Mucosal melanomas of different anatomic sites share a common global DNA methylation profile with cutaneous melanoma but show location-dependent patterns of genetic and epigenetic alterations.

Cutaneous, ocular, and mucosal melanomas are histologically indistinguishable tumors that are driven by a different spectrum of genetic alterations. With current methods, identification of the site of origin of a melanoma metastasis is challenging. DNA methylation profiling has shown promise for the identification of the site of tumor origin in various settings. Here we explore the DNA methylation landscape of melanomas from different sites and analyze if different melanoma origins can be distinguished by their epigenetic profile. We performed DNA methylation analysis, next generation DNA panel sequencing, and copy number analysis of 82 non-cutaneous and 25 cutaneous melanoma samples. We further analyzed eight normal melanocyte cell culture preparations. DNA methylation analysis separated uveal melanomas from melanomas of other primary sites. Mucosal, conjunctival, and cutaneous melanomas shared a common global DNA methylation profile. Still, we observed location-dependent DNA methylation differences in cancer-related genes, such as low frequencies of RARB (7/63) and CDKN2A promoter methylation (6/63) in mucosal melanomas, or a high frequency of APC promoter methylation in conjunctival melanomas (6/9). Furthermore, all investigated melanomas of the paranasal sinus showed loss of PTEN expression (9/9), mainly caused by promoter methylation. This was less frequently seen in melanomas of other sites (24/98). Copy number analysis revealed recurrent amplifications in mucosal melanomas, including chromosomes 4q, 5p, 11q and 12q. Most melanomas of the oral cavity showed gains of chromosome 5p with TERT amplification (8/10), while 11q amplifications were enriched in melanomas of the nasal cavity (7/16). In summary, mucosal, conjunctival, and cutaneous melanomas show a surprisingly similar global DNA methylation profile and identification of the site of origin by DNA methylation testing is likely not feasible. Still, our study demonstrates tumor location-dependent differences of promoter methylation frequencies in specific cancer-related genes together with tumor site-specific enrichment for specific chromosomal changes and genetic mutations. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel-Lindau disease-related tumours.

AIMS: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. METHODS: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. RESULTS: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). CONCLUSION: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.

Intracranial Pressure and Intracranial Elastance Monitoring in Neurocritical Care.

Patients with acute brain injuries tend to be physiologically unstable and at risk of rapid and potentially life-threatening decompensation due to shifts in intracranial compartment volumes and consequent intracranial hypertension. Invasive intracranial pressure (ICP) monitoring therefore remains a cornerstone of modern neurocritical care, despite the attendant risks of infection and damage to brain tissue arising from the surgical placement of a catheter or pressure transducer into the cerebrospinal fluid or brain tissue compartments. In addition to ICP monitoring, tracking of the intracranial capacity to buffer shifts in compartment volumes would help in the assessment of patient state, inform clinical decision making, and guide therapeutic interventions. We review the anatomy, physiology, and current technology relevant to clinical management of patients with acute brain injury and outline unmet clinical needs to advance patient monitoring in neurocritical care.

Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity.

Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas-including the prognostically relevant SDH mutations-are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.

Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience.

Recently, we described a machine learning approach for classification of central nervous system tumors based on the analysis of genome-wide DNA methylation patterns [6]. Here, we report on DNA methylation-based central nervous system (CNS) tumor diagnostics conducted in our institution between the years 2015 and 2018. In this period, more than 1000 tumors from the neurosurgical departments in Heidelberg and Mannheim and more than 1000 tumors referred from external institutions were subjected to DNA methylation analysis for diagnostic purposes. We describe our current approach to the integrated diagnosis of CNS tumors with a focus on constellations with conflicts between morphological and molecular genetic findings. We further describe the benefit of integrating DNA copy-number alterations into diagnostic considerations and provide a catalog of copy-number changes for individual DNA methylation classes. We also point to several pitfalls accompanying the diagnostic implementation of DNA methylation profiling and give practical suggestions for recurring diagnostic scenarios.

