Extent of Microstructural Tissue Damage Correlates with Hemodynamic Failure in High-Grade Carotid Occlusive Disease: An MRI Study Using Quantitative T2 and DSC Perfusion.

BACKGROUND AND PURPOSE: Chronic hemodynamic impairment in high-grade carotid occlusive disease is thought to cause microstructural abnormalities that might be subclinical or lead to subtle symptoms including cognitive impairment. Quantitative MR imaging allows assessing pathologic structural changes beyond macroscopically visible tissue damage. In this study, high-resolution quantitative T2 mapping combined with DSC-based PWI was used to investigate quantitative T2 changes as a potential marker of microstructural damage in relation to hemodynamic impairment in patients with unilateral high-grade carotid occlusive disease. MATERIALS AND METHODS: Eighteen patients with unilateral high-grade ICA or MCA stenosis/occlusion were included in the study. T2 values and deconvolved perfusion parameters, including relative CBF, relative CBV, and the relative CBF/relative CBV ratio as a potential indicator of local cerebral perfusion pressure, were determined within areas with delayed TTP and compared with values from contralateral unaffected areas after segmentation of normal-appearing hypoperfused WM and cortical regions. Hemispheric asymmetry indices were calculated for all parameters. RESULTS: Quantitative T2 was significantly prolonged (P < .01) in hypoperfused tissue and correlated significantly (P < .01) with TTP delay and relative CBF/relative CBV reduction in WM. Significant correlations (P < .001) between TTP delay and the relative CBF/relative CBV ratio were found both in WM and in cortical areas. CONCLUSIONS: Quantitative T2 can be used as a marker of microstructural tissue damage even in normal-appearing GM and WM within a vascular territory affected by high-grade carotid occlusive disease. Furthermore, the extent of damage correlates with the degree of hemodynamic failure measured by DSC perfusion parameters.

Effects of aerobic exercise on brain metabolism and grey matter volume in older adults: results of the randomised controlled SMART trial.

There is mounting evidence that aerobic exercise has a positive effect on cognitive functions in older adults. To date, little is known about the neurometabolic and molecular mechanisms underlying this positive effect. The present study used magnetic resonance spectroscopy and quantitative MRI to systematically explore the effects of physical activity on human brain metabolism and grey matter (GM) volume in healthy aging. This is a randomised controlled assessor-blinded two-armed trial (n=53) to explore exercise-induced neuroprotective and metabolic effects on the brain in cognitively healthy older adults. Participants (age >65) were allocated to a 12-week individualised aerobic exercise programme intervention (n=29) or a 12-week waiting control group (n=24). The main outcomes were the change in cerebral metabolism and its association to brain-derived neurotrophic factor (BDNF) levels as well as changes in GM volume. We found that cerebral choline concentrations remained stable after 12 weeks of aerobic exercise in the intervention group, whereas they increased in the waiting control group. No effect of training was seen on cerebral N-acetyl-aspartate concentrations, nor on markers of neuronal energy reserve or BDNF levels. Further, we observed no change in cortical GM volume in response to aerobic exercise. The finding of stable choline concentrations in the intervention group over the 3 month period might indicate a neuroprotective effect of aerobic exercise. Choline might constitute a valid marker for an effect of aerobic exercise on cerebral metabolism in healthy aging.

Quantitative MR Imaging of Brain Tissue and Brain Pathologies.

Measurement of basic quantitative magnetic resonance (MR) parameters (e.g., relaxation times T1, T2*, T2 or respective rates R (1/T)) corrected for radiofrequency (RF) coil bias yields different conventional and new tissue contrasts as well as volumes for tissue segmentation. This approach also provides quantitative measures of microstructural and functional tissue changes. We herein demonstrate some prospects of quantitative MR imaging in neurological diagnostics and science.

White matter damage is related to ataxia severity in SCA3.

Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

Age-related changes of cerebral autoregulation: new insights with quantitative T2'-mapping and pulsed arterial spin-labeling MR imaging.

