[1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects.

BACKGROUND: Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer's disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid. METHODS: 24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aß+) and 16 Aß- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC. RESULTS: LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aß+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress. CONCLUSION: The data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.

DOTATATE PET/MR Imaging Differentiates Secondary-Progressive from de Novo World Health Organization Grade 3 Meningiomas.

BACKGROUND AND PURPOSE: WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (68Ga) DOTATATE PET/MR imaging. MATERIALS AND METHODS: Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (68Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes. RESULTS: Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P = .0021). CONCLUSIONS: Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support (68Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications.

[Ga68] DOTATATE PET/MRI-Guided Radiosurgical Treatment Planning and Response Assessment in Meningiomas.

BACKGROUND: Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. METHODS: Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and PFS was evaluated using Cox regression. RESULTS: 27 patients with 64 tumors (26% WHO-1, 41% WHO-2, 26% WHO-3, 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) (mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (p < 0.0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. CONCLUSIONS: DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant, however it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery.

Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis.

BACKGROUND: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). OBJECTIVES: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. METHODS: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR-), presence/absence of 18F-FDG (PET+/PET-), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(-), MR(-)PET(+)FOCAL, MR(-)PET(+)DIFFUSE, MR(-)PET(-). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/-)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. RESULTS: Patients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. CONCLUSIONS: Hybrid MR/PET image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image-based classification may have use in prognostication and treatment management in CS.

The potential of a medium-cost long axial FOV PET system for nuclear medicine departments.

PURPOSE: Total body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative. METHODS: Several medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows. CONCLUSIONS: A medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options.

Evaluating diagnostic accuracy and determining optimal diagnostic thresholds of different approaches to [68Ga]-DOTATATE PET/MRI analysis in patients with meningioma.

Multiple approaches with [68Ga]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of different approaches to quantitative brain [68Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method. Patients with suspected meningioma were imaged prospectively with [68Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), using follow-up pathology and MRI as reference standard. Lesions were reclassified using the following methods: absolute maximum SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), SUVR to the pituitary gland (SUVRpit), and SUVR to the normal brain parenchyma (SUVRnorm). Diagnostic performance of the four methods was compared using contingency tables and McNemar's test. Previously published pre-determined thresholds were assessed where applicable. The optimal thresholds for each method were identified using Youden's J statistics. 166 meningiomas and 41 PTC lesions were identified across 62 patients. SUV, SUVRsss, SUVRpit, and SUVRnorm of meningioma were significantly higher than those of PTC (P < 0.0001). The optimal thresholds for SUV, SUVRsss, SUVRpit, and SUVRnorm were 4.7, 3.2, 0.3, and 62.6, respectively. At the optimal thresholds, SUV had the highest specificity (97.6%) and SUVRsss had the highest sensitivity (86.1%). An ROC analysis of SUV, SUVRsss, SUVRpit, and SUVRnorm revealed AUC of 0.932, 0.910, 0.915, and 0.800, respectively (P < 0.0001). Developing a diagnostic threshold is key to wider clinical translation of [68Ga]-DOTATATE PET/MRI in meningioma evaluation. We found that the SUVRsss method may have the most robust combination of sensitivity and specificity in the diagnosis of meningioma in the post-treatment setting, with the optimal threshold of 3.2. Future studies validating our findings in different patient populations are needed to continue optimizing the diagnostic performance of [68Ga]-DOTATATE PET/MRI in meningioma patients.Trial registration: ClinicalTrials.gov Identifier: NCT04081701. Registered 9 September 2019. https://clinicaltrials.gov/ct2/show/NCT04081701 .

Physical performance of adaptive axial FOV PET scanners with a sparse detector block rings or a checkerboard configuration.

