1 Junji Moriya1, Shingo Kakeda1, Johji Nishimura1, Tetsuya Yoneda2, Toru Sato1, Yasuhiro Hiai2, Norihiro Ohnari1, Okada Kazumasa3, Haruki Hayashi4, Eiji Matsusue5, Yukunori Korogi1 1) Department of Radiology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu , Japan. 2) Department of course of Radiological Sciences, Kumamoto University School of Health Sciences 3) Department of Neurology, University of Occupational and Environmental Health School of Medicine 4) Department of Anatomy and Anthropology, School of Medicine, University of Occupational and Environmental Health. 5) Division of Radiology, Department of Pathophysiological and Therapeutic Science,Faculty of Medicine, Tottori University A novel tract imaging of the brain stem using phase difference enhanced imaging technique: normal anatomy and multiple system atrophy

2 Introduction The brain stem concentrates structures of vital importance in a relatively small area. However, many internal structures of the brain stem cannot be clearly delineated on conventional MR images. According to the previous diffusion tensor imaging (DTI) reports, the superior, middle, and inferior cerebellar peduncles and corticospinal tract have been identified. However, the distinction of the medial lemniscus, central tegmental tract, and medial and dorsal longitudinal fasciculi have not been clearly defined using DTI(1,2). 1.Radiology. 2004;230: AJNR. 2004;25:

3 Introduction Recently, we have developed new phase-weighted MR imaging, “Phase Difference Enhanced Imaging (PADRE)”, in which phase difference between objective and surrounding tissue was selected in order to enhance the contrast of objective tissue. By choosing appropriate phase differences, we were able to create various contrasts of tissues.

4 Purpose To develop a new tract imaging technique for visualizing the small fiber tracts of the brain stem, and for detecting the pathological changes in a multiple system atrophy (MSA) using a PADRE technique.

5 PADRE technique surrounding tissue object phase PADRE selects the phase difference between the object and surrounding tissue, and enhances them selectively. Source imge PADRE phase

6 Materials and Methods PADRE Images  3T MR system (Signa EXCITE 3T; GE Healthcare)  three-dimensional fast spoiled gradient-echo (3D fast SPGR) sequence  TR=45 msec, TE=/28 msec, imaging time = 12 minutes, 22 cm field of view, 512 x 512 matrix, and 1.4-mm thick sections. High spatial resolution (voxel size of 0.4 x 0.4 x 1.4 mm 3 )

7 Materials and Methods Normal Anatomic Analysis  6 healthy volunteers (3 female, 3 male; mean age: 27.5 years ± 1.38; range: years)  Brain stem anatomy on the PADRE images was assessed on the basis of anatomic knowledge.  PADRE vs Conventional MRI images (SPGR, T2WI) and SWI

8 Materials and Methods Analysis of the Anatomy of MSA  MSA-C (n=3), MSA-P (n=2), spinocerebellar ataxia (SCA) type 6 (n=2), SCA type 8 (n=1), and cortical cerebellar atrophy (CCA) (n=1).  Comparison of PADRE images between healthy volunteers and patients.  PADRE images were evaluated on the basis of the existing anatomical postmortem data regarding MSA.

9 Medial lemniscus Corticospinal fibers Spinothalamic tract Marjorie A. England, Jennifer Wakely: Color Atlas of the BRAIN & SPINAL CORD p194 Result Normal Anatomic Analysis PADRE

10 Result Normal Anatomic Analysis Medial longitudinal fasciculus Superior cerebellar peduncle Central tegmental tract PADRE Transverse pontine fibers inferior cerebellar peduncle PADRE

11 Result Normal Anatomic Analysis Spinothalamic tract c 6 Medial lemniscus medial longitudinal fasciculus superior cerebellar peduncle coronal image sagittal image

12 SPGR T2WI PADRE vs SWI-like image, T2WI, SPGR SWI-like image vs

13 * * * * Healthy volunteer MSA-C MSA-PCCA Pathology of MSA-C Result ; Analysis of the Anatomy of MSA (*)superior cerebellar peduncles (←) medial longitudinal fasciculus ( ▼ ) transverse pontine fibers

14 Healthy volunteer MSA-C MSA-P CCA Pathology of MSA-C (←) inferior cerebellar peduncles Result ; Analysis of the Anatomy of MSA

15 Result Summary of Image Findings (-) M64/CCA (-) F58/SCA6 (-) (+)(-) M59/SCA6 (-) F83/MSA-P (-)(+) (-) F57/MSA-P (-)(+)(++)(-)(+)M59/MSA-C (+)(++) (-)(++)F64/MSA-C (+)(++) (-)(++)M50/MSA-C Hot cross bun sign Brain stem atrophy Atrophy of ICP Atrophy of SCP Disappearance of TPF T2WI findings PADRE findings Age/ Sex Type TPF = transverse pontine fibers, SCP = superior cerebellar peduncles, ICP = inferior cerebellar peduncles Early stage MSA-C

16 T2WI Early stage MSA-C PADRE 59y. m. Duration of symptoms (10 months) (←) inferior cerebellar peduncles ( ▼ ) transverse pontine fibers PADRE T2WI

17 PADRE identified the various fine fiber tracts in the brain stem. superior and inferior cerebellar peduncles spinothalamic tract medial lemniscus medial longitudinal fasciculus central tegmental tract corticospinal tract transverse pontine fibers Discussion 1 →Difficult to appreciate these fibers in conventional MRI or SWI.

18 PADRE identified the various fine fiber tracts in the brain stem superior and inferior cerebellar peduncles spinothalamic tract medial lemniscus medial longitudinal fasciculus central tegmental tract corticospinal tract transverse pontine fibers Discussion 1 PADRE technique may enhance the visibility of nerve fiber bundles and provide a novel tract imaging of the brain stem.

19 MSA-C PADRE images showed the disappearance of transverse pontine fibers and the atrophy of the inferior cerebellar peduncles, while the superior cerebellar peduncles were recognizable with normal or nearly normal. MSA-P, CCA, and SCA6 PADRE images showed no degeneration of the transverse pontine fibers; the inferior cerebellar peduncles were also nearly normal or only mildly atrophic. Discussion 2 These findings match those expected on the basis of histopathology.

20 PADRE technique clinical utility of MRI in differentiating MSA from other conditions useful tool for the detection of the abnormalities during the early stage of MSA. Discussion 3 Our PADRE technique can detect the changes of the small internal structures of the brain stem in MSA with visual assessment.

21 Conclusion PADRE technique can offer a new microscopic tract imaging of the brain stem.