Ventricular function in congenital diaphragmatic hernia: a systematic review and meta-analysis.

There is emerging evidence supporting ventricular function as a prognostic factor in congenital diaphragmatic hernia (CDH). The present systematic review and meta-analysis aimed to determine the predictive value of early ventricular function for survival and extracorporeal membrane oxygenation (ECMO) requirement in newborns with CDH. PubMed, Google Scholar, Cochrane Central Register, Clinical Trial Registry, and Opengrey were accessed. Studies evaluating associations between echocardiographic ventricular function measured ≤ 48 h after birth and survival or ECMO requirement were included. Two independent authors extracted the following data: study and participant characteristics, prognostic factors, and outcome-related data. Eleven studies met the inclusion criteria. Five studies reported on survival, two on ECMO, and four on both outcomes. A moderate risk of bias was found in most of the studies, mainly because of selection, prognostic factors, and confounding biases. For survival (899 participants), pooled sensitivity and specificity were 86% (95% confidence interval [CI], 77-92%) and 44% (95% CI, 25-65%), respectively, in normal left ventricular function. For ECMO need (815 participants), pooled sensitivity and specificity were 39.8% (95% CI, 27-52%) and 88% (95% CI, 80-96%), respectively, in left ventricular dysfunction. Overall certainty of the evidence was graded very low for survival and low for ECMO. Inconsistent reporting of echocardiographic measurements and lack of adjustment for confounding factors were major limitations.Conclusion: Early ventricular dysfunction is a potential prognostic factor in CDH. Standardized echocardiographic measurement reporting and high-quality studies are needed to further elucidate its prognostic significance. What is Known: • Evidence supports the predictive value of echocardiographic measurements in CDH ≤ 24-48 h post-birth. • Ventricular dysfunction has been proposed as a prognostic risk factor. What is New: • Right and left ventricular functions were promising predictors of survival and ECMO requirement in neonates with CDH. • Test characteristics of ventricular function were determined as predictors of survival or need for ECMO. Specific echocardiographic markers of ventricular function can be valuable in determining prognosis.

Cardiac uptake patterns in routine 18F-FDG PET-CT scans: A pictorial review.

Broad variability of 18F-Fluoro-2-deoxyglucose (FDG) uptake is noted in myocardium while performing FDG PET-CT scans for viability, infection, or oncologic purposes. While most of the uptakes are considered non-specific, presence of underlying cardiac disease is seldom encountered. With this presentation, our intent is to pictorially highlight the variable FDG uptake patterns associated with the normal variations, benign, and malignant disease.

External Validation of the Neonatal Mortality Risk-2000 Score to Predict In-Hospital Mortality in Neonates Weighing 2000 g or Less.

The authors aimed to externally validate the Neonatal Mortality Risk-2000 (NMR-2000) score, a simplified tool to predict in-hospital mortality in the setting of a tertiary care hospital. They conducted a single-center prospective cohort study on neonates weighing ≤ 2000 g who were admitted to a neonatal intensive care unit within 6 h of age. The predictors included in the NMR-2000 score were birth weight, SpO2 at admission, and the highest level of respiratory support during the first 24 h of life. The outcome was in-hospital mortality. Among 243 neonates ≤ 2000 g, there were 94 (38.7%) deaths. The area under the receiver operating characteristic curve value for the NMR score was 0.84 (95% CI 0.79-0.89) in the present sample. The calibration slope was 1, and the intercept was 0. The NMR-2000 score had good discriminating ability and calibration to predict in-hospital mortality.

Resolving fetal hydrops - A rare entity.

Non-immune hydrops fetalis (NIHF) is abnormal accumulation of serous fluid in ≥2 interstitial spaces with no evidence of maternal red cell alloimmunization. Leaving a few treatable conditions, it is generally considered as a sign of poor fetal outcome. Bi-allelic variants in THSD1 have been found to be to be associated with phenotypes ranging from lethal NIHF to persistent edema. Here, we report a family with non-immune hydrops in two successive pregnancies. Whole exome sequencing in second pregnancy identified a homozygous truncating variant in THSD1 (NM_018676:c.892G>T:p.Glu298Ter). Postnatal follow up showed gradual resolution of the accumulated fluid and normal development. This report further strengthens the association of variants in THSD1 with NIHF.

