Detection of invasive ductal carcinoma in quadrant breast areas by electrical impedance tomography implemented with gaussian relaxation-time distribution (EIT-GRTD).

Invasive ductal carcinoma (IDC) in breast specimens has been detected in the quadrant breast area: (I) upper outer, (II) upper inner, (III) lower inner, and (IV) lower outer areas by electrical impedance tomography implemented with Gaussian relaxation-time distribution (EIT-GRTD). The EIT-GRTD consists of two steps which are (1) the optimum frequencyfoptselection and (2) the time constant enhancement of breast imaging reconstruction.foptis characterized by a peak in the majority measurement pair of the relaxation-time distribution functionγ,which indicates the presence of IDC.γrepresents the inverse of conductivity and indicates the response of breast tissues to electrical currents across varying frequencies based on the Voigt circuit model. The EIT-GRTD is quantitatively evaluated by multi-physics simulations using a hemisphere container of mimic breast, consisting of IDC and adipose tissues as normal breast tissue under one condition with known IDC in quadrant breast area II. The simulation results show that EIT-GRTD is able to detect the IDC in four layers atfopt= 30, 170 Hz. EIT-GRTD is applied in the real breast by employed six mastectomy specimens from IDC patients. The placement of the mastectomy specimens in a hemisphere container is an important factor in the success of quadrant breast area reconstruction. In order to perform the evaluation, EIT-GRTD reconstruction images are compared to the CT scan images. The experimental results demonstrate that EIS-GRTD exhibits proficiency in the detection of the IDC in quadrant breast areas while compared qualitatively to CT scan images.

Sex differences in chest electrical impedance tomography findings.

Objective.Electrical impedance tomography (EIT) has been used to determine regional lung ventilation distribution in humans for decades, however, the effect of biological sex on the findings has hardly ever been examined. The aim of our study was to determine if the spatial distribution of ventilation assessed by EIT during quiet breathing was influenced by biological sex.Approach.219 adults with no known acute or chronic lung disease were examined in sitting position with the EIT electrodes placed around the lower chest (6th intercostal space). EIT data were recorded at 33 images/s during quiet breathing for 60 s. Regional tidal impedance variation was calculated in all EIT image pixels and the spatial distribution of the values was determined using the established EIT measures of centre of ventilation in ventrodorsal (CoVvd) and right-to-left direction (CoVrl), the dorsal and right fraction of ventilation, and ventilation defect score.Main results.After exclusion of one subject due to insufficient electrode contact, 218 data sets were analysed (120 men, 98 women) (age: 53 ± 18 vs 50 ± 16 yr (p= 0.2607), body mass index: 26.4 ± 4.0 vs 26.4 ± 6.6 kg m-2(p= 0.9158), mean ± SD). Highly significant differences in ventilation distribution were identified between men and women between the right and left chest sides (CoVrl: 47.0 ± 2.9 vs 48.8 ± 3.3% of chest diameter (p< 0.0001), right fraction of ventilation: 0.573 ± 0.067 vs 0.539 ± 0.071 (p= 0.0004)) and less significant in the ventrodorsal direction (CoVvd: 55.6 ± 4.2 vs 54.5 ± 3.6% of chest diameter (p= 0.0364), dorsal fraction of ventilation: 0.650 ± 0.121 vs 0.625 ± 0.104 (p= 0.1155)). Ventilation defect score higher than one was found in 42.5% of men but only in 16.6% of women.Significance.Biological sex needs to be considered when EIT findings acquired in upright subjects in a rather caudal examination plane are interpreted. Sex differences in chest anatomy and thoracoabdominal mechanics may explain the results.

