ENIGMA OCD working group

Teleconference 19th of February 2015

2 PM GMT (Greenwich Mean Time) Amsterdam/Barcelona/Berlin/Zurich/Munchen/Rome/Milan 3 PM

Sao Paulo noonTokyo/Kyoto/Seoul 11 PM

Cape Town 2 PMLos Angeles 6 AM

New York/Toronto/Michigan/Boston 9 AMBangalore 7.30 PM

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses3. draft form analysis plans, for additional subcortical meta-analyses4. preparation mega-analyses on pooled raw data5. expert-subgroups for specific topics/analyses6. funding7. status GWAS8. future meetings

Please, send me (oa.vandenheuvel@vumc.nl) an email as soon as your site ‘on the line’, with the name of the person representing the site during the TC.

Take care of the quality of the TC: (un)mute your line by pressing 16!!

Agenda1. status subcortical meta-analyses

1. Quality control guidelines2. Putamen / pallidum segmentations (comparison alternatives)3. Status per site and overall overview

2. planning cortical meta-analyses3. draft form analysis plans, for additional subcortical meta-

analyses4. preparation mega-analyses on pooled raw data5. expert-subgroups for specific topics/analyses6. funding7. status GWAS8. future meetings

Subcortical segmentations FreeSurferQuality Check Important to verify that the FreeSurfer

reconstructions are free from errors and excluded if necessary

Look at histograms find corresponding outliers in LandRVolumes

and evaluate segmentation Perform outlier detection

Note that, an outlier does not automatically means a bad segmentation

Quality check with webpages

A few examples of bad segmentations cover• The shape of the structure is not

delineated properly• Part of the segmentation of one structure

overlaps with that of another adjacent structure

• Part of the structure is left out• Asymmetrical delineation

note that if a subject has skewed head position in the scanner, the structures may appear asymmetrical while they are in fact not

Shape of the structure is not delineated properly

Overlapping structuresSegmented pallidum overlapswith putamen

Part of the structure is left out

Parts of the bilateral putamenare left out

Asymmetrical delineation

Asymmetrical, butskewed head position

Asymmetrical, badsegmentation

Tips for quality checking Always verify poor segmentations in

FSLview FSLview gives you a 3D representation instead

of a 2D (improving your judgment) Adjust contrasts (T1 and segmentation colors)

to evaluate segmentations

Issue: Pallidum segmentationsFreeSurfer

Issue: Putamen segmentationsFreeSurfer

Putamen and pallidum segmentationsFreeSurfer 5.0 vs 5.3

• overall quality approximately equal (in favor of FreeSurfer 5.3)• not always the same subjects get excluded in both versions• repeated in other datasets (1.5T and outside VUmc Amsterdam)

FSL First vs FreeSurfer 5.3 FIRST is a model-based segmentation tool The shape models used in FIRST are

constructed from manually segmented images

Before segmentation images were ‘neckcropped’ and ‘skullstripped’ using BET

While making the quality check webpages for FIRST, images are normalized to standard MNI space

Putamen and pallidum segmentations FIRST

• Overall quality improved with FIRST segmentation• Number of exclusions less in FIRST segmentations• Note that not always the same subjects get excluded

(but great overlap ±70%)

Putamen segmentation (1)

FIRST (good) FreeSurfer 5.3 (bad)

Putamen segmentation (2)

FIRST (bad blue) FreeSurfer 5.3 (good blue)

Pallidum segmentation (1)

FIRST (good) FreeSurfer 5.3 (bad)

Pallidum segmentation (2)

FIRST (blue bad) FreeSurfer 5.3 (blue ok)

Poor segmentations child MRI scans Input from ENIGMA PI’s (Thompson’s group,

meeting Feb 25, 2015 in Amsterdam)? Input from ADHD and autism working group

(meeting February 25, 2015)? Additional ideas?

Current status per sitePlease, check whether the information is

correct and let us know whether the planning (see slide 47) is feasible for your site.

