Low-intensity ultrasound activates vestibular otolith organs through acoustic radiation force.

The present study examined the efficacy of 5 MHz low-intensity focused ultrasound (LiFU) as a stimulus to remotely activate inner ear vestibular otolith organs. The otolith organs are the primary sensory apparati responsible for detecting orientation of the head relative to gravity and linear acceleration in three-dimensional space. These organs also respond to loud sounds and vibration of the temporal bone. The oyster toadfish, Opsanus tau, was used to facilitate unobstructed acoustic access to the otolith organs in vivo. Single-unit responses to amplitude-modulated LiFU were recorded in afferent neurons identified as innervating the utricle or the saccule. Neural responses were equivalent to direct mechanical stimulation, and arose from the nonlinear acoustic radiation force acting on the otolithic mass. The magnitude of the acoustic radiation force acting on the otolith was measured ex vivo. Results demonstrate that LiFU stimuli can be tuned to mimic directional forces occurring naturally during physiological movements of the head, loud air conducted sound, or bone conducted vibration.

Prediction of Carotid Intraplaque Hemorrhage Using Adventitial Calcification and Plaque Thickness on CTA.

BACKGROUND AND PURPOSE: Carotid intraplaque hemorrhage is associated with stroke, plaque thickness, stenosis, ulceration, and adventitial inflammation. Conflicting data exist on whether calcification is a marker of plaque instability, and no data exist on adventitial calcification. Our goal was to determine whether adventitial calcification and soft plaque (a rim sign) help predict carotid intraplaque hemorrhage. MATERIALS AND METHODS: This was a retrospective cohort study of 96 patients who underwent carotid MRA and CTA within 1 month, from 2009 to 2016. We excluded occlusions (n = 4) and near occlusions (n = 0), leaving 188 carotid arteries. Intraplaque hemorrhage was detected by using MPRAGE. Calcification, adventitial pattern, stenosis, maximum plaque thickness (total, soft, and hard), ulceration, and intraluminal thrombus on CTA were recorded. Atherosclerosis risk factors and medications were recorded. We used mixed-effects multivariable Poisson regression, accounting for 2 vessels per patient. For the final model, backward elimination was used with a threshold of P < .10. Receiver operating characteristic analysis determined intraplaque hemorrhage by using the area under the curve. RESULTS: Our final model included the rim sign (prevalence ratio = 11.9, P < .001) and maximum soft-plaque thickness (prevalence ratio = 1.2, P = .06). This model had excellent intraplaque hemorrhage prediction (area under the curve = 0.94), outperforming the rim sign, maximum soft-plaque thickness, NASCET stenosis, and ulceration (area under the curve = 0.88, 0.86, 0.77, and 0.63, respectively; P < .001). Addition of the rim sign performed better than each marker alone, including maximum soft-plaque thickness (area under the curve = 0.94 versus 0.86, P < .001), NASCET stenosis (area under the curve = 0.90 versus 0.77, P < .001), and ulceration (area under the curve = 0.90 versus 0.63, P < .001). CONCLUSIONS: The CTA rim sign of adventitial calcification with internal soft plaque is highly predictive of carotid intraplaque hemorrhage.

In vivo evaluation of a breast-specific magnetic resonance guided focused ultrasound system in a goat udder model.