Objective.Using Monte-Carlo simulations, we evaluated the physical performance of a hypothetical state-of-the-art clinical PET scanner with adaptive axial field-of-view (AFOV) based on the validated GATE model of the Siemens Biograph VisionTMPET/CT scanner.Approach.Vision consists of 16 compact PET rings, each consisting of 152 mini-blocks of 5 × 5 Lutetium Oxyorthosilicate crystals (3.2 × 3.2 × 20 mm3). The Vision 25.6 cm AFOV was extended by adopting (i) a sparse mini-block ring (SBR) configuration of 49.6 cm AFOV, with all mini-block rings interleaved with 16 mm axial gaps, or (ii) a sparse mini-block checkerboard (SCB) configuration of 51.2 cm AFOV, with all mini-blocks interleaved with gaps of 16 mm (transaxial) × 16 mm (axial) width in checkerboard pattern. For sparse configurations, a 'limited' continuous bed motion (limited-CBM) acquisition was employed to extend AFOVs by 2.9 cm. Spatial resolution, sensitivity, image quality (IQ), NECR and scatter fraction were assessed per NEMA NU2-2012.Main Results.All IQ phantom spheres were distinguishable with all configurations. SBR and SCB percent contrast recovery (% CR) and background variability (% BV) were similar (p-value > 0.05). Compared to Vision, SBR and SCB %CRs were similar (p-values > 0.05). However, SBR and SCB %BVs were deteriorated by 30% and 26% respectively (p-values < 0.05). SBR, SCB and Vision exhibited system sensitivities of 16.6, 16.8, and 15.8 kcps MBq-1, NECRs of 311 kcps @35 kBq cc-1, 266 kcps @25.8 kBq cc-1, and 260 kcps @27.8 kBq cc-1, and scatter fractions of 31.2%, 32.4%, and 32.6%, respectively. SBR and SCB exhibited a smoother sensitivity reduction and noise enhancement rate from AFOV center to its edges. SBR and SCB attained comparable spatial resolution in all directions (p-value > 0.05), yet, up to 1.5 mm worse than Vision (p-values < 0.05).Significance.The proposed sparse configurations may offer a clinically adoptable solution for cost-effective adaptive AFOV PET with either highly-sensitive or long-AFOV acquisitions.

Dynamic 68Ga-DOTATATE PET/MRI in the Diagnosis and Management of Intracranial Meningiomas.

Purpose To evaluate dynamic gallium 68 (68Ga) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) brain PET/MRI as an adjunct modality in meningioma, enabling multiparametric standardized uptake value (SUV) and Patlak net binding rate constant (Ki) imaging, and to optimize static acquisition period. Materials and Methods In this prospective study (ClinicalTrials.gov no. NCT04081701, DOMINO-START), 68Ga-DOTATATE PET/MRI-derived time-activity curves (TACs) were measured in 84 volumes of interest in 19 participants (mean age, 63 years; range, 36-89 years; 13 women; 2019-2021) with meningiomas. Region- and voxel-specific Ki were determined using Patlak analysis with a validated population-based reference tissue TAC model built from an independent data set of nine participants. Mean and maximum absolute and relative-to-superior-sagittal-sinus SUVs were extracted from the entire 50 minutes (SUV50) and last 10 minutes (SUV10) of acquisition. SUV versus Ki Spearman correlation, SUV and Ki meningioma versus posttreatment-change Mann-Whitney U tests, and SUV50 versus SUV10 Wilcoxon matched-pairs signed rank tests were performed. Results Absolute and relative maximum SUV50 demonstrated a strong positive correlation with Patlak Ki in meningioma (r = 0.82, P < .001 and r = 0.85, P < .001, respectively) and posttreatment-change lesions (r = 0.88, P = .007 and r = 0.83, P = .02, respectively). Patlak Ki images yielded higher lesion contrast by mitigating nonspecific background signal. All SUV50 and SUV10 metrics differed between meningioma and posttreatment-change regions (P < .001). Within the meningioma group, SUV10 attained higher mean scores than SUV50 (P < .001). Conclusion Combined SUV and Patlak Ki68Ga-DOTATATE PET/MRI enabled multiparametric evaluation of meningioma, offering the potential to enhance lesion contrast with Ki imaging and optimize the SUV measurement postinjection window. Keywords: Molecular Imaging-Clinical Translation, Neuro-Oncology, PET/MRI, Dynamic, Patlak ClinicalTrials.gov registration no. NCT04081701 © RSNA, 2022.

