KR102396266B1 - Method to provide information necessary for CMT type 1 diagnosis by sciatic nerve evaluation using MRI - Google Patents

Abstract

The present invention relates to a method of providing information necessary for diagnosing CMT type 1 through sciatic nerve measurement using MRI.

Description

{Method to provide information necessary for CMT type 1 diagnosis by sciatic nerve evaluation using MRI}

The present invention relates to a method of providing information necessary for diagnosing CMT type 1 through sciatic nerve measurement using MRI.

Charcot-Marie-Tooth disease (hereinafter, CMT) is a group of diseases with various phenotypes and is the most common hereditary neuromuscular disease. It is often accompanied by motor and sensory disturbances of the peripheral nervous system, characterized by symmetrical distal muscle degeneration and sensory loss, most pronounced in the lower extremities.

CMT is traditionally classified into two types. Type 1, the more frequent form of demyelination characterized by a slow nerve conduction velocity (NCV), and type 2, an axonal form with normal or slightly reduced NCV but mainly reduced amplitude of motor and sensory responses.

Although the diagnosis of CMT is most often made clinically, it may not be diagnosed until clear clinical signs such as Pes cavus or hammer toe develop. Therefore, studies are underway to use radiology to help evaluate CMT patients.

Anatomical changes in the peripheral nerves of CMT patients have been reported to be nerve hypertrophy, including nerve bundle expansion, by previous studies. Also, in more advanced diseases, studies have been reported that analyze findings that are secondary to nerve abnormalities in muscles controlled by peripheral nerves through magnetic resonance imaging (MRI). However, there have been few reports of attempts to quantitatively analyze the peripheral nerves of CMT patients through medical imaging.

DTI (Diffusion Tensor Imaging) is a new imaging technology in the field of MRI that can obtain direction information on the diffusion of water molecules in living tissues. Using the anisotropic diffusion properties of neural tissue, DTI can provide useful quantitative data such as fractional anisotropy (FA) or mean diffusivity (MD). With these parameters, DTI holds great promise for the evaluation of degeneration and regeneration of neural structures.

Axial diffusivity (AD) and radial diffusivity (RD), which indicate the diffusivity in the vertical direction parallel to the direction of the fiber, are parameters of DTI with high clinical value. Studies have shown that these parameters are related to axonal and myelin integrity.

DTI was initially applied to brain imaging, but in recent years, numerous studies have been conducted on its application in peripheral nerve imaging. However, very few studies have attempted to apply DTI to peripheral nerves other than the median nerve.

Republic of Korea Patent Publication No. 10-2015-0085462 (2015.07.23.)

Therefore, the present inventors tried to confirm that the DTI parameters can indicate the difference between the demyelinated sciatic nerve of CMT type 1 and the normal sciatic nerve of a healthy control group.

Therefore, the present invention conducted a prospective comparative study including CMT type 1 patients and healthy controls to confirm the potential value of DTI in diagnosing sciatica, DTI parameters and cross-sectional area (CSA) of the sciatic nerve. We tried to confirm the significant difference between these two groups.

An object of the present invention is to provide a method for providing information necessary for diagnosing CMT type 1 through sciatic nerve analysis using MRI.

The present invention relates to a method of providing information necessary for diagnosing CMT type 1 through sciatic nerve measurement using MRI.

The present inventors were able to distinguish diffusion tensor imaging (DTI) parameters and cross-sectional area (CSA) in the sciatic nerve of Charcot-Marie-Tooth disease (CMT) type 1 (demyelinated form) patients and controls. I wanted to evaluate whether it could be done.

Therefore, 18 CMT type 1 patients and 18 age/sex matched volunteers were tested. Magnetic resonance imaging including DTI and axial T2-weighted Dixon sequences were performed for each subject. Region-of-interest analysis was performed independently by two radiologists on each side of the sciatic nerve at four levels:

Level 1: hamstring tendon origin;

Level 2: lesser trochanter of the femur;

Level 3: gluteus maximus tendon insertion; and

Level 4: mid-femur.

Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were calculated.

The cross-sectional area (CSA) of the sciatic nerve was measured using axial water-only images at each level. Comparison of DTI parameters between the two groups was performed using a two-sample t test and a Mann-Whitney U test.

FA was significantly lower in all four measurement levels in CMT patients than in controls. RD, MD, and CSA were significantly higher at all four measurement levels in CMT patients. AD was found to be significantly higher at level 2 in CMT patients.

