Diagnostic accuracy of shuttle CT angiography (CTA) and helical CTA in the diagnosis of vasospasm.

PURPOSE: To evaluate the diagnostic accuracy of computed tomography angiography (CTA) acquired with shuttle technique (CTAs) and helical CTA (CTAh) for vasospasm, using digital subtraction angiography (DSA) obtained within 24 h as reference standard. METHODS: Thirty-six patients with suspected vasospasm in the setting of aneurysmal subarachnoid hemorrhage (ASAH, 30/36) or acute inflammatory/infectious conditions (6/36) who underwent CTAs (17/36) or CTAh (19/36) followed by DSA within 24 h were identified retrospectively. Presence of vasospasm in the proximal cerebral arterial segments was assessed qualitatively and semi-quantitatively on CTA and subsequent DSA. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated. Inter-rater variability was assessed using Cohen's kappa. RESULTS: On CTAs, 35% of patients had low and 65% had high vasospasm burden. On CTAh, 37% had low and 63% had high vasospasm burden. ROC analysis demonstrated an AUC of 0.87 for CTAs (95%CI 0.67-1.00, p = 0.015) and 0.88 for CTAh (0.72-1.00, p = 0.028). Cohen's kappa was 0.843 (95%CI 0.548-1.000). Thresholding with Youden's J index, CTAs had a sensitivity of 85.71% (95%CI 48.69 to 99.27) and specificity of 66.67% (35.42 to 87.94). CTAh had sensitivity of 100% (56.55 to 100.00) and specificity of 78.57% (52.41 to 92.43). CONCLUSION: CTAs and CTAh yielded similar sensitivity, specificity, and AUC values on ROC analysis for the detection of vasospasm using DSA as reference standard. Our findings suggest that CTAs is a promising alternative to CTAh especially in patients requiring serial imaging, given its potential advantages of decreased radiation exposure, contrast dose, and cost-effectiveness.

Statistical Parametric Mapping in Amyloid Positron Emission Tomography.

Alzheimer's disease (AD), the most common cause of dementia, has limited treatment options. Emerging disease modifying therapies are targeted at clearing amyloid-ß (Aß) aggregates and slowing the rate of amyloid deposition. However, amyloid burden is not routinely evaluated quantitatively for purposes of disease progression and treatment response assessment. Statistical Parametric Mapping (SPM) is a technique comparing single-subject Positron Emission Tomography (PET) to a healthy cohort that may improve quantification of amyloid burden and diagnostic performance. While primarily used in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, SPM's utility in amyloid PET for AD diagnosis is less established and uncertainty remains regarding optimal normal database construction. Using commercially available SPM software, we created a database of 34 non-APOE ε4 carriers with normal cognitive testing (MMSE > 25) and negative cerebrospinal fluid (CSF) AD biomarkers. We compared this database to 115 cognitively normal subjects with variable AD risk factors. We hypothesized that SPM based on our database would identify more positive scans in the test cohort than the qualitatively rated [11C]-PiB PET (QR-PiB), that SPM-based interpretation would correlate better with CSF Aß42 levels than QR-PiB, and that regional z-scores of specific brain regions known to be involved early in AD would be predictive of CSF Aß42 levels. Fisher's exact test and the kappa coefficient assessed the agreement between SPM, QR-PiB PET, and CSF biomarkers. Logistic regression determined if the regional z-scores predicted CSF Aß42 levels. An optimal z-score cutoff was calculated using Youden's index. We found SPM identified more positive scans than QR-PiB PET (19.1 vs. 9.6%) and that SPM correlated more closely with CSF Aß42 levels than QR-PiB PET (kappa 0.13 vs. 0.06) indicating that SPM may have higher sensitivity than standard QR-PiB PET images. Regional analysis demonstrated the z-scores of the precuneus, anterior cingulate and posterior cingulate were predictive of CSF Aß42 levels [OR (95% CI) 2.4 (1.1, 5.1) p = 0.024; 1.8 (1.1, 2.8) p = 0.020; 1.6 (1.1, 2.5) p = 0.026]. This study demonstrates the utility of using SPM with a "true normal" database and suggests that SPM enhances diagnostic performance in AD in the clinical setting through its quantitative approach, which will be increasingly important with future disease-modifying therapies.

Molecular structure and thermodynamic predictions to create highly sensitive microRNA biosensors.

Many studies have established microRNAs (miRNAs) as post-transcriptional regulators in a variety of intracellular molecular processes. Abnormal changes in miRNA have been associated with several diseases. However, these changes are sometimes subtle and occur at nanomolar levels or lower. Several biosensing hurdles for in situ cellular/tissue analysis of miRNA limit detection of small amounts of miRNA. Of these limitations the most challenging are selectivity and sensor degradation creating high background signals and false signals. Recently we developed a reporter+probe biosensor for let-7a that showed potential to mitigate false signal from sensor degradation. Here we designed reporter+probe biosensors for miR-26a-2-3p and miR-27a-5p to better understand the effect of thermodynamics and molecular structures of the biosensor constituents on the analytical performance. Signal changes from interactions between Cy3 and Cy5 on the reporters were used to understand structural aspects of the reporter designs. Theoretical thermodynamic values, single stranded conformations, hetero- and homodimerization structures, and equilibrium concentrations of the reporters and probes were used to interpret the experimental observations. Studies of the sensitivity and selectivity revealed 5-9 nM detection limits in the presence and absence of interfering off-analyte miRNAs. These studies will aid in determining how to rationally design reporter+probe biosensors to overcome hurdles associated with highly sensitive miRNA biosensing.