Diagnostics — Open Access Journal

Shear wave elastography with ultrasound is a noninvasive method used for measuring stiffness in the human body. Shear wave elastography can be used for accurately and quantitatively measuring stiffness. However, its disadvantage is that the stiffness value can vary significantly because the region of interest (ROI) setting depends on the diagnostic operator. In this study, a stiffness measurement program using color mapping in shear wave elastography was developed to address the above-mentioned disadvantage. Color map and color ratios were obtained and evaluated for major lower limb muscles (i.e., biceps femoris, medial gastrocnemius, rectus femoris, and tibialis anterior) at active voluntary contraction. According to the result, when the developed program was used, a small standard deviation compared to the conventional stiffness measurement method, such as kilopascal or meter per second unit using ROIs, was measured in all cases. In conclusion, our results demonstrate that the stiffness measurement method using our program is expected to improve reliability in shear wave elastography ultrasound imaging. Full article

: Background: The Somnotouch-Non-Invasive-Blood-Pressure (NIBP) device delivers raw data consisting of electrocardiography and photoplethysmography for estimating blood pressure (BP) over 24 hours using pulse-transit-time. The study’s aim was to analyze the impact on 24-hour BP results when processing raw data by two different software solutions delivered with the device. Methods: We used data from 234 participants. The Somnotouch-NIBP measurements were analyzed using the Domino-light and Schiller software and compared. BP values differing > 5 mmHg were regarded as relevant and explored for their impact on BP classification (normotension vs. hypertension). Results: Mean (±standard deviation) absolute systolic/diastolic differences for 24-hour mean BP were 1.5 (±1.7)/1.1 (±1.3) mm Hg. Besides awake systolic BP (p = 0.022), there were no statistically significant differences in systolic/diastolic 24-hour mean, awake, and asleep BP. Twenty four-hour mean BP agreement (number (%)) between the software solutions within 5, 10, and 15 mmHg were 222 (94.8%), 231 (98.7%), 234 (100%) for systolic and 228 (97.4%), 232 (99.1%), 233 (99.5%) for diastolic measurements, respectively. A BP difference of >5 mmHg was present in 24 (10.3%) participants leading to discordant classification in 4–17%. Conclusion: By comparing the two software solutions, differences in BP are negligible at the population level. However, at the individual level there are, in a minority of cases, differences that lead to different BP classifications, which can influence the therapeutic decision. Full article

Background: Mucopolysaccharidoses (MPS) are a group of inherited metabolic diseases caused by impaired function or absence of lysosomal enzymes involved in degradation of glycosaminoglycans. Clinically, MPS are skeletal dysplasias, characterized by cartilage abnormalities and disturbances in the process of endochondral ossification. Histologic abnormalities of growth cartilage have been reported at advanced stages of the disease, but information regarding growth plate pathology progression either in humans or in animal models, as well as its pathophysiology, is limited. Methods: Histological analyses of distal femur growth plates of wild type (WT) and mucopolysaccharidosis type VI (MPS VI) rats at different stages of development were performed, including quantitative data. Experimental findings were then analyzed in a theoretical scenario. Results: Histological evaluation showed a progressive loss of histological architecture within the growth plate. Furthermore, in silico simulation suggest the abnormal cell distribution in the tissue may lead to alterations in biochemical gradients, which may be one of the factors contributing to the growth plate abnormalities observed, highlighting aspects that must be the focus of future experimental works. Conclusion: The results presented shed some light on the progression of growth plate alterations observed in MPS VI and evidence the potentiality of combined theoretical and experimental approaches to better understand pathological scenarios, which is a necessary step to improve the search for novel therapeutic approaches. Full article

