Tractography of the parahippocampal gyrus and material specific memory impairment in unilateral temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is associated with disrupted memory function. The structural changes underlying this memory impairment have not been demonstrated previously with tractography. METHODS: We performed a tractography analysis of diffusion magnetic resonance imaging scans in 18 patients with unilateral TLE undergoing presurgical evaluation, and in 10 healthy controls. A seed region in the anterior parahippocampal gyrus was selected from which to trace the white matter connections of the medial temporal lobe. A correlation analysis was carried out between volume and mean fractional anisotropy (FA) of the connections, and pre-operative material specific memory performance. RESULTS: There was no significant difference between the left and right sided connections in controls. In the left TLE patients, the connected regions ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region, and left-sided connections in control subjects. Significant correlations were found in left TLE patients between left and right FA, and verbal and non-verbal memory respectively. CONCLUSION: Tractography demonstrated the alteration of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline in chronic temporal lobe epilepsy.

Imaging language pathways predicts postoperative naming deficits.

Naming difficulties are a well recognised, but difficult to predict, complication of anterior temporal lobe resection (ATLR) for refractory epilepsy. We used MR tractography preoperatively to demonstrate the structural connectivity of language areas in patients undergoing dominant hemisphere ATLR. Greater lateralisation of tracts to the dominant hemisphere was associated with greater decline in naming function. We suggest that this method has the potential to predict language deficits in patients undergoing ATLR.

Preoperative fMRI predicts memory decline following anterior temporal lobe resection.

BACKGROUND: Anterior temporal lobe resection (ATLR) benefits many patients with refractory temporal lobe epilepsy (TLE) but may be complicated by material specific memory impairments, typically of verbal memory following left ATLR, and non-verbal memory following right ATLR. Preoperative memory functional MRI (fMRI) may help in the prediction of these deficits. OBJECTIVE: To assess the value of preoperative fMRI in the prediction of material specific memory deficits following both left- and right-sided ATLR. METHODS: We report 15 patients with unilateral TLE undergoing ATLR; eight underwent dominant hemisphere ATLR and seven non-dominant ATLR. Patients performed an fMRI memory paradigm which examined the encoding of words, pictures and faces. RESULTS: Individual patients with relatively greater ipsilateral compared with contralateral medial temporal lobe activation had greater memory decline following ATLR. This was the case for both verbal memory decline following dominant ATLR and for non-verbal memory decline following non-dominant ATLR. For verbal memory decline, activation within the dominant hippocampus was predictive of postoperative memory change whereas activation in the non-dominant hippocampus was not. CONCLUSION: These findings suggest that preoperative memory fMRI may be a useful non-invasive predictor of postoperative memory change following ATLR and provide support for the functional adequacy theory of hippocampal function. They also suggest that fMRI may provide additional information, over that provided by neuropsychology, for use in the prediction of postoperative memory decline.

Magnetization transfer ratio in Alzheimer disease: comparison with volumetric measurements.

BACKGROUND AND PURPOSE: Alzheimer disease (AD) is accompanied by macroscopic atrophy on volumetric MR imaging. A few studies have also demonstrated reduction in magnetization transfer ratio (MTR), suggesting microstructural changes in remaining brain tissue. This study assessed the value of measuring MTR in addition to volumetric MR in differentiating patients with AD from control subjects. MATERIALS AND METHODS: Volumetric T1-weighted images and 3D MTR maps were obtained from 18 patients with AD and 18 age-matched control subjects. Whole-brain (WB) and total hippocampal (Hc) volumes were measured using semiautomated techniques and adjusted for total intracranial volume. Mean MTR was obtained for WB and in the Hc region. Histogram analysis was performed for WB MTR. Among patients, associations between volumetric and MTR parameters and the Mini-Mental State Examination (MMSE) were explored. RESULTS: Patients with AD had significantly reduced WB volume (P<.0001) and mean WB MTR (P=.002) and Hc volume (P<.0001) and Hc mean MTR (P<.0001) compared with control subjects. Histogram analysis of WB MTR revealed significant reduction in the 25th percentile point in patients with AD (P=.03). Both WB volume and mean MTR were independently associated with case-control status after adjusting for the other using linear regression models. However, measuring Hc mean MTR added no statistically significant discriminatory value over and above Hc volume measurement alone. Of all MR imaging parameters, only WB volume was significantly correlated with MMSE (r=0.47, P=.048). CONCLUSIONS: This study demonstrates the independent reduction of WB volume and mean MTR in AD. This suggests that the 2 parameters reflect complementary aspects of the AD pathologic lesion at macrostructural and microstructural levels.

