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Merlo, Sabina, Valentina Bello, Elisabetta Bodo, and Sara Pizzurro. "A VCSEL-Based NIR Transillumination System for Morpho-Functional Imaging." Sensors 19, no. 4 (February 19, 2019): 851. http://dx.doi.org/10.3390/s19040851.
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Transillumination with non-ionizing radiation followed by the observation of transmitted and diffused light is the simplest, and probably the oldest method to obtain qualitative information on the internal structure of tissues or body sections. Although scattering precludes formation of high-definition image (unless complex techniques are employed), low resolution pictures complemented by information on the functional condition of the living sample can be extracted. In this context, we have investigated a portable optoelectronic instrumental configuration for efficient transillumination and image detection, even in ambient day-light, of in vivo samples with thickness up to 5 cm, sufficient for visualizing macroscopic structures. Tissue illumination is obtained with an extended source consisting in a matrix of 36 near infrared Vertical Cavity Surface Emitting Lasers (VCSELs) that is powered by a custom designed low-voltage current driver. In addition to the successful acquisition of morphological images of the hand dorsal vein pattern, functional detection of physiological parameters (breath and hearth rate) is achieved non-invasively by means of a monochrome camera, with a Complementary Metal Oxide Semiconductor (CMOS) sensor, turned into a wavelength selective image detector using narrow-band optical filtering.
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Cicchi, Riccardo, Alessandro Sturiale, Gabriella Nesi, Dimitrios Kapsokalyvas, Giovanni Alemanno, Francesco Tonelli, and Francesco S. Pavone. "Multiphoton morpho-functional imaging of healthy colon mucosa, adenomatous polyp and adenocarcinoma." Biomedical Optics Express 4, no. 7 (June 24, 2013): 1204. http://dx.doi.org/10.1364/boe.4.001204.
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Di Leo, Milena, Maria Chiara Petrone, Raffaella Alessia Zuppardo, Giulia Martina Cavestro, Paolo Giorgio Arcidiacono, Pier Alberto Testoni, and Alberto Mariani. "Pancreatic morpho-functional imaging as a diagnostic approach for chronic asymptomatic pancreatic hyperenzymemia." Digestive and Liver Disease 48, no. 11 (November 2016): 1330–35. http://dx.doi.org/10.1016/j.dld.2016.08.109.
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Tolentino, Leida C., and Natasha Tokowicz. "ACROSS LANGUAGES, SPACE, AND TIME." Studies in Second Language Acquisition 33, no. 1 (February 21, 2011): 91–125. http://dx.doi.org/10.1017/s0272263110000549.
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This review examines whether similarity between the first language (L1) and second language (L2) influences the (morpho)syntactic processing of the L2, using both neural location and temporal processing information. Results from functional magnetic resonance imaging (fMRI) and event-related potential (ERP) studies show that nonnative speakers can exhibit nativelike online L2 (morpho)syntactic processing behavior and neural patterns. These findings are contrary to predictions of the shallow structure hypothesis for syntactic processing (Clahsen & Felser, 2006a, 2006b). The data are in line with predictions of the (morpho)syntactic domain of the unified competition model of L2 acquisition (MacWhinney, 2005): Differences in L2 processing as compared to the L1 (or to native speakers of the L2) were generally associated with constructions that were crosslinguistically dissimilar or unique to the L2. The processing of crosslinguistically similar constructions generally produced no differences in brain activity between the L1 and L2. Overall, the available data suggest that cross-language similarity is an important factor that influences L2 (morpho)syntactic processing.
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Incoronato, Mariarosaria, Anna Maria Grimaldi, Peppino Mirabelli, Carlo Cavaliere, Chiara Anna Parente, Monica Franzese, Stefania Staibano, et al. "Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study." Cancers 11, no. 6 (June 22, 2019): 876. http://dx.doi.org/10.3390/cancers11060876.
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The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. A total of 77 untreated female BC patients underwent same-day PET/MR and blood collection, and 78 healthy donors were recruited as negative controls. The expression profile of 84 human miRNAs was screened by using miRNA PCR arrays and validated by real-time PCR. The validated miRNAs were correlated with the quantitative imaging parameters extracted from the primary BC samples. Circulating miR-125b-5p and miR-143-3p were upregulated in BC plasma and able to discriminate BC patients from healthy subjects (miR-125-5p area under the receiver operating characteristic ROC curve (AUC) = 0.85 and miR-143-3p AUC = 0.80). Circulating CA15-3, a soluble form of the transmembrane glycoprotein Mucin 1 (MUC-1) that is upregulated in epithelial cancer cells of different origins, was combined with miR-125b-5p and improved the diagnostic accuracy from 70% (CA15-3 alone) to 89% (CA15-3 plus miR-125b-5p). MiR-143-3p showed a strong and significant correlation with the stage of the disease, apparent diffusion coefficient (ADCmean), reverse efflux volume transfer constant (Kepmean) and maximum standardized uptake value (SUVmax), and it might represent a biomarker of tumour aggressiveness. Similarly, miR-125b-5p was correlated with stage and grade 2 but inversely correlated with the forward volume transfer constant (Ktransmean) and proliferation index (Ki67), suggesting a potential role as a biomarker of a relatively more favourable prognosis. In situ hybridization (ISH) experiments revealed that miR-143-3p was expressed in endothelial tumour cells, miR-125-5p in cancer-associated fibroblasts, and neither in epithelial tumour cells. Our results suggested that miR-125-5p and miR-143-3p are potential biomarkers for the risk stratification of BC, and Kaplan-Maier plots confirmed this hypothesis. In addition, the combined use of miR-125-b-5p and CA15-3 enhanced the diagnostic accuracy up to 89%. This is the first study that correlates circulating miRNAs with in vivo quantified tumour biology through PET/MR biomarkers. This integration elucidates the link between the plasmatic increase in these two potential circulating biomarkers and the biology of untreated BC. In conclusion, while miR-143-3b and miR-125b-5p provide valuable information for prognosis, a combination of miR-125b-5p with the tumour marker CA15-3 improves sensitivity for BC detection, which warrants consideration by further validation studies.
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Agafonova, I. G., V. N. Kotelnikov, and B. I. Geltcer. "Estimation of the morpho-functional status of the hypertensive Wistar rats using diffusion-weighted imaging." Bulletin of Experimental Biology and Medicine 171, no. 2 (2021): 247–52. http://dx.doi.org/10.47056/0365-9615-2021-171-2-247-252.
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Jiménez-Ortega, Elisa, Ana Ureba, José Antonio Baeza, Ana Rita Barbeiro, Marcin Balcerzyk, Ángel Parrado-Gallego, Amadeo Wals-Zurita, Francisco Javier García-Gómez, and Antonio Leal. "Accurate, robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy." PLOS ONE 14, no. 1 (January 9, 2019): e0210549. http://dx.doi.org/10.1371/journal.pone.0210549.
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Pruna, Xavier. "Morpho-functional evaluation of osteomeatal complex in chronic sinusitis by coronal CT." European Radiology 13, no. 6 (June 2003): 1461–68. http://dx.doi.org/10.1007/s00330-002-1644-3.
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Oikonomou, Evangelos, Panagiotis Theofilis, Stamatios Lampsas, Ourania Katsarou, Konstantinos Kalogeras, Georgios Marinos, Aikaterini Tsatsaragkou, et al. "Current Concepts and Future Applications of Non-Invasive Functional and Anatomical Evaluation of Coronary Artery Disease." Life 12, no. 11 (November 7, 2022): 1803. http://dx.doi.org/10.3390/life12111803.
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Over the last decades, significant advances have been achieved in the treatment of coronary artery disease (CAD). Proper non-invasive diagnosis and appropriate management based on functional information and the extension of ischemia or viability remain the cornerstone in the fight against adverse CAD events. Stress echocardiography and single photon emission computed tomography are often used for the evaluation of ischemia. Advancements in non-invasive imaging modalities such as computed tomography (CT) coronary angiography and cardiac magnetic resonance imaging (MRI) have not only allowed non-invasive imaging of coronary artery lumen but also provide additional functional information. Other characteristics regarding the plaque morphology can be further evaluated with the latest modalities achieving a morpho-functional evaluation of CAD. Advances in the utilization of positron emission tomography (PET), as well as software advancements especially regarding cardiac CT, may provide additional prognostic information to a more evidence-based treatment decision. Since the armamentarium on non-invasive imaging modalities has evolved, the knowledge of the capabilities and limitations of each imaging modality should be evaluated in a case-by-case basis to achieve the best diagnosis and treatment decision. In this review article, we present the most recent advances in the noninvasive anatomical and functional evaluation of CAD.
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Cicchi, Riccardo, and Francesco Saverio Pavone. "Multimodal nonlinear microscopy: A powerful label-free method for supporting standard diagnostics on biological tissues." Journal of Innovative Optical Health Sciences 07, no. 05 (September 2014): 1330008. http://dx.doi.org/10.1142/s1793545813300085.
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The large use of nonlinear laser scanning microscopy in the past decade paved the way for potential clinical application of this imaging technique. Modern nonlinear microscopy techniques offer promising label-free solutions to improve diagnostic performances on tissues. In particular, the combination of multiple nonlinear imaging techniques in the same microscope allows integrating morphological with functional information in a morpho-functional scheme. Such approach provides a high-resolution label-free alternative to both histological and immunohistochemical examination of tissues and is becoming increasingly popular among the clinical community. Nevertheless, several technical improvements, including automatic scanning and image analysis, are required before the technique represents a standard diagnostic method. In this review paper, we highlight the capabilities of multimodal nonlinear microscopy for tissue imaging, by providing various examples on colon, arterial and skin tissues. The comparison between images acquired using multimodal nonlinear microscopy and histology shows a good agreement between the two methods. The results demonstrate that multimodal nonlinear microscopy is a powerful label-free alternative to standard histopathological methods and has the potential to find a stable place in the clinical setting in the near future.
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Agafonova, Irina G., Vladimir N. Kotelnikov, Boris I. Geltcer, Natalya G. Kolosova, and Valentin A. Stonik. "The Morpho-Functional Characteristics of Cerebral and Renal Arteries After Induced Arterial Hypertension in Rats Using Magnetic Resonance Imaging." Applied Magnetic Resonance 48, no. 9 (July 8, 2017): 911–19. http://dx.doi.org/10.1007/s00723-017-0914-9.
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Ribeiro, Aline Moreira, Larissa Guerra Nammur, Elaine Cristine Lemes Mateus-Vasconcelos, Cristine Homsi Jorge Ferreira, Valdair Francisco Muglia, and Harley Francisco de Oliveira. "Pelvic floor muscles after prostate radiation therapy: morpho-functional assessment by magnetic resonance imaging, surface electromyography and digital anal palpation." International braz j urol 47, no. 1 (February 2021): 120–30. http://dx.doi.org/10.1590/s1677-5538.ibju.2019.0765.
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Haase, Albrecht, Elisa Rigosi, Elisa Frasnelli, Federica Trona, Francesco Tessarolo, Claudio Vinegoni, Gianfranco Anfora, Giorgio Vallortigara, and Renzo Antolini. "A multimodal approach for tracing lateralisation along the olfactory pathway in the honeybee through electrophysiological recordings, morpho-functional imaging, and behavioural studies." European Biophysics Journal 40, no. 11 (September 29, 2011): 1247–58. http://dx.doi.org/10.1007/s00249-011-0748-6.
