mri april 2015 mayo cliff jack bret borowski matt bernstein arvin forghanian-arani jeff gunter dave...
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MRI April 2015Mayo Cliff JackBret Borowski Matt BernsteinArvin Forghanian-
Arani Jeff GunterDave Jones Kejal KantarciRob Reid Denise Reyes Matt SenjemKaely ThostensonPrashanthi Vemuri Chad Ward
Funded MRI InvestigatorsCharlie DeCarli – UCD
Nick Fox – UCL
Mike Weiner/Duygu Tosun – SFVA
Paul Thompson – USC
Danielle Harvey – biostats
MR Company collaboratorsDan Rettmann – GE Mayo
Pete Kollasch – Siemens, Mayo
Yansong Zhao - Philips, BU
ADNI 3 protocol – all sequences in all subjects 3D T1 volume
3D FLAIR T2* GRE ASL –3D, pCASL, background suppression TF-fMRI – 2 tiered, use capability of advanced
systems Advanced - 10 minute, multi band, sub second TR Basic – 10 minute, 3 sec TR
dMRI - 2 tiered, use capability of advanced systems Advanced - 2 b-shells with 48/64 encoding
directions Basic – single shell b=1000
Coronal high res T2 – hippocampal subfields
ADNI 3 MRI protocol rationale 3D T1, FLAIR, T2*GRE
3D T1 (MPRAGE, IR-FSPGR) most precise longitudinal measure (biomarker or
clinical/psych) – core for multi modality comparisons
Associations with tau PET (and other measures) FLAIR
Disease detection – safety standard, clinical reads Associations of CVD with tau PET (and other
measures) Possible improved results with 3D
T2* GRE MCB detection, all clinical trials
ADNI 3 MRI protocol rationale ASL, dMRI, TF-fMRI
Promising associations, but not strong enough to recommend including in trials using ADNI 2 methods
Significant developments since ADNI 2 given in other fields, improved methods =
better diagnostic performance multi modality comparisons in deeply
phenotyped subjects Opportunity to see if advanced methods cross
the diagnostic “value” threshold in ADNI environment
ADNI 3 MRI protocol rationale ASL, dMRI, TF-fMRI
field continues to seek methods which can be used in Phase 2 which provide an early signal of treatment response
measures of brain function may detect neuronal response to therapeutic reduction in toxic molecular species (e.g. soluble Ab or tau)
2016 advanced is 2022 routine – do not want methods to be outmoded by end of ADNI 3 grant cycle
Grantsmanship – novelty
Approach to “experimental sequences ” from ADNI 2 – leveraging the best in class
from other efforts dMRI and TF-MRI – human
connectome project (HCP) ASL – ISMRM expert work group Phantom – NIST/ISMRM QMRI
committee
dMRI approach advanced, HCP-like – 2 shells, b=1000
& 2000 Better ROI-based MD, FA measures Enable adding ROI-based kurtosis measures Enable tractography Enable cortical hub to hub connectivity analyses
Basic – single shell, b=1000 Compatibility – equivalent of basic
dMRI in every subject at no time penalty extract b1000 shell from advanced acquisitions
Rooted in multi center real world trial environment
ADNI 3 dMRI b shell sampling illustrated
2.0 mm isotropic for both
advanced basic
#(b = 0) 18 6
#(b = 1000) 48 48
#(b = 2000) 64 0
Arrangement
Advanced (Multiband, Multishell)skyra
BasicGE 750
EPI Distortion
Correcting EPI Distortion By Acquiring b = 0 volumes with
both P->A and A->P Phase Encoding Directions
TF-fMRI approach
advanced, HCP-like – 10 min, sub second TR, MB More precise measure of time series (temporal
resolution) Less noisy node to node, ICA, graph theory
measures Directly measure physiological parameters Time varying connectivity metrics
Basic – 10 minute, ~3 sec TR Compatibly advanced and basic
down sample advanced time series to 1 volume/~3 sec
MB Acquisition TR=482ms 20 minutes test data from healthy
volunteer Spatial resolution 3x3x3mm MB=8 which has 4x multiplexing and 2x
in plane acceleration Downsampled by cubic spline
interpolation at multiples of 3.0 sec interpolant includes information from
about same “receiver on” time as a fully sampled data – SNR’s of fully sampled TR=3 data ~ downsampled
Downsampling MB fMRI
pseudo-continuous labeling with background suppression
segmented three-dimensional readout without vascular crushing gradients
and calculation and presentation of both label/control difference images and CBF maps
GE product now; Siemens d13; Philips 3D GraSE now testing
3D pCASL CBF map, volunteer, GE
• 8 Channel Head Coil• Acquisition Orientation: Axial• FOV: 22 cm• TR/TE: 11000/147.0 ms• TI: 2250 ms• Resolution: 3.6*0.86*1.14 (ST*FE*PE)• Scan time: 4:25 (mins:sec)
GE Standard 2D FLAIR
GE V25 3D FLAIR + T2 Prep + PROMO
• 24 Channel Head Coil• Acquisition Orientation: Sagittal• FOV: 25.6 cm• TR/TE: 7600/115.0 ms• TI: 1968 ms• Resolution: 1.4*1*1.14 (ST*FE*PE)• Scan time: 5:14 (mins:sec)
MR Phantom: ADNI Experience
