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Biomedical subjects

E A Hoffman

Publications and source records attributed to E A Hoffman.

At least 19 recordsLinked to original sources
PubMed2006

Myocilin-associated exosomes in human ocular samples.

Mutations in myocilin result in ocular hypertension, likely due to decreased drainage of aqueous humor through the trabecular meshwork. Since less myocilin is found in the aqueous humor of those with disease-causing mutations, understanding myocilin's role in the aqueous humor is of clinical importance. Recently, myocilin was shown to exit cultured trabecular meshwork cells in association with shed vesicles called exosomes. To examine relevance of this finding in a physiological setting, the present study examined three different types of ocular samples for the presence of myocilin-associated exosomes. Using differential centrifugation steps, we found myocilin associated with exosomes isolated from effluent collected from human anterior segments in organ culture and aqueous humor obtained from human cadaveric eyes or from patients undergoing excisional surgery. Similar to results with cultured cells, myocilin associated predominately with exosomes in fresh samples, appeared mostly soluble at later times, and had biochemical properties (density of 1.13-1.19 g/ml in linear sucrose gradient) similar to those characteristics of exosomes. These data indicate that exosomes are present and may facilitate the transport of myocilin into the extracellular space of human ocular cells.

Aqueous Humor↗
PubMed2006

In vivo micro-CT lung imaging via a computer-controlled intermittent iso-pressure breath hold (IIBH) technique.

Respiratory research with mice using micro-computed tomography (micro-CT) has been predominantly hindered by the limited resolution and signal-to-noise ratio (SNR) as a result of respiratory motion artefacts. In this study, we develop a novel technique for capturing the lung microstructure in vivo using micro-CT, through a computer-controlled intermittent iso-pressure breath hold (IIBH), to reduce respiratory motion, increasing resolution and SNR of reconstructed images. We compare four gating techniques, i.e. no gating, late expiratory (LE) gating, late inspiratory (LI) gating and finally intermittent iso-pressure breath hold (IIBH) gating. Quantitatively, we compare several common image analysis methods used to extract valuable physiologic and anatomic information from the respiratory system, and show that the IIBH technique produces the most representative and repeatable results.

Animals↗
PubMed2006

Coiled-coil targeting of myocilin to intracellular membranes.

Mutations in myocilin (MYOC) associate with glaucoma and ocular hypertension. Unfortunately, the specific role of MYOC, a widely expressed protein of unknown function, in ocular hypertension is unknown. Since MYOC localizes both to intracellular membranes and to the cytosol, we tested the hypothesis that MYOC is a cytosolic protein that associates with cellular membranes via its coiled-coil domain. Using green fluorescent protein (GFP) chimeras in expression and metabolic labeling studies, we observed that MYOC's putative signal peptide failed to traffic GFP into the secretory machinery and out of transfected cells. Next, we tested which of MYOC's three folding domains were responsible for targeting. In cell fractionation and immunofluorescence microscopy studies, the coiled-coil, but not the helix-turn-helix or olfactomedin domains, was necessary and sufficient to target GFP chimeras to cell membranes. Interestingly, a vesicular phenotype required sequential addition of the helix-turn-helix and olfactomedin domains to the coiled-coil. Taken together, these data indicate that the coiled-coil domain, not the putative signal sequence, is responsible for the targeting of MYOC to the secretory machinery.

Animals↗
PubMed2004

Three-dimensional path planning for virtual bronchoscopy.

Multidetector computed-tomography (MDCT) scanners provide large high-resolution three-dimensional (3-D) images of the chest. MDCT scanning, when used in tandem with bronchoscopy, provides a state-of-the-art approach for lung-cancer assessment. We have been building and validating a lung-cancer assessment system, which enables virtual-bronchoscopic 3-D MDCT image analysis and follow-on image-guided bronchoscopy. A suitable path planning method is needed, however, for using this system. We describe a rapid, robust method for computing a set of 3-D airway-tree paths from MDCT images. The method first defines the skeleton of a given segmented 3-D chest image and then performs a multistage refinement of the skeleton to arrive at a final tree structure. The tree consists of a series of paths and branch structural data, suitable for quantitative airway analysis and smooth virtual navigation. A comparison of the method to a previously devised path-planning approach, using a set of human MDCT images, illustrates the efficacy of the method. Results are also presented for human lung-cancer assessment and the guidance of bronchoscopy.

Algorithms↗
PubMed2002

Laser fluorescence bronchoscopy for detection of fluorescent reporter genes in airway epithelia.

