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Background PSMA-PET 1 has shown good concordance with histology, but there is a need to investigate the ability of PSMA-PET to delineate DIL 2 boundaries for guided biopsy and focal therapy planning. Objective To determine threshold and margin combinations that satisfy the following criteria: ≥95% sensitivity with max specificity and ≥95% specificity with max sensitivity. Design, setting and participants We registered pathologist-annotated whole-mount mid-gland prostatectomy histology sections cut in 4.4 mm intervals from 12 patients to pre-surgical PSMA-PET/MRI by mapping histology to ex-vivo imaging to in-vivo imaging. We generated PET-derived tumor volumes using boundaries defined by thresholded PET volumes from 1–100% of SUV 3 max in 1% intervals. At each interval, we applied margins of 0–30 voxels in one voxel increments, giving 3000 volumes/patient. Outcome measurements Mean and standard deviation of sensitivity and specificity for cancer detection within the 2D oblique histologic planes that intersected with the 3D PET volume for each patient. Results and limitations A threshold of 67% SUV max with an 8.4 mm margin achieved a (mean ± std.) sensitivity of 95.0 ± 7.8% and specificity of 76.4 ± 14.7%. A threshold of 81% SUV max with a 5.1 mm margin achieved sensitivity of 65.1 ± 28.4% and specificity of 95.1 ± 5.2%. Conclusions Preliminary evidence of thresholding and margin expansion of PSMA-PET images targeted at DILs validated with histopathology demonstrated excellent mean sensitivity and specificity in the setting of focal therapy/boosting and guided biopsy. These parameters can be used in a larger validation study supporting clinical translation.

Adults’ linguistic background influences their sequential statistical learning of an artificial language characterized by conflicting forward-going and backward-going transitional probabilities. English-speaking adults favor backward-going transitional probabilities, consistent with the head-initial structure of English. Korean-speaking adults favor forward-going transitional probabilities, consistent with the head-final structure of Korean. These experiments assess when infants develop this directional bias. In the experiments, 7-month-old infants showed no bias for forward-going or backward-going regularities. By 13 months, however, English-learning infants favored backward-going transitional probabilities over forward-going transitional probabilities, consistent with English-speaking adults. This indicates that statistical learning rapidly adapts to the predominant syntactic structure of the native language. Such adaptation may facilitate subsequent learning by highlighting statistical structures that are likely to be informative in the native linguistic environment. Ministry of Education (MOE) We are grateful to Sook Whan Cho and Hongoak Yun for facilitating data collection at Asan Hospital in Seoul, South Korea, and Jae-un Kim and Young-In Lee for running Experiment 2. Support came from a Start Up Grant and a Singapore Ministry of Education Tier 1 grant (RG81/14) to L.O.

An ongoing prospective study is acquiring preoperative imaging data for men with prostate cancer (PCa) using the molecular imaging agent [ F]-DCFPyL targeted against prostate-specific membrane antigen (PSMA). To date, six men (of a planned accrual of 24) with clinically localized, biopsy-proven PCa have undergone preoperative [ F]-DCFPyL positron emission tomography (PET) imaging and multiparametric magnetic resonance imaging acquired using a hybrid PET/MRI system. Lesions identified by [ F]-DCFPyL uptake on PET/MRI were characterized in terms of maximum standardized uptake value (SUV ) and volume using a boundary threshold of 40% SUV . Following surgery, all prostatectomy specimens were processed using a whole-mount technique for accurate deformable co-registration and correlation with PCa foci defined on digitized pathology images. Well-defined intraprostatic dominant lesions were identified by [ F]-DCFPyL PET/MRI (mean SUV 11.4 ± 8.25; mean volume 2.2 ± 2.4 cm ) in all six men. Co-registered digitized whole-mount pathology for the first case revealed that intense [ F]-DCFPyL uptake (SUV 27 ± 1.1 cm ) and multiparametric MRI changes (Prostate Imaging Reporting and Data System score of 4) were highly correlated with a 0.5-cm dominant (largest) lesion with Gleason pattern 4 PCa in the right mid peripheral zone. A smaller focus (0.01 cm ) of lower-grade PCa (Gleason pattern 3) had much lower uptake (SUV 2.7). These early prospective data show that dominant intraprostatic lesions could be identified in all six men using [ F]-DCFPyL as an imaging probe. Trial accrual will continue to quantify in terms of spatial concordance the ability of [ F]-DCFPyL to identify the location and characterize the grade of intraprostatic cancer foci in clinically localized PCa. Patient summary: Positron emission tomography using a novel probe called [ F]-DCFPyL directed against the prostate-specific membrane antigen protein was able to identify locations of prostate cancer in the prostate glands of men undergoing imaging before surgery. In the future, such imaging may allow better targeting of treatment to the portion of the prostate containing the most aggressive components of cancer rather than treating the whole prostate in a uniform fashion. [ F]-DCFPyL positron emission tomography/magnetic resonance imaging shows promise for identifying high-grade intraprostatic foci of prostate cancer in a spatially accurate fashion to facilitate targeted biopsy and treatment. 18 18 18 18 3 18 3 3 3 18 18 18 18 max max max max