MR tractography predicts visual field defects following temporal lobe resection.

A superior homonymous quadrantanopia is a well recognized complication of anterior temporal lobe resection and occurs because of disruption of the Meyer loop, the anterior part of the optic radiation. The authors used diffusion tensor imaging tractography to visualize the optic radiation before and after surgery, demonstrating the disruption of Meyer loop in a patient who developed a quadrantanopia. Preoperative imaging of the optic radiation will be useful in predicting visual field defects following temporal lobe resection.

Material-specific lateralization of memory encoding in the medial temporal lobe: blocked versus event-related design.

Lesion-deficit studies have provided evidence for a functional dissociation between the left medial temporal lobe (MTL) mediating verbal memory encoding and right MTL mediating non-verbal memory encoding. While a small number of functional MRI studies have demonstrated similar findings, none has looked specifically for material-specific lateralization using subsequent memory effects. In addition, in many fMRI studies, encoding activity has been located in posterior MTL structures, at odds with lesion-deficit and positron emission tomography (PET) evidence. In this study, we used an event-related fMRI memory encoding paradigm to demonstrate a material-specific lateralization of encoding in the medial temporal lobes of ten healthy control subjects. Activation was left-lateralized for word encoding, bilateral for picture encoding, and right-lateralized for face encoding. Secondly, we demonstrated the locations of activations revealed using an event-related analysis to be more anterior than those revealed using a blocked analysis of the same data. This suggests that anterior MTL structures underlie memory encoding as judged by subsequent memory effects, and that more posterior activity detected in other fMRI studies is related to deficiencies of blocked designs in the analysis of memory encoding.

Whole-brain T2 mapping demonstrates occult abnormalities in focal epilepsy.

OBJECTIVES: To examine the cerebral structure of 14 patients with partial seizures and acquired lesions, 20 patients with malformations of cortical development (MCDs), and 45 patients with partial seizures and normal conventional MRI using whole-brain T2 mapping and statistical parametric mapping (SPM). METHODS: T2 maps were calculated, and individual patients were compared with a group of 30 control subjects using SPM. RESULTS: T2 mapping and objective voxel-by-voxel statistical comparison identified regions of increased T2 signal in all 14 patients with acquired nonprogressive cerebral lesions and partial seizures. In all of these, the areas of increased T2 signal concurred with abnormalities identified on visual inspection of conventional MRI. In 18 of 20 patients with MCDs, SPM detected regions of increased T2 signal, all of which corresponded to abnormalities identified on visual inspection of conventional MRI. In addition, in both groups, there were areas that were normal on conventional imaging, which demonstrated abnormal T2 signal. Voxel-by-voxel statistical analysis identified increased T2 signal in 23 of the 45 patients with cryptogenic focal epilepsy. In 20 of these, the areas of increased T2 signal concurred with epileptiform EEG abnormality and clinical seizure semiology. Group analysis of MRI-negative patients with electroclinical seizure onset localizing to the left and right temporal and left and right frontal regions revealed increased T2 signal within the white matter of each respective lobe. CONCLUSIONS: T2 mapping analyzed using statistical parametric mapping was sensitive in patients with malformations of cortical development and acquired cerebral damage. Increased T2 signal in individual and grouped MRI-negative patients suggests that minor structural abnormalities exist in occult epileptogenic cerebral lesions.

Optimized interleaved whole-brain 3D double inversion recovery (DIR) sequence for imaging the neocortex.

For a substantial number of individuals with neurological disorders, a conventional MRI scan does not reveal any obvious etiology; however, it is believed that abnormalities in the neocortical gray matter (GM) underlie many of these disorders. Attempts to image the neocortex are hindered by its thin, convoluted structure, and the partial volume (PV) effect. Therefore, we developed a 3D version of the double inversion recovery (DIR) sequence that incorporates an optimized interleaved (OIL) strategy to improve efficiency and allow high-quality, high-resolution imaging of GM.

Noninvasive in vivo demonstration of the connections of the human parahippocampal gyrus.

MR tractography techniques provide a method for noninvasively studying white matter pathways in vivo. In this study we have used diffusion tensor imaging (DTI) and the fast marching tractography (FMT) algorithm to plot the structural connectivity of the human parahippocampal gyrus (PHG) in 10 healthy subjects, using seed points selected in the anterior parahippocampal gyrus. Our results demonstrate connectivity between the parahippocampal gyrus and the anterior temporal lobe, orbitofrontal areas, posterior temporal lobe and extrastriate occipital lobe via the lingual and fusiform gyri. We also demonstrate for the first time noninvasively direct connectivity between the parahippocampal gyrus and the hippocampus itself. These results agree with previous histological tract-tracing studies in animals. The connections demonstrated between neocortical areas and the hippocampus via the parahippocampal gyrus may provide the structural basis for theoretical models of memory and higher visual processing.