Current methods for detecting successful gene transfer to airway epithelia involve obtaining a sample of the target tissue. This may affect the longevity of expression of the transgene under evaluation. We describe a laser fluorescence bronchoscopic system that can detect the expression of the fluorescent protein, green fluorescence protein (GFP), in the airway of monkeys that have been transfected with adenovirus, without the need for obtaining tissue. This technique will have applications in pre-clinical and clinical studies of gene transfer to airway epithelia and other surface epithelia accessible by endoscopy.

Adenoviridae↗
PubMed2001

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry.

OBJECTIVES: This study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation. BACKGROUND: Magnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo. METHODS: Circumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites. RESULTS: Paired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001). CONCLUSIONS: Magnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.

Animals↗
PubMed2001

Automatic lung segmentation for accurate quantitation of volumetric X-ray CT images.

Segmentation of pulmonary X-ray computed tomography (CT) images is a precursor to most pulmonary image analysis applications. This paper presents a fully automatic method for identifying the lungs in three-dimensional (3-D) pulmonary X-ray CT images. The method has three main steps. First, the lung region is extracted from the CT images by gray-level thresholding. Then, the left and right lungs are separated by identifying the anterior and posterior junctions by dynamic programming. Finally, a sequence of morphological operations is used to smooth the irregular boundary along the mediastinum in order to obtain results consistent with those obtained by manual analysis, in which only the most central pulmonary arteries are excluded from the lung region. The method has been tested by processing 3-D CT data sets from eight normal subjects, each imaged three times at biweekly intervals with lungs at 90% vital capacity. We present results by comparing our automatic method to manually traced borders from two image analysts. Averaged over all volumes, the root mean square difference between the computer and human analysis is 0.8 pixels (0.54 mm). The mean intrasubject change in tissue content over the three scans was 2.75% +/- 2.29% (mean +/- standard deviation).

Algorithms↗
PubMed2001

Three-dimensional vocal tract imaging and formant structure: varying vocal register, pitch, and loudness.

Although advances in techniques for image acquisition and analysis have facilitated the direct measurement of three-dimensional vocal tract air space shapes associated with specific speech phonemes, little information is available with regard to changes in three-dimensional (3-D) vocal tract shape as a function of vocal register, pitch, and loudness. In this study, 3-D images of the vocal tract during falsetto and chest register phonations at various pitch and loudness conditions were obtained using electron beam computed tomography (EBCT). Detailed measurements and differences in vocal tract configuration and formant characteristics derived from the eight measured vocal tract shapes are reported.

Humans↗
PubMed2001

The relationship of vocal tract shape to three voice qualities.

Three-dimensional vocal tract shapes and consequent area functions representing the vowels [i, ae, a, u] have been obtained from one male and one female speaker using magnetic resonance imaging (MRI). The two speakers were trained vocal performers and both were adept at manipulation of vocal tract shape to alter voice quality. Each vowel was performed three times, each with one of the three voice qualities: normal, yawny, and twangy. The purpose of the study was to determine some ways in which the vocal tract shape can be manipulated to alter voice quality while retaining a desired phonetic quality. To summarize any overall tract shaping tendencies mean area functions were subsequently computed across the four vowels produced within each specific voice quality. Relative to normal speech, both the vowel area functions and mean area functions showed, in general, that the oral cavity is widened and tract length increased for the yawny productions. The twangy vowels were characterized by shortened tract length, widened lip opening, and a slightly constricted oral cavity. The resulting acoustic characteristics of these articulatory alterations consisted of the first two formants (F1 and F2) being close together for all yawny vowels and far apart for all the twangy vowels.

Adult↗
PubMed2000

Distinct representations of eye gaze and identity in the distributed human neural system for face perception.

Face perception requires representation of invariant aspects that underlie identity recognition as well as representation of changeable aspects, such as eye gaze and expression, that facilitate social communication. Using functional magnetic resonance imaging (fMRI), we investigated the perception of face identity and eye gaze in the human brain. Perception of face identity was mediated more by regions in the inferior occipital and fusiform gyri, and perception of eye gaze was mediated more by regions in the superior temporal sulci. Eye-gaze perception also seemed to recruit the spatial cognition system in the intraparietal sulcus to encode the direction of another's gaze and to focus attention in that direction.

Adult↗
PubMed1999

Repetitive transcranial magnetic stimulation of the dominant hemisphere can disrupt visual naming in temporal lobe epilepsy patients.