DTI evaluation of the sciatic nerve can differentiate the demyelinating neuropathology of patients with CMT type 1 from normal nerves. In addition, it was confirmed that CSA of the sciatic nerve is a parameter for diagnosing neurological abnormalities in CMT type 1 patients.

Hereinafter, the present invention will be described in more detail.

One embodiment of the present invention relates to a method of providing information necessary for diagnosing Charcot-Marie-Tooth disease type 1A, comprising the following steps.

acquiring an axial T2-weighted MRI image of the sciatic nerve;

Sciatic nerve visualization step of visualizing a region of interest from the T2-weighted MRI image;

calculating a cross-sectional area (CSA) of the sciatic nerve; and

Calculating the DTI parameters of the sciatic nerve.

In the present invention, the cross-sectional area of the sciatic nerve is the hamstring tendon origin, the lesser trochanter of the femur, the gluteus maximus tendon insertion, and the mid-femur. -femur) may be measured at one or more sites selected from the group consisting of, for example, it may be measured at all four sites.

In the present invention, the parameter is from the group consisting of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). It may be one or more selected types, for example, may be all of the above four.

In the present invention, the parameters are hamstring tendon origin, lesser trochanter of the femur, gluteus maximus tendon insertion, and mid-femur. It may be measured at one or more sites selected from the group consisting of, for example, it may be measured at all four sites.

In the present invention, the MRI image may be obtained using diffusion tensor imaging (DTI), but is not limited thereto.

The present invention relates to a method of providing information necessary for diagnosing CMT type 1 through sciatic nerve measurement using MRI.

1A is an axial Dickson water-only image showing a region-of-interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type 1 patient according to an embodiment of the present invention.
1B is an axial Dickson water-only image showing a region-of-interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type I patient according to an embodiment of the present invention.
1C is an axial Dickson water-only image showing a region-of-interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type I patient according to an embodiment of the present invention.
1D is an axial Dickson water-only image showing a region-of-interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type I patient according to an embodiment of the present invention.
FIG. 1E is a _b800 map image showing a region of interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type I patient according to an embodiment of the present invention.
FIG. 1f is a _b800 map image showing a region of interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type I patient according to an embodiment of the present invention.
1G is a _b800 map image showing a region of interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type I patient according to an embodiment of the present invention.
1H is a _b800 map image showing a region of interest (ROI) analysis of the sciatic nerve of a 24-year-old CMT type I patient according to an embodiment of the present invention.
1I is a diagram showing four types of levels on which ROI analysis is performed according to an embodiment of the present invention.
FIG. 2A is a water-only image showing a region-of-interest analysis (ROI) result of a sciatic nerve of a 25-year-old male volunteer according to an embodiment of the present invention.
2B is a water-only image showing a region of interest analysis (ROI) result of a sciatic nerve of a 25-year-old male volunteer according to an embodiment of the present invention.
FIG. 2C is a water-only image showing a region-of-interest analysis (ROI) result of a sciatic nerve of a 25-year-old male volunteer according to an embodiment of the present invention.
2D is a water-only image showing a region of interest analysis (ROI) result of a sciatic nerve of a 25-year-old male volunteer according to an embodiment of the present invention.
FIG. 2E is a water-only image showing a region-of-interest analysis (ROI) result of a sciatic nerve of a 25-year-old male volunteer according to an embodiment of the present invention.
FIG. 2f is a water-only image showing a region-of-interest analysis (ROI) result of the sciatic nerve of a 26-year-old CMT type 1 patient according to an embodiment of the present invention.
2G is a water-only image image showing a region-of-interest analysis (ROI) result of the sciatic nerve of a 26-year-old CMT type 1 patient according to an embodiment of the present invention.
FIG. 2H is a water-only image showing a region-of-interest analysis (ROI) result of the sciatic nerve of a 26-year-old CMT type 1 patient according to an embodiment of the present invention.
2I is a water-only image image showing a region of interest (ROI) analysis of the sciatic nerve of a 26-year-old CMT type 1 patient according to an embodiment of the present invention.
FIG. 2J is a water-only image showing a region-of-interest analysis (ROI) result of the sciatic nerve of a 26-year-old CMT type 1 patient according to an embodiment of the present invention.
Figure 3a is a graph showing a comparison of the average value of the FA for each measurement level in the volunteer group and the CMT patient group according to an embodiment of the present invention.
Figure 3b is a graph showing comparison of the average value of AD for each measurement level in the volunteer group and the CMT patient group according to an embodiment of the present invention.
Figure 3c is a graph showing the comparison of the average value of the RD for each measurement level in the volunteer group and the CMT patient group according to an embodiment of the present invention.
3D is a graph showing a comparison of the average value of the MD for each measurement level of the volunteer group and the CMT patient group according to an embodiment of the present invention.
3E is a graph showing a comparison of the average value of CSA for each measurement level of a volunteer group and a CMT patient group according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

