Signal intensity of superficial white matter on phase difference enhanced imaging as a landmark of the perirolandic cortex

Abstract

Background

The superficial white matter (SWM), which fills the space between the deep white matter and the cortex, has not been well characterized.

Purpose

To determine whether the assessment of the relative signal intensity (SI) of the SWM in the precentral and postcentral gyri on phase difference enhanced (PADRE) images contributes in establishing anatomical landmark.

Material and Methods

The study population consisted of 43 normal subjects (28 women, 15 men; mean age, 52.9 years; age range, 22–90 years). By the consensus of two observers, the precentral gyri, postcentral gyri, and superior frontal cortex (SFC) were identified based on the established anatomical methods. The SI of the SWM in the precentral and postcentral gyri on PADRE images was divided into three grades in comparison with that of the SFC: Grade I, isointense; Grade II, slightly hypointense; and Grade III, markedly hypointense.

Results

The SWM in the precentral and postcentral gyri showed hypointensity on PADRE images. In the SI analyses of the PADRE images, the Grade I, Grade II, and Grade III appearances were found in one (1%), 20 (23%), and 65 (76%) of the 86 precentral gyri (43 subjects), respectively, and in one (1%), 23 (27%), and 62 (72%) of the 86 postcentral gyri, respectively.

Conclusion

On PADRE images, the perirolandic SWM showed hypointensity compared to other cerebral cortices, which probably reflects differences in the concentrations of the nerve fibers, as well as the higher myelin content. PADRE may be useful for the identification of the central sulcus by assessing the SI of the SWM.

Keywords

Magnetic resonance imaging (MRI)phase difference enhanced imaging superficial white matter precentral gyrus central sulcus

Introduction

The anatomy of the deep white matter regions, which consist of large axonal bundles, has been well-characterized by anatomical and histological studies (1,2). However, the superficial white matter (SWM), which fills the space between the deep white matter and the cortex, has not been well characterized. For example, the SWM is known to contain short cortical association fibers, but the regional differences in their volume among the gyri have not been sufficiently defined.

Phase imaging techniques, including susceptibility-weighted imaging (SWI), may demonstrate excellent image contrast and reveal anatomical structures that are not visible on the corresponding magnitude images (3 –6). A new phase-weighted magnetic resonance imaging (MRI) technique “Phase Difference Enhanced Imaging (PADRE)” has been developed, in which the phase difference between the target and surrounding tissue is selected in order to enhance the contrast of the target tissue (7). Choosing the appropriate phase differences allows the variations in tissue contrast to be noted using single (imaged) MR data. Some of the PADRE images offered a new level of contrast that could not be obtained by any of the preceding phase techniques (7). A previous report found that the high-spatial-resolution PADRE images delineated various fiber tracts, such as the optic radiation, central tegmental tract, and the medial and dorsal longitudinal fascicules (7,8). Based on these findings, the authors speculated that the myelination of the nerve fiber was one of the factors that determined the signal intensity on PADRE. Therefore, the use of PADRE might allow for identification of the anatomical features of the myelin densities in the SWM regions.

The identification of the precentral and postcentral gyri is important when surgical intervention is being planned. Several anatomic methods of identifying the precentral and postcentral gyri on MR images have been developed (9 –11). Some authors have identified them on the basis of the signal intensity (SI) of the perirolandic cortex on T2-weighted (T2W) (12) and FLAIR (13) images. Kakeda et al. have reported that the perirolandic cortices are hypointense compared to other cerebral cortices on phase-weighted MRI (6). Although many previous MR studies have shown the relative SI differences in the perirolandic cortex, there have been no studies comparing the SI of the SWM in the precentral and postcentral gyri with that in other gyri. The purpose of the present study was to evaluate the relative SI of the perirolandic SWM on PADRE images.