BACKGROUND AND PURPOSE: Cerebral perfusion and O(2) metabolism are affected by physiologic age-related changes. High-resolution motion-corrected quantitative T2'-imaging and PASL were used to evaluate differences in deoxygenated hemoglobin and CBF of the gray matter between young and elderly healthy subjects. Further combined T2'-imaging and PASL were investigated breathing room air and 100% O(2) to evaluate age-related changes in cerebral autoregulation. MATERIALS AND METHODS: Twenty-two healthy volunteers 60-88 years of age were studied. Two scans of high-resolution motion-corrected T2'-imaging and PASL-MR imaging were obtained while subjects were either breathing room air or breathing 100% O(2). Manual and automated regions of interest were placed in the cerebral GM to extract values from the corresponding maps. Results were compared with those of a group of young healthy subjects previously scanned with the identical protocol as that used in the present study. RESULTS: There was a significant decrease of cortical CBF (P < .001) and cortical T2' values (P < .001) between young and elderly healthy subjects. In both groups, T2' remained unchanged under hyperoxia compared with normoxia. Only in the younger but not in the elderly group could a significant (P = .02) hyperoxic-induced decrease of the CBF be shown. CONCLUSIONS: T2'-mapping and PASL in the cerebral cortex of healthy subjects revealed a significant decrease of deoxygenated hemoglobin and of CBF with age. The constant deoxyHb level breathing 100% O(2) compared with normoxia in young and elderly GM suggests an age-appropriate cerebral autoregulation. At the younger age, hyperoxic-induced CBF decrease may protect the brain from hyperoxemia.

The tremor network targeted by successful VIM deep brain stimulation in humans.

OBJECTIVE: Deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM) is a treatment option in medically intractable tremor, such as essential tremor or tremor-dominant Parkinson disease (PD). Although functional studies demonstrated modulation of remote regions, the structural network supporting this is as yet unknown. In this observational study, we analyzed the network mediating clinical tremor modulation. METHODS: We studied 12 patients undergoing VIM stimulation for debilitating tremor. We initiated noninvasive diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover, we tested for the contribution of primary motor projections in this structural correlate of a functional tremor network, comparing the connectivity of effective DBS contacts with those of adjacent, but clinically ineffective, stimulation sites. RESULTS: VIM stimulation resulted in decrease of tremor and improvement in quality of life. Tractography initiated from the effective stimulation site reconstructed a highly reproducible network of structural connectivity comprising motor cortical, subcortical, and cerebellar sites and the brainstem, forming the anatomic basis for remote effects of VIM stimulation. This network is congruent with functional imaging studies in humans and with thalamic projections found in the animal literature. Connectivity to the primary motor cortex seemed to play a key role in successful stimulation. CONCLUSIONS: Patients undergoing DBS provide a unique opportunity to assess an electrophysiologically defined seed region in human thalamus, a technique that is usually restricted to animal research. In the future, preoperative tractography could aid with stereotactic planning of individual subcortical target points for stimulation in tremor and in other disease entities.

[Innovative MRI techniques in Parkinson's disease]. / Innovative MRT-Verfahren bei idiopathischem Parkinson-Syndrom.

Brain imaging enables the investigation of brain morphology and function in patients with Parkinson's disease (PD). Innovative magnetic resonance imaging (MRI) techniques have recently been established as a new research tool in PD. They are based on the investigation of neuronal tissue properties (MR relaxometry, SWI, DWI, DTI, VBM) and of cerebral perfusion and neuronal activity (ASL, fcMRI). Besides a better understanding of the pathophysiology of PD, these innovative MR techniques might be suitable for measuring progression of PD and the effect of therapeutic interventions on brain functioning. In the clinical setting, they could help to advance the differential diagnosis of parkinsonian disorders.

T1 mapping using spoiled FLASH-EPI hybrid sequences and varying flip angles.

