Diagnostic Performance of [18F]TFB PET/CT Compared with Therapeutic Activity [131I]Iodine SPECT/CT and [18F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma.

[18F]tetrafluoroborate ([18F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [18F]TFB PET with high-activity posttherapeutic [131I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [18F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [131I]iodine therapy (range, 5.00-10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [18F]TFB PET/CT 40 min after injection of a median of 321 MBq of [18F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [131I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [18F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [131I]iodine positive, 32 lesions were [18F]TFB positive, and 52 were [18F]FDG positive. Three of the 30 [131I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [18F]TFB uptake and [18F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, -0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [18F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [131I]iodine scans. Therefore, it may help in the selection of patients for [131I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [18F]TFB uptake seems to be inversely correlated with [18F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC.

Dispersion-corrected extracorporeal arterial input functions in PET studies of mice: a comparison to intracorporeal microprobe measurements.

BACKGROUND: Kinetic modelling of dynamic PET typically requires knowledge of the arterial radiotracer concentration (arterial input function, AIF). Its accurate determination is very difficult in mice. AIF measurements in an extracorporeal shunt can be performed; however, this introduces catheter dispersion. We propose a framework for extracorporeal dispersion correction and validated it by comparison to invasively determined intracorporeal AIFs using implanted microprobes. RESULTS: The response of an extracorporeal radiation detector to radioactivity boxcar functions, characterised by a convolution-based dispersion model, gave best fits using double-gamma variate and single-gamma variate kernels compared to mono-exponential kernels for the investigated range of flow rates. Parametric deconvolution with the optimal kernels was performed on 9 mice that were injected with a bolus of 39 ± 25 MBq [18F]F-PSMA-1007 after application of an extracorporeal circulation for three different flow rates in order to correct for dispersion. Comparison with synchronous implantation of microprobes for invasive aortic AIF recordings showed favourable correspondence, with no significant difference in terms of area-under-curve after 300 s and 5000 s. One-tissue and two-tissue compartment model simulations were performed to investigate differences in kinetic parameters between intra- and extracorporeally measured AIFs. Results of the modelling study revealed kinetic parameters close to the chosen simulated values in all compartment models. CONCLUSION: The high correspondence of simultaneously intra- and extracorporeally determined AIFs and resulting model parameters establishes a feasible framework for extracorporeal dispersion correction. This should allow more precise and accurate kinetic modelling in small animal experiments.

Tumor-Targeted Interleukin 2 Boosts the Anticancer Activity of FAP-Directed Radioligand Therapeutics.

We studied the antitumor efficacy of a combination of 177Lu-labeled radioligand therapeutics targeting the fibroblast activation protein (FAP) (OncoFAP and BiOncoFAP) with the antibody-cytokine fusion protein L19-interleukin 2 (L19-IL2) providing targeted delivery of interleukin 2 to tumors. Methods: The biodistribution of 177Lu-OncoFAP and 177Lu-BiOncoFAP at different molar amounts (3 vs. 250 nmol/kg) of injected ligand was studied via SPECT/CT in mice bearing subcutaneous HT-1080.hFAP tumors, and self-absorbed tumor and organ doses were calculated. The in vivo anticancer effect of 5 MBq of the radiolabeled preparations was evaluated as monotherapy or in combination with L19-IL2 in subcutaneously implanted HT-1080.hFAP and SK-RC-52.hFAP tumors. Tumor samples from animals treated with 177Lu-BiOncoFAP, L19-IL2, or both were analyzed by mass spectrometry-based proteomics to identify therapeutic signatures on cellular and stromal markers of cancer and on immunomodulatory targets. Results: 177Lu-BiOncoFAP led to a significantly higher self-absorbed dose in FAP-positive tumors (0.293 ± 0.123 Gy/MBq) than did 177Lu-OncoFAP (0.157 ± 0.047 Gy/MBq, P = 0.01) and demonstrated favorable tumor-to-organ ratios at high molar amounts of injected ligand. Administration of L19-IL2 or 177Lu-BiOncoFAP as single agents led to cancer cures in only a limited number of treated animals. In 177Lu-BiOncoFAP-plus-L19-IL2 combination therapy, complete remissions were observed in all injected mice (7/7 complete remissions for the HT-1080.hFAP model, and 4/4 complete remissions for the SK-RC-52.hFAP model), suggesting therapeutic synergy. Proteomic studies revealed a mechanism of action based on the activation of natural killer cells, with a significant enhancement of the expression of granzymes and perforin 1 in the tumor microenvironment after combination treatment. Conclusion: The combination of OncoFAP-based radioligand therapeutics with concurrent targeting of interleukin 2 shows synergistic anticancer effects in the treatment of FAP-positive tumors. This experimental finding should be corroborated by future clinical studies.

