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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

MRI

ICAD 2010


Outline
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


Previous adni session
Previous ADNI session

Dx, prediction, rates of change, sample size

  • Brewer/Dale – Freesurfer

  • Barnes/Fox

  • Schuff – all the above also APOE and CSF effects


Adni 1 image analysis results
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





Adni 1 image analysis results1
ADNI 1 image analysis results Controls

  • 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]


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


Csf ab and decreased brain volume in cognitively normal elderly cdr 0 fagan et al annals 2009
CSF AB and decreased brain volume in cognitively normal elderly (CDR 0) Fagan et al Annals 2009


Dynamic biomarkers of the alzheimer s pathological cascade
Dynamic Biomarkers of the Alzheimer’s Pathological Cascade elderly (CDR 0)

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


Mri icad 2010

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


Mri icad 2010

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


Mri icad 2010

Vemuri et al, ePub Annals of Neurology, 2010


Conclusions concerning image corrections
Conclusions concerning image corrections baseline biomarkers – univariately

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)


Conclusions adni phantom
Conclusions ADNI phantom baseline biomarkers – univariately

  • 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


Outline1
Outline baseline biomarkers – univariately

  • 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


Go adni 2 mri protocol rational
GO/ADNI 2 MRI protocol - rational baseline biomarkers – univariately

  • 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


Go adni 2 mri 3t protocol
GO/ADNI 2 MRI 3T Protocol baseline biomarkers – univariately

  • 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)


Go adni 2 mri core protocol
GO/ADNI 2 MRI baseline biomarkers – univariately 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?


Mri icad 2010

Phillips MPRAGE unaccel 9:06 baseline biomarkers – univariately

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


Mri icad 2010

Long TE gradient echo scan baseline biomarkers – univariately

Micro

Hemorrhages

Superficial

Hemosiderosis


Go adni 2 experimental sub studies every subject gets one type
GO/ADNI 2 experimental sub-studies baseline biomarkers – univariately – 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.


Qc of experimental sequences
QC of experimental sequences baseline biomarkers – univariately

  • 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


Dti color coded fa maps
DTI - Color Coded FA Maps baseline biomarkers – univariately

From Kantarci et al, in press Neurology


Mri icad 2010

Page 1 of 10 baseline biomarkers – univariately


Go adni 2 protoocls
GO/ADNI 2 protoocls baseline biomarkers – univariately

http://www.loni.ucla.edu/ADNI/Research/Cores/index.shtml