History of the Tinnitus Research Consortium.

This article describes the creation and accomplishments of the Tinnitus Research Consortium (TRC), founded and supported through philanthropy and intended to enrich the field of tinnitus research. Bringing together a group of distinguished auditory researchers, most of whom were not involved in tinnitus research, over the fifteen years of its life it developed novel research approaches and recruited a number of new investigators into the field. The purpose of this special issue is to highlight some of the significant accomplishments of the investigators supported by the TRC. This article is part of a Special Issue entitled "Tinnitus".

3D and 4D sonography and magnetic resonance in the assessment of normal and abnormal CNS development: alternative or complementary.

Advanced transvaginal neurosonography has revealed normal and abnormal intracranial morphology. Transvaginal three-dimensional (3D) sonography demonstrates bony structure, multiplanar analysis of inside detailed morphology, tomographic ultrasound imaging in any cutting sections, 3D sonoangiography and volume calculation of ventricles and/or intracranial lesions. Longitudinal assessment of normal and abnormal central nervous system (CNS) development is done by serial scanning. However, the transvaginal high-frequency approach has several limitations due to lack of penetration and cranial bone ossification with advanced gestational age. Magnetic resonance neuroimaging enabled observation of the whole intracranial cavity, brainstem and cortical gyral/sulcal development. On the other hand, neuro-sonography has advantages in detecting intracranial calcification, vascular abnormalities, intratumoral vascularity and bone dysplasia. Moreover, 3D ultrasound demonstrates extra CNS abnormalities, strongly associated with CNS abnormalities. Any less-invasive modalities can be used for a CNS anomaly screening scan and ultrasound is no doubt the first choice. Once CNS abnormality is suspected, it is suggested to use the different technologies according to what is looked for in each abnormal CNS case. Of course, MR and 3D ultrasound imaging should be complementary as well as alternative.

In vivo assessment of macrophage CNS infiltration during disruption of the blood-brain barrier with focused ultrasound: a magnetic resonance imaging study.

Focused ultrasound has been discovered to locally and reversibly increase permeability of the blood-brain barrier (BBB). However, inappropriate sonication of the BBB may cause complications, such as hemorrhage and brain tissue damage. Tissue damage may be controlled by selecting optimal sonication parameters. In this study, we sought to investigate the feasibility of labeling cells with superparamagnetic iron oxide particles to assess the inflammatory response during focused-ultrasound-induced BBB opening. We show that infiltration of phagocytes does not occur using optimal parameters of sonication. Taken together, the results of our study support the usefulness and safety of focused-ultrasound-induced BBB opening for enhancing drug delivery to the brain. These findings may have implications for the optimization of sonication parameters.

A biomathematical modeling approach to central nervous system radioligand discovery and development.

UNLABELLED: The development of a successful PET or SPECT molecular imaging probe is a complex, time-consuming, and expensive process that suffers from high attrition. To address this problem, we have developed a biomathematical modeling approach that aims to predict the in vivo performance of radioligands directly from in silico/in vitro data. METHODS: The method estimates the in vivo nondisplaceable and total uptake of a ligand in a target tissue using a standard input function and a 1-tissue-compartment model with a parsimonious parameter set (influx rate constant K(1), efflux rate constant k(2), and binding potential BP(ND)) whose values are predicted from in silico/in vitro data including lipophilicity, molecular volume, free fraction in plasma and tissue, target density, affinity, perfusion, capillary surface area, and apparent aqueous volume in plasma and tissue. The coefficient of variation of the BP(ND) (%COV[BP(ND)]) metric, derived from Monte Carlo simulations, is used to estimate the in vivo performance of candidate compounds. A total of 28 compounds for 10 targets was evaluated using our method to predict their in vivo performance and validated against measured in vivo PET data in the Yorkshire/Danish Landrace pig. RESULTS: The predicted K(1), k(2), and BP(ND) values were generally consistent with the values estimated from in vivo PET data. The model resulted in small %COV[BP(ND)] values for widely accepted good ligands such as (11)C-flumazenil (2.02%) and (11)C-raclopride (2.55%), whereas higher values resulted from poor ligands such as (11)C-(R)-PK11195 (13.34%). Of 4 candidates for the GlyT1 transporter, the model selected (11)C-GSK931145 (2.11%) as the most promising ligand, which was consistent with historical decisions made on the in vivo PET data. CONCLUSION: A biomathematical modeling approach has the potential to predict the in vivo performance of ligands from in silico/in vitro data and aid in the development of molecular imaging probes.

Central nervous system imaging. When is CT more appropriate than MRI?

Over the past 25 years, the development of noninvasive imaging techniques has allowed exquisite display of the anatomic structures of the brain and spinal cord in normal and disease states. CT remains useful because of short imaging times, widespread availability, ease of access, sensitive detection of calcification and hemorrhage, and resolution of bony detail. MRI offers superior soft-tissue contrast, excellent visualization of vascular structures, fewer artifacts, and imaging in any plane. Cost and use of ionizing radiation are considerations in choosing the most appropriate procedure. In the future, CT and MRI applications that concentrate on functional and physiologic display of the CNS will add greatly to the clinical utility of these imaging tools.

Health policy analysis and magnetic resonance imaging. The case of the New York State Demonstration Project.

In the absence of controlled clinical trials, the diffusion of magnetic resonance imaging (MRI) has been driven by market forces and the perceived benefits of this technology. To date, all projective needs for MRI use are based on a consensus impression of a medical panel on the role of MRI for DRG or International Classification of Diseases, Ninth Revision, codes. Since an impression of future utilization is not particularly precise, the focus of The New York State MRI Demonstration Project, which approved the acquisition of MRIs at 14 medical centers in 1983, was to determine the actual use of MRI in a medical setting. In a 3-year period, all sites performed 16,095 MRI examinations with 6647 subjects also receiving computed tomography (CT). The results of this study were as follows: (1) 88% of MRIs performed were of the central nervous system (CNS), (2) low level of utilization in the chest and abdomen reflects both a problem with MRI motion artifacts and the failure of MRI to compete with established diagnostic modalities such as mammography, CT scanning, and ultrasonography, (3) for the CNS 18% (1037/5876) studies were positive on MRI but negative by CT, (4) only 1.4% (n = 85) of cases were lesions detected by CT and missed by MRI, and (5) for 81% of the 4754 examinations, MRI and CT were in agreement. Based on the number of lesions observed, the image contrast, and the overall radiologist's impression, MRI was rated superior to CT in 50-60% of the CNS cases. The projected need, based on this study, is for one MRI per 430,000 population in New York State. Also as newer MR imaging protocols evolve, patient use should increase, with the technical cost per study becoming approximately +250 for a scanner performing 3900 studies per year with a +1 million operating expense. At the present time, the best predictive index of MRI utilization is the need for CNS examinations.