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Purpose: To evaluate short-acting bronchodilator effects in chronic obstructive pulmonary disease (COPD) by using hyperpolarized helium 3 (³He) magnetic resonance (MR) imaging, spirometry, and plethysmography., Materials and Methods: Fourteen ex-smokers with COPD provided written informed consent to a local ethics board-approved and Health Insurance and Portability Accountability Act-compliant protocol and underwent hyperpolarized ³He and hydrogen 1 MR imaging, spirometry, and plethysmography before and a mean of 25 minutes ± 2 (standard deviation) after administration of 400 μg salbutamol. Distribution of ³He gas was evaluated by using semiautomated segmentation of ³He voxel intensities, where cluster 1 represented regions of signal void or ventilation defect volume (VDV), and clusters 2-5 (C2-C5) represented gradations of signal intensity from hypointensity (C2) to hyperintensity (C5). ³He ventilation defect percentage (VDP) was calculated as VDV normalized to the thoracic cavity volume. Comparisons of pre- and post-salbutamol means were performed by using a two-way mixed-design repeated measures analysis of variance, and comparisons of the magnitude of the treatment effect between pulmonary function and ³He MR imaging measurements were performed by using effect size (ES) calculations. The relationships between pulmonary function and ³He MR imaging findings were determined by using Spearman correlation coefficients., Results: After salbutamol administration, there were significant changes in forced expiratory volume in 1 second (FEV₁) (P = .001), total lung capacity (P = .04), and functional residual capacity (P = .03), as well as VDP (P < .0001) and ³He gas distribution (C2, P = .01; C3, P = .03; C4, P < .0001; and C5, P = .02). Treatment ES was greater for ³He VDP than for FEV(1) (0.50 vs 0.22). There was a significant correlation between baseline VDP and post-salbutamol FEV₁ change (r = -0.77, P = .001). Although five patients were classified as bronchodilator responders and nine patients were classified as bronchodilator nonresponders according to American Thoracic Society and European Respiratory Society criteria, there was no significant difference in the magnitude of the ³He MR imaging changes after salbutamol administration between responder groups., Conclusion: ³He MR imaging depicted significant improvements in the distribution of ³He gas after bronchodilator therapy in ex-smokers with COPD with and those without clinically important changes in FEV₁., (© RSNA, 2011.)

The past two decades have witnessed developments of new imaging techniques that provide three-dimensional images about the interior of the human body in a manner never before available. Ultrasound (US) imaging is an important cost-effective technique used routinely in the management of a number of diseases. However, two-dimensional viewing of three-dimensional anatomy, using conventional two-dimensional US, limits our ability to quantify and visualize the anatomy and guide therapy, because multiple two-dimensional images must be integrated mentally. This practice is inefficient, and may lead to variability and incorrect diagnoses. Investigators and companies have addressed these limitations by developing three-dimensional US techniques. Thus, in this paper, we review the various techniques that are in current use in three-dimensional US imaging systems, with a particular emphasis placed on the geometric accuracy of the generation of three-dimensional images. The principles involved in three-dimensional US imaging are then illustrated with a diagnostic and an interventional application: (i) three-dimensional carotid US imaging for quantification and monitoring of carotid atherosclerosis and (ii) three-dimensional US-guided prostate biopsy.

Rationale and Objectives: To better understand imaging measurement precision and reproducibility and to provide guidance for measurements in individual cystic fibrosis (CF) subjects, we evaluated CF adults on two occasions 7 ± 2 days apart using spirometry, plethysmography, and hyperpolarized helium-3 ((3)He) magnetic resonance imaging (MRI)., Materials and Methods: Twelve CF subjects underwent spirometry, plethysmography, and (3)He MRI twice within 7 ± 2 days, reporting (3)He ventilation defect volume (VDV) and ventilation defect percent (VDP)., Results: Based on measurement variability, the smallest detectable difference (SDD) for (3)He VDV and VDP was determined to be 120 mL and 2%, respectively. Although no significant difference in spirometry or plethysmography was detected after 7 days, there was a significant difference in mean (3)He VDV (130 mL ± 250 mL, P < .0001) and VDP (3% ± 4%, P < .0001), although baseline and 7-day measurements were highly correlated (VDV: r = .85, P = .001; VDP: r = .94, P < .0001). We estimated the sample sizes required to detect a 5%/7%/10% change in (3)He VDP as 60/15/5 subjects per group., Conclusion: Hyperpolarized (3)He MRI VDP measurement precision resulted in an SDD for individual CF subjects of 2%, indicating that changes greater than this can be attributed to lung functional changes and not measurement error. After 7 days, significant changes in mean (3)He VDV and VDP were detected and these changes were not reflected by changes in pulmonary function measurements. These findings demonstrate the high sensitivity and reproducibility of (3)He MRI functional imaging that permits the use of relatively small samples sizes in CF interventional studies., (Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Emphysema and small airway obstruction are the pathological hallmarks of chronic obstructive pulmonary disease (COPD). The aim of this pilot study in a small group of chronic obstructive pulmonary disease (COPD) patients was to quantify hyperpolarized helium-3 ((3)He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for (3)He MRI in detecting the lung structural and functional COPD phenotypes., Materials and Methods: We evaluated 20 ex-smokers with stage I (n=1), stage II (n=9) and stage III COPD (n=10). All subjects underwent same-day plethysmography, spirometry, (1)H MRI and hyperpolarized (3)He MRI at 3.0T. (3)He ventilation defect percent (VDP) was generated from (3)He static ventilation images and (1)H thoracic images and the (3)He apparent diffusion coefficient (ADC) was derived from diffusion-weighted MRI., Results: Based on the relative contribution of normalized ADC and VDP, there was evidence of a predominant (3)He MRI measurement in seven patients (n=3 mainly ventilation defects or VDP dominant (VD), n=4 mainly increased ADC or ADC dominant (AD)). Analysis of variance (ANOVA) showed significantly lower ADC for subjects with predominantly elevated VDP (p=0.02 compared to subjects with predominantly elevated ADC; p=0.008 compared to mixed group) and significantly decreased VDP for subjects with predominantly elevated ADC (p=0.003, compared to mixed group)., Conclusion: In this small pilot study, a preliminary analysis shows the potential for (3)He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

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.

