Motometrics: A Toolbox for Annotation and Efficient Analysis of Motor Evoked Potentials.

Stimulating the nervous system and measuring muscle response offers a unique opportunity to interrogate motor system function. Often, this is performed by stimulating motor cortex and recording muscle activity with electromyography; the evoked response is called the motor evoked potential (MEP). To understand system dynamics, MEPs are typically recorded through a range of motor cortex stimulation intensities. The MEPs increase with increasing stimulation intensities, and these typically produce a sigmoidal response curve. Analysis of MEPs is often complex and analysis of response curves is time-consuming. We created an MEP analysis software, called Motometrics, to facilitate analysis of MEPs and response curves. The goal is to combine robust signal processing algorithms with a simple user interface. Motometrics first enables the user to annotate data files acquired from the recording system so that the responses can be extracted and labeled with the correct subject and experimental condition. The software enables quick visual representations of entire datasets, to ensure uniform quality of the signal. It then enables the user to choose a variety of response curve analyses and to perform near real time quantification of the MEPs for quick feedback during experimental procedures. This is a modular open source tool that is compatible with several popular electrophysiological systems. Initial use indicates that Motometrics enables rapid, robust, and intuitive analysis of MEP response curves by neuroscientists without programming or signal processing expertise.

Chronic softening spinal cord stimulation arrays.

OBJECTIVE: We sought to develop a cervical spinal cord stimulator for the rat that is durable, stable, and does not perturb the underlying spinal cord. APPROACH: We created a softening spinal cord stimulation (SCS) array made from shape memory polymer (SMP)-based flexible electronics. We developed a new photolithographic process to pattern high surface area titanium nitride (TiN) electrodes onto gold (Au) interconnects. The thiol-ene acrylate polymers are stiff at room temperature and soften following implantation into the body. Durability was measured by the duration the devices produced effective stimulation and by accelerated aging in vitro. Stability was measured by the threshold to provoke an electromyogram (EMG) muscle response and by measuring impedance using electrochemical impedance spectroscopy (EIS). In addition, spinal cord modulation of motor cortex potentials was measured. The spinal column and implanted arrays were imaged with MRI ex vivo, and histology for astrogliosis and immune reaction was performed. MAIN RESULTS: For durability, the design of the arrays was modified over three generations to create an array that demonstrated activity up to 29 weeks. SCS arrays showed no significant degradation over a simulated 29 week period of accelerated aging. For stability, the threshold for provoking an EMG rose in the first few weeks and then remained stable out to 16 weeks; the impedance showed a similar rise early with stability thereafter. Spinal cord stimulation strongly enhanced motor cortex potentials throughout. Upon explantation, device performance returned to pre-implant levels, indicating that biotic rather than abiotic processes were the cause of changing metrics. MRI and histology showed that softening SCS produced less tissue deformation than Parylene-C arrays. There was no significant astrogliosis or immune reaction to either type of array. SIGNIFICANCE: Softening SCS arrays meet the needs for research-grade devices in rats and could be developed into human devices in the future.

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

KEY POINTS: Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. ABSTRACT: Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system.

Clinically Relevant Levels of 4-Aminopyridine Strengthen Physiological Responses in Intact Motor Circuits in Rats, Especially After Pyramidal Tract Injury.

BACKGROUND: 4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. OBJECTIVE: To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. METHODS: In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. RESULTS: We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. CONCLUSION: Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.

Decreased subcortical cholinergic arousal in focal seizures.

Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function, including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a critical mechanism for loss of consciousness in focal temporal lobe seizures.

Rhythmic 3-4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures.