Material and Methods

Subjects

The study was approved by the institutional review board, and informed consent was not required by the institutional review board for this study. Between April 2013 and May 2014, consecutive patients, who were referred for brain MRI, were prospectively evaluated. The following criteria were used for inclusion in the study: (i) patients who underwent a brain MR examination with 3D multi-echo spoiled GRE sequence using a 3T MR system; (ii) normal findings in a neurological examination; (iii) no history of neurological disease, malignancy, or brain surgery; and (iv) normal results of a brain MR examination. Therefore, the study population consisted of 43 normal subjects (28 women, 15 men; mean age, 52.9 years; age range, 22–90 years; age distribution, 20–29 years [n = 7], 30–39 years [n = 6], 40–49 years [n = 9], 50–59 years [n = 4], 60–69 years [n = 6], 70–90 years [n = 11]) who fulfilled such criteria were included. The MR images were reviewed in consensus by two neuroradiologists. The indications for MRI included headache (n = 20), a follow-up study for a cranial aneurysm (n = 10), dizziness (n = 5), stiff neck (n = 5), and the healthy volunteers recruited for the volunteer study (n = 3).

Magnetic resonance imaging (MRI)

All studies were performed on a 3-T MRI system (Signa EXCITE 3 T; GE Healthcare, Milwaukee, WI, USA) using a dedicated eight-channel phased-array coil (USA Instruments, Aurora, OH, USA). PADRE images were obtained with a 3D multi-echo spoiled gradient echo (GRE) sequence. The imaging parameters included: coronal planes covering the brain; number of echo times (TE), 11; first TE, 4.5 ms; uniform TE spacing, 5 ms; repetition time, 58.4 ms; flip angle, 15°; bandwidth per pixel, ±62.5 Hz; field of view, 22 × 16.5 cm; acquisition matrices, 320 × 416; slice thickness, 1.5 mm and an imaging time of 7 min 1 s. A parallel imaging method (the array spatial sensitivity encoding technique) was used with a reduction factor of two.

PADRE technique

The method used for the PADRE technique was described in a previous report (7). One of the major concepts responsible for the power of the PADRE technique is the “phase difference selection” which enhances the magnetic properties of the target tissue. SWI, for example, selects only a phase difference related to vessels, especially to the veins. PADRE, however, classifies and selects various phase differences, $Δ θ$ , in order to enhance the different tissues, and enhances all of them on the magnitude image $| ρ |$ by the enhancing function $w (Δ θ)$ . Finally, the PADRE image $ρ_{PADRE}$ is reconstructed as:

ρ_{PADRE} = w (Δ θ) | ρ | .

The reconstitution parameters of PADRE were optimized on the basis of the previous results (7). In addition, the SWI-like images were also reconstructed from the MR data.

Optimization of TE

Because the 3D multi-echo spoiled GRE sequence used in this study consisted of 11 kinds of TE, we were able to create the PADRE images with different TE of 4.5, 9.4, 14.4, 19.3, 24.3, 29.2, 34.1, 39.1, 44.0, 49.0, and 53.9 ms. Therefore, to investigate the effects of varying the TE on the contrast of the nerve fiber, PADRE images were acquired for three healthy volunteers (a 22-year-old woman, a 45-year-old man, and a 53-year-old man), and two radiologists (SK, SI) evaluated the delineation of the four layers at the optic radiation (tapetum, internal sagittal stratum, external sagittal stratum, and adjacent white matter) according to the previous study (Fig. 1) (8). The same radiologists also evaluated the overall image quality of the PADRE images.

Fig. 1.

An axial PADRE image (TE, 34.1 ms) of a healthy volunteer. On the PADRE image, a high SI layer (T), a median SI layer (I), a low SI layer (E), and another high SI layer (WM) were clearly seen as four separate layers. These four layers on the PADRE image respectively corresponded to the tapetum (T), internal sagittal stratum (I), external sagittal stratum (E), and adjacent white matter (WM).

For the reconstructed parameters such as the filter size, the PADRE techniques which were described in the previous report were used, except for the TE, which was optimized as noted above (7).

Image interpretation

For this study, the 86 gyri in 43 subjects were evaluated. The SI of the precentral and postcentral gyri was independently interpreted on both PADRE and SWI-like images by two neuroradiologists (JM, NO) (12). The radiologists were blinded to the MRI sequence. The superior frontal cortex (SFC) was used for reference. For both PADRE and SWI-like images, each image was analyzed separately, and only one sequence was shown at a time. For the SI of the SWM, the precentral and the postcentral gyri were divided into three grades: Grade I, isointense to the SFC; Grade II, slightly hypointense to the SFC; Grade III, markedly hypointense to the SFC.

The inter-observer variability was calculated as a weighted κ value. The strength of agreement was considered fair for κ values of 0.21–0.40, moderate for κ values of 0.41–0.60, good for κ values of 0.61–0.80, and excellent for κ values of 0.81 or greater.

