MRI Fiber Tracking May Be Potential Biomarker of SMA Course, Response to Therapy, Study Suggests

A type of magnetic resonance imaging (MRI) called diffusion tensor imaging (DTI) allows unique tracking of nerve fibers and could be used to detail changes in the spinal nerve fibers of people with spinal muscular atrophy (SMA), a study reports.

DTI could offer new insights into SMA development, help monitor disease course, and provide early biomarkers of patients’ response to therapies such as Spinraza (nusinersen) or Zolgensma, researchers say.

The study, “Magnetic resonance imaging of the cervical spinal cord in spinal muscular atrophy,” was published in the journal Neuroimage: Clinical.

Diffusion tensor imaging (DTI) is an increasingly popular MRI technique among clinicians and researchers for studying the complex architecture of nerve cell connections in living humans, both in health and disease.

It is a non-invasive method that uses existing MRI technology and requires no new equipment, contrast agents, or chemical tracers.

DTI has exceptional sensitivity for water movements inside the white matter tracts of the brain and spinal cord. The white matter is the tissue through which messages pass within the central nervous system, comprised of the brain and spinal cord. It owes its name to a white, fatty substance called myelin that insulates and protects the nerve fibers that constitute the white matter.

By tracking nerve fibers’ activity, DTI provides a very detailed map of the structural organization and status of the nerve tissue. So detailed, in fact, it is used by surgeons to see which parts of the brain need to be protected during surgery.

The technique also has been used to examine in detail the brain, muscles, peripheral nerves, and the spinal cord of people with neuromuscular diseases, including SMA.

Given DTI’s potential to provide researchers with biomarkers of neurological changes, scientists at the University Medical Center Utrecht, in the Netherlands, sought to use it for people with SMA. The team investigated the value of using this technique to track changes in the spinal cord and spinal nerves of SMA patients.

They developed a protocol to specifically look at the cervical spinal cord — the portion of the spinal cord situated in the neck region, between vertebrae C4-C8, that innervates the head, neck, shoulders, arms, and hands — as well as its related nerve roots. The nerve roots are the bundles of nerve fibers exiting the spinal cord toward the rest of the body, including the muscles.

The dorsal root, closer to the back, is the sensory root and carries sensory information to the brain. The ventral root, closer to the front part of the body, is the motor root and carries motor information from the brain.

Researchers scanned 10 patients with SMA type 2 and types 3a and 3b, ages 17 to 73. They also scanned 20 healthy people (controls).

Using standard MRI and DTI they investigated several parameters, including the cross-sectional area (CSA) of the spinal cord at each spinal segment, and the diameter (thickness) of ventral and dorsal nerve roots. The team also evaluated four diffusion parameters, used to investigate the structural properties of nervous tissue. These included fractional anisotropy, which measures the direction and molecular speed inside nerve fiber tracts, and mean diffusivity, or the length of the diffusion in a specific orientation. The researchers also investigated axial diffusivity, which represents the diffusivity along the main axis, and radial diffusivity, which represents the diffusion perpendicular to the nerve.

In people with SMA, the spinal cord area was slightly smaller compared with controls. However, this difference was not statistically significant.

But DTI data revealed that SMA patients had significantly higher axial diffusivity signals in the grey matter — a part of the nervous tissue composed mostly of nerve cell bodies and nerve fibers not surrounded by myelin. There also were lower values of mean, axial, and radial diffusivity, a difference that was more pronounced at nerve roots closer to the head (C3-C5).

According to the scientists, this finding is in line with the characteristic pattern of muscle weakness in SMA. In this neurodegenerative disease, muscles closer to the center of the body — called proximal muscles — are usually more affected than muscles closer to the extremities, such as those in the hands and feet. Those are called distal muscles.

“We showed feasibility of an advanced 3 T MRI protocol that allowed differences to be determined between patients and healthy controls, confirming the potential of this technique to assess pathological [disease-causing] mechanisms in SMA,” the researchers said.

“The results suggest that, when further developed, MRI and DTI might provide unique anatomical and functional biomarkers to monitor SMA progression and treatment effects,” they concluded.