Transcript
Page 1: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Velo-Cardio-Facial Syndrome

PRINCIPAL INVESTIGATOR:

Marek Kubicki, MD, PhD

INVESTIGATORS:

Zora Kikinis, PhDSylvain Bouix, PhDMarc Niethammer, PhDMartha Shenton, PhDChristine Finn, MDRaju Kucherlapati, MD

RESEARCH ASSISTANT:Kate Smith, BA

Page 2: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Velo-Cardio-Facial Syndrome (VCFS)

• Deletion of the fragment of short arm of the 22nd chromosome (single copies of 30 to 45 genes missing)

• Prevalence 1 in every 4000 newborns

• Clinical symptoms:– "velum" latin meaning soft palate

– “kardia" greek meaning heart

– "facial" latin having to do with the face

• Cognitive symptoms:– Psychomotor deficits

– Learning and memory disabilities

– Emotional abnormalities (flat affect and poor social interaction).

– High incidence for schizophrenia and/or bipolar disorder in adult (30% VCFS patients develop schizophrenia), and 4-5 genes have been suggested to be related to schizophrenia (COMT- attention, memory, prefrontal function; RTN4R- axonal regeneration and plasticity)

Page 3: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Aims

• Etiology of schizophrenia and

related diseases

• Prognosis of mental health diseases in VCFS

• Early intervention

Page 4: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Project

• Subject recruitment

• Psychological interview

• DNA analysis, genotyping of the 22q11.2 region

• Brain imaging (MRI, DTI and fMRI)

• Analysis of imaging data, and genetic correlations

Page 5: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Imaging Data Available

Two stages:

• Available now:

7 VCFS and 7 matched control cases scanned on 1.5 T magnet (DTI and structural scans)

15 schizophrenics and 15 control cases scanned on 3T magnet (DTI and fMRI) plus 1.5T chronic schizophrenia data (DTI and structural scans)

• Available by the end of the year:

15 VCFS and 15 matched control cases scanned on 3T magnet (DTI, structural scans and fMRI)

Page 6: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Hypotheses Regions that we want to study with MRI- DLPC (executive function, memory)

- Orbital Frontal Gyrus (emotion)

- Cingulate Gyrus (attention, emotion)

- Hippocampus (memory, learning)

Tracts that we want to study with DTI (frontal-temporal connections):- Fornix (memory)

- Arcuate Fasciculus (language)

- Cingulum Bundle (attention)

- Uncinate Fasciculus (emotion, affective flattening)

Networks that want to study with fMRI :- Memory, attention, emotion, language (semantic processing)

Page 7: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Specific Requirements

- Automatic DLPC segmentation.

- Automatic segmentation of other structures (orbital frontal cortex, cingulate gyrus, hippocampus).

- Tools for measuring anatomical connectivity between these regions (optimal path analysis, stochastic tractography).

- “Default network” and “rest” fMRI analysis.

- Anatomical (DTI), and functional (fMRI) connectivity analysis.

Page 8: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Progress So Far

- Automatic DLPC segmentation.

- John and Brad finished the slicer2 module, its being tested and used for first episode schizophrenia study now.

- Automatic segmentation of other structures (orbital frontal cortex, cingulate gyrus, hippocampus).

- We have limited experience with freesurfer and cingulate, have not tried Killian’s segmentation for anything other than STG.

- Tools for measuring anatomical connectivity between these regions (optimal path analysis, stochastic tractography).

- Optimal Path Analysis- we used it, but its not yet in the slicer, there might be some problems with it. Same with Stochastic tractography.

- “Default network” fMRI analysis, functional connectivity analysis.

- Polina and Sandy might have some tools, but we have not tried them yet.

Page 9: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Potential Challenges for Segmentation/Registration

• Different brain shape

• Thicker skull

• Brain atrophy

• Congenital abnormalities

• Brain asymmetry

• White matter lesions

Page 10: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

Segmentation/Registration

Beneficial algorithms/software:

• Automatic segmentation procedures tailored for VCFS (atlas?).• Automatic parameterization of segmentation algorithm (e.g., optimal parameter selection for EM segmenter based on training data).• Robust and easy to use registration.

Capabilities for batch processing.

Page 11: Velo-Cardio-Facial Syndrome

National Alliance for Medical Image Computing http://na-mic.org

May, 2007

VCFS Schizophrenia Candidate Genes

• COMT (controls dopamine degradation in prefrontal cortex, related to attention and memory)

• RTN4R (also known as Nogo 66, related to axonal regeneration and plasticity)

• PRODH

• ZDH8

• SNAP29

• TBX1


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