Ga-PSMA-11 (4.89 ± 1.34 %ID/g). The first proof-of-concept studies with the clinically relevant candidate 68 Ga-Glu-urea-Lys-HBED-CC-IRDye800CW reinforced a fast, specific enrichment in PSMA-positive tumors, with rapid background clearance. With regard to intraoperative navigation, a specific fluorescence signal was detected in PSMA-expressing tissue. Conclusion: This study demonstrated that PSMA-11-derived dual-labeled dye conjugates are feasible for providing PSMA-specific pre-, intra-, and postoperative detection of prostate cancer lesions and have high potential for future clinical translation. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250.

PubMed

Muselaers, Constantijn H J; Rijpkema, Mark; Bos, Desirée L; Langenhuijsen, Johan F; Oyen, Wim J G; Mulders, Peter F A; Oosterwijk, Egbert; Boerman, Otto C

2015-08-01

Tumor targeted optical imaging using antibodies labeled with near infrared fluorophores is a sensitive imaging modality that might be used during surgery to assure complete removal of malignant tissue. We evaluated the feasibility of dual modality imaging and image guided surgery with the dual labeled anti-carbonic anhydrase IX antibody preparation (111)In-DTPA-G250-IRDye800CW in mice with intraperitoneal clear cell renal cell carcinoma. BALB/c nu/nu mice with intraperitoneal SK-RC-52 lesions received 10 μg DTPA-G250-IRDye800CW labeled with 15 MBq (111)In or 10 μg of the dual labeled irrelevant control antibody NUH-82 (20 mice each). To evaluate when tumors could be detected, 4 mice per group were imaged weekly during 5 weeks with single photon emission computerized tomography/computerized tomography and the fluorescence imaging followed by ex vivo biodistribution studies. As early as 1 week after tumor cell inoculation single photon emission computerized tomography and fluorescence images showed clear delineation of intraperitoneal clear cell renal cell carcinoma with good concordance between single photon emission computerized tomography/computerized tomography and fluorescence images. The high and specific accumulation of the dual labeled antibody conjugate in tumors was confirmed in the biodistribution studies. Maximum tumor uptake was observed 1 week after inoculation (mean ± SD 58.5% ± 18.7% vs 5.6% ± 2.3% injected dose per gm for DTPA-G250-IRDye800CW vs NUH-82, respectively). High tumor uptake was also observed at other time points. This study demonstrates the feasibility of dual modality imaging with dual labeled antibody (111)In-DTPA-G250-IRDye800CW in a clear cell renal cell carcinoma model. Results indicate that preoperative and intraoperative detection of carbonic anhydrase IX expressing tumors, positive resection margins and metastasis might be feasible with this approach. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Imaging, Virtual Planning, Design, and Production of Patient-Specific Implants and Clinical Validation in Craniomaxillofacial Surgery

PubMed Central

Dérand, Per; Rännar, Lars-Erik; Hirsch, Jan-M

2012-01-01

The purpose of this article was to describe the workflow from imaging, via virtual design, to manufacturing of patient-specific titanium reconstruction plates, cutting guide and mesh, and its utility in connection with surgical treatment of acquired bone defects in the mandible using additive manufacturing by electron beam melting (EBM). Based on computed tomography scans, polygon skulls were created. Following that virtual treatment plans entailing free microvascular transfer of fibula flaps using patient-specific reconstruction plates, mesh, and cutting guides were designed. The design was based on the specification of a Compact UniLOCK 2.4 Large (Synthes®, Switzerland). The obtained polygon plates were bent virtually round the reconstructed mandibles. Next, the resections of the mandibles were planned virtually. A cutting guide was outlined to facilitate resection, as well as plates and titanium mesh for insertion of bone or bone substitutes. Polygon plates and meshes were converted to stereolithography format and used in the software Magics for preparation of input files for the successive step, additive manufacturing. EBM was used to manufacture the customized implants in a biocompatible titanium grade, Ti6Al4V ELI. The implants and the cutting guide were cleaned and sterilized, then transferred to the operating theater, and applied during surgery. Commercially available software programs are sufficient in order to virtually plan for production of patient-specific implants. Furthermore, EBM-produced implants are fully usable under clinical conditions in reconstruction of acquired defects in the mandible. A good compliance between the treatment plan and the fit was demonstrated during operation. Within the constraints of this article, the authors describe a workflow for production of patient-specific implants, using EBM manufacturing. Titanium cutting guides, reconstruction plates for fixation of microvascular transfer of osteomyocutaneous bone grafts, and mesh to replace resected bone that can function as a carrier for bone or bone substitutes were designed and tested during reconstructive maxillofacial surgery. A clinically fit, well within the requirements for what is needed and obtained using traditional free hand bending of commercially available devices, or even higher precision, was demonstrated in ablative surgery in four patients. PMID:23997858

Imaging, virtual planning, design, and production of patient-specific implants and clinical validation in craniomaxillofacial surgery.

PubMed

Dérand, Per; Rännar, Lars-Erik; Hirsch, Jan-M

2012-09-01

The purpose of this article was to describe the workflow from imaging, via virtual design, to manufacturing of patient-specific titanium reconstruction plates, cutting guide and mesh, and its utility in connection with surgical treatment of acquired bone defects in the mandible using additive manufacturing by electron beam melting (EBM). Based on computed tomography scans, polygon skulls were created. Following that virtual treatment plans entailing free microvascular transfer of fibula flaps using patient-specific reconstruction plates, mesh, and cutting guides were designed. The design was based on the specification of a Compact UniLOCK 2.4 Large (Synthes(®), Switzerland). The obtained polygon plates were bent virtually round the reconstructed mandibles. Next, the resections of the mandibles were planned virtually. A cutting guide was outlined to facilitate resection, as well as plates and titanium mesh for insertion of bone or bone substitutes. Polygon plates and meshes were converted to stereolithography format and used in the software Magics for preparation of input files for the successive step, additive manufacturing. EBM was used to manufacture the customized implants in a biocompatible titanium grade, Ti6Al4V ELI. The implants and the cutting guide were cleaned and sterilized, then transferred to the operating theater, and applied during surgery. Commercially available software programs are sufficient in order to virtually plan for production of patient-specific implants. Furthermore, EBM-produced implants are fully usable under clinical conditions in reconstruction of acquired defects in the mandible. A good compliance between the treatment plan and the fit was demonstrated during operation. Within the constraints of this article, the authors describe a workflow for production of patient-specific implants, using EBM manufacturing. Titanium cutting guides, reconstruction plates for fixation of microvascular transfer of osteomyocutaneous bone grafts, and mesh to replace resected bone that can function as a carrier for bone or bone substitutes were designed and tested during reconstructive maxillofacial surgery. A clinically fit, well within the requirements for what is needed and obtained using traditional free hand bending of commercially available devices, or even higher precision, was demonstrated in ablative surgery in four patients.

Combination of Fluorescence-Guided Surgery With Photodynamic Therapy for the Treatment of Cancer

PubMed Central

He, Jun; Yang, Leping; Yi, Wenjun; Fan, Wentao; Wen, Yu; Miao, Xiongying; Xiong, Li

2017-01-01

Specific visualization of body parts is needed during surgery. Fluorescence-guided surgery (FGS) uses a fluorescence contrast agent for in vivo tumor imaging to detect and identify both malignant and normal tissues. There are several advantages and clinical benefits of FGS over other conventional medical imaging modalities, such as its safety, effectiveness, and suitability for real-time imaging in the operating room. Recent advancements in contrast agents and intraoperative fluorescence imaging devices have led to a greater potential for intraoperative fluorescence imaging in clinical applications. Photodynamic therapy (PDT) is an alternative modality to treat tumors, which uses a light-sensitive drug (photosensitizers) and special light to destroy the targeted tissues. In this review, we discuss the fluorescent contrast agents, some newly developed imaging devices, and the successful clinical application of FGS. Additionally, we present the combined strategy of FGS with PDT to further improve the therapeutic effect for patients with cancer. Taken together, this review provides a unique perspective and summarization of FGS. PMID:28849712

White light-informed optical properties improve ultrasound-guided fluorescence tomography of photoactive protoporphyrin IX

NASA Astrophysics Data System (ADS)

Flynn, Brendan P.; DSouza, Alisha V.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

2013-04-01

Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025 μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations.

Compact wearable dual-mode imaging system for real-time fluorescence image-guided surgery

PubMed Central

Zhu, Nan; Huang, Chih-Yu; Mondal, Suman; Gao, Shengkui; Huang, Chongyuan; Gruev, Viktor; Achilefu, Samuel; Liang, Rongguang

2015-01-01

Abstract. A wearable all-plastic imaging system for real-time fluorescence image-guided surgery is presented. The compact size of the system is especially suitable for applications in the operating room. The system consists of a dual-mode imaging system, see-through goggle, autofocusing, and auto-contrast tuning modules. The paper will discuss the system design and demonstrate the system performance. PMID:26358823

Fluorescence quantum yield measurements of fluorescent proteins: a laboratory experiment for a biochemistry or molecular biophysics laboratory course.

PubMed

Wall, Kathryn P; Dillon, Rebecca; Knowles, Michelle K

2015-01-01

Fluorescent proteins are commonly used in cell biology to assess where proteins are within a cell as a function of time and provide insight into intracellular protein function. However, the usefulness of a fluorescent protein depends directly on the quantum yield. The quantum yield relates the efficiency at which a fluorescent molecule converts absorbed photons into emitted photons and it is necessary to know for assessing what fluorescent protein is the most appropriate for a particular application. In this work, we have designed an upper-level, biochemistry laboratory experiment where students measure the fluorescence quantum yields of fluorescent proteins relative to a standard organic dye. Four fluorescent protein variants, enhanced cyan fluorescent protein (ECFP), enhanced green fluorescent protein (EGFP), mCitrine, and mCherry, were used, however the methods described are useful for the characterization of any fluorescent protein or could be expanded to fluorescent quantum yield measurements of organic dye molecules. The laboratory is designed as a guided inquiry project and takes two, 4 hr laboratory periods. During the first day students design the experiment by selecting the excitation wavelength, choosing the standard, and determining the concentration needed for the quantum yield experiment that takes place in the second laboratory period. Overall, this laboratory provides students with a guided inquiry learning experience and introduces concepts of fluorescence biophysics into a biochemistry laboratory curriculum. © 2014 The International Union of Biochemistry and Molecular Biology.

Activatable fluorescent probes in fluorescence-guided surgery: Practical considerations.

PubMed

Mochida, Ai; Ogata, Fusa; Nagaya, Tadanobu; Choyke, Peter L; Kobayashi, Hisataka

2018-02-15

Fluorescence-guided imaging during surgery is a promising technique that is increasingly used to aid surgeons in identifying sites of tumor and surgical margins. Of the two types of fluorescent probes, always-on and activatable, activatable probes are preferred because they produce higher target-to-background ratios, thus improving sensitivity compared with always-on probes that must contend with considerable background signal. There are two types of activatable probes: 1) enzyme-reactive probes that are normally quenched but can be activated after cleavage by cancer-specific enzymes (activity-based probes) and 2) molecular-binding probes which use cancer targeting moieties such as monoclonal antibodies to target receptors found in abundance on cancers and are activated after internalization and lysosomal processing (binding-based probes). For fluorescence-guided intraoperative surgery, enzyme-reactive probes are superior because they can react quickly, require smaller dosages especially for topical applications, have limited side effects, and have favorable pharmacokinetics. Enzyme-reactive probes are easier to use, fit better into existing work flows in the operating room and have minimal toxicity. Although difficult to prove, it is assumed that the guidance provided to surgeons by these probes results in more effective surgeries with better outcomes for patients. In this review, we compare these two types of activatable fluorescent probes for their ease of use and efficacy. Published by Elsevier Ltd.

Tumor acidity-activatable TAT targeted nanomedicine for enlarged fluorescence/magnetic resonance imaging-guided photodynamic therapy.

PubMed

Gao, Meng; Fan, Feng; Li, Dongdong; Yu, Yue; Mao, Kuirong; Sun, Tianmeng; Qian, Haisheng; Tao, Wei; Yang, Xianzhu

2017-07-01

Nanoparticles simultaneously integrated the photosensitizers and diagnostic agents represent an emerging approach for imaging-guided photodynamic therapy (PDT). However, the diagnostic sensitivity and therapeutic efficacy of nanoparticles as well as the heterogeneity of tumors pose tremendous challenges for clinical imaging-guided PDT treatment. Herein, a polymeric nanoparticle with tumor acidity (pH e )-activatable TAT targeting ligand that encapsulates the photosensitizer chlorin e6 (Ce6) and chelates contrast agent Gd 3+ is successfully developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided precision PDT. We show clear evidence that the resulting nanoparticle DA TAT-NP [its TAT lysine residues' amines was modified by 2,3-dimethylmaleic anhydride (DA)] efficiently avoids the rapid clearance by reticuloendothelial system (RES) by masking of the TAT peptide, resulting in the significantly prolonged circulation time in the blood. Once accumulating in the tumor tissues, DA TAT-NP is reactivated by tumor acidity to promote cellular uptake, resulting in enlarged fluorescence/MR imaging signal intensity and elevated in vivo PDT therapeutic effect. This concept provides new avenues to design tumor acidity-activatable targeted nanoparticles for imaging-guided cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

PubMed

Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

2017-03-01

Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal intensity value prior to 5-ALA administration (1.537±0.021 and 1.577±0.023, respectively; P=0.0055). No significant differences were observed in the AO group. These results suggest that the 5-ALA-induced PpIX enhanced the T2 signal intensity in HGG. Therefore, 5-ALA may be a potentially useful MRI contrast reagent for HGG.

Intraoperative brain tumor resection cavity characterization with conoscopic holography

NASA Astrophysics Data System (ADS)

Simpson, Amber L.; Burgner, Jessica; Chen, Ishita; Pheiffer, Thomas S.; Sun, Kay; Thompson, Reid C.; Webster, Robert J., III; Miga, Michael I.

2012-02-01

Brain shift compromises the accuracy of neurosurgical image-guided interventions if not corrected by either intraoperative imaging or computational modeling. The latter requires intraoperative sparse measurements for constraining and driving model-based compensation strategies. Conoscopic holography, an interferometric technique that measures the distance of a laser light illuminated surface point from a fixed laser source, was recently proposed for non-contact surface data acquisition in image-guided surgery and is used here for validation of our modeling strategies. In this contribution, we use this inexpensive, hand-held conoscopic holography device for intraoperative validation of our computational modeling approach to correcting for brain shift. Laser range scan, instrument swabbing, and conoscopic holography data sets were collected from two patients undergoing brain tumor resection therapy at Vanderbilt University Medical Center. The results of our study indicate that conoscopic holography is a promising method for surface acquisition since it requires no contact with delicate tissues and can characterize the extents of structures within confined spaces. We demonstrate that for two clinical cases, the acquired conoprobe points align with our model-updated images better than the uncorrected images lending further evidence that computational modeling approaches improve the accuracy of image-guided surgical interventions in the presence of soft tissue deformations.

Detection of Head and Neck Cancer in Surgical Specimens Using Quantitative Hyperspectral Imaging.

PubMed

Lu, Guolan; Little, James V; Wang, Xu; Zhang, Hongzheng; Patel, Mihir R; Griffith, Christopher C; El-Deiry, Mark W; Chen, Amy Y; Fei, Baowei

2017-09-15

Purpose: This study intends to investigate the feasibility of using hyperspectral imaging (HSI) to detect and delineate cancers in fresh, surgical specimens of patients with head and neck cancers. Experimental Design: A clinical study was conducted in order to collect and image fresh, surgical specimens from patients ( N = 36) with head and neck cancers undergoing surgical resection. A set of machine-learning tools were developed to quantify hyperspectral images of the resected tissue in order to detect and delineate cancerous regions which were validated by histopathologic diagnosis. More than two million reflectance spectral signatures were obtained by HSI and analyzed using machine-learning methods. The detection results of HSI were compared with autofluorescence imaging and fluorescence imaging of two vital-dyes of the same specimens. Results: Quantitative HSI differentiated cancerous tissue from normal tissue in ex vivo surgical specimens with a sensitivity and specificity of 91% and 91%, respectively, and which was more accurate than autofluorescence imaging ( P < 0.05) or fluorescence imaging of 2-NBDG ( P < 0.05) and proflavine ( P < 0.05). The proposed quantification tools also generated cancer probability maps with the tumor border demarcated and which could provide real-time guidance for surgeons regarding optimal tumor resection. Conclusions: This study highlights the feasibility of using quantitative HSI as a diagnostic tool to delineate the cancer boundaries in surgical specimens, and which could be translated into the clinic application with the hope of improving clinical outcomes in the future. Clin Cancer Res; 23(18); 5426-36. ©2017 AACR . ©2017 American Association for Cancer Research.

Medical laser application: translation into the clinics

NASA Astrophysics Data System (ADS)

Sroka, Ronald; Stepp, Herbert; Hennig, Georg; Brittenham, Gary M.; Rühm, Adrian; Lilge, Lothar

2015-06-01

Medical laser applications based on widespread research and development is a very dynamic and increasingly popular field from an ecological as well as an economic point of view. Conferences and personal communication are necessary to identify specific requests and potential unmet needs in this multi- and interdisciplinary discipline. Precise gathering of all information on innovative, new, or renewed techniques is necessary to design medical devices for introduction into clinical applications and finally to become established for routine treatment or diagnosis. Five examples of successfully addressed clinical requests are described to show the long-term endurance in developing light-based innovative clinical concepts and devices. Starting from laboratory medicine, a noninvasive approach to detect signals related to iron deficiency is shown. Based upon photosensitization, fluorescence-guided resection had been discovered, opening the door for photodynamic approaches for the treatment of brain cancer. Thermal laser application in the nasal cavity obtained clinical acceptance by the introduction of new laser wavelengths in clinical consciousness. Varicose veins can be treated by innovative endoluminal treatment methods, thus reducing side effects and saving time. Techniques and developments are presented with potential for diagnosis and treatment to improve the clinical situation for the benefit of the patient.

Optical imaging-guided cancer therapy with fluorescent nanoparticles

PubMed Central

Jiang, Shan; Gnanasammandhan, Muthu Kumara; Zhang, Yong

2010-01-01

The diagnosis and treatment of cancer have been greatly improved with the recent developments in nanotechnology. One of the promising nanoscale tools for cancer diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs, quantum dots and upconversion NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. Furthermore, the emerging development of novel multi-functional NPs, which can be conjugated with several functional molecules simultaneously including targeting moieties, therapeutic agents and imaging probes, provides new potentials for clinical therapies and diagnostics and undoubtedly will play a critical role in cancer therapy. In this article, we review the types and characteristics of fluorescent NPs, in vitro and in vivo imaging of cancer using fluorescent NPs and multi-functional NPs for imaging-guided cancer therapy. PMID:19759055

Multifunctional gold nanorods for image-guided surgery and photothermal therapy

NASA Astrophysics Data System (ADS)

Barriere, Clement; Qi, Ji; Garcia-Allende, P. Beatriz; Newton, Richard; Elson, Daniel S.

2012-03-01

Nanoparticles are viewed as a promising tool for numerous medical applications, for instance imaging and photothermal therapy (PTT) has been proposed using gold nanorods. We are developing multi-functional gold nanorods (m-GNRs) which have potential for image guided endoscopic surgery of tumour tissue with a modified laparoscope system. A new synthesis method potentially allows any useful acid functionalised molecules to be bonded at the surface. We have created fluorescent m-GNRs which can be used for therapy as they absorb light in the infrared, which may penetrate deep into the tissue and produce localised heating. We have performed a tissue based experiment to demonstrate the feasibility of fluorescence guided PTT using m- GNRs. Ex vivo tests were performed using sheep heart. This measurement, correlated with the fluorescence signal of the m-GNRs measured by the laparoscope allows the clear discrimination of the artery system containing m-GNRs. A laser diode was used to heat the m-GNRs and a thermal camera was able to record the heat distribution. These images were compared to the fluorescence images for validation.

Fabrication et caracterisation de cristaux photoniques pour exaltation de fluorescence

NASA Astrophysics Data System (ADS)

Gascon, Annabelle

2011-12-01

In today's world, there is a pressing need for point-of-care molecular analysis that is fast, inexpensive and transportable. Lab-on-a- chips are designed to fulfill that need. They are micro-electromechanical systems (MEMS), fabricated with microelectronic techniques, that use the analytes physical properties to detect their presence in liquid samples. This detection can be performed by attaching the analyte to quantum dots. These quantum dots are semiconducting nanoparticles with narrow fluorescence band. In our project, we use a tuneable system with a two-slab photonic crystal that serves as a tuneable optical filter, detecting the presence and wavelength of these quantum dots. Photonic crystals are dielectrics with a variable refractive index, with a period near the visible light wavelength. They are called photonic crystals because they have a photonic band gap just as atomic crystals, periodic structure of atoms, have an electronic band gap. They are photonic because photons instead of electrons propagate through them. They can also enhance fluorescence from quantum dots at the photonic crystals guided resonance wavelength. My project objectives are to: (1) Fabricate two-slab photonic crystal, (2) Characterize photonic crystals, (3) Place quantum dots on photonic crystals, (4) Measure fluorescence enhancement. The device made during this project consists of a silicon wafer on which were deposited a 200 nm silicon nitride layer, then a 200 nm silicon dioxide layer and finally another 200 nm silicon nitride layer. An electron-beam lithography defines the photonic crystals and the MEMS. The photonic crystals are square lattices of holes 180 nm in diameter, at a period of 460 nm, etched through the two silicon nitride slabs. The two slabs are etched in a single step of Reactive Ion Etching (RIE). Then, the silicon under the photonic crystal is etched from the backside up to the nitride by deep-RIE. Finally, the oxide layer is removed in order to completely suspend the two-slab photonic crystal. The M EMS can change the gap between the two slabs in order to tune the guided resonance wavelength. An optical set-up is used to trace the photonic crystals transmission and reflection spectrum, in order to know the guided resonance position. A supercontinuum source illuminates the device at a normal incidence angle for wavelength between 400 nm and 800 nm. High-resolution spectra are obtained with a CCD camera spectrometer. Different types of one-slab photonic crystals are analyzed with this approach: we observe guided resonance peaks near 550 nm, 615 nm and 700 nm. Finally, a quantum dots microdrop is placed on the photonic crystal. The quantum dots emission wavelength matches with the photonic crystal guided resonance. A hyperspectral fluorescence microscope excites quantum dots between 436 nm and 483 nm, detects emission greater than 500 nm and plots a fluorescence wavelength spectrum. This set-up measures and compares the fluorescence of the quantum dots placed on and next to the photonic crystals. Our results show that the fluorescence is 30 times higher on the photonic crystals, but the fluorescence wavelength corresponds neither to the quantum dots emission nor to the photonic crystal guided resonance. In conclusion, this master thesis project demonstrates that it is possible to fabricate two-slab photonic crystals in silicon nitride and to plot their transmission and reflection spectra in order to find their guided resonance position. A fluorescence enhancement is visible, but at a different wavelength than of the quantum dots.

Huge mediastinal liposarcoma resected by clamshell thoracotomy: a case report.

PubMed

Toda, Michihito; Izumi, Nobuhiro; Tsukioka, Takuma; Komatsu, Hiroaki; Okada, Satoshi; Hara, Kantaro; Ito, Ryuichi; Shibata, Toshihiko; Nishiyama, Noritoshi

2017-12-01

Liposarcoma is the single most common soft tissue sarcoma. Because mediastinal liposarcomas often grow rapidly and frequently recur locally despite adjuvant chemotherapy and radiotherapy, they require complete excision. Therefore, the feasibility of achieving complete surgical excision must be carefully considered. We here report a case of a huge mediastinal liposarcoma resected via clamshell thoracotomy. A 64-year-old man presented with dyspnea on effort. Cardiomegaly had been diagnosed 6 years previously, but had been left untreated. A computed tomography scan showed a huge (36 cm diameter) anterior mediastinal tumor expanding into the pleural cavities bilaterally. The tumor comprised mostly fatty tissue but contained two solid areas. Echo-guided needle biopsies were performed and a diagnosis of an atypical lipomatous tumor was established by pathological examination of the biopsy samples. Surgical resection was performed via a clamshell incision, enabling en bloc resection of this huge tumor. Although there was no invasion of surrounding organs, the left brachiocephalic vein was resected because it was circumferentially surrounded by tumor and could not be preserved. The tumor weighed 3500 g. Pathologic examination of the resected tumor resulted in a diagnosis of a biphasic tumor comprising dedifferentiated liposarcoma and non-adipocytic sarcoma with necrotic areas. The patient remains free of recurrent tumor 20 months postoperatively. Clamshell incision provides an excellent surgical field and can be performed safely in patients with huge mediastinal liposarcomas.

Sampling in Atypical Endometrial Hyperplasia: Which Method Results in the Lowest Underestimation of Endometrial Cancer? A Systematic Review and Meta-analysis.

PubMed

Bourdel, Nicolas; Chauvet, Pauline; Tognazza, Enrica; Pereira, Bruno; Botchorishvili, Revaz; Canis, Michel

2016-01-01

Our objective was to identify the most accurate method of endometrial sampling for the diagnosis of complex atypical hyperplasia (CAH), and the related risk of underestimation of endometrial cancer. We conducted a systematic literature search in PubMed and EMBASE (January 1999-September 2013) to identify all registered articles on this subject. Studies were selected with a 2-step method. First, titles and abstracts were analyzed by 2 reviewers, and 69 relevant articles were selected for full reading. Then, the full articles were evaluated to determine whether full inclusion criteria were met. We selected 27 studies, taking into consideration the comparison between histology of endometrial hyperplasia obtained by diagnostic tests of interest (uterine curettage, hysteroscopically guided biopsy, or hysteroscopic endometrial resection) and subsequent results of hysterectomy. Analysis of the studies reviewed focused on 1106 patients with a preoperative diagnosis of atypical endometrial hyperplasia. The mean risk of finding endometrial cancer at hysterectomy after atypical endometrial hyperplasia diagnosed by uterine curettage was 32.7% (95% confidence interval [CI], 26.2-39.9), with a risk of 45.3% (95% CI, 32.8-58.5) after hysteroscopically guided biopsy and 5.8% (95% CI, 0.8-31.7) after hysteroscopic resection. In total, the risk of underestimation of endometrial cancer reaches a very high rate in patients with CAH using the classic method of evaluation (i.e., uterine curettage or hysteroscopically guided biopsy). This rate of underdiagnosed endometrial cancer leads to the risk of inappropriate surgical procedures (31.7% of tubal conservation in the data available and no abdominal exploration in 24.6% of the cases). Hysteroscopic resection seems to reduce the risk of underdiagnosed endometrial cancer. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Orbit-associated tumors: navigation and control of resection using intraoperative computed tomography.

PubMed

Terpolilli, Nicole A; Rachinger, Walter; Kunz, Mathias; Thon, Niklas; Flatz, Wilhelm H; Tonn, Jörg-Christian; Schichor, Christian

2016-05-01

OBJECT Treatment of skull base lesions is complex and usually requires a multidisciplinary approach. In meningioma, which is the most common tumor entity in this region, resection is considered to be the most important therapeutic step to avoid tumor recurrence. However, resection of skull base lesions with orbital or optic nerve involvement poses a challenge due to their anatomical structure and their proximity to eloquent areas. Therefore the main goal of surgery should be to achieve the maximum extent of resection while preserving neurological function. In the postoperative course, medical and radiotherapeutic strategies may then be successfully used to treat possible tumor residues. Methods to safely improve the extent of resection in skull base lesions therefore are desirable. The current study reports the authors' experience with the use of intraoperative CT (iCT) combined with neuronavigation with regard to feasibility and possible benefits of the method. METHODS Those patients with tumorous lesions in relationship to the orbit, sphenoid wing, or cavernous sinus who were surgically treated between October 2008 and December 2013 using iCT-based neuronavigation and in whom an intraoperative scan was obtained for control of resection were included. In all cases a second iCT scan was performed under sterile conditions after completion of navigation-guided microsurgical tumor resection. The surgical strategy was adapted accordingly; if necessary, resection was continued. RESULTS Twenty-three patients (19 with WHO Grade I meningioma and 4 with other lesions) were included. The most common clinical symptoms were loss of visual acuity and exophthalmus. Intraoperative control of resection by iCT was successfully obtained in all cases. Intraoperative imaging changed the surgical approach in more than half (52.2%) of these patients, either because iCT demonstrated unexpected residual tumor masses or because the second scan revealed additional tumor tissue that was not detected in the first scan due to overlay by osseous tumor parts; in these cases resection was continued. In the remaining cases resection was concluded as planned because iCT verified the surgeon's microscopic estimation of tumor resection status. Postoperative visual outcome was favorable in more than 80% of patients. CONCLUSIONS Intraoperative CT allows control of resection in case of uncertainty and can help to improve the extent of maximal safe resection, especially in case of osseous tumor parts and masses within the orbit.

Navigation and Image Injection for Control of Bone Removal and Osteotomy Planes in Spine Surgery.

PubMed

Kosterhon, Michael; Gutenberg, Angelika; Kantelhardt, Sven Rainer; Archavlis, Elefterios; Giese, Alf

2017-04-01

In contrast to cranial interventions, neuronavigation in spinal surgery is used in few applications, not tapping into its full technological potential. We have developed a method to preoperatively create virtual resection planes and volumes for spinal osteotomies and export 3-D operation plans to a navigation system controlling intraoperative visualization using a surgical microscope's head-up display. The method was developed using a Sawbone ® model of the lumbar spine, demonstrating feasibility with high precision. Computer tomographic and magnetic resonance image data were imported into Amira ® , a 3-D visualization software. Resection planes were positioned, and resection volumes representing intraoperative bone removal were defined. Fused to the original Digital Imaging and Communications in Medicine data, the osteotomy planes were exported to the cranial version of a Brainlab ® navigation system. A navigated surgical microscope with video connection to the navigation system allowed intraoperative image injection to visualize the preplanned resection planes. The workflow was applied to a patient presenting with a congenital hemivertebra of the thoracolumbar spine. Dorsal instrumentation with pedicle screws and rods was followed by resection of the deformed vertebra guided by the in-view image injection of the preplanned resection planes into the optical path of a surgical microscope. Postoperatively, the patient showed no neurological deficits, and the spine was found to be restored in near physiological posture. The intraoperative visualization of resection planes in a microscope's head-up display was found to assist the surgeon during the resection of a complex-shaped bone wedge and may help to further increase accuracy and patient safety. Copyright © 2017 by the Congress of Neurological Surgeons

Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls

NASA Astrophysics Data System (ADS)

Zanello, Marc; Poulon, Fanny; Pallud, Johan; Varlet, Pascale; Hamzeh, H.; Abi Lahoud, Georges; Andreiuolo, Felipe; Ibrahim, Ali; Pages, Mélanie; Chretien, Fabrice; di Rocco, Federico; Dezamis, Edouard; Nataf, François; Turak, Baris; Devaux, Bertrand; Abi Haidar, Darine

2017-02-01

Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

Safety and Efficacy of Modified Preoperative Lung Nodule Microcoil Localization Without Pleural Marking: A Pilot Study.

PubMed

Kha, Lan-Chau T; Hanneman, Kate; Donahoe, Laura; Chung, Taebong; Pierre, Andrew F; Yasufuku, Kazuhiro; Keshavjee, Shafique; Mayo, John R; Paul, Narinder S; Nguyen, Elsie T

2016-01-01

The purpose of this pilot study was to evaluate the safety and efficacy of preoperative computed tomography (CT)-guided percutaneous microcoil lung nodule localization without pleural marking compared with the established technique with pleural marking. Sixty-three consecutive patients (66.7% female, mean age 61.6±11.4 y) with 64 lung nodules resected between October 2008 and January 2014 were retrospectively evaluated. Of the nodules, 29.7% (n=19) had microcoil deployment with pleural marking (control group) and 70.3% (n=45) had microcoil deployment without pleural marking (pilot group). Clinical, pathologic, and imaging characteristics, radiation dose, CT procedure and operating room time, and complete resection and complication rates were compared between the pilot and control groups. There was no significant difference in nodule size (P=0.552) or distance from the pleural surface (P=0.222) between the pilot and control groups. However, mean procedure duration (53.6±18.3 vs. 72.8±25.3 min, P=0.001) and total effective radiation dose (5.1±2.6 vs. 7.1±4.9 mSv, P=0.039) were significantly lower in the pilot group compared with the control group. CT procedure-related complications (P=0.483) [including pneumothoraces (P=0.769) and pulmonary hemorrhage (P=1.000)], operating room time (P=0.926), complete resection rates (P=0.520), intraoperative complications (P=0.549), and postoperative complications (P=1.000) were similar between the pilot and control groups. Preoperative CT-guided lung nodule microcoil localization performed without visceral pleural marking appears to decrease the CT procedure time and radiation dose while maintaining equivalent complete resection rates and procedural and surgical complications, when compared with microcoil localization performed with pleural marking.

Non-rigid registration of 3D ultrasound for neurosurgery using automatic feature detection and matching.

PubMed

Machado, Inês; Toews, Matthew; Luo, Jie; Unadkat, Prashin; Essayed, Walid; George, Elizabeth; Teodoro, Pedro; Carvalho, Herculano; Martins, Jorge; Golland, Polina; Pieper, Steve; Frisken, Sarah; Golby, Alexandra; Wells, William

2018-06-04

The brain undergoes significant structural change over the course of neurosurgery, including highly nonlinear deformation and resection. It can be informative to recover the spatial mapping between structures identified in preoperative surgical planning and the intraoperative state of the brain. We present a novel feature-based method for achieving robust, fully automatic deformable registration of intraoperative neurosurgical ultrasound images. A sparse set of local image feature correspondences is first estimated between ultrasound image pairs, after which rigid, affine and thin-plate spline models are used to estimate dense mappings throughout the image. Correspondences are derived from 3D features, distinctive generic image patterns that are automatically extracted from 3D ultrasound images and characterized in terms of their geometry (i.e., location, scale, and orientation) and a descriptor of local image appearance. Feature correspondences between ultrasound images are achieved based on a nearest-neighbor descriptor matching and probabilistic voting model similar to the Hough transform. Experiments demonstrate our method on intraoperative ultrasound images acquired before and after opening of the dura mater, during resection and after resection in nine clinical cases. A total of 1620 automatically extracted 3D feature correspondences were manually validated by eleven experts and used to guide the registration. Then, using manually labeled corresponding landmarks in the pre- and post-resection ultrasound images, we show that our feature-based registration reduces the mean target registration error from an initial value of 3.3 to 1.5 mm. This result demonstrates that the 3D features promise to offer a robust and accurate solution for 3D ultrasound registration and to correct for brain shift in image-guided neurosurgery.

Integrating magnetic resonance imaging postprocessing results into neuronavigation for electrode implantation and resection of subtle focal cortical dysplasia in previously cryptogenic epilepsy.

PubMed

Wellmer, Jörg; Parpaley, Yaroslav; von Lehe, Marec; Huppertz, Hans-Jürgen

2010-01-01

Focal cortical dysplasias (FCDs) are highly epileptogenic lesions. Surgical removal is frequently the best treatment option for pharmacoresistant epilepsy. However, subtle FCDs may remain undetected even after high-resolution magnetic resonance imaging (MRI). Morphometric MRI analysis, which compares the individual brain with a normal database, can facilitate the detection of FCDs. We describe how the results of normal database-based MRI postprocessing can be used to guide stereotactic electrode implantation and subsequent resection of lesions that are suspected to be FCDs. A presurgical evaluation was conducted on a 19-year-old woman with pharmacoresistant hypermotor seizures. Conventional high-resolution MRI was classified as negative for epileptogenic lesions. However, morphometric analysis of the spatially normalized MRI revealed abnormal gyration and blurring of the gray-white matter junction, which was suggestive of a small and deeply seated FCD in the left frontal lobe. The brain region highlighted by morphometric analysis was marked as a region of interest, transferred back to the original dimension of the individual MRI, and imported into a neuronavigation system. This allowed the region of interest-targeted stereotactic implantation of 2 depth electrodes, by which seizure onset was confirmed in the lesion. The electrodes also guided the final resection, which rendered the patient seizure-free. The lesion was histologically classified as FCD Palmini and Lüders IIB. Transferring normal database-based MRI postprocessing results into a neuronavigation system is a new and worthwhile extension of multimodal neuronavigation. The combination of resulting regions of interest with functional and anatomic data may facilitate planning of electrode implantation for invasive electroencephalographic recordings and the final resection of small or deeply seated FCDs.

Therapy of Pancreatic Neuroendocrine Tumors: Fine Needle Intervention including Ethanol and Radiofrequency Ablation

PubMed Central

Lakhtakia, Sundeep

2017-01-01

Pancreatic neuroendocrine tumors (PNETs) are increasingly being detected, though usually as incidental findings. Majority of the PNETs are non-functional and surgical resection is the standard of care for most of them. However, in patients with small PNETs localized within the pancreas, who are unfit or unwilling for surgery, alternate methods of treatment are needed. Direct methods of ablation of PNETs, using either ethanol injection or radiofrequency ablation (RFA), are emerging as effective methods. The limited literature available as case reports or case series on endoscopic ultrasound (EUS)-guided local ablation using either ethanol or RFA has demonstrated safety and efficacy along with short- to medium-term sustained relief. Long-term benefits with these local ablative therapies are awaited. Comparative studies are needed to show which of these two competing technologies is superior. Finally, comparative trials of EUS-guided ablation with surgical resection in terms of efficacy and safety will ensure their place in the management algorithm. PMID:29207860

Automating the design of resection guides specific to patient anatomy in knee replacement surgery by enhanced 3D curvature and surface modeling of distal femur shape models.

PubMed

Cerveri, Pietro; Manzotti, Alfonso; Confalonieri, Norberto; Baroni, Guido

2014-12-01

Personalized resection guides (PRG) have been recently proposed in the domain of knee replacement, demonstrating clinical outcome similar or even superior to both manual and navigated interventions. Among the mandatory pre-surgical steps for PRG prototyping, the measurement of clinical landmarks (CL) on the bony surfaces is recognized as a key issue due to lack of standardized methodologies, operator-dependent variability and time expenditure. In this paper, we focus on the reliability and repeatability of an anterior-posterior axis, also known as Whiteside line (WL), of the distal femur proposing automatic surface processing and modeling methods aimed at overcoming some of the major concerns related to the manual identification of such CL on 2D images and 3D models. We show that the measurement of WL, exploiting the principle of mean-shifting surface curvature, is highly repeatable and coherent with clinical knowledge. Copyright © 2014 Elsevier Ltd. All rights reserved.

An Intraoperative β- Detecting Probe for Radio-Guided Surgery in Tumour Resection

NASA Astrophysics Data System (ADS)

Russomando, Andrea; Bellini, Fabio; Bocci, Valerio; Collamati, Francesco; De Lucia, Erika; Faccini, Riccardo; Marafini, Michela; Mattei, Ilaria; Chiodi, Giacomo; Patera, Vincenzo; Recchia, Luigi; Sarti, Alessio; Sciubba, Adalberto; Camillocci, Elena Solfaroli; Paramatti, Riccardo; Voena, Cecilia; Donnarumma, Raffaella; Mancini-Terracciano, Carlo; Morganti, Silvio

2016-10-01

The development of the β- based radio-guided surgery aims to extend the technique to those tumours where surgery is the only possible treatment and the assessment of the resection would most profit from the low background around the lesion, as for brain tumours. To validate the technique, prototypes of the intraoperative β- probe have been developed. This paper discusses the design details of one of the prototypes and its tests performed in laboratory. In such tests particular care has to be taken to reproduce the surgical field conditions. The tests showed that the prototype under study has 70% efficiency on electrons with an energy threshold at 540 keV, a point-like resolution of 2.8±0.1 mm, and a sensitivity to photons lower than 1%. The tests also demonstrated, with an innovative technique to produce specific phantoms, that 0.5 ml residuals can be safely identified in 1 s with tumor-non-tumor ratio equal to 10.

A Compressive Sensing Approach for Glioma Margin Delineation Using Mass Spectrometry

PubMed Central

Gholami, Behnood; Agar, Nathalie Y. R.; Jolesz, Ferenc A.; Haddad, Wassim M.; Tannenbaum, Allen R.

2013-01-01

Surgery, and specifically, tumor resection, is the primary treatment for most patients suffering from brain tumors. Medical imaging techniques, and in particular, magnetic resonance imaging are currently used in diagnosis as well as image-guided surgery procedures. However, studies show that computed tomography and magnetic resonance imaging fail to accurately identify the full extent of malignant brain tumors and their microscopic infiltration. Mass spectrometry is a well-known analytical technique used to identify molecules in a given sample based on their mass. In a recent study, it is proposed to use mass spectrometry as an intraoperative tool for discriminating tumor and non-tumor tissue. Integration of mass spectrometry with the resection module allows for tumor resection and immediate molecular analysis. In this paper, we propose a framework for tumor margin delineation using compressive sensing. Specifically, we show that the spatial distribution of tumor cell concentration can be efficiently reconstructed and updated using mass spectrometry information from the resected tissue. In addition, our proposed framework is model-free, and hence, requires no prior information of spatial distribution of the tumor cell concentration. PMID:22255629

Hyperspectral imaging fluorescence excitation scanning for colon cancer detection

NASA Astrophysics Data System (ADS)

Leavesley, Silas J.; Walters, Mikayla; Lopez, Carmen; Baker, Thomas; Favreau, Peter F.; Rich, Thomas C.; Rider, Paul F.; Boudreaux, Carole W.

2016-10-01

Optical spectroscopy and hyperspectral imaging have shown the potential to discriminate between cancerous and noncancerous tissue with high sensitivity and specificity. However, to date, these techniques have not been effectively translated to real-time endoscope platforms. Hyperspectral imaging of the fluorescence excitation spectrum represents new technology that may be well suited for endoscopic implementation. However, the feasibility of detecting differences between normal and cancerous mucosa using fluorescence excitation-scanning hyperspectral imaging has not been evaluated. The goal of this study was to evaluate the initial feasibility of using fluorescence excitation-scanning hyperspectral imaging for measuring changes in fluorescence excitation spectrum concurrent with colonic adenocarcinoma using a small pre-pilot-scale sample size. Ex vivo analysis was performed using resected pairs of colorectal adenocarcinoma and normal mucosa. Adenocarcinoma was confirmed by histologic evaluation of hematoxylin and eosin (H&E) permanent sections. Specimens were imaged using a custom hyperspectral imaging fluorescence excitation-scanning microscope system. Results demonstrated consistent spectral differences between normal and cancerous tissues over the fluorescence excitation range of 390 to 450 nm that could be the basis for wavelength-dependent detection of colorectal cancers. Hence, excitation-scanning hyperspectral imaging may offer an alternative approach for discriminating adenocarcinoma from surrounding normal colonic mucosa, but further studies will be required to evaluate the accuracy of this approach using a larger patient cohort.

Using a Guided Machine Learning Ensemble Model to Predict Discharge Disposition following Meningioma Resection.

PubMed

Muhlestein, Whitney E; Akagi, Dallin S; Kallos, Justiss A; Morone, Peter J; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola B

2018-04-01

Objective  Machine learning (ML) algorithms are powerful tools for predicting patient outcomes. This study pilots a novel approach to algorithm selection and model creation using prediction of discharge disposition following meningioma resection as a proof of concept. Materials and Methods  A diversity of ML algorithms were trained on a single-institution database of meningioma patients to predict discharge disposition. Algorithms were ranked by predictive power and top performers were combined to create an ensemble model. The final ensemble was internally validated on never-before-seen data to demonstrate generalizability. The predictive power of the ensemble was compared with a logistic regression. Further analyses were performed to identify how important variables impact the ensemble. Results  Our ensemble model predicted disposition significantly better than a logistic regression (area under the curve of 0.78 and 0.71, respectively, p  = 0.01). Tumor size, presentation at the emergency department, body mass index, convexity location, and preoperative motor deficit most strongly influence the model, though the independent impact of individual variables is nuanced. Conclusion  Using a novel ML technique, we built a guided ML ensemble model that predicts discharge destination following meningioma resection with greater predictive power than a logistic regression, and that provides greater clinical insight than a univariate analysis. These techniques can be extended to predict many other patient outcomes of interest.

First Experience of Ultrasound-guided Percutaneous Ablation for Recurrent Hepatoblastoma after Liver Resection in Children

PubMed Central

Liu, Baoxian; Zhou, Luyao; Huang, Guangliang; Zhong, Zhihai; Jiang, Chunlin; Shan, Quanyuan; Xu, Ming; Kuang, Ming; Xie, Xiaoyan

2015-01-01

This study aimed to summarize the first experience with ultrasound-guided percutaneous ablation treatment (PAT) for recurrent hepatoblastoma (HB) after liver resection in children. From August 2013 to October 2014, PAT was used to treat 5 children with a total of 8 recurrent HB (mean size, 1.4 ± 0.8 cm; size range, 0.7–3.1 cm), including 4 patients with 7 tumors in the liver and 1 patient with 1 tumor in the lung. Technical success was achieved in all patients (5/5, 100%). The complete ablation rate after the first ablation session was 80% (4/5) on a patient-by-patient basis and 87.5% (7/8) on a tumor-by-tumor basis. Only 1 patient developed a fever with temperature >39 °C; it lasted 4 days after radiofrequency ablation (RFA) and was resolved by conservative therapy. During the follow-up period, new intrahepatic recurrences after PAT were detected in two patients. One died due to tumor progression 4 months after ablation. The median overall survival time after PAT was 13.8 months. PAT is a safe and promising therapy for children with recurrent HB after liver resection, and further investigation in large-scale randomized clinical trials is required to determine its role in the treatment of this disease. PMID:26578035

Direct observation of laser guided corona discharges

PubMed Central

Wang, Tie-Jun; Wei, Yingxia; Liu, Yaoxiang; Chen, Na; Liu, Yonghong; Ju, Jingjing; Sun, Haiyi; Wang, Cheng; Lu, Haihe; Liu, Jiansheng; Chin, See Leang; Li, Ruxin; Xu, Zhizhan

2015-01-01

Laser based lightning control holds a promising way to solve the problem of the long standing disaster of lightning strikes. But it is a challenging project due to insufficient understanding of the interaction between laser plasma channel and high voltage electric filed. In this work, a direct observation of laser guided corona discharge is reported. Laser filament guided streamer and leader types of corona discharges were observed. An enhanced ionization took place in the leader (filament) through the interaction with the high voltage discharging field. The fluorescence lifetime of laser filament guided corona discharge was measured to be several microseconds, which is 3 orders of magnitude longer than the fluorescence lifetime of laser filaments. This work could be advantageous towards a better understanding of laser assisted leader development in the atmosphere. PMID:26679271

Noncontact point spectroscopy guided by two-channel fluorescence imaging in a hamster cheek pouch model

NASA Astrophysics Data System (ADS)

Yang, Victor X.; Yeow, Jenny; Lilge, Lothar D.; Kost, James; Mang, Thomas S.; Wilson, Brian C.

1999-07-01

A system for in vivo, fluorescence image-guided, non-contact point fluorescence spectroscopy is presented. A 442 nm HeCd laser is used as the fluorescence excitation source. An intensified CCD serves as the detector for both imaging and spectroscopy, on which two regions of 300 X 300 pixels were used for green (500 +/- 18 nm) and red (630 +/- 18 nm) imaging channels, and a strip of 600 X 120 pixels are used for emission spectroscopy (450 - 750 nm). At a working distance of 40 mm, the system has a spatial resolution of 0.16 mm and a spectral resolution of 5 nm. System performance is demonstrated in a carcinogenesis model in hamsters, where tumors were induced by painting DMBA in the cheek pouch. Autofluorescence and Photofrin-induced fluorescence measurements were performed every 2 weeks during the 18 weeks of tumor induction. Punch biopsies on selected animals were taken for histological staging. The results show that autofluorescence fluorescence can distinguish dysplasia from normal mucosal tissue model, utilizing the peak red intensity (or the red-to-green intensity ratio). Photofrin-induced fluorescence was superior to autofluorescence for differentiating high grade dysplasia from invasive cancer.

[The technique of sleeve resection on the bronchial and pulmonary vascular tree].

PubMed

Branscheid, D; Beshay, M

2013-06-01

Sleeve resections of the lungs have affected the oncologic radicality, parenchyma and lung function-saving resections and extended the indications for operations in thoracic surgery. Whenever lung amputations can be avoided by bronchoplastic and/or angioplastic procedures with the same radicality, sleeve resection should be performed. In centrally located distinct malignomas, intraluminal tumor growth (T3) infiltrations of peribronchial or extrabronchial areas, the lobular ostia and the pulmonary artery (T2/T3) as well as lymph node involvement (N1/N2), these procedures give a better qualitative survival and lower morbidity and mortality rates. Broncoscope-guided localization of a double lumen tube and routine anesthesia monitoring are mandatory. Before performing sleeve resections a complete lymph node dissection should be done without denuding the area of the anastomosis and sparing the bronchial arteries. Preoperative endoscopic biopsies, knowledge of the topography and mobilization of the vascular and bronchial tree, subtile operation techniques, perioperative and postoperative videobronchoscopic guidance as well as intraoperative frozen sections and a tension-free and smooth anastomosis, avoid postoperative complications. Depending on the blood supply of the bronchial tree a vascularized flap is indicated. Operability can therefore be achieved in elderly patients with limited pulmonary function, particularly those under adjuvant or neoadjuvant therapy who are no longer suitable for pneumonectomy.

Extra-luminal detection of assumed colonic tumor site by near-infrared laparoscopy.

PubMed

Zako, Tamotsu; Ito, Masaaki; Hyodo, Hiroshi; Yoshimoto, Miya; Watanabe, Masayuki; Takemura, Hiroshi; Kishimoto, Hidehiro; Kaneko, Kazuhiro; Soga, Kohei; Maeda, Mizuo

2016-09-01

Localization of colorectal tumors during laparoscopic surgery is generally performed by tattooing into the submucosal layer of the colon. However, faint and diffuse tattoos may lead to difficulties in recognizing cancer sites, resulting in inappropriate resection of the colon. We previously demonstrated that yttrium oxide nanoparticles doped with the rare earth ions (ytterbium and erbium) (YNP) showed strong near-infrared (NIR) emission under NIR excitation (1550 nm emission with 980 nm excitation). NIR light can penetrate deep tissues. In this study, we developed an NIR laparoscopy imaging system and demonstrated its use for accurate resection of the colon in swine. The NIR laparoscopy system consisted of an NIR laparoscope, NIR excitation laser diode, and an NIR camera. Endo-clips coated with YNP (NIR clip), silicon rubber including YNP (NIR silicon mass), and YNP solution (NIR ink) were prepared as test NIR markers. We used a swine model to detect an assumed colon cancer site using NIR laparoscopy, followed by laparoscopic resection. The NIR markers were fixed at an assumed cancer site within the colon by endoscopy. An NIR laparoscope was then introduced into the abdominal cavity through a laparoscopy port. NIR emission from the markers in the swine colon was successfully recognized using the NIR laparoscopy imaging system. The position of the markers in the colon could be identified. Accurate resection of the colon was performed successfully by laparoscopic surgery under NIR fluorescence guidance. The presence of the NIR markers within the extirpated colon was confirmed, indicating resection of the appropriate site. NIR laparoscopic surgery is useful for colorectal cancer site recognition and accurate resection using laparoscopic surgery.

Gross total resection rates in contemporary glioblastoma surgery: results of an institutional protocol combining 5-aminolevulinic acid intraoperative fluorescence imaging and brain mapping.

PubMed

Schucht, Philippe; Beck, Jürgen; Abu-Isa, Janine; Andereggen, Lukas; Murek, Michael; Seidel, Kathleen; Stieglitz, Lennard; Raabe, Andreas

2012-11-01

Complete resection of contrast-enhancing tumor has been recognized as an important prognostic factor in patients with glioblastoma and is a primary goal of surgery. Various intraoperative technologies have recently been introduced to improve glioma surgery. To evaluate the impact of using 5-aminolevulinic acid and intraoperative mapping and monitoring on the rate of complete resection of enhancing tumor (CRET), gross total resection (GTR), and new neurological deficits as part of an institutional protocol. One hundred three consecutive patients underwent resection of glioblastoma from August 2008 to November 2010. Eligibility for CRET was based on the initial magnetic resonance imaging assessed by 2 reviewers. The primary end point was the number of patients with CRET and GTR. Secondary end points were volume of residual contrast-enhancing tissue and new postoperative neurological deficits. Fifty-three patients were eligible for GTR/CRET (n = 43 newly diagnosed glioblastoma, n = 10 recurrent); 13 additional patients received surgery for GTR/CRET-ineligible glioblastoma. GTR was achieved in 96% of patients (n = 51, no residual enhancement >0.175 cm); CRET was achieved in 89% (n = 47, no residual enhancement). Postoperatively, 2 patients experienced worsening of preoperative hemianopia, 1 patient had a new mild hemiparesis, and another patient sustained sensory deficits. Using 5-aminolevulinic acid imaging and intraoperative mapping/monitoring together leads to a high rate of CRET and an increased rate of GTR compared with the literature without increasing the rate of permanent morbidity. The combination of safety and resection-enhancing intraoperative technologies was likely to be the major drivers for this high rate of CRET/GTR.

Imaging-guided thoracoscopic resection of a ground-glass opacity lesion in a hybrid operating room equipped with a robotic C-arm CT system.

PubMed

Hsieh, Chen-Ping; Hsieh, Ming-Ju; Fang, Hsin-Yueh; Chao, Yin-Kai

2017-05-01

The intraoperative identification of small pulmonary nodules through video-assisted thoracoscopic surgery remains challenging. Although preoperative CT-guided nodule localization is commonly used to detect tumors during video-assisted thoracoscopic surgery (VATS), this approach carries inherent risks. We report the case of a patient with stage I lung cancer presenting as an area of ground-glass opacity (GGO) in the right upper pulmonary lobe. He successfully underwent a single-stage, CT-guided localization and removal of the pulmonary nodule within a hybrid operating room (OR) equipped with a robotic C-arm.

Efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer.

PubMed

Lee, Jae Seung; Lee, Seo Yeon; Kim, Woo Jung; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Jeong, Byong Chang

2012-12-01

The aim of this study was to evaluate the efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer. In a prospective design, we included patients who had a bladder lesion suggesting bladder cancer. Patients with massive hematuria, urethral Foley catheter insertion, chronic retention state, or urinary tract infection were excluded. After the bladder was emptied, hexaminolevulinate was gently administered into the bladder. One hour later, cystoscopy under white light and blue light was performed. After marking the lesions confirmed with white light or blue light, transurethral resection of the bladder lesion and pathologic confirmation were done. Transurethral resection of the lesions that were negative in both white and blue light was also performed. From April 2010 to September 2010, 30 patients were enrolled. From the total of 30 patients (25 men and 5 women; mean age, 60.4±9.22 years), 134 specimens were extracted. Among these, 101 specimens showed positive results by blue light cystoscopy (BLC). The sensitivity of BLC and white light cystoscopy (WLC) was 92.3% and 80.8%, respectively (p=0.021). The specificity of BLC and WLC was 48% and 49.1%, respectively (p>0.05). The positive and negative predictive values of BLC were 71.2% and 81.8%, respectively, whereas those of WLC were 72.0% and 68.6%, respectively. With WLC, 48 specimens showed negative findings, but of that group, 15 specimens (31.2%) were revealed to be malignant with BLC. There were no significant side effects in the 24 hours after the instillation of hexaminolevulinate. Photodynamic diagnosis with hexaminolevulinate helps to find tumors that could be missed by use of WLC only. Photodynamic diagnosis might be valuable in complete resection as well as for more accurate diagnosis of bladder tumor.

Locoregional disease patterns in well-differentiated and dedifferentiated retroperitoneal liposarcoma: implications for the extent of resection?

PubMed

Tseng, William W; Madewell, John E; Wei, Wei; Somaiah, Neeta; Lazar, Alexander J; Ghadimi, Markus P; Hoffman, Aviad; Pisters, Peter W T; Lev, Dina C; Pollock, Raphael E

2014-07-01

Well-differentiated (WD)/dedifferentiated (DD) liposarcoma is the most common soft tissue sarcoma of the retroperitoneum. The frequency of distant metastasis is low and the major burden of disease is locoregional. We sought to define the patterns of locoregional disease to help guide surgical decision making. Data were collected from 247 patients with de novo or recurrent tumors treated at our institution from 1993 to early 2012. The number and location of tumors at both initial presentation and subsequent locoregional recurrence were determined by combined analysis of operative dictations and radiologic imaging. Thirty-four percent of patients had multifocal locoregional disease (two or more tumors) at initial presentation to our institution, including 9 % who had tumors at synchronous remote retroperitoneal sites. The impact of multifocal disease on overall survival was dependent on histologic subtype (WD vs. DD) and disease presentation (de novo vs. recurrence) at the time of resection. Among patients with initial unifocal disease, 57 % progressed to multifocal locoregional disease with subsequent recurrence, including 11 % with new tumors outside of the original resection field. No clinicopathologic or treatment-related variable, including the type or extent of resection, was predictive of either multifocal or 'outside field' progression. Multifocal disease is common in patients with WD/DD retroperitoneal liposarcoma, and tumors can also develop at remote, locoregional sites. Surgical resection remains the primary method of locoregional control in this disease; however, the aggressiveness of resection should be individualized, with consideration of both tumor and patient-related factors.

Using fluorescence lymphangiography to define the ileocolic mesentery: proof of concept for the watershed area using real-time imaging.

PubMed

Keller, D S; Joshi, H M; Rodriguez-Justo, M; Walsh, D; Coffey, J C; Chand, M

2017-09-01

Recent advances in mesenteric science have demonstrated that the mesentery is a continuous structure with a 'watershed' area at the mesenteric apex between the right colon and terminal ileum, where lymphatic flow can proceed either proximally or distally. With this new understanding of the anatomy, functional features are emerging, which can have an impact on surgical management. Fluorescence lymphangiography or lymphoscintigraphy with indocyanine green allows real-time visualization of lymphatic channels, which highlights sentinel lymph nodes and may facilitate identification of the ideal margins for mesenteric lymphadenectomy during bowel resection for colon cancer. By using this novel technology, it is possible to demonstrate a watershed area in the ileocolic region and may facilitate more precise mesenteric dissection. In the present study, we provide proof of concept for the ileocolic watershed area using fluorescence lymphangiography.

Concepts and Preliminary Data Toward the Realization of Image-guided Liver Surgery

PubMed Central

Cash, David M.; Miga, Michael I.; Glasgow, Sean C.; Dawant, Benoit M.; Clements, Logan W.; Cao, Zhujiang; Galloway, Robert L.; Chapman, William C.

2013-01-01

Image-guided surgery provides navigational assistance to the surgeon by displaying the surgical probe position on a set of preoperative tomograms in real time. In this study, the feasibility of implementing image-guided surgery concepts into liver surgery was examined during eight hepatic resection procedures. Preoperative tomographic image data were acquired and processed. Accompanying intraoperative data on liver shape and position were obtained through optically tracked probes and laser range scanning technology. The preoperative and intraoperative representations of the liver surface were aligned using the iterative closest point surface matching algorithm. Surface registrations resulted in mean residual errors from 2 to 6 mm, with errors of target surface regions being below a stated goal of 1 cm. Issues affecting registration accuracy include liver motion due to respiration, the quality of the intraoperative surface data, and intraoperative organ deformation. Respiratory motion was quantified during the procedures as cyclical, primarily along the cranial–caudal direction. The resulting registrations were more robust and accurate when using laser range scanning to rapidly acquire thousands of points on the liver surface and when capturing unique geometric regions on the liver surface, such as the inferior edge. Finally, finite element models recovered much of the observed intraoperative deformation, further decreasing errors in the registration. Image-guided liver surgery has shown the potential to provide surgeons with important navigation aids that could increase the accuracy of targeting lesions and the number of patients eligible for surgical resection. PMID:17458587

In Situ Biosynthesis of Fluorescent Platinum Nanoclusters: Toward Self-Bioimaging-Guided Cancer Theranostics.

PubMed

Chen, Donghua; Zhao, Chunqiu; Ye, Jing; Li, Qiwei; Liu, Xiaoli; Su, Meina; Jiang, Hui; Amatore, Christian; Selke, Matthias; Wang, Xuemei

2015-08-19

Among the noble-metal clusters, very few reports about platinum clusters were used as bioimaging probes of tumors except as a reducing catalyst. It is first established herein that the biocompatible platinum nanoclusters are spontaneously biosynthesized by cancerous cells (i.e., HepG2 (human hepatocarcinoma), A549 (lung cancer), and others) rather than noncancerous cells (i.e., L02 (human embryo liver cells)) when incubated with micromolar chloroplatinic acid solutions. These in situ biosynthesized platinum nanoclusters could be readily realized in a biological environment and emit a bright fluorescence at 460 nm, which could be further utilized to facilitate an excellent cancer-cell-killing efficiency when combined with porphyrin derivatives for photothermal treatment. This raises the possibility of providing a promising and precise bioimaging strategy for specific fluorescent self-biomarking of tumor locations and realizing fluorescence imaging-guided photothermal therapy of tumors.

Clinical application of indocyanine green-fluorescence imaging during hepatectomy

PubMed Central

Ishizawa, Takeaki; Saiura, Akio

2016-01-01

In hepatobiliary surgery, the fluorescence and bile excretion of indocyanine green (ICG) can be used for real-time visualization of biological structure. Fluorescence cholangiography is used to obtain fluorescence images of the bile ducts following intrabiliary injection of 0.025−0.5 mg/mL ICG or intravenous injection of 2.5 mg ICG. Recently, the latter technique has been used in laparoscopic/robotic cholecystectomy. Intraoperative fluorescence imaging can be used to identify subcapsular hepatic tumors. Primary and secondary hepatic malignancy can be identified by intraoperative fluorescence imaging using preoperative intravenous injection of ICG through biliary excretion disorders that exist in cancerous tissues of hepatocellular carcinoma (HCC) and in non-cancerous hepatic parenchyma around adenocarcinoma foci. Intraoperative fluorescence imaging may help detect tumors to be removed, especially during laparoscopic hepatectomy, in which visual inspection and palpation are limited, compared with open surgery. Fluorescence imaging can also be used to identify hepatic segments. Boundaries of hepatic segments can be visualized following injection of 0.25−2.5 mg/mL ICG into the portal veins or by intravenous injection of 2.5 mg ICG following closure of the proximal portal pedicle toward hepatic regions to be removed. These techniques enable identification of hepatic segments before hepatectomy and during parenchymal transection for anatomic resection. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool that can enhance the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery. PMID:27500144

Invasive intraductal papillary mucinous neoplasm vs. sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes

PubMed Central

Wasif, Nabil; Bentrem, David J.; Farrell, James J.; Ko, Clifford Y.; Hines, Oscar J.; Reber, Howard A.; Tomlinson, James S.

2010-01-01

Introduction Although invasive intraductal papillary mucinous neoplasms (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. We compare survival and identify prognostic factors following resection for invasive IPMN vs. stage-matched PAC. Methods The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was utilized to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Results Patients with resected invasive IPMN experienced improved overall survival when compared to resected PAC (median survival 21mos vs. 14mos, p<0.001). Stratification by nodal status demonstrated no difference in survival among node positive patients, however, median survival of resected, node negative, invasive IPMN was significantly improved compared to node negative PAC (34mos vs. 18mos, p <0.001). On multivariate analysis PAC histology was an adverse predictor of overall survival (HR 1.31, 95% CI 1.15-1.50) compared to invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR 1.98, 95% CI 1.50- 2.60), high tumor grade (HR 1.74, 95% CI 1.31- 2.31), tumor size >2cm (HR 1.50, 95% CI 1.04- 2.19), and age >66 years (HR 1.33, 95% CI 1.03- 1.73) were adverse predictors of survival. Conclusions Although node negative invasive IPMN shows improved survival following resection compared to node negative PAC, the natural history of node positive invasive IPMN mimics that of node positive PAC. We also identify adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis following resection of invasive IPMN. PMID:20564064

Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes.

PubMed

Wasif, Nabil; Bentrem, David J; Farrell, James J; Ko, Clifford Y; Hines, Oscar J; Reber, Howard A; Tomlinson, James S

2010-07-15

Although invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. The authors compared survival and identify prognostic factors after resection for invasive IPMN versus stage-matched PAC. The Surveillance, Epidemiology, and End Results database (1991-2005) was used to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection. Patients with resected invasive IPMN experienced improved overall survival when compared with resected PAC (median survival, 21 vs 14 months; P<.001). Stratification by nodal status demonstrated no difference in survival among lymph node-positive patients; however, median survival of resected, lymph node-negative, invasive IPMN was significantly improved compared with lymph node-negative PAC (34 vs 18 months; P<.001). On multivariate analysis, PAC histology was an adverse predictor of overall survival (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.50) compared with invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR, 1.98; 95% CI, 1.50-2.60), high tumor grade (HR, 1.74; 95% CI, 1.31-2.31), tumor size>2 cm (HR, 1.50; 95% CI, 1.04-2.19), and age>66 years (HR, 1.33; 95% CI, 1.03-1.73) were adverse predictors of survival. Although lymph node-negative invasive IPMN showed improved survival after resection compared with lymph node-negative PAC, the natural history of lymph node-positive invasive IPMN mimicked that of lymph node-positive PAC. The authors also identified adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis after resection of invasive IPMN. Copyright (c) 2010 American Cancer Society.

Preoperative Portal Vein Embolization Tailored to Prepare the Liver for Complex Resections: Initial Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baere, T. de, E-mail: debaere@igr.fr; Robinson, J. M.; Deschamps, F.

The purpose of this study was to evaluate the safety and efficacy of preoperative portal vein embolization (PVE) tailored to prepare the liver for complex and extended resections. During the past 5 years, 12 PVEs were performed in noncirrhotic patients with liver metastases from colon cancer (n = 10), choroidal melanoma (n = 1), and leiomyosarcoma (n = 1) to prepare complex anatomical liver resections in patients with small future remnant livers. These liver resections planned to preserve only segment IV in four patients, segments IV, V, and VIII in four patients, segments II, III, VI, and VII in threemore » patients, and segments V and VI in one patient. PVE was performed under general anesthesia with a flow-guided injection of a mixture of cyanoacrylate and Lipiodol using a 5-Fr catheter. All portal branches feeding the liver segments to be resected were successfully embolized with cyanoacrylate except one, which was occluded with coils due to the risk of reflux with cyanoacrylate. After a mean of 32 days, CT volumetry revealed a mean hypertrophy of the unembolized liver of 47 {+-} 25% (range, 21-88%). Liver resections could be performed in 10 patients but were canceled in 2, due to the occurrence of a new hepatic tumor in one and an insufficiently increased volume in the other. Among the 10 patients who underwent the liver resection, 1 died of postoperative sepsis, 3 died 3 to 32 months after surgery, including 1 death unrelated to cancer, and 6 were alive after 6 to 36 months after surgery. In conclusion, in this preliminary report, PVE appears to be feasible and able to induce hypertrophy of the future remnant liver before a complex and extended hepatectomy. Further evaluation is needed in a larger cohort.« less

Computed Tomography-Assisted Thoracoscopic Surgery: A Novel, Innovative Approach in Patients With Deep Intrapulmonary Lesions of Unknown Malignant Status.

PubMed

Kostrzewa, Michael; Kara, Kerim; Rathmann, Nils; Tsagogiorgas, Charalambos; Henzler, Thomas; Schoenberg, Stefan O; Hohenberger, Peter; Diehl, Steffen J; Roessner, Eric D

2017-06-01

Minimally invasive resection of small, deep intrapulmonary lesions can be challenging due to the difficulty of localizing them during video-assisted thoracoscopic surgery (VATS). We report our preliminary results evaluating the feasibility of an image-guided, minimally invasive, 1-stop-shop approach for the resection of small, deep intrapulmonary lesions in a hybrid operating room (OR). Fifteen patients (5 men, 10 women; mean age, 63 years) with a total of 16 solitary, deep intrapulmonary nodules of unknown malignant status were identified for intraoperative wire marking. Patients were placed on the operating table for resection by VATS. A marking wire was placed within the lesion under 3D laser and fluoroscopic guidance using a cone beam computed tomography system. Then, wedge resection by VATS was performed in the same setting without repositioning the patient. Complete resection with adequate safety margins was confirmed for all lesions. Marking wire placement facilitated resection in 15 of 16 lesions. Eleven lesions proved to be malignant, either primary or secondary; 5 were benign. Mean lesion size was 7.7 mm; mean distance to the pleural surface was 15.1 mm (mean lesion depth-diameter ratio, 2.2). Mean procedural time for marking wire placement was 35 minutes; mean VATS duration was 36 minutes. Computed tomography-assisted thoracoscopic surgery is a new, safe, and effective procedure for minimally invasive resection of small, deeply localized intrapulmonary lesions. The benefits of computed tomography-assisted thoracoscopic surgery are 1. One-stop-shop procedure, 2. Lower risk for the patient (no patient relocation, no marking wire loss), and 3. No need to coordinate scheduling between the CT room and OR.

18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management.

PubMed

Kommidi, Harikrishna; Guo, Hua; Nurili, Fuad; Vedvyas, Yogindra; Jin, Moonsoo M; McClure, Timothy D; Ehdaie, Behfar; Sayman, Haluk B; Akin, Oguz; Aras, Omer; Ting, Richard

2018-05-10

[ 18/19 F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [ 19 F]-4 is radiolabeled with a radiochemical yield that is ≥27% and a molar activity of 190 ± 50 mCi/μmol in a <1 h, one-step, aqueous isotopic exchange reaction. [ 19 F]-4 allows PSMA expression to be imaged by fluorescence (FL) and [ 18 F]-PET. PC3-PIP (PSMA-positive, EC 50 = 6.74 ± 1.33 nM) cancers are specifically delineated in mice that bear 3 million (18 mg) PC3-PIP and PC3 (control, PSMA-negative) cells. Colocalization of [ 18/19 F]-4 PET, fluorescence, scintillated biodistribution, and PSMA expression are observed.

Fluorescent Proteins: A Cell Biologist's User Guide

PubMed Central

Snapp, Erik Lee

2009-01-01

Fluorescent Proteins (FPs) have revolutionized cell biology. The value of labeling and visualizing proteins in living cells is evident from thousands of publications since the cloning of Green Fluorescent Protein (GFP). Biologists have been flooded with a cornucopia of FPs; however, the FP toolbox has not necessarily been optimized for cell biologists. Common FP plasmids are suboptimal for FP-fusion protein construction. More problematic are commercial and investigator-constructed FP-fusion proteins that disrupt important cellular targeting information. Even when cell biologists correctly construct FP-fusion proteins, it is rarely self-evident which FP should be used. Important FP information, such as oligomer formation or photostability, is often unsearchable or anecdotal. This brief guide is offered to assist in correctly exploiting FPs in cells. PMID:19819147

Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model.

PubMed

Perry, Kyle A; Enestvedt, C Kristian; Hosack, Luke W; Pham, Thai H; Diggs, Brian S; Teh, Swee; Orloff, Susan; Winn, Shelly; Hunter, John G; Sheppard, Brett C

2010-05-01

Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells. Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral hepatectomy. In 14 days after resection, the rats were killed, the residual right lobe tumors were measured, and tissue was procured for RNA extraction. Transcript levels of VEGF messenger RNA (mRNA) were quantified with reverse transcriptase-polymerase chain reaction (RT-PCR), and VEGF serum levels were measured by enzyme-linked immunoassay (ELISA) both before resection and at the time of tissue harvest. None of the animals had development satellite liver lesions or distant metastases in the abdomen or thorax. The median residual tumor volume was 320 mm(3) in the open group compared with 180 mm(3) in the laparoscopic group (p = 0.164). The animals that underwent open resection had a 1.3-fold increase in VEGF mRNA transcript levels compared with the laparoscopic resection group (p = 0.008). The serum VEGF levels were not significantly different between the laparoscopic and open groups at baseline (open tumor resection [OR], 23.7 +/- 12.0 pg/ml; laparoscopic tumor resection [LR], 30.7 +/- 15.5 pg/ml; p = 0.334) nor at the time of tissue harvest (OR, 19.9 +/- 19.6 pg/ml; LR, 26.9 +/- 34.5 pg/ml; p = 0.549). Laparoscopic hepatic resection produces decreased VEGF mRNA expression in residual hepatoma cells compared with open resection. Decreased stimulation of angiogenesis promoters in the tumor microenvironment after minimally invasive liver resection may contribute to a lower residual disease burden and ultimately lead to a lower recurrence rate.

Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV

PubMed Central

Onoyama, Haruna; Kamiya, Mako; Kuriki, Yugo; Komatsu, Toru; Abe, Hiroyuki; Tsuji, Yosuke; Yagi, Koichi; Yamagata, Yukinori; Aikou, Susumu; Nishida, Masato; Mori, Kazuhiko; Yamashita, Hiroharu; Fujishiro, Mitsuhiro; Nomura, Sachiyo; Shimizu, Nobuyuki; Fukayama, Masashi; Koike, Kazuhiko; Urano, Yasuteru; Seto, Yasuyuki

2016-01-01

Early detection of esophageal squamous cell carcinoma (ESCC) is an important prognosticator, but is difficult to achieve by conventional endoscopy. Conventional lugol chromoendoscopy and equipment-based image-enhanced endoscopy, such as narrow-band imaging (NBI), have various practical limitations. Since fluorescence-based visualization is considered a promising approach, we aimed to develop an activatable fluorescence probe to visualize ESCCs. First, based on the fact that various aminopeptidase activities are elevated in cancer, we screened freshly resected specimens from patients with a series of aminopeptidase-activatable fluorescence probes. The results indicated that dipeptidylpeptidase IV (DPP-IV) is specifically activated in ESCCs, and would be a suitable molecular target for detection of esophageal cancer. Therefore, we designed, synthesized and characterized a series of DPP-IV-activatable fluorescence probes. When the selected probe was topically sprayed onto endoscopic submucosal dissection (ESD) or surgical specimens, tumors were visualized within 5 min, and when the probe was sprayed on biopsy samples, the sensitivity, specificity and accuracy reached 96.9%, 85.7% and 90.5%. We believe that DPP-IV-targeted activatable fluorescence probes are practically translatable as convenient tools for clinical application to enable rapid and accurate diagnosis of early esophageal cancer during endoscopic or surgical procedures. PMID:27245876

Fluorescent imaging of cancerous tissues for targeted surgery

PubMed Central

Bu, Lihong; Shen, Baozhong; Cheng, Zhen

2014-01-01

To maximize tumor excision and minimize collateral damage is the primary goal of cancer surgery. Emerging molecular imaging techniques have to “image-guided surgery” developing into “molecular imaging-guided surgery”, which is termed “targeted surgery” in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling “targeted surgery” to be a component of “targeted therapy”. Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields. PMID:25064553

Fluorescence and Magnetic Resonance Dual-Modality Imaging-Guided Photothermal and Photodynamic Dual-Therapy with Magnetic Porphyrin-Metal Organic Framework Nanocomposites

NASA Astrophysics Data System (ADS)

Zhang, Hui; Li, Yu-Hao; Chen, Yang; Wang, Man-Man; Wang, Xue-Sheng; Yin, Xue-Bo

2017-03-01

Phototherapy shows some unique advantages in clinical application, such as remote controllability, improved selectivity, and low bio-toxicity, than chemotherapy. In order to improve the safety and therapeutic efficacy, imaging-guided therapy seems particularly important because it integrates visible information to speculate the distribution and metabolism of the probe. Here we prepare biocompatible core-shell nanocomposites for dual-modality imaging-guided photothermal and photodynamic dual-therapy by the in situ growth of porphyrin-metal organic framework (PMOF) on Fe3O4@C core. Fe3O4@C core was used as T2-weighted magnetic resonance (MR) imaging and photothermal therapy (PTT) agent. The optical properties of porphyrin were well remained in PMOF, and PMOF was therefore selected for photodynamic therapy (PDT) and fluorescence imaging. Fluorescence and MR dual-modality imaging-guided PTT and PDT dual-therapy was confirmed with tumour-bearing mice as model. The high tumour accumulation of Fe3O4@C@PMOF and controllable light excitation at the tumour site achieved efficient cancer therapy, but low toxicity was observed to the normal tissues. The results demonstrated that Fe3O4@C@PMOF was a promising dual-imaging guided PTT and PDT dual-therapy platform for tumour diagnosis and treatment with low cytotoxicity and negligible in vivo toxicity.

Hyperspectral imaging fluorescence excitation scanning for colon cancer detection

PubMed Central

Leavesley, Silas J.; Walters, Mikayla; Lopez, Carmen; Baker, Thomas; Favreau, Peter F.; Rich, Thomas C.; Rider, Paul F.; Boudreaux, Carole W.

2016-01-01

Abstract. Optical spectroscopy and hyperspectral imaging have shown the potential to discriminate between cancerous and noncancerous tissue with high sensitivity and specificity. However, to date, these techniques have not been effectively translated to real-time endoscope platforms. Hyperspectral imaging of the fluorescence excitation spectrum represents new technology that may be well suited for endoscopic implementation. However, the feasibility of detecting differences between normal and cancerous mucosa using fluorescence excitation-scanning hyperspectral imaging has not been evaluated. The goal of this study was to evaluate the initial feasibility of using fluorescence excitation-scanning hyperspectral imaging for measuring changes in fluorescence excitation spectrum concurrent with colonic adenocarcinoma using a small pre-pilot-scale sample size. Ex vivo analysis was performed using resected pairs of colorectal adenocarcinoma and normal mucosa. Adenocarcinoma was confirmed by histologic evaluation of hematoxylin and eosin (H&E) permanent sections. Specimens were imaged using a custom hyperspectral imaging fluorescence excitation-scanning microscope system. Results demonstrated consistent spectral differences between normal and cancerous tissues over the fluorescence excitation range of 390 to 450 nm that could be the basis for wavelength-dependent detection of colorectal cancers. Hence, excitation-scanning hyperspectral imaging may offer an alternative approach for discriminating adenocarcinoma from surrounding normal colonic mucosa, but further studies will be required to evaluate the accuracy of this approach using a larger patient cohort. PMID:27792808

Basaloid large cell lung carcinoma presenting as cutaneous metastasis at the colostomy site after abdominoperineal resection for rectal carcinoma.

PubMed

Sabater-Marco, Vicente; García-García, José Angel; Roig-Vila, José Vicente

2013-08-01

The occurrence of a tumor at the colostomy site after abdominoperineal resection for rectal carcinoma is rare and it may be related to a previously resected carcinoma or another primary tumor. We report a 61-year-old man who developed an ulcerated skin nodule at her colostomy site 6 years after resection of a rectal adenocarcinoma. Histopathologically, the skin nodule was composed of atypical large and pleomorphic cells with high mitotic rate and they were arranged in nests and within lymphatic channels in the dermis. The neoplastic cells were immunoreactive for cytokeratin (CK) AE1/3, CK7, CK34ßE12, epithelial membrane antigen and vimentin while detection of human papillomavirus and Epstein-Barr virus DNA was negative. A diagnosis of basaloid large cell carcinoma of pulmonary origin was suggested and it was confirmed by computed tomography-guided fine needle aspiration of a right subpleural mass. A metastatic tumor at the colostomy site is an exceptional finding and may be the first manifestation of lung cancer, especially if it consist of pleomorphic large cells with high mitotic rate and basaloid immunophenotype. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Partial lumbosacral transitional vertebra resection for contralateral facetogenic pain.

PubMed

Brault, J S; Smith, J; Currier, B L

2001-01-15

Case report of surgically treated mechanical low back pain from the facet joint contralateral to a unilateral anomalous lumbosacral articulation (Bertolotti's syndrome). To describe the clinical presentation, diagnostic evaluation, and management of facet-related low back pain in a 17-year-old cheerleader and its successful surgical treatment with resection of a contralateral anomalous articulation. Lumbosacral transitional vertebrae are common in the general population. Bertolotti's syndrome is mechanical low back pain associated with these transitional segments. Little is known about the pathophysiology and mechanics of these vertebral segments and their propensity to be pain generators. Treatment of this syndrome is controversial, and surgical intervention has been infrequently reported. A retrospective chart analysis and radiographic review were performed. Repeated fluoroscopically guided injections implicated a symptomatic L6-S1 facet joint contralateral to an anomalous lumbosacral articulation. Eventually, a successful surgical outcome was achieved with resection of the anomalous articulation. Clinicians should consider the possibility that mechanical low back pain may occur from a facet contralateral to a unilateral anomalous lumbosacral articulation, even in a young patient. Although reports of surgical treatment of Bertolotti's syndrome are infrequent, resection of the anomalous articulation provided excellent results in this patient, presumably because of reduced stresses on the symptomatic facet.

Anterior Impingement Syndrome of the Ankle Caused by Osteoid Osteoma in the Talar Neck Treated with Arthroscopy and 3D C-Arm-Based Imaging.

PubMed

Ikegami, Masachika; Matsumoto, Takumi; Chang, Song Ho; Kobayashi, Hiroshi; Shinoda, Yusuke; Tanaka, Sakae

2017-01-01

Osteoid osteoma in periarticular lesions tends to have an unusual presentation that likely leads to a delayed or missed diagnosis compared with a typical osteoid osteoma in the metaphysis or diaphysis of the long bone. In cases that are unresponsive to conservative treatment, surgical interventions including en bloc resection, computed tomography-guided percutaneous treatment, and arthroscopic resection have been performed; however, these methods frequently result in inadequate tumor resection and recurrence. Here we present a case of a 16-year-old girl with osteoid osteoma in the talar neck presenting as anterior impingement syndrome due to marked synovitis in the ankle joint which was successfully treated without complications by arthroscopic synovectomy and tumor resection followed by intraoperative 3D C-arm-based imaging confirming complete tumor lesion removal. Her pain was relieved immediately after the surgery, and there was no recurrence at 12 months of follow-up. This is the first case report of the surgical treatment of the osteoid osteoma in the talar neck with the combination methods of arthroscopy and 3D C-arm-based imaging.

Optimized path planning for soft tissue resection via laser vaporization

NASA Astrophysics Data System (ADS)

Ross, Weston; Cornwell, Neil; Tucker, Matthew; Mann, Brian; Codd, Patrick

2018-02-01

Robotic and robotic-assisted surgeries are becoming more prevalent with the promise of improving surgical outcomes through increased precision, reduced operating times, and minimally invasive procedures. The handheld laser scalpel in neurosurgery has been shown to provide a more gentle approach to tissue manipulation on or near critical structures over classical tooling, though difficulties of control have prevented large scale adoption of the tool. This paper presents a novel approach to generating a cutting path for the volumetric resection of tissue using a computer-guided laser scalpel. A soft tissue ablation simulator is developed and used in conjunction with an optimization routine to select parameters which maximize the total resection of target tissue while minimizing the damage to surrounding tissue. The simulator predicts the ablative properties of tissue from an interrogation cut for tuning and simulates the removal of a tumorous tissue embedded on the surface of healthy tissue using a laser scalpel. We demonstrate the ability to control depth and smoothness of cut using genetic algorithms to optimize the ablation parameters and cutting path. The laser power level, cutting rate and spacing between cuts are optimized over multiple surface cuts to achieve the desired resection volumes.

[Laparoscopic Local Resection for a Gastric GIST with Ulcer Locating Near to the Esophagogastric Junction - A Case Report].

PubMed

Tanaka, Yoshihiro; Kosuga, Toshiyuki; Komatsu, Shuhei; Okamoto, Kazuma; Shoda, Katsutoshi; Arita, Tomohiro; Konishi, Hirotaka; Morimura, Ryo; Murayama, Yasutoshi; Shiozaki, Atsushi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Fujiwara, Hitoshi; Otsuji, Eigo

2017-11-01

A 39-year-old woman visited our hospital because of epigastric pain. Gastrointestinal endoscopy revealed a gastric submucosal tumor, 30mm in size, with ulcer locating near to the esophagogastric junction, and it was diagnosed with GIST by the endoscopic ultrasonography-guided fine needle aspiration. Then, she underwent laparoscopic surgery for the removal of gastric GIST. After peeling around the upper stomach, the local resection of the stomach was performed with linear staplers in the minor axis direction under the vision of the endoscope and laparoscope. Histopathological examinations confirmed that the tumor was GIST with an intermediate risk, and all surgical margins were free of GIST cells. Local resection with the laparoscopy endoscopy cooperative surgery(LECS)technique is a very useful way of the removal of gastric GISTs locating near to the esophagogastric junction in terms of the remnant gastric functions. Meanwhile, because the standard LECS requires the opening of the gastric lumen, there remains concerns about the intraperitoneal tumor dissemination for the gastric GIST with ulcer. We herein reported a case of laparoscopic local resection for a gastric GIST with ulcer locating near to the esophagogastric junction without gastric opening.

A New Technique of Radiofrequency-assisted Ultrasound-guided Needle-localized Laparoscopic Resection of Disappearing Colorectal Liver Metastases.

PubMed

Yigitbas, Hakan; Yazici, Pinar; Taskin, Halit E; Okoh, Alexis K; Dural, Cem; Aydin, Nail; Berber, Eren

2017-02-01

The management of disappearing colorectal liver metastases in the postadjuvant chemotherapy setting is challenging. We describe a novel technique that facilitates laparoscopic resection of disappearing metastatic liver lesions with great precision. Details of this new technique are described in 2 patients with colorectal cancer synchronously metastatic to the liver. Both patients had small indistinct intraparenchymal liver lesions after adjuvant chemotherapy. A video displays the steps of the procedure. Both patients presented with colorectal cancer with synchronous liver metastasis. They received FOLFOX regimen after resection of their primary. They both responded to adjuvant chemotherapy. On repeat posttreatment imaging, the liver lesions became smaller and indistinct. With laparoscopic ultrasound, subtle parenchymal heterogeneities were identified. The lesions were initially ablated with a wide radiofrequency ablation zone. Then, without removing the needle, the prongs were deployed to the borders of the parenchymal heterogeneity. Using an ultrasonic vessel sealer, the lesions were resected. Final pathology identified 1 viable focus of cancer in each patient. Both patients were discharged home uneventfully on their second postoperative day. There were no complications. We have described a novel technique that could facilitate precise resection of intraparenchymal small indistinct or disappearing liver metastases of colorectal origin. This option should be kept within the armamentarium of the laparoscopic liver surgeon managing patients with malignant liver tumors.

