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Introduction: 4D flow cardiovascular magnetic resonance (CMR) is a versatile technique to non-invasively assess cardiovascular hemodynamics. With developing technology, choice in sequences and acquisition parameters is expanding and it is important to assess if data acquired with these different variants can be directly compared, especially when combining datasets within research studies. For example, sequences may allow a choice in gating techniques or be limited to one method, yet there is not a direct comparison investigating how gating selection impacts quantifications of the great vessels, semilunar and atrioventricular valves and ventricles. Thus, this study investigated if quantifications across the heart from contemporary 4D flow sequences are comparable between two commonly used 4D flow sequences reliant on different ECG gating techniques. Methods: Forty participants (33 healthy controls, seven patients with coronary artery disease and abnormal diastolic function) were prospectively recruited into a single-centre observational study to undergo a 3T-CMR exam. Two acquisitions, a k-t GRAPPA 4D flow with prospective gating (4Dprosp) and a modern compressed sensing 4D flow with retrospective gating (4Dretro), were acquired in each participant. Images were analyzed for volumes, flow rates and velocities in the vessels and four valves, and for biventricular kinetic energy and flow components. Data was compared for group differences with paired t-tests and for agreement with Bland-Altman and intraclass correlation (ICC). Results: Measurements primarily occurring during systole of the great vessels, semilunar valves and both left and right ventricles did not differ between acquisition types (p > 0.05 from t-test) and yielded good to excellent agreement (ICC: 0.75-0.99). Similar findings were observed for the majority of parameters dependent on early diastole. However, measurements occurring in late diastole or those reliant on the entire-cardiac cycle such as flow component volumes along with diastolic kinetic energy values were not similar between 4Dprosp and 4Dretro acquisitions resulting in poor agreement (ICC < 0.50). Discussion: Direct comparison of measurements between two different 4D flow acquisitions reliant on different gating methods demonstrated systolic and early diastolic markers across the heart should be compatible when comparing these two 4D flow sequences. On the other hand, late diastolic and intraventricular parameters should be compared with caution.
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OBJECTIVES: Epicardial adipose tissue (EAT) remodeling is associated with atrial fibrillation (AF). Left atrial (LA) EAT dispersion on cardiac CT is a non-invasive imaging biomarker reflecting EAT heterogeneity. We aimed to investigate the association of LA EAT dispersion with AF recurrence after pulmonary vein isolation (PVI). METHODS: In a prospective registry of consecutive patients undergoing first PVI, mean EAT attenuation values were measured on contrast-enhanced cardiac CT scans in Hounsfield units (HU) within low (- 195 to - 45 HU) and high (- 44 to - 15 HU) threshold EAT compartments around the left atrium (LA). EAT dispersion was defined as the difference between the mean HU values within the two EAT compartments. Continuous variables were compared between groups using the Mann-Whitney U test and cox proportional hazard models were used to calculate hazard ratios of predictors of 1-year AF recurrence. RESULTS: A total of 208 patients were included, 135 with paroxysmal AF and 73 with persistent AF. LA EAT dispersion was significantly larger in patients with persistent compared to paroxysmal AF (52.6 HU vs. 49.9 HU; p = 0.001). After 1 year of follow-up, LA EAT dispersion above the mean (> 50.8 HU) was associated with a higher risk of AF recurrence (HR 2.3, 95% CI 1.5-3.6; p < 0.001). It retained its predictive value when corrected for age, sex, body mass index, LA volume, and AF type (HR 2.8, 95% CI 1.6-4.6; p < 0.001). CONCLUSION: A larger LA EAT dispersion on contrast-enhanced cardiac CT scans, reflecting EAT heterogeneity, is independently associated with AF recurrence after PVI. CLINICAL RELEVANCE STATEMENT: Based on LA EAT dispersion assessment, a more accurate risk stratification and patient selection may be possible based on a pre-procedural cardiac CT when planning PVI. KEY POINTS: ⢠Epicardial adipose tissue (EAT) remodeling is associated with atrial fibrillation (AF). ⢠A larger left atrial EAT dispersion in a pre-procedural cardiac CT was associated with a higher 1-year AF recurrence risk after pulmonary vein isolation. ⢠A pre-procedural cardiac CT with left atrial EAT dispersion assessment may provide a more accurate risk stratification and patient selection for PVI.
