Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

The overall goal of the following pipeline is to better understand aging and dementia. By obtaining MRI derived measures of regional brain atrophy and neuroimaging biomarkers of small vessel disease. This is achieved by first generating a skull stripped brain mask, and a basic brain tissue segmentation to accurately quantify the total intracranial volumes.

As a second step, a TRIFE lesion segmentation is completed to quantify and classify lesion subtypes for accurate imaging biomarker measurements of small vessel disease. Next anatomical landmarking is performed on each individual to ate the brain into 26 standardized regions of interest. Results are obtained that show differential regional neurodegeneration and vasculopathy patterns between disease groups based on brain tissue atrophy, measures, and lesion volumetrics obtained from structural MRI.

Our analysis approach can help address key questions in brain imaging of aging and dementia. The personalized pipeline we have developed allows researchers and clinicians alike to better understand diagnosis, progression, and treatment response in individual people as well as different patient groups. It is especially useful for people who have cerebral small vessel disease in combination with neurodegenerative disorders.

This is very common in the elderly, especially in Alzheimer's disease. The pipeline can also be applied to people with other neurological disorders such as vascular dementia and stroke, frontal temporal dementia, traumatic brain injury, and multiple sclerosis. Visual demonstration of this method is critical as the manual intervention steps can be complex.

This requires a combination of a strong knowledge base in neuroanatomy as well as a strong competency and computer skills. Many of these steps are best communicated through a format. This video will allow the user to properly visualize the anatomical structures in question and show the computational interventions required.

Demonstrating the procedure will be our lab manager, Christopher Scott, and RIN Imaging analyst, Alicia McNeely and Courtney Beek. To begin open the software and load a T one weighted image and the automatic skull stripped total intracranial vault mask overlay or TIV auto. Then use the paintbrush tool to begin editing the TIV auto to add in or recapture brain that the TIV auto has not accounted for.

Select active drawing label as label one and draw over as all labels to recapture color, DIV auto areas, or carefully recapture the non-colored areas. Use the paintbrush to repaint the TIV auto mask. Check each and every slice carefully to make sure only brain tissue is painted green as label one and all non brainin tissue has another label.

If it is difficult to paint, use the closed polygon tool, recapture the TIV auto as appropriate and delete the TIV auto as appropriate. When satisfied with TIV modifications, save the image as TIV edit to begin ventricular reassignment. Load the seg image over the T one IHC image, then adjust the drawing labels to appropriate colors.

Next reassign CSF Voxels by using the flood fill tool, toggle back and forth between flood filling and drawing limits by pressing the space. Bar limits are used to prevent the flood fill from filling certain areas of the ventricle that are considered periventricular black holes or part of white matter hyperintensities. Use the T one weighted image as a guide as to what to fill and what not to fill for the temporal lobe.

Lateral ventricles segmentation can be toggled on and off with the S key. When finished, save the segmentation for removal of the brainstem, cerebellum and sub tentorial structures. Select the polygon tool and with segmentation off, scroll to the first slice on which the cerebellum begins.

Then left click to draw a polygon over the dura surrounding the cerebellum and along the base of the brainstem across the calli. Then right click to close the polygon and click accept to delete that area of the segmentation. The area will now show the T one beneath indicating that it is no longer included in the segmentation.

Once the cerebral peduncle separate, begin also removing the brainstem and spinal cord. Now scroll up through the image slice by slice to verify that the only portions of the segmentation that remain are cerebral brain tissue. When finished, save the segmentation.

To begin load the ISO image and the mat file for a CPC alignment First, zoom in closely using the navigation tool. Then use the pitch up, down and elevate up down tools to adjust the axial view so that the anterior commissure is at its thickest and the posterior commissure is straight across. This should end up forming a nice keyhole shape.

Readjust the view to bring the eyeballs into the field of view. Now adjust the roll by balancing the eyeballs in the axial view. The axial slices should look evenly balanced while scrolling through the image.

One slice at a time adjust ya by making sure that the vertical cross hair passes through the mid sagittal plane. In the axial view, sometimes it may be difficult to get the plane to line up perfectly due to natural curvature of the brain at the poles, create the best fit possible. To begin load the image for landmark identification.

First, click the AC radio button on the left to select the landmark to define. Then click on the AC in the axial view. Next, click the PC radio button on the left, and then on the PC on the axial image.

Now click the PE radio button to define the posterior edge of the brain on that slice, and then click on the most posterior part of the brain, either on the left or the right. This will fill in values for a coronal slice, which will be used momentarily. Click the ca radio button to define the central canal.

Then scroll down 10 slices from the current axial view and click on the center of the central canal. This fills in the value for sagittal slice, which will be used now as a starting point to find the mid sagittal plane. Next, click on the M radio button to define the mid sagittal plane.

Then click on the LPR radio button to define the left pre occipital notch and the RPR radio button to define the right hemisphere pre occipital notch. For object map creation, click the LSC radio button to define the left superior central sulcus. Left click to place a marker on the dura above the sulcus.

Click on the LOP radio button to define the left occipital parietal sulcus. This sulcus tracing runs from the dura to the tentorium cere for surface rendered tracings. Begin tracing the Sylvie and fissure from the posterior to anterior end, beginning at the point at which it bifurcates into small, ascending and descending rami.

Now click the lc radio button to trace the left central sulcus. Start from the inferior end at the point of Sylvie and fissure directly below the termination of the sulcus. Finish tracing the sulcus at the superior end until it is difficult to follow the curvature of the brain.

Finally, click on the right button under 3D viewpoint and repeat the steps for the right Sylvie and fissure and the right central sulcus for lesion segmentation with PD or T two scans. First, review all available imaging, including the T one, PD and T two to inform the decision about what to capture as the brain lesion. Then use the paintbrush tool to paint label two over label one to signify the areas with the lesion.

The segmentation can be toggled on and off with the S key. Also, paint label one over label two to signify any false positives or errors for scans with flare imaging. Again, use all available imaging as necessary to inform the decision about what areas constitute the lesion.

Then use the paintbrush to change the labels to signify the lesion and false positives. When satisfied with lesion segmentation modifications, save the final edited image. Here we can see two examples showing SABRE landmarking procedures.

The axial slice on the left shows the A CPC aligned T one with the ac, the PC and posterior edge landmark placements. The 3D surface rendered T one has Sian fissure and central sulcus delineation. This axial PD has an automatically generated lesion overlay and manually edited lesion overlay.

This is an example of the manual relabeling procedure that is completed as part of the lesion explorer process, and here we can see an example of the manual relabeling procedure that is completed as a part of the flex process. The axial flare has an automatically generated lesion overlay and a manually edited lesion overlay. See the manuscript accompanying this video for methods of assessing interrater reliability of the brain extraction procedures.

While attempting this procedure, it's important to remember that there is anatomical variation from subject to subject, and although this protocol provides guidelines to follow, experience and anatomical knowledge is crucial to ensure success once mastered, this technique can be done in an hour to an hour and a half per Subject following this procedure. Other methods like segmentation of Rika Robins basis cholinergic hyperintensities, and stroke tracings can be performed. This allows researchers to answer additional questions such as the contribution of specific vascular injury in the study of dementia.

After watching this video, you should have a good understanding of how to accurately and reliably implement the lesion Explorer MRI processing pipeline for volumetric analysis as part of the Sabre Brain Tools. This software is available for free. Download online@sabrebrainlab.ca.