A new $2.9 million grant will use brain images from thousands of patients with endometriosis to better understand treatment response.

BY KATHARINE GAMMON

CHRONIC PAIN ASSOCIATED WITH ENDOMETRIOSIS — a condition where tissue similar to the uterus lining (endometrium) grows outside the uterus — affects millions of females in the United States. Some get relief from hormone therapy or hysterectomies, but those treatments don’t work for everyone, leaving a significant portion of patients suffering.

Now, with funds from a new federal grant, USC researchers seeks to use brain imaging to determine which treatments will work for which patients. That’s the idea behind a $2.9-million grant from the National Institute of Child Health and Human Development/National Institute of Neurological Disorders and Stroke led by Associate Professor Jason Kutch. The study also includes interdisciplinary research collaborators from the University of Michigan as well as the USC Stevens Institute for Neuroimaging and Neuroinformatics.

Is the Thalamus Responsible?

For years, Kutch has been studying the brain image markers of centralized pain — pain all over the body. But this study takes that research a step further, trying to link certain brain features to outcomes.

“We became really interested in this idea,” he said. “Could we link the concept of centralized pain to something meaningful: How will a pelvic pain patient respond to treatment?”

The study will use neuroimaging data from more than 1,000 patients to predict treatment outcomes —as well as identify early markers of pain in adolescence. Kutch points out that many women aren’t diagnosed with chronic pain until midlife, but that pain actually started in adolescence.

“The project grew out of that desire to take what we had learned in the studies we already published and then start to apply it to a more treatment-focused perspective,” Kutch said. “The next step after that would be more prospective studies, where we tried to detect these markers even before a person went into treatment.”

The researchers will also assess whether individuals in the study had successful treatment outcomes or experienced chronic pain recurrence. They are also creating computational predictive models to determine treatment response and identify which aspects of brain alterations are driving accurate predictions.

Kutch has a hypothesis that the thalamus — an egg-shaped structure in the middle of your brain that relays motor and sensory information — is key to understanding differences in how endometriosis sufferers may respond to treatments.

“It’s kind of this sensory hub that distributes not only pain information, but also sensory information all across the brain and in all of the chronic overlapping pain conditions,” he said. “I think there’s a lot of evidence pointing to this concept of centralized pain at the thalamus, and we’re getting a little bit more evidence that that might be the case.”

An Interdisciplinary Collaboration

Neha Jahanshad, who is working with Kutch on the study, says she became connected to the project from a former student both Kutch and Jahanshad had in common. She points out that the overall aim is to compile together one of the largest datasets of brain imaging in endometriosis to study the female-specific brain, and to identify the complex network of alterations in the presence of endometriosis and chronic pelvic pains. “Together, this can lead us to understand how people may respond to specific treatments,” she said. “Individually targeted treatments are essential for minimizing complications and side effects while maximizing efficacy.”

Working across disciplines can lead to new insights — for everyone. “We need to be able to combine clinical expertise in female health, specifically endometriosis and its treatment options; the neurology of chronic pain; structural and functional brain imaging; and, of course, expertise in data science and computational models,” Jahanshad said.

Kutch explained that his ultimate goal is to create a more comprehensive view of what is happening inside and outside a patient with pain, to make sure that treatments are tailored to the person. “We want to fit together what’s going on in their body with what’s going on in their brain in a more holistic way.”