Een Multicenter MRI protocol voor de evaluatie en kwantificering van diepe veneuze trombose

The overall goal of the following experiment is to use magnetic resonance imaging or MRI in a multicenter setting to evaluate deep vein thrombosis or DVT. This is accomplished by first inserting an intravenous line into the subject and positioning them into the MRI scanner. Images are acquired using two methods.

The first method called direct thrombus imaging evaluates fresh thrombus using a three DT one weighted gradient ECHO scan. The second method, Mr.Venography is performed after the injection of a long circulating contrast agent and then imaging with another three DT one weighted gradient echo scan. This method allows quantification of total thrombus volume.

After images are acquired at various imaging centers, they are transferred to a dedicated central core laboratory for analysis. The results show that this approach for imaging deep vein thrombosis is feasible, robust, and reliable with excellent inter and intra observer reproducibility and minimal bias between two separate observers. So this study shows a method for using magnetic resonance imaging to evaluate a very serious clinical condition called deep venous thrombosis, or D-V-T-D-V-T is difficult to diagnose clinically and and to quantify objectively.

Traditionally, DVT is diagnosed in the clinical setting using a D dimer assay, followed by compression ultrasound. However, compression ultrasound cannot reliably detect DVT in the pelvis and in the distal limbs. Therefore, we propose to use MRI to reliably and objectively quantify DVT volume from pelvis to the calf.

In a multicenter clinical trial, it is important to robustly acquire images of good quality that are not subject to user error or bias, and that can be acquired on a variety of magnetic resonance imaging systems. In our study, we proposed the use of a simple 3D gradient echo imaging acquisition method in conjunction with a long circulating contrast agent to robustly acquire such images in various centers, and also provide a reliable method for analysis of these acquired images in a central core laboratory. After preparing the subject for imaging, place an intravenous line in their antecubital vein for the injection of the contrast agent.

Measure creatinine clearance to ensure that the subject's kidney function is adequate for imaging. With contrast. Place the subject in a supine feet first position.

In the MRI machine and position the appropriate coils on the regions to be scanned using Velcro straps as needed to secure the coils oils. Turn on the centering laser and move the table until the laser cross beams are located just below the subject's knees. Accept this position for the ISO center of the scan and move the patient table to the center position of the scanner bore.

Perform bilateral imaging of both legs and lower pelvis according to the text protocol. Execute the imaging protocol from the scanner console by selecting each protocol step from the protocol window and dragging it to the execution list. Once ready, run the sequence by pressing scan, execute, or equivalent button After acquiring 2D gradient, echo localizers, according to the text protocol, to distinguish between acute and chronic venous thrombosis, acquire T one weighted 3D gradient echo or GRE sequences using parameters in this table.

This represents the direct thrombus imaging approach, or DTHI administer the contrast agent intravenously into the subject at a dose of 0.03 millimoles per kilogram, and a rate of two milliliters per second, and use 20 milliliters of saline to flush. Let the contrast agent circulate for five minutes to ensure a steady state in the blood pool. Acquire post contrast 3D gradient echo sequences at three locations using the sequence parameters in these tables.

This represents the Mr.Venography approach for imaging. After the scan is completed, remove the subject from the MRI scanner and take out the intravenous line. Ask the subject to change out of their gown and exit the facility to carry out image analysis.

Have a trained image analyst running an FDA approved open source image processing software such as OSI md. Load all DICOM images from both MRI visits of a subject into the image processing software by selecting, import, and compare the two imaging time points of the MRV series for each subject. To ensure adequate spatial coverage and registration across time points, select the 3D MPR tool in the viewer to provide simultaneous browsing of image data in three orthogonal views.

After identifying vessels with deep vein thrombosis or DVT, establish the position of the thrombus in three dimensional space. From the curved NPR plane, A 3D bezier path will be displayed in creation mode. Delineate the center line of the vein by selecting the contour path tool.

Place points repeatedly on any of the orthogonal NPR views to straighten the entire vessel of interest in editing mode. Make adjustments when necessary to ensure that the vessel is entirely straightened when the contour path is accurately delineated at the center line of the vessel. Save the file by selecting the curved path icon and export the file.

Generate one millimeter axial slices perpendicular to the curved path, and save as dicom. Observe the curved path, straightened vessel, and corresponding axial images for quantifying DVT. From MRV images on the axial DICOM images, use the closed polygon ROI tool to manually segment regions of interest encompassing the thrombus after saving ROIs and ROI metrics.

According to the text protocol. On the axial pre contrast images compute the volume of fresh thrombus by manually drawing regions of interest. DVT measured by DTHI in conjunction with the MRV images will be depicted as shown here, as shown here.

For MRV thrombus volume measurements, the intra and inter reader variability by intraclass correlation coefficients was 0.98 and 0.96 respectively. Bland Altman analysis also showed no bias for both intra and inter observer assessments. DTHI derived thrombus volume, intra and inter reader variability by intraclass.

Correlation coefficients were 0.88 and 0.95 respectively. Bland Altman analysis showed no bias for intra observer assessments. However, as demonstrated here, there was a significant bias observed for inter observer variability.

This indicates poorer reproducibility for the volumes measured by DTHI compared to MRV. For example. The following video animation shows the treatment effects of a novel oral factor 10, a inhibitor on deep vein thrombosis volume over a two week treatment period.

Using the approach described in this protocol. This form of image acquisition using the protocol described here, has never been done before in a clinical trial setting. The image acquisition steps we propose are simple to implement, yet are independent of scanner operator skill, thereby providing robust image acquisition.

We can also use this method to evaluate the efficacy of novel methods to treat DVT. After watching this video, you should have a good understanding of how to acquire and analyze images for evaluating deep vein thrombosis. Using MRI.