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White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human wholebrain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

Pancreatic degenerative lesions of identical nature could be induced in bonnet monkeys (Macaca radiata) fed protein-deficient tapioca or cassava starch-based and cornstarch-based diets for 3 or 5 months. Marked to severe lobular and acinar cell atrophy in animals fed low-protein diets resembled human pancreatic atrophy resulting from protein deficiency. Animals fed low-protein, high-carbohydrate diets showed lesions akin to tropical chronic calculus pancreatopathy with diabetes mellitus. The pancreatic lesions comprised moderate to marked acinar cell atrophy, marked islet hyperplasia or nesidioblastosis with hypertrophy and mucoid metaplasia of the duct epithelium. Mucoid vasculopathy of the pancreatic artery and arterioles was observed in all animals given proteindeficient diets. It was enhanced in those given additional carbohydrate. Identical lesions were observed after using either

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BACKGROUND A limitation of diffusion tensor imaging (DTI)-based tractography is peritumoral edema that confounds traditional diffusion-based magnetic resonance metrics. OBJECTIVE To augment fiber-tracking through peritumoral regions by performing novel edema correction on clinically feasible DTI acquisitions and assess the accuracy of the fiber-tracks using intraoperative stimulation mapping (ISM), task-based functional magnetic resonance imaging (fMRI) activation maps, and postoperative follow-up as reference standards. METHODS Edema correction, using our bi-compartment free water modeling algorithm (FERNET), was performed on clinically acquired DTI data from a cohort of 10 patients presenting with suspected high-grade glioma and peritumoral edema in proximity to and/or infiltrating language or motor pathways. Deterministic fiber-tracking was then performed on the corrected and uncorrected DTI to identify tracts pertaining to the eloquent region involved (language or motor). Tracking results were compared visually and quantitatively using mean fiber count, voxel count, and mean fiber length. The tracts through the edematous region were verified based on overlay with the corresponding motor or language task-based fMRI activation maps and intraoperative ISM points, as well as at time points after surgery when peritumoral edema had subsided. RESULTS Volume and number of fibers increased with application of edema correction; concordantly, mean fractional anisotropy decreased. Overlay with functional activation maps and ISM-verified eloquence of the increased fibers. Comparison with postsurgical follow-up scans with lower edema further confirmed the accuracy of the tracts. CONCLUSION This method of edema correction can be applied to standard clinical DTI to improve visualization of motor and language tracts in patients with glioma-associated peritumoral edema.

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Functional MRI (fMRI) has provided much insight into the changes in the neuronal activity on the basis of blood oxygen level dependent (BOLD) phenomenon. The dynamic changes in the metabolites can be detected using functional proton magnetic resonance spectroscopy (H-fMRS). The strategy of combining fMRI and H-fMRS would facilitate the understanding of the neurochemical interpretation of the BOLD signal. The dorsolateral prefrontal region is critically involved in the processing of working memory (WM), as demonstrated by the studies involving the neuroimaging, neuropsychological, and electrophysiological experiments. In this study, we tested the association between BOLD signal and changes in brain metabolites in the left dorsolateral prefrontal region using N-back verbal WM task. We used single-voxel task-based H-MRS acquired in the left dorsolateral prefrontal region and fMRI during the performance of N-back verbal WM task to investigate the association between changes in metabolites and BOLD response in 10 healthy participants. The correlation between changes in metabolites and percent signal change was examined by the Pearson correlation. The Pearson correlation analysis revealed a significant positive correlation between the BOLD signal and glutamate/glutamine in the left dorsolateral prefrontal region during the verbal WM. Our finding suggests that glutamate/glutamine cycle plays a critical role in the neuronal activation as reflected by the changes in the BOLD response.

ObjectiveWe examined the effect of risk alleles of polymorphisms of three schizophrenia risk genes that mediate monoamine signalling in the brain on regional brain volumes of schizophrenia and healthy control subjects. The risk alleles and the gene polymorphisms studied were: Val allele of catechol o-methyltransferase (COMT) rs4680 polymorphism; short allele of 5-hydroxy tryptamine transporter linked polymorphic region (5HTTLPR) polymorphism; and T allele of 5-hydroxy tryptamine 2A (5HT2A) rs6314 polymorphism.MethodsThe study was carried out on patients with recent onset schizophrenia (n=41) recruited from the outpatient department of National Institute of Mental Health and Neurosciences, Bangalore, India and healthy control subjects (n=39), belonging to South Indian Dravidian ethnicity. Individual and additive effects of risk alleles of the above gene polymorphisms on brain morphometry were explored using voxel-based morphometry.ResultsIrrespective of phenotypes, individuals with the risk allele T of the rs6314 polymorphism of 5HT2A gene showed greater (at cluster-extent equivalent to family wise error-correction [FWEc] p<0.05) regional brain volumes in the left inferior temporal and left inferior occipital gyri. Those with the risk alleles of the other two polymorphisms showed a trend (at p<0.001, uncorrected) towards lower regional brain volumes. A trend (at p<0.001, uncorrected) towards additive effects of the above 3 risk alleles (subjects with 2 or 3 risk alleles vs. those with 1 or no risk alleles) on brain morphology was also noted.ConclusionThe findings of the present study have implications in understanding the role of individual and additive effects of genetic variants in mediating regional brain morphometry in health and disease.