Rapid identification of pediatric brain tumors with differential mobility spectrometry.

Introduction: Brain tumors are a major source of disease burden in pediatric population, with the most common tumor types being pilocytic astrocytoma, ependymoma and medulloblastoma. In every tumor entity, surgery is the cornerstone of treatment, but the importance of gross-total resection and the corresponding patient prognosis is highly variant. However, real-time identification of pediatric CNS malignancies based on the histology of the frozen sections alone is especially troublesome. We propose a novel method based on differential mobility spectrometry (DMS) analysis for rapid identification of pediatric brain tumors. Methods: We prospectively obtained tumor samples from 15 pediatric patients (5 pilocytic astrocytomas, 5 ependymomas and 5 medulloblastomas). The samples were cut into 36 smaller specimens that were analyzed with the DMS. Results: With linear discriminant analysis algorithm, a classification accuracy (CA) of 70% was reached. Additionally, a 75% CA was achieved in a pooled analysis of medulloblastoma vs. gliomas. Discussion: Our results show that the DMS is able to differentiate most common pediatric brain tumor samples, thus making it a promising additional instrument for real-time brain tumor diagnostics.

The Detection of Bacteria in the Maxillary Sinus Secretion of Patients With Acute Rhinosinusitis Using an Electronic Nose: A Pilot Study.

OBJECTIVE: Detecting bacteria as a causative pathogen of acute rhinosinusitis (ARS) is a challenging task. Electronic nose technology is a novel method for detecting volatile organic compounds (VOCs) that has also been studied in association with the detection of several diseases. The aim of this pilot study was to analyze maxillary sinus secretion with differential mobility spectrometry (DMS) and to determine whether the secretion demonstrates a different VOC profile when bacteria are present. METHODS: Adult patients with ARS symptoms were examined. Maxillary sinus contents were aspirated for bacterial culture and DMS analysis. k-Nearest neighbor and linear discriminant analysis were used to classify samples as positive or negative, using bacterial cultures as a reference. RESULTS: A total of 26 samples from 15 patients were obtained. After leave-one-out cross-validation, k-nearest neighbor produced accuracy of 85%, sensitivity of 67%, specificity of 94%, positive predictive value of 86%, and negative predictive value of 84%. CONCLUSIONS: The results of this pilot study suggest that bacterial positive and bacterial negative sinus secretion release different VOCs and that DMS has the potential to detect them. However, as the results are based on limited data, further conclusions cannot be made. DMS is a novel method in disease diagnostics and future studies should examine whether the method can detect bacterial ARS by analyzing exhaled air.

Identifying chronic rhinosinusitis without nasal polyps by analyzing aspirated nasal air with an electronic nose based on differential mobility spectrometry.

BACKGROUND: The diagnosis of chronic rhinosinusitis (CRS) is a complicated procedure. An electronic nose (eNose) is a novel method that detects disease from gas-phase mixtures, such as human breath. AIMS/OBJECTIVES: To determine whether an eNose based on differential mobility spectrometry (DMS) can detect chronic rhinosinusitis without nasal polyps (CRSsNP) by analyzing aspirated nasal air. MATERIALS AND METHODS: Adult patients with CRSsNP were examined. The control group consisted of patients with septal deviation. Nasal air was aspirated into a collection bag and analyzed with DMS. The DMS data were classified using regularized linear discriminant analysis (LDA) models with 10-fold cross-validation. RESULTS: The accuracy of the DMS to distinguish CRSsNP from patients with septal deviation was 69%. Sensitivity and specificity were 67 and 70%, respectively. Bonferroni-corrected statistical differences were clearly noted. When a subgroup with more severe inflammatory disease was compared to controls, the classification accuracy increased to 82%. CONCLUSIONS: The results of this feasibility study demonstrate that CRSsNP can potentially be differentiated distinguished from patients with similar nasal symptoms by analyzing the aspirated nasal air using DMS. Further research is warranted to evaluate the ability of this novel method in the differential diagnostics of CRS.

Method for the Intraoperative Detection of IDH Mutation in Gliomas with Differential Mobility Spectrometry.

