Complementing the pulp proteome via sampling with a picosecond infrared laser (PIRL).

OBJECTIVES: The aim of this investigation was the detailed analysis of the human pulp proteome using the new picosecond infrared laser (PIRL)-based sampling technique, which is based on a completely different mechanism compared to mechanical sampling. Proteome analysis of healthy pulp can provide data to define changes in the proteome associated with dental disease. MATERIAL AND METHODS: Immediately after extraction of the entire, undamaged tooth, 15 wisdom teeth were deep frozen in liquid nitrogen and preserved at -80°C. Teeth were crushed, and the excised frozen pulps were conditioned for further analysis. The pulps were sampled using PIRL, and the aspirates digested with trypsin and analyzed with mass spectrometry. Pulp proteins were categorized according to their gene ontology terminus. Proteins identified exclusively in this study were searched in the Human Protein Atlas (HPA) for gaining information about the main known localization and function. RESULTS: A total of 1348 proteins were identified in this study. The comparison with prior studies showed a match of 72%. Twenty-eight percent of the proteins were identified exclusively in this study. Considering HPA, almost half of these proteins were assigned to tissues that could be pulp specific. CONCLUSION: PIRL is releasing proteins from the dental pulp which are not dissolved by conventional sampling techniques. Clinical Relevance The presented data extend current knowledge on dental pulp proteomics in healthy teeth and can serve as a reference for studies on pulp proteomics in dental disease.

Mass Spectrometric Lipid Profiles of Picosecond Infrared Laser-Generated Tissue Aerosols Discriminate Different Brain Tissues.

BACKGROUND AND OBJECTIVES: A picosecond infrared laser (PIRL) has recently been demonstrated to cut biological tissue without scar formation based on the minimal destructive action on the surrounding cells. During cutting with PIRL, the irradiated tissue is ablated by a cold vaporization process termed desorption by impulsive vibrational excitation. In the resulting aerosol, all molecules are dissolved in small droplets and even labile biomolecules like proteins remain intact after ablation. It is hypothesized that these properties enable the PIRL in combination with mass spectrometry as an intelligent laser scalpel for guided surgery. In this study, it was tested if PIRL-generated tissue aerosols are applicable for direct analysis with mass spectrometry, and if the acquired mass spectra can be used to discriminate different brain areas. MATERIALS AND METHODS: Brain tissues were irradiated with PIRL. The aerosols were collected and directly infused into a mass spectrometer via electrospray ionization without any sample preparation or lipid extraction. RESULTS: The laser produced clear cuts with no marks of burning. Lipids from five different classes were identified in the mass spectra of all samples. By principal component analysis the different brain areas were clearly distinguishable from each other. CONCLUSIONS: The results demonstrate the potential for real-time analysis of lipids with a PIRL-based laser scalpel, coupled to a mass spectrometer, for the discrimination of tissues during surgeries. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

How Well Do Self-Supervised Models Transfer to Medical Imaging?

Self-supervised learning approaches have seen success transferring between similar medical imaging datasets, however there has been no large scale attempt to compare the transferability of self-supervised models against each other on medical images. In this study, we compare the generalisability of seven self-supervised models, two of which were trained in-domain, against supervised baselines across eight different medical datasets. We find that ImageNet pretrained self-supervised models are more generalisable than their supervised counterparts, scoring up to 10% better on medical classification tasks. The two in-domain pretrained models outperformed other models by over 20% on in-domain tasks, however they suffered significant loss of accuracy on all other tasks. Our investigation of the feature representations suggests that this trend may be due to the models learning to focus too heavily on specific areas.

Mass spectrometry-based intraoperative tumor diagnostics.

In surgical oncology, decisions regarding the amount of tissue to be removed can have important consequences: the decision between preserving sufficient healthy tissue and eliminating all tumor cells is one to be made intraoperatively. This review discusses the latest technical innovations for a more accurate tumor margin localization based on mass spectrometry. Highlighting the latest mass spectrometric inventions, real-time diagnosis seems to be within reach; focusing on the intelligent knife, desorption electrospray ionization, picosecond infrared laser and MasSpec pen, the current technical status is evaluated critically concerning its scientific and medical practice.

Homogenization of tissues via picosecond-infrared laser (PIRL) ablation: Giving a closer view on the in-vivo composition of protein species as compared to mechanical homogenization.