The importance of preoperative tissue sampling for mobile spine chordomas: literature review and report of two cases.

PubMed

Zuccato, Jeffrey A; Witiw, Christopher D; Keith, Julia; Dyer, Erin; Saghal, Arjun; da Costa, Leodante

2018-01-01

Pre-operative biopsy and diagnosis of chordomas of the mobile spine is indicated as en bloc resections improve outcomes. This review of the management of mobile spine chordomas includes two cases of unexpected mobile spine chordomas where a preoperative tissue diagnosis was decided against and may have altered surgical decision-making. Two lumbar spine chordomas thought to be metastatic and primary bony lesions preoperatively were not biopsied before surgery and eventual pathology revealed chordoma. Preoperative diagnoses were questioned during surgery after an intraoperative tissue diagnosis of chordoma in one case and unclear pathology with non-characteristic tumor morphology in the other. The surgical plan was altered in these cases to maximize resection as en bloc resection reduces the risk of local recurrence in chordoma. Mobile spine chordomas are rare and en bloc resection is recommended, contrary to the usual approach to more common spine tumors. Since en bloc resection of spine chordomas improves disease free survival, it has been recommended that tissue diagnosis be obtained preoperatively when chordoma is considered in the differential diagnosis, in order to guide surgical planning. We present two cases where a preoperative biopsy was considered but not obtained after neuroradiology consultation and imaging review, which may have been managed differently if the diagnosis of spine chordomas were known pre-operatively.

Recent advances in near-infrared fluorescence-guided imaging surgery using indocyanine green.

PubMed

Namikawa, Tsutomu; Sato, Takayuki; Hanazaki, Kazuhiro

2015-12-01

Near-infrared (NIR) fluorescence imaging has better tissue penetration, allowing for the effective rejection of excitation light and detection deep inside organs. Indocyanine green (ICG) generates NIR fluorescence after illumination by an NIR ray, enabling real-time intraoperative visualization of superficial lymphatic channels and vessels transcutaneously. The HyperEye Medical System (HEMS) can simultaneously detect NIR rays under room light to provide color imaging, which enables visualization under bright light. Thus, NIR fluorescence imaging using ICG can provide for excellent diagnostic accuracy in detecting sentinel lymph nodes in cancer and microvascular circulation in various ischemic diseases, to assist us with intraoperative decision making. Including HEMS in this system could further improve the sentinel lymph node mapping and intraoperative identification of blood supply in reconstructive organs and ischemic diseases, making it more attractive than conventional imaging. Moreover, the development of new laparoscopic imaging systems equipped with NIR will allow fluorescence-guided surgery in a minimally invasive setting. Future directions, including the conjugation of NIR fluorophores to target specific cancer markers might be realistic technology with diagnostic and therapeutic benefits.

Tryptophan autofluorescence imaging of neoplasms of the human colon

NASA Astrophysics Data System (ADS)

Banerjee, Bhaskar; Renkoski, Timothy; Graves, Logan R.; Rial, Nathaniel S.; Tsikitis, Vassiliki Liana; Nfonsom, Valentine; Pugh, Judith; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs

2012-01-01

Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal dysplasia. The emission spectra of cells isolated from human adenocarcinoma and normal mucosa of the colon were studied and showed markedly greater emission intensity from cancerous cells compared to cells obtained from the surrounding normal mucosa. A proto-type multispectral imaging system optimized for ultraviolet macroscopic imaging of tissue was used to obtain autofluorescence images of surgical specimens of colonic neoplasms and normal mucosa after resection. Fluorescence images did not display the expected greater emission from the tumor as compared to the normal mucosa, most probably due to increased optical absorption and scattering in the tumors. Increased fluorescence intensity in neoplasms was observed however, once fluorescence images were corrected using reflectance images. Tryptophan fluorescence alone may be useful in differentiating normal and cancerous cells, while in tissues its autofluorescence image divided by green reflectance may be useful in displaying neoplasms.

Computer-aided design and manufacturing of surgical templates and their clinical applications: a review.

PubMed

Chen, Xiaojun; Xu, Lu; Wang, Wei; Li, Xing; Sun, Yi; Politis, Constantinus

2016-09-01

The surgical template is a guide aimed at directing the implant placement, tumor resection, osteotomy and bone repositioning. Using it, preoperative planning can be transferred to the actual surgical site, and the precision, safety and reliability of the surgery can be improved. However, the actual workflow of the surgical template design and manufacturing is quite complicated before the final clinical application. The major goal of the paper is to provide a comprehensive reference source of the current and future development of the template design and manufacturing for relevant researchers. Expert commentary: This paper aims to present a review of the necessary procedures in the template-guided surgery including the image processing, 3D visualization, preoperative planning, surgical guide design and manufacturing. In addition, the template-guided clinical applications for various kinds of surgeries are reviewed, and it demonstrated that the precision of the surgery has been improved compared with the non-guided operations.

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

PubMed

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Visualization of subcapsular hepatic malignancy by indocyanine-green fluorescence imaging during laparoscopic hepatectomy.

PubMed

Kudo, Hiroki; Ishizawa, Takeaki; Tani, Keigo; Harada, Nobuhiro; Ichida, Akihiko; Shimizu, Atsushi; Kaneko, Junichi; Aoki, Taku; Sakamoto, Yoshihiro; Sugawara, Yasuhiko; Hasegawa, Kiyoshi; Kokudo, Norihiro

2014-08-01

Although laparoscopic hepatectomy has increasingly been used to treat cancers in the liver, the accuracy of intraoperative diagnosis may be inferior to that of open surgery because the ability to visualize and palpate the liver surface during laparoscopy is relatively limited. Fluorescence imaging has the potential to provide a simple compensatory diagnostic tool for identification of cancers in the liver during laparoscopic hepatectomy. In 17 patients who were to undergo laparoscopic hepatectomy, 0.5 mg/kg body weight of indocyanine green (ICG) was administered intravenously within the 2 weeks prior to surgery. Intraoperatively, a laparoscopic fluorescence imaging system obtained fluorescence images of its surfaces during mobilization of the liver. In all, 16 hepatocellular carcinomas (HCCs) and 16 liver metastases (LMs) were resected. Of these, laparoscopic ICG fluorescence imaging identified 12 HCCs (75%) and 11 LMs (69%) on the liver surfaces distributed over Couinaud's segments 1-8, including the 17 tumors that had not been identified by visual inspections of normal color images. The 23 tumors that were identified by fluorescence imaging were located closer to the liver surfaces than another nine tumors that were not identified by fluorescence imaging (median [range] depth 1 [0-5] vs. 11 [8-30] mm; p < 0.001). Like palpation during open hepatectomy, laparoscopic ICG fluorescence imaging enables real-time identification of subcapsular liver cancers, thus facilitating estimation of the required extent of hepatic mobilization and determination of the location of an appropriate hepatic transection line.

Mediastinal hemangiopericytoma.

PubMed

Horikawa-Kyo, Youko; Tanaka, Takeo; Tanano, Hirofumi; Kitayama, Yasuhiro; Karakawa, Shuhei; Taniyama, Kiyomi

2009-08-01

Mediastinal hemangiopericytoma (HPC) was diagnosed in a 3-year-old female. The incidence of this tumor is rare in children, and few data are available to guide clinical management. The surgical resection was incomplete and she received adjuvant radiation therapy and chemotherapy. The patient is alive without adverse events 6 years after diagnosis. (c) 2009 Wiley-Liss, Inc.

EGF targeted fluorescence molecular tomography as a predictor of PDT outcomes in pancreas cancer models

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; Isabelle, Martin E.; O'Hara, Julia; Hasan, Tayyaba; Pogue, Brian W.

2010-02-01

Verteporfin photodynamic therapy (PDT) is a promising adjuvant therapy for pancreas cancer and investigations for its use are currently underway in both orthotopic xenograft mouse models and in human clinical trials. The mouse models have been studied extensively using magnetic resonance (MR) imaging as a measure of surrogate response to verteporfin PDT and it was found that tumor lines with different levels of aggression respond with varying levels to PDT. MR imaging was successful in determining the necrotic volume caused by PDT but there was difficultly in distinguishing inflamed tissues and regions of surviving tumor. In order to understand the molecular changes within the tumor immediately post-PDT we propose the implementation of MR-guided fluorescence molecular tomography (FMT) in conjunction with an exogenously administered fluorescently labeled epidermal growth factor (EGF-IRDye800CW, LI-COR Biosciences). We have previously shown that MR-guided FMT is feasible in the mouse abdomen when multiple regions of fluorescence are considered from contributing internal organs. In this case the highly aggressive AsPC-1 (+EGFR) orthotopic tumor was implanted in SCID mice, interstitial verteporfin PDT (1mg/kg, 20J/cm) was performed when the tumor reached ~60mm3 and both tumor volume and EGF binding were followed with MR-guided FMT.

Impact of Virtual and Augmented Reality Based on Intraoperative Magnetic Resonance Imaging and Functional Neuronavigation in Glioma Surgery Involving Eloquent Areas.

PubMed

Sun, Guo-Chen; Wang, Fei; Chen, Xiao-Lei; Yu, Xin-Guang; Ma, Xiao-Dong; Zhou, Ding-Biao; Zhu, Ru-Yuan; Xu, Bai-Nan

2016-12-01

The utility of virtual and augmented reality based on functional neuronavigation and intraoperative magnetic resonance imaging (MRI) for glioma surgery has not been previously investigated. The study population consisted of 79 glioma patients and 55 control subjects. Preoperatively, the lesion and related eloquent structures were visualized by diffusion tensor tractography and blood oxygen level-dependent functional MRI. Intraoperatively, microscope-based functional neuronavigation was used to integrate the reconstructed eloquent structure and the real head and brain, which enabled safe resection of the lesion. Intraoperative MRI was used to verify brain shift during the surgical process and provided quality control during surgery. The control group underwent surgery guided by anatomic neuronavigation. Virtual and augmented reality protocols based on functional neuronavigation and intraoperative MRI provided useful information for performing tailored and optimized surgery. Complete resection was achieved in 55 of 79 (69.6%) glioma patients and 20 of 55 (36.4%) control subjects, with average resection rates of 95.2% ± 8.5% and 84.9% ± 15.7%, respectively. Both the complete resection rate and average extent of resection differed significantly between the 2 groups (P < 0.01). Postoperatively, the rate of preservation of neural functions (motor, visual field, and language) was lower in controls than in glioma patients at 2 weeks and 3 months (P < 0.01). Combining virtual and augmented reality based on functional neuronavigation and intraoperative MRI can facilitate resection of gliomas involving eloquent areas. Copyright © 2016 Elsevier Inc. All rights reserved.

Open-source do-it-yourself multi-color fluorescence smartphone microscopy

PubMed Central

Sung, Yulung; Campa, Fernando; Shih, Wei-Chuan

2017-01-01

Fluorescence microscopy is an important technique for cellular and microbiological investigations. Translating this technique onto a smartphone can enable particularly powerful applications such as on-site analysis, on-demand monitoring, and point-of-care diagnostics. Current fluorescence smartphone microscope setups require precise illumination and imaging alignment which altogether limit its broad adoption. We report a multi-color fluorescence smartphone microscope with a single contact lens-like add-on lens and slide-launched total-internal-reflection guided illumination for three common tasks in investigative fluorescence microscopy: autofluorescence, fluorescent stains, and immunofluorescence. The open-source, simple and cost-effective design has the potential for do-it-yourself fluorescence smartphone microscopy. PMID:29188104

Fluorescence imaging in the upper gastrointestinal tract for the detection of dysplasic changes

NASA Astrophysics Data System (ADS)

Sukowski, Uwe; Ebert, Bernd; Ortner, Marianne; Mueller, Karsten; Voderholzer, W.; Weber-Eibel, J.; Dietel, M.; Lochs, Herbert; Rinneberg, Herbert H.

2001-10-01

During endoscopy of the esophagus fluorescence images were recorded at a delay of 20 ns after pulsed laser excitation simultaneously with conventional reflected white light images. To label malignant cells (dysplasia, tumor) 5-aminolaevulinic acid was applied prior to fluorescence guided bi-opsy. In this way pre-malignant and malignant lesions were detected not seen previously during routine endoscopy.

Fluorescent supramolecular micelles for imaging-guided cancer therapy

NASA Astrophysics Data System (ADS)

Sun, Mengmeng; Yin, Wenyan; Dong, Xinghua; Yang, Wantai; Zhao, Yuliang; Yin, Meizhen

2016-02-01

A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy.A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA-b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00450d

Fiber-optic fluorescence imaging

PubMed Central

Flusberg, Benjamin A; Cocker, Eric D; Piyawattanametha, Wibool; Jung, Juergen C; Cheung, Eunice L M; Schnitzer, Mark J

2010-01-01

Optical fibers guide light between separate locations and enable new types of fluorescence imaging. Fiber-optic fluorescence imaging systems include portable handheld microscopes, flexible endoscopes well suited for imaging within hollow tissue cavities and microendoscopes that allow minimally invasive high-resolution imaging deep within tissue. A challenge in the creation of such devices is the design and integration of miniaturized optical and mechanical components. Until recently, fiber-based fluorescence imaging was mainly limited to epifluorescence and scanning confocal modalities. Two new classes of photonic crystal fiber facilitate ultrashort pulse delivery for fiber-optic two-photon fluorescence imaging. An upcoming generation of fluorescence imaging devices will be based on microfabricated device components. PMID:16299479

Factors associated with a primary surgical approach for sinonasal squamous cell carcinoma.

PubMed

Cracchiolo, Jennifer R; Patel, Krupa; Migliacci, Jocelyn C; Morris, Luc T; Ganly, Ian; Roman, Benjamin R; McBride, Sean M; Tabar, Viviane S; Cohen, Marc A

2018-03-01

Primary surgery is the preferred treatment of T1-T4a sinonasal squamous cell carcinoma (SNSCC). Patients with SNSCC in the National Cancer Data Base (NCDB) were analyzed. Factors that contributed to selecting primary surgical treatment were examined. Overall survival (OS) in surgical patients was analyzed. Four-thousand seven hundred and seventy patients with SNSCC were included. In T1-T4a tumors, lymph node metastases, maxillary sinus location, and treatment at high-volume centers were associated with selecting primary surgery. When primary surgery was utilized, tumor factors and positive margin guided worse OS. Adjuvant therapy improved OS in positive margin resection and advanced T stage cases. Tumor and non-tumor factors are associated with selecting surgery for the treatment of SNSCC. When surgery is selected, tumor factors drive OS. Negative margin resection should be the goal of a primary surgical approach. When a positive margin resection ensues, adjuvant therapy may improve OS. © 2017 Wiley Periodicals, Inc.

Management of necrotising appendicitis associated with widespread necrotising enterocolitis of the small and large bowel and perforated duodenal ulcer.

PubMed

Gupta, Vaibhav; Zani, Augusto; Jackson, Paul; Singh, Shailinder

2015-06-08

A 7-year-old boy presented in septic shock secondary to appendicitis with generalised peritonitis. Following crystalloid resuscitation, he underwent surgery. Faecopurulent contamination and free air were found. This was secondary to a perforated and gangrenous appendix, multiple large and small bowel segments with perforations, patches of necrosis, interspersed with healthy bowel and segments of questionable viability. There was also a perforated duodenal ulcer. Necrotic segments were resected using a 'clip-and-drop' technique to shorten operative duration and guide resection to preserve bowel length. After six laparotomies and multiple bowel resections, the child was discharged home with an ileostomy that was subsequently reversed. He is currently on a normal diet and pursuing all activities appropriate for his age. Perforated appendicitis can be associated with widespread bowel necrosis and multiple perforations. A conservative damage limitation approach using the 'clip-and-drop' technique and relook laparotomies is useful in the management of extensive bowel necrosis in children. 2015 BMJ Publishing Group Ltd.

Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up.

PubMed

Della Puppa, Alessandro; Lombardi, Giuseppe; Rossetto, Marta; Rustemi, Oriela; Berti, Franco; Cecchin, Diego; Gardiman, Marina Paola; Rolma, Giuseppe; Persano, Luca; Zagonel, Vittorina; Scienza, Renato

2017-01-01

The purpose of the study was to evaluate the clinical outcome of the association of BCNU wafers implantation and 5-aminolevulinic acid (5-ALA) fluorescence in the treatment of patients with newly diagnosed glioblastoma (ndGBM). Clinical and surgical data from patients who underwent 5-ALA surgery followed by BCNU wafers implantation were retrospectively evaluated (20 patients, Group I) and compared with data of patients undergoing surgery with BCNU wafers alone (42 patients, Group II) and 5-ALA alone (59 patients, Group III). Patients undergoing 5-ALA assisted resection followed by BCNU wafers implantation (Group I) resulted long survivors (>3 years) in 15 % of cases and showed a median PFS and MS of 11 and 22 months, respectively. Patients treated with BCNU wafers presented a significantly higher survival when tumor was removed with the assistance of 5-ALA (22 months with vs 18 months without 5-ALA, p < 0.0001); these data could be partially explained by the significantly higher CRET achieved in patients operated with 5-ALA assistance (80 % with vs 47 %% without 5-ALA). Moreover, patients of Group I showed a significant increased survival compared with Group III (5-ALA without BCNU) (22 months with vs 21 months without BCNU wafers, p = 0.0025) even with a comparable CRET (80 % vs 76 %, respectively). The occurrence of adverse events related to wafers did not significantly increase with 5-ALA (20 % with and 19 % without 5-ALA) and did not impact in survival outcome. In conclusion, our experience shows that on selected ndGBM patients 5-ALA technology and BCNU wafers implantation show a synergic action on patients' outcome without increasing adverse events occurrence.

Fluorescence cytology with 5-aminolevulinic acid in EUS-guided FNA as a method for differentiating between malignant and benign lesions (with video).

PubMed

Ikeura, Tsukasa; Takaoka, Makoto; Uchida, Kazushige; Shimatani, Masaaki; Miyoshi, Hideaki; Kato, Kota; Ohe, Chisato; Uemura, Yoshiko; Kaibori, Masaki; Kwon, A-Hon; Okazaki, Kazuichi

2015-01-01

EUS-guided FNA (EUS-FNA) has been increasingly performed to obtain specimens for the pathological evaluation of patients with GI and pancreaticobiliary masses as well as lymphadenopathies of unknown origin. Photodynamic diagnosis by using 5-aminolebulinic acid (ALA) has been reported to be useful for enabling the visual differentiation between malignant and normal tissue in various cancers. To evaluate the diagnostic accuracy of fluorescence cytology with ALA in EUS-FNA. A prospective study. A single center. A total of 28 consecutive patients who underwent EUS-FNA for the pathological diagnosis of a pancreaticobiliary mass lesion or intra-abdominal lymphadenopathy of unknown origin. Patients were orally administered ALA 3 to 6 hours before EUS-FNA. The sample was obtained via EUS-FNA for fluorescence cytology and conventional cytology. A single gastroenterologist performed the fluorescence cytology by using fluorescence microscopy after the procedure, independently of the conventional cytology by pathologists. The accuracy of fluorescence cytology with ALA in the differentiation between benign and malignant lesions by comparing the results of fluorescence cytology with the final diagnosis. Of the 28 patients included in the study, 22 were considered as having malignant lesions and 6 patients as having benign lesions. Fluorescence cytology could correctly discriminate between benign and malignant lesions in all patients. Therefore, both the sensitivity and specificity of fluorescence cytology were 100% in our study. Fluorescence cytology was performed by only 1 gastroenterologist with a small number of patients. Fluorescence cytology with ALA in EUS-FNA may be an effective and simple method for differentiating between benign and malignant lesions. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Imaging Primary Mouse Sarcomas After Radiation Therapy Using Cathepsin-Activatable Fluorescent Imaging Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuneo, Kyle C.; Mito, Jeffrey K.; Javid, Melodi P.

2013-05-01

Purpose: Cathepsin-activated fluorescent probes can detect tumors in mice and in canine patients. We previously showed that these probes can detect microscopic residual sarcoma in the tumor bed of mice during gross total resection. Many patients with soft tissue sarcoma (STS) and other tumors undergo radiation therapy (RT) before surgery. This study assesses the effect of RT on the ability of cathepsin-activated probes to differentiate between normal and cancerous tissue. Methods and Materials: A genetically engineered mouse model of STS was used to generate primary hind limb sarcomas that were treated with hypofractionated RT. Mice were injected intravenously with cathepsin-activatedmore » fluorescent probes, and various tissues, including the tumor, were imaged using a hand-held imaging device. Resected tumor and normal muscle samples were harvested to assess cathepsin expression by Western blot. Uptake of activated probe was analyzed by flow cytometry and confocal microscopy. Parallel in vitro studies using mouse sarcoma cells were performed. Results: RT of primary STS in mice and mouse sarcoma cell lines caused no change in probe activation or cathepsin protease expression. Increasing radiation dose resulted in an upward trend in probe activation. Flow cytometry and immunofluorescence showed that a substantial proportion of probe-labeled cells were CD11b-positive tumor-associated immune cells. Conclusions: In this primary murine model of STS, RT did not affect the ability of cathepsin-activated probes to differentiate between tumor and normal muscle. Cathepsin-activated probes labeled tumor cells and tumor-associated macrophages. Our results suggest that it would be feasible to include patients who have received preoperative RT in clinical studies evaluating cathepsin-activated imaging probes.« less

Exciting New Advances in Neuro-Oncology

PubMed Central

Van Meir, Erwin G.; Hadjipanayis, Costas G.; Norden, Andrew D.; Shu, Hui-Kuo; Wen, Patrick Y.; Olson, Jeffrey J.

2010-01-01

Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development for patients, their families, and medical professionals alike. PMID:20445000

Structure-guided wavelength tuning in far-red fluorescent proteins

PubMed Central

Ng, Ho-Leung; Lin, Michael Z.

2017-01-01

In recent years, protein engineers have succeeded in tuning the excitation spectra of natural fluorescent proteins from green wavelengths into orange and red wavelengths, resulting in the creation of a series of fluorescent proteins with emission in the far-red portions of the optical spectrum. These results have arisen from the synergistic combination of structural knowledge of fluorescent proteins, chemical intuition, and high-throughput screening methods. Here we review structural features found in autocatalytic far-red fluorescent proteins, and discuss how they add to our understanding of the biophysical mechanisms of wavelength tuning in biological chromophores. PMID:27468111

Accuracy of experimental mandibular osteotomy using the image-guided sagittal saw.

PubMed

Pietruski, P; Majak, M; Swiatek-Najwer, E; Popek, M; Szram, D; Zuk, M; Jaworowski, J

2016-06-01

The aim of this study was to perform an objective assessment of the accuracy of mandibular osteotomy simulations performed using an image-guided sagittal saw. A total of 16 image-guided mandibular osteotomies were performed on four prefabricated anatomical models according to the virtual plan. Postoperative computed tomography (CT) image data were fused with the preoperative CT scan allowing an objective comparison of the results of the osteotomy executed with the virtual plan. For each operation, the following parameters were analyzed and compared independently twice by two observers: resected bone volume, osteotomy trajectory angle, and marginal point positions. The mean target registration error was 0.95±0.19mm. For all osteotomies performed, the mean difference between the planned and actual bone resection volumes was 8.55±5.51%, the mean angular deviation between planned and actual osteotomy trajectory was 8.08±5.50°, and the mean difference between the preoperative and the postoperative marginal point positions was 2.63±1.27mm. In conclusion, despite the initial stages of the research, encouraging results were obtained. The current limitations of the navigated saw are discussed, as well as the improvements in technology that should increase its predictability and efficiency, making it a reliable method for improving the surgical outcomes of maxillofacial operations. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Fluorescence guided lymph node biopsy in large animals using direct image projection device

NASA Astrophysics Data System (ADS)

Ringhausen, Elizabeth; Wang, Tylon; Pitts, Jonathan; Akers, Walter J.

2016-03-01

The use of fluorescence imaging for aiding oncologic surgery is a fast growing field in biomedical imaging, revolutionizing open and minimally invasive surgery practices. We have designed, constructed, and tested a system for fluorescence image acquisition and direct display on the surgical field for fluorescence guided surgery. The system uses a near-infrared sensitive CMOS camera for image acquisition, a near-infra LED light source for excitation, and DLP digital projector for projection of fluorescence image data onto the operating field in real time. Instrument control was implemented in Matlab for image capture, processing of acquired data and alignment of image parameters with the projected pattern. Accuracy of alignment was evaluated statistically to demonstrate sensitivity to small objects and alignment throughout the imaging field. After verification of accurate alignment, feasibility for clinical application was demonstrated in large animal models of sentinel lymph node biopsy. Indocyanine green was injected subcutaneously in Yorkshire pigs at various locations to model sentinel lymph node biopsy in gynecologic cancers, head and neck cancer, and melanoma. Fluorescence was detected by the camera system during operations and projected onto the imaging field, accurately identifying tissues containing the fluorescent tracer at up to 15 frames per second. Fluorescence information was projected as binary green regions after thresholding and denoising raw intensity data. Promising results with this initial clinical scale prototype provided encouraging results for the feasibility of optical projection of acquired luminescence during open oncologic surgeries.

Wide-field fluorescent microscopy on a cell-phone.

PubMed

Zhu, Hongying; Yaglidere, Oguzhan; Su, Ting-Wei; Tseng, Derek; Ozcan, Aydogan

2011-01-01

We demonstrate wide-field fluorescent imaging on a cell-phone, using compact and cost-effective optical components that are mechanically attached to the existing camera unit of the cell-phone. Battery powered light-emitting diodes (LEDs) are used to side-pump the sample of interest using butt-coupling. The pump light is guided within the sample cuvette to excite the specimen uniformly. The fluorescent emission from the sample is then imaged with an additional lens that is put in front of the existing lens of the cell-phone camera. Because the excitation occurs through guided waves that propagate perpendicular to the detection path, an inexpensive plastic color filter is sufficient to create the dark-field background needed for fluorescent imaging. The imaging performance of this light-weight platform (~28 grams) is characterized with red and green fluorescent microbeads, achieving an imaging field-of-view of ~81 mm(2) and a spatial resolution of ~10 μm, which is enhanced through digital processing of the captured cell-phone images using compressive sampling based sparse signal recovery. We demonstrate the performance of this cell-phone fluorescent microscope by imaging labeled white-blood cells separated from whole blood samples as well as water-borne pathogenic protozoan parasites such as Giardia Lamblia cysts.

Live imaging using adaptive optics with fluorescent protein guide-stars

PubMed Central

Tao, Xiaodong; Crest, Justin; Kotadia, Shaila; Azucena, Oscar; Chen, Diana C.; Sullivan, William; Kubby, Joel

2012-01-01

Spatially and temporally dependent optical aberrations induced by the inhomogeneous refractive index of live samples limit the resolution of live dynamic imaging. We introduce an adaptive optical microscope with a direct wavefront sensing method using a Shack-Hartmann wavefront sensor and fluorescent protein guide-stars for live imaging. The results of imaging Drosophila embryos demonstrate its ability to correct aberrations and achieve near diffraction limited images of medial sections of large Drosophila embryos. GFP-polo labeled centrosomes can be observed clearly after correction but cannot be observed before correction. Four dimensional time lapse images are achieved with the correction of dynamic aberrations. These studies also demonstrate that the GFP-tagged centrosome proteins, Polo and Cnn, serve as excellent biological guide-stars for adaptive optics based microscopy. PMID:22772285

Detecting fluorescence hot-spots using mosaic maps generated from multimodal endoscope imaging

NASA Astrophysics Data System (ADS)

Yang, Chenying; Soper, Timothy D.; Seibel, Eric J.

2013-03-01

Fluorescence labeled biomarkers can be detected during endoscopy to guide early cancer biopsies, such as high-grade dysplasia in Barrett's Esophagus. To enhance intraoperative visualization of the fluorescence hot-spots, a mosaicking technique was developed to create full anatomical maps of the lower esophagus and associated fluorescent hot-spots. The resultant mosaic map contains overlaid reflectance and fluorescence images. It can be used to assist biopsy and document findings. The mosaicking algorithm uses reflectance images to calculate image registration between successive frames, and apply this registration to simultaneously acquired fluorescence images. During this mosaicking process, the fluorescence signal is enhanced through multi-frame averaging. Preliminary results showed that the technique promises to enhance the detectability of the hot-spots due to enhanced fluorescence signal.

The utility of indocyanine green near infrared fluorescent imaging in the identification of parathyroid glands during surgery for primary hyperparathyroidism.