Isocitrate dehydrogenase (IDH) mutation status is an important factor for surgical decision-making: patients with IDH-mutated tumors are more likely to have a good long-term prognosis, and thus favor aggressive resection with more survival benefit to gain. Patients with IDH wild-type tumors have generally poorer prognosis and, therefore, conservative resection to avoid neurological deficit is favored. Current histopathological analysis with frozen sections is unable to identify IDH mutation status intraoperatively, and more advanced methods are therefore needed. We examined a novel method suitable for intraoperative IDH mutation identification that is based on the differential mobility spectrometry (DMS) analysis of the tumor. We prospectively obtained tumor samples from 22 patients, including 11 IDH-mutated and 11 IDH wild-type tumors. The tumors were cut in 88 smaller specimens that were analyzed with DMS. With a linear discriminant analysis (LDA) algorithm, the DMS was able to classify tumor samples with 86% classification accuracy, 86% sensitivity, and 85% specificity. Our results show that DMS is able to differentiate IDH-mutated and IDH wild-type tumors with good accuracy in a setting suitable for intraoperative use, which makes it a promising novel solution for neurosurgical practice.

Detection of cultured breast cancer cells from human tumor-derived matrix by differential ion mobility spectrometry.

The primary treatment of breast cancer is the surgical removal of the tumor with an adequate healthy tissue margin. An intraoperative method for assessing surgical margins could optimize tumor resection. Differential ion mobility spectrometry (DMS) is applicable for tissue analysis and allows for the differentiation of malignant and benign tissues. However, the number of cancer cells necessary for detection remains unknown. We studied the detection threshold of DMS for cancer cell identification with a widely characterized breast cancer cell line (BT-474) dispersed in a human myoma-based tumor microenvironment mimicking matrix (Myogel). Predetermined, small numbers of cultured BT-474 cells were dispersed into Myogel. Pure Myogel was used as a zero sample. All samples were assessed with a DMS-based custom-built device described as "the automated tissue laser analysis system" (ATLAS). We used machine learning to determine the detection threshold for cancer cell densities by training binary classifiers to distinguish the reference level (zero sample) from single predetermined cancer cell density levels. Each classifier (sLDA, linear SVM, radial SVM, and CNN) was able to detect cell density of 3700 cells µL-1 and above. These results suggest that DMS combined with laser desorption can detect low densities of breast cancer cells, at levels clinically relevant for margin detection, from Myogel samples in vitro.

Laser desorption tissue imaging with Differential Mobility Spectrometry.

Pathological gross examination of breast carcinoma samples is sometimes laborious. A tissue pre-mapping method could indicate neoplastic areas to the pathologist and enable focused sampling. Differential Mobility Spectrometry (DMS) is a rapid and affordable technology for complex gas mixture analysis. We present an automated tissue laser analysis system for imaging approaches (iATLAS), which utilizes a computer-controlled laser evaporator unit coupled with a DMS gas analyzer. The system is demonstrated in the classification of porcine tissue samples and three human breast carcinomas. Tissue samples from eighteen landrace pigs were classified with the system based on a pre-designed matrix (spatial resolution 1-3 mm). The smoke samples were analyzed with DMS, and tissue classification was performed with several machine learning approaches. Porcine skeletal muscle (n = 1030), adipose tissue (n = 1329), normal breast tissue (n = 258), bone (n = 680), and liver (n = 264) were identified with 86% cross-validation (CV) accuracy with a convolutional neural network (CNN) model. Further, a panel tissue that comprised all five tissue types was applied as an independent validation dataset. In this test, 82% classification accuracy with CNN was achieved. An analogous procedure was applied to demonstrate the feasibility of iATLAS in breast cancer imaging according to 1) macroscopically and 2) microscopically annotated data with 10-fold CV and SVM (radial kernel). We reached a classification accuracy of 94%, specificity of 94%, and sensitivity of 93% with the macroscopically annotated data from three breast cancer specimens. The microscopic annotation was applicable to two specimens. For the first specimen, the classification accuracy was 84% (specificity 88% and sensitivity 77%). For the second, the classification accuracy was 72% (specificity 88% and sensitivity 24%). This study presents a promising method for automated tissue imaging in an animal model and lays foundation for breast cancer imaging.

