Objective: The aim of this study was to establish the diagnostic accuracy of high-field magnetic resonance imaging (MRI) at 7 Tesla (T) compared with that of stereomicroscopic autopsy for assessing first trimester fetuses.Methods: Nine consecutive cases of first trimester fetuses resulting from spontaneous and therapeutic pregnancy termination were considered. The cases were divided into two groups according to gestational age: the Embryo Group with cases of nine to 10 gestational weeks (GWs) and the Fetus Group with cases of 13 GWs. The first group was scanned using three-dimensional fast imaging with steady state precession (3D FISP), and the second group was scanned using a two-dimensional (2D) turbo spin-echo high-resolution T2-weighted imaging (T2 WI) protocol. A radiologist and two embryologists interpreted the images. All cases were evaluated by invasive autopsy, with pathologist blinded to the imaging results. In total, the database included 270 items for evaluation (9 cases × 30 structures/case). Results:The global agreement between fetal high-field virtopsy and microscopic or stereomicroscopic autopsy was evaluated using 225 evaluation items visible by both methods. Overall, using microscopic examination and stereomicroscopic autopsy as the gold standard, fetal high-field virtopsy had a sensitivity of 94.6% [95% CI, 87.2-98.3] and a specificity of 97.6% [95% CI, 95-98.8]. The positive predictive value (PPV) was 93% [95% CI, 85.7-96.6], and the negative predictive value (NPV) was
Purpose: Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals that enable a better visualization of internal body structures. In this study, we present the synthesis, MRI signal enhancement capabilities, in vitro as well as in vivo cytotoxicity results of gold-coated iron oxide nanoparticles (Fe 3 O 4 @AuNPs) as potential contrast agents. Methods: Fe 3 O 4 @AuNPs were obtained by synthesizing iron oxide nanoparticles and gradually coating them with gold. The obtained Fe 3 O 4 @AuNPs were characterized by spectroscopies, transmission electron microscopy (TEM) and energy dispersive X-ray diffraction. The effect of the nanoparticles on the MRI signal was tested using a 7T Bruker PharmaScan system. Cytotoxicity tests were made in vitro on Fe 3 O 4 @AuNP-treated retinal pigment epithelium cells by WST-1 tests and in vivo by following histopathological changes in rats after injection of Fe 3 O 4 @AuNPs. Results: Stable Fe 3 O 4 @AuNPs were successfully prepared following a simple and fast protocol (<1h worktime) and identified using TEM. The cytotoxicity tests on cells have shown biocompatibility of Fe 3 O 4 @AuNPs at small concentrations of Fe (<1.95×10 −8 mg/ cell). Whereas, at higher Fe concentrations (eg 7.5×10 −8 mg/cell), cell viability decreased to 80.88±5.03%, showing a mild cytotoxic effect. MRI tests on rats showed an optimal Fe 3 O 4 @AuNPs concentration of 6mg/100g body weight to obtain high-quality images. The histopathological studies revealed significant transient inflammatory responses in the time range from 2 hours to 14 days after injection and focal cellular alterations in several organs, with the lung being the most affected organ. These results were confirmed by hyperspectral microscopic imaging of the same, but unstained tissues. In most organs, the inflammatory responses and sublethal cellular damage appeared to be transitory, except for the kidneys, where the glomerular damage indicated progression towards glomerular sclerosis. Conclusion: The obtained stable, gold covered, iron oxide nanoparticles with reduced cytotoxicity, gave a negative T 2 signal in the MRI, which makes them suitable for candidates as contrast agent in small animal MRI applications.