PubMed

Zaidi, Nisar; Bucak, Emre; Okoh, Alexis; Yazici, Pinar; Yigitbas, Hakan; Berber, Eren

2016-06-01

Intraoperative adjuncts for the localization of parathyroid glands in parathyroid surgery are limited. The aim of this study is to assess the usefulness of indocyanine green (ICG) near-infrared (NIR) fluorescent imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT). ICG imaging was performed in 33 patients undergoing parathyroidectomy (PTX). Thyroid and parathyroid ICG uptake were assessed and independently verified on a grading scale. Clinical variables were recorded and analyzed for factors associated with ICG uptake. Of 112 glands identified by naked eye, 104 (92.9%) demonstrated ICG uptake. Concomitant ICG fluorescence was identified in the thyroid in all patients. There was a trend toward increased ICG fluorescence in patients <60 years of age (P = 0.05). A higher degree of fluorescence was seen in patients presenting with pre-operative calcium values >11 mg/dl (P = 0.04) and in those parathyroids larger than 10 mm (P < 0.01). All patients had biochemically proven cure. No patients who underwent subtotal PTX (n = 6) developed postoperative hypoparathyroidism. ICG can reliably localize parathyroid glands during PTX and additionally allow for assessment of parathyroid perfusion in patients undergoing subtotal resection. Concomitant fluorescence of the thyroid gland limits ICG's usefulness in directing the course of PTX. J. Surg. Oncol. 2016;113:771-774. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Indocyanine green fluorescence imaging in hepatobiliary surgery.

PubMed

Majlesara, Ali; Golriz, Mohammad; Hafezi, Mohammadreza; Saffari, Arash; Stenau, Esther; Maier-Hein, Lena; Müller-Stich, Beat P; Mehrabi, Arianeb

2017-03-01

Indocyanine green (ICG) is a fluorescent dye that has been widely used for fluorescence imaging during hepatobiliary surgery. ICG is injected intravenously, selectively taken up by the liver, and then secreted into the bile. The catabolism and fluorescence properties of ICG permit a wide range of visualization methods in hepatobiliary surgery. We have characterized the applications of ICG during hepatobiliary surgery into: 1) liver mapping, 2) cholangiography, 3) tumor visualization, and 4) partial liver graft evaluation. In this literature review, we summarize the current understanding of ICG use during hepatobiliary surgery. Intra-operative ICG fluorescence imaging is a safe, simple, and feasible method that improves the visualization of hepatobiliary anatomy and liver tumors. Intravenous administration of ICG is not toxic and avoids the drawbacks of conventional imaging. In addition, it reduces post-operative complications without any known side effects. ICG fluorescence imaging provides a safe and reliable contrast for extra-hepatic cholangiography when detecting intra-hepatic bile leakage following liver resection. In addition, liver tumors can be visualized and well-differentiated hepatocellular carcinoma tumors can be accurately identified. Moreover, vascular reconstruction and outflow can be evaluated following partial liver transplantation. However, since tissue penetration is limited to 5-10mm, deeper tissue cannot be visualized using this method. Many instances of false positive or negative results have been reported, therefore further characterization is required. Copyright © 2016 Elsevier B.V. All rights reserved.

[Application of hepatic segment resection combined with rigid choledochoscope in the treatment of complex hepatolithiasis guided by three-dimensional visualization technology].

PubMed

Xiang, Nan; Fang, Chihua

2015-05-01

To study the value of hepatic segment resection combined with rigid choledochoscope by the three-dimensional (3D) visualization technology in the diagnosis and treatment of complex hepatolithiasis. Enhance computed tomography (CT) data of 46 patients with complex hepatolithiasis who were admitted to the Zhujiang Hospital of the Southern Medical University from July 2010 to June 2014 were collected.All of the CT data were imported into the medical image three-dimensional visualization system (MI-3DVS) for 3D reconstruction and individual 3D types. The optimal scope of liver resection and the remnant liver volume were determined according to the individualized liver segments which were made via the distribution and variation of hepatic vein and portal vein, the distribution of bile duct stones and stricture of the bile duct, which provided guidance for intraoperative hepatic lobectomy and rigid choledochoscope for the remnant calculus lithotripsy. Outcomes of individual 3D types: 10 cases of type I, 11 cases of IIa, 23 cases of IIb, 2 cases of IIc, 19 cases coexisted with history of biliary surgery. The variation of hepatic artery was appeared 6 cases. The variation of portal vein was appeared 8 cases. The remaining liver volume for virtual hepatic lobectomy controlled more than 50%. Eighteen cases underwent left lateral hepatectomy, 8 cases underwent left liver resection, 8 cases underwent right posterior lobe of liver resection, 4 cases underwent the right hepatic resection, 4 cases underwent IV segment liver resection, 2 cases underwent right anterior lobe of liver resection, 2 cases underwent left lateral hepatectomy combined with right posterior lobe of liver resection, 26 cases underwent targeting treatment of rapid choledochoscope and preumatic lithotripsy. The actual surgical procedure was consistent with the preoperative surgical planning. There was no postoperative residual liver ischemia,congestion, liver failure occurred in this study. The intraoperative calculus clearance rate was 91.3% (42/46) because 4 cases of postoperatively residual calculi were not suitable for one stage management due to suppurative cholangitis but removed calculus successfully with rigid choledochoscope through T tube fistula. Hepatic segment resection combined with rigid choledochoscope under the guidance of three-dimensional visualization technology achieves accurate preoperative diagnosis and higher complete stone clearance rate of complicated hepatolithiasis.

Hyperspectral imaging fluorescence excitation scanning for detecting colorectal cancer: pilot study

NASA Astrophysics Data System (ADS)

Leavesley, Silas J.; Wheeler, Mikayla; Lopez, Carmen; Baker, Thomas; Favreau, Peter F.; Rich, Thomas C.; Rider, Paul F.; Boudreaux, Carole W.

2016-03-01

Optical spectroscopy and hyperspectral imaging have shown the theoretical potential to discriminate between cancerous and non-cancerous tissue with high sensitivity and specificity. To date, these techniques have not been able to be effectively translated to endoscope platforms. Hyperspectral imaging of the fluorescence excitation spectrum represents a new technology that may be well-suited for endoscopic implementation. However, the feasibility of detecting differences between normal and cancerous mucosa using fluorescence excitation-scanning hyperspectral imaging has not been evaluated. The objective of this pilot study was to evaluate the changes in the fluorescence excitation spectrum of resected specimen pairs of colorectal adenocarcinoma and normal colorectal mucosa. Patients being treated for colorectal adenocarcinoma were enrolled. Representative adenocarcinoma and normal colonic mucosa specimens were collected from each case. Specimens were flash frozen in liquid nitrogen. Adenocarcinoma was confirmed by histologic evaluation of H&E permanent sections. Hyperspectral image data of the fluorescence excitation of adenocarcinoma and surrounding normal tissue were acquired using a custom microscope configuration previously developed in our lab. Results demonstrated consistent spectral differences between normal and cancerous tissues over the fluorescence excitation spectral range of 390-450 nm. We conclude that fluorescence excitation-scanning hyperspectral imaging may offer an alternative approach for differentiating adenocarcinoma and surrounding normal mucosa of the colon. Future work will focus on expanding the number of specimen pairs analyzed and will utilize fresh tissues where possible, as flash freezing and reconstituting tissues may have altered the autofluorescence properties.

Analysis of surgical margins in oral cancer using in situ fluorescence spectroscopy.

PubMed

Francisco, Ana Lucia Noronha; Correr, Wagner Rafael; Pinto, Clóvis Antônio Lopes; Gonçalves Filho, João; Chulam, Thiago Celestino; Kurachi, Cristina; Kowalski, Luiz Paulo

2014-06-01

Oral cancer is a public health problem with high prevalence in the population. Local tumor control is best achieved by complete surgical resection with adequate margins. A disease-free surgical margin correlates with a lower rate of local recurrence and a higher rate of disease-free survival. Fluorescence spectroscopy is a noninvasive diagnostic tool that can aid in real-time cancer detection. The technique, which evaluates the biochemical composition and structure of tissue fluorescence, is relatively simple, fast and, accurate. This study aimed to compare oral squamous cell carcinoma lesions to surgical margins and the mucosa of healthy volunteers by fluorescence spectroscopy. The sample consisted of 56 individuals, 28 with oral squamous cell carcinoma and 28 healthy volunteers with normal oral mucosa. Thirty six cases (64.3%) were male and the mean age was 60.9 years old. The spectra were classified and compared to histopathology to determine fluorescence efficiency for diagnostic discrimination of tumors. In the analysis of the other cases we observed discrimination between normal mucosa, injury and margins. At two-year follow up, three individuals had local recurrence, and in two cases investigation fluorescence in the corresponding area showed qualitative differences in spectra between the recurrence area and the area without recurrence at the same anatomical site in the same patient. In situ analysis of oral mucosa showed the potential of fluorescence spectroscopy as a diagnostic tool that can aid in discrimination of altered mucosa and normal mucosa. Copyright © 2014 Elsevier Ltd. All rights reserved.

The utility of 5-aminolevulinic acid-mediated photodynamic diagnosis in the detection of intraoperative bile leakage.

PubMed

Inoue, Yoshihiro; Imai, Yoshiro; Fujii, Kensuke; Hirokawa, Fumitoshi; Hayashi, Michihiro; Uchiyama, Kazuhisa

2017-06-01

The purpose of this retrospective study was to evaluate the utility of the new intraoperative bile leakage test as a preventive measure of postoperative bile leakage. 737 patients were retrospectively analyzed with respect to the management of intra- and post-operative bile leakage. Nine (8.3%) of 109 patients evaluated using conventional white light fluorescent imaging were recognized as having intra-operative bile leakage. However, performance of 5-aminolevulinic acid (5-ALA)-mediated PDD detected bile leakage intraoperatively not only in these 9 patients, but also in an additional 6 patients, such that 'red fluorescence' at the cut surface of the liver, was visualized in a total of 15 patients. The postoperative courses of most patients were uneventful, and postoperative bile leakages occurred in only one (0.9%) patient. 5-ALA fluorescence imaging may be needed to prevent postoperative bile leakage in patients at high risk for this surgical complication after hepatic resection. Copyright © 2016 Elsevier Inc. All rights reserved.

Image updating for brain deformation compensation in tumor resection

NASA Astrophysics Data System (ADS)

Fan, Xiaoyao; Ji, Songbai; Olson, Jonathan D.; Roberts, David W.; Hartov, Alex; Paulsen, Keith D.

2016-03-01

Preoperative magnetic resonance images (pMR) are typically used for intraoperative guidance in image-guided neurosurgery, the accuracy of which can be significantly compromised by brain deformation. Biomechanical finite element models (FEM) have been developed to estimate whole-brain deformation and produce model-updated MR (uMR) that compensates for brain deformation at different surgical stages. Early stages of surgery, such as after craniotomy and after dural opening, have been well studied, whereas later stages after tumor resection begins remain challenging. In this paper, we present a method to simulate tumor resection by incorporating data from intraoperative stereovision (iSV). The amount of tissue resection was estimated from iSV using a "trial-and-error" approach, and the cortical shift was measured from iSV through a surface registration method using projected images and an optical flow (OF) motion tracking algorithm. The measured displacements were employed to drive the biomechanical brain deformation model, and the estimated whole-brain deformation was subsequently used to deform pMR and produce uMR. We illustrate the method using one patient example. The results show that the uMR aligned well with iSV and the overall misfit between model estimates and measured displacements was 1.46 mm. The overall computational time was ~5 min, including iSV image acquisition after resection, surface registration, modeling, and image warping, with minimal interruption to the surgical flow. Furthermore, we compare uMR against intraoperative MR (iMR) that was acquired following iSV acquisition.

Recent technological advances in pediatric brain tumor surgery.

PubMed

Zebian, Bassel; Vergani, Francesco; Lavrador, José Pedro; Mukherjee, Soumya; Kitchen, William John; Stagno, Vita; Chamilos, Christos; Pettorini, Benedetta; Mallucci, Conor

2017-01-01

X-rays and ventriculograms were the first imaging modalities used to localize intracranial lesions including brain tumors as far back as the 1880s. Subsequent advances in preoperative radiological localization included computed tomography (CT; 1971) and MRI (1977). Since then, other imaging modalities have been developed for clinical application although none as pivotal as CT and MRI. Intraoperative technological advances include the microscope, which has allowed precise surgery under magnification and improved lighting, and the endoscope, which has improved the treatment of hydrocephalus and allowed biopsy and complete resection of intraventricular, pituitary and pineal region tumors through a minimally invasive approach. Neuronavigation, intraoperative MRI, CT and ultrasound have increased the ability of the neurosurgeon to perform safe and maximal tumor resection. This may be facilitated by the use of fluorescing agents, which help define the tumor margin, and intraoperative neurophysiological monitoring, which helps identify and protect eloquent brain.

[Effect of transurethral resection of the prostate on the state of patients with ischemic heart disease].

PubMed

Belugin, R S; Zabusov, A V; Zhemchugov, A V

2004-01-01

The water-salt equilibrium and the degree of endogenous intoxication (albumin fluorescence test) were examined in 60 patients with transurethral resection of the prostate (TURP), 40 of whom had ischemic heart disease (IHD). Body temperature, ECG, ST segment and echocardioscopy were daily monitored perioperatively in all patients. The results showed a lack of any pronounced changes in the water-salt equilibrium in TURP that lasted up to 1.5 hours and included big volumes of 5% glucose; they were also indicative of a lower postoperative binding albumin ability, which is normally most pronounced in patients with hyperthermia. As for the IHD patients, hyperthermia was found to be concurrent in them with the onset of ischemia of the myocardium and with its low contractive ability, which can be referred to as a significant factor in case of the above patients.

Augmented microscopy with near-infrared fluorescence detection

NASA Astrophysics Data System (ADS)

Watson, Jeffrey R.; Martirosyan, Nikolay; Skoch, Jesse; Lemole, G. Michael; Anton, Rein; Romanowski, Marek

2015-03-01

Near-infrared (NIR) fluorescence has become a frequently used intraoperative technique for image-guided surgical interventions. In procedures such as cerebral angiography, surgeons use the optical surgical microscope for the color view of the surgical field, and then switch to an electronic display for the NIR fluorescence images. However, the lack of stereoscopic, real-time, and on-site coregistration adds time and uncertainty to image-guided surgical procedures. To address these limitations, we developed the augmented microscope, whereby the electronically processed NIR fluorescence image is overlaid with the anatomical optical image in real-time within the optical path of the microscope. In vitro, the augmented microscope can detect and display indocyanine green (ICG) concentrations down to 94.5 nM, overlaid with the anatomical color image. We prepared polyacrylamide tissue phantoms with embedded polystyrene beads, yielding scattering properties similar to brain matter. In this model, 194 μM solution of ICG was detectable up to depths of 5 mm. ICG angiography was then performed in anesthetized rats. A dynamic process of ICG distribution in the vascular system overlaid with anatomical color images was observed and recorded. In summary, the augmented microscope demonstrates NIR fluorescence detection with superior real-time coregistration displayed within the ocular of the stereomicroscope. In comparison to other techniques, the augmented microscope retains full stereoscopic vision and optical controls including magnification and focus, camera capture, and multiuser access. Augmented microscopy may find application in surgeries where the use of traditional microscopes can be enhanced by contrast agents and image guided delivery of therapeutics, including oncology, neurosurgery, and ophthalmology.

ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients.

PubMed

Lee, Cheol; Park, Jeong Whan; Suh, Ja Hee; Nam, Kyung Han; Moon, Kyung Chul

2013-10-01

Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases. We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases. One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin. We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.

Synthesis of a Fluorescently Labeled 68Ga-DOTA-TOC Analog for Somatostatin Receptor Targeting.

PubMed

Ghosh, Sukhen C; Hernandez Vargas, Servando; Rodriguez, Melissa; Kossatz, Susanne; Voss, Julie; Carmon, Kendra S; Reiner, Thomas; Schonbrunn, Agnes; Azhdarinia, Ali

2017-07-13

Fluorescently labeled imaging agents can identify surgical margins in real-time to help achieve complete resections and minimize the likelihood of local recurrence. However, photon attenuation limits fluorescence-based imaging to superficial lesions or lesions that are a few millimeters beneath the tissue surface. Contrast agents that are dual-labeled with a radionuclide and fluorescent dye can overcome this limitation and combine quantitative, whole-body nuclear imaging with intraoperative fluorescence imaging. Using a multimodality chelation (MMC) scaffold, IRDye 800CW was conjugated to the clinically used somatostatin analog, 68 Ga-DOTA-TOC, to produce the dual-labeled analog, 68 Ga-MMC(IRDye 800CW)-TOC, with high yield and specific activity. In vitro pharmacological assays demonstrated retention of receptor-targeting properties for the dual-labeled compound with robust internalization that was somatostatin receptor (SSTR) 2-mediated. Biodistribution studies in mice identified the kidneys as the primary excretion route for 68 Ga-MMC(IRDye 800CW)-TOC, along with clearance via the reticuloendothelial system. Higher uptake was observed in most tissues compared to 68 Ga-DOTA-TOC but decreased as a function of time. The combination of excellent specificity for SSTR2-expressing cells and suitable biodistribution indicate potential application of 68 Ga-MMC(IRDye 800CW)-TOC for intraoperative detection of SSTR2-expressing tumors.

Clinical application of photodynamic medicine technology using light-emitting fluorescence imaging based on a specialized luminous source.

PubMed

Namikawa, Tsutomu; Fujisawa, Kazune; Munekage, Eri; Iwabu, Jun; Uemura, Sunao; Tsujii, Shigehiro; Maeda, Hiromichi; Kitagawa, Hiroyuki; Fukuhara, Hideo; Inoue, Keiji; Sato, Takayuki; Kobayashi, Michiya; Hanazaki, Kazuhiro

2018-04-04

The natural amino acid 5-aminolevulinic acid (ALA) is a protoporphyrin IX (PpIX) precursor and a new-generation photosensitive substance that accumulates specifically in cancer cells. When indocyanine green (ICG) is irradiated with near-infrared (NIR) light, it shifts to a higher energy state and emits infrared light with a longer wavelength than the irradiated NIR light. Photodynamic diagnosis (PDD) using ALA and ICG-based NIR fluorescence imaging has emerged as a new diagnostic technique. Specifically, in laparoscopic examinations for serosa-invading advanced gastric cancer, peritoneal metastases could be detected by ALA-PDD, but not by conventional visible-light imaging. The HyperEye Medical System (HEMS) can visualize ICG fluorescence as color images simultaneously projected with visible light in real time. This ICG fluorescence method is widely applicable, including for intraoperative identification of sentinel lymph nodes, visualization of blood vessels in organ resection, and blood flow evaluation during surgery. Fluorescence navigation by ALA-PDD and NIR using ICG imaging provides good visualization and detection of the target lesions that is not possible with the naked eye. We propose that this technique should be used in fundamental research on the relationship among cellular dynamics, metabolic enzymes, and tumor tissues, and to evaluate clinical efficacy and safety in multicenter cooperative clinical trials.

Indocyanine green fluorescence-guided parathyroidectomy for primary hyperparathyroidism.

PubMed

DeLong, Jonathan C; Ward, Erin P; Lwin, Thinzar M; Brumund, Kevin T; Kelly, Kaitlyn J; Horgan, Santiago; Bouvet, Michael

2018-02-01

Our aim was to evaluate the ease and utility of using indocyanine green fluorescence angiography for intraoperative localization of the parathyroid glands. Indocyanine green fluorescence angiography was performed during 60 parathyroidectomies for primary hyperparathyroidism during a 22-month period. Indocyanine green was administered intravenously to guide operative navigation using a commercially available fluorescence imaging system. Video files were graded by 3 independent surgeons for strength of enhancement using an adapted numeric scoring system. There were 46 (77%) female patients and 14 (23%) male patients whose ages ranged from 17 to 87 (average 60) years old. Of the 60 patients, 43 (71.6%) showed strong enhancement, 13 (21.7%) demonstrated mild to moderate vascular enhancement, and 4 (6.7%) exhibited little or no vascular enhancement. Of the 54 patients who had a preoperative sestamibi scan, a parathyroid adenoma was identified in 36, while 18 failed to localize. Of the 18 patients who failed to localize, all 18 patients (100%) had an adenoma that fluoresced on indocyanine green imaging. The operations were performed safely with minimal blood loss and short operative times. Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly with minimal risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a fluorimeter using laser-induced single-shot fluorescence lifetime spectroscopy

NASA Astrophysics Data System (ADS)

Eisum, Niels H.; Lynggaard-Jensen, Anders

1990-08-01

The developed laboratory prototype fluorimeter is the first step to a new in-situ instrument, and is based on a pulsed nitrogen laser (pumping a color dye laser and the laserbeam passing through a frequency doubler) with a pulse width less than 1 nsec. With such a short excitation pulse it is possible to measure the exponential decay of the fluorescence from the aromatic compounds and thus determine the fluorescence lifetime-curves, which are typically in the region of 5-40 nsec. The emitted fluorescence is collected simultaneously in 35 channels in the wavelength region 250-600 nm. If the fluorescence falls within the transmission areas of the interference filters in each channel the light will be collected by a plastic light guide (doped PMMA) in the actual channel and transmitted to the channels photo multiplier tube (PMT). (The use of the plastic light guide improves the sensitivity). The signal from the PMT is passed on to a 200 MHz 8-bit flash AID-converter connected to a local memory. From this local memory the digital lifetime curves from each channel are transmitted to a computer for presentation of the 3-dimensional spectrum. This spectrum has been obtained with a single laser shot.

Chip-scale fluorescence microscope based on a silo-filter complementary metal-oxide semiconductor image sensor.

PubMed

Ah Lee, Seung; Ou, Xiaoze; Lee, J Eugene; Yang, Changhuei

2013-06-01

We demonstrate a silo-filter (SF) complementary metal-oxide semiconductor (CMOS) image sensor for a chip-scale fluorescence microscope. The extruded pixel design with metal walls between neighboring pixels guides fluorescence emission through the thick absorptive filter to the photodiode of a pixel. Our prototype device achieves 13 μm resolution over a wide field of view (4.8 mm × 4.4 mm). We demonstrate bright-field and fluorescence longitudinal imaging of living cells in a compact, low-cost configuration.

Surgical resection versus liver transplantation for hepatocellular carcinoma within the Hangzhou criteria: a preoperative nomogram-guided treatment strategy.

PubMed

Li, Yang; Ruan, Dan-Yun; Jia, Chang-Chang; Zhao, Hui; Wang, Guo-Ying; Yang, Yang; Jiang, Nan

2017-10-15

With the expansion of surgical criteria, the comparative efficacy between surgical resection (SR) and liver transplantation (LT) for hepatocellular carcinoma is inconclusive. This study aimed to develop a prognostic nomogram for predicting recurrence-free survival of hepatocellular carcinoma patients after resection and explored the possibility of using nomogram as treatment algorithm reference. From 2003 to 2012, 310 hepatocellular carcinoma patients within Hangzhou criteria undergoing resection or liver transplantation were included. Total tumor volume, albumin level, HBV DNA copies and portal hypertension were included for constructing the nomogram. The resection patients were stratified into low- and high-risk groups by the median nomogram score of 116. Independent risk factors were identified and a visually orientated nomogram was constructed using a Cox proportional hazards model to predict the recurrence risk for SR patients. The low-risk SR group had better outcomes compared with the high-risk SR group (3-year recurrence-free survival rate, 71.1% vs 35.9%; 3-year overall survival rate, 89.8% vs 78.9%, both P<0.001). The high-risk SR group was associated with a worse recurrence-free survival rate but similar overall survival rate compared with the transplantation group (3-year recurrence-free survival rate, 35.9% vs 74.1%, P<0.001; 3-year overall survival rate, 78.9% vs 79.6%, P>0.05). This nomogram offers individualized recurrence risk evaluation for hepatocellular carcinoma patients within Hangzhou criteria receiving resection. Transplantation should be considered the first-line treatment for high-risk patients. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

Compact point-detection fluorescence spectroscopy system for quantifying intrinsic fluorescence redox ratio in brain cancer diagnostics

NASA Astrophysics Data System (ADS)

Liu, Quan; Grant, Gerald; Li, Jianjun; Zhang, Yan; Hu, Fangyao; Li, Shuqin; Wilson, Christy; Chen, Kui; Bigner, Darell; Vo-Dinh, Tuan

2011-03-01

We report the development of a compact point-detection fluorescence spectroscopy system and two data analysis methods to quantify the intrinsic fluorescence redox ratio and diagnose brain cancer in an orthotopic brain tumor rat model. Our system employs one compact cw diode laser (407 nm) to excite two primary endogenous fluorophores, reduced nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. The spectra were first analyzed using a spectral filtering modulation method developed previously to derive the intrinsic fluorescence redox ratio, which has the advantages of insensitivty to optical coupling and rapid data acquisition and analysis. This method represents a convenient and rapid alternative for achieving intrinsic fluorescence-based redox measurements as compared to those complicated model-based methods. It is worth noting that the method can also extract total hemoglobin concentration at the same time but only if the emission path length of fluorescence light, which depends on the illumination and collection geometry of the optical probe, is long enough so that the effect of absorption on fluorescence intensity due to hemoglobin is significant. Then a multivariate method was used to statistically classify normal tissues and tumors. Although the first method offers quantitative tissue metabolism information, the second method provides high overall classification accuracy. The two methods provide complementary capabilities for understanding cancer development and noninvasively diagnosing brain cancer. The results of our study suggest that this portable system can be potentially used to demarcate the elusive boundary between a brain tumor and the surrounding normal tissue during surgical resection.

Intraoperative Near-infrared Imaging for Parathyroid Gland Identification by Auto-fluorescence: A Feasibility Study.

PubMed

De Leeuw, Frederic; Breuskin, Ingrid; Abbaci, Muriel; Casiraghi, Odile; Mirghani, Haïtham; Ben Lakhdar, Aïcha; Laplace-Builhé, Corinne; Hartl, Dana

2016-09-01

Parathyroid glands (PGs) can be particularly hard to distinguish from surrounding tissue and thus can be damaged or removed during thyroidectomy. Postoperative hypoparathyroidism is the most common complication after thyroidectomy. Very recently, it has been found that the parathyroid tissue shows near-infrared (NIR) auto-fluorescence which could be used for intraoperative detection, without any use of contrast agents. The work described here presents a histological validation ex vivo of the NIR imaging procedure and evaluates intraoperative PG detection by NIR auto-fluorescence using for the first time to our knowledge a commercially available clinical NIR imaging device. Ex vivo study on resected operative specimens combined with a prospective in vivo study of consecutive patients who underwent total or partial thyroid, or parathyroid surgery at a comprehensive cancer center. During surgery, any tissue suspected to be a potential PG by the surgeon was imaged with the Fluobeam 800 (®) system. NIR imaging was compared to conventional histology (ex vivo) and/or visual identification by the surgeon (in vivo). We have validated NIR auto-fluorescence with an ex vivo study including 28 specimens. Sensitivity and specificity were 94.1 and 80 %, respectively. Intraoperative NIR imaging was performed in 35 patients and 81 parathyroids were identified. In 80/81 cases, the fluorescence signal was subjectively obvious on real-time visualization. We determined that PG fluorescence is 2.93 ± 1.59 times greater than thyroid fluorescence in vivo. Real-time NIR imaging based on parathyroid auto-fluorescence is fast, safe, and non-invasive and shows very encouraging results, for intraoperative parathyroid identification.

A fluorescence-based imaging approach to pharmacokinetic analysis of intracochlear drug delivery.

PubMed

Ayoob, Andrew M; Peppi, Marcello; Tandon, Vishal; Langer, Robert; Borenstein, Jeffrey T

2018-04-05

Advances in microelectromechanical systems (MEMS) technologies are enhancing the development of intracochlear delivery devices for the treatment of hearing loss with emerging pharmacological therapies. Direct intracochlear delivery addresses the limitations of systemic and intratympanic delivery. However, optimization of delivery parameters for these devices requires pharmacokinetic assessment of the spatiotemporal drug distribution inside the cochlea. Robust methods of measuring drug concentration in the perilymph have been developed, but lack spatial resolution along the tonotopic axis or require complex physiological measurements. Here we describe an approach for quantifying distribution of fluorescent drug-surrogate probe along the cochlea's sensory epithelium with high spatial resolution enabled by confocal fluorescence imaging. Fluorescence from FM 1-43 FX, a fixable endocytosis marker, was quantified using confocal fluorescence imaging of whole mount sections of the organ of Corti from cochleae resected and fixed at several time points after intracochlear delivery. Intracochlear delivery of FM 1-43 FX near the base of the cochlea produces a base-apex gradient of fluorescence in the row of inner hair cells after 1 h post-delivery that is consistent with diffusion-limited transport along the scala tympani. By 3 h post-delivery there is approximately an order of magnitude decrease in peak average fluorescence intensity, suggesting FM 1-43 FX clearance from both the perilymph and inner hair cells. The increase in fluorescence intensity at 72 h post-delivery compared to 3 h post-delivery may implicate a potential radial transport pathway into the scala media. Copyright © 2018 Elsevier B.V. All rights reserved.

Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management

PubMed Central

Lim, Chul-Hyun; Cho, Young-Seok

2016-01-01

Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID:26811631

[Application of 3D virtual reality technology with multi-modality fusion in resection of glioma located in central sulcus region].

PubMed

Chen, T N; Yin, X T; Li, X G; Zhao, J; Wang, L; Mu, N; Ma, K; Huo, K; Liu, D; Gao, B Y; Feng, H; Li, F

2018-05-08

Objective: To explore the clinical and teaching application value of virtual reality technology in preoperative planning and intraoperative guide of glioma located in central sulcus region. Method: Ten patients with glioma in the central sulcus region were proposed to surgical treatment. The neuro-imaging data, including CT, CTA, DSA, MRI, fMRI were input to 3dgo sczhry workstation for image fusion and 3D reconstruction. Spatial relationships between the lesions and the surrounding structures on the virtual reality image were obtained. These images were applied to the operative approach design, operation process simulation, intraoperative auxiliary decision and the training of specialist physician. Results: Intraoperative founding of 10 patients were highly consistent with preoperative simulation with virtual reality technology. Preoperative 3D reconstruction virtual reality images improved the feasibility of operation planning and operation accuracy. This technology had not only shown the advantages for neurological function protection and lesion resection during surgery, but also improved the training efficiency and effectiveness of dedicated physician by turning the abstract comprehension to virtual reality. Conclusion: Image fusion and 3D reconstruction based virtual reality technology in glioma resection is helpful for formulating the operation plan, improving the operation safety, increasing the total resection rate, and facilitating the teaching and training of the specialist physician.

Neoadjuvant radiotherapeutic strategies in pancreatic cancer

PubMed Central

Roeder, Falk

2016-01-01

This review summarizes the current status of neoadjuvant radiation approaches in the treatment of pancreatic cancer, including a description of modern radiation techniques, and an overview on the literature regarding neoadjuvant radio- or radiochemotherapeutic strategies both for resectable and irresectable pancreatic cancer. Neoadjuvant chemoradiation for locally-advanced, primarily non- or borderline resectable pancreas cancer results in secondary resectability in a substantial proportion of patients with consecutively markedly improved overall prognosis and should be considered as possible alternative in pretreatment multidisciplinary evaluations. In resectable pancreatic cancer, outstanding results in terms of response, local control and overall survival have been observed with neoadjuvant radio- or radiochemotherapy in several phase I/II trials, which justify further evaluation of this strategy. Further investigation of neoadjuvant chemoradiation strategies should be performed preferentially in randomized trials in order to improve comparability of the current results with other treatment modalities. This should include the evaluation of optimal sequencing with newer and more potent systemic induction therapy approaches. Advances in patient selection based on new molecular markers might be of crucial interest in this context. Finally modern external beam radiation techniques (intensity-modulated radiation therapy, image-guided radiation therapy and stereotactic body radiation therapy), new radiation qualities (protons, heavy ions) or combinations with alternative boosting techniques widen the therapeutic window and contribute to the reduction of toxicity. PMID:26909133

Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC

PubMed Central

Petersen, Lars F.; Klimowicz, Alexander C.; Otsuka, Shannon; Elegbede, Anifat A.; Petrillo, Stephanie K.; Williamson, Tyler; Williamson, Chris T.; Konno, Mie; Lees-Miller, Susan P.; Hao, Desiree; Morris, Don; Magliocco, Anthony M.; Bebb, D. Gwyn

2017-01-01

Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients. PMID:28418844

Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.

PubMed

Petersen, Lars F; Klimowicz, Alexander C; Otsuka, Shannon; Elegbede, Anifat A; Petrillo, Stephanie K; Williamson, Tyler; Williamson, Chris T; Konno, Mie; Lees-Miller, Susan P; Hao, Desiree; Morris, Don; Magliocco, Anthony M; Bebb, D Gwyn

2017-06-13

Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This effect was pronounced in stage II/III patients, even after adjusting for other clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

Lesion guided stereotactic radiofrequency thermocoagulation for palliative, in selected cases curative epilepsy surgery.

PubMed

Wellmer, Jörg; Parpaley, Yaroslav; Rampp, Stefan; Popkirov, Stoyan; Kugel, Harald; Aydin, Ümit; Wolters, Carsten H; von Lehe, Marec; Voges, Jürgen

2016-03-01

Resective epilepsy surgery is an established treatment option in patients with pharmacoresistant, lesion related epilepsy. Yet, if the presurgical work-up proves multi-focal organization of the epileptogenic zone, or the area of intended resection is close to eloquent brain areas, patients may decide against resections because of an unfavorable risk-benefit-ratio. We assess if lesion guided cortical stereotactic radiofrequency thermocoagulation (L-RFTC) is a potential surgical alternative in these patients. We performed seven procedures of L-RFTC. Three patients had monofocal epilepsy arising close to eloquent structures; in four, invasive pre-surgical workup documented monofocal seizure onset but strong interictal epileptic activity also independent and distant from the seizure onset zone. L-RFTC was restricted to the lesional area (=seizure onset site). 12 to 37 months after RFTC worthwhile seizure improvement was achieved in 6 patients. One patient became seizure free following complete coagulation of a focal cortical dysplasia, two had had 1-2 auras under tapered but not under continued medication. In one patient only subclinical seizures persisted. In one patient hypermotor seizures were transformed into milder short tonic seizures and another one had a seizure reduction by 50%. Only one patient did not profit at all. One patient developed a persisting neurological deficit. In patients with complex epileptogenic zones L-RFTC can lead to worthwhile seizure reduction. This qualifies this procedure as a palliative surgical technique with potential good risk-benefit ratio. In patients with small focal cortical dysplasias L-RFTC may even allow minimal-invasive surgery with curative intention. Copyright © 2016 Elsevier B.V. All rights reserved.

A goggle navigation system for cancer resection surgery

NASA Astrophysics Data System (ADS)

Xu, Junbin; Shao, Pengfei; Yue, Ting; Zhang, Shiwu; Ding, Houzhu; Wang, Jinkun; Xu, Ronald

2014-02-01

We describe a portable fluorescence goggle navigation system for cancer margin assessment during oncologic surgeries. The system consists of a computer, a head mount display (HMD) device, a near infrared (NIR) CCD camera, a miniature CMOS camera, and a 780 nm laser diode excitation light source. The fluorescence and the background images of the surgical scene are acquired by the CCD camera and the CMOS camera respectively, co-registered, and displayed on the HMD device in real-time. The spatial resolution and the co-registration deviation of the goggle navigation system are evaluated quantitatively. The technical feasibility of the proposed goggle system is tested in an ex vivo tumor model. Our experiments demonstrate the feasibility of using a goggle navigation system for intraoperative margin detection and surgical guidance.

5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement

PubMed Central

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A.; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Background Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. Methods We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. Results A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Conclusions Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift. PMID:24204718

An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models.

PubMed

Metildi, Cristina A; Kaushal, Sharmeela; Lee, Claudia; Hardamon, Chanae R; Snyder, Cynthia S; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

2012-06-01

The aim of this study was to improve fluorescence laparoscopy of pancreatic cancer in an orthotopic mouse model with the use of a light-emitting diode (LED) light source and optimal fluorophore combinations. Human pancreatic cancer models were established with fluorescent FG-RFP, MiaPaca2-GFP, BxPC-3-RFP, and BxPC-3 cancer cells implanted in 6-week-old female athymic mice. Two weeks postimplantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source or a Stryker X8000 xenon light source 24 hours after tail-vein injection of CEA antibodies conjugated with Alexa 488 or Alexa 555. Cancer lesions were detected and localized under each light mode. Intravital images were also obtained with the OV-100 Olympus and Maestro CRI Small Animal Imaging Systems, serving as a positive control. Tumors were collected for histologic analysis. Fluorescence laparoscopy with a 495-nm emission filter and an LED light source enabled real-time visualization of the fluorescence-labeled tumor deposits in the peritoneal cavity. The simultaneous use of different fluorophores (Alexa 488 and Alexa 555), conjugated to antibodies, brightened the fluorescence signal, enhancing detection of submillimeter lesions without compromising background illumination. Adjustments to the LED light source permitted simultaneous detection of tumor lesions of different fluorescent colors and surrounding structures with minimal autofluorescence. Using an LED light source with adjustments to the red, blue, and green wavelengths, it is possible to simultaneously identify tumor metastases expressing fluorescent proteins of different wavelengths, which greatly enhanced the signal without compromising background illumination. Development of this fluorescence laparoscopy technology for clinical use can improve staging and resection of pancreatic cancer. Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement.

PubMed

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Pure laparoscopic hepatectomy with augmented reality-assisted indocyanine green fluorescence versus open hepatectomy for hepatocellular carcinoma with liver cirrhosis: A propensity analysis at a single center.

PubMed

Cheung, Tan To; Ma, Ka Wing; She, Wong Hoi; Dai, Wing Chiu; Tsang, Simon Hing Yin; Chan, Albert Chi Yan; Chok, Kenneth Siu Ho; Lo, Chung Mau

2018-05-10

Laparoscopic hepatectomy is considered an acceptable treatment of choice in selected patients with primary hepatocellular carcinoma (HCC). Whether indocyanine green (ICG) immunofluorescence, a new technology, may improve surgery outcomes has yet to be tested. The aim of the present study was to investigate and compare the effect of ICG fluorescence imaging on the outcomes of pure laparoscopic hepatectomy and open hepatectomy for primary HCC with background cirrhosis. From January 2015 to June 2016, 20 patients with HCC and liver cirrhosis underwent laparoscopic hepatectomy with ICG immunofluorescence. The outcomes of pure laparoscopic hepatectomy with ICG immunofluorescence were compared with those of open hepatectomy. To avoid selection bias, patients were propensity score matched in a ratio of 1 : 6, with 20 patients in the laparoscopic group and 120 in the open group. The laparoscopic group had 20 patients, and the open group had 120 patients. The laparoscopic group had less blood loss (125 vs 450 mL, P < 0.001), a shorter operation time (200 vs 250 min, P = 0.003), and a shorter hospital stay (5 vs 6 days, P < 0.001). The complication rate was 0% in the laparoscopic group compared to 15.0% in the open group (P = 0.135). All patients in the laparoscopic group had negative margin involvement. Four patients (3.3%) in the open resection group had positive margin involvement. Two patients in the ICG immunofluorescence group had additional lesions identified and resected during operation. Pure laparoscopic hepatectomy with ICG immunofluorescence for primary HCC can be carried out safely with favorable short-term outcomes even in cirrhotic patients. Better identification of the bile duct structure and better assessment of the tumor resection margin and perfusion are advantages of this new technique. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

PubMed

Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

2014-04-01

The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

Fluorescence imaging to study cancer burden on lymph nodes

NASA Astrophysics Data System (ADS)

D'Souza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

2015-03-01

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue along with a cancer targeting tracer, Affibody labeled with IRDYE800CW and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

Laparoscopic resection for diverticular disease.

PubMed

Bruce, C J; Coller, J A; Murray, J J; Schoetz, D J; Roberts, P L; Rusin, L C

1996-10-01

The role of laparoscopic surgery in treatment of patients with diverticulitis is unclear. A retrospective comparison of laparoscopic with conventional surgery for patients with chronic diverticulitis was performed to assess morbidity, recovery from surgery, and cost. Records of patients undergoing elective resection for uncomplicated diverticulitis from 1992 to 1994 at a single institution were reviewed. Laparoscopic resection involved complete intracorporeal dissection, bowel division, and anastomosis with extracorporeal placement of an anvil. Sigmoid and left colon resections were performed laparoscopically in 25 patients and by open technique in 17 patients by two independent operating teams. No significant differences existed in age, gender, weight, comorbidities, or operations performed. In the laparoscopic group, three operations were converted to open laparotomy (12 percent) because of unclear anatomy. Major complications occurred in two patients who underwent laparoscopic resection, both requiring laparotomy, and in one patient in the conventional surgery group who underwent computed tomographic-guided drainage of an abscess. Patients who underwent laparoscopic resection tolerated a regular diet sooner than patients who underwent conventional surgery (3.2 +/- 0.9 vs. 5.7 +/- 1.1 days; P < 0.001) and were discharged from the hospital earlier (4.2 +/- 1.1 vs. 6.8 +/- 1.1 days; P < 0.001). Overall costs were higher in the laparoscopic group than the open surgery group ($10,230 +/- 49.1 vs. $7,068 +/- 37.1; P < 0.001) because of a significantly longer total operating room time (397 +/- 9.1 vs. 115 +/- 5.1 min; P < 0.001). Follow-up studies with a mean of one year revealed two port site infections in the laparoscopic group and one wound infection in the open group. Of patients undergoing conventional resection, one patient experienced a postoperative bowel obstruction that was managed nonoperatively, and, in one patient, an incarcerated incisional hernia developed that required urgent laparotomy. Laparoscopic resection in patients with chronic diverticulitis is safe, with faster recovery and shorter hospital stay compared with conventional open surgery. Higher cost of operating room usage time makes the laparoscopic technique difficult to justify economically. Simplification of operating room use and better case selection may improve cost-effectiveness of the laparoscopic approach.

[Determinants of long-term survival in 38 patients with carcinoma of ampulla of Vater treated by local resection].

PubMed

Liu, Ning; Liang, Han; Li, Qiang; Wang, Dian-chang; Zhang, Ru-peng; Wang, Jia-cang; Hao, Xi-shan

2005-10-01

To investigate determinants of long-term survival for carcinoma of ampulla of Vater treated by local resection. The clinical and pathological data of 38 such patients treated by local resection from 1983 to 2003 were retrospectively analyzed. According to UICC staging system, there were T1 30, T2 7 and T3 1. Lymph nodes were involved in 4 during operation which was present in primary lesions larger than 2 cm across. All patients were treated by local resection. At first, external palpation was carried out to ascertain accessibility. Then with the duodenum opened, direct exploration was carried out. On deciding for resection, the common bile duct was probe explored which guided the circumferential ring resection 1 cm, away from the tumor, including all layers of duodenum, ampula and partial bile and terminal pancreatic ducts and the posterial wall of duodenum was completed in steps. Meticulous care was taken not to suture the pancreatic duct and endotheliation was ensured at the mouth of common bile duct and duodenum. The basal tissue was frozen sectioned to ensure negative stumps. The gall bladder of 6 patients was also resected. SPSS 10.0 software was used in data processing, log-rank test used in univariate analysis and Cox equation for multivariate analysis and Kaplan-Meirer method for the survival rates. Thirty-eight patients received local resection giving an operative mortality of 0% and morbidity of 13.2%. The 1-, 5- and 10-year survival rate was 83.5%, 51.4%, and 38.9%, respectively, with a median survival of 3.35 years. Up to now, 13 patients have survived for more than five years and 2 patients beyond ten years. The tumour size, tumour grading, lymph node status and UICC stage were significant prognostic factors in univariate analysis. However, only lymph node status was a statistically independent predictor of prognosis in multivariate analysis. Local excision is safe giving low morbidity and good survival in carefully selected cases. Preferably it is indicated only in high risk patients with a pT1 and well differentiated ampullary cancer smaller than 1 cm in diameter.

Endoscopic ampullectomy: a practical guide

PubMed Central

Bassan, Milan

2012-01-01

Endoscopic ampullectomy is a minimally invasive method of treating superficial lesions of the ampulla of Vater. With careful patient selection and lesion assessment it is a safe and efficacious therapeutic procedure that can obviate the need for potentially major surgical intervention. Strategies for safe and successful endoscopic ampullectomy with a focus on resection technique and recognition and management of complications are presented. PMID:22586547

Overview of FDA approval paths optical surgical navigation

NASA Astrophysics Data System (ADS)

Jacobs, Paula M.

2017-02-01

The development of drugs and devices to guide surgical resection of tumors in the United States requires the approval of the US Food and Drug Administration. Because these combine a drug and a device, the regulatory pathways can be confusing, particularly to academics or small companies. This paper discusses some of the issues and provides some guidance in this area.

A head-mounted display-based personal integrated-image monitoring system for transurethral resection of the prostate.

PubMed

Yoshida, Soichiro; Kihara, Kazunori; Takeshita, Hideki; Fujii, Yasuhisa

2014-12-01

The head-mounted display (HMD) is a new image monitoring system. We developed the Personal Integrated-image Monitoring System (PIM System) using the HMD (HMZ-T2, Sony Corporation, Tokyo, Japan) in combination with video splitters and multiplexers as a surgical guide system for transurethral resection of the prostate (TURP). The imaging information obtained from the cystoscope, the transurethral ultrasonography (TRUS), the video camera attached to the HMD, and the patient's vital signs monitor were split and integrated by the PIM System and a composite image was displayed by the HMD using a four-split screen technique. Wearing the HMD, the lead surgeon and the assistant could simultaneously and continuously monitor the same information displayed by the HMD in an ergonomically efficient posture. Each participant could independently rearrange the images comprising the composite image depending on the engaging step. Two benign prostatic hyperplasia (BPH) patients underwent TURP performed by surgeons guided with this system. In both cases, the TURP procedure was successfully performed, and their postoperative clinical courses had no remarkable unfavorable events. During the procedure, none of the participants experienced any HMD-wear related adverse effects or reported any discomfort.

Five years follow-up of implant-prosthetic rehabilitation on a patient after mandibular ameloblastoma removal and ridge reconstruction by fibula graft and bone distraction

PubMed Central

Oteri, Giacomo; Ponte, Francesco Saverio De; Pisano, Michele; Cicciù, Marco

2012-01-01

This case report presents a combination of surgical and prosthetic solutions applied to a case of oral implant rehabilitation in post-oncologic reconstructed mandible. Bone resection due to surgical treatment of large mandibular neoplasm can cause long-span defects. Currently, mandibular fibula free flap graft is widely considered as a reliable technique for restoring this kind of defect. It restores the continuity of removed segment and re-establishes the contour of the lower jaw. However, the limited height of grafted fibula does not allow the insertion of regular length implants, therefore favouring vertical distraction osteogenesis as an important treatment choice. This report presents a patient affected by extensive mandibular ameloblastoma who underwent surgical reconstruction by fibula free flap because of partial mandibular resection. Guided distraction osteoneogenesis technique was applied to grafted bone, in order to obtain adequate bone height and to realize a prosthetically guided placement of 8 fixtures. After osseointegration, the patient was rehabilitated with a full arch, screw-retained prosthetic restoration. At five-years follow up, excellent integration of grafted tissue, steady levels of bone around the fixtures and healthy peri-implant tissues were reported. PMID:22623943

A user's guide to localization-based super-resolution fluorescence imaging.

PubMed

Dempsey, Graham T

2013-01-01

Advances in far-field fluorescence microscopy over the past decade have led to the development of super-resolution imaging techniques that provide more than an order of magnitude improvement in spatial resolution compared to conventional light microscopy. One such approach, called Stochastic Optical Reconstruction Microscopy (STORM) uses the sequential, nanometer-scale localization of individual fluorophores to reconstruct a high-resolution image of a structure of interest. This is an attractive method for biological investigation at the nanoscale due to its relative simplicity, both conceptually and practically in the laboratory. Like most research tools, however, the devil is in the details. The aim of this chapter is to serve as a guide for applying STORM to the study of biological samples. This chapter will discuss considerations for choosing a photoswitchable fluorescent probe, preparing a sample, selecting hardware for data acquisition, and collecting and analyzing data for image reconstruction. Copyright © 2013 Elsevier Inc. All rights reserved.

An ultrasound-guided fluorescence tomography system: design and specification

NASA Astrophysics Data System (ADS)

D'Souza, Alisha V.; Flynn, Brendan P.; Kanick, Stephen C.; Torosean, Sason; Davis, Scott C.; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

2013-03-01

An ultrasound-guided fluorescence molecular tomography system is under development for in vivo quantification of Protoporphyrin IX (PpIX) during Aminolevulinic Acid - Photodynamic Therapy (ALA-PDT) of Basal Cell Carcinoma. The system is designed to combine fiber-based spectral sampling of PPIX fluorescence emission with co-registered ultrasound images to quantify local fluorophore concentration. A single white light source is used to provide an estimate of the bulk optical properties of tissue. Optical data is obtained by sequential illumination of a 633nm laser source at 4 linear locations with parallel detection at 5 locations interspersed between the sources. Tissue regions from segmented ultrasound images, optical boundary data, white light-informed optical properties and diffusion theory are used to estimate the fluorophore concentration in these regions. Our system and methods allow interrogation of both superficial and deep tissue locations up to PpIX concentrations of 0.025ug/ml.

Can basal cell carcinoma lateral border be determined by fluorescence diagnosis?: Verification by Mohs micrographic surgery.

PubMed

El Hoshy, Khaled; Bosseila, Manal; El Sharkawy, Dina; Sobhi, Rehab

2016-06-01

The preferential accumulation of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in neoplastic cells supports its potential use in the photodetection of epithelial tumours through porphyrin fluorescence. To assess the validity of fluorescence diagnosis (FD) as an efficient pre-surgical in vivo imaging tool for defining the lateral boundaries of various types of basal cell carcinomas (BCCs). The BCC tumour area was determined for 27 patients using FD digitalized imaging system, where the accumulation of PpIX in tumour tissue in relation to normal tissue was measured. Subsequently, BCCs were excised according to the complete area defined by FD using Mohs micrographic surgery (MMS). Of the 27 BCCs, the FD margin of the lesion coincided with the histopathological picture in 12 BCCs (44.44%). The mean value of accumulation factor (AF) was 2.7. Although 17 pigmented BCCs showed attenuated or absent fluorescence in the center, fluorescence at their periphery was used as a guide for excision, and statistically, the pigmentation of the BCCs showed no effect on the results of the FD efficacy (p=1.0). Fluorescence diagnosis of BCC may be beneficial as a guide to the safety margin needed before MMS. The safety margin is decided according to the FD tumour diameter in relation to the clinical tumour diameter. Copyright © 2016 Elsevier B.V. All rights reserved.

Photosensitizer conjugated iron oxide nanoparticles for simultaneous in vitro magneto-fluorescent imaging guided photodynamic therapy.

PubMed

Nafiujjaman, Md; Revuri, Vishnu; Nurunnabi, Md; Cho, Kwang Jae; Lee, Yong-Kyu

2015-04-04

In this study, photosensitizer conjugated iron oxide nanoparticles were strategically designed and prepared for simultaneous PDT and dual-mode fluorescence/MR imaging. The MRI contrast agent Fe3O4 was modified by APTES to functionalize the surface and further to link with heparin-pheophorbide-A conjugates.

Compact instrument for fluorescence image-guided surgery

NASA Astrophysics Data System (ADS)

Wang, Xinghua; Bhaumik, Srabani; Li, Qing; Staudinger, V. Paul; Yazdanfar, Siavash

2010-03-01

Fluorescence image-guided surgery (FIGS) is an emerging technique in oncology, neurology, and cardiology. To adapt intraoperative imaging for various surgical applications, increasingly flexible and compact FIGS instruments are necessary. We present a compact, portable FIGS system and demonstrate its use in cardiovascular mapping in a preclinical model of myocardial ischemia. Our system uses fiber optic delivery of laser diode excitation, custom optics with high collection efficiency, and compact consumer-grade cameras as a low-cost and compact alternative to open surgical FIGS systems. Dramatic size and weight reduction increases flexibility and access, and allows for handheld use or unobtrusive positioning over the surgical field.

Review of fluorescence guided surgery visualization and overlay techniques

PubMed Central

Elliott, Jonathan T.; Dsouza, Alisha V.; Davis, Scott C.; Olson, Jonathan D.; Paulsen, Keith D.; Roberts, David W.; Pogue, Brian W.

2015-01-01

In fluorescence guided surgery, data visualization represents a critical step between signal capture and display needed for clinical decisions informed by that signal. The diversity of methods for displaying surgical images are reviewed, and a particular focus is placed on electronically detected and visualized signals, as required for near-infrared or low concentration tracers. Factors driving the choices such as human perception, the need for rapid decision making in a surgical environment, and biases induced by display choices are outlined. Five practical suggestions are outlined for optimal display orientation, color map, transparency/alpha function, dynamic range compression, and color perception check. PMID:26504628

Novel bright-emission small-molecule NIR-II fluorophores for in vivo tumor imaging and image-guided surgery† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00251c Click here for additional data file.

PubMed Central

Sun, Yao; Ding, Mingmin; Zeng, Xiaodong; Xiao, Yuling; Wu, Huaping; Zhou, Hui; Ding, Bingbing; Qu, Chunrong; Hou, Wei; Er-bu, AGA; Zhang, Yejun; Cheng, Zhen

2017-01-01

Though high brightness and biocompatible small NIR-II dyes are highly desirable in clinical or translational cancer research, their fluorescent cores are relatively limited and their synthetic processes are somewhat complicated. Herein, we have explored the design and synthesis of novel NIR-II fluorescent materials (H1) without tedious chromatographic isolation with improved fluorescence performance (QY ≈ 2%) by introducing 2-amino 9,9-dialkyl-substituted fluorene as a donor into the backbone. Several types of water-soluble and biocompatible NIR-II probes: SXH, SDH, and H1 NPs were constructed via different chemical strategies based on H1, and then their potential to be used in in vivo tumor imaging and image-guided surgery in the NIR-II region was explored. High levels of uptake were obtained for both passive and active tumor targeting probes SXH and SDH. Furthermore, high resolution imaging of blood vessels on tumors and the whole body of living mice using H1 NPs for the first time has demonstrated precise NIR-II image-guided sentinel lymph node (SLN) surgery. PMID:28507722

A Case Report of Salvage Radiotherapy for a Patient with Recurrent Gastric Cancer and Multiple Comorbidities Using Real-time MRI-guided Adaptive Treatment System

PubMed Central

Jeon, Seung Hyuck; Chie, Eui Kyu

2018-01-01

The stomach is one of the most deforming organs caused by respiratory motions and daily variation by food intake. Applying radiotherapy has been quite a challenge due to the high risk of missing the target as well as radiation exposure to large volumes of normal tissue. However, real-time magnetic resonance (MR)-guided radiotherapy with adaptive planning could focus the high dose radiation to the target area while minimizing neighboring normal tissue exposure and compensate for not only daily but real-time variation. Here is a case report of a patient with recurrent gastric cancer and multiple co-morbidities, unsuitable for both resection and chemotherapy, who underwent MR guided adaptive radiotherapy. PMID:29900091

Novel Treatment Planning of Hemimandibular Hyperplasia by the Use of Three-Dimensional Computer-Aided-Design and Computer-Aided-Manufacturing Technologies.

PubMed

Hatamleh, Muhanad M; Yeung, Elizabeth; Osher, Jonas; Huppa, Chrisopher

2017-05-01

Hemimandibular hyperplasia is characterized by an obvious overgrowth in the size of the mandible on one side, which can extend up to the midline causing facial asymmetry. Surgical resection of the overgrowth depends heavily on the skill and experience of the surgeon. This report describes a novel methodology of applying three-dimensional computer-aided-design and computer-aided-manufacturing principles in improving the outcome of surgery in 2 mandibular hyperplasia patients. Both patients had their cone beam computer tomography (CBCT) scan performed. CMF Pro Plan software (v. 2.1) was used to process the scan data into virtual 3-dimensional models of the maxilla and mandible. Head tilt was adjusted manually by following horizontal reference. Facial asymmetry secondary to mandibular hypertrophy was obvious on frontal and lateral views. Simulation functions were followed including mirror imaging of the unaffected mandibular side into the hyperplastic side and position was optimized by translation and orientation functions. Reconstruction of virtual symmetry was assessed and checked by running 3-dimensional measurements. Then, subtraction functions were used to create a 3-dimensional template defining the outline of the lower mandibular osteotomy needed. Precision of mandibular teeth was enhanced by amalgamating the CBCT scan with e-cast scan of the patient lower teeth. 3-Matic software (v. 10.0) was used in designing cutting guide(s) that define the amount of overgrowth to be resected. The top section of the guide was resting on the teeth hence ensuring stability and accuracy while positioning it. The guide design was exported as an .stl file and printed using in-house 3-dimensional printer in biocompatible resin. Three-dimensional technologies of both softwares (CMF Pro Plan and 3-Matic) are accurate and reliable methods in the diagnosis, treatment planning, and designing of cutting guides that optimize surgical correction of hemimandibular hyperplasia at timely and cost-effect manner.

Comparison of pre/post-operative CT image volumes to preoperative digitization of partial hepatectomies: a feasibility study in surgical validation

NASA Astrophysics Data System (ADS)

Dumpuri, Prashanth; Clements, Logan W.; Li, Rui; Waite, Jonathan M.; Stefansic, James D.; Geller, David A.; Miga, Michael I.; Dawant, Benoit M.