Results

Optimization of the TE

The best delineation of the four layers at the optic radiation was obtained at a TE of 34.1 or a TE of 39.1 ms, and the better overall image quality was obtained at a TE of 34.1 ms (Fig. 2). Therefore, for the evaluations of the perirolandic SWM, a TE of 34.1 ms was chosen.

Fig. 2.

Comparison of various TEs in the PADRE images obtained from a healthy volunteer (a 22-year-old woman). Magnitude images with a 19.3 ms (a), 29.2 ms (b), 34.1 ms (c), and 53.9 ms (d) TE. The best delineation of the four layers at the optic radiation was obtained at a TE of 34.1 ms.

SI of the perirolandic SWM

In all subjects, the SWM was seen as a low SI area on the PADRE images, but not on SWI-like images (Fig. 3). The results of the grading of the SWM (43 subjects) on the PADRE images are summarized in Table 1. Grade II and Grade III appearances were found in 20 (23%) and 65 (76%) of the 86 precentral gyri, and 23 (27%) and 62 (72%) of the 86 postcentral gyri, respectively. A grade I appearance was found in only one gyrus (1%) for both the precentral and postcentral gyri. Therefore, for both the precentral and postcentral gyri, 99% of the SWM was hypointense (slightly or markedly) on PADRE images (Fig. 3a). On the other hand, all of the SWM were isointense (Grade I) for both the precentral and postcentral gyri on the SWI-like images (Fig. 3b).

Fig. 3.

A PADRE image (a) and SWI-like image (b) of a 29-year-old woman. On the PADRE image, the SWM of the precentral (arrows) and postcentral (arrowheads) gyri were markedly hypointense. In contrast, the SWM of both gyri were isointense on the SWI-like image (arrows: central sulcus).

Table 1.

The signal intensity of the superficial white matter on the PADRE images.

	Precentral gyri (n = 86)	Postcentral gyri (n = 86)
Grade I	1 (1%)	1 (1%)
Grade II	20 (23%)	23 (27%)
Grade III	65 (76%)	62 (72%)

The data in brackets are the number of gyri and the data in parentheses are the percentages.

Grade I, isointense to the superior frontal cortex (SFC); Grade II, slightly hypointense to the SFC; Grade III, markedly hypointense to the SFC.

Fig. 4 shows the distribution of the SI of the SWM according to the subject’s age. For the precentral and postcentral gyri, a Grade III appearance was found in 100% (14/14) and 93% (13/14) of the subjects in the 20–29-year-old age group, in 83% (10/12) and 75% (9/12) in the 30–39-year-old age group, in 100% (18/18) and 94% (17/18) in the 40–49-year-old age group, in 50% (4/8) and 63% (5/8) in the 50–59-year-old age group, in 58% (7/12) and 58% (7/12) in the 60–69-year-old age group, and in 55% (12/22) and 50% (11/22) of the subjects in the 70–90-year-old age group, respectively. Thus, the frequency of Grade III decreased with age, especially in subjects older than 50 years (Fig. 5a). For both the precentral and postcentral gyri, a Grade I appearance was found for one gyrus in a subject older than 70 years (Fig. 5b). The κ values for the inter-observer variability between two radiologists were 0.85 for the PADRE images and 1.00 for SWI-like images; these values corresponded with excellent inter-observer agreement.

Fig. 4.

The distribution of the SI of the SWM according to the subject’s age: (a) precentral gyri, (b) postcentral gyri. In the elderly subjects (aged ≥50 years), the SWM tended not to be markedly hypointense.

Fig. 5.

PADRE images obtained from a 61-year-old man (a) and a 78-year-old man (b). On the PADRE image of a 61-year-old man, the SWM of the precentral (arrows) and postcentral (arrowhead) gyri were slightly hypointense, whereas the SWM of both gyri were isointense on the PADRE image of a 78-year-old man (arrows: central sulcus).

Discussion

We investigated the SI of the SWM using the PADRE technique. In past investigations, many small or common fiber tracts were identified in the brain stem with the PADRE technique (7). Our study extended these efforts to depict the SWM, where descriptions by the previous anatomical or histological studies have been scarce. The results demonstrated that, in all subjects, the SWM was seen as a low SI area on the PADRE images, but not on SWI-like images. An interesting finding was that, for the SI of the SWM, the precentral and the postcentral gyri were hypointense to the SFC, which can be used as an additional landmark for identification of the central sulcus. Moreover, the SWM mapping with PADRE may also provide new perspectives in the investigation of various diseases which have SWM involvement.