Initial Results of 68Ga-FAPI-46 PET/MRI to Assess Response to Neoadjuvant Chemotherapy in Breast Cancer.

Improving imaging-based response after neoadjuvant chemotherapy (NAC) in breast cancer assessment could obviate histologic confirmation of pathologic complete response (pCR) and facilitate deescalation of chemotherapy or surgery. Fibroblast activation protein inhibitor (FAPI) PET/MRI is a promising novel molecular imaging agent for the tumor microenvironment with intense uptake in breast cancer. We assessed the diagnostic performance of follow-up breast 68Ga-FAPI-46 (68Ga-FAPI) PET/MRI in classifying the response status of local breast cancer and lymph node metastases after completion of NAC and validated this approach immunohistochemically. Methods: In women who completed NAC for invasive breast cancer, follow-up 68Ga-FAPI PET/MRI and corresponding fibroblast activation protein (FAP) immunostainings were retrospectively analyzed. Metrics of 68Ga-FAPI uptake and FAP immunoreactivity in women with or without pCR were compared using the Mann-Whitney U test. Diagnostic performance to detect remnant invasive cancer was calculated for tracer uptake metrics using receiver-operating-characteristic curves and for masked readers' visual assessment categories of PET/MRI and MRI alone. Results: Thirteen women (mean age ± SD, 47 ± 9 y) were evaluated. Seven of the 13 achieved pCR in the breast and 6 in the axilla. FAP immunoreactivity was significantly associated with response status. The 68Ga-FAPI PET/MRI mean breast tumor-to-background ratio was 0.9 (range, 0.6-1.2) for pCR and 2.1 (range, 1.4-3.1) for no pCR (P = 0.001). Integrated PET/MRI could classify breast response correctly in all 13 women based on readers' visual assessment or tumor-to-background ratio. Evaluation of MRI alone resulted in at least 2 false-positives. For lymph nodes, PET/MRI readers had at least 2 false-negative classifications, whereas MRI alone resulted in 2 false-negatives and 1 false-positive. Conclusion: To our knowledge, this was the first analysis of 68Ga-FAPI PET/MRI for response assessment after NAC for breast cancer. The diagnostic performance of PET/MRI in a small study sample trended toward a gain over MRI alone, clearly supporting future prospective studies.

Lesion Quantification Accuracy of Digital 90Y PET Imaging in the Context of Dosimetry in Systemic Fibroblast Activation Protein Inhibitor Radionuclide Therapy.

