Книги по МРТ КТ на английском языке / MR Imaging in White Matter Diseases of the Brain and Spinal Cord - K Sartor Massimo Filippi Nicola De Stefano Vincent Dou

26.2.2.2 Non-conventional MR

Presently, no study addressed possible diffusion or MT ratio changes in FTD.

26.2.2.2.1 1H-MRS

In a relatively large study comparing the MRS findings in the frontal and temporo-parietal cortical gray matter of two groups of patients with FTD and AD and a control group, Ernst et al. (1997) observed a significant reduction of NAA and increase of mI concentrations in the frontal lobe of patients with FTD but not of patients with AD. A distinct increase of lactate was seen in the frontal lobe of three out of 14 FTD patients. Using MRS data alone, 92% of the FTD patients were correctly differentiated from AD patients and control subjects.

b

Fig. 26.2a,b. Fronto-temporal dementia. Axial proton density (a) and T2 weighted (b) images show asymmetric atrophy of the frontal lobes which is accompanied by diffuse hyperintensity of the subcortical white matter more evident in proton density image (arrowhead) in a patient with sporadic FTD

26.3

Degenerative Ataxias

Degenerative ataxias are a variety of inherited or sporadic diseases sharing the clinical features of progressive gait and coordination disturbances. In the last decade many of the genetic abnormalities underlying inherited ataxias were discovered and molecular screening tests are now available (Subramony and Filla 2001) with improved diagnostic accuracy and better genotype/phenotype correlation. The neuro-

pathological examination shows three main patterns of distribution of loss of bulk and neurodegeneration, namely olivopontocerebellar atrophy (OPCA), spinal atrophy (SA) and cortical cerebellar atrophy (CCA) (Lowe et al. 1997). Each pattern is observed in either sporadic and genetically defined disease. Olivopontocerebellar degeneration is a neuropathological process characterized by neuronal loss, gliosis, wallerian degeneration and ultimately atrophy of the inferior olives, pons, middle cerebellar peduncles and cerebellum. Myelin stains demonstrates diffuse white matter damage in the brainstem and cerebellum with sparing of the corticospinal tracts and of the superior cerebellar peduncles. In SA the pathological hallmark is neuronal loss and shrinkage in the Clarke column of the spinal cord and in the spinal ganglion cells with macroscopic degeneration of the spinocerebellar and gracilis and cuneatus tracts of the spinal cord which is better appreciated on myelin stains. Secondary neuronal loss in the brainstem predominantly involves the accessory cuneate and gracile nuclei of the medulla. The cerebellar cortex is spared but there is cell loss in the dentate nuclei. In CCA, diffuse loss of Purkinje cells in the ganglial layer of the cerebellar cortex is the main pathological finding with secondary loss of cells in the inferior olives. White matter is macroscopically spared.

26.3.1 Conventional MR

The features of OPCA on conventional MRI were defined using subjective evaluation of morphology and signal intensity of the brainstem and cerebellum (Savoiardo et al. 1990; Ormerod et al. 1994). In particular, Savoiardo et al. (1990) reported in sporadic and inherited OPCA characteristic thinning of the ventral pons and diffusely increased signal intensity of the brainstem, middle cerebellar peduncles and cerebellar white matter in proton density weighted images with sparing of the corticospinal tracts and of the superior cerebellar peduncles (Fig. 26.3). The signal changes are far less apparent in T2 weighted images (Fig. 26.3). They were observed in advanced but not in early cases of SCA1 and SCA2 (Mascalchi et al. 1998; Giuffrida et al. 1999) and were not reported in other studies of patients with inherited or sporadic OPCA (Wullner et al. 1993; Ormerod et al. 1994), conceivably also reflecting the subjectivity of the visual evaluation.

