Erratum: Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies: erratum.

[This corrects the article on p. 5994 in vol. 14, PMID: 38021143.].

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies.

In this work, we used a hybrid time domain near-infrared spectroscopy (TD-NIRS) and diffuse correlation spectroscopy (DCS) device to retrieve hemoglobin and blood flow oscillations of skeletal muscle microvasculature. We focused on very low (VLF) and low-frequency (LF) oscillations (i.e., frequency lower than 0.145 Hz), that are related to myogenic, neurogenic and endothelial activities. We measured power spectral density (PSD) of blood flow and hemoglobin concentration in four muscles (thenar eminence, plantar fascia, sternocleidomastoid and forearm) of 14 healthy volunteers to highlight possible differences in microvascular hemodynamic oscillations. We observed larger PSDs for blood flow compared to hemoglobin concentration, in particular in case of distal muscles (i.e., thenar eminence and plantar fascia). Finally, we compared the PSDs measured on the thenar eminence of healthy subjects with the ones measured on a septic patient in the intensive care unit: lower power in the endothelial-dependent frequency band, and larger power in the myogenic ones were observed in the septic patient, in accordance with previous works based on laser doppler flowmetry.

An Isolated CNN Architecture for Classification of Finger-Tapping Tasks Using Initial Dip Images: A Functional Near-Infrared Spectroscopy Study.

This work investigates the classification of finger-tapping task images constructed for the initial dip duration of hemodynamics (HR) associated with the small brain area of the left motor cortex using functional near-infrared spectroscopy (fNIRS). Different layers (i.e., 16-layers, 19-layers, 22-layers, and 25-layers) of isolated convolutional neural network (CNN) designed from scratch are tested to classify the right-hand thumb and little finger-tapping tasks. Functional t-maps of finger-tapping tasks (thumb, little) were constructed for various durations (0.5 to 4 s with a uniform interval of 0.5 s) for the initial dip duration using a three gamma functions-based designed HR function. The results show that the 22-layered isolated CNN model yielded the highest classification accuracy of 89.2% with less complexity in classifying the functional t-maps of thumb and little fingers associated with the same small brain area using the initial dip. The results further demonstrated that the active brain area of the two tapping tasks from the same small brain area are highly different and well classified using functional t-maps of the initial dip (0.5 to 4 s) compared to functional t-maps generated for delayed HR (14 s). This study shows that the images constructed for initial dip duration can be helpful in the future for fNIRS-based diagnosis or cortical analysis of abnormal cerebral oxygen exchange in patients.

Presentation and Management of Orbito-Ocular Malignancies in a Tertiary Institution in Southwest Nigeria.

Purpose: The aim of this study was to review the management of orbito-ocular malignancies in the Departments of Radiotherapy and Ophthalmology, Lagos University Teaching Hospital, between January 1997 and December 2011 in comparison to previous and recent studies globally. Materials and Methods: This was a retrospective study of orbito-ocular malignancies seen at the Departments of Radiotherapy and Ophthalmology, Lagos University Teaching Hospital from 1997 to 2011. Case files and treatment cards were retrieved through the Medical Records department and the information required was extracted with the aid of a data extraction form. Results: A total of 98 cases with histologically confirmed orbito-ocular malignancies seen during the 15-year study period were analysed. Retinoblastoma (51 [52.0%]) was the most common orbito-ocular malignancies seen in children, whereas squamous cell carcinoma of the conjunctiva (25 [25.5%]) was the most common in adults. Seventeen (17%) patients had a combination of radiotherapy, surgery, and chemotherapy. Thirty (33%) had enucleation, whereas 33 (36%) had exenteration. Thirty-six patients had chemotherapy, whereas 44 patients benefited from radiotherapy, and radical treatment was offered to 24 patients. Total radical treatment dose was 35-65 Gy in 20-35 fractions over 4-7 weeks. Most of the patients (84 [85.7%]) were lost to follow up. Five (5.1%) died from disease progression and four (4.1%) are still alive and on regular follow-up. Conclusion: This study showed that the use of multimodality treatment was implemented but did not improve survival because the majority of patients presented late. The need for a collaborative effort in early detection and prompt referral for treatment of cancer cases cannot be overemphasised.

