Anatomical distribution of 3He apparent diffusion coefficients in severe chronic obstructive pulmonary disease

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.     

Hyperpolarized He magnetic resonance imaging: Preliminary evaluation of phenotyping potential in chronic obstructive pulmonary disease

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 (³He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for ³He 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, ¹H MRI and hyperpolarized ³He MRI at 3.0 T. ³He ventilation defect percent (VDP) was generated from ³He static ventilation images and ¹H thoracic images and the ³He 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 ³He 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 ³He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies.     

Hyperpolarized helium‐3 magnetic resonance imaging of chronic obstructive pulmonary disease exacerbation

A chronic obstructive pulmonary disease (COPD) exsmoker underwent pulmonary function tests and hyperpolarized helium‐3 (³He) magnetic resonance imaging (MRI) serially over 4 years, twice prior to and twice following an acute exacerbation (AE). About 2.5 years pre‐AE, ³He ventilation defect percent (VDP) was 16%, the apparent diffusion coefficient (ADC) was 0.34 cm²/s, and forced expiratory volume in 1 sec (FEV₁) was 41%_pred. Six months pre‐AE, VDP and ADC were worse (29% and 0.38 cm²/s, respectively) without worsening FEV₁ (47%_pred). After hospitalization and AE treatment, VDP was 20%, whereas FEV₁ did not improve (45%_pred); 16 months post‐AE, both VDP and ADC remained improved and similar to 4 years prior. J. Magn. Reson. Imaging 2013;37:1223–1227. © 2012 Wiley Periodicals, Inc.     

Nuclear magnetic resonance imaging of airways in humans with use of hyperpolarized 3He

The nuclear spin polarization of noble gases can be enhanced strongly by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable ³He atoms has been shown to produce enormous polarization on the order of 0.4–0.6. This is about 10⁵ times larger than the polarization of water protons at thermal equilibrium used in conventional MRI. We demonstrate that hyper-polarized ³He gas can be applied to nuclear magnetic resonance imaging of organs with air-filled spaces in humans. In vivo ³He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T. Anatomical details of the upper respiratory tract and of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.     

Quantitative H and hyperpolarized He magnetic resonance imaging: Comparison in chronic obstructive pulmonary disease and healthy never-smokers

Objective

The aim of this study was to quantitatively evaluate the relationship between short echo time pulmonary ¹H magnetic resonance imaging (MRI) signal intensity (SI) and ³He MRI apparent diffusion coefficients (ADC), high-resolution computed tomography (CT) measurements of emphysema, and pulmonary function measurements.

Materials and methods

Nine healthy never-smokers and 11 COPD subjects underwent same-day plethysmography, spirometry, short echo time ((TE) = 1.2 ms) ¹H and diffusion-weighted hyperpolarized ³He MRI (b = 1.6 s/cm²) at 3.0 T. In addition, for COPD subjects only, CT densitometry was also performed.

Results

Mean ¹H SI was significantly greater for never-smokers (12.1 ± 1.1 arbitrary units (AU)) compared to COPD subjects (10.9 ± 1.3 AU, p = 0.04). The ¹H SI AP-gradient was also significantly greater for never-smokers (0.40 AU/cm, R² = 0.94) compared to COPD subjects (0.29 AU/cm, R² = 0.968, p = 0.05). There was a significant correlation between ¹H SI and ³He ADC (r = −0.58, p = 0.008) and significant correlations between ¹H MR SI and CT measurements of emphysema (RA₉₅₀, r = −0.69, p = 0.02 and HU₁₅, r = 0.66, p = 0.03).

Conclusions

The significant and moderately strong relationship between ¹H SI and ³He ADC, as well as between ¹H SI and CT measurements of emphysema suggests that these imaging methods and measurements may be quantifying similar tissue changes in COPD and that pulmonary ¹H SI may be used to monitor emphysema as a complement to CT and noble gas MRI.     