First real-time imaging of bronchoscopic lung volume reduction by electrical impedance tomography.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) with one-way endobronchial valves (EBV) has better outcomes when the target lobe has poor collateral ventilation, resulting in complete lobe atelectasis. High-inspired oxygen fraction (FIO2) promotes atelectasis through faster gas absorption after airway occlusion, but its application during BLVR with EBV has been poorly understood. We aimed to investigate the real-time effects of FIO2 on regional lung volumes and regional ventilation/perfusion by electrical impedance tomography (EIT) during BLVR with EBV. METHODS: Six piglets were submitted to left lower lobe occlusion by a balloon-catheter and EBV valves with FIO2 0.5 and 1.0. Regional end-expiratory lung impedances (EELI) and regional ventilation/perfusion were monitored. Local pocket pressure measurements were obtained (balloon occlusion method). One animal underwent simultaneous acquisitions of computed tomography (CT) and EIT. Regions-of-interest (ROIs) were right and left hemithoraces. RESULTS: Following balloon occlusion, a steep decrease in left ROI-EELI with FIO2 1.0 occurred, 3-fold greater than with 0.5 (p < 0.001). Higher FIO2 also enhanced the final volume reduction (ROI-EELI) achieved by each valve (p < 0.01). CT analysis confirmed the denser atelectasis and greater volume reduction achieved by higher FIO2 (1.0) during balloon occlusion or during valve placement. CT and pocket pressure data agreed well with EIT findings, indicating greater strain redistribution with higher FIO2. CONCLUSIONS: EIT demonstrated in real-time a faster and more complete volume reduction in the occluded lung regions under high FIO2 (1.0), as compared to 0.5. Immediate changes in the ventilation and perfusion of ipsilateral non-target lung regions were also detected, providing better estimates of the full impact of each valve in place. TRIAL REGISTRATION: Not applicable.

Absolute values of regional ventilation-perfusion mismatch in patients with ARDS monitored by electrical impedance tomography and the role of dead space and shunt compensation.

BACKGROUND: Assessment of regional ventilation/perfusion (V'/Q) mismatch using electrical impedance tomography (EIT) represents a promising advancement for personalized management of the acute respiratory distress syndrome (ARDS). However, accuracy is still hindered by the need for invasive monitoring to calibrate ventilation and perfusion. Here, we propose a non-invasive correction that uses only EIT data and characterized patients with more pronounced compensation of V'/Q mismatch. METHODS: We enrolled twenty-one ARDS patients on controlled mechanical ventilation. Cardiac output was measured invasively, and ventilation and perfusion were assessed by EIT. Relative V'/Q maps by EIT were calibrated to absolute values using the minute ventilation to invasive cardiac output (MV/CO) ratio (V'/Q-ABS), left unadjusted (V'/Q-REL), or corrected by MV/CO ratio derived from EIT data (V'/Q-CORR). The ratio between ventilation to dependent regions and perfusion reaching shunted units ( V D ' /QSHUNT) was calculated as an index of more effective hypoxic pulmonary vasoconstriction. The ratio between perfusion to non-dependent regions and ventilation to dead space units (QND/ V DS ' ) was calculated as an index of hypocapnic pneumoconstriction. RESULTS: Our calibration factor correlated with invasive MV/CO (r = 0.65, p < 0.001), showed good accuracy and no apparent bias. Compared to V'/Q-ABS, V'/Q-REL maps overestimated ventilation (p = 0.013) and perfusion (p = 0.002) to low V'/Q units and underestimated ventilation (p = 0.011) and perfusion (p = 0.008) to high V'/Q units. The heterogeneity of ventilation and perfusion reaching different V'/Q compartments was underestimated. V'/Q-CORR maps eliminated all these differences with V'/Q-ABS (p > 0.05). Higher V D ' / Q SHUNT correlated with higher PaO2/FiO2 (r = 0.49, p = 0.025) and lower shunt fraction (ρ = - 0.59, p = 0.005). Higher Q ND / V DS ' correlated with lower PEEP (ρ = - 0.62, p = 0.003) and plateau pressure (ρ = - 0.59, p = 0.005). Lower values of both indexes were associated with less ventilator-free days (p = 0.05 and p = 0.03, respectively). CONCLUSIONS: Regional V'/Q maps calibrated with a non-invasive EIT-only method closely approximate the ones obtained with invasive monitoring. Higher efficiency of shunt compensation improves oxygenation while compensation of dead space is less needed at lower airway pressure. Patients with more effective compensation mechanisms could have better outcomes.