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Filatova, T. A. "Assessment of the hand osteoarthritis activity in real clinical practice: possibilities and opportunities." Medical Herald of the South of Russia 12, no. 2 (July 4, 2021): 70–80. http://dx.doi.org/10.21886/2219-8075-2021-12-2-70-80.
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Objective: to study the functional disorder, joint structural changes with acute phase parameters, and interleukin-1 beta (IL-1β) in patients with hand osteoarthritis (HOA). Materials and methods: the study included 52 women with HOA, the mean age was 63.4 (10.0) years old. The degree of functional impairment was evaluated according to the visual analogue scale (VAS) and the author’s questionnaire. The laboratory study included an assessment of ESR, C-reactive protein (CRP), and IL-1β levels in the blood. The instrumental diagnostic was performed by X-ray, ultrasonography (US), and magnetic resonance imaging (MRI) of the hand joints. Results: no significant data were obtained on the dependence of the severity of structural and functional disorders from ESR, CRP, and IL-1β levels (r<0.5; rs<0.5). Conclusions: there was no correlation between HOA activity and CRP and IL-1β levels but some authors propose to use highly sensitive methods to detect CRP. The application of highly sensitive methods for CRP detection could reveal the association between this indicator and the HOA activity. The absence of dependence between IL-1β level and morpho-functional parameters agrees with the data obtained by other researchers. It is possible that the evaluation of the IL-1β level in dynamics can be useful for assessing the treatment response but this requires further studies.
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Sperlongano, Simona, Antonello D’Andrea, Donato Mele, Vincenzo Russo, Valeria Pergola, Andreina Carbone, Federica Ilardi, et al. "Left Ventricular Deformation and Vortex Analysis in Heart Failure: From Ultrasound Technique to Current Clinical Application." Diagnostics 11, no. 5 (May 17, 2021): 892. http://dx.doi.org/10.3390/diagnostics11050892.
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Heart failure (HF) is a leading cause of cardiovascular morbidity and mortality. However, its symptoms and signs are not specific or can be absent. In this context, transthoracic echocardiography plays a key role in diagnosing the various forms of HF, guiding therapeutic decision making and monitoring response to therapy. Over the last few decades, new ultrasound modalities have been introduced in the field of echocardiography, aiming at better understanding the morpho-functional abnormalities occurring in cardiovascular diseases. However, they are still struggling to enter daily and routine use. In our review article, we turn the spotlight on some of the newest ultrasound technologies; in particular, analysis of myocardial deformation by speckle tracking echocardiography, and intracardiac flow dynamics by color Doppler flow mapping, highlighting their promising applications to HF diagnosis and management. We also focus on the importance of these imaging modalities in the selection of responses to cardiac resynchronization therapy.
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Panatier, Aude, Misa Arizono, and U. Valentin Nägerl. "Dissecting tripartite synapses with STED microscopy." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1654 (October 19, 2014): 20130597. http://dx.doi.org/10.1098/rstb.2013.0597.
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The concept of the tripartite synapse reflects the important role that astrocytic processes are thought to play in the function and regulation of neuronal synapses in the mammalian nervous system. However, many basic aspects regarding the dynamic interplay between pre- and postsynaptic neuronal structures and their astrocytic partners remain to be explored. A major experimental hurdle has been the small physical size of the relevant glial and synaptic structures, leaving them largely out of reach for conventional light microscopic approaches such as confocal and two-photon microscopy. Hence, most of what we know about the organization of the tripartite synapse is based on electron microscopy, which does not lend itself to investigating dynamic events and which cannot be carried out in parallel with functional assays. The development and application of superresolution microscopy for neuron–glia research is opening up exciting experimental opportunities in this regard. In this paper, we provide a basic explanation of the theory and operation of stimulated emission depletion (STED) microscopy, outlining the potential of this recent superresolution imaging modality for advancing our understanding of the morpho-functional interactions between astrocytes and neurons that regulate synaptic physiology.
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Collantoni, E., P. Meneguzzo, E. Tenconi, R. Manara, P. Santonastaso, and A. Favaro. "Structural Covariance Networks in Anorexia Nervosa (AN): A Multimodal Graph Theoretical Analysis." European Psychiatry 41, S1 (April 2017): S282. http://dx.doi.org/10.1016/j.eurpsy.2017.02.131.
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IntroductionThe possibility of evaluating cortical morphological and structural features on the basis of their covariance patterns is becoming increasingly important in clinical neuroscience, because their organizational principles reveal an inter-regional structural dependence which derive from a complex mixture of developmental, genetic and environmental factors.ObjectivesIn this study, we describe cortical network organization in anorexia nervosa using a MRI morpho-structural covariance analysis based on cortical thickness, gyrification and fractal dimension.AimAim of the research is to evaluate any alterations in structural network properties measured with graph theory from multi-modal imaging data in AN.MethodsThirty-eight patients with acute AN, 38 healthy controls and 20 patients in full remission from AN underwent MRI scanning. Surface extraction was completed using FreeSurfer package. Graph analysis was performed using graph analysis toolbox.ResultsIn acute patients, the covariance analysis among cortical thickness values showed a more segregated pattern and a reduction of global integration indexes. In the recovered patients group, we noticed a similar global trend without statistically significant differences for any single parameter. According to gyrification indexes, the covariance network showed a trend towards high segregation both in acute and recovered patients. We did not observe any significant difference in the covariance networks in the analysis of fractal dimension.ConclusionsThe presence of increased segregation properties in cortical covariance networks in AN may be determined by a retardation of neurodevelopmental trajectories or by an energy saving adaptive response. The differences between the analyzed parameters likely depend on their different morpho-functional meanings.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Marslen-Wilson, William D., and Lorraine K. Tyler. "Morphology, language and the brain: the decompositional substrate for language comprehension." Philosophical Transactions of the Royal Society B: Biological Sciences 362, no. 1481 (March 29, 2007): 823–36. http://dx.doi.org/10.1098/rstb.2007.2091.
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This paper outlines a neurocognitive approach to human language, focusing on inflectional morphology and grammatical function in English. Taking as a starting point the selective deficits for regular inflectional morphology of a group of non-fluent patients with left hemisphere damage, we argue for a core decompositional network linking left inferior frontal cortex with superior and middle temporal cortex, connected via the arcuate fasciculus. This network handles the processing of regularly inflected words (such as joined or treats ), which are argued not to be stored as whole forms and which require morpho-phonological parsing in order to segment complex forms into stems and inflectional affixes. This parsing process operates early and automatically upon all potential inflected forms and is triggered by their surface phonological properties. The predictions of this model were confirmed in a further neuroimaging study, using event-related functional magnetic resonance imaging (fMRI), on unimpaired young adults. The salience of grammatical morphemes for the language system is highlighted by new research showing that similarly early and blind segmentation also operates for derivationally complex forms (such as darkness or rider ). These findings are interpreted as evidence for a hidden decompositional substrate to human language processing and related to a functional architecture derived from non-human primate models.
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Moretti, D. V., D. Paternicò, A. Prestia, G. Binetti, O. Zanetti, and G. B. Frisoni. "Theta Frequency is Associated to Morpho-Strcutural and Perfusional Modifications in Subjects with Mild Cognitive Impairment." Journal of Psychology and Psychotherapy Research 1, no. 1 (February 5, 2014): 3–13. http://dx.doi.org/10.12974/2313-1047.2014.01.01.1.
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Background: In an attempt to find non-invasive biomarkers, researchers have investigated the feasibility of neuroimaging tools, such as MR, SPECT as well as neurophysiological measurements using EEG. The increase of theta frequency has been associated with mild cognitive impairment (MCI) and related to both grey matter (GM) changes of thalamus and basal ganglia and SPECT modifications. Objective: To study the association of prognostic theta frequency with specific GM and perfusional changes of thalamus and basal ganglia to detect biomarkers early predictive of mild cognitive impairment. Methods: 74 adult subjects with mild cognitive impairment underwent EEG recording and high resolution 3D magnetic resonance imaging (MRI). Moreover, 27 adult subjects with mild cognitive impairment underwent also perfusion single-photon emission computed tomography (SPECT) evaluation. The theta/gamma ratio was computed for each subject. Three groups were obtained according to increasing tertiles values of theta/gamma ratio. Grey matter density differences between groups were investigated using a Voxel Based Morphometry technique. Results: Subjects with higher theta/gamma ratio and increase of theta frequency showed minor atrophy in putamina nuclei bilaterally and a lower hippocampal perfusion in subjects with mild cognitive impairment. Conclusion: The integrated analysis of EEG and morpho-functional markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.
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Vieira, Jefferson Luis, and Edimar Alcides Bocchi. "Letter by Vieira and Bocchi Regarding Article, “Association Between Ambient Air Pollution and Cardiac Morpho-Functional Phenotypes: Insights From the UK Biobank Population Imaging Study”." Circulation 139, no. 15 (April 9, 2019): 1857–58. http://dx.doi.org/10.1161/circulationaha.118.038033.
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Caldarella, Carmelo, Barbara Muoio, Maria Antonietta Isgrò, Emilio Porfiri, Giorgio Treglia, and Luca Giovanella. "The role of fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the response to tyrosine-kinase inhibitors in patients with metastatic primary renal cell carcinoma." Radiology and Oncology 48, no. 3 (September 1, 2014): 219–27. http://dx.doi.org/10.2478/raon-2013-0067.
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Abstract Background. Positron emission tomography-computed tomography (PET-CT) using fluorodeoxyglucose (FDG) is increasingly used in the evaluation of patients with advanced renal cell carcinoma (RCC), primarily for staging purposes. The aim of this paper is to perform a systematic review about the usefulness of PET-CT using FDG in response assessment after treatment with tyrosine-kinase inhibitors (TKIs) in patients with advanced RCC. Materials and methods. The scientific literature about the role of PET-CT using FDG in the assessment of response to treatment with TKIs in patients affected by advanced RCC was systematically reviewed. Results. Seven studies about the role of PET-CT using FDG in the response assessment after treatment with TKIs (essentially sunitinib and sorafenib) in advanced RCC were retrieved in full-text and analysed, to determine the predictive role of this morpho-functional imaging method on patient outcome. Conclusions. To date, the role of PET-CT using FDG in evaluating the response to TKIs in metastatic RCC patients is still not well defined, partly due to heterogeneity of available studies; however, PET-CT reveals potential role for the selection of patients undergoing therapy with TKIs. The use of contrast-enhanced PET-CT appears to be promising for a “multi-dimensional” evaluation of treatment response in these patients.
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Aung, Nay, and Steffen E. Petersen. "Response by Aung and Petersen to Letter Regarding Article, “Association Between Ambient Air Pollution and Cardiac Morpho-Functional Phenotypes: Insights From the UK Biobank Population Imaging Study”." Circulation 139, no. 15 (April 9, 2019): 1859–60. http://dx.doi.org/10.1161/circulationaha.119.039916.