Assessment of different quantification metrics of [18F]-NaF PET/CT images of patients with abdominal aortic aneurysm.

BACKGROUND: We aim to assess the spill-in effect and the benefit in quantitative accuracy for [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) using the background correction (BC) technique. METHODS: Seventy-two datasets of patients diagnosed with AAA were reconstructed with ordered subset expectation maximization algorithm incorporating point spread function (PSF). Spill-in effect was investigated for the entire aneurysm (AAA), and part of the aneurysm excluding the region close to the bone (AAAexc). Quantifications of PSF and PSF+BC images using different thresholds (% of max. SUV in target regions-of-interest) to derive target-to-background (TBR) values (TBRmax, TBR90, TBR70 and TBR50) were compared at 3 and 10 iterations. RESULTS: TBR differences were observed between AAA and AAAexc due to spill-in effect from the bone into the aneurysm. TBRmax showed the highest sensitivity to the spill-in effect while TBR50 showed the least. The spill-in effect was reduced at 10 iterations compared to 3 iterations, but at the expense of reduced contrast-to-noise ratio (CNR). TBR50 yielded the best trade-off between increased CNR and reduced spill-in effect. PSF+BC method reduced TBR sensitivity to spill-in effect, especially at 3 iterations, compared to PSF (P-value ≤ 0.05). CONCLUSION: TBR50 is robust metric for reduced spill-in and increased CNR.

Scan-rescan measurement repeatability of 18F-FDG PET/MR imaging of vascular inflammation.

Non-invasive positron emission tomography (PET) of vascular inflammation and atherosclerotic plaque by identifying increased uptake of 18F-fluordeoxyglucose (18F-FDG) is a powerful tool for monitoring disease activity, progression, and its response to therapy. 18F-FDG PET/computed tomography (PET/CT) of the aorta and carotid arteries has become widely used to assess changes in inflammation in clinical trials. However, the recent advent of hybrid PET/magnetic resonance (PET/MR) scanners has advantages for vascular imaging due to the reduction in radiation exposure and improved soft tissue contrast of MR compared to CT. Important for research and clinical use is an understanding of the scan-rescan repeatability of the PET measurement. While this has been studied for PET/CT, no data is currently available for vascular PET/MR imaging. In this study, we determined the scan-rescan measurement repeatability of 18F-FDG PET/MR in the aorta and carotid arteries was less than 5%, comparable to similar findings for 18F-FDG PET/CT.

Population-based input function for TSPO quantification and kinetic modeling with [11C]-DPA-713.