PURPOSE: This work further evaluates the functionality, efficacy, and safety of a new breast-specific magnetic resonance guided high intensity focused ultrasound (MRgFUS) system in an in vivo goat udder model. METHODS: Eight female goats underwent an MRgFUS ablation procedure using the breast-specific MRgFUS system. Tissue classification was achieved through the 3D magnetic resonance imaging (MRI) acquisition of several contrasts (T1w, T2w, PDw, 3-point Dixon). The MRgFUS treatment was performed with a grid trajectory executed in one or two planes within the glandular tissue of the goat udder. Temperature was monitored using a 3D proton resonance frequency (PRF) MRI technique. Delayed contrast enhanced-MR images were acquired immediately and 14 days post MRgFUS treatment. A localized tissue excision was performed in one animal and histological analysis was performed. Animals were available for adoption at the conclusion of the study. RESULTS: The breast-specific MRgFUS system was able to ablate regions ranging in size from 0.4 to 3.6 cm(3) in the goat udder model. Tissue damage was confirmed through the correlation of thermal dose measurements obtained with realtime 3D MR thermometry to delayed contrast enhanced-MR images immediately after the treatment and 14 days postablation. In general, lesions were longer in the ultrasound propagation direction, which is consistent with the dimensions of the ultrasound focal spot. Thermal dose volumes had better agreement with nonenhancing areas of the DCE-MRI images obtained 14 days after the MRgFUS treatment. CONCLUSIONS: The system was able to successfully ablate lesions up to 3.6 cm(3). The thermal dose volume was found to correlate better with the 14-day postablation nonenhancing delayed contrast enhanced-MR image volumes. While the goat udder is not an ideal model for the human breast, this study has proven the feasibility of using this system on a wide variety of udder shapes and sizes, demonstrating the flexibility that would be required in order to treat human subjects.

An 11-channel radio frequency phased array coil for magnetic resonance guided high-intensity focused ultrasound of the breast.

In this study, a radio frequency phased array coil was built to image the breast in conjunction with a magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) device designed specifically to treat the breast in a treatment cylinder with reduced water volume. The MRgHIFU breast coil was comprised of a 10-channel phased array coil placed around an MRgHIFU treatment cylinder where nearest-neighbor decoupling was achieved with capacitive decoupling in a shared leg. In addition a single loop coil was placed at the chest wall making a total of 11 channels. The radio frequency coil array design presented in this work was chosen based on ease of implementation, increased visualization into the treatment cylinder, image reconstruction speed, temporal resolution, and resulting signal-to-noise ratio profiles. This work presents a dedicated 11-channel coil for imaging of the breast tissue in the MRgHIFU setup without obstruction of the ultrasound beam and, specifically, compares its performance in signal-to-noise, overall imaging time, and temperature measurement accuracy to that of the standard single chest-loop coil typically used in breast MRgHIFU.

Diagnosis and management of asbestosis.

Asbestos-related illness usually arises at least 10 to 20 years after initial exposure. In many instances, patients may be unaware of the source of exposure. Although community-based exposures are unusual, recent events indicate that both communities and workers may have had significant exposure to asbestos contained within vermiculite. Physicians should obtain a medical history as outlined above when examining workers or community members who believe they have been significantly exposed to vermiculite. In addition, pulmonary function testing and chest radiographs should be obtained. If these are normal and there is no ongoing exposure, it is likely that no further evaluation is required. Physicians should have a radiologist familiar with occupational lung diseases read films. Patients may ask that a "B" reader, a physician who is certified by the National Institute for Occupational Safety and Health to read x-rays for changes related to the pneumoconioses, review their films. Facilitating smoking cessation and providing routine immunizations are important secondary preventive measures. Workers exposed to asbestos should receive ongoing screening as specified by the Occupational Safety and Health Administration. Over the last several decades, numerous epidemiologic studies have evaluated the efficacy of lung cancer screening. Period chest radiographs and sputum cytology have not been shown to increase lung cancer survival rates. Recent studies have demonstrated the potential benefit of scanning in the early detection of lung cancer. Although encouraging, these studies do not yet support the use of imaging for the routine screening of high-risk populations as required by the Occupational Safety and Health Administration.

A multiple wavelength algorithm in color image analysis and its applications in stain decomposition in microscopy images.

