The overall goal of the following experiment is to use physiological techniques combined with magnetic resonance imaging to measure the distribution of pulmonary perfusion non-invasively under differing inspired oxygen conditions. This is achieved by first training a subject to breath hold at functional residual capacity during image acquisition, and to breathe during the interval between images to allow collection of multiple images. As a second step, the subject is fitted with the face mask and the inspiratory and expiratory tubing is attached in order to supply the differing gas mixtures to the subject and to collect expiratory gas samples to make metabolic measurements.
Next in the MRI scanner, after a localizer image, arterial spin labeling and the multi echo fast gradient, echo sequences are used in order to obtain pulmonary blood flow and proton density images. The resultant images are quantified to give the distribution of pulmonary blood flow expressed in milliliters per minute per gram derived from the two different MR images. The main advantage of this technique is that pulmonary perfusion is non-invasively measured in vivo without exposure to ionizing radiation, allowing repeated measurements.
This method can provide insight into the mechanisms that control the spatial distribution of pulmonary perfusion, and it can also be used to study other physiological mechanisms within the MS scan environment. Demonstrating the procedures today will be TSIA rye, a graduate student Sebastian Verta and RU Carlos SA postdoctoral fellows from our lab Prior to running the experiment. First obtain written and informed consent from the research subject and have him or her fill out an MRI safety screening form.
Also perform a physical exam pulmonary function test and a training session in which the subject learns how to hold his or her breath at functional residual capacity. Or FRC begin setting up the breathing equipment by first fitting the mask on the subject's face. With a mesh attachment, the mask is equipped with a pre sterilized, non rebreathing valve and tubes.
Be sure to check the mask for leaks. Set up the gas bags in the scanner room and connect these to a tank in the MRI console room. This should be set up such that gas can be added to the bag by the investigator through manipulation of the gas tank.
Regulator assure that the gas bag is within view. As during the experiment, the investigator must monitor the bag through the console room window to ensure the gas volume is sufficient. Otherwise, the subject may not be able to inspire the fraction of inspired oxygen of hyperoxic and hypoxic gases in this case are 1.0 and 0.125 Respectively and room air can be used for the normoxic gas.
Assure that the expiratory breathing tube is sufficiently long enough to connect from the subject in the MR Scanner through a wave guide and to the metabolic cart in the MR console room. The metabolic cart seen here measures the volume of expired air as well as mixed expiratory oxygen and carbon dioxide concentrations. Based on these parameters, it also calculates various respiratory volumes.
EG, the tidal volume VO two VC O2, as well as respiratory quotient. Have the subject lie supine feet first on the scanner bed, and use pillows and foam pads to maximize comfort. Next, connect the inspiratory breathing tube to the inspiratory side of the subject's mask.
The tube will be used to administer either hyperoxic and hypoxic gases or normoxic air from the Mylar bags via a switching valve. Also place an EKG pad on the subject's chest. This will allow the arterial spin labeling Mr.Sequence to be gated to the QRS complex in the subject's electrocardiogram.
Be sure to check the valve to assure it is functioning Normally. Provide earplugs to protect the subject from scanner noise. Also, since the subject is wearing a mask and unable to easily communicate with the study personnel position a squeeze ball in the subject's hand and tape this in place.
This allows for communication with the investigators if assistance is needed. Last, place a pulse oximeter on the subject's finger to monitor oxygen saturation, which is critical when the subject is exposed to hypoxia. Now, place two Mr Phantoms on the subject's chest.
These phantoms should be used to quantify the MR signal during the post-processing. Then place the torso coil over the phantoms. The torso coil is used to increase the signal to noise ratio of the MR image compared with the body coil by reducing the physical distance between the receiver and the subject.
Finally, cover the subject with a blanket to ensure comfort before sending him or her into the center of the MR scanner bore. Once the subject is in the scanner, the operator should frequently talk to the subject in order to make sure that he or she is comfortable and to remind the subject to use the squeeze ball if assistance is needed. And we are gonna set up for the localizer, which is the first scan.
It's gonna take about 30 seconds. I want you to just relax and breathe normally while all the bangs and clicks go on. Be sure to monitor the EKG oxygen saturation tidal volume VO O2 and VC O2.The first few minutes of monitoring are especially important to ensure good quality data.
