scholarly journals Challenges of Post-measurement Histology for the Dielectric Characterisation of Heterogeneous Biological Tissues

Sensors ◽  
2020 ◽  
Vol 20 (11) ◽  
pp. 3290
Author(s):  
Alessandra La Gioia ◽  
Martin O’Halloran ◽  
Emily Porter

The dielectric properties of biological tissues are typically measured using the open-ended coaxial probe technique, which is based on the assumption that the tissue sample is homogeneous. Therefore, for heterogeneous tissue samples, additional post-measurement sample processing is conducted. Specifically, post-measurement histological analysis may be performed in order to associate the measured dielectric properties with the tissue types present in a heterogeneous sample. Accurate post-measurement histological analysis enables identification of the constituent tissue types that contributed to the measured dielectric properties, and their relative distributions. There is no standard protocol for conducting post-measurement histological analysis, which leads to high numbers of excluded tissue samples and inconsistencies in the resulting reported data for heterogeneous tissues. To this extent, this study examines the post-measurement histological process and the challenges in associating the acquired dielectric properties with the different tissue types present in heterogeneous samples. The results demonstrate that the histological process inevitably alters the morphology of samples, thus introducing errors in the interpretation of the dielectric properties acquired from heterogeneous biological samples. Notably, sample size was seen to shrink by up to 90% through the histological process, meaning that sensing volume determined from fresh tissues is not directly applicable to histology images.

Sensors ◽  
2020 ◽  
Vol 20 (7) ◽  
pp. 2060 ◽  
Author(s):  
Gertjan Maenhout ◽  
Tomislav Markovic ◽  
Ilja Ocket ◽  
Bart Nauwelaers

Open-ended coaxial probes are widely used to gather dielectric properties of biological tissues. Due to the lack of an agreed data acquisition protocol, several environmental conditions can cause inaccuracies when comparing dielectric data. In this work, the effect of a different measurement probe-to-tissue contact pressure was monitored in the frequency range from 0.5 to 20 GHz. Therefore, we constructed a controlled lifting platform with an integrated pressure sensor to exert a constant pressure on the tissue sample during the dielectric measurement. In the pressure range from 7.74 kPa to 77.4 kPa, we observed a linear correlation of − 0.31 ± 0.09 % and − 0.32 ± 0.14 % per kPa for, respectively, the relative real and imaginary complex permittivity. These values are statistically significant compared with the reported measurement uncertainty. Following the literature in different biology-related disciplines regarding pressure-induced variability in measurements, we hypothesize that these changes originate from squeezing out the interstitial and extracellular fluid. This process locally increases the concentration of membranes, cellular organelles, and proteins in the sensed volume. Finally, we suggest moving towards a standardized probe-to-tissue contact pressure, since the literature has already demonstrated that reprobing at the same pressure can produce repeatable data within a 1% uncertainty interval.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
Martin Proescholdt ◽  
Amer Haj ◽  
Christian Doenitz ◽  
Nils Ole Schmidt ◽  
Zeev Bomzon

Abstract INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (GBM). One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity, which depends on the dielectric properties of the tumor tissue. In this study we determined the dielectric properties of GBM by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor were analyzed separately. METHODS A cohort of 38 patients with newly diagnosed GBM were analyzed. Tissue probes were acquired from the vital tumor area and perinecrotic compartment. The tissue was measured immediately to avoid artifacts. A fragment was dissected from each tissue sample and was placed into a cylindrical cell with a known diameter. The impedance was recorded at frequencies 20Hz-1MHz using a software specifically developed for this study, which controls the LCR meter. The measured impedance was translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe was fixed, and stained with H&E to visualize cellularity, luxol fast blue to analyze the myelinated fiber content and against factor VIII related antigen to assess tumor vascularity. RESULTS We found significant differences between the conductivity and permittivity of tissue samples from each individual tumor (mean conductivity [S/m]: 0.302; range: 0.607 – 0.100; mean permittivity [Farad/m]: 3519.8; range: 11182.5 – 135.7). Consistently, the perinecrotic areas displayed lower conductivity values compared to the solid tumor compartments. Histological analysis revealed significantly higher cellularity and lower myelinated fiber content in tissue samples with high conductivity and permittivity. CONCLUSION The dielectric properties of GBM show a high intratumoral heterogeneity which correlate to the extent of cellularity and myelin fiber content within the tissue.


2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 137-137
Author(s):  
Tracy M. Layton ◽  
Karen Messer ◽  
John P. Pierce ◽  
Lisa Madlensky ◽  
Lisa Cadmus ◽  
...  

