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Biomedical subjects

John P Mugler

Publications and source records attributed to John P Mugler.

15 recordsLinked to original sources

Evaluation of emphysema severity and progression in a rabbit model: comparison of hyperpolarized 3He and 129Xe diffusion MRI with lung morphometry.

The apparent diffusion coefficients (ADCs) of hyperpolarized (3)He and (129)Xe gases were measured in the lungs of rabbits with elastase-induced emphysema and correlated against the mean chord length from lung histology. In vivo measurements were performed at baseline and 2, 4, 6, and 8 wk after instillation of elastase (mild and moderate emphysema groups) or saline (control group). ADCs were determined from acquisitions that used two b values. To investigate the effect of b value on the results, b-value pairs of 0 and 1.6 s/cm(2) and 0 and 4.0 s/cm(2) were used for (3)He, and b-value pairs of 0 and 5.0 s/cm(2) and 0 and 10.0 s/cm(2) were used for (129)Xe. At 8 wk after instillation, the rabbits were euthanized, and the lungs were analyzed histologically and morphometrically. ADCs for the rabbits in the control group did not change significantly from baseline to week 8, whereas ADCs for the rabbits in the emphysema groups increased significantly (P < 0.05) for all gas and b-value combinations except (129)Xe with the b-value pair of 0 and 5.0 s/cm(2). The largest percent change in mean ADC from baseline to week 8 (15.3%) occurred with (3)He and the b-value pair of 0 and 1.6 s/cm(2) for rabbits in the moderate emphysema group. ADCs (all b values) were strongly correlated (r = 0.62-0.80, P < 0.001) with mean chord lengths from histology. These results further support the ability of diffusion-weighted MRI with hyperpolarized gases to detect regional and global structural changes of emphysema within the lung.

Animals↗

Human gray matter: feasibility of single-slab 3D double inversion-recovery high-spatial-resolution MR imaging.

The purpose of this study was to develop and prospectively evaluate the feasibility of a single-slab three-dimensional (3D) double inversion-recovery, or DIR, sequence for magnetic resonance imaging at 1.5 T. The study was approved by the local ethics committee, and informed consent was obtained from six healthy control subjects (one woman, five men; age range, 26-47 years) and two patients with multiple sclerosis (one woman, aged 39; one man, aged 56). Gray matter (GM)-only images were obtained by selectively suppressing cerebrospinal fluid (CSF) and white matter (WM) signals. Whole-brain high-spatial-resolution 3D images (1.2 x 1.2 x 1.3 mm) were acquired within 10 minutes. Cortical and deep GM structures were clearly delineated from WM and CSF, and there were regional differences in GM signal intensity. No flow artifacts from blood or CSF were observed. These GM images with high spatial resolution are suitable to identify cortical pathologic conditions and can potentially be used for segmentation purposes to determine cortical thickness or volume.

Adult↗

Detection of lesions in multiple sclerosis by 2D FLAIR and single-slab 3D FLAIR sequences at 3.0 T: initial results.

The aim of this study was to compare conventional 2D FLAIR and single-slab 3D FLAIR sequences in the detection of lesions in patients with multiple sclerosis. Eight patients with MS were examined at 3.0 T by using a 2D FLAIR sequence and a single-slab 3D FLAIR sequence. A comparison of lesion detectability was performed for the following regions: periventricular, nonperiventricular/juxtacortical and infratentorial. The contrast-to-noise ratios (CNRs) between lesions and brain tissue and CSF were calculated for each sequence. A total of 424 lesions were found using the 2D FLAIR sequence, while with the 3D FLAIR sequence 719 lesions were found. With the 2D FLAIR sequence, 41% fewer lesions were detected than with the 3D FLAIR sequence. Further, 40% fewer supratentorial and 62.5% fewer infratentorial lesions were found with the 2D FLAIR sequence. In images acquired with the 3D FLAIR sequence, the lesions had significantly higher CNRs than in images acquired with the 2D FLAIR sequence. These are the first results using a single-slab 3D FLAIR sequence at 3.0 T for detection of lesions in patients with MS. With the 3D FLAIR sequence significantly higher CNRs were achieved and significantly more lesions in patients with MS were detected.

