Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old.

BACKGROUND: Current studies suggest an interaction between vascular mechanisms and neurodegenerative processes that leads to late-onset Alzheimer disease (AD). We tested whether AD pathology was associated with white matter hyperintensities (WMH) or cerebral infarcts in the oldest old individuals. METHODS: Brains from 132 subjects over 85 years old, who came to autopsy from the Vantaa 85+ population-based cohort, were scanned by postmortem MRI and examined for neuropathologic changes. Coronal images were analyzed to determine the degree of frontal and parietal periventricular WMH (PVWMH) and deep WMH (DWMH) and cerebral infarcts. Neuropathologic variables included Consortium to Establish a Registry for Alzheimer's Disease scores for neuritic plaques and Braak staging among subjects in 5 groups: normal aging (NA), borderline with insufficient AD pathology, AD, AD plus other pathology, and other primary degenerative diseases. RESULTS: Frontal DWMH were detected in >50% of the sample. Both frontal PVWMH and DWMH were significantly more extensive in the AD group compared to the NA group or the NA and borderline groups combined. Frontal PVWMH and DWMH were also associated with increased Braak staging (p = 0.03) and the neuritic plaque load (p = 0.01). Further analysis revealed there were a greater number of cerebral infarcts associated with frontal DWMH (p = 0.03) but not with frontal PVWMH. CONCLUSIONS: Our study showed an association between neurofibrillary pathology and frontal PVWMH and DWMH (rather than parietal), as a surrogate of small vessel disease, particularly in very old community-dwelling individuals.

The significance of medial temporal lobe atrophy: a postmortem MRI study in the very old.

BACKGROUND: Medial temporal lobe atrophy (MTA) is a sensitive radiologic marker for Alzheimer disease (AD) and associated with cognitive impairment. The value of MTA in the oldest old (>85 years old) is largely unknown. METHODS: A total of 132 formalin-fixed brains from the Vantaa 85+ community-based study were subjected to postmortem MRI. Visual ratings of MTA were determined in a blinded fashion and compared with neuropathologic findings and clinical assessment (dementia according to Diagnostic and Statistical Manual of Mental Disorders-III-R). RESULTS: A strong relationship was found between MTA scores and Alzheimer pathology (p < 0.001). The previously proposed cutoff MTA score >2 correctly excluded subjects with no or borderline Alzheimer-type pathology (45/48), but was not very sensitive for AD (modified National Institute on Aging-Reagan Institute criteria). MTA scores >2 were also found in subjects with other primary neurodegenerative hippocampal pathology including hippocampal sclerosis, Lewy-related pathology, and argyrophilic grain disease, either alone or in combination with Alzheimer-type pathology. High MTA scores were associated with clinical dementia-in this subgroup, sensitivity was 63% and specificity 69% for AD. CONCLUSION: Medial temporal lobe atrophy (MTA) on postmortem MRI is sensitive to primary degenerative hippocampal pathology in the very old, but not specific for Alzheimer-type pathology. MTA scores of 2 or less are not frequently associated with dementia.

Diffusion and perfusion-weighted magnetic resonance imaging techniques in stroke recovery.

Most of the functional recovery after stroke takes place during the first three months after the insult. The neuronal mechanisms underlying this recovery are presently mostly unknown. However, in order to create efficient rehabilitation programs, it is of great importance to uncover these mechanisms. Multiple imaging techniques have been employed for the detection and characterization of ischemic lesions in the brain as well as monitoring of processes associated with stroke recovery. Diffusion and perfusion-weighted magnetic resonance imaging techniques are easy and fast to perform and provide significant information about the ischemic lesion and the hypoperfusion surrounding the lesion at both micro and macrovascular level. More sensitive detection and accurate characterization of the lesion will help in choosing the therapeutic strategies. Methods for monitoring brain function recovery will provide a better understanding of the basic mechanisms of plasticity in the brain, and will serve as a tool for the evaluation of therapeutic interventions, which may eventually include, for example, stem cell transplantation. With the help of these diagnostic tools it may become possible to tailor individual rehabilitation programs.

