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Hyperpolarized 3helium magnetic resonance ventilation imaging of the lung in cystic fibrosis: comparison with high resolution CT and spirometry.

The purpose of this study was to compare hyperpolarized 3helium magnetic resonance imaging (3He MRI) of the lungs in adults with cystic fibrosis (CF) with high-resolution computed tomography (HRCT) and spirometry. Eight patients with stable CF prospectively underwent 3He MRI, HRCT, and spirometry within 1 week. Three-dimensional (3D) gradient-echo sequence was used during an 18-s breath-hold following inhalation of hyperpolarized 3He. Each lung was divided into six zones; 3He MRI was scored as percentage ventilation per lung zone. HRCT was scored using a modified Bhalla scoring system. Univariate (Spearman rank) and multivariate correlations were performed between 3He MRI, HRCT, and spirometry. Results are expressed as mean+/-SD (range). Spirometry is expressed as percent predicted. There were four men and four women, mean age = 31.9+/-9 (20-46). Mean forced expiratory volume in 1 s (FEV)1 = 52%+/-29 (27-93). Mean 3He MRI score = 74%+/-25 (55-100). Mean HRCT score = 48.8+/-24 (13.5-83). The correlation between 3He MRI and HRCT was strong (R = +/-0.89, p < 0.001). Bronchiectasis was the only independent predictor of 3He MRI; 3He MRI correlated better with FEV1 and forced vital capacity (FVC) (R = 0.86 and 0.93, p < 0.01, respectively) than HRCT (R = +/-0.72 and +/-0.81, p < 0.05, respectively). This study showed that 3He MRI correlates strongly with structural HRCT abnormalities and is a stronger correlate of spirometry than HRCT in CF.

Adult↗

Leukoaraiosis in asymptomatic adult offspring of individuals with Alzheimer's disease.

The presence of white matter changes on magnetic resonance imaging (MRI), which has been referred to by Hachinski (1987) as leukoaraiosis, is frequently noted in elderly individuals in conditions ranging from health to frank dementia. This study involved the use of MRI to document cerebral structure if 41 healthy 50-60-year-old individuals, 28 of whom were offspring of Alzheimer's disease victims. On visual inspection of spin-echo images, 13 of the 28 offspring showed white matter lesions whereas all of the controls were free of leukoaraiosis. This statistically significant difference suggests that the presence of leukoaraiosis might be of importance in understanding changes in the white matter among populations at increased risk for Alzheimer's disease.

Alzheimer Disease↗

Human corpus callosum in aging and Alzheimer's disease: a magnetic resonance imaging study.

The involvement of the corpus callosum in aging and Alzheimer's disease (AD) is not clear. We measured cross sectional areas of the entire corpus callosum (CC), as well as the front 20% (genu), middle 60% (body), and posterior 20% (splenium) of the structure from a midsagittal MRI slice in AD patients (N = 20), and young (N = 16) and old (N = 13) control subjects. We found that mean CC area in young controls was 570 +/- 107 mm2. Aging did not significantly affect the mean area of the CC (562 +/- 98 mm2). A small, significant reduction was seen in AD in comparison to the young control group (480 +/- 133 mm2). However, AD is accompanied by a large and statistically significant reduction in the genu area in comparison to both young and old control subjects. A trend toward an age-dependent reduction in the body area is also accentuated in AD patients who showed significantly smaller callosal bodies than young controls. We conclude that selective changes within corpus callosum accompany aging and AD pathology.

Adult↗

Brain SPECT imaging of neuropsychiatric disorders.

Brain imaging has become an integral part of the evaluation of neurological and psychiatric disorders. Functional imaging techniques, SPECT and PET, together with structural modalities, CT and MRI, are widely employed. Functional imaging studies are routinely used in the diagnostic workup of patients with well-characterized neurological disorders, such as epilepsy and brain tumors, and have a growing role in research on psychiatric disorders without known mechanisms such as depression and schizophrenia. Furthermore, many well-defined neurological disorders manifest prominent psychiatric symptomatology which may pose difficulties in differential diagnosis. This review addresses the current knowledge of SPECT findings in patients who present with psychiatric phenomena, associated with disorders at the interface of neurology and psychiatry.

Alzheimer Disease↗

VBR in schizophrenia: relationship to family history of psychosis and season of birth.

Ventricular enlargement has been consistently demonstrated in schizophrenia using both CT and MRI. Despite this, the structural changes that underlie increased ventricle-brain ratio (VBR) and its relationship to environmental factors (intrauterine viral exposure, obstetric complications, etc.) and family history of schizophrenia remain poorly defined. Increased VBR has been shown in some studies to correlate with an absence of family history of schizophrenia and with Winter-Spring birth. In an attempt to obtain a clearer picture of the contribution of environmental and genetic factors to VBR, we studied 54 patients with DSM III-R schizophrenia. VBR was determined from head CT scans via computerized planimetry. Family history of psychosis and non-psychotic mood disorder was determined with the family informant method. Season of birth was encoded in several ways, including season, trimester and dichotomously. Patients without a family history of psychosis had significantly larger VBR than patients with such a history; family history of mood disorder was not related to VBR. Season of birth was not predictive of VBR. Family history of psychosis and season of birth were not related to each other. These results are in line with prior work demonstrating an association between increased VBR and sporadic (non-familial) schizophrenia. We did not find a relationship between VBR and season of birth, which suggests that risk of perinatal viral exposure and other seasonal environmental factors may not account for the ventricular enlargement in non-familial schizophrenia observed in our sample.

Adult↗

Regional brain gray matter volume differences in patients with bipolar disorder as assessed by optimized voxel-based morphometry.

BACKGROUND: Structural magnetic resonance imaging (MRI) studies of regions of interest in brain have been inconsistent in demonstrating volumetric differences in subjects with bipolar disorder (BD). Voxel-based morphometry (VBM) provides an unbiased survey of the brain, can identify novel brain areas, and validates previously hypothesized regions. We conducted both optimized VBM, comparing MRI gray matter volume, and traditional VBM, comparing MRI gray matter density, in 11 BD subjects and 31 healthy volunteers. To our knowledge, these are the first VBM analyses of BD. METHODS: Segmented MRI gray matter images were normalized into standardized stereotactic space, modulated to allow volumetric analysis (optimized only), smoothed, and compared at the voxel level with statistical parametric mapping. RESULTS: Optimized VBM showed that BD subjects had smaller volume in left ventromedial temporal cortex and bilateral cingulate cortex and larger volume in left insular/frontoparietal operculum cortex and left ventral occipitotemporal cortex. Traditional VBM showed that BD subjects had less gray matter density in left ventromedial temporal cortex and greater gray matter density in left insular/frontoparietal operculum cortex and bilateral thalamic cortex. Exploratory analyses suggest that these abnormalities might differ according to gender. CONCLUSIONS: Bipolar disorder is associated with volumetric and gray matter density changes that involve brain regions hypothesized to influence mood.

Adolescent↗

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.

Adult↗

Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study.

BACKGROUND: Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD. METHODS: Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored. RESULTS: VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age. CONCLUSIONS: These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.

Adult↗

Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study.

The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) exerts its actions in part via blockade of serotonin and dopamine reuptake. Many animal and human studies have demonstrated long-lasting reductions in measures of central nervous system (CNS) serotonin function following MDMA administration. One emerging role of serotonin function in the CNS is a positive trophic effect via stimulation of intracellular signaling pathways and trophic factors. We hypothesized that human MDMA users might display neocortical gray matter reductions due to loss of serotonergically mediated trophic effects on cortical cells. However, unlike animal models, most human MDMA users worldwide are polydrug users, thereby complicating the assessment of MDMA toxicity in this group. Structural magnetic resonance imaging (MRI) scans of 31 MDMA polydrug users versus 29 non-MDMA users were compared using voxel-based morphometry (VBM) to assess regional brain gray and white matter concentration. VBM employs gray/white matter segmentation and statistical parametric mapping (SPM) analysis to calculate a voxel-wise comparison of regional gray or white matter concentration. Using this method, we consistently found several brain regions having decreased gray matter concentration in MDMA polydrug users. These regions were localized to neocortex in bilateral Brodmann area (BA) 18, left BA 21, and left BA 45, as well as bilateral cerebellum, and midline brainstem. Overall, these preliminary findings suggest that MDMA polydrug users have multiple regions of gray matter reduction, potentially accounting for previously reported neuropsychiatric impairments in MDMA users. Additional animal model and human studies of the CNS effects of MDMA and combined MDMA-polydrug toxicity are needed to further explain these findings. Potential explanations for our results including pre-existing brain differences predisposing to MDMA polydrug use, direct MDMA and polydrug toxicity, indirect changes due to MDMA and polydrug toxicity, or combinations of all these factors.

