Imaging Characteristics of Clear Cell Papillary Renal Cell Carcinoma: Identifying the Sheep in Wolf's Clothing.

OBJECTIVE: This study aimed to describe the characteristics of computed tomography (CT) and magnetic resonance imaging (MRI) of clear cell papillary renal cell carcinoma (CCPRCC). METHODS: This retrospective study comprised 27 patients diagnosed with 29 tumors of CCPRCC. The study was approved by the Medical Ethics Committee and the requirement for the informed consent was waived. The inclusion criteria stipulated pathology-confirmed CCPRCCs with at least one preoperative imaging examination, including CT or MRI. Two experienced radiologists independently analyzed the imaging characteristics, including size, location, growth mode, morphology, texture, density, and enhancement pattern. Paired t-test was used to compare differences in CT Hounsfield unit values and apparent diffusion coefficient (ADC) imaging between the tumor and the renal cortex. RESULTS: The mean age of the 27 patients was 57.0 ± 14.2 years. Nineteen patients underwent CT, while 12 underwent MRI (There are 4 patients underwent not only CT but also MRI). Among the cases, 26 (96%) were single, and 1 (4%) was multiple, consisting of three lesions. Out of the 29 tumors, 15 (52%) were located in the left kidney and 14 (48%) in the right kidney. The mean tumor diameter was 3.3 ± 1.7 cm. Furthermore, 19 (66%), 3 (10%), and 7 (24%) tumors were solid, cystic, mixed solid, and cystic type, respectively. The growth mode was endogenous and exogenous in 8 (28%) and 21 (72%) tumors, respectively. The tumor shape was irregular and round in 5 (17%) and 24 (83%) tumors, respectively. The CT value of the tumor was approximately 33.2 ± 9.8 HU, which was not significantly different from that of the renal cortex(31.1 ± 6.3HU)(p = 0.343). Furthermore, 7 (24%), 12 (41%), and 3 (10%) had calcification, cystic degeneration, and hemorrhage, respectively. In 12 tumors, hypointense and hyperintense were predominant on T1 and T2-weighted images, respectively. The tumor capsule was found at the edge of 12 tumors. The average ADC value of the tumor (1.54 ± 0.74 × 10-3 mm2/s) and that of the renal cortex(1.68 ± 0.63×10-3mm2 /s) was not statistically significantly different (p = 0.260). The enhancement scanning revealed "wash-in and wash-out" enhancement in 19 (68%) tumors, continuous or progressive enhancement in 6 (21%) tumors, and enhanced cystic wall and central separation in 3 (11%) tumors. CONCLUSION: CCPRCC occurs more likely in middle-aged and elderly individuals, and the tumor is prone to cystic degeneration, with rare bleeding and calcification, and no obvious limitation on MRI diffusion-weighted imaging, which enhancement form performs as mainly "wash-in and washout," but the final diagnosis depends on histopathology.

Unenhanced magnetic resonance imaging of papillary thyroid carcinoma with emphasis on diffusion kurtosis imaging.

Background: The aim of this study was to investigate the value of unenhanced magnetic resonance imaging (MRI) with diffusion kurtosis imaging (DKI) in diagnosing papillary thyroid carcinoma (PTC). Methods: In all, 77 consecutive patients comprising a total of 77 thyroid nodules were enrolled in this study. Of these nodules, 41 were histopathologically confirmed PTCs and 36 were benign nodules. All patients underwent thyroid MRI including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and DKI. All the images were assessed by 2 radiologists. The signal intensity ratio (SIR) of these nodules on T1WI and T2WI, the apparent diffusion coefficient (ADC) from DWI, and mean diffusivity (MD) and mean kurtosis (MK) from DKI were measured. Morphological features on these images were also evaluated. Univariate and multivariate logistic regression analyses were used to evaluate the value of these parameters as potential predictors of PTC. Results: In the univariate analyses, the features that significantly indicated PTC were decreased ADC value (P<0.001), decreased MD value (P<0.001), increased MK value (P<0.001), younger age (P=0.001), female tendency (P=0.049), smaller tumor diameter (P<0.001), solid component (P<0.001), and irregular margin (P<0.001). In the multivariate analysis, decreased MD value (odds ratio =25.321; P=0.001), smaller diameter (odds ratio =13.751; P=0.006), and irregular margin (odds ratio =16.003; P=0.003) were independent risk factors for PTC. The combined predictor of MD, diameter, and margin showed an area under the receiver operating characteristic (ROC) curve of 0.996 in diagnosing PTC, with an optimal cutoff value of 0.69 (95.1% sensitivity, 100.0% specificity). Conclusions: Lower MD value from DKI, smaller diameter, and irregular margin are useful predictive biomarkers for PTC.

