The Key Role of Pain Catastrophizing in the Disability of Patients with Acute Back Pain.

PURPOSE: This study investigated the role of anxiety sensitivity, resilience, pain catastrophizing, depression, pain fear-avoidance beliefs, and pain intensity in patients with acute back pain-related disability. METHOD: Two hundred and thirty-two patients with acute back pain completed questionnaires on anxiety sensitivity, resilience, pain catastrophizing, fear-avoidance beliefs, depression, pain intensity, and disability. RESULTS: A structural equation modelling analysis revealed that anxiety sensitivity was associated with pain catastrophizing, and resilience was associated with lower levels of depression. Pain catastrophizing was positively associated with fear-avoidance beliefs and pain intensity. Depression was associated with fear-avoidance beliefs, but was not associated with pain intensity. Finally, catastrophizing, fear-avoidance beliefs, and pain intensity were positively and significantly associated with acute back pain-related disability. CONCLUSION: Although fear-avoidance beliefs and pain intensity were associated with disability, the results showed that pain catastrophizing was a central variable in the pain experience and had significant direct associations with disability when pain was acute. Anxiety sensitivity appeared to be an important antecedent of catastrophizing, whereas the influence of resilience on the acute back pain experience was limited to its relationship with depression.

Pulmonary hyperpolarized (129) Xe morphometry for mapping xenon gas concentrations and alveolar oxygen partial pressure: Proof-of-concept demonstration in healthy and COPD subjects.

PURPOSE: Diffusion-weighted (DW) hyperpolarized (129) Xe morphometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro-structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pA O2 ) maps by extracting the unrestricted diffusion coefficient (D0 ) of xenon as a morphometric parameter. METHODS: In this proof-of-concept demonstration, morphometry was performed using multi b-value (0, 12, 20, 30 s/cm(2) ) DW hyperpolarized (129) Xe images obtained in four never-smokers and four COPD ex-smokers. Morphometric parameters and D0 maps were computed and the latter used to generate [Xe] and pA O2 maps. Xenon concentration phantoms estimating a range of values mimicking those observed in vivo were also investigated. RESULTS: Xenon D0 was significantly increased (P = 0.035) in COPD (0.14 ± 0.03 cm(2) /s) compared with never-smokers (0.12 ± 0.02 cm(2) /s). COPD ex-smokers also had significantly decreased [Xe] (COPD = 8 ± 7% versus never-smokers = 13 ± 8%, P = 0.012) and increased pA O2 (COPD = 18 ± 3% versus never-smokers = 15 ± 3%, P = 0.009) compared with never-smokers. Phantom measurements showed the expected dependence of D0 on [Xe] over the range of concentrations anticipated in vivo. CONCLUSION: DW hyperpolarized (129) Xe MRI morphometry can be used to simultaneously map [Xe] and pA O2 in addition to providing micro-structural biomarkers of emphysematous destruction in COPD. Phantom measurements of D0 ([Xe]) supported the hypotheses that differences in subjects may reflect differences in functional residual capacity.

Psychological profiles and prescription opioid misuse, craving, and withdrawal in people with chronic pain.

BACKGROUND: The negative consequences of prescription opioid misuse and opioid use disorder make it relevant to identify factors associated with this problem in individuals with chronic pain. This cross-sectional study aimed at identifying subgroups of people with chronic pain based on their psychological profiles, prescription opioid misuse, craving, and withdrawal. METHODS: The sample comprised 185 individuals with chronic pain. We performed hierarchical cluster analysis on impulsivity, anxiety sensitivity, pain acceptance, pain intensity, opioid misuse, craving, and withdrawal. RESULTS: The four-cluster solution was the optimal one. Misuse, craving, and anxiety sensitivity were higher among people in the Severe-problems cluster than among people in the other three clusters. Withdrawal was the highest in the High-withdrawal cluster. Impulsivity was higher among people in the Severe-problems and High-withdrawal clusters than those in the Moderate-problems and Mild-problems clusters. Pain acceptance was higher among people in the Mild-problems cluster than among people in the other three clusters. Anxiety sensitivity and misuse were higher among people in the Moderate-problems cluster than among people in the Mild-problems cluster. CONCLUSIONS: These results support that impulsivity, anxiety sensitivity, and pain acceptance are useful constructs to identify subgroups of people with chronic pain according to their level of prescription opioid misuse, craving, and withdrawal. The results of this study may help in selecting the early intervention most suitable for each of the identified profiles. SIGNIFICANCE: The psychological profile of individuals with chronic pain, prescription opioid misuse, craving, and withdrawal is characterized by fearing anxiety-related symptoms due to the catastrophic interpretation of such symptoms and reacting impulsively to negative moods. In contrast, participants with high pain acceptance had less prescription opioid misuse, craving, and withdrawal. The profiles identified in this study could help clinicians select targets for intervention among profiles with similar needs and facilitate early interventions to prevent opioid misuse onset or aggravation.

Three-dimensional ultrasound of carotid atherosclerosis: semiautomated segmentation using a level set-based method.

PURPOSE: Three-dimensional ultrasound (3D US) of the carotid artery provides measurements of arterial wall and plaque [vessel wall volume (VWV)] that are complementary to the one-dimensional measurement of the carotid artery intima-media thickness. 3D US VWV requires an observer to delineate the media-adventitia boundary (MAB) and lumen-intima boundary (LIB) of the carotid artery. The main purpose of this work was to develop and evaluate a semiautomated segmentation algorithm for delineating the MAB and LIB of the carotid artery from 3D US images. METHODS: To segment the MAB and LIB, the authors used a level set method and combined several low-level image cues with high-level domain knowledge and limited user interaction. First, the operator initialized the algorithm by choosing anchor points on the boundaries, identified in the images. The MAB was segmented using local region- and edge-based energies and an energy that encourages the boundary to pass through anchor points from the preprocessed images. For the LIB segmentation, the authors used local and global region-based energies, the anchor point-based energy, as well as a constraint promoting a boundary separation between the MAB and LIB. The data set consisted of 231 2D images (11 2D images per each of 21 subjects) extracted from 3D US images. The image slices were segmented five times each by a single observer using the algorithm and the manual method. Volume-based, region-based, and boundary distance-based metrics were used to evaluate accuracy. Moreover, repeated measures analysis was used to evaluate precision. RESULTS: The algorithm yielded an absolute VWV difference of 5.0% +/- 4.3% with a segmentation bias of -0.9% +/- 6.6%. For the MAB and LIB segmentations, the method gave absolute volume differences of 2.5% +/- 1.8% and 5.6% +/- 3.0%, Dice coefficients of 95.4% +/- 1.6% and 93.1% +/- 3.1%, mean absolute distances of 0.2 +/- 0.1 and 0.2 +/- 0.1 mm, and maximum absolute distances of 0.6 +/- 0.3 and 0.7 +/- 0.6 mm, respectively. The coefficients of variation of the algorithm (5.1%) and manual methods (3.9%) were not significantly different, but the average time saved using the algorithm (2.8 min versus 8.3 min) was substantial. CONCLUSIONS: The authors generated and tested a semiautomated carotid artery VWV measurement tool to provide measurements with reduced operator time and interaction, with high Dice coefficients, and with necessary required precision.

Zinc-dependent structure of a single-finger domain of yeast ADR1.

In the proposed "zinc finger" DNA-binding motif, each repeat unit binds a zinc metal ion through invariant Cys and His residues and this drives the folding of each 30-residue unit into an independent nucleic acid-binding domain. To obtain structural information, we synthesized single and double zinc finger peptides from the yeast transcription activator ADR1, and assessed the metal-binding and DNA-binding properties of these peptides, as well as the solution structure of the metal-stabilized domains, with the use of a variety of spectroscopic techniques. A single zinc finger can exist as an independent structure sufficient for zinc-dependent DNA binding. An experimentally determined model of the single finger is proposed that is consistent with circular dichroism, one- and two-dimensional nuclear magnetic resonance, and visual spectroscopy of the single-finger peptide reconstituted in the presence of zinc.

Anatomical pulmonary magnetic resonance imaging segmentation for regional structure-function measurements of asthma.

