Sickle cell disease (SCD) causes vaso-occlusion, ischemia, and end-organ infarction that causes acute pain episodes, also known as vaso-occlusive crises (VOC). Understanding the mechanism underlying VOC is critical to identify patients at risk and for accurate diagnosis while in VOC. PET imaging with the probe 68 Ga-PRGD2 that binds integrin αvβ3 identified areas of increased binding of sickle RBC to the endothelium in VOC. Simultaneous PET-MR imaging could provide additional information on tissue changes associated with VOC. Thus, we imaged a patient with SCD with 68 Ga-PRGD2 in combination with MRI by using PET-MR 3T scanner.
The triplicate copy of amyloid precursor protein gene (APP; chromosome 21) in Down syndrome (DS) genetically predisposes adults with DS to over production of amyloid-β (Aβ) leading to increased Aβ plaque deposition and a higher prevalence of Alzheimer's disease (AD) and dementia. Patterned localization of Aβ plaques are a hallmark of AD. This study investigated the relationship between co-localized Aβ deposition and cortical atrophy in non-demented adults with DS. Sixty-seven non-demented adults with DS (38M, 29F; 37±7yrs) underwent [11C]PiB PET and anatomical T1-weighted MRI. Cortical thickness in six AD-vulnerable ROIs (ie. entorhinal cortex, fusiform gyrus, parahippocampal gyrus, cingulate isthmus, posterior cingulate, and precuneus) was obtained from T1-weighted images using FreeSurfer (6.0.0). Parametric standard uptake value ratio (SUVR) images were generated in native T1 space with cerebellar gray matter as a reference region. Linear regression, adjusted for age, was used to investigate PiB status group (Aβ- vs. Aβ+) differences in cortical thickness as well as investigate the effect of local and global amyloid burden on cortical thickness. No differences in cortical atrophy were observed between the Aβ- and Aβ+ groups (Table 1). Secondary analyses revealed significant (p<.0001) positive correlations between age and global PiB retention, and significant negative correlations (p<.05) between age and cortical thickness in the precuneus, cingulate isthmus, parahippocampal gyrus, and fusiform. Further, regression analyses displayed significant (p <.05) negative correlations between co-localized PiB SUVR and cortical thickness in the precuneus, entorhinal cortex, and fusiform gyrus, and which remained significant in the precuneus and entorhinal cortex when correcting for age (Table 2). Similarly, significant (p <.05) negative correlations were present between global Aβ burden and cortical thickness in the precuneus, cingulate isthmus, posterior cingulate, and fusiform gyrus, with the correlation remaining significant in the precuneus after adjustment for age (Table 3). The robust association between age and amyloid accumulation precludes discrimination of the effects of normative age-related atrophy and Aβ deposition. However, when combined with our previously published longitudinal analysis of this cohort these results suggest that early Aβ aggregation has local and global deleterious effects on brain structure.
Trisomy of chromosome 21 in Down syndrome results in an overexpression of the gene encoding amyloid precursor protein and an early presence of β-amyloid plaques in the brain. [11C]PiB is a commonly used PET radiotracer for detecting the presence of β-amyloid plaques. A novel outcome metric of global amyloid load (AβL) was developed to provide a quantitative index of the progression of this pathophysiology1. This study aims to implement and assess longitudinal AβL change in DS. Participants with DS from two related longitudinal biomarker studies (N=100; 38.5±8.2 years) underwent [11C]PiB PET scans. During this ongoing longitudinal study, participants underwent two, three, and four PiB scans (n=52, 35, and 7 respectively; 2.3±0.6 years apart). ROI definition from T1w MRI scans was performed with FreeSurfer 5.3.0. SUVr images were generated from 50-70min PET frames using cerebellar gray matter as a reference region. PET images were spatially normalized to MNI152 space using a DS-specific PET template, and AβL was calculated from the SUVr data and DS-specific canonical images of Aβ carrying capacity (K) and PiB non-specific binding (NS) (Figure 1). Longitudinal AβL and global SUVr change (%change/year with 95% CI) were calculated and compared between PiB(-) and PiB(+) groups (based on global SUVr >1.36). A positive correlation was observed between AβL and age (Pearson's r=0.64; Figure 2). Figure 3 displays the group comparison between AβL and SUVr change. In the PiB(-) group, longitudinal AβL showed a mean change of 0.78%[0.48,1.09] compared to 1.43%[0.86,2.00] for SUVr. Similarly, AβL showed a mean change of 3.68%[2.91,4.45] compared to 5.64%[4.42,6.86] for SUVr in the PiB(+) group.