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Sartini, Stefano, Davide Lattanzi, Michael Di Palma, David Savelli, Silvia Eusebi, Piero Sestili, Riccardo Cuppini, and Patrizia Ambrogini. "Maternal Creatine Supplementation Positively Affects Male Rat Hippocampal Synaptic Plasticity in Adult Offspring." Nutrients 11, no. 9 (August 27, 2019): 2014. http://dx.doi.org/10.3390/nu11092014.
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Creatine plays a crucial role in developing the brain, so much that its genetic deficiency results in mental dysfunction and cognitive impairments. Moreover, creatine supplementation is currently under investigation as a preventive measure to protect the fetus against oxidative stress during difficult pregnancies. Although creatine use is considered safe, posing minimal risk to clinical health, we found an alteration in morpho-functional maturation of neurons when male rats were exposed to creatine loads during brain development. In particular, increased excitability and enhanced long-term potentiation (LTP) were observed in the hippocampal pyramidal neurons of weaning pups. Since these effects were observed a long time after creatine treatment had been terminated, long-lasting modifications persisting into adulthood were hypothesized. Such modifications were investigated in the present study using morphological, electrophysiological, and calcium imaging techniques applied to hippocampal Cornu Ammonis 1 (CA1) neurons of adult rats born from dams supplemented with creatine. When compared to age-matched controls, the treated adult offspring were found to retain enhanced neuron excitability and an improved LTP, the best-documented neuronal substrate for memory formation. While translating data from rats to humans does have limitations, our findings suggest that prenatal creatine supplementation could have positive effects on adult cognitive abilities.
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Giordano, A., F. Cinti, R. Canese, G. Carpinelli, G. Colleluori, A. Di Vincenzo, G. Palombelli, et al. "The Adipose Organ Is a Unitary Structure in Mice and Humans." Biomedicines 10, no. 9 (September 14, 2022): 2275. http://dx.doi.org/10.3390/biomedicines10092275.
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Obesity is the fifth leading cause of death worldwide. In mice and humans with obesity, the adipose organ undergoes remarkable morpho-functional alterations. The comprehension of the adipose organ function and organization is of paramount importance to understand its pathology and formulate future therapeutic strategies. In the present study, we performed anatomical dissections, magnetic resonance imaging, computed axial tomography and histological and immunohistochemical assessments of humans and mouse adipose tissues. We demonstrate that most of the two types of adipose tissues (white, WAT and brown, BAT) form a large unitary structure fulfilling all the requirements necessary to be considered as a true organ in both species. A detailed analysis of the gross anatomy of mouse adipose organs in different pathophysiological conditions (normal, cold, pregnancy, obesity) shows that the organ consists of a unitary structure composed of different tissues: WAT, BAT, and glands (pregnancy). Data from autoptic dissection of 8 cadavers, 2 females and 6 males (Age: 37.5 ± 9.7, BMI: 23 ± 2.7 kg/m2) and from detailed digital dissection of 4 digitalized cadavers, 2 females and 2 males (Age: 39 ± 14.2 years, BMI: 22.8 ± 4.3 kg/m2) confirmed the mixed (WAT and BAT) composition and the unitary structure of the adipose organ also in humans. Considering the remarkable endocrine roles of WAT and BAT, the definition of the endocrine adipose organ would be even more appropriate in mice and humans.
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Haubner, M., A. Lösch, F. Eckstein, M. D. Seemann, W. van Eimeren, M. Reiser, and K. H. Englmeier. "Hybrid Rendering of Multidimensional Image Data." Methods of Information in Medicine 36, no. 01 (January 1997): 1–10. http://dx.doi.org/10.1055/s-0038-1634687.
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Abstract:The most important rendering methods applied in medical imaging are surface and volume rendering techniques. Each approach has its own advantages and limitations: Fast surface-oriented methods are able to support real-time interaction and manipulation. The underlying representation, however, is dependent on intensive image processing to extract the object surfaces. In contrast, volume visualization is not necessarily based on extensive image processing and interpretation. No data reduction to geometric primitives, such as polygons, is required. Therefore, the process of volume rendering is currently not operating in real time. In order to provide the radiological diagnosis with additional information as well as to enable simulation and preoperative treatment planning we developed a new hybrid rendering method which combines the advantages of surface and volume presentation, and minimizes the limitations of these approaches. We developed a common data representation method for both techniques. A preprocessing module enables the construction of a data volume by interpolation as well as the calculation of object surfaces by semiautomatic image interpretation and surface construction. The hybrid rendering system is based on transparency and texture mapping features. It is embedded in a user-friendly open system which enables the support of new application fields such as virtual reality and stereolithography. The efficiency of our new method is described for 3-D subtraction angiography and the visualization of morpho-functional relationships.
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Alongi, Pierpaolo, Alessandro Stefano, Albert Comelli, Alessandro Spataro, Giuseppe Formica, Riccardo Laudicella, Helena Lanzafame, et al. "Artificial Intelligence Applications on Restaging [18F]FDG PET/CT in Metastatic Colorectal Cancer: A Preliminary Report of Morpho-Functional Radiomics Classification for Prediction of Disease Outcome." Applied Sciences 12, no. 6 (March 13, 2022): 2941. http://dx.doi.org/10.3390/app12062941.
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The aim of this study was to investigate the application of [18F]FDG PET/CT images-based textural features analysis to propose radiomics models able to early predict disease progression (PD) and survival outcome in metastatic colorectal cancer (MCC) patients after first adjuvant therapy. For this purpose, 52 MCC patients who underwent [18F]FDGPET/CT during the disease restaging process after the first adjuvant therapy were analyzed. Follow-up data were recorded for a minimum of 12 months after PET/CT. Radiomics features from each avid lesion in PET and low-dose CT images were extracted. A hybrid descriptive-inferential method and the discriminant analysis (DA) were used for feature selection and for predictive model implementation, respectively. The performance of the features in predicting PD was performed for per-lesion analysis, per-patient analysis, and liver lesions analysis. All lesions were again considered to assess the diagnostic performance of the features in discriminating liver lesions. In predicting PD in the whole group of patients, on PET features radiomics analysis, among per-lesion analysis, only the GLZLM_GLNU feature was selected, while three features were selected from PET/CT images data set. The same features resulted more accurately by associating CT features with PET features (AUROC 65.22%). In per-patient analysis, three features for stand-alone PET images and one feature (i.e., HUKurtosis) for the PET/CT data set were selected. Focusing on liver metastasis, in per-lesion analysis, the same analysis recognized one PET feature (GLZLM_GLNU) from PET images and three features from PET/CT data set. Similarly, in liver lesions per-patient analysis, we found three PET features and a PET/CT feature (HUKurtosis). In discrimination of liver metastasis from the rest of the other lesions, optimal results of stand-alone PET imaging were found for one feature (SUVbwmin; AUROC 88.91%) and two features for merged PET/CT features analysis (AUROC 95.33%). In conclusion, our machine learning model on restaging [18F]FDGPET/CT was demonstrated to be feasible and potentially useful in the predictive evaluation of disease progression in MCC.
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Palmisano, Anna, Marco Piccoli, Caterina Beatrice Monti, Tamara Canu, Federica Cirillo, Angela Napolitano, Laura Perani, et al. "Single-shot morpho-functional and structural characterization of the left-ventricle in a mouse model of acute ischemia-reperfusion injury with an optimized 3D IntraGate cine FLASH sequence at 7T MR." Magnetic Resonance Imaging 68 (May 2020): 127–35. http://dx.doi.org/10.1016/j.mri.2020.01.015.
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Kuperberg, Gina R., Phillip J. Holcomb, Tatiana Sitnikova, Douglas Greve, Anders M. Dale, and David Caplan. "Distinct Patterns of Neural Modulation during the Processing of Conceptual and Syntactic Anomalies." Journal of Cognitive Neuroscience 15, no. 2 (February 1, 2003): 272–93. http://dx.doi.org/10.1162/089892903321208204.
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The aim of this study was to gain further insights into how the brain distinguishes between meaning and syntax during language comprehension. Participants read and made plausibility judgments on sentences that were plausible, morpho-syntactically anomalous, or pragmatically anomalous. In an event-related potential (ERP) experiment, morphosyntactic and pragmatic violations elicited significant P600 and N400 effects, respectively, replicating previous ERP studies that have established qualitative differences in processing conceptually and syntactic anomalies. Our main focus was a functional magnetic resonance imaging (fMRI) study in which the same subjects read the same sentences presented in the same pseudorandomized sequence while performing the same task as in the ERP experiment. Rapid-presentation event-related fMRI methods allowed us to estimate the hemodynamic response at successive temporal windows as the sentences unfolded word by word, without assumptions about the shape of the underlying response function. Relative to nonviolated sentences, the pragmatic anomalies were associated with an increased hemodynamic response in left temporal and inferior frontal regions and a decreased response in the right medial parietal cortex. Relative to nonviolated sentences, the morphosyntactic anomalies were associated with an increased response in bilateral medial and lateral parietal regions and a decreased response in left temporal and inferior frontal regions. Thus, overlapping neural networks were modulated in opposite directions to the two types of anomaly. These fMRI findings document both qualitative and quantitative differences in how the brain distinguishes between these two types of anomalies. This suggests that morphosyntactic and pragmatic information can be processed in different ways but by the same neural systems.
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Shirokov, N. E., V. A. Kuznetsov, A. M. Soldatova, D. V. Krinochkin, and L. M. Malishevskii. "Comparative analysis of patients with cardiac resynchronization therapy depending on septal flash presence." Medical Visualization, no. 3 (September 4, 2019): 44–53. http://dx.doi.org/10.24835/1607-0763-2019-3-44-53.
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Aim. To assess clinical and morpho-functional features of the heart in patients with congestive heart failure (CHF) after cardiac resynchronization therapy (CRT) depending on septal flash (SF).Materials and methods. The study enrolled 60 patients (92.0% men, 8.0% women; mean age 54.5 ± 10.4 years; 70.0% had left bundle branch block (LBBB) with II-IV NYHA functional class CHF. SF (mechanical anomaly of interventricular septum (IVS) movement) is determined according to speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI). Patients were divided into two groups: with SF (I group, n = 10) and without SF (II group, n = 50).Results. At baseline the groups did not differ in main clinical characteristics including QRS width and LBBB. Mechanical interventricular delay was higher in group I (65.5 ms [53.5; 95.5] vs 31.0 ms [15.0; 64.5]; р = 0.026). Basal segment of IVS longitudinal strain (LS) delay by STE (257.5 ms [156.3; 293.8] vs 323.5 ms [262.5; 377.8]; р = 0.024) and LS delay by TDI (204.0 ms [170.8; 260.3] vs 434.0 ms [370.0; 489.0]; р < 0.001) were significantly lower in group with SF. According to logistic regression a combination of LS apical segment of IVS by STE (HR 0.607; 95% Cl 0.369–0.989; р = 0.048) and LS delay basal segment of IVS by TDI (HR 0.969; 95% Cl 0.0945–0.993; р = 0.011) had a relationship with SF. According to ROC analysis sensitivity and specificity of this model in SF definition in patients with CRT were 87.5% and 86.5% (AUC = 0.939; p < 0.01). Mean changes in LV ESV (52.0 ml [32.5; 72.8] vs 19,0 ml [1.3; 40.0]; р = 0.002) and LV ejection fraction (EF) (13.0% [5.5; 18.8] vs 4.0% [2.0; 9.0]; р = 0.002) were significantly higher in patients with SF. All patients in group I had a superresponse to CRT (ESV LV decrease ≥30%); 42.0% patients in group II were superresponders (р < 0.001).Conclusion. SF could be determined by STE and TDI. SF is associated with severe mechanical interventricular dyssynchrony and superresponse to CRT. Patients with SF have significantly better LV EF dynamics after CRT.
