Correlation between therapy response assessment using FDG PET/CT and histopathologic tumor regression grade in hepatic metastasis of colorectal carcinoma after neoadjuvant therapy

Purpose: To evaluate the correlation between change in FDG uptake before and after chemotherapy in hepatic metastases of colorectal carcinoma (HCRC) and a histopathologic tumor regression grade (TRG). Methods: In patients with HCRC, PET/CT data prior to hepatic surgery were retrospectively analyzed under an IRB waiver. The maximum standard uptake value (SUVmax) was measured before and after chemotherapy. The relative change of FDG activity in the identified lesions was calculated (dSUV). Histopathological specimens of resected metastases were graded on a 5-score TRG scale. A TRG of 1-3 was rated as a responding to therapy, whereas TRG 4-5 were regarded as non-responding lesions. Results: 31 lesions were identified in 23 patients. Mean SUVmax before and after therapy was 6.9±3.7 and 3.5±1.8, respectively. The area under the receiver operator characteristic curve revealed a conclusive correlation between TRG and dSUV (AUC 0.773; 95% confidence interval 0.599-0.946) with a cut off at 41% decrease in FDG activity yielding a sensitivity and specificity of 72 and 75%, respectively. Conclusion: A relative change in FDG activity (dSUV) of more than 41% decrease correlated significantly with histopathological tumor regression and might be a prognostic tool for response to chemotherapy in HCR

Microtubules regulate disassembly of epithelial apical junctions

BACKGROUND: Epithelial tight junction (TJ) and adherens junction (AJ) form the apical junctional complex (AJC) which regulates cell-cell adhesion, paracellular permeability and cell polarity. The AJC is anchored on cytoskeletal structures including actin microfilaments and microtubules. Such cytoskeletal interactions are thought to be important for the assembly and remodeling of apical junctions. In the present study, we investigated the role of microtubules in disassembly of the AJC in intestinal epithelial cells using a model of extracellular calcium depletion. RESULTS: Calcium depletion resulted in disruption and internalization of epithelial TJs and AJs along with reorganization of perijunctional F-actin into contractile rings. Microtubules reorganized into dense plaques positioned inside such F-actin rings. Depolymerization of microtubules with nocodazole prevented junctional disassembly and F-actin ring formation. Stabilization of microtubules with either docetaxel or pacitaxel blocked contraction of F-actin rings and attenuated internalization of junctional proteins into a subapical cytosolic compartment. Likewise, pharmacological inhibition of microtubule motors, kinesins, prevented contraction of F-actin rings and attenuated disassembly of apical junctions. Kinesin-1 was enriched at the AJC in cultured epithelial cells and it also accumulated at epithelial cell-cell contacts in normal human colonic mucosa. Furthermore, immunoprecipitation experiments demonstrated association of kinesin-1 with the E-cadherin-catenin complex. CONCLUSION: Our data suggest that microtubules play a role in disassembly of the AJC during calcium depletion by regulating formation of contractile F-actin rings and internalization of AJ/TJ proteins

PET/MR imaging of bone lesions - implications for PET quantification from imperfect attenuation correction

Purpose: Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging. Methods: In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference. Results: Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2 ± 5.4 % (range 1.5-30.8%) and 3.2 ± 1.7 % (range 0.2-4%), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9 ± 3.4% (range 9.9-23.5%) and for osteolytic spine lesions, 7.2 ± 1.7% (range 4.9-9.3%), respectively. Conclusion: CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake values in PET/MR imagin

Projects of Digital Philosophy in the Context of the Development of Digital Humanities