Hyperpolarized 3He magnetic resonance imaging of ventilation defects in healthy elderly volunteers: initial findings at 3.0 Tesla

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.     

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.     

Hyperpolarized (3)He MRI of mouse lung.

Hyperpolarized (3)He images of mouse lung are presented. Ventilation images and measurements of (3)He apparent diffusion coefficient (ADC) are reported in healthy mice, and preliminary studies of emphysema and lung cancer in mice are described using these techniques. The design and operation of an electronically controlled small-animal ventilator to deliver the hyperpolarized gas and control animal respiration are described. Images are acquired using an asymmetric gradient echo imaging method to enhance the signal-to-noise ratio of the rapidly diffusing (3)He. In mice with elastase-induced emphysema, the whole-lung average ADC is greater by approximately 25%, a statistically significant difference, compared to healthy animals. By contrast, mice exposed to cigarette smoke for up to 12 months reveal no statistically relevant increases in ADC, although emphysema was not confirmed in these mice. A study of lung cancer (melanoma) in mice is also presented. While tumors are shown to cause substantial ventilation defects in the lung, these defects appear confined to the cancerous regions and do not extend to large-scale regions of the lung distal to the tumors.     

Imaging phenotypes of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. COPD is defined by irreversible airflow obstruction. It is a heterogeneous disease affecting the airways and/or the parenchyma with different severity during the course of the disease. These different aspects of COPD can be addressed by imaging using a combination of morphological and functional techniques. Computed tomography (CT) is the technique of choice for morphological imaging of the lung parenchyma and airways. This morphological information is to be accomplished by functional information about ventilation and perfusion, mainly provided by magnetic resonance imaging (MRI). The comprehensive diagnostic possibilities of CT complemented by MRI will allow for a more sensitive detection, phenotype-driven characterization, and dedicated therapy monitoring of the disease.     

Hyperpolarized 3He ventilation defects and apparent diffusion coefficients in chronic obstructive pulmonary disease: preliminary results at 3.0 Tesla

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.     

Clinical aspects of the apparent diffusion coefficient in 3He MRI: results in healthy volunteers and patients after lung transplantation

PURPOSE: To measure the apparent diffusion coefficient (ADC) after inhalation of hyperpolarized (3)He in healthy volunteers and lung transplant recipients, and demonstrate the gravity dependence of ADC values. MATERIALS AND METHODS: Six healthy volunteers, 10 patients after single-lung transplantation, and six patients after double-lung transplantation were examined at 1.5T during inspiration and expiration. The inhalation of 300 mL of hyperpolarized (3)He was performed with a computer-controlled delivery device. A two-dimensional fast low-angle shot (FLASH) sequence measured the (3)He diffusive gas movement. From these data the ADC was calculated. RESULTS: The mean ADC was 0.143 cm(2)/second in healthy individuals, 0.162 cm(2)/second in transplanted healthy lungs, and 0.173 cm(2)/second in rejected transplanted lungs, whereas it was 0.216 cm(2)/second in native fibrotic lungs and 0.239 cm(2)/second in emphysematous lungs. The difference in mean ADC values among healthy lungs, healthy transplanted lungs, and native diseased lungs was significant (P < 0.001). In inspiration the healthy volunteers showed higher ADC values in the anterior than in the posterior parts of the lungs. In expiration this gradient doubled. CONCLUSION: An anterior-posterior (A/P) gradient was found in inspiration and expiration in healthy lungs. Healthy, transplanted, and native diseased lungs had significantly different mean ADC values. From our preliminary results, (3)He MRI appears to be sensitive for detecting areas of abnormal ventilation in transplanted lungs.     

