Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images

• Published in: The Lancet (British edition) Vol. 358; no. 9277; pp. 201 - 205
• Main Authors: Fox, Nick C, Crum, William R, Scahill, Rachael I, Stevens, John M, Janssen, John C, Rossor, Martin N
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 21-07-2001; Lancet; Elsevier Limited
• Subjects: Algorithms; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Atrophy; Biological and medical sciences; Brain - pathology; Case-Control Studies; Cognitive ability; Disease Progression; Female; Follow-Up Studies; Humans; Investigative techniques, diagnostic techniques (general aspects); Longitudinal studies; Magnetic Resonance Imaging - methods; Male; Medical diagnosis; Medical sciences; Middle Aged; Nervous system; NMR; Nuclear magnetic resonance; Offspring; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Subtraction Technique; Time Factors; Vascular diseases; Human; Nervous system diseases; Compression; Statistical analysis; Radiodiagnosis; Alzheimer disease; Medical screening; Nuclear magnetic resonance imaging; Cerebral disorder; Voxel; Central nervous system disease; Medical imagery; Early; Degenerative disease; Technique; Aggravation
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(01)05408-3

Early diagnosis and monitoring of the progression of Alzheimer's disease is important for the development of therapeutic strategies. To detect the earliest structural brain changes, individuals need to be studied before symptom onset. We used an imaging technique known as voxel-compression mapping to localise progressive atrophy in patients with preclinical Alzheimer's disease
Four symptom-free individuals from families with early-onset Alzheimer's disease with known autosomal dominant mutations underwent serial magnetic resonance imaging (MRI) over 5–8 years. All four became symptomatic during follow-up. 20 individuals with a clinical diagnosis of probable Alzheimer's disease and 20 control participants also underwent serial MR imaging. A non-linear fluid matching algorithm was applied to register repeat scans onto baseline imaging. Jacobian determinants were used to create the voxel-compression maps.
Progressive atrophy was revealed in presymptomatic individuals, with posterior cingulate and neocortical temporoparietal cortical losses, and medial temporal-lobe atrophy. In patients with known Alzheimer's disease, atrophy was widespread apart from in the primary motor and sensory cortices and cerebellum, reflecting the clinical phenomenology.
Voxel-compression maps confirmed early involvement of the medial temporal lobes, but also showed posterior cingulate and temporoparietal cortical losses at presymptomatic stage. This technique could be applied diagnostically and used to monitor the effects of therapeutic intervention.