Stains have been used in optical microscopy to visualize the distribution and intensity of substances to which they are attached. Quantitative measures of optical density in the microscopic images can in principle be used to determine the amount of the stain. When multiple dyes are used to simultaneously visualize several substances to which they are specifically attached, quantification of each stain cannot be made using any single wavelength because attenuation from the several stain components contributes to the total optical density. Although various dyes used as optical stains are perceived as specific colors, they, in fact, have complex attenuation spectra. In this paper, we present a technique for multiple wavelength image acquisition and spectral decomposition based upon the Lambert-Beer absorption law. This algorithm is implemented based on the different spectral properties of the various stain components. By using images captured at N wavelengths, N components with different colors can be separated. This algorithm is applied to microscopy images of doubly and triply labeled prostate tissue sections. Possible applications are discussed.

A quantitative study of ramped radio frequency, magnetization transfer, and slab thickness in three-dimensional time-of-flight magnetic resonance angiography in a patient population.

RATIONALE AND OBJECTIVES: The authors compare the effectiveness of various magnetic resonance (MR) angiography acquisition strategies in enhancing the visibility of small intracranial vessels. METHODS: Blood vessel contrast-to-noise ratio (CNR) in time-of-flight MR angiography was studied as a function of vessel size and several selectable imaging parameters. Contrast-to-noise measurements were made on 257 vessel segments ranging in size from 0.3 mm to 4.2 mm in patients who recently had undergone intraarterial cerebral angiography. Imaging parameters studied included magnetization transfer, spatially variable radio frequency (RF) pulse profile (ramped RF), and imaging slab thickness. RESULTS: The combination of thin slabs (16 slices/slab), ramped RF, and magnetization transfer resulted in the highest CNR for all but the smallest vessel sizes. The smallest vessels (< 0.5 mm) had the highest CNR, using the thick slab (64 slices/slab) with ramped RF and magnetization transfer. Magnetization transfer always improved vessel CNR, but the improvement diminished as the slab thickness was reduced. The CNR increased with a decrease in slab thickness for all but the smallest vessel sizes. CONCLUSIONS: Overall, the results provide a quantitative demonstration that inflow enhancement of blood is reduced for small vessels. Thus, whereas magnetization transfer is important at all vessel sizes, it becomes the primary factor in improving the visibility of the smallest vessels.

High resolution 3D imaging of the inner ear with a modified fast spin-echo pulse sequence.

A fast spin-echo pulse sequence is described that produces high resolution images of the inner ear without susceptibility artifacts. It uses thin overlapping slices that can be reformatted in multiple projections to provide a view of the 3D geometry of inner ear structures, such as the cochlea, vestibule, semicircular canals, and internal auditory canal. It has proven useful in screening adults for the presence of acoustic schwannoma and in identifying structural congenital lesions in children with sensorineural hearing loss.

Correlation of survival with quantitative tissue staining of prostate specific acid phosphatase in patients with prostate carcinoma by using microscopic image analysis: a preliminary report of correlative studies on RTOG protocols 75-06, 77-06, and 83-07.

PURPOSE: We have previously shown that the intensity (graded semiquantitatively as 1-4+) of tissue prostate-specific acid phosphatase (PSAP) staining determined immunocytochemically in a cohort of prostate carcinoma patients from Radiation Therapy Oncology Group Protocols (RTOG) protocols 75-06 and 77-06 correlated with survival. The extent of this staining was heterogeneous and was estimated. The extent of staining was not found to be significantly associated with survival. We undertook the present quantitative study to see if the improved precision and reliability of measurement of the intensity and extent of prostate specific acid phosphatase staining would confirm and extend our previous observations. METHODS AND MATERIALS: Patient cohorts representative of the entire group were obtained from RTOG 75-06 plus 77-06 and 83-07. The RTOG 77-06 plus 75-06 patients (No-Hormone population) did not receive preradiation hormonal therapy. RTOG 83-07 patients (Prehormone population) received one of two types of preradiation chemical androgen ablation. In this study, histologic slides of tumors were immunocytochemically stained for PSAP by the peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as a substrate and hematoxylin as a nuclear counterstain. The intensity and extent of immunocytochemical PSAP staining (IPSAP stain) was quantified using our dual wavelength and batch mode image process technique. RESULTS: Our study of 151 cases confirmed that overall survival of patients in both populations was positively correlated with the intensity and extent of IPSAP stain. Results of the two studies were similar. The statistical significance of the relationship of both extent and intensity was greater in the cohort from protocol 83-07, which was the patient group receiving pretreatment with hormones. In a Cox multiple regression analysis including clinical stage, Gleason and M. D. Anderson grades, and the cohort of patients (Prehormone or No-Hormone group) as covariables, both the intensity and extent of the IPSAP stain significantly correlated with survival along with M. D. Anderson grade of the tumor. CONCLUSION: Quantitative image analysis of the IPSAP stain predicts survival in patients treated with external beam radiotherapy with and without prior hormonal therapy.