Non-invasive Visualization and Characterization of Bile Canaliculus Formation Using Refractive Index Tomography.

The vital role of bile canaliculus (BC) in liver function is closely related to its morphology. Electron microscopy has contributed to understanding BC morphology; however, its invasiveness limits its use in living specimens. Here, we report non-invasive characterization of BC formation using refractive index (RI) tomography. First, we investigated and characterized the RI distribution of BCs in two-dimensional (2D) cultured HepG2 cells. BCs were identified based on their distinct morphology and functionality, as confirmed using a fluorescence-labeled bile acid analog. The RI distribution of BCs exhibited three common features: (1) luminal spaces with a low RI between adjacent hepatocytes; (2) luminal spaces surrounded by a membranous structure with a high RI; and (3) multiple microvillus structures with a high RI within the lumen. Second, we demonstrated the characterization of BC structures in a three-dimensional (3D) culture model, which is more relevant to the in vivo environment but more difficult to evaluate than 2D cultures. Various BC structures were identified inside HepG2 spheroids with the three features of RI distribution. Third, we conducted comparative analyses and found that the BC lumina of spheroids had higher circularity and lower RI standard deviation than 2D cultures. We also addressed comparison of BC and intracellular lumen-like structures within a HepG2 spheroid, and found that the BC lumina had higher RI and longer perimeter than intracellular lumen-like structures. Our demonstration of the non-destructive, label-free visualization and quantitative characterization of living BC structures will be a basis for various hepatological and pharmaceutical applications.

Electrical impedance tomography provides information of brain injury during total aortic arch replacement through its correlation with relative difference of neurological biomarkers.

Postoperative neurological dysfunction (PND) is one of the most common complications after a total aortic arch replacement (TAAR). Electrical impedance tomography (EIT) monitoring of cerebral hypoxia injury during TAAR is a promising technique for preventing the occurrence of PND. This study aimed to explore the feasibility of electrical impedance tomography (EIT) for warning of potential brain injury during total aortic arch replacement (TAAR) through building the correlation between EIT extracted parameters and variation of neurological biomarkers in serum. Patients with Stanford type A aortic dissection and requiring TAAR who were admitted between December 2021 to March 2022 were included. A 16-electrode EIT system was adopted to monitor each patient's cerebral impedance intraoperatively. Five parameters of EIT signals regarding to the hypothermic circulatory arrest (HCA) period were extracted. Meanwhile, concentration of four neurological biomarkers in serum were measured regarding to time before and right after surgery, 12 h, 24 h and 48 h after surgery. The correlation between EIT parameters and variation of serum biomarkers were analyzed. A total of 57 TAAR patients were recruited. The correlation between EIT parameters and variation of biomarkers were stronger for patients with postoperative neurological dysfunction (PND(+)) than those without postoperative neurological dysfunction (PND(-)) in general. Particularly, variation of S100B after surgery had significantly moderate correlation with two parameters regarding to the difference of impedance between left and right brain which were MRAIabs and TRAIabs (0.500 and 0.485 with p < 0.05, respectively). In addition, significantly strong correlations were seen between variation of S100B at 24 h and the difference of average resistivity value before and after HCA phase (ΔARVHCA), the slope of electrical impedance during HCA (kHCA) and MRAIabs (0.758, 0.758 and 0.743 with p < 0.05, respectively) for patients with abnormal S100B level before surgery. Strong correlations were seen between variation of TAU after surgery and ΔARVHCA, kHCA and the time integral of electrical impedance for half flow of perfusion (TARVHP) (0.770, 0.794 and 0.818 with p < 0.01, respectively) for patients with abnormal TAU level before surgery. Another two significantly moderate correlations were found between TRAIabs and variation of GFAP at 12 h and 24 h (0.521 and 0.521 with p < 0.05, respectively) for patients with a normal GFAP serum level before surgery. The correlations between EIT parameters and serum level of neurological biomarkers were significant in patients with PND, especially for MRAIabs and TRAIabs, indicating that EIT may become a powerful assistant for providing a real-time warning of brain injury during TAAR from physiological perspective and useful guidance for intensive care units.

