Changes in brain morphology in patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common disease that leads to daytime sleepiness and cognitive impairment. Attempts to investigate changes in brain morphology that may underlie these impairments have led to conflicting conclusions. This study was undertaken to aim to resolve this confusion, and determine whether OSA is associated with changes in brain morphology in a large group of patients with OSA, using improved voxel-based morphometry analysis, an automated unbiased method of detecting local changes in brain structure. METHODS: 60 patients with OSA (mean apnoea hypopnoea index 55 (95% CI 48 to 62) events/h, 3 women) and 60 non-apnoeic controls (mean apnoea hypopnoea index 4 (95% CI 3 to 5) events/h, 5 women) were studied. Subjects were imaged using T1-weighted 3-D structural MRI (69 subjects at 1.5 T, 51 subjects at 3 T). Differences in grey matter were investigated in the two groups, controlling for age, sex, site and intracranial volume. Dedicated cerebellar analysis was performed on a subset of 108 scans using a spatially unbiased infratentorial template. RESULTS: Patients with OSA had a reduction in grey matter volume in the right middle temporal gyrus compared with non-apnoeic controls (p<0.05, corrected for topological false discovery rate across the entire brain). A reduction in grey matter was also seen within the cerebellum, maximal in the left lobe VIIIb close to XI, extending across the midline into the right lobe. CONCLUSION: These data show that OSA is associated with focal loss of grey matter that could contribute to cognitive decline. Specifically, lesions in the cerebellum may result in both motor dysfunction and working memory deficits, with downstream negative consequences on tasks such as driving.

Structural abnormalities remote from the seizure focus: a study using T2 relaxometry at 3 T.

OBJECTIVE: To determine the extent and severity of mesial temporal and subcortical signal abnormalities in patients with partial epilepsy. METHODS: T2 relaxation time maps were acquired in 50 consecutive patients and 55 control subjects on a 3 T MRI scanner. Twenty-two patients had hippocampal sclerosis (HS), 16 had malformations of cortical development (MCD), and 12 had no obvious MR abnormalities (normal MR). The following eight regions were measured bilaterally: hippocampus, anterior temporal lobe (ATL) white matter, amygdala, frontal lobe white matter, caudate, putamen, pallidum, and thalamus. RESULTS: In patients with HS, increased T2 relaxation times were found in the ipsilateral hippocampus and ATL but not in subcortical nuclei. In patients with MCD, increased T2 relaxation times were found in the temporal lobe (hippocampus, ATL) and in subcortical areas (caudate, putamen, and pallidum); in patients with normal MR, increased T2 relaxation times were found in the hippocampus and putamen. The degree of abnormality did not correlate with the duration of epilepsy or the estimated seizure load. CONCLUSIONS: Mesial temporal structures show increased T2 relaxation times not only in patients with hippocampal sclerosis but also in patients with a seizure focus remote from the hippocampus. Patients with normal MR and focal malformations of cortical development have increased T2 relaxation times in subcortical structures. Therefore, abnormalities in T2 relaxation time can be found remote from the seizure focus. They cannot be simply attributed to secondary seizure effects.

Acute changes in MRI diffusion, perfusion, T(1), and T(2) in a rat model of oligemia produced by partial occlusion of the middle cerebral artery.

