The T1-dark-rim: A novel imaging sign for detecting smoldering inflammation in multiple sclerosis.

PURPOSE: Paramagnetic rim lesions (PRLs), usually identified in susceptibility-weighted imaging (SWI), are a promising prognostic biomarker of disability progression in multiple sclerosis (MS). However, SWI is not routinely performed in clinical practice. The objective of this study is to define a novel imaging sign, the T1-dark rim, identifiable in a standard 3DT1 gradient-echo inversion-recovery sequence, such as 3D T1 turbo field echo (3DT1FE) and explore its performance as a SWI surrogate to define PRLs. METHODS: This observational cross-sectional study analyzed MS patients who underwent 3T magnetic resonance imaging (MRI) including 3DT1TFE and SWI. Rim lesions were evaluated in 3DT1TFE, processed SWI, and SWI phase and categorized as true positive, false positive, or false negative based on the value of the T1-dark rim in predicting SWI phase PRLs. Sensitivity and positive predictive values of the T1-dark rim for detecting PRLs were calculated. RESULTS: Overall, 80 rim lesions were identified in 63 patients (60 in the SWI phase and 78 in 3DT1TFE; 58 true positives, 20 false positives, and two false negatives). The T1-dark rim demonstrated 97% sensitivity and 74% positive predictive value for detecting PRLs. More PRLs were detected in the SWI phase than in processed SWI (60 and 57, respectively). CONCLUSION: The T1-dark rim sign is a promising and accessible novel imaging marker to detect PRLs whose high sensitivity may enable earlier detection of chronic active lesions to guide MS treatment escalation. The relevance of T1-dark rim lesions that are negative on SWI opens up a new field for analysis.

Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial.

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39-1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360-842] vs. 870 mg [IQR 364-1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00-17.5] vs. 18.5 days [3.00-53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05-2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19. Clinical Trial Registration: Identifier [NCT04341038/EudraCT: 2020-001445-39].

Precise enhancement quantification in post-operative MRI as an indicator of residual tumor impact is associated with survival in patients with glioblastoma.

Glioblastoma is the most common primary brain tumor. Standard therapy consists of maximum safe resection combined with adjuvant radiochemotherapy followed by chemotherapy with temozolomide, however prognosis is extremely poor. Assessment of the residual tumor after surgery and patient stratification into prognostic groups (i.e., by tumor volume) is currently hindered by the subjective evaluation of residual enhancement in medical images (magnetic resonance imaging [MRI]). Furthermore, objective evidence defining the optimal time to acquire the images is lacking. We analyzed 144 patients with glioblastoma, objectively quantified the enhancing residual tumor through computational image analysis and assessed the correlation with survival. Pathological enhancement thickness on post-surgical MRI correlated with survival (hazard ratio: 1.98, p < 0.001). The prognostic value of several imaging and clinical variables was analyzed individually and combined (radiomics AUC 0.71, p = 0.07; combined AUC 0.72, p < 0.001). Residual enhancement thickness and radiomics complemented clinical data for prognosis stratification in patients with glioblastoma. Significant results were only obtained for scans performed between 24 and 72 h after surgery, raising the possibility of confounding non-tumor enhancement in very early post-surgery MRI. Regarding the extent of resection, and in agreement with recent studies, the association between the measured tumor remnant and survival supports maximal safe resection whenever possible.

Minimizing acquisition-related radiomics variability by image resampling and batch effect correction to allow for large-scale data analysis.

OBJECTIVE: To identify CT-acquisition parameters accounting for radiomics variability and to develop a post-acquisition CT-image correction method to reduce variability and improve radiomics classification in both phantom and clinical applications. METHODS: CT-acquisition protocols were prospectively tested in a phantom. The multi-centric retrospective clinical study included CT scans of patients with colorectal/renal cancer liver metastases. Ninety-three radiomics features of first order and texture were extracted. Intraclass correlation coefficients (ICCs) between CT-acquisition protocols were evaluated to define sources of variability. Voxel size, ComBat, and singular value decomposition (SVD) compensation methods were explored for reducing the radiomics variability. The number of robust features was compared before and after correction using two-proportion z test. The radiomics classification accuracy (K-means purity) was assessed before and after ComBat- and SVD-based correction. RESULTS: Fifty-three acquisition protocols in 13 tissue densities were analyzed. Ninety-seven liver metastases from 43 patients with CT from two vendors were included. Pixel size, reconstruction slice spacing, convolution kernel, and acquisition slice thickness are relevant sources of radiomics variability with a percentage of robust features lower than 80%. Resampling to isometric voxels increased the number of robust features when images were acquired with different pixel sizes (p < 0.05). SVD-based for thickness correction and ComBat correction for thickness and combined thickness-kernel increased the number of reproducible features (p < 0.05). ComBat showed the highest improvement of radiomics-based classification in both the phantom and clinical applications (K-means purity 65.98 vs 73.20). CONCLUSION: CT-image post-acquisition processing and radiomics normalization by means of batch effect correction allow for standardization of large-scale data analysis and improve the classification accuracy. KEY POINTS: • The voxel size (accounting for the pixel size and slice spacing), slice thickness, and convolution kernel are relevant sources of CT-radiomics variability. • Voxel size resampling increased the mean percentage of robust CT-radiomics features from 59.50 to 89.25% when comparing CT scans acquired with different pixel sizes and from 71.62 to 82.58% when the scans were acquired with different slice spacings. • ComBat batch effect correction reduced the CT-radiomics variability secondary to the slice thickness and convolution kernel, improving the capacity of CT-radiomics to differentiate tissues (in the phantom application) and the primary tumor type from liver metastases (in the clinical application).

