Validity of apparent diffusion coefficient hyperpolarized 3He-MRI using MSCT and pulmonary function tests as references

Purpose

To compare apparent diffusion coefficient (ADC) measurements from hyperpolarized (HP) helium (³He)-magnetic resonance imaging (MRI) with quantitative data from multislice Computed Tomography (CT) (MSCT) of the whole lungs and pulmonary function tests (PFT).

Materials and methods

Twenty-seven subjects, 22 with established emphysema and 5 with preclinical emphysema defined by PFT criteria, were examined with HP ³He-MRI and MSCT. Mean age was 55 (±12) years, 18 female and 9 male. Mean ADC from ³He-MRI was compared with emphysema index (EI), 15th percentile and mean lung density (MLD) values from MSCT. Both mean ADC and MSCT data were compared to PFT, especially percent of predicted diffusing capacity of carbon monoxide (%predicted DLCO), using Pearson's correlation test.

Results

Mean ADC and standard deviation values were 0.392 ± 0.119 cm²/s for the established emphysema group and 0.216 ± 0.046 for the pre-clinical emphysema group. MSCT values for the established emphysema group and pre-clinical emphysema group were: EI (%) 11 ± 12 and 0.4 ± 0.6, respectively; 15th percentile (Hounsfield Units (HU)), −956 ± 25 and −933 ± 13, respectively and MLD (HU) −877 ± 20 and −863 ± 15, respectively. Correlations between mean ADC and EI and 15th percentile were both r = 0.90 and for MLD r = 0.59. There was higher correlation between mean ADC and %predicted DLCO (r = 0.90) than between EI and %predicted DLCO (r = 0.76).

Conclusion

HP ³He-MRI correlates well with density measurements from MSCT and agrees better than MSCT with %predicted DLCO which is the PFT most related to emphysema.     

3He-MRI in follow-up of lung transplant recipients

The aim of this study was to evaluate the possible contribution of ³He-MRI to detect obliterative bronchiolitis (OB) in the follow-up of lung transplant recipients. Nine single- and double-lung transplanted patients were studied by an initial and a follow-up ³He-MRI study. Images were evaluated subjectively by estimation of ventilation defect area and quantitatively by individually adapted threshold segmentation and subsequent calculation of ventilated lung volume. Bronchiolitis obliterans syndrome (BOS) was diagnosed using pulmonary function tests. At ³He-MRI, OB was suspected if ventilated lung volume had decreased by 10% or more at the follow-up MRI study compared with the initial study. General accordance between pulmonary function testing and ³He-MRI was good, although subjective evaluation of ³He-MRI underestimated improvement in ventilation as obtained by pulmonary function tests. The ³He-MRI indicated OB in 6 cases. According to pulmonary function tests, BOS was diagnosed in 5 cases. All diagnoses of BOS were also detected by ³He-MRI. In 2 of these 5 cases, ³He-MRI indicated OB earlier than pulmonary function tests. The results support the hypothesis that ³He-MRI may be sensitive for early detection of OB and emphasize the need for larger prospective follow-up studies.     

Hyperpolarized 3He MRI in asthma measurements of regional ventilation following allergic sensitization and challenge in mice--preliminary results

RATIONALE AND OBJECTIVES: Quantitative regional measurement of physiological parameters of lung may improve both early detection of asthma and its response to treatment by elucidating the characteristics of airway obstruction. Recent emergence of hyperpolarized helium-3 magnetic resonance imaging as a sensitive pulmonary imaging tool has shown great potential in capturing important structural and functional aspects of normal and diseased lungs. The objective of this study was to investigate regional ventilation changes in the mouse lung following allergen sensitization and challenge. MATERIALS AND METHODS: A murine model of allergic airway inflammation was created in mice following allergen challenge using Af and IgE-mediated asthma. The creation of model was verified using pulmonary function test and histology. Regional fractional ventilation was then measured in the animals using hyperpolarized 3He MRI on a pixel-by-pixel basis with a planar resolution of 0.24 mm. The sensitized and healthy animals were then compared statistically to assess the potential sensitivity of this technique in detection of such pulmonary abnormalities. RESULTS: In this work, we have demonstrated for the first time the quantitative measurement of regional ventilation in normal and asthmatic mice. Results of this study show significant changes in regional ventilation in murine model of allergic airway sensitization compared with that in normal control animals. CONCLUSION: Further development of this technique can potentially serve as a quantitative marker to investigate the physiology of allergen-induced airway hyperresponsiveness and to assist in disease treatment and prevention.     

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.     