Oligemic regions, in which the cerebral blood flow is reduced without impaired energy metabolism, have the potential to evolve toward infarction and remain a target for therapy. The aim of this study was to investigate this oligemic region using various MRI parameters in a rat model of focal oligemia. This model has been designed specifically for remote-controlled occlusion from outside an MRI scanner. Wistar rats underwent remote partial MCAO using an undersize 0.2 mm nylon monofilament with a bullet-shaped tip. Cerebral blood flow (CBF(ASL)), using an arterial spin labeling technique, the apparent diffusion coefficient of water (ADC), and the relaxation times T(1) and T(2) were acquired using an 8.5 T vertical magnet. Following occlusion there was a decrease in CBF(ASL) to 35 +/- 5% of baseline throughout the middle cerebral artery territory. During the entire period of the study there were no observed changes in the ADC. On occlusion, T(2) rapidly decreased in both cortex and basal ganglia and then normalized to the preocclusion values. T(1) values rapidly increased (within approximately 7 min) on occlusion. In conclusion, this study demonstrates the feasibility of partially occluding the middle cerebral artery to produce a large area of oligemia within the MRI scanner. In this region of oligemic flow we detect a rapid increase in T(1) and decrease in T(2). These changes occur before the onset of vasogenic edema. We attribute the acute change in T(2) to increased amounts of deoxyhemoglobin; the mechanisms underlying the change in T(1) require further investigation.

The measurement of diffusion and perfusion in biological systems using magnetic resonance imaging.

The aim of this review is to describe two recent developments in the use of magnetic resonance imaging (MRI) in the study of biological systems: diffusion and perfusion MRI. Diffusion MRI measures the molecular mobility of water in tissue, while perfusion MRI measures the rate at which blood is delivered to tissue. Therefore, both these techniques measure quantities which have direct physiological relevance. It is shown that diffusion in biological systems is a complex phenomenon, influenced directly by tissue microstructure, and that its measurement can provide a large amount of information about the organization of this structure in normal and diseased tissue. Perfusion reflects the delivery of essential nutrients to tissue, and so is directly related to its status. The concepts behind the techniques are explained, and the theoretical models that are used to convert MRI data to quantitative physical parameters are outlined. Examples of current applications of diffusion and perfusion MRI are given. In particular, the use of the techniques to study the pathophysiology of cerebral ischaemia/stroke is described. It is hoped that the biophysical insights provided by this approach will help to define the mechanisms of cell damage and allow evaluation of therapies aimed at reducing this damage.

Measuring cerebral blood flow using magnetic resonance imaging techniques.

Magnetic resonance imaging techniques measuring CBF have developed rapidly in the last decade, resulting in a wide range of available methods. The most successful approaches are based either on dynamic tracking of a bolus of a paramagnetic contrast agent (dynamic susceptibility contrast) or on arterial spin labeling. This review discusses their principles, possible pitfalls, and potential for absolute quantification and outlines clinical and neuroscientific applications.

Reperfusion in a gerbil model of forebrain ischemia using serial magnetic resonance FAIR perfusion imaging.

BACKGROUND AND PURPOSE: Existing methods for the quantitative measurement of the changing cerebral blood flow (CBF) during reperfusion suffer from poor spatial or temporal resolution. The aim of this study was to implement a recently developed MRI technique for quantitative perfusion imaging in a gerbil model of reperfusion. Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive procedure that uses blood water as an endogenous tracer. METHODS: Bilateral forebrain ischemia of 4 minutes' duration was induced in gerbils (n=8). A modified version of FAIR with improved time efficiency was used to provide CBF maps with a time resolution of 2.8 minutes after recirculation had been initiated. Quantitative diffusion imaging was also performed at intervals during the reperfusion period. RESULTS: On initiating recirculation after the transient period of ischemia, the FAIR measurements demonstrated either a symmetrical, bilateral pattern of flow impairment (n=4) or an immediate side-to-side difference that became apparent with respect to the cerebral hemispheres in the imaged slice (n=4). The flow in each hemisphere displayed a pattern of recovery close to the preocclusion level or, alternatively, returned to a lower level before displaying a delayed hypoperfusion and a subsequent slow recovery. The diffusion measurements during this latter response suggested the development of cell swelling during the reperfusion phase in the striatum. CONCLUSIONS: The CBF during the reperfusion period was monitored with a high time resolution, noninvasive method. This study demonstrates the utility of MRI techniques in following blood flow changes and their pathophysiological consequences.

Implementation of quantitative FAIR perfusion imaging with a short repetition time in time-course studies.