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Pochapinskyi, O., G. Lavrenchuk, N. Atamaniuk, and A. Chernyshov. "SELECTION AND TESTING OF EXPERIMENTAL MODELS OF NORMAL AND MALIGNANT HUMAN CELLS IN VITRO AND EVALUATION OF THEIR SENSITIVITY RANGE TO THE NEUTRON/CAPTURE AND PHOTON-CAPTURE AGENTS AND PHOTOSENSITIZERS." Проблеми радіаційної медицини та радіобіології = Problems of Radiation Medicine and Radiobiology 26 (2021): 260–72. http://dx.doi.org/10.33145/2304-8336-2021-26-260-272.
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Objective: to investigate the structural and morpho-functional changes in test systems of malignant (A-549 cell line) and normal (fibroblasts of the 6th passage) human cells during incubation with gadolinium-containing photon-capture agent «Dotavist» and photosensitizer «Fotolon». Methods. The passaged (continuously interweaved) cell culture technique on normal human fibroblasts and malignant human cells; cytological, biophysical, statistical methods. Results. The cytotoxic properties of «Dotavist» gadolinium-containing photon-capturing agent and «Photolon» photosensitizer in a wide range of concentrations (5, 10, 25, 50, 100 and 200 μl/ml) were studied by the morphofunctional characteristics (growth kinetics, proliferative and mitotic activity, presence of atypical cells) in the in vitro test systems of malignant (non-small cell lung cancer cell line A-549) and normal (6th passage fibroblasts) human cells. It was found that the cytotoxic properties of «Dotavist» in test systems of malignant and normal cells are expressed under its administration in high concentrations (100 and 200 μl/ml). During incubation with «Photolon» photosensitizer the cytotoxic effect on malignant cells was determined at the lowest concentrations (5 and 10 μl/ml). Photosensitizer administration in the increasing concentrations has lead to genotoxic effects. Cytotoxic effect of photosensitizer on the normal human fibroblasts was evident in the 5-200 μl/ml concentration range. There was a moderate decrease in mitotic activity along with increasing concentration. Genotoxic properties of photosensitizer were evident at 25 μl/ml concentration and above. Conclusion. Study results of the effectiveness of neutron-capture and photon-capture technologies by the sensitivity assay in the in vitro test systems of human malignant cells (non-small cell lung cancer cell line A-549) and normal cells (transplantable human fibroblast culture, the 6th passage) to the gadolinium-containing photon-capture «Dotavist» agent and «Photolon» photosensitizer in different concentrations provide the basis for pre-clinical stage of evaluating the effectiveness of medications used in binary technologies. Key words: culture of human malignant cells, culture of human fibroblasts, neutron-capture agent, photon-capture agent, photosensitizer, proliferation, mitotic index.
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Chistyakova, M. V., A. V. Govorin, T. V. Kalinkina, N. A. Medvedeva, and Ya V. Kudryavtseva. "Remodeling of the right heart and hepatolienal circulation in patients with coronavirus infection." Siberian Journal of Clinical and Experimental Medicine 37, no. 4 (January 17, 2023): 70–76. http://dx.doi.org/10.29001/2073-8552-2022-37-4-70-76.
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Aim. To study the condition of the right heart and hepatolienal circulation in patients three months after COVID-19.Material and Methods. A total of 87 patients aged on average 36.2 years who were treated for COVID-19 three months before underwent echocardiography and the study of hepatolienal blood flow. Patients were divided into groups: group 1 comprised patients with CT 0; group 2 comprised patients with bilateral pneumonia CT 1–2, and group 3 comprised patients with CT 3–4. Control group comprised 22 patients who did not undergo COVID–19.Results. In patients of group 1, the diastolic velocity of the transtricuspid flow increased by 24% compared to the control p <0.001. The ratio of diastolic velocities E/A and Em/Am decreased in all groups, and the greatest abnormalities were found in group 3. In group 3, systolic pressure in the pulmonary artery increased; the right ventricle, fibrous ring, right branch of the pulmonary artery, and diameters of the inferior vena cava, portal vein, and splenic veins increased. There was a decrease in the flow rate in the splenic vein (14%), and sizes of the liver and spleen increased. Correlations were established between increased pressure in the pulmonary artery and functional parameters of the heart and hepatolienal blood flow as well as between morpho-functional parameters of the heart and indicators of the portal vein, p < 0.001.Conclusion. Three months after the coronavirus infection, patients with mild and moderate severity of the disease developed subclinical abnormalities in the diastolic function of the right ventricle. In patients with severe viral pneumonia, there was also increased pressure in pulmonary artery; the dilatations of the right ventricle, pulmonary artery, splenic vein, and portal veins developed along with a decrease in the flow rate in the splenic vein and increases in the liver and spleen.
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Alberti, C., M. Mediago, G. Chiapello, D. Bernardi, and G. Arena. "Retroperitoneal Fibrosis, Today: An Updating of Knowledges on this Subjet." Urologia Journal 73, no. 2 (April 2006): 205–16. http://dx.doi.org/10.1177/039156030607300201.
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Retroperitoneal fibrosis (RPF) is characterized, at first, by a replacement of the normal retroperitoneal tissue by an active granulomatosis inflammation (cellular phase), and at a later stage by a fibrous scar tissue (established fibrotic phase). The aetiology of secondary RPFs includes several drugs (notably methysergide, ergotamine, pergolide, hydralazine), both chronic atherosclerotic aortitis-periaortitis and inflammatory aortic aneurisms, autoimmune diseases such as different forms of systemic vasculitis and collagen diseases, histiocytosis such as Erdheim-Chester syndrome, desmoplastic reactions to retroperitoneal malignancy carcinoid syndrome, retroperitoneal accidentally and surgically occurred traumas, abdominal radiation therapy. On the contrary, the causes of idiopathic RPF remain uncertain; its pathogenesis is associated to immuno-mediated mechanisms. The inflammatory process can involve retroperitoneal vessels, ureters, peri- and pararenal spaces, mesenteric small intestine, duodenum, psoas muscles, and can spread to mediastinal space. Diagnosis and characterization of the polyphase inflammatory evolution require integrated approaches including laboratory tests, morpho-functional imaging and, sometimes, histopathologic assessment. In the early stages, the management of RPF ranges from the removal of identifiable etiologic agents to the interfering with the inflammatory immuno-mediated process by means of several drugs. Unfortunately, many effective immunosuppressive drugs induce adverse reactions unrelated to their specific immunosuppressive action; this is the reason why the biopharmacology research today is struggling towards the identification of molecular targets having their expression restricted to immune cells and/or cytokines. Moreover, the progression of atheromatous aortitis to RPF could be prevented by statins which are able to interfere with the inflammatory pathway as well as to induce the well-known reduction in the levels of atherogenic lipoproteins. In the late established fibrotic stage, either open surgery or endourologic, laparoscopic procedures are performed; nevertheless neoadiuvant and adiuvant corticosteroid-immunosuppressive treatments are mandatory in order to avoid any relapse of the disease.
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Shirokov, N. E., A. M. Soldatova, D. V. Krinochkin, and V. A. Kuznetsov. "Traditional Criteria of Mechanical and Electrical Dyssynchrony as a Predictor of Super-Response in Patients with Cardiac Resynchronization Therapy." Siberian Journal of Clinical and Experimental Medicine 37, no. 4 (January 18, 2023): 124–28. http://dx.doi.org/10.29001/2073-8552-2022-37-4-124-128.
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Aim: To evaluate clinical and morpho-functional predictors of super-response to cardiac resynchronization therapy (CRT) in patients with heart failure and reduced ejection fraction (HFrEF) in the short-term period after implantation.Material and Methods. The study enrolled 86 patients (88.4% men, 54.0 ± 8.9 years mean age, New York Heart Association (NYHA) class II–IV). Patients were examined at baseline and in dynamics (mean follow-up was 10.6 ± 3.6 months). According to the change in left ventricular (LV) end-systolic volume (ESV) patients were divided into two groups: Group I (n = 19) with a decrease in LV ESV ≥ 30% (super-responders (SR) and Group II (n = 67) – decrease in LV ESV < 30% (non-super-responders (non-SR). Parameters of mechanical dyssynchrony (MD) were assessed in the two groups including LV pre-ejection period, interventricular mechanical delay (IVMD), intraventricular delay (IVD).Results. At baseline, traditional parameters of MD were higher in SR: LV pre-ejection period (156.8 ± 35.4 ms vs 135.0 ± 35.6 ms; p = 0.021) and IVMD (73.0 [43.0; 108.0] ms vs 47.0 [19.5; 70.0] ms; p = 0.017). Logistic regression results showed that female gender (HR 7.048; 95% CI 1.496–33.206; p = 0.014) and QRS width (HR 1.017; 95% CI 1.000–1.034; p = 0.048) had an independent association with super-response.Conclusion. In patients with HFrEF, more severe mechanical and electrical dyssynchrony is associated with super-response to CRT in a short-term follow-up period.
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Shirokov, N. E., V. A. Kuznetsov, A. M. Soldatova, S. M. Diachkov, and D. V. Krinochkin. "DYNAMICS OF MECHANICAL DYSSYNCHRONY IN PATIENTS WITH SUPERRESPONSE TO CARDIAC RESYNCHRONISATION THERAPY WITH A LONG-TERM FOLLOW-UP." Siberian Medical Journal 33, no. 2 (July 14, 2018): 42–50. http://dx.doi.org/10.29001/2073-8552-2018-33-2-42-50.
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Aim. The aim is to assess clinical features of organism and morpho-functional properties of heart and to study the dynamics of mechanical dyssynchrony in patients with congestive heart failure and superresponse to cardiac resynchronization therapy.Material and Methods. 72 patients were examined (mean age 54.3±8.9 years) at baseline and during follow-up visits: 10.5±3.7 months, 52.0±21.4 months. Patients were divided into groups: I group (n=31) with decrease of left ventricle endsystolic volume ≥30% (superresponders) and II group (n=41) — decrease of left ventricle endsystolic volume <30% (nonsuperresponders).Results. At baseline there were differences in the presence of myocardial infarction (22.5% in I group vs 46.3% in II group; p=0.038), the groups were comparable in severity of electrical and mechanical dyssynchrony. Left ventricle pre-ejection period in I group was statistically significantly decreased at both control visits, in group II there was no significant change. Right ventricular pre-ejection period significantly increased only in I group at the second control visit compared to baseline values. The mechanical interventricular delay significantly decreased in I group at both control visits compared to baseline values, in II group only at first control visit. The Intraventricular dyssynchrony assessed by tissue doppler imaging significantly decreased in both groups compared to baseline values. The survival rate in I group was 87.1%, in group II was 65.9% (Log-Rank test p=0.038).Discussion. Based on the results of the subanalysis of the Echo-CRT study, it was shown that a decrease in mechanical dyssynchrony in patients with cardiac resynchronization therapy is associated with a lower incidence of hospitalization due to heart failure or death. Persistent or worsening dyssynchrony according to echocardiography may be a marker of a severity of the disease in patients with congestive heart failure and has a prognostic value. It is important to note that in our study the described facts confirm the preservation of cardiac resynchronization therapy effect with long follow-up in superresponders and limited cardiac resynchronization therapy effect with short follow-up in nonsuperresponders.Conclusion. Superresponse is associated with a decrease of mechanical dyssynchrony with a long-term follow-up also with a higher survival rate.