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging.

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.

Magnetization transfer imaging in focal epilepsy.

OBJECTIVES: To test the hypothesis that magnetization transfer imaging (MTI), analyzed on a voxel-by-voxel basis, would identify areas of abnormal magnetization transfer ratio (MTR) in patients with focal epilepsy. METHODS: The authors used MTI maps and statistical parametric mapping (SPM) to objectively compare the cerebral structures of 15 patients with malformations of cortical development (MCD), 10 with partial seizures and acquired lesions, and 42 with partial seizures and normal conventional MRI with those of 30 control subjects. RESULTS: Significant reductions of MTR were identified in all 10 patients with acquired nonprogressive cerebral lesions and partial seizures. In all, the areas of decreased MTR concurred with abnormalities identified on visual inspection of conventional MRI. In 13 of the 15 patients with MCD, SPM detected regions of significantly reduced MTR, all of which corresponded to abnormalities identified on visual inspection of conventional MRI. In addition, in both groups, there were areas that were normal on conventional imaging that demonstrated abnormal MTR. There was a significant reduction of MTR in 15 of the 42 patients with cryptogenic focal epilepsy. In all of these, the areas of reduced MTR concurred with epileptiform EEG abnormality and clinical seizure semiology. CONCLUSIONS: Magnetization transfer imaging analyzed using statistical parametric mapping was sensitive in identifying malformations of cortical development and acquired cerebral lesions. Abnormalities of magnetization transfer ratio in individual MRI-negative patients suggest that minor structural disorganization exists in occult epileptogenic cerebral lesions.

From diffusion tractography to quantitative white matter tract measures: a reproducibility study.

The aim of this study is to propose methods for assessing the reproducibility of diffusion tractography algorithms in future clinical studies and to show their application to the tractography algorithm developed in our unit, fast marching tractography (FMT). FMT estimates anatomical connectivity between brain regions using the information provided by diffusion tensor imaging. Three major white-matter pathways were investigated in 11 normal subjects--anterior callosal fibers, optic radiations, and pyramidal tracts. FMT was used to generate maps of connectivity metric, and regions of voxels with highest connectivity metric to an anatomically defined starting point were identified for each tract under investigation. The reproducibilities of tract-"normalized" volume (NV) and fractional anisotropy (FA) measurements were assessed over such regions. The values of tract volumes are consistent with the postmortem data. Coefficients of variation (CVs) for FA and NV ranged from 1.7 to 7.1% and from 2.2 to 18.6%, respectively. CVs were lowest in the anterior callosal fibers (range: 1.7- 7.8%), followed by the optic radiations (range: 1.2-18.6%) and pyramidal tracts (range: 2.6-15.5%), suggesting that fiber organization plays a role in determining the level of FMT reproducibility. In conclusion, these findings underline the importance of assessing the reliability of diffusion tractography before investigating white matter pathology.

In vivo intravoxel incoherent motion measurements in the human placenta using echo-planar imaging at 0.5 T.

This paper presents the first in vivo measurements of intravoxel incoherent motion in the human placenta, obtained using the pulsed gradient spin echo (PGSE) sequence. The aims of this study were two-fold. The first was to provide an initial estimate of the values of the IVIM parameters in this organ, which are currently unknown. The second aim was then to use these results to optimize the sequence timings for future studies. The moving blood fraction (f), diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured. The average value of f was 26 +/- 6 % (mean +/- SD), D was 1.7 +/- 0.5 x 10(-3) mm2/sec, and D* was 57 +/- 41 x 10(-3) mm2/sec. For the optimized values of b, the expected percentage uncertainty in the fitted values of f, D, and D* for the placenta were sigmaf/f = 14.9%, sigmaD/D = 14.3%, sigmaD*/D* = 44.9%, for an image signal-to-noise of 20:1, and a total imaging time of 800 sec.

Fat delays emptying but increases forward and backward antral flow as assessed by flow-sensitive magnetic resonance imaging.