PURPOSE: Pulmonary magnetic-resonance-imaging (MRI) and x-ray computed-tomography have provided strong evidence of spatially and temporally persistent lung structure-function abnormalities in asthmatics. This has generated a shift in their understanding of lung disease and supports the use of imaging biomarkers as intermediate endpoints of asthma severity and control. In particular, pulmonary (1)H MRI can be used to provide quantitative lung structure-function measurements longitudinally and in response to treatment. However, to translate such biomarkers of asthma, robust methods are required to segment the lung from pulmonary (1)H MRI. Therefore, their objective was to develop a pulmonary (1)H MRI segmentation algorithm to provide regional measurements with the precision and speed required to support clinical studies. METHODS: The authors developed a method to segment the left and right lung from (1)H MRI acquired in 20 asthmatics including five well-controlled and 15 severe poorly controlled participants who provided written informed consent to a study protocol approved by Health Canada. Same-day spirometry and plethysmography measurements of lung function and volume were acquired as well as (1)H MRI using a whole-body radiofrequency coil and fast spoiled gradient-recalled echo sequence at a fixed lung volume (functional residual capacity + 1 l). We incorporated the left-to-right lung volume proportion prior based on the Potts model and derived a volume-proportion preserved Potts model, which was approximated through convex relaxation and further represented by a dual volume-proportion preserved max-flow model. The max-flow model led to a linear problem with convex and linear equality constraints that implicitly encoded the proportion prior. To implement the algorithm, (1)H MRI was resampled into ∼3 × 3 × 3 mm(3) isotropic voxel space. Two observers placed seeds on each lung and on the background of 20 pulmonary (1)H MR images in a randomized dataset, on five occasions, five consecutive days in a row. Segmentation accuracy was evaluated using the Dice-similarity-coefficient (DSC) of the segmented thoracic cavity with comparison to five-rounds of manual segmentation by an expert observer. The authors also evaluated the root-mean-squared-error (RMSE) of the Euclidean distance between lung surfaces, the absolute, and percent volume error. Reproducibility was measured using the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for two observers who repeated segmentation measurements five-times. RESULTS: For five well-controlled asthmatics, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) was 83% ± 7% and FEV1 was 86 ± 9%pred. For 15 severe, poorly controlled asthmatics, FEV1/FV C = 66% ± 17% and FEV1 = 72 ± 27%pred. The DSC for algorithm and manual segmentation was 91% ± 3%, 92% ± 2% and 91% ± 2% for the left, right, and whole lung, respectively. RMSE was 4.0 ± 1.0 mm for each of the left, right, and whole lung. The absolute (percent) volume errors were 0.1 l (∼6%) for each of right and left lung and ∼0.2 l (∼6%) for whole lung. Intra- and inter-CoV (ICC) were <0.5% (>0.91%) for DSC and <4.5% (>0.93%) for RMSE. While segmentation required 10 s including ∼6 s for user interaction, the smallest detectable difference was 0.24 l for algorithm measurements which was similar to manual measurements. CONCLUSIONS: This lung segmentation approach provided the necessary and sufficient precision and accuracy required for research and clinical studies.

Visualization of domains in rigid ganglioside/phosphatidylcholine bilayers: Ca2+ effects.

We have considered the extent to which details of lectin binding directly visualized by freeze-etch electron microscopy are consistent with current concepts of ganglioside arrangement in phosphatidylcholine bilayer membranes. Native lectins in general seem appropriate labels for this type of study. Wheat germ agglutinin, Ricinus communis agglutinin, and peanut agglutinin are adequately resolved on membrane surfaces as spherical particles of diameters 6 nm, 10 nm, and 13 nm, respectively (uncorrected for platinum shadow thickness). The finite areas covered by these markers correspond to some 56, 157, and 265 lipid molecules, respectively, on the surfaces of the shadowed rigid phosphatidylcholine matrices employed here; and this constitutes a basic limitation to the precision with which one can localize a given glycolipid receptor. Ricinus communis agglutinin provides a marker whose size permits adequate quantitation of bound material while minimally obscuring detail. Using it we estimated the size limits of GM1-enriched domains, since this is the ganglioside which has shown the greatest evidence of discontinuous distribution in our hands (Peters, M.W., Mehlhorn, I.E., Barber, K.R. and Grant, C.W.M. (1984) Biochim. Biophys. Acta 778, 419-428). Results of such analyses indicate the probable existence of phase separated domains selectively enriched in GM1 up to 60 nm in extent (5600 lipid molecules) for rigid dipalmitoylphosphatidylcholine membranes bearing up to 14 mol% GM1. Similar observations were true of rigid bilayers of dimyristoylphosphatidylcholine; however, if domains enriched in GM1 exist in fluid dimyristoylphosphatidylcholine, they are on the order of 6 nm or less in diameter (or are dispersed by lectin binding). Employing the small lectin, wheat germ agglutinin, which binds to all gangliosides, we then examined the effect of exposure to Ca2+ ions (while in the fluid state) on the ganglioside 'domain structure' referred to above in rigid dipalmitoylphosphatidylcholine host matrices. GM1, GD1a and GT1b were studied at 0, 2 and 10 mM Ca2+ concentrations. It was demonstrated by spin label measurements that the dipalmitoylphosphatidylcholine matrix retained its basic melting characteristics in the presence of added Ca2+ and ganglioside under these conditions. Within the technique's functional resolution limit of some 6 nm we were unable to identify any effect of Ca2+ in physiological concentration on ganglioside topography as reflected by bound lectin distribution.(ABSTRACT TRUNCATED AT 400 WORDS)

