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Frederic Lange

Publications and source records attributed to Frederic Lange.

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Multimodal Imaging System Combining Hyperspectral and Laser Speckle Imaging for In Vivo Hemodynamic and Metabolic Monitoring

We present the development and validation of a novel multimodal optical imaging platform that integrates hyperspectral imaging (HSI) and laser speckle contrast imaging (LSCI) to enable real-time, non-invasive mapping of tissue oxygenation, perfusion and metabolism, via blood flowmetry and targeting of oxy- (HbO2), deoxyhemoglobin (HHb), as well as oxidized cytochrome-c-oxidase (oxCCO). The system architecture features a single high-speed camera and dual optical path, with synchronized alternating illumination: a filtered, supercontinuum laser for HSI and a He-Ne laser for LSCI. The system performances were evaluated through in vivo experiments on rat spinal cord under normoxic and hypoxic conditions, revealing coherent physiological changes in hemodynamics, metabolism and relative blood flow index (rBFI). These results demonstrate the potential of the platform for functional tissue imaging and quantitative dynamic monitoring of both oxygen delivery and consumption.

physics.med-ph

2bNIRS: a portable, multi-distance, broadband oximeter and cytochrome-c-oxidase monitoring system for in vivo applications

Conventional near-infrared spectroscopy (NIRS) instruments typically employ 2-3 wavelengths for monitoring tissue haemodynamics. However, the use of broadband illumination (hundreds of wavelengths) unlocks also the targeting of tissue metabolism by exploiting the wide differential-redox peak of absorption of cytochrome-c-oxidase (CCO). For this purpose, we present here a novel, broadband (780-900nm), multi-distance NIRS system, called 2bNIRS. Compact and portable (20 x 30 x 40 cm3), 2bNIRS was validated using a dynamic, optical phantom con-taining blood and yeast, and benchmarked against a multi-wavelength time-domain NIRS (TD-NIRS) system. Validation confirmed its accuracy in tracking haemody-namic and metabolic changes, with superior oximetry performance achieved via our BRUNO algorithm, which integrates broadband spectral fitting with spatially-re-solved analysis. Preliminary in vivo, human applications demonstrated 2bNIRS ap-plicability to monitoring both muscle tissue, during arm cuff occlusions, and the brain, during frontal cortex activation.

physics.med-ph

A Novel Portable and Wearable Broadband Near-Infrared Spectroscopy Device for In-Vivo Oxygenation and Metabolism Measurements

Broadband NIRS (bNIRS) is an extension of fNIRS that provides the same assessment of oxygenation biomarkers along with a valuable marker for oxygen metabolism at a cellular level, the oxidation state of cytochrome-c-oxidase (oxCCO). bNIRS implements many (100s) NIR wavelengths in the full NIR spectrum to address this and provide insight to tissue energetics. To supply these many wavelengths of light, broadband sources are required, and spectrometers are employed to distinguish power per wavelength. Current multi-channel bNIRS instruments are bulky and only semi-portable due to technological limitations. We propose a design for a bNIRS device that has been miniaturized to allow for portable use. This design leverages the innovations in photonic devices that have created a new line of microspectrometers and broadband NIR high-power LEDs; the Hamamatsu SMD-type spectrometer C14384MA and the Ushio SMBBIR45-1100 LED. This first-of-itskind device, referred to as microCYRIL (after its two predecessors CYRIL and miniCYRIL), has been developed for oxygenation and metabolism measurements with dual channel operation. To verify functionality, concentration changes in oxygenated (HbO2) and deoxygenated (HHb) haemoglobin and oxCCO were successfully tracked during a cuff-induced venous and arterial occlusion.

physics.med-ph

A transportable hyperspectral imaging setup based on fast, high-density spectral scanning for in situ quantitative biochemical mapping of fresh tissue biopsies

Histopathological examination of surgical biopsies, such as in glioma and glioblastoma resection, is hindered in current clinical practice by the long times required for the laboratory analysis and pathological screening, typically taking several days or even weeks to be completed. We propose here a transportable, high-density, spectral-scanning based hyperspectral imaging setup, named HyperProbe1, that can provide in situ, fast biochemical analysis and mapping of fresh surgical tissue samples, right after excision, and without the need of fixing or staining. HyperProbe1 is based on spectral scanning via supercontinuum laser illumination filtered with acousto-optic tuneable filters. Such methodology allows the user to select any number and type of wavelength bands in the visible and near-infrared range between 510 and 900 nm (up to 79), and to reconstruct 3D hypercubes composed of high-resolution, widefield images of the surgical samples, where each pixel is associated with a complete spectrum. The system is applied on 11 fresh surgical biopsies of glioma from routine patients, including different grades of tumour classification. Quantitative analysis of the composition of the tissue is performed via fast spectral unmixing to reconstruct mapping of major biomarkers. We also provided a preliminary attempt to infer tumour classification based on differences of composition in the samples, suggesting the possibility to use lipid content and differential cytochrome-c-oxidase concentrations to distinguish between lower and higher grade gliomas. A proof-of-concept of the performances of HyperProbe1 for quantitative, biochemical mapping of surgical biopsies is demonstrated, paving the way for improving current post-surgical, histopathological practice via non-destructive, in situ streamlined screening of fresh tissue samples in a matter of minutes after excision.

physics.med-ph

Identifying chromophore fingerprints of brain tumor tissue on hyperspectral imaging using principal component analysis

Hyperspectral imaging (HSI) is an optical technique that processes the electromagnetic spectrum at a multitude of monochromatic, adjacent frequency bands. The wide-bandwidth spectral signature of a target object's reflectance allows fingerprinting its physical, biochemical, and physiological properties. HSI has been applied for various applications, such as remote sensing and biological tissue analysis. Recently, HSI was also used to differentiate between healthy and pathological tissue under operative conditions in a surgery room on patients diagnosed with brain tumors. In this article, we perform a statistical analysis of the brain tumor patients' HSI scans from the HELICoiD dataset with the aim of identifying the correlation between reflectance spectra and absorption spectra of tissue chromophores. By using the principal component analysis (PCA), we determine the most relevant spectral features for intra- and inter-tissue class differentiation. Furthermore, we demonstrate that such spectral features are correlated with the spectra of cytochrome, i.e., the chromophore highly involved in (hyper) metabolic processes. Identifying such fingerprints of chromophores in reflectance spectra is a key step for automated molecular profiling and, eventually, expert-free biomarker discovery.

q-bio.QM