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Tejido Adiposo , Fibrilación Atrial , Pericardio , Venas Pulmonares , Recurrencia , Tomografía Computarizada por Rayos X , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Masculino , Femenino , Tejido Adiposo/diagnóstico por imagen , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Pericardio/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Estudios Prospectivos , Anciano , Medios de Contraste , Ablación por Catéter/métodos , Sistema de Registros , Tejido Adiposo EpicárdicoRESUMEN
OBJECTIVES: Gadolinium-based contrast agents (GBCAs) are routinely used in magnetic resonance imaging (MRI) examinations. However, there is limited knowledge about the interaction with and distribution of the drug in human cells. This lack of knowledge is surprising, given that the first interaction of the drug occurs with blood cells. Moreover, recent studies reported gadolinium (Gd) deposition within organs, such as the brain. Hence, this study is aiming to determine the uptake of GBCA in blood cells of patients undergoing contrast-enhanced MRI (ce-MRI) examination. MATERIALS AND METHODS: Human blood was exposed to either gadoterate meglumine (Gd-DOTA) or Eu-DOTA in vitro or was collected from patients undergoing ce-MRI with Gd-DOTA. Uptake of contrast agents (CAs) by blood cells was quantified by Gd measurements using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) or, to confirm Gd-DOTA uptake, by a complementary method using Eu-DOTA by time-resolved fluorescence spectroscopy, respectively. RESULTS: Uptake of Gd-DOTA or Eu-DOTA into white blood cells (WBCs) ex vivo was detectable by SC-ICP-MS and time-resolved fluorescence spectroscopy. The intracellular concentrations were estimated to be in the range of 1-3 µM. However, no CA uptake into erythrocytes was detected with either method. In total, 42 patients between 30 and 84 years old (24 men, 18 women) were enrolled. White blood cells' uptake of Gd was measured by SC-ICP-MS. Isolated WBCs from patients who underwent ce-MRI examination showed substantial Gd uptake; however, the studied patient group showed an inhomogeneous distribution of Gd uptake. Measurements immediately after MRI examination indicated 21-444 attogram/WBC, corresponding to an intracellular Gd concentration in the range from 0.2 to 5.5 µM. CONCLUSIONS: This study confirms the ex vivo uptake of GBCA by WBCs and provides the first evidence that GBCA is indeed taken up by WBCs in vivo by patients undergoing ce-MRI examination. However, the observed Gd uptake in WBCs does not follow a log-normal distribution commonly observed in the fields of environmental studies, biology, and medicine. Whether cellular uptake of GBCA is linked to the observed deposition of Gd remains unclear. Therefore, studying the interaction between GBCA and human cells may clarify crucial questions about the effects of Gd on patients after MRI examinations.
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Medios de Contraste , Compuestos Heterocíclicos , Compuestos Organometálicos , Masculino , Animales , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Gadolinio DTPA , Modelos Animales , Compuestos Organometálicos/efectos adversos , Eritrocitos , Encéfalo , Imagen por Resonancia Magnética/métodosAsunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Disección de la Aorta Torácica , Procedimientos Endovasculares , Humanos , Resultado del Tratamiento , Aneurisma de la Aorta Torácica/cirugía , Estudios Retrospectivos , Aorta Torácica/cirugía , StentsRESUMEN
AIMS: The frequency of severe femoral retroversion is unclear in patients with femoroacetabular impingement (FAI). This study aimed to investigate mean femoral version (FV), the frequency of absolute femoral retroversion, and the combination of decreased FV and acetabular retroversion (AR) in symptomatic patients with FAI subtypes. METHODS: A retrospective institutional review board-approved observational study was performed with 333 symptomatic patients (384 hips) with hip pain due to FAI evaluated for hip preservation surgery. Overall, 142 patients (165 hips) had cam-type FAI, while 118 patients (137 hips) had mixed-type FAI. The allocation to each subgroup was based on reference values calculated on anteroposterior radiographs. CT/MRI-based measurement of FV (Murphy method) and AV were retrospectively compared among five FAI subgroups. Frequency of decreased FV < 10°, severely decreased FV < 5°, and absolute femoral retroversion (FV < 0°) was analyzed. RESULTS: A significantly (p < 0.001) lower mean FV was found in patients with cam-type FAI (15° (SD 10°)), and in patients with mixed-type FAI (17° (SD 11°)) compared to severe over-coverage (20° (SD 12°). Frequency of decreased FV < 10° was significantly (p < 0.001) higher in patients with cam-type FAI (28%, 46 hips) and in patients with over-coverage (29%, 11 hips) compared to severe over-coverage (12%, 5 hips). Absolute femoral retroversion (FV < 0°) was found in 13% (5 hips) of patients with over-coverage, 6% (10 hips) of patients with cam-type FAI, and 5% (7 hips) of patients with mixed-type FAI. The frequency of decreased FV< 10° combined with acetabular retroversion (AV < 10°) was 6% (8 hips) in patients with mixed-type FAI and 5% (20 hips) in all FAI patients. Of patients with over-coverage, 11% (4 hips) had decreased FV < 10° combined with acetabular retroversion (AV < 10°). CONCLUSION: Patients with cam-type FAI had a considerable proportion (28%) of decreased FV < 10° and 6% had absolute femoral retroversion (FV < 0°), even more for patients with pincer-type FAI due to over-coverage (29% and 13%). This could be important for patients evaluated for open hip preservation surgery or hip arthroscopy, and each patient requires careful personalized evaluation. Cite this article: Bone Jt Open 2022;3(7):557-565.
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Background The association of epicardial adipose tissue (EAT) and its metabolic activity with atrial fibrillation (AF) is an area of active investigation. Left atrial (LA) enhancing EAT (e-EAT) at cardiac CT may be a noninvasive surrogate marker for the metabolic activity of EAT. Purpose To determine the relationship between LA e-EAT and recurrence after AF ablation. Materials and Methods In a secondary analysis of a prospective registry of consecutive patients (from July 2018 to December 2019) undergoing first AF ablation, total and LA EAT were segmented on preprocedural noncontrast- and contrast-enhanced cardiac CT scans. LA e-EAT volume fraction was defined as the LA EAT volume difference between the noncontrast- and contrast-enhanced scan divided by the total LA EAT volume on the noncontrast-enhanced scan (threshold values, -15 HU to -195 HU). Continuous variables were compared between groups by using the Mann-Whitney U test. Cox proportional hazard models were used to calculate hazard ratios of predictors of 1-year AF recurrence. Results A total of 212 patients (mean age, 64 years; 159 men) who underwent a first AF ablation were included (paroxysmal AF, 64%; persistent AF, 36%). The LA EAT volume was higher in patients with persistent versus paroxysmal AF (50 cm3 [IQR, 37-72] vs 37 [IQR, 27-49]; P < .001), but no difference was found for LA e-EAT (P = .09). After 1 year of follow-up, AF recurrence rate was 77 of 212 (36%). LA e-EAT above the mean (>33%) was associated with a higher risk of AF recurrence (hazard ratio [HR], 2.1; 95% CI: 1.3, 3.3; P < .01). In a multivariable Cox regression analysis, LA e-EAT retained its predictive value when corrected for sex, age, AF phenotype, LA volume index, and LA EAT volume (HR, 1.9; 95% CI: 1.1, 3.1; P = .02). Conclusion Left atrial enhancing epicardial adipose tissue was independently associated with recurrence after atrial fibrillation ablation. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Stojanovska in this issue.
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Fibrilación Atrial , Ablación por Catéter , Tejido Adiposo/diagnóstico por imagen , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Atrios Cardíacos , Humanos , Recurrencia , Tomografía Computarizada por Rayos X/métodosRESUMEN
Introduction: In patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction. Methods: A group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain. Results: In healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p < 0.001) and augmented peak circumferential systolic strain (-3.3 ± 1.6%, p < 0.001). At the end of apnea, myocardial signal intensity had increased (+9.1 ± 5.3%, p < 0.001) and strain had normalized to baseline. CAD patients had a similar global oxygenation response to hyperventilation (-5.8 ± 9.6%, p = 0.085) but showed no change in peak strain from their resting state (-1.3 ± 1.6%), which was significantly attenuated in comparison the strain response observed in controls (p = 0.008). With apnea, the CAD patients showed an attenuated global oxygenation response to apnea compared to controls (+2.7 ± 6.2%, p < 0.001). This was accompanied by a significant depression of peak strain (3.0 ± 1.7%, p < 0.001), which also differed from the control response (p = 0.025). Regional analysis demonstrated that post-stenotic myocardium was most susceptible to de-oxygenation and systolic strain abnormalities during respiratory maneuvers. CMR measures at rest were unable to discriminate post-stenotic territory (p > 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone. Conclusion: In myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia.