Differentiation of aspirated nasal air from room air using analysis with a differential mobility spectrometry-based electronic nose: a proof-of-concept study.

Over the last few decades, breath analysis using electronic nose (eNose) technology has become a topic of intense research, as it is both non-invasive and painless, and is suitable for point-of-care use. To date, however, only a few studies have examined nasal air. As the air in the oral cavity and the lungs differs from the air in the nasal cavity, it is unknown whether aspirated nasal air could be exploited with eNose technology. Compared to traditional eNoses, differential mobility spectrometry uses an alternating electrical field to discriminate the different molecules of gas mixtures, providing analogous information. This study reports the collection of nasal air by aspiration and the subsequent analysis of the collected air using a differential mobility spectrometer. We collected nasal air from ten volunteers into breath collecting bags and compared them to bags of room air and the air aspirated through the device. Distance and dissimilarity metrics between the sample types were calculated and statistical significance evaluated with Kolmogorov-Smirnov test. After leave-one-day-out cross-validation, a shrinkage linear discriminant classifier was able to correctly classify 100% of the samples. The nasal air differed (p< 0.05) from the other sample types. The results show the feasibility of collecting nasal air by aspiration and subsequent analysis using differential mobility spectrometry, and thus increases the potential of the method to be used in disease detection studies.

Differential mobility spectrometry imaging for pathological applications.

Pathologic examination of clinical tissue samples is time consuming and often does not involve the comprehensive analysis of the whole specimen. Automated tissue analysis systems have potential to make the workflow of a pathologist more efficient and to support in clinical decision-making. So far, these systems have been based on application of mass spectrometry imaging (MSI). MSI provides high fidelity and the results in tissue identification are promising. However, the high cost and need for maintenance limit the adoption of MSI in the clinical setting. Thus, there is a need for new innovations in the field of pathological tissue imaging. In this study, we show that differential ion mobility spectrometry (DMS) is a viable option in tissue imaging. We demonstrate that a DMS-driven solution performs with up to 92% accuracy in differentiating between two grossly distinct animal tissues. In addition, our model is able to classify the correct tissue with 81% accuracy in an eight-class setting. The DMS-based system is a significant innovation in a field dominated by mass-spectrometry-based solutions. By developing the presented platform further, DMS technology could be a cost-effective and helpful tool for automated pathological analysis.

Differential mobility spectrometry classification of bacteria.

Aim: Rapid identification of bacteria would facilitate timely initiation of therapy and improve cost-effectiveness of treatment. Traditional methods (culture, PCR) require reagents, consumables and hours to days to complete the identification. In this study, we examined whether differential mobility spectrometry could classify most common bacterial species, genera and between Gram status within minutes. Materials & methods: Cultured bacterial sample gaseous headspaces were measured with differential mobility spectrometry and data analyzed using k-nearest-neighbor and leave-one-out cross-validation. Results: Differential mobility spectrometry achieved a correct classification rate 70.7% for all bacterial species. For bacterial genera, the rate was 77.6% and between Gram status, 89.1%. Conclusion: Largest difficulties arose in distinguishing bacteria of the same genus. Future improvement of the sensor characteristics may improve the classification accuracy.

Identifying brain tumors by differential mobility spectrometry analysis of diathermy smoke.

OBJECTIVE: There is a need for real-time, intraoperative tissue identification technology in neurosurgery. Several solutions are under development for that purpose, but their adaptability for standard clinical use has been hindered by high cost and impracticality issues. The authors tested and preliminarily validated a method for brain tumor identification that is based on the analysis of diathermy smoke using differential mobility spectrometry (DMS). METHODS: A DMS connected to a special smoke sampling system was used to discriminate brain tumors and control samples ex vivo in samples from 28 patients who had undergone neurosurgical operations. They included meningiomas (WHO grade I), pilocytic astrocytomas (grade I), other low-grade gliomas (grade II), glioblastomas (grade IV), CNS metastases, and hemorrhagic or traumatically damaged brain tissue as control samples. Original samples were cut into 694 smaller specimens in total. RESULTS: An overall classification accuracy (CA) of 50% (vs 14% by chance) was achieved in 7-class classification. The CA improved significantly (up to 83%) when the samples originally preserved in Tissue-Tek conservation medium were excluded from the analysis. The CA further improved when fewer classes were used. The highest binary classification accuracy, 94%, was obtained in low-grade glioma (grade II) versus control. CONCLUSIONS: The authors' results show that surgical smoke from various brain tumors has distinct DMS profiles and the DMS analyzer connected to a special sampling system can differentiate between tumorous and nontumorous tissue and also between different tumor types ex vivo.