Adult↗

Assessment of lung development using hyperpolarized helium-3 diffusion MR imaging.

PURPOSE: To determine whether hyperpolarized helium-3 (HHe) diffusion MR can detect the expected enlargement of alveoli that occurs with lung growth during childhood. MATERIALS AND METHODS: A total of 29 normal subjects aged four to 30 years underwent HHe diffusion MR imaging with the b-value pair 0, 1.6 second/cm(2). A second acquisition during a separate breathhold was performed using the b-value pair 0, 4 second/cm(2) to evaluate the dependence on b-value. The mean apparent diffusion coefficient (ADC) and lung volume for each acquisition and each subject was determined. RESULTS: Subjects as young as four years of age were able to cooperate with the imaging procedure. The mean ADC increased with increasing subject age (r = 0.8; P < 0.001), with a 55% increase in mean ADC from the youngest to oldest subject. Lung volumes measured on MR were highly repeatable for the two HHe MR acquisitions (r = 0.980, P < 0.001). The mean ADC values measured with the two different b-value pairs were highly correlated (r = 0.975; P < 0.001), but the higher b-value pair resulted in slightly lower mean ADCs (P < 0.001). CONCLUSION: HHe diffusion MR appears to detect the expected increase in alveolar size during childhood, and thus HHe MR may be a noninvasive method to assess development of the lung microstructure.

Adolescent↗

Time dependence of 3He diffusion in the human lung: measurement in the long-time regime using stimulated echoes.

A stimulated-echo-based technique was developed to measure the long-time-scale apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breath-hold acquisition. Computer simulations were used to evaluate the performance of the technique and guide the selection of appropriate parameter values for obtaining accurate ADC values. The technique was used in 10 healthy subjects and two subjects with chronic obstructive pulmonary disease (COPD) to measure the global ADC for diffusion times between a few tenths of a second and several seconds, and to acquire spatial maps of the ADC for a diffusion time of 1.5 s. The reproducibility of the technique and its sensitivity to the direction of diffusion sensitization were also investigated. In healthy subjects, global ADC values decreased by severalfold over the range of diffusion times measured (mean values = 0.039 and 0.023 cm2/s at diffusion times of 0.61 and 1.54 s, respectively). ADC maps were generally uniform, with mean values similar to the corresponding global values. For the two COPD subjects, global ADC values were substantially greater than those of every healthy subject at all diffusion times measured. In addition, regional elevations of ADC values were far more conspicuous on long-time-scale ADC maps than on short-time-scale ADC maps.

Adult↗

Evaluation of asthma with hyperpolarized helium-3 MRI: correlation with clinical severity and spirometry.

