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Objective: Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting.Methods: MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2* mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed.Results: SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN.Conclusion: SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting. [ABSTRACT FROM AUTHOR]

Importance: Children born very preterm are at risk for long-term neurodevelopmental sequelae. Prophylactic high-dose recombinant human erythropoietin (rhEpo) shortly after birth has not been shown to improve cognitive, motor, and behavioral development at 2 and 5 years., Objective: To investigate whether early high-dose rhEpo is associated with better executive functions and processing speed-late-maturing cognitive functions-in school-aged children born very preterm., Design, Setting, and Participants: This single-center cohort study was a prospective, observational follow-up study of a multicenter neonatal clinical trial; 365 children born very preterm (mean gestational age, 29.3 weeks [range, 26.0-31.9 weeks]) who had been enrolled in the Swiss EPO Neuroprotection Trial at birth between 2005 and 2012, and who were included in the primary outcome analyses at 2 years, were eligible to be recruited for the EpoKids study between 2017 and 2021 when they were at school age. Term-born children were additionally recruited and included in a control group. Data were analyzed between May and September 2022., Exposure: Administration of rhEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 2 days of life as part of the Swiss EPO Neuroprotection Trial., Main Outcome and Measures: A comprehensive neuropsychological test battery assessed executive functions and processing speed, and parents reported on their child's executive functions in everyday life to test the hypothesis that early high-dose rhEpo administration is associated with better cognitive outcomes at school age., Results: In the EpoKids study, 214 children born very preterm (58.6% of 365 children in eligible cohort) were assessed at a mean age of 10.4 years (range, 6.9-13.4 years); 117 (54.7%) were boys. There was no evidence that the 117 children who had received rhEpo differed from the 97 children who had received placebo in any of the 15 executive function and processing speed tests, nor in parent-rated executive functions (estimates ranged from -0.138 to 0.084, all 95% CIs included 0). Irrespective of rhEpo or placebo allocation, children born very preterm scored lower on 11 of 15 executive function and processing speed tests than term-born peers (estimates ranged from 0.112 to 0.255, 95% CIs did not include 0)., Conclusion and Relevance: This study found no evidence for a positive association between prophylactic early high-dose rhEpo administration and long-term neurodevelopmental outcomes after very preterm birth. These results suggest that a comprehensive approach, including pharmacological and nonpharmacological prevention and intervention strategies, is needed to support these children's neurodevelopmental outcome.