Unobtrusive Vital Sign Monitoring in Automotive Environments-A Review.

This review provides an overview of unobtrusive monitoring techniques that could be used to monitor some of the human vital signs (i.e., heart activity, breathing activity, temperature and potentially oxygen saturation) in a car seat. It will be shown that many techniques actually measure mechanical displacement, either on the body surface and/or inside the body. However, there are also techniques like capacitive electrocardiogram or bioimpedance that reflect electrical activity or passive electrical properties or thermal properties (infrared thermography). In addition, photopleythysmographic methods depend on optical properties (like scattering and absorption) of biological tissues and-mainly-blood. As all unobtrusive sensing modalities are always fragile and at risk of being contaminated by disturbances (like motion, rapidly changing environmental conditions, triboelectricity), the scope of the paper includes a survey on redundant sensor arrangements. Finally, this review also provides an overview of automotive demonstrators for vital sign monitoring.

Monitoring of Cardiorespiratory Signals Using Thermal Imaging: A Pilot Study on Healthy Human Subjects.

Heart rate (HR) and respiratory rate (RR) are important parameters for patient assessment. However, current measurement techniques require attachment of sensors to the patient’s body, often leading to discomfort, stress and even pain. A new algorithm is presented for monitoring both HR and RR using thermal imaging. The cyclical ejection of blood flow from the heart to the head (through carotid arteries and thoracic aorta) leads to periodic movements of the head; these vertical movements are used to assess HR. Respiratory rate is estimated by using temperature fluctuations under the nose during the respiratory cycle. To test the viability and feasibility of this approach, a pilot study was conducted with 20 healthy subjects (aged 18⁻36 and 1 aged 50 years). The study consisted of two phases: phase A (frontal view acquisitions) and phase B (side view acquisitions). To validate the results, photoplethysmography and thoracic effort (piezoplethysmography) were simultaneously recorded. High agreement between infrared thermography and ground truth/gold standard was achieved. For HR, the root-mean-square errors (RMSE) for phases A and B were 3.53 ± 1.53 and 3.43 ± 1.61 beats per minute, respectively. For RR, the RMSE between thermal imaging and piezoplethysmography stayed around 0.71 ± 0.30 breaths per minute (phase A). This study demonstrates that infrared thermography may be a promising, clinically relevant alternative for the assessment of HR and RR.

RheoStim: Development of an Adaptive Multi-Sensor to Prevent Venous Stasis.

Chronic venous insufficiency of the lower limbs is often underestimated and, in the absence of therapy, results in increasingly severe complications, including therapy-resistant tissue defects. Therefore, early diagnosis and adequate therapy is of particular importance. External counter pulsation (ECP) therapy is a method used to assist the venous system. The main principle of ECP is to squeeze the inner leg vessels by muscle contractions, which are evoked by functional electrical stimulation. A new adaptive trigger method is proposed, which improves and supplements the current therapeutic options by means of pulse synchronous electro-stimulation of the muscle pump. For this purpose, blood flow is determined by multi-sensor plethysmography. The hardware design and signal processing of this novel multi-sensor plethysmography device are introduced. The merged signal is used to determine the phase of the cardiac cycle, to ensure stimulation of the muscle pump during the filling phase of the heart. The pulse detection of the system is validated against a gold standard and provides a sensitivity of 98% and a false-negative rate of 2% after physical exertion. Furthermore, flow enhancement of the system has been validated by duplex ultrasonography. The results show a highly increased blood flow in the popliteal vein at the knee.

System Description and First Application of an FPGA-Based Simultaneous Multi-Frequency Electrical Impedance Tomography.

