Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

Value of PET ECG gating in a cross-validation study of cardiac function assessment by PET/MR imaging.

BACKGROUND: This work investigated the impact of different cardiac gating methods on the assessment of cardiac function by FDG-PET in a cross-validation PET/MR study. METHODS AND RESULTS: MR- and PET-based left ventricular end-diastolic, end-systolic volumes, and ejection fraction (EDV, ESV, and EF) were delineated in 30 patients with a PET/MR examination. Cardiac PET imaging was performed using three ECG gating methods: fixed number of gates per beat (STD), STD with a beat acceptance window (STD-BR), and fixed gate duration (FW). High MR-PET correlations were found in all the values. ESVs correlated better than EDVs and EFs: Pearson's r coefficient [0.92, 0.92, 0.92] in ESV vs [0.75, 0.81, 0.80] in EDV and [0.79, 0.91, 0.87] in EF, for each method [STD, STD-BR, FW]. Biases with respect to MRI for all the evaluated PET methods were less than 13% in EDV, 5% in ESV, and 14% in EF, but with wide limits of agreements, in the range (59-68)% in EDV, (65-70)% in ESV, and (49-71)% in EF. STD showed the strongest disagreement, while there were no marked differences between STD-BR and FW. CONCLUSION: Based on these findings, PET- and MR-based cardiac function parameters were highly correlated but in substantial disagreement with variabilities introduced by the selected PET ECG gating method. The most significant differences were associated with the ECG gating method susceptible to highly irregular beats, while similar performance was observed in the methods using uniform adjustment of gates width per beat with the beat acceptance window, and fixed gate width along all the beats. Thus, strict quality controls of R peak detection are needed to minimize its impact on the function assessment.

Multi-center study of inter-rater reproducibility, image quality, and diagnostic accuracy of CZT versus conventional SPECT myocardial perfusion imaging.

BACKGROUND: Cadmium-zinc-telluride (CZT)-based detectors exhibit higher diagnostic sensitivity in myocardial perfusion imaging (MPI) than conventional Anger-MPI for detection of coronary artery disease (CAD); however, reduced specificity and diagnostic accuracy of CZT-MPI were observed. This study aims to compare these different camera systems and to examine the degree of inter-rater reproducibility among readers with varying experience in MPI. METHODS: 83 patients who underwent double stress/rest examinations using both a CZT and conventional SPECT cameras within one visit were included. Anonymized and randomized MPI-images were distributed to 15 international readers using a standardized questionnaire. Subsequent coronary angiography findings of ten patients served as a reference for analysis of sensitivity and specificity. RESULTS: Image quality was significantly better in CZT-MPI with significantly lower breast attenuation (P < 0.05). CZT-MPI exhibited higher sensitivity than Anger-MPI (87.5% vs. 62.5%) and significantly reduced specificity (40% vs. 100%). Readers experienced with both camera systems had the highest inter-rater agreement indicating higher reproducibility (CZT 0.54 vs. conv. 0.49, P < 0.05). CONCLUSIONS: Higher diagnostic sensitivity of CZT-MPI offers advantages in detection of CAD yet potentially of at the cost of reduced specificity, therefore it requires special training and a differentiated evaluation approach, especially for non-experienced readers with such camera systems.

Visualization of fibroblast activation using 68Ga-FAPI PET/CT after pulmonary vein isolation with pulsed field compared with cryoballoon ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation modality for atrial fibrillation (AF) ablating myocardium by electroporation without tissue-heating. With its different mechanism of tissue ablation, it is assumed that lesion creation is divergent to thermal energy sources. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT targets FAP-alpha expressed by activated fibroblasts. We aimed to assess 68Ga-FAPI uptake in pulmonary veins as surrogate for ablation damage after PFA and cryoballoon ablation (CBA). METHODS: 26 patients (15 PFA, 11 CBA) underwent 68Ga-FAPI-PET/CT after ablation. Standardized uptake values (SUV) and fibroblast-activation volumes of localized tracer uptake were assessed. RESULTS: Patient characteristics were comparable between groups. In PFA, focal FAPI uptake was only observed in 3/15 (20%) patients, whereas in the CBA cohort, 10/11 (90.9%) patients showed atrial visual uptake. We observed lower values of SUVmax (2.85 ± 0.56 vs 4.71 ± 2.06, P = 0.025) and FAV (1.13 ± 0.84 cm3 vs 3.91 ± 2.74 cm3, P = 0.014) along with a trend towards lower SUVpeak and SUVmean in PFA vs CBA patients, respectively. CONCLUSION: Tissue response with respect to fibroblast activation seems to be less pronounced in PFA compared to established thermal ablation systems. This functional assessment might contribute to a better understanding of lesion formation in thermal and PFA ablation potentially contributing to better safety outcomes.

Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.

Whole-body uptake classification and prostate cancer staging in 68Ga-PSMA-11 PET/CT using dual-tracer learning.

PURPOSE: In PSMA-ligand PET/CT imaging, standardized evaluation frameworks and image-derived parameters are increasingly used to support prostate cancer staging. Clinical applicability remains challenging wherever manual measurements of numerous suspected lesions are required. Deep learning methods are promising for automated image analysis, typically requiring extensive expert-annotated image datasets to reach sufficient accuracy. We developed a deep learning method to support image-based staging, investigating the use of training information from two radiotracers. METHODS: In 173 subjects imaged with 68Ga-PSMA-11 PET/CT, divided into development (121) and test (52) sets, we trained and evaluated a convolutional neural network to both classify sites of elevated tracer uptake as nonsuspicious or suspicious for cancer and assign them an anatomical location. We evaluated training strategies to leverage information from a larger dataset of 18F-FDG PET/CT images and expert annotations, including transfer learning and combined training encoding the tracer type as input to the network. We assessed the agreement between the N and M stage assigned based on the network annotations and expert annotations, according to the PROMISE miTNM framework. RESULTS: In the development set, including 18F-FDG training data improved classification performance in four-fold cross validation. In the test set, compared to expert assessment, training with 18F-FDG data and the development set yielded 80.4% average precision [confidence interval (CI): 71.1-87.8] for identification of suspicious uptake sites, 77% (CI: 70.0-83.4) accuracy for anatomical location classification of suspicious findings, 81% agreement for identification of regional lymph node involvement, and 77% agreement for identification of metastatic stage. CONCLUSION: The evaluated algorithm showed good agreement with expert assessment for identification and anatomical location classification of suspicious uptake sites in whole-body 68Ga-PSMA-11 PET/CT. With restricted PSMA-ligand data available, the use of training examples from a different radiotracer improved performance. The investigated methods are promising for enabling efficient assessment of cancer stage and tumor burden.

Visualization of thermal damage using 68 Ga-FAPI-PET/CT after pulmonary vein isolation.

PURPOSE: 68 Ga-fibroblast-activation protein inhibitor (FAPI) positron emission tomography (PET) is a novel technique targeting FAP-alpha. This protein is expressed by activated fibroblasts which are the main contributors to tissue remodeling. The aim of this proof-of-concept study was to assess 68 Ga-FAPI uptake in the pulmonary vein (PV) region of the left atrium after pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) and radiofrequency (RFA) as a surrogate for thermal damage. METHODS: Twelve PVI patients (5 RFA, 7 CBA) underwent 68 Ga-FAPI-PET 20.5 ± 12.8 days after PVI. Five patients without atrial fibrillation or previous ablation served as controls. Standardized uptake values of localized tracer uptake were calculated. RESULTS: Focal FAPI uptake around the PVs was observed in 10/12 (83.3%) PVI patients, no uptake was observed in 2 PVI patients and all controls. Patients after PVI had higher FAPI uptake in PVs compared to controls (SUVmax: 4.3 ± 2.2 vs. 1.6 ± 0.2, p < 0.01; SUVpeak: 2.9 ± 1.4 vs. 1.3 ± 0.2, p < 0.01). All CBA patients had an intense uptake, while in the RFA, group 2 (40%), 1 (20%), and 2 (40%) patients had an intense, moderate, and no uptake, respectively. We observed higher uptake values (SUVpeak) in CBA compared to RFA patients (4.4 ± 1.5 vs. 2.5 ± 0.8, p = 0.02). CONCLUSION: We demonstrate in-vivo visualization of 68 Ga-FAPI uptake as a surrogate for fibroblast activation after PVI. CBA seems to cause more pronounced fibroblast activation following tissue injury than RFA. Future studies are warranted to assess if this modality can contribute to a better understanding of the mechanisms of AF recurrence after PVI by lesion creation and gap assessment.

The added value of PSMA PET/MR radiomics for prostate cancer staging.

PURPOSE: To evaluate the performance of combined PET and multiparametric MRI (mpMRI) radiomics for the group-wise prediction of postsurgical Gleason scores (psGSs) in primary prostate cancer (PCa) patients. METHODS: Patients with PCa, who underwent [68 Ga]Ga-PSMA-11 PET/MRI followed by radical prostatectomy, were included in this retrospective analysis (n = 101). Patients were grouped by psGS in three categories: ISUP grades 1-3, ISUP grade 4, and ISUP grade 5. mpMRI images included T1-weighted, T2-weighted, and apparent diffusion coefficient (ADC) map. Whole-prostate segmentations were performed on each modality, and image biomarker standardization initiative (IBSI)-compliant radiomic features were extracted. Nine support vector machine (SVM) models were trained: four single-modality radiomic models (PET, T1w, T2w, ADC); three PET + MRI double-modality models (PET + T1w, PET + T2w, PET + ADC), and two baseline models (one with patient data, one image-based) for comparison. A sixfold stratified cross-validation was performed, and balanced accuracies (bAcc) of the predictions of the best-performing models were reported and compared through Student's t-tests. The predictions of the best-performing model were compared against biopsy GS (bGS). RESULTS: All radiomic models outperformed the baseline models. The best-performing (mean ± stdv [%]) single-modality model was the ADC model (76 ± 6%), although not significantly better (p > 0.05) than other single-modality models (T1w: 72 ± 3%, T2w: 73 ± 2%; PET: 75 ± 5%). The overall best-performing model combined PET + ADC radiomics (82 ± 5%). It significantly outperformed most other double-modality (PET + T1w: 74 ± 5%, p = 0.026; PET + T2w: 71 ± 4%, p = 0.003) and single-modality models (PET: p = 0.042; T1w: p = 0.002; T2w: p = 0.003), except the ADC-only model (p = 0.138). In this initial cohort, the PET + ADC model outperformed bGS overall (82.5% vs 72.4%) in the prediction of psGS. CONCLUSION: All single- and double-modality models outperformed the baseline models, showing their potential in the prediction of GS, even with an unbalanced cohort. The best-performing model included PET + ADC radiomics, suggesting a complementary value of PSMA-PET and ADC radiomics.

The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy-a multicenter retrospective analysis.

PURPOSE: This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort. METHODS: Patients who underwent 68 Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS. RESULTS: Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values ≥ median (p = 0.071), SUVmax values ≥ 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1-4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results. CONCLUSION: The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology-Genitourinary.

Gating failure can result in underestimation of cardiac function in myocardial perfusion scintigraphy.

Here, we present a case with a pacemaker due to an atrioventricular (AV) block 2 Mobitz type, in whom a gating failure resulted in a relevant underestimation of cardiac function in myocardial perfusion scintigraphy. A set of quality control steps for gating errors is proposed.

Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04.

Our previous study has demonstrated the feasibility of noninvasive imaging of fibroblast activation protein (FAP)-expression after myocardial infarction (MI) in MI-territory in a rat model with 68Ga-FAPI-04-PET. In the current extended clinical case, we sought to delineate cardiac uptake of 68Ga-FAPI-04 in a patient after MI with clinical indication for the evidence of fibroblast activation. Carcinoma patients without cardiac disease underwent 68Ga-FAPI-04-PET/CT as control. The patient with one-vessel disease underwent dynamic 68Ga-FAPI-04-cardiac-PET/CMR for 60 minutes. Correlation of cardiac 68Ga-FAPI-04 uptake with clinical findings, ECG, echocardiography, coronary-arteriography and enhanced cardiac-MRI with T1 MOLLI and ECV mapping were performed. No uptake was found in normal myocardium and in mature scar. A focal intense 68Ga-FAPI-04 uptake with continuous wash-out in the infarct territory of coronary occlusion correlating with T1 and ECV mapping was observed. The uptake of 68Ga-FAPI-04 extends beyond the actual infarcted area and overestimates the infarct size as confirmed by follow-up CMR.

Almost 10 years of PET/MR attenuation correction: the effect on lesion quantification with PSMA: clinical evaluation on 200 prostate cancer patients.

PURPOSE: After a decade of PET/MR, the case of attenuation correction (AC) remains open. The initial four-compartment (air, water, fat, soft tissue) Dixon-based AC scheme has since been expanded with several features, the latest being MR field-of-view extension and a bone atlas. As this potentially changes quantification, we evaluated the impact of these features in PET AC in prostate cancer patients. METHODS: Two hundred prostate cancer patients were examined with either 18F- or 68Ga-prostate-specific membrane antigen (PSMA) PET/MR. Qualitative and quantitative analysis (SUVmean, SUVmax, correlation, and statistical significance) was performed on images reconstructed using different AC schemes: Dixon, Dixon+MLAA, Dixon+HUGE, and Dixon+HUGE+bones for 18F-PSMA data; Dixon and Dixon+bones for 68Ga-PSMA data. Uptakes were compared using linear regression against standard Dixon. RESULTS: High correlation and no visually perceivable differences between all evaluated methods (r > 0.996) were found. The mean relative difference in lesion uptake of 18F-PSMA and 68Ga-PSMA remained, respectively, within 4% and 3% in soft tissue, and within 10% and 9% in bones for all evaluated methods. Bone registration errors were detected, causing mean uptake change of 5% in affected lesions. CONCLUSIONS: Based on these results and the encountered bone atlas registration inaccuracy, we deduce that including bones and extending the MR field-of-view did not introduce clinically significant differences in PSMA diagnostic accuracy and tracer uptake quantification in prostate cancer pelvic lesions, facilitating the analysis of serial studies respectively. However, in the absence of ground truth data, we advise against atlas-based methods when comparing serial scans for bone lesions.

Multiparametric PET and MRI of myocardial damage after myocardial infarction: correlation of integrin αvß3 expression and myocardial blood flow.

PURPOSE: Increased angiogenesis after myocardial infarction is considered an important favorable prognostic parameter. The αvß3 integrin is a key mediator of cell-cell and cell-matrix interactions and an important molecular target for imaging of neovasculature and repair processes after MI. Thus, imaging of αvß3 expression might provide a novel biomarker for assessment of myocardial angiogenesis as a prognostic marker of left ventricular remodeling after MI. Currently, there is limited data available regarding the association of myocardial blood flow and αvß3 integrin expression after myocardial infarction in humans. METHODS: Twelve patients were examined 31 ± 14 days after MI with PET/CT using [18F]Galacto-RGD and [13N]NH3 and with cardiac MRI including late enhancement on the same day. Normal myocardium (remote) and areas of infarction (lesion) were identified on the [18F]Galacto-RGD PET/CT images by correlation with [13N]NH3 PET and cardiac MRI. Lesion/liver-, lesion/blood-, and lesion/remote ratios were calculated. Blood flow and [18F]Galacto-RGD uptake were quantified and correlated for each myocardial segment (AHA 17-segment model). RESULTS: In 5 patients, increased [18F]Galacto-RGD uptake was notable within or adjacent to the infarction areas with a lesion/remote ratio of 46% (26-83%; lesion/blood 1.15 ± 0.06; lesion/liver 0.61 ± 0.18). [18F]Galacto-RGD uptake correlated significantly with infarct size (R = 0.73; p = 0.016). Moreover, it correlated significantly with restricted blood flow for all myocardial segments (R = - 0.39; p < 0.0001) and even stronger in severely hypoperfused areas (R = - 0.75; p < 0.0001). CONCLUSION: [18F]Galacto-RGD PET/CT allows the visualization and quantification of myocardial αvß3 expression as a key player in angiogenesis in a subset of patients after MI. αvß3 expression was more pronounced in patients with larger infarcts and was generally more intense but not restricted to areas with more impaired blood flow, proving that tracer uptake was largely independent of unspecific perfusion effects. Based on these promising results, larger prospective studies are warranted to evaluate the potential of αvß3 imaging for assessment of myocardial angiogenesis and prediction of ventricular remodeling.

Multimodal assessment of right ventricle overload-metabolic and clinical consequences in pulmonary arterial hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH) increased afterload leads to adaptive processes of the right ventricle (RV) that help to maintain arterio-ventricular coupling of RV and preserve cardiac output, but with time the adaptive mechanisms fail. In this study, we propose a multimodal approach which allows to estimate prognostic value of RV coupling parameters in PAH patients. METHODS: Twenty-seven stable PAH patients (49.5 ± 15.5 years) and 12 controls underwent cardiovascular magnetic resonance (CMR). CMR feature tracking analysis was performed for RV global longitudinal strain assessment (RV GLS). RV-arterial coupling was evaluated by combination of RV GLS and three proposed surrogates of RV afterload-pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC). 18-FDG positron emission tomography (PET) analysis was used to assess RV glucose uptake presented as SUVRV/LV. Follow-up time of this study was 25 months and the clinical end-point was defined as death or clinical deterioration. RESULTS: Coupling parameters (RV GLS/PASP, RV GLS/PVR and RV GLS*PAC) significantly correlated with RV function and standardized uptake value (SUVRV/LV). Patients who experienced a clinical end-point (n = 18) had a significantly worse coupling parameters at the baseline visit. RV GLS/PASP had the highest area under curve in predicting a clinical end-point and patients with a value higher than (-)0.29%/mmHg had significantly worse prognosis. It was also a statistically significant predictor of clinical end-point in multivariate analysis (adjusted R2 = 0.68; p < 0.001). CONCLUSIONS: Coupling parameters are linked with RV hemodynamics and glucose metabolism in PAH. Combining CMR and hemodynamic measurements offers more comprehensive assessment of RV function required for prognostication of PAH patients. TRIAL REGISTRATION: NCT03688698, 09/26/2018, retrospectively registered; Protocol ID: 2017/25/N/NZ5/02689.

Diagnostic performance of quantitative and qualitative parameters for the diagnosis of aortic graft infection using [18F]-FDG PET/CT.

PURPOSE: The aim of this study was the evaluation of quantitative and qualitative parameters for the diagnosis of aortic graft infection (AGI) using [18F]-FDG PET/CT. METHODS: PET/CT was performed in 50 patients with clinically suspected AGI. 12 oncological patients with aortic repair but without suspicion of AGI were included in the analysis to serve as control cohort. The [18F]-FDG uptake pattern around the graft was assessed using (a) a five-point visual grading scale (VGS), (b) SUVmax and (c) different graft-to-background ratios (GBRs). The diagnostic performance of VGS, SUVmax and GBRs was assessed and compared by ROC analysis. RESULTS: 28 infected and 34 uninfected grafts were identified by standard of reference. SUVmax and VGS were the most powerful predictors for the diagnosis of AGI according to the area under the curve (AUC 0.988 and 0.983, respectively) without a significant difference compared to GBRs. SUVmax and VGS showed congruent and accurate findings in 54 patients (i.e. either both positive or negative), yielding sensitivity and specificity (100%) in this subgroup of patients. CONCLUSION: Quantitative analysis by SUVmax and qualitative analysis by VGS are highly effective in the diagnosis of AGI and should be tested as an outcome measure in prospective trials.

Dynamic 2D and 3D mapping of hyperpolarized pyruvate to lactate conversion in vivo with efficient multi-echo balanced steady-state free precession at 3 T.

The aim of this study was to acquire the transient MRI signal of hyperpolarized tracers and their metabolites efficiently, for which specialized imaging sequences are required. In this work, a multi-echo balanced steady-state free precession (me-bSSFP) sequence with Iterative Decomposition with Echo Asymmetry and Least squares estimation (IDEAL) reconstruction was implemented on a clinical 3 T positron-emission tomography/MRI system for fast 2D and 3D metabolic imaging. Simulations were conducted to obtain signal-efficient sequence protocols for the metabolic imaging of hyperpolarized biomolecules. The sequence was applied in vitro and in vivo for probing the enzymatic exchange of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate. Chemical shift resolution was achieved using a least-square, iterative chemical species separation algorithm in the reconstruction. In vitro, metabolic conversion rate measurements from me-bSSFP were compared with NMR spectroscopy and free induction decay-chemical shift imaging (FID-CSI). In vivo, a rat MAT-B-III tumor model was imaged with me-bSSFP and FID-CSI. 2D metabolite maps of [1-13 C]pyruvate and [1-13 C]lactate acquired with me-bSSFP showed the same spatial distributions as FID-CSI. The pyruvate-lactate conversion kinetics measured with me-bSSFP and NMR corresponded well. Dynamic 2D metabolite mapping with me-bSSFP enabled the acquisition of up to 420 time frames (scan time: 180-350 ms/frame) before the hyperpolarized [1-13 C]pyruvate was relaxed below noise level. 3D metabolite mapping with a large field of view (180 × 180 × 48 mm3 ) and high spatial resolution (5.6 × 5.6 × 2 mm3 ) was conducted with me-bSSFP in a scan time of 8.2 seconds. It was concluded that Me-bSSFP improves the spatial and temporal resolution for metabolic imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate compared with either of the FID-CSI or EPSI methods reported at 3 T, providing new possibilities for clinical and preclinical applications.

Hybrid PET/MR imaging for the prediction of left ventricular recovery after percutaneous revascularisation of coronary chronic total occlusions.

PURPOSE: To evaluate myocardial viability assessment with hybrid 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/magnetic resonance imaging ([18F]FDG-PET/MR) in predicting left ventricular (LV) wall motion recovery after percutaneous revascularisation of coronary chronic total occlusion (CTO). METHODS AND RESULTS: Forty-nine patients with CTO and corresponding wall motion abnormality (WMA) underwent [18F]FDG-PET/MR imaging for viability assessment prior to percutaneous revascularisation. After 3-6 months, 23 patients underwent follow-up MR to evaluate wall motion recovery. In total, 124 segments were assigned to the CTO territories, while 80 segments displayed impaired wall motion. Of these, 68% (54) were concordantly viable in PET and MR; conversely, only 2 segments (2%) were assessed non-viable by both modalities. However, 30% showed a discordant viability pattern, either PET non-viable/MR viable (3 segments, 4%) or PET viable/MR non-viable (21 segments, 26%), and the latter revealed a significant wall motion improvement at follow-up (p = 0.033). Combined imaging by [18F]FDG-PET/MR showed a fair accuracy in predicting myocardial recovery after CTO revascularisation (PET/MR area under ROC curve (AUC) = 0.72, p = 0.002), which was superior to LGE-MR (AUC = 0.66) and [18F]FDG-PET (AUC = 0.58) alone. CONCLUSION: Hybrid PET/MR imaging prior to CTO revascularisation predicts more accurately the recovery of dysfunctional myocardium than PET or MR alone. Its complementary information may identify regions of viable myocardium with increased potential for functional recovery.

Accuracy of cardiac functional parameters measured from gated radionuclide myocardial perfusion imaging in mice.

BACKGROUND: Quantitative cardiac contractile function assessment is the primary indicator of disease progression and therapeutic efficacy in small animals. Operator dependency is a major challenge with commonly used echocardiography. Simultaneous assessment of cardiac perfusion and function in nuclear scans would reduce burden on the animal and facilitate longitudinal studies. We evaluated the accuracy of contractile function measurements obtained from electrocardiogram-gated nuclear perfusion imaging compared with anatomic imaging. METHODS AND RESULTS: In healthy C57Bl/6N mice (n = 11), 99mTc-sestamibi SPECT and 13N-ammonia PET underestimated left ventricular volumes (23 to 28%, P = 0.02) compared to matched anatomic images, though ejection fraction (LVEF) was comparable (%, SPECT: 73 ± 8 vs CMR: 72 ± 6, P = 0.1). At 1 week after myocardial infarction (n = 13), LV volumes were significantly lower in perfusion images compared to CMR and contrast CT (P = 0.003), and LVEF was modestly overestimated (%, SPECT: 37 ± 8, vs CMR: 27 ± 7, P = 0.003). Nuclear images exhibited good intra- and inter-reader agreement. Perfusion SPECT accurately calculated infarct size compared to histology (r = 0.95, P < 0.001). CONCLUSIONS: Cardiac function can be calculated by gated nuclear perfusion imaging in healthy mice. After infarction, perfusion imaging overestimates LVEF, which should be considered for comparison to other modalities. Combined functional and infarct size analysis may optimize imaging protocols and reduce anaesthesia duration for longitudinal studies.

Respiratory- and cardiac motion-corrected simultaneous whole-heart PET and dual phase coronary MR angiography.

PURPOSE: To develop a framework for efficient and simultaneous acquisition of motion-compensated whole-heart coronary MR angiography (CMRA) and left ventricular function by MR and myocardial integrity by PET on a 3T PET-MR system. METHODS: An acquisition scheme based on a dual-phase CMRA sequence acquired simultaneously with cardiac PET data has been developed. The framework is integrated with a motion-corrected image reconstruction approach, so that non-rigid respiratory and cardiac deformation fields estimated from MR images are used to correct both the CMRA (respiratory motion correction for each cardiac phase) and the PET data (respiratory and cardiac motion correction). The proposed approach was tested in a cohort of 8 healthy subjects and 6 patients with coronary artery disease. Left ventricular (LV) function estimated from motion-corrected dual-phase CMRA was compared to the gold standard estimated from a stack of 2D CINE images for the healthy subjects. Relative increase of signal in motion-corrected PET images compared to uncorrected images was computed for standard 17-segment polar maps for each patient. RESULTS: Motion-corrected dual-phase CMRA images allow for visualization of the coronary arteries in both systole and diastole for all healthy subjects and cardiac patients. LV functional indices from healthy subjects result in good agreement with the reference method, underestimating stroke volume by 3.07 ± 3.26 mL and ejection fraction by 0.30 ± 1.01%. Motion correction improved delineation of the myocardium in PET images, resulting in an increased 18 F-FDG signal of up to 28% in basal segments of the myocardial wall compared to uncorrected images. CONCLUSION: The proposed motion-corrected dual-phase CMRA and cardiac PET produces co-registered good quality images in both modalities in a single efficient examination of ~13 min.

Myocardial perfusion quantification using simultaneously acquired 13 NH3 -ammonia PET and dynamic contrast-enhanced MRI in patients at rest and stress.

PURPOSE: Systematic differences with respect to myocardial perfusion quantification exist between DCE-MRI and PET. Using the potential of integrated PET/MRI, this study was conceived to compare perfusion quantification on the basis of simultaneously acquired 13 NH3 -ammonia PET and DCE-MRI data in patients at rest and stress. METHODS: Twenty-nine patients were examined on a 3T PET/MRI scanner. DCE-MRI was implemented in dual-sequence design and additional T1 mapping for signal normalization. Four different deconvolution methods including a modified version of the Fermi technique were compared against 13 NH3 -ammonia results. RESULTS: Cohort-average flow comparison yielded higher resting flows for DCE-MRI than for PET and, therefore, significantly lower DCE-MRI perfusion ratios under the common assumption of equal arterial and tissue hematocrit. Absolute flow values were strongly correlated in both slice-average (R2 = 0.82) and regional (R2 = 0.7) evaluations. Different DCE-MRI deconvolution methods yielded similar flow result with exception of an unconstrained Fermi method exhibiting outliers at high flows when compared with PET. CONCLUSION: Thresholds for Ischemia classification may not be directly tradable between PET and MRI flow values. Differences in perfusion ratios between PET and DCE-MRI may be lifted by using stress/rest-specific hematocrit conversion. Proper physiological constraints are advised in model-constrained deconvolution.