Label-Free Three-Dimensional Morphological Characterization of Cell Death Using Holographic Tomography.

This study presents a novel label-free approach for characterizing cell death states, eliminating the need for complex molecular labeling that may yield artificial or ambiguous results due to technical limitations in microscope resolution. The proposed holographic tomography technique offers a label-free avenue for capturing precise three-dimensional (3D) refractive index morphologies of cells and directly analyzing cellular parameters like area, height, volume, and nucleus/cytoplasm ratio within the 3D cellular model. We showcase holographic tomography results illustrating various cell death types and elucidate distinctive refractive index correlations with specific cell morphologies complemented by biochemical assays to verify cell death states. These findings hold promise for advancing in situ single cell state identification and diagnosis applications.

Bias correction for phase-based cr-MREPT using low resolution B1+ magnitude.

ObjectiveFull-form Magnetic Resonance Electrical Properties Tomography (MREPT) requires bothB1+magnitude and phase information. SinceB1+phase can be obtained faster and with higher SNR compared toB1+magnitude, several phase-based methods have been developed for conductivity imaging. However, phase-based methods suffer from a concave bias due to the assumption that∇|B1+|is negligible in the ROI.ApproachIn this paper, we re-derive the central equation of phase-based cr-MREPT without assuming that∇|B1+|is negligible and thus propose a correction method directly integrated into the equation system.Main resultsProposed method successfully corrects the concave bias on both simulated and experimental data and significantly increases image quality.SignificanceThe proposed correction method depends on a very low-resolution|B1+|map, and therefore the imaging time does not increase significantly for obtainingB1+magnitude. Moreover, correction can be achieved using simulatedB1+magnitude, hence completely removing the additional imaging requirement.

[Research of electrical impedance tomography based on multilayer artificial neural network optimized by Hadamard product for human-chest models].

Electrical impedance tomography (EIT) is a non-radiation, non-invasive visual diagnostic technique. In order to improve the imaging resolution and the removing artifacts capability of the reconstruction algorithms for electrical impedance imaging in human-chest models, the HMANN algorithm was proposed using the Hadamard product to optimize multilayer artificial neural networks (MANN). The reconstructed images of the HMANN algorithm were compared with those of the generalized vector sampled pattern matching (GVSPM) algorithm, truncated singular value decomposition (TSVD) algorithm, backpropagation (BP) neural network algorithm, and traditional MANN algorithm. The simulation results showed that the correlation coefficient of the reconstructed images obtained by the HMANN algorithm was increased by 17.30% in the circular cross-section models compared with the MANN algorithm. It was increased by 13.98% in the lung cross-section models. In the lung cross-section models, some of the correlation coefficients obtained by the HMANN algorithm would decrease. Nevertheless, the HMANN algorithm retained the image information of the MANN algorithm in all models, and the HMANN algorithm had fewer artifacts in the reconstructed images. The distinguishability between the objects and the background was better compared with the traditional MANN algorithm. The algorithm could improve the correlation coefficient of the reconstructed images, and effectively remove the artifacts, which provides a new direction to effectively improve the quality of the reconstructed images for EIT.

3D Multiparametric Photoacoustic Computed Tomography of Primary and Metastatic Tumors in Living Mice.

Photoacoustic computed tomography (PACT), an emerging imaging modality in preclinical cancer research, can provide multiparametric 3D information about structures, physiological functions, and pharmacokinetics. Here, we demonstrate the use of high-definition 3D multiparametric PACT imaging of both primary and metastatic tumors in living mice to noninvasively monitor angiogenesis, carcinogenesis, hypoxia, and pharmacokinetics. The high-definition PACT system with a 1024-element hemispherical ultrasound transducer array provides an isotropic spatial resolution of 380 µm, an effective volumetric field-of-view of 12.8 mm × 12.8 mm × 12.8 mm without scanning, and an acquisition time of <30 s for a whole mouse body. Initially, we monitor the structural progression of the tumor microenvironment (e.g., angiogenesis and vessel tortuosity) after tumor cell inoculation. Then, we analyze the change in oxygen saturation of the tumor during carcinogenesis, verifying induced hypoxia in the tumor's core region. Finally, the whole-body pharmacokinetics are photoacoustically imaged after intravenous injection of micelle-loaded IR780 dye, and the in vivo PACT results are validated in vivo and ex vivo by fluorescence imaging. By employing the premium PACT system and applying multiparametric analyses to subcutaneous primary tumors and metastatic liver tumors, we demonstrate that this PACT system can provide multiparametric analyses for comprehensive cancer research.