137 Background: An online self-reported clinical care intake form was provided to new surgery patients of the Moores UCSD Breast Care Clinic, as part of a pilot project in collaboration with the University of California Athena Breast Health Network. Clinical care goals were 1) to reduce clinic time by pre-visit collection of patient histories, co-morbidities, and medications and 2) provide patient reported data to clinicians and the electronic medical record (EMR). Clinical research goals were to 1) identify individuals diagnosed with breast cancer, 2) collect baseline measures related to co-morbidities, psychosocial parameters, and lifestyle factors and 3) increase research opportunities and enrollment. Methods: We developed an online intake form for patients to complete at home prior to their appointment. Patients were informed to complete the intake form before their appointment and were sent instructions via email. Patients without an email address had the opportunity to complete their intake form on an iPad in clinic. A summary of intake form answers was uploaded into the EMR for all patients. Patients could consent to future contact, to have their intake data kept in a research registry and/or to provide a blood or tissue sample. Results: From March 2010 to May 2013, 1,224 sequential new breast surgery clinic patients were contacted to complete the online intake form as part of their clinical care. 890 patients completed the intake form prior to their visit (73%). 802 of the 890 patients consented to contact for future research opportunities (90%) and 624 of the 802 consented to share data and EMR access for research (78%). We have coordinated enrollment with our ongoing UCSD biorepository study and have collected 210 blood and 51 tissue samples. Additionally, using future contact consent, we recruited more than 100 participants to multiple lifestyle and survey-based clinical studies. Conclusions: The use of an online intake form is well accepted by patients and provides patient reported data to all clinicians involved in patient care. In conjunction with consented EMR access, these data can be evaluated routinely for quality and efficiency purposes. Initial consent for future contact greatly facilitates participant recruitment to research studies.


2011 ◽  
Vol 57 (11) ◽  
pp. 1545-1555 ◽  
Author(s):  
Vladimír Reiser ◽  
Ryan C Smith ◽  
Jiyan Xue ◽  
Marc M Kurtz ◽  
Rong Liu ◽  
...  

BACKGROUND With expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD). METHODS We used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured. RESULTS The quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting. CONCLUSIONS The TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.


Author(s):  
J. D. Shelburne ◽  
Peter Ingram ◽  
Victor L. Roggli ◽  
Ann LeFurgey

At present most medical microprobe analysis is conducted on insoluble particulates such as asbestos fibers in lung tissue. Cryotechniques are not necessary for this type of specimen. Insoluble particulates can be processed conventionally. Nevertheless, it is important to emphasize that conventional processing is unacceptable for specimens in which electrolyte distributions in tissues are sought. It is necessary to flash-freeze in order to preserve the integrity of electrolyte distributions at the subcellular and cellular level. Ideally, biopsies should be flash-frozen in the operating room rather than being frozen several minutes later in a histology laboratory. Electrolytes will move during such a long delay. While flammable cryogens such as propane obviously cannot be used in an operating room, liquid nitrogen-cooled slam-freezing devices or guns may be permitted, and are the best way to achieve an artifact-free, accurate tissue sample which truly reflects the in vivo state. Unfortunately, the importance of cryofixation is often not understood. Investigators bring tissue samples fixed in glutaraldehyde to a microprobe laboratory with a request for microprobe analysis for electrolytes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su Bin Kim ◽  
In Ho Song ◽  
Yoo Sung Song ◽  
Byung Chul Lee ◽  
Arun Gupta ◽  
...  

Abstract[68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.


Author(s):  
Robin Verjans ◽  
Annette H. Bruggink ◽  
Robby Kibbelaar ◽  
Jos Bart ◽  
Aletta Debernardi ◽  
...  

AbstractBiobanks play a crucial role in enabling biomedical research by facilitating scientific use of valuable human biomaterials. The PALGA foundation—a nationwide network and registry of histo- and cytopathology in the Netherlands—was established to promote the provision of data within and between pathology departments, and to make the resulting knowledge available for healthcare. Apart from the pathology data, we aimed to utilize PALGA’s nationwide network to find and access the rich wealth of Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples for scientific use.  We implemented the Dutch National TissueArchive Portal (DNTP) to utilize PALGA’s nationwide network for requesting FFPE tissue samples. The DNTP consists of (1) a centrally organized internet portal to improve the assessing, processing, harmonization, and monitoring of the procurement process, while (2) dedicated HUB-employees provide practical support at peripheral pathology departments. Since incorporation of the DNTP, both the number of filed requests for FFPE tissue samples and the amount of HUB-mediated support increased 55 and 29% respectively. In line, the sample procurement duration time decreased significantly (− 47%). These findings indicate that implementation of the DNTP improved the frequency, efficiency, and transparency of FFPE tissue sample procurement for research in the Netherlands. To conclude, the need for biological resources is growing persistently to enable precision medicine. Here, we access PALGA’s national, pathology network by implementation of the DNTP to allow for efficient, consistent, and transparent exchange of FFPE tissue samples for research across the Netherlands.


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