Alzheimer’s disease (AD) pathology causes microstructural changes in the brain. These changes, if quantified with magnetic resonance imaging (MRI), could be studied for use as an early biomarker for AD. The aim of our study was to determine if T(1) relaxation, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) metrics could reveal changes within the hippocampus and surrounding white matter structures in ex vivo transgenic mouse brains overexpressing human amyloid precursor protein with the Swedish mutation. Delineation of hippocampal cell layers using DTI color maps allows more detailed analysis of T(1)-weighted imaging, DTI, and qMTI metrics, compared with segmentation of gross anatomy based on relaxation images, and with analysis of DTI or qMTI metrics alone. These alterations are observed in the absence of robust intracellular Aβ accumulation or plaque deposition as revealed by histology. This work demonstrates that multiparametric quantitative MRI methods are useful for characterizing changes within the hippocampal substructures and surrounding white matter tracts of mouse models of AD.

Block detector designs, utilizing a pixelated scintillator array coupled to a photosensor array in a light-sharing design, are commonly used for positron emission tomography (PET) imaging applications. In practice, the spatial sampling of these designs is limited by the crystal pitch, which must be large enough for individual crystals to be resolved in the detector flood image. Replacing the conventional 2D scintillator array with an array of phoswich elements, each consisting of an optically coupled side-by-side scintillator pair, may improve spatial sampling in one direction of the array without requiring resolving smaller crystal elements. To test the feasibility of this design, a 4 × 4 phoswich array was constructed, with each phoswich element consisting of two optically coupled, 3 . 17 × 1 . 58 × 10 mm 3 LSO crystals co-doped with cerium and calcium. The amount of calcium doping was varied to create a ‘fast’ LSO crystal with decay time of 32.9 ns and a ‘slow’ LSO crystal with decay time of 41.2 ns. Using a Hamamatsu R8900U-00-C12 position-sensitive photomultiplier tube (PS-PMT) and a CAEN V1720 250 MS/s waveform digitizer, we were able to show effective discrimination of the fast and slow LSO crystals in the phoswich array. Although a side-by-side phoswich array is feasible, reflections at the crystal boundary due to a mismatch between the refractive index of the optical adhesive ( n = 1 . 5 ) and LSO ( n = 1 . 82 ) caused it to behave optically as an 8 × 4 array rather than a 4 × 4 array. Direct coupling of each phoswich element to individual photodetector elements may be necessary with the current phoswich array design. Alternatively, in order to implement this phoswich design with a conventional light sharing PET block detector, a high refractive index optical adhesive is necessary to closely match the refractive index of LSO.

Purpose The clinical utility of FDG-PET in diagnosing frontotemporal dementia (FTD) has been well demonstrated over the past decades. On the contrary, the diagnostic value of arterial spin labelling (ASL) MRI – a relatively new technique – in clinical diagnosis of FTD has yet to be confirmed. Using simultaneous PET/MRI, we evaluated the diagnostic performance of ASL in identifying pathological abnormalities in FTD (FTD) to determine whether ASL can provide similar diagnostic value as FDG-PET. Methods ASL and FDG-PET images were compared in 10 patients with FTD and 10 healthy older adults. Qualitative and quantitative measures of diagnostic equivalency were used to determine the diagnostic utility of ASL compared to FDG-PET. Sensitivity, specificity, and inter-rater reliability were calculated for each modality from scores of subjective visual ratings and from analysis of regional mean values in thirteen a priori regions of interest (ROI). To determine the extent of concordance between modalities in each patient, individual statistical maps generated from comparison of each patient to controls were compared between modalities using the Jaccard similarity index (JI). Results Visual assessments revealed lower sensitivity, specificity and inter-rater reliability for ASL (66.67%/62.12%/0.2) compared to FDG-PET (88.43%/90.91%/0.61). Across all regions, ASL performed lower than FDG-PET in discriminating patients from controls (areas under the receiver operating curve: ASL = 0.75 and FDG-PET = 0.87). In all patients, ASL identified patterns of reduced perfusion consistent with FTD, but areas of hypometabolism exceeded hypoperfused areas (group-mean JI = 0.30 ± 0.22). Conclusion This pilot study demonstrated that ASL can detect similar spatial patterns of abnormalities in individual FTD patients compared to FDG-PET, but its sensitivity and specificity for discriminant diagnosis of a patient from healthy individuals remained unmatched to FDG-PET. Further studies at the individual level are required to confirm the clinical role of ASL in FTD management., Highlights • ASL-CBF and FDG-PET are moderate-to-strongly correlated in FTD brains. • FDG-PET produced higher specificity, sensitivity and diagnostic accuracy compared to ASL-CBF. • In all patients, hypometabolic regions identified in individual statistical maps extended beyond hypoperfused regions.

Objective Hybrid PET/MRI may improve detection of seizure-onset zone (SOZ) in drug-resistant epilepsy (DRE), however, concerns over PET bias from MRI-based attenuation correction (MRAC) have limited clinical adoption of PET/MRI. This study evaluated the diagnostic equivalency and potential clinical value of PET/MRI against PET/CT in DRE. Materials and methods MRI, FDG-PET and CT images (n = 18) were acquired using a hybrid PET/MRI and a CT scanner. To assess diagnostic equivalency, PET was reconstructed using MRAC (RESOLUTE) and CT-based attenuation correction (CTAC) to generate PET/MRI and PET/CT images, respectively. PET/MRI and PET/CT images were compared qualitatively through visual assessment and quantitatively through regional standardized uptake value (SUV) and z-score assessment. Diagnostic accuracy and sensitivity of PET/MRI and PET/CT for SOZ detection were calculated through comparison to reference standards (clinical hypothesis and histopathology, respectively). Results Inter-reader agreement in visual assessment of PET/MRI and PET/CT images was 78 % and 81 %, respectively. PET/MRI and PET/CT were strongly correlated in mean SUV (r = 0.99, p Conclusion We demonstrate here that PET/MRI with optimal MRAC can yield similar diagnostic performance as PET/CT. Nevertheless, further exploration of the potential added value of PET/MRI is necessary before clinical adoption of PET/MRI for epilepsy imaging.

Between the first and the second year of life, children improve in their ability to use phonemic contrasts when learning label–object pairings. This improvement may be related to children’s experience with the distribution of phonemes across lexical forms. Because phonemes typically occur in different lexical frames (e.g., /d/ and /t/ in “doggy” and “teddy” rather than “doggy” and “toggy”), familiarity with words makes similar phonemes more distinct through acquired distinctiveness. In a series of simulations, we demonstrate that English input has the distributional characteristics necessary to facilitate use of phonemic contrasts as a function of increasing familiarity with the lexicon. Further, these simulations support a novel prediction: that less common phonemes should take longer to be used productively. We tested this prediction with children between 18 and 25 months, and found that the relatively infrequent /s/ and /z/ contrast takes longer to emerge than frequent contrasts such as /b/–/d/ or /d/–/t/.

Selective sustained attention is vital for higher order cognition. Although endogenous and exogenous factors influence selective sustained attention, assessment of the degree to which these factors influence performance and learning is often challenging. We report findings from the Track-It task, a paradigm that aims to assess the contribution of endogenous and exogenous factors to selective sustained attention within the same task. Behavioral accuracy and eye-tracking data on the Track-It task were correlated with performance on an explicit learning task. Behavioral accuracy and fixations to distractors during the Track-It task did not predict learning when exogenous factors supported selective sustained attention. In contrast, when endogenous factors supported selective sustained attention, fixations to distractors were negatively correlated with learning. Similarly, when endogenous factors supported selective sustained attention, higher behavioral accuracy was correlated with greater learning. These findings suggest that endogenously and exogenously driven selective sustained attention, as measured through different conditions of the Track-It task, may support different kinds of learning.

Considerable research indicates that learners are sensitive to probabilistic structure in laboratory studies of artificial language learning. However, the artificial and simplified nature of the stimuli used in the pioneering work on the acquisition of statistical regularities has raised doubts about the scalability of such learning to the complexity of natural language input. In this review, we explore a central prediction of statistical learning accounts of language acquisition – that sensitivity to statistical structure should be linked to real language processes – via an examination of: (1) recent studies that have increased the ecological validity of the stimuli; (2) studies that suggest statistical segmentation produces representations that share properties with real words; (3) correlations between individual variability in statistical learning ability and individual variability in language outcomes; and (4) atypicalities in statistical learning in clinical populations characterized by language delays or deficits.

Background Magnetic resonance imaging (MRI) of transgenic mouse models of Alzheimer's disease is valuable to understand better the structural changes that occur in the brain and could provide a means to test drug treatments. A hallmark pathological feature of Alzheimer's disease is atrophy of the hippocampus, which is an early biomarker of the disease. MRI can be used to detect and monitor this biomarker. Method Repeated measurements using in vivo 3D T 2 -weighted imaging of mice were used to assess the methods. Each mouse was imaged twice in one week and twice the following week and no changes in volume were expected. The hippocampus was segmented both manually and semi-automatically. Registration was done to gain information on shape changes. The volumes from each mouse were compared intra-mouse, between mice and to hippocampus volume values in the literature. Results A reliable method was developed which was able to detect difference in volumes of hippocampus between mice when performed by a single individual. The semi-automated segmentation was unable to detect the same level of differences. The semi-automated segmentation method gave larger hippocampus volumes, with 78–87% reliability between the manual and semi-automated segmentation. Although more accurate, the manual segmentation is laborious and suffers from inter- and intra-variability. Conclusion These results suggest that manual segmentation is still considered the most reliable segmentation method for small structures. However, if performing longitudinal studies, where there is at least one year between imaging sessions, the segmentation should be done all at once at the end of all the imaging sessions. If segmentation is done after each imaging session, with at least a year passing between segmentations, very small variations in volumes can be missed. This method provides a means to quantify the volume of the hippocampus in a live mouse using manual segmentation, which is the first step toward studying hippocampus atrophy in a mouse model of Alzheimer's disease.

Selective sustained attention (SSA) is crucial for higher-order cognition. Factors promoting SSA are described as exogenous or endogenous. However, there is little research specifying how these factors interact during development – due, largely, to the paucity of developmentally-appropriate paradigms. We report findings from a novel paradigm designed to investigate SSA in preschoolers. The findings indicate that this task (1) has good psychometric and parametric properties, and (2) allows investigation of exogenous and endogenous factors within the same task, making it possible to attribute changes in performance to different mechanisms of attentional control rather than to differences in engagement in different tasks.

Several recent experiments indicate that, when learning words, children are not as sensitive to phonemic differences (e.g., /d/ vs. /t/) as they are in discrimination tasks [Pater, J., Stager, C. L., & Werker, J. F. (2004). The perceptual acquisition of phonological contrasts. Language, 80, 384–402; Stager, C. L., & Werker, J. F. (1997). Infants listen for more phonetic detail in speech perception than in word-learning tasks. Nature, 388, 381–382]. In particular, 14-month-olds who can hear the difference between similar words such as “daw” and “taw” treat these labels as interchangeable when they refer to newly learned objects. We hypothesize that experience with the distribution of phonemes in their native language helps children use these phonemic distinctions in a word-learning task. Children receive distributional information when they experience different phonemes in different words. To test this hypothesis, we exposed children to two kinds of words: words in which phonemes occurred in very similar contexts, and words in which phonemes occurred in dissimilar contexts. Children who experienced phonemes in dissimilar contexts were more successful in using the contrast between the phonemes in a word-learning task.

18F-Fluorocholine (18F-FCH) Hybrid PET/MRI in the Evaluation of Men With Suspected Prostate Cancer Recurrence Following Definitive Local Therapy T.W. Zhang, Z. Kassam, I. Rachinsky, C. Romagnoli, D.P. D’Souza, B. Ahmad, V.M. Venkatesan, J. Chin, S. Pautler, J. Butler, J.D. Thiessen, A. Lozanski, P. Chung, C. Menard, T.Y. Lee, and G.S. Bauman; London Regional Cancer Program, London, ON, Canada, Western University, London, ON, Canada, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada

The effects of intracerebral implants of steroid hormones on scent marking in the female gerbil (Meriones unguiculatus) were studied in two experiments. In Experiment 1 various steroids were implanted alone or in combination into the preoptic and anterior hypothalamic area of ovariectomized females. Unilateral implants of testosterone + estrogen, estrogen, estrogen + progesterone, testosterone and testosterone + progesterone stimulated a significant level of marking when compared to controls. Experiment 2 utilized bilateral implants of estrogen dissolved in paraffin in order to explore the distribution hormone sensitive areas in the brain which might be important in the regulation of scent marking in the female gerbil. Pellets of estrogen-paraffin were implanted stereotaxically into either the anterior hypothalamus, preoptic area, septum, hippocampus, thalamus, amygdala or anterior olfactory nucleus of ovariectomized females. Total dosage of hormone implanted was 8.2–8.4 μg. A significant level of marking resulted in animals receiving implants into the anterior hypothalamus, preoptic area and septum when compared to controls. Marking appeared at about the same rate in each of these groups; however, the level of marking attained differed. By the last trial, anterior hypothalamic implanted animals were marking significantly more often than animals in either the preoptic or septum groups. Although there was no evidence of ieakage from the brain, the data suggested that some rapid diffusion of hormone, largely restricted to the brain, was taking place or that the three areas were differentially responsive to the hormone. The data do indicate that some localization of function does exist with respect to regulation of scent marking in the female.

The Mongolian gerbil regularly marks objects in an open field by rubbing them with a midventral sebaceous scent gland. A method and apparatus useful for the study of this response are described. The marking and gland size are sexually dimorphic, with the male marking about twice as frequently as the female and possessing a gland roughly twice the size. Ventral marking in males is positively correlated with urination and defecation, and it is suggested that all three of these activities may in some situations be territorial scent marking responses.

Scent marking is common for many species, and affords olfactory cues for a variety of social reactions. The Mongolian gerbil ( Meriones unguiculatus ) marks objects with a ventral sebaceous scent gland. In both paired and triplet male encounters, animals marking most frequently generally become dominant. Grouping, however, can have the additional effect of depressing marking and morphological indices of androgen activity. In related studies it was demonstrated that males are attracted to the sebum coming from the scent glands of other males but not to sebum from females. Females show no obvious reference. These studies add support to the notion that gerbil marking has territorial significance and serves recognition functions.