Autofluorescence imaging within the liver: a promising tool for the detection and characterization of primary liver tumors.

OBJECTIVES: To assess the performance of 405 nm-induced autofluorescence for the characterization of primary liver nodules on ex vivo resected specimens. MATERIALS AND METHODS: Forty resected liver specimens bearing 53 primary liver nodules were included in this IRB-approved prospective study. Intratissular spectroscopic measurements were performed using a 25-G fibered-needle on all ex vivo specimens: 5 autofluorescence measurements were performed in both nodules and adjacent parenchyma. The spectra derivatives of the 635 and 670 nm autofluorescence peaks observed in nodules and in adjacent liver parenchyma were compared (Kruskal-Wallis and Mann-Whitney when appropriate). RESULTS: A total of 42 potentially evolutive primary liver nodules-34 hepatocellular carcinomas, 4 intrahepatic cholangiocarcinomas, 4 hepatocellular adenomas-and 11 benign nodules-5 focal nodular hyperplasias, 6 regenerative nodules-were included. Both 635 and 670 nm Δderivatives were significantly higher in benign as compared to potentially evolutive (PEV) nodules (respectively 32.9 ± 4.5 vs 15.3 ± 1.4; p < 0.0001 and 5.7 ± 0.6 vs 2.5 ± 0.1; p < 0.0001) with respective sensitivity and specificity of 78% and 91% for distinguishing PEV from benign nodules. CONCLUSION: 405 nm-induced autofluorescence enables the discrimination of benign from PEV primary liver nodules, suggesting that autofluorescence imaging could be used to optimize US targeted liver biopsies. KEY POINTS: • 405 nm-induced autofluorescence can distinguish liver tumors from the adjacent liver parenchyma. • The analysis of autofluorescence imaging observed within primary liver tumors can discriminate benign tumors from those requiring follow-up or targeted liver biopsy. • In current practice, autofluorescence imaging could be embedded within biopsy needle, to enable, in addition to ultrasound guidance, optimal targeting of liver nodules which could optimize tissue sampling.

Development of a New Negative Obstacle Sensor for Augmented Electric Wheelchair.

Due to pathologies or age-related problems, in some disabled people, motor impairment is associated with cognitive and/or visual impairments. This combination of limitations unfortunately leads to an inability to move around independently. Indeed, their situation does not allow them to use a conventional electric wheelchair, for safety reasons, and for the moment there is no other technological solution providing safe movement capacity. This lack of access to an autonomous travel solution has the consequence of weakening the intellectual, personal, social, cultural and moral development, as well as the life expectancy, of the people concerned. In this context, our team is working on the development of an optoelectronic system that secures the displacement of electric wheelchairs. This is a large project that requires the development of several functionalities such as: the anti-collision of the wheelchair with its environment, the prevention of falls from the wheelchair on uneven levels, and the adaptation of the system mechanically and electronically to the majority of commercially available electric wheelchair models, among others. In this article, we introduce our solution for detecting dangerous height differences, also called "negative obstacles", through the creation of a dedicated sensor. This sensor works by optical triangulation and can embed several laser beams in order to extend its detection zone. It has the particularity of being robust in direct sunlight and rain and has a sufficiently high measurement rate to be suitable for the displacement of electric wheelchairs. We develop an adapted algorithm, and point out compromises, in particular between the orientation of the laser beams and the maximal speed of the wheelchair.

Tom Pouce III, an Electronic White Cane for Blind People: Ability to Detect Obstacles and Mobility Performances.

We present a protocol for evaluating the efficiency of an electronic white cane for improving the mobility of blind people. The electronic cane used during the test is the Tom Pouce III, made of LIDAR sensors (light detection and ranging) with tactile feedback. The protocol comprises two parts. The first part, the "detection test", evaluates the efficiency of the sensors in the Tom Pouce III for detecting the obstacles found in everyday life (thin and large poles, apertures) under different environmental conditions (darkness, sun light, rain). The second part of the test, the "mobility test", compares the ability of blind participants to cross a 25 m path by avoiding obstacles with the simple white cane and the electronic cane. The 12 blind participants had between 2 and 20 years of experience of everyday usage of Tom Pouce devices. The results show a significant improvement in the capacity to avoid obstacles with the electronic cane relative to the simple white cane, and there was no speed difference. There was no correlation between the results and the years of experience of the users.

Preclinical ex vivo evaluation of the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses.

OBJECTIVES: To assess the diagnostic performance of a new device for in situ label-free fluorescence spectral analysis of breast masses in freshly removed surgical specimens, in preparation for its clinical development. METHODS: Sixty-four breast masses from consenting patients who had undergone either a lumpectomy or a mastectomy were included. Label-free fluorescence spectral acquisitions were obtained with a 25G fibre-containing needle inserted into the mass. Data from benign and malignant masses were compared to establish the most discriminating thresholds and measurement algorithms. Accuracy was verified using the bootstrap method. RESULTS: The final histological examination revealed 44 invasive carcinomas and 20 benign lesions. The maximum intensity of fluorescence signal was discriminant between benign and malignant masses (p < .0001) whatever their sizes. Statistical analysis indicated that choosing five random measurements per mass was the best compromise to obtain high sensitivity and high negative predictive value with the fewest measurements. Thus, malignant tumours were identified with a mean sensitivity, specificity, negative and positive predictive value of 98.8%, 85.4%, 97.2% and 93.5%, respectively. CONCLUSION: This new in situ tissue autofluorescence evaluation device allows accurate discrimination between benign and malignant breast masses and deserves clinical development. KEY POINTS: • A new device allows in situ label-free fluorescence analysis of ex vivo breast masses • Maximum fluorescence intensity discriminates benign from malignant masses (p < .0001) • Five random measurements allow a high negative predictive value (97.2%).