A greedy regularized block Kaczmarz method for accelerating reconstruction in magnetic particle imaging.

Objective.Magnetic particle imaging (MPI) is an emerging medical tomographic imaging modality that enables real-time imaging with high sensitivity and high spatial and temporal resolution. For the system matrix reconstruction method, the MPI reconstruction problem is an ill-posed inverse problem that is commonly solved using the Kaczmarz algorithm. However, the high computation time of the Kaczmarz algorithm, which restricts MPI reconstruction speed, has limited the development of potential clinical applications for real-time MPI. In order to achieve fast reconstruction in real-time MPI, we propose a greedy regularized block Kaczmarz method (GRBK) which accelerates MPI reconstruction.Approach.GRBK is composed of a greedy partition strategy for the system matrix, which enables preprocessing of the system matrix into well-conditioned blocks to facilitate the convergence of the block Kaczmarz algorithm, and a regularized block Kaczmarz algorithm, which enables fast and accurate MPI image reconstruction at the same time.Main results.We quantitatively evaluated our GRBK using simulation data from three phantoms at 20 dB, 30 dB, and 40 dB noise levels. The results showed that GRBK can improve reconstruction speed by single orders of magnitude compared to the prevalent regularized Kaczmarz algorithm including Tikhonov regularization, the non-negative Fused Lasso, and wavelet-based sparse model. We also evaluated our method on OpenMPIData, which is real MPI data. The results showed that our GRBK is better suited for real-time MPI reconstruction than current state-of-the-art reconstruction algorithms in terms of reconstruction speed as well as image quality.Significance.Our proposed method is expected to be the preferred choice for potential applications of real-time MPI.

Mechanism of acoustic pressure spectrum shifting toward lower frequencies in applied current thermoacoustic imaging.

Objective. Thermoacoustic tomography (TAT) is a promising imaging technique used for early cancer diagnosis, tumor therapy, animal study and brain imaging. Although it is widely known that the TAT frequency response depends on the pulse width of the source and the size of the object, a thorough comprehension of the quantitative frequency modulation in TAT and the mechanism governing the shift in the thermoacoustic pressure spectrum towards lower frequencies with respect to the excitation source is still lacking. This study aims to understand why the acoustic pressure spectrum and the final voltage signals shift towards lower frequencies in TAT.Approach. We employed a linear time-invariant model. In the proposed model, the applied current thermoacoustic imaging (ACTAI) process is divided into the thermoacoustic stage and the acoustoelectric stage. These two stages are characterized by the thermoacoustic transfer function(TATF) and the transducer transfer function (TDTF), respectively. We confirmed the effectiveness of our model through a rigorous examination involving both simulations and experiments.Main results. Simulation results indicate that the TATF behaves as a low-pass filter. The inherent low-pass nature induces a shift towards low frequencies in the acoustic pressure spectrum. Experiments further confirm this behavior, demonstrating that the final electrical voltage also shifts towards low frequencies. Notably, employing the proposed model, there is a remarkable consistency between the main frequency bands of the synthesized and measured final voltage spectrum.Significance. The proposed model thoroughly explains how the TATF causes shifts to low frequencies in both the acoustic pressure spectrum and the final voltage spectrum in TAT. These insights deepen our understanding of optimizing TAT systems in the frequency domain, including aspects like filter design and transducer selection. Furthermore, we underscore the potential significance of this discovery for medical applications, particularly in the context of cancer diagnosis.

Noise-based correction for electrical impedance tomography.

Objective.Noisy measurements frequently cause noisy and inaccurate images in impedance imaging. No post-processing technique exists to calculate the propagation of measurement noise and use this to suppress noise in the image. The objectives of this work were (1) to develop a post-processing method for noise-based correction (NBC) in impedance tomography, (2) to test whether NBC improves image quality in electrical impedance tomography (EIT), (3) to determine whether it is preferable to use correlated or uncorrelated noise for NBC, (4) to test whether NBC works within vivodata and (5) to test whether NBC is stable across model and perturbation geometries.Approach.EIT was performedin silicoin a 2D homogeneous circular domain and an anatomically realistic, heterogeneous 3D human head domain for four perturbations and 25 noise levels in each case. This was validated by performing EIT for four perturbations in a circular, saline tank in 2D as well as a human head-shaped saline tank with a realistic skull-like layer in 3D. Images were assessed on the error in the weighted spatial variance (WSV) with respect to the true, target image. The effect of NBC was also tested forin vivoEIT data of lung ventilation in a human thorax and cortical activity in a rat brain.Main results.On visual inspection, NBC maintained or increased image quality for all perturbations and noise levels in 2D and 3D, both experimentally andin silico. Analysis of the WSV showed that NBC significantly improved the WSV in nearly all cases. When the WSV was inferior with NBC, this was either visually imperceptible or a transformation between noisy reconstructions. Forin vivodata, NBC improved image quality in all cases and preserved the expected shape of the reconstructed perturbation.Significance.In practice, uncorrelated NBC performed better than correlated NBC and is recommended as a general-use post-processing technique in EIT.

Determination of optimal positive end-expiratory pressure using electrical impedance tomography in infants under general anesthesia: Comparison between supine and prone positions.

AIMS: This study determined the optimal positive end-expiratory pressure levels in infants in supine and prone positions under general anesthesia using electrical impedance tomography (EIT). METHODS: This prospective observational single-centre study included infants scheduled for surgery in the prone position. An electrical impedance tomography sensor was applied after inducing general anesthesia. The optimal positive end-expiratory pressure in the supine position was determined in a decremental trial based on EIT and compliance. Subsequently, the patient's position was changed to prone. Electrical impedance tomography parameters, including global inhomogeneity index, regional ventilation delay, opening pressure, the centre of ventilation, and pendelluft volume, were continuously obtained up to 1 h after prone positioning. The optimal positive end-expiratory pressure in the prone position was similarly determined. RESULTS: Data from 30 infants were analyzed. The mean value of electrical impedance tomography-based optimal positive end-expiratory pressure in the prone position was significantly higher than that in the supine position [10.9 (1.6) cmH2O and 6.1 (0.9) cmH2O, respectively (p < .001)]. Significant differences were observed between electrical impedance tomography- and compliance-based optimal positive end-expiratory pressure. Peak and mean airway, plateau, and driving pressures increased 1 h after prone positioning compared with those in the supine position. In addition, the centre of ventilation for balance in ventilation between the ventral and dorsal regions improved. CONCLUSION: The prone position required higher positive end-expiratory pressure than the supine position in mechanically ventilated infants under general anesthesia. EIT is a promising tool to find the optimal positive end-expiratory pressure, which needs to be individualized.

Assessment of water quality using entropy-weighted quality index, statistical methods and electrical resistivity tomography, Moti village, northern Pakistan.