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Tregubova, Mariia O., Kostyantyn V. Rudenko, Svitlana V. Fedkiv, Polina A. Danchenko, Yurii I. Vitkovskyi, and Mykhailo S. Ishchenko. "Cardiac Multislice Computed Tomography in the Detection of Phenotypic Polymorphism of Hypertrophic Cardiomyopathy." Ukrainian Journal of Cardiovascular Surgery 30, no. 2 (June 24, 2022): 59–66. http://dx.doi.org/10.30702/ujcvs/22.30(02)/tr029-5966.
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Background. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease with a prevalence of 1 case per 500 people and is the most common cause of sudden cardiac death in young patients. As clinical manifestations and electrocardiographic data are nonspecific and diverse, noninvasive imaging techniques play a key role in the detection of HCM and the understanding of its pathophysiology.
The aim. To evaluate the possibilities of ECG-synchronized cardiac multislice computed tomography (MSCT) as a highly informative diagnostic tool for assessing the morpho-functional state of the heart in patients with HCM.
Materials and methods. This was a retrospective analysis conducted at the National Amosov Institute of Cardiovascular Surgery from January 2020 to December 2021. We examined 221 cardiac MSCT scans of patients who underwent the examination to assess the spread of myocardial hypertrophy. Particular attention was paid to the presence of crypts at different levels of the left ventricle (LV), anatomical features of the mitral valve and subvalvular apparatus. The presence of systolic pulling of the anterior mitral valve to the interventricular septum, myocardial mass, LV end-diastolic, LV end-systolic volumes and the corresponding indices of body surface area, ejection fraction were determined and calculated during the functional analysis. Additionally, the anatomy and patency of the coronary arte ries were assessed. The studies were performed on a 640-slice Canon Aquilion One CT scanner with retrospective ECG gating and subsequent image processing. The studies were transferred to a workstation for review and evaluation by a team of radiologists.
Results. The mean patient age was 46 ± 23 years, 48% were male. Mean maximal LV wall thickness was 19 mm (range 16–34). In 159 patients (71.9%), there was an asymmetric form of HCM with a predominant thickening of the anterior and anteroseptal segments of the left ventricle at the basal and midventricular levels. Fifty-four (24.4%) patients had symmetric form of HCM. The midventricular form of HCM was detected in 4 patients (1.8%). Apical form of HCM was detected in 3 patients (1.3%). One patient was diagnosed with a tumor-like variant of HCM (0.5%). In 198 patients (89.6%), systolic anterior motion of the mitral valve to the interventricular septum was found. In 95 cases (42.9%), morphological abnormality, abnormality of the number or attachment of the papillary muscles were detected. Forty-eight myocardial crypts were detected in 44 patients (21.7%). In 194 patients (87.7%), patent coronary arteries without signs of stenosis were found, 68 patients (30.7%) had 74 myocardial bridges (33.4%).
Conclusions. HCM is a genetic heart disease with enormous phenotypic diversity. Due to its high spatial resolution, cardiac MSCT is an accurate diagnostic tool, which allows to assess the morphofunctional state of the LV, mitral valve, subvalvular apparatus, as well as to analyze the anatomy and narrowing of coronary arteries in patients with HCM.
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Pepe, Alessia, Antonella Meloni, Maria Giovanna Neri, Massimo Allò, Elena Facchini, Tommaso Casini, Aurelio Maggio, et al. "Changes of Cardiac Iron and Function during Pregnancy in Trasfusion-Dependent Thalassemia Patients." Blood 126, no. 23 (December 3, 2015): 3367. http://dx.doi.org/10.1182/blood.v126.23.3367.3367.
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Abstract Background. The aim of this study was to assess the changes in cardiac and hepatic iron overload and in morpho-functional cardiac parameters by Magnetic Resonance Imaging (MRI) in transfusion-dependent thalassemia patients who got pregnant and interrupted their chelation treatment. Methods. Among the956 women with hemoglobinopathies in reproductive age enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project, we selected 17 women with thalassemia (14 with thalassemia major and 3 with transfusion-dependent thalassemia intermedia) who had a pregnancy with successful delivery and who performed a MRI scan before and after the pregnancy. Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Results. The pre-pregnancy MRI was performed 15.02±5.31 months before the delivery while the post-partum MRI was performed 5.73±4.45 months later. For 16 new-mothers the post-partum MRI was performed after the restart of the chelation therapy, specifically 3.95 ± 4.10 months later. One new-mother performed the post-partum MRI about 3 months before restarting the chelation therapy. The table shows the MRI parameters at the two MRIs. The pre-pregnancy and the post-partum global heart T2* values and number of pathological segments were comparable. Two patients with a normal global heart T2* value (>20 ms) before pregnancy showed a pathological post-partum value. After pregnancy there was a significant increase of MRI liver iron concentration (LIC) values. At the pre-partum MRI six (35.3%) patients had a MRI LIC < 3 mg/g/dw while at the post-partum MRI all patients had a pathological MRI LIC. Among the biventricular volumetric and functional parameters, there was a significant increase of right ventricular (RV) end-systolic volume index and a significant reduction of RV ejection fraction. Conclusion. In some transfusion-dependent patients, cessation of chelation therapy allows rapid iron overload. Pregnant women with thalassemia should be monitored carefully for iron loading and cardiac status before they embark upon a pregnancy and afterwards and consideration should be given to offering desferrioxamine chelation therapy immediately after delivery. In women showing severe iron overload before pregnancy desferrioxamine should be started after the middle of the second trimester. The negative impact on the RV parameters could reflect the effect of the high cardiac output state independent of the physiological changes during pregnancy. Table 1. Changes in MRI parameters following the pregnancy. Before pregnancy Post pregnancy Mean difference P-value Global Heart (ms) 33.27 ± 6.72 34.09 ± 9.46 0.82 ± 8.07 0.523 N seg. With T2* < 20 ms 1.71 ± 2.93 2.35 ± 4.72 0.65 ± 5.44 0.953 LIC (mg/g dw) 4.08 ± 3.55 16.89 ± 8.89 12.82 ± 8.19 <0.0001 LV EDVI (ml/m2) 76.53 ± 8.46 78.53 ± 10.42 2.00 ± 11.95 0.500 LV ESVI (ml/m2) 27.06 ± 3.96 29.24 ± 5.67 2.18 ± 5.37 0.114 LV SVI (ml/m2) 49.41 ± 7.19 47.41 ± 7.28 -2.00 ± 9.69 0.408 LV mass index (g/m2) 51.53 ± 8.43 54.76 ± 9.54 3.24 ± 6.66 0.062 LV EF (%) 64.00 ± 4.64 62.53 ± 4.68 -1.47 ± 5.86 0.317 RV EDVI (ml/m2) 73.24 ± 9.47 75.76 ± 10.94 2.53 ± 11.94 0.395 RV ESVI (ml/m2) 24.24 ± 6.06 27.82 ± 6.44 3.59 ± 6.43 0.035 RV SVI (ml/m2) 47.47 ± 8.35 47.41 ± 7.28 - 0.06 ± 10.69 0.982 RV EF (%) 66.82 ± 5.43 63.06 ± 5.51 3.77 ± 5.84 0.017 Disclosures Pepe: ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau; Chiesi: Speakers Bureau.
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Tataranni, Tiziana, Francesca Agriesti, Carmela Mazzoccoli, Vitalba Ruggieri, Fiorella D'Auria, Franca Falzetti, Mauro Di Ianni, Pellegrino Musto, Nazzareno Capitanio, and Claudia Piccoli. "Redox Signaling in Adult Stem Cell Biology: A New Target Controlling Pluripotency and Differentiation. What about Iron Chelators?." Blood 120, no. 21 (November 16, 2012): 2299. http://dx.doi.org/10.1182/blood.v120.21.2299.2299.
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Abstract Abstract 2299 Introduction Hematopoietic stem cells (HSCs) constitute a reservoir of undifferentiated cells that can be committed, upon appropriate stimuli, in the haematic lineages. Although residing in a bone-marrow hypoxic microenvironment (niche) and mainly relying on anaerobic glycolysis, HSCs are endowed with mitochondria. Recently, specific interest has been focused on HSCs mitochondria and on their role as reactive oxygen species (ROS) generators during the early phases of commitment. Indeed, consolidated evidences highlight the importance of redox signalling in the homeostasis of fundamental processes in cell adaptive biology and particularly in controlling the balance between self-renewal and differentiation of stem cells. HSCs constitutively generate low levels of ROS produced by both mitochondrial respiratory chain and NADPH oxidases (NOXs). ROS would act as secondary messengers, modulating the expression of master transcription factors leading or (pre)conditioning stem cells towards differentiation. Myelodisplastic syndrome (MDS) is characterized by disturbance of the HSC differentiation and most MDS patients are treated with iron chelators to compensate for the iron overload consequent to the blood cell transfusion-based standard therapy. Intriguingly, a robust percentage of patients, treated with the iron chelator deferasirox (DFX), recover correct HSCs differentiation whereas other chelators, like deferoxamine (DFO) did not. In the presented study we investigated the effect of DFX and DFO on the redox homeostasis of hematopoietic stem/progenitor cells (HSPCs) in order to get insights on the differential effect of iron chelators in rescuing altered hematopoiesis. Materials and Methods Human HSPCs were isolated from peripheral blood (PB) or bone marrow (BM) of G-CSF-treated or untreated healthy donors, respectively, by immuno-selection against the specific markers CD133 and CD34 and resulted >99% immunophenotypically homogeneous. Mitochondrial respiratory activity was measured in intact HSPCs by high resolution oxymetry. Morpho-functional features of HSPC-mitochondria, expression of the HSPC-surface commitment markers and ROS level were analyzed by laser scanning confocal microscopy (LSCM) and flow cytometry using specific probes or antibodies. HSPCs were treated with 100 mM DFX or DFO for 24 hrs. Results Measurement of oxygen consumption rate as well as molecular analyses in PB-HSPCs confirmed a poor mitochondrial oxidative phosphorylation phenotype. LSCM imaging of mitochondria in either PB- and BM-HSCs displayed a punctuate rather than interconnected network. However, co-staining of mitochondria and CD34/CD133 stemness-markers revealed a striking inverse correlation. Finally HSPCs produced DCF-detectable and DPI-inhibitable ROS attributable to constitutive NOX activity and related to stabilization of the hypoxia-inducibile factor (HIF1a) under normoxic condition. DFX treatment of HSPCs resulted in a significant up-regulation of ROS level whereas no significant change was observed following DFO treatment. Importantly, the DFX-mediated ROS production was insensitive to treatment with low NOX-inhibiting concentration of DPI but was abrogated by high concentration of DPI thus pointing to mitochondria as ROS source. Conclusions Our results show that HSCs in the early phase of commitment undergo a progressive increase of mitochondrial mass indicating the need of a bioenergetic up-regulation to cope with the oncoming energy-demanding proliferative/differentiative phenotype. Redox signaling, mediated by ROS production and likely triggered by changes in the environmental oxygen tension, appears to be essential in regulating HSC self-renewal and preservation of pluripotency. DFX treatment, by modulating ROS production, might lead to activation of redox-sensitive key factors able to restore the hematopoietic function in MDS patients. This effect seemingly is independent on the iron-chelating property of DFX but pertains to additional pharmacological properties that warren further investigation. Disclosures: No relevant conflicts of interest to declare.
