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What 3.2 needs from 1 and 2 I. Needs from genetics (Kennedy and Potkin): 1) Use test file genotypes to begin to operationalize genetic and imaging data analyses – the test file for the Potkin N=28 sample has real BDNF and SNAP25 gene data available. – We need imaging phenotypes (segmentations) to get started: eg whole brain grey matter vs BDNF, SNAP25; then brain subregions eg hippocampus, dorsal parietal, etc) – From March 05 after ethics approval in Toronto, will have data for many more genes available eg Dopamine D1, D2, BDNF haplotypes, myelin system genes…) What 3.2 needs from 1 and 2 The most important need (requirement!) is the integration of existing and newly modified tools to be interoperable in a stable, efficient environment to support the following: Anatomically accurate and functionally meaningful segmentations Optimal, dedicated, neuroanatomist-friendly tractography program Integration of a neuroscientist-friendly tractography with segmentations, other functional data (SEM, PET, fMRI, fa/ADC, etc) Further integration of these with genetic data Interactive, dyNAMIC, Visualization of large, multi-scale, multi-subject, multi-modal data What 3.2 needs from 1 and 2 I. Needs from genetics (con’t) 2) Examine the PEDSPLIT software to understand the first steps to test two genes in the same sample (problems: the current program is for parent-to-child transmission of gene variants – we need to generalize to non-familial singleton cases. Next important step will be to modify this program or invent another one that will analyze more than 2 genes simultaneously) What 3.2 needs from 1 and 2 II. Anatomical accuracy and integrated data-Jim Fallon 1- Anatomical accuracy Tannenbaum – apply Fallon rule–based averaged functional anatomical unit for DLPFC for 27 of the UCI 28 scz patients 2- Integrating anatomical, functional data COMT effects McCarthy Kilpatrick Sem corr= -.46 fa/ADC= .72/a +.26 .67/e +.42 .75/d +.26 .45/b +.72 .35/c 2- Integrating anatomical, functional data II. Anatomical accuracy, tractography and integrated data-Jim Fallon 2- Integration of data Need to integrate the population and individual subject tractography, with multiple standard segmentations, plus functional anatomical units, functional imaging data, structural equation modeling, etc to create more sophisticated circuitry diagrams. -Problem with existing automatic segmentations is that you can only segment the cortex in FreeSurfer automatically. Then you can only bring into Slicer the cortical surface with the colorized labels but have no way of overlaying the labels on the anatomical slices in Slicer. When you then add fMRI statistical data in Slicer you can see the “blobs” in the slices views but without the anatomical labels it isn’t integrated well. That is to say, the surface labeled object from FreeSurfer doesn’t contain the imported statistical maps and the T1 anatomicals as the slices views. -Same as above for subcortical structures which currently aren’t available via automated segmentations. -Integrate tractography growing tools (fiber tracts+QBALL gliphs+FA/ADC, etc) with cortical and subcortical parcellations and statistical activation data, eg. SPMs, structural equation modeling, fMRI. II. Anatomical accuracy, integrated data and tractography3- Tractography needs and analyses: a) We need a seeding/ROI “ABCD filter by March 1 ILF Occipito-temporal pathways Inferior longitudinal fasciculus Occipito-temporal pathways Unwelcome extended family Members: Loop of Flechsig-Meyer Occipito-temporal pathways C A Need for ABCD filters together with hand-made tractography 3)Immediate needs in order to start the tractography analyses b) We need a quick easy way to modify segmented areas, eg, for us in tractography we need more than segmented cortical areas, we need the lobular white matter beneath cortex to capture the tracts. Also need automated subcortical segmentations available in connecting tracts. C A How to segment these ‘grey’ Areas? Typical cortical segmentation Need to fill in the sublobular white matter to capture tract stems for growing tracts Immediate needs in order to start the tractography analyses c) We need to get up close to most tracts to grow them. However, when you draw in close and start growing fibers, you don’t know where they end up going, since they leave the field of view. So you end up growing extraneous fibers, and then when you pull back to low mag, you realize you have to delete half of them. So, multiple images are needed to view at low and high mag simultaneously. Seeding and admiring the tracts from afar: The computer scientist’s approach Up close and Personal; the warm and fuzzy neuroanatomist’s Also need to create “Armor piercing bullets”. Perhaps Q-Ball can help greatly here, but we’d need the tractography and the approach directional glyphs visible in the same window. II. Anatomical accuracy b) From Tannenbaum lab – apply Fallon rule–based averaged functional anatomical units for other brain areas More segmentations than found in present seg programs are needed, ie, Functional-Anatomical-Units, eg, eye fields, parietal attentional, superior temporal gyrus subdivisions SEF 6 8 6 7 4 40 39 Standard Brodmann segmentation FEFs FEFa FEFi PEF Second level needs for tractography, still pressing a) The features mentioned should be on a tractography menu with icons/pictures/circuits so that it is visually intuitive for use by a learning-impaired neuroanatomist. b) Easy, intuitive import of other tools and databases such as Freesurfer, Taliarach, Q-Ball, Leventon, LONI, CSAIL, fa/ADC statistical analyses, literature, etc. info. c) Need to agree on the meaning of the tracts and structures in the context of endophenotypic clinical, genetic, cognitive, etc data d) Need for highly trained students and techs to learn all the techniques AND the biology. It took me 30 years to begin to understand the neuroanatomy of the entire brain and I’m really not sure I can teach another human or a computer do do this in under 5 years. There are only a handful of “arrow neuroanatomists” who know the entire brain, and the few of us still alive are either dying, being politically redistricted, or assasinated. e) Need a standard RGB color palette that doesn’t need to be imported each time f) Deep voxels and visualization g) Need to integrate all the data into hybrid visualizations Falko Kuester’s UCI hybrid reality visualization laboratory. The images depict multiple SMART board displays of 2D orthogonal slices and a synchronized 3D stereoscopic projection system using Kuester-developed software and middleware. Time series image sequences (4D) and ability to annotate images are available but not depicted Also need more shirts like his. h) The tools are difficult for someone like me to use. If the only thing I want to do is tractography, I have to press the same 20 buttons or more every time I lay down a tract. Some of the terminology is confusing and ambiguous and the learning curve is pretty darn steep. A 2 Gig laptop quickly gets overwhelmed after the first tract is drawn, so there are numerous crashes, and deleting just one fiber may take 5 minutes….. Last, but perhaps most important overall… THE TRACTOGRAPHERS NEED A SEPARATE FRONT END ON SLICER DEDICATED JUST TO DTI, USING INTUITIVE ICONS AND UNAMBIGUOUS TERMINOLOGY, AND INTEGRATING ALL PRESENTLY AVAILABLE TOOLS FROM NAMIC COLLABORATORS. THE PROGAM NEEDS TO RUN MUCH FASTER AND CONSUME LESS ‘EXTRANEOUS’ SUBROUTINES, MEMORY, AND TASKS. REPEAT STEPS NEED TO BE SCRIPTED INTO ONE-STROKE BUTTON PRESSES. TAKE ALL THE BEST TOOLS AND INTEGRATE THEM INTO A SINGLE MACHINE/SOFTWARE WORKING