The presence of SARS-CoV-2 in the middle ear reveals the etiopathogenesis of otitis media in COVID-19, as well as an epidemiological risk during otologic examination and surgical procedures in COVID-19 patients. The study included 8 deceased patients with COVID-19. Tissue samples from the middle ear were subjected to virology, histopathology, scanning (SEM) and transmission (TEM) electron microscopy investigation. Ethmoidal mucosa samples were processed for virology analyses. qPCR resulted positive for 75% of nasal mucosa samples and 50% of middle ear samples. Ct values showed lower viral loads in middle ear samples. A proportion of 66.6% patients with positive results in the nasal mucosa showed positive results in the middle ear, and the subtype analysis of the complete genome sequences indicated B.1.1.7 lineage for all samples. In histopathological and SEM samples, no pathological aspects were identified. TEM revealed on the background of death critical alteration of cellular morphology, suggestive structures resembling SARS-CoV-2, goblet cells and immune cells. SARS-CoV-2 can be present in the middle ear of COVID-19 patients even if there is not clinical evidence of acute otitis media. Otolaryngologists could be particularly exposed to COVID-19 infection.
(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most studied rhinological disorders. Modifications of the respiratory nasal mucosa in COVID-19 patients are so far unknown. This paper presents a comparative morphological characterization of the respiratory nasal mucosa in CRSwNP versus COVID-19 and tissue interleukin (IL)-33 concentration. (2) Methods: We analyzed CRSwNP and COVID-19 samples through histopathology, scanning and transmission electron microscopy and performed proteomic determination of IL-33. (3) Results: Histopathologically, stromal edema (p < 0.0001) and basal membrane thickening (p = 0.0768) were found more frequently in CRSwNP than in COVID-19. Inflammatory infiltrate was mainly eosinophil-dominant in CRSwNP and lymphocyte-dominant in COVID-19 (p = 0.3666). A viral cytopathic effect was identified in COVID-19. Scanning electron microscopy detected biofilms only in CRSwNP, while most COVID-19 samples showed microbial aggregates (p = 0.0148) and immune cells (p = 0.1452). Transmission electron microscopy of CRSwNP samples identified biofilms, mucous cell hyperplasia (p = 0.0011), eosinophils, fibrocytes, mastocytes, and collagen fibers. Extracellular suggestive structures for SARS-CoV-2 and multiple Golgi apparatus in epithelial cells were detected in COVID-19 samples. The tissue IL-33 concentration in CRSwNP (210.0 pg/7 μg total protein) was higher than in COVID-19 (52.77 pg/7 μg total protein) (p < 0.0001), also suggesting a different inflammatory pattern. (4) Conclusions: The inflammatory pattern is different in each of these disorders. Results suggested the presence of nasal dysbiosis in both conditions, which could be a determining factor in CRSwNP and a secondary factor in COVID-19.
Objective To determine the diagnostic value of virtual autopsy using post mortem-MRI (pm-MRI) at 3Tesla (T) compared to classic autopsy for the confirmation of fetal structural anomalies and secondly to establish which cases of termination of pregnancy would benefit mostly from a virtual autopsy. Methods In each of 32 fetuses included in the study, 32 anatomical structures were assessed, after termination of pregnancy in the second trimester. All cases were evaluated by prenatal ultrasonography, virtual autopsy and classic autopsy, and then divided into four groups: Cerebral Group, Cardiac Group, Renal Group and Other Group (miscellaneous group). The concordance of virtual autopsy with classic autopsy was calculated overall and for each group and each structural item. Also, the concordance between the two methods was assessed using a diagnostic error score (DgE_score), calculated as the absolute value of the difference between the number of malformations detected by classic autopsy per case (CA score) and the number of malformations detected at virtual autopsy per case (VA score). Results Overall virtual autopsy demonstrated a diagnostic sensitivity (Se) compared to classic autopsy of 67.33% [95% CI 57.28–76.33], with a