In this work a method for considerably improving the signal-to-noise ratio (SNR) in T(1) maps based on the variable flip angle approach is proposed, employing spoiled fast low angle shot (FLASH) echo-planar imaging (EPI) hybrid sequences with two echoes per excitation. In phantom measurements it could be verified that the SNR improvement in the underlying images translated into an SNR increase in the T(1) maps exceeding theoretical predictions. Even a hybrid sequence with an 18% shorter measurement time than a standard FLASH readout with identical spatial coverage and resolution yielded an SNR gain of 23% in the resulting T(1) maps. Hybrid sequences with either identical measurement time (9:05 min) or bandwidth (9:30 min) yielded gains of 60% and 67%, respectively. These results could be confirmed by measurements on four healthy volunteers. The image quality of T(1) maps based on hybrid sequences was excellent and the SNR improvement was clearly visible. The measured SNR gains in T(1) maps were between 20% (shortest sequence, white matter) and 66% (sequence with identical bandwidth, gray matter). The resulting T(1) values were comparable, with a slight tendency toward higher values in the hybrid sequences. In summary, without prolonging experiment durations the method proposed yields SNR gains that are commonly achieved by acquiring two averages.

Influence of RF spoiling on the stability and accuracy of T1 mapping based on spoiled FLASH with varying flip angles.

There is increasing interest in quantitative T(1) mapping techniques for a variety of applications. Several methods for T(1) quantification have been described. The acquisition of two spoiled gradient-echo data sets with different flip angles allows for the calculation of T(1) maps with a high spatial resolution and a relatively short experimental duration. However, the method requires complete spoiling of transverse magnetization. To achieve this goal, RF spoiling has to be applied. In this work it is investigated whether common RF spoiling techniques are sufficiently effective to allow for accurate T(1) quantification. It is shown that for most phase increments the apparent T(1) can deviate considerably from the true value. Correct results may be achieved with phase increments of 118.2 degrees or 121.8 degrees. However, for these values the method suffers from instabilities. In contrast, stable results are obtained with a phase increment of 50 degrees. An algorithm is presented that allows for the calculation of corrected T(1) maps from the apparent values. The method is tested both in phantom experiments and in vivo by acquiring whole-brain T(1) maps of the human brain.

Fast structural brain imaging using an MDEFT sequence with a FLASH-EPI hybrid readout.

A sequence for the fast acquisition of T1 weighted structural brain images with whole brain coverage and isotropic resolution of 1mm is presented. It is based on MDEFT with a FLASH-EPI hybrid readout. Several techniques for artefact suppression are implemented, like echo time shifting, asymmetric k-space sampling, and navigator echo acquisition. It is shown experimentally that the hybrid MDEFT sequence with a total duration of 8min yields approximately the same signal-to-noise and contrast-to-noise ratios as a 12min standard MDEFT sequence based on a FLASH readout. Further experiments show that echo time shifting suppresses artefacts in the vicinity of the scalp and in areas suffering from field inhomogeneities and that the concept of asymmetric k-space sampling reduces the susceptibility to head movement.

Removing the effects of CSF partial voluming on fitted CBF and arterial transit times using FAIR, a pulsed arterial spin labelling technique.

FAIR, an arterial spin labelling technique, provides non-invasive, quantitative CBF values and arterial transit times deltat. This paper focuses on the negative impact of CSF partial voluming on FAIR results. To understand and solve this problem, we performed a theoretical analysis and a range of simulations. We then acquired FAIR data from a volunteer to illustrate our findings. We found that the determinant effect of CSF is a delayed zero-crossing during inversion recovery. The subtraction of magnitude inversion recovery data in FAIR generates erroneous negative data and distorted fit results: we simulated that for CSF percentages of 0-40%, CBF and deltat will be progressively overestimated by up to 50%. For higher CSF percentages the errors were found to increase steeply. We explored a straightforward solution: taking the magnitude of the FAIR data before fitting. This provided a remarkably strong antidote against the effects of CSF partial voluming: for CSF percentages of 0-40%, simulations now gave CBF values accurate within 1%, and deltat within 5%. The fit remained robust for high CSF fractions. Our analysis and simulations demonstrate that using magnitude FAIR data minimises the detrimental effects of CSF partial voluming. Data from a healthy volunteer illustrate these results.