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Pepe, Alessia, Antonella Meloni, Giancarlo Carulli, Esther Natalie Oliva, Francesco Arcioni, Sergio Storti, Maria Giovanna Neri, et al. "Prospective Changes of Cardiac and Hepatic Iron and Cardiac Function in Low and Intermediate-1 Risk MDS Patients." Blood 124, no. 21 (December 6, 2014): 1911. http://dx.doi.org/10.1182/blood.v124.21.1911.1911.
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Abstract Background: In patients with myelodysplastic syndrome (MDS) no longitudinal studies on myocardial and hepatic iron and on cardiac function and fibrosis are available in literature. So, the aim of our study was to assess the changes in cardiac and hepatic iron overload and the morpho-functional cardiac parameters by Magnetic Resonance Imaging (MRI) in MDS patients enrolled in the MIOMED (Myocardial Iron Overload in MyElodysplastic Diseases) study who performed the follow-up (FU) MRI at 12 months. Methods: MIOMED is an observational, MRI multicentre study in low and intermediate-1 risk MDS patients who have not received regular iron chelation therapy. Out of the 51 MDS patients enrolled, 48 underwent the baseline MRI exam and 28 performed the MRI FU. This analysis was limited to patients who performed both the MRIs. Mean age was 72.8±7.6 years and 8 patients were females. MIO was assessed using a multislice multiecho T2* approach. Hepatic T2* values were assessed in a homogeneous tissue area and converted into liver iron concentration (LIC). Biventricular function parameters were quantified by cine sequences. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) acquisitions. Results: The FU MRI was not performed for the following reasons: 4 deaths and 16 patient refusal. At baseline only one patient showed cardiac iron overload (global heart T2*=14.8 ms) but he recovered at the FU (global heart T2*=28.8 ms). He was not transfused. Out of the 27 patients without significant cardiac iron at the baseline, 26 maintained the same status at the FU while one showed cardiac iron (global heart T2*=12.3 ms). Thirteen patients (8 transfusion-dependent - TD) had hepatic iron overload (MRI LIC≥3mg/g/dw) at the baseline.For this subgroup, the baseline and the FU LIC values were, respectively, 14.9±12.0 mg/g/dw and 20.1±16.1 mg/g/dw. The increase in MRI LIC values was not significant (P=0.196). Out of the 11 patients with a baseline MRI LIC<3 mg/g/dw, two (13.3%) showed hepatic iron at the FU. Only one patient was TD but both patients had not received any chelation therapy. Serum ferritin levels were comparable at both the MRIs (923±618 vs 1168±1004 ng/ml; P=0.150). Due mainly to technical reasons, biventricular function was assesses at both baseline and FU MRIs in 22 patients. At baseline 6 patients showed a reduced left ventricular ejection fraction (LVEF) and 4 of them recovered at the FU. All patients had a baseline global heart T2*>20 ms (one with 2 segmental T2* values<20 ms). At baseline 5 patients showed a reduced right ventricular EF (RV EF) and all recovered at the FU. One patient with normal LV EF at baseline showed pathological LV EF at the and 2 patients with normal RV EF at baseline showed reduced RV EF at the FU (one patient suffered from pulmonary hypertension). At the FU we detected a significant increase in the LV end-diastolic volume index (EDVI) (mean difference: 6.5±11.3 ml/m2; P=0.015) as well as in the RV EDVI (mean difference: 7.8±9.3 ml/m2; P=0.002). The change in the LV mass index between the 2 MRIs was not significant. For 18 patients the presence of myocardial fibrosis was investigated at both baseline and FU MRIs, and this subgroup was considered. Eight patients had myocardial fibrosis at the baseline. One patient showed a subendocardial ischemic pattern and seven patients showed a non-ischemic pattern and myocardial fibrosis was detected for all of them also at the FU. At the FU one new occurrence of non-ischemic myocardial fibrosis was detected. Conclusion. The new occurrences of cardiac iron, reduced cardiac function, increased LV and RV EDVI and myocardial fibrosis and the worsening in MRI LIC values suggest the need of performing periodic MRI scans, in order to better manage these patients. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Oliva: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Speakers Bureau.
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Sinha, Sutapa, Wei Ding, Tammy Price-Troska, Reona Sakemura, Shulan Tian, Charla R. Secreto, Xiaosheng Wu, et al. "Identification of a Novel Role for PD-1 Signaling in Promotion Tumor Proliferation in B-Cell Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 10–12. http://dx.doi.org/10.1182/blood-2020-136550.
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Introduction: PD-1 inhibits the cytotoxic T-cell functions via the interaction with its ligands (PDL1 and PDL2). Recently, our group showed a selective response (~40%) with PD-1 blocking antibody pembrolizumab in patients with Richter transformation (RT), particularly after prior exposure to ibrutinib (Wei Ding et al, Blood, 2017). Additionally, PD-1 showed an increased expression in tumor B-cells of patients with RT (Rong He et al, AJSP, 2018). Here we investigated the functional implications of the PD-1 signaling axis in lymphoma B-cell pathobiology. Methods: 26 CLL-involved lymph node (LN) and 20 RT-involved LN samples were tested for PD-1 expression by immunohistochemistry (mouse clone NAT105, Abcam). Then, we checked PD-1 expression in 10 lymphoma cell lines and 1 CLL cell line (MEC-1) by both, flow cytometry and Western blot (WB) analysis. Over-expression of PD-1 using pLEX-lentiviral system (Thermo Scientific) was evaluated for in vitro cell cycle regulation and in vivo tumor growth. Overexpression of PD-1 was further examined on the regulation of cell signaling pathways using human phospho kinase array kit (R&D) and WB analysis. Gene expression signatures in CLL and RT patients were also identified by Illumina-based RNA sequencing using Formalin-Fixed Paraffin-embedded (FFPE)-nodal tissue obtained by clinical biopsy (Tempus Labs; Chicago, IL). Results: The expression of PD-1 was significantly increased in RT-LN compared to CLL-LN (mean ± SEM in RT vs. CLL, 30.6% ± 4.7% vs. 11.5% ± 2.8%, p < 0.001) [Fig 1A]. PD-1 expression was highest in patients with RT where the last prior CLL therapy was ibrutinib. To test the role of PD-1 in lymphoma B-cells, its expression was assessed in lymphoma and CLL cell lines. The expression of PD-1 was found to be variable, but at very low-levels in lymphoma lines OCI-LY7 and OCI-LY19 (data not shown). Constitutive lentiviral (pLEX-PD-1)-mediated overexpression of PD-1 in OCI-LY7 and OCI-LY19 cells led to increased cell growth (1.4 and 1.9 fold compared to original lines on day 4, respectively, Fig 1BI-II), which was further confirmed by cell cycle analysis which showed an increase in S phase by 20.4% and 24.53% in OCI-LY7 and OCI-LY19 cells (Fig 1B III), respectively. When the luciferase + PD-1 expressing OCI-LY7 cells were injected intravenously (1X106 cells) into NSG mice, increased tumor growth was observed at 22 days of follow up by bioluminescence imaging (p<0.01, Fig 1C). Using phospho-kinase array, an overall decrease of phosphorylation was detected on multiple sites of p53 (S392, S15, S46) and CHK2 (T68) (data not shown). This finding was further confirmed by WB analyses (Fig1DI). In addition, decreased of total p53 and increased phosphorylation on both SHP-1 and SHP-2 were found in PD-1 overexpressing OCI-LY19 and OCI-LY17 cell lines (Fig 1DI). Immunoprecipitation experiments with anti-PD1 antibody showed that PD-1 was in the same complex with SHP-1 and SHP-2 in OCI-LY7 cells but only with SHP-2 in OCI-LY19 cells (Fig 1DII). In parallel, mRNA sequencing was performed on 11 nodal tissues from either RT (n=8) or progressive CLL (n=3) after they developed clinical progression. The expression of PD-1 (PDCD1) was positively correlated with the expression of SHP-1 (PTPN6, r=0.56) and Cyclin E1 (CCNE1, r=0.62), implicating a direct role of PD-1 in regulating cellular proliferation and the induction in phosphatase expression in RT and CLL. Conclusion: Our data support the notion that PD-1 overexpression in lymphoma cells modifies cell proliferation in vitro and in vivo and regulates the function of phosphatase SHP and p53- pathways. These findings also indicate that aggressive lymphoma or CLL leukemic cells have the ability to hijack the PD-1 pathway and may result in downregulation of the p53 mediated DNA repair. This novel information provide for new strategies to further evaluate the interaction of checkpoint signals with DNA repair pathway, and possibly provide novel targets for Richter's transformation. Disclosures Ding: alexion: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Astra Zeneca: Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; DTRM: Research Funding; MEI Pharma: Membership on an entity's Board of Directors or advisory committees. Sakemura:Humanigen: Patents & Royalties. Parikh:Janssen: Honoraria, Research Funding; Merck: Research Funding; Pharmacyclics: Honoraria, Research Funding; Ascentage Pharma: Research Funding; GlaxoSmithKline: Honoraria; MorphoSys: Research Funding; AstraZeneca: Honoraria, Research Funding; Verastem Oncology: Honoraria; Genentech: Honoraria; AbbVie: Honoraria, Research Funding; TG Therapeutics: Research Funding. Wang:Novartis: Research Funding; Incyte: Research Funding; Innocare: Research Funding. Liu:Eisal: Research Funding; Genentech: Research Funding; GRAIL: Research Funding; Menarini Silicon Biosystems: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Tesaro: Research Funding. Braggio:DASA: Consultancy; Bayer: Other: Stock Owner; Acerta Pharma: Research Funding. Ansell:Seattle Genetics: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; ADC Therapeutics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol Myers Squibb: Research Funding. Kenderian:Sunesis: Research Funding; Tolero: Research Funding; Torque: Consultancy; BMS: Research Funding; Gilead: Research Funding; Kite: Research Funding; Humanigen: Consultancy, Patents & Royalties, Research Funding; Mettaforge: Patents & Royalties; Novartis: Patents & Royalties, Research Funding; MorphoSys: Research Funding; Lentigen: Research Funding; Juno: Research Funding. Kay:Acerta Pharma: Research Funding; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Juno Theraputics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; MEI Pharma: Research Funding; Sunesis: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Agios Pharma: Membership on an entity's Board of Directors or advisory committees; Cytomx: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees.
