Activity In PET Research Articles

Internal Audit to Monitor the Injected Activity in PET/CT Using Control Charts.

In an effort to limit the risks associated with medical radiation exposure, the last century witnessed the development of dose control mechanisms, recommended by the International Commission on Radiological Protection. This organization recommends the optimization of radiation protection to provide the highest level of safety that may reasonably be achievable. Adhering to the "as low as reasonably achievable" principle, the purpose of this study was to monitor the 18F-FDG injected activity in PET and optimize the radiation protection through an internal audit process. This monitoring allows the identification of opportunities for improvement in patient care and safety, as well as to establish a periodic review of the medical unit reference levels. The methodology is based on short run Quesenberry (Q) statistics and normalized nonconstant sample size (Z-chart) control charts. Anonymized data from 512 patients were selected from a set of 18F-FDG PET/CT (Siemens, Biograph 6) examinations performed during 10 months. The analyzed variable was the ratio between the 18F-FDG injected activity (MBq) and patient weight (kg). Mean injected 18F-FDG activity was 347.811 ± 64.967 MBq corresponding to a mean effective dose of 6.608 ± 1.234 mSv. The ratio between the 18F-FDG injected activity and the body mass of patients was reduced from 5.243 ± 0.716 to 5.171 ± 0.672 MBq/kg during the statistical data analysis. The study demonstrates that control charts can be a useful tool to signal situations where patients receive an activity significantly different from the standard practice in a medical unit. The use of joint control charts is a suitable tool for detecting nonoptimized radiopharmaceutical administration. This analysis provides opportunities to evaluate and improve the quality of practice in nuclear medicine. This methodology constitutes an internal audit that may help health care professionals to make appropriate decisions to ensure all patients receive the safest and most appropriate care.

Safety and early efficacy results of phase 1 study of affinity tuned and trackable AIC100 CAR T cells in ICAM-1 positive relapsed and/or refractory advanced poorly differentiated and anaplastic thyroid cancers.

6095 Background: ICAM-1, a cell surface glycoprotein, is overexpressed in most ATC and PDTC. AIC100 is a 3rd-generation CAR T cell with micromolar affinity to ICAM-1, tuned lower than most CARs used to date in pre-/clinical studies. Affinity tuned AIC100 are expected to selectively bind and kill tumor cells while safely sparing healthy cells. AIC100 also co-expresses somatostatin receptor 2 (SSTR2), which enables in vivo monitoring of AIC100 distribution and expansion by DOTATATE PET/CT scan. Methods: The objectives of this phase 1 dose escalation study are to assess the safety, preliminary efficacy and to determine RP2D of AIC100 in patients with ICAM-1+ relapsed/refractory PDTC or ATC. 3 dose levels (DL) are being explored-DL1 at 1x 107, DL2 at 1 x 108 and DL3 at 5 x 108 AIC100. AIC100 is received as a single infusion two days after completing lymphodepletion with Fludarabine/Cyclophosphamide. FDG and DOTATATE PET/CT scans are used to assess response and to track AIC100 in vivo, respectively. Response is assessed by RECIST1.1, starting at end of treatment (day 42 post AIC100). AIC100 is manufactured using AffyImmune’s Tune and Track CAR T cell platform. Results: As of Feb 14, 2023, 6 pts (4 ATC; 2 PDTC) with a median age of 59.5 yrs (48-70) were infused with AIC100, 3 each in DL 1 and 2. AIC100 was successfully manufactured for all patients and all infusion products met target transduction efficiency. No serious adverse events or DLTs were reported. Two patients had grade 1 CRS. No ICANs was reported. In 3 evaluable patients in DL1, 1 patient had stable disease with decreased FDG activity in PET that correlated with increased activity in the DOATATE scan. From the 3 pts infused in the DL2, one is evaluable for efficacy at day 42. This is a patient with relapsed ATC who achieved PR with 42% reduction in target tumor lesion and remains in PR at 3 mths. The target lesion in this patient showed increased DOTATE avidity at d14 post AIC100 infusion. This was followed by decreased FDG and DOTATE avidity at d42 post AIC100 infusion, concomitant with decreased size, suggesting biological activity 42 days after CAR T infusion. Evaluation of CAR transgene demonstrated transient peripheral blood CAR T cell expansion. The second patient couldn’t be assessed due to early withdrawal for disease-related toxicity. The 3rd patient in DL2 remains in the DLT period, pending efficacy evaluation. Conclusions: AIC100 demonstrated an excellent safety profile in DL1/DL2 treated patients with ATC and PDTC with no DLTs observed. The objective and relatively durable partial response in the first evaluable patient in the DL2, a patient with metastatic ATC who failed multiple lines of therapy, is unprecedented and very encouraging. Further investigations of AIC100 are ongoing at DL2 and DL3 to determine the RP2D. Clinical trial information: NCT04420754 .