Absence seizures are transient episodes of impaired consciousness accompanied by 3-4 Hz spike-wave discharge on electroencephalography (EEG). Human functional magnetic resonance imaging (fMRI) studies have demonstrated widespread cortical decreases in the blood oxygen-level dependent (BOLD) signal that may play an important role in the pathophysiology of these seizures. Animal models could provide an opportunity to investigate the fundamental mechanisms of these changes, however they have so far failed to consistently replicate the cortical fMRI decreases observed in human patients. This may be due to important differences between human seizures and animal models, including a lack of cortical development in rodents or differences in the frequencies of rodent (7-8 Hz) and human (3-4 Hz) spike-wave discharges. To examine the possible contributions of these differences, we developed a ferret model that exhibits 3-4 Hz spike-wave seizures in the presence of a sulcated cortex. Measurements of BOLD fMRI and simultaneous EEG demonstrated cortical fMRI increases during and following spike-wave seizures in ferrets. However unlike human patients, significant fMRI decreases were not observed. The lack of fMRI decreases was consistent across seizures of different durations, discharge frequencies, and anesthetic regimes, and using fMRI analysis models similar to human patients. In contrast, generalized tonic-clonic seizures under the same conditions elicited sustained postictal fMRI decreases, verifying that the lack of fMRI decreases with spike-wave was not due to technical factors. These findings demonstrate that 3-4 Hz spike-wave discharge in a sulcated animal model does not necessarily produce fMRI decreases, leaving the mechanism for this phenomenon open for further investigation.

Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model.

The beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in the form of electrical evoked potentials, but also to cortico-thalamo-cortical network activity (spike-wave discharges, SWD and afterdischarges), white matter changes representing extra cortico-thalamic functions and depressive-like behavior were investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal months 2-3 or 4-5), or ethosuximide for 4 months (2-5) in their drinking water, while control rats drank plain water. EEG measurements were made during treatment, and 6 days and 2 months post treatment. Behavioral test were also done 6 days post treatment. DTI was performed ex vivo post treatment. SWD were suppressed during treatment, and 6 days and 2 months post treatment in the 4 month treated group, as well as the duration of AD elicited by cortical electrical stimulation 6 days post treatment. Increased fractional anisotropy in corpus callosum and internal capsula on DTI was found, an increased P8 evoked potential amplitude and a decreased immobility in the forced swim test. Shorter treatments with ETX had no large effects on any parameter. Chronic ETX has widespread effects not only within but also outside the circuitry in which SWD are initiated and generated, including preventing epileptogenesis and reducing depressive-like symptoms. The treatment of patients before symptom onset might prevent many of the adverse consequences of chronic epilepsy.

Increased resting functional connectivity in spike-wave epilepsy in WAG/Rij rats.

PURPOSE: Functional magnetic resonance imaging (fMRI)-based resting functional connectivity is well suited for measuring slow correlated activity throughout brain networks. Epilepsy involves chronic changes in normal brain networks, and recent work demonstrated enhanced resting fMRI connectivity between the hemispheres in childhood absence epilepsy. An animal model of this phenomenon would be valuable for investigating fundamental mechanisms and testing therapeutic interventions. METHODS: We used fMRI-based resting functional connectivity for studying brain networks involved in absence epilepsy. Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) exhibit spontaneous episodes of staring and unresponsiveness accompanied by spike-wave discharges (SWDs) resembling human absence seizures in behavior and electroencephalography (EEG). Simultaneous EEG-fMRI data in epileptic WAG/Rij rats in comparison to nonepileptic Wistar controls were acquired at 9.4 T. Regions showing cortical fMRI increases during SWDs were used to define reference regions for connectivity analysis to investigate whether chronic seizure activity is associated with changes in network resting functional connectivity. KEY FINDINGS: We observed high degrees of cortical-cortical correlations in all WAG/Rij rats at rest (when no SWDs were present), but not in nonepileptic controls. Strongest connectivity was seen between regions most intensely involved in seizures, mainly in the bilateral somatosensory and adjacent cortices. Group statistics revealed that resting interhemispheric cortical-cortical correlations were significantly higher in WAG/Rij rats compared to nonepileptic controls. SIGNIFICANCE: These findings suggest that activity-dependent plasticity may lead to long-term changes in epileptic networks even at rest. The results show a marked difference between the epileptic and nonepileptic animals in cortical-cortical connectivity, indicating that this may be a useful interictal biomarker associated with the epileptic state.

Focal BOLD fMRI changes in bicuculline-induced tonic-clonic seizures in the rat.

Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG), these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABA(A) receptor antagonist, was injected systemically and seizure activity was observed on EEG as high-amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high-resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which "generalized" tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans.

Cortical deactivation induced by subcortical network dysfunction in limbic seizures.

Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model that, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional magnetic resonance imaging (fMRI) that electrically stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, whereas frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged on by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures.