Children and adolescents born very preterm are at risk of cognitive impairment, particularly affecting executive functions. To date, the neural correlates of these cognitive differences are not yet fully understood, although converging evidence points to a pattern of structural and functional brain alterations, including reduced brain volumes, altered connectivity, and altered brain activation patterns. In very preterm neonates, alterations in brain perfusion have also been reported, but the extent to which these perfusion alterations persist into later childhood is not yet known. This study evaluated global and regional brain perfusion, measured with arterial spin labelling (ASL) MRI, in 26 very preterm children and adolescents and 34 term-born peers. Perfusion was compared between groups and relative to executive function (EF) scores, derived from an extensive EF battery assessing working memory, cognitive flexibility, and planning. Very preterm children and adolescents showed regions of altered perfusion, some of which were also related to EF scores. Most of these regions were located in the right hemisphere and included regions like the thalamus and hippocampus, which are known to play a role in executive functioning and can be affected by prematurity. In addition, perfusion decreased with age during adolescence and showed a significant interaction between birth status and sex, such that very preterm girls showed lower perfusion than term-born girls, but this trend was not seen in boys. Taken together, our results indicate a regionally altered perfusion in very preterm children and adolescents, with age and sex related changes during adolescence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Thalamocortical connections are altered following very preterm birth but it is unknown whether structural and functional alterations are linked and how they contribute to neurodevelopmental deficits. We used a multimodal approach in 27 very preterm and 35 term-born children and adolescents aged 10-16 years: Structural thalamocortical connectivity was quantified with two measures derived from probabilistic tractography of diffusion tensor data, namely the volume of thalamic segments with cortical connections and mean fractional anisotropy (FA) within the respective segments. High-density sleep EEG was recorded and sleep spindles were identified at each electrode. Sleep spindle density and integrated spindle activity (ISA) were calculated to quantify functional thalamocortical connectivity. In term-born participants, the volume of the global thalamic segment with cortical connections was strongly related to sleep spindles across the entire head (mean r ​= ​.53 ​± .10; range ​= ​0.35 to 0.78). Regionally, the volume of the thalamic segment connecting to frontal brain regions correlated with sleep spindle density in two clusters of electrodes over fronto-temporal brain regions (.42 ​± .06; 0.35 to 0.51 and 0.43 ​± .08; 0.35 to 0.62) and the volume of the thalamic segment connecting to parietal brain regions correlated with sleep spindle density over parietal brain regions (mean r ​= ​.43 ​± .07; 0.35 to 0.61). In very preterm participants, the volume of the thalamic segments was not associated with sleep spindles. In the very preterm group, mean FA within the global thalamic segment was negatively correlated with ISA over a cluster of frontal and temporo-occipital brain regions (mean r ​= ​-.53 ​± .07; -.41 to -.72). No association between mean FA and ISA was found in the term-born group. With this multimodal study protocol, we identified a potential misalignment between structural and functional thalamocortical connectivity in children and adolescents born very preterm. Eventually, this may shed further light on the neuronal mechanisms underlying neurodevelopmental sequelae of preterm birth., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The optimization of magnetic resonance spectroscopy (MRS) sequences allows improved diagnosis and prognosis of neurological and psychological disorders. Thus, to assess the test-retest and intersequence reliability of such MRS sequences in quantifying metabolite concentrations is of clinical relevance., Purpose: To evaluate the test-retest and intersequence reliability of three MRS sequences to estimate GABA and Glx = Glutamine+Glutamate concentrations in the human brain., Study Type: Prospective., Subjects: Eighteen healthy participants were scanned twice (range: 1 day to 1 week between the two sessions) with identical protocols., Field Strength/sequence: 3T using a 32-channel SENSE head coil in the PCC region; PRESS, JPRESS, and MEGA-PRESS sequences., Assessment: Metabolite concentrations were estimated using LCModel (for PRESS and MEGA-PRESS) and ProFit2 (for JPRESS)., Statistical Tests: The test-retest reliability was evaluated by Wilcoxon signed-rank tests, Pearson's r correlation coefficients, intraclass-correlation coefficients (ICC), coefficients of variation (CV), and by Bland-Altman (BA) plots. The intersequence reliability was assessed with Wilcoxon signed-rank tests, Pearson's r correlation coefficients, and BA plots., Results: For GABA, only the MEGA-PRESS sequence showed a moderate test-retest correlation (r = 0.54, ICC = 0.5, CV = 8.8%) and the BA plots indicated good agreement (P > 0.05) for all sequences. JPRESS provided less precise results and PRESS was insensitive to GABA. For Glx, the r and ICC values for PRESS (r = 0.87, ICC = 0.9, CV = 2.9%) and MEGA-PRESS (r = 0.70, ICC = 0.7, CV = 5.3%) reflect higher correlations, compared with JPRESS (r = 0.39, ICC = 0.4, CV = 20.1%)., Data Conclusion: MEGA-PRESS and JPRESS are suitable for the reliable detection of GABA, the first being more precise. The three sequences included in the study can measure Glx concentrations., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1181-1191., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background: Multiple sedation regimes may be used to facilitate pediatric MRI scans. These regimes might affect cerebral blood flow and hemodynamics to varying degrees, particularly in children who may be vulnerable to anesthetic side effects., Purpose: To compare the effects of propofol monosedation solely (Pm group) vs. a combination of propofol and ketamine (KP group) on brain hemodynamics and perfusion., Study Type: Prospective double-blind randomized trial., Field Strength/sequences: 1.5T and 3T. 2D-Cine phase contrast (2D-Cine PC) and pseudocontinuous arterial spin labeling (ASL)., Population: Children aged from 3 months to 10 years referred for MRI with deep sedation were randomized into either the KP or the Pm group. Perfusion images were acquired with ASL followed by single-slice 2D-Cine PC acquired between the cervical vertebra C2 and C3., Assessment: Average whole-brain perfusion (WBP ml.min -1 .100 ml -1 ) was extracted from the ASL perfusion maps and total cerebrovascular blood flow (CVF) was quantified by bilaterally summing the flow in the vertebral and the internal carotid arteries. The CVF values were converted to units of ml.min -1 .100 g -1 to calculate the tissue CVF 100g (ml.min -1 .100 g -1 ). Images were assessed by a neuroradiologist and data from n = 81 (ASL) and n = 55 (PC) cases with no apparent pathology were entered into the analysis., Statistical Tests: Multivariate analysis of covariance was performed to compare drug sedation effects on WBP, CVF, and CVF 100g ., Results: No significant difference in arterial flow was observed (P = 0.57), but the KP group showed significantly higher WBP than the Pm group, covarying for scanner and age (P = 0.003). A correlation analysis showed a significant positive correlation between mean WBP (ml.min -1 .100 g -1 ) and mean CVF 100g ., Data Conclusion: The KP group showed higher perfusion but no significant difference in vascular flow compared with the Pm group. WBP and CVF 100g correlated significantly, but ASL appeared to have more susceptibility to perfusion differences arising from the different sedation regimes., Level of Evidence: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1433-1440., (© 2019 International Society for Magnetic Resonance in Medicine.)

The formation of resting-state functional networks in infancy has been reported to be strongly impacted by very preterm birth. Studies in childhood and adolescence have largely focused on language processing networks and identified both decreased and increased functional connectivity. It is unclear, however, whether functional connectivity strength is altered globally in children and adolescents born very preterm and whether these alterations are related to the frequently occurring cognitive deficits. Here, resting-state functional MRI was assessed in a group of 32 school-aged children and adolescents born very preterm with normal intellectual and motor abilities and 39 healthy term-born peers. Functional connectivity within and between a comprehensive set of well-established resting-state networks was compared between the groups. IQ and executive function abilities were tested with standardized tasks and potential associations with connectivity strength were explored. Functional connectivity was weaker in the very preterm compared to the term-born group between the sensorimotor network and the visual and dorsal attention network, within the sensorimotor network and within the central executive network. In contrast, functional connectivity was stronger in the very preterm group between the sensorimotor network and parts of the salience and the central executive network. Little evidence was found that these alterations underlie lower IQ or poorer executive function abilities. This study provides evidence for a long-lasting impact of very preterm birth on the organization of resting-state networks. The potential consequence of these alterations for other neurodevelopmental domains than the ones investigated in the current study warrants further investigation., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities., Methods: We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls., Results: In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions., Conclusions: The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.

Executive function deficits are among the most frequent sequela of very preterm birth but the underlying neuronal mechanisms are not fully understood. We used high-density electroencephalography (EEG) recordings during sleep to assess alterations in the functional neuroanatomy of executive processes in adolescents born very preterm. The topographical distribution of sleep slow wave activity (SWA; 1-4.5 Hz EEG power) has previously been used to map cognitive abilities and is known to reflect the intensity of the prior use of the respective neuronal networks. We assessed 38 adolescents born before 32 weeks of gestation [age at assessment: 12.9 (SD: 1.7), range: 10.6-16.7 years] and 43 term-born peers [13.1 (2.0), 10.0-16.9]. Executive function abilities were quantified with a composite score derived from a comprehensive task battery. All-night high-density EEG (128 electrodes) was recorded and SWA of the first hour of sleep was calculated. Abilities were significantly poorer in the very preterm compared to the term-group, particularly, if the tasks demands were high (p < .01). The score was positively correlated with sleep SWA in a cluster of 15 electrodes over frontal and negatively in a cluster of 14 electrodes over central brain regions after controlling for age at assessment and correcting for multiple comparisons. Within the frontal cluster, sleep SWA was higher in very preterm compared to term-born participants when controlling for executive function performance and age at assessment (p = .02). No difference in SWA between very preterm and term-born participants was found for the central cluster (p = .29). Our results demonstrate a local increase of sleep SWA over brain regions associated with executive processes in adolescents born very preterm compared to similarly performing term-born peers. Thus, sleep SWA seems to map the higher effort needed for executive function tasks in adolescents born very preterm., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Very preterm birth is often associated with executive function deficits later in life. The transition to adolescence increases personal autonomy, independence and, in parallel, the demands placed on executive functions at home and in school., Aim: To assess the impact of increasing demands on executive function performance in very preterm children and adolescents with normal intellectual and motor functions., Methods: Forty-one very preterm children and adolescents with normal intellectual and motor functions and 43 healthy term-born peers were assessed at a mean age of 13.0 years (SD: 1.9; range: 10.0-16.9). A comprehensive battery of performance-based executive function measures with different demand levels as well as a parent-rating questionnaire evaluating executive functions relevant for everyday life was applied. Standardized mean differences between groups of d ≥ .41 were regarded as clinically relevant., Results: No group differences were found at the lowest demand levels of working memory (d=.09), planning (d=-.01), cognitive flexibility (d=-.21) and verbal fluency (d=-.14) tasks, but very preterm participants scored significantly below their term-born peers in the most demanding levels (d=-.50, -.59, -.43 and -.55, respectively). These differences were clinically relevant. Executive functions relevant for everyday life were strongly impaired in very preterm participants, e.g., global executive composite (d=-.66)., Conclusion: Very preterm children and adolescents with normal intellectual and motor functions are at high risk for executive function deficits that may only become apparent with increasing demands, potentially leading to academic and other deficits., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.

While the neurobiological basis and developmental course of attention-deficit/hyperactivity disorder (ADHD) have not yet been fully established, an imbalance between inhibitory/excitatory neurotransmitters is thought to have an important role in the pathophysiology of ADHD. This study examined the changes in cerebral levels of GABA+, glutamate and glutamine in children and adults with ADHD using edited magnetic resonance spectroscopy. We studied 89 participants (16 children with ADHD, 19 control children, 16 adults with ADHD and 38 control adults) in a subcortical voxel (children and adults) and a frontal voxel (adults only). ADHD adults showed increased GABA+ levels relative to controls (P = 0.048), while ADHD children showed no difference in GABA+ in the subcortical voxel (P > 0.1), resulting in a significant age by disorder interaction (P = 0.026). Co-varying for age in an analysis of covariance model resulted in a nonsignificant age by disorder interaction (P = 0.06). Glutamine levels were increased in children with ADHD (P = 0.041), but there was no significant difference in adults (P > 0.1). Glutamate showed no difference between controls and ADHD patients but demonstrated a strong effect of age across both groups (P < 0.001). In conclusion, patients with ADHD show altered levels of GABA+ in a subcortical voxel which change with development. Further, we found increased glutamine levels in children with ADHD, but this difference normalized in adults. These observed imbalances in neurotransmitter levels are associated with ADHD symptomatology and lend new insight in the developmental trajectory and pathophysiology of ADHD.

Marked changes in brain physiology and structure take place between childhood and adulthood, including changes in functional connectivity and changes in the balance between main excitatory and inhibitory neurotransmitters glutamate (Glu) and GABA. The balance of these neurotransmitters is thought to underlie neural activity in general and functional connectivity networks in particular, but so far no studies have investigated the relationship between human development related differences in these neurotransmitters and concomitant changes in functional connectivity. GABA+/H2O and Glu/H2O levels were acquired in a group of healthy children, adolescents, and adults in a subcortical (basal ganglia) region, as well as in a frontal region in adolescents and adults. Our results showed higher GABA+/Glu with age in both the subcortical and the frontal voxel, which were differentially associated with significantly lower Glu/H2O with age in the subcortical voxel and by significantly higher GABA+/H2O with age in the frontal voxel. Using a seed-to-voxel analysis, we were further able to show that functional connectivity between the putamen (seed) and other subcortical structures was lower with age. Lower subcortical Glu/H2O with age mediated the lower connectivity in the dorsal putamen. Based on these results, and the potential role of Glu in synaptic pruning, we suggest that lower Glu mediates a reduction of local connectivity during human development., (Copyright © 2015 the authors 0270-6474/15/358433-09$15.00/0.)

Purpose: Idiopathic generalized epilepsies (IGE) comprise a group of clinical syndromes associated with spike wave discharges, putatively linked to alterations in neurotransmission. The purpose of this study was to investigate whether patients with IGE have altered glutamine and γ-aminobutyric acid (GABA) levels indicative of altered excitatory and inhibitory neurotransmission in frontal regions., Materials and Methods: Single-voxel MEGA-edited PRESS magnetic resonance imaging (MRI) spectra were acquired from a 30-mL voxel in the dorsolateral prefrontal cortex in 13 patients with IGE (8 female) and 16 controls (9 female) at 3T. Metabolite concentrations were derived using LCModel. Differences between groups were investigated using an unpaired t-test., Results: Patients with IGE were found to have significantly higher glutamine than controls (P = 0.02). GABA levels were also elevated in patients with IGE (P = 0.03)., Conclusion: Patients with IGE have increased frontal glutamine and GABA compared with controls. Since glutamine has been suggested to act as a surrogate for metabolically active glutamate, it may represent a marker for excitatory neurotransmission., (© 2014 Wiley Periodicals, Inc.)

Background: Schizophrenia is a severe mental disorder affecting approximately 1% of the worldwide population. Yet, schizophrenia-like experiences (schizotypy) are very common in the healthy population, indicating a continuum between normal mental functioning and the psychosis found in schizophrenic patients. A continuum between schizotypy and schizophrenia would be supported if they share the same neurobiological origin. Two such neurobiological markers of schizophrenia are: (1) a reduction of sleep spindles (12-15 Hz oscillations during nonrapid eye movement sleep), likely reflecting deficits in thalamo-cortical circuits and (2) increased glutamine and glutamate (Glx) levels in the thalamus. Thus, this study aimed to investigate whether sleep spindles and Glx levels are related to schizotypal personality traits in healthy subjects., Methods: Twenty young male subjects underwent 2 all-night sleep electroencephalography recordings (128 electrodes). Sleep spindles were detected automatically. After those 2 nights, thalamic Glx levels were measured by magnetic resonance spectroscopy. Subjects completed a magical ideation scale to assess schizotypy., Results: Sleep spindle density was negatively correlated with magical ideation (r = -.64, P < .01) and thalamic Glx levels (r = -.70, P < .005). No correlation was found between Glx levels in the thalamus and magical ideation (r = .12, P > .1)., Conclusions: The common relationship of sleep spindle density with schizotypy and thalamic Glx levels indicates a neurobiological overlap between nonclinical schizotypy and schizophrenia. Thus, sleep spindle density and magical ideation may reflect the anatomy and efficiency of the thalamo-cortical system that shows pronounced impairment in patients with schizophrenia., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite improved survival, many preterm infants undergo subsequent neurodevelopmental impairment. To date, no neuroprotective therapies have been implemented into clinical practice. Erythropoietin, a haematopoietic cytokine used for treatment of anaemia of prematurity, has been shown to have neuroprotective and neuroregenerative effects on the brain in many experimental studies. The aim of the study was to assess the effect of recombinant human erythropoietin on the microstructural development of the cerebral white matter using tract-based spatial statistics performed at term equivalent age. A randomized, double-blind placebo-controlled, prospective multicentre study applying recombinant human erythropoietin in the first 42 h after preterm birth entitled 'Does erythropoietin improve outcome in preterm infant' was conducted in Switzerland (NCT00413946). Preterm infants were given recombinant human erythropoietin (3000 IU) or an equivalent volume of placebo (NaCl 0.9%) intravenously before 3 h of age after birth, at 12-18 h and at 36-42 h after birth. High resolution diffusion tensor imaging was obtained at 3 T in 58 preterm infants with mean (standard deviation) gestational age at birth 29.75 (1.44) weeks, and at scanning at 41.1 (2.09) weeks. Imaging was performed at a single centre. Voxel-wise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics to test for differences in fractional anisotropy between infants treated with recombinant human erythropoietin and placebo using a general linear model, covarying for the gestational age at birth and the corrected gestational age at the time of the scan. Preterm infants treated with recombinant human erythropoietin demonstrated increased fractional anisotropy in the genu and splenium of the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterally. Mean fractional anisotropy was significantly higher in preterm infants treated with recombinant human erythropoietin than in those treated with placebo (P < 0.001). We conclude that early recombinant human erythropoietin administration improves white matter development in preterm infants assessed by diffusion tensor imaging and tract-based spatial statistics., (© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Although posttraumatic stress disorder (PTSD) is associated with a variety of structural and functional brain changes, the molecular pathophysiological mechanisms underlying these macroscopic alterations are unknown. Recent studies support the existence of an altered excitation-inhibition balance in PTSD. Further, there is preliminary evidence from blood-sample studies suggesting heightened oxidative stress in PTSD, potentially leading to neural damage through excessive brain levels of free radicals. In this study we investigated PTSD (n=12) and non-PTSD participants (n=17) using single-voxel proton magnetic resonance spectroscopy (MRS) in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). We found significantly higher levels of γ-amino butyric acid (GABA) (a primary inhibitory neurotransmitter) and glutathione (a marker for neuronal oxidative stress) in PTSD participants. Atypically high prefrontal inhibition as well as oxidative stress may be involved in the pathogenesis of PTSD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship to clinical outcome in at-risk individuals is unknown. Glutamate concentration was measured in the left thalamus and anterior cingulate cortex (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of attenuated positive symptoms and overall functioning were assessed. Measures were repeated in 51 UHR and 33 Control subjects after a mean of 18 months. UHR subjects were allocated to either remission (no longer meeting UHR criteria) or non-remission (meeting UHR or psychosis criteria) status on follow-up assessment. Thalamic glutamate levels at presentation were lower in the UHR non-remission (N=29) compared with the remission group (N=22) (t(49)=3.03; P=0.004), and were associated with an increase in the severity of total positive symptoms over time (r=-0.33; df=47; P=0.02), most notably abnormal thought content (r=-0.442; df=47; P=0.003). In the UHR group, ACC glutamate levels were lower at follow-up compared with baseline (F(80)=4.28; P=0.04). These findings suggest that measures of brain glutamate function may be useful as predictors of clinical outcome in individuals at high risk of psychosis.

Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.

Objective: Objective biomarkers for attention-deficit/hyperactivity disorder (ADHD) could improve diagnostics or treatment monitoring of this psychiatric disorder. The resting electroencephalogram (EEG) provides non-invasive spectral markers of brain function and development. Their accuracy as ADHD markers is increasingly questioned but may improve with pattern classification., Methods: This study provides an integrated analysis of ADHD and developmental effects in children and adults using regression analysis and support vector machine classification of spectral resting (eyes-closed) EEG biomarkers in order to clarify their diagnostic value., Results: ADHD effects on EEG strongly depend on age and frequency. We observed typical non-linear developmental decreases in delta and theta power for both ADHD and control groups. However, for ADHD adults we found a slowing in alpha frequency combined with a higher power in alpha-1 (8-10Hz) and beta (13-30Hz). Support vector machine classification of ADHD adults versus controls yielded a notable cross validated sensitivity of 67% and specificity of 83% using power and central frequency from all frequency bands. ADHD children were not classified convincingly with these markers., Conclusions: Resting state electrophysiology is altered in ADHD, and these electrophysiological impairments persist into adulthood., Significance: Spectral biomarkers may have both diagnostic and prognostic value., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current 'state-of-the-art' in the field of GABA-edited MRS at 3T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA., (Copyright © 2012 Elsevier Inc. All rights reserved.)

While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.

Functional magnetic resonance imaging (fMRI) techniques allow definition of cortical nodes that are presumed to be components of large-scale distributed brain networks involved in cognitive processes. However, very few investigations examine whether such functionally defined areas are in fact structurally connected. Here, we used combined fMRI and diffusion MRI-based tractography to define the cortical network involved in saccadic eye movement control in humans. The results of this multimodal imaging approach demonstrate white matter pathways connecting the frontal eye fields and supplementary eye fields, consistent with the known connectivity of these regions in macaque monkeys. Importantly, however, these connections appeared to be more prominent in the right hemisphere of humans. In addition, there was evidence of a dorsal frontoparietal pathway connecting the frontal eye field and the inferior parietal lobe, also right hemisphere dominant, consistent with specialization of the right hemisphere for directed attention in humans. These findings demonstrate the utility and potential of using multimodal imaging techniques to define large-scale distributed brain networks, including those that demonstrate known hemispheric asymmetries in humans.

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.

Context: Alterations in glutamatergic neurotransmission and cerebral cortical dysfunction are thought to be central to the pathophysiology of psychosis, but the relationship between these 2 factors is unclear., Objective: To investigate the relationship between brain glutamate levels and cortical response during executive functioning in people at high risk for psychosis (ie, with an at-risk mental state [ARMS])., Design: Subjects were studied using functional magnetic resonance imaging while they performed a verbal fluency task, and proton magnetic resonance spectroscopy was used to measure their brain regional glutamate levels., Setting: Maudsley Hospital, London, England., Patients and Other Participants: A total of 41 subjects: 24 subjects with an ARMS and 17 healthy volunteers (controls)., Main Outcome Measures: Regional brain activation (blood oxygen level-dependent response); levels of glutamate in the anterior cingulate, left thalamus, and left hippocampus; and psychopathology ratings at the time of scanning., Results: During the verbal fluency task, subjects with an ARMS showed greater activation than did controls in the middle frontal gyrus bilaterally. Thalamic glutamate levels were lower in the ARMS group than in control group. Within the ARMS group, thalamic glutamate levels were negatively associated with activation in the right dorsolateral prefrontal and left orbitofrontal cortex, but positively associated with activation in the right hippocampus and in the temporal cortex bilaterally. There was also a significant group difference in the relationship between cortical activation and thalamic glutamate levels, with the control group showing correlations in the opposite direction to those in the ARMS group in the prefrontal cortex and in the right hippocampus and superior temporal gyrus., Conclusions: Altered prefrontal, hippocampal, and temporal function in people with an ARMS is related to a reduction in thalamic glutamate levels, and this relationship is different from that in healthy controls.

Purpose: To evaluate the reproducibility of γ-amino-butyric acid (GABA) and glutamate concentrations derived using three different spectral fitting methods, and to investigate gender-related differences in neurotransmitter levels., Materials and Methods: Single voxel MEGA-edited PRESS MR spectra were acquired from a 30-mL voxel in the dorso-lateral prefrontal cortex in 14 adult volunteers (7 female) at 3 Tesla (3T). For each participant, four consecutive resting spectra were acquired within the same scanning session. Metabolite concentrations were derived using LCModel, jMRUI, and locally written peak fitting software. The within-session reproducibility for each analysis method was calculated as the average coefficient of variation (CV) of the GABA and Glx (glutamate+glutamine) concentrations. Gender differences in GABA and Glx were evaluated using a two-tailed unpaired t-test., Results: LCModel provided the best reproducibility for both GABA (CV 7%) and Glx (CV 6%). GABA, Glx, and glutamate concentrations were significantly higher in the male participants, (P = 0.02, P = 0.001, and P < 0.001, respectively)., Conclusion: GABA and glutamate can be quantified in vivo with high reproducibility (CV 6-7%) using frequency-domain spectral fitting methods like LCModel. However, the GABA and glutamate concentrations vary significantly between men and women, emphasizing the importance of gender-matching for studies investigating differences in neurotransmitter concentrations between mixed-cohort groups., (Copyright © 2011 Wiley-Liss, Inc.)

It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing., (Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.)

People with autistic spectrum disorders (ASD, including Asperger syndrome) may have developmental abnormalities in the amygdala-hippocampal complex (AHC). However, in vivo, age-related comparisons of both volume and neuronal integrity of the AHC have not yet been carried out in people with Asperger syndrome (AS) versus controls. We compared structure and metabolic activity of the right AHC of 22 individuals with AS and 22 healthy controls aged 10-50 years and examined the effects of age between groups. We used structural magnetic resonance imaging (sMRI) to measure the volume of the AHC, and magnetic resonance spectroscopy ((1)H-MRS) to measure concentrations of N-acetyl aspartate (NAA), creatine+phosphocreatine (Cr+PCr), myo-inositol (mI) and choline (Cho). The bulk volume of the amygdala and the hippocampus did not differ significantly between groups, but there was a significant difference in the effect of age on the hippocampus in controls. Compared with controls, young (but not older) people with AS had a significantly higher AHC concentration of NAA and a significantly higher NAA/Cr ratio. People with AS, but not controls, had a significant age-related reduction in NAA and the NAA/Cr ratio. Also, in people with AS, but not controls, there was a significant relationship between concentrations of choline and age so that choline concentrations reduced with age. We therefore suggest that people with AS have significant differences in neuronal and lipid membrane integrity and maturation of the AHC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Animal models of psychosis propose that striatal hyperdopaminergia is driven by abnormalities in hippocampal glutamatergic neurotransmission, but this has never been tested in humans., Methods: Sixteen individuals with an at-risk mental state for psychosis (ARMS) and 12 control subjects underwent proton magnetic resonance spectroscopy to estimate hippocampal glutamate and [18F]DOPA positron emission tomography to index striatal dopamine function. The relationship between hippocampal glutamate and striatal dopamine, as well as their relationship with prodromal symptoms, was determined using linear regression., Results: In ARMS subjects, but not controls, there was a significant negative relationship between hippocampal glutamate levels and striatal [18F]DOPA uptake (p = .03). Within the ARMS sample, striatal [18F]DOPA uptake was correlated with severity of abnormal beliefs (p = .03), there was a trend for hippocampal glutamate levels to be correlated with disordered speech (p = .06) and a trend for the interaction between hippocampal glutamate and [18F]DOPA uptake to predict later transition to psychosis (p = .07)., Conclusions: The relationship between hippocampal glutamate and striatal dopamine systems is altered in people at high risk of psychosis, and the degree to which it is changed may be related to the risk of transition to psychosis. Pharmacologic modulation of the glutamate system before the onset of psychosis might ameliorate this risk., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Arterial spin labeling is a fully noninvasive magnetic resonance perfusion imaging method, ideally suited to pediatric perfusion imaging. We describe an 8-year-old boy with sickle cell disease, extensive right-hemispheric cerebral infarction, and crossed-cerebellar diaschisis apparent on arterial spin labeling perfusion magnetic resonance imaging. To our knowledge, this is the first case of crossed-cerebellar diaschisis demonstrated with arterial spin labeling, highlighting the potential value of perfusion magnetic resonance imaging in the clinical evaluation and follow-up of crossed-cerebellar diaschisis, and the suitability of arterial spin labeling methods for routine perfusion imaging in pediatric patients., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: The glutamate model of schizophrenia proposes that altered glutamatergic neurotransmission is fundamental to the development of the disorder. In addition, its potential to mediate neurotoxicity raises the possibility that glutamate dysfunction could underlie neuroanatomic changes in schizophrenia. Here we determine whether changes in brain glutamate are present in subjects at ultra high risk of developing psychosis and whether these changes are related to reductions in cortical gray matter volume., Methods: Twenty-seven individuals with an at-risk mental state and a group of 27 healthy volunteers underwent proton magnetic resonance spectroscopy and volumetric proton magnetic resonance imaging using a 3-Tesla scanner. Glutamate and glutamine levels were measured in anterior cingulate, left hippocampus, and left thalamus. These measures were then related to cortical gray matter volume., Results: At-risk mental state (ARMS) subjects had significantly lower levels of glutamate than control subjects in the thalamus (p < .05) but higher glutamine in the anterior cingulate (p < .05). Within the ARMS group, the level of thalamic glutamate was directly correlated with gray matter volume in the medial temporal cortex and insula (p < .01)., Conclusions: This study provides the first evidence that brain glutamate function is perturbed in people with prodromal signs of schizophrenia and that glutamatergic dysfunction is associated with a reduction in gray matter volume in brain regions thought to be critical to the pathogenesis of the disorder. These findings support the hypothesis that drugs affecting the glutamate system may be of benefit in the early stages of psychotic illness.