A new prototype of a multi-frequency electrical impedance tomography system is presented. The system uses a field-programmable gate array as a main controller and is configured to measure at different frequencies simultaneously through a composite waveform. Both real and imaginary components of the data are computed for each frequency and sent to the personal computer over an ethernet connection, where both time-difference imaging and frequency-difference imaging are reconstructed and visualized. The system has been tested for both time-difference and frequency-difference imaging for diverse sets of frequency pairs in a resistive/capacitive test unit and in self-experiments. To our knowledge, this is the first work that shows preliminary frequency-difference images of in-vivo experiments. Results of time-difference imaging were compared with simulation results and shown that the new prototype performs well at all frequencies in the tested range of 60 kHz-960 kHz. For frequency-difference images, further development of algorithms and an improved normalization process is required to correctly reconstruct and interpreted the resulting images.

An adaptive Kalman filter approach for cardiorespiratory signal extraction and fusion of non-contacting sensors.

BACKGROUND: Extracting cardiorespiratory signals from non-invasive and non-contacting sensor arrangements, i.e. magnetic induction sensors, is a challenging task. The respiratory and cardiac signals are mixed on top of a large and time-varying offset and are likely to be disturbed by measurement noise. Basic filtering techniques fail to extract relevant information for monitoring purposes. METHODS: We present a real-time filtering system based on an adaptive Kalman filter approach that separates signal offsets, respiratory and heart signals from three different sensor channels. It continuously estimates respiration and heart rates, which are fed back into the system model to enhance performance. Sensor and system noise covariance matrices are automatically adapted to the aimed application, thus improving the signal separation capabilities. We apply the filtering to two different subjects with different heart rates and sensor properties and compare the results to the non-adaptive version of the same Kalman filter. Also, the performance, depending on the initialization of the filters, is analyzed using three different configurations ranging from best to worst case. RESULTS: Extracted data are compared with reference heart rates derived from a standard pulse-photoplethysmographic sensor and respiration rates from a flowmeter. In the worst case for one of the subjects the adaptive filter obtains mean errors (standard deviations) of -0.2 min(-1) (0.3 min(-1)) and -0.7 bpm (1.7 bpm) (compared to -0.2 min(-1) (0.4 min(-1)) and 42.0 bpm (6.1 bpm) for the non-adaptive filter) for respiration and heart rate, respectively. In bad conditions the heart rate is only correctly measurable when the Kalman matrices are adapted to the target sensor signals. Also, the reduced mean error between the extracted offset and the raw sensor signal shows that adapting the Kalman filter continuously improves the ability to separate the desired signals from the raw sensor data. The average total computational time needed for the Kalman filters is under 25% of the total signal length rendering it possible to perform the filtering in real-time. CONCLUSIONS: It is possible to measure in real-time heart and breathing rates using an adaptive Kalman filter approach. Adapting the Kalman filter matrices improves the estimation results and makes the filter universally deployable when measuring cardiorespiratory signals.

The MAIN Shirt: a textile-integrated magnetic induction sensor array.

A system is presented for long-term monitoring of respiration and pulse. It comprises four non-contact sensors based on magnetic eddy current induction that are textile-integrated into a shirt. The sensors are technically characterized by laboratory experiments that investigate the sensitivity and measuring depth, as well as the mutual interaction between adjacent pairs of sensors. The ability of the device to monitor respiration and pulse is demonstrated by measurements in healthy volunteers. The proposed system (called the MAIN (magnetic induction) Shirt) does not need electrodes or any other skin contact. It is wearable, unobtrusive and can easily be integrated into an individual's daily routine. Therefore, the system appears to be a suitable option for long-term monitoring in a domestic environment or any other unsupervised telemonitoring scenario.

Open cranium model for the study of cerebrovascular dynamics in intracranial hypertension.