Study population

The sample size required to find a meaningful difference in mean FA of the sciatic nerve between CMT type 1 and the control group was calculated prospectively with an alpha value of 0.05 and a beta value of 0.2. The expected difference in FA between the two groups was assumed to be 0.1 (standard deviation, 0.1) based on the results of previous studies:

The sample size (N) was calculated using the following formula:

[formula]

N = 2(1.96+0.84) ² σ ² /δ ²

(σ and δ are standard deviations of FA, expected mean difference of FAs between two groups)

The calculated sample size for each group was 16. The expected dropout rate was set at 10%, so the number of patients per group was 18.

As shown in Tables 1 to 4, between February and June 2017, 18 patients with CMT type 1 diagnosed through genetic analysis and electrophysiological studies underwent MRI examination.

Patient Number Gender Age Age at Symptom Onset Age at Initial Diagnosis Charcot-Marie-Tooth Neuropathy Score Functional Disability Scale One male 24 12 14 7 One 2 female 23 10 12 7 One 3 female 34 20 25 6 One 4 female 35 12 28 16 2 5 male 27 8 20 16 2 6 female 25 8 20 17 2 7 female 28 13 24 18 2 8 male 34 10 29 11 One 9 female 31 8 26 9 One 10 male 29 11 27 16 2 11 female 33 One 34 6 One 12 female 32 One 31 9 One 13 male 36 7 36 21 3 14 male 26 15 26 11 One 15 male 26 25 25 14 2 16 female 20 15 20 15 3 17 male 22 10 21 5 One 18 female 22 16 22 9 One

Motor nerve studies median motor nerve Ulnar motor nerve Patient
Number Side TL;
(ms) CMAP
(mV) MNCV
(m/s) TL;
(ms) CMAP
(mV) MNCV
(m/s) One Right 8.7 19.3 20.2 6.7 12.7 18.6 Left 9.3 18.7 19.6 6.4 9.5 16.7 2 Right 8.5 11.4 18.8 6.0 8.7 17.3 Left 9.3 12.2 17.6 6.9 11.3 16.5 3 Right 8.0 9.2 16.9 5.8 7.3 18.1 Left 7.7 11.6 18.1 6.4 7.8 19.0 4 Right A A A 8.2 3.0 11.4 Left 15.1 0.5 12.1 8.7 2.2 12.4 5 Right 10.6 9.4 15.8 7.8 8.9 14.4 Left 10.2 70.0 16.2 7.2 6.9 13.8 6 Right 11.0 8.2 10.8 10.4 4.2 10.2 Left 10.2 7.5 10.5 9.0 4.8 10.2 7 Right 10.4 0.9 15.1 5.9 2.8 19.6 Left 11.9 1.3 16.1 7.7 1.5 18.9 8 Right 7.4 10.5 21.6 5.3 12.0 21.1 Left 7.4 11.5 22.9 4.9 10.7 21.3 9 Right 7.3 10.0 17.0 5.0 9.2 17.0 Left 7.5 10.6 17.4 5.8 8.0 18.4 10 Right 7.1 17.9 18.6 6.1 8.7 16.4 Left 7.7 16.2 19.0 6.6 9.9 15.2 11 Right 8.0 7.9 22.8 5.9 8.5 22.6 Left 8.3 7.5 22.0 5.3 10.1 21.5 12 Right 5.4 1.8 40.0 4.6 8.8 43.7 Left 5.7 2.7 44.1 4.4 11.0 39.6 13 Right 9.3 10.6 20.0 5.8 9.1 19.0 Left 8.4 10.3 19.1 6.3 10.9 18.9 14 Right 8.3 7.5 14.3 8.0 10.3 13.2 Left 8.7 9.0 14.4 8.4 10.2 13.3 15 Right 8.9 9.3 22.3 7.3 10.3 21.1 Left 10.1 11.5 22.9 7.4 13.5 19.3 16 Right 9.0 7.3 15.8 9.7 4.3 16.7 Left 8.0 7.7 16.3 7.5 4.6 16.6 17 Right 9.1 8.0 20.0 7.7 11.9 17.7 Left 9.2 14.4 18.8 8.0 14.1 17.7 18 Right 9.0 10.2 29.7 7.0 4.4 22.6 Left 8.6 11.3 27.8 6.8 5.9 21.3 Normal value < 3.9 > 6.0 > 50.5 < 3.0 > 8.0 > 51.1

