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.

Tau PET and relative cerebral blood flow in dementia with Lewy bodies: A PET study.

PURPOSE: Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. METHODS: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. RESULTS: Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stß = 0.72) and category fluency (stß = 0.69) tests. Lower parietal R1 was related to lower delayed (stß = 0.50) and immediate (stß = 0.48) recall, VOSP number location (stß = 0.70) and fragmented letters (stß = 0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stß = 0.61), all p < 0.05. CONCLUSION: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.

Partial-volume correction in dynamic PET-CT: effect on tumor kinetic parameter estimation and validation of simplified metrics.

BACKGROUND: Partial-volume effects generally result in an underestimation of tumor tracer uptake on PET-CT for small lesions, necessitating partial-volume correction (PVC) for accurate quantification. However, investigation of PVC in dynamic oncological PET studies to date is scarce. The aim of this study was to investigate PVC's impact on tumor kinetic parameter estimation from dynamic PET-CT acquisitions and subsequent validation of simplified semi-quantitative metrics. Ten patients with EGFR-mutated non-small cell lung cancer underwent dynamic 18F-fluorothymidine PET-CT before, 7 days after, and 28 days after commencing treatment with a tyrosine kinase inhibitor. Parametric PVC was applied using iterative deconvolution without and with highly constrained backprojection (HYPR) denoising, respectively. Using an image-derived input function with venous parent plasma calibration, we estimated full kinetic parameters VT, K1, and k3/k4 (BPND) using a reversible two-tissue compartment model, and simplified metrics (SUV and tumor-to-blood ratio) at 50-60 min post-injection. RESULTS: PVC had a non-linear effect on measured activity concentrations per timeframe. PVC significantly changed each kinetic parameter, with a median increase in VT of 11.8% (up to 25.1%) and 10.8% (up to 21.7%) without and with HYPR, respectively. Relative changes in kinetic parameter estimates vs. simplified metrics after applying PVC were poorly correlated (correlations 0.36-0.62; p < 0.01). PVC increased correlations between simplified metrics and VT from 0.82 and 0.81 (p < 0.01) to 0.90 and 0.88 (p < 0.01) for SUV and TBR, respectively, albeit non-significantly. PVC also increased correlations between treatment-induced changes in simplified metrics vs. VT at 7 (SUV) and 28 (SUV and TBR) days after treatment start non-significantly. Delineation on partial-volume corrected PET images resulted in a median decrease in metabolic tumor volume of 14.3% (IQR - 22.1 to - 7.5%), and increased the effect of PVC on kinetic parameter estimates. CONCLUSION: PVC has a significant impact on tumor kinetic parameter estimation from dynamic PET-CT data, which differs from its effect on simplified metrics. However, it affected validation of these simplified metrics both as single measurements and as biomarkers of treatment response only to a small extent. Future dynamic PET studies should preferably incorporate PVC. TRIAL REGISTRATION: Dutch Trial Register, NTR3557 .

De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.

Mixed acid-base disorder secondary to topiramate use in traumatic brain injury.

We report a case of a man with traumatic brain injury. He was started on to prophylactic topiramate which led to a mixed acid-base disorder. He had severe metabolic acidosis secondary to renal tubular acidification defect and respiratory alkalosis secondary to hyperventilation. Withdrawal of the offending drug led to the prompt resolution of the acid-base disturbance.

UTE-T2∗ mapping detects sub-clinical meniscus injury after anterior cruciate ligament tear.

OBJECTIVE: Meniscus tear is a known risk factor for osteoarthritis (OA). Quantitative assessment of meniscus degeneration, prior to surface break-down, is important to identification of early disease potentially amenable to therapeutic interventions. This work examines the diagnostic potential of ultrashort echo time-enhanced T2∗ (UTE-T2∗) mapping to detect human meniscus degeneration in vitro and in vivo in subjects at risk of developing OA. DESIGN: UTE-T2∗ maps of 16 human cadaver menisci were compared to histological evaluations of meniscal structural integrity and clinical magnetic resonance imaging (MRI) assessment by a musculoskeletal radiologist. In vivo UTE-T2∗ maps were compared in 10 asymptomatic subjects and 25 ACL-injured patients with and without concomitant meniscal tear. RESULTS: In vitro, UTE-T2∗ values tended to be lower in histologically and clinically normal meniscus tissue and higher in torn or degenerate tissue. UTE-T2∗ map heterogeneity reflected collagen disorganization. In vivo, asymptomatic meniscus UTE-T2∗ values were repeatable within 9% (root-mean-square average coefficient of variation). Posteromedial meniscus UTE-T2∗ values in ACL-injured subjects with clinically diagnosed medial meniscus tear (n=10) were 87% higher than asymptomatics (n=10, P<0.001). Posteromedial menisci UTE-T2∗ values of ACL-injured subjects without concomitant medial meniscal tear (n=15) were 33% higher than asymptomatics (P=0.001). Posterolateral menisci UTE-T2∗ values also varied significantly with degree of joint pathology (P=0.001). CONCLUSION: Significant elevations of UTE-T2∗ values in the menisci of ACL-injured subjects without clinical evidence of subsurface meniscal abnormality suggest that UTE-T2∗ mapping is sensitive to sub-clinical meniscus degeneration. Further study is needed to determine whether elevated subsurface meniscus UTE-T2∗ values predict progression of meniscal degeneration and development of OA.

MRI, CT, scintigraphic and histological features of a vanishing scapular eosinophilic granuloma.

INTRODUCTION: Vanishing bone lesions have been previously described in patients with eosinophilic granuloma. MATERIALS AND METHODS: We present the magnetic resonance imaging, computed tomography, scintigraphic and histological findings in a 26-year-old woman presenting with a painful scapular mass that subsequently completely resolved, compatible with the diagnosis of eosinophilic granuloma. CONCLUSION: Clinicians should be aware of the multimodality appearances and natural history of resolving eosinophilic granuloma.

[Rare mesenchymal lesions in siblings. Two case reports]. / Seltene mesenchymale Läsionen bei Geschwisterkindern. Zwei Fallberichte.

We report on a 15-month-old boy presenting a juvenile active ossifying fibroma in the right nasal cavity and the sibling, a 9-month-old girl with a mesenchymal hamartoma of the chest wall. The two lesions showed many similarities. Both lesions are present at the time of birth or in early life with local obstructive or compressive effects. The lesions have a similar mixture of mature and immature mesenchymal tissue with areas of ossification. The entities present a tumor-like development with an abnormal mixture of tissue indigenous to the specific area of the body without notable atypical cytologic features. These features are typical criteria for hamartoma lesions.

Rare mesenchymal lesions: Hamartoma of the chest wall and juvenile active ossifying fibroma in siblings.

Mesenchymal hamartomas of the thorax are known as rare dysontogenetic tumorous non-neoplastic lesions. The juvenile active ossifying fibroma (JAOF) also is considered as a benign tumor like lesion of the mesenchymal connective tissue. The authors report the cases of 2 siblings-a 2-year-old girl with a hamartoma of the chest wall and her 4-year-old brother with a JAOF. The girl had bilocular mesenchymal hamartoma in the area of the 8(th) rib diagnosed in the first year of life, which was surgically removed completely. Her brother had been treated for JAOF of the right nasal sinus area diagnosed at the age of 15 months. Both lesions are extremely rare mutations of the local tissue, which occur typically in early childhood and continue benignly after surgical resection, but such a familial occurrence in siblings has not yet been reported. Furthermore, according to the histologic findings, the JAOF also could be seen as a hamartomatous lesion.

Latex allergy in pediatric surgery is dependent on repeated operations in the first year of life.

BACKGROUND/PURPOSE: Patients with spina bifida represent the highest risk group for hypersensitivity to latex. Recognized risk factors for these patients are repeated surgery and an atopic disposition. Little is known about children operated on in the first year of life for reasons other than spina bifida. METHODS: Eighty-six patients (mean age, 10.2 years) with gastrointestinal or urologic surgery were investigated for the number, type, and date of surgical interventions. Additionally, skin prick tests and provocation tests were performed to classify sensitized and symptomatic latex-allergic individuals. RESULTS: Twenty-seven patients were regarded as sensitized to latex (31.4%). Twenty patients were classified as being atopic (25.6%). Atopic patients were significantly more often sensitized and provocation positive compared with nonsensitized and provocation-negative ones (P <.01). Children already operated on in the first year of life (n = 44) with a positive provocation showed significantly higher latex-specific IgE-values than individuals with a negative outcome (P <.0001). The total number of operations and degree of sensitization showed a significant correlation; more than 8 surgical interventions during the first year of life significantly increased the risk of clinically relevant allergy to latex. CONCLUSION: This study emphasizes that individuals undergoing surgical interventions during infancy should be handled latex free from the very beginning of life.

Anterior approach for knee arthrography.

OBJECTIVE: To develop a new method of magnetic resonance arthrography (MRA) of the knee using an anterior approach analogous to the portals used for knee arthroscopy. DESIGN: An anterior approach to the knee joint was devised mimicking anterior portals used for knee arthroscopy. Seven patients scheduled for routine knee MRA were placed in a decubitus position and under fluoroscopic guidance a needle was advanced from a position adjacent to the patellar tendon into the knee joint. After confirmation of the needle tip location, a dilute gadolinium solution was injected. RESULTS AND CONCLUSION: All the arthrograms were technically successful. The anterior approach to knee MRA has greater technical ease than the traditional approach with little patient discomfort.