Differentiation of calcified regions and iron deposits in the ageing brain on conventional structural MR images

Abstract

Purpose: In the human brain, minerals such as iron and calcium accumulate increasingly with age. They typically appear hypointense on T2*-weighted MRI sequences. This study aims to explore the differentiation and association between calcified regions and noncalcified iron deposits on clinical brain MRI in elderly, otherwise healthy subjects. Materials and Methods:Mineral deposits were segmented on co-registered T1-and T2*-weighted sequences from 100 1.5 Tesla MRI datasets of community-dwelling individuals in their 70s. To differentiate calcified regions from noncalcified iron deposits we developed a method based on their appearance on T1-weighted images, which was validated with a purpose-designed phantom. Joint T1-and T2*-weighted intensity histograms were constructed to measure the similarity between the calcified and noncalcified iron deposits using a Euclidean distance based metric.Results: We found distinct distributions for calcified regions and noncalcified iron deposits in the cumulative joint T1-and T2*-weighted intensity histograms across all subjects (correlations ranging from 0.02 to 0.86; mean ¼ 0.26 6 0.16; t ¼ 16.93; P < 0.001) consistent with differences in iron and calcium signal in the phantom. The mean volumes of affected tissue per subject for calcified and noncalcified deposits were 236.74 6 309.70 mm 3 and 283.76 6 581.51 mm 3 ; respectively. There was a positive association between the mineral depositions (b ¼ 0.32, P < 0.005), consistent with existing literature reports. Conclusion:Calcified mineral deposits and noncalcified iron deposits can be distinguished from each other by signal intensity changes on conventional 1.5T T1-weighted MRI and are significantly associated in brains of elderly, otherwise healthy subjects.

Brain iron deposits and lifespan cognitive ability

“…We used visual ratings of microbleeds (Cordonnier et al 2007), a validated quantitative approach to assess regional multifocal T2*W hypointensities as a surrogate of the multifocal brain ID load (Glatz et al 2013, 2015; Valdés Hernández et al 2011, 2014), a validated semi-automatic WMH segmentation method (Valdés Hernández et al 2010, 2013b) and measures obtained from comprehensive batteries of cognitive tests, in an attempt to address our main research questions. In addition to the robust assessment of the imaging markers, other strengths of this paper are the analysis of the role that WMH play in the effect that iron deposits have in cognition, explored here for the first time, and the use of several validated measures of cognitive ability in a large cohort of community-dwelling older individuals to explore the association between intelligence and iron deposits in later life.…”

“…Moreover, old micro-/macro-haemorrhages can appear as calcifications on conventional MRI (Bradley 1993; Valdés Hernández et al 2014) and, therefore, were not included in the volume of brain iron deposition. Although there is always an overlap in the intensities that indicate the presence of calcified and non-calcified iron deposits due to the coalescence of both minerals in many regions as a consequence of metabolic processes and the degradation of the non-soluble iron molecules (Haacke et al 2005), the sequence combination of T1W and T2*W (Valdés Hernández et al 2014) and the filter implemented as part of the automatic method that assessed the corpus striatum iron deposits (Glatz et al 2015), ensured that heavily calcified regions were not included.…”

“…Although there is always an overlap in the intensities that indicate the presence of calcified and non-calcified iron deposits due to the coalescence of both minerals in many regions as a consequence of metabolic processes and the degradation of the non-soluble iron molecules (Haacke et al 2005), the sequence combination of T1W and T2*W (Valdés Hernández et al 2014) and the filter implemented as part of the automatic method that assessed the corpus striatum iron deposits (Glatz et al 2015), ensured that heavily calcified regions were not included. This is a difference with the computational method used in Penke et al (2012).…”

“…This is a difference with the computational method used in Penke et al (2012). Although it is known that these calcified regions are strongly and directly associated with the iron deposits assessed (Valdés Hernández et al 2014), it has been proposed that calcification is the latest stage in the iron degradation and accumulation processes with a neuroprotective effect (Casanova and Araque 2003). We would not predict that the inclusion of these old micro-/macro-haemorrhages would have changed the associations found between iron deposition and cognitive abilities at old age, but it may be possible that the role of early life general cognitive ability in the vascular degeneration that occurs at old age, represented by the presence of brain iron deposits, may have been underestimated.…”

“…For extracting and quantifying the brain volume occupied by iron deposits, we used the pre-processing pipeline described in Glatz et al (2012, 2015) and applied computational methods that use T1W and T2*W MRI sequences to ensure that we only include non-calcified regions rich in methemoglobin, hemosiderin and/or ferritin (Valdés Hernández et al 2012, 2014; Vymazal et al 1999). …”