scanners are much more stable now vs 2005 –hence less need to correct for scan to scan geometry fluctuation
use phantom to track scanners through upgrade and maintenance cycles – qualification and re qualification
Phantoms are helpful for establishing comparability of new models of scanners as the come along
ADNI Phantom Designed by ADNI MRI core along with
Rich Mallozzi (GE), Josh Levy(Phantom Labs) in 2004/2005
produced at Phantom Labs in upstate NY – Josh Levy
Priced in the range of $6k per unit Freely available analysis package
distributed via ADNI website – Jeff Gunter (Mayo)
Commercial analysis available from ImageOwl (a Phantom Labs partner)
NIST-ISMRM System Phantom
ISMRM Standards and Quantitative MR committee has developed a quantitative MRI phantom design
Provides similar geometric fidelity measurements to ADNI phantom (that component strongly influenced by ADNI phantom experience)
WITH resolution and slice thickness assessments inspired by ACR-NEMA phantom
AND NIST validated T1, T2, PD arrays
NIST-ISMRM System Phantom
ADNI phantom
NIST-ISMRM System Phantom
“Open Source” philosophy – anybody welcome to manufacture them Currently only vendor has done it more expensive than ADNI phantom –
target price is lower if production can be increased
Analysis software is currently immature (work in progress) – will be open source
NIST-ISMRM System Phantom Specs
• Diameter: 201 mm• Contrast cells, 20 mm ID spheres:• 14 spheres T1 spread (20ms-2s)• 14 spheres T2 spread (8ms–800ms)• 14 spheres proton density• True dimensional/positional accuracy of 0.1 mm on all key elements• Resolution insert with hole/slot arrays (hole dimensions from 1 mm
down to 0.4 mm with 1.2 mm spacing)• Wedges for slice profiling (Two 80 mm x 8mm wedges at a 10° angle)• Physical and MR key to precisely determine phantom alignment• Physical and MR readable serial numbers• NIST verified T1, T2, and dimensional properties• Public domain 3D model, parameter spread sheet
Plan for phantoms in ADNI 3 Use: to qualify and requalify scanners
But ADNI phantoms in field for 10yrs Keep existing ADNI phantoms that are in
the field until they age out of use and need repair/replacement
Previous pharma studies have some ADNI phantoms in storage at Mayo which could be folded into the ADNI fleet as replacements needed
When that supply is exhausted, roll in NIST/ISMRM phantom to replace ADNI phantoms?
Comparison testing this summer
MR measures - Maintain current set of funded MR investigators with roles adapted
to ADNI 3 Structural MRI measures BSI – UCL (Fox) Freesurfer – SFVA (Tosun ) TBM – USC (Thompson) TBM-Syn – Mayo (‘Jack’)
Cerebrovascuar disease – UC Davis (DeCarli) AIRA H (CMB) – Mayo (‘Jack’) ASL – SFVA (Tosun) TF-fMRI – Mayo (‘Jack’) dMRI - USC (Thompson) Hipp subfields – SFVA (Mueller)
Site query
ADNI 3 is predicated on modern scanning methods
Have not been given access to most modern scanner at some sites
Letter to site PIs from Mike – enlisting help in gaining access
will not do dMRI, ASL, TF-fMRI on scanners that can not meet spec for basic protocol
Summary: High res subfield volumetry vs. standard hippocampal volumetry
• Requires special high resolution sequence (8.1 min acquisition time wo acceleration). BUT, acceleration by factor 2 is possible Loss of S/N likely to be compensated by reduced susceptibility to motion.
• Has potential to reduce the sample sizes needed to detect effects of early AD (amyloid positivity, differentiation between EMCI and normal) by a factor 2 to 3 compared to traditional hippocampal volumetry.
• Fully automated algorithms allowing for subfield segmentation of the entire hippocampus available, dedicated longitudinal processing available or being developed. Most algorithms also include parcellation of extrahippocampal mesial temporal structures, e.g. entorhinal cortex, BA36.
Group, (AD, EMCI, LMCI, normal), Normal vs EMCI, detection of hippocampal volume loss in EMCI compared to Amyloid in Normal: subfield volume loss due to amyloid positivity, all analyses corrected for age, ICV
SNAP
Annals Neurol 2012 Objectives Operationalize the NIA-AA criteria How do cognitively normal subjects
(n=450) in MCSA distribute in the NIA-AA scheme?
Proportions of cog normal preclinical A stage Annals, 2012
43%
3%12%
16%
A-N+; suspected non-AD pathophysiology (SNAP) – 23%
suspected pathological basis of SNAP:
heterogeneous Annals 2012 Non-AD pathology
cerebro-vascular disease, Lewy body disease, grain disease, TDP43, hippocampal sclerosis
Medial temporal tauopathy wo amyloidosis - Braak 1997, 2011; Delacourte 2002; Duyckaerts 1997; Price and Morris 1999; Crary 2014 (PART)
Aging