During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation-induced lung injury, and transplantation. This review focuses on the state-of-the-art of HP (3)He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine. Particular attention is given to functional imaging approaches related to ventilation and diffusion-weighted imaging with applications in chronic obstructive pulmonary disease, cystic fibrosis, asthma, and radiation-induced lung injury. The strengths and challenges of the application of (3)He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques., (Copyright © 2010 Wiley-Liss, Inc.)

We aimed to evaluate the potential for the use of hyperpolarized helium-3 magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) surrogates of alveolar size, together with literature-based morphological parameters in a theoretical model of lung mechanics to simulate noninvasive transpulmonary pressure-volume curves. Fourteen ex-smokers with chronic obstructive pulmonary disease (COPD) (n = 8 stage II, n = 6 stage III/IV COPD) and five age-matched never-smokers, provided written, informed consent and were evaluated at baseline and 26 + or - 2 mo later (n = 15 subjects) using plethysmography, spirometry, and (3)He MRI at 3.0 T. Total lung capacity, residual volume, and literature-based morphological parameters were used with alveolar volumes derived from (3)He ADC to simulate noninvasive pressure-volume curves. The resultant anterior-posterior transpulmonary pressure gradient was significantly decreased for stage II COPD (P < 0.01) and stage III COPD subjects (P < 0.001) compared with healthy volunteers. Both COPD subgroups showed increased alveolar radius compared with healthy subjects (P < 0.01, stage II COPD; P < 0.001, stage III COPD). In addition, surface area and surface tension were significantly increased in stage III COPD compared with healthy volunteers (P < 0.01). These results suggest that (3)He MRI provides a potential noninvasive approach to evaluate lung mechanics regionally and further supports the use of ADC values as a regional noninvasive probe of pulmonary microstructure and compliance.

Purpose: To quantitatively evaluate a small pilot group of ex-smokers with chronic obstructive pulmonary disease (COPD) and healthy volunteers during approximately 2 years by using hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging., Materials and Methods: All subjects provided written informed consent to the study protocol, which was approved by the local research ethics board and Health Canada and was compliant with the Personal Information Protection and Electronic Documents Act and HIPAA. Hyperpolarized (3)He MR imaging, hydrogen 1 MR imaging, spirometry, and plethysmography were performed in 15 ex-smokers with COPD and five healthy volunteers (with the same mean age and age range) at baseline and 26 months +/- 2 (standard deviation) later. Apparent diffusion coefficients (ADCs) derived from (3)He MR imaging were calculated from diffusion-weighted (3)He MR images, and (3)He ventilation defect volume (VDV) and ventilation defect percentage (VDP) were generated after manual segmentation of (3)He MR spin-density images., Results: For subjects with COPD, significant increases in (3)He MR imaging-derived VDV (P = .03), VDP (P = .006), and ADC (P = .02) were detected, whereas there was no significant change in forced expiratory volume in 1 second (FEV(1)) (P = .97). For healthy never-smokers, there was no significant change in imaging or pulmonary function measurements at follow-up. There was a significant correlation between changes in FEV(1) and changes in VDV (r = -0.70, P = .02) and VDP (r = -0.70, P = .03)., Conclusion: For this small pilot group of ex-smokers with COPD, (3)He MR imaging-derived VDV, VDP, and ADC measurements worsened significantly, but there was no significant change in FEV(1), suggesting increased sensitivity of hyperpolarized (3)He MR imaging for depicting COPD changes during short time periods.

Purpose: To quantitatively evaluate local carotid arterial statin effects in 3D US images using multiclassifier image texture analysis tools., Methods: Texture analysis tools were used to evaluate the effect of 80 mg atorvastatin administered daily to patients with carotid stenosis compared to those treated with placebo. Using three-dimensional carotid ultrasound images, 270 texture features from seven texture techniques were extracted from manually segmented carotid arteries based on the intima-media boundary [vessel wall (VW)]. Individual texture features were compared to the previously determined changes in VW volume (VWV) using the distance between classes, the Wilcoxon rank sum test, and accuracy of the classifiers. Texture features that resulted in maximal classification accuracy from each texture technique were selected using Pudil's sequential floating forward selection (SFFS) as a method of ranking each technique. Finally, SFFS-selected texture features from all texture techniques were used in combination with 24 classifier fusion techniques to improve classification accuracy., Results: Using the measurement of change in VWV, the distance between classes (DBC), Wilcoxon rank sum (WRS) p-value, and median accuracy measures (ACC) were 0.3798, 0.076, and 54.50%, respectively. Texture features improved the detection of statin-related changes using DBC to 0.5199, using WRS to 0.002, and ACC to 63.87%, respectively. The texture techniques that most differentiated between atorvastatin and placebo classes were Fourier power spectrum and Laws texture energy measures. The average classification accuracy between atorvastatin and placebo classes was improved from 57.22 +/- 12.11% using VWV to 97.87 +/- 3.93% using specific texture features. Furthermore, the use of specific texture features resulted in the average area under the receiver-operator characteristic curve (AUC) a value of 0.9988 +/- 0.0069 compared to 0.617 +/- 0.15 using carotid VWV., Conclusions: Based on DBC, WRS, ACC, and AUC texture features derived from 3D carotid ultrasound were observed to be more sensitive in detecting statin-related changes in carotid atherosclerosis than VWV suggesting that texture classifiers can be used to detect changes in carotid atherosclerosis after therapy.

