A MR imaging method to study the distribution of pulmonary blood flow under a variety of physiological conditions, in this case exposure to three different inspired oxygen concentrations: hypoxia, normoxia, and hyperoxia, is described. This technique utilizes human pulmonary physiology research techniques in an MR scanning environment.
This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects during normoxia (inspired O2, fraction (FIO2) = 0.21) hypoxia (FIO2 = 0.125), and hyperoxia (FIO2 = 1.00). In addition, the physiological responses of the subject are monitored in the MR scan environment. MR images were obtained on a 1.5 T GE MRI scanner during a breath hold from a sagittal slice in the right lung at functional residual capacity. An arterial spin labeling sequence (ASL-FAIRER) was used to measure the spatial distribution of pulmonary blood flow 1,2 and a multi-echo fast gradient echo (mGRE) sequence 3 was used to quantify the regional proton (i.e. H2O) density, allowing the quantification of density-normalized perfusion for each voxel (milliliters blood per minute per gram lung tissue).
With a pneumatic switching valve and facemask equipped with a 2-way non-rebreathing valve, different oxygen concentrations were introduced to the subject in the MR scanner through the inspired gas tubing. A metabolic cart collected expiratory gas via expiratory tubing. Mixed expiratory O2 and CO2 concentrations, oxygen consumption, carbon dioxide production, respiratory exchange ratio, respiratory frequency and tidal volume were measured. Heart rate and oxygen saturation were monitored using pulse-oximetry. Data obtained from a normal subject showed that, as expected, heart rate was higher in hypoxia (60 bpm) than during normoxia (51) or hyperoxia (50) and the arterial oxygen saturation (SpO2) was reduced during hypoxia to 86%. Mean ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.76 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia.
Representative quantified ASL data showed that the mean density normalized perfusion was 8.86 ml/min/g during hypoxia, 8.26 ml/min/g during normoxia and 8.46 ml/min/g during hyperoxia, respectively. In this subject, the relative dispersion4, an index of global heterogeneity, was increased in hypoxia (1.07 during hypoxia, 0.85 during normoxia, and 0.87 during hyperoxia) while the fractal dimension (Ds), another index of heterogeneity reflecting vascular branching structure, was unchanged (1.24 during hypoxia, 1.26 during normoxia, and 1.26 during hyperoxia).
Overview. This protocol will demonstrate the acquisition of data to measure the distribution of pulmonary perfusion noninvasively under conditions of normoxia, hypoxia, and hyperoxia using a magnetic resonance imaging technique known as arterial spin labeling (ASL).
Rationale: Measurement of pulmonary blood flow and lung proton density using MR technique offers high spatial resolution images which can be quantified and the ability to perform repeated measurements under several different physiological conditions. In human studies, PET, SPECT, and CT are commonly used as the alternative techniques. However, these techniques involve exposure to ionizing radiation, and thus are not suitable for repeated measurements in human subjects.
1. Subject recruitment
2. Preparation
3. Undergoing the magnetic resonance study
4. MR scanning
5. Post processing
Post processing is completed using custom developed software within the MATLAB programming environment.
6. Representative results
Physiological data are given in Table 1. Heart rate was increased in hypoxia and saturation was decreased. Ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.72 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia. The exposure to hypoxia increases both ventilation and tidal volume, while the hyperoxia decreases ventilation and tidal volume.
Three density normalized perfusion images collected during the three different inspired oxygen concentrations (Hypoxia: 0.125, Normoxia: 0.21, and Hyperoxia: 1.00) obtained from one subject (male, 30 years of age) are shown in Figure 1. The results of the data analysis of perfusion heterogeneity are given in Table 2. It can be seen that hypoxia increased the relative dispersion however the other indices were largely unchanged.
Figure 2 shows the effect of inspired oxygen concentrations on the vertical distribution of density normalized perfusion, averaged every 1 cm below 10 cm height from the most dependent part of lung and above 10 cm. All data points above 10 cm are averaged and displayed as one data point.