Цель исследования – посредством сравнительного анализа определить основные формы существования цифровой философии как части Digital Humanities. Гипотезой выступает ризоматическая структура цифровой философии, не имеющей единого смыслового или организационного центра, состоящей из множества иногда комплементарных, иногда разнородных исследовательских проектов, имеющих различные цели, методы и генезис, в рамках которых цифровое может выступать методом исследования, или его предметом, или даже онтологически понимаемой метафорой в случае цифровой онтологии. На основании сравнительного анализа представленных в научной литературе исследований выделяются и характеризуются основные линии в развитии цифровой философии, являющиеся наиболее широко представленными родственными исследовательскими проектами: цифровая онтология, визиософия, цифровая социальная философия и цифровая философская антропология, философия цифровых медиа, критическая цифровая философия, или киберскептицизм. Предложена классификация исследовательских проектов цифровой философии на основании выделения двух подходов: философско-цифрового, стремящегося осмыслить цифровизацию с позиций классических философских методологий, и ориентированных прежде всего на рефлексию и критику цифровизации, и цифро-философского, стремящегося к расширению философской методологии посредством цифровых инструментов и созданию новых, обусловленных цифровизацией, форм философствованияThe research aims to determine the main forms of existence of digital philosophy as part of Digital Humanities through comparative analysis. The hypothesis is the rhizomatic structure of digital philosophy, which does not have a single semantic or organizational center, consisting of many sometimes complementary, sometimes heterogeneous research projects with different goals, methods and genesis, within which the digital can act as a research method, or its subject, or even an ontologically understood metaphor in the case of digital ontology. Based on a comparative analysis of the research presented in the scientific literature, the main lines in the development of digital philosophy are identified and characterized, which are the most widely represented related research projects: digital ontology, visiosophy, digital social philosophy and digital philosophical anthropology, philosophy of digital media, critical digital philosophy or cyberscepticism. The classification of research projects of digital philosophy is proposed based on the identification of two approaches: philosophical-digital, seeking to comprehend digitalization from the standpoint of classical philosophical methodologies, and focused primarily on reflection and criticism of digitalization, and digital-philosophical, seeking to expand philosophical methodology through digital tools, and the creation of new forms of philosophizing due to digitalizatio

PET/MR imaging of bone lesions - implications for PET quantification from imperfect attenuation correction

PURPOSE: Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging. METHODS: In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference. RESULTS: Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2 ± 5.4 % (range 1.5-30.8 %) and 3.2 ± 1.7 % (range 0.2-4 %), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9 ± 3.4 % (range 9.9-23.5 %) and for osteolytic spine lesions, 7.2 ± 1.7 % (range 4.9-9.3 %), respectively. CONCLUSION: CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake values in PET/MR imaging

Protein kinase C activation disrupts epithelial apical junctions via ROCK-II dependent stimulation of actomyosin contractility

<p>Abstract</p> <p>Background</p> <p>Disruption of epithelial cell-cell adhesions represents an early and important stage in tumor metastasis. This process can be modeled <it>in vitro </it>by exposing cells to chemical tumor promoters, phorbol esters and octylindolactam-V (OI-V), known to activate protein kinase C (PKC). However, molecular events mediating PKC-dependent disruption of epithelial cell-cell contact remain poorly understood. In the present study we investigate mechanisms by which PKC activation induces disassembly of tight junctions (TJs) and adherens junctions (AJs) in a model pancreatic epithelium.</p> <p>Results</p> <p>Exposure of HPAF-II human pancreatic adenocarcinoma cell monolayers to either OI-V or 12-O-tetradecanoylphorbol-13-acetate caused rapid disruption and internalization of AJs and TJs. Activity of classical PKC isoenzymes was responsible for the loss of cell-cell contacts which was accompanied by cell rounding, phosphorylation and relocalization of the F-actin motor nonmuscle myosin (NM) II. The OI-V-induced disruption of AJs and TJs was prevented by either pharmacological inhibition of NM II with blebbistatin or by siRNA-mediated downregulation of NM IIA. Furthermore, AJ/TJ disassembly was attenuated by inhibition of Rho-associated kinase (ROCK) II, but was insensitive to blockage of MLCK, calmodulin, ERK1/2, caspases and RhoA GTPase.</p> <p>Conclusion</p> <p>Our data suggest that stimulation of PKC disrupts epithelial apical junctions via ROCK-II dependent activation of NM II, which increases contractility of perijunctional actin filaments. This mechanism is likely to be important for cancer cell dissociation and tumor metastasis.</p