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BACKGROUND: The pathophysiology of heart failure with preserved ejection fraction is not well understood, but evidence strongly suggests involvement of microvascular dysfunction. We studied the myocardial oxygenation reserve as a direct marker of coronary vascular function and its relation to myocardial deformation and tissue characteristics by cardiovascular magnetic resonance (CMR). METHODS: In a dual-center case-control study, patients with heart failure and preserved ejection fraction (>50%) and healthy controls older than 50 years underwent quantitative CMR for ventricular volumes and functional assessment with feature tracking, as well as tissue characterization (T1, T2, extracellular volume). Coronary vascular function was measured by oxygenation-sensitive (OS)-CMR of the myocardial oxygenation response to a vasoactive breathing maneuver. RESULTS: Twenty-nine patients completed the CMR exam. Compared with cutoffs derived from 12 control subjects, circumferential peak strain was attenuated in 97% of patients. Native T1 was elevated in 93%, extracellular volume was elevated in 83%. Sixty-six percent of patients revealed either regional or global myocardial edema, defined by an increased myocardial T2. An attenuated global myocardial oxygenation reserve (<4.4%) was observed in 96% of the patients (1.7±3.9% versus 9.1±5.3% in controls, P<0.001). This was correlated with septal wall thickness (r=-0.54, P=0.003), edema (myocardial T2; ß=-0.26% oxygenation-sensitive/ms [95% CI, -0.49 to -0.03], P=0.029), and reduced diastolic strain rate (ß=1.50% oxygenation-sensitive/s-1 [95% CI, 0.06-2.90], P=0.042). CONCLUSIONS: In patients with clinical heart failure with preserved ejection fraction, vascular dysfunction as measured by an attenuated myocardial oxygenation reserve is associated with myocardial edema, a thicker septum, and diastolic dysfunction. A quantitative comprehensive CMR exam including oxygenation-sensitive-CMR allows for comprehensive imaging-based phenotyping of heart failure with preserved ejection fraction.
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Insuficiencia Cardíaca , Biomarcadores , Estudios de Casos y Controles , Humanos , Imagen por Resonancia Cinemagnética , Espectroscopía de Resonancia Magnética , Miocardio/patología , Valor Predictivo de las Pruebas , Volumen Sistólico/fisiología , Función Ventricular IzquierdaRESUMEN
Cisplatin (cisPt) is an important drug that is used against various cancers, including advanced lung cancer. However, drug resistance is still a major ongoing problem and its investigation is of paramount interest. Here, a high-resolution magic angle spinning (HR-MAS) NMR study is presented deciphering the metabolic profile of non-small cell lung cancer (NSCLC) cells and metabolic adaptations at different levels of induced cisPt-resistance, as well as in their de-induced counterparts (cells cultivated in absence of cisPt). In total, fifty-three metabolites were identified and quantified in the 1H-HR-MAS NMR cell spectra. Metabolic adaptations to cisPt-resistance were detected, which correlated with the degree of resistance. Importantly, de-induced cell lines demonstrated similar metabolic adaptations as the corresponding cisPt-resistant cell lines. Metabolites predominantly changed in cisPt resistant cells and their de-induced counterparts include glutathione and taurine. Characteristic metabolic patterns for cisPt resistance may become relevant as biomarkers in cancer medicine.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , Metaboloma , Resonancia Magnética Nuclear Biomolecular , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patologíaRESUMEN
Platinum compounds such as cisplatin (cisPt) embody the backbone of combination chemotherapy protocols against advanced lung cancer. However, their efficacy is primarily limited by inherent or acquired platinum resistance, the origin of which has not been fully elucidated yet, although of paramount interest. Using single cell inductively coupled plasma mass spectrometry (SC-ICP-MS), this study quantifies cisPt in single cancer cells and for the first time in isolated nuclei. A comparison of cisPt uptake was performed between a wild type (wt) cancer cell line and related resistant sublines. In both, resistant cells, wt cells, and their nuclei, cisPt uptake was measured at different incubation times. A lower amount of cisPt was found in resistant cell lines and their nuclei compared to wt cells. Moreover, the abundance of internalized cisPt decreased with increasing resistance. Interestingly, concentrations of cisPt found within the nuclei were higher than compared to cellular concentrations. Here, we show, that SC-ICP-MS allows precise and accurate quantification of metallodrugs in both single cells and cell organelles such as nuclei. These findings pave the way for future applications investigating the potency and efficacy of novel metallodrugs developed for cancer treatment.
