Superresolution US Reveals Unexpected Nerve Blood Flow
Higher tibial nerve blood flow challenges diabetic peripheral neuropathy assumptions
Superresolution US may offer a new way to detect diabetic peripheral neuropathy (DPN) by revealing subtle microvascular changes in the tibial nerve.
In a study published in Radiology, lead author Fang Liu, MD, of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and colleagues reported increased nerve blood flow and vascularity in patients with neuropathy and ulcers, challenging the long-held assumption that the condition is driven mainly by reduced blood flow.
“The study describes an objective US test to detect alterations in tibial nerve blood flow that correlate with diabetic neuropathy—even before the clinical symptoms manifest. If this tool proves to be accurate and reliable, the clinical implications are huge,” said Levon N. Nazarian, MD, a professor of radiology and radiology in orthopedic surgery and chief of musculoskeletal imaging at the Hospital of the University of Pennsylvania in Philadelphia, who authored an editorial on the study.
New View of Microvasculature in DPN
Patients with diabetes mellitus commonly develop DPN, which may result in a range of effects including localized numbness, ulcers, infections and skeletal damage. According to Dr. Nazarian, the underlying causes of DPN have long been debated.
Microvascular changes are generally accepted as a factor, though how large a part they play is still controversial. Efforts to better understand their role in DPN have been limited by imaging resolution. Existing methods to study microvascular networks typically show either vessel structure or blood flow, but not together.
To overcome this challenge, Dr. Liu and his team proposed superresolution US to map microvascular networks at a 10-µm resolution by tracking the movement of microbubbles in these vessels.
Superresolution US delivers both structural and functional information at once. “In US of nerves, we usually detect abnormalities by an alteration in size, morphology and echotexture. However, we generally do not get information on how the nerve is functioning—that role is reserved for electromyography (EMG),” Dr. Nazarian explained. “This study allows radiologists to use US-depicted microcirculation as a surrogate for nerve function.”
Unexpected Results Complicate DPN Model
The study followed 100 individuals, comparing the microvasculature of patients with diabetes who had DPN and lower limb ulcers, those with diabetes but without DPN, and a control group of patients without diabetes or DPN.
Patients were injected with a contrast agent microbubble solution and imaged over the course of 15 seconds by a stationary probe.
The findings were unexpected. The team observed increased blood flow and vascularity within the tibial microvasculature of patients with neuropathy and ulcers, even though the prevailing model indicates that nerve perfusion should decline.
Dr. Nazarian credits the technique’s increased resolution with making this direct observation possible. “The exquisite resolution afforded by this contrast-enhanced US technique provides unique information by allowing direct visualization and characterization of intraneural blood vessels,” he said.
While the findings are promising, Dr. Nazarian said that there are some important caveats. The most notable are the makeup of the patient groups and the practical hurdles to wider use.
All of the patients with ulcers and neuropathy also had peripheral artery disease (PAD) and were older on average. Dr. Nazarian identified these as factors that can be clarified in future studies. “If there is inflammation in the soft tissues related to ulcers, then that could cause increased flow in the extremity and be a potential confounder. PAD and older age also are known to be associated with alterations in blood flow,” he said.
Dr. Nazarian also noted logistical hurdles of this method. “The authors use a state-of-the-art imaging system combined with the administration of US contrast agents. Most practitioners who see patients with diabetes mellitus would not have access to the level of US technology described in this study,” he said.
“The exquisite resolution afforded by this contrast-enhanced US technique provides unique information by allowing direct visualization and characterization of intraneural blood vessels.”
— LEVON NAZARIAN, MD
The method also poses technical and financial barriers. “There would be a large learning curve, especially for those who are not experienced in medical imaging and nerve US,” Dr. Nazarian explained.” It would also be essential that there is sufficient reimbursement to cover the costs of both US equipment and contrast agents.”
With these limitations in mind, Dr. Nazarian noted the long road ahead for widespread clinical adoption of this technique. “We aren’t quite ready for clinical use,” he said. “A prospective randomized investigation is needed to develop firm diagnostic criteria—ideally thresholds for various flow parameters above which DPN can be confidently diagnosed.”
Still, Dr. Nazarian said the technology could have broad clinical implications. “If validated, US could be used in the routine screening of patients with diabetes mellitus to enable earlier and more aggressive control of serum glucose to prevent the onset of neuropathy or at least mitigate its severity,” he said.
Dr. Nazarian emphasizes the broader potential uses of this technique. “This could be used in a range of neuropathies,” he said. “Since compressive neuropathies are so common throughout the body, these techniques could contribute to diagnosing equivocal cases.”
Overall, the study points to a future for superresolution US that extends beyond DPN to nerve imaging more broadly. “Contrast-enhanced color flow imaging of nerves can help US make the transition from giving only morphologic information to giving physiologic information that provides insight into nerve function,” Dr. Nazarian said.
For More Information
Access the Radiology study, “Evaluation of Tibial Nerve Microcirculation in Diabetes Mellitus at Superresolution US,” and the related editorial, “Peripheral Nerve Sonography: Crossing the Bridge from Morphologic to Functional Imaging.”
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