Background: It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis., Methods and Results: In a 2-year Dietary Intervention Randomized Controlled Trial-Carotid (DIRECT-Carotid) study, participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness, measured with standard B-mode ultrasound, and carotid vessel wall volume (VWV), measured with carotid 3D ultrasound. Of 140 complete images of participants (aged 51 years; body mass index, 30 kg/m(2); 88% men), higher baseline carotid VWV was associated with increased intima-media thickness, age, male sex, baseline weight, blood pressure, and insulin levels (P<0.05 for all). After 2 years of dietary intervention, we observed a significant 5% regression in mean carotid VWV (-58.1 mm(3;) 95% confidence interval, -81.0 to -35.1 mm(3); P<0.001), with no differences in the low-fat, Mediterranean, or low-carbohydrate groups (-60.69 mm(3), -37.69 mm(3), -84.33 mm(3), respectively; P=0.28). Mean change in intima-media thickness was -1.1% (P=0.18). A reduction in the ratio of apolipoprotein B(100) to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group (P=0.001). Participants who exhibited carotid VWV regression (mean decrease, -128.0 mm(3); 95% confidence interval, -148.1 to -107.9 mm(3)) compared with participants who exhibited progression (mean increase, +89.6 mm(3); 95% confidence interval, +66.6 to +112.6 mm(3)) had achieved greater weight loss (-5.3 versus -3.2 kg; P=0.03), greater decreases in systolic blood pressure (-6.8 versus -1.1 mm Hg; P=0.009) and total homocysteine (-0.06 versus +1.44 mumol/L; P=0.04), and a higher increase of apolipoprotein A1 (+0.05 versus -0.00 g/L; P=0.06). In multivariate regression models, only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV (beta=0.23; P=0.01) and intima-media thickness (beta=0.28; P=0.008) levels., Conclusions: Two-year weight loss diets can induce a significant regression of measurable carotid VWV. The effect is similar in low-fat, Mediterranean, or low-carbohydrate strategies and appears to be mediated mainly by the weight loss-induced decline in blood pressure. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00160108.

Purpose: Therapeutic radiation doses for thoracic tumors are significantly restricted to decrease the risk of nontumor tissue damage, yet radiation-induced lung injury (RILI) still occurs in over 1/3 of thoracic radiation treatment cases. Although RILI can be clinically monitored using pulmonary function measurements, the regional functional effects of the injury are not well understood. Hyperpolarized 3He magnetic resonance imaging provides measurements of regional lung function and structure with high spatial and temporal resolution; the authors use this tool longitudinally for the first time in seven subjects after clinical diagnosis of RILI in order to better understand regional changes in lung function and structure post-RILI., Methods: All subjects underwent spirometry, plethysmography, and MRI at 3.0 T 35.1 +/- 12.2 weeks after radiation therapy commenced. Thoracic 1H, static 3He ventilation, and 3He diffusion-weighted images were acquired to generate the 3He apparent diffusion coefficient (ADC) and 3He percent ventilated volume (PVV). Four subjects returned 22.0 +/- 0.8 weeks after baseline imaging for follow-up spirometry and 3He MRI measurements of ADC and PVV., Results: At baseline, PVV was significantly different (p = 0.025) and lower in the ipsilateral diseased lung (55 +/- 29%) compared to the contralateral nondiseased lung (88 +/- 5%). Longitudinally, significant increases were observed for 3He MRI PVV (16% +/- 6%, p = 0.012) and 3He MRI ADC (0.02 +/- 0.01 cm2/s, p = 0.003) in the contralateral lung only, in the four subjects who returned for follow-up, while no changes in the ipsilateral lung were reported., Conclusions: Hyperpolarized 3He MRI was well tolerated in all subjects with moderate to severe RILI. Functional improvements and microstructural changes were observed in the contralateral lung, while the ipsilateral lung remained stable, suggesting that functional compensatory changes may have occurred in the contralateral lung due to ipsilateral lung radiation-induced injury.

Quantitative measurements of the progression (or regression) of carotid plaque burden are important in monitoring patients and evaluating new treatment options. We previously developed a quantitative metric to analyze changes in carotid plaque morphology from 3-D ultrasound (US) on a point-by-point basis. This method requires multiple segmentations of the arterial wall and lumen boundaries to obtain the local standard deviation (SD) of vessel-wall-plus-plaque thickness (VWT) so that t-tests could be used to determine whether a change in VWT is statistically significant. However, the requirement for multiple segmentations makes clinical trials laborious and time-consuming. Therefore, this study was designed to establish the relationship between local segmentation SD and local signal difference on the arterial wall and lumen boundaries. We propose metrics to quantify segmentation SD and signal difference on a point-by-point basis, and studied whether the signal difference at arterial wall or lumen boundaries could be used to predict local segmentation SD. The ability to predict the local segmentation SD could eliminate the need of repeated segmentations of a 2-D transverse image to obtain the local segmentation standard deviation, thereby making clinical trials less laborious and saving time. Six subjects involved in this study were associated with different degrees of atherosclerosis: three carotid stenosis subjects with mean plaque area >3 cm(2) and >60% carotid stenosis were involved in a clinical study evaluating the effect of atorvastatin, a cholesterol-lowering and plaque-stabilizing drug; and three subjects with carotid plaque area >0.5 cm(2) were subjects with moderate atherosclerosis. Our results suggest that when local signal difference is higher than 8 greyscale value (GSV), the local segmentation SD stabilizes at 0.05 mm and is thus predictable. This information provides a target value of local signal difference on the arterial boundaries that should be achieved to obtain an accurate prediction of local segmentation SD. (E-mail: bcychiu@alumni.uwo.ca).