Combined positron emission tomography and computed tomography (PET/CT) might improve the accuracy of PET tracer quantification by providing the exact tumour contour from coregistered CT images. We compared various semiquantitative approaches for the characterization of solitary pulmonary nodules (SPNs) using F-18 fluorodeoxyglucose PET/CT.The final diagnosis of 49 SPNs (46 patients) was based on histopathology (n=33) or patient follow-up (n=16). The regions of interest (ROIs) were drawn around lesions based on the CT tumour contour and mirrored to the coregistered PET images. Quantification of F-18 fluorodeoxyglucose uptake was accomplished by calculating the standardized uptake value (SUV) using three different methods based on: activity from the maximum-valued pixel within the tumour (SUV-max); the mean ROI activity within the transaxial slice containing the maximum-valued pixel (SUV-mean); and the mean activity over the full tumour volume (SUV-vol). SUVs were corrected for partial volume effects and normalized by body surface area, lean body weight, and blood glucose. Recovery coefficients for partial-volume correction were derived from phantom studies. The ability of various SUVs to differentiate between benign and malignant SPNs was determined by calculating the area under the receiver operating characteristic (ROC) curves.Twenty-six SPNs were malignant and 23 were benign. The area under the ROC curve was 0.78 for SUV-mean, 0.83 for SUV-max, and 0.78 for SUV-vol. SUV-max and its normalizations yielded the highest area under the ROC curve (0.83-0.85); SUV-mean-partial volume corrected-lean body weight resulted in the lowest area under the ROC curve (0.76). At a specificity of 80%, SUV-max-body surface area provided the highest sensitivity (81%) and accuracy (80%) to detect malignant SPN. Using SUV-max with a cutoff of 2.4 at a specificity of 80% resulted in a sensitivity of 62% (accuracy 71%).Various normalizations applied to SUV-max provided the highest diagnostic accuracy for characterization of SPNs. Quantification methods using the exact tumour contour derived from CT in combined PET/CT imaging (ROI mean activity within a single transaxial slice and mean tumour volume activity) did not result in improved differentiation between benign and malignant SPN. Obtaining SUV-max might be sufficient in the clinical setting.
Images produced by gamma camera coincidence (GCC) techniques have a much lower count-density than those produced by dedicated PET scanners. The authors examine the effects of attenuation and attenuation correction on GCC images using gamma-camera emission data and PET emission and transmission data from phantom and human studies. The effects studied include contrast, noise, and general image quality. Results show that lung lesion contrast is improved but the signal-to-noise ratio is slightly degraded by the application of attenuation correction. Additionally, the corrected images do not contain the distortions of the uncorrected images and they more accurately show the activity distribution of the imaged object. The noise studies suggest that statistically appropriate transmission data for implementing an attenuation correction can be acquired in a small fraction of the time used for an emission scan.
1788 Objectives Heterogeneity in blood-brain-barrier (BBB) permeability confounds quantification of 18F-Fluorothymidine (FLT) PET of glioblastoma multiforme (GBM). Dynamic contrast enhanced MRI (DCE-MRI) measures permeability of tumor vasculature via the modeling parameter Ktrans. We explore a Ktrans based ROI definition method for quantifying FLT PET data. Methods N=3 GBM patients received baseline (BL) and early therapy assessment (ETA; 2 wks post-radio-chemo-therapy) dynamic FLT PET (Siemens HR+) and DCE-MRI (Siemens 3T TimTrio or 3T mMR) scans. PET acquisitions (68min) commenced with injection of 5mCi of FLT. DCE-MRI scans initiated with injection (Medrad injector) of 0.1mmol/kg of contrast agent (Magnevist). Voxelwise maps of Ktrans were computed from ETA DCE-MRI using a modified Tofts model and image based input function. Subject BL PET, ETA PET, and ETA Ktrans maps were co-registered to ETA contrast enhanced MRI (PMOD 3.5, PMOD Technologies Ltd). Two ROI were derived from each subject’s ETA Ktrans map using a threshold equal to half the maximum Ktrans value: voxels with Ktrans above the threshold formed the high Ktrans ROI, while voxels with Ktrans below the threshold formed the low Ktrans ROI. 2-tissue compartment modeling was used to compute subject specific FLT flux (KFLT ) for each ROI at each timepoint. Results Comparison of KFLT between high and low Ktrans ROI at BL showed larger KFLT values in the high Ktrans ROI compared to low Ktrans ROI for all subjects, while at ETA KFLT was larger in the high Ktrans ROI compared to the low Ktrans ROI for 2 of 3 subjects. KFLT decreased between BL and ETA timepoints in both the high and low Ktrans ROI for 2 subjects. For the third subject KFLT decreased between BL and ETA in the high Ktrans ROI, but increased in the low Ktrans ROI. Conclusions Regions of high Ktrans (suggesting comparatively higher BBB permeability) are associated with higher KFLT values compared to regions of low Ktrans. Research Support US National Institutes of Health research grants U01CA140230 and P30CA047904.