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Cisplatino/farmacología , Resistencia a Antineoplásicos/fisiología , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Humanos , Espectrometría de Masas/métodos , Neoplasias/tratamiento farmacológico , Análisis de la Célula Individual/métodos , Análisis EspectralRESUMEN
BACKGROUND: The native balanced steady state with free precession (bSSFP) magnetic resonance angiography (MRA) technique has been shown to provide high diagnostic image quality for thoracic aortic disease. This study compares a 3D radial respiratory self-navigated native MRA (native-SN-MRA) based on a bSSFP sequence with conventional Cartesian, 3D, contrast-enhanced MRA (CE-MRA) with navigator-gated respiration control for image quality of the entire thoracic aorta. METHODS: Thirty-one aortic native-SN-MRA were compared retrospectively (63.9 ± 10.3 years) to 61 CE-MRA (63.1 ± 11.7 years) serving as a reference standard. Image quality was evaluated at the aortic root/ascending aorta, aortic arch and descending aorta. Scan time was recorded. In 10 patients with both MRA sequences, aortic pathologies were evaluated and normal and pathologic aortic diameters were measured. The influence of artifacts on image quality was analyzed. RESULTS: Compared to the overall image quality of CE-MRA, the overall image quality of native-SN-MRA was superior for all segments analyzed (aortic root/ascending, p < 0.001; arch, p < 0.001, and descending, p = 0.005). Regarding artifacts, the image quality of native-SN-MRA remained superior at the aortic root/ascending aorta and aortic arch before and after correction for confounders of surgical material (i.e., susceptibility-related artifacts) (p = 0.008 both) suggesting a benefit in terms of motion artifacts. Native-SN-MRA showed a trend towards superior intraindividual image quality, but without statistical significance. Intraindividually, the sensitivity and specificity for the detection of aortic disease were 100% for native-SN-MRA. Aortic diameters did not show a significant difference (p = 0.899). The scan time of the native-SN-MRA was significantly reduced, with a mean of 05:56 ± 01:32 min vs. 08:51 ± 02:57 min in the CE-MRA (p < 0.001). CONCLUSIONS: Superior image quality of the entire thoracic aorta, also regarding artifacts, can be achieved with native-SN-MRA, especially in motion prone segments, in addition to a shorter acquisition time.
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Aorta Torácica , Enfermedades de la Aorta , Aorta Torácica/diagnóstico por imagen , Enfermedades de la Aorta/diagnóstico por imagen , Medios de Contraste , Humanos , Imagenología Tridimensional , Angiografía por Resonancia Magnética , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Posttraumatic pulmonary artery pseudoaneurysm is a very rare, yet potentially lethal complication after thoracic trauma. Pulmonary artery pseudoaneurysm is associated with high mortality. Still literature highlights that untreated, lesions can enlarge, rupture, and lead to exsanguination and death. We present a case of a posttraumatic peripheral pulmonary artery pseudoaneurysm with complete disappearance after one year. This case confirms that conservative treatment can be an effective option in asymptomatic and stable patients.
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Aneurisma Falso/etiología , Arteria Pulmonar , Intento de Suicidio , Traumatismos Torácicos/complicaciones , Heridas Penetrantes/complicaciones , Aneurisma Falso/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Traumatismos Torácicos/diagnóstico , Tomografía Computarizada por Rayos X , Heridas Penetrantes/diagnósticoRESUMEN
As artificial intelligence (AI) systems begin to make their way into clinical radiology practice, it is crucial to assure that they function correctly and that they gain the trust of experts. Toward this goal, approaches to make AI "interpretable" have gained attention to enhance the understanding of a machine learning algorithm, despite its complexity. This article aims to provide insights into the current state of the art of interpretability methods for radiology AI. This review discusses radiologists' opinions on the topic and suggests trends and challenges that need to be addressed to effectively streamline interpretability methods in clinical practice. Supplemental material is available for this article. © RSNA, 2020 See also the commentary by Gastounioti and Kontos in this issue.
