Cerebral diffusion tensor imaging in tuberous sclerosis

Cerebral diffusion tensor imaging in tuberous sclerosis

European Journal of Radiology 71 (2009) 249–252 Cerebral diffusion tensor imaging in tuberous sclerosis Changfu Piao a , Aihong Yu b , Kuncheng Li a,...

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European Journal of Radiology 71 (2009) 249–252

Cerebral diffusion tensor imaging in tuberous sclerosis Changfu Piao a , Aihong Yu b , Kuncheng Li a,∗ , Yuping Wang c , Wen Qin a , Sufang Xue c a b

Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053, China Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital University of Medical Sciences, China c Department of Neurology, Xuanwu Hospital, Capital University of Medical Sciences, China Received 13 November 2007; received in revised form 17 April 2008; accepted 21 April 2008

Abstract Purpose: The purpose of this study was to investigate the features of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in cortical tubers and white-matter lesions in patients with tuberous sclerosis (TS) using diffusion tensor imaging (DTI). Materials and methods: Conventional magnetic resonance imaging (MRI) and DTI were performed in 14 patients with clinically established TS. Based on these DT images, ADC and FA maps were generated. The ADC values in 32 cortical tubers, and the ADC and FA values in 18 white-matter lesions were measured and compared with those of the corresponding contralateral regions. Results: Compared with the corresponding contralateral regions, cortical tubers of TS patients had significantly higher ADC values (P < 0.001); white-matter lesions had significantly higher ADC values (P < 0.001) and significantly lower FA values (P < 0.001). Conclusion: DTI is a useful tool for demonstrating changes in cortical tubers and white-matter lesions resulting from TS. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Tuberous sclerosis; MRI; Diffusion tensor imaging

1. Introduction Tuberous sclerosis (TS) is a heredofamilial neurocutanous syndrome with multisystem involvement that includes the brain, kidney, skin, retina, heart, lung and bone [1]. It is a disorder of cell migration, proliferation, and differentiation with an incidence of 1 in 6000 live births. Results of linkage studies of familial TS cases have demonstrated autosomal dominant inheritance, and two causative genes have been identified: TSC1 on chromosome band 9q34 and TSC2 on chromosome band 16p13.3 [2] and [3]. Clinical manifestations of TS are variable. The typical clinical triad of adenoma sebaceum, seizures, and mental retardation has been refined, revealing the complexity of the disorder. The brain is the most frequently affected organ in TS, which may produce four major types of CNS lesions—cortical tubers, white-matter abnormalities, subependymal nodules and subependymal giant-cell astrocytomas [4]. Conventional MRI is routinely used for detecting major CNS lesions. However, this technique cannot reveal the subtle



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0720-048X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2008.04.017

microstructural characteristics of TS. Diffusion tensor imaging (DTI) provides a quantitative analysis of the magnitude and directionality of water diffusion in three-dimensional space in vivo and reflects microstructural and functional properties of tissue, based on the principle of anisotropic water molecular diffusion [5]. The two main parameters determined by DTI are the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) [6]. ADC can be altered by pathologic processes that modify tissue integrity; FA reflects asymmetry in the motion of the fluid. Motion of the fluid within the brain is normally restricted to movement along the same axis as the axon or myelin sheath. When neurons or myelin sheaths are damaged, the FA decreases because the fluid can move freely along various axes [7]. This technique, which has previously been used to reveal pathological changes in various neurological conditions including Alzheimer’s disease [8], multiple sclerosis [9] and epilepsy [10,11], may detect pathological processes that change microstructural tissue characteristics and water-diffusion properties non-invasively and provide important information for clinical applications [12]. Two previous studies [4,12] described DTI findings in TS patients using small sample sizes. The purpose of this study was to more thoroughly investigate the features of ADC and FA in