Flow-sensitive alternating inversion recovery (FAIR) is a pulsed arterial spin labeling magnetic resonance imaging method for perfusion quantification. In its standard implementation for quantification with full longitudinal relaxation between acquisitions, its use in time-course investigations of rapidly changing flow values is limited. The time efficiency can be improved by decreasing the repetition time but quantification becomes problematic. This situation is further complicated if a whole-body radiofrequency transmit coil is not used since fresh blood spins will flow in from outside the coil. To alleviate these problems, the use of global pre-saturation is proposed. The resulting expression for the flow signal depends on the relationship between the imaging parameters and the coil inflow time and can be significantly simplified under certain combinations of these parameters. With this implementation of FAIR, quantitative flow maps of gerbil brains were obtained with a 3 minute time resolution in a study of the effects of reperfusion. The pre-occlusion flow measurements were in good agreement with values obtained by the standard FAIR implementation and by other techniques, but the low values following occlusion were underestimated due to the increased transit times.

Early changes in water diffusion, perfusion, T1, and T2 during focal cerebral ischemia in the rat studied at 8.5 T.

The time evolution of water diffusion, perfusion, T1, and T2 is investigated at high magnetic field (8.5 T) following permanent middle cerebral artery occlusion in the rat. Cerebral blood flow maps were obtained using arterial spin tagging. Although the quantitative perfusion measurements in ischemic tissue still pose difficulties, the combined perfusion and diffusion data nevertheless distinguish between a "moderately affected area," with reduced perfusion but normal diffusion; and a "severely affected area," in which both perfusion and diffusion are significantly reduced. Two novel magnetic resonance imaging observations are reported, namely, a decrease in T2 and an increase in T1, both within the first few minutes of ischemia. The rapid initial decrease in T2 is believed to be associated with an increase in deoxyhemoglobin levels, while the initial increase in T1 may be related to several factors, such as flow effects, an alteration in tissue oxygenation, and changes in water environment.

Rapid T2* mapping using interleaved echo planar imaging.

Magnetic resonance imaging methods that are sensitive to T2* are widely used in the study of blood oxygenation changes, most notably in functional studies of the brain. In these studies the signal intensity change in T2*-weighted imaging is related to the coupling of cerebral blood flow and metabolism. Rapid measurement of T2* itself would offer a valuable method to quantify blood oxygenation changes indirectly and monitor their time course. An interleaved echoplanar imaging (EPI) sequence is presented here that allows maps of T2* to be generated in a few seconds. The sequence benefits from reduced geometric distortion and an improved point spread function compared with single-shot EPI. A comparison among a set of T2*-weighted interleaved EPI images, single-shot EPI, and conventional gradient-echo and spin-echo methods is made using a compartmentalized doped water phantom. The interleaved sequence yields accurate T2* values when compared with reference measurements made using the slower gradient-echo technique. Data acquired from the rat brain at 2.35 T prior to and during an anoxic challenge show, with high temporal resolution, the reduction in T2* associated with increased levels of deoxyhemoglobin.

A quantitative method for fast diffusion imaging using magnetization-prepared TurboFLASH.

For the in vivo measurement of the apparent diffusion coefficient (ADC), it is desirable for the total imaging time to be as short as possible. One technique is based on a TurboFLASH acquisition in which the diffusion gradients are inserted into a driven equilibrium Fourier transform (DEFT) combination of hard pulses. However, this sequence has the disadvantage that eddy current-induced inhomogeneities lead to incomplete refocusing of the magnetization during the diffusion preparation and to incorrect ADC values. A modification to the sequence is suggested that eliminates this error by phase-cycling the second 90 degrees pulse of the preparation. This study also investigates the effect of a reduced delay time between acquisitions on the accuracy of the measurement. The quality of the TurboFLASH sequence is demonstrated by experimental validation on an agar phantom and in vivo on the rat brain using a high-field (8.5 T) system. Reduction of the interexperiment delay time is shown to be achievable to a certain degree without compromising the measurement accuracy.