Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Beyond Diffusion Tensor MRI Methods for Improved Characterization of the Brain after Ischemic Stroke: A Review.

Ischemic stroke is a worldwide problem, with 15 million people experiencing a stroke annually. MR imaging is a valuable tool for understanding and assessing brain changes after stroke and predicting recovery. Of particular interest is the use of diffusion MR imaging in the nonacute stage 1-30 days poststroke. Thousands of articles have been published on the use of diffusion MR imaging in stroke, including several recent articles reviewing the use of DTI for stroke. The goal of this work was to survey and put into context the recent use of diffusion MR imaging methods beyond DTI, including diffusional kurtosis, generalized fractional anisotropy, spherical harmonics methods, and neurite orientation and dispersion models, in patients poststroke. Early studies report that these types of beyond-DTI methods outperform DTI metrics either in being more sensitive to poststroke changes or by better predicting outcome motor scores. More and larger studies are needed to confirm the improved prediction of stroke recovery with the beyond-DTI methods.

Seroprevalence of Taenia solium antibodies in Vellore district, south India.

Although Taenia solium neurocysticercosis is the cause of almost one-third of epilepsy in Vellore district, south India, the level of exposure to T. solium in the district is not known. This study determined the seroprevalence of cysticercus antibodies in seizure-free, study subjects aged 2-60 years from urban and rural areas of Vellore district. Cysticercus antibodies, as determined by immunoblots, were noted in 15.9% of 1063 people and were significantly higher in the rural population (17.7%) compared with the urban population (6.0%). Twenty-four percent of the rural population and 12% of the urban population ate pork. One-third of all households in the district had one or more members seropositive for cysticercus antibodies. The high index of exposure to T. solium in south India calls for improved animal husbandry and sanitation.

Metastatic renal cell carcinoma presenting as a circumscribed orbital mass.

PURPOSE: To report a case of renal cell carcinoma presenting as a well-circumscribed orbital tumor. METHODS: Retrospective interventional case report. RESULTS: A 60-year-old woman presented with proptosis of the left eye. Imaging showed a well circumscribed tumor in the region of the medial rectus muscle. Excision biopsy revealed a diagnosis of metastatic renal cell carcinoma that was confirmed on abdominal imaging. CONCLUSIONS: Renal cell carcinoma can rarely present as a well-circumscribed orbital mass and should be included in the differential diagnosis of such lesions.

Integration of diverse information in working memory within the frontal lobe.

Ability to integrate diverse forms of information in current thought, or working memory, is essential for human reasoning and problem solving. We used functional imaging to identify brain regions preferentially involved in maintaining integrated versus unintegrated information in working memory. For equal amounts of verbal and spatial information, activation of prefrontal cortex was greater for maintaining integrated rather than unintegrated representations. Posterior brain regions showed the opposite pattern. These results demonstrate frontal-lobe specialization in maintaining working-memory representations that integrate verbal and spatial information. The role of prefrontal cortex in integrating multiple forms of information in working memory may underlie its unique contribution to high-level cognition that demands flexible mental representations.

Neural substrates of word generation during stroke recovery: the influence of cortical hypoperfusion.

Several studies have demonstrated reorganization of cognitive and motor function caused by stroke. This study examined the influence of hypoperfused brain regions, in addition to the area of the infarct itself, on reorganization of the cognitive processes underlying word generation in stroke patients. In addition, we also sought to determine the influence of hypoperfusion on the blood oxygen level dependent/(BOLD) effect. Subjects with left and right subacute or chronic subcortical strokes, along with normal controls, were imaged while performing a verbal fluency task (word generation). The study population included six normal subject and six stroke patients with subcortical infarcts and cortical hypoperfusion in the middle cerebral artery territory who had recovered or improved markedly in word fluency. While normal subjects displayed a left-lateralized fronto-temporo-parietal and bilateral cingulo-striatal-thalamic-cerebellar network, the activation pattern of stroke patients was determined both by the hypoperfused regions and infarcted areas of the brain. Specifically, patients showed diminished BOLD effect in the cortical regions that were hypoperfused, even though their infarcts were subcortical, and showed increased BOLD effect in the homologous regions of the normal hemisphere. This finding raises the possibility that cortical hypoperfusion in the absence of infarct can cause shift of language functions to the opposite, intact hemisphere. However, reduced BOLD effect in the task relative to rest was found in hypoperfused regions in two patients, raising the possibility that regional function persisted, even though vascular reactivity was impaired. Results illustrate the complexities of functional imaging studies of recovery in patients with vascular lesions.

Low functional robustness in mesial temporal lobe epilepsy.

OBJECTIVES: Brain functional topology was investigated in patients with mesial temporal lobe epilepsy (mTLE) by means of graph theory measures in two differentially defined graphs. Measures of segregation, integration, and centrality were compared between subjects with mTLE and healthy controls (HC). METHODS: Eleven subjects with mTLE (age 36.5±10.9years) and 15 age-matched HC (age 36.8±14.0years) participated in this study. Both anatomically and functionally defined adjacency matrices were used to investigate the measures. Binary undirected graphs were constructed to study network segregation by calculating global clustering and modularity, and network integration by calculating local and global efficiency. Node degree and participation coefficient were also computed in order to investigate network hubs and their classification into provincial or connector hubs. Measures were investigated in a range of low to medium graph density. RESULTS: The group of patients presented lower global segregation than HC while showing higher global but lower local integration. They also failed to engage regions that comprise the default-mode network (DMN) as hubs such as bilateral medial frontal regions, PCC/precuneus complex, and right inferior parietal lobule, which were present in controls. Furthermore, the cerebellum in subjects with mTLE seemed to be playing a major role in the integration of their functional networks, which was evident through the engagement of cerebellar regions as connector hubs. CONCLUSIONS: Functional networks in subjects with mTLE presented both global and local abnormalities compared to healthy subjects. Specifically, there was significant separation between groups, with lower global segregation and slightly higher global integration observed in patients. This could be indicative of a network that is working as a whole instead of in segregated or specialized communities, which could translate into a less robust network and more prone to disruption in the group with epilepsy. Furthermore, functional irregularities were also observed in the group of patients in terms of the engagement of cerebellar regions as hubs while failing to engage DMN-related areas as major hubs in the network. The use of two differentially defined graphs synergistically contributed to findings.

Recovery of slow-5 oscillations in a longitudinal study of ischemic stroke patients.

Functional networks in resting-state fMRI are identified by characteristics of their intrinsic low-frequency oscillations, more specifically in terms of their synchronicity. With advanced aging and in clinical populations, this synchronicity among functionally linked regions is known to decrease and become disrupted, which may be associated with observed cognitive and behavioral changes. Previous work from our group has revealed that oscillations within the slow-5 frequency range (0.01-0.027 Hz) are particularly susceptible to disruptions in aging and following a stroke. In this study, we characterized longitudinally the changes in the slow-5 oscillations in stroke patients across two different time-points. We followed a group of ischemic stroke patients (n = 20) and another group of healthy older adults (n = 14) over two visits separated by a minimum of three months (average of 9 months). For the stroke patients, one visit occurred in their subacute window (10 days to 6 months after stroke onset), the other took place in their chronic window (> 6 months after stroke). Using a mid-order group ICA method on 10-minutes eyes-closed resting-state fMRI data, we assessed the frequency distributions of a component's representative time-courses for differences in regards to slow-5 spectral power. First, our stroke patients, in their subacute stage, exhibited lower amplitude slow-5 oscillations in comparison to their healthy counterparts. Second, over time in their chronic stage, those same patients showed a recovery of those oscillations, reaching near equivalence to the healthy older adult group. Our results indicate the possibility of an eventual recovery of those initially disrupted network oscillations to a near-normal level, providing potentially a biomarker for stroke recovery of the cortical system. This finding opens new avenues in infra-slow oscillation research and could serve as a useful biomarker in future treatments aimed at recovery.

Platelet-free calcium and vascular calcium uptake in ethanol-induced hypertensive rats.

This study examined the effect of moderate ethanol intake on systolic blood pressure, platelet cytosolic free calcium, aortic calcium, and rubidium-86 uptake in Wistar-Kyoto rats. Twelve Wistar-Kyoto rats, aged 6 weeks, were given 5% ethanol in drinking water the first week followed by 10% ethanol in drinking water for the next 6 weeks. Twelve control animals were given regular tap water. Systolic blood pressure in the ethanol-treated rats was significantly higher (p less than 0.05) than that in controls after 1 week and remained higher throughout the study. At 13 weeks of age, platelet cytosolic free calcium and calcium uptake by aortas were significantly higher (p less than 0.001) in ethanol-treated animals as compared with those in controls. Ethanol intake did not affect aortic ouabain-sensitive 86Rb uptake. The in vitro effect of ethanol on calcium-45 and 86Rb uptake was also investigated in aortas of untreated Wistar-Kyoto rats at 13 weeks of age. In vitro ethanol (2.5-20 mmols/l) did not significantly affect 45Ca and 86Rb uptake in rat aortas. The increases in systolic blood pressure, platelet cytosolic free calcium, and vascular calcium uptake suggest that increases in cytosolic free calcium and calcium uptake mechanisms are associated with ethanol-induced hypertension.

Deuterium oxide normalizes blood pressure and vascular calcium uptake in Dahl salt-sensitive hypertensive rats.

This study examined the effect of 25% deuterium oxide in drinking water on systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas of Dahl salt-sensitive rats on 0.4% (low) and 8% (high) sodium chloride (salt) diet. Twenty-four rats were divided into four groups. Groups I and II were on the low salt diet and groups III and IV on the high salt diet from 6 weeks of age. Additionally, at 10 weeks of age groups I and III were placed on 100% water and groups II and IV on 25% deuterium oxide. At 14 weeks, systolic blood pressure, uptakes of calcium, and rubidium 86 by aortas were significantly higher (p less than 0.01) in rats on the high salt diet as compared with those on the low salt diet. Deuterium oxide intake normalized systolic blood pressure and aortic calcium uptake but not aortic rubidium 86 uptake in hypertensive rats on the high salt diet. Deuterium oxide had no effect on blood pressure or aortic calcium uptake in rats on the low salt diet. The parallel increase in systolic blood pressure and vascular calcium uptake suggests that increased calcium uptake mechanisms are associated with hypertension in salt-sensitive Dahl rats. Furthermore, deuterium oxide appears to normalize elevated blood pressure in salt-sensitive hypertensive rats by normalizing elevated vascular (aortic) calcium uptake.

Comparison of patients with idiopathic calcium phosphate and calcium oxalate stones.

Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.

Hemispheric asymmetries and individual differences in visual concept learning as measured by functional MRI.

Dynamic changes in brain regions active while learning novel visual concepts were examined in humans using functional magnetic resonance imaging. Participants learned to distinguish between exemplars of two categories, formed as distortions of different unseen prototype stimuli. Regions of the right hemisphere (dorsolateral prefrontal and inferior parietal areas) were active early in learning and throughout task performance, whereas homologous portions of the left hemisphere were active only in later stages of learning. Left dorsolateral prefrontal activation was found only in participants who showed superior conceptual learning. Such a progression from initial right-hemisphere processing of specific instances to bilateral activity as left-hemisphere conceptual processes are recruited may underlie the development of many forms of visual knowledge.

Unusual increases in serum lactate dehydrogenase isoenzyme-5 activity caused by severe congestive cardiac failure: two case reports.

Two cases of congestive cardiac failure had unusually high activities of serum lactate dehydrogenase and lactate dehydrogenase isoenzyme-5. Values for isoenzyme-5 exceeding 87% of the total serum activity, and increases of 228- to 380-fold of the upper reference limit, are very uncommon.

A method for functional magnetic resonance imaging of olfaction.

A method for generating olfactory stimuli for humans within a functional magnetic resonance imaging (fMRI) experimental design is described. The system incorporates a nasal-mask in which the change from odorant to no-odorant conditions occurs in less than 500 ms and is not accompanied by visual, auditory, tactile, or thermal cues. The mask provides an ordorant-free environment following prolonged ordorant presence. Specific imaging parameters that are conducive to the study of the human olfactory system are described. In a pilot study performed using these methods, the specific patterns of activation observed converged with published experimental and clinical findings.

Increased calcium uptake in vascular tissue by plasma of patients with essential hypertension.

Plasma factors have been implicated in causing increased calcium uptake and cytosolic (Ca++) in vascular tissue leading to hypertension. We compared the effect of plasma from hypertensive and normotensive subjects on rat aortic calcium uptake. Plasma from hypertensive subjects was fractionated and the fractions assessed for their activity on aortic calcium uptake. Aortic calcium uptake was significantly higher in plasma from hypertensives as compared to normotensives (p less than 0.05). There was a significant positive correlation between diastolic blood pressure and aortic calcium uptake (r = 0.645; p = 0.002). There was a significant positive correlation between percentage ideal body weight and aortic calcium uptake in normotensives and hypertensives (r = 0.522; p less than 0.05). The calcium uptake stimulatory activity in plasma of hypertensives was found in nonesterified fatty acid and cholesterol ester fractions.

Lipids as endogenous Na,K-ATPase inhibitors in plasma of healthy individuals and in dialysis dependent patients.

We assayed plasma Na,K-ATPase inhibitory activity due to total lipids and lipid fractions. The effect of dialysis on the Na,K-ATPase inhibitory activity was also studied. Plasma lipid extracts from 11 healthy volunteers and 9 dialysis-dependent patients (pre and post dialysis) were separated into neutral lipids and phospholipids. Further fractionation was by thin layer chromatography. These lipid fractions were analyzed for Na,K-ATPase inhibitory activity by displacement of [3H]-ouabain from hog brain Na,K-ATPase. Total inhibitory activity was significantly increased (p less than 0.001) in the post-dialysis plasma compared to pre-dialysis plasma of the same patient group and to controls (482, 85 and 78 nmol/L respectively; means of the groups in digoxin equivalents). The major inhibitory activity was associated with non-esterified fatty acids with modest contributions from four other lipid fractions. Our results show that endogenous lipids are major plasma Na,K-ATPase inhibitors in vitro under these assay conditions.

Neural substrates of mathematical reasoning: a functional magnetic resonance imaging study of neocortical activation during performance of the necessary arithmetic operations test.

Brain activation was examined using functional magnetic resonance imaging during mathematical problem solving in 7 young healthy participants. Problems were selected from the Necessary Arithmetic Operations Test (NAOT; R. B. Ekstrom, J. W. French, H. H. Harman, & D. Dermen, 1976). Participants solved 3 types of problems: 2-operation problems requiring mathematical reasoning and text processing, 1-operation problems requiring text processing but minimal mathematical reasoning, and 0-operation problems requiring minimal text processing and controlling sensorimotor demands of the NAOT problems. Two-operation problems yielded major activations in bilateral frontal regions similar to those found in other problem-solving tasks, indicating that the processes mediated by these regions subserve many forms of reasoning. Findings suggest a dissociation in mathematical problem solving between reasoning, mediated by frontal cortex, and text processing, mediated by temporal cortex.

Striatal activation during acquisition of a cognitive skill.

The striatum is thought to play an essential role in the acquisition of a wide range of motor, perceptual, and cognitive skills, but neuroimaging has not yet demonstrated striatal activation during nonmotor skill learning. Functional magnetic resonance imaging was performed while participants learned probabilistic classification, a cognitive task known to rely on procedural memory early in learning and declarative memory later in learning. Multiple brain regions were active during probabilistic classification compared with a perceptual-motor control task, including bilateral frontal cortices, occipital cortex, and the right caudate nucleus in the striatum. The left hippocampus was less active bilaterally during probabilistic classification than during the control task, and the time course of this hippocampal deactivation paralleled the expected involvement of medial temporal structures based on behavioral studies of amnesic patients. Findings provide initial evidence for the role of frontostriatal systems in normal cognitive skill learning.

Taenia solium metacestode glycoproteins as diagnostic antigens for solitary cysticercus granuloma in Indian patients.

Taenia solium metacestode glycoproteins specific for lentil lectin were evaluated as diagnostic antigens for solitary cysticercus granulomas in Indian patients, using both an ELISA and immunoblotting. In 250 patients suspected to have neurocysticercosis and subjected to a computerized tomography scan or magnetic resonance imaging, the proteins were diagnostic by the ELISA in 86 patients (80%) and by immunoblots in 67 (62%) of 107 patients with solitary cysticerus granuloma. Among 100 non-cysticercosis patients, the ELISA and immunoblot were negative in 94% and 97% respectively. No cross-reactions were observed with sera from patients with central nervous system tuberculosis. Proteins of

Age differences in prefrontal cortical activity in working memory.

Working memory (WM) declines with advancing age. Brain imaging studies indicate that ventral prefrontal cortex (PFC) is active when information is retained in WM and that dorsal PFC is further activated for retention of large amounts of information. The authors examined the effect of aging on activation in specific PFC regions during WM performance. Six younger and 6 older adults performed a task in which, on each trial, they (a) encoded a 1- or 6-letter memory set, (b) maintained these letters over 5-s. and (c) determined whether or not a probe letter was part of the memory set. Comparisons of activation between the 1- and 6-letter conditions indicated age-equivalent ventral PFC activation. Younger adults showed greater dorsal PFC activation than older adults. Older adults showed greater rostral PFC activation than younger adults. Aging may affect dorsal PFC brain regions that are important for WM executive components.