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cortical tubers and white-matter lesions in patients with TS using DTI using a larger sample size. 2. Materials and methods 2.1. Clinical material We studied 14 patients (eight male, six female; mean age 15.1 ± 8.7 years, range 6–38 years) with a clinical and radiologic diagnosis of TS. The main clinical manifestations included seizures in 14 patients, mental retardation in thirteen patients, facial, truncal angiofibromas or ungula angiofibromas in 11 patients, hypopigmented macules in 7 patients, shagreen patches in 6 patients, and renal hamartoma (angiomyolipoma) in 4 patients. 2.2. MR scanning Imaging was performed with a 1.5-T MR scanner (Sonata Siemens, Germany). A routine cranial MRI was performed using the following sequences: spin echo, T1weighed sequence (TR/TE 450/15 ms; FOV 230 mm × 208 mm; matrix 256 × 256; section thickness 3 mm); T2-weighted sequence (TR/TE 4000/90 ms; FOV 230 mm × 208 mm; matrix 256 × 256; section thickness 3 mm); FLAIR sequence (TR/TI/TE 8500/180/135 ms; FOV 230 mm × 208 mm; matrix 256 × 256; section thickness 3 mm). DT images were acquired by using a single-shot echo-planar pulse sequence; imaging parameters were: TR: 6100 ms, TE: 106 ms, flip angle 90◦ , acquisition matrix 128 × 128, FOV 230 mm × 230 cm, section thickness 3-mm with no gap, 8 averages. Two b values (0, 1000 s/mm2 ) were applied in 6 non-collinear directions. The total acquisition time for DT images was 435 s. 2.3. Data analysis After image acquisition, the data were transferred to an independent workstation (Leonardo, Siemens) for calculation of the DTI indices. The maps of ADC and FA were generated from the obtained diffusion tensor images using software provided by the manufacturer. MRIcro software (MRIcro, Nottingham University, http:// www.psycholog-y.nottingham.ac.uk/sta./cr1/mricro.html) was used for data analysis. Following diagnosis of the lesions using the FLAIR sequence, corresponding regions of interest (ROIs) were manually drawn within the cortical tubers and white-matter lesions on the b = 0 images by a radiologist with 10 years of experience. Afterwards, the ROIs were automatically transferred to the same regions on the calculated ADC and FA maps using the MRIcro software. ROIs were also placed in the contralateral corresponding normal-appearing regions. Calcified tubers were excluded in the study. Also, DT indices were not measured in tubers smaller than 5 mm in diameter to avoid contamination from adjacent normal-appearing brain parenchyma. We studied 32 cortical tubers and 18 white-matter lesions (Fig. 1). ADC and FA values are presented as means (mm2 /s × 10−4 ) ± standard deviations. The ADC values

Fig. 1. A 17-year-old male patient with TS. (a) Axial FLAIR image shows multiple hyperintense tubers (arrows) and white-matter lesions (arrowheads) scattered in the frontal, temporal and parietal areas on both sides. (b) and (c) ADC and FA images at the same level show placement of the ROIs within a tuber (arrow), white-matter lesion (arrowhead) and contralateral corresponding normal-appearing regions.

C. Piao et al. / European Journal of Radiology 71 (2009) 249–252 Table 1 Comparison of ADC (mm2 /s × 10−4 ) and FA (mean ± S.D.) in the different groups

ADC cortical tuber ADC white-matter lesions FA white-matter lesions

Lesion

Contralateral to the lesion

P-Value

10.47 ± 1.49 10.62 ± 1.35 0.27 ± 0.06

8.89 ± 1.00 9.16 ± 0.93 0.53 ± 0.33

<0.001 <0.001 <0.001

in cortical tubers, and the ADC and FA values in white-matter lesions were assessed and compared with the corresponding regions of the contralateral, normal-appearing sites in the same TS patient. Statistical analysis was performed using Student’s t-test (SPSS 11.5). A P-value less than 0.05 was accepted as significant. 3. Results The measurements of the DT indices of cortical tubers, white-matter lesions and the corresponding, contralateral, normal-appearing regions in the patients with TS are presented in Table 1. As shown in Table 1, the ADC values were significantly higher in cortical tubers, compared with the corresponding contralateral regions (P < 0.001). We also found a statistically significant increase in the ADC (P < 0.001) and a decrease in FA (P < 0.001) in the white-matter lesions, compared with the contralateral white-matter (P < 0.001) in the same patients. 4. Discussion Two earlier studies using diffusion tensor imaging (DWI) showed a significant increase in ADC values in both cortical tubers [13] and white-matter lesions [14] of patients with TS. Similar results were found in our study. Additionally, we found a statistically significant decrease in FA in the white-matter lesions compared with the contralateral white matter in the same patients. Our results strengthen previous reports describing DTI findings in TS patients [4,12]. Compared with these two studies, we were able to apply eight averages in this study, which improved the SNR (signal to noise ratio) greatly. This improvement allowed us to use a thinner section thickness (3 mm) than theirs (4–6 mm). This improvement in the imaging parameters decreased the partial volume effect, resulting in a more accurate quantitative analysis. Increased ADCs may reflect histopathological changes in the brains of patients with TS. Histologically, the normal cortical architecture is disrupted within a tuber and effaced by abnormally oriented dysmorphic neurons, reactive astrocytes and bior multinucleated giant eosinophilic cells, which may exhibit both neuronal and gliotic features. Thus, both the disruption of normal cortical architecture and the presence of atypical cells may contribute to the observed increase in ADC values [12,15]. In the white-matter lesions of TS patients, a pathological study [16] demonstrated that hypomyelination, gliosis, and heterotopic cells were all present. These changes may lead to a loss