This study was designed to evaluate 3-D ultrasound (3DUS)-derived vessel wall volume (VWV), a 3-D measurement of the carotid artery intima and media, including atherosclerotic plaque, in patients enrolled in a randomized placebo-controlled three-month study of intensive atorvastatin treatment. Thirty-five subjects with carotid stenosis >60% who provided written informed consent and completed a randomized, double-blind, placebo-controlled study were evaluated at baseline and at three months after receiving either 80 mg atorvastatin (16 subjects, nine male, mean age 68+/-8.6 y) or placebo (19 subjects, 15 male, mean age 70+/-9.4 y) daily. 3DUS images were acquired and 3DUS VWV was manually segmented by a single observer. Individual lumen and wall segmentation contours were also used to generate carotid atherosclerosis thickness difference maps by establishing correspondence between points along the vessel wall and lumen segmentation contour surfaces, and digitally subtracting registered baseline and follow-up thickness maps. 3DUS VWV increased by 70+/-140 mm(3) (+4.9+/-10.3%) in the placebo group and decreased by 30+/-110 mm(3) (-1.4+/-7.7%) in the atorvastatin group (p<0.05). Two-dimensional maps generated from the VWV measurements show localized heterogeneity and vessel wall thickness changes for all subjects, mainly in the common carotid artery. Carotid 3DUS VWV is a quantitative measure of atherosclerosis burden including the intima, media and plaque, with sensitivity to detect changes over short periods of time. Quantitative VWV thickness difference maps provide visual evidence of the spatial and temporal dynamics of carotid artery changes.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by both small airway and parenchymal abnormalities. There is increasing evidence to suggest that these two morphologic phenotypes, although related, may have different clinical presentations, prognosis, and therapeutic responses to medications. With the advent of novel imaging modalities, it is now possible to evaluate these two morphologic phenotypes in large clinical studies using noninvasive or minimally invasive methods such as computed tomography (CT), magnetic resonance imaging (MRI), and optical coherence tomography (OCT). In this article, we provide an overview of these imaging modalities in the context of COPD and discuss their strengths as well as their limitations for providing quantitative COPD phenotypes.

Quantitative measurements of carotid atherosclerosis can be determined using three-dimensional ultrasound (3DUS). This pilot study involved the development of prospective cardiac gating of 3DUS carotid images to reduce cardiac cycle-derived arterial pulsatility. The method developed uses electrocardiograph signal detection of the cardiac cycle R wave with imaging acquisition delayed in time (deltat) after the R wave is detected. Pulsatility of the common carotid artery was measured by calculating the mean percentage change in arterial cross-sectional area (%deltaA) in moderate atherosclerosis (MA) patients (12% +/- 1%) and healthy volunteers (HVs) (16% +/- 3%) and found that %deltaA was significantly higher for HV than for MA (p = 0.016) when no cardiac gating was used. The cardiac gating method was tested with deltat = 250 ms and deltat = 400 ms in young healthy volunteers and rheumatoid arthritis (RA) patients. For all 3DUS measurements acquired without gating, there was a significant association between %deltaA and age (r2 = 0.20, p = 0.035), and mean %deltaA (in HV and RA) was 13% +/- 5% [95% confidence interval (CI) = 10%-17%]. For deltat = 250 ms mean %deltaA was significantly different and decreased to 7% +/- 3% (95% CI = 5%-10%) and for deltat = 400 ms it was significantly different and decreased to 6% +/- 1% (95% CI = 6%-7%) (p = 0.001 for both comparisons). There was no significant difference in mean %deltaA between gating conditions (p = 0.8); however, the 95% CI for %deltaA was decreased for deltat = 400 ms as compared to deltat = 250 ms. Both gating methods also significantly decreased %deltaA to below the reference standard of 12% +/- 1% for MA (p < 0.01 for both comparisons), suggesting that prospective cardiac gating of carotid 3DUS reduces pulsatility effects in HV and RA to levels lower than observed for much older MA patients.

Purpose: To evaluate differences in carotid atherosclerosis measured using magnetic resonance imaging (MRI) and three-dimensional ultrasound (3DUS)., Materials and Methods: Ten subject volunteers underwent carotid 3DUS and MRI (multislice black blood fast spin echo, T1-weighted contrast, double inversion recovery, 0.5 mm in-plane resolution, 2 mm slice, 3.0 T) within 1 hour. 3DUS and MR images were manually segmented by two observers providing vessel wall and lumen contours for quantification of vessel wall volume (VWV) and generation of carotid thickness maps., Results: MRI VWV (1040 +/- 210 mm(3)) and 3DUS VWV (540 +/- 110 mm(3)) were significantly different (P < 0.0001). When normalized for the estimated adventitia volume, mean MRI VWV decreased 240 +/- 50 mm(3) and was significantly different from 3DUS VWV (P < 0.001). Two-dimensional carotid maps showed qualitative evidence of regional differences in the plaque and vessel wall thickness between MR and 3DUS in all subjects. Power Doppler US confirmed that heterogeneity in the common carotid artery in all patients resulted from apparent flow disturbances, not atherosclerotic plaque., Conclusion: MRI and 3DUS VWV were significantly different and carotid maps showed homogeneous thickness differences and heterogeneity in specific regions of interest identified as MR flow artifacts in the common carotid artery.