BACKGROUND: Accurate characterization of asthma severity is difficult due to the variability of symptoms. Hyperpolarized helium-3 MRI (H(3)HeMR) is a new technique in which the airspaces are visualized, depicting regions with airflow obstruction as "ventilation defects." The objective of this study was to compare the extent of H(3)HeMR ventilation defects with measures of asthma severity and spirometry. METHODS: Patients with a physician diagnosis of asthma and normal control subjects underwent H(3)HeMR. For each person, the number and size of ventilation defects were scored and the average number of ventilation defects per slice (VDS) was calculated. The correlations of the imaging findings with measures of asthma severity and spirometry were determined. RESULTS: There were 58 patients with asthma (mild-intermittent, n = 13; mild-persistent, n = 13; moderate-persistent, n = 20; and severe-persistent, n = 12) and 18 control subjects. Mean +/- SE VDS for asthmatics was significantly greater than for control subjects (0.99 +/- 0.15 vs 0.26 +/- 0.22, p = 0.004). Among asthmatics, VDS was significantly higher for the group with moderate-persistent and severe-persistent disease than for the group with mild-intermittent and mild-persistent disease (1.37 +/- 0.24 vs 0.53 +/- 0.12, p < 0.001). VDS correlated significantly with FEV(1)/FVC (r = - 0.51, p = 0.002), forced expiratory flow between 25% and 75% from the beginning of FVC (FEF(25-75%)) percentage of predicted for height, sex, and race (%predicted) [r = - 0.50, p = 0.001], and FEV(1) %predicted (r = - 0.40, p = 0.002), but not with FVC %predicted (r = - 0.26, p = 0.057) and peak expiratory flow %predicted (r = - 0.16, p = 0.231). Many asthmatics had an elevated VDS, but their spirometric indexes, except FEF(25%-75%), were normal. Most ventilation defects were < 3 cm in size for all asthmatics. In the group of patients with moderate-to-severe persistent asthma, there were more defects > or =3 cm than in the group with mild-intermittent and mild-persistent disease (p = 0.021). CONCLUSIONS: Regional changes of airflow obstruction in asthmatics depicted by H(3)HeMR correlate with measures of asthma severity and spirometry.

Adolescent↗

Hyperpolarized 3He lung imaging at 0.5 and 1.5 Tesla: a study of susceptibility-induced effects.

Hyperpolarized (3)He MRI of the human lung was performed at 0.54 and 1.5 T using identical software and hardware (except for RF coils) at both field strengths. The T(*) (2) of (3)He gas in the lung was measured, and the effects of magnetic-susceptibility-induced field inhomogeneities on the appearance of interleaved-spiral and interleaved-echo-planar lung images at 1.5 T were compared to those at 0.54 T. Mean T(*) (2) values for (3)He gas in the healthy human lung were 26.8 +/- 1.5 ms and 67.9 +/- 1.3 ms at 1.5 and 0.54 T, respectively. At 0.54 T, interleaved-spiral images showed markedly less blurring due to susceptibility effects compared to images acquired at 1.5 T. At both 0.54 and 1.5 T, interleaved-echo-planar images appeared essentially identical to corresponding GRE images, even though the data-sampling period per echo and echo time were substantially longer for the interleaved-echo-planar images acquired at 0.54 T.

Echo-Planar Imaging↗

Detection of age-dependent changes in healthy adult lungs with diffusion-weighted 3He MRI.

RATIONALE AND OBJECTIVES: To investigate changes in lung microstructure in healthy adult subjects with no smoking history using diffusion-weighted 3He MRI. MATERIALS AND METHODS: Diffusion magnetic resonance imaging using hyperpolarized helium 3 (3He) was applied to healthy volunteers to explore the dependence of lung microstructural changes with age, reflected by changes in the apparent diffusion coefficient (ADC) of 3He in lung air spaces. Data from three sites (University of Virginia (UVa), N = 25; University of Wisconsin (UW), N = 8; University of Nottingham (UN), N = 11) were combined in pooled analysis, including a total of N = 44 subjects (age range, 18-69 years; average age, 41.7 +/- 16.7 years). RESULTS: ADC was found to depend on age at all three sites (UW, R = +0.95, P = .0003; UVa, R = +0.74, P < .0001; UN, R = +0.96, P < .0001). Increases in mean ADCs with age appeared similar across sites (UW, +0.0017 cm2 s(-1) y(-1); UVa, +0.0015 cm2 s(-1) y(-1); pooled, +0.0015 cm2 s(-1) y(-1); P = .71). In a regional analysis performed on UW data, the increase in ADC affected all regions of the lung, but the apical and middle regions showed a greater increase compared with the base of the lung. CONCLUSION: Results suggest the observed age dependence of the ADC may be caused by changes in lung microstructure that increase alveolar volume during the aging process.

Adolescent↗

Magnetic resonance imaging of the body trunk using a single-slab, 3-dimensional, T2-weighted turbo-spin-echo sequence with high sampling efficiency (SPACE) for high spatial resolution imaging: initial clinical experiences.

PURPOSE: The authors conducted a clinical evaluation of single-slab, 3-dimensional, T2-weighted turbo-spin-echo (TSE) with high sampling efficiency (SPACE) for high isotropic body imaging with large field-of-view (FoV). MATERIALS AND METHODS: Fifty patients were examined in clinical routine with SPACE (regions of interest: pelvis n=30, lower spine n=12, upper spine n=6, extremities n=4) at 1.5 T. For achieving a high sampling efficiency, parallel imaging, high turbofactor, and magnetization restore pulses were used. In contrast to a conventional TSE imaging technique with constant flip angle refocusing, the refocusing pulse train of the SPACE sequence consists of variable flip angle radiofrequency pulses along the echo train. RESULTS: Signal-to-noise ratio and contrast-to-noise ratio of SPACE images were of sufficient diagnostic value. The possibility of image reconstruction in multiple planes was of clinical relevance in all cases and simplified data analysis. CONCLUSION: The achievement of 3-dimensional, T2-weighted TSE magnetic resonance imaging with isotropic and high spatial resolution and interactive 3-dimensional visualization essentially improve the diagnostic potential of magnetic resonance imaging.

Abdominal Neoplasms↗

Functional MRI of the lung using hyperpolarized 3-helium gas.

Lung imaging has traditionally relied on x-ray methods, since proton MRI is limited to some extent by low proton density in the lung parenchyma and static field inhomogeneities in the chest. The relatively recent introduction of MRI of hyperpolarized noble gases has led to a rapidly evolving field of pulmonary MRI, revealing functional information of the lungs, which were hitherto unattainable. This review article briefly describes the physical background of the technology, and subsequently focuses on its clinical applications. Four different techniques that have been used in various human investigations are discussed: ventilation distribution, ventilation dynamics, and small airway evaluation using diffusion imaging and oxygen uptake assessment.

Administration, Inhalation↗

Exploring lung function with hyperpolarized (129)Xe nuclear magnetic resonance.

With the use of polarization-transfer pulse sequences and hyperpolarized (129)Xe NMR, gas exchange in the lung can be measured quantitatively. However, harnessing the inherently high sensitivity of this technique as a tool for exploring lung function requires a fundamental understanding of the xenon gas-exchange and diffusion processes in the lung, and how these may differ between healthy and pathological conditions. Toward this goal, we employed NMR spectroscopy and imaging techniques in animal models to investigate the dependence of the relative xenon gas exchange rate on the inflation level of the lung and the tissue density. The spectroscopic results indicate that gas exchange occurs on a time scale of milliseconds, with an average effective diffusion constant of about 3.3 x 10(-6)cm(2)/s in the lung parenchyma. Polarization-transfer imaging pulse sequences, which were optimized based on the spectroscopic results, detected regionally increased gas-exchange rates in the lung, indicative of increased tissue density secondary to gravitational compression. By exploiting the gas-exchange process in the lung to encode physiologic parameters, these methods may be extended to noninvasive regional assessments of lung-tissue density and the alveolar surface-to-volume ratio, and allow lung pathology to be detected at an earlier stage than is currently possible.

Algorithms↗

Rapid hyperpolarized 3He diffusion MRI of healthy and emphysematous human lungs using an optimized interleaved-spiral pulse sequence.

