Different FreeSurfer versions might generate different statistical outcomes in case-control comparison studies.

PURPOSE: Neuroimaging pipelines have long been known to generate mildly differing results depending on various factors, including software version. While considered generally acceptable and within the margin of reasonable error, little is known about their effect in common research scenarios such as inter-group comparisons between healthy controls and various pathological conditions. The aim of the presented study was to explore the differences in the inferences and statistical significances in a model situation comparing volumetric parameters between healthy controls and type 1 diabetes patients using various FreeSurfer versions. METHODS: T1- and T2-weighted structural scans of healthy controls and type 1 diabetes patients were processed with FreeSurfer 5.3, FreeSurfer 5.3 HCP, FreeSurfer 6.0 and FreeSurfer 7.1, followed by inter-group statistical comparison using outputs of individual FreeSurfer versions. RESULTS: Worryingly, FreeSurfer 5.3 detected both cortical and subcortical volume differences out of the preselected regions of interest, but newer versions such as FreeSurfer 5.3 HCP and FreeSurfer 6.0 reported only subcortical differences of lower magnitude and FreeSurfer 7.1 failed to find any statistically significant inter-group differences. CONCLUSION: Since group averages of individual FreeSurfer versions closely matched, in keeping with previous literature, the main origin of this disparity seemed to lie in substantially higher within-group variability in the model pathological condition. Ergo, until validation in common research scenarios as case-control comparison studies is included into the development process of new software suites, confirmatory analyses utilising a similar software based on analogous, but not fully equivalent principles, might be considered as supplement to careful quality control.

Heavy drinking from adolescence to young adulthood is associated with an altered cerebellum.

Excessive alcohol use results in cerebellar damage in adults, but there has been less research on how alcohol use during adolescence affects the cerebellum. In this study, we observed that heavy drinking from adolescence to young adulthood was associated with altered volumes of cerebellar lobules. The study included two groups consisting of 33 heavy-drinking and 25 light-drinking participants. The heavy-drinking participants were highly functional young adults without alcohol use disorder, but with a history of regular heavy alcohol consumption. The participants were 13-18 years old at baseline and were followed for 10 years. At the age of 21-28 years, the participants underwent magnetic resonance imaging (MRI). From the MR images, the cerebellum was segmented into 12 lobules using the CERES pipeline. Heavy drinking did not influence the absolute cerebellar volume, but changes were observed in posterior cerebellar lobules associated with motor and cognitive functions. The absolute volume (p = 0.038) and gray matter volume (p = 0.034) of Crus II (hemispheres combined) were smaller in the heavy-drinking group. Furthermore, the relative volume of the right VIIIB lobule was larger in the HD group (p = 0.036). However, there were no differences in the absolute right VIIIB volumes (p = 0.198) between the groups. Our results suggest changes in the cerebellum in healthy young adults with a history of heavy drinking from adolescence. The exact implications and significance of these findings require further research.

Structural Alterations in Deep Brain Structures in Type 1 Diabetes.

Even though well known in type 2 diabetes, the existence of brain changes in type 1 diabetes (T1D) and both their neuroanatomical and clinical features are less well characterized. To fill the void in the current understanding of this disease, we sought to determine the possible neural correlate in long-duration T1D at several levels, including macrostructural, microstructural cerebral damage, and blood flow alterations. In this cross-sectional study, we compared a cohort of 61 patients with T1D with an average disease duration of 21 years with 54 well-matched control subjects without diabetes in a multimodal MRI protocol providing macrostructural metrics (cortical thickness and structural volumes), microstructural measures (T1-weighted/T2-weighted [T1w/T2w] ratio as a marker of myelin content, inflammation, and edema), and cerebral blood flow. Patients with T1D had higher T1w/T2w ratios in the right parahippocampal gyrus, the executive part of both putamina, both thalami, and the cerebellum. These alterations were reflected in lower putaminal and thalamic volume bilaterally. No cerebral blood flow differences between groups were found in any of these structures, suggesting nonvascular etiologies of these changes. Our findings implicate a marked nonvascular disruption in T1D of several essential neural nodes engaged in both cognitive and motor processing.

