Study No. 3

Title: MR Imaging (MRI) and Proton Spectroscopy (1H-MRS) In Neuroborreliosis

Background and Significance:

Since the discovery of the agent of Lyme disease by Burgdorger in 1981, borreliosis has been commonly recognized as an infection of the nervous system. Diagnosis of neuroborroliosis is based on clinical features and serology. Since its morphological chances on CT or MRI are unfortunately infrequent and nonspecific, additional specificity could be added using proton magnetic resonance spectroscopy (1H-MRS). This technique can yield information on metabolic disturbances even absent any MRI abnormality. Our aim, therefore, is to examine the metabolic parameters in the human brain with 1H-MRS in neuroborreliosis patients, an undertaking which to the best of our knowledge has not been described.

Specific Aims:

We hypothesize that chronic Lyme neuroborreliosis patients will exhibit both diffuse abnormalities throughout their brain as well as foci or greater disease related activity. These will reflect in imaging (MRI) abnormalities-lesions; as well as in metabolic (detected by 1H-MRS) abnormalities in normal appearing tissue. To test this hypothesis we propose to quantify their extent and the sensitivity of either modality (MRI and MRS) to damage induced by neuroborreliosis in the brains of Lyme neuroborreliosis and healthy age and gender matched contemporaries using:

  1. Atrophy and lesion load: T1 and T2 weighted MRI will be done to quantify the brain's structural integrity via the age related global, white matter (WM) and gray matter (GM) atrophy (percent of the total intracranial volume) and the presence (number and volume) of disease related lesions.
  2. Localized and global 1H-MRS to characterize:

    1. Metabolic abnormalities in MRI visible lesions as well as in normal-appearing tissue. This will be done with three dimensional 1H-MRS to localized ( at 1 cm spatial resolution) energy, demyelination, oxidative and neuronal damage processes by monitoring their surrogate markers: creatine, chloride, lactate and N-acetyl aspartate (NAA).
    2. The global [whole brain, all GM and all WM] NAA concentration. Since NAA is a neuronal marker, comparison of its whole-brain concentration in patients with matched controls will yield the total load of their diseases as well as in its two main tissue types, even if any pathology is MRI-occult.

Experimental Design: The Scans will each involve a 1 hour scan in a 3 Tesla whole-body clinical imager at NYU Radiology 650 First Avenue Center for Biomedical Imaging. The protocol for Aims 1 and 2, above will comprise the following MRI (1-3) and MRS (4-6) sequences:

Sequence

Probing

Duration

1. T-1 weighted MP-RAGE

Whole-brain GM and EM tissue volume

7 min.

2. T2-weighted FSE

lesions

5 min.

3. T2-weighted FLAIR

Periventricular lesions

7 min.

4. Shimming

(needed for the next two sequences)

5 min.

5. Whole brain NAA

Global neuronal integrity

10 min.

6. 3D 1H-MRS1

Localized brain metabolism

30 min.



Total:

 

64 min