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Harvard and Google Scientists Studying Connectomics Create Massive Highly Detailed 3D Nanoscale Model of Human Neural Tissue

Jun 17, 2024 | Digital Pathology, Laboratory Instruments & Laboratory Equipment, Laboratory News, Laboratory Pathology, Laboratory Resources, Laboratory Testing

Ten year collaboration between Google and Harvard may lead to a deeper understanding of the brain and new clinical laboratory diagnostics

With all our anatomic pathology and clinical laboratory science, we still do not know that much about the structure of the brain. But now, scientists at Harvard University and Google Research studying the emerging field of connectomics have published a highly detailed 3D reconstruction of human brain tissue that allows visualization of neurons and their connections at unprecedented nanoscale resolutions.

Further investigation of the nano-connections within the human brain could lead to novel insights about the role specific proteins and molecules play in the function of the brain. Though it will likely be years down the road, data derived from this study could be used to develop new clinical laboratory diagnostic tests.

The data to generate the model came from Google’s use of artificial intelligence (AI) algorithms to color-code Harvard’s electron microscope imaging of a cubic millimeter of neural tissue—equivalent to a half-grain of rice—that was surgically removed from an epilepsy patient.

“That tiny square contains 57,000 cells, 230 millimeters of blood vessels, and 150 million synapses, all amounting to 1,400 terabytes of data,” according to the Harvard Gazette, which described the project as “the largest-ever dataset of human neural connections.”

“A terabyte is, for most people, gigantic, yet a fragment of a human brain—just a minuscule, teeny-weeny little bit of human brain—is still thousands of terabytes,” said neuroscientist Jeff W. Lichtman, MD, PhD, Jeremy R. Knowles Professor of Molecular and Cellular Biology, whose Lichtman Lab at Harvard University collaborated on the project with researchers from Google. The two labs have been working together for nearly 10 years on this project, the Harvard Gazette reported.

Lichtman’s lab focuses on the emerging field of connectomics, defined “as understanding how individual neurons are connected to one another to form functional networks,” said neurobiologist Wei-Chung Allen Lee, PhD, Assistant Professor of Neurology, Harvard Medical School, in an interview with Harvard Medical News. “The goal is to create connectomes—or detailed structural maps of connectivity—where we can see every neuron and every connection.” Lee was not involved with the Harvard/Google Research study.

The scientists published their study in the journal Science titled, “A Petavoxel Fragment of Human Cerebral Cortex Reconstructed at Nanoscale Resolution.”

“The human brain uses no more power than a dim incandescent light bulb, yet it can accomplish feats still not possible with the largest artificial computing systems,” wrote Google Research scientist Viren Jain, PhD (above), in a blog post. “To understand how requires a level of understanding more profound than knowing what part of the brain is responsible for what function. The field of connectomics aims to achieve this by precisely mapping how each cell is connected to others.” Google’s 10-year collaboration with Harvard University may lead to new clinical laboratory diagnostics. (Photo copyright: Google Research.)

Study Data and Tools Freely Available

Along with the Science paper, the researchers publicly released the data along with analytic and visualization tools. The study noted that the dataset “is large and incompletely scrutinized,” so the scientists are inviting other researchers to assist in improving the model.

“The ability for other researchers to proofread and refine this human brain connectome is one of many ways that we see the release of this paper and the associated tools as not only the culmination of 10 years of work, but the beginning of something new,” wrote Google Research scientist Viren Jain, PhD, in a blog post that included links to the online resources.

One of those tools—Neuroglancer—allows any user with a web browser to view 3D models of neurons, axons, synapses, dendrites, blood vessels, and other objects. Users can rotate the models in xyz dimensions.

Users with the requisite knowledge and skills can proofread and correct the models by signing up for a CAVE (Connectome Annotation Versioning Engine) account.

Researchers Found Several Surprises

To perform their study, Lichtman’s team cut the neural tissue into 5,000 slices, each approximately 30 nanometers thick, Jain explained in the blog post. They then used a multibeam scanning electron microscope to capture high-resolution images, a process that took 326 days.