Intensity patterns at the peaks of brain activity in fMRI and PET are highly correlated with neural models of spatial integration.

Spatial integration during the brain's cognitive activity prompts changes in energy used by different neuroglial populations. Nevertheless, the organisation of such integration in 3D ‐brain activity remains undescribed from a quantitative standpoint. In response, we applied a cross‐correlation between brain activity and integrative models, which yielded a deeper understanding of information integration in functional brain mapping. We analysed four datasets obtained via fundamentally different neuroimaging techniques (functional magnetic resonance imaging [fMRI] and positron emission tomography [PET]) and found that models of spatial integration with an increasing input to each step of integration were significantly more correlated with brain activity than models with a constant input to each step of integration. In addition, marking the voxels with the maximal correlation, we found exceptionally high intersubject consistency with the initial brain activity at the peaks. Our method demonstrated for the first time that the network of peaks of brain activity is organised strictly according to the models of spatial integration independent of neuroimaging techniques. The highest correlation with models integrating an increasing at each step input suggests that brain activity reflects a network of integrative processes where the results of integration in some neuroglial populations serve as an input to other neuroglial populations.

S9. NEUROIMAGING AND NEUROPHYSIOLOGY BIOMARKERS OF SCHIZOTYPAL PERSONALITY DISORDER: A SYSTEMATIC REVIEW

BackgroundSchizotypal personality disorder (SPD) is a cluster A personality disorder affecting 1.0% of general population, characterised by disturbances in cognition and reality testing dimensions, affect regulation, and interpersonal function. SPD shares similar but attenuated phenomenological, genetic, and neurobiological abnormalities with schizophrenia (SCZ) and is described as part of the continuum of schizophrenia spectrum disorders. Neuroimaging and neurophysiology are the main non-invasive techniques for the investigation of brain structure and function, so they play a crucial role in psychiatric research and for their applications into clinical practice. The present review aims to systematically identify the major neuroimaging and neurophysiology biomarkers of SPD.MethodsThe present review has been conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The protocol was prospectively registered in PROSPERO - International prospective register of systematic reviews. The systematic review was performed to summarise the most comprehensive and updated evidence on functional neuroimaging and neurophysiology findings obtained through different techniques (DW-MRI, DTI, PET, SPECT, fMRI, MRS, EEG) in subjects with SPD.ResultsThe search initially yielded 218 records. After study selection and reference screening, the final set comprised 52 studies. Of the 52 studies included in this review, 9 were on DW-MRI and DTI, 11 were on PET and SPECT, 11 were on fMRI and MRS, and 21 were on EEG. Although it was complex to synthesise all the functional abnormalities found in the included studies into a single, unified, pathogenetic pathway, a common theme that emerged was the dysfunction of brain circuits including striatal, frontal, temporal, limbic regions, and their networks. This dysfunction may be the result of a dysregulation along the dopaminergic pathways and lead to deficits or defects in processes that organise a person’s cognitive-perceptual evaluation of the environment and the relatedness to him/herself. As for the limitations, a quantitative data synthesis was not planned for this work, therefore no meta-analytical integrations are presented in this review. The results of individual neuroimaging studies, in fact, are not comparable due to small and heterogeneous samples, analytical flexibility, or differences in imaging modalities and behavioral tasks.DiscussionBrain abnormalities in SPD are similar, but less marked, than those found in SCZ, and they do not mirror each other. In fact, different patterns of functional abnormalities in SPD and SCZ have been found in this systematic review, suggesting the ‘presence’ of possible compensatory factors, protecting subjects with SPD from frank psychosis and providing diagnostic specificity. Specifically, SPD differentiates from SCZ by showing: (a) milder frontal-striatal-temporal white matter dysconnectivity in DTI studies, (b) lesser frontal and striatal dysfunction and a decreased striatal dopaminergic activity in PET and SPECT studies, respectively, (c) different patterns of dysfunctional activation of frontal-striatal-thalamic circuitry during attentional processing in fMRI studies, and (d) milder alterations in EEG sensory gating and no evidence of alterations in EEG auditory or visual processing.

MRI-Based Attenuation Correction for PET/MRI Using Multiphase Level-Set Method.

Inaccuracy in MR image-based attenuation correction (MR-AC) leads to errors in quantification and the misinterpretation of lesions in brain PET/MRI studies. To resolve this problem, we proposed an improved ultrashort echo time MR-AC method that was based on a multiphase level-set algorithm with main magnetic field (B0) inhomogeneity correction. We also assessed the feasibility of this level-set-based MR-AC method (MR-AC(level)), compared with CT-AC and MR-AC provided by the manufacturer of the PET/MRI scanner (MR-AC(mMR)). Ten healthy volunteers and 20 Parkinson disease patients underwent(18)F-FDG and(18)F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET scans, respectively, using both PET/MRI and PET/CT scanners. The level-set-based segmentation algorithm automatically delimited air, bone, and soft tissue from the ultrashort echo time MR images. For the comparison, MR-AC maps were coregistered to reference CT. PET sinogram data obtained from PET/CT studies were then reconstructed using the CT-AC, MR-AC(mMR), and MR-AC(level) maps. The accuracies of SUV, SUVr (SUV and its ratio to the cerebellum), and specific-to-nonspecific binding ratios obtained using MR-AC(level) and MR-AC(mMR) were compared with CT-AC using region-of-interest- and voxel-based analyses. There was remarkable improvement in the segmentation of air cavities and bones and the quantitative accuracy of PET measurement using the level set. Although the striatal and cerebellar activities in (18)F-FP-CIT PET and frontal activity in (18)F-FDG PET were significantly underestimated by the MR-AC(mMR), the MR-AC(level) provided PET images almost equivalent to the CT-AC images. PET quantification error was reduced by a factor of 3 using MR-AC(level) (SUV error < 10% in MR-AC(level) and < 30% in MR-AC(mMR) [version VB18P], and < 5% in MR-AC(level) and < 15% in MR-AC(mMR) [VB20P]). The results of this study indicate that our new multiphase level-set-based MR-AC method improves the quantitative accuracy of brain PET in PET/MRI studies.

Metabolic Changes Induced by Electrical Stimulation of Prelemniscal Radiations for the Treatment of Parkinson Disease

Objective: The aim of this work was to study mechanisms of action of electrical stimulation of prelemniscal radiations (Raprl) in the treatment of Parkinson disease, using 2-deoxy-2-fluoro-D-glucose (¹⁸F-FDG) Positron Emission Tomography (PET/CT). Materialand Methods: Five patients with PD and predominant unilateral tremor, rigidity and bradykinesia underwent deep brain stimulation (DBS) in contralateral Raprl that improved symptoms from 82.4 to 94.5%. ¹⁸F-FDG PET studies were performed before electrode implantation and after DBS therapy. Changes in metabolic activity in PET were evaluated by the maximal standardized uptake value (MSUV) and statistical parametric mapping (SPM) for regions of interest (ROIs) ipsilateral and contralateral to the stimulation site. ROIs were derived from a preoperative probabilistic tractography and included primary motor, supplementary motor and orbitofrontal cortices: Raprl, ventrolateral thalamus, putamen and cerebellum. Results: No significant MSUV changes occurred in ROIs contralateral to Raprl-DBS. In contrast, MSUV decreased ipsilateral to DBS in Raprl, the thalamus, and the primary and supplementary motor cortices. SPM analysis showed metabolic changes which were significantly different after DBS therapy in all ROIs ipsilateral to DBS compared to those in the contralateral side. Conclusion: Raprl-DBS decreases the metabolic activity of areas anatomically related to its fiber composition. Improvement of symptoms may result from a decrease in pathological overactivity of circuits related to the ROIs.

The assessment of time-of-flight on image quality and quantification with reduced administered activity and scan times in 18F-FDG PET.

The last decade has seen considerable technological innovations in PET detectors with the availability, among other advances, of time-of-flight (TOF). TOF has been shown to increase the signal-to-noise ratio (SNR), which should allow for a reduction in acquired counts while maintaining image quality. Fifty-eight patients referred for routine F-flurodeoxyglucose ((18)F-FDG) oncology PET studies were included in this study. Patients with weight below or above 100 kg were prescribed 350 or 400 MBq of (18)F-FDG, respectively. Listmode data were acquired for 2.5 min per bed position and reconstructed with ordered-subset expectation maximization (OSEM) reconstruction. TOF reconstruction was performed on reduced-count data, with two levels of reduction (-20 and -40% for patients <100 kg and -16 and -30% for patients >100 kg) achieved by clipping the listmode data. Liver SNR, mediastinum mean standardized uptake value (SUV(mean)), and lesion maximum standardized uptake value (SUV(max)) were measured in all images. All images were visually assessed as adequate or suboptimal. No significant difference was seen in mediastinum SUV(mean) or lesion SUV(max) when comparing reduced-count TOF with full-count OSEM images. Compared with the original OSEM images, liver SNR was higher for TOF images using the more conservative -20% reduction of counts (P < 0.001, Wilcoxon's signed-rank test), whereas no significant statistical difference was seen with -40% reductions. Incorporation of TOF allows for a reduction in acquired counts; this method has been implemented at our institution, with administered activity reduced for all patients to 280 MBq and a reduction in scan times for all but the largest patients. This has significantly reduced the patient radiation dose and improved scanner flexibility and throughput.

The effect of patient positioning aids on PET quantification in PET/MR imaging

Clinical PET/MR requires the use of patient positioning aids to immobilize and support patients for the duration of the combined examination. Ancillary immobilization devices contribute to overall attenuation of the PET signal, but are not detected with conventional MR sequences and, hence, are ignored in standard MR-based attenuation correction (MR-AC). We report on the quantitative effect of not accounting for the attenuation of patient positioning aids in combined PET/MR imaging. We used phantom and patient data acquired with positioning aids on a PET/CT scanner (Biograph 16, HI-REZ) to mimic PET/MR imaging conditions. Reference CT-based attenuation maps were generated from measured (original) CT transmission images (origCT-AC). We also created MR-like attenuation maps by following the same conversion procedure of the attenuation values except for the prior delineation and subtraction of the positioning aids from the CT images (modCT-AC). First, a uniform (68)Ge cylinder was positioned centrally in the PET/CT scanner and fixed with a vacuum mattress (10cm thick) and, in a repeat examination, with MR positioning foam pads. Second, 16 patient datasets were selected for subsequent processing. All patients were regionally immobilized with positioning aids: a vacuum mattress for head/neck imaging (nine patients) and a foam mattress for imaging of the lower extremities (seven patients). PET images were reconstructed following CT-based attenuation and scatter correction using the original and modified (MR-like) CT images: PET(origCT-AC) and PET(modCT-AC), respectively. PET images following origCT-AC and modCT-AC were compared visually and in terms of mean differences of voxels with a standardized uptake value of at least 1.0. In addition, we report maximum activity concentration in lesions for selected patients. In the phantom study employing the vacuum mattress the average voxel activity in PET(modCT-AC) was underestimated by 6.4% compared to PET(origCT-AC), with 3.4% of the PET voxels being underestimated by 10% or more. When the MR foam pads were not accounted for during AC, PET(modCT-AC) was underestimated by 1.1% on average, with none of the PET voxels being underestimated by 10% or more. Evaluation of the head/neck patient data showed a decrease of 8.4% ([(68)Ga]DOTATOC) and 7.4% ([(18)F]FDG) when patient positioning aids were not accounted for during AC, while the corresponding decrease was insignificant for the lower extremities. Depending on the size and density of the positioning aids used, a regionally variable underestimation of PET activity following AC is observed when positioning aids are not accounted for. This underestimation may become relevant in combined PET/MR imaging of patients with neuropsychiatric indications, but appears to be of no clinical relevance in imaging the extremities.

