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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 59, Num. 2, 2011, pp. 266-269

Neurology India, Vol. 59, No. 2, March-April, 2011, pp. 266-269

Case Report

A Hot Cross Bun sign from diffusion tensor imaging and tractography perspective

Kok Beng Loh1, Kartini Rahmat1, Shen-Yang Lim2, Norlisah Ramli3

1 Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
2 Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
3 University Malaya Research Imaging Centre, Kuala Lumpur, Malaysia

Correspondence Address: Kok Beng Loh, Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia, kokbeng.loh@gmail.com

Date of Submission: 08-Dec-2010
Date of Decision: 11-Dec-2010
Date of Acceptance: 06-Jan-2011

Code Number: ni11071

PMID: 21483130

DOI: 10.4103/0028-3886.79143

Abstract

A "Hot Cross Bun" sign on T2-weighted MRI was described as a result of selective loss of myelinated transverse pontocerebellar fibers and neurons in the pontine raphe with preservation of the pontine tegmentum and corticospinal tracts (CST). However, neuropathologic studies showed contradicting results with no sparing of the CST. This is a pictorial and quantitative demonstration of the sign on diffusion tensor imaging and tractography, which provides the imaging evidence that is consistent with neuropathologic findings.

Keywords: Diffusion tensor imaging, "Hot Cross Bun" sign, multi-system atrophy-C, tractography

Introduction

The "Hot Cross Bun" sign [Figure - 1] is described as a cruciform hyperintensity in the pons on axial T2-weighted (T2W) magnetic resonance (MR) images of the brain. [1] The sign is commonly seen in patients with multiple system atrophy (MSA) with predominant cerebellar ataxia (MSA-C). It was postulated as a result of selective loss of myelinated transverse pontocerebellar fibers and neurons in the pontine raphe with preservation of the pontine tegmentum and corticospinal tracts (CST). [2] Although the CST appear relatively preserved on T2W MRI as seen in the "Hot Cross Bun" sign, neuropathologic studies commonly demonstrate degeneration of the CST in MSA. [3],[4] This may indicate insensitivity of T2W MRI in demonstrating corticospinal tract involvement in MSA.

Diffusion tensor imaging (DTI) has been shown to be sensitive in detecting white matter changes. [5],[6] It can be useful in demonstrating corticospinal tract involvement in MSA-C that is not shown on T2W MRI. The aim of the study is to illustrate the "Hot Cross Bun" sign from a DTI perspective.

Case Report

A 43-year-old female patient with clinical probable MSA-C [as defined by the consensus diagnostic criteria [7] ] and "Hot Cross Bun" sign on T2W imaging, as well as an age- and gender-matched healthy volunteer, were recruited for the DTI study. The patient had 1 year history of progressive gait unsteadiness and 2 months of urinary incontinence. In addition, she also demonstrated severe cerebellar ataxia, moderate parkinsonism, as well as pyramidal signs (generalized hyperreflexia and bilateral extensor plantar responses, but no limb weakness). A drop in the systolic blood pressure of >30 mm Hg from a lying position to standing was documented.

MR protocol

All images were acquired with slices parallel to anterior commissure (AC)-posterior commissure (PC) line, on a GE SignaHDx 1.5T MR scanner (Milwaukee, Wisconsin, USA), with an 8-channel arrayed RF coil. Using single-shot spin echo-echo planar sequence (SSSE-EPI), each DTI volume was acquired with diffusion gradients applied in 32 noncollinear directions and b-value of 1000 s/mm 2 . Twenty-seven 3-mm thick slices was acquired for each direction, with a field of view (FOV) of 240 × 240 mm 2 and matrix size of 128 × 128, zero-filled to 256 × 256. One set of reference images with least diffusion weighting (b=0 s/mm 2 ) was also acquired. Other imaging parameters were TR = 8000 ms; TE = 80 ms; and SENSE reduction factor = 2.0. A T2-weighted sequence was acquired for anatomic guidance.

Data analysis

Four regions of interest (ROI)-corticospinal tract (CST), transverse pontocerebellar fibers (TPC), pons, and cerebellum [Figure - 2]-were identified by a neuroradiologist with 10 years experience and a radiology trainee who was blinded to Hot Cross Bun sign. The "MRI Atlas of Human White Matter" [8] was used as anatomy reference by the radiology trainee. The fractional anisotropy (FA), mean diffusivity (MD) values of ROIs, and fiber tractography were obtained using a public domain software, DSI-Studio (developed by Fang-Cheng Yeh from the Advanced Biomedical MRI Lab, National Taiwan University Hospital, Taiwan, and made available at http://dsi-studio.labsolver.org/Download/). The ROI was drawn on the FA map itself as the T2W images cannot be overlaid on the FA map by DSI studio due to difference in resolution.

The streamline (Runge-Kutta) tracking method was used to perform the tractography with the following parameters: FA threshold of 0.15, turning angle of 40°, initial direction with main fiber, step size of 2.5 mm, interpolation angle of 60°, smoothing of 0.5, and length constraint set between 10 and 1000 mm. The FA threshold and the turning angle are 2 main parameters determining how the fibers are tracked from the ROI. FA threshold only allows fiber tracking from the pixels with FA value equal or above the threshold. Therefore, high FA threshold produces less fiber and low FA threshold produces more fiber. However, setting the FA threshold too low (<0.1) is not recommended as it may produce false fibers. The turning angle serves as a termination criterion for fiber tracking. If 2 consecutive moving directions have crossing angles above this threshold, the tracking will be terminated. A high turning angle produces more fiber but there is also a higher probability of false fibers. Therefore, selection of the optimal FA threshold and turning angle are important for optimal fiber tracking with minimal false fibers.