We used repetitive transcranial magnetic stimulation (rTMS) to study visual naming in 14 patients with temporal lobe epilepsy. Ten had left hemisphere language by Wada testing and all experienced speech arrest with rTMS of the motor speech area in the left frontal lobe. One left-hander had speech arrest with stimulation of sites on both sides. Subjects were asked to name pictures or read words presented on a computer monitor. rTMS was delivered on half of the trials. Stimulation sites were the motor speech area in the left frontal lobe, the mirror site on the right, and the left and right mid superior and posterior temporal lobes. rTMS at left hemisphere sites caused more naming errors than did right hemisphere rTMS. All individual subjects, except two who had temporal lobe resections and the one with bilateral speech arrest, produced more naming errors with rTMS of left hemisphere sites. There was no significant effect on word reading. rTMS at the left hemisphere and right frontal sites produced reductions in reaction time for picture naming, but not for word reading. This was observed for both correct and incorrect responses. This study shows that left hemisphere rTMS can disrupt visual naming selectively.

Adult↗
PubMed1999

The effect of face inversion on activity in human neural systems for face and object perception.

The differential effect of stimulus inversion on face and object recognition suggests that inverted faces are processed by mechanisms for the perception of other objects rather than by face perception mechanisms. We investigated the face inversion using functional magnetic resonance imaging (fMRI). The principal effect of face inversion on was an increased response in ventral extrastriate regions that respond preferentially to another class of objects (houses). In contrast, house inversion did not produce a similar change in face-selective regions. Moreover, stimulus inversion had equivalent, minimal effects for faces in in face-selective regions and for houses in house-selective regions. The results suggest that the failure of face perception systems with inverted faces leads to the recruitment of processing resources in object perception systems, but this failure is not reflected by altered activity in face perception systems.

Brain↗
PubMed1999

Pulmonary CT image classification with evolutionary programming.

RATIONALE AND OBJECTIVES: It is often difficult to classify information in medical images from derived features. The purpose of this research was to investigate the use of evolutionary programming as a tool for selecting important features and generating algorithms to classify computed tomographic (CT) images of the lung. MATERIALS AND METHODS: Training and test sets consisting of 11 features derived from multiple lung CT images were generated, along with an indicator of the target area from which features originated. The images included five parameters based on histogram analysis, 11 parameters based on run length and co-occurrence matrix measures, and the fractal dimension. Two classification experiments were performed. In the first, the classification task was to distinguish between the subtle but known differences between anterior and posterior portions of transverse lung CT sections. The second classification task was to distinguish normal lung CT images from emphysematous images. The performance of the evolutionary programming approach was compared with that of three statistical classifiers that used the same training and test sets. RESULTS: Evolutionary programming produced solutions that compared favorably with those of the statistical classifiers. In separating the anterior from the posterior lung sections, the evolutionary programming results were better than two of the three statistical approaches. The evolutionary programming approach correctly identified all the normal and abnormal lung images and accomplished this by using less features than the best statistical method. CONCLUSION: The results of this study demonstrate the utility of evolutionary programming as a tool for developing classification algorithms.

Algorithms↗
PubMed1999

Interstitial lung disease: A quantitative study using the adaptive multiple feature method.

We have previously described an adaptive multiple feature method (AMFM) for the objective assessment of global and regional changes in pulmonary parenchyma to detect emphysema. This computerized method uses a combination of statistical and fractal texture features for characterization of lung tissues based upon high resolution computed tomography (HRCT) scans. This present study was a substantial extension of the AMFM to simultaneously discriminate between multiple pulmonary disease processes. Normal subjects and those with emphysema, idiopathic pulmonary fibrosis (IPF), or sarcoidosis were studied. The AMFM was compared with two currently utilized computer-based methods: mean lung density (MLD) and the histogram analysis (HIST). Globally, when comparing two-subject groups the AMFM overall accuracy was 2 to 18% better than the overall accuracy of MLD and as much as 36% better than the accuracy of the HIST methods. In three-subject group discrimination tasks, the AMFM performed 7 to 27% better than the MLD and 4 to 36% better than the HIST methods. Finally, in discriminating all four subject groups at a time, the AMFM overall accuracy was 81%, which was 21% better than the MLD and 25% better than the HIST method. In most three-subject group comparisons and in the four-subject group comparison, the AMFM was significantly (p < 0.01) better than the MLD and HIST methods. Next, the AMFM was applied to local discrimination between normal and each disease group individually. The normal versus emphysema, normal versus IPF, and normal versus sarcoidosis samples were discriminated with an accuracy of 95, 86, and 77%, respectively. The AMFM is an objective quantitative method that can be adapted for successful discrimination of multiple parenchymal lung diseases.

Diagnosis, Computer-Assisted↗
PubMed1999

Computer recognition of regional lung disease patterns.