INTRODUCTION: Quantitative positron emission tomography (PET) studies of neurodegenerative diseases typically require the measurement of arterial input functions (AIF), an invasive and risky procedure. This study aims to assess the reproducibility of [11C]DPA-713 PET kinetic analysis using population-based input function (PBIF). The final goal is to possibly eliminate the need for AIF. MATERIALS AND METHODS: Eighteen subjects including six healthy volunteers (HV) and twelve Parkinson disease (PD) subjects from two [11C]-DPA-713 PET studies were included. Each subject underwent 90 min of dynamic PET imaging. Five healthy volunteers underwent a test-retest scan within the same day to assess the repeatability of the kinetic parameters. Kinetic modeling was carried out using the Logan total volume of distribution (VT) model. For each data set, kinetic analysis was performed using a patient-specific AIF (PSAIF, ground-truth standard) and then repeated using the PBIF. PBIF was generated using the leave-one-out method for each subject from the remaining 17 subjects and after normalizing the PSAIFs by 3 techniques: (a) Weightsubject×DoseInjected, (b) area under AIF curve (AUC), and (c) Weightsubject×AUC. The variability in the VT measured with PSAIF, in the test-retest study, was determined for selected brain regions (white matter, cerebellum, thalamus, caudate, putamen, pallidum, brainstem, hippocampus, and amygdala) using the Bland-Altman analysis and for each of the 3 normalization techniques. Similarly, for all subjects, the variabilities due to the use of PBIF were assessed. RESULTS: Bland-Altman analysis showed systematic bias between test and retest studies. The corresponding mean bias and 95% limits of agreement (LOA) for the studied brain regions were 30% and ± 70%. Comparing PBIF- and PSAIF-based VT estimate for all subjects and all brain regions, a significant difference between the results generated by the three normalization techniques existed for all brain structures except for the brainstem (P-value = 0.095). The mean % difference and 95% LOA is -10% and ±45% for Weightsubject×DoseInjected; +8% and ±50% for AUC; and +2% and ± 38% for Weightsubject×AUC. In all cases, normalizing by Weightsubject×AUC yielded the smallest % bias and variability (% bias = ±2%; LOA = ±38% for all brain regions). Estimating the reproducibility of PBIF-kinetics to PSAIF based on disease groups (HV/PD) and genotype (MAB/HAB), the average VT values for all regions obtained from PBIF is insignificantly higher than PSAIF (%difference = 4.53%, P-value = 0.73 for HAB; and %difference = 0.73%, P-value = 0.96 for MAB). PBIF also tends to overestimate the difference between PD and HV for HAB (% difference = 32.33% versus 13.28%) and underestimate it in MAB (%difference = 6.84% versus 20.92%). CONCLUSIONS: PSAIF kinetic results are reproducible with PBIF, with variability in VT within that obtained for the test-retest studies. Therefore, VT assessed using PBIF-based kinetic modeling is clinically feasible and can be an alternative to PSAIF.

[68Ga]-DOTATATE PET/MRI as an adjunct imaging modality for radiation treatment planning of meningiomas.

BACKGROUND: Meningiomas express high levels of somatostatin receptor 2 (SSTR2). SSTR2-targeted PET imaging with [68Ga]-DOTATATE can aid with distinguishing residual meningioma from reactive changes in the postoperative setting. We present initial dosimetric analyses, acute events, and local control data utilizing [68Ga]-DOTATATE PET/MRI-assisted target delineation for prospectively-treated intermediate-risk meningiomas. METHODS: Twenty-nine patients underwent DOTATATE PET/MRI meningioma evaluation in 2019. Eight patients with 9 postoperative meningiomas met RTOG 0539 intermediate-risk criteria (recurrent WHO grade I, 1/9; WHO grade II, 8/9). Target volumes were created using DOTATATE PET/MRI to determine residual disease and received a nominal dose of 35.0 Gy over 5 fractions. For comparison, cases were recontoured and planned with MRI alone per RTOG 0539 guidelines. Mean and maximum equivalent 2 Gy doses were generated for target volumes and organs at risk (OAR) within 1 cm of the PTV and compared using Wilcoxon matched pairs signed rank test. RESULTS: DOTATATE PET/MRI-guided planning significantly reduced mean PTV (11.12 cm3 compared to 71.39 cm3 based on MRI alone, P < .05) and mean and max dose to the whole brain, optic nerves, and scalp. PET/MRI plans resulted in at least 50% reduction of mean and max doses to the lens, eyes, chiasm, cochlea, brainstem, and hippocampi. One patient experienced focal alopecia. There were no local recurrences at 6 months. CONCLUSION: Incorporating DOTATATE-PET/MRI for postoperative target delineation in patients with intermediate-risk intracranial meningiomas results in PTV reduction and decreased OAR dose. Our findings warrant larger studies evaluating DOTATATE-PET/MRI in the radiotherapeutic planning of postoperative meningiomas.