Therapy with 90Y-labeled fibroblast activation protein inhibitors (90Y-FAPIs) was recently introduced as a novel treatment concept for patients with solid tumors. Lesion and organ-at-risk dosimetry is part of assessing treatment efficacy and safety and requires reliable quantification of tissue uptake. As 90Y quantification is limited by the low internal positron-electron pair conversion rate, the increased effective sensitivity of digital silicon photomultiplier-based PET/CT systems might increase quantification accuracy and, consequently, allow for dosimetry in 90Y-FAPI therapy. The aim of this study was to explore the conditions for reliable lesion image quantification in 90Y-FAPI radionuclide therapy using a digital PET/CT system. Methods: Two tumor phantoms were filled with 90Y solution using different sphere activity concentrations and a constant signal-to-background ratio of 40. The minimum detectable activity concentration was determined, and its dependence on acquisition time (15 vs. 30 min per bed position) and smoothing levels (all-pass vs. 5-mm gaussian filter) was investigated. Quantification accuracy was evaluated at various activity concentrations to estimate the minimum quantifiable activity concentration using contour-based and oversized volume-of-interest-based quantification approaches. A ±20% deviation range between image-derived and true activity concentrations was regarded as acceptable. Tumor dosimetry for 3 patients treated with 90Y-FAPI is presented to project the phantom results to clinical scenarios. Results: For a lesion size of 40 mm and a clinical acquisition time of 15 min, both minimum detectable and minimum quantifiable activity concentrations were 0.12 MBq/mL. For lesion sizes of greater than or equal to 30 mm, accurate quantification was feasible for detectable lesions. Only for the smallest 10-mm sphere, the minimum detectable and minimum quantifiable activity concentrations differ substantially (0.43 vs. 1.97 MBq/mL). No notable differences between the 2 quantification approaches were observed. For the investigated tumors, absorbed dose estimates with reliable accuracy were achievable. Conclusion: For lesion sizes and activity concentrations that are expected to be observed in patients treated with 90Y-FAPI, quantification with reasonable accuracy is possible. Further dosimetry studies are needed to thoroughly investigate the efficacy and safety of 90Y-FAPI therapy.

Respiratory motion correction in F-18-FDG PET/CT impacts lymph node assessment in lung cancer patients.

BACKGROUNDS: Elastic motion correction in PET has been shown to increase image quality and quantitative measurements of PET datasets affected by respiratory motion. However, little is known on the impact of respiratory motion correction on clinical image evaluation in oncologic PET. This study evaluated the impact of motion correction on expert readers' lymph node assessment of lung cancer patients. METHODS: Forty-three patients undergoing F-18-FDG PET/CT for the staging of suspected lung cancer were included. Three different PET reconstructions were investigated: non-motion-corrected ("static"), belt gating-based motion-corrected ("BG-MC") and data-driven gating-based motion-corrected ("DDG-MC"). Assessment was conducted independently by two nuclear medicine specialists blinded to the reconstruction method on a six-point scale [Formula: see text] ranging from "certainly negative" (1) to "certainly positive" (6). Differences in [Formula: see text] between reconstruction methods, accounting for variation caused by readers, were assessed by nonparametric regression analysis of longitudinal data. From [Formula: see text], a dichotomous score for N1, N2, and N3 ("negative," "positive") and a subjective certainty score were derived. SUV and metabolic tumor volumes (MTV) were compared between reconstruction methods. RESULTS: BG-MC resulted in higher scores for N1 compared to static (p = 0.001), whereas DDG-MC resulted in higher scores for N2 compared to static (p = 0.016). Motion correction resulted in the migration of N1 from tumor free to metastatic on the dichotomized score, consensually for both readers, in 3/43 cases and in 2 cases for N2. SUV was significantly higher for motion-corrected PET, while MTV was significantly lower (all p < 0.003). No significant differences in the certainty scores were noted. CONCLUSIONS: PET motion correction resulted in significantly higher lymph node assessment scores of expert readers. Significant effects on quantitative PET parameters were seen; however, subjective reader certainty was not improved.

First experiences with dynamic renal [68Ga]Ga-DOTA PET/CT: a comparison to renal scintigraphy and compartmental modelling to non-invasively estimate the glomerular filtration rate.

PURPOSE: The determination of the glomerular filtration rate (GFR) is decisive for a variety of clinical issues, for example, to monitor the renal function in radionuclide therapy patients. Renal scintigraphy using glomerularly filtered tracers allows combined acquisition of renograms and GFR estimation but requires repeated blood sampling for several hours. In contrast, dynamic PET imaging using the glomerularly filtered tracer [68Ga]Ga-DOTA bears the potential to non-invasively estimate the GFR by compartmental kinetic modelling. Here, we report the, to our knowledge, first comparison of human renal dynamic [68Ga]Ga-DOTA PET imaging in comparison to renal scintigraphy and compare PET-derived to serum creatinine-derived GFR measurements. METHODS: Dynamic [68Ga]Ga-DOTA PET data were acquired for 30 min immediately after tracer injection in 12 patients. PET and renal scintigraphy images were visually interpreted in a consensus read by three nuclear medicine physicians. The functional renal cortex was segmented to obtain time-activity curves. The arterial input function was estimated from the PET signal in the abdominal aorta. Single-compartmental tracer kinetic modelling was performed to calculate the GFR using complete 30-min (GFRPET-30) and reduced 15-min PET data sets (GFRPET-15) to evaluate whether a shorter acquisition time is sufficient for an accurate GFR estimation. A modified approach excluding minutes 2 to 10 was applied to reduce urinary spill-over effects. Serum creatinine-derived GFRCKD (CKD-EPI-formula) was used as reference standard. RESULTS: PET image interpretation revealed the same findings as conventional scintigraphy (2/12 patients with both- and 1/12 patients with right-sided urinary obstruction). Model fit functions were substantially improved for the modified approach to exclude spill-over. Depending on the modelling approach, GFRCKD and both GFRPET-30 and GFRPET-15 were well correlated with interclass correlation coefficients (ICCs) from 0.74 to 0.80 and Pearson's correlation coefficients (PCCs) from 0.74 to 0.81. For a subgroup of patients with undisturbed urinary efflux (n = 9), correlations were good to excellent (ICCs from 0.82 to 0.95 and PCCs from 0.83 to 0.95). Overall, GFRPET-30 and GFRPET-15 were excellently correlated (ICCs from 0.96 to 0.99 and PCCs from 0.96 to 0.99). CONCLUSION: Renal [68Ga]Ga-DOTA PET can be a suitable alternative to conventional scintigraphy. Visual assessment of PET images and conventional renograms revealed comparable results. GFR values derived by non-invasive single-compartmental-modelling of PET data show a good correlation to serum creatinine-derived GFR values. In patients with undisturbed urinary efflux, the correlation was excellent. Dynamic PET data acquisition for 15 min is sufficient for visual evaluation and GFR derivation.

Hybrid CMR- and FDG-PET-Imaging Gives New Insights Into the Relationship of Myocardial Metabolic Activity and Fibrosis in Patients With Becker Muscular Dystrophy.

BACKGROUND: Cardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course. PURPOSE: Since the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach. METHODS: Hybrid CMR- and FDG-PET-imaging was performed in N = 14 patients with BMD on a whole-body Biograph mMR system (Siemens, Erlangen, Germany). The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 min starting with tracer injection. Uptake values from 60 to 65 min p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake. RESULTS: A characteristic pattern of LGE in the LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. There was one patient without any LGE. Segmental FDG uptake was 88 ± 6% in the LV lateral wall vs. 77 ± 10% in the septal wall (p < 0.001). There was an inverse relationship between segmental FDG activity compared to segmental LGE extent (r = -0.33, p = 0.089). There were N = 6 LGE-positive patients with a segmental difference in FDG uptake of >15% in the LV lateral wall compared to the septal wall = ΔFDG-high group (lateral FDG = 91±3% vs. septal FDG = 69±8%; p < 0.001) while the remaining N = 7 LGE-positive patients showed a segmental difference in FDG uptake of ≤ 15% = ΔFDG-low group (lateral FDG = 85±7% vs. septal FDG = 83 ± 5%; p = 0.37). Patients in the ΔFDG-high group showed only a minor difference in the LGE extent between the LV lateral wall vs. septal wall (p = 0.09) whereas large differences were observed in the ΔFDG-low group (p < 0.004). CONCLUSIONS: Segmental FDG uptake-reflecting myocardial metabolic activity-is higher in the LV free wall of BMD patients-possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging.

Simultaneous FAPI PET/MRI Targeting the Fibroblast-Activation Protein for Breast Cancer.