Pulmonary Endogenous Fluorescence Allows the Distinction of Primary Lung Cancer from the Perilesional Lung Parenchyma.

BACKGROUND: Pre-therapeutic pathological diagnosis is a crucial step of the management of pulmonary nodules suspected of being non small cell lung cancer (NSCLC), especially in the frame of currently implemented lung cancer screening programs in high-risk patients. Based on a human ex vivo model, we hypothesized that an embedded device measuring endogenous fluorescence would be able to distinguish pulmonary malignant lesions from the perilesional lung tissue. METHODS: Consecutive patients who underwent surgical resection of pulmonary lesions were included in this prospective and observational study over an 8-month period. Measurements were performed back table on surgical specimens in the operative room, both on suspicious lesions and the perilesional healthy parenchyma. Endogenous fluorescence signal was characterized according to three criteria: maximal intensity (Imax), wavelength, and shape of the signal (missing, stable, instable, photobleaching). RESULTS: Ninety-six patients with 111 suspicious lesions were included. Final pathological diagnoses were: primary lung cancers (n = 60), lung metastases of extra-thoracic malignancies (n = 27) and non-tumoral lesions (n = 24). Mean Imax was significantly higher in NSCLC targeted lesions when compared to the perilesional lung parenchyma (p<0,0001) or non-tumoral lesions (p<0,0001). Similarly, photobleaching was more frequently found in NSCLC than in perilesional lung (p<0,0001), or in non-tumoral lesions (p<0,001). Respective associated wavelengths were not statistically different between perilesional lung and either primary lung cancers or non-tumoral lesions. Considering lung metastases, both mean Imax and wavelength of the targeted lesions were not different from those of the perilesional lung tissue. In contrast, photobleaching was significantly more frequently observed in the targeted lesions than in the perilesional lung (p≤0,01). CONCLUSION: Our results demonstrate that endogenous fluorescence applied to the diagnosis of lung nodules allows distinguishing NSCLC from the surrounding healthy parenchyma and from non-tumoral lesions. Inconclusive results were found for lung metastases due to the heterogeneity of this population.

Towards an optical biopsy for the diagnosis of breast cancer in vivo by endogenous fluorescence spectroscopy.

The techniques of medical imaging allow the detection of suspect lesions in the breast, but they do not always evidence the malignant nature of these lesions. Breast biopsies and histological analyses are therefore implemented to establish a diagnosis. In order to reduce the number of these invasive procedures, a portable clinical system was designed based upon the excitation of Endogenous Fluorescence in vivo at 405 nm via a fiber-optics probe included in a disposable needle of small diameter (<1 mm). From the fluorescence signal, the authors are able to discriminate between diseased and healthy areas of human breast biopsies. Stronger fluorescence intensity and systematic spectral red shift of the tumor areas were observed. These results are confirmed by confocal microscopy. This new instrument is promising for the minimally invasive diagnosis of breast tumors in vivo with an appreciable limitation of patient trauma and of operational and financial cost.

Spatially selective laser irradiation method controlled by real-time image analysis: optical aspects.

We present a spatially selective irradiation method for laser treatment of biological surfaces. The purpose is to irradiate only the pathological targets and to preserve the healthy surrounding parts. We are interested here in the optical arrangement of the device and in the evaluation of its physical limitations before it is used for medical purposes. The method uses real-time image analysis applied to the video imagery of the surface to be treated. The result of the image analysis generates the control signal to a spatial light modulator, allowing us to project an adequate repartition of laser irradiance on the surface to be treated. Experimental results demonstrate a spatial selectivity of approximately 10 microm for a 6.7 mm x 5 mm field. The optical system has no moving parts (unlike galvanometric scanners) and is able to irradiate multiple targets simultaneously with different doses.

Real time control of the spatial selectivity during laser treatment of a biological surface.

We propose a new irradiation technique to improve the spatial selectivity and the dose control during a laser treatment of a biological surface. The technique is based on the use of a spatial light modulator to project a rectangular laser image of 8 mm x 5 mm. The spatial distribution of the irradiation is controlled in real time by image analysis applied to the acquired image of the surface to be treated. The aim is to discriminate between the target areas to be irradiated and the surrounding parts to be preserved. The resolution is about 12 microm and is limited by the resolution of the camera and the spatial light modulator. For treatments of a large surface we use an intensity correlator to measure the displacement and to avoid an unwanted second irradiation on a target.