Partial Volume Correction Increases the Sensitivity of 18F-Florbetapir-Positron Emission Tomography for the Detection of Early Stage Amyloidosis

Purpose: To test whether correcting for unspecific signal from the cerebral white matter increases the sensitivity of amyloid-PET for early stages of cerebral amyloidosis.Methods: We analyzed 18F-Florbetapir-PET and cerebrospinal fluid (CSF) Aβ42 data from 600 older individuals enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including people with normal cognition, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) dementia. We determined whether three compartmental partial volume correction (PVC-3), explicitly modeling signal spill-in from white matter, significantly improved the association of CSF Aβ42 levels with global 18F-Florbetapir-PET values compared with standard processing without PVC (non-PVC) and a widely used two-compartmental PVC method (PVC-2). In additional voxel-wise analyses, we determined the sensitivity of PVC-3 compared with non-PVC and PVC-2 for detecting early regional amyloid build-up as modeled by decreasing CSF Aβ42 levels. For replication, we included an independent sample of 43 older individuals with subjective memory complaints from the INveStIGation of AlzHeimer’s PredicTors cohort (INSIGHT-preAD study).Results: In the ADNI sample, PVC-3 18F-Florbetapir-PET values normalized to whole cerebellum signal showed significantly stronger associations with CSF Aβ42 levels than non-PVC or PVC-2, particularly in the lower range of amyloid levels. These effects were replicated in the INSIGHT-preAD sample. PVC-3 18F-Florbetapir-PET data detected regional amyloid build-up already at higher (less abnormal) CSF Aβ42 levels than non-PVC or PVC-2 data.Conclusion: A PVC approach that explicitly models unspecific white matter binding improves the sensitivity of amyloid-PET for identifying the earliest stages of cerebral amyloid pathology which has implications for future primary prevention trials.

A multicentre and multi-national evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project

Purpose Patient-specific dosimetry is required to ensure the safety of molecular radiotherapy and to predict response. Dosimetry involves several steps, the first of which is the determination of the activity of the radiopharmaceutical taken up by an organ/lesion over time. As uncertainties propagate along each of the subsequent steps (integration of the time–activity curve, absorbed dose calculation), establishing a reliable activity quantification is essential. The MRTDosimetry project was a European initiative to bring together expertise in metrology and nuclear medicine research, with one main goal of standardizing quantitative 177Lu SPECT/CT imaging based on a calibration protocol developed and tested in a multicentre inter-comparison. This study presents the setup and results of this comparison exercise. Methods The inter-comparison included nine SPECT/CT systems. Each site performed a set of three measurements with the same setup (system, acquisition and reconstruction): (1) Determination of an image calibration for conversion from counts to activity concentration (large cylinder phantom), (2) determination of recovery coefficients for partial volume correction (IEC NEMA PET body phantom with sphere inserts), (3) validation of the established quantitative imaging setup using a 3D printed two-organ phantom (ICRP110-based kidney and spleen). In contrast to previous efforts, traceability of the activity measurement was required for each participant, and all participants were asked to calculate uncertainties for their SPECT-based activities. Results Similar combinations of imaging system and reconstruction lead to similar image calibration factors. The activity ratio results of the anthropomorphic phantom validation demonstrate significant harmonization of quantitative imaging performance between the sites with all sites falling within one standard deviation of the mean values for all inserts. Activity recovery was underestimated for total kidney, spleen, and kidney cortex, while it was overestimated for the medulla. Conclusion This international comparison exercise demonstrates that harmonization of quantitative SPECT/CT is feasible when following very specific instructions of a dedicated calibration protocol, as developed within the MRTDosimetry project. While quantitative imaging performance demonstrates significant harmonization, an over- and underestimation of the activity recovery highlights the limitations of any partial volume correction in the presence of spill-in and spill-out between two adjacent volumes of interests.

Characterization of point-spread function specification error on Geometric Transfer Matrix partial volume correction in [11C]PiB amyloid imaging

Purpose Partial-volume correction (PVC) using the Geometric Transfer Matrix (GTM) method is used in positron emission tomography (PET) to compensate for the effects of spatial resolution on quantitation. We evaluate the effect of misspecification of scanner point-spread function (PSF) on GTM results in amyloid imaging, including the effect on amyloid status classification (positive or negative). Methods Twenty-nine subjects with Pittsburgh Compound B ([11C]PiB) PET and structural T1 MR imaging were analyzed. FreeSurfer 5.3 (FS) was used to parcellate MR images into regions-of-interest (ROIs) that were used to extract radioactivity concentration values from the PET images. GTM PVC was performed using our “standard” PSF parameterization [3D Gaussian, full-width at half-maximum (w) of approximately 5 mm]. Additional GTM PVC was performed with “incorrect” parameterizations, taken around the correct value. The result is a set of regional activity values for each of the GTM applications. For each case, activity values from various ROIs were combined and normalized to produce standardized uptake value ratios (SUVRs) for nine standard [11C]PiB quantitation ROIs and a global region. GTM operating-point characteristics were determined from the slope of apparent SUVR versus w curves. Results Errors in specification of w on the order of 1 mm (3D) mainly produce only modest errors of up to a few percent. An exception was the anterior ventral striatum in which fractional errors of up to 0.29 per millimeter (3D) of error in w were observed. Conclusion While this study does not address all the issues regarding the quantitative strengths and weakness of GTM PVC, we find that with reasonable caution, the unavoidable inaccuracies associated with PSF specification do not preclude its use in amyloid quantitation.

The effect of calibration factors and recovery coefficients on 177Lu SPECT activity quantification accuracy: a Monte Carlo study

Background Different gamma camera calibration factor (CF) geometries have been proposed to convert SPECT data into units of activity concentration. However, no consensus has been reached on a standardised geometry. The CF is dependent on the selected geometry and is further affected by partial volume effects. This study investigated the effect of two CF geometries and their corresponding recovery coefficients (RCs) on the quantification accuracy of 177Lu SPECT images using Monte Carlo simulations. Methods The CF geometries investigated were (i) a radioactive-sphere surrounded by non-radioactive water (sphere-CF) and (ii) a cylindrical phantom uniformly filled with radioactive water (cylinder-CF). Recovery coefficients were obtained using the sphere-CF and cylinder-CF, yielding the sphere-RC and cylinder-RC values, respectively, for partial volume correction (PVC). The quantification accuracy was evaluated using four different-sized spheres (15.6–65.4 ml) and a kidney model with known activity concentrations inside a cylindrical, torso and patient phantom. Images were reconstructed with the 3D OS-EM algorithm incorporating attenuation, scatter and detector-response corrections. Segmentation was performed using the physical size and a small cylindrical volume inside the cylinder for the sphere-CF and cylinder-CF, respectively. Results The sphere quantification error (without PVC) was better for the sphere-CF (≤ − 5.54%) compared to the cylinder-CF (≤ − 20.90%), attributed to the similar geometry of the quantified and CF spheres. Partial volume correction yielded comparable results for the sphere-CF-RC (≤ 3.47%) and cylinder-CF-RC (≤ 3.53%). The accuracy of the kidney quantification was poorer (≤ 22.34%) for the sphere-CF without PVC compared to the cylinder-CF (≤ 2.44%). With PVC, the kidney quantification results improved and compared well for the sphere-CF-RC (≤ 3.50%) and the cylinder-CF-RC (≤ 3.45%). Conclusion The study demonstrated that upon careful selection of CF-RC combinations, comparable quantification errors (≤ 3.53%) were obtained between the sphere-CF-RC and cylinder-CF-RC, when all corrections were applied.