Violent persons with schizophrenia and comorbid disorders: a functional magnetic resonance imaging study.

The main goal of this functional Magnetic Resonance Imaging (fMRI) study was to verify the hypothesis that seriously violent persons with Sz and the co-morbid diagnoses of an Antisocial Personality Disorder (APD) and a Substance Use Disorder (Sz+APD+SUD) would present a different pattern of prefrontal functioning than seriously violent persons with Sz only. In support with the main hypothesis, frontal basal cortices were significantly less activated in persons with Sz+APD+SUD during the execution of a go/no-go task than in persons with Sz only and non-violent persons without a mental illness. In contrast, significantly higher activations in frontal motor, premotor and anterior cingulate regions were observed in the Sz+APD+SUD group than in the Sz-only group.

ApoE polymorphism and acute stroke: a study with diffusion- and perfusion-weighted MRI and MR angiography.

OBJECTIVES: We examined whether the apolipoprotein E (ApoE) allele epsilon4 influences imaging findings in stroke as assessed by diffusion- (DWI) and perfusion-weighted (PWI) magnetic resonance imaging, and MR angiography (MRA). METHODS: Eight ApoE epsilon4 carriers and 15 non-carriers with acute ischemic stroke in the anterior circulation underwent DWI, PWI, and MRA within 24 h of stroke. DWI and PWI were repeated a week later. The apparent diffusion coefficient, relative cerebral volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time were measured in three subregions on day one. RESULTS: In the ischemic core and the area of infarct growth, rCBV values were significantly higher in the epsilon4 carriers compared with the non-carriers. Based on the MRA findings, collateral blood flow was better in the epsilon4 carriers than in the non-carriers. Under the comparable severity of hypoperfusion, the hypoperfused area proceeded to infarction later or did not proceed to infarction at all in the non-carriers. CONCLUSION: These preliminary data suggest that in the ApoE allele epsilon4 carriers the threshold for the brain tissue to survive hypoperfusion versus to proceed to infarction seems to be different from that of the non-carriers.

A cluster mass permutation test with contextual enhancement for fMRI activation detection.

Gaussian random field (GRF)-based methods are commonly used for statistical inference and to control the family-wise error rate (FWE) in neuroimaging. They require that the error fields are reasonable lattice approximations to an underlying continuous multivariate Gaussian random field and have differentiable and invertible spatial autocorrelation function. Permutation test estimates the distribution of the test statistic from the data and adjusts automatically for the FWE. Here we present a new analysis procedure, the cluster mass permutation test with contextual enhancement (CMPCE), and compare it to GRF. In CMPCE, the data are first pre-whitened to remove temporal autocorrelations. The FWE rates, the cluster detection probability and delineation accuracy of CMPCE and GRF were compared using measured null data and null data containing simulated activations. We also applied both methods to an fMRI experiment where tactile somatosensory stimulation into the right hand was used. When analyzing the FWE using null data, both CMPCE and GRF gave significantly higher FWEs (CMPCE up to 0.12, GRF up to 0.18) than the nominal significance level 0.05, indicating that the pre-whitening, motion correction or high-pass filtering partially failed. In the simulated activation data, CMPCE gave less falsely classified voxels for the same cluster detection probability level than GRF. The maximal cluster detection probability was on the other hand higher in the GRF-based method. Both methods gave qualitatively similar results in the tactile fMRI data. CMPCE seems to be a promising fMRI analysis method, especially if high delineation accuracy is required.

Assessing the outcome of stroke: a comparison between MRI and clinical stroke scales.

OBJECTIVES: To assess the correlation of diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) findings with the severity of acute neurologic deficit and their ability to predict short and long-term clinical outcomes of stroke. The ability of DWI and PWI to predict the outcome was compared with the ability of clinical stroke scales to predict the outcome. METHODS: Forty-eight patients with acute stroke underwent diffusion DWI and PWI on the first and eighth day after the ictus. Clinical and functional scales were carried out before each scan and 3 months after the stroke. RESULTS: The volumes of both the DWI and the PWI lesions correlated well with the acute neurologic deficit and the final outcome. The first day PWI (r = 0.64) and the National Institutes of Health Stroke Scale (NIHSS) scores (r = 0.70) correlated well with the final outcome. However, in logistic regression analysis, only the NIHSS score at the acute stage was the only independent predictor of the long-term clinical outcome. CONCLUSION: While the PWI and DWI lesion volumes correlated well with the outcome of the stroke, the imaging measurements did not improve the prognostic power over plain clinical stroke scale scores.

Poststroke depression and lesion location revisited.

Seventy patients with one brain infarct on magnetic resonance imaging (MRI) were studied 3 months after ischemic stroke by a standardized protocol to detail side, site, type, and extent of the brain infarct, as well as severity of white matter lesions and brain atrophy. Depression was diagnosed by DSM-III-R and DSM-IV criteria. The brain infarcts that affected structures of the frontal-subcortical circuits, (i.e., the pallidum and caudate, especially on the left side) predisposed stroke patients to depression. The size of the infarcts at these sites in the depressed patients was larger. Using a logistic regression analysis, the authors found that a brain infarct that affected pallidum was a strong independent MRI correlate for poststroke depression (odds ratio = 7.2).

EEG minimum-norm estimation compared with MEG dipole fitting in the localization of somatosensory sources at S1.

OBJECTIVE: Dipole models, which are frequently used in attempts to solve the electromagnetic inverse problem, require explicit a priori assumptions about the cerebral current sources. This is not the case for solutions based on minimum-norm estimates. In the present study, we evaluated the spatial accuracy of the L2 minimum-norm estimate (MNE) in realistic noise conditions by assessing its ability to localize sources of evoked responses at the primary somatosensory cortex (SI). METHODS: Multichannel somatosensory evoked potentials (SEPs) and magnetic fields (SEFs) were recorded in 5 subjects while stimulating the median and ulnar nerves at the left wrist. A Tikhonov-regularized L2-MNE, constructed on a spherical surface from the SEP signals, was compared with an equivalent current dipole (ECD) solution obtained from the SEFs. RESULTS: Primarily tangential current sources accounted for both SEP and SEF distributions at around 20 ms (N20/N20m) and 70 ms (P70/P70m), which deflections were chosen for comparative analysis. The distances between the locations of the maximum current densities obtained from MNE and the locations of ECDs were on the average 12-13 mm for both deflections and nerves stimulated. In accordance with the somatotopical order of SI, both the MNE and ECD tended to localize median nerve activation more laterally than ulnar nerve activation for the N20/N20m deflection. Simulation experiments further indicated that, with a proper estimate of the source depth and with a good fit of the head model, the MNE can reach a mean accuracy of 5 mm in 0.2-microV root-mean-square noise. CONCLUSIONS: When compared with previously reported localizations based on dipole modelling of SEPs, it appears that equally accurate localization of S1 can be obtained with the MNE. SIGNIFICANCE: MNE can be used to verify parametric source modelling results. Having a relatively good localization accuracy and requiring minimal assumptions, the MNE may be useful for the localization of poorly known activity distributions and for tracking activity changes between brain areas as a function of time.

MRI correlates of executive dysfunction in patients with ischaemic stroke.

Executive dysfunction (ED) may lead to problem behaviour and impaired activities of daily living in many neuropsychiatric disorders, but the neuroanatomical correlates of ED are still not well known. Different aspects of executive functions were studied by widely used neuropsychological tests in 214 elderly patients 3 months after ischaemic stroke, and a sum score of eight different measures was counted in each patient. The number and site of brain infarcts as well as severity and location of white matter lesions (WMLs) and brain atrophy on magnetic resonance imaging were recorded and compared between patients with and without ED. ED was present in 73 (34.1%) of the 214 patients. The mean frequency of brain infarcts in the brain and in the left hemisphere was higher in the patients with ED. Lesions affecting the frontal-subcortical circuits (e.g. pallidum, corona radiata or centrum semiovale) were more frequent in patients with ED than in those without. Also, patients with pontine brain infarcts frequently had ED, but this may have been due to more extensive ischaemic changes in these patients in general. Mean number of brain infarcts affecting the pons and posterior centrum semiovale on the left side, moderate to severe medial temporal atrophy, the Fazekas white matter score, the Mini-Mental State Examination score and low education were independent correlates of ED. Brain infarcts and WML affecting the frontal-subcortical circuits or the pons may increase risk for ED in stroke patients.

Cerebral hemodynamics in a healthy population measured by dynamic susceptibility contrast MR imaging.

PURPOSE: To establish reference data and to study age-dependency for cerebral perfusion in various regions of the brain in a healthy population. MATERIAL AND METHODS: Eighty healthy subjects of both genders from 22 to 85 years of age were studied with spin echo echo-planar dynamic susceptibility contrast MR imaging (DSC MRI) at 1.5 T. Cerebral blood volume (CBV), cerebral blood flow (CBF), and contrast agent mean transit time (MTT) were calculated bilaterally for 20 distinct neuroanatomic structures. RESULTS: In gray matter, the following values were found (mean +/- SD): CBV (4.6 +/- 1.0 ml/100 g), CBF (94.2 +/- 23.0 ml/100 g/min), and MTT (3.0 +/- 0.6 s), and in white matter: CBV (1.3 +/- 0.4 ml/100 g), CBF (19.6 +/- 5.8 ml/100 g/min), and MTT (4.3 +/- 0.7 s). The perfusion parameters did not change with age, except for a tendency to an increase in gray matter MTT and CBV. Males exhibited higher MTT and CBV than females. No hemispheric difference was found in either gender. CONCLUSION: Cerebral hemodynamics can be assessed with DSC MRI. Age itself seems to have only a marginal effect on cerebral perfusion in healthy population.

Detecting the subregion proceeding to infarction in hypoperfused cerebral tissue: a study with diffusion and perfusion weighted MRI.

Diffusion and perfusion weighted MRI have been widely used in ischaemic stroke. We studied 17 patients in whom ischaemic areas showed an ischaemic core, an area of infarct growth and hypoperfused but ultimately surviving tissue. Apparent diffusion coefficients (ADC) were measured on days 1, 2, and 8 in the three subregions and in contralateral control areas. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were measured in these regions on day 1 perfusion maps. On day 1, the ischaemic core had very low ADC and CBF and increased MTT. The ADC in the ischaemic core gradually increased during the week. The area of infarct growth on day 1 had slightly but significantly decreased ADC (96% of control, P=0.028), moderately decreased CBF and increased MTT. On day 1 the hypoperfused but surviving tissue had slightly but significantly increased ADC (103% of control, P=0.001), mildly decreased CBF and increased CBV and MTT. The ADC of the area of infarct growth decreased to the same level as in the ischaemic core on days 2 and 8. That of surviving tissue was still above normal on day 2 (103% of control), but had returned to the normal level by day 8. Measurement of ADC combined with perfusion MRI may help distinguish different subregions in acutely hypoperfused brain.

Magnetic resonance imaging correlates of depression after ischemic stroke.

BACKGROUND: Depression affects up to 40% of patients with ischemic stroke. The relationship between site and size of brain infarcts and poststroke depression is still not well characterized. Further possible contribution and interaction of white matter lesions and brain atrophy has not been studied previously. We conducted a magnetic resonance image-based study of the radiologic correlates of depression in a large, well-defined series of patients with ischemic stroke. METHODS: Modified DSM-III-R and DSM-IV criteria were used to diagnose depressive disorders during a comprehensive psychiatric evaluation in 275 of 486 consecutive patients aged 55 to 85 years 3 to 4 months after ischemic stroke. A standardized magnetic resonance imaging protocol detailed side, site, type, and extent of brain infarcts and extent of white matter lesions and brain atrophy. RESULTS: Depressive disorders were diagnosed in 109 patients (40%). Patients with depression had a higher number and larger volume of infarcts affecting the prefrontosubcortical circuits, especially the caudate, pallidum, and genu of internal capsule, with left-sided predominance. Extent of white matter lesions and atrophy did not differ in patients with and without depression. Independent correlates of poststroke depression in a logistic regression model were mean frequency of infarcts in the genu of internal capsule on the left side (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.0-10.1), mean frequency of infarcts in the pallidum of any side (OR, 1.6; 95% CI, 1.1-2.3), and mean volume of infarcts in the right occipital lobe (OR, 0.98; 95% CI, 0.96-0.99). CONCLUSION: Lesions affecting the prefrontosubcortical circuits, especially on the left side, are correlates of depression after ischemic stroke.

Evidence for dissociation of spatial and nonspatial auditory information processing.

Several lines of evidence suggest that visual information processing is segregated into the ventral "what" and dorsal "where" pathways. But the question whether information processing in the auditory system is also parceled to spatial and nonspatial domains remains open. In the present study, we performed simultaneous EEG and MEG recordings during auditory location and pitch delayed matching-to-sample tasks to find out whether working memory processing of the auditory stimulus attribute affects the transient components of the evoked potentials. In both tasks, identical blocks of tone stimuli of one of two frequencies were presented in one of two locations; the only difference between the tasks was the instruction to attend either to the frequency or to the location. In the match condition, the N1 latency was shorter and the N1m amplitude larger in the location task compared to the pitch task. Furthermore, the right-hemisphere generator of N1m elicited in the match condition of the location task was situated significantly medially to the N1m generator in the match condition of the pitch task. Latency and amplitude task-related differences in the N1/N1m components as well as the source location differences indicate at least partial segregation of neuronal mechanisms involved in working memory processing of spatial and nonspatial auditory information.

Multiple-slice spin lock imaging of head and neck tumors at 0.1 Tesla: exploring appropriate imaging parameters with reference to T2-weighted spin-echo technique.

RATIONALE AND OBJECTIVES: Spin lock imaging has been shown to be useful in characterizing head and neck tumors. The purposes of this study were to explore and develop multiple-slice spin lock gradient-echo (SL-GRE) sequences for head and neck imaging and to compare the tumor contrast on SL images to spin-echo (SE) T2-weighted images at 0.1 T. METHODS: On the basis of measured relaxation times of tumors and head and neck tissues, the authors evaluated with signal equations the effect of imaging parameters on tissue contrast produced by the SL-GRE sequence. In the clinical study, 34 patients with pathologically verified head and neck tumors were imaged with multiple-slice SL-GRE (repetition time 1500 ms/echo time 30 ms) out-of-phase fat/water sequences and compared with T2-weighted SE (repetition time 1500 ms/echo time 120 ms) sequences. The conspicuity of tumors was evaluated by calculating the contrast-to-noise ratios (CNRs). RESULTS: The combination of a short echo time of 30 ms and the length of locking pulses in the range of 10 to 35 ms produced optimal CNRs for head and neck tumor imaging. The measured CNRs and subjective evaluation for tumor detection were satisfactory with both imaging sequences. However, the CNRs between tumors and salivary gland tissues were significantly greater with the SL sequence than with the T2-weighted sequence. CONCLUSIONS: The multiple-slice SL-GRE technique provides image contrast comparable to that of SE T2-weighted imaging for head and neck tumors at 0.1 T. With short locking pulse lengths and echo times, wide anatomic coverage and reduced motion and susceptibility artifacts can be achieved. The out-of-phase SL technique is useful in imaging salivary gland tumors.

Effects of acoustic gradient noise from functional magnetic resonance imaging on auditory processing as reflected by event-related brain potentials.

The processing of sound changes and involuntary attention to them has been widely studied with event-related brain potentials (ERPs). Recently, functional magnetic resonance imaging (fMRI) has been applied to determine the neural mechanisms of involuntary attention and the sources of the corresponding ERP components. The gradient-coil switching noise from the MRI scanner, however, is a challenge to any experimental design using auditory stimuli. In the present study, the effects of MRI noise on ERPs associated with preattentive processing of sound changes and involuntary switching of attention to them were investigated. Auditory stimuli consisted of frequently presented "standard" sounds, infrequent, slightly higher "deviant" sounds, and infrequent natural "novel" sounds. The standard and deviant sounds were either sinusoidal tones or musical chords, in separate stimulus sequences. The mismatch negativity (MMN) ERP associated with preattentive sound change detection was elicited by the deviant and novel sounds and was not affected by the prerecorded background MRI noise (in comparison with the condition with no background noise). The succeeding positive P3a ERP responses associated with involuntary attention switching elicited by novel sounds were also not affected by the MRI noise. However, in ERPs to standard tones and chords, the P1, N1, and P2 peak latencies were significantly prolonged by the MRI noise. Moreover, the amplitude of the subsequent "exogenous" N2 to the standard sounds was significantly attenuated by the presence of MRI noise. In conclusion, the present results suggest that in fMRI the background noise does not interfere with the imaging of auditory processing related to involuntary attention.

Contextual clustering for analysis of functional MRI data.

We present a contextual clustering procedure for statistical parametric maps (SPM) calculated from time varying three-dimensional images. The algorithm can be used for the detection of neural activations from functional magnetic resonance images (fMRI). An important characteristic of SPM is that the intensity distribution of background (nonactive area) is known whereas the distributions of activation areas are not. The developed contextual clustering algorithm divides an SPM into background and activation areas so that the probability of detecting false activations by chance is controlled, i.e., hypothesis testing is performed. Unlike the much used voxel-by-voxel testing, neighborhood information is utilized, an important difference. This is achieved by using a Markov random field prior and iterated conditional modes (ICM) algorithm. However, unlike in the conventional use of ICM algorithm, the classification is based only on the distribution of background. The results from our simulations and human fMRI experiments using visual stimulation demonstrate that a better sensitivity is achieved with a given specificity in comparison to the voxel-by-voxel thresholding technique. The algorithm is computationally efficient and can be used to detect and delineate objects from a noisy background in other applications.

Working memory of identification of emotional vocal expressions: an fMRI study.

The distribution of brain activation during working memory processing of emotional vocal expressions was studied using functional magnetic resonance imaging (fMRI) in eight female subjects performing n-back tasks with three load levels (0-back, 1-back, and 2-back tasks). The stimuli in the n-back tasks were the Finnish female name [Saara] uttered in an astonished, angry, frightened, commanding, and scornful mode, and the subjects were instructed to memorize the emotional connotation of the stimuli. Subregions in the prefrontal, parietal, and visual association areas were load-dependently activated during the performance of the n-back tasks. The most consistently activated areas in the prefrontal region were detected in the inferior frontal gyrus corresponding to Brodmann's areas (BAs) 44 and 45 and in the middle and superior frontal gyri (BAs 6/8). Activation was also found in the inferior parietal lobe and intraparietal sulcus (BAs 40/7) and visual association areas including the lingual and fusiform gyri. The results suggest that a distributed neuronal network in occipital, parietal, and frontal areas is involved in working memory processing of emotional content of aurally presented information.

Fetal shoulder measurements by fast and ultrafast MRI techniques.

The purpose of this study was to evaluate magnetic resonance imaging (MRI) of fetal shoulder measurements of fetuses with suspected macrosomia. The actual fetal shoulder measurements made immediately after birth were compared with measurements obtained by fast and ultrafast MRI techniques antepartum. Eight singleton diabetic pregnant mothers underwent MRI examination with fast imaging in steady-state precession (TrueFISP) and spin-echo (SE) and gradient-echo (GE) echo-planar (EPI) sequences to show the fetal shoulder width. The actual shoulder width was measured immediately postpartum by a neonatologist. There was a statistically significant correlation between the MRI measurements and the actual shoulder width (P < 0.001 - P < 0.05) for all sequences. TrueFISP (r = 0.98, P < 0.001) was superior to EPI sequences (r = 0.88, P < 0.01 for SE EPI and r = 0.80, P < 0.05 for GE EPI). The images of all three sequences used were free of major motion artifacts. Fast and ultrafast sequences seem to be reliable for fetal shoulder measurements and the TrueFISP was the most accurate sequence compared to SE and GE echo-planar sequences. J. Magn. Reson. Imaging 2001;13:938-942.