Ischemic stroke prediction of patients with carotid atherosclerotic stenosis via multi-modality fused network.

Carotid atherosclerotic stenosis of the carotid artery is an important cause of ischemic cerebrovascular disease. The aim of this study was to predict the presence or absence of clinical symptoms in unknown patients by studying the existence or lack of symptoms of patients with carotid atherosclerotic stenosis. First, a deep neural network prediction model based on brain MRI imaging data of patients with multiple modalities is constructed; it uses the multi-modality features extracted from the neural network as inputs and the incidence of diagnosis as output to train the model. Then, a machine learning-based classification algorithm is developed to utilize the clinical features for comparison and evaluation. The experimental results showed that the deep learning model using imaging data could better predict the clinical symptom classification of patients. As part of preventive medicine, this study could help patients with carotid atherosclerosis narrowing to prepare for stroke prevention based on the prediction results.

Accuracy and reproducibility of the O-RADS MRI risk stratification system based on enhanced non-DCE MRI in the assessment of adnexal masses.

OBJECTIVE: Evaluation of the diagnostic performance and reproducibility of the Ovarian-Adnexal Reporting and Data System (O-RADS) Magnetic Resonance Imaging (MRI) risk stratification system based on enhanced non-dynamic contrast-enhanced (non-DCE) MRI in the diagnosis of adnexal masses. METHODS: Patients who underwent conventional pelvic enhanced non-DCE MRI examination within one month prior to surgery formed the study population. Two experienced radiologists independently evaluated the images and assigned a score according to the O-RADS MRI risk stratification system. One of the radiologists reviewed the images and reassigned the scores after three months. Intra- and inter-observer agreement was evaluated with the k coefficient value. The adnexal masses that attained scores between 1 and 3 were considered benign, while those with scores of 4 or 5 were considered malignant. Analyses were conducted to determine the sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curve, which were then used for evaluating the diagnostic efficacy of the developed system based on enhanced non-DCE MRI scan. The reference standard was histology. RESULTS: A total of 308 patients (mean age: 42.09 ± 12.42 years, age range: 20-84 years) were enrolled in the study. Among the 362 adnexal masses from the included patients, there were 320 benign masses and 42 malignant masses. In the case of three readers, there were no malignant tumors scored 1-2. The O-RADS MRI score ≥ 4 was associated with malignancy resulted in a good diagnostic efficacy with the areas under the curve (AUC) values of 0.918 (95 % CI, 0.864-0.972), 0.905 (95 % CI, 0.842-0.968), and 0.882 (95 % CI, 0.815-0.950), the sensitivity values of 90.5 % (95 % CI, 87.5-93.5 %), 85.7 % (95 % CI, 82.1-89.3 %), and 83.3 % (95 % CI, 79.5-87.2 %), and the specificity values of 93.1 % (95 % CI, 90.5-95.7 %), 95.3 % (95 % CI, 93.1-97.5 %), and 93.1 % (95 % CI, 90.5-95.7 %) obtained for the three readers, respectively. Excellent intra-observer agreement and inter-observer agreement were observed with the k values of 0.883 (95 % CI, 0.814-0.952) and 0.848 (95 % CI, 0.770-0.926), respectively. CONCLUSIONS: The O-RADS MRI risk stratification system based on enhanced non-DCE MRI scans exhibited high accuracy and reproducibility in the prediction of adnexal masses malignancy. Enhanced non-DCE MRI scan may offer an alternative diagnostic tool when DCE is not possible.