Quantitation of prostate-specific acid phosphatase in prostate cancer: reproducibility and correlation with subjective grade.

In this study, we quantitatively evaluated the intensity and extent of prostate-specific acid phosphatase in immunocytochemically stained prostate carcinoma tissue sections by using a dual-wave-length-based image processing technique. Tissue sections were doubly stained in a standard way, i.e., prostate-specific acid phosphatase was immunocytochemically labeled by peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as the substrate and hematoxylin as a nuclear counterstain. Statistical analysis in this study indicated that the quantitative measures of the prostate-specific acid phosphatase staining (PAP-DAB) are reproducible. We found that the quantitative intensity was generally proportional to the subjective intensity (graded as 1 to 4+) of PAP-DAB. Although the quantitative extent measurements compared with the subjective estimates of the percentage of tumor showing staining with PAP-DAB had a similar tendency, there were significant overlaps between extent of tumor staining falling in the mid-ranges. Because subjective grading of immunocytochemical prostate-specific acid phosphatase has been thought to be a useful marker of tumor differentiation in patients with prostate carcinoma, we also evaluated the relationship of the quantitative measures of PAP-DAB staining to other predictors of patient outcome, including histologic grades (Gleason score and MD Anderson grading scheme) and clinical stage. We confirmed that quantitative intensity and extent of PAP-DAB staining were independent of histologic grades and stage, just as the subjective measures of intensity and extent were found to be. Possible explanations of this lack of correlation are discussed.

Experiences of a state-sponsored notification and screening program for asbestos workers.

Worker notification can involve a broad range of activities including medical screening, personal and mass communications, cohort identification and tracing, and even litigation. The inclusion or exclusion of various supporting activities in a worker notification program may pose significant medical, public health, financial, logistical, and even legal implications for targeted individuals as well as for the agencies involved. This report describes some experiences in a state-sponsored notification and screening program of approximately 4,500 asbestos workers in Minnesota. In this program, a variety of factors led to the decision to provide medical screening to 1,101 workers and 451 spouses. It is anticipated that another 3,400 workers will be notified but not screened. A follow-up survey of notified workers showed overwhelming support for this program. It is estimated that this program will cost more than $650,000 by its completion. The decision to institute medical screening and other support activities should be made with careful consideration of the diverse implications of these activities to the individuals, communities, and agencies involved.

Cerebral MR angiography with multiple overlapping thin slab acquisition. Part II. Early clinical experience.

In a prospective, multicenter study of 164 patients, cerebral magnetic resonance (MR) angiography with multiple overlapping thin slab acquisition was evaluated for image quality and diagnostic accuracy. Of the 164 patients, 87 (53%) underwent either correlative cut-film angiography or surgery. The overall image quality was excellent in 90% of patient studies. Eighteen of 19 aneurysms were detected with MR angiography. The parent artery, the anatomy of the neck and dome, and the size were correctly shown in 17 of the 19 aneurysms. All 19 vascular malformations were seen with MR angiography. Venous malformations and single pedicle arteriovenous malformations were completely defined with MR angiography, while complete definition of complex arteriovenous malformations was frequently difficult. In cerebral tumors, the arteries and veins important in surgical planning were accurately shown in all cases. In ischemic cerebrovascular disease, MR angiography depicted all stenoses and occlusions of first- and second-order cerebral arteries. The inability to depict intraluminal filling defects in any but the large central arteries limited the ability of MR angiography to enable the specific diagnosis of embolic stroke.