Posture-dependent human 3He lung imaging in an open-access MRI system: initial results

RATIONALE AND OBJECTIVES: The human lung and its functions are extremely sensitive to orientation and posture, and debate continues as to the role of gravity and the surrounding anatomy in determining lung function and heterogeneity of perfusion and ventilation. However, study of these effects is difficult. The conventional high-field magnets used for most hyperpolarized (3)He magnetic resonance imaging (MRI) of the human lung, and most other common radiologic imaging modalities including positron emission tomography and computed tomography, restrict subjects to lying horizontally, minimizing most gravitational effects. MATERIALS AND METHODS: In this article, we review the motivation for posture-dependent studies of human lung function and present initial imaging results of human lungs in the supine and vertical body orientations using inhaled hyperpolarized (3)He gas and an open-access MRI instrument. The open geometry of this MRI system features a "walk-in" capability that permits subjects to be imaged in vertical and horizontal positions and potentially allows for complete rotation of the orientation of the imaging subject in a two-dimensional plane. RESULTS: Initial results include two-dimensional lung images acquired with approximately 4 x 8 mm in-plane resolution and three-dimensional images with approximately 2-cm slice thickness. CONCLUSIONS: Effects of posture variation are observed, including posture-related effects of the diaphragm and distension of the lungs while vertical.     

Oxygen-sensitive <Superscript>3</Superscript>He-MRI in bronchiolitis obliterans after lung transplantation

Oxygen-sensitive ³He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO₂) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive ³He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acqiured on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, ³He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO₂ in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (−1.75 mbar/s versus −0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive ³He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive ³He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients.     

A breathing lung phantom for 81mKr lung ventilation studies its use in dosimetry and quality control

The construction of a breathing lung phantom that can be used to measure the amount of radioactive gas in the lungs as well as to determine the absorbed dose is described. For a lung ventilation study that consists of 6 views of 300 kents each, an effective dose equivalent of 50 Sv was calculated. The phantom is also suitable for comparison of different generator systems.     

Alveolar oxygen partial pressure and oxygen depletion rate mapping in rats using 3He ventilation imaging.

A hyperpolarized 3He ventilation imaging protocol was implemented to assess alveolar pO2 values and the oxygen depletion rate in rats. The imaging protocol, which is based on spiral k-space sampling, was designed to acquire a high signal-to-noise ratio (SNR) T1-weighted ventilation series of images in a single breath-hold. Simulations were performed to estimate the accuracy and dependence of the pO2 imaging protocol on the image SNR and the RF flip-angle determination. The imaging protocol was validated in vitro in phantoms and in vivo in rats. Imaging sessions were carried out for different inhaled O2 concentrations ranging from 20% to 40%. Parametric maps of alveolar pO2 and oxygen depletion rate were generated from the series of images. For each investigated animal, the differences in measured alveolar pO2 values are in agreement with the changes in inhaled O2 concentration. The oxygen depletion rates, ranging between 0.7 and 8.0 mbar s-1, are in close agreement with the published values for healthy rats.     

不同b值下的ADC值对肺部病变诊断的价值

目的:评价不同b值下的ADC值在肺良恶性占位性病变诊断中的应用价值。方法:70例患者行不同b值(分别为0、500、700、900s/mm2)的DWI扫描,对70个病灶进行分析,全部病灶依据术后病理或穿刺活检病理为标准,对所获资料采用两独立样本t检验进行统计学分析。结果:b值为500、700、900s/mm2时,良性组与恶性组之间ADC值的差异均有统计学意义(P<0.01)。以恶性组ADC值95%可信区间上限作为诊断阈值,则b值为500、700、900s/mm2时,诊断阈值分别为1.687×10-3 mm2/s、1.465×10-3 mm2/s、1.543×10-3 mm2/s。应用ROC曲线分析不同b值时ADC阈值诊断恶性病变的作用,显示b值为700s/mm2时价值最大,其诊断敏感度、特异度、准确性、阳性和阴性预测值分别为92.86%、76.92%、82.50%、93.57%和66.67%。结论:b值为700s/mm2时获得的ADC值效能较高。     

Improvement of multislice oxygen-enhanced MRI of the lung by fully automatic non-rigid image registration

Purpose

In oxygen-enhanced magnetic resonance imaging of the lung (O2-MRI), motion artifacts related to breathing hamper the quality of the parametric O2-maps. In this study, fully automatic non-rigid image registration was assessed as a post-processing method to improve the quality of O2-MRI.