Influence of Repetitive Transcranial Magnetic Stimulation on Human Neurochemistry and Functional Connectivity: A Pilot MRI/MRS Study at 7 T.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method commonly used in the disciplines of neuroscience, neurology, and neuropsychiatry to examine or modulate brain function. Low frequency rTMS (e.g., 1 Hz) is associated with a net suppression of cortical excitability, whereas higher frequencies (e.g., 5 Hz) purportedly increase excitability. Magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rsfMRI) allow investigation of neurochemistry and functional connectivity, respectively, and can assess the influence of rTMS in these domains. This pilot study investigated the effects of rTMS on the primary motor cortex using pre and post MRS and rsfMRI assessments at 7 T. Seven right-handed males (age 27 ± 7 y.o.) underwent single-voxel MRS and rsfMRI before and about 30-min after rTMS was administered outside the scanner for 20-min over the primary motor cortex of the left (dominant) hemisphere. All participants received 1-Hz rTMS; one participant additionally received 5-Hz rTMS in a separate session. Concentrations of 17 neurochemicals were quantified in left and right motor cortices. Connectivity metrics included fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) of both motor cortices, strength of related brain networks, and inter-hemispheric connectivity. The group-analysis revealed few trends (i.e., uncorrected for multiple comparisons), including a mean increase in the concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) after the inhibitory rTMS protocol as compared to baseline in the stimulated (left) motor cortex (+8%, p = 0.043), along with a slight increase of total creatine (+2%, p = 0.018), and decrease of aspartate (-18%, p = 0.016). Additionally, GABA tended to decrease in the contralateral hemisphere (-6%, p = 0.033). No other changes of metabolite concentrations were found. Whereas functional connectivity outcomes did not exhibit trends of significant changes induced by rTMS, the percent changes of few connectivity metrics in both hemispheres were negatively correlated with GABA changes in the contralateral hemisphere. While studies in larger cohorts are needed to confirm these preliminary findings, our results indicate the safety and feasibility of detecting changes in key metabolites associated with neurotransmission after a single 1-Hz rTMS session, establishing the construct for future exploration of the neurochemical, and connectivity mechanisms of cortical responses to neuromodulation.

Effects of long-term adolescent alcohol consumption on white matter integrity and their correlations with metabolic alterations.

Alcohol-related white matter (WM) microstructural changes have not been fully elucidated in adolescents. We aimed to investigate influences of subclinical alcohol use during adolescence on WM microstructure and to characterize those with serum metabolic alterations. 35 moderate-to-heavy drinkers (15 males, 20 females) and 27 controls (12 males, 15 females) were selected based on their ten-year Alcohol Use Disorders Identification Test scores measured at three time points. Magnetic resonance imaging was conducted at endpoint time. Whole brain analysis of fractional anisotropy (FA) was performed. Diffusivity indices in the significant regions were computed for between-group comparisons and correlation analyses with serum metabolite concentrations. Decreased FA was found in moderate-to-heavy drinking men in anterior corpus callosum, superior/anterior corona radiata and right inferior fronto-occipital fasciculus, accompanied by increased radial diffusivity and a smaller area of reduced axial diffusivity, which correlated with serum metabolites playing roles in energy metabolism, myelination and axonal degeneration. No significant difference in FA was detected between female or mixed-gender moderate-to-heavy drinking subjects and controls, supporting gender differences in the relationship between adolescent alcohol use and neurodevelopmental trajectories. Future researches with longitudinal imaging data are warranted for comprehensive evaluation on potentially reversible effects of alcohol use over adolescent brain.

Functional and structural asymmetry in primary motor cortex in Asperger syndrome: a navigated TMS and imaging study.

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.

Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes.