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of structural barriers to water motion, resulting in a significant increase in ADC and a decrease in FA values. It should be made clear that an elevated ADC is not specific for tubers and that a decreased FA is not specific for tuberous sclerosis white-matter lesions. Pathological changes in various neurological conditions may lead to a loss of structural barriers to water motion and thus result in significant abnormality in ADC and FA values. Previous studies have investigated the features of DTI in normal-appearing white matter of patients with TS and compared them with healthy controls. Makki et al. [17] reported higher ADC values and lower FA values in normal-appearing white matter of TS patients. These results indicate that many of the disorganized foci are microscopic and, therefore, are not depicted using conventional MRI. Diffusion tensor MR imaging offers increased sensitivity over conventional MR imaging in assessing microstructural malformation or damage in the brain. However, in contrast to the study by Makki et al. [17], Peng et al. [4] found there were no significant differences in either ADC and FA values in the normal-appearing white matter of patients with TS. DT features of normal-appearing white matter were not assessed in the present study, and further evaluation in a larger number of patients will be done. Additionally, a relatively small number of gradient directions was used in this study. Further studies using more gradient directions in a 3T scanner, which may yield more detailed information on such subtle abnormalities, are needed to confirm our findings. 5. Conclusion Using DTI, we found a significant increase in ADC values in both cortical tubers and white-matter lesions compared to the contralateral normal-appearing brain in patients with TS. Also, we obtained a statistically significant decrease in FA in white-matter lesions. Those results are consistent with histopathological findings in TS. Therefore, DTI is a useful tool for demonstrating cortical tubers and white-matter lesion changes resulting from TS. Abnormality in DT indices may provide important information for the clinical assessment and pathophysiology of TS patients. Acknowledgments We thank Drs. Rhoda E. and Edmund F. Perozzi for English editing assistance. References [1] Garaci FG, Floris R, Bozzao A, Manenti G, Simonetti A, Lupattelli T, et al. Increased brain apparent diffusion coefficient in tuberous sclerosis. Radiology 2004;232(2):461–5. [2] Fryer AE, Chalmers AH, Osborne JP. Examining the parents of children with tuberous sclerosis. Lancet 1986;2(8521–8522):1467. [3] Kandt RS, Haines L, Smith M, Northrup H, Gardner RJ, Short MP, et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet 1992;2(1):37–41. [4] Peng SS, Lee WT, Wang YH, Huang KM. Cerebral diffusion tensor images in children with tuberous sclerosis: a preliminary report. Pediatr Radiol 2004;34(5):387–92.

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[5] Pierpaoli C, Jezzard P, Basser PJ, Bamett A, Di Chiro G. Diffusion tensor MR imaging of the human brain. Radiology 1996;201(3):637–48. [6] Masutani Y, Aoki S, Abe O, Hayashi N, Otomo K. MR diffusion tensor imaging: recent advance and new techniques for diffusion tensor visualization. Eur J Radiol 2003;46(1):53–66. [7] Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M. MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 1986;161(2):401–7. [8] Bozzali M, Falini A, Franceschi M, Cercignani M, Zuffi M, Scotti G, et al. White matter damage in Alzheimer disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2002;72(6):742–6. [9] Cassol E, Ranjeva JP, Ibarrola D, M´ekies C, Manelfe C, Clanet M, et al. Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter. Mult Scler 2004;10(2):188–96. [10] Thivard L, Lehericy S, Krainik A, Adam C, Dormont D, Chiras J, et al. Diffusion tensor imaging in medial temporal lobe epilepsy with hippocampal sclerosis. Neuroimage 2005;28(3):682–90. [11] Concha L, Beaulieu C, Wheatley BM, Gross DW. Bilateral white matter diffusion changes persist after epilepsy surgery. Epilepsia 2007;48(5):931–40.

[12] Karadag D, Mentzel HJ, G¨ullmar D, Rating T, L¨obel U, Brandl U, et al. Diffusion tensor imaging in children and adolescents with tuberous sclerosis. Pediatr Radiol 2005;35(10):980–3. [13] Jansen FE, Braun KP, van Nieuwenhuizen O, Huiskamp G, Vincken KL, van Huffelen AC, et al. Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber in patients with tuberous sclerosis. Arch Neurol 2003;60(11):1580–4. [14] Sener RN. Tuberous sclerosis: diffusion MRI findings in the brain. Eur Radiol 2002;12(1):138–43. [15] Mizuguchi M, Takashima S. Neuropathology of tuberous sclerosis. Brain Dev 2001;23(7):508–15. [16] Yagishita A, Arai N. Cortical tubers without other stigmata of tuberous sclerosis: imaging and pathological findings. Neuroradiology 1999;41(6):428–32. [17] Makki MI, Chugani DC, Janisse J, Chuqani HT. Characteristics of Abnormal Diffusivity in normal-appearing white matter investigated with diffusion tensor MR imaging in tuberous cclerosis complex. AJNR Am J Neuroradiol 2007;28(9):1662–7.