Materials and methods

Twenty healthy volunteers were investigated on a 1.5 T MR system. O2-MRI was obtained in four coronal sections using an IR-HASTE sequence with TE/TI of 12/1200 ms. Each section was repeatedly imaged during oxygen and room-air ventilation. Spatial differences among the images were corrected by fully automatic non-rigid registration. Signal variability, relative enhancement ratio between oxygen and room air images, and spatial heterogeneity of lung enhancement were assessed before and after image registration.

Results

Motion artifacts were corrected in 5–10 s. Non-rigid registration reduced signal variability of the source images and heterogeneity of the O2-maps by 1.1 ± 0.2% and 11.2 ± 2.9%, respectively (p < 0.0001). Registration did not influence O2 relative enhancement ratio (p = 0.06).

Conclusion

Fully automatic non-rigid image registration improves the quality of multislice oxygen-enhanced MRI of the lung.     

A contrast-oriented algorithm for FDG-PET-based delineation of tumour volumes for the radiotherapy of lung cancer: derivation from phantom measurements and validation in patient data

Purpose  An easily applicable algorithm for the FDG-PET-based delineation of tumour volumes for the radiotherapy of lung cancer was developed by phantom measurements and validated in patient data. Methods  PET scans were performed (ECAT-ART tomograph) on two cylindrical phantoms (phan1, phan2) containing glass spheres of different volumes (7.4–258 ml) which were filled with identical FDG concentrations. Gradually increasing the activity of the fillable background, signal-to-background ratios from 33:1 to 2.5:1 were realised. The mean standardised uptake value (SUV) of the region-of-interest (ROI) surrounded by a 70% isocontour (mSUV₇₀) was used to represent the FDG accumulation of each sphere (or tumour). Image contrast was defined as: where BG is the mean background − SUV. For the spheres of phan1, the threshold SUVs (TS) best matching the known sphere volumes were determined. A regression function representing the relationship between TS/(mSUV₇₀ − BG) and C was calculated and used for delineation of the spheres in phan2 and the gross tumour volumes (GTVs) of eight primary lung tumours. These GTVs were compared to those defined using CT. Results  The relationship between TS/(mSUV₇₀ − BG) and C is best described by an inverse regression function which can be converted to the linear relationship . Using this algorithm, the volumes delineated in phan2 differed by only −0.4 to +0.7 mm in radius from the true ones, whilst the PET-GTVs differed by only −0.7 to +1.2 mm compared with the values determined by CT. Conclusion  By the contrast-oriented algorithm presented in this study, a PET-based delineation of GTVs for primary tumours of lung cancer patients is feasible.     

Application of a 3D volume 19FMR imaging protocol for mapping oxygen tension (pO2) in perfluorocarbons at low field

A limited flip angle gradient-echo 3D volume acquisition imaging protocol for mapping partial pressure of oxygen (pO₂) in perfluorocarbon compounds (PFCs) at low field (0.14 T) is presented. The pO₂ measurement method is based on the paramagnetic effect of dissolved molecular oxygen (O₂) which reduces the PFC ¹⁹F T_1? Specific objectives related to imaging of PFCs through use of the protocol include improved image signal-to-noise characteristics and elimination of ¹⁹F chemical shift artifacts. A parametric Wiener deconvolution filtering algorithm is used for suppression of ¹⁹F chemical shift artifacts. Application of the protocol is illustrated in a series of calculated pO₂ maps of a gas equilibrated, multi-chamber phantom containing perfluorotributylamine (FC-43). The utility of the protocol is demonstrated in vivo through images of a commercially available perfluorocarbon based blood substitute emulsion containing FC-43 sequestered in the liver and spleen of a rat.     

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.     

Accuracy of segmented MR velocity mapping to measure small vessel pulsatile flow in a phantom simulating cardiac motion

The purpose of this study was to investigate the accuracy of conventional, segmented, and echo-shared MR velocity mapping sequences to measure pulsatile flow in small moving vessels using a phantom with simulated cardiac motion. The phantom moved either cyclically in-plane, through-plane, in- and through-plane, or was stationary. The mean error in average flow was -2% +/- 3% (mean +/- SD) for all sequences under all conditions, with or without background correction, as long as the region of interest (ROI) size was equal to the vessel cross-sectional size. Overestimation of flow as a result of an oversized ROI was less than 20%, and independent of field of view (FOV) and matrix, as long as the offset in angle between the imaging plane and flow direction was less than 10 degrees. Segmented velocity mapping sequences are surprisingly accurate in measuring average flow and render flow profiles in small moving vessels despite the blurring in the images due to vessel motion. J. Magn. Reson. Imaging 2001;13:722-728.     

