Citations

A considerable amount of effort has been made to seek the acoustic correlates of reduced speech intelligibility in dysarthria, although some acoustic variables are under debate: For example, articulation rate, F2 slope, and vowel space have been frequently discussed in previous studies as acoustic predictors of speech intelligibility of dysarthria [Kim (2007)]. One variable that is not well understood, with respect to its effect on speech intelligibility in dysarthria, is level of presentation. This includes level generated by a speaker as well as level of presentation after the speaker has recorded utterances. Clearly, variations in level of presentation of recorded utterances will have some effect when an intelligibility test requires some segmental analysis (as in a minimal pairs test), but the potential effect when speech intelligibility is scaled is not so clear. This is an important question because of the frequent use of scaled intelligibility in dysarthria research. In this presentation, we will report data on how scaled speech intelligibility is affected by level of presentation of speech samples produced by speakers with various types and severity of dysarthria. [Work supported by NIH DC00319.]

The mechanical response of tissues to external forces has gained considerable interest in medical diagnosis. Typically, a force is needed to produce displacement in the tissue for estimation of the tissue’s elasticity. One approach is to apply an external force on the body’s surface. Another emerging technique is to generate a localized force inside the tissue with ultrasound. Shear waves can be used in bulky tissues for estimating the tissue’s elasticity. The bending wave can be generated and measured in vessels for noninvasive estimation of a vessel’s elasticity. We have found that the Rayleigh surface wave can be generated on the tissue’s surface, [X. Zhang et al., Proc. International Congress on Ultrasonics, Vienna, April 9–13, 2007], [X. Zhang et al., IEEE Trans. Medical Imaging, 26, 843–852 (2007)]. In our method, a localized radiation force of ultrasound is remotely and noninvasively applied inside the tissue. This force can generate the shear wave as well as compression wave inside the tissue. However, only the surface wave can exist on the body’ surface. The surface wave can be used to estimate and image the stiffness of tissue. Some results of using the surface wave are presented.

Thyroid imaging with conventional ultrasound scanners does not always lead to conclusive results. Furthermore, current ultrasound imaging technology has difficulty in detecting important microcalcifications. Ambiguities in ultrasound and other thyroid imaging methods lead to a large number of unnecessary biopsies. For these reasons, alternative imaging methods capable of detecting both microcalcifications and lesions in thyroid are of great interest. This paper describes recent results on imaging human thyroids with vibro-acoustography. Experiments were conducted on eight excised human thyroids from autopsy. The specimens were each imbedded in a block of gel to simulate the surrounding tissue and to facilitate scanning. Three types of images were acquired from each specimen: X-ray, B-mode ultrasound, and vibro-acoustography. Anatomical details seen in the images were correlated and image quality was compared. X-ray images displayed calcifications with high contrast, but did not show anatomical details of soft tissue. B-mode displayed some soft tissue structures; however, the speckle masked the details and reduced the contrast. Vibro-acoustography displayed calcifications, anatomical details, and some nodules where they existed. Furthermore, vibro-acoustography images displayed tissue structures with high contrast and free from speckle. It is concluded that vibro-acoustography may be a suitable technique for thyroid imaging.

Modulating ultrasound can create dynamic ultrasound radiation force to induce local tissue vibration. Using different types of modulating signals produces radiation force with weighted multifrequency components. Modulation signals with frequency fr produce force with components at multiples of fr. Both amplitude modulation (AM) and double sideband suppressed carrier (DSB-SC) amplitude modulation were explored. Different waveforms were investigated such as sine, square, triangle, and sawtooth for modulating continuous wave ultrasound. A 3.0 MHz transducer produced ultrasound which was measured with a needle hydrophone and used to derive and analyze the spectrum of the radiation force function. The modulated ultrasound was used to vibrate a steel sphere in a gelatin phantom, and the motion was measured using a laser vibrometer. The measured spectra were used to find the frequency response of the sphere. Different modulating signals were used to produce multifrequency radiation force. The sphere frequency response was recovered using different modulating signals. Weighted multifrequency radiation force was produced by modulating ultrasound with different signals. Application of multifrequency radiation force can be used to measure the frequency response of objects or tissue. [This work was supported in part by grants EB002167, EB002640, and CA091956 from NIH.]

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation–contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm.

Cardiac I Kr is a critical repolarizing current in the heart and a target for inherited and acquired long-QT syndrome (LQTS). Biochemical and functional studies have demonstrated that I Kr channels are heteromers composed of both hERG 1a and 1b subunits, yet our current understanding of I Kr functional properties derives primarily from studies of homooligomers of the original hERG 1a isolate. Here, we examine currents produced by hERG 1a and 1a/1b channels expressed in HEK-293 cells at near-physiological temperatures. We find that heteromeric hERG 1a/1b currents are much larger than hERG 1a currents and conduct 80% more charge during an action potential. This surprising difference corresponds to a 2-fold increase in the apparent rates of activation and recovery from inactivation, thus reducing rectification and facilitating current rebound during repolarization. Kinetic modeling shows these gating differences account quantitatively for the differences in current amplitude between the 2 channel types. Drug sensitivity was also different. Compared to homomeric 1a channels, heteromeric 1a/1b channels were inhibited by E-4031 with a slower time course and a corresponding 4-fold shift in the IC 50 . The importance of hERG 1b in vivo is supported by the identification of a 1b-specific A8V missense mutation in 1/269 unrelated genotype-negative LQTS patients that was absent in 400 control alleles. Mutant 1bA8V expressed alone or with hERG 1a in HEK-293 cells dramatically reduced 1b protein levels. Thus, mutations specifically disrupting hERG 1b function are expected to reduce cardiac I Kr and enhance drug sensitivity, and represent a potential mechanism underlying inherited or acquired LQTS.

We examined the use of telemedicine for improving access to care in a work-site clinic. A prospective study of 100 patients was conducted over a four-month period in a work site that housed 700 employees. Sinusitis (10 visits), upper respiratory tract infections (9 visits), otitis media (9 visits), hypertension (9 visits) and back pain (8 visits) were the most common reasons for the visits. In 99 visits, clinicians were of the opinion that the telemedicine visit felt similar to a face-to-face visit. For most of the visits (67), patients strongly agreed or agreed that telemedicine had a positive effect on their relationship with the health-care provider. The otoscope, microscope and stethoscope telemedicine peripherals were important in aiding diagnosis (and ruling out other causes) in about 55% of the visits (upper respiratory tract infection, sinusitis, otitis media, cough, sore throat, nevi, rhinitis and ear wax related concerns). The ability for the patient to watch their ENT examination and see any associated abnormalities was appreciated by many patients. Physicians, nurses and patients were capable of using the technology with little training.

Background and Purpose— Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The c ombined approach to l ysis utilizing e ptifibatide a nd r ecombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. Methods— The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke–funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 μg/kg bolus followed by 0.75 μg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. Results— Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 ( P =0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 ( P =0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA–only arm ( P =0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. Conclusions— The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.