Fully automated preoperative segmentation of temporal bone structures from clinical CT scans.

Middle- and inner-ear surgery is a vital treatment option in hearing loss, infections, and tumors of the lateral skull base. Segmentation of otologic structures from computed tomography (CT) has many potential applications for improving surgical planning but can be an arduous and time-consuming task. We propose an end-to-end solution for the automated segmentation of temporal bone CT using convolutional neural networks (CNN). Using 150 manually segmented CT scans, a comparison of 3 CNN models (AH-Net, U-Net, ResNet) was conducted to compare Dice coefficient, Hausdorff distance, and speed of segmentation of the inner ear, ossicles, facial nerve and sigmoid sinus. Using AH-Net, the Dice coefficient was 0.91 for the inner ear; 0.85 for the ossicles; 0.75 for the facial nerve; and 0.86 for the sigmoid sinus. The average Hausdorff distance was 0.25, 0.21, 0.24 and 0.45 mm, respectively. Blinded experts assessed the accuracy of both techniques, and there was no statistical difference between the ratings for the two methods (p = 0.93). Objective and subjective assessment confirm good correlation between automated segmentation of otologic structures and manual segmentation performed by a specialist. This end-to-end automated segmentation pipeline can help to advance the systematic application of augmented reality, simulation, and automation in otologic procedures.

THE AUTODIGESTION HYPOTHESIS AND RECEPTOR CLEAVAGE IN DIABETES AND HYPERTENSION.

One of the key features of cardiovascular complications, such as hypertension or diabetes, is that they often appear at the same time in the same individual together with other forms of co-morbidities. While clinically a recognized phenomenon, no molecular mechanism for such co-morbidities has received universal acceptance. We propose a new hypothesis that provides a molecular basis for co-morbidities in hypertension due to unchecked proteolytic activity and receptor destruction. Testing of the hypothesis in the spontaneously hypertensive rat reveals an unchecked matrix metalloproteinase and serine protease activity in plasma and on several cardiovascular and parenchymal cells. The elevated proteolytic activity causes extracellular cleavage of multiple receptor types, such that cleavage of one receptor type leads to loss of the function carried out by this receptor. Proteolytic cleavage of the extracellular domain of the ß(2) adrenergic receptor in arteries and arterioles causes vasoconstriction and elevation of the central blood pressure while cleavage of the extracellular domain of the insulin receptor leads to insulin resistance and lack of transmembrane glucose transport. A diverse set of cell dysfunctions in the spontaneously hypertensive rat are accompanied by cleavage of the membrane receptors that are involved in these functions. Chronic inhibition of the unchecked protease activity in the spontaneously hypertensive rat serves to restore the extracellular receptor density and alleviates the corresponding cell dysfunctions. The mild unchecked proteolytic activity in the spontaneously hypertensive rat points towards a chronic autodigestion process as a contributor to the end organ injury encountered in this rat strain. The presence of various soluble receptors, which consist of extracellular fragments of membrane receptors, in the plasma of hypertensive and diabetic patients suggest that the autodigestion process may also be present in man.