EJNMMI Physics最新文献

Background: Tumour dosimetry after radionuclide therapy using ¹⁷⁷Lu-labelled radiopharmaceuticals requires determination of the ¹⁷⁷Lu mean concentration, but this is challenging as tumours are often small, or ¹⁷⁷Lu activity is present in nearby organs or other tumours. Here we present a comparison of methods for determination of ¹⁷⁷Lu mean concentration, and in turn absorbed tumour dose, applied to a small number of patients with prostate cancer treated by [¹⁷⁷Lu]Lu-PSMA I&T. For application of each method, specific criteria on tumour diameter and tumour-background ratio must be fulfilled.

Results: Eighteen tumours in 9 patients were analyzed. Several methods, the so-called Small Volume of Interest (VOI) with a 20 mm diameter sphere, Large VOI and Isocontour methods, were found to be in good agreement. Relative to the chosen reference method (Isocontour method with partial volume correction), the relative percentage differences of ¹⁷⁷Lu concentration using either of these methods were in the range (-23)-26%. The relative differences of absorbed doses were in the range (-16)-19%.

Conclusions: The agreement between the methods permits a comparison between dosimetry studies, where some of these methods are applied. As the application criteria are complementary, it is possible to include both small (> 15 mm diameter) solitary tumours and larger (> 30 mm diameter), possibly non-solitary, tumours in a dosimetry study.

Background: Planar scintigraphy remains commonplace in clinical practice and has been used for quantification and dosimetry estimation over an expanding range of gamma-emitting radionuclides in recent years. Applications of planar scintigraphy, in combination with SPECT/CT imaging, can add value to radiopharmaceutical development in preclinical models and in translation to human use. The aim of this study was to demonstrate whole-body quantitative accuracy in mice using pinhole collimated planar scintigraphy on a preclinical SPECT/CT system, following corrections to sensitivity variations across the field of view.

Results: Planar projections were acquired using short imaging time frames, thus allowing for dynamic biodistribution data to be collected and compared to the known injected activity and whole-body SPECT data. Encapsulation of [^99mTc]TcO₄^- in a supramolecular cage was used to demonstrate the visual and quantitative changes in biodistribution over time, as compared to [^99mTc]TcO₄^- alone. For these radiopharmaceuticals, whole-body quantification was 98.7 ± 7.3% of the decay-corrected true injected activity, as opposed to 74.8 ± 7.5% when calculated without a sensitivity correction. Similarly, the final planar scintigraphy frame acquired at 1-hour post-injection quantitatively agreed with activity values returned from the whole-body SPECT: 99.5 ± 10.6% (final frame, planar) vs. 99.1 ± 5.5% (SPECT). Regions of interest (ROIs) over selected organs between planar scintigraphy and SPECT were also in good agreement. Quantitative accuracy of planar scintigraphy was further validated in a preclinical tumour model of prostate cancer using [¹⁶¹Tb]Tb-PSMA-617. In this case, the whole-body planar value was 94.6 ± 3.6% of the recorded injected activity and, consistent with ^99mTc findings, was underestimated without sensitivity correction (76.6 ± 3.1%). Tumour uptake values were equivalent between corrected planar scintigraphy (5.2%IA) and SPECT (5.3%IA) at 1-hour post-injection.

Conclusions: Using a common radionuclide and one of emerging radiotherapeutic interest, whole-body injected activity and organ-specific ROI values obtained by planar scintigraphy strongly correlated to the true injected activity and values obtained by SPECT following sensitivity-based corrections. The addition of quantitative dynamic planar scintigraphy into the preclinical workflow followed by SPECT imaging adds value to pharmacokinetic and dosimetry assessments of novel gamma-emitting radiopharmaceuticals in imaging and therapeutic applications.

Background: Single Photon Emission Computed Tomography (SPECT) is increasingly used as a quantitative modality, especially in the context of Molecular Radiotherapy, where the measurements are used as input to absorbed dose calculations for patient-specific dosimetry. Establishing measurement traceability is an essential step in providing confidence in quantitative measurements. This requires an unbroken chain of calibrations where uncertainties must be reported in all stages of calibration and for the final measurement result. Traceability ensures that a measurement result can be related to an underlying standard, allowing harmonisation of data, and facilitating comparison of results between sites.