In this study, we retrospectively analyzed the anatomical MRI data acquired from 52 subjects with type 1 diabetes (26M/26F, 36 ± 11 years old, A1C = 7.2 ± 0.9%) and 50 age, sex and BMI frequency-matched non-diabetic controls (25M/25F, 36 ± 14 years old). The T1D group was further sub-divided based on whether subjects had normal, impaired, or indeterminate awareness of hypoglycemia (n = 31, 20, and 1, respectively). Our goals were to test whether the gray matter (GM) volumes of selected brain regions were associated with diabetes status as well as with the status of hypoglycemia awareness. T1D subjects were found to have slightly smaller volume of the whole cortex as compared to controls (-2.7%, p = 0.016), with the most affected brain region being the frontal lobe (-3.6%, p = 0.024). Similar differences of even larger magnitude were observed among the T1D subjects based on their hypoglycemia awareness status. Indeed, compared to the patients with normal awareness of hypoglycemia, patients with impaired awareness had smaller volume of the whole cortex (-7.9%, p = 0.0009), and in particular of the frontal lobe (-9.1%, p = 0.006), parietal lobe (-8.0%, p = 0.015) and temporal lobe (-8.2%, p = 0.009). Such differences were very similar to those observed between patients with impaired awareness and controls (-7.6%, p = 0.0002 in whole cortex, -9.1%, p = 0.0003 in frontal lobe, -7.8%, p = 0.002 in parietal lobe, and -6.4%, p = 0.019 in temporal lobe). On the other hand, patients with normal awareness did not present significant volume differences compared to controls. No group-differences were observed in the occipital lobe or in the anterior cingulate, posterior cingulate, hippocampus, and thalamus. We conclude that diabetes status is associated with a small but statistically significant reduction of the whole cortex volume, mainly in the frontal lobe. The most prominent structural effects occurred in patients with impaired awareness of hypoglycemia (IAH) as compared to those with normal awareness, perhaps due to the long-term exposure to recurrent episodes of hypoglycemia. Future studies aimed at quantifying relationships of structural outcomes with functional outcomes, with cognitive performance, as well as with parameters describing glucose variability and severity of hypoglycemia episodes, will be necessary to further understand the impact of T1D on the brain.

Biodegradable biliary stents have a different effect than covered metal stents on the expression of proteins associated with tissue healing in benign biliary strictures.

BACKGROUND: Benign biliary strictures (BBS) are primarily treated endoscopically with covered self-expandable metal stents (CSEMS). Biodegradable biliary stents (BDBS) may be the future of endoscopic therapy of BBS. The aim was to assess the expression of proteins related to tissue healing in BBS compared with the intact bile duct (BD), and to study the protein expression after therapy with CSEMS or BDBS. METHODS: Pigs with ischemic BBS were endoscopically treated either with BDBS or CSEMS. Samples were harvested from pigs with intact BD (n = 5), untreated BBS (n = 5), and after six months of therapy with BDBS (n = 4) or CSEMS (n = 5) with subsequent histologic analysis. Two-dimensional electrophoresis with protein identification was performed to evaluate protein expression patterns. RESULTS: In BBS, the expression of galectin-2 and annexin-A4 decreased, compared to intact BD. Treatment with biodegradable stents normalized galectin-2 level; with CSEMS therapy it remained low. Transgelin expression of intact BD and BBS remained low after BDBS treatment but increased after CSEMS therapy. Histologic analysis did not show unwanted foreign body reaction or hyperplasia in the BD in either group. CONCLUSIONS: The expression of proteins related to tissue healing in BBS is different after treatment with biodegradable stents and CSEMS. Treatment with biodegradable stents may bring protein expression towards what is seen in intact BD. BDBS seem to have a good biocompatibility.