Motor nerve studies peroneal nerve Tibial nerve Patient
Number Side TL;
(ms) CMAP
(mV) MNCV
(m/s) TL;
(ms) CMAP
(mV) MNCV
(m/s) One Right 13.2 1.2 18.2 10.2 8.0 19.1 Left 13.5 0.4 18.7 10.0 7.8 20.8 2 Right 11.1 0.8 15.1 10.7 4.1 18.5 Left 11.6 0.8 15.3 10.2 3.6 17.1 3 Right A A A 13.6 1.0 18.2 Left A A A A A A 4 Right A A A A A A Left A A A A A A 5 Right A A A 11.4 0.5 12.7 Left A A A 10.6 1.0 14.4 6 Right A A A 12.6 0.5 10.0 Left A A A 10.4 0.6 13.7 7 Right A A A 16.9 0.4 19.2 Left A A A 11.3 0.2 A 8 Right 7.4 2.7 20.2 8.6 3.3 23.4 Left 9.0 2.7 20.8 11.9 0.7 20.8 9 Right A A A 8.1 1.8 13.1 Left 17.3 0.2 14.8 11.3 0.7 14.3 10 Right A A A 12.2 0.6 14.3 Left 11.0 1.6 13.0 12.0 0.2 16.2 11 Right 9.6 4.6 19.5 10.5 7.7 19.3 Left 12.9 2.9 17.2 10.5 7.7 19.3 12 Right 8.2 3.1 31.8 9.1 3.3 36.6 Left 7.6 4.2 34.2 5.0 10.0 26.7 13 Right 10.2 0.6 16.4 7.1 2.0 16.4 Left 9.4 0.8 17.6 7.8 2.3 18.6 14 Right 12.1 1.4 12.6 11.9 1.2 14.2 Left A A A 9.5 2.4 15.3 15 Right 12.5 0.6 19.0 8.2 0.3 15.2 Left 12.3 1.5 16.3 8.5 0.5 14.4 16 Right 16.5 0.3 13.7 21.2 0.9 15.1 Left A A A 20.1 0.3 17.3 17 Right 16.8 2.6 16.9 12.3 4.7 17.4 Left 16.3 0.9 16.5 14.5 3.2 17.4 18 Right 9.0 1.8 21.8 7.5 6.3 26.5 Left 9.1 1.1 24.9 9.9 4.9 28.4 Normal value < 3.9 > 6.0 > 50.5 < 3.0 > 8.0 > 51.1

sensory nerve studies median sensory nerve Ulnar sensory nerve Sural nerve Patient
Number Side SNAP
(μV) SNCV
(m/s) SNAP
(μV) SNCV
(m/s) SNAP
(μV) SNCV
(m/s) One Right 4.5 15.9 1.2 14.4 A A Left 3.6 15.5 1.5 14.2 A A 2 Right 3.3 15.5 2.1 14.3 A A Left 4.4 14.1 1.7 14.0 A A 3 Right 1.9 14.1 2.0 15.5 A A Left 3.8 14.5 2.1 14.9 A A 4 Right A A A A A A Left A A A A A A 5 Right 4.5 16.9 8.3 17.4 A A Left 6.3 18.6 6.4 17.4 A A 6 Right A A A A A A Left A A A A A A 7 Right A A A A A A Left A A A A A A 8 Right 3.3 20.0 1.8 21.1 1.1 19.7 Left 1.8 19.4 2.5 17.9 1.1 19.7 9 Right 5.6 16.9 1.7 17.2 A A Left 3.2 17.6 1.9 16.1 A A 10 Right 3.2 16.1 1.8 14.5 A A Left 4.1 15.9 2.4 14.4 A A 11 Right 1.5 18.1 1.4 18.2 A A Left 1.6 18.4 2.5 17.5 A A 12 Right 5.9 28.8 5.7 31.2 4.4 27.5 Left 6.1 27.6 4.9 30.6 3.0 25.9 13 Right 1.6 15.4 0.9 16.7 A A Left 2.0 14.8 2.0 17.6 A A 14 Right 1.4 14.7 1.7 14.2 A A Left 3.0 14.5 1.2 14.8 A A 15 Right 1.2 16.4 A A A A Left 0.7 14.1 1.6 16.1 A A 16 Right 1.0 12.9 A A A A Left 1.3 13.0 A A A A 17 Right 1.8 16.0 0.7 13.0 A A Left 2.4 14.2 1.1 13.2 A A 18 Right 3.1 17.4 A A A A Left 3.4 19.7 1.2 17.4 A A Normal value > 8.8 > 39.3 > 7.9 > 37.5 > 6.0 > 32.1