PET/MR Imaging of Somatostatin Receptor Expression and Tumor Vascularity in Meningioma: Implications for Pathophysiology and Tumor Outcomes.

BACKGROUND AND PURPOSE: Meningiomas, the most common primary intracranial tumor, are vascular neoplasms that express somatostatin receptor-2 (SSTR2). The purpose of this investigation was to evaluate if a relationship exists between tumor vascularity and SSTR2 expression, which may play a role in meningioma prognostication and clinical management. MATERIALS AND METHODS: Gallium-68-DOTATATE PET/MRI with dynamic contrast-enhanced (DCE) perfusion was prospectively performed. Clinical and demographic patient characteristics were recorded. Tumor volumes were segmented and superimposed onto parametric DCE maps including flux rate constant (Kep), transfer constant (Ktrans), extravascular volume fraction (Ve), and plasma volume fraction (Vp). Meningioma PET standardized uptake value (SUV) and SUV ratio to superior sagittal sinus (SUVRSSS) were recorded. Pearson correlation analyses were performed. In a random subset, analysis was repeated by a second investigator, and intraclass correlation coefficients (ICCs) were determined. RESULTS: Thirty-six patients with 60 meningiomas (20 WHO-1, 27 WHO-2, and 13 WHO-3) were included. Mean Kep demonstrated a strong significant positive correlation with SUV (r = 0.84, p < 0.0001) and SUVRSSS (r = 0.81, p < 0.0001). When stratifying by WHO grade, this correlation persisted in WHO-2 (r = 0.91, p < 0.0001) and WHO-3 (r = 0.92, p = 0.0029) but not WHO-1 (r = 0.26, p = 0.4, SUVRSSS). ICC was excellent (0.97-0.99). CONCLUSION: DOTATATE PET/MRI demonstrated a strong significant correlation between tumor vascularity and SSTR2 expression in WHO-2 and WHO-3, but not WHO-1 meningiomas, suggesting biological differences in the relationship between tumor vascularity and SSTR2 expression in higher-grade meningiomas, the predictive value of which will be tested in future work.

Assessing the qualitative and quantitative impacts of simple two-class vs multiple tissue-class MR-based attenuation correction for cardiac PET/MR.

BACKGROUND: Hybrid PET/MR imaging has significant potential in cardiology due to its combination of molecular PET imaging and cardiac MR. Multi-tissue-class MR-based attenuation correction (MRAC) is necessary for accurate PET quantification. Moreover, for thoracic PET imaging, respiration is known to lead to misalignments of MRAC and PET data that result in PET artifacts. These factors can be addressed by using multi-echo MR for tissue segmentation and motion-robust or motion-gated acquisitions. However, the combination of these strategies is not routinely available and can be prone to errors. In this study, we examine the qualitative and quantitative impacts of multi-class MRAC compared to a more widely available simple two-class MRAC for cardiac PET/MR. METHODS AND RESULTS: In a cohort of patients with cardiac sarcoidosis, we acquired MRAC data using multi-echo radial gradient-echo MR imaging. Water-fat separation was used to produce attenuation maps with up to 4 tissue classes including water-based soft tissue, fat, lung, and background air. Simultaneously acquired 18F-fluorodeoxyglucose PET data were subsequently reconstructed using each attenuation map separately. PET uptake values were measured in the myocardium and compared between different PET images. The inclusion of lung and subcutaneous fat in the MRAC maps significantly affected the quantification of 18F-fluorodeoxyglucose activity in the myocardium but only moderately altered the appearance of the PET image without introduction of image artifacts. CONCLUSION: Optimal MRAC for cardiac PET/MR applications should include segmentation of all tissues in combination with compensation for the respiratory-related motion of the heart. Simple two-class MRAC is adequate for qualitative clinical assessment.