Posttranslational modifications and proteolytic processing regulate almost all physiological processes. Dysregulation can potentially result in pathologic protein species causing diseases. Thus, tissue species proteomes of diseased individuals provide diagnostic information. Since the composition of tissue proteomes can rapidly change during tissue homogenization by the action of enzymes released from their compartments, disease specific protein species patterns can vanish. Recently, we described a novel, ultrafast and soft method for cold vaporization of tissue via desorption by impulsive vibrational excitation (DIVE) using a picosecond-infrared-laser (PIRL). Given that DIVE extraction may provide improved access to the original composition of protein species in tissues, we compared the proteome composition of tissue protein homogenates after DIVE homogenization with conventional homogenizations. A higher number of intact protein species was observed in DIVE homogenates. Due to the ultrafast transfer of proteins from tissues via gas phase into frozen condensates of the aerosols, intact protein species were exposed to a lesser extent to enzymatic degradation reactions compared with conventional protein extraction. In addition, total yield of the number of proteins is higher in DIVE homogenates, because they are very homogenous and contain almost no insoluble particles, allowing direct analysis with subsequent analytical methods without the necessity of centrifugation. BIOLOGICAL SIGNIFICANCE: Enzymatic protein modifications during tissue homogenization are responsible for changes of the in-vivo protein species composition. Cold vaporization of tissues by PIRL-DIVE is comparable with taking a snapshot at the time of the laser irradiation of the dynamic changes that occur continuously under in-vivo conditions. At that time point all biomolecules are transferred into an aerosol, which is immediately frozen.

Bone ablation without thermal or acoustic mechanical injury via a novel picosecond infrared laser (PIRL).

BACKGROUND AND OBJECTIVE: A precise means to cut bone without significant thermal or mechanical injury has thus far remained elusive. A novel non-ionizing ultrafast pulsed picosecond infrared laser (PIRL) may provide the solution. Tissue ablation with the PIRL occurs via a photothermal process with thermal and stress confinement, resulting in efficient material ejection greatly enhanced through front surface spallation photomechanical effects. By comparison, the Er:YAG laser (EYL) ablates via photothermal and cavitation-induced photomechanical effects without thermal or acoustic confinement, leading to significant collateral tissue injury. This study compared PIRL and EYL bone ablation by infrared thermography (IRT), environmental scanning electron microscopy (ESEM), and histology. STUDY DESIGN: Prospective, comparative, ex vivo animal model. SETTING: Optics laboratory. SUBJECTS AND METHODS: Ten circular area defects were ablated in ex vivo chicken humeral cortex using PIRL and EYL at similar average power (~70 mW) under IRT. Following fixation, ESEM and undecalcified light microscopy images were obtained and examined for signs of cellular injury. RESULTS: Peak rise in surface temperature was negligible and lower for PIRL (1.56 °C; 95% CI, 0.762-2.366) compared to EYL ablation (12.99 °C; 95% CI, 12.189-13.792) (P < .001). ESEM and light microscopy demonstrated preserved cortical microstructure following PIRL ablation in contrast to diffuse thermal injury seen with EYL ablation. Microfractures were not observed. CONCLUSION: Ablation of cortical bone using the PIRL generates negligible and significantly less heat than EYL ablation while preserving cortical microstructure. This novel laser has great potential in advancing surgical techniques where precision osseous manipulation is required.

A novel tool in laryngeal surgery: preliminary results of the picosecond infrared laser.

OBJECTIVES/HYPOTHESIS: Conventional lasers ablate tissue through photothermal, photomechanical, and/or photoionizing effects, which may result in collateral tissue damage. The novel nonionizing picosecond infrared laser (PIRL) selectively energizes tissue water molecules using ultrafast pulses to drive ablation on timescales faster than energy transport to minimize collateral damage to adjacent cells. STUDY DESIGN: Animal cadaver study. METHODS: Cuts in porcine laryngeal epithelium, lamina propria, and cartilage were made using PIRL and carbon dioxide (CO2) laser. Lateral damage zones and cutting gaps were histologically compared. RESULTS: The mean widths of epithelial (8.5 µm), subepithelial (10.9 µm), and cartilage damage zones (8.1 µm) were significantly lower for cuts made by PIRL compared with CO2 laser (p < 0.001). Mean cutting gaps in vocal fold (174.7 µm) and epiglottic cartilage (56.3 µm) were significantly narrower for cuts made by PIRL compared with CO2 laser (P < 0.01, P < 0.05). CONCLUSION: PIRL ablation demonstrates superiority over CO2 laser in cutting precision with less collateral tissue damage.