PURPOSE: To develop and validate an interleaved-spiral diffusion pulse sequence capable of hyperpolarized (3)He MR imaging of the whole lung in less than 10 seconds. MATERIALS AND METHODS: Hyperpolarized (3)He diffusion measurements were performed in seven healthy volunteers and five patients with emphysema using an interleaved-spiral pulse sequence that provided 11 contiguous 15-mm thick coronal ADC maps, with an in-plane resolution of 3.9 mm, covering the whole lung in 5.5 seconds. The resulting means and SDs of ADC values were compared statistically to those from a gradient-echo pulse sequence with identical resolution and diffusion-weighting gradients that acquired five ADC maps in 10.5 seconds. RESULTS: High-quality diffusion-weighted interleaved-spiral images covering the whole lung were obtained, and showed no significant susceptibility-induced image degradation compared to corresponding gradient-echo images. On a subject-by-subject basis, the means and SDs of ADC values for the interleaved-spiral technique were not statistically different from those for the gradient-echo technique. The mean ADC values from the two techniques were highly correlated on a section-by-section basis (R = 0.99). CONCLUSION: The interleaved-spiral diffusion pulse sequence permits rapid acquisition of contiguous ADC maps covering the whole lung during a short breath-hold period, and provides ADC values that are statistically equivalent to those from standard gradient-echo techniques.

Adult↗

Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge.

BACKGROUND: Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases. OBJECTIVE: We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge. METHODS: Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test. RESULTS: Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV(1) (r = 0.71, P <.002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV(1). The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P <.02) and extent (P <.02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure. CONCLUSION: HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge.

Adolescent↗

Quantitative analysis of MRI signal abnormalities of brain white matter with high reproducibility and accuracy.

PURPOSE: To assess the reproducibility and accuracy compared to radiologists of three automated segmentation pipelines for quantitative magnetic resonance imaging (MRI) measurement of brain white matter signal abnormalities (WMSA). MATERIALS AND METHODS: WMSA segmentation was performed on pairs of whole brain scans from 20 patients with multiple sclerosis (MS) and 10 older subjects who were positioned and imaged twice within 30 minutes. Radiologist outlines of WMSA on 20 sections from 16 patients were compared with the corresponding results of each segmentation method. RESULTS: The segmentation method combining expectation-maximization (EM) tissue segmentation, template-driven segmentation (TDS), and partial volume effect correction (PVEC) demonstrated the highest accuracy (the absolute value of the Z-score was 0.99 for both groups of subjects), as well as high interscan reproducibility (repeatability coefficient was 0.68 mL in MS patients and 1.49 mL in aging subjects). CONCLUSION: The addition of TDS to the EM segmentation and PVEC algorithms significantly improved the accuracy of WMSA volume measurements, while also improving measurement reproducibility.

Aging↗

Emphysema: hyperpolarized helium 3 diffusion MR imaging of the lungs compared with spirometric indexes--initial experience.

PURPOSE: To quantitatively evaluate hyperpolarized helium 3 ((3)He) diffusion magnetic resonance (MR) images of the lung in patients with emphysema and to determine whether apparent diffusion coefficients (ADCs) measured with MR imaging correlate with spirometric indexes. MATERIALS AND METHODS: Hyperpolarized (3)He diffusion MR imaging was performed in 16 healthy volunteers and 11 patients. Coronal diffusion-sensitized MR images were obtained during suspended respiration after inhalation of laser-polarized (3)He gas, and images of the ADC were calculated. Spirometry was performed immediately before imaging. The mean and SD of the ADCs were compared between subject groups and were correlated with spirometric indexes. RESULTS: ADC images were homogeneous in volunteers, but demonstrated regional variations in patients. The mean and SD of the ADCs for patients were significantly larger (P <.002) than those for volunteers. The mean ADCs for all subjects correlated with the percentage of predicted forced expiratory volume in 1 second, or FEV(1), (r = -0.797, P <.001) and the ratio of FEV(1) to forced vital capacity, or FVC, (r = -0.930, P <.001). ADC images in patients demonstrated a significant increase (P <.001) in the ADCs in the upper regions compared with the lower regions of the lung. CONCLUSION: Hyperpolarized (3)He diffusion MR imaging demonstrated potential for use in evaluating the global and regional severity of emphysema.

Adult↗