Background/aims: Stereotactic postoperative imaging is essential for verification of the position of electrodes implanted for deep brain stimulation (DBS). MRI offers superior visualisation of the DBS targets relative to CT, but previous adverse incidents have heightened concerns about risks of postoperative MRI. Preoperative MRI fused with postoperative CT offers an alternative method for evaluating electrode position, but before this method can be clinically applied, the image registration accuracy must be established. The purpose of this study was to quantitatively assess the accuracy of three different image registration and fusion methods., Methods: Preoperative stereotactic MRI and postoperative stereotactic CT were acquired from 20 patients under- going DBS surgery (35 electrodes in total). The postoperative CT was registered and fused with the preoperative MRI, using three different registration algorithms. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position between the CT and fused CT/MRI was used to evaluate the registration accuracy., Results: The mean error along the lateral, anteroposterior, and vertical axes was 0.5, 0.5, and 1 mm, respectively., Conclusions: CT/MRI fusion provides a safe, practical technique for postoperative identification of DBS electrodes., (Copyright 2009 S. Karger AG, Basel.)

The neurobiological basis for attention deficit hyperactivity disorder (ADHD) has not yet been fully established, although there is a growing body of evidence pointing to functional and structural abnormalities involving the basal ganglia, cerebellum, and regions of frontal grey matter. The purpose of this study was to investigate regional cerebral perfusion in adults with ADHD and age-matched control subjects, and to assess the perfusion response to stimulant treatment in the ADHD group using a non-invasive magnetic resonance perfusion imaging technique. Whole-brain cerebral perfusion images were acquired from nine right-handed male patients with ADHD and eleven age-matched control subjects using a continuous arterial spin labelling (CASL) technique. The ADHD group was assessed once on their normal treatment and once after withdrawing from treatment for at least one week. An automated voxel-based analysis was used to identify regions where the cerebral perfusion differed significantly between the ADHD and control groups, and where the perfusion altered significantly with stimulant treatment. Regional cerebral perfusion was increased in the ADHD group in the left caudate nucleus, frontal and parietal regions. Psychomotor stimulant treatment acted to normalise perfusion in frontal cortex and the caudate nucleus with additional decreases in parietal and parahippocampal regions. These findings highlight the potential sensitivity of non-invasive perfusion MRI techniques like CASL in the evaluation of perfusion differences due to illness and medication treatment, and provide further evidence that persistence of ADHD symptomatology into adulthood is accompanied by abnormalities in frontal and striatal brain regions.