Optimisation of the 3D MDEFT sequence for anatomical brain imaging: technical implications at 1.5 and 3 T.

An algorithm for the optimisation of 3D Modified Driven Equilibrium Fourier Transform (MDEFT) sequences for T1-weighted anatomical brain imaging is presented. Imaging parameters are optimised for a clinical whole body scanner and a clinical head scanner operating at 1.5 and 3 T, respectively. In vivo studies show that the resulting sequences allow for the whole brain acquisition of anatomical scans with an isotropic resolution of 1 mm and high contrast-to-noise ratio (CNR) in an acceptable scan time of 12 min. Typical problems related to the scanner-specific hardware configurations are discussed in detail, especially the occurrence of flow artefacts in images acquired with head transmit coils and the enhancement of scalp intensities in images acquired with phased array receive coils. It is shown both theoretically and experimentally that these problems can be avoided by using spin tagging and fat saturation.

Optimized EPI for fMRI studies of the orbitofrontal cortex.

A common problem in gradient-echo echo planar imaging (EPI) is the occurrence of image distortions and signal losses caused by susceptibility gradients near air/tissue interfaces. Since EPI is frequently used for functional magnetic resonance imaging experiments based on the blood oxygenation level-dependent effect, functional studies of certain brain regions affected by susceptibility gradients, such as the temporal lobes and the orbitofrontal cortex, may be compromised. In this work a method for signal recovery in certain regions of the orbitofrontal cortex is presented. The influence of in-plane susceptibility gradients is reduced by optimization of the imaging slice orientation. Through-plane susceptibility gradients are partly compensated by means of a moderate preparation gradient pulse similar to z-shimming. In contrast to several other techniques proposed in the literature for reducing susceptibility effects, this method does not compromise the temporal resolution and is therefore applicable to event-related studies.

Compensation of susceptibility-induced BOLD sensitivity losses in echo-planar fMRI imaging.

Gradient-echo echo-planar imaging is a standard technique in functional magnetic resonance imaging (fMRI) experiments based on the blood oxygenation level-dependent (BOLD) effect. A major problem is the occurrence of susceptibility gradients near air/tissue interfaces. As a consequence, the detection of neuronal activation may be greatly compromised in certain brain areas, especially in the temporal lobes and in the orbitofrontal cortex. Common approaches to overcome this problem, such as z-shimming or the use of tailored radio frequency pulses, usually compensate only for susceptibility gradients in the slice selection direction. In the present study, the influence of susceptibility gradients in the phase encoding direction is investigated both theoretically and experimentally. It is shown that these gradients influence the effective echo time TE and may reduce considerably the local BOLD sensitivity, even in the case of acceptable image intensities. A compensation method is proposed and tested in an fMRI experiment based on a hypercapnic challenge. The results suggest that the compensation method allows for the detection of activation in brain areas which are usually unavailable for BOLD studies.

RF inhomogeneity compensation in structural brain imaging.

Three-dimensional T(1)-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) sequences with centric phase encoding (PE) in the inner loop provide structural brain images with a high spatial resolution and high tissue contrast. A disadvantage of this sequence type is the susceptibility to inhomogeneities of the radiofrequency (RF) coil, which may result in poor image contrast in some peripheral regions. A special excitation pulse is presented which compensates for these effects in both the head/foot and anterior/posterior directions. This pulse has a duration of only 1.3 ms and is thus compatible with the short repetition times (TRs) required for MP-RAGE imaging. It is shown experimentally that images acquired with the compensation pulse may be segmented without using intensity correction algorithms during data postprocessing.

Optimization of 3-D MP-RAGE sequences for structural brain imaging.

An optimized MR sequence for structural three-dimensional brain scans is presented, giving good T(1) contrast and excellent white matter/gray matter segmentation. Modification of the usual linear phase encoding order to centric phase encoding restores the contrast loss, which usually occurs after magnetization preparation during the acquisition process when large volumes are imaged. The deleterious effects on the point-spread function are compensated by means of an appropriate k-space filter. RF coil inhomogeneities are corrected by means of shaped excitation pulses. High contrast-to-noise images of the entire brain with 1 mm isotropic resolution can be obtained in 12 min. The contrast-to-noise-ratio is about 100% higher than for sequences based on linear phase encoding.