Identification of breast tumors from diathermy smoke by differential ion mobility spectrometry.

INTRODUCTION: Breast cancer is the most frequent cancer in women worldwide. The primary treatment is breast-conserving surgery or mastectomy with an adequate clearance margin. Diathermy blade is used extensively in breast-conserving surgery. Surgical smoke produced as a side product has cancer-specific molecular features. Differential mobility spectrometry (DMS) is a rapid and affordable technology for analysis of complex gas mixtures. In our study we examined surgical smoke from malignant and benign breast tissue created with a diathermy blade using DMS. MATERIAL AND METHODS: Punch biopsies of 4 mm diameter from breast cancer surgical specimens were taken during gross dissection of fresh surgical specimen and placed in a well plate. The measurement system is a custom-built device called automatic tissue analysis system (ATAS) based on a DMS sensor. Each specimen was incised with a diathermy blade and the surgical smoke was analyzed. RESULTS: We examined 106 carcinoma samples from 21 malignant breast tumors. Benign samples (n = 198) included macroscopically normal mammary gland (n = 82), adipose tissue (n = 88) and vascular tissue (n = 28). The classification accuracy when comparing malignant samples to all benign samples was 87%. The sensitivity was 80% and the specificity was 90%. The classification accuracy of carcinomas to ductal and lobular was 94%, 47%, respectively. CONCLUSIONS: Benign and malignant breast tissue can be identified with ATAS. These results lay foundation for intraoperative margin assessment with DMS from surgical smoke.

In vitro detection of common rhinosinusitis bacteria by the eNose utilising differential mobility spectrometry.

Acute rhinosinusitis (ARS) is a sudden, symptomatic inflammation of the nasal and paranasal mucosa. It is usually caused by respiratory virus infection, but bacteria complicate for a small number of ARS patients. The differential diagnostics between viral and bacterial pathogens is difficult and currently no rapid methodology exists, so antibiotics are overprescribed. The electronic nose (eNose) has shown the ability to detect diseases from gas mixtures. Differential mobility spectrometry (DMS) is a next-generation device that can separate ions based on their different mobility in high and low electric fields. Five common rhinosinusitis bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa) were analysed in vitro with DMS. Classification was done using linear discriminant analysis (LDA) and k-nearest neighbour (KNN). The results were validated using leave-one-out cross-validation and separate train and test sets. With the latter, 77% of the bacteria were classified correctly with LDA. The comparative figure with KNN was 79%. In one train-test set, P. aeruginosa was excluded and the four most common ARS bacteria were analysed with LDA and KNN; the correct classification rate was 83 and 85%, respectively. DMS has shown its potential in detecting rhinosinusitis bacteria in vitro. The applicability of DMS needs to be studied with rhinosinusitis patients.

Tissue Identification in a Porcine Model by Differential Ion Mobility Spectrometry Analysis of Surgical Smoke.

Electrosurgery is widely used in various surgical operations. When tissue is cut with high-frequency current, the cell contents at the incision area evaporate and together with water and possible soot particles, form surgical smoke. The smoke contains cell metabolites, and therefore, possible biomarkers for cancer or bacterial infection. Thus, the analysis of surgical smoke could be used in intraoperative medical diagnostics. We present a method that can be used to detect the characteristics of various tissue types by means of differential ion mobility spectrometry (DMS) analysis of surgical smoke. We used our method to test tissue identification with ten different porcine tissues. We classified the DMS responses with cross-validated linear discriminant analysis models. The classification accuracy in a measurement set with ten tissue types was 95%. The presented tissue identification by DMS analysis of surgical smoke is a proof-of-concept, which opens the possibility to research the method in diagnosing human tissues and diseases in the future.

The characterization of surgical smoke from various tissues and its implications for occupational safety.

Electrosurgery produces surgical smoke. Different tissues produce different quantities and types of smoke, so we studied the particle characteristics of this surgical smoke in order to analyze the implications for the occupational health of the operation room personnel. We estimated the deposition of particulate matter (PM) from surgical smoke on the respiratory tract of operation room personnel using clinically relevant tissues from Finnish landrace porcine tissues including skeletal muscle, liver, subcutaneous fat, renal pelvis, renal cortex, lung, bronchus, cerebral gray and white matter, and skin. In order to standardize the electrosurgical cuts and smoke concentrations, we built a customized computer-controlled platform. The smoke particles were analyzed with an electrical low pressure impactor (ELPI), which measures the concentration and aerodynamic size distribution of particles with a diameter between 7 nm and 10 µm. There were significant differences in the mass concentration and size distribution of the surgical smoke particles depending on the electrocauterized tissue. Of the various tissues tested, liver yielded the highest number of particles. In order to better estimate the health hazard, we propose that the tissues can be divided into three distinct classes according to their surgical smoke production: 1) high-PM tissue for liver; 2) medium-PM tissues for renal cortex, renal pelvis, and skeletal muscle; and 3) low-PM tissues for skin, gray matter, white matter, bronchus, and subcutaneous fat.

A survey on the feasibility of surface EMG in facial pacing.

A survey on the feasibility of surface electromyography (EMG) measurements in facial pacing is presented. Pacing for unilateral facial paralysis consists of the measurement of activity from the healthy side of the face and functional electrical stimulation to reanimate the paralyzed one. The goal of this study is to evaluate the feasibility of surface EMG as a measurement method to detect muscle activations and to determine their intensities. Prior work is discussed, and results from experiments where 12 participants carried out a set of facial movements are presented. EMG was registered from zygomaticus major (smile), orbicularis oris (lip pucker), orbicularis oculi (eye blink), corrugator supercilii (frown), and masseter (chew). Most important facial functions that are limited due to the paralysis are blinking, smiling, and puckering. With majority of the participants, crosstalk between the measured EMG channels was found to be acceptably small to be able to pace smiling and puckering based on detecting their contraction intensities from the healthy side. However, pacing blinking based on orbicularis oculi EMG measurement does not seem possible due to crosstalk from other muscles, but the electro-oculographic (EOG) signals that couple to the same measurement channel could help to detect eye blinks and trigger stimuli. Futhermore, masseter greatly disturbs EMG measurement of most facial muscles, which needs to be addressed in the pacing system to avoid falsely interpreting its activity as the activity of another muscle.

Effects of sensor type and sensor location on signal quality in bed mounted ballistocardiographic heart rate and respiration monitoring.

Sleeping is a crucial part of our circadian rhythm and the quality of sleep has substantial impact on the quality of life in general and the overall well-being of a person. That is why sleep related physiological measurements have been in the focus of many scientific studies along the years, and why a large number of different measurement methods have been developed for this purpose. The ability to monitor heart rate respiration without any sensors or electrodes being directly attached to the body is extremely useful especially in long-term monitoring and it allows automated daily measurements without any medical staff present. This is the reason why ballistocardiographic force sensors and accelerometers have been introduced alongside electrocardiography (ECG) and thermistors or respiration belts as a means to monitor the heart rate and respiration during sleep. While ECG remains as the most reliable and accurate method for heart rate monitoring, the development of unobtrusive monitoring methods has improved to the point where the commercialization of such sleep monitoring systems has been possible. In this paper, the signals of five sensors and sensor placement combinations for measuring physiological parameters from a sleeping person are evaluated and compared in terms of their measurement sensitivities and waveform quality. The sensors are accelerometer and film type force sensors made of PVDF and EMFi material placed under the mattress topper and PVDF and EMFi sensors placed under the bed posts.