MRI and SPECT neuroimaging in mild cognitive impairment and Alzheimer's disease

Abstract

This thesis concerns measurements of regional brain volumes using Magnetic Resonance Imaging (MRI) and of regional cerebral blood flow (CBF) using Single Photon Emission Computed Tomography (SPECT) in patients investigated for suspected dementia. In the first study (I), visually rated MRI-, SPECT and EEG-pathology were compared between patients with Alzheimer's disease (AD) and patients with Frontal Lobe Dementia (FLD). Patients with AD had predominantly parietal lobe atrophy and blood flow reduction whereas patients with FLD had a more pronounced frontal lobe hypoperfusion without a corresponding atrophy. A measure of the difference between frontal and parietal hypoperfusion gave the best separation between AD and FLD patients. This indicates that hypoperfusion preceeds atrophy in FLD and consequently that SPECT imaging of CBF is a better method than MRI to support the clinical separation of AD and FLD.

In the second study (II), a method for quantitative measurements of regional brain volumes from 3-dimensionally reconstructed MRI was implemented and evaluated. The accuracy of the method was +1.5% and the intra-operator error in repeated scanning was less than 5% for all tissues and regions studied. In the third study (III), we evaluated a methodology for MRI-guided SPECT measurements of CBF based on computer software that supported manual alignment of MRI and SPECT image sets. The accuracy and reliability of the method allowed the detection of both atrophy and hypoperfusion of the medial temporal lobes in patients with AD. In study IV, the previously evaluated methods were used to investigate brain atrophy and hypoperfusion in patients with familial AD caused by the Swedish APP mutation. The results showed that a reduction of lateral temporal CBF, preceeding atrophy, was related to the early stage of AD in this family.

In study V, automatic co-registration of MRI and SPECT brain image sets using the uniformity index method was found to have high accuracy. Changes of medial temporal and temporo-parietal regions were evaluated in patients with mild cognitive impairment (MCI) and AD. AD patients had atrophy and CBF reduction of both regions, although the most significant change was found in the CBF of the temporo-parietal region. MCI patients showed a significant reduction only of CBF in the temporo-parietal region.

To summarize, these studies show that combined analysis of MRI and SPECT based on automatic co-registration has high accuracy and reliability. The results also indicate that reduction of CBF preceeds atrophy, both in FLD and AD. In FLD, changes are largly confined to the frontal lobes and in AD the earliest changes seem to be in the temporo-parietal and not in the medial temporal regions. Future longitudinal studies have the possibility to examine if this method for combined MRI and SPECT imaging of the brain can have predictive value regarding progression of cognitive decline and development of AD in patients with MCI.