Conventional MRI using manual or semiautomatic measurements of the morphology or volume

of the cerebellum, brainstem and cervical spinal cord demonstrates the three neuropathological patterns in vivo (Wullner et al. 1993; Mascalchi et al. 1994; Burk et al.1996; Klockgether et al.1998).In particular, using an array of area and linear measurements, Wullner et al. (1993) defined the morphometric criteria for an in vivo diagnosis of OPCA, SA and CCA based on the distribution of atrophy. Recently the technique of VBM was applied to the evaluation of the distribution and severity of the atrophic changes in a genetically determined variant of OPCA, namely spinocerebellar ataxia type 2 (Brenneis et al. 2003). Significant white matter loss in the cerebellar hemispheres, pons, and midbrain was accompanied with supratentorial cortical and subcortical grey matter atrophy.

MRI studies in patients with SA pointed out marked atrophy of the spinal cord and medulla (Wullner et al. 1993) which in FA are combined to symmetric signal changes of the posterior and lateral columns of the cervical spinal cord on T2 or T2* weighted images (Mascalchi et al. 1994) (Fig. 26.4). This feature is not specific and can be observed in other conditions including combined sclerosis due to vitamin B12 deficiency. At variance with OPCA and CCA, atrophy of the brainstem and cerebellum is not remarkable in SA (Wullner et al. 1993).

In CCA conventional MRI shows atrophy of the cerebellar vermis and hemisphere with normal brainstem volume and no signal changes (Wullner et al. 1993).

MR imaging based morphometry measurements or subjective evaluation of brainstem and cerebellar atrophy were analyzed with respect to disease duration in two studies (Burk et al. 1996; Giuffrida et al. 1999) and no correlation was found in either SCA1 or SCA2. In a recent study using voxel based morphometry, Brenneis et al. (2003) found a correlation between atrophy of the cerebellar hemispheres and severity of cerebellar symptoms in nine patients with SCA2.

26.3.2 Non-conventional MR

26.3.2.1 1H-MRS

MRS studies in patients with degenerative ataxias included relatively small numbers of patients (Davie et al. 1995; Mascalchi et al. 1998, 2002; Boesch et al. 2001). They consistently reported

a decrease of the concentration of NAA or of the NAA/Cr ratio in the deep cerebellum and pons of patients with sporadic or inherited OPCA, SA, and CCA. A reduction of Cho/Cr ratio in the same sites was observed in OPCA patients only (Mascalchi et al. 1998, 2002). Lactate peaks were occasionally observed in OPCA patients (Boesch et al. 2001; Mascalchi et al. 2002). In OPCA a correlation with the severity of the clinical deficit was observed for the reduction of the NAA/Cr ratio in the pons but not for the atrophy measurements (Mascalchi et al. 2002).

26.3.2.2 MTI

To date, no study with MT has focused on patients with degenerative ataxia.

26.3.2.3 Di usion MR

D maps of the brainstem and cerebellum were obtained 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 neurological deficit (Della Nave et al. 2004).

The patients were representative of the different types of degenerative ataxias and were classified based on the MRI morphometry data in OPCA, SA, and CCA. The inclusion of patients with genetically proven spinocerebellar ataxia type 1 and 2 (SCA1 and SCA2) but without overt brainstem and cerebellar atrophy gave the opportunity to evaluate the pathological process leading to OPCA in a relatively early phase. Region-of-interest analysis showed a significant increase of D in the middle cerebellar peduncles, medulla, pons, and peridentate white matter of our patients with OPCA due to SCA1 and SCA2. Interestingly, similar findings were observed in patients with SCA1 and SCA2 without overt atrophy changes. Histogram analysis confirmed differences between SCA1 or SCA2 patients (OPCA or undefined) and controls for the 25th and 50th percentiles of the brainstem and cerebellum D (Fig. 26.3). However, only in SCA1 and SCA2 patients with OPCA, the brainstem and cerebellar D were combined with increase of the cerebral D. This result is consistent with the development of supratentorial changes in the advanced phases of OPCA (Klockgether et al. 1998; Giuffrida et al. 1999).Although the exact pathological correlate of increase of the D in the brainstem and the cerebellum cannot be established, it presumably reflects the wallerian degeneration of the white matter observed in OPCA. More speculative is the signifi-