The objective of this systematic review was to analyze the current state of the art of imaging-derived biomarkers predictive of genetic alterations and immunotherapy targets in lung cancer. We included original research studies reporting the development and validation of imaging feature-based models. The overall quality, the standard of reporting and the advancements towards clinical practice were assessed. Eighteen out of the 24 selected articles were classified as “high-quality” studies according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The 18 “high-quality papers” adhered to Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) with a mean of 62.9%. The majority of “high-quality” studies (16/18) were classified as phase II. The most commonly used imaging predictors were radiomic features, followed by visual qualitative computed tomography (CT) features, convolutional neural network-based approaches and positron emission tomography (PET) parameters, all used alone or combined with clinicopathologic features. The majority (14/18) were focused on the prediction of epidermal growth factor receptor (EGFR) mutation. Thirty-five imaging-based models were built to predict the EGFR status. The model’s performances ranged from weak (n = 5) to acceptable (n = 11), to excellent (n = 18) and outstanding (n = 1) in the validation set. Positive outcomes were also reported for the prediction of ALK rearrangement, ALK/ROS1/RET fusions and programmed cell death ligand 1 (PD-L1) expression. Despite the promising results in terms of predictive performance, image-based models, suffering from methodological bias, require further validation before replacing traditional molecular pathology testing. Full article

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in over 2.7 million infected individuals and over 190,000 deaths and growing. Assertions in the literature suggest that respiratory disorders due to COVID-19 commonly present with pneumonia-like symptoms which are radiologically confirmed as opacities. Radiology serves as an adjunct to the reverse transcription-polymerase chain reaction test for confirmation and evaluating disease progression. While computed tomography (CT) imaging is more specific than chest X-rays (CXR), its use is limited due to cross-contamination concerns. CXR imaging is commonly used in high-demand situations, placing a significant burden on radiology services. The use of artificial intelligence (AI) has been suggested to alleviate this burden. However, there is a dearth of sufficient training data for developing image-based AI tools. We propose increasing training data for recognizing COVID-19 pneumonia opacities using weakly labeled data augmentation. This follows from a hypothesis that the COVID-19 manifestation would be similar to that caused by other viral pathogens affecting the lungs. We expand the training data distribution for supervised learning through the use of weakly labeled CXR images, automatically pooled from publicly available pneumonia datasets, to classify them into those with bacterial or viral pneumonia opacities. Next, we use these selected images in a stage-wise, strategic approach to train convolutional neural network-based algorithms and compare against those trained with non-augmented data. Weakly labeled data augmentation expands the learned feature space in an attempt to encompass variability in unseen test distributions, enhance inter-class discrimination, and reduce the generalization error. Empirical evaluations demonstrate that simple weakly labeled data augmentation (Acc: 0.5555 and Acc: 0.6536) is better than baseline non-augmented training (Acc: 0.2885 and Acc: 0.5028) in identifying COVID-19 manifestations as viral pneumonia. Interestingly, adding COVID-19 CXRs to simple weakly labeled augmented training data significantly improves the performance (Acc: 0.7095 and Acc: 0.8889), suggesting that COVID-19, though viral in origin, creates a uniquely different presentation in CXRs compared with other viral pneumonia manifestations. Full article

Aim: Beyond brain computed tomography (CT) scan, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) hold paramount importance in neuro-oncology. The aim of this narrative review is to discuss the literature from 2015 to 2020, showing advantages or complementary information of fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) PET imaging to the anatomical and functional data offered by MRI in patients with glioma. Methods: A comprehensive Pubmed/MEDLINE literature search was performed to retrieve original studies, with a minimum of 10 glioma patients, published from 2015 until the end of April 2020, on the use of ¹⁸F-FDG PET in conjunction with MRI. Results: Twenty-two articles were selected. Combined use of the two modalities improves the accuracy in predicting prognosis, planning treatments, and evaluating recurrence. Conclusion: According to the recent literature, ¹⁸F-FDG PET provides different and complementary information to MRI and may enhance performance in the whole management of gliomas. Therefore, integrated PET/MRI may be particularly useful in gliomas, since it could provide accurate morphological and metabolic information in one-shoot examination and improve the diagnostic value compared to each of procedures. Full article