BACKGROUND: Significant research has been devoted to developing noninvasive approaches to neuromonitoring. Clinical validation of such approaches is often limited, with minimal data available in the clinically relevant elevated ICP range. NEW METHOD: To allow ultrasound-guided placement of an intraventricular catheter and to perform simultaneous long-duration ICP and ultrasound recordings of cerebral blood flow, we developed a large unilateral craniectomy in a swine model. We also used a microprocessor-controlled actuator for intraventricular saline infusion to reliably and reversibly manipulate ICP according to pre-determined profiles. RESULTS: The model was reproducible, resulting in over 80 hours of high-fidelity, multi-parameter physiological waveform recordings in twelve animals, with ICP ranging from 2 to 78 mmHg. ICP elevations were reversible and reproducible according to two predetermined profiles: a stepwise elevation up to an ICP of 30-35 mmHg and return to normotension, and a clinically significant plateau wave. Finally, ICP was elevated to extreme levels of greater than 60 mmHg, simulating extreme clinical emergency. COMPARISON WITH EXISTING METHODS: Existing methods for ICP monitoring in large animals typically relied on burr-hole approaches for catheter placement. Accurate catheter placement can be difficult in pigs, given the thickness of their skull. Additionally, ultrasound is significantly attenuated by the skull. The open cranium model overcomes these limitations. CONCLUSIONS: The hemicraniectomy model allowed for verified placement of the intraventricular catheter, and reversible and reliable ICP manipulation over a wide range. The large dural window additionally allowed for long-duration recording of cerebral blood flow velocity from the middle cerebral artery.

Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas.

The combination of DNA methylation analysis with histopathological and genetic features allows for a more accurate risk stratification and classification of meningiomas. Nevertheless, the implications of this classification for patients with grade 2 meningiomas, a particularly heterogeneous tumor entity, are only partially understood. We correlate the outcomes of histopathologically confirmed grade 2 meningioma with an integrated molecular-morphologic risk stratification and determine its clinical implications. Grade 2 meningioma patients treated at our institution were re-classified using an integrated risk stratification involving DNA methylation array-based data, copy number assessment and TERT promoter mutation analyses. Grade 2 meningioma cases according to the WHO 2021 criteria treated between 2007 and 2021 (n = 100) were retrospectively analyzed. The median clinical and radiographic follow-up periods were 59.8 and 54.4 months. A total of 38 recurrences and 17 deaths were observed. The local control rates of the entire cohort after 2-, 4-, and 6-years were 84.3%, 68.5%, and 50.8%, with a median local control time of 77.2 months. The distribution of the integrated risk groups were as follows: 31 low, 54 intermediate, and 15 high risk cases. In the multivariable Cox regression analysis, integrated risk groups were significantly associated with the risk of local recurrence (hazard ratio (HR) intermediate: 9.91, HR high-risk: 7.29, p < 0.01). Gross total resections decreased the risk of local tumor progression (HR gross total resection: 0.19, p < 0.01). The comparison of 1p status and integrated risk groups (low vs. intermediate/high) revealed nearly identical local control rates within their respective subgroups. In summary, only around 50% of WHO 2021 grade 2 meningiomas have an intermediate risk profile. Integrated molecular risk stratification is crucial to guide the management of patients with grade 2 tumors and should be routinely applied to avoid over- and undertreatment, especially concerning the use of adjuvant radiotherapy.

Eliminating the Trade-off Between Resolution and Sampling Rate in Magnetic Induction Based Cardiorespiratory Sensors.

This paper proposes a novel algorithm that allows a significant improvement of the resolution of frequency modulated magnetic induction sensors while providing high sampling rates. We have implemented this approach in a frequency modulated magnetic induction sensor and our first measurements demonstrate the improvement of the sensor's signal quality.

A Novel Type of IDH-wildtype Glioma Characterized by Gliomatosis Cerebri-like Growth Pattern, TERT Promoter Mutation, and Distinct Epigenetic Profile.