cance of the mild changes in the supratentorial compartment. The region-of-interest analysis of D in our SA patients matched the above changes showing a significant increase in the medulla only. In agreement with the substantial paucity of the brainstem and cerebellar changes in SA, the histogram and volume analysis failed to show significant changes in the infratentorial compartment. The diffuse mild increase of the brainstem and cerebellar D, possibly reflecting a microscopic damage of the cerebellar brainstem tracts and the normal cerebral D, are consistent with the neuropathological description of CCA.

In the relatively large group of patients with olivopontocerebellar degeneration due to SCA1 and SCA2, i.e., including patients with OPCA and undefined morphological pattern, we observed a correlation between the median value of the brainstem and cerebellum D histogram and with an index of brainstem and cerebellar atrophy.

26.4

Motor Neuron Disease

This is a neurodegenerative condition characterized by dysfunction and loss of upper and lower motor neurons that are variably combined producing a spectrum of clinical syndromes from primary lateral sclerosis (PLS), in which a selective damage of the upper motor neuron occurs, to progressive spinal muscular atrophy, in which the damage is restricted to the spinal cord motor neurons (Chan et al. 1999). More frequently, the clinical signs of upper and lower motor neurons are observed altogether in the patient at a certain point in the disease course and this condition is termed amyotrophic lateral sclerosis (ALS).

Upper motor neuron damage implies a wallerian degeneration of the corticospinal tracts which can be tracked from the precentral gyrus to the lateral and anterior columns of the spinal cord (Lowe et al. 1997).

26.4.1 Conventional MR

Proton density and T2 weighted images show abnormally increased signal of the corticospinal tracts in the brains of patients with ALS and PLS (Goodin et al. 1988; Marti-Fabregas et al. 1990). The signal changes in the spinal cord are better demonstrated

using axial T2* weighted gradient echo images in the cervical spine (Mascalchi et al. 1995).

The advent in the clinical protocols of turbo spinecho (TSE) sequences and in particular the FLAIR TSE in which the normal parieto-pontine tract appears relatively hyperintense to the surrounding white matter, especially at the level of the internal capsule and cerebral peduncles, required redefinition of the diagnostic value of this feature. Hecht et al. (2001) reported that the hyperintensity of the corticospinal tracts in FLAIR images is distinctly abnormal when observed in the subcortical precentral gyrus, the centrum semiovale, the crus cerebri, the pons, and medulla oblongata (Fig. 26.5). Moreover, quantitative studies demonstrated that even in the internal capsule the pyramidal tract signal in FLAIR images is higher in patients with ALS and PLS as compared to healthy controls. Zhang et al. (2003) reported a sensitivity of 56% and specificity of 94% of hyperintensity of the subcortical white matter on FLAIR images for the diagnosis of ALS. The same study reported a 74% sensitivity and 67% specificity for evidence of a dark line along the posterior rim of the precentral gyrus which is assumed to reflect a T2 shortening effect due to excessive iron deposition, fibrillary gliosis, and macrophage infiltration.Follow-up examinations demonstrated that both corticospinal tract hyperintensity and the cortical rim hypointensity were unchanged (Hecht et al. 2001; Zhang et al. 2003).

26.4.2 Non-conventional MR

26.4.2.1 1H-MRS

1H-MRS studies in patients with motor neuron disease predominantly employed single voxels located in the motor cortex and subcortical white matter (Kalra et al. 1998; Chan et al. 1999; Bowen et al. 2000; Sarchielli et al. 2001). Using a semiquantitative approach and a long TE acquisition, Chan et al. (1999) found that the NAA/Cr ratio in the precentral region enabled separation of patients with ALS and PLS from healthy controls and that the spectroscopic were more sensitive than the conventional MR imaging findings (Fig. 26.5). A correlation between the decrease of the NAA concentration in the precentral region and the severity of the neurological deficit was reported in two studies (Bowen et al. 2000; Sarchielli et al. 2001). Similar 1H-MRS findings were observed when the