Phase images from gradient echo sequences allow the depicting of brain structures in greater detail than the corresponding conventional magnitude images. However, the origin of susceptibility contrast in the brain structures is not fully understood. There have been many speculations about the mechanism underlying the contrast of the phase images; these have included the different levels of myelin (14), the relative volume and oxygenation state of blood (15,16), the iron deposition (6,14,17), the chemical exchange between water and macromolecular protons (18), and the orientation of underlying white matter fibers with respect to the main magnetic field (19). We first attempted to optimize the TE for the PADRE images to enhance the myelin densities. It was previously demonstrated that the optic radiation is richer in myelin than in other white matter areas (20). Histologically, the external sagittal stratum of the optic radiation has large axons and thick myelin sheaths. In contrast, both the axons and myelin sheaths of the internal sagittal stratum are small (21). Therefore, the PADRE images in this study were optimized to enhance the observation of these differences in myelin densities.

We found that the SWM was seen as a low SI area on PADRE images, but not on the SWI-like images, which were more sensitive to iron (6,22). These results also suggest that the hypointense SWM on PADRE images may reflect the myelin density, not the iron deposition. Compared to the SWM of the other gyri in PADRE images, 99% of those of both the precentral and postcentral gyri were hypointense (slightly or markedly) in this study, indicating a higher myelin content. Our results suggest that the perirolandic SWM contains a larger amount of nerve fibers that consist of not only the large axonal bundles, but also the short association fibers (U-fibers). Although the regional differences in the myelin content of the SWM have not been described previously, the SWM in the main gyri, such as the precentral gyrus, in which the important afferent or efferent fibers project to or from, might be expected to be heavily myelinated. ortex m, ts our result y, Moreover, in a previous neuroimaging study, the main cortex (primary motor cortex, primary somatosensory cortex, primary visual cortex, auditory association cortex, or Broca’s area) have been shown to be heavily myelinated (23). This may also indicate that its SWM contains a larger amount of nerve fibers that connected with those within the cortices.

Previous investigators have reported an increasing incidence of hypointensity of the motor and somatosensory cortices on both T2W and FLAIR images with increasing age (12,24); they assumed that these hypointensities may reflect age-related neuronal degeneration and the accumulation of iron-laden macrophages (25). Moreover, another previous study demonstrated an increased incidence of hyperintensity of the SWM in the precentral gyrus on FLAIR images with increasing age (25), reporting that the SWM hyperintensity on FLAIR was seen in more than 50% of normal subjects at ages in the range of 61–80 years. This evidence supports our results; the frequency of a Grade III appearance decrease with age, especially in subjects older than 50 years. We postulated that our perirolandic SWM findings may be due to the secondary degeneration of myelinated fibers which was mediated by the age-related GM changes.

The main limitation of this study is the lack of a histopathological confirmation of the findings. Our anatomical analysis on PADRE images defined the low SI area in the SWM to be the myelin density. However, we could not validate our findings easily, because the exact anatomical appearance of the SWM has not been well-characterized by previous histological studies. Therefore, we cannot completely exclude the possibility that parts of the low SI area in the SWM that we identified were false positives. Moreover, the lack of low SI areas by PADRE does not necessarily mean that there was no myelin in such areas. Another limitation is that we evaluated only normal subjects. Therefore, further studies will be necessary to determine whether our method is equally useful for locating the central sulcus in the diseased state. In addition, further studies of SWM will be necessary to determine whether the PADRE imaging is useful for evaluating diseases, or perhaps for determining the SWM involvement, which has been suggested in certain diseases, such as amyotrophic lateral sclerosis (26), multiple sclerosis, and progressive multifocal leukoencephalopathy (PML) (27).

In conclusion, on PADRE images with the optimized TE, the perirolandic SWM was hypointense to the SWM of other gyri, which probably reflects differences in the concentration of the nerve fibers, as well as the higher myelin content. PADRE may be useful for identifying the central sulcus by assessing the SI of the SWM. The depiction of the myelin density in the SWM may make it possible to investigate the SWM involvement in brain diseases.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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