Diffuse gliomas in adults encompass a heterogenous group of central nervous system neoplasms. In recent years, extensive (epi-)genomic profiling has identified several glioma subgroups characterized by distinct molecular characteristics, most importantly IDH1/2 and histone H3 mutations. A group of 16 diffuse gliomas classified as "adult-type diffuse high-grade glioma, IDH-wildtype, subtype F (HGG-F)" was identified by the DKFZ v12.5 Brain Tumor Classifier . Histopathologic characterization, exome sequencing, and review of clinical data was performed in all cases. Based on unsupervised t -distributed stochastic neighbor embedding and clustering analysis of genome-wide DNA methylation data, HGG-F shows distinct epigenetic profiles separate from established central nervous system tumors. Exome sequencing demonstrated frequent TERT promoter (12/15 cases), PIK3R1 (11/16), and TP53 mutations (5/16). Radiologic characteristics were reminiscent of gliomatosis cerebri in 9/14 cases (64%). Histopathologically, most cases were classified as diffuse gliomas (7/16, 44%) or were suspicious for the infiltration zone of a diffuse glioma (5/16, 31%). None of the cases demonstrated microvascular proliferation or necrosis. Outcome of 14 patients with follow-up data was better compared to IDH-wildtype glioblastomas with a median progression-free survival of 58 months and overall survival of 74 months (both P <0.0001). Our series represents a novel type of adult-type diffuse glioma with distinct molecular and clinical features. Importantly, we provide evidence that TERT promoter mutations in diffuse gliomas without further morphologic or molecular signs of high-grade glioma should be interpreted in the context of the clinicoradiologic presentation as well as epigenetic profile and may not be suitable as a standalone marker for glioblastoma, IDH-wildtype.

Identification of dental pain sensation based on cardiorespiratory signals.

The aim of this study is to investigate the feasibility of the detection of brief periods of pain sensation based on cardiorespiratory signals during dental pain triggers. Twenty patients underwent dental treatment and reported their pain events by pressing a push button while ECG, PPG, and thoracic effort signals were simultaneously recorded. Potential pain-indicating features were calculated from the physiological data (sample length of 6 s) and were used for supervised learning of a Random forest pain detector. The best feature combination was determined by Feature forward selection. The best feature combination comprises nine feature groups consisting of four respiratory and five cardiac related groups. The final algorithm achieved a sensitivity of 87% and a specificity of 63% with an AUC of 0.828. Using supervised learning it is possible to train an algorithm to differentiate between short time intervals of pain and no pain solely based on cardiorespiratory signals. An on-site and real-time detection and rating of pain sensations would allow a precise, individuum- and treatment-tailored administration of local anesthesia. Severe phases of pain could be paused or avoided, this would allow more comfortable treatment and yield better patient compliance.

Distortion of the Intracranial Pressure Waveform by Extraventricular Drainage System.

OBJECTIVE: To investigate whether intracranial pressure (ICP) waveform measurements obtained from extraventricular drainage (EVD) systems are suitable for the calculation of intracranial elastance (ICE) or cerebrovascular pressure autoregulation (PAR) indices. METHODS: The transfer characteristic of an EVD system is investigated by its step and frequency responses with focus on the low frequency (LF) range from 0.02 to 0.065 Hz (important in PAR) and the location of the system's first resonance frequency (important for ICE). The effects of opening the distal end of the EVD for drainage of cerebrospinal fluid and the presence of trapped air bubbles are also investigated. RESULTS: The EVD system exhibits a first resonant frequency below 4 Hz, resulting in significant distortion of the measured ICP waveform. The frequency response in the LF range only remains flat when the EVD is closed. Opening the drain results in drops in magnitude and phase along the entire frequency range above DC. Air bubbles close to the EVD catheter tip affect the LF range while an air bubble close to the pressure transducer further decreases the first resonant frequency. Tests with actual ICP waveforms confirmed EVD-induced waveform distortions that can lead to erroneous ICE estimation. CONCLUSION: EVD-based ICP measurements distort the waveform morphology. PAR indices based on LF information are only valid if the EVD is closed. EVD-based ICE estimation is to be avoided. SIGNIFICANCE: ICP waveform analyses to derive information about ICE and PAR should be critically questioned if only EVD derived ICP signals are at hand.

Classification of chronic venous diseases based on skin temperature patterns.

