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= <small>v3.6.1</small> [[Image:Slicer3-6Announcement-v1.png‎|150px]]  Slicer Registration Library Case 18: <br>   =
=== Input ===
{| style="color:#bbbbbb; " cellpadding="10" cellspacing="0" border="0"
|[[Image:Reglib_C18_Thumb1.jpg|100px|lleft|this is the main fixed reference image. All images are ev. aligned into this space]] 
|[[Image:Reglib_C18_Thumb2.jpg|100px|lleft|this is the main fixed reference image. All images are ev. aligned into this space]] 
|[[Image:RegArrow_Affine.png|70px|lleft]] 
|[[Image:Reglib_C04_Thumb_.jpg|100px|lleft|this is the intra-subject moving image. ]]
|-
|exam 1: PD
|exam 1: T2
|
|exam 1: T1-Gd
|-
|[[Image:RegArrow_AffineVert.png|70px|lleft]] 
|
|
|
|-
|[[Image:Reglib_C04_Thumb_PD2.jpg|100px|lleft|this is the inter-subject moving image, but also the reference for exam 2]]
|[[Image:Reglib_C04_Thumb_T22.jpg|100px|lleft|this is the inter-subject moving image, but also the reference for exam 2]]
|[[Image:RegArrow_Affine.png|70px|lleft]] 
|[[Image:Reglib_C04_Thumb_Gd2.jpg|100px|lleft|this is the moving image. ]]
|-
|exam 2: PD
|exam 2: T2
|
|exam 2: T1-Gd
|}

=== Modules ===
*'''Slicer 3.6.1 recommended modules:  [http://www.slicer.org/slicerWiki/index.php/Modules:BRAINSFit BrainsFit], [http://www.slicer.org/slicerWiki/index.php/Modules:RegisterImages-Documentation-3.6 Expert Automated Registration]

===Objective / Background ===
This scenario occurs in many forms whenever we wish to assess change in a series of multi-contrast MRI. The follow-up scan(s) are to be aligned with the baseline, but also the different series within each exam need to be co-registered, since the subject may have moved between acquisitions. Hence we have a set of nested registrations. This particular exam features a dual echo scan (PD/T2), where the two structural scans are aligned by default. The post-contrast T1-GdDTPA scan however is not necessarily aligned with the dual echo. Also the post-contrast scan is taken with a clipped field of view (FOV) and a lower axial resolution, with 4mm slices and a 1mm gap (which we treat here as a de facto 5mm slice).
=== Download ===
*Data:
**[[Media:RegLib_C18_Data.zip‎|'''Registration Library Case 04: MS Multi-contrast series (PD,T2, T1-GdDTPA): Lesion change assessment''' <small> (Data,Presets, Solution, zip file 17 MB) </small>]]
*Presets
**[[Media:RegLib_C18_Presets_BrainsFit.mrml‎|Registration Presets (BrainsFit) <small> (mrml file ,12kB) </small>]]  
**[[Projects:RegistrationDocumentation:ParameterPresetsTutorial|Link to User Guide: How to Load/Save Registration Parameter Presets]]</small>
*Documentation
**see Methods section below for step-by-step instructions

=== Keywords ===
MRI, brain, head, intra-subject, multiple sclerosis, MS, multi-contrast, change assessment, dual echo, nested registration

===Input Data===
*reference/fixed : PD.1 baseline exam , 0.9375 x 0.9375 x 3 mm voxel size, axial acquisition, RAS orientation. 
*fixed  T2.1 baseline exam , 0.9375 x 0.9375 x 3 mm voxel size, axial acquisition, RAS orientation.  -> (aligned with PD.1, not used for registering)
*moving: T1.1 (GdDTPA contrast-enhanced scan)  baseline exam 0.9375 x 0.9375 x 5 mm voxel size, axial acquisition.
*moving: PD.2 follow-up exam 0.9375 x 0.9375 x 3 mm voxel size, axial acquisition.
*moving: T2.2 follow-up exam 0.9375 x 0.9375 x 3 mm voxel size, axial acquisition. -> same orientation as PD2, will have same transform applied
*moving:T1.2-GdDTPA   follow-up exam0.9375 x 0.9375 x 5 mm voxel size, axial acquisition. -> undergoes 2 transforms: first to PD.2, then to PD.1