2009-02-01

Preoperative planning combined with image-guidance has shown promise towards increasing the accuracy of liver resection procedures. The purpose of this study was to validate one such preoperative planning tool for four patients undergoing hepatic resection. Preoperative computed tomography (CT) images acquired before surgery were used to identify tumor margins and to plan the surgical approach for resection of these tumors. Surgery was then performed with intraoperative digitization data acquire by an FDA approved image-guided liver surgery system (Pathfinder Therapeutics, Inc., Nashville, TN). Within 5-7 days after surgery, post-operative CT image volumes were acquired. Registration of data within a common coordinate reference was achieved and preoperative plans were compared to the postoperative volumes. Semi-quantitative comparisons are presented in this work and preliminary results indicate that significant liver regeneration/hypertrophy in the postoperative CT images may be present post-operatively. This could challenge pre/post operative CT volume change comparisons as a means to evaluate the accuracy of preoperative surgical plans.

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases

PubMed Central

Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

2016-01-01

Background The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). Summary and Key Messages (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response. PMID:27995091

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases.

PubMed

Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

2016-11-01

The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response.

[Modern Management of Pancoast Tumour].

PubMed

Marra, Alessandro

2018-06-01

Pancoast or superior pulmonary sulcus tumour is a subset of lung carcinoma that invades the structures of the thoracic inlet - first ribs, distal roots of the brachial plexus, stellate ganglion, vertebrae, and subclavian vessels. The first symptom is usually shoulder pain; consequently, most patients are initially treated for osteoarthritis. Late diagnosis is common. Success of therapy depends on an accurate staging: standard imaging with CT scan of the chest, PET-CT scan, brain MRI are needed to rule out distant metastases, endobronchial ultrasound-guided needle biopsy (EBUS-TBNA) or mediastinoscopy are mandatory for reliable nodal staging. An MRI of the thoracic inlet allows to clearly define the boundaries of local invasion. Modern management of Pancoast tumour includes induction concurrent chemoradiotherapy followed by surgical resection. As compared with historical series treated by preoperative radiation, a trimodally approach did enhance complete resection rates and perhaps long-term survival - from about 30% 5-year survival rate to 60% in R0-resected patients. In patients who have unresectable but non-metastatic Pancoast tumours and appropriate performance status, definitive concurrent chemoradiotherapy and radiotherapy are recommended options. Georg Thieme Verlag KG Stuttgart · New York.

Magnetically guiding and orienting integrated chemical sensors

NASA Astrophysics Data System (ADS)

Anker, Jeffrey N.; Lee, Yong-Eun Koo; Kopelman, Raoul

2014-08-01

Fluorescent microsensors for detecting pH and oxygen were positioned and oriented using magnetic tweezers. These multifunctional integrated microsensors were fabricated by physically linking together nano-components including magnetic nanoparticles, fluorescent nanoparticles, and metal hemisphere-shells. Two such microsensors are magnetic roll-shaped polystyrene particles with 120 nm fluorescent oxygen-sensing ormosil nanospheres that are physically pressed ("breaded") into the roll surface, and 4-5 µm fluorescent microspheres that are capped with a 50 nm thick metal hemispherical shell. The magnetic tweezers consisted of an iron wire that was magnetized in an external magnetic field. Rotating this external field oriented and rotated the microsensors.

Strategy of Surgical Resection for Glioma Based on Intraoperative Functional Mapping and Monitoring

PubMed Central

TAMURA, Manabu; MURAGAKI, Yoshihiro; SAITO, Taiichi; MARUYAMA, Takashi; NITTA, Masayuki; TSUZUKI, Shunsuke; ISEKI, Hiroshi; OKADA, Yoshikazu

2015-01-01

A growing number of papers have pointed out the relationship between aggressive resection of gliomas and survival prognosis. For maximum resection, the current concept of surgical decision-making is in “information-guided surgery” using multimodal intraoperative information. With this, anatomical information from intraoperative magnetic resonance imaging (MRI) and navigation, functional information from brain mapping and monitoring, and histopathological information must all be taken into account in the new perspective for innovative minimally invasive surgical treatment of glioma. Intraoperative neurofunctional information such as neurophysiological functional monitoring takes the most important part in the process to acquire objective visual data during tumor removal and to integrate these findings as digitized data for intraoperative surgical decision-making. Moreover, the analysis of qualitative data and threshold-setting for quantitative data raise difficult issues in the interpretation and processing of each data type, such as determination of motor evoked potential (MEP) decline, underestimation in tractography, and judgments of patient response for neurofunctional mapping and monitoring during awake craniotomy. Neurofunctional diagnosis of false-positives in these situations may affect the extent of resection, while false-negatives influence intra- and postoperative complication rates. Additionally, even though the various intraoperative visualized data from multiple sources contribute significantly to the reliability of surgical decisions when the information is integrated and provided, it is not uncommon for individual pieces of information to convey opposing suggestions. Such conflicting pieces of information facilitate higher-order decision-making that is dependent on the policies of the facility and the priorities of the patient, as well as the availability of the histopathological characteristics from resected tissue. PMID:26185825

Removing interictal fast ripples on electrocorticography linked with seizure freedom in children.

PubMed

Wu, J Y; Sankar, R; Lerner, J T; Matsumoto, J H; Vinters, H V; Mathern, G W

2010-11-09

Fast ripples (FR, 250-500 Hz) detected with chronic intracranial electrodes are proposed biomarkers of epileptogenesis. This study determined whether resection of FR-containing neocortex recorded during intraoperative electrocorticography (ECoG) was associated with postoperative seizure freedom in pediatric patients with mostly extratemporal lesions. FRs were retrospectively reviewed in 30 consecutive pediatric cases. ECoGs were recorded at 2,000 Hz sampling rate and visually inspected for FR, with reviewer blinded to the resection and outcome. Average age at surgery was 9.1 ± 6.7 years, ECoG duration was 11.8 ± 8.1 minutes, and postoperative follow-up was 27 ± 4 months. FRs were undetected in 6 ECoGs with remote or extensive lesions. FR episodes (n = 273) were identified in ECoGs from 24 patients, and in 64% FRs were independent of spikes, sharp waves, voltage attenuation, and paroxysmal fast activity. Of these 24 children, FR-containing cortex was removed in 19 and all became seizure-free, including 1 child after a second surgery. The remaining 5 children had incomplete FR resection and all continued with seizures postoperatively. In 2 ECoGs, the location of electrographic seizures matched FR location. FR-containing cortex was found outside of MRI and FDG-PET abnormalities in 6 children. FRs were detected during intraoperative ECoG in 80% of pediatric epilepsy cases, and complete resection of FR cortex correlated with postoperative seizure freedom. These findings support the view that interictal FRs are excellent surrogate markers of epileptogenesis, can be recorded during brief ECoG, and could be used to guide future surgical resections in children.

Surgical protocol and outcome for sigmoidovesical fistula secondary to diverticular disease of the left colon: A retrospective cohort study.

PubMed

El-Haddad, Hany M; Kassem, Mohamed I; Sabry, Ahmed A; Abouelfotouh, Ahmed

2018-06-11

Diverticular disease of sigmoid colon can rarely be complicated by a connective track to urinary bladder. Pneumaturia and fecaluria are the pathognomonic symptoms. Resection surgery is the preferred treatment to overcome the renal sequellae of the disease. The purpose of this study is to propose a guiding classification to help general surgeons during surgical management of diverticular disease complicated by sigmoidovesical fistula (SVF). The data of 40 cases with colovesical fistula due to diverticular disease of sigmoid colon were retrospectively analyzed. Clinicopathological variables, imaging reports, types of treatment and patient outcome were evaluated. There were 36 men (90%) and four women (10%) in which the ages ranged from 32 to 79 with a mean of 58.1 years. Pneumaturia was the most common presenting symptom in 38 cases (95%) followed by urinary symptoms in 35 cases (87.5%) then fecaluria in 33 cases (82.5%). 37 patients underwent surgical resection while three patients were in poor general condition to withstand major resection. 16 patients underwent one stage resection and anastomosis, 16 patients were managed by two stage procedure and the remaining 5 patients were treated by three stages operation. Adequately performed CT followed by colonoscopy is the mainstay for diagnosis. Type 1 SVF should be treated in a single stage by complete resection and immediate anastomosis without a stoma. Type 2 cases are best managed in two stages while those with type 3 SVF are emergently managed by three stage procedure. Treatment of type 4 should be individualized. Copyright © 2018. Published by Elsevier Ltd.

Routes for virtually guided endoscopic liver resection of subdiaphragmatic liver tumors.

PubMed

Aoki, Takeshi; Murakami, Masahiko; Fujimori, Akira; Koizumi, Tomotake; Enami, Yuta; Kusano, Tomokazu; Matsuda, Kazuhiro; Yamada, Kosuke; Nogaki, Koji; Wada, Yusuke; Hakozaki, Tomoki; Goto, Satoru; Watanabe, Makoto; Otsuka, Koji

2016-03-01

Laparoscopic and thoracoscopic/laparoscopic hepatectomy is a safe procedure that has potential advantages over open surgery. However, deeply positioned liver tumors require expert laparoscopic and thoracoscopic/laparoscopic hepatectomy techniques. Using simulated preoperative three-dimensional virtual endoscopy (P3DVE) guidance, we demonstrate herein that a thoracoscopic approach (TA), thoracoscopic-laparoscopic approach (TLA), and laparoscopic approach (LA) are all feasible and safe routes for performing pure laparoscopic and thoracoscopic/laparoscopic resection of liver tumors located in the 4a, 7, and 8 liver subdiaphragmatic areas. Thirty-eight patients underwent laparoscopic and thoracoscopic/laparoscopic partial liver resection (TA 13 cases, TLA two cases, and LA 23 cases) of the subdiaphragmatic area at Showa University Hospital. All surgical approaches were preoperatively determined based on preoperative 3D virtual endoscopic simulation (P3DVES) visualization and findings using the image processing software SYNAPSE VINCENT(®). Laparoscopic and thoracoscopic/laparoscopic liver resection was successfully performed for all cases under P3DVE instruction. The mean operative times using TA, TLA, and LA approaches were 193, 185, and 190 min, respectively. Mean blood loss during TA, TLA, and LA was 179, 138, and 73 g, respectively. No patients required conversion to open surgery, and there were no deaths, although there were three cases of Clavien-Dindo grade I in TA along with three cases of grade I and one case of grade II in LA. TA, TLA, and LA routes performed under P3DVE instruction are feasible and safe to perform for pure laparoscopic and thoracoscopic/laparoscopic liver resection in selected patients with lesions located in the hepatic subdiaphragmatic area.

Augmented Reality Guidance for the Resection of Missing Colorectal Liver Metastases: An Initial Experience.

PubMed

Ntourakis, Dimitrios; Memeo, Ricardo; Soler, Luc; Marescaux, Jacques; Mutter, Didier; Pessaux, Patrick

2016-02-01

Modern chemotherapy achieves the shrinking of colorectal cancer liver metastases (CRLM) to such extent that they may disappear from radiological imaging. Disappearing CRLM rarely represents a complete pathological remission and have an important risk of recurrence. Augmented reality (AR) consists in the fusion of real-time patient images with a computer-generated 3D virtual patient model created from pre-operative medical imaging. The aim of this prospective pilot study is to investigate the potential of AR navigation as a tool to help locate and surgically resect missing CRLM. A 3D virtual anatomical model was created from thoracoabdominal CT-scans using customary software (VR RENDER(®), IRCAD). The virtual model was superimposed to the operative field using an Exoscope (VITOM(®), Karl Storz, Tüttlingen, Germany). Virtual and real images were manually registered in real-time using a video mixer, based on external anatomical landmarks with an estimated accuracy of 5 mm. This modality was tested in three patients, with four missing CRLM that had sizes from 12 to 24 mm, undergoing laparotomy after receiving pre-operative oxaliplatin-based chemotherapy. AR display and fine registration was performed within 6 min. AR helped detect all four missing CRLM, and guided their resection. In all cases the planned security margin of 1 cm was clear and resections were confirmed to be R0 by pathology. There was no postoperative major morbidity or mortality. No local recurrence occurred in the follow-up period of 6-22 months. This initial experience suggests that AR may be a helpful navigation tool for the resection of missing CRLM.

Multi-Channel Hyperspectral Fluorescence Detection Excited by Coupled Plasmon-Waveguide Resonance

PubMed Central

Du, Chan; Liu, Le; Zhang, Lin; Guo, Jun; Guo, Jihua; Ma, Hui; He, Yonghong

2013-01-01

We propose in this paper a biosensor scheme based on coupled plasmon-waveguide resonance (CPWR) excited fluorescence spectroscopy. A symmetrical structure that offers higher surface electric field strengths, longer surface propagation lengths and depths is developed to support guided waveguide modes for the efficient excitation of fluorescence. The optimal parameters for the sensor films are theoretically and experimentally investigated, leading to a detection limit of 0.1 nM (for a Cy5 solution). Multiplex analysis possible with the fluorescence detection is further advanced by employing the hyperspectral fluorescence technique to record the full spectra for every pixel on the sample plane. We demonstrate experimentally that highly overlapping fluorescence (Cy5 and Dylight680) can be distinguished and ratios of different emission sources can be determined accurately. This biosensor shows great potential for multiplex detections of fluorescence analytes. PMID:24129023

Indocyanine green detects sentinel lymph nodes in early breast cancer.

PubMed

Liu, Jun; Huang, Linping; Wang, Ning; Chen, Ping

2017-04-01

Objective To explore the clinical value of indocyanine green (ICG) for the fluorescence-guided detection of sentinel lymph nodes (SLNs) during sentinel lymph node biopsy (SLNB) in patients with early breast cancer. Methods This retrospective study included female patients with breast cancer. Patients were administered methylene blue and ICG using standard techniques. All SLNs that were collected during surgery were submitted for pathological examination. SLNs were defined as those that were either fluorescent, blue, fluorescent and blue or palpably suspicious. Surgical complications, axillary recurrence, distant metastasis and overall survival rates were observed postoperatively. Results A total of 60 patients were enrolled in the study. The fluorescence detection rate of SLNs was 100% ( n = 177), with a mean of 2.95 SLNs per patient. The methylene blue staining rate was 88.3% ( n = 106), with a mean of 1.77 SLNs per patient. Pathological assessment of intraoperative frozen specimens revealed SLN metastases in 10 patients, who immediately underwent axillary lymph node dissection. No patient had axillary recurrence or distant metastases, with a survival rate of 100%. Patients who underwent SLNB showed good appearance in the axillary wound, with no limited shoulder joint abduction and upper limb oedema. Conclusion Fluorescence-guided SLNB has several advantages and is suitable for clinical application.

Stereoscopic Integrated Imaging Goggles for Multimodal Intraoperative Image Guidance

PubMed Central

Mela, Christopher A.; Patterson, Carrie; Thompson, William K.; Papay, Francis; Liu, Yang

2015-01-01

We have developed novel stereoscopic wearable multimodal intraoperative imaging and display systems entitled Integrated Imaging Goggles for guiding surgeries. The prototype systems offer real time stereoscopic fluorescence imaging and color reflectance imaging capacity, along with in vivo handheld microscopy and ultrasound imaging. With the Integrated Imaging Goggle, both wide-field fluorescence imaging and in vivo microscopy are provided. The real time ultrasound images can also be presented in the goggle display. Furthermore, real time goggle-to-goggle stereoscopic video sharing is demonstrated, which can greatly facilitate telemedicine. In this paper, the prototype systems are described, characterized and tested in surgeries in biological tissues ex vivo. We have found that the system can detect fluorescent targets with as low as 60 nM indocyanine green and can resolve structures down to 0.25 mm with large FOV stereoscopic imaging. The system has successfully guided simulated cancer surgeries in chicken. The Integrated Imaging Goggle is novel in 4 aspects: it is (a) the first wearable stereoscopic wide-field intraoperative fluorescence imaging and display system, (b) the first wearable system offering both large FOV and microscopic imaging simultaneously, (c) the first wearable system that offers both ultrasound imaging and fluorescence imaging capacities, and (d) the first demonstration of goggle-to-goggle communication to share stereoscopic views for medical guidance. PMID:26529249

Intraoperative photodynamic treatment for high-grade gliomas

NASA Astrophysics Data System (ADS)

Dupont, C.; Reyns, N.; Deleporte, P.; Mordon, S.; Vermandel, M.

2017-02-01

Glioblastoma (GBM) is the most common primary brain tumor. Its incidence is estimated at 5 to 7 new cases each year for 100 000 inhabitants. Despite reference treatment, including surgery, radiation oncology and chemotherapy, GBM still has a very poor prognosis (median survival of 15 months). Because of a systematic relapse of the tumor, the main challenge is to improve local control. In this context, PhotoDynamic Therapy (PDT) may offer a new treatment modality. GBM recurrence mainly occurs inside the surgical cavity borders. Thus, a new light applicator was designed for delivering light during a PDT procedure on surgical cavity borders after Fluorescence Guided Resection. This device combines an inflatable balloon and a light source. Several experimentations (temperature and impermeability tests, homogeneity of the light distribution and ex-vivo studies) were conducted to characterize the device. An abacus was created to determine illumination time from the balloon volume in order to reach a therapeutic fluence value inside the borders of the surgical cavity. According to our experience, cavity volumes usually observed in the neurosurgery department lead to an acceptable average lighting duration, from 20 to 40 minutes. Thus, extra-time needed for PDT remains suitable with anesthesia constraints. A pilot clinical trial is planned to start in 2017 in our institution. In view of the encouraging results observed in preclinical or clinical, this intraoperative PDT treatment can be easily included in the current standard of care.

Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection

PubMed Central

Tummers, Willemieke S.; Warram, Jason M.; Tipirneni, Kiranya E.; Fengler, John; Jacobs, Paula; Shankar, Lalitha; Henderson, Lori; Ballard, Betsy; Pogue, Brian W.; Weichert, Jamey P.; Bouvet, Michael; Sorger, Jonathan; Contag, Christopher H.; Frangioni, John V.; Tweedle, Michael F.; Basilion, James P.; Gambhir, Sanjiv S.; Rosenthal, Eben L.

2017-01-01

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting. PMID:28428283

Feasibility of Raman spectroscopy in vitro after 5-ALA-based fluorescence diagnosis in the bladder

NASA Astrophysics Data System (ADS)

Grimbergen, M. C. M.; van Swol, C. F. P.; van Moorselaar, R. J. A.; Mahadevan-Jansen, A.,; Stone, N.

2006-02-01

Photodynamic diagnosis (PDD) has become popular in bladder cancer detection. Several studies have however shown an increased false positive biopsies rate under PDD guidance compared to conventional cystoscopy. Raman spectroscopy is an optical technique that utilizes molecular specific, inelastic scattering of light photons to interrogate biological tissues, which can successfully differentiate epithelial neoplasia from normal tissue and inflammations in vitro. This investigation was performed to show the feasibility of NIR Raman spectroscopy in vitro on biopsies obtained under guidance of 5-ALA induced PPIX fluorescence imaging. Raman spectra of a PPIX solution was measured to obtain a characteristic signature for the photosensitzer without contributions from tissue constituents. Biopsies were obtained from patients with known bladder cancer instilled with 50ml, 5mg 5-ALA two hours prior to trans-urethral resection of tumor (TURT). Additional biopsies were obtained at a fluorescent and non-fluorescent area, snap-frozen in liquid nitrogen and stored at -80 °C. Each biopsy was thawed before measurements (10sec integration time) with a confocal Raman system (Renishaw Gloucestershire, UK). The 830 nm excitation (300mW) source is focused on the tissue by a 20X ultra-long-working-distance objective. Differences in fluorescence background between the two groups were removed by means of a special developed fluorescence subtraction algorithm. Raman spectra from ALA biopsies showed different fluorescence background which can be effectively removed by a fluorescence subtraction algorithm. This investigation shows that the interaction of the ALA induced PPIX with Raman spectroscopy in bladder samples. Combination of these techniques in-vivo may lead to a viable method of optical biopsies in bladder cancer detection.

Intraoperative Detection of Superficial Liver Tumors by Fluorescence Imaging Using Indocyanine Green and 5-aminolevulinic Acid.

PubMed

Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Iida, Hiroya; Okumura, Tadayoshi; Sakaguchi, Tatsuma; Inoue, Kentaro; Ikeura, Tsukasa; Asano, Hiroaki; Kon, Masanori

2016-04-01

Indocyanine green (ICG) and the porphyrin precursor 5-aminolevulinic acid (5-ALA) have been approved as fluorescence imaging agents in the clinical setting. This study evaluated the usefulness of fluorescence imaging with both ICG and 5-ALA for intraoperative identification of latent small liver tumors. There were 48 patients who had main tumors within 5 mm of the liver surface. 5-ALA hydrochloride was orally administered to patients 3 h before surgery. ICG had been intravenously injected within 14 days prior to surgery. Intraoperatively, after visual inspection, manual palpation and ultrasonography fluorescence images of the liver surface were obtained with ICG and 5-ALA prior to resection. With ICG, the sensitivity, specificity and accuracy for detecting the preoperatively identified main tumors were 96%, 50% and 94%, respectively. Twelve latent small tumors were newly detected on the liver surface using ICG, five of which proved to be carcinomas. With 5-ALA, the sensitivity, specificity and accuracy for detecting the main tumors were 57%, 100% and 58%, respectively. Five latent small tumors were newly detected using 5-ALA; all were carcinomas. Overall, five new tumors were detected by both ICG and 5-ALA fluorescence imaging; two were hepatocellular carcinomas (HCCs) and three were metastases of colorectal cancer. The sensitivity and specificity of ICG fluorescence imaging for main tumor detection were relatively high and low, respectively, but the opposite was true of 5-ALA imaging. Fluorescence imaging using 5-ALA may provide greater specificity in the detection of surface-invisible malignant liver tumors than using ICG fluorescence imaging alone. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Electron Microscopy of Living Cells During in Situ Fluorescence Microscopy

PubMed Central

Liv, Nalan; van Oosten Slingeland, Daan S. B.; Baudoin, Jean-Pierre; Kruit, Pieter; Piston, David W.; Hoogenboom, Jacob P.

2016-01-01

We present an approach toward dynamic nanoimaging: live fluorescence of cells encapsulated in a bionanoreactor is complemented with in situ scanning electron microscopy (SEM) on an integrated microscope. This allows us to take SEM snapshots on-demand, that is, at a specific location in time, at a desired region of interest, guided by the dynamic fluorescence imaging. We show that this approach enables direct visualization, with EM resolution, of the distribution of bioconjugated quantum dots on cellular extensions during uptake and internalization. PMID:26580231

Measuring Norfloxacin Binding to Trypsin Using a Fluorescence Quenching Assay in an Upper-Division, Integrated Laboratory Course

ERIC Educational Resources Information Center

Hicks, Katherine A.

2016-01-01

Fluorescence quenching assays are often used to measure dissociation constants that quantify the binding affinity between small molecules and proteins. In an upper-division undergraduate laboratory course, where students work on projects using a guided inquiry-based approach, a binding titration experiment at physiological pH is performed to…

Understanding Fluorescence Measurements through a Guided-Inquiry and Discovery Experiment in Advanced Analytical Laboratory

ERIC Educational Resources Information Center

Wilczek-Vera, Grazyna; Salin, Eric Dunbar

2011-01-01

An experiment on fluorescence spectroscopy suitable for an advanced analytical laboratory is presented. Its conceptual development used a combination of the expository and discovery styles. The "learn-as-you-go" and direct "hands-on" methodology applied ensures an active role for a student in the process of visualization and discovery of concepts.…

Near infrared fluorescence for image-guided surgery

PubMed Central

2012-01-01

Near infrared (NIR) image-guided surgery holds great promise for improved surgical outcomes. A number of NIR image-guided surgical systems are currently in preclinical and clinical development with a few approved for limited clinical use. In order to wield the full power of NIR image-guided surgery, clinically available tissue and disease specific NIR fluorophores with high signal to background ratio are necessary. In the current review, the status of NIR image-guided surgery is discussed along with the desired chemical and biological properties of NIR fluorophores. Lastly, tissue and disease targeting strategies for NIR fluorophores are reviewed. PMID:23256079

Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillams, Alice, E-mail: alliesorting@gmail.com; Khan, Zahid; Osborn, Peter

2013-06-15

Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, andmore » factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.« less

Radioactive Seed Localization or Wire-guided Localization of Nonpalpable Invasive and In Situ Breast Cancer: A Randomized, Multicenter, Open-label Trial.

PubMed

Langhans, Linnea; Tvedskov, Tove F; Klausen, Thomas L; Jensen, Maj-Britt; Talman, Maj-Lis; Vejborg, Ilse; Benian, Cemil; Roslind, Anne; Hermansen, Jonas; Oturai, Peter S; Bentzon, Niels; Kroman, Niels

2017-07-01

To compare the rate of positive resection margins between radioactive seed localization (RSL) and wire-guided localization (WGL) after breast conserving surgery (BCS). WGL is the current standard for localization of nonpalpable breast lesions in BCS, but there are several difficulties related to the method. From January 1, 2014 to February 4, 2016, patients with nonpalpable invasive breast cancer or DCIS visible on ultrasound were enrolled in this randomized, multicenter, open-label clinical trial, and randomly assigned to RSL or WGL. The primary outcome was margin status after BCS. Secondary outcomes were duration of the surgical procedure, weight of surgical specimen, and patients' pain perception. Analyses were performed by intention-to-treat (ITT) and per protocol. Out of 444 eligible patients, 413 lesions representing 409 patients were randomized; 207 to RSL and 206 to WGL. Twenty-three did not meet inclusion criteria, chose to withdraw, or had a change in surgical management and were excluded. The remaining 390 lesions constituted the ITT population. Here, resection margins were positive in 23 cases (11.8%) in the RSL group compared with 26 cases (13.3%) in the WGL group (P = 0.65). The per-protocol analysis revealed no difference in margin status (P = 0.62). There were no significant differences in the duration of the surgical procedure (P = 0.12), weight of the surgical specimen (P = 0.54) or the patients' pain perception (P = 0.28). RSL offers a major logistic advantage, as localization can be done several days before surgery without any increase in positive resection margins compared with WGL.

A global goodness-of-fit test for receiver operating characteristic curve analysis via the bootstrap method.

PubMed

Zou, Kelly H; Resnic, Frederic S; Talos, Ion-Florin; Goldberg-Zimring, Daniel; Bhagwat, Jui G; Haker, Steven J; Kikinis, Ron; Jolesz, Ferenc A; Ohno-Machado, Lucila

2005-10-01

Medical classification accuracy studies often yield continuous data based on predictive models for treatment outcomes. A popular method for evaluating the performance of diagnostic tests is the receiver operating characteristic (ROC) curve analysis. The main objective was to develop a global statistical hypothesis test for assessing the goodness-of-fit (GOF) for parametric ROC curves via the bootstrap. A simple log (or logit) and a more flexible Box-Cox normality transformations were applied to untransformed or transformed data from two clinical studies to predict complications following percutaneous coronary interventions (PCIs) and for image-guided neurosurgical resection results predicted by tumor volume, respectively. We compared a non-parametric with a parametric binormal estimate of the underlying ROC curve. To construct such a GOF test, we used the non-parametric and parametric areas under the curve (AUCs) as the metrics, with a resulting p value reported. In the interventional cardiology example, logit and Box-Cox transformations of the predictive probabilities led to satisfactory AUCs (AUC=0.888; p=0.78, and AUC=0.888; p=0.73, respectively), while in the brain tumor resection example, log and Box-Cox transformations of the tumor size also led to satisfactory AUCs (AUC=0.898; p=0.61, and AUC=0.899; p=0.42, respectively). In contrast, significant departures from GOF were observed without applying any transformation prior to assuming a binormal model (AUC=0.766; p=0.004, and AUC=0.831; p=0.03), respectively. In both studies the p values suggested that transformations were important to consider before applying any binormal model to estimate the AUC. Our analyses also demonstrated and confirmed the predictive values of different classifiers for determining the interventional complications following PCIs and resection outcomes in image-guided neurosurgery.

Image-guided, intensity-modulated radiation therapy (IG-IMRT) for skull base chordoma and chondrosarcoma: preliminary outcomes.

