Abstract Early intervention research in schizophrenia has suggested that brain structural alterations might be present in subjects at high risk of developing psychosis. The heterogeneity of regional ...effects of these changes, which is established in schizophrenia, however, has not been explored in prodromal or high-risk populations. We used high-resolution MRI and voxel-based morphometry (VBM8) to analyze grey matter differences in 43 ultra high-risk subjects for psychosis (meeting ARMS criteria, identified through CAARMS interviews), 24 antipsychotic–naïve first-episode schizophrenia patients and 49 healthy controls (groups matched for age and gender). Compared to healthy controls, resp., first-episode schizophrenia patients had reduced regional grey matter in left prefrontal, insula, right parietal and left temporal cortices, while the high-risk group showed reductions in right middle temporal and left anterior frontal cortices. When dividing the ultra-high-risk group in those with a genetic risk vs. those with attenuated psychotic symptoms, the former showed left anterior frontal, right caudate, as well as a smaller right hippocampus, and amygdala reduction, while the latter subgroup showed right middle temporal cortical reductions (each compared to healthy controls). Our findings in a clinical psychosis high-risk cohort demonstrate variability of brain structural changes according to subgroup and background of elevated risk, suggesting frontal and possibly also hippocampal/amygdala changes in individuals with genetic susceptibility. Heterogeneity of structural brain changes (as seen in schizophrenia) appears evident even at high-risk stage, prior to potential onset of psychosis.
The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection ...strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.
Abstract While schizophrenia and bipolar disorder have been assumed to share phenotypic and genotypic features, there is also evidence for overlapping brain structural correlates, although it is ...unclear whether these relate to shared psychotic features. In this study, we used voxel-based morphometry (VBM8) in 34 schizophrenia patients, 17 euthymic bipolar I disorder patients (with a history of psychotic symptoms), and 34 healthy controls. Our results indicate that compared to healthy controls schizophrenia patients show grey matter deficits (p < 0.05, FDR corrected) in medial and right dorsolateral prefrontal, as well as bilaterally in ventrolateral prefrontal and insular cortical areas, thalamus (bilaterally), left superior temporal cortex, and minor medial parietal and parietooccipital areas. Comparing schizophrenia vs. bipolar I patients (p < 0.05, FDR corrected) yielded a similar pattern, however, there was an additional significant reduction in schizophrenia patients in the (posterior) hippocampus bilaterally, left dorsolateral prefrontal cortex, and left cerebellum. Compared to healthy controls, the deficits in bipolar I patients only reached significance at p < 0.001 (uncorr.) for a minor parietal cluster, but not for prefrontal areas. Our results suggest that the more extensive prefrontal, thalamic, and hippocampal deficits that might set apart schizophrenia and bipolar disorder might not be related to mere appearance of psychotic symptoms at some stage of the disorders.
Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to ...antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.
To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.
The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.
In total, 45 1H-MRS studies contributed data.
Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor.
Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL).
In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean SD age, 30.3 10.4 years) and 1197 healthy volunteers (mean SD age, 27.5 8.8 years). The MFC Glu (F1,1211.9 = 4.311, P = .04) and Glx (F1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4 = 47.533, P < .001; cerebrospinal fluid-corrected Glu, F1,1216.7 = 5.610, P = .02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, -0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.
Findings from this mega-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia.
The application of deep neural networks for segmentation in medical imaging has gained substantial interest in recent years. In many cases, this variant of machine learning has been shown to ...outperform other conventional segmentation approaches. However, little is known about its general applicability. Especially the robustness against image modifications (e.g., intensity variations, contrast variations, spatial alignment) has hardly been investigated. Data augmentation is often used to compensate for sensitivity to such changes, although its effectiveness has not yet been studied. Therefore, the goal of this study was to systematically investigate the sensitivity to variations in input data with respect to segmentation of medical images using deep learning. This approach was tested with two publicly available segmentation frameworks (DeepMedic and TractSeg). In the case of DeepMedic, the performance was tested using ground truth data, while in the case of TractSeg, the STAPLE technique was employed. In both cases, sensitivity analysis revealed significant dependence of the segmentation performance on input variations. The effects of different data augmentation strategies were also shown, making this type of analysis a useful tool for selecting the right parameters for augmentation. The proposed analysis should be applied to any deep learning image segmentation approach, unless the assessment of sensitivity to input variations can be directly derived from the network.
Abstract Purpose To evaluate low budget 3D printing technology to create MRI compatible components. Material and methods A 3D printer is used to create customized MRI compatible components, a ...loop-coil platform and a multipart mouse fixation. The mouse fixation is custom fit for a dedicated coil and facilitates head fixation with bite bar, anesthetic gas supply and biomonitoring sensors. The mouse fixation was tested in a clinical 3T scanner. Results All parts were successfully printed and proved MR compatible. Both design and printing were accomplished within a few days and the final print results were functional with well defined details and accurate dimensions ( Δ < 0.4 mm). MR images of the mouse head clearly showed reduced motion artifacts, ghosting and signal loss when using the fixation. Conclusions We have demonstrated that a low budget 3D printer can be used to quickly progress from a concept to a functional device at very low production cost. While 3D printing technology does impose some restrictions on model geometry, additive printing technology can create objects with complex internal structures that can otherwise not be created by using lathe technology. Thus, we consider a 3D printer a valuable asset for MRI research groups.
Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder, characterised by widespread white matter damage. There is growing evidence that disturbances in iron metabolism ...contribute to white matter alterations.
We analysed the data of susceptibility-weighted imaging (SWI) of white matter in a cohort of 27 patients with ALS and 30 healthy age-matched controls.
Signal alterations were found on SWI in the corpus callosum; along the corticospinal tract (subcortical motor cortex, posterior limb of the internal capsule and brainstem levels) and in the subgyral regions of frontal, parietal, temporal, occipital and limbic lobes. Alterations of white matter in the corpus callosum correlated with disease severity as assessed by the revised ALS functional rating scale.
SWI is capable of indicating iron and myelin disturbances in white matter of ALS patients. The SWI patterns observed in this study suggest that widespread alterations due to iron disturbances occur in patients with ALS and correlate with disease severity.
Segmentation of the human cranial bone from MRI data is challenging, because compact bone is characterized by very short transverse relaxation times and typically produces no signal when using ...conventional magnetic resonance imaging (MRI) sequences. In this work, we propose a fully automated segmentation algorithm, which uses dual-echo, ultra-short echo-time (UTE) MRI data. The segmentation was initialized by interval thresholding of approximated T2* relaxation time maps in the range of 1ms<T2*<3ms. This parameter range was derived from a manual region-of-interest analysis of high resolution data of the cranial layers, resulting in average T2* relaxation times of 1.7±0.3ms in the lamina externa, 2.5±0.3ms in the diploe and 1.7±0.2ms in the lamina interna. Segmentations were performed based on data of 8 healthy volunteers that were acquired with different acquisition parameters and spatial resolutions to test the stability of the algorithm. Comparison with computed tomography data demonstrated close agreement with the segmented UTE MRI data. Visualization of the segmented cranial bone was performed by volumetric rendering and by using the approximated T2* values for color coding, clearly visualizing the cranial sutures as well as their intersections.
Brainstem and midbrain nuclei are closely linked to cognitive performance and autonomic function. To advance the localization in this area, precise functional imaging is fundamental. In this study, ...we used a sophisticated fMRI technique as well as physiological recordings to investigate the involvement of brainstem/midbrain nuclei in cognitive control during a Stroop task. The temporal signal-to-noise ratio (tSNR) increased due to physiological noise correction (PNC) especially in regions adjacent to arteries and cerebrospinal fluid. Within the brainstem/cerebellum template an average tSNR of 68 ± 16 was achieved after the simultaneous application of a high-resolution fMRI, specialized co-registration, and PNC. The analysis of PNC data revealed an activation of the substantia nigra in the Stroop interference contrast whereas no significant results were obtained in the midbrain or brainstem when analyzing uncorrected data. Additionally, we found that pupil size indicated the level of cognitive effort. The Stroop interference effect on pupillary responses was correlated to the effect on reaction times (
= 0.464,
< 0.05). When Stroop stimuli were modulated by pupillary responses, we observed a significant activation of the LC in the Stroop interference contrast. Thus, we demonstrated the beneficial effect of PNC on data quality and statistical results when analyzing neuronal responses to a cognitive task. Parametric modulation of task events with pupillary responses improved the model of LC BOLD activations in the Stroop interference contrast.
The human brainstem, which comprises a multitude of axonal nerve fibers and nuclei, plays an important functional role in the human brain. Depicting its anatomy non-invasively with high spatial ...resolution may thus in turn help to better relate normal and pathological anatomical variations to medical conditions as well as neurological and peripheral functions. We explored the potential of high-resolution magnetic resonance imaging (MRI) at 7 T for depicting the intricate anatomy of the human brainstem in vivo by acquiring and generating images with multiple contrasts: T 2-weighted images, quantitative maps of longitudinal relaxation rate (R 1 maps) and effective transverse relaxation rate (Formula: see text maps), magnetic susceptibility maps, and direction-encoded track-density images. Images and quantitative maps were compared with histological stains and anatomical atlases to identify nerve nuclei and nerve fibers. Among the investigated contrasts, susceptibility maps displayed the largest number of brainstem structures. Contrary to R 1 maps and T 2-weighted images, which showed rather homogeneous contrast, Formula: see text maps, magnetic susceptibility maps, and track-density images clearly displayed a multitude of smaller and larger fiber bundles. Several brainstem nuclei were identifiable in sections covering the pons and medulla oblongata, including the spinal trigeminal nucleus and the reticulotegmental nucleus on magnetic susceptibility maps as well as the inferior olive on R 1, Formula: see text, and susceptibility maps. The substantia nigra and red nuclei were visible in all contrasts. In conclusion, high-resolution, multi-contrast MR imaging at 7 T is a versatile tool to non-invasively assess the individual anatomy and tissue composition of the human brainstem.
PDF