Tumor contour irregularity on preoperative imaging: a practical and useful prognostic parameter for papillary renal cell carcinoma.

OBJECTIVES: To illustrate tumor contour irregularity on preoperative imaging with a practical method and further determine its value in predicting disease-free survival (DFS) in patients with pRCC (papillary renal cell carcinoma). METHODS: We performed a retrospective single-institution review of 267 Chinese pRCC patients between March 2009 and May 2019. Contour irregularity on cross-section was classified into smooth but distorted margin, unsmooth and sharply nodular margin, and blurred margin. Then, the ratio of the cross-section numbers of irregularity and the total tumor was defined as the contour irregular degree (CID). Cox regression and Kaplan-Meier analysis were performed to analyze the impact of CID on DFS. Then, the prognostic performance of CID was compared with pRCC risk stratification published by Leibovich et al. RESULTS: The median follow-up was 45 months (IQR: 23-69), in which 27 (10%) patients had metastasis or recurrence. Observed DFS rates were 95%, 90%, and 88% at 1, 3, and 5 years. The CID was an independent prognostic factor of DFS (HR = 1.048, 95% CI = 1.029-1.068, p < 0.001). The Kaplan-Meier plot showed that high-risk patients (CID ≥ 50%) tended to have a significantly shorter DFS (p < 0.001). The CID and Leibovich's pRCC model for DFS prediction had a C-index of 0.934 (95% CI = 0.907-0.961) and 0.833 (95% CI = 0.739-0.927) respectively. CONCLUSIONS: With our standard and practical method, the CID can be a reliable imaging marker for DFS prediction in patients with pRCC. KEY POINTS: • The updated contour irregularity was an independent parameter for predicting disease-free survival in patients with pRCC. • High-risk pRCC patients (contour irregular degree ≥ 50%) tended to have a shorter disease-free survival. • Tumor contour irregularity in pRCC risk stratification outperformed Leibovich's model from our cohort.

A Large Stokes Shift Fluorescent Protein Constructed from the Fusion of Red Fluorescent mCherry and Far-Red Fluorescent BDFP1.6.

Phycobiliproteins are constituents of phycobilisomes that can harvest orange, red, and far-red light for photosynthesis in cyanobacteria and red algae. Phycobiliproteins in the phycobilisome cores, such as allophycocyanins, absorb far-red light to funnel energy to the reaction centers. Therefore, allophycocyanin subunits have been engineered as far-red fluorescent proteins, such as BDFP1.6. However, most current fluorescent probes have small Stokes shifts, which limit their applications in multicolor bioimaging. mCherry is an excellent fluorescent protein that has maximal emittance in the red spectral range and a high fluorescence quantum yield, and thus, can be used as a donor for energy transfer to a far-red acceptor, such as BDFP1.6, by FRET. In this study, mCherry was fused with BDFP1.6, which resulted in a highly bright far-red fluorescent protein, BDFP2.0, with a large Stokes shift (≈79 nm). The excitation energy was absorbed maximally at 587 nm by mCherry and transferred to BDFP1.6 efficiently; thus emitting strong far-red fluorescence maximally at 666 nm. The effective brightness of BDFP2.0 in mammalian cells was 4.2-fold higher than that of iRFP670, which has been reported as the brightest far-red fluorescent protein. The large Stokes shift of BDFP2.0 facilitates multicolor bioimaging. Therefore, BDFP2.0 not only biolabels mammalian cells, including human cells, but also biolabels various intracellular components in dual-color imaging.

Chromophorylation of cyanobacteriochrome Slr1393 from Synechocystis sp. PCC 6803 is regulated by protein Slr2111 through allosteric interaction.