Brain positron emission tomography imaging with 18Fluorine-fluorodeoxyglucose (FDG-PET) has demonstrated utility in suspected autoimmune encephalitis. Visual and/or assisted image reading is not well established to evaluate hypometabolism/hypermetabolism. We retrospectively evaluated patients with autoimmune encephalitis between 2003 and 2018. Patients underwent EEG, brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) sampling and autoantibodies testing. Individual FDG-PET images were evaluated by standard visual reading and assisted by voxel-based analyses, compared to a normal database. For the latter, three different methods were performed: two based on statistical surface projections (Siemens syngo.via Database Comparison, and 3D-SSP Neurostat) and one based on statistical parametric mapping (SPM12). Hypometabolic and hypermetabolic findings were grouped to identify specific patterns. We found six cases with definite diagnosis of autoimmune encephalitis. Two cases had anti-LGI1, one had anti-NMDA-R and two anti-CASPR2 antibodies, and one was seronegative. ¹⁸F-FDG-PET metabolic abnormalities were present in all cases, regardless of the method of analysis. Medial–temporal and extra-limbic hypermetabolism were more clearly depicted by voxel-based analyses. We found autoantibody-specific patterns in line with the literature. Statistical surface projection (SSP) methods (Neurostat and syngo.via Database Comparison) were more sensitive and localized larger hypermetabolic areas. As it may lead to comparable and accurate results, visual analysis of FDG-PET studies for the diagnosis of autoimmune encephalitis benefits from voxel-based analysis, beyond the approach based on MRI, CSF sample and EEG. Full article

Objectives: Venous diseases in the lower extremities long lacked an objective diagnostic tool prior to the advent of the triggered angiography non-contrast-enhanced (TRANCE) technique. Methods: An observational study with retrospective data analysis. Materials: Between April 2017 and June 2019, 66 patients were evaluated for venous diseases through TRANCE-magnetic resonance imaging (MRI) and were grouped according to whether they had occlusive venous (OV) disease, a static venous ulcer (SU), or symptomatic varicose veins (VV). The clinical appliance of TRANCE-MRI was analysed by groups. Results: In total, 63 patients completed the study. TRANCE-MRI could identify venous thrombosis, including that of the abdominal and pelvic vessels, and it enabled the timely treatment of underlying diseases in patients with OV disease. TRANCE-MRI was statistically compared with the duplex scan, the gold standard to exclude deep vein thrombosis (DVT) in the legs, with regard to their abilities to detect venous thrombosis by using Cohen’s kappa coefficient at a compatible value of 0.711. It could provide the occlusion degree of the peripheral artery for treating an SU. Finally, TRANCE-MRI can be used to outline all collateral veins and occult thrombi before treating symptomatic or recurrent VV to ensure a perfect surgical plan and to avoid complications. Conclusions: TRANCE-MRI is an innovative tool in the treatment of versatile venous pathology in the lower extremities and is widely used for vascular diseases in our institution. Full article

The evaluation of the clustering of magnetic resonance imaging (MRI) signs into MRI types and their relationship with circulating markers of vascular wall damage were performed in 96 patients with cerebral small vessel disease (cSVD) (31 men and 65 women; mean age, 60.91 ± 6.57 years). The serum concentrations of the tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), and hypoxia-inducible factor 1-α (HIF-1α) were investigated in 70 patients with Fazekas stages 2 and 3 of white matter hyperintensities (WMH) and 21 age- and sex-matched volunteers with normal brain MRI using ELISA. The cluster analysis excluded two patients from the further analysis due to restrictions in their scanning protocol. MRI signs of 94 patients were distributed into two clusters. In the first group there were 18 patients with Fazekas 3 stage WMH. The second group consisted of 76 patients with WMH of different stages. The uneven distribution of patients between clusters limited the subsequent steps of statistical analysis; therefore, a cluster comparison was performed in patients with Fazekas stage 3 WMH, designated as MRI type 1 and type 2 of Fazekas 3 stage. There were no differences in age, sex, degree of hypertension, or other risk factors. MRI type 1 had significantly more widespread WMH, lacunes in many areas, microbleeds, atrophy, severe cognitive and gait impairments, and was associated with downregulation of VEGF-A compared with MRI type 2. MRI type 2 had more severe deep WMH, lacunes in the white matter, no microbleeds or atrophy, and less severe clinical manifestations and was associated with upregulation of TNF-α compared with MRI type 1. The established differences reflect the pathogenetic heterogeneity of cSVD and explain the variations in the clinical manifestations observed in Fazekas stage 3 of this disease. Full article