Seventeen patients underwent genetic analysis were diagnosed with CMT type 1A. All of them had copies of peripheral myelin protein 22 (PMP22). One patient, who did not undergo genetic testing, was diagnosed with CMT type 1 based on clinical history and electrophysiological results, and showed severe demyelinating sensorimotor polyneuropathy. The cohort was restricted to patients aged 20 to 40 years (mean age, 30.1 ± 4.3 years, age range 23 to 37 years, 8 males and 10 females). There was no other neuromuscular disease or diabetes. They had no contraindications to MRI, such as claustrophobia or metal in the body. Patients were enrolled on a first-come, first-served basis.

As shown in Table 5, 18 healthy controls matched in age and gender were recruited on the bulletin board of our institution, and 18 volunteers without a history of peripheral neuropathy, lower extremity disease, or MRI contraindications were recruited.

Subject Number Gender Age One male 27 2 female 26 3 female 34 4 female 33 5 male 29 6 female 34 7 female 28 8 male 32 9 female 38 10 male 29 11 female 33 12 female 33 13 male 34 14 male 28 15 male 28 16 female 25 17 male 25 18 female 26

A neurologist with 21 years of experience performed a physical examination to assess neurological abnormalities prior to MRI. 18 control subjects (mean age 28.2 ± 1.2 years old, age range 20 to 36 years old, 8 males, 10 females) were confirmed to have no neurological abnormalities on physical examination.

Approval from the research committee was obtained, and all patients and volunteers provided written informed consent prior to MRI. Since dropout did not occur in either the patient group or the control group, data from 18 patients in each group were used for the analysis.

Magnetic resonance imaging acquisition

Magnetic resonance imaging (MRI) was acquired using a 3.0-T MRI system (Ingenia, Philips Healthcare) using a 16-channel front coil and a rear built-in coil. The following MRI sequences were obtained for morphological imaging of the patient:

Axial T1-weighted turbo spin echo sequence (TR/TE, 450-650/15 ms, section thickness 2 mm, cross gap 1 mm, field 350 x 350 mm, acquisition matrix 320 x 320, imaging time 162 s, number of slices 67);

Coronal T1-weighted turbo spin echo sequence (TR/TE, 450-650/15 ms, section field of view, 200 mm, number of slices, 25);

axial T2-weighted Dixon sequence (TR/cm ² ); and

Transverse T2-weighted Dixon sequence (TE, 4635.5/80 ms, section thickness 2 mm, cross spacing 1 mm, field of view 350 x 350, acquisition matrix 320 x 320, imaging time 194 s, number of slices 67).

Water-only, fat-only, in-phase, and out-of-phase images were obtained from the Dixon sequence.

DTI was performed using single-shot echo plane imaging and reverse recovery technique for fat suppression (TR/TE, 7576.4/78.5 ms, cross-sectional thickness, 3 mm, no intersecting gap, field of view, 350 x 350, acquisition matrix, 128 Х 128, acquisition time 651.6 s, number of slices 67, delta [time from the center of the first gradient to the center of the second gradient]/delta [the plateau duration of the diffusion gradient], 39.5/27.1 ms). Images were obtained at the level from the anterior iliac spine to the femur through the distal femur in the axial plane.

Parallel imaging was performed using sensitivity encoding (SENSE; Philips Healthcare). Diffusion gradients were applied in 6 directions with b values of 0 and 800 s/mm ² . Diffusion encoding was performed with unipolar gradient pulses.

Data analysis

First, two radiologists rated DTI image quality by consensus, which is defined by several factors including motion artifacts and diagnostic acceptability. The following 4 rating scale was used:

1: very bad;

2: Not good;

3: Slight limitation in image quality but no pathological loss; and

4: Optimal.

Grades 3 and 4 were considered acceptable.

DICOM images were converted to NIfTI format using the dcm2nii tool (nitrc.org/projects/dcm2nii/) and the diffuse gradient directions were extracted. Parametric maps of FA, AD, RD and MD were calculated using Diffusion Toolkit software (trackvis.org/dtk) to generate diffusion maps. Two radiologists (14 and 5 years of experience in musculoskeletal radiology, respectively) independently performed ROI analysis using MRIcro® software (mricro.com, version 1.4). To clarify the location of the sciatic nerve in DTI, axial, b0 maps and coronal T1 and T2 water-only images displayed on a separate monitor were used as references. ROIs were drawn on each side of the sciatic nerve at four levels (Figures 1 and 2):

Level 1: hamstring tendon origin;

Level 2: lesser trochanter of the femur;

Level 3: gluteus maximus tendon insertion;

Level 4: mid-femur.