Cyanobacteriochromes (CBCRs) are photochromic proteins in cyanobacteria that act as photosensors. CBCRs bind bilins as chromophores and sense nearly the entire visible spectrum of light, but the regulation of the chromophorylation of CBCRs is unknown. Slr1393 from Synechocystis sp. PCC 6803 is a CBCR containing three consecutive GAF (cGMP phosphodiesterase, adenylyl cyclase, and FhlA protein) domains, of which only the third one (Slr1393g3) can be phycocyanobilin-chromophorylated. The protein Slr2111 from Synechocystis sp. PCC 6803 includes a cystathionine ß-synthase (CBS) domain pair of an as yet unknown function at its N terminus. CBS domains are often characterized as sensors of cellular energy status by binding nucleotides. In this work, we demonstrate that Slr2111 strongly interacts with Slr1393 in vivo and in vitro, which generates a complex in a 1:1 molar ratio. This tight interaction inhibits the chromophorylation of Slr1393g3, even if the chromophore is present. Instead, the complex stability and thereby the chromophorylation of Slr1393 are regulated by the binding of nucleotides (ATP, ADP, AMP) to the CBS domains of Slr2111 with varying affinities. It is demonstrated that residues Asp-53 and Arg-97 of Slr2111 are involved in nucleotide binding. While ATP binds to Slr2111, the association between the two proteins gets weaker and chromophorylation of Slr1393 are enabled. In contrast, AMP binding to Slr2111 leads to a stronger association, thereby inhibiting the chromophorylation. It is concluded that Slr2111 acts as a sensor of the cellular energy status that regulates the chromophorylation of Slr1393 and thereby its function as a light-driven histidine kinase.

Assessment of pancreatic colloid carcinoma using 18F-FDG PET/CT compared with MRI and enhanced CT.

Pancreatic colloid carcinoma (CC) is a rare sub-type of pancreatic adenocarcinoma which has an improved prognosis compared with pancreatic ductal carcinoma. Consequently, the early detection of CC by imaging may be of great significance in guiding patient management and therapeutic decisions. The present study aimed to analyze 18F-FDG PET/CT findings of CC in comparison to MRI and CT. PET/CT findings in 5 patients with CC were retrospectively reviewed based on visual interpretation and semi-quantitative index of SUVmax and TNR. Four patients received dual-time-point PET/CT scans. Additionally, one patient underwent contrast-enhanced CT scan, one MRI, and three received both. A total of five lesions were detected in five patients. Visually, two cases presented with mild FDG uptake, two with moderate and one with high. The mean of SUVmax and TNR was 5.1±2.2 and 2.8±0.7, respectively. Compared with CCs with low SUVmax, CCs with high SUVmax were more aggressive. No distant metastases were observed in five cases. Among four patients with dual-time-point PET/CT imaging, SUVmax increased in three cases and decreased in one case. The mean early and delayed SUVmax were 4.2±1.1 and 4.7±1.9, respectively (P>0.05). Radiological findings mainly included septated cystic components, internal sponge-like contrast-enhancement, calcification and 'salt-and-pepper sign' on MRI T2-weighted imaging. Thus, PET/CT provided additional information on metabolic tumor activity as well as locoregional and distant staging, which are important prognostic markers and may improve further patient management. However, PET/CT did not show any findings in addition to MRI and contrast-enhanced CT that were unique to CC and allowed a clear differentiation from other pancreatic malignancies.

18F-FDG PET/CT characteristics of pulmonary sclerosing hemangioma vs. pulmonary hamartoma.

The radiological features of pulmonary sclerosing hemangioma (PSH) and pulmonary hamartoma are poorly specified. Thus, the present study aimed to compare and analyze the characteristics of fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in PSH versus pulmonary hamartoma. 18F-FDG PET/CT characteristic findings of 12 patients with PSH and 14 patients with pulmonary hamartoma were retrospectively reviewed. A total of 12 lesions were detected from the 12 patients with PSH, of which 3 masses exhibited calcification. The mean diameter and standardized maximum uptake value (SUVmax) were 1.9±0.7 cm and 2.6±1.0, respectively, and there was no significant correlation between the lesion size and SUVmax (P>0.05). For the 14 patients with pulmonary hamartoma, 14 lesions were found, of which 4 exhibited calcification. The mean diameter and SUVmax were 1.7±0.8 cm and 1.5±0.6, respectively, and there was a significant correlation between the size and SUVmax (r=0.625, r2=0.391, P<0.05). Although there was no significant difference between the size of PSH and pulmonary hamartoma (P>0.05), the SUVmax of PSH was significantly higher than that of pulmonary hamartoma (P<0.05). Moreover, the SUVmax of 1.95 was applied as a cutoff for the diagnosis of PSH, and the resulting sensitivity and specificity for PET/CT to differentiate PSH from pulmonary hamartoma were 83.3 and 78.6%, respectively. Although the morphological features were not specific, PSH showed significantly higher FDG accumulation than pulmonary hamartoma on PET/CT imaging, which may aid the differential diagnosis. Further studies with larger populations are warranted to confirm these study results.