Merkel Cell Carcinoma of the Left Cheek With Testicular Metastasis: An Uncommon Occurrence.

Merkel cell carcinoma (MCC) is an infrequent and aggressive neuroendocrine tumor of the skin. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is an effective imaging technique with good diagnostic accuracy that may be used to help stage MCC and for detecting unexpected recurrences and distant metastatic disease. Other causes of testicular neoplasms, such as primary testicular tumors, lymphomas, or anaplastic small cell melanomas, are difficult to differentiate from MCC testicular metastases on imaging, and tumor markers and histopathology will help confirm it. The current case is a 65-year-old non-immunocompromised male with Merkel cell carcinoma who was incidentally identified with testicular metastases on PET/CT and confirmed on histopathology.

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

CONTEXT: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. OBJECTIVE: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. METHODS: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. RESULTS: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. CONCLUSIONS: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

Improvement in Successful Extubation in Newborns After a Protocol-driven Approach: A Quality Improvement Initiative.

OBJECTIVE: To reduce extubation failure rate by implementing protocol-driven ventilation and extubation strategies. METHODS: Quality improvement project in a level II neonatal care unit from April 2017 to January 2018. Ventilation and extubation protocols implemented from 1 August, 2017. 18 ventilated newborns in the pre-protocol period, 16 in Plan-do-check-act (PDCA) cycle I and 17 in PDCA cycle II. Primary outcome was extubation failure within the first 72 h of extubation. RESULTS: Extubation failure rate reduced from 41.7% (pre-protocol period) to 23.8% (PDCA 1 and 2, OR 0.44, 95% CI 0.12 to 1.59, P = 0.21). Median time to first extubation attempt significantly decreased (71.5 h to 38 h, P=0.046). CONCLUSIONS: A protocolized approach through quality improvement initiative demonstrated a sustained improvement in successful extubation with a significant reduction in the median time to first extubation attempt in ventilated newborns.

Congenital Arhinia: A Rare Case Report and Review of Literature.

Congenital absence of nose (Arhinia) is extremely rare. A male baby was born at term via uncomplicated vaginal delivery and presented with complete arhinia, bilateral microphthalmia, lower eyelid coloboma and feeding difficulty. Reconstructive surgery was postponed until preschool age. On follow up at 1 year of age baby is feeding liquid and semisolid food and growing well.

Quantitative Analysis of Dynamic 123I-mIBG SPECT Imaging Data in Healthy Humans with a Population-Based Metabolite Correction Method.

UNLABELLED: Conventional 2-dimensional planar imaging of (123)I-metaiodobenzylguanidine ((123)I-mIBG) is not fully quantitative. To develop a more accurate quantitative imaging approach, we investigated dynamic SPECT imaging with kinetic modeling in healthy humans to obtain the myocardial volume of distribution (VT) for (123)I-mIBG. METHODS: Twelve healthy humans underwent 5 serial 15-min SPECT scans at 0, 15, 90, 120, and 180 min after bolus injection of (123)I-mIBG on a hybrid cadmium zinc telluride SPECT/CT system. Serial venous blood samples were obtained for radioactivity measurement and radiometabolite analysis. List-mode data of all the scans were binned into frames and reconstructed with attenuation and scatter corrections. Myocardial and blood-pool volumes of interest were drawn on the reconstructed images to derive the myocardial time-activity curve and input function. A population-based blood-to-plasma ratio (BPR) curve was generated. Both the population-based metabolite correction (PBMC) and the individual metabolite correction (IMC) curves were generated for comparison. VT values were obtained from different compartment models, using different input functions with and without metabolite and BPR corrections. RESULTS: The BPR curve reached the peak value of 2.1 at 13 min after injection. Parent fraction was approximately 58% ± 13% at 15 min and stabilized at approximately 40% ± 5% by 180 min after injection. Two radiometabolite species were observed. When the reversible 2-tissue-compartment fit was used, the mean VT value was 29.0 ± 12.4 mL/cm(3) with BPR correction and PBMC, a 188% ± 32% increase compared with that without corrections. There was significant difference in VT with BPR correction (P = 2.3e-04) as well as with PBMC (P = 1.6e-05). The mean difference in VT between PBMC and IMC was -3% ± 8%, which was insignificant (P = 0.39). The intersubject coefficients of variation after PBMC (43%) and IMC (42%) were similar. CONCLUSION: The myocardial VT of (123)I-mIBG was established in healthy humans for the first time. Accurate kinetic modeling of (123)I-mIBG requires both BPR and metabolite corrections. Population-based BPR correction and metabolite correction curves were developed, allowing more convenient absolute quantification of dynamic (123)I-mIBG SPECT images.