volume of interest was placed in the brainstem pontomedullary region and medulla (Cwik et al. 1998; Pioro et al. 1999). With employment of short TE techniques some additional features of the 1H- MRS changes of upper motor neuron dysfunction were recognized. Thus, an increase of Gln+Glu/Cr ratio was observed in the medulla, suggesting a role for Glu excitotoxicity in the ALS pathogenesis (Pioro et al. 1999), and increase of the concentration of the Cho and myo-inositol was reported in the precentral region (Bowen et al. 2000). In a longitudinal MRS imaging study a progressive decrease of the NAA, Cr and Cho concentrations were observed in the motor region, but not in nonmotor regions (Suhy et al. 2002).

Kalra et al. (1998, 2003) evaluated with a volume of interest placed in the precentral region the response of treatment with new drugs in patients with upper motor neuron disease and documented a positive response to riluzole whereas gabapentin had no effect on the decline of the NAA/Cr ratio.

26.4.2.2 MTI

decreased in the corticospinal tract in patients with ALS before clinical onset of signs of upper motor neuron deficit (Sach et al. 2004), thus contributing to earlier diagnosis of MND.

26.5 Conclusions

Conventional MR imaging can show macroscopic white matter signal changes in degenerative diseases of the CNS which are a useful diagnostic tool for FTD, OPCA, SA, and PLS/ALS.

Non-conventional MR, including DTI, MT and 1H-MRS, demonstrates abnormalities of the white matter in almost every degenerative disease of the CNS. These white matter changes are variably correlated to the severity of the clinical deficit and are currently evaluated as markers of disease progression and possible surrogate markers in pharmacological trials.

Kato et al. (1997) reported a significant decrease of the MT ratio in the posterior limb of the internal capsule of patients with upper motor neuron dysfunction. The MT change was present also in patients without signal changes on conventional MR imaging.

26.4.2.3 Di usion MR

The strong diffusion anisotropy of the normal corticospinal fibers and the occurrence of anterograde degeneration in cases of MND and PLS justified investigation of the potential of diffusion MR imaging for the diagnosis of motor neuron disease. In a diffusion tensor MR imaging study including patients with clinically definite, probable and possible ALS, Ellis et al. (1999) observed a significant increase in the mean diffusivity and decrease of the fractional anisotropy along the corticospinal tracts. The mean diffusivity correlated with the disease duration, whereas the fractional anisotropy correlated with measures of disease severity. In a recent diffusion tensor MR imaging study Ulug et al. (2004) observed an increase of the mean diffusivity of the internal capsules in patients with primary lateral sclerosis which was highly correlated with a decrease of fractional anisotropy. Finally, fractional anisotropy was

References

Adachi M, Hosoya T, Yamaguchi K et al (2000) Diffusionand T2 weighted MRI of the transverse pontine fibers in spinocerebellar degeneration. Neuroradiology 42:803-809

Adams RD, Victor M (1985) Degenerative diseases of the nervous system. In: Adams RD, Victor M (eds) Principles of neurology, 3rd edn. McGraw Hill, New York, pp 859-901

Ashburner J, Friston KJ (2000) Voxel-based morphometry

– the methods. Neuroimage 11:805-821

Baron JC, Chetelat G, Desgranges B et al (2001) In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer’s disease. Neuroimage 14:298-309

Boesch SM, Schoecke M, Burk K et al (2001) Proton magnetic resonance spectroscopic imaging reveals differences in spinocerebellar ataxia types 2 and 6. J Magn Reson Imaging 13:553-559

Bozzali M, Franceschi M, Falini A et al (2001) Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI. Neurology 57:1135-1137

Bozzali M, Falini A, Franceschi M et al (2002) White matter damage in Alzheimer’s disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry 72:742-746