Cardiac complications from multisystem inflammatory syndrome associated with prior COVID-19 infection.

Multisystem inflammatory syndrome in adults (MIS-A) is a systemic inflammatory condition that presents roughly 4-6 weeks after initial COVID-19 infection. Patients typically present with persistent fevers, widespread rash, abdominal pain, vomiting and diarrhoea, and new-onset neurological symptoms. Cardiac dysfunction is a prominent feature of COVID-19 sequelae due to the abundance of ACE2 receptors on cardiac tissue. Delayed diagnosis due to the novelty of MIS-A can lead to cardiac complications like heart failure and shock, which could result in chronic cardiac disease. Avoidance of complications and chronic illness is possible with prompt corticosteroid therapy. Despite patient recovery to baseline level of function, surveillance of cardiac function to screen for chronic cardiac disease in the follow-up period is recommended. We present a case of MIS-A in a young man, compare his presentation with other similar cases and discuss implications of delayed diagnosis.

Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict PET Image Quality of Three Generations EGFR TKI in Advanced-Stage NSCLC Patients.

INTRODUCTION: Epidermal growth factor receptor (EGFR) mutated NSCLC is best treated using an EGFR tyrosine kinase inhibitor (TKI). The presence and accessibility of EGFR overexpression and mutation in NSCLC can be determined using radiolabeled EGFR TKI PET/CT. However, recent research has shown a significant difference between image qualities (i.e., tumor-to-lung contrast) in three generation EGFR TKIs: 11C-erlotinib, 18F-afatinib and 11C-osimertinib. In this research we aim to develop a physiological pharmacokinetic (PBPK)-model to predict tumor-to-lung contrast and as a secondary outcome the uptake of healthy tissue of the three tracers. METHODS: Relevant physicochemical and drug specific properties (e.g., pKa, lipophilicity, target binding) for each TKI were collected and applied in established base PBPK models. Key hallmarks of NSCLC include: immune tumor deprivation, unaltered tumor perfusion and an acidic tumor environment. Model accuracy was demonstrated by calculating the prediction error (PE) between predicted tissue-to-blood ratios (TBR) and measured PET-image-derived TBR. Sensitivity analysis was performed by excluding each key component and comparing the PE with the final mechanistical PBPK model predictions. RESULTS: The developed PBPK models were able to predict tumor-to-lung contrast for all EGFR-TKIs within threefold of observed PET image ratios (PE tumor-to-lung ratio of -90%, +44% and -6.3% for erlotinib, afatinib and osimertinib, respectively). Furthermore, the models depicted agreeable whole-body distribution, showing high tissue distribution for osimertinib and afatinib and low tissue distribution at high blood concentrations for erlotinib (mean PE, of -10.5%, range -158%-+190%, for all tissues). CONCLUSION: The developed PBPK models adequately predicted the image quality of afatinib and osimertinib and erlotinib. Some deviations in predicted whole-body TBR lead to new hypotheses, such as increased affinity for mutated EGFR and active influx transport (erlotinib into excreting tissues) or active efflux (afatinib from brain), which is currently unaccounted for. In the future, PBPK models may be used to predict the image quality of new tracers.

Advanced quantitative evaluation of PET systems using the ACR phantom and NiftyPET software.

PURPOSE: A novel phantom-imaging platform, a set of software tools, for automated and high-precision imaging of the American College of Radiology (ACR) positron emission tomography (PET) phantom for PET/magnetic resonance (PET/MR) and PET/computed tomography (PET/CT) systems is proposed. METHODS: The key feature of this platform is the vector graphics design that facilitates the automated measurement of the knife-edge response function and hence image resolution, using composite volume of interest templates in a 0.5 mm resolution grid applied to all inserts of the phantom. Furthermore, the proposed platform enables the generation of an accurate µ $\mu$ -map for PET/MR systems with a robust alignment based on two-stage image registration using specifically designed PET templates. The proposed platform is based on the open-source NiftyPET software package used to generate multiple list-mode data bootstrap realizations and image reconstructions to determine the precision of the two-stage registration and any image-derived statistics. For all the analyses, iterative image reconstruction was employed with and without modeled shift-invariant point spread function and with varying iterations of the ordered subsets expectation maximization (OSEM) algorithm. The impact of the activity outside the field of view (FOV) was assessed using two acquisitions of 30 min each, with and without the activity outside the FOV. RESULTS: The utility of the platform has been demonstrated by providing a standard and an advanced phantom analysis including the estimation of spatial resolution using all cylindrical inserts. In the imaging planes close to the edge of the axial FOV, we observed deterioration in the quantitative accuracy, reduced resolution (FWHM increased by 1-2 mm), reduced contrast, and background uniformity due to the activity outside the FOV. Although it slows convergence, the PSF reconstruction had a positive impact on resolution and contrast recovery, but the degree of improvement depended on the regions. The uncertainty analysis based on bootstrap resampling of raw PET data indicated high precision of the two-stage registration. CONCLUSIONS: We demonstrated that phantom imaging using the proposed methodology with the metric of spatial resolution and multiple bootstrap realizations may be helpful in more accurate evaluation of PET systems as well as in facilitating fine tuning for optimal imaging parameters in PET/MR and PET/CT clinical research studies.

Control of Transcranial Direct Current Stimulation Duration by Assessing Functional Connectivity of Near-Infrared Spectroscopy Signals.

Transcranial direct current stimulation (tDCS) has been shown to create neuroplasticity in healthy and diseased populations. The control of stimulation duration by providing real-time brain state feedback using neuroimaging is a topic of great interest. This study presents the feasibility of a closed-loop modulation for the targeted functional network in the prefrontal cortex. We hypothesize that we cannot improve the brain state further after reaching a specific state during a stimulation therapy session. A high-definition tDCS of 1[Formula: see text]mA arranged in a ring configuration was applied at the targeted right prefrontal cortex of 15 healthy male subjects for 10[Formula: see text]min. Functional near-infrared spectroscopy was used to monitor hemoglobin chromophores during the stimulation period continuously. The correlation matrices obtained from filtered oxyhemoglobin were binarized to form subnetworks of short- and long-range connections. The connectivity in all subnetworks was analyzed individually using a new quantification measure of connectivity percentage based on the correlation matrix. The short-range network in the stimulated hemisphere showed increased connectivity in the initial stimulation phase. However, the increase in connection density reduced significantly after 6[Formula: see text]min of stimulation. The short-range network of the left hemisphere and the long-range network gradually increased throughout the stimulation period. The connectivity percentage measure showed a similar response with network theory parameters. The connectivity percentage and network theory metrics represent the brain state during the stimulation therapy. The results from the network theory metrics, including degree centrality, efficiency, and connection density, support our hypothesis and provide a guideline for feedback on the brain state. The proposed neuro-feedback scheme is feasible to control the stimulation duration to avoid overdosage.

Performance Assessment of a Commercial Continuous-Wave Near-Infrared Spectroscopy Tissue Oximeter for Suitability for Use in an International, Multi-Center Clinical Trial.

Despite the wide range of clinical and research applications, the reliability of the absolute oxygenation measurements of continuous wave near-infrared spectroscopy sensors is often questioned, partially due to issues of standardization. In this study, we have compared the performances of 13 units of a continuous wave near-infrared spectroscopy device (PortaMon, Artinis Medical Systems, NL) to test their suitability for being used in the HEMOCOVID-19 clinical trial in 10 medical centers around the world. Detailed phantom and in vivo tests were employed to measure the precision and reproducibility of measurements of local blood oxygen saturation and total hemoglobin concentration under different conditions: for different devices used, different operators, for probe repositioning over the same location, and over time (hours/days/months). We have detected systematic differences between devices when measuring phantoms (inter-device variability, <4%), which were larger than the intra-device variability (<1%). This intrinsic variability is in addition to the variability during in vivo measurements on the forearm muscle resulting from errors in probe positioning and intrinsic physiological noise (<9%), which was also larger than the inter-device differences (<3%) during the same test. Lastly, we have tested the reproducibility of the protocol of the HEMOCOVID-19 clinical trial; that is, forearm muscle oxygenation monitoring during vascular occlusion tests over days. Overall, our conclusion is that these devices can be used in multi-center trials but care must be taken to characterize, follow-up, and statistically account for inter-device variability.

Harmonisation of PET/CT contrast recovery performance for brain studies.

PURPOSE: In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were developed. METHODS: Twelve clinical PET/CT systems (4 GE, 4 Philips, 4 Siemens, including SiPM-based "digital" systems) were used to acquire 30-min PET scans of a Hoffman 3D Brain phantom filled with ~ 33 kBq·mL-1 [18F]FDG. Scan data were reconstructed using various reconstruction settings. The images were rigidly coregistered to a template (voxel size 1.17 × 1.17 × 2.00 mm3) onto which several volumes of interest (VOIs) were defined. Recovery coefficients (RC) and grey matter to white matter ratios (GMWMr) were derived for eroded (denoted in the text by subscript e) and non-eroded grey (GM) and white (WM) matter VOIs as well as a mid-phantom cold spot (VOIcold) and VOIs from the Hammers atlas. In addition, left-right hemisphere differences and voxel-by-voxel differences compared to a reference image were assessed. RESULTS: Systematic differences were observed for reconstructions with and without point-spread-function modelling (PSFON and PSFOFF, respectively). Normalising to image-derived activity, upper and lower limits ensuring image comparability were as follows: for PSFON, RCGMe = [0.97-1.01] and GMWMre = [3.51-3.91] for eroded VOI and RCGM = [0.78-0.83] and GMWMr = [1.77-2.06] for non-eroded VOI, and for PSFOFF, RCGMe = [0.92-0.99] and GMWMre = [3.14-3.68] for eroded VOI and RCGM = [0.75-0.81] and GMWMr = [1.72-1.95] for non-eroded VOI. CONCLUSIONS: To achieve inter-scanner comparability, we propose selecting reconstruction settings based on RCGMe and GMWMre as specified in "Results". These proposed standards should be tested prospectively to validate and/or refine the harmonisation criteria.

Grey zone amyloid burden affects memory function: the SCIENCe project.

PURPOSE: To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. METHODS: We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [18F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BPND) and standardized uptake value ratio (SUVr50-70) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BPND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen's kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19-0.29 BPND/1.28-1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope. RESULTS: As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BPND thresholds (range kappa 0.65-0.70 versus 0.60-0.63). All thresholds predicted memory decline (range beta - 0.29 to - 0.21, all p < 0.05). Analyses in subgroups showed memory slopes gradually became steeper with higher amyloid load (all p for trend < 0.05). Participants with a low amyloid burden benefited from a practice effect (i.e. increase in memory), whilst high amyloid burden was associated with memory decline. Memory slopes of individuals in the grey zone were intermediate. CONCLUSION: We provide evidence that not only high but also grey zone amyloid burden subtly impacts memory function. Therefore, in case a binary classification is required, we suggest using a relatively low threshold which includes grey zone amyloid pathology.

Quantification of [18F]afatinib using PET/CT in NSCLC patients: a feasibility study.