Methods: The process of establishing measurement traceability for quantitative SPECT is demonstrated for the therapeutic radionuclide ¹⁷⁷Lu using a common, phantom based, calibration method. Phantoms with activities of ¹⁷⁷Lu, measured using a traceably calibrated radionuclide calibrator, were used to perform the calibration. The calibration was validated using 3D-printed anthropomorphic organ phantom inserts mimicking clinically relevant geometries. For all measurements, traceability to primary standards for radioactivity is demonstrated along with an accompanying calibration chain and statement of uncertainty.

Results: For all activity measurements the dominant component in the activity uncertainty budget was the uncertainty on the radionuclide calibrator calibration factor, resulting in an average combined standard uncertainty of 1.57%. The resulting uncertainty on the SPECT Image Calibration Factor was 1.6%. An optional additional correction was included in the calibration to provide volume-based partial volume correction (PVC). Measurement traceability was extended for measurands using this additional correction. The activity recovery in the organ phantoms with PVC applied was 96(7)% for both the kidney and spleen.

Conclusions: A manufacturer independent methodology for establishing measurement traceability for quantitative SPECT is demonstrated for ¹⁷⁷Lu, using a radionuclide calibrator previously calibrated against national standards. The ability to establish measurement traceability for quantitative SPECT using standard clinical equipment, and the limitations of traceability are presented.

Background: For patients investigated with radiopharmaceuticals, it is important to be able to perform valid calculations of the absorbed dose in organs and tissues. An internal dosimetry computer program, IDAC-Dose2.1, has been updated to be based on the ICRP specific absorbed fractions and computational framework of internal dose assessment for 12 adult and paediatric reference individuals given in ICRP Publication 133 and 155. The updated dosimetry software intended for nuclear medicine is named IDAC-Dose2.2. The calculations are based on radionuclide decay scheme of ICRP Publication 107. Biokinetic models can be based on up to 83 different source regions irradiating 48 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry software, DCAL ver. 2022, that employs the same computational framework and is used for occupational and environmental intakes of radionuclides. IDAC-Dose2.2 calculates absorbed doses to the 2 adult and 10 paediatric,15-yrs, 10-yrs, 5-yrs, 1-yr, 100 days (infant) and 0 day (new-born), sex specific ICRP reference phantoms. It has an additional sub-module which can interpolate the calculated absorbed dose and effective dose to an arbitrary age between 0 and 20 years (20 years = adult) or an arbitrary weight of 3.5-73 kg for male and 3.5-64 kg for female instead of only using the 6 fixed phantoms ages.

Results: IDAC-Dose2.2 was applied on three frequently used radiopharmaceuticals: intravenously administered 2-[¹⁸F]FDG, orally administered ^99mTc-pertechnetate and ¹³¹I-iodide. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated for 2-[¹⁸F]FDG: 0.017mSv/MBq, 0.020 mSv/MBq, 0.029 mSv/MBq, 0.044 mSv/MBq, 0.075 mSv/MBq, 0.16 mSv/MBq 0.16 mSv/MBq for adult, 15-, 10-, 5-, 1-year old, 100 days (infant) and 0 day (newborn), respectively. Effective dose of 0.034 mSv/MBq was also calculated for 2-[¹⁸F]FDG to a reference person of 8-years old. For the same three radiopharmaceuticals, S-values were generated for all phantoms in IDAC-Dose2.2 and validated against the dosimetry program DCAL, showing identical results.

Conclusions: The internal dosimetry program IDAC-Dose was updated to include all 12 specific sets of absorbed fractions of the ICRP adult and paediatric reference phantoms and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for preadults in diagnostic nuclear medicine. The sub-module for age or weight interpolation of absorbed doses follows the ICRP computational framework used for members of the public. IDAC-Dose2.2 will used by the ICRP for absorbed and effective dose calculations in diagnostic nuclear medicine. The results from other software, which uses the same primer d