We have developed an objective, reproducible, and automated means for the regional evaluation of the pulmonary parenchyma from computed tomography (CT) scans. This method, known as the Adaptive Multiple Feature Method (AMFM) assesses as many as 22 independent texture features in order to classify a tissue pattern. In this study, the six tissue patterns characterized were: honeycombing, ground glass, bronchovascular, nodular, emphysemalike, and normal. The lung slices were evaluated regionally using 31 x 31 pixel regions of interest. In each region of interest, an optimal subset of texture features was evaluated to determine which of the six patterns the region could be characterized as. The computer output was validated against experienced observers in three settings. In the first two readings, when the observers were blinded to the primary diagnosis of the subject, the average computer versus observer agreement was 44.4 +/- 8.7% and 47.3 +/- 9.0%, respectively. The average interobserver agreement for the same two readings were 48.8 +/- 9.1% and 52.2 +/- 10.0%, respectively. In the third reading, when the observers were provided the primary diagnosis, the average computer versus observer agreement was 51.7 +/- 2.9% where as the average interobserver agreement was 53.9 +/- 6.2%. The kappa statistic of agreement between the regions, for which the majority of the observers agreed on a pattern type, versus the computer was found to be 0.62. For regional tissue characterization, the AMFM is 100% reproducible and performs as well as experienced human observers who have been told the patient diagnosis.

Diagnosis, Computer-Assisted↗
PubMed1998

Mechanics of the single left ventricle: a study in ventricular-ventricular interaction II.

BACKGROUND: Left ventricular (LV) effects on right ventricular (RV) function are well known. Less is understood about the effect of the RV on systemic LV mechanics. To determine this interaction, we compared systemic LVs with and without an RV mechanically coupled to them. METHODS AND RESULTS: MR myocardial tagging was used to examine 18 subjects with systemic LVs: 10 with functional single LVs (SLV) and 8 normal subjects (NL). Tracking the systolic motion of the intersecting stripes were used to determine regional twist and radial motion. Finite strain analysis was applied to derive principal strains at the atrioventricular valve (AVV) and apical short-axis levels and in 4 anatomic wall regions. Similar E1 (circumferential shortening) strain and heterogeneity of strain were noted between SLV and NL except in the septal wall. At the septal wall, NL displayed greater absolute strain (AVV=-0.16+/-0.02, apex=-0.17+/-0.02) and less heterogeneity of strain than SLV (AVV= -0.12+/-0.02, apex=-0.13+/-0.02). Similar E2 (wall thickening) strain and heterogeneity of strain were also noted between SLV and NL except again at the septal wall. At the septal wall, SLV displayed greater absolute E2 strain (AVV=0.17+/-0.08, apex=0.19+/-0.09) and less heterogeneity of strain than NL (AVV=0.07+/-0.07, apex=0.05+/-0.05). SLV twisted significantly less counterclockwise than NL in 6 of 8 wall regions and actually twisted clockwise at the AVV lateral wall. Although there was no significant difference between groups in radial wall motion, the septal and inferior walls of SLV demonstrated significantly less radial motion compared with other SLV walls. CONCLUSIONS: A major influence of the RV on systemic LV strain and radial motion occurs in the septal wall, whereas absence of the RV causes marked differences in LV twist. These findings may yield clues to the long-term functioning of the SLV and be useful in determining strategies for RV augmentation of LV function.

Adolescent↗
PubMed1998

Quantitative pulmonary imaging: spatial and temporal considerations in high-resolution CT.

RATIONALE AND OBJECTIVES: The authors performed this study to determine how scanner temporal resolution affects image quality in high-resolution computed tomography (CT)-based quantitative analysis of lung parenchyma. MATERIALS AND METHODS: A 37-kg, anesthetized white pig, in which 1.5-mm-diameter radiopaque markers were bronchoscopically implanted, was scanned supine with electron-beam CT and spiral CT scanners. Images were first acquired during apnea at functional residual capacity with electron-beam CT at a single level with multiple scan apertures. Without altering body posture, the animal was transported to the spiral CT scanner and scanned at the same lung volume and level. The animal was then euthanized and rescanned with spiral CT. All images were reconstructed with high-spatial-frequency algorithms resident on the respective scanners. RESULTS: High-resolution CT images of the live animal in the spiral scanner showed substantial cardiogenic motion artifacts for markers both near and distant from the heart. The matched postmortem images showed no motion artifacts. While line-pair phantom scans showed reduced spatial resolution of electron-beam CT compared with spiral CT scans, the electron-beam CT images of the markers in the live animal were free of artifacts, even with scan apertures of up to 700 msec. CONCLUSION: Motion artifacts may be accentuated by differences in high-resolution CT implementations. Applications such as lung parenchyma texture analysis, which regionally quantifies the subtle tissue density variations, will likely benefit from short scanning apertures.

Animals↗