Iterative reconstruction incorporating background correction improves quantification of [18F]-NaF PET/CT images of patients with abdominal aortic aneurysm.

BACKGROUND: A confounding issue in [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) is the spill in contamination from the bone into the aneurysm. This study investigates and corrects for this spill in contamination using the background correction (BC) technique without the need to manually exclude the part of the AAA region close to the bone. METHODS: Seventy-two (72) datasets of patients with AAA were reconstructed with the standard ordered subset expectation maximization (OSEM) algorithm incorporating point spread function (PSF) modelling. The spill in effect in the aneurysm was investigated using two target regions of interest (ROIs): one covering the entire aneurysm (AAA), and the other covering the aneurysm but excluding the part close to the bone (AAAexc). ROI analysis was performed by comparing the maximum SUV in the target ROI (SUVmax(T)), the corrected cSUVmax (SUVmax(T) - SUVmean(B)) and the target-to-blood ratio (TBR = SUVmax(T)/SUVmean(B)) with respect to the mean SUV in the right atrium region. RESULTS: There is a statistically significant higher [18F]-NaF uptake in the aneurysm than normal aorta and this is not correlated with the aneurysm size. There is also a significant difference in aneurysm uptake for OSEM and OSEM + PSF (but not OSEM + PSF + BC) when quantifying with AAA and AAAexc due to the spill in from the bone. This spill in effect depends on proximity of the aneurysms to the bone as close aneurysms suffer more from spill in than farther ones. CONCLUSION: The background correction (OSEM + PSF + BC) technique provided more robust AAA quantitative assessments regardless of the AAA ROI delineation method, and thus it can be considered as an effective spill in correction method for [18F]-NaF AAA studies.

Physical performance of a long axial field-of-view PET scanner prototype with sparse rings configuration: A Monte Carlo simulation study.

PURPOSE: There is a growing interest in extending the axial fields-of-view (AFOV) of PET scanners. One major limitation for the widespread clinical adoption of such systems is the multifold increase in the associated material costs. In this study, we propose a cost-effective solution to extend the PET AFOV using a sparse detector rings configuration. The corresponding physical performance was validated using Monte Carlo simulations. METHODS: Monte Carlo model of the Siemens BiographTM mCT PET/CT, with a 21.8 cm AFOV and a set of compact rings of LSO crystals was developed as a gold standard. The mCT configuration was then modified by interleaving the LSO crystals in the axial direction within each detector block with 4 mm physical gaps (equivalent to the LSO crystal axial dimension) thus extending the AFOV to 43.6 cm (Ex-mCT). The physical performances of the two MC models were assessed and then compared using NEMA NU 2-2007 standards. RESULTS: Ex-mCT showed <0.2 mm difference in transaxial spatial resolution, and, 0.8 mm and 0.3 mm deterioration in axial spatial resolution, compared to the mCT, at 1 and 10 cm off-center of the transaxial field-of-view respectively. The system sensitivities for the mCT and Ex-mCT models were 9.4 ± 0.2 and 10.75 ± 0.2 cps/kBq respectively. The higher sensitivity of Ex-mCT was due to four additional detector rings required to double the mCT AFOV. PET images of the NEMA Image Quality (IQ) phantom showed no artifacts due to detector rings sparsity, and all spheres were visible in both configurations. Ex-mCT achieved percent contrast recoveries within 5.6% of those of the mCT for all spheres and a maximum of 36% higher background variability at the center of the AFOV. The Ex-mCT, however, showed a more uniform noise distribution over an axial range of almost twice the length of the mCT AFOV. CONCLUSIONS: Using the proposed sparse detector-ring configuration, the AFOV of current generation PET systems can be doubled while maintaining the original number and volume of detector crystal elements, and without jeopardizing the system's overall physical performance. Despite an increase in the noise level, the Ex-mCT exhibited an improved noise uniformity.

Comparison of Correction Techniques for the Spill in Effect in Emission Tomography.

