The Monocle Sign on 18F-FDG PET Indicates Contralateral Peripheral Facial Nerve Palsy.

BACKGROUND: The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign. PATIENTS AND METHODS: A total of 85 patients with unilateral FNP were included into our study, thereof 73 with peripheral FNP and 12 with central FNP. FDG uptake (SUVmax, SUVmean, total lesion glycolysis) was measured in both orbicularis oculi muscles (OOMs). FDG uptake of paretic and nonparetic muscles was compared in patients with FNP (Wilcoxon test and Mann-Whitney U test) and was also compared with FDG uptake in 33 patients without FNP (Mann-Whitney U test). SUVmax ratios of OOM were compared. A receiver operating characteristic curve and Youden Index were used to determine the optimal cutoff SUVmax ratio for the prevalence of contralateral peripheral FNP. RESULTS: The SUVmax ratio of OOM was significantly higher in patients with peripheral FNP compared with patients with central FNP and those without FNP (1.70 ± 0.94 vs 1.16 ± 0.09 vs 1.18 ± 0.21, respectively; P < 0.001). The SUVmax ratio of OOM yielded an area under the curve (AUC) of 0.719 (95% confidence interval, 0.630-0.809), with an optimal cutoff of 1.41, yielding a specificity of 94.4% and a sensitivity of 44.1% for identifying contralateral peripheral FNP. One hundred percent specificity is achieved using a cutoff of 1.91 (sensitivity, 29.4%). CONCLUSIONS: Asymmetrically increased FDG uptake of the OOM (the "monocle sign") indicates contralateral peripheral FNP. A nearly 2-fold higher SUVmax represents a practically useful cutoff.

BSREM for Brain Metastasis Detection with 18F-FDG-PET/CT in Lung Cancer Patients.

The aim of the study was to analyze the use of block sequential regularized expectation maximization (BSREM) with different ß-values for the detection of brain metastases in digital fluorine-18 labeled 2-deoxy-2-fluoro-D-glucose (18F-FDG) PET/CT in lung cancer patients. We retrospectively analyzed staging/restaging 18F-FDG PET/CT scans of 40 consecutive lung cancer patients with new brain metastases, confirmed by MRI. PET images were reconstructed using BSREM (ß-values of 100, 200, 300, 400, 500, 600, 700) and OSEM. Two independent blinded readers (R1 and R2) evaluated each reconstruction using a 4-point scale for general image quality, noise, and lesion detectability. SUVmax of metastases, brain background, target-to-background ratio (TBR), and contrast recovery (CR) ratio were recorded for each reconstruction. Among all reconstruction techniques, differences in qualitative parameters were analyzed using non-parametric Friedman test, while differences in quantitative parameters were compared using analysis of variances for repeated measures. Cohen's kappa (k) was used to measure inter-reader agreement. The overall detectability of brain metastases was highest for BSREM200 (R1: 2.83 ± 1.17; R2: 2.68 ± 1.32) and BSREM300 (R1: 2.78 ± 1.23; R2: 2.68 ± 1.36), followed by BSREM100, which had lower accuracy owing to noise. The highest median TBR was found for BSREM100 (R1: 2.19 ± 1.05; R2: 2.42 ± 1.08), followed by BSREM200 and BSREM300. Image quality ratings were significantly different among reconstructions (p < 0.001). The median quality score was higher for BSREM100-300, and both noise and metastases' SUVmax decreased with increasing ß-value. Inter-reader agreement was particularly high for the detectability of photopenic metastases and blurring (all k > 0.65). BSREM200 and BSREM300 yielded the best results for the detection of brain metastases, surpassing both BSREM400 and OSEM, typically used in clinical practice.

Histopathological Features of Parathyroid Adenoma and 18F-Choline Uptake in PET/MR of Primary Hyperparathyroidism.

BACKGROUND: The aim of this study was to assess the relationship between the histopathological properties of hyperfunctioning parathyroids and parathyroid 18F-choline uptake. PATIENTS AND METHODS: A total of 31 parathyroid adenomas were retrospectively analyzed in patients with primary hyperparathyroidism and preoperative 18F-choline PET/MR. PET/MR parameters of parathyroid glands (SUVmax and target-to-background ratio in early-phase [EP] and late-phase [LP]), MRI volume, preoperative parathyroid hormone (PTH) serum concentration, and postoperative histopathology (predominant cell type and growth pattern of adenoma cells, location and size of adenoma) were assessed. The relationship of PET/MR parameters, PTH, and histological parameters was determined using linear regression, Spearman correlation and Kruskal-Wallis test. RESULTS: The median volume of parathyroid adenoma was 421.78 ± 142.46 mm3 (46.39-4412.69). Adenomas were predominantly composed of chief, water-clear, and oncocytic/oxyphilic cells in 27/31, 2/31, and 2/31 cases, respectively. The growth pattern was predominantly solid, follicular, and trabecular in 18/31, 8/31, and 5/31, respectively. The SUVmax was 6.71 ± 3.39 in EP and 6.91 ± 3.97 in LP. Follicular growth pattern had slightly higher EP SUVmax (trabecular: 4.12 ± 0.56; solid: 6.62 ± 3.19; follicular: 8.56 ± 3.96; P = 0.046). Spearman correlation showed strong positive correlation between volume and both EP and LP SUVmax (0.626; P = 0.0001 and 0.576; P = 0.0001, respectively). Linear regression analysis revealed significant correlation between PTH level and EP and LP SUVmax (both P = 0.001); in contrast, no correlation was found between PTH level and both cell type and growth pattern. CONCLUSIONS: Our findings suggest that 18F-choline uptake of parathyroid adenomas might be associated both with the histological growth pattern and adenoma volume, but not with a specific cell type.

Clinical evaluation of data-driven respiratory gating for PET/CT in an oncological cohort of 149 patients: impact on image quality and patient management.

OBJECTIVES: To evaluate the impact of fully automatic motion correction by data-driven respiratory gating (DDG) on positron emission tomography (PET) image quality, lesion detection and patient management. MATERIALS AND METHODS: A total of 149 patients undergoing PET/CT for cancer (re-)staging were retrospectively included. Patients underwent a PET/CT on a digital detector scanner and for every patient a PET data set where DDG was enabled (PETDDG) and as well as where DDG was not enabled (PETnonDDG) was reconstructed. All PET data sets were evaluated by two readers which rated the general image quality, motion effects and organ contours. Further, both readers reviewed all scans on a case-by-case basis and evaluated the impact of PETDDG on additional apparent lesion, change of report, and change of management. RESULTS: In 85% (n = 126) of the patients, at least one bed position was acquired using DDG, resulting in mean scan time increase of 4:37 min per patient in the whole study cohort (n = 149). General image quality was not rated differently for PETnonDDG and PETDDG images (p = 1.000) while motion effects (i.e. indicating general blurring) was rated significantly lower in PETDDG images and organ contours, including liver and spleen, were rated significantly sharper using PETDDG as compared to PETnonDDG (all p < 0.001). In 27% of patients, PETDDG resulted in a change of the report and in a total of 12 cases (8%), PETDDG resulted in a change of further clinical management. CONCLUSION: Deviceless DDG provided reliable fully automatic motion correction in clinical routine and increased lesion detectability and changed management in a considerable number of patients. ADVANCES IN KNOWLEDGE: DDG enables PET/CT with respiratory gating to be used routinely in clinical practice without external gating equipment needed.

Cross-Comparison of 4-Dimensional Flow Magnetic Resonance Imaging and Intraoperative Middle Cerebral Artery Pressure Measurements Before and After Superficial Temporal Artery-Middle Cerebral Artery Bypass Surgery.

BACKGROUND: The hemodynamic changes after superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery are unclear. OBJECTIVE: To clarify the hemodynamics by comparing flow parameters obtained by 4-dimensional (4D) flow magnetic resonance imaging (MRI) and intraoperative MCA pressure measurement. METHODS: We recruited 23 patients who underwent STA-MCA bypass surgery for internal carotid artery (ICA) or MCA stenosis. We monitored intraoperative MCA, STA, and radial artery (RA) pressure. All patients underwent 4D flow MRI preoperatively and 3 wk after surgery to quantify the blood flow volume (BFV) of the ipsilateral ICA (BFViICA), contralateral ICA (BFVcICA), basilar artery (BFVBA), ipsilateral STA (BFViSTA), and contralateral STA (BFVcSTA). The sum of intracranial BFV was defined as BFVtotal. We compared BFV parameters and intraoperative pressure. RESULTS: BFViSTA significantly increased after surgery (P < .001). BFViICA and BFVBA significantly decreased after surgery (BFViICAP = .005; BFVBAP = .02). No significant difference was observed between BFVcICA before and after surgery. As a result, BFVtotal postoperatively increased by 6.8%; however, no significant difference was observed. Flow direction at M1 changed from antegrade to unclear after surgery in 5 patients. Intraoperative MCA pressure and MCA/RA pressure ratio significantly increased after surgery (P < .001). We found a stronger positive correlation between MCA pressure increase ratio and BFVtotal increase ratio in patients with lower pre-MCA pressure (r = 0.907, P < .001). CONCLUSION: The visual and quantitative assessment of 4D flow MRI revealed that intracranial blood flow changes complementarily after STA-MCA bypass surgery. 4D flow MRI may detect the improvement of cerebral perfusion pressure.

Improved detection of in-transit metastases of malignant melanoma with BSREM reconstruction in digital [18F]FDG PET/CT.

OBJECTIVES: To compare block sequential regularized expectation maximization (BSREM) and ordered subset expectation maximization (OSEM) for the detection of in-transit metastasis (ITM) of malignant melanoma in digital [18F]FDG PET/CT. METHODS: We retrospectively analyzed a cohort of 100 [18F]FDG PET/CT scans of melanoma patients with ITM, performed between May 2017 and January 2020. PET images were reconstructed with both OSEM and BSREM algorithms. SUVmax, target-to-background ratio (TBR), and metabolic tumor volume (MTV) were recorded for each ITM. Differences in PET parameters were analyzed with the Wilcoxon signed-rank test. Differences in image quality for different reconstructions were tested using the Man-Whitney U test. RESULTS: BSREM reconstruction led to the detection of 287 ITM (39% more than OSEM). PET parameters of ITM were significantly different between BSREM and OSEM reconstructions (p < 0.001). SUVmax and TBR were higher (76.5% and 77.7%, respectively) and MTV lower (49.5%) on BSREM. ITM missed with OSEM had significantly lower SUVmax (mean 2.03 vs. 3.84) and TBR (mean 1.18 vs. 2.22) and higher MTV (mean 2.92 vs. 1.01) on OSEM compared to BSREM (all p < 0.001). CONCLUSIONS: BSREM detects significantly more ITM than OSEM, owing to higher SUVmax, higher TBR, and less blurring. BSREM is particularly helpful in small and less avid lesions, which are more often missed with OSEM. KEY POINTS: • In melanoma patients, [18F]FDG PET/CT helps to detect in-transit metastases (ITM), and their detection is improved by using BSREM instead of OSEM reconstruction. • BSREM is particularly useful in small lesions.

FDG-PET/CT: novel method for viability assessment of livers perfused ex vivo.

PURPOSE: Ex vivo liver machine perfusion is a promising option to rescue marginal liver grafts mitigating the donated organ shortage. Recently, a novel liver perfusion machine that can keep injured liver grafts alive for 1 week ex vivo was developed and reported in Nature Biotechnology. However, liver viability assessment ex vivo is an unsolved issue and the value of 18F-fluorodeoxyglucose (FDG)-PET/CT for such purpose was explored. MATERIALS AND METHODS: Discarded two human and six porcine liver grafts underwent FDG-PET/CT for viability assessment after 1 week of ex vivo perfusion. PET parameters [standardized uptake value (SUV)max, SUVmean, SUVpeak and total lesion glycolysis] were compared between hepatic lobes and between porcine and human livers. The prevalence of FDG-negative organ parts was recorded. The estimated effective radiation dose for PET/CT was calculated. RESULTS: All organs were viable with essentially homogeneous FDG uptake. Of note, viability was preserved in contact areas disclosing the absence of pressure necrosis. Four porcine and two human organs had small superficial FDG-negative areas confirmed as biopsy sites. Total lesion glycolysis was significantly higher in the right hepatic lobe (P = 0.012), while there was no significant difference of SUVmax, SUVmean and SUVpeak between hepatic lobes. There was no significant difference in FDG uptake parameters between porcine and human organs. The estimated effective radiation dose was 1.99 ± 1.67 mSv per organ. CONCLUSION: This study demonstrates the feasibility of FDG-PET/CT for viability assessment of ex vivo perfused liver grafts after 1 week.

Impact of PET data driven respiratory motion correction and BSREM reconstruction of 68Ga-DOTATATE PET/CT for differentiating neuroendocrine tumors (NET) and intrapancreatic accessory spleens (IPAS).

To evaluate whether quantitative PET parameters of motion-corrected 68Ga-DOTATATE PET/CT can differentiate between intrapancreatic accessory spleens (IPAS) and pancreatic neuroendocrine tumor (pNET). A total of 498 consecutive patients with neuroendocrine tumors (NET) who underwent 68Ga-DOTATATE PET/CT between March 2017 and July 2019 were retrospectively analyzed. Subjects with accessory spleens (n = 43, thereof 7 IPAS) and pNET (n = 9) were included, resulting in a total of 45 scans. PET images were reconstructed using ordered-subsets expectation maximization (OSEM) and a fully convergent iterative image reconstruction algorithm with ß-values of 1000 (BSREM1000). A data-driven gating (DDG) technique (MOTIONFREE, GE Healthcare) was applied to extract respiratory triggers and use them for PET motion correction within both reconstructions. PET parameters among different samples were compared using non-parametric tests. Receiver operating characteristics (ROC) analyzed the ability of PET parameters to differentiate IPAS and pNETs. SUVmax was able to distinguish pNET from accessory spleens and IPAs in BSREM1000 reconstructions (p < 0.05). This result was more reliable using DDG-based motion correction (p < 0.003) and was achieved in both OSEM and BSREM1000 reconstructions. For differentiating accessory spleens and pNETs with specificity 100%, the ROC analysis yielded an AUC of 0.742 (sensitivity 56%)/0.765 (sensitivity 56%)/0.846 (sensitivity 62%)/0.840 (sensitivity 63%) for SUVmax 36.7/41.9/36.9/41.7 in OSEM/BSREM1000/OSEM + DDG/BSREM1000 + DDG, respectively. BSREM1000 + DDG can accurately differentiate pNET from accessory spleen. Both BSREM1000 and DDG lead to a significant SUV increase compared to OSEM and non-motion-corrected data.

Multiparametric flow analysis using four-dimensional flow magnetic resonance imaging can detect cerebral hemodynamic impairment in patients with internal carotid artery stenosis.

PURPOSE: MRI-based risk stratification should be established to identify patients with internal carotid artery stenosis (ICS) who require further PET or SPECT evaluation. This study assessed whether multiparametric flow analysis using time-resolved 3D phase-contrast (4D flow) MRI can detect cerebral hemodynamic impairment in patients with ICS. METHODS: This retrospective study analyzed 26 consecutive patients with unilateral ICS (21 men; mean age, 71 years) who underwent 4D flow MRI and acetazolamide-stress brain perfusion SPECT. Collateral flow via the Willis ring was visually evaluated. Temporal mean flow volume rate (Net), pulsatile flow volume (ΔV), and pulsatility index (PI) at the middle cerebral artery were measured. Cerebral vascular reserve (CVR) was calculated from the SPECT dataset. Patients were assigned to the misery perfusion group if the CVR was < 10% and to the nonmisery perfusion group if the CVR was ≥ 10%. Parameters showing a significant difference in both groups were statistically evaluated. RESULTS: Affected side ΔV, ratio of affected to contralateral side Net (rNet), and ratio of affected to contralateral side ΔV were significantly correlated to CVR (p = 0.030, p = 0.010, p = 0.015, respectively). Absence of retrograde flow at the posterior communicating artery was observed in the misery perfusion group (p = 0.020). Combined cut-off values of the affected side ΔV (0.18 ml) and rNet (0.64) showed a sensitivity and specificity of 100% and 77.8%, respectively. CONCLUSION: Multiparametric flow analysis using 4D flow MRI can detect misery perfusion by comprehensively assessing blood flow data, including blood flow volume, pulsation, and collateral flow.

Fluoro-deoxy-glucose uptake in the mylohyoid muscle: a common misconception.

AIM: The mylohyoid muscle is often believed to exhibit high physiologic fluoro-deoxy-glucose (FDG) uptake. Aim of this study was to use PET/MR for adequately assessing the normal FDG distribution in floor of the mouth (FOM) muscles and neighboring major salivary glands. MATERIALS AND METHODS: Patients scanned with a simultaneous PET/MRI system for initial staging or follow-up of head and neck tumors, with no malignant lesions in salivary glands or in FOM, were included. Volumes-of-interest (VOIs) were positioned separately for bilateral mylohyoid, digastric, genioglossus, and geniohyoid muscles, based on T2-weighted and T1-weighted images, and for bilateral parotid, submandibular, and sublingual glands in the same way. SUVmax was measured for each VOI. RESULTS: Six hundred and ninety-two VOIs were positioned. FDG uptake in mylohyoid (SUVmax = 1.94 ± 0.37) and digastric muscles (SUVmax = 2.01 ± 0.37) were significantly higher compared to that in geniohyoid (SUVmax = 1.67 ± 0.53) and genioglossus muscles (SUVmax = 1.75 ± 0.54) (Friedman's test; P < 0.001). FDG uptake in the sublingual glands (SUVmax = 3.77 ± 1.63) was significantly higher compared to the parotid glands (SUVmax = 2.34 ± 0.60) and submandibular glands (SUVmax = 2.51 ± 0.59) (Wilcoxon signed-ranks test; P < 0.001). FDG uptake in sublingual glands was significantly higher than FDG uptake in the mylohyoid muscles (P < 0.001). FDG uptake in the parotid, submandibular, and sublingual glands was inversely correlated to the age of subjects (Spearman' rho coefficient: -0.397/P = 0.004; -0.329/P = 0.021; -0.535/P < 0.001, respectively). CONCLUSION: The sublingual glands yield the highest physiologic FDG uptake in the FOM. High FDG uptake in the mylohyoid muscle is a common misconception.

The Monocle Sign in FDG-PET: A Sign of Contralateral Facial Nerve Palsy.

We report three cases of unilateral F-FDG uptake in the orbicularis oculi muscle in subjects with contralateral peripheral facial nerve palsy. We argue that this asymmetric uptake pattern in fact reflects lack of metabolism on the side affected by facial nerve palsy, owing to denervation. Since the unilateral periorbital uptake resembles a monocle, we chose to call this finding the monocle sign. The monocle sign should not be confused with inflammation or tumor, but should prompt a neurological assessment for facial nerve palsy and a potential underlying disease.

Four-Dimensional Flow MRI Analysis of Cerebral Blood Flow Before and After High-Flow Extracranial-Intracranial Bypass Surgery With Internal Carotid Artery Ligation.

BACKGROUND: The hemodynamic changes that occur after high-flow (extracranial-intracranial) EC-IC bypass surgery with internal carotid artery (ICA) ligation are not well known. OBJECTIVE: To assess blood flow changes after high-flow EC-IC bypass with ICA ligation by time-resolved 3-dimensional phase-contrast (4D Flow) magnetic resonance imaging (MRI). METHODS: We enrolled 11 patients who underwent high-flow EC-IC bypass. 4D Flow MRI was performed before and after surgery to quantify the blood flow volume (BFV) of the ipsilateral ICA (BFViICA), bypass artery (BFVbypass), contralateral ICA (BFVcICA), and basilar artery (BFVBA). Subsequently, we calculated the total BFV (BFVtotal = BFViICA + BFVcICA + BFVBA [before surgery], BFVcICA + BFVBA + BFVbypass [after surgery]). The BFV changes after bypass was statistically analyzed. RESULTS: BFVbypass was slightly lower than BFViICA, but the difference was not statistically significant (3.84 ± 0.94 vs 4.42 ± 1.38 mL/s). The BFVcICA and BFVBA significantly increased after bypass surgery (BFVcICA 5.89 ± 1.44 vs 7.22 ± 1.37 mL/s [P = .0018], BFVBA 3.06 ± 0.41 vs 4.12 ± 0.38 mL/s [P < .001]). The BFVtotal significantly increased after surgery (13.37 ± 2.58 vs 15.18 ± 1.77 mL/s [P = .015]). There was no evidence of hyperperfusion syndrome in any cases. CONCLUSION: After high-flow EC-IC bypass with permanent ICA ligation, the bypass artery could partially compensate for the loss of BFV of the sacrificed ICA. The increased flow of the contralateral ICA and BA supply collateral blood flow. Clinically irrelevant hyperperfusion was observed.

4D Flow MR Imaging of Ophthalmic Artery Flow in Patients with Internal Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: To assess the clinical feasibility of time-resolved 3D phase contrast (4D Flow) MRI assessment of the ophthalmic artery (OphA) flow in patients with internal carotid artery stenosis (ICS). MATERIALS AND METHODS: Twenty-one consecutive patients with unilateral ICS were recruited. 4D Flow MRI and acetazolamide-stress brain perfusion single photon emission computed tomography (SPECT) were performed. The flow direction on the affected-side OphA was categorized into native flow (anterograde or unclear) and non-native flow (retrograde flow) based on 4D Flow MRI. In the affected-side middle cerebral artery (MCA) territory, the ratio of rest cerebral blood flow to normal control (RCBFMCA) and cerebral vascular reserve (CVRMCA) were calculated from SPECT dataset. High-risk patients were defined based on the previous large cohort study (RCBFMCA < 80% and CVRMCA < 10%). RESULTS: Eleven patients had native OphA flow (4 anterograde, 7 unclear) and the remaining 10 had non-native OphA flow. RCBFMCA and CVRMCA each were significantly lower in non-native flow group (84.9 ± 18.9% vs. 69.8 ± 7.3%, P < 0.05; 36.4 ± 20.6% vs. 17.0 ± 15.0%, P < 0.05). Four patients in the non-native flow group and none in the native flow group were confirmed as high-risk (Sensitivity/Specificity, 1.00/0.65). CONCLUSION: The 6 min standard 4D Flow MRI assessment of OphA in patients with ICS can predict intracranial hemodynamic impairment.

4D flow MRI assessment of extracranial-intracranial bypass: qualitative and quantitative evaluation of the hemodynamics.

INTRODUCTION: Our aim was to assess the feasibility of using time-resolved 3D phase-contrast (4D flow) MRI to characterize extracranial-intracranial (EC-IC) bypass. METHODS: We enrolled 32 patients who underwent EC-IC bypass (15 men, 17 women; mean age 66.4 years). In all, 16 underwent radial artery graft (RAG) bypass and 16 underwent superficial temporal artery (STA) bypass. 4D flow MRI, time-of-flight (TOF) magnetic resonance angiography (MRA), and computed tomography angiography (CTA) were performed. Bypass patency, flow direction, and blood flow volume (BFV) of each artery were determined by 4D flow MRI. Arterial diameters were measured by TOF-MRA and CTA. We compared RAG and STA bypasses by evaluating the flow direction and BFV of each artery. We evaluated the correlation between arterial diameters (measured by CTA or MRA) and the BFV and the detectability of flow direction (measured by 4D flow MRI) of each artery. RESULTS: 4D flow MRI confirmed the patency of each bypass artery. Flow direction of the M1 segment of the middle cerebral artery and BFV in the bypass artery differed between RAG and STA groups (p < 0.01). BFV in the bypass slightly correlated with the diameters on CTA (p < 0.05, R (2) = 0.287). Of the 29 arteries in the circle of Willis, nine were not depicted on 4D flow MRI. Cutoff values for arterial diameters on CTA and TOF-MRA for detecting the artery on 4D flow MRI were 2.4 and 1.8 mm, respectively. CONCLUSION: 4D flow MRI provided unique information for characterizing EC-IC bypasses, although this detectability is limited when addressing small arteries with slow flow.