INTRODUCTION: Only a subgroup of non-small cell lung cancer (NSCLC) patients benefit from treatment using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as afatinib. Tumour uptake of [18F]afatinib using positron emission tomography (PET) may identify those patients that respond to afatinib therapy. Therefore, the aim of this study was to find the optimal tracer kinetic model for quantification of [18F]afatinib uptake in NSCLC tumours. METHODS: [18F]Afatinib PET scans were performed in 10 NSCLC patients. The first patient was scanned for the purpose of dosimetry. Subsequent patients underwent a 20-min dynamic [15O]H2O PET scan (370 MBq) followed by a dynamic [18F]afatinib PET scan (342 ± 24 MBq) of 60 or 90 min. Using the Akaike information criterion (AIC), three pharmacokinetic plasma input models were evaluated with both metabolite-corrected sampler-based input and image-derived (IDIF) input functions in combination with discrete blood samples. Correlation analysis of arterial on-line sampling versus IDIF was performed. In addition, perfusion dependency and simplified measures were assessed. RESULTS: Ten patients were included. The injected activity of [18F]afatinib was 341 ± 37 MBq. Fifteen tumours could be identified in the field of view of the scanner. Based on AIC, tumour kinetics were best described using an irreversible two-tissue compartment model and a metabolite-corrected sampler-based input function (Akaike 50%). Correlation of plasma-based input functions with metabolite-corrected IDIF was very strong (r2 = 0.93). The preferred simplified uptake parameter was the tumour-to-blood ratio over the 60- to 90-min time interval (TBR60-90). Tumour uptake of [18F]afatinib was independent of perfusion. CONCLUSION: The preferred pharmacokinetic model for quantifying [18F]afatinib uptake in NSCLC tumours was the 2T3K_vb model. TBR60-90 showed excellent correlation with this model and is the best candidate simplified method. TRIAL REGISTRATION: https://eudract.ema.europa.eu/ nr 2012-002849-38.

International standards for fetal brain structures based on serial ultrasound measurements from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured using ultrasound, in healthy, well-nourished women at low risk of impaired fetal growth and poor perinatal outcome, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicenter, longitudinal study. The sample analyzed was selected randomly from the overall FGLS population, ensuring an equal distribution among the eight diverse participating sites and of three-dimensional (3D) ultrasound volumes across pregnancy (range: 15-36 weeks' gestation). We measured, in planes reconstructed from 3D ultrasound volumes of the fetal head at different timepoints in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle, atrium of the posterior horn of the lateral ventricle (PV) and cisterna magna (CM). Fractional polynomials were used to construct the standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were selected at random. After exclusions, 3D ultrasound volumes from 442 fetuses born without a congenital malformation were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures, except the PV, showed increasing size with gestational age, and the size of the POF, SF, PV and CM showed increasing variability. The 3rd , 5th , 50th , 95th and 97th smoothed centiles are presented. The 5th centiles for the POF and SF were 3.1 mm and 4.7 mm at 22 weeks' gestation and 4.6 mm and 9.9 mm at 32 weeks, respectively. The 95th centiles for the PV and CM were 8.5 mm and 7.5 mm at 22 weeks and 8.6 mm and 9.5 mm at 32 weeks, respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcome. We recommend these as international standards for the assessment of measurements obtained using ultrasound from fetal brain structures. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Correction to: Letter to the Editor re: Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake.

The article was updated to correct the following errors due to an error in production.

Quality-improvement program for ultrasound-based fetal anatomy screening using large-scale clinical audit.

OBJECTIVE: A large-scale audit and peer review of ultrasound images may improve sonographer performance, but is rarely performed consistently as it is time-consuming and expensive. The aim of this study was to perform a large-scale audit of routine fetal anatomy scans to assess if a full clinical audit cycle can improve clinical image-acquisition standards. METHODS: A large-scale, clinical, retrospective audit was conducted of ultrasound images obtained during all routine anomaly scans performed from 18 + 0 to 22 + 6 weeks' gestation at a UK hospital during 2013 (Cycle 1), to build a baseline understanding of the performance of sonographers. Targeted actions were undertaken in response to the findings with the aim of improving departmental performance. A second full-year audit was then performed of fetal anatomy ultrasound images obtained during the following year (Cycle 2). An independent pool of experienced sonographers used an online tool to assess all scans in terms of two parameters: scan completeness (i.e. were all images archived?) and image quality using objective scoring (i.e. were images of high quality?). Both were assessed in each audit at the departmental level and at the individual sonographer level. A random sample of 10% of scans was used to assess interobserver reproducibility. RESULTS: In Cycle 1 of the audit, 103 501 ultrasound images from 6257 anomaly examinations performed by 22 sonographers were assessed; in Cycle 2, 153 557 images from 6406 scans performed by 25 sonographers were evaluated. The analysis was performed including the images obtained by the 20 sonographers who participated in both cycles. Departmental median scan completeness improved from 72% in the first year to 78% at the second assessment (P < 0.001); median image-quality score for all fetal views improved from 0.83 to 0.86 (P < 0.001). The improvement was greatest for those sonographers who performed poorest in the first audit; with regards to scan completeness, the poorest performing 15% of sonographers in Cycle 1 improved by more than 30 percentage points, and with regards to image quality, the poorest performing 11% in Cycle 1 showed a more than 10% improvement. Interobserver repeatability of scan completeness and image-quality scores across different fetal views were similar to those in the published literature. CONCLUSIONS: A clinical audit and a set of targeted actions helped improve sonographer scan-acquisition completeness and scan quality. Such adherence to recommended clinical acquisition standards may increase the likelihood of correct measurement and thereby fetal growth assessment, and should allow better detection of abnormalities. As such a large-scale audit is time consuming, further advantages would be achieved if this process could be automated. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.

Personalizing NSCLC therapy by characterizing tumors using TKI-PET and immuno-PET.

Non-small cell lung cancer (NSCLC) therapy has entered a rapidly advancing era of precision medicine with an ever increasing number of drugs directed against a variety of specific tumor targets. Amongst these new agents, tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) are most frequently used. However, as only a sensitive subgroup of patients benefits from targeting drugs, predictive biomarkers are needed. Positron emission tomography (PET) may offer such a biomarker for predicting therapy efficacy. Some of the TKIs and mAbs that are in clinical use can be radioactively labeled and used as tracers. PET can visualize and quantify tumor specific uptake of radiolabeled targeting drugs, allowing for characterization of their pharmacokinetic behavior. In this review, the clinical potential of PET using radiolabeled TKIs (TKI-PET) and mAbs (immuno-PET) in NSCLC is discussed, and an overview is provided of the most relevant preclinical and clinical studies.

Cerebral microglia activation in hepatitis C virus infection correlates to cognitive dysfunction.

Hepatitis C virus (HCV) infection may induce chronic fatigue and cognitive dysfunction. Virus replication was proven within the brain and HCV-positive cells were identified as microglia and astrocytes. We hypothesized that cerebral dysfunction in HCV-afflicted patients is associated with microglia activation. Microglia activation was assessed in vivo in 22 patients with chronic HCV infection compared to six healthy controls using [(11) C]-PK11195 Positron Emission Tomography (PET) combined with magnetic resonance tomography for anatomical localization. Patients were subdivided with regard to their PCR status, Fatigue Impact Scale score (FIS) and attention test sum score (ATS). A total of 12 patients (54.5%) were HCV PCR positive [of which 7 (58.3%) had an abnormal FIS and 7 (58.3%) an abnormal ATS], 10 patients (45.5%) were HCV PCR negative (5 (50%) each with an abnormal FIS or ATS). Patients without attention deficits showed a significantly higher accumulation of [(11) C]-PK11195 in the putamen (P = 0.05), caudate nucleus (P = 0.03) and thalamus (P = 0.04) compared to controls. Patients with and without fatigue did not differ significantly with regard to their specific tracer binding in positron emission tomography. Preserved cognitive function was associated with significantly increased microglia activation with predominance in the basal ganglia. This indicates a probably neuroprotective effect of microglia activation in HCV-infected patients.