ABSTRACT
Multiple sclerosis (MS) is a chronic disease with a progressing and evolving course. Serial imaging with MRI is the mainstay in monitoring and managing MS patients. In this work we demonstrate the performance of a locally developed computer-assisted detection (CAD) software used to track temporal changes in brain MS lesions. CAD tracks changes in T2-bright MS lesions between two time points on a 3D high-resolution isotropic FLAIR MR sequence of the brain acquired at 3 Tesla. The program consists of an image-processing pipeline, and displays scrollable difference maps used as an aid to the neuroradiologist for assessing lesional change. To assess the value of the software we have compared diagnostic accuracy and duration of interpretation of the CAD-assisted and routine clinical interpretations in 98 randomly chosen, paired MR examinations from 88 patients (68 women, 20 men, mean age 43.5, age range 21-75) with a diagnosis of definite MS. The ground truth was determined by a three-expert panel. In case-wise analysis, CAD interpretation showed higher sensitivity than a clinical report (87% vs 77%, respectively). Lesion-wise analysis demonstrated improved sensitivity of CAD over a routine clinical interpretation of 40%-48%. Mean software-assisted interpretation time was 2.7 min. Our study demonstrates the potential of including CAD software in the workflow of neuroradiology practice for the detection of MS lesional change. Automated quantification of temporal change in MS lesion load may also be used in clinical research, e.g., in drug trials.
Subject(s)
Brain/pathology , Magnetic Resonance Imaging , Multiple Sclerosis/pathology , Software , Adult , Aged , Area Under Curve , Brain/physiopathology , Brain Mapping , Disease Progression , Female , Follow-Up Studies , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Sensitivity and Specificity , Young AdultABSTRACT
We report two cases in which MR imaging was used to diagnose multiple cerebral aneurysms caused by cardiac myxoma. In one case, the diagnosis was confirmed with cerebral angiography. Myxomatous aneurysms characteristically appeared on T1-weighted images as contrast-enhancing focal fusiform dilatations of distal segments of the cerebral arteries. On T2-weighted images, these myxomatous aneurysms appeared as low signal intensity flow voids, sometimes associated with cerebral infarctions.
Subject(s)
Brain Neoplasms/secondary , Cerebral Arterial Diseases/diagnosis , Heart Neoplasms/diagnosis , Intracranial Aneurysm/diagnosis , Magnetic Resonance Imaging , Myxoma/diagnosis , Neoplastic Cells, Circulating , Vascular Neoplasms/secondary , Aged , Brain Neoplasms/diagnosis , Brain Neoplasms/etiology , Cerebral Angiography , Cerebral Arterial Diseases/etiology , Cerebral Arteries/pathology , Diagnosis, Differential , Female , Humans , Imaging, Three-Dimensional , Intracranial Aneurysm/etiology , Magnetic Resonance Angiography , Neoplastic Cells, Circulating/pathology , Vascular Neoplasms/diagnosis , Vascular Neoplasms/etiologyABSTRACT
Secretion of neurotransmitter at the synapse and in secretory cells depends on the availability of vesicles for exocytosis. Rapid endocytosis is responsible for initiating local vesicle recycling and is essential during sustained neurotransmission. Although exocytosis is triggered by Ca(2+) influx and modulated by serine/threonine kinases, relatively little is known about the regulation of rapid endocytosis. Our data suggest that rapid endocytosis is controlled by tyrosine phosphorylation. Treatment of bovine adrenal chromaffin cells with tyrphostin 23, a protein tyrosine kinase inhibitor, dramatically slowed the time course of rapid endocytosis. In contrast, there was no effect on either the amount or rate of exocytosis. Application of orthovanadate, Zn(2+), or poly(Glu, Tyr) (4:1), each of which is a tyrosine phosphatase inhibitor, reversed the effect of tyrphostin 23 on rapid endocytosis. Thus rapid endocytosis, like exocytosis, is subject to regulation by intracellular signaling pathways.
