Real and simulated PET images.

<p>(a) A labeled MRI of a single subject. High-resolution MRI (GE Signa 1.5 T, T1-weighted images, 1 mm slice thickness) of each subject's brain was acquired and transformed into standardized stereotaxic space <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023298#pone.0023298-Talairach1" target="_blank">[16]</a> using automated feature-matching to the MNI template <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023298#pone.0023298-Collins1" target="_blank">[17]</a>, then segmented for striatum (yellow), grey matter (light blue), white matter (dark green), CSF (dark blue), skin/skull/muscle (light green), and cerebellum (not shown) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023298#pone.0023298-Collins2" target="_blank">[18]</a>. A spherical region-of-interest in the left caudate nucleus was manually defined at X = −12, Y = 16, Z = 8 (radius 6 mm, 99 voxels, orange). (b) Real summed PET image of a single subject. (c) Simulated summed PET image of a single subject with 0% changes in the left caudate BP. (d) Simulated summed PET image of a single subject with 20% decrease in the left caudate BP. The reduced signal is apparent in the left caudate nucleus (arrow).</p

The similar results of t-test and f-test on real data.

<p>(a) t-test between left DLPFC stimulation vs. vertex stimulation (control condition): The t-map is overlaid upon the averaged MRI of all subjects in standard MNI space (published with permission from Ko et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023298#pone.0023298-Ko2" target="_blank">[9]</a>). (b) f-test of all three stimulation condition (left DLPFC, right DLPFC and vertex stimulation): As the right DLPFC stimulation had no significant effect on BP in these regions, the f-map shows the similar pattern of t-map of left DLPFC vs. vertex stimulation.</p

Peak-cluster identified in the left caudate nucleus using different f-tests from real [¹¹C]raclopride PET study [9].

<p>Peak-cluster identified in the left caudate nucleus using different f-tests from real [¹¹C]raclopride PET study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023298#pone.0023298-Ko2" target="_blank">[9]</a>.</p

Sensitivity of different f-test from simulated [¹¹C]raclopride PET.

<p>BP was modulated for 99 voxels in the left caudate nucleus (spherical VOI centered at X = −12, Y = 16, Z = 8 with 6 mm radius).</p><p>Max f reflects the highest f-value observed in the f-test parametric map.</p

Averaged Durbin-Watson statistics-map over 10 subjects with (a) real [¹¹C]raclopride PET and (b) simulated [¹¹C]raclopride PET.

<p>All PET images from both real and simulated data passed the Durbin-Watson test, i.e., the statistics were >1.65 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023298#pone.0023298-Durbin1" target="_blank">[21]</a>.</p

Comparison of [¹⁸F]FEPPA regional total distribution volume (<i>V</i>_<i>T</i>) between healthy control subjects and AD patients calculated with PBIF75 for HABs (left) and MABs (right).

<p>(<i>cf</i>. figure 1 in ref [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177785#pone.0177785.ref007" target="_blank">7</a>]). PBIF75 estimation led to the same conclusion as the previously published with ASIF: [¹⁸F]FEPPA <i>V</i>_<i>T</i> in AD patients is on average 13–48% higher than HC (A Factorial ANOVA with genotype and age as covariate showed: p<0.05 in the Temporal, Prefrontal, Parietal and Occipital and p = 0.4 in the hippocampus). Images were partial volume effect corrected prior to TAC extraction. * p< 0.05 in ANOVA within group.</p

Population based input function.

<p>A) Average (n = 24) time evolution of unmetabolized [¹⁸F]FEPPA in plasma from HC (n = 8), PD (n = 8) and AD (n = 8) subjects. The inner plot shows details of the first 100 seconds post injection. B) The area under the curve of the input functions created from arterial blood sampling did not differ between 21 HC, 18 AD and 16 PD.</p

Comparison of total distribution volume (<i>V</i>_<i>T</i>) between healthy controls and PD patients calculated with ASIF and PBIF75 for putamen (left) and caudate (right).

<p>Estimation with PBIF75 led to same conclusion as with the ASIF; that there is no difference from disease (p = 0.2 in Caudate and p = 0.8 in the Putamen using PBIF vs p = 0.4 in Caudate and p = 0.7 in Putamen using ISIF) and that there is a difference due to genotype (p = 0.001 in Caudate and p = 0.002 in Putamen using PBIF vs p = 0.001 in the Caudate and p = 0.0008 in Putamen using ASIF). Images were partial volume effect corrected prior to TAC extraction.</p

Bland-altman plot of <i>V</i>_<i>T</i> assessed by ASIF (2-TCM) and PBIF75 (Logan plot) for 7 regions of interest in healthy controls.

<p>FEPPA <i>V</i>_<i>T</i><i>s</i> derived by Logan PBIF75 plot slightly underestimated (Bias < 1 mL/cm³) those derived with 2-TCM. (A) In MABs (n = 7), the 95% limits of agreement (dashed <i>lines</i>) was between -0.7 to 1.3 mL/cm³ and no systematic bias was observed (r = 0.12, p = 0.6). (B) In HABs (n = 14), the 95% limits of agreement (dashed lines) was between -2.2 to 4.2 mL/cm³ and no systematic bias was observed (r = 0.08, p = 0.7).</p

Total distribution volume (<i>V</i>_<i>T</i>) calculated using ASIF (2-TCM) and PBIF75 (Logan plot).

<p>In Temporal, Prefrontal, Hippocampus, Parietal and Occipital regions stratified as HAB and MAB groups. ASIF showed an average reduction of 29% in <i>V</i>_<i>T</i> across ROIs while PBIF showed a reduction of 26%. 5/7 ROIs survived the multiple region Bonferroni adjustment using ASIF and only 2/7 passed the Bonferroni adjustment using PBIF75. Images were partial volume effect corrected prior to TAC extraction. * p< 0.05, ** p<0.01 *** p< 0.001.</p