Arnold (CAN) Memory of understanding (still waiting for

the properly checked MOU!!) Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status running recon-all please, proceed a.s.a.p.!

Benedetti (ITA) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Beucke (DEU) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status quality checking data

Cheng (CHN) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status recon-all VUmc is waiting for remaining data (must be uploaded) to be preprocessed at VUmc Amsterdam (NLD)

Denys (NLD) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Fitzgerald (USA) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status quality checking data

Gruner (USA) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status quality checking data

van den Heuvel (NLD) Memory of understanding Putamen/pallidum images Histograms + Summarystats (1.5T data) R statistical output (1.5T data)

Current Status FINISHED subcortical analyses 1.5T data R statistical analyses 3.0T data

Hoexter (BRA) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status checking outliers on histograms

Huyser (NLD)Analyses performed by van den Heuvel (NLD)

Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Koch (DEU) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Kwon (KOR) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status quality checking data

Lazaro (ESP) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status preparing for R analyses

Mataix-Cols (SWE)Analyses performed by van den Heuvel (NLD)

Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status recon-all (we are solving issues with converting hdr format files)

Menchon (ESP) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status quality checking data

Nakamae (JPN) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Nakao (JPN) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status recon-all please, proceed a.s.a.p.!

Reddy (IND) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status quality checking

Rosenberg (USA)Analyses performed by Fitzgerald/Hanna (USA)

Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status agreement with Wayne State University for data transfer

Simpson (USA) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Soreni (USA) Memory of understanding (still waiting for

properly checked MOU!!) Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status running recon-all please, proceed a.s.a.p.!

Spalletta (ITA) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Stein (ZAF) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Tolin (USA) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status checking histograms

Walitza (CHE) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Wang (CHN) Memory of understanding Putamen/pallidum images Histograms + Summarystats R statistical output

Current Status FINISHED subcortical analyses

Memory of Understanding Arnold Soreni

Benedetti Huyser Reddy Beucke Koch

Rosenberg Cheng Kwon Simpson Denys Lazaro Spalletta Fitzgerald Mataix-Cols Stein Gruner Menchon Tolin van den Heuvel Nakamae Walitza Hoexter Nakao Wang

Have sent putamen/pallidum images

Arnold Mataix-Cols Rosenberg Cheng Nakao Soreni Hoexter

Benedetti Koch Simpson Beucke Kwon Spalletta Denys Lazaro Stein Fitzgerald Menchon Tolin Gruner Nakamae Walitza Huyser Reddy Wang van den Heuvel

First instructionsHistograms & Summarystats

Arnold Hoexter Reddy Beucke Kwon Rosenberg Cheng Mataix-Cols Soreni Fitzgerald Menchon Tolin Gruner Nakao

Finished: Benedetti Koch Spalletta Denys Lazaro Stein Huyser Nakamae Walitza van den Heuvel Simpson Wang

Second instructionsR statistical analyses Arnold Hoexter Nakao Beucke Kwon Reddy Cheng Lazaro Rosenberg Fitzgerald Mataix-Cols Soreni Gruner Menchon Tolin

Finished: Benedetti Koch Spalletta Denys Nakamae Stein van den Heuvel Simpson Walitza Huyser Spalletta Wang

Planning meta-analyses for the subcortical volumes Decision on the putamen / pallidum segmentations

> February 25, 2015 Solution for segmentation pediatric MRIs

> March 2015 All sites finished all steps for the subcortical analyses (in FS 5.3),

including analyses in R > March 31, 2015

Meta-analyses (van den Heuvel / Boedhoe at VUmc) > April 2015

Discussion on results during TC, May 28, 2015 Draft paper

> May/June 2015

Feasible?If so, let’s try to meet these deadlines!

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses

is dependent on progress subcortical analyses, but to be started a.s.a.p. (at least for the sites that already finished the subcortical analyses).