Subject(s)
Adrenal Medulla/physiology , Calcium/metabolism , Chromaffin Cells/physiology , Endocytosis , Enzyme Inhibitors/pharmacology , Tyrphostins/pharmacology , Adrenal Medulla/cytology , Animals , Cattle , Cells, Cultured , Chromaffin Cells/cytology , Chromaffin Cells/drug effects , Endocytosis/drug effects , Exocytosis/drug effects , Exocytosis/physiology , Intercellular Signaling Peptides and Proteins , Kinetics , Peptides/pharmacology , Phosphorylation , Phosphotyrosine/metabolism , Protein Tyrosine Phosphatases/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Vanadates/pharmacology , Zinc/pharmacologyABSTRACT
The pleiotropic weaver disease is caused by the mutation of a single amino acid in the G-protein-linked inwardly rectifying K+ channel, GIRK2. In homozygous (wv/wv) animals, the disease is characterized by loss of cerebellar and dopaminergic mesencephalic neurons as well as testicular cells, which produce ataxia, fine tremors, and sterility, respectively. Heterozygous (wv/+) animals show no obvious motor impairments, although some loss of both cerebellar and dopaminergic neurons is observed and wv/+ males become sterile at 3.5 months of age. Abnormal influxes of Na+ and Ca2+ have been linked to cerebellar cell death in wv/wv animals, but it's not clear whether similar changes are observed in wv/+ animals. To discover whether changes in K+-channel function or intracellular Ca2+ concentrations ([Ca2+]i) play a role in the augmented cell loss observed in wv/+ animals when compared with +/+ animals, we studied cultured cerebellar granule cells prepared from either wv/+ or +/+ animals. Resting [Ca2+]i was elevated in wv/+ relative to +/+ animals. Further, depolarizations of cells with elevated K+ solutions elicited much smaller changes in [Ca2+]i in wv/+ animals than in +/+ animals, presumably due to altered GIRK2 channel function. Both wv/+ and +/+ cells showed similar changes in [Ca2+]i when cells were depolarized by glutamate (1 mM), suggesting that both glutamate receptors and Ca2+ channels were unchanged in wv/ + animals. In summary, our results suggest that wv/+ cerebellar granule cells exhibit elevated resting [Ca2+]i levels and altered K+-channel function, which may contribute to the developmental abnormalities and increased cell death observed.
Subject(s)
Cerebellum/drug effects , Heterozygote , Neurons/drug effects , Potassium Channels, Inwardly Rectifying , Potassium Channels/drug effects , Potassium/pharmacology , Animals , Calcium/metabolism , Cerebellum/cytology , Cerebellum/metabolism , Female , G Protein-Coupled Inwardly-Rectifying Potassium Channels , Glutamic Acid/pharmacology , Mice , Mice, Neurologic Mutants , Neurons/metabolismABSTRACT
1. Changes in cell capacitance were monitored in whole-cell patch-clamp recordings from calf adrenal chromaffin cells using a software-based phase-tracking technique. Rapid endocytosis and exocytosis were observed in extracellular solutions containing either Ca2+ or Ba2+. 2. There was no significant difference in the magnitude or the time course of rapid endocytosis of cells stimulated in Ca2+ as compared to Ba2+. When cells were pretreated with caffeine and thapsigargin in order to deplete intracellular Ca2+ stores, rapid endocytosis in Ba2+ was not affected. This indicates that Ba2+ itself is capable of supporting rapid endocytosis. 3. The application of the calmodulin inhibitor calmidazolium via the intracellular pipette solution did not inhibit rapid endocytosis. Although our findings are inconsistent with an immediate requirement for calmodulin in rapid endocytosis, they do not rule out an involvement on a longer time scale. 4. While rapid endocytosis was not affected by the substitution of Ca2+ with Ba2+, the maximum rate of exocytosis was higher in cells stimulated in Ca2+ than in Ba2+. Since Ba2+ currents were much larger than Ca2+ currents during depolarizations to +10 mV (the test potential used in these experiments), Ba2+ appears to be less efficient at promoting exocytosis than Ca2+.