In positron emission tomography (PET) imaging, accurate clinical assessment is often affected by the partial volume effect (PVE) leading to overestimation (spill-in) or underestimation (spill-out) of activity in various small regions. The spill-in correction, in particular, can be very challenging when the target region is close to a hot background region. Therefore, this study evaluates and compares the performance of various recently developed spill-in correction techniques, namely: background correction (BC), local projection (LP), and hybrid kernelized (HKEM) methods. We used a simulated digital phantom and [18F]-NaF PET data of three patients with abdominal aortic aneurysms (AAA) acquired with Siemens Biograph mMR™ and mCT™ scanners respectively. Region of Interest (ROI) analysis was performed and the extracted SUV mean , SUV max and target-to-background ratio (TBR) scores were compared. Results showed substantial spill-in effects from hot regions to targeted regions, which are more prominent in small structures. The phantom experiment demonstrated the feasibility of spill-in correction with all methods. For the patient data, large differences in SUV mean , SUV max and TBR max scores were observed between the ROIs drawn over the entire aneurysm and ROIs excluding some regions close to the bone. Overall, BC yielded the best performance in spill-in correction in both phantom and patient studies.

Hybrid PET- and MR-driven attenuation correction for enhanced 18F-NaF and 18F-FDG quantification in cardiovascular PET/MR imaging.

BACKGROUND: The standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from 18F-Sodium Fluoride (18F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18F-NaF and 18F-Fluorodeoxyglucose (18F-FDG) PET/MR cardiovascular imaging. METHODS: We introduce 5-class Ki/MR-AC for (i) 18F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) 18F-FDG-only data, with a streamlined simultaneous administration of 18F-FDG and 18F-NaF at 4:1 ratio (R4:1), or (iii) for 18F-FDG-only or both 18F-FDG and 18F-NaF dual-tracer data, by administering 18F-NaF 90 minutes after an equal 18F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD). RESULTS: In rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (18F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18F-FDG:18F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (18F-FDG) and 15.5% (18F-NaF) at carotid bifurcations and 21.6% (18F-FDG) and 22.5% (18F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication. CONCLUSIONS: Ki-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18F-NaF and 18F-FDG contrast and quantification in bone tissues and carotid walls.

Imager-4D: New Software for Viewing Dynamic PET Scans and Extracting Radiomic Parameters from PET Data.

Extensive research is currently being conducted into dynamic positron emission tomography (PET) acquisitions (including dynamic whole-body imaging) as well as extraction of radiomic features from imaging modalities. We describe a new PET viewing software known as Imager-4D that provides a facile means of viewing and analyzing dynamic PET data and obtaining associated quantitative metrics including radiomic parameters. The Imager-4D was programmed in the Java language utilizing the FX extensions. It is executable on any system for which a Java w/FX compliant virtual machine is available. The software incorporates the ability to view and analyze dynamic data acquired with different types of dynamic protocols. For image display, the program maintains a built-in library of 62 different lookup tables with monochromatic and full-color distributions. The Imager-4D provides multiple display layouts and can display fused images. Multiple methods of volume-of-interest (VOI) selection are available. Dynamic analysis features, such as image summation and full Patlak analysis, are also available. The user interface includes window width and level, blending, and zoom functionality. VOI sizes are adjustable and data from VOIs can either be displayed numerically or graphically within the software or exported. An example case of a 50-year-old woman with metastatic colorectal cancer and thyroiditis is included and demonstrates the steps for a user to obtain standard PET parameters, dynamic data, and radiomic features using selected VOIs. The Imager-4D represents a novel PET viewer that allows the user to view dynamic PET data, to derive dynamic and radiomic parameters from that data, and to combine dynamic data with radiomics ("dynomics"). The Imager-4D is available as a free download. This software has the potential to speed the adoption of advanced analysis of dynamic PET data into routine clinical use.