; for the PRONIA Consortium IMPORTANCE Social and occupational impairments contribute to the burden of psychosis and depression. There is a need for risk stratification tools to inform personalized functional-disability preventive strategies for individuals in at-risk and early phases of these illnesses. OBJECTIVE To determine whether predictors associated with social and role functioning can be identified in patients in clinical high-risk (CHR) states for psychosis or with recent-onset depression (ROD) using clinical, imaging-based, and combined machine learning; assess the geographic, transdiagnostic, and prognostic generalizability of machine learning and compare it with human prognostication; and explore sequential prognosis encompassing clinical and combined machine learning. DESIGN, SETTING, AND PARTICIPANTS This multisite naturalistic study followed up patients in CHR states, with ROD, and with recent-onset psychosis, and healthy control participants for 18 months in 7 academic early-recognition services in 5 European countries. Participants were recruited between February 2014 and May 2016, and data were analyzed from April 2017 to January 2018. AIN OUTCOMES AND MEASURES Performance and generalizability of prognostic models. RESULTS A total of 116 individuals in CHR states (mean [SD] age, 24.0 [5.1] years; 58 [50.0%] female) and 120 patients with ROD (mean [SD] age, 26.1 [6.1] years; 65 [54.2%] female) were followed up for a mean (SD) of 329 (142) days. Machine learning predicted the 1-year social-functioning outcomes with a balanced accuracy of 76.9% of patients in CHR states and 66.2% of patients with ROD using clinical baseline data. Balanced accuracy in models using structural neuroimaging was 76.2% in patients in CHR states and 65.0% in patients with ROD, and in combined models, it was 82.7% for CHR states and 70.3% for ROD. Lower functioning before study entry was a transdiagnostic predictor. Medial prefrontal and temporo-parietooccipital gray matter volume (GMV) reductions and cerebellar and dorsolateral prefrontal GMV increments had predictive value in the CHR group; reduced mediotemporal and increased prefrontal-perisylvian GMV had predictive value in patients with ROD. Poor prognoses were associated with increased risk of psychotic, depressive, and anxiety disorders at follow-up in patients in the CHR state but not ones with ROD. Machine learning outperformed expert prognostication. Adding neuroimaging machine learning to clinical machine learning provided a 1.9-fold increase of prognostic certainty in uncertain cases of patients in CHR states, and a 10.5-fold increase of prognostic certainty for patients with ROD. CONCLUSIONS AND RELEVANCE Precision medicine tools could augment effective therapeutic strategies aiming at the prevention of social functioning impairments in patients with CHR states or with ROD.

A method is presented to estimate the acquisition geometry of a pinhole single photon emission computed tomography (SPECT) camera with a circular detector orbit. This information is needed for the reconstruction of tomographic images. The calibration uses the point source projection locations of a tomographic acquisition of three point sources located at known distances from each other. It is shown that this simple phantom provides the necessary and sufficient information for the proposed calibration method. The knowledge of two of the distances between the point sources proves to be essential. The geometry is estimated by fitting analytically calculated projections to the measured ones, using a simple least squares Powell algorithm. Some mild a priori knowledge is used to constrain the solutions of the fit. Several of the geometrical parameters are however highly correlated. The effect of these correlations on the reconstructed images is evaluated in simulation studies and related to the estimation accuracy. The highly correlated detector tilt and electrical shift are shown to be the critical parameters for accurate image reconstruction. The performance of the algorithm is finally demonstrated by phantom measurements. The method is based on a single SPECT scan of a simple calibration phantom, executed immediately after the actual SPECT acquisition. The method is also applicable to cone-beam SPECT and X-ray CT.

A well-known problem with maximum likelihood reconstruction in emission tomography is the excessive noise propagation. To prevent this, the objective function is often extended with a Gibbs prior favoring smooth solutions. We hypothesize that the following three requirements should produce a useful and conservative Gibbs prior for emission tomography: 1) the prior function should be concave to ensure that the posterior has a unique maximum; 2) the prior should penalize relative differences rather than absolute differences; 3) the prior should be tolerant for "large" differences between neighboring pixels. The second requirement should avoid tuning problems caused by the large dynamic range of activity values in the reconstructed image. A simple function has been derived that meets these three requirements. Our initial evaluations indicate that the prior behaves as intended.Index Terms-Maximum-a-posteriori reconstruction, maximum likelihood, positron emission tomography (PET).

Previously, we developed a method to determine the acquisition geometry of a pinhole camera. This information is needed for the correct reconstruction of pinhole single photon emission computed tomography images. The method uses a calibration phantom consisting of three point sources and their positions in the field of view (FOV) influence the accuracy of the geometry estimate. This paper proposes two particular configurations of point sources with specific positions and orientations in the FOV for optimal image reconstruction accuracy. For the proposed calibration setups, inaccuracies of the geometry estimate due to noise in the calibration data, only cause subresolution inaccuracies in reconstructed images. The calibration method also uses a model of the point source configuration, which is only known with limited accuracy. The study demonstrates, however, that, with the proposed calibration setups, the error in reconstructed images is comparable to the error in the phantom model.

Previously, the noise characteristics obtained with penalized-likelihood reconstruction [or maximum a posteriori (MAP)] have been compared to those obtained with postsmoothed maximum-likelihood (ML) reconstruction, for emission tomography applications requiring uniform resolution. It was found that penalized-likelihood reconstruction was not superior to postsmoothed ML. In this paper, a similar comparison is made, but now for applications where the noise suppression is tuned with anatomical information. It is assumed that limited but exact anatomical information is available. Two methods were compared. In the first method, the anatomical information is incorporated in the prior of a MAP-algorithm and is, therefore, imposed during MAP-reconstruction. The second method starts from an unconstrained ML-reconstruction, and imposes the anatomical information in a postprocessing step. The theoretical analysis was verified with simulations: small lesions were inserted in two different objects, and noisy PET data were produced and reconstructed with both methods. The resulting images were analyzed with bias-noise curves, and by computing the detection performance of the nonprewhitening observer and a channelized Hotelling observer. Our analysis and simulations indicate that the postprocessing method is inferior, unless the noise correlations between neighboring pixels are taken into account. This can be done by applying a so-called prewhitening filter. However, because the prewhitening filter is shift variant and object dependent, it seems that MAP reconstruction is the more efficient method.