This study aims at determining the thickness of the tear lipid layer (LL) observed from a placido-disc-based tear film analyzer. We prospectively collected reflections of placido-disk LL images using a tear film analyzer (Keratograph^® 5M, Oculus) from subjects with dry eye symptoms. The LL thickness (LLT) over the inferior half of the cornea was estimated with the use of interference color analysis and the preprocessing of images with and without ring segmentation were obtained and analyzed. Moreover, LLTs before and after 1 h of applying topical ointment (Duratears, Alcon) were compared to validate the estimation of LLT. Our results suggested that the tear LLT can be assessed using a placido-disk-based tear film analyzer and interference color analysis. We verified a high correlation between non-segmented and segmented LL images and estimated LLT increase after applying ointment. In addition, we concluded that LLT can be evaluated by direct interference analysis without segmentation preprocessing. Full article

Background: Inconclusive bone scans are a challenge but there is no consensus about follow-up imaging. We evaluated the use of ⁶⁸gallium-labelled prostate-specific membrane antigen (⁶⁸Ga-PSMA) PET/CT if ¹⁸F-sodium fluoride (¹⁸F-NaF) PET/CT was inconclusive. Methods: This retrospective study included patients with no previously known bone metastases who had one or more equivocal bone lesions on ¹⁸F-NaF PET/CT and underwent additional ⁶⁸Ga-PSMA PET/CT. The bone lesions were deemed as true metastases or not based on follow-up by surveying supplemental imaging modalities and hospital records. A subgroup of patients with “most valid follow-up” was created, which included patients with unmeasurable PSA after prostatectomy or subsequent imaging (additional ¹⁸F-NaF PET/CT, ⁶⁸Ga-PSMA PET/CT, CT, or MRI). Results: Of the 2918 patients referred for ¹⁸F-NaF PET/CT from the department of urology in the inclusion period, 51 (1.7%) were inconclusive regarding bone metastases and underwent additional ⁶⁸Ga-PSMA PET/CT. Thirteen of these patients (25%) were ultimately diagnosed with bone metastases. Patient-based sensitivity, specificity, and accuracy of additional ⁶⁸Ga-PSMA PET/CT were 100%, 95%, and 96%, respectively. In patients with “most valid follow-up”, the same parameters were 100%, 93%, and 94%, respectively. Conclusion: ⁶⁸Ga-PSMA PET/CT is an excellent complementary modality in when ¹⁸F-NaF PET/CT is equivocal. Full article

The first step leading to metastasis, or for the acquisition of local invasiveness, involves changes in the phenotype of neoplastic cells in the primary tumor. The epithelial–mesenchymal transition (EMT) is a process that determines the acquisition of a form and a transcriptional program that are characteristic of mesenchymal cells, in epithelial cells. The factors involved in this process are E-cadherin and N-cadherin adhesion proteins and some transcription factors such as Slug and Twist. EMT is a site-specific mechanism that is also active in embryogenesis—embryonic cells are affected if invested in certain points, probably due to the signals emanating from the cells or groups of surrounding cells. It is known that neuroendocrine neoplasms have a biological behavior that differs in grading, staging, and site. The aim of our study was to investigate the immunohistochemical expression of EMT factors (Twist, Slug, and E-cadherin) in the neuroendocrine neoplasms of the gastrointestinal tract, the pancreas, and lungs, in 65 cases retrieved from the archives of the Department of Pathology, of three hospitals. The immunoscores were compared in each site and correlated with the clinico-pathological parameters. Statistical evaluation revealed an association between the higher Twist immunoscore and higher grading (p value < 0.0001) and staging (p value = 0.0055). Slug was detected only in pancreatic cases where its reduced expression was associated with a higher grading (p value = 0.0033). This data could be of diagnostic utility in the case of metastases from neuroendocrine neoplasm, to define the site of the primitive tumor when the traditional immunohistochemical panel is not sufficient. In summary, our results indicated, first that the EMT is also an active process in neuroendocrine neoplasms. To the best of our knowledge, this was the first study that evaluated the expression of EMT factors in neuroendocrine neoplasms of different districts. Full article