Development of spike-wave seizures in C3H/HeJ mice.

C3H/HeJ mice have been reported to have relatively early onset of spike-wave discharges (SWD), and a defective AMPA receptor subunit Gria4 as the genetic cause. We investigated the time course of SWD development through serial EEG recordings in C3H/HeJ mice to better characterize this model. We found that at immature postnatal ages of 5-15 days, rare SWD-like events were observed at an average rate of 3 per hour, and with relatively broad spikes, irregular rhythm, slow frequency (5-6 Hz), and short duration (mean 1.75 s). This was followed by a transitional period of increasing SWD incidence, which then stabilized in mature animals at age 26-62 days, with SWD at an average rate of 45 per hour, narrower spike morphology, regular rhythm, higher frequency (7-8 Hz), and longer duration (mean 3.40s). This sequence of maturational changes in SWD development suggests that effects of early intervention could be tested in C3H/HeJ mice over the course of a few weeks, rather than a few months as in rats, greatly facilitating future research on anti-epileptogenesis.

Remote effects of focal hippocampal seizures on the rat neocortex.

Seizures have both local and remote effects on nervous system function. Whereas propagated seizures are known to disrupt cerebral activity, little work has been done on remote network effects of seizures that do not propagate. Human focal temporal lobe seizures demonstrate remote changes including slow waves on electroencephalography (EEG) and decreased cerebral blood flow (CBF) in the neocortex. Ictal neocortical slow waves have been interpreted as seizure propagation; however, we hypothesize that they reflect a depressed cortical state resembling sleep or coma. To investigate this hypothesis, we performed multimodal studies of partial and secondarily generalized limbic seizures in rats. Video/EEG monitoring of spontaneous seizures revealed slow waves in the frontal cortex during behaviorally mild partial seizures, contrasted with fast polyspike activity during convulsive generalized seizures. Seizures induced by hippocampal stimulation produced a similar pattern, and were used to perform functional magnetic resonance imaging weighted for blood oxygenation and blood volume, demonstrating increased signals in hippocampus, thalamus and septum, but decreases in orbitofrontal, cingulate, and retrosplenial cortex during partial seizures, and increases in all of these regions during propagated seizures. Combining these results with neuronal recordings and CBF measurements, we related neocortical slow waves to reduced neuronal activity and cerebral metabolism during partial seizures, but found increased neuronal activity and metabolism during propagated seizures. These findings suggest that ictal neocortical slow waves represent an altered cortical state of depressed function, not propagated seizure activity. This remote effect of partial seizures may cause impaired cerebral functions, including loss of consciousness.

Unusual clinical and MRI features of a cerebellopontine angle medulloepithelioma. Case report and review of literature.

We describe for the first time an unusual location and clinical presentation of medulloepithelioma, a rare embryonal tumor. A 5-year-old child presented with sudden onset of bilateral hearing loss. On imaging, the lesion appeared to be extra axial and was located in the right cerebello-pontine (CP) angle, extending into middle fossa along the trigeminal ganglion and in front of the brain stem into the opposite CP angle. It did not show any enhancement following contrast administration and had restricted diffusion on diffusion-weighted imaging, simulating an epidermoid. However, in vivo localized proton MR spectroscopy revealed a creatine peak dominated by a large choline resonance, peak of glycine with lactate/lipid and invisible N-acetylaspartate suggestive of a neoplastic lesion and not an epidermoid. Only subtotal resection could be performed and the patient had a stormy post-operative course due to extensive dissemination of the disease.

Comparison of the magnetization transfer ratio and fluid-attenuated inversion recovery imaging signal intensity in differentiation of various cystic intracranial mass lesions and its correlation with biological parameters.