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Nijak, Aleksandra, Eline Simons, Bert Vandendriessche, Dieter Van de Sande, Erik Fransen, Ewa Sieliwończyk, Ilse Van Gucht, et al. "Morpho-functional comparison of differentiation protocols to create iPSC-derived cardiomyocytes." Biology Open 11, no. 2 (February 15, 2022). http://dx.doi.org/10.1242/bio.059016.
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ABSTRACT Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) offer an attractive platform for cardiovascular research. Patient-specific iPSC-CMs are very useful for studying disease development, and bear potential for disease diagnostics, prognosis evaluation and development of personalized treatment. Several monolayer-based serum-free protocols have been described for the differentiation of iPSCs into cardiomyocytes, but data on their performance are scarce. In this study, we evaluated two protocols that are based on temporal modulation of the Wnt/β-catenin pathway for iPSC-CM differentiation from four iPSC lines, including two control individuals and two patients carrying an SCN5A mutation. The SCN5A gene encodes the cardiac voltage-gated sodium channel (Nav1.5) and loss-of-function mutations can cause the cardiac arrhythmia Brugada syndrome. We performed molecular characterization of the obtained iPSC-CMs by immunostaining for cardiac specific markers and by expression analysis of selected cardiac structural and ionic channel protein-encoding genes with qPCR. We also investigated cell growth morphology, contractility and survival of the iPSC-CMs after dissociation. Finally, we performed electrophysiological characterization of the cells, focusing on the action potential (AP) and calcium transient (CT) characteristics using patch-clamping and optical imaging, respectively. Based on our comprehensive morpho-functional analysis, we concluded that both tested protocols result in a high percentage of contracting CMs. Moreover, they showed acceptable survival and cell quality after dissociation (>50% of cells with a smooth cell membrane, possible to seal during patch-clamping). Both protocols generated cells presenting with typical iPSC-CM AP and CT characteristics, although one protocol (that involves sequential addition of CHIR99021 and Wnt-C59) rendered iPSC-CMs, which were more accessible for patch-clamp and calcium transient experiments and showed an expression pattern of cardiac-specific markers more similar to this observed in human heart left ventricle samples.
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Cerrito, L. F., A. Schiavone, M. Moretti, L. Ferri, C. Bergamini, M. Dal Porto, G. Benfari, et al. "P311 Morpho-functional myocardial alteration during trastuzumab therapy: anything beyond cardiotoxicity?" European Heart Journal - Cardiovascular Imaging 21, Supplement_1 (January 1, 2020). http://dx.doi.org/10.1093/ehjci/jez319.164.
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Abstract Background Trastuzumab (TZ) has a primary role in the therapy of HER-2 positive breast cancer but has potential negative effect on left ventricular (LV) function that define cardiotoxicity (CT). Decrease in LV longitudinal strain (GLS) and in left atrial (LA) function observed by peak atrial longitudinal strain (PALS), besides LA remodeling, has already been described as predictors of TZ-related CT. However these parameters haven’t been observed together and regardless of CT. Purpose to describe overall atrial and ventricular morpho-functional variations during TZ therapy. Methods HER-2 positive metastasis-free breast cancer patientsreferring to our Echo-lab were prospectively recruited. Trans-thoracic echocardiography was performed before starting TZ and every 3 up to 12 months. LV volumes and ejection fraction (LVEF), indexed LA volume (LAVI), LA deformation parameters, and multiple diastolic parameters were collected. 2D-Speckle tracking analysis was performed at baseline and at each examination using Philips’ QLAB software. Results Eligible patients were 64. 53 of these (82,8%) had a complete follow-up at 12 months and were included in the analysis. 42 patients (79,3%) were treated with both TZ and anthracyclines. During follow-up CT occurred in 7 patients (10,9%). Mean baseline parameters were: age 54 ± 13 years,LVEF 63,3 ±3,2%, GLS -21,2 ± 2,1%, LAVI 24,4 ±6,9 ml/mq, peak atrial contraction strain (PACS) 22,9 ±6,5%, PALS 51,1 ± 11,5%. Deformation analysis was feasible in 95% of patients. None of the echocardiographic parameters regarding diastolic function and LV volumes showed significant variations. Analyzing overall populations data during the 1 year of follow-up, we reported a decrease trend of GLS (p for time <0.0001) with an early drop during the first 6 months of TZ therapy with a subsequent "plateau" phase, and a reductionof LVEFover time (p for time <0.0001) with a continuous gradual decreasefor the whole follow-up (but still within the normal value span). On top LA functional parameters showed a decreasing trend: PALS (p for time <0.0001) and PACS (p for time <0.0001) showed both decrease trend since the first months of therapy, lasting for the entire follow-up. Also we reported a notable LAVI dilation during the first 6 months of TZ therapy (p for time <0.0001) followed by a plateau phase, and combining LAVI and PALS (LAVI/PALS) we noted an increase trend (p for time <0.0001). These data are showed in Figure I. Conclusions Our results suggest that deformation analysis is useful to study LV and LA functional remodeling during TZ therapy. Actual recommendations for the identification of CT are based upon a joint evaluation of LVEF and GLS, but our study show significant variations of other morpho-functional parameters regardless of CT. These changes could be used as indicators of subclinical damage involving the entire heart and the analysis of different deformation indexes could improve the early detection of CT. Abstract P311 Figure. Morpho-functional variations
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Moroni, A., L. Tondi, A. Camporeale, V. Milani, S. Pica, M. Pieroni, F. Pieruzzi, et al. "Left atrial morpho-functional changes in hypertrophic cardiomyopathy and Fabry disease: a CMR-feature tracking study." European Heart Journal - Cardiovascular Imaging 22, Supplement_2 (June 1, 2021). http://dx.doi.org/10.1093/ehjci/jeab090.075.
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Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular (LV) diastolic dysfunction (DD) is a hallmark of hypertrophic cardiomyopathy (HCM) and its phenocopies, such as Fabry disease (FD). Together with left atrial (LA) size, LA function is emerging as a sensitive marker of the adaptive changes to backward transmission of LV cardiac filling pressure, thus implementing DD assessment. Additionally, both HCM and FD are characterized by a primitive atrial myopathy, but LA morpho-functional changes in HCM and FD have never been directly compared. More recently, LA strain by Cardiovascular Magnetic Resonance Feature Tracking (CMR-FT) has been demonstrated to be a feasible and reproducible tool to explore LA function. Purpose To compare LA morpho-functional changes in HCM and FD and to explore their correlation with tissue alterations. Methods 15 HCM and 15 sex-, age- and LV mass index-matched FD patients underwent CMR (Magnetom Aera 1.5T, Siemens) and Doppler Echocardiography for LV diastolic function assessment (E/e’ and DD grading from 0 to 3). LA phasic function was evaluated by CMR-FT strain (Qstrain Medis). The software output included passive (εe, conduit function), active (εa, booster pump function) and total strain (εs, reservoir function), along with LA volumes and ejection fraction (EF). Late gadolinium enhancement (LGE) was quantified as a percentage of LV mass using the standard deviations (SDs) method (≥ 5 SDs). Interstitial fibrosis was assessed by extracellular volume (ECV) quantification in remote myocardium. All patients were in sinus rhythm. Results In the HCM group, the proportion of patients with DD grade 2-3 was only slightly higher than in FD (p 0.26). Accordingly, no significant difference was found in E/e’ value (p 0.78). Compared to FD, HCM patients showed more severe LA morpho-functional changes, including larger LA end-systolic volume (ESV) (113 ± 35 vs 84 ± 23 ml), lower LA EF (37 ± 7 vs 44 ± 9 %) and a greater reduction of εs (-20 ± 5 vs -25 ± 6 %) and εa (-10 ± 4 vs -15 ± 4 %) (all p < 0.05). LV size and function and the burden of fibrosis (LGE quantification and ECV) were comparable between the two groups. Interestingly, in HCM population, unlike in FD, LA morpho-functional measurements significantly correlated with tissue characterization parameters (LA ESV with LGE, r 0.56, p 0.03; εs and εa with ECV, r -0.51, p 0.05 and r -0.59, p 0.02, respectively). Conclusions LA morpho-functional alterations are much more severe in HCM compared to FD with similar degree of LV hypertrophy. A more severe atrial myopathy or different mechanisms of atrial damage in the two cardiomyopathies may explain these findings. LA CMR-FT analysis may represent a sensitive tool to discriminate between HCM and FD, although larger studies are needed to confirm this finding and the possible correlation with the occurrence of atrial arrhythmias and thromboembolic risk.
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Steinke, Eva, Olaf Sommerburg, Simon Y. Graeber, Cornelia Joachim, Christiane Labitzke, Gyde Nissen, Isabell Ricklefs, et al. "TRACK-CF prospective cohort study: Understanding early cystic fibrosis lung disease." Frontiers in Medicine 9 (January 6, 2023). http://dx.doi.org/10.3389/fmed.2022.1034290.
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BackgroundLung disease as major cause for morbidity in patients with cystic fibrosis (CF) starts early in life. Its large phenotypic heterogeneity is partially explained by the genotype but other contributing factors are not well delineated. The close relationship between mucus, inflammation and infection, drives morpho-functional alterations already early in pediatric CF disease, The TRACK-CF cohort has been established to gain insight to disease onset and progression, assessed by lung function testing and imaging to capture morpho-functional changes and to associate these with risk and protective factors, which contribute to the variation of the CF lung disease progression.Methods and designTRACK-CF is a prospective, longitudinal, observational cohort study following patients with CF from newborn screening or clinical diagnosis throughout childhood. The study protocol includes monthly telephone interviews, quarterly visits with microbiological sampling and multiple-breath washout and as well as a yearly chest magnetic resonance imaging. A parallel biobank has been set up to enable the translation from the deeply phenotyped cohort to the validation of relevant biomarkers. The main goal is to determine influencing factors by the combined analysis of clinical information and biomaterials. Primary endpoints are the lung clearance index by multiple breath washout and semi-quantitative magnetic resonance imaging scores. The frequency of pulmonary exacerbations, infection with pro-inflammatory pathogens and anthropometric data are defined as secondary endpoints.DiscussionThis extensive cohort includes children after diagnosis with comprehensive monitoring throughout childhood. The unique composition and the use of validated, sensitive methods with the attached biobank bears the potential to decisively advance the understanding of early CF lung disease.Ethics and trial registrationThe study protocol was approved by the Ethics Committees of the University of Heidelberg (approval S-211/2011) and each participating site and is registered at clinicaltrials.gov (NCT02270476).
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Liu, NF, and MZ Gao. "LYMPHATIC SYSTEM MALFORMATIONS IN NOONAN SYNDROME: TWO CASE REPORTS AND IMAGING ANALYSIS." Lymphology 53, no. 2 (November 10, 2020). http://dx.doi.org/10.2458/lymph.4657.