COVID-19 and Ischemic Stroke: Clinical and Neuroimaging Findings.

BACKGROUND AND PURPOSE: SARS-CoV-2 causes multiorgan disease due to altered coagulability and microangiopathy. Patients may have an increased risk of cerebrovascular accidents (CVA). Our objective was to analyze clinical and neuroimaging characteristics of patients with ischemic CVA during the pandemic peak in our region, in order to identify atypical presentations. METHODS: We performed a cross-sectional analysis of patients admitted under code-stroke protocol to our center with a final diagnosis of ischemic brain infarction. We analyzed the main imaging and demographic characteristics and reviewed neuroimaging for atypical presentations. RESULTS: One-hundred patients with confirmed ischemic CVA were included. Nineteen had positive polymerase chain reaction testing for SARS-CoV-2 on admission. These patients had a lower prevalence of proximal arterial occlusion on imaging, higher in-hospital mortality, and worse baseline disability. No differences were identified in affected vascular territory, volume of infarction, initial CT stroke score, prevalence of hemorrhagic transformation, gender, age, cardiovascular risk factors, time to admission, symptom severity on entry, or decision to treat with thrombolysis or mechanical thrombectomy. Prevalence of COVID-19 in our code-stroke sample was higher than that for our province during this time period. CONCLUSION: The COVID-19 group had more in-hospital mortality, less proximal arterial occlusion on CT or MR angiography, and lower baseline modified Rankin Scale score. We suggest a possibly higher proportion of microangiopathic involvement or undetected distal large-vessel occlusion in the COVID-19 stroke group. Excess mortality was explained by severe respiratory failure. Otherwise, stroke patients with COVID-19 did not differ demographically or clinically from those without the illness.

Acute effect of static exercise in patients with aortic regurgitation assessed by cardiovascular magnetic resonance: role of left ventricular remodelling.

OBJECTIVE: In patients with aortic regurgitation (AR), the effect of static exercise (SE) on global ventricular function and AR severity has not been previously studied. METHODS: Resting and SE cardiovascular magnetic resonance (CMR) were prospectively performed in 23 asymptomatic patients with AR. RESULTS: During SE, we observed a decrease in regurgitant volume in both end-diastolic (EDV) and end-systolic (ESV) volume in both ventricles, as well as a slight decrease in LV ejection fraction (EF). Interestingly, responses varied depending on the degree of LV remodelling. Among patients with a greater degree of LV remodelling, we observed a decrease in LVEF (56 ± 4 % at rest vs 48 ± 7 % during SE, p = 0.001) as a result of a lower decrease in LVESV (with respect to LVEDV. Among patients with a lower degree of LV remodelling, LVEF remained unchanged. RVEF remained unchanged in both groups. CONCLUSIONS: In patients with AR, SE provoked a reduction in preload, LV stroke volume, and regurgitant volume. In those patients with higher LV remodelling, we observed a decrease in LVEF, suggesting a lower LV contractile reserve. KEY POINTS: • In patients with aortic regurgitation, static exercise reduced preload volume. • In patients with aortic regurgitation, static exercise reduced stroke volume. • In patients with aortic regurgitation, static exercise reduced regurgitant volume. • In patients with greater remodelling, static exercise unmasked a lower contractile reserve. • Effect of static exercise on aortic regurgitation was assessed by cardiac MR.

Liver fat deposition and mitochondrial dysfunction in morbid obesity: An approach combining metabolomics with liver imaging and histology.

AIM: To explore the usefulness of magnetic resonance imaging (MRI) and spectroscopy (MRS) for assessment of non-alcoholic fat liver disease (NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesity-induced NAFLD in an observational, prospective, single-site, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described (1)H NMR-based metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from (1)H NMR spectra obtained after surgery were omitted due to technical limitations. RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, which excluded the presence of non-alcoholic steatohepatitis (NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the -CH3 peak (0.9 ppm), the -CH2- peak (1.3 ppm, mostly triglyceride) and the -CH=CH- peak (2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may help to explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients. CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose.