Background: Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder in which tau neurofibrillary tangles are a pathological hallmark closely associated with cognitive dysfunction and neurodegeneration. In this study, we used brain tau data to investigate AD heterogeneity by identifying and characterizing the subpopulations among patients. We included 615 cognitively normal and 159 AD brain ¹⁸F-flortaucipr PET scans, along with T1-weighted MRI from the Alzheimer Disease Neuroimaging Initiative database. A three dimensional-convolutional neural network model was employed for AD detection using standardized uptake value ratio (SUVR) images. The model-derived saliency maps were generated and employed as informative image features for clustering AD participants. Among the identified subpopulations, statistical analysis of demographics, neuropsychological measures, and SUVR were compared. Correlations between neuropsychological measures and regional SUVRs were assessed. A generalized linear model was utilized to investigate the sex and APOE ε4 interaction effect on regional SUVRs.

Results: Two distinct subpopulations of AD patients were revealed, denoted as S_Hi and S_Lo. Compared to the S_Lo group, the S_Hi group exhibited a significantly higher global tau burden in the brain, but both groups showed similar cognition distribution levels. In the S_Hi group, the associations between the neuropsychological measurements and regional tau deposition were weakened. Moreover, a significant interaction effect of sex and APOE ε4 on tau deposition was observed in the S_Lo group, but no such effect was found in the S_Hi group.

Conclusion: Our results suggest that tau tangles, as shown by SUVR, continue to accumulate even when cognitive function plateaus in AD patients, highlighting the advantages of PET in later disease stages. The differing relationships between cognition and tau deposition, and between gender, APOE4, and tau deposition, provide potential for subtype-specific treatments. Targeting gender-specific and genetic factors influencing tau deposition, as well as interventions aimed at tau's impact on cognition, may be effective.

Background: ¹⁵O-water positron emission tomography (PET) is considered the gold standard method for non-invasive measurement of cerebral blood flow (CBF). However, previously published average CBF values in healthy subjects have varied greatly and the cause of these variations remains unclear. This study investigates how image reconstruction methods and spatial resolution affect CBF measurements with ¹⁵O-water PET.

Methods: Eight healthy subjects each underwent dynamic ¹⁵O-water PET scans with continuous arterial blood sampling. Images were reconstructed using two different algorithms; ordered subset expectation maximisation and block sequential regularised expectation maximalisation with varying reconstruction parameters. CBF was estimated for the whole brain, grey matter, and central white matter. Reconstruction-specific effective spatial resolution was estimated using phantom measurements and simulations.

Results: The mean whole brain CBF was 0.48 mL/cm³/min and showed little dependence on the image reconstruction method. Grey matter CBF varied between 0.52 and 0.57 mL/cm³/min, and central white matter CBF between 0.20 and 0.28 mL/cm³/min. Regional CBF showed great dependence on effective spatial resolution with a negative correlation between grey matter CBF and resolution (r = -0.96) and a positive correlation between central white matter and resolution (r = 0.93).

Conclusion: This study concludes that grey matter and central white matter CBF, but not whole brain CBF measured with quantitative ¹⁵O-water PET is reconstruction method dependent, mainly due to varying spatial resolution with consequent partial volume effects. Variations in published CBF values cannot be explained solely by reconstruction methods or spatial resolution.

Background: Positron emission tomography (PET) with a [¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) tracer is of growing importance in the management of glioblastoma for the estimation of tumor extent and extraction of diagnostic and prognostic parameters. Robust and accurate glioblastoma segmentation methods are essential to maximize the benefits of this imaging modality. Given the importance of setting the foreground threshold during manual tumor delineation, this study investigates the added value of incorporating such prior knowledge to guide the automated segmentation and improve performance. Two segmentation networks were trained based on the nnU-Net guidelines: one with the [¹⁸F]FET PET image as sole input, and one with an additional input channel for the threshold map. For the latter, we investigate the benefit of manually obtained thresholds and explore automated prediction and generation of such maps. A fully automated pipeline was constructed by selecting the best performing threshold prediction approach and cascading this with the tumor segmentation model.

Results: The proposed two-channel network shows increased performance with guidance of threshold maps originating from the same reader whose ground-truth tumor label the prediction is compared to (DSC = 0.901). When threshold maps were generated by a different reader, performance reverted to levels comparable to the one-channel network and inter-reader variability. The proposed full pipeline achieves results on par with current state of the art (DSC = 0.807).