Carotid plaque surface irregularity and ulcerations play an important role in the risk of ischemic stroke. Ulcerated or fissured plaque, characterized by irregular surface morphology, exposes thrombogenic materials to the bloodstream, possibly leading to life- or brain-threatening thrombosis and embolization. Therefore, the quantification of plaque surface irregularity is important to identify high-risk plaques that would likely lead to vascular events. Although a number of studies have characterized plaque surface irregularity using subjective classification schemes with two or more categories, only a few have quantified surface irregularity using an objective and continuous quantity, such as Gaussian or mean curvature. In this work, our goal was to use both Gaussian and mean curvatures for identifying ulcers from 3D carotid ultrasound (US) images of human subjects. Before performing experiments using patient data, we verified the numerical accuracy of the surface curvature computation method using discrete spheres and tori with different sampling intervals. We also showed that three ulcers of the vascular phantom with 2 mm, 3 mm and 4 mm diameters were associated with high Gaussian and mean curvatures, and thus, were easily detected. Finally, we demonstrated the application of the proposed method for detecting ulcers on luminal surfaces, which were segmented from the 3D US images acquired for two human subjects.

The aim of this study was to compare the sensitivity of three ultrasound phenotypes of carotid atherosclerosis in a longitudinal study of patients with diabetic nephropathy. B-mode ultrasound-derived intima-media thickness (IMT), total plaque area (TPA) as well as three-dimensional ultrasound (3DUS) vessel wall volume (VWV) of the common carotid artery (CCA) (VWV(CCA)) and internal carotid artery (ICA). (VWV(CCA+ICA)) were all evaluated in subjects enrolled in a randomized placebo-controlled double blind study of vitamin B therapy. Of 106 subjects randomized, 77 subjects were scanned at baseline and 2.3 +/- 1 y later (range: 0.5 to 4.5 y); of these subjects, 71 had images of sufficient quality for complete analysis of all three measurements. Subjects were analyzed according to the two treatment groups (A and B) and the analysis was performed blinded to treatment group description to prevent any potential for bias in future analyses. There were differences in sensitivity to longitudinal changes observed in all the ultrasound measurements. Specifically, there was no difference in IMT change between treatment groups (0.02 +/- 0.07 mm/y and 0.02 +/- 0.1 mm/y p = 0.15, group A and B, respectively, rates not different from zero [p > 0.05]) or TPA rate between treatment groups (0.09 +/- 0.2 cm(2)/y, significantly different from 0, p = 0.013 and -0.02 +/- 0.3 cm(2)/y in group A and B, respectively). However, the VWV(CCA+ICA) rate of change was significantly greater than 0 for group B (53 +/- 110 mm(3)/y) (p = 0.008), which was significantly (p = 0.034) higher than the rate of change of VWV(CCA+ICA) (nonsignificant, p = 0.6) for group A (-12 +/- 137 mm(3)/y). The relationship between DeltaVWV and DeltaIMT was significant, such that in group A, DeltaVWV(CCA) was positively associated with DeltaIMT (r = 0.44, p < 0.05), and in group B, DeltaVWV(CCA) was negatively correlated with DeltaIMT (r = -0.44, p < 0.01). These results suggest that 3DUS-derived VWV provides necessary and sufficient sensitivity and specificity to measure longitudinal changes in small numbers of carotid atherosclerosis patients at risk of disease progression and over short periods of time.

Atherosclerosis at the carotid bifurcation can result in cerebral emboli, which in turn can block the blood supply to the brain causing ischemic strokes. Noninvasive imaging tools that better characterize arterial wall, and atherosclerotic plaque structure and composition may help to determine the factors which lead to the development of unstable lesions, and identify patients at risk of plaque disruption and stroke. Carotid magnetic resonance (MR) imaging allows for the characterization of carotid vessel wall and plaque composition, the characterization of normal and pathological arterial wall, the quantification of plaque size, and the detection of plaque integrity. On the other hand, various ultrasound (US) measurements have also been used to quantify atherosclerosis, carotid stenosis, intima-media thickness, total plaque volume, total plaque area, and vessel wall volume. Combining the complementary information provided by 3D MR and US carotid images may lead to a better understanding of the underlying compositional and textural factors that define plaque and wall vulnerability, which may lead to better and more effective stroke prevention strategies and patient management. Combining these images requires nonrigid registration to correct the nonlinear misalignments caused by relative twisting and bending in the neck due to different head positions during the two image acquisition sessions. The high degree of freedom and large number of parameters associated with existing nonrigid image registration methods causes several problems including unnatural plaque morphology alteration, high computational complexity, and low reliability. Thus, a "twisting and bending" model was used with only six parameters to model the normal movement of the neck for nonrigid registration. The registration technique was evaluated using 3D US and MR carotid images at two field strengths, 1.5 and 3.0 T, of the same subject acquired on the same day. The mean registration error between the segmented carotid artery wall boundaries in the target US image and the registered MR images was calculated using a distance-based error metric after applying a "twisting and bending" model based nonrigid registration algorithm. An average registration error of 1.4 +/- 0.3 mm was obtained for 1.5 T MR and 1.5 +/- 0.4 mm for 3.0 T MR, when registered with 3D US images using the nonrigid registration technique presented in this paper. Visual inspection of segmented vessel surfaces also showed a substantial improvement of alignment with this nonrigid registration technique compared to rigid registration.

