Age-related microstructural and physiological changes in normal brain measured by MRI γ-metrics derived from anomalous diffusion signal representation.

Nowadays, increasing longevity associated with declining cerebral nervous system functions, suggests the need for continued development of new imaging contrast mechanisms to support the differential diagnosis of age-related decline. In our previous papers, we developed a new imaging contrast metrics derived from anomalous diffusion signal representation and obtained from diffusion-weighted (DW) data collected by varying diffusion gradient strengths. Recently, we highlighted that the new metrics, named γ-metrics, depended on the local inhomogeneity due to differences in magnetic susceptibility between tissues and diffusion compartments in young healthy subjects, thus providing information about myelin orientation and iron content within cerebral regions. The major structural modifications occurring in brain aging are myelinated fibers damage in nerve fibers and iron accumulation in gray matter nuclei. Therefore, we investigated the potential of γ-metrics in relation to other conventional diffusion metrics such as DTI, DKI and NODDI in detecting age-related structural changes in white matter (WM) and subcortical gray matter (scGM). DW-images were acquired in 32 healthy subjects, adults and elderly (age range 20-77 years) using 3.0T and 12 b-values up to 5000 s/mm2. Association between diffusion metrics and subjects' age was assessed using linear regression. A decline in mean γ (Mγ) in the scGM and a complementary increase in radial γ (γ⊥) in frontal WM, genu of corpus callosum and anterior corona radiata with advancing age were found. We suggested that the increase in γ⊥ might reflect declined myelin density, and Mγ decrease might mirror iron accumulation. An increase in D// and a decrease in the orientation dispersion index (ODI) were associated with axonal loss in the pyramidal tracts, while their inverted trends within the thalamus were thought to be linked to reduced architectural complexity of nerve fibers. γ-metrics together with conventional diffusion-metrics can more comprehensively characterize the complex mechanisms underlining age-related changes than conventional diffusion techniques alone.

Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease.

BACKGROUND: Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer's disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI). METHODS: Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD. RESULTS: Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD. CONCLUSIONS: This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.

Functional Anatomy of the Thalamus as a Model of Integrated Structural and Functional Connectivity of the Human Brain In Vivo.

While methods of measuring non-invasively both, functional and structural brain connectivity are available, the degree of overlap between them is still unknown. In this paper this issue is addressed by investigating the connectivity pattern of a brain structure with many, well characterized structural connections, namely the thalamus. Diffusion-weighted and resting state (RS) functional MRI (fMRI) data were collected in a group of 38 healthy participants. Probabilistic tractography was performed to parcellate the thalamus into regions structurally connected to different cortical areas. The resulting regions were used as seeds for seed-based analysis of RS fMRI data. The tractographic parcellation was thus cross-validated against functional connectivity data by evaluating the overlap between the functional and structural thalamo-cortical connections originating from the parcellated regions. Our data show only a partial overall correspondence between structural and functional connections, in the same group of healthy individuals, thus suggesting that the two approaches provide complementary and not overlapping information. Future studies are warranted to extend the results we obtained in the thalamus to other structures, and to confirm that the mechanisms behind functional connectivity are more complex than just expressing structural connectivity.

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct.

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns.