White matter lesions and cognition: it's time for randomized trials to preserve intelligence.
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Biomedical subjects
Publications and source records attributed to J Ross Mitchell.
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Perfusion-weighted imaging (PWI) measures can predict tissue outcome in acute ischemic stroke. Accuracy might be improved if differential tissue susceptibility to ischemia is considered. We present a novel voxel-by-voxel analysis to characterize cerebral blood flow (CBF) separately in gray (GM) and white matter (WM). Ten patients were scanned with inversion-recovery spin-echo EPI (IRSEPI), diffusion-weighted imaging (DWI), PWI<6 h from onset and fluid attenuated inversion-recovery (FLAIR) at 30 days. Image processing included coregistration to PWI, automatic segmentation of IRSEPI into GM, WM and CSF and semiautomatic segmentation of DWI/FLAIR to derive the acute and 30-day lesions. Five tissue compartments were defined: (1) 'Core' (abnormal acutely and at 30 days), (2) 'Growth' (or 'infarcted penumbra', abnormal only at 30 days), (3) 'Reversed' (abnormal acutely but normal at 30 days), (4) 'MTT-Delayed ' (tissue with delayed mean transit time but not part of the acute or 30-day lesion), and (5) 'Normal' brain. Cerebral blood flow in GM and WM of each compartment was obtained from quantitative maps. Gray matter and WM mean CBF in the growth region differed by 5.5 mL/100 g min (P=0.015). Mean CBF also differed significantly within normal and MTT-Delayed compartments. The difference in the reversed region approached statistical significance. In core, GM and WM CBF did not differ. The results suggest separate ischemic thresholds for GM and WM in stroke penumbra.
It is thought that gray and white matter (GM and WM) have different perfusion and diffusion thresholds for cerebral infarction in humans. We sought to determine these thresholds with voxel-by-voxel, tissue-specific analysis of co-registered acute and follow-up magnetic resonance (MR) perfusion- and diffusion-weighted imaging. Quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and apparent diffusion coefficient (ADC) maps were analyzed from nine acute stroke patients (imaging acquired within 6 h of onset). The average values of each measure were calculated for GM and WM in normally perfused tissue, the region of recovered tissue and in the final infarct. Perfusion and diffusion thresholds for infarction were determined on a patient-by-patient basis in GM and WM separately by selecting thresholds with equal sensitivities and specificities. Gray matter has higher thresholds for infarction than WM (P<0.009) for CBF (20.0 mL/100 g min in GM and 12.3 mL/100 g min in WM), CBV (2.4 mL/100 g in GM and 1.7 mL/100 g in WM), and ADC (786 x 10(-6) mm(2)/s in GM and 708 x 10(-6) mm(2)/s in WM). The MTT threshold for infarction in GM is lower (P=0.014) than for WM (6.8 secs in GM and 7.1 secs in WM). A single common threshold applied to both tissues overestimates tissue at risk in WM and underestimates tissue at risk in GM. This study suggests that tissue-specific analysis of perfusion and diffusion imaging is required to accurately predict tissue at risk of infarction in acute ischemic stroke.
The recently developed S-transform (ST) combines features of the Fourier and Wavelet transforms; it reveals frequency variation over both space and time. It is a potentially powerful tool that can be applied to medical image processing including texture analysis and noise filtering. However, calculation of the ST is computationally intensive, making conventional implementations too slow for many medical applications. This problem was addressed by combining parallel and vector computations to provide a 25-fold reduction in computation time. This approach could help accelerate many medical image processing algorithms.
PURPOSE: High-frequency oscillations (HFOs) in the range of > or = 80 Hz have been recorded in neocortical and hippocampal brain structures in vitro and in vivo and have been associated with physiologic and epileptiform neuronal population activity. Frequencies in the fast-ripple range (> 200 Hz) are believed to be exclusive to epileptiform activity and have been recorded in vitro, in vivo, and in epilepsy patients. Although the presence of HFOs is well characterized, their temporal evolution in the context of transition to seizure activity is not well understood. METHODS: With an in vitro low-magnesium model of spontaneous seizures, we obtained extracellular field recordings (hippocampal regions CA1 and CA3) of interictal, preictal, and ictal activity. Recordings were subjected to power-frequency analysis, in time, by using a local multiscale Fourier transform. The power spectrum was computed continuously and was quantified for each epileptiform discharge into four frequency ranges spanning subripple, ripple, and two fast-ripple frequency bands. RESULTS: A statistically significant increasing trend was observed in the subripple (0-100 Hz), ripple (100-200 Hz), and fast-ripple 1 (200-300 Hz) frequency bands during the epoch corresponding to the transition to seizure (preictal to ictal). CONCLUSIONS: Temporal patterns of HFOs during epileptiform activity are indicative of dynamic changes in network behavior, and their characterization may offer insights into pathophysiologic processes underlying seizure initiation.