Conclusions: Incorporating a threshold map can significantly improve tumor segmentation performance when it aligns well with the ground-truth label. However, the current inability to reliably reproduce these maps-both manually and automatically-or the ground-truth tumor labels, restricts the achievable accuracy for automated glioblastoma segmentation on [¹⁸F]FET PET, highlighting the need for more consistent definitions of such ground-truth delineations.

Background: Validation of threshold-based PET segmentation and PET quantification is typically performed with fillable phantoms. Theoretical considerations show that the inactive walls of the phantom cavities introduce a contrast dependence of the volume-reproducing threshold (VRT), potentially leading to segmentation errors and therefore miscalculations of target volumes. The goal of this study was to experimentally show the contrast independence of the VRT when using wall-less phantoms.

Results: Radioactive spheres were produced according to NEMA specifications (D = 10/13/17/22/28/37 mm) using a stereolithographic (SLA) 3D printer. For comparison, hollow spheres were filled with a similar activity concentration. Image data from both sphere types were acquired with five different signal-to-background ratios (SBR = 2/4/6/8/10) using a Siemens mCT 20 and a Biograph 64 TruePoint PET/CT system. Results from wall-less and fillable spheres were compared to evaluate contrast dependence and segmentation accuracy based on VRT and intensity profiles. Wall-less phantoms demonstrated consistent VRT values, with a coefficient of variation of 2% over all SBRs, indicating independence from contrast. Conversely, fillable phantoms exhibited significant VRT variability, with a coefficient of variation (CV) of 9% over all SBRs and up to 40% volume overestimation at low contrast. Additionally, activity distribution in the printed spheres was evaluated using PET-based statistical analysis and autoradiography. The PET intensity distribution in the printed material was highly uniform (CV = 4.2%), with a Kullback-Leibler divergence near zero and no statistically significant difference to the fillable spheres. Autoradiography revealed microscopic regions with elevated counts, showing a CV of 11.7%, which was effectively reduced to 2.4% after Gaussian filtering.

Conclusions: The theoretical predictions of a significant influence of inactive walls in low-contrast images and contrast-independent VRT in wall-less phantoms were successfully confirmed. SLA 3D printing of phantoms is a promising method for the reliable evaluation of PET quantification methods, particularly in low-contrast scenarios commonly encountered in clinical settings.

Background: The image quality of positron emission tomography (PET) can be significantly enhanced by using time-of-flight (TOF) and depth-of-interaction (DOI) information. PET detectors are pivotal in determining the TOF and DOI capabilities of PET scanners.

Methods: This study developed and evaluated TOF-DOI PET detectors based on the dual-ended readout method and lutetium-yttrium oxyorthosilicate (LYSO) arrays with two different pitches and reflector configurations. Specifically, the performance of detectors based on three types of LYSO arrays with 20 mm thickness, 8 × 8 arrays with a 3.2 mm pitch, 16 × 16 arrays with a 1.6 mm pitch and normal reflectors, and 16 × 16 arrays with a 1.6 mm pitch and partial short reflectors, were assessed. Hamamatsu S14161-3050-08 silicon photomultiplier arrays were used as the photodetectors, and PETsys TOFPET2 was used as the readout electronics.

Results: The flood histograms showed that all crystals in the three types of LYSO arrays were clearly resolved. The detectors based on the 8 × 8 LYSO arrays provided a coincidence timing resolution (CTR) of 207 ± 5 ps and a DOI resolution of 3.9 ± 0.6 mm. The detectors based on the 16 × 16 LYSO arrays with normal reflectors provided a CTR of 218 ± 7 ps and a DOI resolution of 2.6 ± 0.2 mm. In comparison, the detector based on the 16 × 16 LYSO arrays with partial short reflectors provided a CTR of 228 ± 11 ps and a DOI resolution of 2.9 ± 0.3 mm, and superior crystal resolvability compared to the detectors based on the 16 × 16 LYSO arrays with normal reflectors.

Conclusion: These detectors are promising candidates for developing whole-body and brain PET scanners, offering effective sensitivity and uniform spatial resolution improvements across the field-of-view.