Objective. Infrared thermography has the potential to complement the classification of chronic venous diseases (CVD), but lacks sophisticated insights on the association between recorded skin temperatures and the severity of CVD. This research aims to identify temperature patterns in the lower legs of patients that are distinct in specific forms of CVD, including florid ulcers.Approach. Infrared images were acquired in a clinical trial with 36 patients and segmented using a region selection algorithm. The regions were analyzed with respect to seven predefined features. The most prominent thermal features were translated into rules to classify CVD.Main results. Patients with mild forms of CVD show local increases in skin temperature by more than 1.5 °C. These regions were 2.0 °C warmer when CVD is more severe. Temperature variations of on average 0.4 °C occurred within venous leg ulcers. Furthermore, these wounds were 1.1 °C-6.3 °C colder than periwound skin.Significance. Temperature patterns characterized by differences in temperature that occur within a few centimeters or millimeters are distinct to specific stages of CVD. These patterns are present in the locations of varicose veins and tissue damages.Significance. The findings increase the body of knowledge on the potential for the early detection of CVD using infrared thermography. Applying the presented algorithms and rules, infrared thermography may become a complementary tool for the objective classification of CVD.

Capacitive ECG Monitoring in Cardiac Patients During Simulated Driving.

OBJECTIVE: This study aims to compare the informative value of a capacitively coupled electrocardiogram (cECG) to a conventional galvanic reference ECG (rECG) in patients after a major cardiac event under simulated driving conditions. Addressed research questions are the comparison and coherence of cECG and rECG by means of the signal quality, the artifact rate, the rate of assessable data for differential diagnosis, the visibility of characteristic ECG structures in cECG, the precision of ECG time intervals, and heart rate (in particular, despite possible waveform deformations due to the cardiac preconditions). METHODS: In a clinical trial, cECG and rECG data were recorded from ten patients after a major cardiac event. The cECG and rECG data were blindly evaluated by two cardiologists with regard to signal quality, artifacts, assessable data for differential diagnosis, visibility of ECG structures, and ECG time intervals. The results were statistically compared. RESULTS: The cECG presented with more artifacts, an inferior signal quality, and less assessable data. However, when the data were assessable, determination of the ECG interval lengths was coherent to the one obtained from the rECG. CONCLUSION: When the signal quality is sufficient, the cECG yields the same informative value as the rECG. SIGNIFICANCE: For certain scenarios, cECG might replace rECG systems. Hence, it is an important research question whether a similar amount of information can be obtained using a cECG system.

A Multi-Modal Sensor for a Bed-Integrated Unobtrusive Vital Signs Sensing Array.

In this paper, we present a novel unobtrusive multi-modal sensor for monitoring of physiological parameters featuring capacitive electrocardiogram (cECG), reflective photoplethysmogram (rPPG), and magnetic induction monitoring (MI) in a single sensor. The sensor system comprises sensor nodes designed and optimized for integration into a grid-like array of multiple sensors in a bed and a central controller box for data collection and processing. Hence, it is highly versatile in application and suitable for unobtrusive monitoring of vital signs, both in a professional setting and a home-care environment. The presented hardware design takes both inter-modal interference between cECG and MI into account as well as intra-modal interference due to cross talk between two MI sensors in close vicinity. In a lab study, we evaluated a prototype of our new multi-modal sensor with two sensor nodes on four healthy subjects. The subjects were lying on the sensors and exercising with a hand grip in order to increase heart rate and thus evaluate our sensor both during changing physiological parameters as well as a wider range of those. Heart beat intervals and heart rate variability were derived from both cECG and rPPG. Breathing intervals were derived from the MI sensor. For heart beat intervals, we achieved an RMSE of 2.3 ms and a correlation of 0.99 using cECG. Similarly, using rPPG, an RMSE of 18.9 ms with a correlation of 0.99 was achieved. With regard to breathing intervals derived from MI, we achieved an RMSE of 1.12 s and a correlation of 0.90.