The relationship between performance on information processing efficiency measures and MRI-derived lesion volume including global and regional T2 and T1 lesion volumes was investigated in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Processing speed, as measured by the Sternberg Memory Scanning Test, was significantly correlated with posterior fossa lesion volume and slowed reaction time in seven out of eight patients (six out of seven with SPMS) with any lesion volume in the posterior fossa suggesting a 'threshold effect'. Processing capacity as measured by the Salthouse Keeping Track Test was not significantly correlated with the MRI measures. Cognitive performance did not correlate with Expanded Disability Status Scale score, depression or fatigue, and patients performed within normal limits on tests of attention/concentration ability. The significant relationship between posterior fossa lesion volume and memory scanning speed in this study suggests that pathological damage in the posterior fossa may contribute to slowed cognitive processing and may be an important direction for future studies of cognitive function in multiple sclerosis. Lack of correlation of cognitive measures with the other MRI measures may be due to low lesion volume relative to other studies, sample composition, and limited pathological specificity of the MRI measures.
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PURPOSE: To compare isotropic (combined diffusion-weighted image [CMB], apparent diffusion coefficient [ADC], TRACE, exponential ADC [eADC], and isotropically-weighted diffusion image [isoDWI]) and anisotropic (relative anisotropy [RA], fractional anisotropy [FA], and volume ratio [VR]) diffusion images collected with fast magnetic resonance (MR) diffusion-weighted (DWI) and diffusion-tensor (DTI) acquisition strategies (each less than one minute) in hyper-acute stroke. MATERIALS AND METHODS: Twenty-one patients suffering from ischemic stroke-imaged within six hours of symptom onset using both DWI and DTI-were analyzed. Regions of interest were placed in the ischemic lesion and in normal contralateral tissue and the percent difference in image intensity was calculated for all nine generated images. RESULTS: The average absolute percent changes for the isotropic strategies were all > 38%, with isoDWI found to have a difference of 50.7% +/- 7.9% (mean +/- standard error, P < 0.001). The ADC maps had the most significant difference (-42.4% +/- 2.0%, P < 0.001, coefficient of variation = 0.22). No anisotropic images had significant differences. CONCLUSION: Anisotropic maps do not consistently show changes in the first six hours of ischemic stroke; therefore, isotropic maps, such as those obtained using DWI, are more appropriate for detecting hyper-acute stroke. Anisotropic images, however, may be useful to differentiate hyper-acute stroke from acute and sub-acute stroke.
PURPOSE: To image and dissect the lumbar spinal cord of guinea pigs with chronic-progressive experimental allergic encephalomyelitis (CP-EAE) and directly correlate the pathology to the magnetic resonance (MR) image data obtained at 4 T and determine if these MR contrasts can accurately differentiate a specific type of pathology from control tissue. MATERIALS AND METHODS: The amount of inflammation, demyelination, and axonal pathology were quantified in the whole cord cross sections. The signal intensities (SIs) for 228 individual regions of interest (ROIs) (normal-appearing white matter (NAWM) and tissue containing inflammation with or without demyelination) were measured directly from the corresponding area on the MR images. RESULTS: Conventional MR contrast SIs and magnetization transfer ratio (MTR) were related to the degree of demyelination and presence of inflammation. MTR and proton density-weighted (PDw) SIs were both moderately related to axonal density. The SIs for NAWM and in lesions containing both cellular infiltrates and demyelination in all conventional MR contrast images were also increased, whereas the MTR was decreased when compared to control tissue. CONCLUSION: The SIs from the conventional MR contrasts and MTR at 4 T were sensitive to the presence of disease within CP-EAE spinal cord, but were not specific to the underlying pathology.
A novel and automated technique is described for removing fMRI image artifacts resulting from motion outside of the imaging field of view. The technique is based on the Stockwell transform (ST), a mathematical operation that provides the frequency content at each time point within a time-varying signal. Using this technique, 1D Fourier transforms (FTs) are performed on raw image data to obtain phase profiles. The time series of phase magnitude for each and every point in the phase profile is then subjected to the ST to obtain a time-frequency spectrum. The temporal location of an artifact is identified based on the magnitude of a frequency component relative to the median magnitude of that frequency's occurrence over all time points. After each artifact frequency is removed by replacing its magnitude with the median magnitude, an inverse ST is applied to regain the MR signal. Brain activity detection within fMRI datasets is improved by significantly reducing image artifacts that overlap anatomical regions of interest. The major advantage of ST-filtering is that artifact frequencies may be removed within a narrow time-window, while preserving the frequency information at all other time points.