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Lymphedema is a well-known complication of Noonan syndrome (NS) but the lymphatic malformations in NS are poorly understood. We report clinical, genetic, and imaging information about a boy and girl with NS and late-onset lower extremity lymphedema. A de novo mission mutation of RIT1 (NM_006912.5) c.246T>A, p.Phe82Leu was identified in the girl, who also showed systemic lymphatic hyperplasia and dysfunction. Magnetic resonance lymphangio-graphy (MRL) of the boy clearly demonstrated segmental dilated and hyperplastic lymphatics with impaired transport function in an affected limb and pelvic region. Indocyanine green lymphography (ICGL) showed delayed and partial enhancement of the lymph vessels in the affected limb but no lymph reflux was detected. No causative mutation was identified in the second case. Lymphoscintigraphy (LSG) failed to show lymph vessels in either of the children. Our study showed that MRL is a reliable and accurate test that can be used to demonstrate morpho-logical and functional defects of the lymphatic system. Moreover, ICGL is sufficiently sensitive to determine the functional condition of peripheral lymph vessels. The combined use of imaging modalities can give an accurate diagnosis of complex lymphatic system anomalies in NS and other syndromic diseases.
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Alareqi, Amal A., Sultan Abdulwadoud Alshoabi, Abdulaziz A. Qurashi, and Abdullgabbar M. Hamid. "Subtle morpho-functional kidney changes in type-2 diabetes mellitus patients: A duplex ultrasound assessment." Pakistan Journal of Medical Sciences 38, no. 3 (January 17, 2022). http://dx.doi.org/10.12669/pjms.38.3.4699.
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Objectives: Diabetes mellitus (DM) is a common endocrine disease with serious effects on multiple organs including the kidneys. This study aimed to investigate the subtle effects of type 2 DM (T2DM) on the kidneys.
Methods: This was a prospective case-control study conducted in the Radiology Department of University of Science and Technology Hospital (USTH) campus, Sana’a, Republic of Yemen, from 1 January 2020 to 31 November 2020. The renal length (RL), renal width (RW), resistive index (RI), and pulsatility index (PI) were prospectively measured in patients with T2DM and healthy controls. The results were compared using the independent samples t-test. Comparisons were likewise performed between patients with controlled DM and patients with uncontrolled DM.
Results: A total of hundred individuals, 50 diabetic patients and 50 controls, were enrolled in this study. Their mean age was 54 ± 7.88 years (range: 40–75 years). The RL, RI, and PI of both kidneys were significantly higher in T2DM than in the control group. Moreover, the RL, RI, PI and creatinine were slightly higher in patients with uncontrolled than in those with controlled DM.
Conclusion: T2DM has significant accentuating effects on the RL, RI and PI associated with low effective renal plasma flow, even before acute kidney injury or chronic kidney disease diagnosis, which may be attenuated by careful regulation of DM. Ultrasound Doppler is a highly valuable imaging modality for evaluating the subtle effects of T2DM on kidney dimensions and blood flow. The RI can be implemented as a tool for the early diagnosis of kidney disease and contribute to slowing the disease progression and preventing renal failure.
doi: https://doi.org/10.12669/pjms.38.3.4699
How to cite this:Alareqi AA, Alshoabi SA, Qurashi AA, Hamid AM. Subtle morpho-functional kidney changes in type-2 diabetes mellitus patients: A duplex ultrasound assessment. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.4699
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Rosa, Pedro Ribeiro, Igor Mychael Melo Ferreira, Guilherme Silva de Mendonca, Fábio Vieira Fernandes, Rodrigo Penha de Almeida, João Lucas O’Connell, and Elmiro Santos Resende. "Severe cardiac insufficiency secondary to cardiotoxicity with clinical and morpho-functional improvement after optimised clinical treatment: case report." Bioscience Journal 36, no. 6 (August 13, 2020). http://dx.doi.org/10.14393/bj-v36n6a2020-48129.
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Many therapies used for cancer (pathology whose cases are progressively increasing in the world) such as chemotherapy and radiotherapy have numerous adverse effects, with cardiotoxicity being one of the most important. This can be defined from the detection, by an imaging method, of a reduction of at least 10% in the left ventricular ejection fraction (LVEF), bringing it to a value below 53%. Anthracyclines (such as Doxorubicin), Trastuzumab, and Taxanes (Docetaxel) are among the most associated chemotherapeutics. To emphasize the importance of optimized treatment for heart failure and to review the main updates on the theme of cardiotoxicity. Case report and bibliographic review on the latest updates to the management of cardiotoxicity and associated heart failure. When correctly identifying the main risk factors associated with chemotherapy and the individual to develop myocardial injury, it is possible to perform the monitoring by means of two main predictors: the myocardial tension strength and the biomarkers. In this sense, changes associated with these predictors may allow early intervention through appropriate treatment and, with the advancement of research, even prevention, mainly using the association of Carvedilol with Enalapril. Continuous monitoring and early initiation of drug therapy for heart failure are clearly associated with a lower degree of myocardial injury and a lower rate of complications. In addition, there is still an increasingly promising possibility in relation to preventive drug therapy, however, there is still a lack of studies on this topic.
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Cipriani, Alberto, Giulia Mattesi, Riccardo Bariani, Annagrazia Cecere, Nicolò Martini, Laura De Michieli, Stefano Da Pozzo, et al. "Cardiac magnetic resonance imaging of arrhythmogenic cardiomyopathy: evolving diagnostic perspectives." European Radiology, July 5, 2022. http://dx.doi.org/10.1007/s00330-022-08958-2.
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Abstract Arrhythmogenic cardiomyopathy (ACM) is a genetically determined heart muscle disease characterized by fibro-fatty myocardial replacement, clinically associated with malignant ventricular arrhythmias and sudden cardiac death. Originally described a disease with a prevalent right ventricular (RV) involvement, subsequently two other phenotypes have been recognized, such as the left dominant and the biventricular phenotypes, for which a recent International Expert consensus document provided upgrade diagnostic criteria (the 2020 “Padua Criteria”). In this novel workup for the diagnosis of the entire spectrum of phenotypic variants of ACM, including left ventricular (LV) variants, cardiac magnetic resonance (CMR) has emerged as the cardiac imaging technique of choice, due to its capability of detailed morpho-functional and tissue characterization evaluation of both RV and LV. In this review, the key role of CMR in the diagnosis of ACM is outlined, including the supplemental value for the characterization of the disease variants. An ACM-specific CMR study protocol, as well as strengths and weaknesses of each imaging technique, is also provided. Key Points • Arrhythmogenic cardiomyopathy includes three different phenotypes: dominant right, biventricular, and dominant left. • In 2020, diagnostic criteria have been updated and cardiac magnetic resonance has emerged as the cardiac imaging technique of choice. • This aim of this review is to provide an update of the current state of art regarding the use of CMR in ACM, with a particular focus on novel diagnostic criteria, CMR protocols, and prognostic significance of CMR findings in ACM.
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Bocchio, Marco, Claire Gouny, David Angulo-Garcia, Tom Toulat, Thomas Tressard, Eleonora Quiroli, Agnès Baude, and Rosa Cossart. "Hippocampal hub neurons maintain distinct connectivity throughout their lifetime." Nature Communications 11, no. 1 (September 11, 2020). http://dx.doi.org/10.1038/s41467-020-18432-6.
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Abstract The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.
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Agbariah, Andrea, Davide Ermacora, Alessandro Ruzzarin, Priscilla Milewski, Chiara Nannelli, Andrea Comunello, and Roberto Cemin. "240 A PEDIATRIC CASE OF BIVENTRICULAR END-STAGE ARRHYTHMOGENIC CARDIOMYOPATHY." European Heart Journal Supplements 24, Supplement_K (December 14, 2022). http://dx.doi.org/10.1093/eurheartjsupp/suac121.576.
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Abstract Background Arrhythmogenic cardiomyopathy (ACM) is a rare heart muscle disease characterized by cardiomyocyte necrosis and fibro-adipose substitution which contribute both to the genesis of malignant ventricular arrhythmias and the morpho-functional alterations of the ventricles. ACM has always been considered a right ventricular disease with secondary involvement of the left ventricle, but recently a left dominant phenotype has been also described. Case report A 14-year-old patient was admitted to our hospital after out-of-hospital cardiac arrest due to ventricular fibrillation, which occurred when she was at rest. A family history of sudden death and dilated cardiomyopathy was retrieved (her brother died at the age of 18 with a dilated heart), but other family members had never been screened to date. Cardiac magnetic resonance imaging (cMRI) appearance was consistent with biventricular dilatation along with severe systolic dysfunction (left ventricular ejection fraction 20%; right ventricular ejection fraction 25%). It showed also thinning and bulging of the basal free wall of the right ventricle proximal to the outflow tract (up to 4 mm) and multiple foci of subepicardial, mid-wall and transmural late gadolinium enhancement (LGE) in both ventricles. Signs of acute decompensated heart failure and a high arrhythmic burden were present. After cardiopulmonary stabilization, she underwent the implantation of a cardioverter-defibrillator (ICD). Conclusion We herein report an uncommon case of biventricular AC (‘definite diagnosis’ according to both Task force criteria 2010 and Padua criteria) with advanced morpho-functional dysfunction occurring already in pediatric age, without any alerting symptom until the cardiac arrest (the typical onset of the ACM in children). It shows how severe biventricular involvement may affect young patients with a rapid progression of the disease. It also stresses the need for a strict follow-up of the family members of a proband since his first diagnosis, highlighting the pivotal role of cMRI in the diagnosis of pediatric disease. This has not been thoroughly studied and lacks sensitive and specific diagnostic criteria.
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Venkatasamy, A., E. Guerin, W. Reichardt, V. Devignot, M. P. Chenard, L. Miguet, B. Romain, et al. "Morpho-functional analysis of patient-derived xenografts reveals differential impact of gastric cancer and chemotherapy on the tumor ecosystem, affecting immune check point, metabolism, and sarcopenia." Gastric Cancer, December 19, 2022. http://dx.doi.org/10.1007/s10120-022-01359-w.
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Abstract Objectives Gastric cancer (GC) is an aggressive disease due to late diagnosis resulting from the lack of easy diagnostic tools, resistances toward immunotherapy (due to low PD-L1 expression), or chemotherapies (due to p53 mutations), and comorbidity factors, notably muscle atrophy. To improve our understanding of this complex pathology, we established patient-derived xenograft (PDX) models and characterized the tumor ecosystem using a morpho-functional approach combining high-resolution imaging with molecular analyses, regarding the expression of relevant therapeutic biomarkers and the presence of muscle atrophy. Materials and methods GC tissues samples were implanted in nude mice. Established PDX, treated with cisplatin or not, were imaged by magnetic resonance imaging (MRI) and analyzed for the expression of relevant biomarkers (p53, PD-L1, PD-1, HER-2, CDX2, CAIX, CD31, a-SAM) and by transcriptomics. Results Three well-differentiated, one moderately and one poorly differentiated adenocarcinomas were established. All retained the architectural and histological features of their primary tumors. MRI allowed in-real-time evaluation of differences between PDX, in terms of substructure, post-therapeutic changes, and muscle atrophy. Immunohistochemistry showed differential expression of p53, HER-2, CDX2, a-SAM, PD-L1, PD-1, CAIX, and CD31 between models and upon cisplatin treatment. Transcriptomics revealed treatment-induced hypoxia and metabolic reprograming in the tumor microenvironment. Conclusion Our PDX models are representative for the heterogeneity and complexity of human tumors, with differences in structure, histology, muscle atrophy, and the different biomarkers making them valuable for the analyses of the impact of platinum drugs or new therapies on the tumor and its microenvironment.