In a small room at Rutgers Cancer Institute, 11 cancer survivors took turns lying inside an MRI scanner with a coil pressed against their thighs. After a brief, vigorous knee extension, researchers watched something no one had seen before: exactly how quickly— or how slowly— their muscle cells rebuilt the cellular fuel exhausted by movement. The findings, published in the journal Biomedicines, represent a potential turning point in understanding why so many people finish cancer treatment with scans that show nothing wrong, yet feel hollowed out, unable to walk to the mailbox or stay awake through dinner.
The research team, led by Leorey Saligan, a professor and the vice dean of research at the Rutgers School of Nursing and a member of the Cancer Prevention and Control Program at Rutgers Cancer Institute, used a specialized imaging technique called phosphorus-31 magnetic resonance spectroscopy. This NIH-validated MRI test allowed them to peer directly into skeletal muscle cells, measuring how efficiently mitochondria—the cellular organelles that generate energy—recovered after exertion. "No one before this had looked deeply into single-cell-specific biology that can drive cancer patient experiences," Saligan said. "There is some previous work on blood mitochondrial levels, but blood composition shifts constantly. Every time you sneeze, your blood cells differ."
The participants, ranging in age from 34 to 70, had undergone treatment for various cancers using surgery, chemotherapy, radiation, immunotherapy, hormone therapy, or some combination. The data revealed clear patterns: participants 65 and older showed about 10% slower muscle energy recovery than younger patients, alongside weaker grip strength, higher self-reported fatigue, and fewer daily steps. Those who had received immunotherapy reported more fatigue, had slower muscle recovery, weaker grip strength, and fewer daily steps than those who hadn't.
But the most striking discovery pointed toward a future where treatment of post-cancer fatigue could become far more precise. Among younger participants, those with worse mitochondrial recovery paradoxically reported less fatigue—and even higher resilience and coping self-efficacy. While the researchers caution this finding could reflect the small sample size, it raises the possibility that subjective fatigue and cellular energy capacity may operate through partially distinct biological pathways. "It just shows that the subjective experience of fatigue is very multidimensional," Saligan said. "It's not only the physical aspect that's dictating that symptom experience."
The study's true value lies in its proof of concept. If 31P-MRS can provide a stable, noninvasive measure of mitochondrial function in cancer survivors, it could eventually serve as a biomarker linking the biology of post-treatment fatigue to the lived experience patients describe. Next steps include replicating the findings with larger cohorts and eventually measuring energy recovery in the brain and skeletal muscle simultaneously. "It is really important to see how soon exercise can really accelerate the recovery of the muscles," Saligan said. "I think that is really critical for exercise dosing, but also timing exercise programs, for survivors."