Collaborative neuroimaging initiative BrainChart helps chart how brains change across the lifespan

Source: Beth­le­hem et al (2020). A graph­i­cal sum­ma­ry of the nor­ma­tive tra­jec­to­ries of the medi­an (50th cen­tile) for each glob­al MRI phe­no­type, and key devel­op­men­tal mile­stones, as a func­tion of age (log-scaled).

For decades, growth charts have been used by pae­di­a­tri­cians as ref­er­ence tools. The charts allow health pro­fes­sion­als to plot and mea­sure a child’s height and weight from birth to young adult­hood. The per­centile scores they pro­vide, espe­cial­ly across mul­ti­ple vis­its, help doc­tors screen for con­di­tions such as obe­si­ty or inad­e­quate growth, which fall at the extremes of these scores.

Mean­while, it is pos­si­ble to mea­sure brain devel­op­ment with imag­ing tech­nolo­gies such as ultra­sound, mag­net­ic res­o­nance imag­ing (MRI) and com­put­erised tomog­ra­phy (CT). The devel­op­ment of these tech­nolo­gies has led to a wealth of research on how the brain changes, and each year, mil­lions of clin­i­cal brain scans are per­formed world­wide. Despite this progress, there are few mea­sures that are used to aid in mon­i­tor­ing brain devel­op­ment. Why?

In con­trast to tra­di­tion­al growth charts, quan­ti­fy­ing brain devel­op­ment and age­ing comes with a host of tech­ni­cal obsta­cles. Sim­ply put, there is no tape mea­sure for the brain. This makes it dif­fi­cult to stan­dard­ise mea­sures across dif­fer­ent stud­ies. The costs and com­plex­i­ty of acquir­ing brain scans mean the data avail­able to gen­er­ate ref­er­ence charts for a sin­gle study is limited.

We sought to address this by stitch­ing togeth­er data across the largest pos­si­ble com­bi­na­tion of exist­ing stud­ies. We con­tact­ed many researchers to see if they would be will­ing to con­tribute to these ref­er­ence charts. As evi­dent from our large dataset, these requests were met with over­whelm­ing enthu­si­asm. This turned a grass­roots project into a col­lab­o­ra­tive glob­al effort span­ning six con­ti­nents and dozens of insti­tu­tions, the results of which have just been report­ed in the jour­nal Nature.

Milestones

The vast amount of data we com­bined allowed us to estab­lish a set of ref­er­ence charts for a num­ber of brain fea­tures across the lifes­pan. This enabled us to pre­cise­ly map the tim­ing of mile­stones in brain devel­op­ment and age­ing. These included:

  • The vol­ume of grey mat­ter (brain cells) increas­es rapid­ly from mid-ges­ta­tion onwards, peak­ing just before we are six years old. It then begins to decrease slowly.
  • The vol­ume of white mat­ter (brain con­nec­tions) also increased rapid­ly from mid-ges­ta­tion through ear­ly child­hood and peaks just before we are 29 years old.
  • The decline in white mat­ter vol­ume begins to accel­er­ate after 50 years.
  • Grey mat­ter vol­ume in the sub­cor­tex (which con­trols bod­i­ly func­tions and basic behav­iour) peaks in ado­les­cence at 14 and a half years old.

Our data also con­tains a mul­ti­tude of peo­ple with dif­fer­ent clin­i­cal diag­noses. Because we can now see how an indi­vid­ual com­pares to oth­ers of the same age and sex, this vari­abil­i­ty allowed us to explore dif­fer­ences between groups of peo­ple. As expect­ed, for exam­ple, peo­ple with neu­rode­gen­er­a­tive con­di­tions such as Alzheimer’s dis­ease tend­ed to have low scores for grey and white mat­ter vol­ume – the most abun­dant brain tis­sue types.

Beyond group-lev­el com­par­isons, these ref­er­ence charts will enable future research to bench­mark indi­vid­u­als in rela­tion to a pop­u­la­tion. We hope this will result in indi­vid­u­al­ly tai­lored and rel­e­vant mea­sure­ments. This progress is par­tic­u­lar­ly impor­tant in the con­text of men­tal ill­ness, that is, peo­ple may share a diag­nos­tic label despite dif­fer­ences in their symp­toms and, per­haps, in what is caus­ing their con­di­tion. Ulti­mate­ly, doc­tors have to treat indi­vid­u­als, not groups, so they need instru­ments that pro­vide per­son­alised information.

Enormous collaborative effort

Although phras­es like “big data” or “open sci­ence” apply to our study, they can gloss over some of the nuances of the col­lab­o­ra­tive process­es that enabled this project. Specif­i­cal­ly, some datasets require sub­stan­tial legal sup­port for data to be shared between insti­tu­tions, while oth­ers can be shared and down­loaded from a pub­lic web­site. Sim­i­lar­ly, some researchers have sub­stan­tial exper­tise or work at insti­tu­tions that receive fund­ing to help organ­ise their data into easy-to-use, open resources.

For oth­ers, how­ev­er, shar­ing data can be a time and resource-drain­ing process. Per­haps most crit­i­cal­ly, there are many pos­si­ble places to share brain scans, each of which requires dif­fer­ent lev­els of cura­tion. All of this trans­lates into a large bur­den on the user when attempt­ing to aggre­gate mul­ti­ple datasets.

Some con­sor­tiums could not par­tic­i­pate in our project because of dis­pro­por­tion­ate author­ship require­ments or stip­u­la­tions about what could and could not be stud­ied with their data. These are impor­tant con­sid­er­a­tions as we, as aca­d­e­m­ic researchers, push toward more open and col­lab­o­ra­tive sci­ence. This work would not be pos­si­ble with­out the col­lec­tive team spir­it from our exist­ing con­trib­u­tors and mem­bers of the sci­en­tif­ic com­mu­ni­ty around us.

The future

There is still much work to be done before these brain charts can be used as ref­er­ence tools by health­care pro­fes­sion­als. The under­ly­ing dataset con­tains both ongo­ing stud­ies, and those that were start­ed as ear­ly as 1990 when MRI machines were in a select few places in the world. So the brain charts can con­stant­ly be updat­ed, expand­ed and refined.

As larg­er datasets become more of the norm, we hope to con­tin­ue to make our ref­er­ence charts more inclu­sive and rep­re­sen­ta­tive. As brain scan­ning becomes cheap­er and increas­ing­ly acces­si­ble (even portable), we hope our brain charts will enable more quan­ti­ta­tive stan­dards and aid neu­ro­sci­en­tif­ic dis­cov­er­ies to par­al­lel these excit­ing tech­no­log­i­cal advances.

One day, if brain scan­ning becomes a nor­mal part of pae­di­atric prac­tice, we hope to be ready with the nec­es­sary meth­ods and tools to pro­vide mean­ing­ful insights for patients and their families.

– Richard Beth­le­hem, Direc­tor of Neu­roimag­ing at the Autism Research Cen­tre and Research Asso­ciate at the Brain Map­ping Unit, at the Uni­ver­si­ty of Cam­bridge, and Jakob Sei­dlitz, Post­doc­tor­al Fel­low at UPen­n’s Lifes­pan Brain Insti­tute. This arti­cle was orig­i­nal­ly pub­lished on The Con­ver­sa­tion.

About SharpBrains

SHARPBRAINS is an independent think-tank and consulting firm providing services at the frontier of applied neuroscience, health, leadership and innovation.
SHARPBRAINS es un think-tank y consultoría independiente proporcionando servicios para la neurociencia aplicada, salud, liderazgo e innovación.

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