Carotid atherosclerosis measurements for eight subjects at baseline and 14 +/- 2 days later were examined using 1.5 T and 3.0 T magnetic resonance imaging (MRI). A single observer blinded to field strength, subject and timepoint manually segmented carotid artery wall and lumen boundaries in randomized images in five measurement trials. Mean increases in the signal-to-noise ratios (SNR) for T1-weighted images acquired at 3.0 T compared to 1.5 T were 90% (scan) and 80% (rescan). Despite significantly improved SNR and contrast-to-noise ratios (CNR) for images acquired at 3.0 T, vessel wall volume (VWV) intra-observer variability was not significantly different using coefficients of variation (COV), and intraclass correlation coefficients (ICC). VWV interscan variability and consistency at both field strengths were not statistically different (1.5 T/3.0 T COV = 5.7%/7.8%, R(2) = 0.96 for 1.5 T and R(2) = 0.87 for 3.0 T). A two-way analysis of variance showed a VWV dependence on field strength but not scan timepoint. In addition, a paired t-test showed significant differences in VWV measured at 3.0 T as compared to 1.5 T. These results suggest that although images acquired at 1.5 T have lower SNR and CNR VWV, measurement variability was not significantly different from 3.0 T VWV and that VWV is field-strength dependent which may be an important consideration for longitudinal studies.

Quantitative measurements of the progression (or regression) of carotid plaque burden are important in monitoring patients and evaluating new treatment options. 3D ultrasound (US) has been used to monitor the progression of carotid artery plaques in symptomatic and asymptomatic patients, and different methods of measuring various ultrasound phenotypes of atherosclerosis have been developed. We have developed a quantitative metric used to analyze changes in carotid plaque morphology from 3D US. This method matched the vertices on the carotid arterial wall surface with those on the luminal surface. Vessel-wall-plus-plaque thickness (VWT) was obtained by computing the distance between each corresponding pair, which was then superimposed on the arterial wall to produce the VWT map. Since the progression of plaque thickness is important in monitoring patients who are at risk for stroke, we also computed the change of VWT by comparing the VWT maps obtained for a patient at two different time points. In this paper, we propose a technique to flatten the 3D VWT and VWT-Change maps in an area-preserving manner, in order to facilitate the visualization and interpretation of these maps.

Rationale and Objectives: We assessed subjects with stage II and stage III chronic obstructive pulmonary disease (COPD) and age-matched healthy volunteers at a single center using (3)He magnetic resonance imaging (MRI) at 3.0 T. Measurements of the (3)He apparent diffusion coefficient (ADC) and center coronal slice (3)He ventilation defect volume (VDV) were examined for same-day and 7-day reproducibility as well as subgroup comparisons., Materials and Methods: Twenty-four subjects who provided written informed consent (15 males; mean age 67 +/-7 years) with stage II (n = 9), stage III COPD (n = 7), and age-matched healthy volunteers (n = 8) were enrolled based on their age and pulmonary function test results. All subjects underwent plethysmography, spirometry, and MRI at 3.0 T. The time frame between scans was 7 +/- 2 minutes (same-day rescan) and again 7 +/- 2 days later (7-day rescan). (3)He ADC and VDV reproducibility was evaluated using linear regression, intraclass correlation coefficients (ICC) and Lin's concordance correlation coefficients (CCC)., Results: ADC reproducibility was high for same-day rescan (r(2) = 0.934) and 7-day rescan (r(2) = 0.960, ICC and CCC of 0.96 and 0.98, respectively). Same-day rescan VDV reproducibility evaluated using the ICC and CCC (0.97 and 0.98, respectively) as well as linear regression (r(2) = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r(2) = 0.576, P < .001, ICC 0.74, CCC 0.75, P < .01)., Conclusions: Hyperpolarized (3)He MRI was well-tolerated in subjects with stage II and stage III COPD. Seven-day repeated scanning was highly reproducible for ADC and moderately reproducible for VDV.

Objective: We compared the intraobserver and interscan variability of carotid atherosclerosis measured using B-mode ultrasound for quantifying intima media thickness (IMT), 3-dimensional ultrasound (3DUS) for quantifying vessel wall volume (VWV) and total plaque volume (TPV), and magnetic resonance imaging (MRI) for measuring VWV. We also evaluated the associations of these measurements and sample sizes required to detect specific changes in patients with moderate atherosclerosis., Methods: Ten patients were evaluated with B-mode ultrasound, MRI, and 3DUS twice within 14 +/- 2 days. Measurements of IMT, MRI VWV, 3DUS VWV, and 3DUS TPV were performed by single observers using manual (VWV and TPV) and semiautomated (IMT) segmentation., Results: Intraobserver coefficients of variation were 3.4% (IMT), 4.7% (3DUS VWV), 6.5% (MRI VWV), and 23.9% (3DUS TPV). Interscan coefficients of variation were 8.1% (MRI VWV), 8.9% (IMT), 13.5% (3DUS VWV), and 46.6% (3DUS TPV). Scan-rescan linear regressions were significant for 3DUS TPV (R(2) = 0.57), 3DUS VWV (R(2) = 0.59), and IMT (R(2) = 0.75) and significantly different (P < .05) for MRI VWV (R(2) = 0.87)., Conclusions: B-mode ultrasound-derived IMT provided the highest intraobserver and interscan reproducibility. Three-dimensional measurements of VWV derived from 3DUS and MRI provided both high sensitivity and high intraobserver and interscan reliability.

Quantitative measurements of carotid plaque burden progression or regression are important in monitoring patients and in evaluation of new treatment options. 3D ultrasound (US) has been used to monitor the progression or regression of carotid artery plaques. This paper reports on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US. The technique used is evaluated using manual segmentations of the arterial wall and lumen from 3D US images acquired in two imaging sessions. To reduce the effect of segmentation variability, segmentation was performed five times each for the wall and lumen. The mean wall and lumen surfaces, computed from this set of five segmentations, were matched on a point-by-point basis, and the distance between each pair of corresponding points served as an estimate of the combined thickness of the plaque, intima, and media (vessel-wall-plus-plaque thickness or VWT). The VWT maps associated with the first and the second US images were compared and the differences of VWT were obtained at each vertex. The 3D VWT and VWT-Change maps may provide important information for evaluating the location of plaque progression in relation to the localized disturbances of flow pattern, such as oscillatory shear, and regression in response to medical treatments.