Acute effect of static exercise on the cardiovascular system: assessment by cardiovascular magnetic resonance.

PURPOSE: The acute effect of static exercise on the global dynamics of the cardiovascular system is poorly understood. The use of cardiovascular magnetic resonance (CMR) may be useful for evaluating this effect. METHODS: A total of 12 healthy individuals underwent CMR imaging at rest and while performing a maximal sustained static exercise (weight elevation with both legs). We analyzed the effects on left and right ventricular function, ascending aorta dynamics, and venous capacitance using standard cine and phase-contrast sequences. RESULTS: We observed excellent reproducibility in the measurements of the images obtained at rest as well as during static exercise. During exercise, we observed reduced left (-35 ± 8 %, p < 0.001) and right (-44 ± 9 %, p < 0.001) ventricle end-diastolic volumes, reduced left (-35 ± 16 %, p < 0.001) and right (-43 ± 8 %, p < 0.001) ventricle end-systolic volumes (both with a significantly greater reduction in the right ventricle), a reduced superior vena cava cross-sectional area (-20 ± 17 %, p = 0.003), and increased left ventricle wall thickness. We estimated that there was an increase in left ventricle contractility. There were no significant changes in the left and right ventricular ejection fractions. During exercise, we noted a tendency toward decreased aortic distensibility and a reduction of ascending aorta systolic expansion. CONCLUSIONS: In healthy individuals, an acute maximal static exercise produced a reduction in the left ventricle, right ventricle, and superior vena cava volumes as well as signs of increased aortic stiffness without increasing left ventricular systolic wall stress. CMR is feasible and useful in evaluating the hemodynamic effects of static exercise.

Systematic analysis of transrectal prostate biopsies using an ink method and specific histopathologic protocol: a prospective study.

Background. Transrectal prostate biopsy is the standard protocol for the screening for prostate cancer. It helps to locate prostatic adenocarcinoma and plan treatment. However, the increasing number of prostate biopsies leads to considerably greater costs for the pathology laboratories. In this study, we compare the traditional method with an ink method in combination with a systematic histopathologic protocol. Methods. Two hundred consecutive transrectal prostate biopsy specimens were received from the radiology department. They were separated into two groups: one hundred were processed as six different specimens in the usual manner. The other one hundred were submitted in six containers, the apex, base, and middle section of which were stained different colours. The samples subject to the ink method were embedded in paraffin and placed in two cassettes which were sectioned using a specific protocol. Results. The comparative study of the nonink and ink methods for histopathologic diagnosis showed no statistical differences as far as diagnostic categories were concerned (P value < .005). The number of PIN diagnoses increased when the ink method was used, but no statistical differences were found. The ink method led to a cost reduction of 48.86%. Conclusions. Our ink method combined with a specific histopathologic protocol provided the same diagnostic quality, tumor location information as the traditional method, and lower pathology expenses.

Dilated aortic root is related to a global aortic dilating diathesis.

OBJECTIVE: The purpose of this study was to analyze the association between the dilatation of the aortic root and the diameters of the rest of the aorta and to identify some related factors that could be used to identify patients at higher risk of presenting with an aortic aneurysm. METHODS: In 71 consecutive patients with a dilated aortic root identified by transthoracic echocardiography, prospective helical computed tomography was performed. Aortic diameters were measured perpendicular to the flow at seven levels in the thoracic and abdominal aorta. RESULTS: Ascending aorta diameter showed a moderate correlation with aortic indexed diameters at the thoracic and abdominal level in tricuspid aortic valve patients (r ranging from 0.37-0.56), whereas in patients with a bicuspid aortic valve, a moderate correlation between the ascending aorta diameters and the thoracic descending aorta diameters was observed (r 0.51-0.53). In a multivariate analysis, age was independently related to indexed diameter at all aortic sites (ß ranging from 0.06-0.12 per year), whereas aortic regurgitation was independently related only to thoracic aorta diameter (ß ranging from 1.17-1.84). Age (P < .0001), body surface area (P < .0001), and grade of aortic valve regurgitation (P = .001) independently predicted aortic volume. CONCLUSION: Different patterns of aortic diameters were observed in patients with dilated aortic root, depending on age, aortic valve morphology, and function. When a dilated aortic root is detected in older patients with a tricuspid aortic valve, an accurate cardiovascular survey that includes the entire aorta is needed. These results provide further evidence about the systemic nature of aortic dilatation.

