ADC mapping of neurodegeneration in the brainstem and cerebellum of patients with progressive ataxias Riccardo Della Nave, a Silvia Foresti, a Carlo Tessa, a Marco Moretti, a Andrea Ginestroni, b Cinzia Gavazzi, a Laura Guerrini, a Fabrizio Salvi, c Silvia Piacentini, b and Mario Mascalchi a, * a Radiodiagnostic Section, Department of Clinical Physiopathology, University of Florence, Florence, Italy b Department of Neurology, University of Florence, Florence, Italy c Department of Neurology, University of Bologna at Bellaria Hospital, Bologna, Italy Received 18 September 2003; revised 20 January 2004; accepted 21 January 2004 Available online 2 April 2004 Analysis of the apparent diffusion coefficient (ADC) maps derived from diffusion-weighted MR imaging is emerging as a reproducible, sensitive, and quantitative tool to evaluate brain damage in diseases of the white and gray matter. To explore the potentials of ADC maps analysis in degenerative ataxias, we examined 28 patients and 26 age- matched controls with T1, T2, and diffusion (b values 0 – 1000 along the three main body axes)-weighted MR images. Twenty-four patients had inherited genetically proven diseases including spinocerebellar ataxia type 1 (SCA1) (n = 9), spinocerebellar ataxia type 2 (SCA2) (n = 8), and Friedreich’s ataxia (FA) (n = 7), whereas four patients had sporadic adult onset pure cerebellar ataxia (three idiopathic, one gluten intolerance). Area and linear measurements of the CNS structures contained in the posterior cranial fossa (PCF) preliminary enabled classification of the patients in the three morphological categories reflecting the gross pathology findings, namely olivoponto- cerebellar atrophy (OPCA) (n = 10: six SCA2 and four SCA1), spinal atrophy (SA) (n = 7: all FA), and cortical cerebellar atrophy (CCA) (n = 4: three idiopathic and one gluten intolerance). Seven patients with SCA1 (n = 5) or SCA2 (n = 2) had morphologic changes reminiscent of OPCA, but their values were still in the lower normal range and were classified as undefined. Mean diffusivity (D ¯ ) maps of the entire brain were generated and D ¯ was measured with regions of interest (ROI) in the medulla, pons, middle cerebellar peduncles, and the peridentate white matter. Moreover, after exclusion of the skull with manual segmentation and of the CSF with application of a threshold value, histograms were obtained for D ¯ of the brainstem and cerebellum and for D ¯ of the cerebral hemispheres. As compared to controls, a (P < 0.001) increase of D ¯ was observed in the medulla, middle cerebellar peduncles, and peridentate white matter in OPCA and undefined patients groups who had also significantly increased values of the 25th and 50th percentiles in the brainstem and cerebellum D ¯ histogram. In CCA (P = 0.01), an increase of the 25th and 50th percentile of the D ¯ value was observed in the brainstem and cerebellum histograms. The SA group showed (P < 0.001) an increased D ¯ in the medulla only. A correlation between clinical severity as assessed with the Inherited Ataxias Clinical Rating Scale (IACRS) and the 50th percentile of the D ¯ value in the brainstem and cerebellum histogram (r = 0.69) was observed in patients with SCA1 or SCA2. Diffusion MR imaging reveals variable patterns of increase of D ¯ in the brainstem, cerebellum, and cerebral hemispheres in degenerative ataxias that match the known distribution of the neuropathological changes. D 2004 Elsevier Inc. All rights reserved. Keywords: Mapping; Neurodegeneration; Ataxias Introduction Apparent diffusion coefficient (ADC) maps obtained from proton diffusion-weighted magnetic resonance imaging (MRI) enable a quantitative, sensitive, and reproducible tool to evaluate brain damage in diseases of the white and gray matter (Bozzali et al., 2001; Cercignani et al., 2001, 2003). Degenerative ataxias are a variety of inherited or sporadic diseases sharing the clinical features of progressive gait and coordination disturbances. Three main patterns of distribution of loss of bulk are observed at the neuropathological examination, namely olivopontocerebellar atrophy (OPCA), cortical cerebellar atrophy (CCA), and spinal atrophy (SA) (Lowe et al., 1997). Conventional MRI using morphometric or volume measure- ments and evaluation of signal changes demonstrates these neuropathological patterns in vivo (Burk et al., 1996; Schols et al., 1997; Klockgether et al., 1998; Mascalchi et al., 1994; Ormerod et al., 1994; Savoiardo et al., 1990; Wullner et al., 1993). However, the findings of conventional MRI usually become apparently late in the disease course and show a poor correlation with the clinical disability. We investigated with ADC maps the brainstem and cerebellum in a series of patients with degenerative ataxias with the aims of evaluating whether the diffusion changes match the distribution of neuropathological findings and correlate with the degree of neu- rological deficit. 1053-8119/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2004.01.035 * Corresponding author. Radiodiagnostica, Dipartimento di Fisiopato- logia Clinica, Universita ` di Firenze Viale Morgagni 85, Zip Code 50134, Firenze, Italy. Fax: +39-055-431970. E-mail address: m.mascalchi@dfc.unifi.it (M. Mascalchi). Available online on ScienceDirect (www.sciencedirect.com.) www.elsevier.com/locate/ynimg NeuroImage 22 (2004) 698 – 705