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Platinum compounds represent the backbone of combined chemotherapy protocols for advanced lung cancer. The mechanisms responsible for its frequent primary or acquired resistance to cisplatin (cisPt)-based chemotherapy remains enigmatic. The availability of two cell lines of the same origin, one resistant and the other sensitive, will facilitate research to reveal the mechanism of resistance formation. Lung adenocarcinoma cells, A240286S (A24), were cultivated in increasing cisPt concentrations over a prolonged time. After a significant increase in IC50 was measured, cultivation of the cells was continued in absence of cisPt and IC50s determined over a long period (>7 months). As a result, a cell line with lasting, high-level cisPt resistance, designated (D-)A24cisPt8.0, was obtained. The cells were cross-resistant to oxaliplatin and to pemetrexed at a low level. Previous publications have claimed that Leucine-rich repeat-containing protein 8 (LRRC8A and LRRC8D) of the volume-regulated anion channels (VRACs) affect cellular resistance to cisPt. Even though cisPt decreased LRRC8D expression levels, we showed by knockdown and overexpression experiments with LRRC8A and D that these proteins do not govern the observed cisPt resistance. The tumor cell sublines described here provide a powerful model to study the mechanisms of resistance to cisPt in lung cancer cells and beyond.
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Background The impact of hyperoxia, that is, supraphysiological arterial partial pressure of O2, on myocardial oxygen balance and function in stable multivessel coronary artery disease (CAD) is poorly understood. In this observational study, we assessed myocardial effects of inhalational hyperoxia in patients with CAD using a comprehensive cardiovascular magnetic resonance exam. Methods and Results Twenty-five patients with stable CAD underwent a contrast-free cardiovascular magnetic resonance exam in the interval between their index coronary angiography and subsequent revascularization. The cardiovascular magnetic resonance exam involved T1 and T2 mapping for tissue characterization (fibrosis, edema) as well as function imaging, from which strain analysis was derived, and oxygenation-sensitive cardiovascular magnetic resonance imaging. The latter modalities were both acquired at room air and after breathing pure O2 by face mask at 10 L/min for 5 minutes. In 14 of the 25 CAD patients (56%), hyperoxia induced poststenotic myocardial deoxygenation with a subsequent oxygenation discordance across the myocardium. Extent of deoxygenation was correlated to degree of stenosis (r=-0.434, P=0.033). Hyperoxia-associated poststenotic deoxygenation was accompanied by ipsiregional reduction of diastolic strain rate (1.39±0.57 versus 1.18±0.65; P=0.045) and systolic radial velocity (37.40±17.22 versus 32.88±13.58; P=0.038). Increased T2, as well as lower cardiac index, and defined abnormal strain parameters on room air were predictive for hyperoxia-induced abnormalities (P<0.05). Furthermore, in patients with prolonged native T1 (>1220 ms), hyperoxia reduced ejection fraction and peak strain. Conclusions Patients with CAD and pre-existent myocardial injury who respond to hyperoxic challenge with strain abnormalities appear susceptible for hyperoxia-induced regional deoxygenation and deterioration of myocardial function. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02233634.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/metabolismo , Hiperoxia/complicaciones , Miocardio/metabolismo , Consumo de Oxígeno/fisiología , Adulto , Anciano , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/terapia , Humanos , Hiperoxia/diagnóstico por imagen , Hiperoxia/metabolismo , Imagen por Resonancia Magnética , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Adulto JovenRESUMEN
We present a multi-scale CFD-based study conducted in a cohort of 11 patients with coarctation of the aorta (CoA). The study explores the potential for implementation of a workflow using non-invasive routinely collected medical imaging data and clinical measurements to provide a more detailed insight into local aortic haemodynamics in order to support clinical decision making. Our approach is multi-scale, using a reduced-order model (1D/0D) and an optimization process for the personalization of patient-specific boundary conditions and aortic vessel wall parameters from non-invasive measurements, to inform a more complex model (3D/0D) representing 3D aortic patient-specific anatomy. The reliability of the modelling approach is investigated by comparing 3D/0D model pressure drop estimation with measured peak gradients recorded during diagnostic cardiac catheterization and 2D PC-MRI flow rate measurements in the descending aorta. The current study demonstrated that the proposed approach requires low levels of user interaction, making it suitable for the clinical setting. The agreement between computed blood pressure drop and catheter measurements is 10 ± 8 mmHg at the coarctation site. The comparison between CFD derived and catheter measured pressure gradients indicated that the model has to be improved, suggesting the use of time varying pressure waveforms to further optimize the tuning process and modelling assumptions.