We measured hyperpolarized 3He magnetic resonance imaging (MRI) apparent diffusion coefficients (ADC) and quantified ADC gradients in each three-by-three voxel region of interest (ROI). Such local ADC gradients can be represented in vector maps showing the magnitude (|G3x3|) and direction of ADC gradients, providing a qualitative visualization tool and quantitative measurement of airway and air space heterogeneity. Twenty-four subjects (15 male, mean age=67+/-7 yr) with global initiative for chronic obstructive lung disease (GOLD) stage II (n=9, mean age 68+/-6 yr), GOLD stage III chronic obstructive pulmonary disease (COPD; n=7, mean age 67+/-8 yr), and age-matched healthy volunteers (n=8, mean age 67+/-6 yr) were enrolled based on their age and spirometry results. Hyperpolarized 3He MRI was performed on a whole body 3.0 Tesla system. Mean 3He ADC and ADC standard deviation were calculated for the center coronal slice, and the mean magnitude and direction of the ADC gradient vectors were calculated for each three-by-three voxel matrix (|G3x3|). While the 3He ADC standard deviation was not significantly different, mean |G3x3| was significantly different between subjects with stage II (0.14+/-0.03 cm/s) and stage III COPD (0.19+/-0.03 cm/s; P<0.005) and between healthy subjects (0.12+/-0.03 cm/s) and those with stage II COPD (P<0.02). The second order statistic |G3x3| may provide a sensitive measure of ADC heterogeneity for ROI representing 9.4x9.4x30 mm or 2.6 cm3 of lung tissue.

Rationale and Objectives: Hyperpolarized (3)He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified (3)He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders., Materials and Methods: Hyperpolarized (3)He magnetic resonance imaging ventilation defect volume (VDV) and ventilation defect score (VDS) were assessed in eight elderly healthy volunteers (mean 67+/-6 years) scanned twice within 7+/-2 minutes and again 7+/-2 days later. A younger cohort of 24 subjects (mean 44+/-10 years) was also scanned for direct comparison. Four observers blinded to scan timepoint and subject identity scored VDS and manually segmented VDV in all center coronal slices., Results: Center coronal slice ventilation defects were observed in six of eight elderly subjects (ages 63-74 years, 5 males) in all scans acquired and in no middle-aged subjects. At the scan timepoint, mean VDS was 2.7 (mean VDV 52+/-34 cm(3)), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53+/-35 cm(3)) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48+/-39 cm(3)). Interscan coefficients of variation (COV) for mean VDV was 1.8% (same-day rescan) and 5.3% (7-day rescan) and interobserver COV ranged from 10-12%., Conclusion: Elderly subjects have ventilation defects that are reproducible in same-day scanning and 7-day scanning visits. The observation of reproducible pulmonary ventilation defects in otherwise healthy elderly volunteers suggests caution must be used in interpreting results from (3)He studies of elderly subjects.

This study was designed to evaluate changes in carotid atherosclerosis using plaque and wall thickness maps derived from three-dimensional ultrasound (3DUS) images. Five subjects with carotid stenosis were scanned at baseline and 3 mo as part of a placebo-controlled intensive statin treatment study and three subjects with moderate atherosclerosis were scanned at baseline and again within 14 +/- 2 d. 3DUS-derived vessel wall volume (VWV) was measured using manual segmentation to provide segmentation contours that were used to generate scan and rescan carotid atherosclerosis thickness maps and thickness difference maps. There was no significant difference in VWV between scan and rescan for the three subjects scanned twice in 2 wk or the single subject treated with placebo. There was a significant difference between scan and rescan VWV for carotid stenosis subjects treated with atorvastatin (p < 0.001). Carotid atherosclerosis thickness difference maps showed visual qualitative evidence of thickness changes in vessel wall and plaque thickness in the common carotid artery for all statin-treated subjects and no change in a placebo-treated subject and subjects scanned twice in 2 wk. Carotid atherosclerosis thickness difference maps generated from 3DUS images provide evidence of vessel wall and plaque thickness changes for all subjects assessed.

Purpose: To evaluate the anatomical distribution of apparent diffusion coefficients (ADC) using hyperpolarized helium-3 (3He) MRI in chronic obstructive pulmonary disease (COPD)., Materials and Methods: Hyperpolarized 3He MRI was performed in eight healthy and seven COPD subjects under breathhold conditions in the supine position to determine ADC values from diffusion-weighted images and evaluate anterior-posterior (AP) and superior-inferior (SI) differences., Results: ADC differences between anterior and posterior slices, DeltaAP, was 0.06 +/-0.01 cm2/second for healthy volunteers and 0.04 +/-0.02 cm2/second for COPD subjects and was significant for each subject (P < 0.01). The AP ADC gradient was -3.98 x 10(-3) +/-0.59 cm2/second/cm for healthy volunteers and -2.04 x 10(-3) +/-0.89 cm2/second/cm for COPD subjects. The difference in ADC between superior and inferior regions of interest (ROIs), DeltaSI, was 0.02 +/-0.02 cm2/second for healthy volunteers and 0.10 +/-0.09 cm2/second for COPD subjects, which was significant for each subject (P < 0.05). The SI ADC gradient was -0.63 x 10(-3) +/-2.23 cm2/second/cm for healthy volunteers and -6.61 x 10(-3) +/-6.68 cm2/second/cm for COPD subjects. DeltaAP, AP-gradient, and SI-gradient were significantly different between healthy volunteers and COPD subjects (P < 0.05)., Conclusion: In all subjects, ADC anatomical differences were significant and mean ADC was dependent on anatomic location and disease status., ((c) 2007 Wiley-Liss, Inc.)