Jain’s team at Google used AI tools to build the model. They “stitched and aligned the image data, reconstructed the three dimensional structure of each cell, including its axons and dendrites, identified synaptic connections, and classified cell types,” he explained.

Jain pointed to “several surprises” that the reconstruction revealed. For example, he noted that “96.5% of contacts between axons and their target cells have just one synapse.” However, he added, “we found a class of rare but extremely powerful synaptic connections in which a pair of neurons may be connected by more than 50 individual synapses.”

In their Science paper, the researchers suggest that “these powerful connections are not the result of chance, but rather that these pairs had a reason to be more strongly connected than is typical,” Jain wrote in the blog post. “Further study of these connections could reveal their functional role in the brain.”

Mysterious Structures

Another anomaly was the presence of “axon whorls,” as Jain described them, “beautiful but mysterious structures in which an axon wraps itself into complicated knots.”

Because the sample came from an epilepsy patient, Jain noted that the whorls could be connected to the disease or therapies or could be found in all brains.

“Given the scale and complexity of the dataset, we expect that there are many other novel structures and characteristics yet to be discovered,” he wrote. “These findings are the tip of the iceberg of what we expect connectomics will tell us about human brains.”

The researchers have a larger goal to create a comprehensive high-resolution map of a mouse’s brain, Harvard Medical News noted. This would contain approximately 1,000 times the data found in the 1-cubic-millimeter human sample.

Dark Daily has been tracking the different fields of “omics” for years, as research teams announce new findings and coin new areas of science and medicine to which “omics” is appended. Connectomics fits that description.

Though the Harvard/Google research is not likely to lead to diagnostic assays or clinical laboratory tests any time soon, it is an example of how advances in technologies are enabling researchers to investigate smaller and smaller elements within the human body.

—Stephen Beale

Related Information:

Researchers Publish Largest-Ever Dataset of Neural Connections

A Petavoxel Fragment of Human Cerebral Cortex Reconstructed at Nanoscale Resolution

Ten Years of Neuroscience at Google Yields Maps of Human Brain

Groundbreaking Images Reveal the Human Brain at Nanoscale Resolution

A New Field of Neuroscience Aims to Map Connections in the Brain

As Primary Care Providers and Health Insurers Embrace Telehealth, How Will Clinical Laboratories Provide Medical Lab Testing Services?

Nov 27, 2019 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing

When patients use telehealth, how do they choose medical laboratories for lab test orders their virtual doctors have authorized?

Doctors On Demand is expanding the nation’s primary care services by launching a virtual care telehealth platform for health insurers and employers. This fits into a growing nationwide trend toward increased use of remote and virtual doctor’s visits. But how should clinical laboratories and anatomic pathology groups prepare for fulfilling virtual doctors’ lab test orders in ways consistent with current scope-of-practice laws?

The rise of virtual care is made possible by innovations in digital and telecommunication technology. Driven by studies showing more patients are opting out of conventional primary care visits that take too much time or are too far away, the healthcare industry is responding by bringing medical services—including pathology and clinical laboratory—closer to patients through retail settings and urgent care clinics.

Many pathologists and clinical laboratory managers are unaware of how swiftly patients are becoming comfortable with getting their primary care needs met by other types of caregivers, including virtually. Recently, the Health Care Cost Institute (HCCI) published data showing that visits to primary care physicians declined 18% from 2012 to 2016 among adults under 65 who had employer-sponsored insurance. However, during these same years, visits with nurse practitioners and physician’s assistants increased by 129%!

Another way that providers are making it easier for patients to access healthcare is through the Internet.

Doctor On Demand, a San Francisco-based virtual care provider, is targeting insurers and employers with its Synapse telehealth platform, which integrates into existing health plan networks and enables virtual primary care, according to a news release.