Background Integrated PET/MRI is a promising modality for breast assessment. The most frequently used tracer, fluorine 18 (18F) fluorodeoxyglucose (FDG), is applied for whole-body staging in advanced breast cancer but has limited accuracy in evaluating primary breast lesions. The fibroblast-activation protein (FAP) is abundantly expressed in invasive breast cancer. FAP-directed PET tracers have recently become available, but results in primary breast tumors remain lacking. Purpose To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 (68Ga)-FAPI-46. Materials and Methods In women with histologically confirmed invasive breast cancer, all primary 68Ga-FAPI-46 breast and whole-body PET/MRI and PET/CT examinations conducted at the authors' center between October 2019 and December 2020 were retrospectively analyzed. MRI lesion characteristics and standardized uptake values (SUVs) were quantified with dedicated software. Mann-Whitney U tests were used to compare tumor SUVs across different tumor types. The Pearson correlation coefficient was calculated between SUV and measures of MRI morphologic characteristics. Results Nineteen women (mean age, 49 years ± 9 [standard deviation]) were evaluated-18 to complement initial staging and one for restaging after therapy for distant metastases. Strong tracer accumulation was observed in all 18 untreated primary breast malignancies (mean maximum SUV [SUVmax] = 13.9 [range, 7.9-29.9]; median lesion diameter = 26 mm [range, 9-155 mm]), resulting in clear tumor delineation across different gradings, receptors, and histologic types. All preoperatively verified LN metastases in 13 women showed strong tracer accumulation (mean SUVmax= 12.2 [range, 3.3-22.4]; mean diameter = 21 mm [range, 14-35 mm]). Tracer uptake established or supported extra-axillary LN involvement in seven women and affected therapy decisions in three women. Conclusion This retrospective analysis indicates use of 68Ga fibroblast-activation protein inhibitor tracers for breast cancer diagnosis and staging. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mankoff and Sellmyer in this issue.

Comparison of two elastic motion correction approaches for whole-body PET/CT: motion deblurring vs gate-to-gate motion correction.

BACKGROUND: Respiratory motion in PET/CT leads to well-known image degrading effects commonly compensated using elastic motion correction approaches. Gate-to-gate motion correction techniques are promising tools for improving clinical PET data but suffer from relatively long reconstruction times. In this study, the performance of a fast elastic motion compensation approach based on motion deblurring (DEB-MC) was evaluated on patient and phantom data and compared to an EM-based fully 3D gate-to-gate motion correction method (G2G-MC) which was considered the gold standard. METHODS: Twenty-eight patients were included in this study with suspected or confirmed malignancies in the thorax or abdomen. All patients underwent whole-body [18F]FDG PET/CT examinations applying hardware-based respiratory gating. In addition, a dynamic anthropomorphic thorax phantom was studied with PET/CT simulating tumour motion under controlled but realistic conditions. PET signal recovery values were calculated from phantom scans by comparing lesion activities after motion correction to static ground truth data. Differences in standardized uptake values (SUV) and metabolic volume (MV) between both reconstruction methods as well as between motion-corrected (MC) and non motion-corrected (NOMC) results were statistically analyzed using a Wilcoxon signed-rank test. RESULTS: Phantom data analysis showed high lesion recovery values of 91% (2 cm motion) and 98% (1 cm) for G2G-MC and 83% (2 cm) and 90% (1 cm) for DEB-MC. The statistical analysis of patient data found significant differences between NOMC and MC reconstructions for SUV max, SUV mean, MV, and contrast-to-noise ratio (CNR) for both reconstruction algorithms. Furthermore, both methods showed similar increases of 11-12% in SUV max and SUV mean after MC. The statistical analysis of the MC/NOMC ratio found no significant differences between the methods. CONCLUSION: Both motion correction techniques deliver comparable improvements of SUV max, SUV mean, and CNR after MC on clinical and phantom data. The fast elastic motion compensation technique DEB-MC may thereby be a valuable alternative to state-of-the art motion correction techniques.

Toward precise arterial input functions derived from DCE-MRI through a novel extracorporeal circulation approach in mice.