To comply with Terminologia Anatomica definition of the CST and transverse pontocerebellar fibers, the fiber tractographs were edited by the neuroradiologist to remove the outlying fibers. The fiber tractographs of the MSA-C patient and a healthy subject were compared qualitatively.

The FA and mean diffusivity (MD) values were obtained for each voxel within the ROI. The average of these FA and MD values were adapted as representative indices for each ROI and compared between the MSA-C patient and the healthy subject.

Results

Fiber tractographs of the healthy subject and MSA-C patient are shown in [Figure - 3], [Figure - 4], [Figure - 5] and [Figure - 6]. Compared with the healthy subject, MSA-C patient showed a decreased volume of fiber bundles corresponding anatomically to the CST fibers, transverse pontocerebellar fibers, pons, and cerebellum.

FA values in the CST, transverse pontocerebellar fibers, pons, and cerebellum in MSA-C were markedly lower than the healthy subject (up to 30%-47% lower). MD values in the CST, transverse pontocerebellar fibers, pons, and cerebellum were markedly higher in MSA than in the healthy subject (up to 30%-48% higher). The similar results are obtained from the ROIs identified by the radiology trainee. The study illustrates neuronal fiber loss in MSA-C with "Hot Cross Bun" sign on DTI and fiber tractography. The fiber loss was demonstrated in the pons, cerebellum, and transverse pontocerebellar fibers without sparing of the CST.

Discussion

FA is one of the most used measures of deviation from isotropy. It reflects the degree of alignment of cellular structures within fiber tracts, as well as their structural integrity. [9] Decreased FA values could reflect destruction of tissue architecture resulting from demyelination, neuronal loss, or gliosis. Mean diffusivity (MD) is a measure of the average molecular motion independent of any tissue directionality but is affected by cellular size and integrity. [10],[11] Mean diffusivity typically increases in demyelination. Marked decrease in FA and increase in MD were observed in the CST, transverse pontocerebellar fibers, pons, and cerebellum in our patient. Loss of fiber bundles at these regions was also observed on fiber tractography. Overall, DTI provides quantitative and qualitative evidence for the degeneration of pons, cerebellum, and transverse pontocerebellar fibers and CST in MSA-C. Corticospinal tract involvement was observed, in keeping with the result of neuropathologic studies. [3],[4] This study demonstrates DTI is sensitive in detecting corticospinal tract degeneration in MSA-C, which T2W MRI is insensitive to detect. This finding is consistent with the recent DTI studies in MSA. [12],[13],[14]

Acknowledgment

Special thanks to Dr Fang-Cheng Yeh from Advanced Biomedical MRI Lab, National Taiwan University Hospital, Taiwan, for providing guidance and support in using DSI studio.

References

1.Shrivastava A. The Hot Cross Bun Sign. Radiology 2007;245:606 -7.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Schrag A, Kingsley D, Phatouros C, Mathias CJ, Lees AJ, Daniel SE, et al. Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatry 1998;65:65-71.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Wenning G, Tison F, Ben Shlomo Y, Daniel S, Quinn N. Multiple system atrophy: A review of 203 pathologically proven cases. Mov Disord 1997;12:133-47.  Back to cited text no. 3    
4.Tsuchiya K, Ozawa E, Haga C, Watabiki S, Ikeda M, Sano M, et al. Constant involvement of the Betz cells and pyramidal tract in multiple system atrophy: A clinicopathological study of seven autopsy cases. Acta Neuropathol 2000;99:628-36.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Schocke MF, Seppi K, Esterhammer R, Kremser C, Mair KJ, Czermak BV, et al. Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease. Neuroimage 2004;21:1443-51.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Blain CR, Barker GJ, Jarosz JM, Coyle NA, Landau S, Brown RG, et al. Measuring brain stem and cerebellar damage in parkinsonian syndromes using diffusion tensor MRI. Neurology 2006;67:2199-205.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71:670-6.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Mori S, Wakana S, Nagae-Poetscher L, Van Zijl P. MRI Atlas of Human White Matter. 1st ed. Amsterdam: Elsevier Science; 2005.  Back to cited text no. 8    
9.Basser P, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B 1996;111:209-19.  Back to cited text no. 9    
10.Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B 1994;103:247-54.  Back to cited text no. 10  [PUBMED]  
11.Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G. Diffusion tensor MR imaging of the human brain. Radiology 1996;201:637-48.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Ito M, Watanabe H, Atsuta N, Senda J, Kawai Y, Tanaka F, et al. Fractional anisotropy values detect pyramidal tract involvement in multiple system atrophy. J Neurol Sci 2008;271:40-6.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Shiga K, Yamada K, Yoshikawa K, Mizuno T, Nishimura T, Nakagawa M. Local tissue anisotropy decreases in cerebellopetal fibers and pyramidal tract in multiple system atrophy. J Neurol 2005;252:589-96.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Ito M, Watanabe H, Kawai Y, Atsuta N, Tanaka F, Naganawa S, et al. Usefulness of combined fractional anisotropy and apparent diffusion coefficient values for detection of involvement in multiple system atrophy. J Neurol Neurosurg Psychiatry 2007;78:722-8.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]

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