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.

Standardizing SPECT/CT dosimetry following radioembolization with yttrium-90 microspheres

Background Multiple post-treatment dosimetry methods are currently under investigation for Yttrium-90 ($$^{90}\hbox {Y}$$ 90 Y ) radioembolization. Within each methodology, a variety of dosimetric inputs exists that affect the final dose estimates. Understanding their effects is essential to facilitating proper dose analysis and crucial in the eventual standardization of radioembolization dosimetry. The purpose of this study is to investigate the dose differences due to different self-calibrations and mass density assignments in the non-compartmental and local deposition methods. A practical mean correction method was introduced that permits dosimetry in images where the quality is compromised by patient motion and partial volume effects. Methods Twenty-one patients underwent $$^{90}\hbox {Y}$$ 90 Y radioembolization and were imaged with SPECT/CT. Five different self-calibrations (FOV, Body, OAR, Liverlung, and Liver) were implemented and dosimetrically compared. The non-compartmental and local deposition method were used to perform dosimetry based on either nominal- or CT calibration-based mass densities. A mean correction method was derived assuming homogeneous densities. Cumulative dose volume histograms, linear regressions, boxplots, and Bland Altman plots were utilized for analysis. Results Up to 270% weighted dose difference was found between self-calibrations with mean dose differences up to 50 Gy in the liver and 23 Gy in the lungs. Between the local deposition and non-compartmental methods, the liver and lung had dose differences within 0.71 Gy and 20 Gy, respectively. The local deposition method’s nominal and CT calibration-based mass density implementations dosimetric metrics were within 1.4% in the liver and 24% in the lungs. The mean lung doses calculated with the CT method were shown to be inflated. The mean correction method demonstrated that the corrected mean doses were greater by up to $$\sim 5$$ ∼ 5 Gy in the liver and lower by up to $$\sim 12$$ ∼ 12 Gy in the lungs. Conclusions The OAR calibration may be utilized as a potentially more accurate and precise self-calibration. The non-compartmental method was found more comparable to the local deposition method in organs that were more homogeneous in mass densities. Due to the potential for inflated lung mean doses, the non-compartmental and local deposition method implemented with nominal mass densities is recommended for more consistent dosimetric results. If patient motion and partial volume effects are present in the liver, our practical correction method will calculate more representative doses in images suboptimal for dosimetry.

Influence of reconstruction parameters of positron emission tomograph scanning on the effect of partial volume of the pathological lesion

In this work, the following tasks were solved: to perform a comparative analysis of data processing methods when calculating recovery factors; to evaluate the influence of time-of-flight technology and PSF function on the recovery factor and the forecast of recovery factor deviation for potential pathological foci with a diameter of 6–8 mm; to evaluate the influence of parameters of iterative reconstruction algorithms, Gaussian filter and axial filters on the recovery factor. The calculation of the recovery factors was carried out on the basis of quantitative characteristics obtained in the analysis of reconstructions of images of the IEC phantom with six spheres installed inside and filled with a radiopharmaceutical. Eight series of experiments with background / sphere activity ratios 1/3, 1/4, 1/6, 1/8, 1/12, 1/14, 1/16, 1/20 were carried out with the same concentration of activity in the spheres during each separate experiment. The forecast of the effect of the partial volume effect on lesions with a diameter of 6 to 8 mm was carried out, taking into account the used reconstruction algorithms. It is advisable to use the results obtained to harmonize diagnostic protocols for scanning with positron emission tomographs using the input parameters of reconstruction algorithms and filters, which will minimize the error in the quantitative assessment of a radiopharmaceutical when analyzing the dynamics of the development of a pathological process, as well as the response of pathology to therapy.

Development of a New Quantification Method Using Partial Volume Effect Correction for Individual Energy Peaks in 111In-pentetreotide SPECT/CT

BackgroundSomatostatin receptor scintigraphy (SRS) using 111In-pentetreotide has no established quantification method. The purpose of this study was to develop a new quantitative method to correct the partial volume effect (PVE) for individual energy peaks in 111In-pentetreotide single-photon emission computed tomography (SPECT). MethodsPhantom experiments were performed to construct a new quantitative method. In the phantom experiments, a NEMA IEC body phantom was used. Acquisition was performed using two energy peaks (171 keV and 245 keV) on the SPECT/CT system. In the SPECT images of each energy peak, the region of interest was set at each hot sphere and lung insert, and the recovery coefficient (RC) was calculated to understand the PVE. A new quantitative index, the indium uptake index (IUI), was calculated using the RC to correct the PVE. The quantitative accuracy of the IUI in the hot sphere was confirmed. Case studies were performed to clarify the quantitative accuracy. In a case study, the relationship between the IUI and the Krenning score, which is used as a visual assessment, was evaluated for each lesion. ResultsThe obtained RCs showed that the energy peak at 171 keV was faster in recovering the effect of PVE than that at 245 keV. The IUI in the 17 mm diameter hot sphere was overestimated by 3.1% at 171 keV and underestimated by 0.5% at 245 keV compared to the actual IUI. In case studies, the relationship between IUI and Krenning score was rs = 0.805 (p < 0.005) at sum, rs = 0.77 (p < 0.005) at 171 keV, and rs = 0.84 (p < 0.005) at 245 keV.Conclusion We have developed a new quantification method for 111In-pentetreotide SPECT/CT using RC-based PVE correction for an individual energy peak of 171 keV. The quantitative accuracy of this method was high even for accumulations of less than 20 mm, and it showed a good relationship with the Krenning score; therefore, the clinical usefulness of IUI was demonstrated.

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.