Aortic vessel wall magnetic resonance imaging at 3.0 Tesla: A reproducibility study of respiratory navigator gated free‐breathing 3D black blood magnetic resonance imaging

The purpose of this study was to evaluate a free‐breathing three‐dimensional (3D) dual inversion‐recovery (DIR) segmented k‐space gradient‐echo (turbo field echo [TFE]) imaging sequence at 3T for the quantification of aortic vessel wall dimensions. The effect of respiratory motion suppression on image quality was tested. Furthermore, the reproducibility of the aortic vessel wall measurements was investigated. Seven healthy subjects underwent 3D DIR TFE imaging of the aortic vessel wall with and without respiratory navigator. Subsequently, this sequence with respiratory navigator was performed twice in 10 healthy subjects to test its reproducibility. The signal‐to‐noise (SNR), contrast‐to‐noise ratio (CNR), vessel wall sharpness, and vessel wall volume (VWV) were assessed. Data were compared using the paired t‐test, and the reproducibility of VWV measurements was evaluated using intraclass correlation coefficients (ICCs). SNR, CNR, and vessel wall sharpness were superior in scans performed with respiratory navigator compared to scans performed without. The ICCs concerning intraobserver, interobserver, and interscan reproducibility were excellent (0.99, 0.94, and 0.95, respectively). In conclusion, respiratory motion suppression substantially improves image quality of 3D DIR TFE imaging of the aortic vessel wall at 3T. Furthermore, this optimized technique with respiratory motion suppression enables assessment of aortic vessel wall dimensions with high reproducibility. Magn Reson Med 61:35–44, 2009. © 2008 Wiley‐Liss, Inc.     

Diffusion-weighted imaging of the abdomen at 3.0 Tesla: image quality and apparent diffusion coefficient reproducibility compared with 1.5 Tesla

Purpose

To compare single‐shot echo‐planar imaging (SS EPI) diffusion‐weighted MRI (DWI) of abdominal organs between 1.5 Tesla (T) and 3.0T in healthy volunteers in terms of image quality, apparent diffusion coefficient (ADC) values, and ADC reproducibility.

Materials and Methods

Eight healthy volunteers were prospectively imaged in this HIPAA‐compliant IRB‐approved study. Each subject underwent two consecutive scans at both 1.5 and 3.0T, which included breathhold and free‐breathing DWI using a wide range of b‐values (0 to 800 s/mm²). A blinded observer rated subjective image quality (maximum score= 8), and a separate observer placed regions of interest within the liver, renal cortices, pancreas, and spleen to measure ADC at each field strength. Paired Wilcoxon tests were used to compare abdominal DWI between 1.5T and 3.0T for specific combinations of organs, b‐values, and acquisition techniques.

Results

Subjective image quality was significantly lower at 3.0T for all comparisons (P = 0.0078– 0.0156). ADC values were similar at 1.5T and 3.0T for all assessed organs, except for lower liver ADC at 3.0T using b0‐500‐600 and breathhold technique. ADC reproducibility was moderate at both 1.5T and 3.0T, with no significant difference in coefficient of variation of ADC between field strengths.

Conclusion

Compared with 1.5T, SS EPI at 3.0T provided generally similar ADC values, however, with worse image quality. Further optimization of abdominal DWI at 3.0T is needed. J. Magn. Reson. Imaging 2011;33:128–135. © 2010 Wiley‐Liss, Inc.     

Multiple regression method for pulmonary apparent diffusion coefficient measurement by hyperpolarized 3He MRI