Changes in mean magnetic resonance imaging (MRI)-derived measurements between patient groups are often used to determine outcomes in therapeutic trials and other longitudinal studies of multiple sclerosis (MS). However, in day-to-day clinical practice the changes within individual patients may also be of interest In this paper, we estimated the measurement error of an automated brain tissue quantification algorithm and determined the thresholds for statistically significant change of MRI-derived T2 lesion volume and brain atrophy in individual patients. Twenty patients with MS were scanned twice within 30 min. Brain tissue volumes were measured using the computer algorithm. Brain atrophy was estimated by calculation of brain parenchymal fraction. The threshold of change between repeated scans that represented statistically significant change beyond measurement error with 95% certainty was 0.65 mL for T2 lesion burden and 0.0056 for brain parenchymal fraction. Changes in lesion burden and brain atrophy below these thresholds can be safely (with 95% certainty) explained by measurement variability alone. These values provide clinical neurologists with a useful reference to interpret MRI-derived measures in individual patients.
BACKGROUND AND PURPOSE: Emergent neurovascular imaging holds promise in identifying new and optimum target populations for thrombolysis in stroke. Recent research has focused on patients with diffusion-weighted MRI (DWI)-perfusion-weighted MRI (PWI) mismatch as a marker of tissue at risk of infarction and a means to select the most suitable candidates for thrombolysis. The present study sought to estimate the reliability of assessing the percentage of DWI-PWI mismatch. METHODS: Thirteen patients with acute strokes had DWI and PWI within 7 hours of symptom onset. Six raters independently created relative mean transit time (rMTT) maps and then compared them with DWI images to assess the percentage of mismatch (PWI>DWI) in 10% increments. The MR scans were reassessed by 4 raters, tracing around the lesions to calculate the volume percentage of mismatch. RESULTS: Visual assessment had an interrater reliability of 0.68 (95% CI, 0.52 to 1.0; SEM=21.6%) and an intrarater reliability of 0.80 (95% CI, 0.47 to 1.0; SEM=16.9%). Hand-drawn assessment had an interrater reliability of 0.66 (95% CI, 0.45 to 1.0; SEM=26.2%) and an intrarater reliability of 0.94 (95% CI, 0.81 to 1.0; SEM=10.9%). CONCLUSIONS: Results from the present study suggest that quantifying mismatch by the human eye is reproducible but not reliable among observers. This raises doubts about using mismatch for clinical decision making and clinical trial enrollment.
MRI is emerging as a promising modality for monitoring carotid atherosclerosis. Multiple MR contrast weightings are required for identification of plaque constituents. In this study, eight MR contrast weightings with proven potential for plaque characterization were used to image carotid endarterectomy specimens. A classification technique was developed to create a tissue-specific map by incorporating information from all MR contrast weightings. The classifier was validated by comparison with micro-CT (calcification only) and with matched histological slices registered to MR images using a nonlinear warping algorithm (other components). A pathologist who was blinded to the classifier results manually segmented digitized histological images. The sensitivity of the classifier, as determined by pixel-by-pixel comparison with the pathologist's segmentation and micro-CT, was 60.4% for fibrous tissue, 83.9% for necrosis, 97.6% for calcification, and 65.2% for loose connective tissue. The corresponding values for specificity were 87.9%, 75.0%, 98.3%, and 94.9%, respectively. In conclusion, multicontrast MRI was successfully used in conjunction with a supervised classification algorithm to identify plaque components in endarterectomy specimens. Furthermore, this methodology will provide a framework for comparing different classification algorithms, and determining which combination of MR contrasts will be most valuable for in vivo plaque imaging.
BACKGROUND: Stroke occurrence appears to be a random event, yet annual and supra-annual periodicity is observed. Recent attention in atherosclerotic disease etiology has focused on infectious and inflammatory mechanisms. Influenza is one such infection that may influence stroke occurrence. METHODS: We explored population-based time series data on stroke occurrence and influenza activity. Using Fourier transformation to isolate low-frequency signals in the data, the inverse transformed time series were regressed using Prais-Winsten regression to correct for serially auto-correlated residuals, to assess the relationship between influenza rates and stroke occurrence rates. RESULTS: Changes in the low-frequency components of influenza activity predicted the changes in low-frequency components of the stroke occurrence data with a delay of about 20 weeks. The delay between changes in influenza activity and subsequent stroke activity was different for different stroke types. Overall, the effect size was small with a tripling of the influenza rate associated with about a 6% change in stroke occurrence rate. CONCLUSIONS: A small proportion of the patterns of stroke occurrence may be explained by variation in influenza activity. Further evaluation of influenza as a triggering agent in stroke is needed.