A single slice of the image was selected for analysis at each level, and ROIs were drawn pixel-by-pixel that fell within carefully visualized neural boundaries. No ROI analysis was performed on the distal femur given the limited resolution, signal-to-noise ratio, and small aperture of the nerve. A radiologist (with 5 years of experience in musculoskeletal radiology) measured the CSA of the sciatic nerve bundle on each level of water-only images for which DTI parameters were measured. Axial T1-weighted images were referenced to confirm the boundaries of the nerve bundles.

Statistical analysis

Statistical analysis was performed using SAS (version 9.4; SAS Institute). Inter-observer agreement on DTI was calculated using intra-class correlation coefficients, which are interpreted as follows:

0.8 - 1.0, excellent;

0.6 - 0.8, good; and

<0.6, disagreement.

DTI parameters and CSA of the sciatic nerve in CMT patients and controls were compared at each level using the appropriate two-sample t test or Mann-Whitney U test. Data from the left and right sciatic nerves were averaged together for comparison. As can be seen in Table 6, the absence of side effects was confirmed for all parameters by the Mann-Whitney U test.

Level 1 Level 2 Level 3 Level 4 FA Left 0.452±0.134 0.443±0.113 0.525±0.149 0.529±0.108 Right 0.453±0.108 0.460±0.137 0.543±0.137 0.532±0.119 P -value 0.979 0.492 0.538 0.936 AD Left 2.402*10 ^-3 ±0.329*10 ^-3 2.257*10 ^-3 ±0.275*10 ^-3 2.113*10 ^-3 ±0.333*10 ^-3 2.364*10 ^-3 ±0.332*10 ^-3 Right 2.383*10 ^-3 ±0.203*10 ^-3 2.201*10 ^-3 ±0.242*10 ^-3 2.135*10 ^-3 ±0.357*10 ^-3 2.268*10 ^-3 ±0.378*10 ^-3 P -value 0.526 0.136 0.469 0.550 RD Left 1.190*10 ^-3 ±0.359*10 ^-3 1.142*10 ^-3 ±0.309*10 ^-3 0.926*10 ^-3 ±0.349*10 ^-3 1.009*10 ^-3 ±0.285*10 ^-3 Right 1.169*10 ^-3 ±0.273*10 ^-3 1.091*10 ^-3 ±0.342*10 ^-3 0.937*10 ^-3 ±0.364*10 ^-3 1.040*10 ^-3 ±0.267*10 ^-3 P -value 0.526 0.183 0.701 0.280 MD Left 1.594*10 ^-3 ±0.318*10 ^-3 1.514*10 ^-3 ±0280*10 ^-3 1.322*10 ^-3 ±0.307*10 ^-3 1.461*10 ^-3 ±0.270*10 ^-3 Right 1.574*10 ^-3 ±0.220*10 ^-3 1.461*10 ^-3 ±0.295*10 ^-3 1.336*10 ^-3 ±0.348*10 ^-3 1.449*10 ^-3 ±0.269*10 ^-3 P -value 0.437 0.102 0.636 0.611 CSA Left 67.094±38.555 72.709±37.583 67.988±37.662 60.670±41.335 Right 65.297±34.577 75.352±36.410 66.518±38.963 62.861±44.631 P -value 0.874 0.688 0.668 0.561

A comparison of body mass index (BMI) between the two groups was performed using the Mann-Whitney U test to confirm the existence of significant differences that may affect CSA of the sciatic nerve. The normality of the data distribution was assessed using the Kolmogorov-Smirnov test. A p value <0.05 was considered significant. To evaluate their performance as discriminators of normal and pathological sciatic nerves, receiver operating characteristic (ROC) curve analysis was performed for parameters with significant differences between the two groups. The Youden index was used to determine the optimal cutoff value for each parameter. Based on optimal cutoff values, area under the curve (AUC) sensitivity, specificity, accuracy and positive and negative predictive values were evaluated for each parameter.

result

After two radiologists consensually assessed DTI image quality, three control images were rated as grade 2 (inappropriate image quality) and were consequently excluded. Other DTI images were considered acceptable (class 3: 8 subjects, class 4: 25 subjects).

As can be seen in Table 7, inter-observer agreement was excellent for analysis of all DTI parameters, and data obtained by one of the reviewers was used for comparison.