If these values are outside of expected values, the calibration must be redone and the face mask and tubing checked for leaks. First, acquire a localizer sequence to obtain the anatomical images in the subject's torso. This is gonna be a localizer lasts about 20 seconds.
Just relax. Breathe normally throughout it. Here we go.
Now set up an arterial spin labeling, a SL farer sequence with a half Fourier acquisition. Use a single shot turbo spin echo imaging scheme such as haste to acquire regional pulmonary perfusion data. Then select the sagittal plane from the portion of the right lung where the anterior to posterior distance is the largest.
A slice thickness of 15 millimeters and a field of view of 40 centimeters by 40 centimeters is typical. Here scans are acquired using a 1.5 Tesla GE HDX ex excite twin speed scanner. The subject will hear a series of loud banging sounds in pairs.
There is a five second interval between these bangs in which the subject should complete one breathing cycle. Breathe in, then breathe out to functional residual capacity. During the banging sound, the subject must hold his or her breath and remain at the FRC lung volume.
Although subjects are familiarized with the breathing technique prior to scanning, the first run of image acquisition should be a test run so that the subject can practice the breathing and breath holding while in the scanner. The MR operator should evaluate the quality of the lung images based on the movement of the diaphragm. If movement is minimal, the A SL measurements can begin monitor the tidal volume while scanning.
The approximate target. Tidal volume of 500 milliliters is consistent with normal ventilation. In the A SL sequence.
Two different cardiac gated images are acquired. The image timing of 80%of the RR interval should be individually set for each subject and experimental condition and ensures that the image contains blood signal from one systolic ejection period when the two images are subtracted, thereby canceling out the stationary signal. The result is a quantitative map of blood delivered to the image plane within one systolic ejection period.
In addition to the A SL images, acquire a lung proton density image using a multi echo fast gradient echo sequence. The measurement of proton density allows the perfusion measurements to be expressed in milliliters per minute per gram, and accounts for lung tissue deformation. Inside the thorax, the subject will hear a continuous noise that will last approximately 10 seconds during this scan and must hold his or her breath and stay at FRC for the duration of the noise.
Relax, breathe normally that looked great For this experiment. Gases of normoxia or room air, hypoxia and hyperoxia are presented in balanced order between subjects. Although these can be varied between subjects if desired, a subject should breathe a particular gas for about 20 minutes in order to establish steady state conditions within the lung tissue before MR measurements of profusion and proton density are acquired.
Then follow the same imaging protocol described in the previous section, the 20 minute period of exposure to the gas before imaging is chosen. Because although the initiation of hypoxic pulmonary vasoconstriction response occurs within seconds, the response to alveolar hypoxia is not maximal until approximately 20 minutes consistent with the goal of this particular study. Post-processing can be done by using MATLAB based custom developed software by using the paired MGRE images from the homogeneous body coil and the in homogeneous torso coil.
All blood flow and proton density images can be corrected for coil in homogeneity on a subject by subject basis. Once the subtracted a SL image is corrected for coil in homogeneity, the regional pulmonary blood flow can be quantified in milliliters of blood per minute per voxel. Then density, normalized perfusion images can be created.
Density normalized perfusion is expressed in units of milliliters of blood per minute per gram of water, and is calculated by dividing the A SL image by the proton density image to give the images of perfusion in milliliters per minute per gram of lung example, physiological data are seen here. Heart rate was increased in hypoxia and saturation was decreased. Ventilation was 8.31 liters per minute.
BTPS during hypoxia, 7.04 liters per minute during normoxia and 6.64 liters per minute. During hyperoxia tidal volume was 0.76 liters for hypoxia, 0.69 liters for normoxia and 0.67 liters for 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 from one subject under the three different inspired oxygen concentrations are shown here. The results of the data analysis of perfusion heterogeneity are given in table two. It can be seen that hypoxia increased the relative dispersion, however, the other indices were largely unchanged.
Once mastered, this technique can be completed in less than two hours if it is performed properly. After watching this video, you should have a good understanding of how to measure pulmonary profusion and form other physiological studies within the MR.Scanner environment.