Isolated sphenoid sinus disease (ISSD) is where there is a group of pathologies characterized by inflammation in one or both sphenoid sinuses. Although computer tomography (CT)-based 3D reconstruction remains the gold standard among noninvasive approaches to ISSD diagnostics, no standardized techniques for direct intraoperative measurements of the sphenoid sinus volume in ISSD patients have been documented. We suggest a novel technique for the intraoperative measurement of the sphenoid sinus volume. Our technique is based on filling the sinus with 0.01% methylene blue solution after an endoscopic endonasal sphenoidotomy. The proposed technique was applied to 40 ISSD patients during surgery. Obtained intraoperative measurements were compared to noninvasive measurements from 3D reconstructions based on preoperative CT scans. Our results demonstrated that the obtained measurements did not exhibit significant differences exceeding 0.4 cm³, with CT-scan-based measurements in 39 out of 40 cases (p < 10⁻⁶, Wilcoxon sign-rank nonparametric test), thus confirming the accuracy of the proposed technique. Disagreements between direct intraoperative and CT-based measurements in a single case have been attributed to the presence of remaining pathological masses in the sinus, which was further confirmed during the secondary check of the operated sinus. Accordingly, we suggest that the agreement between the CT-based and intraoperative volume measurements can be used as an indicator of the successful elimination of all pathological masses from the sinus without having to perform an adequate exposure of the entire sphenoid sinus to reduce intraoperative bleeding. The proposed technique is accurate and does not require the involvement of specialized intraoperative CT scanners and avoids additional radiation exposure for the patient during an additional postoperation CT scan to confirm the success of the surgery. Full article

The diagnosis of neurocognitive disorders associated with HIV infection, alcohol, and tobacco using CSF or neuroimaging are invasive or expensive methods, respectively. Therefore, extracellular vesicles (EVs) can serve as reliable noninvasive markers due to their bidirectional transport of cargo from the brain to the systemic circulation. Hence, our objective was to investigate the expression of astrocytic (GFAP) and neuronal (L1CAM) specific proteins in EVs circulated in the plasma of HIV subjects, with and without a history of alcohol consumption and tobacco smoking. The protein expression of GFAP (p < 0.01) was significantly enhanced in plasma EVs obtained from HIV-positive subjects and alcohol users compared to healthy subjects, suggesting enhanced activation of astrocytes in those subjects. The L1CAM expression was found to be significantly elevated in cigarette smokers (p < 0.05). However, its expression was not found to be significant in HIV subjects and alcohol users. Both GFAP and L1CAM levels were not further elevated in HIV-positive alcohol or tobacco users compared to HIV-positive nonsubstance users. Taken together, our data demonstrate that the astrocytic and neuronal-specific markers (GFAP and L1CAM) can be packaged in EVs and circulate in plasma, which is further elevated in the presence of HIV infection, alcohol, and/or tobacco. Thus, the astroglial marker GFAP and neuronal marker L1CAM may represent potential biomarkers targeting neurological dysfunction upon HIV infection and/or alcohol/tobacco consumption. Full article

Radial nerve palsy is not uncommon after humeral shaft fractures. Ultrasound-guided hydrodissection is an emerging treatment for nerve entrapment. Two cases of radial nerve injury after humeral shaft fractures with plate fixation are presented. Shear wave elastography was used to identify hardened scars surrounding the nerve, causing entrapment. These areas were marked on the skin as targets for ultrasound-guided hydrodissection. Each patient experienced full recovery of their radial nerve function. Shear wave elastography may be used to precisely identify sites of neural entrapment by scar tissue and accurately guide perineural hydrodissection, particularly in complex postoperative cases. Full article