Three-dimensional segmentation of three-dimensional ultrasound carotid atherosclerosis using sparse field level sets.

PURPOSE: Three-dimensional ultrasound (3DUS) vessel wall volume (VWV) provides a 3D measurement of carotid artery wall remodeling and atherosclerotic plaque and is sensitive to temporal changes of carotid plaque burden. Unfortunately, although 3DUS VWV provides many advantages compared to measurements of arterial wall thickening or plaque alone, it is still not widely used in research or clinical practice because of the inordinate amount of time required to train observers and to generate 3DUS VWV measurements. In this regard, semiautomated methods for segmentation of the carotid media-adventitia boundary (MAB) and the lumen-intima boundary (LIB) would greatly improve the time to train observers and for them to generate 3DUS VWV measurements with high reproducibility. METHODS: The authors describe a 3D algorithm based on a modified sparse field level set method for segmenting the MAB and LIB of the common carotid artery (CCA) from 3DUS images. To the authors' knowledge, the proposed algorithm is the first direct 3D segmentation method, which has been validated for segmenting both the carotid MAB and the LIB from 3DUS images for the purpose of computing VWV. Initialization of the algorithm requires the observer to choose anchor points on each boundary on a set of transverse slices with a user-specified interslice distance (ISD), in which larger ISD requires fewer user interactions than smaller ISD. To address the challenges of the MAB and LIB segmentations from 3DUS images, the authors integrated regional- and boundary-based image statistics, expert initializations, and anatomically motivated boundary separation into the segmentation. The MAB is segmented by incorporating local region-based image information, image gradients, and the anchor points provided by the observer. Moreover, a local smoothness term is utilized to maintain the smooth surface of the MAB. The LIB is segmented by constraining its evolution using the already segmented surface of the MAB, in addition to the global region-based information and the anchor points. The algorithm-generated surfaces were sliced and evaluated with respect to manual segmentations on a slice-by-slice basis using 21 3DUS images. RESULTS: The authors used ISD of 1, 2, 3, 4, and 10 mm for algorithm initialization to generate segmentation results. The algorithm-generated accuracy and intraobserver variability results are comparable to the previous methods, but with fewer user interactions. For example, for the ISD of 3 mm, the algorithm yielded an average Dice coefficient of 94.4% ± 2.2% and 90.6% ± 5.0% for the MAB and LIB and the coefficient of variation of 6.8% for computing the VWV of the CCA, while requiring only 1.72 min (vs 8.3 min for manual segmentation) for a 3DUS image. CONCLUSIONS: The proposed 3D semiautomated segmentation algorithm yielded high-accuracy and high-repeatability, while reducing the expert interaction required for initializing the algorithm than the previous 2D methods.

Poster - Thur Eve - 16: Four-dimensional x-ray computed tomography and hyperpolarized 3 He magnetic resonance imaging of gas distribution in lung cancer.