specificity (Sp) of 98.37% [95% CI 97.33–99.09], a positive predictive value (PPV) of 81.93% [95% CI 71.95–89.52], a negative predictive value (NPV) of 96.49% [95% CI 95.11–97.57] achieving a diagnostic accuracy of 95.31% [95% CI 93.83–96.52]. Overall, no statistic significant correlation was demonstrated between DgE_score and the gestational age of the fetuses or between DgE_score and the weight of the fetuses, but a significant correlation was revealed between the virtual autopsy and classic autopsy score. The diagnostic utility of virtual autopsy using pm-MRI at 3 T as compared to classic autopsy for each category of termination of pregnancy revealed in the Cerebral Group a Se of 80.00% [95% CI 28.36–99.49], with a 96.30% [95% CI 81.03–99.91], a PPV of 80.00% [95% CI 35.75–96.64] a NPV of 96.30% [95% CI 81.81–99.34], with a diagnostic accuracy of 93.75% [95% CI 79.19% to 99.23] and a Cohen’s Kappa coefficient of 0.76 [95% CI 0.4494–1.0765]; in the Renal Group a Se and Sp of 100%, but in the Cardiac Group the Se was only 60.00% [95% CI 26.24–87.84], Sp 75% [95% CI 34.91–96.81], the PPV 75.00% [95% CI 44.92–91.69], NPV 60% [95% CI 38.87–77.96], with a diagnostic accuracy of 66.67% [95% CI 40.99–86.66] and a Cohen’s Kappa coefficient of 0.32 [95% CI -0.07–0.76]. Conclusions The results support virtual autopsy using pm-MRI at 3T as a reliable alternative to classic autopsy for the non-forensic analysis of second trimester fetuses. Analyzing the diagnostic utility of virtual autopsy using pm-MRI at 3 T for the confirmation of prenatal ultrasound findings in second trimester fetuses as compared to classic autopsy, the best results were obtained in the Cerebral and Renal Group. Reserved results were found in the Cardiac Group. Therefore, for the pregnancies with termination of pregnancy for cerebral or renal abnormalities, virtual autopsy by pm-MRI at 3T can be taken into consideration as a first-line investigation to confirm the prenatal findings.
The examination of very small fetal hearts requires special equipment and a specialist that are not available in many general pathology laboratories. Compared to conventional examination, the four-chamber cardiac dissection (4CCD) method can be performed by any pathologist using instruments generally available in pathology services. The aim of this study is to evaluate the efficiency of the 4CCD method in the examination of small fetal hearts using post-mortem magnetic resonance imaging (pm-MRI) at 7T as the standard. Twelve fetuses with gestational ages between 13 and 19 weeks have been included in this study. All fetuses underwent pm-MRI examination prior to pathologic examination. The 4CCD method was used for the cardiac examination in all cases following the same guidelines for cardiac sectioning. The 4CCD was able to identify all cardiac anatomic structures as compared to pm-MRI at 7T, demonstrating a sensibility of 95.8% (95% CI, 94.5–95.8) and specificity of 100% (95% CI, 32.3–100). The overall accuracy in identifying cardiac anatomic structures was 95.8% (95% CI, 93.4–95.8). Additionally, the 4CCD method was able to detect cardiac anomalies with an overall diagnostic accuracy of 91% (95% CI, 85.8–94.2), sensibility of 67.6% (95% CI, 54.5–75.3), and specificity of 97% (95% CI, 93.7–99) as compared to pm-MRI at 7T. The four-chamber view dissection method can be considered as an alternative to the conventional inflow–outflow dissection method in selected cases.
Twin reversed arterial perfusion (TRAP) sequence is a rare and severe complication specific to monochorionic twin pregnancies, involving the presence of an acardiac twin and a structurally normal co-twin (pump twin). We report on the case of a33-year-old female with a biamniotic monochorionic twin pregnancy complicated with TRAP sequence and polyhydramnios. The patient underwent fetoscopic termination of the acardiac twin and at 34 gestational weeks (GW) was readmitted with aretroplacental hematoma. The patient gave birth through caesarean section to a living female fetus, weighing 1480 g. To the best of our knowledge, this is the first case reporting a twin pregnancy with TRAP sequence complicated with retroplacental hematoma.
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