Motion robust MR fingerprinting scan to image neonates with prenatal opioid exposure

Background: A noninvasive and sensitive imaging tool is needed to assess the fast-evolving baby brain. However, using MRI to study non-sedated babies faces roadblocks, including high scan failure rates due to subjects motion and the lack of quantitative measures for assessing potential developmental delays. This feasibility study explores whether MR Fingerprinting scans can provide motion-robust and quantitative brain tissue measurements for non-sedated infants with prenatal opioid exposure, presenting a viable alternative to clinical MR scans. Assessment: MRF image quality was compared to pediatric MRI scans using a fully crossed, multiple reader multiple case study. The quantitative T1 and T2 values were used to assess brain tissue changes between babies younger than one month and babies between one and two months. Statistical Tests: Generalized estimating equations (GEE) model was performed to test the significant difference of the T1 and T2 values from eight white matter regions of babies under one month and those are older. MRI and MRF image quality were assessed using Gwets second order auto-correlation coefficient (AC2) with its confidence levels. We used the Cochran-Mantel-Haenszel test to assess the difference in proportions between MRF and MRI for all features and stratified by the type of features. Results: In infants under one month of age, the T1 and T2 values are significantly higher (p<0.005) compared to those between one and two months. A multiple-reader and multiple-case study showed superior image quality ratings in anatomical features from the MRF images than the MRI images. Conclusions: This study suggested that the MR Fingerprinting scans offer a motion-robust and efficient method for non-sedated infants, delivering superior image quality than clinical MRI scans and additionally providing quantitative measures to assess brain development

Risk-based MRI-directed diagnostic pathway outperforms non-risk-based pathways in suspected prostate cancer biopsy-naïve men: a large cohort validation study

Objectives: To investigate and compare the performance of different proposed diagnostic pathways in a cohort of biopsy-naïve men at risk for prostate cancer (PCa), in terms of biopsy avoidance, accurate diagnosis of clinically significant prostate cancer (csPCa), and reduction in overdiagnosis of clinically insignificant cancer (cisPCa), with particular focus on a recently suggested “risk-based” MRI-directed diagnostic pathway. Methods: Single-center, retrospective cohort study, including 499 biopsy-naïve men at risk for PCa. All men underwent PI-RADS-compliant prostate MRI, transrectal ultrasound fusion-guided targeted (TBx), and systematic biopsy (SBx). Five diagnostic pathways were retrospectively evaluated and compared for. Outcome measures were biopsy avoidance, combined with missed csPCa and detected cisPCa. csPCa and cisPCa were defined as ISUP grade group ≥ 2 and grade = 1, respectively. Chi-square test was used for statistical analysis. Decision curve analyses were used to compare the benefits of the pathways across a range of biopsy thresholds. Results: The prevalence (detection-focused [reference] pathway) of csPCa and cisPCa was 52.9% (264/499) and 23.0% (115/499). MRI-focused pathway (no biopsy in PI-RADS 1–2 men) did not significantly reduce ISUP ≥ 2 cancer detection (52.1% (260/499); p = 0.13), but significantly reduced ISUP 1 cancers diagnosed (20.6% (103/499); p < 0.01), and biopsy avoidance was 11.8% (59/499). The risk-based MRI-directed pathway (no biopsy in low-risk PI-RADS 1–3 men) resulted in a small reduction of ISUP ≥ 2 diagnosed (51.7% (258/499); p = 0.04), however non-significant when compared to MRI-focused pathway (p = 0.625). Moreover, the risk-based pathway further reduced detection of ISUP 1 (18.6% (93/499); p < 0.01), and biopsy avoidance was 19.2% (96/499). Decision curve analysis showed maximized net benefit of the risk-based pathway, for the range of threshold probabilities between 6.25 and 65%. Conclusion: The risk-based MRI-directed pathway for prostate cancer diagnosis was optimal in balancing accurate diagnosis, reducing overdiagnosis, and maximizing biopsy avoidance. This substantial evidence should inform guideline recommendations towards using “risk-based” MRI-directed biopsy decisions in biopsy-naïve men at risk of significant prostate cancer. Key Points: • Our study recognizes the added value of prostate MRI and MR-targeted biopsies in order to propose clinical diagnostic pathways for prostate cancer, towards maximizing the potential avoidance of unnecessary biopsies, while maintaining optimal detection rate of clinically significant prostate cancer. • The risk-based MRI-directed pathway incorporates risk factors such as PSA density, digital rectal examination, and family history to further refine the initial stratification of patients based on PI-RADS scores. • In this study, the risk-based pathway had the most optimal performance in terms of combination of outcomes, with the highest rate of biopsy avoidance (19.2%), while keeping a high detection rate of clinically significant prostate cancer (51.7%), when compared to the reference standard (52.9%)

Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2

BackgroundPost-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis.MethodsA cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL).Results415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p&lt;.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p&lt;.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p&lt;.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)].ConclusionsPASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics