Performance of visual, manual, and automatic coronary calcium scoring of cardiac 13N-ammonia PET/low dose CT.

BACKGROUND: Coronary artery calcium is a well-known predictor of major adverse cardiac events and is usually scored manually from dedicated, ECG-triggered calcium scoring CT (CSCT) scans. In clinical practice, a myocardial perfusion PET scan is accompanied by a non-ECG triggered low dose CT (LDCT) scan. In this study, we investigated the accuracy of patients' cardiovascular risk categorisation based on manual, visual, and automatic AI calcium scoring using the LDCT scan. METHODS: We retrospectively enrolled 213 patients. Each patient received a 13N-ammonia PET scan, an LDCT scan, and a CSCT scan as the gold standard. All LDCT and CSCT scans were scored manually, visually, and automatically. For the manual scoring, we used vendor recommended software (Syngo.via, Siemens). For visual scoring a 6-points risk scale was used (0; 1-10; 11-100; 101-400; 401-100; > 1 000 Agatston score). The automatic scoring was performed with deep learning software (Syngo.via, Siemens). All manual and automatic Agatston scores were converted to the 6-point risk scale. Manual CSCT scoring was used as a reference. RESULTS: The agreement of manual and automatic LDCT scoring with the reference was low [weighted kappa 0.59 (95% CI 0.53-0.65); 0.50 (95% CI 0.44-0.56), respectively], but the agreement of visual LDCT scoring was strong [0.82 (95% CI 0.77-0.86)]. CONCLUSIONS: Compared with the gold standard manual CSCT scoring, visual LDCT scoring outperformed manual LDCT and automatic LDCT scoring.

Relation between pharmacological stress ECG, 13NH3-PET/CT outcome and the occurrence of cardiac events during follow-up in women with chest pain.

AIM: Evaluation of major adverse cardiovascular events (MACE) in women referred for NH3-PET/CT in relation to scan outcome and pharmacological stress ECG (PxECG) results. PATIENTS AND METHODS: Six hundred twenty-four women, referred for NH3-PET/CT between 2012 and 2016, were included. Demographic data and MACE during follow-up (407 ± 207 days) were retrieved from electronic patient charts. NH3-PET/CT was scored as either normal or abnormal. PxECG was scored as negative, non-diagnostic or positive. PxECG was compared with NH3-PET/CT and related to MACE. RESULTS: The NH3-PET/CT was normal in 482/624 (77%) and abnormal in 142/624 (23%). PxECG was negative in 234/624 (38%), non-diagnostic in 365/624 (58%) and positive in 25/624 (4%). NH3-PET/CT was normal in 87, 71 and 72% with normal, nondiagnostic and positive PxECG, respectively. 41/624(7%) experienced a MACE, 38 with abnormal NH3-PET/CT versus three with normal NH3-PET/CT (P < 0.001). MACE occurred in 5/234 (0.9%), 31/365 (8%) and 5/25 (20%) with normal, non-diagnostic and positive PxECG, respectively (P < 0.001). No MACEs were seen in 204 with both normal PxECG and NH3-PET/CT versus 5/30(17%) with normal PxECG but abnormal NH3-PET/. No MACE occurred in 3/260(1%) with non-diagnostic PxECG and normal NH3-PET/CT versus 28/105(27%) with non-diagnostic PxECG and abnormal NH3-PET/CT. 0/18 with positive PxECG and normal NH3-PET/CT showed MACE versus 5/7(71%) with a positive PxECG and abnormal NH3-PET/CT. CONCLUSION: Normal NH3-PET/CT is most prevalent in women with normal PxECG. The occurrence of MACE during follow-up is more frequently related to an abnormal NH3-PET/CT than to PxECG. Furthermore, in women with positive PxECG but normal NH3-PET/CT no MACE are to be expected.

Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study.

Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). METHODS: Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5-26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions). RESULTS: RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml). CONCLUSION: Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT.

Evaluation of PET/CT in patients with stage III malignant cutaneous melanoma.

In order to evaluate if patients with stage III-IV MCM are eligible for curative treatment PET/CT is performed. Since the diagnostic value of PET/CT is not unambiguously, a retrospective cohort study is performed to tailor optimal indication of PET/CT in patients with stage III MCM. A retrospective cohort study was conducted of all patients with stage III disease in a large oncologic teaching hospital in which PET/CT was performed from 2012 to 2016. The primary tumor- and regional lymph node characteristics were assessed to predict distant metastasis seen on PET/CT. A total of 73 patients were included of which 18% were restaged as stage IV by PET/CT. Twenty percent of the patients with a positive lymph node and 14% of patients with in transit metastasis or satellite lesions were restaged to stage IV. T-classification, ulceration and N-classification did not predict distant metastasis. Localization of the primary tumor significantly differed (P = 0.004). Localization on the head/neck resulted in a 32 greater odds of distant metastasis (P = 0.008). After a median follow-up of 36 months, 13 out of 60 (27%) stage III MCM patients were restaged as stage IV after the first performed PET/CT. This retrospective cohort study resulted in restaging of 18% of the stage III MCM patients by PET/CT, with therapeutic consequences. Patients with stage III MCM on the head/neck seem to have more distant spreading of the tumor than other localizations. Further investigation is needed, with larger sample sizes, to guide optimal indication of PET/CT.

Cardiac Displacement During 13N-Ammonia Myocardial Perfusion PET/CT: Comparison Between Adenosine- and Regadenoson-Induced Stress.

This study investigated differences in cardiac displacement during adenosine stress versus regadenoson stress in 13N-ammonia (13NH3) MP PET/CT scans. Methods: In total, 61 myocardial perfusion PET/CT scans were acquired using either adenosine (n = 30) or regadenoson (n = 31) as a stressor. For both groups, cardiac displacement during rest and stress was measured 3-dimensionally, relative to either a fixed reference frame or the previous frame, in each 1-min frame of a list-mode PET acquisition of 25 min. All stress scans were additionally evaluated for the presence of motion artifacts. Also, the tolerability of the agents and the occurrence of side effects were compared between groups. Results: Significantly larger cardiac displacement during stress was detected in the adenosine group than in the regadenoson group, reflected by both maximal cardiac displacement (P = 0.022) and mean cardiac displacement (P = 0.001). The duration of the movement was typically shorter in the regadenoson group. Frames with cardiac displacement of at least 5 mm were observed nearly twice as frequently when adenosine was used instead of regadenoson. Conclusion: The displacement during regadenoson stress is of lower amplitude and shorter duration than that during adenosine stress and may therefore contribute to a lower incidence of motion artifacts on PET/CT scans.

18F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes: Detection Rate, Image Quality, Activity Kinetics, and Biodistribution.

There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For 68Ga-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For 18F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of 18F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer. Methods: Images were acquired 60 and 120 min after injection of 18F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points. Results: Our data showed a significantly increasing uptake of 18F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P < 0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-to-noise ratio of 11.93 was found for images acquired 120 min after injection (P < 0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15). Conclusion:18F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate of prostate cancer characteristic lesions than images at 60 min after injection. Further studies are needed to elucidate the best imaging time point for 18F-DCFPyL.

Type 2 diabetes mellitus correlates with systolic function during myocardial stress perfusion scanning with Nitrogen-13 ammonia PET.

BACKGROUND: The influence of type 2 diabetes mellitus (DM2) on systolic function is partially determined by the coronary vasodilator function, nevertheless, an independent effect is suspected. We evaluated the relationship between DM2 and systolic function considering PET quantitative myocardial perfusion. METHODS: We analyzed 585 patients without a previous myocardial infarction referred to a rest and adenosine stress Nitrogen-13 ammonia PET. A bootstrapped multiple linear regression analysis was performed using DM2, stress myocardial blood flow (sMBF), myocardial perfusion reserve (MPR), and clinical risk factors as predictors and LVEF as the outcome variable; an interaction term was additionally investigated. RESULTS: Two hundred and ninety male and 295 female patients (mean age 65.3 ± 9.9 and 67.4 ± 10 years, respectively) were included. 57.1% presented hypertension, 16% smoking, 37.6% hypercholesterolemia, 33.8% family history for CAD, and 15.2% DM2. The mean MPR was 2.13 ± 0.48 and 2.21 ± 0.60, mean sMBF was 2.01 ± 0.51 and 2.15 ± 0.54, and mean LVEF was 63% ± 10.4 and 67% ± 10.1 for diabetics and non-diabetics, respectively. A significant relation was detected for sMBF (B = 5.830 95% CI [3.505, 9.549], P = .001) and DM2 (B = -2.599 95% CI [-5.125, -0.119], P = .03) with LVEF. The interaction (DM2 × sMBF) yielded no significance (P = .512). CONCLUSION: DM2 influences PET-measured systolic function in patients without previous myocardial infarction independently from myocardial perfusion parameters. Our study supports the importance of DM2 as an independent risk factor for deteriorating systolic function.

Occurrence of typical perfusion defects attributed to jailed or occluded side branch after ramus descendens anterior stenting in a patient cohort referred for 13NH3 myocardial PET/CT.

AIM: Coronary stenting is frequently accompanied by occlusion or jailing of side branches. This can cause small reversible or persistent perfusion defects on myocardial perfusion single photon emission computed tomography studies, but data from NH3 myocardial perfusion PET/computed tomography (CT) are lacking. This study aimed to describe the occurrence of perfusion defects in patients with ramus descendes anterior (RDA) stents on myocardial perfusion imaging as measured by NH3 PET/CT. METHODS: From 10 September 2013 till 29 August 2014, 53 consecutive RDA-stented patients, who were referred for NH3 PET/CT, were entered into a database. All scans were evaluated for the occurrence of reversible or persisting perfusion defects within the RDA flow territory, which was categorized as normal, infarction, ischemia, or as a small persisting defect after stent placement or small area of ischemia after stent placement, attributable to side-branch occlusion (SBO). RESULTS: Of the 53 patients [65±10 years, male : female 33 (62%) : 20 (38%)] with an RDA stent, 29 had received a stent in the proximal RDA, 18 in the mid-RDA, and six in both the proximal and the mid-RDA.NH3-measured myocardial perfusion was scored as normal in 26 (49%), as infarction in 5 (9%), and as ischemia in 2 patients (4%). Six patients (11%) showed a small persisting defect within the RDA flow territory, whereas 14 patients (26%) showed a small area of ischemia in the RDA territory. CONCLUSION: myocardial perfusion abnormalities attributed to SBO are frequently observed on NH3 PET/CTs of patients with RDA stents. In the present cohort, 38% of patients showed such small defects in the RDA territory, which proved to be reversible in 70% of the cases. Recognizing and reporting SBO-related perfusion abnormalities will help clinicians to interpret NH3 myocardial PET/CT properly.

Ruling out coronary artery disease in women with atypical chest pain: results of calcium score combined with coronary computed tomography angiography and associated radiation exposure.

BACKGROUND: To assess the presence of coronary artery disease (CAD) in women with atypical chest pain with low or intermediate risk for significant CAD by means of calcium scoring (CaSc) combined with coronary computed tomography angiography (CCTA) and to estimate the equivalent radiation dose in women. PATIENTS AND METHODS: From December 2011 until July 2013, all consecutively performed cardiac CTs in women with atypical chest pain were included prospectively in the present study. Both CaSc and CCTA were obtained by a dual source flying focal spot 2×64 slice Somatom Definition Flash. Absence of CAD was defined as CaSc 0 and absence of noncalcified plaques. Presence of CAD was determined as CaSc>0 and/or presence of noncalcified plaques. The impact on patient management was also scored within our patient cohort. RESULTS: A total of 1033 procedures in 1014 women (mean age 59±10 years; mean BMI 26±8) were analyzed. In 520 (51%) women, CAD was absent. In 494 (49%) women, CAD was diagnosed, and in this subgroup the mean CaSc was 137±229. Thirty-seven (7%) of 494 women with CAD showed only noncalcified plaques. The mean equivalent radiation dose for the cardiac CTs of 1014 women was 2.2±1.6 mSv. CONCLUSION: Combined CaSc and CCTA excludes CAD in approximately 50% of women with atypical chest pain, and delivers a modest radiation dose of 2.2±1.6 mSv. CCTA has a substantial impact on patient management and can thus be advocated as first diagnostic tool in excluding CAD in women with atypical chest pain in terms of latest generation equipment with emphasize on radiation reduction techniques.

The independent functioning of the orchidopexied congenital undescended testis as assessed by positron emission tomography/computed tomography.

Fertility after orchidopexied undescended testes (UDT) is impaired. Although fertility parameters are known to be more favorable in unilateral cases than in bilateral cases, the exact contribution of the unilateral orchidopexied UDT to fertility is unknown. We used testicular (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-uptake assessed by positron emission tomography/computed tomography (PET/CT) to investigate the function of the orchidopexied unilateral congenital UDT, compared to its normally descended counterpart. We hypothesize that the contribution of the orchidopexied unilateral congenital UDT to fertility in adulthood is low. Eleven men who underwent orchidopexy for congenital UDT at the age of 1.9 ± 1.4 (range, 4.5 months -4.0) years were seen in follow-up at the age of 24.1 ± 2.3 (20.6-28.0) years. All underwent physical examination, testicular ultrasonography and PET/CT. Testicular (18)F-FDG-uptake was expressed as the peak Standardized Uptake Value (SUVpeak). The mean SUVpeak of the orchidopexied UDT was 2.74 ± 0.48 (2.13-3.47), which was significantly lower than its counterpart (P = 0.021). Besides, there was no correlation between the testicular volume and the SUVpeak. The orchidopexied congenital UDT has been shown to be less metabolically active than its contralateral counterpart. Nevertheless, we suggest that the operated testes function to some degree.

Characteristics of a new system for monitoring the leakage factor during regional hyperthermic isolated limb perfusion.

RATIONALE: A new system is presented and evaluated for real-time monitoring of blood leakage during hyperthermic isolated limb perfusion (HILP) surgery, the Veenstra HILP system. This system incorporates two software models to determine blood leakage: a single-nuclide algorithm and a newly developed dual-nuclide algorithm. The latter algorithm has the advantage that, in principle, it is independent of system sensitivity and thus independent of changes in geometrical efficiency. A physical description of the system is given, together with the required hardware and software specifications. METHODS: In-vitro measurements, corresponding to the intended clinical use, are presented to investigate the relevant performance characteristics of the system: count rate linearity, measurement uncertainty, response time, and accuracy. As the Veenstra HILP system provides the opportunity to use different filter settings and averaging time, the influence of these settings on the time response and measurement uncertainty is described. RESULTS: Count rate linearity was better than 1% for the count rate domain typically observed during HILP procedures. The response time of the system degrades with increasing total averaging time. In contrast, measurement uncertainty in the blood leakage factor improves with increasing radiotracer count rates and increasing total averaging time. For both blood leakage algorithms, measurement accuracy is better than 1.0 and 1.5%, respectively. CONCLUSION: Measurements have shown that the system is well suited for the real-time monitoring of blood leakage during HILP surgery. Furthermore, a good agreement was observed between the theoretical and measured response time and measurement uncertainty.

Left ventricular volume assessment by planar radionuclide ventriculography evaluated by MRI.

BACKGROUND: Assessment of left ventricular (LV) ejection fraction (LVEF) and LV volume are essential for the evaluation of prognosis in cardiac disease. LVEF and LV volumes can be measured with several imaging modalities, such as magnetic resonance imaging (MRI) or computed tomography; however, these are relatively expensive and time consuming. In contrast, planar radionuclide ventriculography (PRV) for LVEF assessment is a cost-effective, fast, and reliable technique, but PRV for LV volumes calculation is less common. AIM: Evaluation of a new hybrid geometrical count-based method (HGCBM) in comparison with two count-based methods (CBMs) and a geometrical method (GM) for the calculation of LV volumes with PRV using MRI as reference. METHODS: Thirty cardiac patients underwent routine PRV with a standard dose of 500 MBq of Tc-pertechnetate and additional cardiac MRI as reference method. LV volumes of PRV data were calculated by four different methods. The CBMs and GM are based on the assumption that the shape of the LV can be approximated by an ellipsoid or sphere, and the new HGCBM extracts the volume from the projected count rates themselves. RESULTS: All methods underestimated the LV volumes as compared with the MRI-measured volumes. The difference (mean+/-SD) of end-diastolic volume (EDV) between PRV and MRI was 33+/-23 ml for GM, 12+/-26 ml for HGCBM, 50+/-38 ml for CBM1, and 13+/-40 ml for CBM2. The correlation coefficients for EDV between PRV methods and MRI were r = 0.90 for GM and r = 0.85 for HGCBM. The CBMs showed poor correlation r = 0.64 with the MRI data and a high SD. The difference of end-systolic volume (ESV) between PRV and MRI was 23+/-19 ml for GM, 9+/-22 ml for HGCBM, 29+/-29 ml for CBM1, and 9+/-28 ml for CBM2. The correlation coefficients for ESV between PRV methods and MRI were r = 0.955 for GM and r = 0.914 for HGCBM, r = 0.85 for CBM1 and CBM2. Although GM showed a slightly higher correlation than HGCBM, the difference of EDV and ESV between PRV and MRI was much higher for GM in comparison with HGCBM. Both CBMs showed poor agreement with MRI data. CONCLUSION: PRV using the new HGCMB method in comparison with other methods is an easy and accurate method to determine LV volumes. However, all methods underestimate ESV and EDV slightly as compared with MRI.

Macroscopic hierarchical surface patterning of porphyrin trimers via self-assembly and dewetting.

The use of bottom-up approaches to construct patterned surfaces for technological applications is appealing, but to date is applicable to only relatively small areas (approximately 10 square micrometers). We constructed highly periodic patterns at macroscopic length scales, in the range of square millimeters, by combining self-assembly of disk-like porphyrin dyes with physical dewetting phenomena. The patterns consisted of equidistant 5-nanometer-wide lines spaced 0.5 to 1 micrometers apart, forming single porphyrin stacks containing millions of molecules, and were formed spontaneously upon drop-casting a solution of the molecules onto a mica surface. On glass, thicker lines are formed, which can be used to align liquid crystals in large domains of square millimeter size.

Tunable command layers for liquid crystal alignment.

A simple method for the construction of a stable, tunable, self-assembled command layer for liquid crystal display purposes is described. A pyridine-functionalized oligosiloxane spontaneously forms an anisotropic, grooved surface on indium-tin-oxide, enabling it to align liquid crystalline molecules. The pyridine functions act as seeds for the epitaxial growth of stacks of highly ordered zinc phthalocyanines, the height of which can be controlled. These stacks increase the interaction between the surface and the liquid crystalline matrix by amplifying the surface ordering into the liquid crystal bulk. By varying the height of the stacks, direct control over the properties of the liquid crystal domains is achieved. These properties can be further tuned by adding to the liquid crystal, micro- and nanomolar concentrations of nitrogen-containing compounds, which are capable of interacting with and dissolving the stacks. The procedures we describe offer possibilities to use such tunable systems in LCD-based sensor devices as well as in solar-cell applications.