Chromophorylation (in Escherichia coli) of allophycocyanin B subunits from far-red light acclimated Chroococcidiopsis thermalis sp. PCC7203.

Cyanobacterial phycobilisomes funnel the harvested light energy to the reaction centers via two terminal emitters, allophycocyanin B and the core-membrane linker. ApcD is the α-subunit of allophycocyanin B responsible for its red-shifted absorbance (λmax 665 nm). Far-red photo-acclimated cyanobacteria contain certain allophycocyanins that show even further red-shifted absorbances (λmax > 700 nm). We studied the chromophorylation of the three far-red induced ApcD subunits ApcD2, ApcD3 and ApcD4 from Chroococcidiopsis thermalis sp. PCC7203 during the expression in E. coli. The complex behavior emphasizes that a variety of factors contribute to the spectral red-shift. Only ApcD2 bound phycocyanobilin covalently at the canonical position C81, while ApcD3 and ApcD4 gave only traces of stable products. The product of ApcD2 was, however, heterogeneous. The major fraction had a broad absorption around 560 nm and double-peaked fluorescence at 615 and 670 nm. A minor fraction was similar to the product of conventional ApcD, with maximal absorbance around 610 nm and fluorescence around 640 nm. The heterogeneity was lost in C65 and C132 variants; in these variants only the conventional product was formed. With ApcD4, a red-shifted product carrying non-covalently bound phycocyanobilin could be detected in the supernatant after cell lysis. While this chromophore was lost during purification, it could be stabilized by co-assembly with a far-red light-induced ß-subunit, ApcB3.

Far-red light photoacclimation: Chromophorylation of FR induced α- and ß-subunits of allophycocyanin from Chroococcidiopsis thermalis sp. PCC7203.

Cyanobacterial light-harvesting complexes, phycobilisomes, can undergo extensive remodeling under varying light conditions. Acclimation to far-red light involves not only generation of red-shifted chlorophylls in the photosystems, but also induction of additional copies of core biliproteins that have been related to red-shifted components of the phycobilisome (Gan et al., Life 5, 4, 2015). We are studying the molecular basis for these acclimations in Chroococcidiopsis thermalis sp. PCC7203. Five far-red induced allophycocyanin subunits (ApcA2, ApcA3, ApcB2, ApcB3 and ApcF2) were expressed in Escherichia coli, together with S-type chromophore-protein lyases and in situ generated chromophore, phycocyanobilin. Only one subunit, ApcF2, shows an unusual red-shift (λAmax~675nm, λFmax~698nm): it binds the chromophore non-covalently, thereby preserving its full conjugation length. This mechanism operates also in two Cys-variants of the induced subunits of bulky APC. All other wild-type subunits bind phycocyanobilin covalently to the conventional Cys-81 under catalysis of the lyase, CpcS1. Although three of them also show binding to additional cysteines, all absorb and fluoresce similar to conventional APC subunits (λAmax~610nm, λFmax~640nm). Another origin of red-shifted complexes was identified, however, when different wild-type α- and ß-subunits of the far-red induced bulky APC were combined in a combinatorial fashion. Strongly red-shifted complexes (λFmax≤722nm) were formed when the α-subunit, PCB-ApcA2, and the ß-subunit, PCB-ApcB2, were generated together in E. coli. This extreme aggregation-induced red-shift of ~90nm of covalently bound chromophores is reminiscent, but much larger, than the ~30nm observed with conventional APC.