Bozzao A, Floris R, Baviera ME et al (2001) Diffusion and perfusion MR imaging in cases of Alzheimer’s disease: correlations with cortical atrophy and lesion load. AJNR Am J Neuroradiol 22:1030-1036

Bowen BC, Pattany PM, Bradley WG et al (2000) MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis. AJNR Am J Neuroradiol 21:647-658

Brenneis C, Bosch SM, Schocke M et al (2003) Atrophy pattern

in SCA2 determined by voxel-based morphometry. Neuroreport 14:1799-1802

Brun A, Englund E (1986) A white matter disorder in dementia of the Alzheimer’s type. Ann Neurol 19:253-262

Burk K, Abele M, Fetter M et al (1996) Autosomal dominant cerebellar ataxia type I. Clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain 119:1497-1505

Catani M, Mecocci P, Tarducci R et al (2000) Proton magnetic resonance spectroscopy reveals similar white matter biochemical changes in patients with chronic hypertension and early Alzheimer’s disease. J Am Geriatr Soc 50:17071710

Cercignani M, Iannucci G, Rocca MA et al (2000) Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI. Neurology 54:1139-1144

Cercignani M, Bammer R, Soriani MP et al (2003) Intersequence and inter-imaging unit variability of diffusiontensor MR imaging histogram-derived metrics of the brain in healthy volunteers. AJNR Am J Neuroradiol 24:638-643

Chan S, Shungu DC, Douglas-Akinwande A et al (1999) Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain. Radiology 212:763-769

Chan D, Fox NC, Jenkins R et al (2001) Rates of global and regional cerebral atrophy in AD and frontotemporal dementia. Neurology 57:1756-1763

Chantal S, Labelle M, Bouchard RW et al (2002) Correlation of regional proton magnetic resonance spectroscopic metabolic changes with cognitive deficits in mild Alzheimer’s disease. Arch Neurol 59:955-962

Chun T, Filippi CG, Zimmerman RD et al (2000) Diffusion changes in the aging human brain; AJNR Am J Neuroradiol 21:1078-1083

Cwik VA, Hanstock CC, Allen PS et al (1998) Estimation of brainstem neuronal loss in amyotrophic lateral sclerosis with in vivo proton magnetic resonance spectroscopy. Neurology 50:72-77

Davie CA, Barker GJ, Webb S et al (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axonal loss. Brain 118:15831592

De Leeuw FE, Barkhof F, Scheltens P (2004) White matter lesions and hippocampal atrophy in Alzheimer’s disease. Neurology 62:310-312

Della Nave R, Foresti S, Tessa C et al (2004) ADC mapping of neurodegeneration in the brainstem and cerebellum of patients with progressive ataxias. NeuroImage (in press)

Dixon RM, Bradley KM, Budge MM et al (2002) Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer’s disease. Brain 125:23322341

Dong Q, Welsh RC, Chevenert TL et al (2004) Clinical applications of diffusion tensor imaging. J Magn Reson Imaging 19:6-18

Ellis CM, Simmons A, Jones DK et al (1999) Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology 53:1051-1058

Ernst T, Chang L, Melchor R (1997) Frontotemporal dementia and early Alzhiemer’s disease: differentiation with frontal lobe H1 MR spectroscopy. Radiology 203:829-836

Fazekas F, Chawluk JB, Alavi A et al (1987) MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJNR Am J Neuroradiol 8:421-426

Frisoni GB, Testa C, Zorzan A et al (2002) Detection of grey matter loss in mild Alzheimer’s disease with voxel based morphometry. J Neurol Neurosurg Psychiatry 73:657-664

Giuffrida S, Saponara R, Restivo DA et al (1999) Supratentorial atrophy in spinocerebellar ataxia type 2: MRI study of patients. J Neurol 246:383-388

Goodin DS, Rowley HA, Olney RK (1988) Magnetic resonance imaging in amyotrophic lateral sclerosis. Ann Neurol 23:418-420