PURPOSE: Dynamic contrast-enhanced MRI can be used in pharmacokinetic models to quantify functional parameters such as perfusion and permeability. However, precise quantification in preclinical models is challenged by the difficulties to dynamically measure the true arterial blood contrast agent concentration. We propose a novel approach toward a precise and experimentally feasible method to derive the arterial input function from DCE-MRI in mice. METHODS: Arterial blood was surgically shunted from the femoral artery to the tail vein and led through an extracorporeal circulation that resided on the head of brain tumor-bearing mice inside the FOV of a 9.4T MRI scanner. Dynamic 3D-FLASH scanning was performed after injection of gadobutrol with an effective resolution of 0.175 × 0.175 × 1 mm and a temporal resolution of 4 seconds. Pharmacokinetic modeling was performed using the extended Tofts and two-compartment exchange model. RESULTS: Arterial input functions measured inside the extracorporeal circulation showed little noise, small interindividual variance, and typical curve shapes. Ex vivo and mass spectrometry validation measurements documented the influence of shunt flow velocity and hematocrit on estimation of contrast agent concentrations. Modeling of tumors and muscles allowed fitting of the recorded dynamic concentrations, resulting in quantitative plausible parameters. CONCLUSION: The extracorporeal circulation allows deriving the contrast agent dynamics in arterial blood with high robustness and at acceptable experimental effort from DCE-MRI, previously not achievable in mice. It sets the basis for quantitative precise pharmacokinetic modeling in small animals to enhance the translatability of preclinical DCE-MRI measurements to patients.

Clinical Evaluation of a Data-Driven Respiratory Gating Algorithm for Whole-Body PET with Continuous Bed Motion.

Respiratory gating is the standard to prevent respiration effects from degrading image quality in PET. Data-driven gating (DDG) using signals derived from PET raw data is a promising alternative to gating approaches requiring additional hardware (e.g., pressure-sensitive belt gating [BG]). However, continuous-bed-motion (CBM) scans require dedicated DDG approaches for axially extended PET, compared with DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort and compared with BG using optimally gated (OG) and fully motion-corrected (elastic motion correction [EMOCO]) reconstructions. Methods: Fifty-six patients with suspected malignancies in the thorax or abdomen underwent whole-body 18F-FDG CBM PET/CT using DDG and BG. Correlation analyses were performed on both gating signals. Besides static reconstructions, OG and EMOCO reconstructions were used for BG and DDG. The metabolic volume, SUVmax, and SUVmean of lesions were compared among the reconstructions. Additionally, the quality of lesion delineation in the different PET reconstructions was independently evaluated by 3 experts. Results: The global correlation coefficient between BG and DDG signals was 0.48 ± 0.11, peaking at 0.89 ± 0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO, and DDG-EMOCO than in static images (P < 0.001; median SUVmax: static, 14.3 ± 13.4; BG-EMOCO, 19.8 ± 15.7; DDG-EMOCO, 20.5 ± 15.6; BG-OG, 19.6 ± 17.1; and DDG-OG, 18.9 ± 16.6). No significant differences between BG-OG and DDG-OG or between BG-EMOCO and DDG-EMOCO were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P < 0.001); no significant difference was found when comparing BG and DDG for either EMOCO or OG reconstruction. Conclusion: DDG-based motion compensation of CBM PET acquisitions outperforms static reconstructions, delivering qualities comparable to BG approaches. The new algorithm may be a valuable alternative for CBM PET systems.

Data-driven, projection-based respiratory motion compensation of PET data for cardiac PET/CT and PET/MR imaging.

BACKGROUND: Respiratory patient motion causes blurring of the PET images that may impact accurate quantification of perfusion and infarction extents in PET myocardial viability studies. In this study, we investigate the feasibility of correcting for respiratory motion directly in the PET-listmode data prior to image reconstruction using a data-driven, projection-based, respiratory motion compensation (DPR-MoCo) technique. METHODS: The DPR-MoCo method was validated using simulations of a XCAT phantom (Biograph mMR PET/MR) as well as experimental phantom acquisitions (Biograph mCT PET/CT). Seven patient studies following a dual-tracer (18F-FDG/13N-NH3) imaging-protocol using a PET/MR-system were also evaluated. The performance of the DPR-MoCo method was compared against reconstructions of the acquired data (No-MoCo), a reference gate method (gated) and an image-based MoCo method using the standard reconstruction-transform-average (RTA-MoCo) approach. The target-to-background ratio (TBRLV) in the myocardium and the noise in the liver (CoVliver) were evaluated for all acquisitions. For all patients, the clinical effect of the DPR-MoCo was assessed based on the end-systolic (ESV), the end-diastolic volumes (EDV) and the left ventricular ejection fraction (EF) which were compared to functional values obtained from the cardiac MR. RESULTS: The DPR-MoCo and the No-MoCo images presented with similar noise-properties (CoV) (P = .12), while the RTA-MoCo and reference-gate images showed increased noise levels (P = .05). TBRLV values increased for the motion limited reconstructions when compared to the No-MoCo reconstructions (P > .05). DPR-MoCo results showed higher correlation with the functional values obtained from the cardiac MR than the No-MoCo results, though non-significant (P > .05). CONCLUSION: The projection-based DPR-MoCo method helps to improve PET image quality of the myocardium without the need for external devices for motion tracking.