Dynamic imaging methods such as four-dimensional computed tomography (4DCT) and static imaging methods such as noble gas magnetic resonance imaging (MRI) deliver direct and regional measurements of lung function even in lung cancer patients in whom global lung function measurements are dominated by tumour burden. The purpose of this study was to directly compare quantitative measurements of gas distribution from static hyperpolarized 3 He MRI and dynamic 4DCT in a small group of lung cancer patients. MRI and 4DCT were performed in 11 subjects prior to radiation therapy. MRI was performed at 3.0T in breath-hold after inhalation 1L of hyperpolarized 3 He gas. Gas distribution in 3 He MRI was quantified using a semi-automated segmentation algorithm to generate percent-ventilated volume (PVV), reflecting the volume of gas in the lung normalized to the thoracic cavity volume. 4DCT pulmonary function maps were generated using deformable image registration of six expiratory phase images. The correspondence between identical tissue elements at inspiratory and expiratory phases was used to estimate regional gas distribution and PVV was quantified from these images. After accounting for differences in lung volumes between 3 He MRI (1.9±0.5L ipsilateral, 2.3±0.7 contralateral) and 4DCT (1.2±0.3L ipsilateral, 1.3±0.4L contralateral) during image acquisition, there was no statistically significant difference in PVV between 3 He MRI (72±11% ipsilateral, 79±12% contralateral) and 4DCT (74±3% ipsilateral, 75±4% contralateral). Our results indicate quantitative agreement in the regional distribution of inhaled gas in both static and dynamic imaging methods. PVV may be considered as a regional surrogate measurement of lung function or ventilation.

Freeze-etch visualization of the outer surface of myoblasts in culture.

The Pfenninger device is one of several types of specimen holders designed to permit freeze-fracture electron microscopy of cultured cells growing attached to solid substrates. It achieves this by directing a fracture plane horizontally through a monolayer of cells frozen with overlying medium (without need for prior disruption of cell attachments or relationships). The end result is a platinum-shadowed replica of the cell membrane hydrophobic interior. Here we describe the features seen when this traditional fracture step is followed by a lengthy etching step, making possible views of the cell membrane outer surface with a resolution 100 X better than that of fluorescence microscopy. Because of the technical difficulties involved, such views have in past been restricted to samples which may be handled in suspension, particularly blood cells and model membranes. Thus we have been able to examine extensive regions of the myoblast outer surface (the so-called etch face) at a magnification that permits visualization of details on the order of individual macromolecules. Prominent clumps of glycocalyx material occupying some 50% of the surface can be readily resolved as a closely spaced network of uniformly distributed 20- to 60-nm irregular granular patches. Receptors for wheat germ agglutinin were found to be associated almost exclusively with these surface prominences, so that bound lectin tended to exist in a uniform distribution of small clusters corresponding to the patches described above. When cells were not fixed until 15 min after lectin addition there was visibly more binding, but in a similar distribution. The details of cell surface architecture recorded here at a resolution of 2-4 nm are well below the limit of resolution of light microscopy and complement existing studies by fluorescence techniques. The presence of surface receptors in small patches reinforces the possibility that some literature observations of receptor interaction may be explained on the basis of direct receptor-receptor contact.

Spectroscopic studies of wild-type and mutant "zinc finger" peptides: determinants of domain folding and structure.

The "zinc finger" model [Miller, J., McLachlan, A. D. & Klug, A. (1985) EMBO J. 4, 1609-1614; Brown, R. S., Sander, C. & Argos, P. (1985) FEBS Lett. 186, 271-274] makes both specific structural and specific functional predictions about zinc finger consensus sequences that can be tested with a combination of genetic, molecular biological, and biophysical techniques. The yeast transcription factor ADR1 contains two adjacent zinc finger domains; genetic and deletion analyses showed that amino acid substitutions and deletions in the zinc finger domains resulted in the loss of protein activity. To test the structural and folding predictions of the zinc finger model, peptides encompassing each of the ADR1 fingers were synthesized (ADR1a and ADR1b) as well as a mutant finger peptide (del138) deleted for a single amino acid residue. The folding and metal-binding characteristics of these were assessed by 1H nuclear magnetic resonance (NMR) and visible spectroscopy. While a single unique conformational species was detected for the two wild-type peptides upon tetrahedral binding of zinc, the deletion peptide did not bind zinc with tetrahedral geometry, nor did it fold into a zinc finger domain. The metal-binding and folding results found with the mutant peptide were similar to those obtained when thiol alkylation or imidazole protonation of the wild-type peptides was performed. These data indicate that ligand spacing and both thiol and imidazole participation in zinc binding are specific and necessary requirements for zinc finger folding, which provides direct support for the initial predictions of the model.