Quantitative peroxidase-antiperoxidase complex-substrate mass determination in tissue sections by a dual wavelength method.

The aim of this study was to develop a method of quantitating prostate-specific acid phosphatase (PSAP) in histologic sections of prostate tumor tissue labeled with the peroxidase-antiperoxidase (PAP) complex technique using diaminobenzidine (DAB) as a substrate. Studies of PAP-DAB- and hematoxylin-stained prostate tissue sections were performed with a black-and-white, computerized microscope image system. The mass of brown reaction product generated in PAP-DAB staining was the indicator of PSAP intensity. The mass of brown reaction product was determined by using a dual wavelength method in which two 10-nm bandpass filters, peaked at 450 and 510 nm in wavelength, were used. The wavelength-dependent ratio of mass absorptivity of PAP-DAB stain (brown product) and that of hematoxylin (blue product) were estimated at wavelengths of 450 and 510 nm by using slides stained with only PAP-DAB or hematoxylin. The accuracy of the mass measurements, investigated by relating the measurement to the true mass of the brown PAP-DAB product, is reported. There was no significant difference between the measurements at magnifications of 10x, 20x, 40x or 60x in the reproducibility investigation. The PSAP stain intensity was quantitatively determined by the difference of the PAP-DAB stain mass per pixel between the tumor and normal cell region. The relationship between the objective measurement and the conventional subjective grades is presented.

A cross-sectional study of pulmonary function in autobody repair workers.

This study evaluated pulmonary function in workers from 39 autobody repair shops. Based on 152 White male workers with known smoking status, the mean percent predicted FEV1, FVC, and FEV1/FVC were 93.6, 96.8, and 96.6, respectively. Twenty-three percent of workers had a FEV1/FVC ratio less than the fifth percentile. Isocyanate levels ranged from nondetectable to 0.06 parts per million (STEL = 0.02 ppm). No shop had an adequate respiratory protection program. We concluded that there was an increase in abnormal pulmonary function in autobody workers. Three recommendations were made to shop owners: functional paint booths should be maintained, respiratory protection programs should be developed, and isocyanate-free paints should be used.

Effects of asbestos-related pleural disease on pulmonary function.

The relationship between loss of pulmonary function and the presence of asbestos-related pleural disease was evaluated for 913 Minnesota asbestos workers. Asbestos-related pleural disease was categorized as circumscribed plaques or diffuse thickening. Compared with workers with normal pleura, workers with plaques had a decreased mean percentage for predicted forced vital capacity (FVC) and predicted forced expiratory volume in 1 s (FEV1.0). Diffuse thickening was associated with more profound decreases in FVC and FEV1.0. No relationship was seen between FEV % [(100 x FEV1.0)/FVC)] and either type of pleural disease. Dyspnea was associated with diffuse thickening more so than plaques. These results remained after control for pack-years of smoking, extent of parenchymal disease, and the presence of pulmonary disease history. Pleural plaques and diffuse pleural thickening were considered independent risk factors for the loss of lung function.

Minnesota highway maintenance worker cohort mortality study: methods and noncancer mortality.

In 1984, the Minnesota Department of Health (MDH) began a cohort mortality study of 4,849 workers to follow up concerns with the health and safety of highway maintenance workers (HMWs). A total of 1,530 deaths had occurred, resulting in a standardized mortality ratio (SMR) of 91 (p less than .01) and an all cancer SMR of 84 (p less than .01). There was a significant elevation in the SMR for chronic renal failure among long-term rural workers (SMR = 676, p less than .05). The SMR was also elevated for transportation injuries. The latter SMR was highest among short-term urban workers (SMR = 280, p less than .01). In addition, the SMR for transportation-related injury deaths tended to increase the later the decade of starting work. The SMRs were 137, 259, 502, and 2,145 for urban workers starting work in the decades 1945-1954, 1955-1964, 1965-1974, and 1975-1984, respectively. This study demonstrates the possible adverse health effects of highway maintenance work and the need to comprehensively evaluate injury mortality among selected occupational cohorts.