Background: We compared the efficiency of two MRI diffusion weighted imaging (DWI) techniques: DWI with SPIR (DWI_SPIR) and DWI with STIR (DWI_STIR), to estimate their eligibility for quantitative assessment of Crohn’s disease activity in children and adults. Methods: In inflamed terminal ileum segments (n = 32 in adults, n = 46 in children), Magnetic Resonance Index of Activity (MaRIA) was calculated, ADC values of both DWI techniques were measured, and the corresponding Clermont scores calculated. ADC values of both DWI techniques were compared between both and within each patient group, assessing their mutual correlation. Correlations between MaRIA and the corresponding ADC values, and Clermont scores based on both DWI techniques were estimated. Results: No correlation between ADC of DWI_SPIR and DWI_STIR was observed (rho = 0.27, p = 0.13 in adults, rho = 0.20, p = 0.17 in children). The correlation between MaRIA and Clermont scores was strong in both techniques—in SPIR, rho = 0.93; p < 0.0005 in adults, rho = 0.98, p < 0.0005 in children, and, in STIR, rho = 0.89; p < 0.0005 in adults, rho = 0.95, p < 0.0005 in children. The correlation between ADC and MaRIA was moderate negative for DWI_STIR (rho = 0.93, p < 0.0005 in adults, rho = 0.95, p < 0.0005 in children), but, in DWI_STIR, no correlation between ADC and MaRIA score was observed in adults (rho = −0.001, p = 0.99), whereas children presented low negative correlation (rho = −0.374, p = 0.01). Conclusions: DWI_STIR is not suitable for quantitative assessment of Crohn’s disease activity both in children and adult patients. Full article

A cyst is a round circumscribed area of low attenuation, surrounded by epithelial or fibrous wall. Cysts can frequently occur on chest computed tomography (CT) and high-resolution computed tomography (HRCT); multiple parenchymal cysts of the lungs are the most typical feature of cystic lung interstitial diseases, characterizing a wide spectrum of diseases—ranging from isolated lung disorders up to diffuse pulmonary diseases. The aim of this review is to analyze scientific literature about cystic lung interstitial diseases and to provide a practical guide for radiologists, focusing on the main morphological features of pulmonary cysts: size, shape, borders, wall, location, and distribution. These features are shown on free-hand drawings and related to HRCT images, in order to help radiologists pursue the correct differential diagnosis between similar conditions. Full article

In the present pictorial we show the ultrasonographic appearances of endometriosis in atypical sites. Scar endometriosis may present as a hypoechoic solid nodule with hyperechoic spots while umbilical endometriosis may appear as solid or partially cystic areas with ill-defined margins. In the case of endometriosis of the rectus muscle, ultrasonography usually demonstrates a heterogeneous hypoechogenic formation with indistinct edges. Inguinal endometriosis is quite variable in its ultrasonographic presentation showing a completely solid mass or a mixed solid and cystic mass. The typical ultrasonographic finding associated with perineal endometriosis is the presence of a solid lesion near to the episiotomy scar. Under ultrasonography, appendiceal endometriosis is characterized by a solid lesion in the wall of the small bowel, usually well defined. Superficial hepatic endometriosis is characterized by a small hypoechoic lesion interrupting the hepatic capsula, usually hyperechoic. Ultrasound endometriosis of the pancreas is characterized by a small hypoechoic lesion while endometriosis of the kidney is characterized by a hyperechoic small nodule. Diaphragmatic endometriosis showed typically small hypoechoic lesions. Only peripheral nerves can be investigated using ultrasound, with a typical solid appearance. In conclusion, ultrasonography seems to have a fundamental role in the majority of endometriosis cases in “atypical” sites, in all the cases where “typical” clinical findings are present. Full article

The glymphatic system is a newly discovered waste drainage pathway in the brain; it plays an important role in many neurological diseases. Ongoing research utilizing various cerebrospinal fluid tracer infusions, either directly or indirectly into the brain parenchyma, is investigating clearance pathways by using distinct imaging techniques. In the present review, we discuss the role of the glymphatic system in various neurological diseases and efflux pathways of brain waste clearance based on current evidence and controversies. We mainly focus on new magnetic resonance imaging (MRI) modeling techniques, along with traditional computational modeling, for a better understanding of the glymphatic system function. Future sophisticated modeling techniques hold the potential to generate quantitative maps for glymphatic system parameters that could contribute to the diagnosis, monitoring, and prognosis of neurological diseases. The non-invasive nature of MRI may provide a safe and effective way to translate glymphatic system measurements from bench-to-bedside. Full article