Application of I-123 HIPDM as a lung imaging agent

N,N,N-Trimethyl-N-(2-Hydroxyl-3-Methyl-5-¹²³I Iodobenzyl)-1,3-Propanediamine · Hcl (¹²³I-HIPDM) has been used for diagnosis of patients with strokes and dementias. Since this radiopharmaceutical is also accumulated in the lung, we routinely performed a lung image or images immediately prior to cerebral planar and SPECT images after a 3–5 mCi ¹²³I-HIPDM injection. During the past 14 months, we obtained 78 (age from 41 to 92 years, average 66.7±8.9 years; 64 males, 14 females) suspected stroke or dementia patients' lung images. All lung images were correlated to chest X-ray (CXR) or CT and other clinical data. Sixty five of 78 patients had normal lungs showing homogeneous distribution of activity throughout the lungs which correlated well to normal CXR and/or CT studies. Abnormal scintigraphic patterns of the 13 patients included lung defect (5 bronchogenic carcinoma with or without atelectasis) and decreased uptake in apices (8 chronic obstructive pulmonary disease). The findings of pulmonary intrathoracic pathologies on lung images with ¹²³I-HIPDM suggests further evaluation of the agent for detection of localized pulmonary diseases and pulmonary physiological studies relating to amine metabolism.This investigation was supported in part by Biomedical Research Support Grant no. RR05374 from the Biomedical Research Support Branch, Division of Research Facilities and Resources, NIH     

Pulmonary hyperpolarized noble gas MRI: Recent advances and perspectives in clinical application

The invention of hyperpolarized (HP) noble gas MRI using helium-3 (³He) or xenon-129 (¹²⁹Xe) has provided a new method to evaluate lung function. Using HP ³He or ¹²⁹Xe for inhalation into the lung air spaces as an MRI contrast agent significantly increases MR signal and makes pulmonary ventilation imaging feasible. This review focuses on important aspects of pulmonary HP noble gas MRI, including the following: (1) functional imaging types, (2) applications for major pulmonary diseases, (3) safety considerations, and (4) future directions. Although it is still challenging to use pulmonary HP noble gas MRI clinically, the technology offers promise for the investigation of the microstructure and function of the lungs.     

Measurement of pulmonary partial pressure of oxygen and oxygen depletion rate with hyperpolarized helium-3 MRI: a preliminary reproducibility study on pig model

RATIONAL AND OBJECTIVES: Pulmonary partial pressure of oxygen (pO(2)) and oxygen depletion rate (R) are two important parameters of lung function. The dependence of hyperpolarized (3)He (HP (3)He) T(1) on local oxygen concentration provides the basis for high-resolution mapping of the regional distributions of pO(2) and R in the lung. Although the oxygen-sensitive HP (3)He magnetic resonance imaging technique has been applied in human subjects and several animal species, reproducibility studies are rarely reported in the literature. This work presents a preliminary reproducibility study on a pig model. In this study, important scan parameters, such as measurement timing and flip angle, are optimized to minimize the noise-induced measurement uncertainty. MATERIALS AND METHODS: In the in vivo study, five normal pigs and one diseased pig with simulated pulmonary emboli were scanned with a small flip angle gradient echo sequence. The pulmonary oxygen measurement was repeated two to four times in each pig. In each measurement, a series of six images were acquired with optimal timing and flip angle. The parametric maps were generated using a bin-based data processing procedure that applied the multiple regression fitting method to extract the pO(2) and R. Variations of global mean, percentiles, and regions of interest were calculated from the maps to analyze reproducibility. RESULTS: The global statistical analyses show that average variation of global mean is 10.7% for pO(2) and 23.8% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) and interquartile range is 14.8% for pO(2) and 30.4% for R. The region-of-interest analysis on the manually selected regions shows that the average variation of mean is 12.6% for pO(2) and 21.9% for R. CONCLUSION: In this work, a preliminary study on the reproducibility of measuring pO(2) and R with HP (3)He magnetic resonance imaging on a pig model is presented.     

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.     

On the use of a (Cf-He) assembly for landmine detection by the neutron back-scattering method

Experiments were carried out to optimize the performance of the neutron back-scattering (NBS) technique in landmine detection using an assembly consisting of three different layers placed above a ²⁵²Cf neuron source, producing about 10⁴ s⁻¹, in conjunction with a ³He detector. The assembly was optimized experimentally. The selected assembly configuration was then examined against different ²⁵²Cf stand-off distances and mine burial depths using dummy landmines. Furthermore, Monte Carlo simulations were performed to study the effect of the shield when a ²⁵²Cf source in the range 10⁴-10⁷ s⁻¹ was employed, and to optimize the geometry for future prototypes.