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MRI ICAD 2010

MRI ICAD 2010. Outline. ADNI 1 - Summarize most important results – internal and external ADNI investigators From ISAB summary of reasoning and pilot work behind final GO/ADNI 2 protocol Summarize QC procedures for new sequences Summarize parameters of sequences.

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MRI ICAD 2010

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  1. MRI ICAD 2010

  2. Outline • ADNI 1 - Summarize most important results – internal and external ADNI investigators • From ISAB • summary of reasoning and pilot work behind final GO/ADNI 2 protocol • Summarize QC procedures for new sequences • Summarize parameters of sequences

  3. Previous ADNI session Dx, prediction, rates of change, sample size • Brewer/Dale – Freesurfer • Barnes/Fox • Schuff – all the above also APOE and CSF effects

  4. ADNI 1 image analysis results • MRI has better longitudinal power to detect change than clinical instruments, resulting in smaller sample sizes for clinical trials in both MCI and AD patients • Provided sample size estimates for powering clinical trials for MCI and AD, comparing various methods • Measurement method matters: some MRI analysis methods had greater longitudinal power than others • best performing MRI measures overall  TBM, BSI, Freesurfer • greater white matter hyperintensity load in AD than control and in MCI than control subjects who would be typically enrolled in therapeutic trials [Carmichael]  use as co variate in clinical trials

  5. Hua et al

  6. Sample Sizes per Arm Needed to Power Treatment Study in AD/MCI

  7. Cross Sectional Separation of Clinically Diagnosed AD vs. Controls

  8. ADNI 1 image analysis results • MRI rates of change in cognitively normal subjects are greater in APOE e4 carriers than non-carriers [Schuff, 2009; Morra, 2009; Fjell, 2010] • lower CSF A42 was associated with a thinner cortex in cognitive healthy controls [Tosun, 2010] • No difference between 1.5T and 3T in group-wise discrimination or sample sizes needed to power trials [Ho, 2009]

  9. Association between low baseline CSF A1-42 concentrations and cortical thickness in cognitive normal elderly - Tosun, 2010

  10. CSF AB and decreased brain volume in cognitively normal elderly (CDR 0) Fagan et al Annals 2009

  11. Dynamic Biomarkers of the Alzheimer’s Pathological Cascade Jack et al, Lancet Neurol 2010; 9: 119-28 Ab Amyloid = CSF Ab42 or amyloid PET imaging; Tau Mediated Neuron Injury and Dysfunction = CSF tau or FDG PET; Brain Structure = structural MRI

  12. Annual change in global PIB ratio and ventricular volume by clinical diagnosis PIB positive subjects (baseline global cortical PIB ≥ 1.5) are represented with triangles and PIB negative subjects (baseline global cortical PIB < 1.5) are represented with circles. Jack et al, Brain 2009 132 (Pt 5):1355-65

  13. ADNI: Predicting time to conversion from MCI to AD from baseline biomarkers – univariately Vemuri et al Neurology 2009

  14. Effect of APOE on biomarkers • AB chaperone • Hypothesis is e4 would selectively affect amyloid biomarker Vemuri et al, ePub Annals of Neurology, 2010

  15. Conclusions concerning image corrections Metric is sample size per arm to detect a 25% rate reduction in AD – question is, do image corrections reduce technical variance in a meaningful way? • 3D Grad warp ~ 10% SS reduction (Gunter, Med Phys, 2009) • Scaling correction ~ 12% SS reduction (Clarkson, NI, 2009), image registration (vs phantom) is preferred method • Intensity correction improves longitudinal precision – esp multi array coils and 3T (Leow NI 2006; Boyes, NI 2008)

  16. Conclusions ADNI phantom • value of scanner monitoring - 20% of all ADNI-1 scans would have been affected by errors of various types had each scanner not been monitored [Gunter, 2009] • Designed ADNI phantom. Has been adopted as the starting point for quantitative MRI phantom by ISMRM and NIST

  17. Outline • ADNI 1 - Summarize most important results – internal and external ADNI investigators • From ISAB • summary of reasoning and pilot work behind final GO/ADNI 2 protocol • Summarize QC procedures for new sequences • Summarize parameters of sequences

  18. GO/ADNI 2 MRI protocol - rational • ADNI 1 carry forward subjects:maintain MRI methodological consistency • same 1.5T scanner, using ADNI 1 1.5T protocol • Discontinue dual 3T/1.5T scans for those in “3T arm” • new GO/ADNI 2 enrollees:modernize and expand MRI protocol • 3T • limit ~ 30-40 minutes (limits # possible sequences in protocol) • only product sequences – ie no WIPs • Core protocol on all scanners, and vendor specific “experimental” sub studies

  19. GO/ADNI 2 MRI 3T Protocol • 3D T1 volume unaccelerated (MPRAGE Siemens and Phillips, IR SPGR GE) • 3D T1 volume 2X accelerated • FLAIR • long TE 2D gradient echo • Experimental: Siemens (ASL), GE (DTI), Phillips (resting state EPI-BOLD) • Phantom (once per day if > 1 ADNI patient)

  20. GO/ADNI 2 MRI Core Protocol • All newly enrolled GO (and ADNI 2) subjects • All vendor systems • 3D T1 volume (MPRAGE Siemens and Phillips, IR SPGR GE) Each MRI exam will contain both an accelerated and a non-accelerated 3D T1 acquisition – * not back-to-back, (3.6%) exam “salvage rate” • FLAIR (instead of PD/T2) – better measures of WMH • long TE 2D gradient echo (e.g., TE = 20 ms)acquisition for micro hemorrhage detection  what is natural history (prevalence and incidence) if MCH and superficial siderosis in a clinical trials population?

  21. Phillips MPRAGE unaccel 9:06 Comparison 3T 3D T1 35 yo volunteer Phillips MPRAGE accel 5:35 GE MPRAGE (ADNI-1) 9:17 GE IR-FSPGR (ADNI-GO) 9:41 GE IR-FSPGR (ADNI-GO) 5:34

  22. Long TE gradient echo scan Micro Hemorrhages Superficial Hemosiderosis

  23. GO/ADNI 2 experimental sub-studies– every subject gets one type • *vendor specific – each not done in every subject • Why? (1) impossible to standardize without WIPs, (2) no product available, (3) limit 30 - 40 min • arterial spin labeling (ASL) perfusion - Siemens • diffusion tensor imaging (DTI) – GE • resting state functional connectivity – Phillips • purpose - to evaluate the feasibility of acquiring useful data in a multi-center (but single vendor) setting - are these techniques useful for clinical trials? Mission of ADNI.

  24. QC of experimental sequences • Will only repeat exam for quality failure of un accelerated 3D T1 • more scans with quality problems in GO/ADNI 2 than ADNI 1 • QC information will be more important • Raw images vs maps • Raw images – QCed at Mayo for protocol compliance, completeness, head coverage, bulk motion, susceptibility artifacts • Maps QCed by individual labs (Thompson, DeCarli, Jack, Schuff) that upload numeric data

  25. DTI - Color Coded FA Maps From Kantarci et al, in press Neurology

  26. Page 1 of 10

  27. GO/ADNI 2 protoocls http://www.loni.ucla.edu/ADNI/Research/Cores/index.shtml

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