PURPOSE: To develop and validate a new multiple regression technique for the separation of flip angle effect in pulmonary apparent diffusion coefficient (ADC) measurement. MATERIALS AND METHODS: Hyperpolarized (3)He MRI (HP (3)He MRI) ADC measurements were performed on phantom, pig, and human models. The diffusion-sensitization sequence is modified from a standard gradient echo (GRE) sequence with a nonlinear progression in the bipolar gradient amplitude with each image. In the self-diffusion phantom experiment, four images were acquired with base gradient factor b(0) = 0.15 second/cm(2); in the pig and human experiment, six images were acquired with base gradient factor b(0) = 1.4 second/cm(2). RESULTS: The self-diffusion coefficient measured in the phantom experiment was 1.98 +/- 0.16 cm(2)/second. The measured uncertainty curve was consistent with the theoretically predicted curve. The measured in vivo ADC values (three coronal slices in the supine direction) were 0.20/0.16/0.13 cm(2)/second and 0.20/0.18/0.16 cm(2)/second for pig and human experiments, respectively. CONCLUSION: With the introduction of a nonlinear progression in the diffusion-sensitization gradients, the multiple regression technique is capable of separating the flip angle effect in ADC measurement. In addition, this technique can perform a rigorous measurement uncertainty analysis and provide the optimal scan parameters that yield best noise performance.     

Recycling of 3He from lung magnetic resonance imaging

We have developed the means to recycle (3) He exhaled by patients after imaging the lungs using magnetic resonance of hyperpolarized (3) He. The exhaled gas is collected in a helium leak proof bag and further compressed into a steel bottle. The collected gas contains about 1-2% of (3) He, depending on the amount administered and the number of breaths collected to wash out the (3) He gas from the lungs. (3) He is separated from the exhaled air using zeolite molecular sieve adsorbent at 77 K followed by a cold head at 8 K. Residual gaseous impurities are finally absorbed by a commercial nonevaporative getter. The recycled (3) He gas features high purity, which is required for repolarization by metastability exchange optical pumping. At present, we achieve a collection efficiency of 80-84% for exhaled gas from healthy volunteers and cryogenic separation efficiency of 95%.     

MR tagging of human lungs using hyperpolarized 3He gas

PURPOSE: To evaluate the use of spin-tagging in conjunction with hyperpolarized gas imaging for monitoring lung ventilation and gas diffusion. METHODS AND MATERIALS: Images were taken at 0.15 T using single shot RARE, with hyperpolarized (3)He gas prepared by the metastability exchange technique. Sinusoidal modulation of the longitudinal magnetization (tag) was produced by two 90-degree rf pulses separated by a gradient pulse. The diffusion of (3)He gas in the lungs was measured by monitoring the decay of the tags. This study was conducted on a 25-year-old, male, healthy volunteer. RESULTS: Clear tags in hyperpolarized (3)He gas both in vivo and in vitro were generated. The relative movement of the lung compared to a static, partial breath-hold was measured following inspiration or expiration. The diffusion coefficient of (3)He in the lungs was found to be 0.02 +/- 0.005 cm(2)seconds(-1). CONCLUSION: The spin-tagging of hyperpolarized (3)He in the lungs is possible, and allows regional lung movements to be measured following inspiration and expiration. It also allows quantification of the diffusion of the (3)He gas.     

Simultaneous measurement of pulmonary partial pressure of oxygen and apparent diffusion coefficient by hyperpolarized 3He MRI

Hyperpolarized ³He (HP ³He) MRI shows promise to assess structural and functional pulmonary parameters in a sensitive, regional, and noninvasive way. Structural HP ³He MRI has applied the apparent diffusion coefficient (ADC) for the detection of disease‐induced lung microstructure changes at the alveolar level, and HP ³He pulmonary partial pressure of oxygen (pO₂) imaging measures the oxygen transfer efficiency between the lung and blood stream. Although both parameters are affected in chronic obstructive pulmonary disease (COPD), a quantitative assessment of the regional correlation of the two parameters has not been reported in the literature. In this work, a single acquisition technique for the simultaneous measurement of ADC and pO₂ is presented. This technique is based on the multiple regression method, in which a general linear estimator is used to retrieve the values of ADC and pO₂ from a series of measurements. The measurement uncertainties are also analytically derived and used to find an optimal measurement scheme. The technique was first tested on a phantom model, and then on an in vivo normal pig experiment. A case study was performed on a COPD patient, which showed that in a region of interest ADC was 29% higher while oxygen depletion rate was 61% lower than the corresponding global average values. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

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.