Functional neuronal anisotropy assessed with neuronavigated transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) can evaluate cortical excitability and integrity of motor pathways via TMS-induced responses. The responses are affected by the orientation of the stimulated neurons with respect to the direction of the TMS-induced electric field. Therefore, besides being a functional imaging tool, TMS may potentially assess the local structural properties. Yet, TMS has not been used for this purpose. NEW METHOD: A novel principle to evaluate the relation between function and structure of the motor cortex is presented. This functional anisotropy is evaluated by an anisotropy index (AI), based on motor evoked potential amplitudes induced with different TMS coil orientations, i.e. different electric field directions at a cortical target. To compare the AI with anatomical anisotropy in an explorative manner, diffusion tensor imaging-derived fractional anisotropy (FA) was estimated at different depths near the stimulation site. RESULTS: AI correlated inversely with cortical excitability through the TMS-induced electric field at motor threshold level. Further, there was a trend of negative correlation between AI and FA. COMPARISON WITH EXISTING METHODS: None of the existing methods alone can detect the relationship between direct motor cortex activation and local neuronal structure. CONCLUSIONS: The AI appears to provide information on the functional neuronal anisotropy of the motor cortex by coupling neurophysiology and neuroanatomy within the stimulated cortical region. The AI could prove useful in the evaluation of neurological disorders and traumas involving concurrent structural and functional changes in the motor cortex. Further studies on patients are needed to confirm the usability of AI.

Long-Term Response to Cholinesterase Inhibitor Treatment Is Related to Functional MRI Response in Alzheimer's Disease.

BACKGROUND: Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors (ChEI) enhances cholinergic activity and alleviates clinical symptoms. However, there is variation in the clinical response as well as system level changes revealed by functional MRI (fMRI) studies. METHODS: We investigated 18 newly diagnosed mild AD patients with fMRI using a face recognition task after a single oral dose of rivastigmine, a single dose of placebo and 1-month treatment with rivastigmine. The clinical follow-up took place at 6 and 12 months. RESULTS: MMSE score difference between baseline and the follow-ups showed a positive correlation with fMRI activation difference between treatment and placebo in the right prefrontal cortex. A negative correlation was found for the left prefrontal cortex and the left fusiform gyrus. In addition, greater signal intensity in the right versus the left fusiform gyrus predicted a response to ChEI with increasing MMSE scores during the follow-up with 77.8% sensitivity and 77.8% specificity. CONCLUSIONS: The increased fMRI activation by cholinergic stimulation in brain areas associated with the processing of the visual task reveals still functioning brain networks and a subsequent positive effect of ChEI on cognition. Thus, fMRI may be useful for identifying AD patients most likely to respond to treatment with ChEI.

Effect of cholinergic stimulation in early Alzheimer's disease - functional imaging during a recognition memory task.

Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (AChEI) enhances cholinergic activity and alleviates clinical symptoms. In the present functional magnetic resonance imaging (fMRI) study, we investigated the effect of the AChEI rivastigmine on cognitive function and brain activation patterns during a face recognition memory task. Twenty patients with newly-diagnosed mild AD were administered a single oral dose of placebo, a single dose of rivastigmine (acute), and twice-daily treatment with rivastigmine for 4 weeks (chronic). After each treatment, the patients underwent a facial recognition task during fMRI. The prefrontal areas known to be involved in face recognition memory processing demonstrated greater fMRI activity in both the acute and chronic rivastigmine conditions compared to the placebo condition. In the same brain areas, differences in both fMRI activation at the map level and regional fMRI signal intensity measures between the placebo and chronic treatment conditions correlated negatively with the Mini- Mental State Examination score. In the chronic rivastigmine condition, patients with better preserved cognitive abilities demonstrated less enhanced prefrontal activity, whereas patients with poorer cognition showed greater prefrontal activity. These findings suggest that the prefrontal attention/working memory systems are already impaired in the early stages of AD and that the effect of cholinergic medication in the brain areas involved in recognition memory, i.e., increased or decreased fMRI activation patterns, depends on the severity of the disease. These findings also suggest the importance of early AChEI treatment in the course of AD, at the point when there is still some cognitive reserve available and the therapy has the highest potential efficacy.

Diffusion tensor imaging and tract-based spatial statistics in Alzheimer's disease and mild cognitive impairment.

We aimed to explore the changes in fractional anisotropy (FA) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by analyzing diffusion tensor imaging (DTI) data using the Tract-Based Spatial Statistics (TBSS). DTI data were collected from 17 AD patients, 27 MCI subjects and 19 healthy controls. Voxel-based analysis with TBSS was used to compare FA among the three groups. Additionally, guided by TBSS findings, a region of interest (ROI)-based analysis along the TBSS skeleton was performed on group-level and the accuracy of the method was assessed by the back-projection of ROIs to the native space FA. Neurofiber tracts with decreased FA included: the parahippocampal white matter, cingulum, uncinate fasciculus, inferior and superior longitudinal fasciculus, corpus callosum, fornix, tracts in brain stem, and cerebellar tracts. Quantitative ROI-analysis further demonstrated the significant decrease on FA values in AD patients relative to controls whereas FA values of MCI patients were found in between the controls and AD patients. We conclude that TBSS is a promising method in examining the degeneration of neurofiber tracts in MCI and AD patients.

Estimation of the onset time of cerebral ischemia using T1rho and T2 MRI in rats.

BACKGROUND AND PURPOSE: Time of ischemia onset is the most critical factor for patient selection for available drug treatment strategies. The purpose of this study was to evaluate the abilities of the absolute longitudinal rotating frame (T(1ρ)) and transverse (T(2)) MR relaxation times to estimate the onset time of ischemia in rats. METHODS: Permanent middle cerebral artery occlusion in rats was used to induce focal cerebral ischemia and animals were imaged with multiparametric MRI at several time points up to 7 hours postischemia. Ischemic parenchyma was defined as tissue with apparent diffusion coefficient of water <70% from that in the contralateral nonischemic brain. RESULTS: The difference in the absolute T(1ρ) and T(2) between ischemic and contralateral nonischemic striatum increased linearly within the first 6 hours of middle cerebral artery occlusion. The slopes for T(1ρ) and T(2) fits for both tissue types were similar; however, the time offsets were significantly longer for both MR parameters in the cortex than in the striatum. CONCLUSIONS: T(1ρ) and T(2) MRI provide estimates for the onset time of cerebral ischemia requiring regional calibration curves from ischemic brain. Assuming that patients with suspected ischemic stroke are scanned by MRI within this timeframe, these MRI techniques may constitute unbiased tools for stroke onset time evaluation potentially aiding the decision-making for drug treatment strategies.

Quantitative MRI predicts long-term structural and functional outcome after experimental traumatic brain injury.

In traumatic brain injury (TBI) the initial impact causes both immediate damage and also launches a cascade of slowly progressive secondary damage. The chronic outcome disabilities vary greatly and can occur several years later. The aim of this study was to find predictive factors for the long-term outcome using multiparametric, non-invasive magnetic resonance imaging (MRI) methodology and a clinically relevant rat model of fluid percussion induced TBI. Our results demonstrated that the multiparametric quantitative MRI (T(2), T(1rho), trace of the diffusion tensor D(av), the extent of hyperintense lesion and intracerebral hemorrhage) acquired during acute and sub acute phases 3 h, 3 days, 9 days and 23 days post-injury has potential to predict the functional and histopathological outcome 6 to 12 months later. The acute D(av) changes in the ipsilateral hippocampus correlated with the chronic spatial learning and memory impairment evaluated using the Morris water maze (p<0.05). Similarly, T(1rho), T(2) and D(av) correlated with hippocampal atrophy and with histologically quantified neurodegeneration (p<0.01). The early lesion volume and quantitative MRI changes in the perilesional region prefigured the final lesion extent (p<0.01). Furthermore, the severity of acute intracerebral hemorrhage correlated with the final cortical atrophy (p<0.05), hippocampal atrophy (p<0.01), and also with the water maze performance (p<0.01). We conclude that, assessment of early quantitative MRI changes in the hippocampus and in the perifocal area may help to predict the long-term outcome after experimental TBI.

Quantitative assessment of water pools by T 1 rho and T 2 rho MRI in acute cerebral ischemia of the rat.

The rotating frame longitudinal relaxation magnetic resonance imaging (MRI) contrast, T(1 rho), obtained with on-resonance continuous wave (CW) spin-lock field is a sensitive indicator of tissue changes associated with hyperacute stroke. Here, the rotating frame relaxation concept was extended by acquiring both T(1 rho) and transverse rotating frame (T(2 rho)) MRI data using both CW and adiabatic hyperbolic secant (HSn; n=1, 4, or 8) pulses in a rat stroke model of middle cerebral artery occlusion. The results show differences in the sensitivity of spin-lock T(1 rho) and T(2 rho) MRI to detect hyperacute ischemia. The most sensitive techniques were CW-T(1 rho) and T(1 rho) using HS4 or HS8 pulses. Fitting a two-pool exchange model to the T(1 rho) and T(2 rho) MRI data acquired from the infarcting brain indicated time-dependent increase in free water fraction, decrease in the correlation time of water fraction associated with macromolecules, and increase in the exchange correlation time. These findings are consistent with known pathology in acute stroke, including vasogenic edema, destructive processes, and tissue acidification. Our results show that the sensitivity of the spin-lock MRI contrast in vivo can be modified using different spin-lock preparation blocks, and that physicochemical models of the rotating frame relaxation may provide insight into progression of ischemia in vivo.

Distinct MRI pattern in lesional and perilesional area after traumatic brain injury in rat--11 months follow-up.

To understand the dynamics of progressive brain damage after lateral fluid-percussion induced traumatic brain injury (TBI) in rat, which is the most widely used animal model of closed head TBI in humans, MRI follow-up of 11 months was performed. The evolution of tissue damage was quantified using MRI contrast parameters T(2), T(1rho), diffusion (D(av)), and tissue atrophy in the focal cortical lesion and adjacent areas: the perifocal and contralateral cortex, and the ipsilateral and contralateral hippocampus. In the primary cortical lesion area, which undergoes remarkable irreversible pathologic changes, MRI alterations start at 3 h post-injury and continue to progress for up to 6 months. In more mildly affected perifocal and hippocampal regions, the robust alterations in T(2), T(1rho), and D(av) at 3 h to 3 d post-injury normalize within the next 9-23 d, and thereafter, progressively increase for several weeks. The severity of damage in the perifocal and hippocampal areas 23 d post-injury appeared independent of the focal lesion volume. Magnetic resonance spectroscopy (MRS) performed at 5 and 10 months post-injury detected metabolic alterations in the ipsilateral hippocampus, suggesting ongoing neurodegeneration and inflammation. Our data show that TBI induced by lateral fluid-percussion injury triggers long-lasting alterations with region-dependent temporal profiles. Importantly, the temporal pattern in MRI parameters during the first 23 d post-injury can indicate the regions that will develop secondary damage. This information is valuable for targeting and timing interventions in studies aiming at alleviating or reversing the molecular and/or cellular cascades causing the delayed injury.

Proton transfer ratio, lactate, and intracellular pH in acute cerebral ischemia.