The purpose of this study was to adapt the hepatic perfusion index (HPI) methodology previously developed for MRI to derive 3D parametric maps of HPI, and to investigate apparent differences in HPI maps between a group of colorectal cancer patients and controls. To achieve this, a new and simpler approach to HPI calculation which does not require measurements from the aorta or portal vein is introduced, and assessed with large liver regions of interest (ROIs) in patients and controls. Several example HPI maps showing localized variation are then presented. The subject group consisted of 12 patients with known colorectal metastases, and 13 control subjects referred for routine contrast-enhanced spine imaging with no history of neoplastic disease. HPI was evaluated from serial T1 volume acquisitions acquired over the course of a Gd-DTPA bolus injection. Regions of abnormal perfusion were visible on the HPI maps derived for the patient group, manifested as areas of locally increased HPI extending around the visible margins of known metastases evident on the conventional contrast-enhanced images. This method for MR voxel-based parametric mapping of HPI has the potential to demonstrate regional variations in perfusion at the segmental and subsegmental level.

Diffusion tensor MRI (DT-MRI) can provide estimates of fiber orientation derived from the orientational dependence of the diffusivity of water molecules, enabling the reconstruction of white matter fiber pathways using tractography methods. However, noise arising from various sources can introduce uncertainty into the estimates of the elements of the diffusion tensor, resulting in errors in fiber orientation estimates such that tractography reconstructions of fiber pathways potentially can be imprecise and inaccurate. Recently, attempts have been made to characterize the uncertainty in DT-MRI-derived parameters using the bootstrap method; however, several questions remain open regarding the number of repeat measurements and bootstraps required to accurately and precisely reconstruct the probability distributions of the DT-MRI parameters. This study investigates the accuracy and precision of the bootstrap method for characterizing distributions of DT-MRI parameters. A number of experimental bootstrap designs and sampling schemes containing different numbers of isotropically distributed gradient vectors are considered, using an idealized system where the true variability in each parameter is known. This study demonstrates that for most DT-MRI experiments, robust results will be obtained if the minimum number of bootstraps is approximately 500, and that at least five repeat samples of each diffusion-weighted intensity should be used for bootstrapping.

There is an increasing body of evidence pointing to a neurobiological basis of personality. The purpose of this study was to investigate the biological bases of the major dimensions of Eysenck's and Cloninger's models of personality using a noninvasive magnetic resonance perfusion imaging technique in 30 young, healthy subjects. An unbiased voxel-based analysis was used to identify regions where the regional perfusion demonstrated significant correlation with any of the personality dimensions. Highly significant positive correlations emerged between extraversion and perfusion in the basal ganglia, thalamus, inferior frontal gyrus and cerebellum and between novelty seeking and perfusion in the cerebellum, cuneus and thalamus. Strong negative correlations emerged between psychoticism and perfusion in the basal ganglia and thalamus and between harm avoidance and perfusion in the cerebellar vermis, cuneus and inferior frontal gyrus. These observations suggest that personality traits are strongly associated with resting cerebral perfusion in a variety of cortical and subcortical regions and provide further evidence for the hypothesized neurobiological basis of personality. These results may also have important implications for functional neuroimaging studies, which typically rely on the modulation of cerebral hemodynamics for detection of task-induced activation since personality effects may influence the intersubject variability for both task-related activity and resting cerebral perfusion. This technique also offers a novel approach for the exploration of the neurobiological correlates of human personality.

The accurate quantification of perfusion with arterial spin labeling (ASL) requires consideration of a number of factors, including the efficiency of the inversion and control pulses used for spin labeling. In this study the effects of spin velocity on continuous ASL efficiency when using the amplitude modulated control strategy were investigated using simulations of the Bloch equations. The inversion efficiency was determined in vivo by combining the simulations with phase-contrast velocity mapping data acquired at the level of the tagging plane. Using this novel method, an average inversion efficiency of 69% was calculated for a group of 28 subjects, in good agreement with experimental data reported previously. There was, however, a large range in inversion efficiency measured across the subject group (50-76%), indicating that the velocity dependence of the amplitude modulated control efficiency may introduce additional variability into the perfusion calculations if not properly taken into account., (Copyright 2006 Wiley-Liss, Inc.)

The aim of the study was to adapt the methodology established for dynamic CT measurements of the hepatic perfusion index (HPI) to MRI, and to assess the potential role of MRI measurements of the HPI in detecting regional alterations in liver perfusion between patients with colorectal liver metastases and normal controls. The HPI was evaluated from serial T(1) volume acquisitions acquired over the course of a Gd-DTPA bolus injection. Time-course data from regions of interest in the liver, spleen and aorta were used to calculate the HPI; and HPI data from control subjects were compared with data from patients with known colorectal metastases. Significant differences were found between the relative portal perfusion and hepatic perfusion indices calculated for the patient and control groups (p<0.005). These results suggest that hepatic perfusion indices can be derived using MRI-based methods, and that these perfusion indices are sensitive to differences in liver perfusion associated with established metastatic liver disease on imaging. This technique may contribute to the early detection of liver metastases, allowing early surgical intervention and improved patient survival.

Magnetic resonance imaging (MRI) after implantation of electrodes in the subthalamic nuclei is currently performed at a number of sites, but a recent adverse incident and changes in MRI technology may heighten safety concerns. In this report, it is demonstrated that given whole-head image data, registration of postimplantation computed tomography to preimplantation MRI can enable verification of the position of electrodes to an accuracy of 2 mm. This registration technique can remove the need for potentially risky postoperative MRI.