Scatter and crosstalk corrections for (99m)Tc/(123)I dual-radionuclide imaging using a CZT SPECT system with pinhole collimators.

PURPOSE: The energy spectrum for a cadmium zinc telluride (CZT) detector has a low energy tail due to incomplete charge collection and intercrystal scattering. Due to these solid-state detector effects, scatter would be overestimated if the conventional triple-energy window (TEW) method is used for scatter and crosstalk corrections in CZT-based imaging systems. The objective of this work is to develop a scatter and crosstalk correction method for (99m)Tc/(123)I dual-radionuclide imaging for a CZT-based dedicated cardiac SPECT system with pinhole collimators (GE Discovery NM 530c/570c). METHODS: A tailing model was developed to account for the low energy tail effects of the CZT detector. The parameters of the model were obtained using (99m)Tc and (123)I point source measurements. A scatter model was defined to characterize the relationship between down-scatter and self-scatter projections. The parameters for this model were obtained from Monte Carlo simulation using SIMIND. The tailing and scatter models were further incorporated into a projection count model, and the primary and self-scatter projections of each radionuclide were determined with a maximum likelihood expectation maximization (MLEM) iterative estimation approach. The extracted scatter and crosstalk projections were then incorporated into MLEM image reconstruction as an additive term in forward projection to obtain scatter- and crosstalk-corrected images. The proposed method was validated using Monte Carlo simulation, line source experiment, anthropomorphic torso phantom studies, and patient studies. The performance of the proposed method was also compared to that obtained with the conventional TEW method. RESULTS: Monte Carlo simulations and line source experiment demonstrated that the TEW method overestimated scatter while their proposed method provided more accurate scatter estimation by considering the low energy tail effect. In the phantom study, improved defect contrasts were observed with both correction methods compared to no correction, especially for the images of (99m)Tc in dual-radionuclide imaging where there is heavy contamination from (123)I. In this case, the nontransmural defect contrast was improved from 0.39 to 0.47 with the TEW method and to 0.51 with their proposed method and the transmural defect contrast was improved from 0.62 to 0.74 with the TEW method and to 0.73 with their proposed method. In the patient study, the proposed method provided higher myocardium-to-blood pool contrast than that of the TEW method. Similar to the phantom experiment, the improvement was the most substantial for the images of (99m)Tc in dual-radionuclide imaging. In this case, the myocardium-to-blood pool ratio was improved from 7.0 to 38.3 with the TEW method and to 63.6 with their proposed method. Compared to the TEW method, the proposed method also provided higher count levels in the reconstructed images in both phantom and patient studies, indicating reduced overestimation of scatter. Using the proposed method, consistent reconstruction results were obtained for both single-radionuclide data with scatter correction and dual-radionuclide data with scatter and crosstalk corrections, in both phantom and human studies. CONCLUSIONS: The authors demonstrate that the TEW method leads to overestimation in scatter and crosstalk for the CZT-based imaging system while the proposed scatter and crosstalk correction method can provide more accurate self-scatter and down-scatter estimations for quantitative single-radionuclide and dual-radionuclide imaging.

Scatter characterization and correction for simultaneous multiple small-animal PET imaging.