In this study, twenty-two water samples were collected from boreholes (BH), and streams to evaluate drinking water quality, its distribution, identification of contamination sources and apportionment for Moti village, northern Pakistan. An atomic absorption spectrophotometer (AAS) is utilized to determine the level of heavy metals in water such as arsenic (As), zinc (Zn), lead (Pb), copper (Cu), cadmium (Cd), manganese (Mn), and ferrous (Fe). Groundwater chemistry and its quantitative driving factors were further explored using multivariate statistical methods, Principal Component Analysis (PCA) and Positive Matrix Factorization (PMF) models. Finally, a total of eight electrical resistivity tomographs (ERTs) were acquired across i) the highly contaminated streams; ii) the villages far away from contaminated streams; and iii) across the freshwater stream. In the Moti village, the mean levels (mg/l) of heavy metals in water samples were 7.2465 (As), 0.4971 (Zn), 0.5056 (Pb), 0.0422 (Cu), 0.0279 (Cd), 0.1579 (Mn), and 0.9253 (Fe) that exceeded the permissible limit for drinking water (such as 0.010 for As and Pb, 3.0 for Zn, 0.003 for Cd and 0.3 for Fe) established by the World Health Organization (WHO, 2008). The average entropy weighted water quality index (EWQI) of 200, heavy metal pollution index (HPI) of 175, heavy metal evaluation index (HEI) of 1.6 values reveal inferior water quality in the study area. Human health risk assessment, consisting of hazard quotient (HQ) and hazard index (HI), exceeded the risk threshold (>1),indicating prevention of groundwater usage. Results obtained from the PCA and PMF models indicated anthropogenic sources (i.e. industrial and solid waste) responsible for the high concentration of heavy metals in the surface and groundwater. The ERTs imaged the subsurface down to about 40 m depths and show the least resistivity values (<11 Ωm) for subsurface layers that are highly contaminated. However, the ERTs revealed relatively high resistivity values for subsurface layers containing fresh or less contaminated water. Filtering and continuous monitoring of the quality of drinking water in the village are highly recommended.

Multispectral optoacoustic tomography of benign parotid tumors in vivo: a prospective observational pilot study.

Parotid lumps are a heterogeneous group of mainly benign but also malignant tumors. Preoperative imaging does not allow a differentiation between tumor types. Multispectral optoacoustic tomography (MSOT) may improve the preoperative diagnostics. In this first prospective pilot trial the ability of MSOT to discriminate between the two most frequent benign parotid tumors, pleomorphic adenoma (PA) and Warthin tumor (WT) as well as to normal parotid tissue was explored. Six wavelengths (700, 730, 760, 800, 850, 900 nm) and the parameters deoxygenated (HbR), oxygenated (HbO2), total hemoglobin (HbT), and saturation of hemoglobin (sO2) were analyzed. Ten patients with PA and fourteen with WT were included (12/12 female/male; median age: 51 years). For PA, the mean values for all measured wave lengths as well as for the hemoglobin parameters were different for the tumors compared to the healthy parotid (all p < 0.05). The mean MSOT parameters were all significantly higher (all p < 0.05) in the WT compared to healthy parotid gland except for HbT and sO2. Comparing both tumors directly, the mean values of MSOT parameters were not different between PA and WT (all p > 0.05). Differences were seen for the maximal MSOT parameters. The maximal tumor values for 900 nm, HbR, HbT, and sO2 were lower in PA than in WT (all p < 0.05). This preliminary MSOT parotid tumor imaging study showed clear differences for PA or WT compared to healthy parotid tissue. Some MSOT characteristics of PA and WT were different but needed to be explored in larger studies.

Array tomography of in vivo labeled synaptic receptors.

Array tomography (AT) allows one to localize sub-cellular components within the structural context of cells in 3D through the imaging of serial sections. Using this technique, the z-resolution can be improved physically by cutting ultra-thin sections. Nevertheless, conventional immunofluorescence staining of those sections is time consuming and requires relatively large amounts of costly antibody solutions. Moreover, epitopes are only readily accessible at the section's surface, leaving the volume of the serial sections unlabeled. Localization of receptors at neuronal synapses in 3D in their native cellular ultrastructural context is important for understanding signaling processes. Here, we present in vivo labeling of receptors via fluorophore-coupled tags in combination with super-resolution AT. We present two workflows where we label receptors at the plasma membrane: first, in vivo labeling via microinjection with a setup consisting of readily available components and self-manufactured microscope table equipment and second, live receptor labeling by using a cell-permeable tag. To take advantage of a near-to-native preservation of tissues for subsequent scanning electron microscopy (SEM), we also apply high-pressure freezing and freeze substitution. The advantages and disadvantages of our workflows are discussed.