Late-fluorescence mammography assesses tumor capillary permeability and differentiates malignant from benign lesions

Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, 10587 Berlin, Germany.
Optics Express (Impact Factor: 3.49). 09/2009; 17(19):17016-33. DOI: 10.1364/OE.17.017016
Source: PubMed


Using scanning time-domain instrumentation we recorded fluorescence projection mammograms on few breast cancer patients prior, during and after infusion of indocyanine green (ICG), while monitoring arterial ICG concentration by transcutaneous pulse densitometry. Late-fluorescence mammograms recorded after ICG had been largely cleared from the blood by the liver, showed invasive carcinomas at high contrast over a rather homogeneous background, whereas benign lesions did not produce (focused) fluorescence contrast. During infusion, tissue concentration contrast and hence fluorescence contrast is determined by intravascular contributions, whereas late-fluorescence mammograms are dominated by contributions from protein-bound ICG extravasated into the interstitium, reflecting relative microvascular permeabilities of carcinomas and normal breast tissue. We simulated intravascular and extravascular contributions to ICG tissue concentration contrast within a two-compartment unidirectional pharmacokinetic model.

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    • "After the intravenous administration of ICG, the vascular hyperpermeability of cancer towards macromolecules results in a higher fluorescence intensity in cancers observed during the extravascular phase than observed around normal tissue. In addition, ICG is cleared from the vascular compartment by the liver.14 After intravenous injection of ICG, the dye quickly binds to globulins preferentially to a1-lipoproteins within 1 to 2 seconds.15 "
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    ABSTRACT: In order to minimize surgical stress and preserve organs, endoscopic or robotic surgery is often performed when conducting head and neck surgery. However, it is impossible to physically touch tumors or to observe diffusely invaded deep organs through the procedure of endoscopic or robotic surgery. In order to visualize and safely resect tumors even in these cases, we propose using an indocyanine green (ICG) fluorescence method for navigation surgery in head and neck cancer. To determine the optimum surgical time for tumor resection after the administration of ICG based on the investigation of dynamic ICG fluorescence imaging. Nine patients underwent dynamic ICG fluorescence imaging for 360 minutes, assessing tumor visibility at 10, 30, 60, 120, 180, and 360 minutes. All cases were scored according to near-infrared (NIR) fluorescence imaging visibility scored from 0 to 5. Dynamic NIR fluorescence imaging under the HyperEye Medical System indicated that the greatest contrast in fluorescent images between tumor and normal tissue could be observed from 30 minutes to 1 hour after the administration of ICG. The optimum surgical time was determined to be between 30 minutes to 2 hours after ICG injection. These findings are particularly useful for detection and safe resection of tumors invading the parapharyngeal space. ICG fluorescence imaging is effective for the detection of head and neck cancer. Preliminary findings suggest that the optimum timing for surgery is from 30 minutes to 2 hours after the ICG injection.
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    • "The purpose of this study was to determine the appropriate tracer kinetic model for characterizing tumour haemodynamics and vascular permeability from DCE optical data. Previous optical studies have used compartmental models (Gurfinkel et al 2000, Cuccia et al 2003, Alacam et al 2006, 2008, Hagen et al 2009, Intes et al 2003); however, this class of models is unable to provide separate estimates of blood flow and vascular permeability. "
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    ABSTRACT: Dynamic contrast-enhanced (DCE) methods are widely used with magnetic resonance imaging and computed tomography to assess the vascular characteristics of tumours since these properties can affect the response to radiotherapy and chemotherapy. In contrast, there have been far fewer studies using optical-based applications despite the advantages of low cost and safety. This study investigated an appropriate kinetic model for optical applications to characterize tumour haemodynamics (blood flow, F, blood volume, V b , and vascular heterogeneity) and vascular leakage (permeability surface-area product, PS). DCE data were acquired with two dyes, indocyanine green (ICG) and 800 CW carboxylate (IRD cbx), from a human colon tumour xenograph model in rats. Due to the smaller molecular weight of IRD cbx (1166 Da) compared to albumin-bound ICG (67 kDa), PS of IRD cbx was significantly larger; however, no significant differences in F and V b were found between the dyes as expected. Error analysis demonstrated that all parameters could be estimated with an uncertainty less than 5% due to the high temporal resolution and signal-to-noise ratio of the optical measurements. The next step is to adapt this approach to optical imaging to generate haemodynamics and permeability maps, which should enhance the clinical interest in optics for treatment monitoring. (Some figures may appear in colour only in the online journal)
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    • "Corlu et al. [23] have demonstrated the first three-dimensional (3-D) ICG-fluorescence-DOT of in vivo human breast cancer. Other groups have also reported more cases of in vivo fluorescence-DOT for human breast applications [28,29]. These preliminary studies have observed a marked fluorescence contrast between the tumorous and normal tissues that originates from the agent accumulation in leaky malignant tissues [30], especially during the late-fluorescence phase [28]. "
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    ABSTRACT: A combined time-domain fluorescence and hemoglobin diffuse optical tomography (DOT) system and the image reconstruction methods are proposed for enhancing the reliability of breast-dedicated optical measurement. The system equipped with two pulsed laser diodes at wavelengths of 780 nm and 830 nm that are specific to the peak excitation and emission of the FDA-approved ICG agent, and works with a 4-channel time-correlated single photon counting device to acquire the time-resolved distributions of the light re-emissions at 32 boundary sites of tissues in a tandem serial-to-parallel mode. The simultaneous reconstruction of the two optical (absorption and scattering) and two fluorescent (yield and lifetime) properties are achieved with the respective featured-data algorithms based on the generalized pulse spectrum technique. The performances of the methodology are experimentally assessed on breast-mimicking phantoms for hemoglobin- and fluorescence-DOT alone, as well as for fluorescence-guided hemoglobin-DOT. The results demonstrate the efficacy of improving the accuracy of hemoglobin-DOT based on a priori fluorescence localization.
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