Evaluating Permeability Surface-Area Product as a Measure of Blood-Brain Barrier Permeability in a Murine Model.

BACKGROUND AND PURPOSE: Permeability surface-area product has been suggested as a marker for BBB permeability with potential applications in clinical care and research. However, few studies have demonstrated its correlation with actual quantitative measurements of BBB permeability. Our aim was to demonstrate the correlation of quantitative permeability surface-area product and BBB permeability in a murine model by histologic confirmation. MATERIALS AND METHODS: Coronal MR imaging was performed on mice treated with mannitol (n = 6) for disruption of the BBB and controls treated with saline (n = 5). Permeability surface-area product was determined by ROI placement and was compared between saline- and mannitol-treated mice. Correlation was made with contrast-enhancement measurements and immunohistologic-stained sections of tripeptidyl peptidase-1 distribution in mice treated with mannitol and saline followed by injection of a viral vector containing the CLN2 gene, which directs production of tripeptidyl peptidase-1. RESULTS: Significantly increased permeability surface-area product was seen in mannitol- compared with saline-treated mice in the whole brain (P = .008), MCA territory (P = .014), and mixed vascular territories (P = .008). These findings were compared with contrast-enhancement measurements of BBB permeability and were correlated with immunohistologic-stained sections demonstrating BBB permeability to a large vector. CONCLUSIONS: Permeability surface-area product is increased in situations with known disruptions of the BBB, as evidenced by immunologic staining of large-vector passage through the BBB and concordance with contrast-enhancement measurements in a murine model. Quantitative permeability surface-area product has potential as an imaging marker of BBB permeability.

Automated calcium burden measurement in internal carotid artery plaque with CT: a hierarchical adaptive approach.

AIM: Calcium burden measurement in internal carotid artery (ICA) plaque could play an important role in assessing stroke risk and stenosis quantification in the ICA. We propose an automatic method for labelling calcified plaques in ICA in CT images. METHODS: Our approach builds upon the mean shift paradigm via an adaptive thresholding strategy. The data consists of single CT slices from 75 patients, with variety of plaque sizes and number of calcium regions. The manual measurements were carried out by a neuroradiologist for benchmarking. The calcium burden was measured as the area of the labelled plaque. Various metrics were employed to compare manual and automated measurements including correlation coefficient (CC), dice similarity (DS), Jacard Index (JI), polyline distance metric (PDM) and precision of merit (PoM). RESULTS: We found that our automated method of calcium area characterization performed accurately compared to manual measurements with CC=0.978, and PoM=0.915. The PDM, DS, and JI, also indicate a good performance with a mean DS=0.85 (SD=0.085), a mean JI=0.747 (SD=0.12), and a mean PDM=0.195 (SD=0.177). CONCLUSION: The proposed approach for calcium burden measurement, yields reasonably accurate labelling of calcified plaque when benchmarked against manual measurements. The approach is independent of the number and size of calcium regions, and the prototype design shows encouraging results to be adaptable to clinical practice.