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Coartación Aórtica/fisiopatología , Hidrodinámica , Modelación Específica para el Paciente , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión , Adulto JovenRESUMEN
PURPOSE: To evaluate the opinion and assessment of radiologists, surgeons and medical students on a number of important topics regarding the future of radiology, such as artificial intelligence (AI), turf battles, teleradiology and 3D-printing. METHOD: An online questionnaire was created using the SurveyMonkey platform targeting radiologists, students and surgeons throughout the German speaking part of Switzerland. A total of 170 people participated in the survey (59 radiologists, 56 surgeons and 55 students). Statistical analysis was carried out using the Kruskal-Wallis test with Dunn's multiple comparison post-hoc tests. RESULTS: While the majority of participants agreed that AI should be included as a support system in radiology (Likert scale 0-10: Median value 8), surgeons were less supportive than radiologists (p = 0.001). Students saw a potential threat of AI as more likely than radiologists did (p = 0.041). When asked whether they were concerned about "turf losses" from radiology to other disciplines, radiologists were much more likely to agree than students (p < 0.001). Of the students that do not intend to specialize in radiology, 26 % stated that AI was one of the reasons. Surgeons advocate the use of teleradiology. CONCLUSIONS: With regard to AI, radiologists expect their workflow to become more efficient and tend to support the use of AI, whereas medical students and surgeons tend to be more skeptical towards this technology. Medical students see AI as a potential threat to diagnostic radiologists, while radiologists themselves are rather afraid of turf losses.
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Inteligencia Artificial/estadística & datos numéricos , Actitud del Personal de Salud , Encuestas de Atención de la Salud/estadística & datos numéricos , Radiólogos/estadística & datos numéricos , Radiología/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Cirujanos/estadística & datos numéricos , Humanos , Radiología/educación , Radiología/tendencias , SuizaRESUMEN
OBJECTIVES: This preclinical study was devised to investigate potential cellular toxicity in human neurons induced by gadolinium-based contrast agents (GBCAs) used for contrast-enhanced magnetic resonance imaging (MRI). Neurons modeling a subset of those in the basal ganglia were tested, because the basal ganglia region is 1 of 2 brain regions that displays the greatest T1-dependent signal hyperintensity changes. METHODS: Eight GBCAs were tested. Dopaminergic neurons modeling a subset of those in the basal ganglia were differentiated from an established human neuroblastoma cell line and exposed to increasing concentrations of each agent for 7 days. The tested dosages ranged from clinically relevant concentrations measured in some autopsy patients who had received repeated injections of contrast for MRI, to higher concentrations to reveal dose-dependent toxicity trends. Cell death, mitochondrial membrane potential, mitochondrial oxidative capacity, and mitochondrial function measured by oxygen consumption were quantified in cells treated with each GBCA or the osmolality control mannitol and compared to untreated cells which served as a negative control. RESULTS: Mannitol caused no change from negative controls in any of the tests, at any concentration tested. For all GBCAs, cell death increased with exposure dose, with toxicity at clinically relevant doses for agents with lower kinetic stability. Reduction of mitochondrial membrane potential and oxidative respiratory function also generally mirrored the agents' structural kinetic stabilities, with greater impairment at lower concentration for the less stable agents. CONCLUSIONS: In human neurons modeling a subset of those in the basal ganglia, these results demonstrate a toxic effect of gadolinium-containing MRI contrast agents on mitochondrial respiratory function and cell viability. Toxicity increases as agent concentration increases and as the kinetic stability of the agent decreases.