Full body 3D reconstruction
A new artificial intelligence framework called MouseMapper allows scientists to examine disease-associated changes throughout the body, with resolution at the cellular level.
Obesity does much more than affecting metabolism and fat storage. It also alters immunological activity, the structure of nerves and the organization of tissues throughout the body, increasing the risk of pathologies such as type 2 diabetes, cardiovascular disease, stroke, neuropathy and cancer.
Despite these widespread effects, scientists lacked tools capable of examine, in high resolutionthe changes associated with disease in an intact organism in its entirety, explains the .
A team of researchers led by Ali Erturkdirector of the Institute for Biological Intelligence (iBIO) at Helmholtz Munich and professor at LMU, developed , a set of deep learning algorithms powered by base models capable of analyzing whole-body biological imaging data.
The system can Automatically identify 31 organs and tissue typeswhile also mapping nerves and immune cells throughout the body, allowing scientists to simultaneously study multiple organ systems in intact mice.
“MouseMapper is based on a baseline model, which means it generalizes well beyond the data it was initially trained with,” says Ying Chenfirst author of the study, which was presented in a recently published in the journal Nature.
AI and Light Sheet Microscopy
To generate maps of the entire body, the scientists marked the mice’s nerves and immune cells with detectable fluorescent markers under the microscope.
They then applied tissue clarification techniques that made the animals transparent without compromising the fluorescent signals, which allowed the researchers to obtain images of the deep zones of intact bodies.
The team used light sheet microscopy advanced technology to generate detailed three-dimensional images of entire mice. The resulting datasets contained tens of millions of cellular structures across different organs and tissues.
MouseMapper automatically analyzed the images, identifying nerves, clusters of immune cells and anatomical regions throughout the body.
This approach allowed researchers to precisely locate points where inflammation and structural damage occurred in tissues — including fat, muscle, liver and peripheral nerves — without having to choose specific regions in advance.
To study the changes associated with obesity, scientists subjected mice to a high-fat diet that caused obesity and metabolic dysfunction similar to those observed in humans.
MouseMapper revealed widespread disruptions in the organization of immune cells and the structure of nerves throughout the body.
One of the most relevant discoveries concerns the trigemeal nervean important facial nerve responsible for sensitivity and motor control. In obese mice, these sensory nerves had much fewer branches and endings, suggesting compromised nerve function.
MouseMapper / Disco Technologies
Nerves (green) muscles (red) bones and organs (white) identified in a MouseMapper image
Behavioral tests also showed that obese mice responded less to sensory stimulation than lean mice, establishing a link between structural damage and reduced sensory function.
The researchers then analyzed the trigeminal ganglionwhich contains the cell bodies of facial sensory neurons. Using spatial proteomics, they identified molecular changes associated with nerve remodeling and inflammation.
Many of these same molecular signatures have also been found in trigeminal tissue of people with obesitywhich suggests that the nervous changes observed in mice could also occur in humans.
In addition to obesity, researchers believe MouseMapper could improve the study of complex diseases that affect multiple organ systems, including the diabetes, cancer, neurodegenerative diseases and autoimmune disorders.
Unlike previous methods focusing on selected tissues or organs, MouseMapper offers an integrated whole-body analysis platform capable of locate disease “foci” throughout the body.
The team also made whole-body datasets publicly available on the Internet, allowing researchers around the world to study obesity-associated changes across tissues and organ systems.
“Our goal is to create a comprehensive framework to understand how diseases affect the body as an interconnected system,” says Ali Ertürk. “Our long-term vision is build digital twins of mice truly realistic, in states of health and illness: atlases at the cellular level that we can consult, disturb and track in silico, computationally.
“Such allow-us-ia accurately identify early changes that a disease causes, design interventions to prevent them and accelerate the discovery of new treatments, while reducing the number of physical experiments we need to perform”, he concludes.