Carotid atherosclerotic lesions are a major cause of stroke and the identification and quantification of such lesions in patients is important for the development of a better understanding of atherogenesis in high risk populations and for the design of studies to assess treatment efficacy. Our objective was to develop and validate a new three-dimensional ultrasound (3DUS) measurement or phenotype of carotid atherosclerosis, vessel wall volume (VWV), which is a three-dimensional measurement of vessel wall thickness and plaque within the carotid arteries measured in 3DUS images. To assess both intraobserver and interscan variability, 3DUS images were acquired from the right and left carotid arteries of ten subjects with carotid atherosclerosis scanned twice within a period of 2 wk. For both VWV and total plaque volume (TPV), an expert observer performed five measurement trials of all images acquired at baseline scan and 2-wk rescan with a 5-d period between measurement trials for images. Images were re-randomized for each measurement trial and both TPV and VWV were measured by observers who were blinded to subject identification for each time-point measurement. Coefficients of variation (COV) and intraclass correlation coefficients (ICC), for VWV measurements indicated higher intraobserver (scan COV = 4.6% ICC = 0.95, rescan COV = 3.4%, ICC = 0.96) and interscan reproducibility (COV = 5.7%, ICC = 0.85) than TPV measurements (intraobserver variability scan COV = 22.7% ICC = 0.85, rescan COV = 21.1% ICC = 0.88 and interscan variability, COV = 31.1%, ICC = 0.83), although absolute variances for both phenotypes were very similar (VWV = 90 mm3, TPV = 80 mm3).

Objective: Hyperpolarized 3He magnetic resonance imaging (3He MRI) at 3.0 Tesla of healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was performed for quantitative evaluation of ventilation defects and apparent diffusion coefficients (ADC) and for comparison to published results acquired at 1.5 Tesla. The reproducibility of 3He ADC and ventilation defects was also assessed in subjects scanned 3 times, twice within 10 minutes, and again within 7 +/- 2 days of the first MRI visit., Materials and Methods: Hyperpolarized 3He MRI was performed in 6 subjects. Two interleaved images with and without additional diffusion sensitization were acquired with the first image serving as a ventilation image from which defect score and volume were measured and the combination of the 2 images used to compute ADC maps and ADC histograms., Results: He MRI at 3.0 Tesla showed increased mean ADC and ADC standard deviation for subjects with COPD compared with healthy volunteers (ADC healthy volunteer (0.24 +/- 0.12 cm2/s), mild-moderate COPD (0.34 +/- 0.14 cm2/s), and severe COPD (0.47 +/- 0.21 cm2/s), and these values were similar to previously reported results acquired at 1.5 Tesla. Reproducibility of mean ADC was high (coefficient of variation 2% in severe COPD, 3% in mild-moderate COPD, 4% in healthy volunteers) across all 3 scans. Higher same-day scan reproducibility was observed for ventilation defect volume compared with 1-week scan reproducibility in this small group of subjects., Conclusions: ADC values for emphysematous lungs were significantly increased compared with healthy lungs in age-matched subjects, and all values were comparable to those reported previously at 1.5 Tesla. Ventilation defect score and ventilation defect volume results were also comparable to results previously reported in COPD subjects Reproducibility of ADC for same-day scan-rescan and 7-day rescan was high and similar to previously reported results.

Background: Biomarkers of carotid atherosclerosis range from those that are widely available and relatively simple to measure such as serum cholesterol levels, and B-mode Ultrasound measurement of intima media thickness (IMT) to those that are more complex and technologically demanding but perhaps potentially more sensitive and specific to disease such as total plaque volume and total plaque area measured from 3-dimensional ultrasound images. In this study we measured and compared intima media thickness (IMT), total plaque volume (TPV) and total plaque area (TPA) in two separate populations, both vulnerable to carotid atherosclerosis., Methods: In total, 88 subjects (mean age 72.8) with carotid stenosis of at least 60%, based on a peak Doppler flow, and 82 subjects (mean age 60.9) with diabetic nephropathy were assessed in a cross-sectional study. Conventional atherosclerotic risk factors were examined and the associations and correlations between these and carotid ultrasound phenotypes measured from B-mode and 3-dimensional ultrasound images were assessed., Results: IMT and TPV were only modestly correlated in the two separate populations (r = .6, p < .01). ANOVA analyses indicated that both IMT and TPV were significantly associated with age (p < .001) and Framingham score (p < .05), but only TPV was associated with diabetes (p < .001) and presence of plaque ulcerations (p < .01), Conclusion: IMT and TPV were modestly correlated in a diabetic patient population and only TPV was associated with diabetes and the presence of plaque ulcerations in a diabetic population and carotid stenosis group. The 3-dimensional information provided by TPV can be critically important in unmasking association with risk factors not observed with less complex single-dimension assessments of carotid atherosclerosis such as those provided by IMT.

Atherosclerosis is an inflammatory process similar to scar formation in the inner wall of the artery. It is the underlying cause of heart attacks and some strokes. Atherosclerotic lesions in the artery wall are called plaques. 3D ultrasound (US) has been used to monitor the progression of carotid vessel plaques in symptomatic and asymptomatic patients. Different ways of measuring various ultrasound phenotypes of atherosclerosis have been developed. Here, we report on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US. In an effort to extend our previous work in plaque thickness analysis, we developed a procedure that facilitates the visualization and comparison of the distribution of plaque thickness by mapping the 3D arterial structure into a 2D plane.

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)