Hypoxia | Normoxia | Hyperoxia | |
Heart Rate (bpm) | 60 | 51 | 50 |
SpO2 | 86 | 99 | 100 |
VE BTPS (L/min) | 8.31 | 7.04 | 6.64 |
Vt BTPS (L) | 0.76 | 0.69 | 0.67 |
FEO2 (%) | 8.85 | 17.27 | – |
FECO2 (%) | 3.41 | 3.60 | 3.20 |
VO2 STPD (L/min) | 0.25 | 0.22 | -* |
VCO2 STPD (L/min) | 0.23 | 0.21 | 0.18 |
Table 1. The physiological data during scanning session.
* When the subject is breathing 100% oxygen, VO2 cannot be easily measured (see 12for details).
Hypoxia | Normoxia | Hyperoxia | |
Relative Dispersion | 1.07 | 0.85 | 0.87 |
Fractal Dimension | 1.24 | 1.26 | 1.26 |
Geometric Standard Deviation | 2.41 | 2.11 | 2.38 |
Table 2. The three indices of pulmonary perfusion heterogeneity.
Figure 1. Effect of three different inspired oxygen concentrations on density normalized perfusion. 1.1: Hypoxia (0.125), 1.2: Normoxia (0.21), 1.3: Hyperoxia (1.00). The scale is 3 cm (white solid line). A: anterior, P: posterior, I: inferior, and S: superior directions, respectively.
Figure 2. Effect of three different inspired oxygen concentrations on the vertical distribution of density normalized perfusion. The density normalized perfusion is averaged within 1 cm bins in the same gravitational plane, starting from 0 cm at the most dependent part of the lung and continuing to the most nondependent portion. All data points above 10 cm are averaged and displayed as one data point.
The error bars represent the standard deviation of the values of the density normalized perfusion within that plane. Hypoxic data are in red, normoxic data are in blue, and hyperoxic data are in green.
This method enables measurement of the effects of inspired oxygen concentration on the spatial distribution of pulmonary blood flow using basic physiological techniques in the MR scan environment. The use of physiological techniques in combination with quantitative proton imaging of the lung is relatively easily implemented.
To ensure a good quality test, the most important step is training the subject to breath-hold at the correct lung volume and in synchrony with the imaging sequence. Since both ASL and proton density images rely on the reproducibility of FRC lung volumes, any diaphragmatic or chest wall movement would lead to misregistration of those images. Well-trained subjects are able to reproduce the FRC lung volume repeatedly in the MR scanner Some subjects hyperventilate in the scanner and thus the investigator must also monitor the tidal volume measured by metabolic cart and offer feedback to the subject to ensure normal breathing. Finally oxygen saturation, particularly during hypoxic exposure must be monitored for subject safety.
Some of the limitations of these techniques are as follows: 1. we can only acquire perfusion data from one slice per breathhold. However our sequence allows for continuous acquisition in between breaths, and thus by using repeated breathholds the entire lung can be imaged in less than 3 minutes. 2. Quantification is dependent on accurate characterization of reference phantoms, and any error in this will be directly reflected in the data. 3. Since the physiological monitoring equipment that we use is located outside of the scanner room, we are unable to make breath-by breath measurements of VO2 and VCO2. 4. Some subjects, particularly young children or elderly patients with lung disease may have difficulty in reproducing the breathing pattern necessary for imaging, although it has been our experience that the vast majority of subjects, including patients, quickly acquire these skills.
The authors have nothing to disclose.
Supported by NIH HL081171, NIH HL080203
Equipment | Company | model |
---|---|---|
MRI | GE | 1.5 T GE HDx EXICITE twinspeed scanner |
Metabolic cart | ParvoMedics | TrueOne 2400 |
Pulse Oximeter | Nonin | 7500 FO |
Spirometer | Medical Technologies Andover | EasyOne diagonostic Spirometer |
Mask | Hans & Rudolph | 7400 series Oro-Nasal Mask, Small, Medium, and Large |
Valve | Hans & Rudolph | Two-way non-rebreathing valves T-Shape™ configuration, 2600 Medium. 2700 Large |
Head Set | Hans & Rudolph | Head cap (Adult size), strap & Locking Clips. |
Pneumatic directional control valve and controller | Hans & Rudolph | Single Piston Sliding-Type™ valve and controller 4285A |
Non-Diffusing gas collection bag | Hans & Rudolph | 6100 (100 liters). |
Tube | VacuMed | Clean-Bor Tubing 108”, 1-3/8” OD fittings |
Phantoms | Mentor | Brest Implant Round, 250cc |
matlab | The MathWorks |