Minnesota Highway Maintenance Worker Study: cancer mortality.

Highway maintenance workers (HMWs) have been exposed to a broad range of potentially toxic substances, including diesel fuels and exhaust, asphalts and tars, herbicides, gasoline, polynuclear aromatic hydrocarbons, benzene, and lead. The number of current and former state, county, and municipal HMWs in the United States exceeds 500,000, yet the health risks of this occupation had never been studied. To fill this void and to respond to the public perception that Minnesota HMWs were at high risk of developing leukemia, an occupational cohort mortality study was conducted of Minnesota HMWs employed between 1945 and 1984. Leukemia mortality in HMWs with 30-39 years of work (standardized mortality ratio [SMR] = 425; 95% confidence interval [CI] = 171-876) and urologic cancer mortality in HMWs with 40-49 year latency (SMR = 292; CI = 117-602) were significantly elevated. The extent to which these and other findings were directly related to work exposures is unknown. Further investigations to resolve the significance of the risks associated with the HMW occupation are currently underway.

Amplified DNA of the Novikoff hepatoma nucleolus is arranged in a 7.3-kilobase tandem repeat.

We have reported previously the cloning and characterization of a nucleolar-localized 5.8-kilobase (kb) EcoRI fragment that is approximately 50-fold more highly reiterated in Novikoff hepatoma tumor cells than in normal rat liver [Parker, D. L., Busch, H., & Rothblum, L. I. (1981) Biochemistry 20, 762]. In the present study, the arrangement of these 5.8-kb EcoRI segments within the Novikoff hepatoma genome was investigated. Through the use of "indirect" restriction site mapping, partial restriction enzyme digestions, and molecular cloning, we have determined that the 5.8-kb EcoRI fragment and a 1.5-kb EcoRI fragment together constitute a 7.3-kb unit. The 7.3-kb unit is present in the hepatoma genome as a tandem repeat and constitutes the unit of the DNA that has been amplified. Studies on the arrangement of homologous sequences in the normal rat genome indicate that the amplified DNA may have been derived by a rearrangement and amplification of the nontranscribed spacer of the ribosomal DNA (rDNA) repeat.

Cloning and characterization of a highly reiterated 5.8-kilobase pair nucleolar EcoRI DNA fragment found in Novikoff hepatoma ascites cells.

The DNA of Novikoff hepatoma ascites cells was found to contain a 3.6-megadalton EcoRI restriction fragment, referred to as EcoRI fragment A (Parker et al., 1979). C0t analyses demonstrated an enrichment of fragment A sequences in Novikoff hepatoma genome relative to normal rat liver DNA. This fragment was cloned in lambda gtWES to determine its molecular structure and sequence organization. The DNA from a positive clone was labeled by nick translation and hybridized to a Southern blot of EcoRI digested Novikoff DNA. Distinct hybrids formed with the region corresponding to fragment A. The greater degree of hybridization to the nucleolar fraction suggested a nucleolar enrichment of fragment A. Fragment A has a PstI site approximately 300 base pairs from one terminus which was used to generate mono-5'-32P-labeled fragments. The larger PStI subfragment, 5500 base pairs, labeled at a single terminus, was used to evolve a restriction enzyme map. The 300 base pair fragment was partially sequenced, revealing the presence of a repetitive sequence "island", TT(GTCT)8(GAAT)5G-. C0t analysis, utilizing the purified clone as a probe, confirmed the enrichment of fragment A sequences in the tumor relative to the normal rat liver control.