**“Through our fully integrated technology platform, we’re putting the patient first and introducing continuity of care not previously available through virtual care solutions,” said** **Hill Ferguson, CEO of Doctor On Demand in** **a statement** **announcing the launch of Synapse on the** **Humana** **(NYSE:HUM) health plan network. (Photo copyright:** ***The Business Journals***.)

How Synapse Works

Humana is using Synapse in its new On Hand virtual primary care plan, the news release states. Humana said its members have no copay for the virtual doctor visits and $5 copays for standard medical laboratory tests and prescriptions. Synapse’s “smart referrals” function sends referrals to in-network clinical laboratories, imaging providers, and pharmacies, Healthcare Dive reported.

“Humana has a deep footprint, and this is a payer looking to create a virtual primary care network as a way to contain cost and thinking about how care is coordinated and delivered,” Josh Berlin, a Principal and Healthcare Co-Practice Leader with advisory firm Citrin Cooperman, told FierceHealthcare.

Changing Primary Care Relationships

Another insurer advancing telehealth is Oscar Health, which offers its own Doctor on Call telehealth platform. The New York City-based health plan reported in a year-end review that 82% of its members had set up a profile that gave them access to a concierge care team and 24/7 telemedicine services, including clinical laboratory test results.

During 2018, Oscar’s concierge teams addressed 1.2 million questions from 77% of its members, the insurer said.

The graphic above, taken from research conducted by the Health Care Cost Institute (HCCI), shows that while virtual primary care has been expanding, conventional visits to primary care physicians fell 18% from 2012 to 2016 among adults under 65 who had employer-sponsored insurance. Simultaneously, visits with nurse practitioners and physician’s assistants increased by 129%! This indicates a shift in how patients view access to primary care physicians and may explain why telehealth is becoming an attractive option. How will clinical laboratories fit into this new healthcare paradigm? (Photo copyright: HCCI.)

Becker’s Hospital Review reports that telehealth usage by Oscar’s members is five times higher than the average for the healthcare industry.

Will Clinical Laboratories Receive Virtual Referrals?

In a way, it has never been easier for patients to see a primary care doctor or research symptoms. Additionally, the Internet makes it possible for patients to self-diagnose, though not always to the benefit of healthcare providers or the patients.

So, how should clinical laboratories respond to this growing expansion of virtual care doctors? Experts advise lab leaders to reach out to health plans soon and determine their inclusion in virtual healthcare networks. Labs also may benefit by making test scheduling and reporting accessible and convenient to insurance company members and consumers choosing telehealth.

During his keynote presentation at the 24th Annual Executive War College in May, Ted Schwab, a Los Angeles area Healthcare Strategist and Entrepreneur, said, “If you use Google in the United States to check symptoms, you’ll find 350 different electronic applications that will give you medical advice—meaning you’ll get a diagnosis over the Internet. These applications are winding their way somewhere through the regulatory process. (See Schwab’s expanded comments on this trend in, “Strategist Explains Key Trends in Healthcare’s Transformation,” The Dark Report, October 14, 2019.)

Schwab advises that in this “time of change” it’s critical for labs to take proactive measures. “What we know today is that providers—including clinical laboratories and pathology groups—who do nothing will get trampled. However, those providers that do something proactively will most likely be the winners as healthcare continues to transform.”

—Donna Marie Pocius

Related Information:

Doctor On Demand Launches Synapse, a New Virtual Care Platform Delivering Next Generation Primary Care for Health Plans and Employer Populations

Telemedicine Startup Doctor On Demand Taps Giant Health Partner to Debut Virtual Primary Care Plan

Doctor On Demand Rolls Out Virtual Care Platform for Primary Care

Humana and Doctor On Demand Launch Virtual Primary Care Plan to Bring More Services With Lower Costs to Patients, Insurers, and Employers

Trends in Primary Care Visits

Humana and Doctor On Demand Launch Virtual Primary Care Plan

Oscar Health’s Telemedicine Use Five Times Greater than Health Insurance Average

Strategist Explains Key Trends in Healthcare’s Transformation

25th Annual Executive War College Conference on Laboratory and Pathology Management