Influenza-like infection can result in diffuse fluordeoxyglucose uptake in the lungs.

A 32-year-old man underwent an F-18 fluordeoxyglucose positron emission tomography (FDG-PET/CT) scan for response assessment of mediastinal bulky non-Hodgkin lymphoma after completion of a CHOP therapy regimen. The F-18 FDG-PET/CT scan showed complete response regarding the mediastinal lesion. However, an unexpected pattern of prominent lung and abdominal muscular uptake was detected. The patient's clinical history was reassessed for differential diagnosis purposes. The medical records confirmed an episode of self-resolved influenza-like infection 4 days before the PET scan.This case underlines the importance of careful history taking before interpretation of PET scans. Viral infections should be included in the differential diagnosis of pulmonary diffuse F-18 FDG uptake.

Subclinical carotid atherosclerosis in HIV-infected patients: role of combination antiretroviral therapy.

BACKGROUND AND PURPOSE: Whether or not combination antiretroviral therapy (CART) alone directly contributes to accelerating atherosclerosis in HIV-infected patients has not been studied in depth. This study aimed to ascertain the relationship between this therapy and subclinical carotid atherosclerosis according to cardiovascular risk. METHODS: Sixty-eight HIV-infected patients with < or =1 cardiovascular risk factors and 64 with > or =2 risk factors completed the study protocol consisting of clinical, laboratory, and vascular evaluation by carotid high-resolution B-mode ultrasonography. Univariate and multivariate logistic regression analyses were performed with the presence of subclinical carotid atherosclerosis, defined by carotid intima-media thickness >0.8 mm or the presence of plaque being the dependent variable. RESULTS: Among the 132 enrolled patients, 93 (70.5%) were on CART and 39 (29.5%) had never been on antiretroviral therapy. In accordance with cardiovascular risk stratification, subclinical carotid atherosclerosis was found in 26.6% (17 of 64 patients) of the very low-risk group (10-year coronary risk <5%), 35.3% (12 of 34 patients) of the low-risk group (10-year coronary risk between 5% and 9%) and 76.5% (26 of 34 patients) of the moderate/high-risk group (10-year coronary risk > or =10%). Thus, 55 (41.7%) of the 132 HIV-infected patients had subclinical carotid atherosclerosis, and independent variables associated with carotid atherosclerosis (odds ratio; 95% CI) were: CART exposure (10.5; 2.8 to 39) and 10-year coronary risk > or =10% (4.2; 1.5 to 12). In very low coronary risk patients (<5%), age (per 10-year increment: 4.01; 1.12 to 14.38), systolic blood pressure (per unit mm Hg 1.07; 1.01 to 1.14), and CART exposure (8.65; 1.54 to 48.54) were independently associated with subclinical carotid atherosclerosis. CONCLUSIONS: CART should be considered a strong, independent predictor for the development of subclinical atherosclerosis in HIV-infected patients, regardless of known major cardiovascular risk factors and atherogenic metabolic abnormalities induced by this therapy.

Atherosclerosis in patients infected with HIV is influenced by a mutant monocyte chemoattractant protein-1 allele.

BACKGROUND: Patients infected with HIV present with premature atherosclerosis, and the 2 diseases share common pathogenic pathways. We investigated mutations in the monocyte chemoattractant protein-1 (MCP-1) and CCR-2 genes, which are known to control aspects of these pathways, to ascertain whether they are involved in atherogenesis in these patients. METHODS AND RESULTS: We performed carotid and femoral artery ultrasonography to detect subclinical atherosclerosis in patients infected with HIV (n=183). MCP-1-2518G and CCR-2 64I polymorphisms were determined in the HIV group and in a population-based control group (n=348). We also determined MCP-1 circulating levels in the HIV group. The presence of MCP-1-2518G in the group of patients with subclinical atherosclerosis was significantly higher than in patients without atherosclerotic lesions (47.5% versus 18.2%, respectively; P<0.001). Furthermore, the patients with atherosclerotic lesions had higher MCP-1 plasma concentrations than did patients without lesions (74.15 [4.03] versus 57.81 [3.67] pg/mL, respectively; P=0.03). When adjusted for known cardiovascular risk factors, the MCP-1-2518G allele was associated with subclinical atherosclerosis (OR 5.72, 95% CI 1.74 to 18.80, P=0.004). Compared with measurements conducted approximately 2.5 years earlier in a subset of 40 patients, intima-media thickness (IMT) in the carotid artery progressed at a mean rate of 0.06 mm/y more rapidly in patients bearing the MCP-1-mutated allele (P=0.08). CONCLUSIONS: HIV-infected patients with the MCP-1-2518G allele have a 5-fold increased risk for atherosclerosis, as assessed by ultrasonography.