1. draft form analysis plans, for additional subcortical meta-analyses

2. preparation mega-analyses on pooled raw data3. expert-subgroups for specific topics/analyses4. funding5. status GWAS6. future meetings

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses3. draft form analysis plans, for additional (sub)cortical meta-

analyses1. See attachment (used in other ENIGMA working groups): comments?2. Forwarded initial ideasNB. A separate analyses plan form will be drafted for the mega-analyses

(on pooled raw data)

4. preparation mega-analyses on pooled raw data5. expert-subgroups for specific topics/analyses6. funding7. status GWAS8. future meetings

Analysis plans - meta-analyses van den Heuvel / Boedhoe

General OCD-control comparison subcortical General OCD-control comparison cortical

(but also possible that another site leads this analyses plan)

....sorry, I received some initial ideas from members, but I can’t find the emails now (between the thousands of ENIGMA-OCD-emails in my box)

... Please fill in the analyses plan form and forward this to me. I will make a list of the ideas and forward it to all members for comments and approval.

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses3. draft form analysis plans, for additional subcortical meta-

analyses4. preparation mega-analyses on pooled raw data

1. Participants2. Ethical approval3. Formation shared database (MRI + phenotype)4. Analyses plans

5. expert-subgroups for specific topics/analyses6. funding7. status GWAS8. future meetings

Pooling raw data for mega-analysis Advantages:

1 group (or more groups in parallel on different analyses plans) can work on the data processing, QC, analyses, and re-analyses without bothering all sides.

Excellent opportunities for specific analyses on clinical phenotype, age effects, co-morbidity, medication effects, etc.

Great opportunity to replicate (+ improve) the OBIC mega-analysis (Am J Psychiatry 2014)

But: We first have to construct the database (based on the

OBIC experience, this is a lot of work (!), and we have to solve data transfer issues, etc.)

Before we can start with analyses on shared database, the data must be checked, cleaned, etc.

Raw data sharing for mega-analysis (1)Site Yes No Maybe

Arnold

Benedetti

Beucke

Cheng

Denys

Fitzgerald

Gruner

van den Heuvel

Hoexter

Huyser

Koch

Kwon

Lazaro

Raw data sharing for mega-analysis (2)Site Yes No Maybe

Mataix-Cols

Menchon

Nakamae

Nakao

Reddy ?

Rosenberg

Simpson

Soreni

Spalletta

Stein

Tolin

Walitza

Wang

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses3. draft form analysis plans, for additional subcortical meta-

analyses4. preparation mega-analyses on pooled raw data5. expert-subgroups for specific topics/analyses

E.g. rs fMRI, DTI, child OCD, imaging-geneticsPlease, email me about your wishes to take initiative to one of these topics!

6. funding7. status GWAS8. future meetings

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses3. draft form analysis plans, for additional subcortical meta-

analyses4. preparation mega-analyses on pooled raw data5. expert-subgroups for specific topics/analyses6. Funding

1. Awarded: NIH grant Paul Thompson2. Not awarded: ERC (Horizon2020) Odile van den Heuvel3. Submitted/pending: Carles Soriano-Mas4. Plans/options: ?

7. status GWAS8. future meetings

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses3. draft form analysis plans, for additional

subcortical meta-analyses4. preparation mega-analyses on pooled raw data5. expert-subgroups for specific topics/analyses6. funding7. status GWAS: Carol/Jim, what’s the status?8. future meetings

Agenda1. status subcortical meta-analyses2. planning cortical meta-analyses3. draft form analysis plans, for additional subcortical meta-analyses4. preparation mega-analyses on pooled raw data5. expert-subgroups for specific topics/analyses6. funding7. status GWAS8

8. future meetings1. ENIGMA working group PI’s

- Feb 25: Thompson et al. (UCS) + Dutch PI’s/members (MDD, OCD, autism, ADHD, addiction working groups)

- June 2015: ENIGMA working group PI’s meeting, prior to HBM, Hawaii

2. ENIGMA OCD working group members- SOBP/APA 2015, Toronto, May 14-16 (SOBP), 16-20 (APA)- HBM 2015, Hawaii, June 14-18Please, email me to inform me about your conference plans, so that I can plan

an informal meeting these conferences.