Data-driven gating in PET: Influence of respiratory signal noise on motion resolution.

PURPOSE: Data-driven gating (DDG) approaches for positron emission tomography (PET) are interesting alternatives to conventional hardware-based gating methods. In DDG, the measured PET data themselves are utilized to calculate a respiratory signal, that is, subsequently used for gating purposes. The success of gating is then highly dependent on the statistical quality of the PET data. In this study, we investigate how this quality determines signal noise and thus motion resolution in clinical PET scans using a center-of-mass-based (COM) DDG approach, specifically with regard to motion management of target structures in future radiotherapy planning applications. METHODS: PET list mode datasets acquired in one bed position of 19 different radiotherapy patients undergoing pretreatment [18 F]FDG PET/CT or [18 F]FDG PET/MRI were included into this retrospective study. All scans were performed over a region with organs (myocardium, kidneys) or tumor lesions of high tracer uptake and under free breathing. Aside from the original list mode data, datasets with progressively decreasing PET statistics were generated. From these, COM DDG signals were derived for subsequent amplitude-based gating of the original list mode file. The apparent respiratory shift d from end-expiration to end-inspiration was determined from the gated images and expressed as a function of signal-to-noise ratio SNR of the determined gating signals. This relation was tested against additional 25 [18 F]FDG PET/MRI list mode datasets where high-precision MR navigator-like respiratory signals were available as reference signal for respiratory gating of PET data, and data from a dedicated thorax phantom scan. RESULTS: All original 19 high-quality list mode datasets demonstrated the same behavior in terms of motion resolution when reducing the amount of list mode events for DDG signal generation. Ratios and directions of respiratory shifts between end-respiratory gates and the respective nongated image were constant over all statistic levels. Motion resolution d/dmax could be modeled as d/dmax=1-e-1.52(SNR-1)0.52, with dmax as the actual respiratory shift. Determining dmax from d and SNR in the 25 test datasets and the phantom scan demonstrated no significant differences to the MR navigator-derived shift values and the predefined shift, respectively. CONCLUSIONS: The SNR can serve as a general metric to assess the success of COM-based DDG, even in different scanners and patients. The derived formula for motion resolution can be used to estimate the actual motion extent reasonably well in cases of limited PET raw data statistics. This may be of interest for individualized radiotherapy treatment planning procedures of target structures subjected to respiratory motion.

PET attenuation correction for flexible MRI surface coils in hybrid PET/MRI using a 3D depth camera.

PET attenuation correction for flexible MRI radio frequency surface coils in hybrid PET/MRI is still a challenging task, as position and shape of these coils conform to large inter-patient variabilities. The purpose of this feasibility study is to develop a novel method for the incorporation of attenuation information about flexible surface coils in PET reconstruction using the Microsoft Kinect V2 depth camera. The depth information is used to determine a dense point cloud of the coil's surface representing the shape of the coil. From a CT template-acquired once in advance-surface information of the coil is extracted likewise and converted into a point cloud. The two point clouds are then registered using a combination of an iterative-closest-point (ICP) method and a partially rigid registration step. Using the transformation derived through the point clouds, the CT template is warped and thereby adapted to the PET/MRI scan setup. The transformed CT template is converted into an attenuation map from Hounsfield units into linear attenuation coefficients. The resulting fitted attenuation map is then integrated into the MRI-based patient-specific DIXON-based attenuation map of the actual PET/MRI scan. A reconstruction of phantom PET data acquired with the coil present in the field-of-view (FoV), but without the corresponding coil attenuation map, shows large artifacts in regions close to the coil. The overall count loss is determined to be around 13% compared to a PET scan without the coil present in the FoV. A reconstruction using the new µ-map resulted in strongly reduced artifacts as well as increased overall PET intensities with a remaining relative difference of about 1% to a PET scan without the coil in the FoV.