Adolescent↗

Early detection of Alzheimer's disease using neuroimaging.

Neuroimaging is being increasingly used to complement clinical assessments in the early detection of Alzheimer's disease (AD). Structural magnetic resonance imaging (MRI) and metabolic positron emission tomography (FDG-PET) are the most clinically used and promising modalities to detect brain abnormalities in individuals who might be at risk for AD but who have not yet developed symptoms. The knowledge of established risk factors for AD enabled investigators to develop enrichment strategies for longitudinal imaging studies to reduce the sample sizes and study duration. The present review focuses on the results obtained by MRI and FDG-PET studies that examined the preclinical AD stages in several at risk populations: (1) individuals from families with autosomal dominant early-onset AD (FAD), (2) patients with mild cognitive impairment (MCI), particularly in memory, who are at very high risk for declining to AD with an estimated decline rate of 10-30% per year, (3) normal young and middle-age subjects carriers of known susceptibility genes for late-onset AD such as the Apolipoprotein E (ApoE) E4 allele, and (4) as age is the main risk factor for AD, normal elderly individuals followed to the onset of MCI and AD. Overall, these studies show that the use of imaging for the early detection of AD is successful even in the earlier stages of disease when clinical symptoms are not fully expressed and the regional brain damage may be limited.

Alzheimer Disease↗

Cold-induced sweating syndrome: a report of two cases and demonstration of genetic heterogeneity.

OBJECTIVES: To characterize the specific autonomic disturbances underlying the cold-induced sweating syndrome (CISS), and to describe a novel genetic variant of this rare recessive disorder. The two not previously reported patients had similar dysmorphic features: abnormal facial appearance, high arched palate, low set rotated ears, flexion deformities of elbows and fingers and scoliosis. Most noticeable were their paradoxical sweat responses: cold ambient temperature induced a profuse sweating over the face, arms and trunk but not over the lower limbs; while in the heat very little sweating occurred primarily on the legs. Testing of autonomic functions demonstrated normal cardiovascular reflexes and postganglionic sympathetic efferent functions. Sural nerve morphology and number of unmyelinated fibers was normal and skin biopsies showed normal appearing eccrine sweat glands. MRI scans revealed no structural brain abnormalities. Oral clonidine, prescribed in one patient, completely suppressed cold-induced sweating. Observed clinical features matched those of two sisters reported from Israel and of two brothers reported from Norway. All six cases presented a similar phenotype. The Norwegian, Israeli and Canadian cases were homozygous or compound heterozygous, respectively, for mutations in the CRLF1 gene on chromosome 19p12 (CISS1). The Australian case, however, had no pathogenic sequence variants in the CRLF1 gene, but was compound heterozygous for mutations in the CLCF1 gene on chromosome 11q13.3 (CISS2). CONCLUSION: The rare cold-induced sweating syndrome is genetically heterogeneous and is probably caused by central and peripheral impairment of sudomotor functions. This is the first detailed report on the clinical consequences of mutations in the CLCF1 gene in humans. Directions for medical therapies are outlined to achieve long term symptom control.

Adult↗

Tuning and comparing spatial normalization methods.

Spatial normalization is a key process in cross-sectional studies of brain structure and function using MRI, fMRI, PET and other imaging techniques. A wide range of 2D surface and 3D image deformation algorithms have been developed, all of which involve design choices that are subject to debate. Moreover, most have numerical parameters whose value must be specified by the user. This paper proposes a principled method for evaluating design choices and choosing parameter values. This method can also be used to compare competing spatial normalization algorithms. We demonstrate the method through a performance analysis of a nonaffine registration algorithm for 3D images and a registration algorithm for 2D cortical surfaces.

Algorithms↗

Transient global amnesia may be caused by cerebral vein thrombosis.

Transient global amnesia (TGA) is a disorder of unknown aetiology, characterized by sudden loss of anterograde memory, in the absence other neurological signs or symptoms, followed by complete recovery in less than 24h. Precipitating actions such as strenuous physical activity or valsalva-like manoeuvres are frequently reported. Since first described in 1958, by Fisher and Adams, the possible pathophysiology has undergone much speculation. Nonconvulsive epileptic seizures, migraine, paradoxical embolism thorough a patent foramen ovale, and transient ischemic attacks have been proposed as potential mechanisms. One of the latest hypotheses is that venous congestion causes either ischemia or induces spreading depression in the medial temporal lobes. It has been demonstrated that retrograde flow in the internal jugular veins occurs more frequently during valsalva manoeuvres in TGA patients than in controls, supporting a dysfunctional venous circulation as part of the pathogenesis. However, earlier hypotheses typically fail to explain the relatively low recurrence rate of TGA, lack of comorbidity and the relation to precipitating events. If cerebral venous hypertension was the solely cause of TGA it would presumably be much more common with very high recurrence rates among those predisposed of the condition. Structural changes observed in MRI and SPECT studies along with reports of mild cognitive impairment lasting much longer than the amnestic episodes, indicate that TGA is less transient and perhaps somewhat less benign than earlier believed. Many cases of TGA seem to be associated with factors of increased risk of cerebral venous thrombosis, such as polycythemia, antiphospholipid antibodies, venous hypertension, female sex and more. We suggest that most cases of TGA may be due to small thrombi in the deep cerebral venous system. Small venous thrombi may difficult to visualize even when using modern imaging technology. Further studies of TGA patients with for example blood analysis of D-dimer together with MR venography or CT venography could be done to evaluate this new hypothesis.

Amnesia, Transient Global↗

The event-related optical signal to electrical stimulation of the median nerve.

The event-related optical signal (EROS) uses near-infrared light to study changes in neuronal optical properties in response to stimuli and endogenous events. EROS responses to electrical stimulation of the median nerve at 1, 5, and 8 Hz were collected from 80 channels in 7 subjects. Optical recording channels were spatially aligned by co-registering the digitized fiber locations with structural magnetic resonance images (MRI) for each subject separately. The co-registered data sets were then transformed into Talairach space to permit alignment across subjects. After alignment, data from channels underlying pixels of a surface projection were combined to produce maps of Z statistics. Waveforms associated with voxels within an a priori region of interest (ROI) over the hand area of primary somatosensory (SI) cortex were compared across the three stimulus frequencies. Reliable early increases in light propagation time (i.e., increased phase delay) were found in SI as early as 16-32 ms of poststimulus for all three frequency conditions, and both an increase in phase delay and a decrease in signal intensity were observed over SI at longer latencies. A split-half analysis of the 8 Hz condition demonstrated the replicability of the response. This represents the first direct comparison of intensity and delay measures of these components of the somatosensory response; further, it shows that these early cortical components are replicable across subjects and correspond well to individual subjects' anatomical landmarks for SI.

Adult↗

Progression of putaminal degeneration in multiple system atrophy: a serial diffusion MR study.

By using diffusion-weighted imaging (DWI), we have recently shown abnormal diffusivity in the putamen of patients with the Parkinson variant of multiple system atrophy (MSA-P) which also correlated with disease severity, indicating the capability of putaminal diffusivity to serve as a marker for disease progression. We therefore performed a serial DWI study in 10 patients with MSA-P compared to 10 patients with Parkinson's disease (PD) to evaluate the dynamic evolution of diffusion properties in the basal ganglia including putamen, caudate nucleus and globus pallidum by means of the trace of the diffusion tensor (Trace(D)). For comparison, we have also analyzed the frequency and semiquantitative grading of MSA-P-related structural changes on conventional MRI including putaminal atrophy, lateral hyperintense margination of the putamen and putaminal signal hypointensity relative to the globus pallidum on T2 MR images. None of the Trace(D) values in the basal ganglia regions in the PD group changed significantly at follow-up compared to baseline. In MSA-P, a significant increase of the Trace(D) was found in the putamen, which correlated with motor progression as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). No significant change of any of the abnormal putaminal findings on routine MRI was obtained. We suggest that abnormal diffusivity in the putamen is sensitive to change over time in MSA-P and correlates with motor progression indicating that DWI may serve to monitor disease progression in MSA-P in an objective and quantitative manner.

Aged↗

Biological motion processing in adolescents with early periventricular brain damage.

The developing brain is traditionally viewed to possess a great compensatory potential. Here we ask whether visual processing of point-light displays depicting human walking is compromised in adolescents who were born premature (between 27 and 33 gestation weeks) and suffer early bilateral damage to periventricular brain regions. Combining psychophysics with volumetric analysis of structural magnetic resonance imaging (MRI), we found that even relatively small periventricular parieto-occipital lesions may result in long-lasting breakdown of visual processing of point-light displays. Analysis of receiver operating characteristic (ROC) curves revealed higher susceptibility of the patients' perceptual system to camouflage of a point-light figure. The lack of difference in sensitivity between former preterms with normal MRI scan and term-born controls indicates that perceptual deficiencies in patients with periventricular leukomalacia (PVL) are not simply due to premature birth. Most importantly, sensitivity in patients even with mild PVL was lower than in both control groups. Display 180 degrees inversion in the image plane, which is known to impair processing of point-light displays, resulted in a substantial reduction of sensitivity so that it no longer differed between the groups. Despite the social and ecological significance of human locomotion, the capacity of the brain to detect biological motion is substantially modulated by periventricular lesions even if they occur very early in life. The findings point to specific restrictions on the brain's spontaneous compensatory plasticity in perceptual development.

Adolescent↗

Anterior and posterior hippocampal volumes in schizophrenia.

BACKGROUND: While the evidence for hippocampal structural abnormalities in schizophrenia is now well accepted, whether there is differentially greater volume loss within specific subregions of the hippocampus remains a matter of some debate. Here we present volume estimates of anterior and posterior hippocampal volumes using a novel morphometric protocol. METHODS: We studied 25 male patients with schizophrenia and 25 age-matched male control subjects. Hippocampal volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images (MRI). Anterior hippocampal volumes were differentiated from posterior hippocampal volumes by the presence of the uncus in coronal slices. RESULTS: While the patients with schizophrenia had significantly smaller overall hippocampal volumes relative to the control group, there was no evidence for a topographically specific pattern of volume loss along the anterior-posterior hippocampal axis. CONCLUSIONS: These results confirm the presence of overall hippocampal volume decreases in patients with schizophrenia, but do not confirm a topographically specific localization of this effect. It appears that the hippocampal volume deficit in schizophrenia is diffuse, a finding that has important consequences for understanding the underlying pathophysiologic mechanisms in schizophrenia.

Adult↗

Developments in general airway management.

Since the 1970s, improvements in airway management have been significant. New imaging modalities such as CT and MRI can display airway structures with unparalleled detail, which improves preoperative planning and the treatment of patients with pathologic processes involving the respiratory tract or with difficult-to-manage airways. Because of the introduction of flexible fiberscopes, pulmonologists and thoracic surgeons can diagnose diseases of the respiratory tract effectively and treat patients with these diseases safely. The use of flexible fiberscopes has expanded rapidly into other medical specialties, including anesthesia and critical care. Modem anesthesiologists now use flexible fiberscopes daily to intubate patients safely, especially when traditional intubating techniques fail. The cost of fiberscopes has decreased dramatically, and their optical systems have improved. Several centers of excellence have been developed where clinicians can learn basic and advanced techniques of fiberoptic intubation. The LMA has shown that the supraglottic airway approach is not only feasible, but also in many situations superior to tracheal intubation. Although the LMA initially was recommended as an alternative to the facemask, its use has expanded, benefiting many children and adults undergoing a variety of diagnostic and therapeutic procedures. Use of an LMA in combination with a flexible fiberscope has opened up new possibilities for treating patients safely and effectively while providing optimal comfort during a procedure and has been particularly beneficial in thoracic surgery. The most recent iteration of the ASA Difficult Airway Algorithm has revised further a systematic approach to the clinical care of patients with different types of difficult-to-manage airways.

Algorithms↗