===Registration Challenges===
*we have multiple nested transforms: each exam is co-registered within itself, and then the exams are aligned to eachother
*potential pathology change can affect the registration
*anisotropic voxel size causes difficulty in rotational alignment
*clipped FOV and low tissue contrast of the post-contrast scan 

===Key Strategies===
*we first register the post-contrast scans within each exam to the PD
*second we register the follow-up PD scan to the baseline PD
*we also move the T2 exam within the same Xform 
*we then nest the first alignment within the second
*because of the contrast differences and anisotropic resolution we use Mutual Information as cost function for better robustness
=== Procedure ===
*'''Load & Center'''
#Load example dataset via OpenScene...
#Go to the ''Data'' module. You should see 6 images (e1_PD, e1_T2 etc.) and 3 solution transforms (Xform_...)
#Set background view to e1_PD and foreground to e2_PD. Toggle to see misalignment
#Center All images
##original images come with different origin settings, which make viewing difficult. We first re-center all images:
##Go to ''Volumes'' module, open ''Info'' tab
##From ''Active Volume'' menu, select each image in turn, then click the ''Center Image'' button
*'''Align Exam 1:''' 1st pass: unmasked
#Open ''Registration / BRAINSFit'' module
##To set all parameters from presets, from the ''ParameterSet'' menu, select "Xf1_e1_FLAIR-T1_unmasked", else choose settings below:
##Fixed Image: e1_T1, moving image: e1_FLAIR
##Registration Phases: select "Initialize with CenterOfHeadAlign",  ''Include Rigid'', "IncludeScaleVersor3D" and ''Include Affine''
##Output Settings: under SlicerLinear Transform, select "Create New Linear Transform'', then select ''Rename" and rename it to ''Xf1_e1_FLAIR-T1''
##Registration Parameters: increase the ''Number of Samples'' field to 200,000
##Leave all other settings at defaults & Click:  ''Apply''. Registration should complete within ~ 30 seconds
##Go back to the ''Data'' module: you should see the e1_FLAIR image moved under the newly created transform
##Select "E1_T1" as background and ''e1_FLAIR'' as new foreground, toggle to see alignment
##you will notice a small but distinct residual translational misalignment, apparent on axial and sagittal slices. This likely arises from dominant edges of the skull. We rerun a 2nd pass with masks

#'''Align Exam 2:'''
##repeat the above steps for ''e2_PD'' as fixed and ''e2_T1Gd'' as moving
##To set all parameters from presets, from the ''ParameterSet'' menu, select Gd2-PD2
#'''Align Exam 2 with Exam 1:'''
##Open ''Registration / BRAINSFit'' module
##To set all parameters from presets, from the ''ParameterSet'' menu, select PD2-PD1, else choose settings below:
##Fixed Image: e1_PD, moving image: e2_PD
##Registration Phases: select ''Include Rigid'' and ''Include Affine''
##Output Settings: under SlicerLinear Transform, select "Create New Linear Transform'', then select ''Rename" and rename it to ''MyXform_PD2-PD1''
##Registration Parameters: change the ''Number of Samples'' field to 200,000
##Leave all other settings at defaults
##Click Apply. Registration should complete within ~ 10 seconds
##Go back to the ''Data'' module: you should see the e2_PD image moved under the newly created transform
##Select ''e2_PD'' as new foreground, toggle to see alignment
#'''Combine Transforms:'''
##move e2_T2 inside the PD2-PD1 transform (same level as e2_PD)
##move XForm_Gd2-PD2 and the image inside (e2_T1Gd) inside the PD2-PD1 transform
##see image below for how the Data Tree should look after nesting the transforms
##Select pairings as fore- and background and click toggle button to check alignment
##inparticular see if e2_T1Gd is aligned with e1_T1Gd
#'''Harden/Export results:''''
##Select each registered image in turn, and from right-click menu select ''Harden Transform''. Then immediately rename the node (via MRML Node Inspector below the MRLML tree tab) to distinguish from the original
##Select the Xform_Gd2-PD2 when inside the XForm-PD2-PD1 and also select 'Harden Transform''. Then immediately rename to ''Xform_Gd2-PD1''.
##Choose ''File/Save'' to save results.
<br>

before registration: [[Image:RegLib_C04_DataTree.png|200px|Orig. MRML Data tree]] 
after registration: [[Image:RegLib_C04_DataTree2.png|200px|Registered. MRML Data tree: exam 2 is within nested affine transforms]]

=== Registration Results===