FA AD RD MD ICC 95% CI ICC 95% CI ICC 95% CI ICC 95% CI Level 1 Right 0.91 0.83-0.95 0.9 0.90-0.90 0.92 0.92-0.92 0.93 0.91-0.91 Left 0.93 0.87-0.97 0.93 0.93-0.93 0.89 0.89-0.89 0.91 0.90-0.90 Level 2 Right 0.96 0.92-0.98 0.88 0.88-0.88 0.95 0.95-0.95 0.9 0.93-0.93 Left 0.95 0.90-0.97 0.94 0.94-0.94 0.96 0.96-0.96 0.93 0.96-0.96 Level 3 Right 0.92 0.84-0.96 0.96 0.96-0.96 0.96 0.96-0.96 0.96 0.96-0.96 Left 0.96 0.92-0.98 0.97 0.97-0.97 0.98 0.98-0.98 0.96 0.98-0.98 Level 4 Right 0.92 0.85-0.96 0.96 0.96-0.96 0.92 0.92-0.92 0.98 0.94-0.94 Left 0.92 0.86-0.96 0.95 0.95-0.95 0.92 0.93-0.93 0.94 0.94-0.94

ICC intraclass coefficient, CI confidence interval, FA fractional anisotropy, AD axial diffusivity, RD radial diffusivity, MD mean diffusivity

As can be seen in Table 8 and Figure 3, the FA value was significantly lower in all 4 levels in CMT patients compared to the control group.

Level 1 Level 2 Level 3 Level 4 FA Controls 0.549 ± 0.098 0.549 ± 0.087 0.628 ± 0.108 0.586 ± 0.118 CMT patients 0.373 ± 0.208 0.370 ± 0.093 0.455 ± 0.124 0.484 ± 0.090 p Value < 0.0001* < 0.0001* < 0.0001* 0.0002* AD Controls 2.384*10 ^-3 ± 0.319*10 ^-3 2.161*10 ^-3 ± 0.194*10 ^-3 2.118*10 ^-3 ± 0.291*10 ^-3 2.238*10 ^-3 ± 0.334*10 ^-3 CMT patients 2.400*10 ^-3 ± 0.238*10 ^-3 2.286*10 ^-3 ± 0.299*10 ^-3 2.129*10 ^-3 ± 0.394*10 ^-3 2.381*10 ^-3 ± 0.375*10 ^-3 p Value 0.8158 0.0446* 0.9003 0.1083 RD Controls 0.892*10 ^-3 ± 0.210*10 ^-3 0.982*10 ^-3 ± 0.389*10 ^-3 0.731*10 ^-3 ± 0.220*10 ^-3 0.885*10 ^-3 ± 0.250*10 ^-3 CMT patients 1.304*10 ^-3 ± 0.293*10 ^-3 1.364*10 ^-3 ± 0.234*10 ^-3 1.098*10 ^-3 ± 0.369*10 ^-3 1.141*10 ^-3 ± 0.249*10 ^-3 p Value < 0.0001* < 0.0001* < 0.0001* < 0.0001* MD Controls 1.445*10 ^-3 ± 0.289*10 ^-3 1.315*10 ^-3 ± 0.187*10 ^-3 1.194*10 ^-3 ± 0.212*10 ^-3 1.336*10 ^-3 ± 0.240*10 ^-3 CMT patients 1.699*10 ^-3 ± 0.204*10 ^-3 1.631*10 ^-3 ± 0.286*10 ^-3 1.442*10 ^-3 ± 0.369*10 ^-3 1.554*10 ^-3 ± 0.256*10 ^-3 p Value < 0.0001* < 0.0001* 0.0050* 0.0008* CSA Controls 43.510 ± 14.468 48.723 ± 17.076 39.003 ± 14.383 29.277 ± 10.598 CMT patients 85.100 ± 39.347 95.119 ± 36.564 90.794 ± 36.664 88.839 ± 41.708 p Value < 0.0001* < 0.0001* < 0.0001* < 0.0001*

Data are displayed as mean values ± standard deviation. * indicates statistical significance.

FA fractional anisotropy, AD axial diffusivity, RD radial diffusivity, MD mean diffusivity, and CSA cross-sectional area.

RD, MD, and CSA were significantly higher at all 4 levels in CMT patients compared to controls. AD was significantly higher at level 2 in CMT patients. There was no significant difference in BMI between the two groups (p = 0.270, volunteers: median ± standard deviation, 21.60 ± 3.09, interquartile range, 20.60 - 25.10, CMT patients: median ± standard deviation, 23.06 ± 4.99, interquartile range, 21.48 - 27.63).

