Characterization of foreign materials in paraffin-embedded pathological specimens using in situ multi-elemental imaging with laser spectroscopy

Abstract

Pathologists typically encounter many disparate exogenous materials in clinical specimens during their routine histopathological examinations, especially within the skin, lymph nodes, and lungs. These foreign substances may be free extracellular deposits or induce several clinical abnormalities or histopathological patterns. However, pathologists almost never investigate or report the chemical nature of exogenous metals in clinical specimens due to a lack of convenient and available technologies. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) technology is evaluated for in situ multi-elemental tissue imaging. The improved procedures allow visualization of the presence of chemical elements contained within paraffin-embedded specimens of medical interest with elemental images that are stackable with conventional histology images. We selected relevant medical situations for which the associated pathology reports were limited to the presence of lymphohistiocytic and inflammatory cells containing granules (a granuloma and a pseudolymphoma) or to lymph nodes or skin tissues containing pigments or foreign substances. Exogenous elements such as aluminum, titanium, copper, and tungsten were identified and localized within the tissues. The all-optical LIBS elemental imaging instrument that we developed is fully compatible with conventional optical microscopy used for pathology analysis. When combined with routine histopathological analysis, LIBS is a versatile technology that might help pathologists establish or confirm diagnoses for a wide range of medical applications, particularly when the nature of external agents present in tissues needs to be investigated.

L’imagerie élémentaire par spectroscopie LIBS

“…Based on our experience and recent literature in the field of imaging the elemental content of animal and human specimens, this review describes the principle and characteristics of the instrument, technical considerations for setting up experiments with LIBS, its advantages, limitations and possibilities for pre-clinical and medical applications. Le sodium (Na) est représenté en rouge (figure adaptée de [19]). B. Accumulation de titane dans un ganglion lymphatique « pigmenté ».…”

“…Ce savoir-faire permet donc d'envisager l'emploi de la technologie LIBS pour analyser au moment du diagnostic ou a posteriori, de très nombreux échantillons présentant un intérêt médical. Dans une troisième étude, nous avons sélectionné des échantillons de patients pour lesquels les anatomopathologistes retrouvaient des anomalies lors de l'examen histo-pathologique [19]. La présence d'anomalies tissulaires (réactions granulomateuses, pigments, vacuoles, ou même corps étrangers) est fréquemment rapportée par les pathologistes lors de leurs analyses de routine, mais leur nature élémentaire est rarement examinée de façon approfondie, principalement par manque de technologies accessibles.…”

“…La technique d'imagerie multi-élémentaire LIBS possède des applications pour la médecine très variées, allant de la visualisation d'éléments endogènes dans des conditions physiologiques ou pathologiques, à la détection in situ de métaux lourds exogènes dans les tissus après exposition professionnelle ou environnementale. Nous avons récemment réalisé une étude de faisabilité [18], puis une étude descriptive de la distribution des éléments endogènes dans différentes biopsies de peau humaine [19]. Ces biopsies cutanées provenaient de tissus sains, mais également de carcinomes à cellules de Merkel, de carcinomes épidermoïdes, et de métastases cutanées de mélanome (Figure 4).…”

Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications

“…Then, its distribution and behavior in tumor-bearing mice were described. For BNCT experiments performed on animals, the chorioallantoic membrane (CAM) model in fertilized chicken eggs was used to establish vascularized glioblastoma in vivo and evaluated the aza-BODIPY/ 10 B-BSH conjugate tumor uptake with optical imaging and laser-induced breakdown spectroscopy [44][45][46][47]. Finally, a neutron beam was used to evaluate the expected toxicity of the neutron-exposed aza-BODIPY/ 10 B-BSH compounds and demonstrated their strong potential as efficient theranostic boron-vectors for promising BNCT applications.…”

“…Thus, the excised tumors collected at day 16 were sliced and analyzed by LIBS imaging for elemental analysis [44] and examine phosphorus (P) and boron (B) content and distribution. P was selected as it is present in every cell and its distribution reflects the area of the tissue itself [47,52]. P was used to delineate the tissue sections (in white in Figure 5d).…”