Hanyu H,Sakurai H,Iwamoto T et al (1998) Diffusion-weighted MR imaging of the hippocampus and temporal lobe white matter in Alzheimer’s disease. J Neurol Sci 156:195-200

Hanyu H, Asano T, Sakurai H et al (1999) Diffusion-weighted and magnetization transfer imaging of the corpus callosum in Alzheimer’s disease. J Neurol Sci 167:37-44

Hecht MJ, Fellner F, Fellner C et al (2001) MRI-FLAIR images of the head show corticospinal tract alterations in ALS patients more frequently than T2, T1and proton densityweighted images. J Neurol Sci 186:37-44

Hecht MJ, Fellner F, Fellner C et al (2002) Hyperintense and hypointense MRI signals of the precentral gyrus and corticospinal tract in ALS: a follow-up examination including FLAIR images. J Neurol Sci 199:59-65

Jack CR, Dickson DW, Parisi JE et al (2002) Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology 58:750-757

Jessen F, Block W, Traber F et al (2001) Decrease of N-acety- laspartate in the MTL correlates with cognitive decline of AD patients. Neurology 57:930-932

Kalra S, Cashman NR, Genge A et al (1998) Recovery of N- acetylasparetate in corticomotor neurons of patients with ALS after riluzole therapy. Neuroreport 9:1757-1761

Kalra S, Cashman NR, Caramanos et al (2003) Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. AJNR Am J Neuroradiol 24:476-480

Kantarci K, Reynolds G, Petersen RC et al (2003) Proton MR spectroscopy in mild cognitive impairment and Alzheimer’s disease: comparison of 1.5 and 3 T. AJNR Am J Neuroradiol 24:843-849

Karas GB, Burton EJ, Rombouts SARB et al (2003) A comprehensive study of gray matter loss in patients with Alzheimer’s disease using optimized voxel-based morphometry. Neuroimage 18:895-907

Kato Y, Matsumura K, Kinosada Y et al (1997) Detection of pyramidal tract lesions in amyotrophic lateral sclerosis with magnetization-transfer measurements. AJNR Am J Neuroradiol 18:1541-1547

Klockgether T, Skalej M, Wedekind D et al (1998) Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3. Brain 121:1678-1693

Kril JJ, Patel S, Harding AJ et al (2002) Patients with vascular dementia due to microvascular pathology have significant hippocampal neuronal loss. J Neurol Neurosurg Psychiatry 72:747-751

Krishnan KRR, Charles HC, Doraiswamy PM et al (2003) Randomized, placebo-controlled trial of the effects of Donezepil on neuronal markers and hippocampal volumes in Alzheimer’s disease. Am J Psychiatry 160:2003-2011

Lowe J (1998) Establishing a pathological diagnosis in degenerative dementias. Brain Pathol 8:403-406

Lowe J, Lennox G, Leigh PN (1997) Disorders of movement

388

and system degeneration. In: Graham DL, Lantos PL (eds) Greenfield’s neuropathology, 6th edn, vol 2. Arnold, London, pp 281-366

Marti-Fabregas J, Pujol J (1990) Selective involvement of the pyramidal tract on magnetic resonance imaging in primary lateral sclerosis. Neurology 40:1799-1800

Mascalchi M, Salvi F, Piacentini S et al (1994) Friedreich ‘s ataxia: MR findings involving the cervical portion of the spinal cord. AJR 163: 187-191

Mascalchi M, Salvi F, Valzania F et al (1995) Cortico-spinal tract degeneration in motor neuron disease: report of two cases. AJNR Am J Neuroradiol 16:878-880

Mascalchi M, Tosetti M, Plasmati R et al (1998) Proton magnetic resonance spectroscopy in an Italian family with spinocerebellar ataxia type 1. Ann Neurol 43:244-252

Mascalchi M Cosottini M, Lolli F et al (2002) MR spectroscopy of the cerebellum and pons in patients with degenerative ataxia. Radiology 223:371-378