PubMed

Sahgal, Arjun; Chan, Michael W; Atenafu, Eshetu G; Masson-Cote, Laurence; Bahl, Gaurav; Yu, Eugene; Millar, Barbara-Ann; Chung, Caroline; Catton, Charles; O'Sullivan, Brian; Irish, Jonathan C; Gilbert, Ralph; Zadeh, Gelareh; Cusimano, Michael; Gentili, Fred; Laperriere, Normand J

2015-06-01

We report our preliminary outcomes following high-dose image-guided intensity modulated radiotherapy (IG-IMRT) for skull base chordoma and chondrosarcoma. Forty-two consecutive IG-IMRT patients, with either skull base chordoma (n = 24) or chondrosarcoma (n = 18) treated between August 2001 and December 2012 were reviewed. The median follow-up was 36 months (range, 3-90 mo) in the chordoma cohort, and 67 months (range, 15-125) in the chondrosarcoma cohort. Initial surgery included biopsy (7% of patients), subtotal resection (57% of patients), and gross total resection (36% of patients). The median IG-IMRT total doses in the chondrosarcoma and chordoma cohorts were 70 Gy and 76 Gy, respectively, delivered with 2 Gy/fraction. For the chordoma and chondrosarcoma cohorts, the 5-year overall survival and local control rates were 85.6% and 65.3%, and 87.8% and 88.1%, respectively. In total, 10 patients progressed locally: 8 were chordoma patients and 2 chondrosarcoma patients. Both chondrosarcoma failures were in higher-grade tumors (grades 2 and 3). None of the 8 patients with grade 1 chondrosarcoma failed, with a median follow-up of 77 months (range, 34-125). There were 8 radiation-induced late effects-the most significant was a radiation-induced secondary malignancy occurring 6.7 years following IG-IMRT. Gross total resection and age were predictors of local control in the chordoma and chondrosarcoma patients, respectively. We report favorable survival, local control and adverse event rates following high dose IG-IMRT. Further follow-up is needed to confirm long-term efficacy. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins

PubMed Central

Mueller, Jenna L.; Fu, Henry L.; Mito, Jeffrey K.; Whitley, Melodi J.; Chitalia, Rhea; Erkanli, Alaattin; Dodd, Leslie; Cardona, Diana M.; Geradts, Joseph; Willett, Rebecca M.; Kirsch, David G.; Ramanujam, Nimmi

2015-01-01

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence. PMID:25994353

Nanotechnology Cancer Therapy and Treatment

Cancer.gov

Nanotechnology offers the means to target therapies directly and selectively to cancerous cells and neoplasms. With these tools, clinicians can safely and effectively deliver chemotherapy, radiotherapy, and the next generation of immuno- and gene therapies to the tumor. Futhermore, surgical resection of tumors can be guided and enhanced by way of nanotechnology tools. Find out how nanotechnology will offer the next generation of our therapeutic arsenal to the patient.

The analgesic efficacy of subcostal transversus abdominis plane block with Mercedes incision.

PubMed

Guo, Jian-Guo; Li, Hui-Ling; Pei, Qing-Qing; Feng, Zhi-Ying

2018-04-10

Conventional perioperative analgesic modalities (e.g. opioids, epidural analgesia) have their own drawbacks, which limit their clinical application. This study investigated the opioid-sparing effectsof the oblique subcostal transversus abdominis plane (OSTAP) blockade with ropivacaine for the patients undergoing open liver resection with a Mercedes incision. 126 patients who were scheduled for open liver resection were enrolled in this study. Patients were randomly assigned to receive bilateral ultrasound-guided OSTAPblocks with either 0.375% ropivacaine (groupT) or 0.9% isotonic saline (group C). Both groups also received intravenous patient-controlled analgesia and intravenous 40 mg parecoxib every 12 h for a total of 3 days. Preoperative and intraoperative parameters, plus intraoperative and postoperative cumulative sufentanil consumption, were recorded. 70 patients were enrolled in the study finally. There were no significant differences between the two groups with respect to preoperative parameters, and surgical and anesthetic characteristics. The intraoperative sufentanil use, cumulative sufentanil consumption at 5 min after extubation, 2 h, 4 h,12 h and 24 h after operation in group T was significantly less than that in group C (P = 0.001, 0.001, 0.000, 0.000, 0.001 and 0.044, respectively). Compared with group C, postoperative NRS pain scores at rest were significantly lower at 2 h and 4 h postoperatively in group T (P = 0.04and 0.02, respectively); NRS scores at the time of coughing were also significantly lower in group T than in group C at all time points except 5 min after extubation (all P < 0.001). Furthermore, compared with group C, the number of intraoperative vasodilator use, the extubation time and the incidence of nausea was reduced in group T. Ultrasound-guided OSTAP block with ropivacaine can significantly decrease the perioperative cumulative dosage of analgesics and improve analgesic effect without obvious side effects for the patients who underwent an open liver resection with Mercedes incision when compared tothe ultrasound-guided OSTAP block with saline. The study protocol was registered at http://www.chictr.org.cn (ChiCTR-TRC- 14004827) on February 19, 2014.

Frey procedure for the treatment of chronic pancreatitis associated with common bile duct stricture.

PubMed

Rebibo, Lionel; Yzet, Thierry; Cosse, Cyril; Delcenserie, Richard; Bartoli, Eric; Regimbeau, Jean-Marc

2013-12-01

The Frey procedure (FP) is the treatment of choice for symptomatic chronic pancreatitis (CP). In cases of biliary stricture, biliary derivation can be performed by choledochoduodenostomy, Roux-en-Y choledochojejunostomy or, more recently, reinsertion of the common bile duct (CBD) into the resection cavity. The objective of the present study was to evaluate the outcomes associated with each of these three types of biliary derivation. We retrospectively analyzed demographic, CP-related, surgical and follow-up data for patients having undergone FP for CP with biliary derivation between 2004 and 2012 in our university medical center. The primary efficacy endpoint was the rate of CBD stricture recurrence. The secondary endpoints were surgical parameters, postoperative complications, postoperative follow-up and the presence of risk factors for secondary CBD stricture. Eighty patients underwent surgery for CP during the study period. Of these, 15 patients received biliary derivation with the FP. Eight of the FPs (53.3%) were combined with choledochoduodenostomy, 4 (26.7%) with choledochojejunostomy and 3 (20.0%) with reinsertion of the CBD into the resection cavity. The mean operating time was 390 minutes. Eleven complications (73.3%) were recorded, including one major complication (6.7%) that necessitated radiologically-guided drainage of an abdominal collection. The mean (range) length of stay was 17 days (8-28) and the median (range) follow-up time was 35.2 months (7.2-95.4). Two patients presented stricture after CBD reinsertion into the resection cavity; one was treated with radiologically-guided dilatation and the other underwent revisional Roux-en-Y choledochojejunostomy. Three patients presented alkaline reflux gastritis (37.5%), one (12.5%) cholangitis and one CBD stricture after FP with choledochoduodenostomy. No risk factors for secondary CBD stricture were identified. As part of a biliary derivation, the FP gave good results. We did not observe any complications specifically related to surgical treatment of the biliary tract. However, CBD reinsertion into the resection cavity appeared to be associated with a higher stricture recurrence rate. In our experience, choledochojejunostomy remains the "gold standard" for the surgical treatment for CBD strictures.

Qualitative and quantitative comparison of colonic microendoscopy image features to histopathology

NASA Astrophysics Data System (ADS)

Prieto, Sandra P.; Powless, Amy J.; Lai, Keith; Laryea, Jonathan A.; Mizell, Jason S.; Muldoon, Timothy J.

2015-03-01

Colorectal cancer is the second leading cause of cancer deaths in the United States, affecting more than 130,000 Americans every year1. Determining tumor margins prior to surgical resection is essential to providing optimal treatment and reducing recurrence rates. Colorectal cancer recurrence can occur in up to 20% of cases, commonly within three years after curative treatment. Typically, when colorectal cancers are resected, a margin of normal tissue on both sides of the tumor is required. The minimum margin required for colon cancer is 5 cm and for the lower rectum 2 cm. However, usually more normal tissue is taken on both sides of the tumor because the blood supply to the entire segment is removed with the surgery and therefore the entire segment must be removed. Anastomotic recurrences may result from inadequate margins. Pathologists look at the margins to ensure that there is no residual tumor and this is usually documented in the pathology report. We have developed a portable, point-of-care fiber bundle microendoscopy imaging system for detection of abnormalities in colonic epithelial microstructure. The system comprises a laptop, a modified fiber bundle image guide with a 1mm active area diameter and custom LabVIEW interface, and is approved for imaging surgically resected colon tissue at the University of Arkansas for Medical Sciences. The microendoscopy probe provides high-resolution images of superficial epithelial histology in real-time to assist surgical guidance and to localize occult regions of dysplasia which may not be visible. Microendoscopy images of freshly resected human colonic epithelium were acquired using the microendoscopy device and subsequently mosaicked using custom post-processing software. Architectural changes in the glands were mapped to histopathology H&E slides taken from the precise location of the microendoscopy images. Qualitatively, glandular distortion and placement of image guide was used to map normal and dysplastic areas of the colonic tumor and surrounding region from microendoscopy images to H&E slides. Quantitative metrics for correlating images were also explored and were obtained by analyzing glandular diameter and spatial distribution as well as image texture.

Preclinical validation of the utility of BLZ-100 in providing fluorescence contrast for imaging canine spontaneous solid tumors

PubMed Central

Fidel, Janean; Kennedy, Katie C.; Dernell, William S.; Hansen, Stacey; Wiss, Valorie; Stroud, Mark R.; Molho, Joshua I.; Knoblaugh, Sue E.; Meganck, Jeffrey; Olson, James M.; Rice, Brad; Parrish-Novak, Julia

2015-01-01

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint™ agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need. PMID:26471914

Detection of human brain tumor infiltration with multimodal multiscale optical analysis

NASA Astrophysics Data System (ADS)

Poulon, Fanny; Metais, Camille; Jamme, Frederic; Zanello, Marc; Varlet, Pascale; Devaux, Bertrand; Refregiers, Matthieu; Abi Haidar, Darine

2017-02-01

Brain tumor surgeries are facing major challenges to improve patients' quality of life. The extent of resection while preserving surrounding eloquent brain areas is necessary to equilibrate the onco-functional. A tool able to increase the accuracy of tissue analysis and to deliver an immediate diagnostic on tumor, could drastically improve actual surgeries and patient survival rates. To achieve such performances a complete optical study, ranging from ultraviolet to infrared, of biopsies has been started by our group. Four different contrasts were used: 1) spectral analysis covering the DUV to IR range, 2) two photon fluorescence lifetime imaging and one photon time domain measurement, 3) second harmonic generation imaging and 4) fluorescence imaging using DUV to IR, one and two photon excitation. All these measurements were done on the endogenous fluorescence of tissues to avoid any bias and further clinical complication due to the introduction of external markers. The different modalities are then crossed to build a matrix of criteria to discriminate tumorous tissues. The results of multimodal optical analysis on human biopsies were compared to the gold standard histopathology.

In vivo optical characterization of pediatric epileptogenic lesions

NASA Astrophysics Data System (ADS)

Lin, W.-C.; Ragheb, J.; Bhatia, S.; Johnson, Mahlon D.; Sandberg, D.; Fernandez, A.; Morrison, G.; Duchowny, M.; Jayakar, P.

2007-02-01

Epileptogenic lesions and their margins are often difficult to define intraoperatively. We hypothesize that optical spectroscopy can detect unique pathophysiological features of epileptogenic lesions in children and hence differentiate them from normal brain. This hypothesis was tested by comparing the in vivo optical and fluorescence characteristics of epileptogenic brain lesions (non-neoplastic) with those of normal brain. Patients were recruited from those receiving epilepsy surgeries at Miami Children's Hospital. Using a portable spectroscopic system, optical characterization of brain was performed intraoperatively. Fluorescence spectra were measured at 337 nm excitation, and diffuse reflectance spectra were measured between 400 and 850 nm. To date, seven epilepsy patients have been enrolled in the study. A couple interesting trends have been observed in the recorded optical spectra. First, sites within the resection zone, as defined by the intracranial electroencephalogram data, often show higher diffuse reflectance signals than normal sites do. This is especially prominent around 500 nm and between 650 and 850 nm. Secondly, several investigated sites with abnormal electroencephalogram and/or pathology show a unique blue shift in their fluorescence spectra, which is not seen in other cases.

A dual-labeled knottin peptide for PET and near-infrared fluorescence imaging of integrin expression in living subjects

PubMed Central

Kimura, Richard H.; Miao, Zheng; Cheng, Zhen; Gambhir, Sanjiv S.; Cochran, Jennifer R.

2010-01-01

Previously, we used directed evolution to engineer mutants of the Ecballium elaterium trypsin inhibitor (EETI-II) knottin that bind to αvβ3 and αvβ5 integrin receptors with low nanomolar affinity, and showed that Cy5.5- or 64Cu-DOTA-labeled knottin peptides could be used to image integrin expression in mouse tumor models using near-infrared fluorescence (NIRF) imaging or positron emission tomography (PET). Here, we report the development of a dual-labeled knottin peptide conjugated to both NIRF and PET imaging agents for multimodality imaging in living subjects. We created an orthogonally-protected peptide-based linker for stoichiometric coupling of 64Cu-DOTA and Cy5.5 onto the knottin N-terminus, and confirmed that conjugation did not affect binding to αvβ3 and αvβ5 integrins. NIRF and PET imaging studies in tumor xenograft models showed that Cy5.5 conjugation significantly increased kidney uptake and retention compared to the knottin peptide labeled with 64Cu-DOTA alone. In the tumor, the dual-labeled 64Cu-DOTA/Cy5.5 knottin probe showed decreased wash-out leading to significantly better retention (p < 0.05) compared to the 64Cu-DOTA-labeled knottin probe. Tumor uptake was significantly reduced (p < 0.05) when the dual-labeled probe was co-injected with an excess of unlabeled competitor and when tested in a tumor model with lower levels of integrin expression. Finally, plots of tumor-to-background tissue ratios for Cy5.5 versus 64Cu uptake were well correlated over several time points post injection, demonstrating pharmacokinetic cross validation of imaging labels. This dual-modality NIRF/PET imaging agent is promising for further development in clinical applications where high sensitivity and high-resolution are desired, such as detection of tumors located deep within the body and image-guided surgical resection. PMID:20131753

Calibrating the photo-thermal response of magneto-fluorescent gold nanoshells.

PubMed

Biswal, Nrusingh C; Ayala-Orzoco, Ciceron; Halas, Naomi J; Joshi, Amit

2011-01-01

We report the photothermal response and Near Infrared (NIR) imaging sensitivities of magneto-fluorescent silica core gold nanocomplexes designed for molecular image guided thermal therapy of cancer. Approximately 160 nm Silica core gold nanoshells were designed to provide NIR fluorescent and Magnetic Resonance (MR) contrast by incorporating FDA approved dye indocyanine green (ICG) and iron-oxide within an outer silica epilayer. The imaging and therapeutic sensitivity, and the stability of fluorescence contrast for 12 microliters of suspension (containing approximately 7.9 × 10(8) or 1.3 femtoMole nanoshells) buried at depths of 2-8 mm in tissue mimicking scattering media is reported.

Fluorescent-protein-based probes: general principles and practices.

PubMed

Ai, Hui-Wang

2015-01-01

An important application of fluorescent proteins is to derive genetically encoded fluorescent probes that can actively respond to cellular dynamics such as pH change, redox signaling, calcium oscillation, enzyme activities, and membrane potential. Despite the large diverse group of fluorescent-protein-based probes, a few basic principles have been established and are shared by most of these probes. In this article, the focus is on these general principles and strategies that guide the development of fluorescent-protein-based probes. A few examples are provided in each category to illustrate the corresponding principles. Since these principles are quite straightforward, others may adapt them to create fluorescent probes for their own interest. Hopefully, the development of the ever-growing family of fluorescent-protein-based probes will no longer be limited to a small number of laboratories specialized in senor development, leading to the situation that biological studies will be bettered assisted by genetically encoded sensors.

Comparison of calibration and standardization approaches for fluorescence guided imaging systems to benchtop fluorescence measurements in cellular systems

NASA Astrophysics Data System (ADS)

Litorja, Maritoni; DeRose, Paul

2018-02-01

Fluorescence measurements are a staple in biomedicine, from research and discovery to more recently, for fluorescenceguided imaging systems for diagnostics and surgery. Measurement validation for clinical imagers is a challenge as it is applied to many different optical systems and probe through matrices with different optical properties in a demanding field environment. In this paper we will present approaches to fluorescence calibration for a field system, in comparison to those used in laboratory instruments for cell measurements or benchtop fluorometers. We will present the common challenges and differences, and lessons from the standardization effort of laboratory fluorescence measurements. We will discuss the conceptually different pathways to measurement traceability, between counting moles of substance and measuring light.

Fluorescence-guided surgery and intervention - An AAPM emerging technology blue paper.

PubMed

Pogue, Brian W; Zhu, Timothy C; Ntziachristos, Vasilis; Paulsen, Keith D; Wilson, Brian C; Pfefer, Joshua; Nordstrom, Robert J; Litorja, Maritoni; Wabnitz, Heidrun; Chen, Yu; Gioux, Sylvain; Tromberg, Bruce J; Yodh, Arjun G

2018-04-10

Fluorescence-guided surgery (FGS) and other interventions are rapidly evolving as a class of technologically driven interventional approaches in which many surgical specialties visualize fluorescent molecular tracers or biomarkers through associated cameras or oculars to guide clinical decisions on pathological lesion detection and excision/ablation. The technology has been commercialized for some specific applications, but also presents technical challenges unique to optical imaging that could confound the utility of some interventional procedures where real-time decisions must be made. Accordingly, the AAPM has initiated the publication of this Blue Paper of The Emerging Technology Working Group (TETAWG) and the creation of a Task Group from the Therapy Physics Committee within the Treatment Delivery Subcommittee. In describing the relevant issues, this document outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS technology and its applications. The presentation is not intended to be conclusive, but rather to inform the field of medical physics and stimulate the discussions needed in the field with respect to a seemingly low-risk imaging technology that has high potential for significant therapeutic impact. This AAPM Task Group is working toward consensus around guidelines and standards for advancing the field safely and effectively. © 2018 American Association of Physicists in Medicine.

Benign Tumors of the Pancreas-Radical Surgery Versus Parenchyma-Sparing Local Resection-the Challenge Facing Surgeons.

PubMed

Beger, Hans G

2018-03-01

Pancreaticoduodenectomy and left-sided pancreatectomy are the surgical treatment standards for tumors of the pancreas. Surgeons, who are requested to treat patients with benign tumors, using standard oncological resections, face the challenge of sacrificing pancreatic and extra-pancreatic tissue. Tumor enucleation, pancreatic middle segment resection and local, duodenum-preserving pancreatic head resections are surgical procedures increasingly used as alternative treatment modalities compared to classical pancreatic resections. Use of local resection procedures for cystic neoplasms and neuro-endocrine tumors of the pancreas (panNETs) is associated with an improvement of procedure-related morbidity, when compared to classical Whipple OP (PD) and left-sided pancreatectomy (LP). The procedure-related advantages are a 90-day mortality below 1% and a low level of POPF B+C rates. Most importantly, the long-term benefits of the use of local surgical procedures are the preservation of the endocrine and exocrine pancreatic functions. PD performed for benign tumors on preoperative normo-glycemic patients is followed by the postoperative development of new onset of diabetes mellitus (NODM) in 4 to 24% of patients, measured by fasting blood glucose and/or oral/intravenous glucose tolerance test, according to the criteria of the international consensus guidelines. Persistence of new diabetes mellitus during the long-term follow-up after PD for benign tumors is observed in 14.5% of cases and after surgery for malignant tumors in 15.5%. Pancreatic exocrine insufficiency after PD is found in the long-term follow-up for benign tumors in 25% and for malignant tumors in 49%. Following LP, 14-31% of patients experience postoperatively NODM; many of the patients subsequently change to insulin-dependent diabetes mellitus (IDDM). The decision-making for cystic neoplasms and panNETs of the pancreas should be guided by the low surgical risk and the preservation of pancreatic metabolic functions when undergoing a limited, local, tissue-sparing procedure.

Liver Resections in a High-Volume Center: Form Standard Procedures to Extreme Surgery and Ultrasound-guided Resections.

PubMed

Botea, Florin; Ionescu, Mihnea; Braşoveanu, Vladislav; Hrehoreţ, Doina; Alexandrescu, Sorin; Grigorie, Mihai; Stanciulea, Oana; Nicolaescu, Diana; Tomescu, Dana; Droc, Gabriela; Ungureanu, Daniela; Fota, Ruxandra; Croitoru, Adina; Gheorghe, Liana; Gheorghe, Cristian; Lupescu, Ioana; Grasu, Mugur; Boroş, Mirela; Dumitru, Radu; Toma, Mihai; Herlea, Vlad; Popescu, Irinel

2017-01-01

Background: Liver resection (LR) is the treatment of choice for most benign and malignant focal liver lesions, as well as in selected patients with liver trauma. Few other therapies can compete with LR in selected cases, such as liver transplantation in hepatocellular carcinoma (HCC) and ablative therapies in small HCCs or liver metastases. The present paper analyses a single center experience in LR, reviewing the indications of LR, the operative techniques and their short-term results. Between January 2000 and December 2016, in "œDan Setlacec" Center of General Surgery and Liver Transplantation were performed 3165 LRs in 3016 patients, for pathologic conditions of the liver. In the present series, liver resections for living-donor liver transplantation were excluded. The median age of the patients was 56 years (mean 58 years; range 1-88), with male/female ratio 1524/1492 and adult/pediatric patient ratio 2973/43. Results: Malignant lesions were the main indication for LR (2372 LRs; 74.9%). Among these, colorectal liver metastases were the most frequent indication (952 LRs; 30.1%), followed by hepatocellular carcinoma (575 patients, 18.2%). The highest number of resected tumors per patient was 21, and the median diameter of the largest tumor was 40 mm (mean 51 mm; range 3-250). Major resections rate was 18.6% (588 LRs) and anatomical LRs were performed in 789 patients (24.9%). The median operative time was 180 minutes (mean 204 minutes; range 45-920). The median blood loss was 500 ml (mean 850 ml; range 500-9500), with a transfusion rate of 41.6% (1316 LRs). The morbidity rate was 40.1% (1270 LRs) and the rate of major complications (Dindo-Clavien IIIa or more) was 13.2% (418 LRs). Mortality rate was 4.2% (127 pts). LRs should be performed in specialized high-volume centers to achieve the best results (low morbidity and mortality rates). Celsius.

Design and validation of a near-infrared fluorescence endoscope for detection of early esophageal malignancy

NASA Astrophysics Data System (ADS)

Waterhouse, Dale J.; Joseph, James; Neves, André A.; di Pietro, Massimiliano; Brindle, Kevin M.; Fitzgerald, Rebecca C.; Bohndiek, Sarah E.

2016-08-01

Barrett's esophagus is a known precursor lesion to esophageal adenocarcinoma. In these patients, early detection of premalignant disease, known as dysplasia, allows curative minimally invasive endoscopic therapy, but is confounded by a lack of contrast in white light endoscopy. Imaging fluorescently labeled lectins applied topically to the tissue has the potential to more accurately delineate dysplasia, but tissue autofluorescence limits both sensitivity and contrast when operating in the visible region. To overcome this challenge, we synthesized near-infrared (NIR) fluorescent wheat germ agglutinin (WGA-IR800CW) and constructed a clinically translatable bimodal NIR and white light endoscope. Images of NIR and white light with a field of view of 63 deg and an image resolution of 182 μm are coregistered and the honeycomb artifact arising from the fiber bundle is removed. A minimum detectable concentration of 110 nM was determined using a dilution series of WGA-IR800CW. We demonstrated ex vivo that this system can distinguish between gastric and squamous tissue types in mouse stomachs (p=0.0005) and accurately detect WGA-IR800CW fluorescence in human esophageal resections (compared with a gold standard imaging system, rs>0.90). Based on these findings, future work will optimize the bimodal endoscopic system for clinical trials in Barrett's surveillance.

Assessment of different excitation wavelengths for photodetecting neoplastic urothelial lesions by laser-induced autofluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Anidjar, Maurice; Cussenot, Oliver; Avrillier, Sigrid; Ettori, Dominique; Teillac, Pierre; Le Duc, Alain

1996-04-01

We have designed a program using laser induced autofluorescence spectroscopy as a possible way to characterize urothelial tumors of the bladder. The autofluorescence spectra were compared between normal, suspicious and tumor areas of human bladder. Three different pulsed laser wavelengths were used for excitation: 308 nm (excimer), 337 nm (nitrogen) and 480 nm (dye laser). Excitation light was delivered by a specially devised multifiber catheter introduced through the working channel of a regular cystoscope under saline irrigation. The fluorescence light was focused into an optical multichannel analyzer detection system. The data was evaluated in 25 patients immediately before resection of a bladder tumor. Spectroscopic results were compared with histopathology. Upon 337 nm and 480 nm excitations, the overall intensity of the fluorescence spectra from bladder tumors was clearly reduced in comparison with normal urothelium, regardless of the stage and the grade of the tumor. upon 308 nm excitation, the shape of tumor fluorescence spectra, including carcinoma in situ, differed drastically from that of normal tissue. In this case, no absolute intensity measurements are needed and clear diagnosis can be achieved from fluorescence intensity ratio (360/440 nm). This spectroscopic study could be particularly useful for the design of a simplified autofluorescence imaging device for real-time routine detection of occult urothelial neoplastic lesions.

Duodenal gangliocytic paraganglioma with lymph node metastasis and an 8-year follow-up: a case report.

PubMed

Barret, Maximilien; Rahmi, Gabriel; Duong van Huyen, Jean-Paul; Landi, Bruno; Cellier, Christophe; Berger, Anne

2012-01-01

Gangliocytic paraganglioma (GP) is a rare tumor, usually located in the second part of the duodenum. On pathological examination, GP is characterized by the association of the histological features of paragangliomas, ganglioneuromas, and carcinoid tumors. Classical clinical presentations are upper gastrointestinal bleeding and abdominal pain. Preoperative diagnosis is difficult because of the submucosal site of the tumor, with usually negative mucosal biopsies. Endoscopic ultrasound helps establish the diagnosis and allows lymph node staging, which will guide the choice of the treatment. If GPs usually follow a benign course, metastatic spread to regional lymph nodes treated by surgical resection alone has been reported. We report a case of GP with lymph node metastases treated by duodenopancreatectomy with long-term disease-free survival, suggesting that surgical resection is a reasonable approach for metastatic GPs.

[Application of diffusion tensor imaging fractography in minimally invasive surgery of brain tumors].

PubMed

Yang, Lei; Zhang, Mao-zhi; Zhang, Wei; Zhao, Yuan-li; Zhao, Ji-zong

2006-05-23

To investigate the effects and prospect of application of diffusion tensor imaging (DTI) fractography in minimally invasive surgery of brain tumors. DTI fractography was performed in 52 patients with malignant brain tumors. Based on the DTI fractography results, 34 of the 52 patients underwent operation under neuro-navigation, and 18 of the 52 patients underwent operation routine minimally invasive craniotomy and tumor resection without neuro-navigation. The rate of total tumor resection was 86.5% (45/52). The mortality was 1.9% (1/52). The disability rate was 11.5% (6/52). No case needed the second operation. DTI fractography has raised the minimally invasive neurosurgery to the level of protecting the nuclei and nerve tracts and guiding intra-operative management of infiltration of deep-seated tumors, especially when combined with neuro-navigation and interventional MRI.

Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence

NASA Astrophysics Data System (ADS)

Xue, Jingwei; Zhao, Zekai; Zhang, Lei; Xue, Lingjing; Shen, Shiyang; Wen, Yajing; Wei, Zhuoyuan; Wang, Lu; Kong, Lingyi; Sun, Hongbin; Ping, Qineng; Mo, Ran; Zhang, Can

2017-07-01

Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours.

PET Probe-Guided Surgery in Patients with Breast Cancer: Proposal for a Methodological Approach.

PubMed

Orsaria, Paolo; Chiaravalloti, Agostino; Fiorentini, Alessandro; Pistolese, Chiara; Vanni, Gianluca; Granai, Alessandra Vittoria; Varvaras, Dimitrios; Danieli, Roberta; Schillaci, Orazio; Petrella, Giuseppe; Buonomo, Oreste Claudio

2017-01-02

Although it is valuable for detecting distant metastases, identifying recurrence, and evaluating responses to chemotherapy, the role of 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography ( 18 F-FDG PET/CT) in assessing locoregional nodal status for initial staging of breast cancer has not yet been well-defined in clinical practice. In the current report, we describe a new PET probe-based clinical approach, with evaluation of the technical performance of a handheld high-energy gamma probe for intraoperative localization of breast carcinomas, and evaluation of lymph node metastases during radio-guided oncological surgery. Three patients underwent a PET/CT scan immediately prior to surgery following the standard clinical protocol. Intraoperatively, tumors were localized and resected with the assistance of a hand-held gamma probe. PET-guided assessment of the presence or absence of regional nodal spread of malignancy was compared with the reference standard of histopathological examination. In all three cases, perioperative 18 F-FDG PET/CT imaging and intraoperative gamma probe detection verified complete resection of the hypermetabolic lesions and demonstrated no additional suspicious occult disease. This innovative approach demonstrates great promise for providing real-time access to metabolic and morphological tumor information that may lead to an optimal disease-tailored approach. In carefully selected indications, a PET probe can be a useful adjunct in surgical practice, but further trials with a larger number of patients need to be performed to verify these findings. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.