This study was investigated how brain atrophy affects the SBR by relying on the Monte Carlo simulation method. Different degrees of brain atrophy severity were modeled by morphological operation to vary the volumes of brain parenchyma and cerebral ventricles. Using this method, it was possible to determine the volume of the brain in detail. By knowing the volume of the brain, we succeeded in investigating the relationship between brain atrophy and SBR.
The striatal VOI mean binding count was significantly correlated with the volume of the BAM background regions (Table 2 and Fig. 3). Specifically, this measured value decreased as the volume of the brain parenchyma regions decreased due to brain atrophy. Similarly, the reference VOI mean binding count showed a significant correlation with the brain parenchyma regions (Table 2 and Fig. 4). As the volume of the brain parenchyma regions decreased, the counts of the reference VOI decreased. These phenomena are usually attributed to the relative increase in cerebral sulci and ventricles regions volume in each VOI due to brain atrophy. To minimize the influence of the partial volume effect, the large striatal VOI is used for calculation of SBR in the Bolt method. Therefore, in the case with brain atrophy, it is possible that regions where [123I ]FP-CIT dose not accumulate such as cerebral sulci and ventricles is included within striatal VOI. It is considered that such contamination of regions where [123I ]FP-CIT does not accumulate cause decreased counts in striatal VOI.
The reference VOI was more strongly affected by brain atrophy as compared to the striatal VOI. It could be explained with Bolt’s analysis procedure . First, when setting the reference VOI, smoothing processing is performed three times within the reference regions and therefore excluding the striatal VOI. In addition, 50% of the highest count of the reference VOI is set as a threshold value. Finally, the area 20 mm inwards from the margins is set as the reference VOI. The advantage of this method is that it takes into account the partial volume effect by excluding the marginal areas of the brain. Therefore, in case of brain atrophy, the affected areas such as cerebral sulci could be excluded. However, the central part of the brain has different consequences. The volumes of the central sulcus and Sylvian fissure also change in brain atrophy. Even if the marginal areas of the brain were excluded, many of these non-integrated areas were not. Consequently, the reference VOI was more strongly affected than the striatal VOI.
The change in the SBR value could be explained from the SBR calculation formula. In the SBR computation, the striatal VOI (VsVOI) volume and the striatum (Vs) volume were kept constant across simulations. VsVOI and Vs were 283.12 cm3 and 22.4 cm3. Therefore, the VsVOI and Vs do not affect the SBR analysis. As a result, only the counts of the striatal VOI total counts (Cstotal) and the mean counts per volume in the reference VOI (Cr) affected the output value in formula 1. That is, the ratio Cstotal/Cr became the crucial parameter for the SBR calculation. From Table 2, the percent change in the reference VOI was larger than the one in the striatal VOI. Therefore, the SBR likely reflects the change of Cr, being inversely related to Cr. Consequently, the SBR was overestimated in the model of cerebral atrophy in which the value of Cr more decreased.
As evident from Table 3 and Fig. 5, the SBR calculated using the Bolt’s approach showed a significant negative correlation with brain atrophy. In other words, the SBR was overestimated as the brain parenchyma volume decreased as a consequence of brain atrophy. Our findings are in accordance with the observations made by Furuta et al., who only altered the size of the brain ventricles .
In this study, brain atrophy particularly affected the reference VOI. Several methods for calculating the SBR rely on a reference VOI corresponding to the whole brain or the occipital lobe. In the SBR analysis of patients with brain atrophy, it should be considered a preferable option to modify the position of the reference VOI depending on of degree of regional brain atrophy. However, Watanabe's report highlighted that the SBR values change with the setting of the reference VOI threshold . Therefore it is risky to shift the setting range of the threshold value and VOI location unnecessarily, and further investigations are needed to ascertain the pros and cons of this option. Alternatively, it might be necessary to introduce a new analysis method independent of a reference VOI. Possible alternatives are estimates only based on the VOI of the striatum or on the accumulation shape of the striatum.
Many patients undergoing [123I ]FP-CIT SPECT examination are elderly. It has been reported that age-related causes brain atrophy[22, 23]. We showed that brain atrophy induced an overestimation of SBR values. This overestimation is a confounding factor for the estimation of the DAT density decrease when the diagnosis of dopaminergic degenerative disorders.
Overestimation of SBR may be a particular problem in diseases in which the whole striatum accumulation decreases such as DLB. It has been shown that SBR estimates decrease in DLB with the time course of the [123I ]FP-CIT SPECT investigation. Recent data analysis research of ENC-DAT shows that SBR decreases with age [24, 25]. However, in cases with advanced brain atrophy due to aging, this effect was counteracted by the related overestimation of the SBR.
In this study, the accumulation of the striatum was constant. Therefore, it is necessary to consider alternative unbiased models to properly measure the decreased striatal [123I ]FP-CIT SPECT accumulation in diseases such as PD and DLB.