Flow has been assessed in the gastric antrum using a velocity-sensitive version of the high-speed magnetic resonance imaging technique, echo planar imaging (EPI). Eight healthy volunteers attended fasted on three separate days and consumed 800 mL of either a 5% glucose (0.2 kcal mL-1), 10% glucose (0.4 kcal mL-1) or an isotonic mixed nutrient meal, Fresubin (1 kcal mL-1, 27.2 g fat). Gastric volumes were obtained at 10-min intervals for 1 h. Flow measurements were performed on a single slice through the antropyloric region 5 and 35 min after meal ingestion. Gastric volumes at 45 min were inversely proportional to the calorie density of the meal with (mean +/- SEM) 89 +/- 10%* of the Fresubin, 64 +/- 5%* of the 10% glucose and 41 +/- 5% of the 5% glucose remaining (*P < 0.005 vs 5% glucose). Substantial forward and backward antral flow was observed after all three meals in the initial 5-min imaging period. AT 35 min flow activity was significantly greater after both the high-calorie meals relative to the 5% meal (total number of flow events: Fresubin = 6.6 +/- 1.7,[symbol: see text] 10% glucose = 9.9 +/- 2.2, [symbol: see text] 5% glucose = 2.5 +/- 0.9,[symbol: see text] P < 0.03,[symbol: see text] P < 0.007 vs 5% glucose, n = 8). Peak forward velocities for the initial phase of emptying tended to be greater for the rapidly emptying 5% meal (5.9 +/- 0.8 cm-1) compared with the Fresubin (3.3 +/- 0.6 cm-1, P < 0.069, n = 8) and the 10% glucose (2.9 +/- 1.0 cm-1, P < 0.068, n = 8) meals. In spite of delayed gastric emptying, high-calorie meals were associated with substantial to and fro movements which may be important for meal tritruration and fat emulsification.

In vivo relaxation time measurements in the human placenta using echo planar imaging at 0.5 T.

This paper presents the first in vivo measurements of the nuclear magnetic resonance relaxation times T1 and T2 at 0.5 T in the human placenta from 20 weeks gestational age until term, in both normal and compromised pregnancies. T1 measurements were performed by using both an inversion recovery sequence and the Look-Locher echo planar imaging (EPI) sequence on a total of 41 women with normal pregnancies and 11 women with compromised pregnancies. T2 measurements were performed by using a spin-echo EPI sequence on 36 women with normal pregnancies and 14 women with compromised pregnancies. In normal pregnancies, both the T1 values measured with the inversion recovery sequence and the T2 values were found to decrease with gestational age, the linear regression results gave T1 = -9.1t + 1538 r2 = 0.23 p = 0.03. T2 = -4.0t + 338 r2=0.47 p =410(-6) where t is the gestational age in weeks, and T1 and T2 are the relaxation times in milliseconds. T1 values measured very rapidly with the Look-Locher EPI sequence, but, therefore, with a much lower signal-to-noise ratio, showed no significant trends. The T1 values measured in the abnormal group were significantly lower than those measured in the normal group. Four out of eight patients with compromised pregnancies had placental T1 values lying outside the 90% confidence limits for the normal population based about the regression line, significantly more than expected by chance (p = 0.005). Ten out of fourteen of the T2 measurements in the abnormal group were below the regression line established for the normal group, with 4 lying below the 90% confidence interval, although these trends were only just significant (p = 0.06 and p = 0.03).

Use of echo planar imaging to demonstrate the effect of posture on the intragastric distribution and emptying of an oil/water meal.

Intragastric distribution of solids and liquids is far from uniform but until recently technical limitations have prevented detailed study. Echo planar imaging (EPI), which can provide high-quality images of intragastric contents, has been used in this study to assess the intragastric distribution of oil and water and gastric emptying in subjects lying on either their left or right side. Eight healthy volunteers underwent four gastric emptying studies after consuming either an aqueous meal (400 mL beef consomme soup + 100 mL water) or a fat/aqueous meal (400 mL soup + 100 mL olive oil) lying on either their left or right side. Using a water suppressed imaging mode the lipid phase was clearly seen layering above the aqueous phase with little evidence of mixing. Gastric emptying of the aqueous meal (A) was not significantly different when lying on the left compared to the right side. However, gastric emptying of the aqueous phase of the fat/aqueous meal (B) was considerably slower when lying on the left compared to the right side, gastric volumes actually increasing over the 90 min of the study P < or = 0.05. When lying on the right side the aqueous phase of meal B emptied significantly slower than meal A. Oil was clearly observed to layer above the water and fill the duodenal cap when subjects lay on their left and the fundus when they lay on their right side. EPI clearly demonstrates the intragastric layering of oil which causes posture to strongly influence gastric emptying. EPI is a tool with great potential to describe the intragastric events following ingestion of complex multiphase meals.