Validity, practical utility and reliability of Actigraph accelerometry for the measurement of habitual physical activity in dogs

To test the validity, practical utility, and reliability of the Actigraph GT3-X accelerometer for measurement of habitual physical activity in pet dogs. In the validation study, 30 dogs wore the accelerometer for 1 day while being filmed. Accelerometer and film were synchronised and 10-minute periods of the filmed records were extracted with dogs in continuous periods of sedentary behaviour, light intensity physical activity indoors, light to moderate intensity physical activity outdoors and vigorous physical activity outdoors. For the practical utility and reliability studies, 20 dogs wore the GT3-X accelerometers for 1 week: practical utility was quantified as data loss and was also assessed by owner questionnaire; reliability was determined by 2 to 7 days of monitoring using the Spearman-Brown prophecy formula. In the validation study, accelerometry output differed significantly between activity intensities (Friedman test, P<0·01). In the practical utility study, no data were lost from any dogs and dog owners reported that accelerometry was well tolerated. Reliability of accelerometry output was high: for 3 days of wear, it was 91% [95% confidence interval (CI) 82 to 96] and for 7 days of wear, it was 94% (CI 88 to 97). The GT3-X accelerometer is valid, practical and reliable for the measurement of habitual physical activity in dogs.

Optimization of the Injected Activity in Dynamic 3D PET: A Generalized Approach Using Patient-Specific NECs as Demonstrated by a Series of 15O-H2O Scans

The magnitude of the injected activity (A(0)) has a direct impact on the statistical quality of PET images. This study aimed to develop a generalized method for maximizing the statistical quality of dynamic PET images by optimizing A(0). Patient-specific noise-equivalent counts (PS-NECs) were used as a metric of the statistical quality of each time frame of a dynamic PET image. Previous methodology developed to extrapolate the NEC as a function of A(0) was extended to dynamic PET, enabling the NEC to be extrapolated as a function of both A(0) and the time after injection. This method allowed A(0) to be optimized after a single scan (at a single A(0)), by maximizing the NEC within the time interval for which the parameter estimation is most sensitive. The extrapolation method was validated by a series of (15)O-H(2)O scans of the body acquired in 3-dimensional mode. Each patient (n = 6) underwent between 3 and 6 scans at 1 bed position. The injected activities were varied over a wide range (140-840 MBq). Noise-equivalent counting rate (NECR) versus A(0) curves and the optimal injected activities were calculated from each injection. PS-NECR versus A(0) curves as extrapolated from different injected activities were consistent (coefficient of variation, typically <5%). The optimal injected activities for an individual, as derived from these curves, were also consistent (maximum coefficient of variation, 4.3%). For abdominal (n = 4) and chest (n = 1) scans, we found optimal injected activities of (15)O-H(2)O in the range of 220-350 MBq for estimating blood perfusion (F) and 660-1,070 MBq for estimating the volume of distribution (V(T)). Higher optimal injected activities were found in the case of a pelvic scan (n = 1; 570 MBq for F and 1,530 MBq for V(T)). PS-NECs are a valid and generic method for optimizing the injected activity in PET, allowing scanning protocols to be improved after the collection of an initial, single dynamic dataset. This generic method can be used to estimate the optimal injected activity, which is specific to the patient, tracer, PET scanner, and body region being scanned.

Physics process level discrimination of detections for GATE: Assessment of contamination in SPECT and spurious activity in PET

The GEANT4 application for tomographic emission (GATE) is one of the most detailed Monte Carlo simulation tools for SPECT and PET. It allows for realistic phantoms, complex decay schemes, and a large variety of detector geometries. However, only a fraction of the information in each particle history is available for postprocessing. In order to extend the analysis capabilities of GATE, a flexible framework was developed. This framework allows all detected events to be subdivided according to their type: In PET, true coincidences from others, and in SPECT, geometrically collimated photons from others. The framework of the authors can be applied to any isotope, phantom, and detector geometry available in GATE. It is designed to enhance the usability of GATE for the study of contamination and for the investigation of the properties of current and future prototype detectors. The authors apply the framework to a case study of Bexxar, first assuming labeling with 124I, then with 131I. It is shown that with 124I PET, results with an optimized window improve upon those with the standard window but achieve less than half of the ideal improvement. Nevertheless, 124I PET shows improved resolution compared to 131I SPECT with triple-energy-window scatter correction.