Anthropomorphic thorax phantom for cardio-respiratory motion simulation in tomographic imaging.

Patient motion during medical imaging using techniques such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), or single emission computed tomography (SPECT) is well known to degrade images, leading to blurring effects or severe artifacts. Motion correction methods try to overcome these degrading effects. However, they need to be validated under realistic conditions. In this work, a sophisticated anthropomorphic thorax phantom is presented that combines several aspects of a simulator for cardio-respiratory motion. The phantom allows us to simulate various types of cardio-respiratory motions inside a human-like thorax, including features such as inflatable lungs, beating left ventricular myocardium, respiration-induced motion of the left ventricle, moving lung lesions, and moving coronary artery plaques. The phantom is constructed to be MR-compatible. This means that we can not only perform studies in PET, SPECT and CT, but also inside an MRI system. The technical features of the anthropomorphic thorax phantom Wilhelm are presented with regard to simulating motion effects in hybrid emission tomography and radiotherapy. This is supplemented by a study on the detectability of small coronary plaque lesions in PET/CT under the influence of cardio-respiratory motion, and a study on the accuracy of left ventricular blood volumes.

Impact of PET acquisition durations on image quality and lesion detectability in whole-body 68Ga-PSMA PET-MRI.

BACKGROUND: While 68Ga-PSMA PET-MRI might be superior to PET-CT with regard to soft tissue assessment in prostate cancer evaluation, it is also known to potentially introduce additional PET image artefacts. Therefore, the impact of PET acquisition duration and attenuation data on artefact occurrence, lesion detectability, and quantification was investigated. To this end, whole-body PET list mode data from 12 patients with prostate cancer were acquired 1 h after injection of 2 MBq/kg [68Ga]HBED-CC-PSMA on a hybrid PET-MRI system. List mode data were further transformed into data sets representing 300, 180, 90, and 30 s acquisition duration per bed position. Standard attenuation and scatter corrections were performed based on MRI-derived attenuation maps, complemented by emission-based attenuation data in areas not covered by MRI. A total of 288 image data sets were reconstructed with varying acquisition durations for emission and attenuation data with and without scatter and prompt gamma correction, and further analysed regarding image quality and diagnostic performance. RESULTS: Decreased PET acquisition durations resulted in a significantly increased incidence of halo artefacts around kidneys and bladder, decreased lesion detectability and lower SUV as well as markedly lower arm attenuation values: Halo artefacts were present in 5 out of 12 cases at 300-s duration, in 6 at 180 s, in 10 at 90 s, and in 11 cases at 30 s. Using attenuation data of the 300 s scans restored artefact occurrence to the original 300-s level. Prompt gamma correction only led to small improvements in terms of artefact occurrence and size. Of the 141 detected lesions in the 300-s images one lesion was not detected at 180 s, 28 at 90 s, and 64 at 30 s. Using the 300-s attenuation map decreased non-detectability of lesions to zero at 180 s, 9 at 90 s, and 52 at 30 s. Attenuation maps at 90 and 30 s demonstrated markedly lower mean arm attenuation values (0.002 cm-1) than those at 300 s (0.084 cm-1), and 180 s (0.062 cm-1). CONCLUSIONS: Short acquisition durations of less than 3 minutes per bed position result in unacceptable image artefacts and decreased diagnostic performance in current whole-body 68Ga-PSMA PET-MRI and should be avoided. Increased image noise and imperfections in generated attenuation maps were identified as a paramount cause for image degradation.