As can be seen in Table 9 below, the highest AUC was 0.921 (level 1) for FA, 0.865 (level 2) for RD, 0.815 (level 2) for MD, and 0.932 (level 3) for CSA.

AUC (95% CI) Optimal cut-off Sensitivity Specificity PPV NPV Accuracy FA Level 1 0.921 (0.846-0.997) 0.478 0.944 0.900 0.919 0.931 0.924 Level 2 0.915 (0.847-0.982) 0.435 0.833 0.900 0.909 0.818 0.864 Level 3 0.845 (0.754-0.937) 0.455 0.639 0.967 0.958 0.690 0.788 Level 4 0.764 (0.642-0.886) 0.559 0.806 0.700 0.763 0.750 0.758 AD Level 2 0.651 (0.516-0.786) 2.398 Х 10 ^-3 0.444 0.900 0.842 0.574 0.652 RD Level 1 0.865 (0.771-0.959) 1.222 Х 10 ^-3 0.750 0.867 0.871 0.743 0.803 Level 2 0.865 (0.774-0.956) 1.036 Х 10 ^-3 0.833 0.833 0.857 0.806 0.833 Level 3 0.790 (0.680-0.900) 1.053 Х 10 ^-3 0.611 0.933 0.917 0.667 0.758 Level 4 0.761 (0.643-0.879) 0.955 Х 10 ^-3 0.778 0.700 0.757 0.724 0.742 MD Level 1 0.787 (0.675-0.899) 1.564 Х 10 ^-3 0.806 0.667 0.744 0.741 0.742 Level 2 0.815 (0.708-0.921) 1.395 Х 10 ^-3 0.806 0.733 0.784 0.759 0.773 Level 3 0.702 (0.571-0.834) 1.516 Х 10 ^-3 0.556 0.900 0.870 0.628 0.712 Level 4 0.740 (0.616-0.863) 1.350 Х 10 ^-3 0.833 0.633 0.732 0.760 0.742 CSA Level 1 0.862 (0.768-0.955) 50.0 0.861 0.767 0.816 0.821 0.818 Level 2 0.875 (0.786-0.963) 64.0 0.861 0.833 0.861 0.833 0.848 Level 3 0.932 (0.863-1.000) 63.1 0.889 0.933 0.941 0.875 0.909 Level 4 0.922 (0.843-1.000) 54.7 0.861 0.967 0.969 0.853 0.909

FA fractional anisotropy, AUC area under the curve, CI confidence interval, PPV positive predictive value, NPV negative predictive value, AD axial diffusivity, RD radial diffusivity, MD mean diffusivity, CSA cross-sectional area

AUC was 0.651 (level 2) for AD. FA had a sensitivity of 94.4% and a specificity of 90.0% in grade 1. The cutoff values for each variable are: FA is 0.435-0.559, RD is 0.955 X 10 ^-3 - 1.222 X 10 ^-3 , MD is 1.350 X 10 ^-3 - 1.564 X 10 ^-3 , CSA is 50.0 - 64.0, AD is It is 2.398 X 10 ^-3 .

Discussion

As can be seen above, the DTI parameters obtained by sciatic nerve analysis were significantly different between the CMT type 1 patient and the control group. FA was significantly lower at all four levels measured, and MD and RD were significantly higher in CMT patients than in volunteers. The diagnostic performance of the control group with each step's parameters and cutoff values for differentiating CMT patients was provided, which can be used as a reference in future studies. All parameters showed high interclass reproducibility. These results imply the clinical applicability of DTI in sciatic nerve evaluation in patients with CMT type 1 and other types of demyelinating neuropathy.

Claims (4)

A method for providing information necessary for diagnosing Charcot-Marie-Tooth disease type 1 comprising the steps of:
An MRI image acquisition step of acquiring an MRI image using diffusion tensor imaging (DTI);
a sciatic nerve visualization step of visualizing a region of interest from the MRI image in units of pixels; and
Calculating the DTI parameters of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) of the sciatic nerve. The method according to claim 1, wherein the cross-sectional area of the sciatic nerve is a hamstring tendon origin, lesser trochanter of the femur, gluteus maximus tendon insertion, and central femur. (mid-femur), which is measured at one or more sites selected from the group consisting of Sarco-Marie-Tooth disease type 1 diagnosis. The method of claim 1, wherein the parameters are hamstring tendon origin, lesser trochanter of the femur, gluteus maximus tendon insertion, and mid-femur. femur), which is measured at one or more sites selected from the group consisting of Sarco-Marie-Tooth disease type 1 diagnosis. delete

Images