PURPOSE: To compare the signal intensity on the fluid attenuated inversion recovery (FLAIR) sequence and magnetization transfer ratios (MTRs) for the differentiation of abscesses from non-abscess cystic brain lesions, and to correlate these MR parameters with the viscosity, viable cell density and total protein concentration of the cystic fluid. MATERIALS AND METHODS: Signal intensity on FLAIR and MTRs from the cystic cavity of lesions were calculated from 33 patients (brain abscess (N = 12) and non-abscess (N = 21)). The fluid from the lesion was aspirated at the time of surgery, and the viscosity, viable cell density, and total protein concentration were measured. RESULTS: Signal intensity on FLAIR correlated significantly with the total protein concentration in abscess (r = 0.60, P < 0.05) and non-abscess lesions (r = 0.41, P < 0.05). However, there was no significant difference (P > 0.05) in the FLAIR signal intensity of the abscess (318.8 +/- 75) and non-abscess group (258 +/- 47). The MTR of the brain abscesses (13 +/- 0.95) was significantly higher (P < 0.05) than that of the non-abscess group (3.5 +/- 0.3). A significant correlation was observed between MTR and viscosity (r = 0.75, P < 0.05), total protein concentration (r = 0.60, P < 0.05), and cell density (r = 0.70, P < 0.05) in brain abscess, and viscosity (r = 0.81, P < 0.05) and total protein concentration (r = 0.41, P < 0.05) in non-abscess lesions. CONCLUSION: It is possible to differentiate brain abscesses from non-abscess cystic lesions using MT imaging. The MTR correlates significantly with the viscosity, viable cell density, and total protein concentration in brain abscess, and with viscosity and total protein concentration in non-abscess lesions. FLAIR signal intensity correlates significantly only with the total protein concentration in abscess and non-abscess lesions.

Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy.

Brain water may increase in hepatic encephalopathy (HE). Diffusion tensor imaging was performed in patients with cirrhosis with or without HE to quantify the changes in brain water diffusivity and to correlate it with neuropsychological (NP) tests. Thirty-nine patients with cirrhosis, with minimal (MHE) or overt HE, were studied and compared to 18 controls. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in corpus callosum, internal capsule, deep gray matter nuclei, periventricular frontal, and occipital white matter regions in both cerebral hemispheres. The MD and FA values from different regions in different groups were compared using analysis of variance and Spearman's rank correlation test. In 10 patients with MHE, repeat studies were performed after 3 weeks of lactulose therapy to look for any change in MD, FA, and NP scores. Significantly increased MD was found with insignificant changes in FA in various regions of brain in patients with MHE or HE compared with controls, indicating an increase in interstitial water in the brain parenchyma without any microstructural changes. A significant correlation was found between MD values from corpus callosum, internal capsule, and NP test scores. After therapy, MD values decreased significantly and there was a corresponding improvement in NP test scores. Further analysis showed that MD values were different for different grades of minimal or overt HE. In conclusion, the increase in MD with no concomitant changes in FA in cirrhosis with minimal or early HE indicates the presence of reversible interstitial brain edema.

Role of diffusion weighted imaging in differentiation of intracranial tuberculoma and tuberculous abscess from cysticercus granulomas-a report of more than 100 lesions.

Restricted diffusion is noted in a large number of non-stroke conditions including tuberculoma. The purpose of this study was to demonstrate spectrum of diffusion weighted imaging (DWI) abnormalities in tuberculomas and tuberculous abscess and to distinguish these from degenerating neurocysticercosis. Seventy tuberculomas and tuberculous abscesses in 30 patients were categorized in three groups depending on the intensity in the core of the lesion on T2 weighted images. Mean apparent diffusion coefficient (ADC) was calculated from the core as well as from the wall of the lesions. Forty-five lesions of neurocysticercosis in different stage of evolution in 12 patients were also included for comparison. The mean ADC value from the core of the T2 hypointense lesions was significantly higher compared to the wall ((1.24+/-0.32)x10(-3) and (1.06+/-0.15)x10(-3)mm(2)/s, respectively), while mean ADC value from the core of mildly T2 hyperintense lesions was significantly lower compared to the wall ((0.80+/-0.08)x10(-3) and (1.08+/-0.13)x10(-3)mm(2)/s, respectively). Truly T2 hyperintense lesions were divided into two subgroups, tuberculomas and tuberculous abscesses; ADC values from the core and the wall of these lesions were (0.74+/-0.13)x10(-3), (0.61+/-0.08)x10(-3) and (1.03+/-0.14)x10(-3), (1.08+/-0.14)x10(-3)mm(2)/s, respectively, and was significantly lower in core as compared to the wall. However, there was no significant difference between ADC values of the tuberculous abscess and the hyperintense tuberculomas. Vesicular and degenerating stages of cysticercus cysts from the core showed ADC values of (1.66+/-0.29)x10(-3) and (1.51+/-0.23)x10(-3)mm(2)/s, respectively, and were significantly higher than the core of all groups of tuberculomas and tuberculous abscess. We conclude that addition of DWI to routine imaging protocol may help in differentiation of tuberculous lesions from degenerating cysticercus granuloma.