PURPOSE: The rapid growth and usage of small-animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However, this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is, first, to characterize the magnitude and spatial distribution of the scatter component in small-animal PET imaging when scanning single and multiple rodents simultaneously and, second, to assess the relevance and evaluate the performance of scatter correction under similar conditions. METHODS: The LabPET™-8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape-based and more realistic voxel-based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single-scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small-animal PET imaging evaluated in terms of image quality and quantitative accuracy. RESULTS: A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single- and multiple-subject imaging. In the LabPET™-8 scanner, the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out-of field-of-view (FOV) scatter fraction (SF) is 1.70, 0.76, and 0.11% for lower energy thresholds of 250, 350, and 400 keV, respectively. The increase in SF ranged between 25 and 64% when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill-over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole-body and rat whole-body anatomical models were improved for multiple imaging studies following scatter correction. CONCLUSIONS: The magnitude and spatial distribution of the scatter component in small-animal PET imaging of single and multiple subjects simultaneously were characterized, and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies, whereas its impact is insignificant in single mouse imaging.

A cone-shaped phantom for assessment of small animal PET scatter fraction and count rate performance.

PURPOSE: Positron emission tomography (PET) image quality deteriorates as the object size increases owing to increased detection of scattered and random events. The characterization of the scatter component in small animal PET imaging has received little attention owing to the small scatter fraction (SF) when imaging rodents. The purpose of this study is first to design and fabricate a cone-shaped phantom which can be used for measurement of object size-dependent SF and noise equivalent count rates (NECR), and second, to assess these parameters for two small animal PET scanners as function of radial offset, object size and lower energy threshold (LET). METHODS: The X-PET™ and LabPET-8™ scanners were modeled as realistically as possible using GATE Monte Carlo simulation platform. The simulation models were validated against experimental measurements in terms of sensitivity, SF and NECR. The dedicated phantom was fabricated in-house using high-density polyethylene. The optimized dimensions of the cone-shaped phantom are 158 mm (length), 20 mm (minimum diameter), 70 mm (maximum diameter) and taper angle of 9°. RESULTS: The relative difference between simulated and experimental results for the LabPET-8™ scanner varied between 0.7% and 10% except for a few results where it was below 16%. Depending on the radial offset from the center of the central axial field-of-view (3-6 cm diameter), the SF for the cone-shaped phantom varied from 26.3% to 18.2%, 18.6 to 13.1% and 10.1 to 7.6% for the X-PET™, whereas it varied from 34.4% to 26.9%, 19.1 to 17.0% and 9.1 to 7.3% for the LabPET-8™, for LETs of 250, 350 and 425 keV, respectively. The SF increases as the radial offset decreases, LET decreases and object size increases. The SF is higher for the LabPET-8™ compared with the X-PET™ scanner. The NECR increases as the radial offset increases and object size decreases. The maximum NECR was obtained at a LET of 350 keV for the LabPET-8™ and 250 keV for the X-PET™. High correlation coefficients for SF and NECR were observed between the cone-shaped phantom and an equivalent volume cylindrical phantom for the three considered axial fields of view. CONCLUSIONS: A single cone-shaped phantom enables the assessment of the impact of three factors, namely radial offset, LET and object size on PET SF and count rate estimates. This phantom is more realistic owing to the non-uniform shape of rodents' bodies compared to cylindrical uniform phantoms and seems to be well suited for evaluation of object size-dependent SF and NECR.

NEMA NU-04-based performance characteristics of the LabPET-8™ small animal PET scanner.