Improvements in diabetic care as measured by HbA1c after a physician education project.

OBJECTIVE: To measure the quality of diabetic care as indicated by HbA1c testing frequency and HbA1c values and to demonstrate improvement in care after an appropriate quality improvement intervention. RESEARCH DESIGN AND METHODS: The quality improvement project used computerized claims and laboratory data relating to HbA1c testing among the private practices of nine physicians caring for diabetic Medicare patients. Nine indicators evaluated three main areas: HbA1c testing frequency, HbA1c values, and frequency of office visits. A quality improvement intervention consisting of a physician component and a patient component was implemented. RESULTS: There were 835 patients and 4,367 visits studied. After the intervention, statistically significant improvements in HbA1c testing frequency and values were noted. Rates of seized opportunities for testing HbA1c improved from 17.7 to 33.9% (P < 0.0001). The percentage of patients with a current HbA1c value improved from 31.3 to 47.6% (P < 0.0001). The median HbA1c values fell from 8.5 to 7.8% (P < 0.006). Patients achieving good or fair control (HbA1c < or = 8%) improved from 43.8 to 56.9% (P = 0.007). The median time between physician visits fell from 70 days to 60 days (P < 0.0001). CONCLUSIONS: The study revealed that HbA1c testing was underused but that after a quality improvement initiative, a significant increase in testing use could be achieved. The quality improvement initiative also resulted in significant improvements in glycemic control. The techniques and interventions used in this study could be used to intervene in larger populations and practice settings to improve medical care for diabetic patients.

Fast T1 mapping on a whole-body scanner.

A method for the fast acquisition of quantitative T1 maps is presented. It is based on the acquisition of a series of snapshot fast low-angle shot (FLASH) images after inversion of the magnetization. A drawback of this method is the necessity for a sufficiently long relaxation delay before each inversion pulse, leading to long experimental times if averaging or segmentation is required. Thus implementation of this method on a whole-body scanner is problematic, as the longer gradient rise times provide prolonged repetition times, which makes segmentation indispensable to provide a sufficient temporal resolution. We present a modification of the method that allows for reduction in the intermediate relaxation delays and thus for considerably reduced experimental durations.

Signal intensities in FLASH-EPI-hybrid sequences.

Theoretical considerations on the signal-to-noise ratio (SNR) in FLASH-EPI-Hybrid imaging were published previously. The purpose of this work was to investigate in vivo the signal intensities in Hybrid images as a function of sequence specific parameters. In detail, the SNR as a function of the number of echoes m per RF excitation, the excitation flip angle alpha, and the dependence on the tissue relaxation times T1 and T2* were studied. In eight healthy subjects brain and abdominal Hybrid images were acquired where m and alpha were changed independently. Signal intensities in human brain, liver, and kidney were evaluated for each Hybrid experiment. Additionally, T1 and T2* values of these tissue types were quantified to allow for a comparison with the theory. An excellent agreement between calculated and measured signal behavior was found. The theory was therefore validated in vivo and can thus be used to optimize the signal-to-noise in Hybrid experiments.

Effect of physician-specific mailouts aimed at increasing influenza immunization rates.

With the Year 2000 goal being 60%, influenza immunization rates for the Medicare elderly in Louisiana remain far below the expected target rate. It is well recognized that physicians are an important group of health care providers who can contribute towards increasing influenza immunization rates for community dwelling elders. As a health care quality improvement effort, in order to increase the 1997 influenza immunization rates for Louisiana, we implemented a physician specific mailout intervention. Medicare Part B claims and influenza immunization datasets were used to compute missed opportunity rates and immunization rates. Compared to rates in 1996, the influenza immunization rate in both groups significantly increased irrespective of the intervention. However, the increase in the intervention group was more than that in the control group, indicating that mailout of indicator rate data to physicians impacts upon practice patterns.