McGowan FC, Filippi M, Campi A (1998) Magnetization transfer imaging: theory and application to multiple sclerosis. J Neurol Neurosurg Psychiatry 64 [Suppl]:23-32

PioroEP,MajorsAW,MitsumotoHetal(1999)1H-MRSevidence of neurodegeneration and excess glutamate+glutamine in ALS medulla. Neurology 53:71-79

Ormerod IEC, Harding AE, Miller DH et al (1994) Magnetic resonance imaging in ataxic disorders. J Neurol Neurosurg Psychiatry 57:51-57

O’Sullivan M, Jones DK, Summers PE et al (2001) Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 57:632-638

Rapaport SI (2002) Hydrogen magnetic resonance spectroscopy in Alzheimer’s disease. Lancet Neurol 1:82

Rose SE, Chen F, Chalk JB et al (2000) Loss of connectivity in Alzheimer’s disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. J Neurol Neurosurg Psychiatry 69:528-530

Rusinek H, de Santi S, Frid D et al (2003) Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Radiology 229:691-696 Sach M, Winkler G, Glauche V et al (2004) Diffusion tensor MRI of early upper motor neuron involvement in amyo-

trophic lateral sclerosis. Brain 127:340-350

Sarchielli P, Pelliccioli GP, Tarducci R et al (2001) Magnetic resonance imaging and 1H magnetic resonance spectroscopy in amyotrophic lateral sclerosis. Neuroradiology 43:189-197

Savoiardo M, Grisoli M (2001) Imaging dementias. Eur Radiol 11:484-492

M. Mascalchi

Savoiardo M, Strada L, Girotti F et al (1990) Olivopontocerebellar atrophy: MR diagnosis and relationship to multisystem atrophy. Radiology 174:693-696

Schaefer PW,Grant PE,Gonzalez RG (2000) Diffusion-weighted MR imaging of the brain. Radiology 217:331-345

Scheltens P, Barkof F, Algra J et al (1990) White matter hypeintensities on magnetic resonance in Alzheimer’s disease and normal aging. Neurobiol Aging 11:263-264

Schuff N, Capizzano AA, Du AT et al (2002) Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD. Neurology 58:928-935

Shonk TK, Moats RA, Gifford P et al (1995) Probable Alzheimer’s disease: diagnosis with proton MR spectroscopy. Radiology 195:65-72

Sjobeck M, Haglund M, Persson A et al (2003) Brain tissue microarrays in dementia research: white matter microvascular pathology in Alzheimer’s disease. Histopathology 23:290-295

Subramony SH, Filla A (2001) Autosomal dominant spinocerebellar ataxia ad infinitum? Neurology 56:287-289

Suhy J, Miller RG, Rule R et al (2002) Early detection and longitudinal changes in amyotrophic lateral sclerosis by 1H MRSI. Neurology 58:773-779

The Lund and Manchester Groups (1994) Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 57:416-418

Ulug AM, Grunewald T, Lin MT et al (2004) Diffusion tensor imaging in the diagnosis of primary lateral sclerosis. J Magn Reson Imaging 19:34-39

Van Buchem MA (1999) Magnetization transfer: applications in neuroradiology. J Comput Assist Tomogr 23 [Suppl 1]: S9-S18

Van der Flier WM,van den Heuvel DMJ,Weverling-Rijnsburger AWE et al (2002) Cognitive decline in AD and mild cognitive impairment is associated with global brain damage. Neurology 59:874-879

Waldman AD, Rai GS (2003) The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer’s disease and vascular dementia: a proton magnetic resonance spectroscopy study. Neuroradiology 45:507-512

Wullner U, Klockgether T, Petersen D (1993) Magnetic resonance imaging in hereditary and idiopathic ataxia. Neurology 43:318-326

Zhang L, Ulug AM, Zimmerman RD et al (2003) The diagnostic utility of FLAIR imaging in clinically verified amyotrophic lateral sclerosis. J Magn Reson Imaging 17:521527