The objective of this study is to characterize the performance of the preclinical avalanche photodiode (APD)-based LabPET-8™ subsystem of the fully integrated trimodality PET/SPECT/CT Triumph™ scanner using the National Electrical Manufacturers Association (NEMA) NU 04-2008 protocol. The characterized performance parameters include the spatial resolution, sensitivity, scatter fraction, counts rate performance and image-quality characteristics. The PET system is fully digital using APD-based detector modules with highly integrated electronics. The detector assembly consists of phoswich pairs of Lu(1.9)Y(0.1)SiO(5) (LYSO) and Lu(0.4)Gd(1.6)SiO(5) (LGSO) crystals with dimensions of 2 × 2 × 14 mm(3) having 7.5 cm axial and 10 cm transverse field of view (FOV). The spatial resolution and sensitivity were measured using a small (22)Na point source at different positions in the scanner's FOV. The scatter fraction and count rate characteristics were measured using mouse- and rat-sized phantoms fitted with an (18)F line source. The overall imaging capabilities of the scanner were assessed using the NEMA image-quality phantom and laboratory animal studies. The NEMA-based radial and tangential spatial resolution ranged from 1.7 mm at the center of the FOV to 2.59 mm at a radial offset of 2.5 cm and from 1.85 mm at the center of the FOV to 1.76 mm at a radial offset of 2.5 cm, respectively. Iterative reconstruction improved the spatial resolution to 0.84 mm at the center of the FOV. The total absolute system sensitivity is 12.74% for an energy window of 250-650 keV. For the mouse-sized phantom, the peak noise equivalent count rate (NECR) is 183 kcps at 2.07 MBq cc(-1), whereas the peak true count rate is 320 kcps at 2.5 MBq cc(-1) with a scatter fraction of 19%. The rat-sized phantom had a scatter fraction of 31%, with a peak NECR of 67 kcps at 0.23 MBq cc(-1) and a peak true count rate of 186 kcps at 0.27 MBq cc(-1). The average activity concentration and percentage standard deviation were 126.97 kBq ml(-1) and 7%, respectively. The performance of the LabPET-8™ scanner was characterized based on the NEMA NU 04-2008 standards. The all in all performance demonstrates that the LabPET-8™ system is able to produce high-quality and highly contrasted images in a reasonable time, and as such it is well suited for preclinical molecular imaging-based research.

Performance evaluation of the FLEX triumph X-PET scanner using the national electrical manufacturers association NU-4 standards.

UNLABELLED: The purpose of this work was to evaluate the performance characteristics of the preclinical X-PET subsystem of the FLEX Triumph PET/CT scanner based on the NU 4-2008 standards of the National Electrical Manufacturers Association (NEMA). METHODS: The performance parameters evaluated include the spatial resolution, scatter fraction, count losses and random coincidences, sensitivity, and image-quality characteristics. The PET detector array consisted of 11,520 individual bismuth germanate crystals arranged in 48 rings and 180 blocks, with an axial field of view (FOV) of 11.6 cm and a inner ring diameter of 16.5 cm. The spatial resolution was measured with a small (22)Na point source (diameter, 0.25 mm) at different radial offsets from the center. Sensitivity was calculated using the same source by stepping the source axially through the axial FOV of the scanner. Scatter fraction and counting-rate performances were determined using a mouse- and rat-sized phantom with an (18)F line source insert. The NEMA image-quality phantom and rodent imaging were also performed to access the overall imaging capabilities of the scanner. RESULTS: Tangential spatial resolution in terms of full width at half maximum varied between 2.2 mm at the center of the FOV and 2.3 mm at a radial offset of 2.5 cm. The radial spatial resolution varied between 2.0 at the center and 4.4 mm at a radial offset of 2.3 cm. The peak system absolute sensitivity was 5.9% at the center of the FOV. The absolute system sensitivity was 0.67 counts/s/Bq, and the relative total system sensitivity was 73.9%. The scatter fraction for the mouse-sized phantom was 7.9%, with a peak true counting rate of 168 kilocounts per second (kcps) at 0.3 MBq/mL and a peak noise-equivalent counting rate of 106 kcps at 0.17 MBq/mL. The rat-sized phantom had a scatter fraction of 21%, with a peak true counting rate of 93 kcps at 0.034 MBq/mL and a peak noise-equivalent counting rate of 49 kcps at 0.02 MBq/mL. Recovery coefficients for the image-quality phantom ranged from 0.13 to 0.88. CONCLUSION: The performance of the X-PET scanner based on the NEMA NU 4-2008 standards was fully characterized. The overall performance demonstrates that the X-PET system is suitable for preclinical research.

Advances in multimodality molecular imaging.

Multimodality molecular imaging using high resolution positron emission tomography (PET) combined with other modalities is now playing a pivotal role in basic and clinical research. The introduction of combined PET/CT systems in clinical setting has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT) and functional or metabolic (PET) information provided in a "one-stop shop" and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI) in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging. This paper discusses recent advances in PET instrumentation and the advantages and challenges of multimodality imaging systems. Future opportunities and the challenges facing the adoption of multimodality imaging instrumentation will also be addressed.