The amide proton transfer ratio (APTR) from the asymmetry of the Z-spectrum was determined in rat brain tissue during and after unilateral middle cerebral artery occlusion (MCAo). Cerebral lactate (Lac) as determined by (1)H NMR spectroscopy, water diffusion, and T(1rho) were quantified as well. Lac concentrations were used to estimate intracellular pH (pH(i)) in the brain during the MCA occlusion. A decrease in APTR during occlusion indicated acidification from 7.1 to 6.79 +/- 0.19 (a drop by 0.3 +/- 0.2 pH units), whereas pH(i) computed from Lac concentration was 6.3 +/- 0.2 (a drop by 0.8 +/- 0.2 pH units). Despite the disagreement between the two methods in terms of the size of the change in the absolute pH(i) during ischemia, DeltaAPTR and pH(i) (and Lac concentration) displayed a strong correlation during the MCAo. Diffusion and T(1rho) indicated cytotoxic edema following MCA occlusion; however, APTR returned slowly toward the values determined in the contralateral hemisphere post-ischemia. These data argue that the APTR during ischemia is affected not only by pH(i) but by other physicochemical factors as well, and indicates different aspects of pathology in the post-ischemic brain compared to those that influence water diffusion and T(1rho).

Quantitative T(1rho) and adiabatic Carr-Purcell T2 magnetic resonance imaging of human occipital lobe at 4 T.

The feasibility of performing quantitative T(1rho) MRI in human brain at 4 T is shown. T(1rho) values obtained from five volunteers were compared with T2 and adiabatic Carr-Purcell (CP) T2 values. Measured relaxation time constants increased in order from T2, CP-T2, T(1rho) both in white and gray matter, demonstrating differential sensitivities of these methods to dipolar interactions and/or proton exchange and diffusion in local microscopic field gradients, which are so-called dynamic averaging (DA) processes. In occipital lobe, all relaxation time constants were found to be higher in white matter than in gray matter, demonstrating contrast denoted as an "inverse transverse relaxation contrast." This contrast persisted despite changing the delay between refocusing pulses or changing the magnitude of the spin-lock field strength, which suggests that it does not originate from DA, as might be induced by the presence of Fe, but rather is related to dipolar interactions in the brain tissue.

Dynamic dephasing changes in developing ischemic cerebral infarction in rats studied by Carr-Purcell T2 magnetic resonance imaging.

Carr-Purcell (CP) T(2) MRI with adiabatic pulses, acquired with varying interecho interval (tau(CP)), was used to study the time course of T(2) and relative dynamic-dephasing contrast in the rat brain. Exposure to 30 min of middle cerebral artery occlusion (MCAo) resulted in an irreversible increase in absolute CP-T(2) relaxation times. This was not associated with signal change in the relative dynamic-dephasing images, as computed by subtracting short tau(CP) CP-T(2) images from long tau(CP) images and normalizing for long tau(CP) images. A day after MCAo strong CP-T(2) hyperintensity and low apparent diffusion coefficient were evident in the striatum with a decline in relative dynamic-dephasing contrast. Low dynamic dephasing contrast prevailed in striatum until day 5 post-MCAo, returning to control levels with similar time course to normalizing T(2) and diffusion. The present results show a novel behavior of dynamic-dephasing contrast in poststroke brain tissue, providing data to assess the age of infarction in association to T(2) images.

Exchange-influenced T2rho contrast in human brain images measured with adiabatic radio frequency pulses.

Transverse relaxation in the rotating frame (T(2rho)) is the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence when no delays are used between pulses in the CP train. The exchange-induced and dipolar interaction contributions (T(2rho,ex) and T(2rho,dd)) depend on the modulation functions of the adiabatic pulses used. In this work adiabatic pulses having different modulation functions were utilized to generate T(2rho) contrast in images of the human occipital lobe at magnetic field of 4 T. T(2rho) time constants were measured using an adiabatic CP pulse sequence followed by an imaging readout. For these measurements, adiabatic full passage pulses of the hyperbolic secant HSn (n = 1 or 4) family having significantly different amplitude-and frequency-modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities) alone was insufficient to fully describe differences in brain tissue water proton T(2rho) time constants. Measurements of the apparent relaxation time constants (T(2) (dagger)) of brain tissue water as a function of the time between centers of pulses (tau(cp)) at 4 and 7 T permitted separation of the DA contribution from that of dipolar relaxation. The methods presented assess T(2rho) relaxation influenced by DA in tissue and provide a means to generate T(2rho) contrast in MRI.