Data underlying the research on Aortic lengths of the subjects estimated from CT images with jugulum to symphysis distance and demographic and anthropometric parameters

The objective of collected dataset was to develop multi-parameter linear models for the estimation of aortic length. The aortic length was determined using the CT images. The jugulum to symphysis distance was measured from body surface with a tape. The demographic and anthropometric parameters were determined either through measurement (e.g. weight of the subject) or using questionnaire

Image registration accuracy of an in-house developed patient transport system for PET/CT+MR and SPECT+CT imaging

OBJECTIVE The aim of this study was to investigate the registration accuracy of a newly developed patient shuttle system that can integrate different scanners by patient transfer without repositioning for 'hardware'-based image fusion. We aimed to assess the registration accuracy of image fusion in two different settings: a trimodality PET/CT+MR system and a SPECT+CT system. MATERIALS AND METHODS In this prospective study, 43 patients underwent either sequential PET/CT and MR (n=31) or sequential SPECT and diagnostic CT (D-CT) (n=12). A side-loading patient shuttle system was used for patient transport. For PET/CT+MR, hardware-only coregistration was performed and then validated with anatomical landmarks on CT and MR. SPECT+D-CT image fusion was performed with external cobalt-57 markers and manual fusion. Registration accuracy was analysed by anatomical landmarks on the attenuation correction CT and the D-CT. RESULTS For the PET/CT+MR system, the mean offset between original CT and MR images in all 31 patients was 8.1±5.7 mm in the X-axis, 5±4 mm in the Y-axis and 4.9±5.6 mm in the Z-axis. The validation of the cobalt-57 marker-assisted SPECT+D-CT fusion yielded offsets of 0.7±1.7 mm in the X-axis, 2.1±1.7 mm in the Y-axis and 0.8±1.8 mm in the Z-axis. CONCLUSION Sequential PET/CT+MR and SPECT+D-CT imaging using a dedicated patient shuttle system is feasible, resulting in mean offsets between data sets of 10.7 mm using the gantry laser system and 2.4 mm with fiducial markers

18F-FDG-PET/MR increases diagnostic confidence in detection of bone metastases compared with 18F-FDG-PET/CT

PURPOSE: The aim of this study was to compare detection, lesion conspicuity and reader confidence of F-fluorodeoxyglucose (F-FDG)-PET/MR and F-FDG-PET/computed tomography (CT) in patients with F-FDG avid bone metastases. MATERIALS AND METHODS: In this prospective study, a total of 30 PET/CT and PET/MRI data sets were performed in 24 patients. Each examination was evaluated for the presence of PET-positive bone lesions consistent with metastatic involvement. Conspicuity of PET-positive bone lesions was evaluated on the corresponding PET/CT and PET/MR images and compared using the Wilcoxon signed-ranks test. Reader confidence was determined to evaluate whether PET/CT or PET/MR was more useful for the assessment of the bone metastases and was compared using Student's t-test. RESULTS: Overall, in both examinations, PET/CT and PET/MRI detected 86 F-FDG-positive bone lesions. On all 30 PET/MRI examinations, at least one morphological correlate for F-FDG-positive bone lesions was found on the MR component (82 out of 86 lesions). PET/CT imaging allowed identification of corresponding structural changes on the CT component in 23 out of 30 studies (65 out of 86 lesions). In lesion-by-lesion analysis, the mean lesion conspicuity was significantly better on T1 fat MR imaging compared with CT imaging (P=0.005). In seven out of 30 studies, a significant increase in reader confidence of PET/MRI compared with PET/CT was found. CONCLUSION: PET/MRI offers higher reader confidence and improved conspicuity in bone metastases compared with PET/CT. However, the overall detection rate was not different. The highest possible clinical impact of PET/MRI appears to be in patients with limited, early bone metastatic disease