Biological correlates of diffusivity in brain abscess.

Restricted diffusion in brain abscess is assumed to be due to a combination of inflammatory cells, necrotic debris, viscosity, and macromolecules present in the pus. We performed diffusion-weighted imaging (DWI) on 41 patients with proven brain abscesses (36 pyogenic and five tuberculous), and correlated the apparent diffusion coefficient (ADC) from the abscess cavity with viable cell density, viscosity, and extracellular-protein content quantified from the pus. On the basis of the correlation between cell density and ADC in animal tumor models and human tumors in the literature, we assumed that the restricted ADC represents the cellular portion in the abscess cavity. We calculated restricted and unrestricted lesion volumes, and modeled cell density over the restricted area with viable cell density per mm(3) obtained from the pus. The mean restricted ADC in the cavity (0.65 +/- 0.01 x 10(-3) mm(2)/s) correlated inversely with restricted cell density in both the pyogenic (r = -0.90, P = <0.05) and tuberculous (0.60 +/- 0.04 x 10(-3) mm(2)/s, r = -0.94, P = <0.05) abscesses. We conclude that viable cell density is the main biological parameter responsible for restricted diffusion in brain abscess, and it is not influenced by the etiological agents responsible for its causation.

High fractional anisotropy in brain abscesses versus other cystic intracranial lesions.

BACKGROUND AND PURPOSE: It is known that intracranial mass lesions are relatively isotropic on diffusion-weighted imaging. The purpose of this study is to report an unusually high fractional anisotropy (FA) and mean diffusivity (D(av)) in the cavity of the brain abscess compared with other cystic lesions. METHODS: We performed diffusion tensor imaging (DTI) in 12 patients with cystic intracranial lesions (pyogenic abscess, n = 5; cysticercus cysts, n = 2; and low-grade astrocytoma, n = 5). Mean FA, D(av) from the lesion core, perifocal edema, and corresponding contralateral normal-appearing regions were measured and compared for relative changes in these parameters. In the abscess cases, we placed regions of interest on areas with FA >0.2 and FA <0.2 to get FA and D(av) values. RESULTS: There were two patterns of FA values in the abscess cavity in all five patients. Part of the abscess showed mean FA = 0.440 +/- 0.135, with D(av) = (0.993 +/- 0.185) x 10(-3) mm(2)/s, whereas other parts had FA = 0.131 +/- 0.039 with D(av) = (0.824 +/- 0.183) x 10(-3) mm(2)/s. The cystic tumors and neurocysticercosis showed very high D(av) = (2.806 +/- 0.25, 2.654 +/- 0.35)x 10(-3) mm(2)/s, with low FA = (0.108 +/- 0.037, 0.08 +/- 0.01), respectively. CONCLUSION: Brain abscess cavity shows regions of increased FA values with restricted mean diffusivity compared with other cystic intracranial lesions. This information may prevent misinterpretation of the DTI information as white matter fiber bundle abnormalities associated with mass lesions.

Diffusion-weighted EPI with magnetization transfer contrast.

Capabilities of diffusion-weighted (DW) and magnetization transfer (MT) imaging are well established for tissue characterization in various pathologies individually. However, the effect of suppression of macromolecules on applying MT pulse on signals associated with DW imaging and resulting change in the apparent diffusion coefficient (ADC) of water molecules has not been demonstrated previously. In the present study, we have performed DW echo planar imaging (EPI) with and without MT preparation pulse to see the effect of macromolecular signal suppression on ADC. A total of 10 normal volunteers and 20 patients with different intracranial cystic lesions [abscesses (n=10), cystic tumors (n=5), arachnoid cysts (n=5)] were subjected to DW imaging (b=0 and 1000 s/mm(2)) with and without MT saturation pulse. Analysis of region of interest (ROI) from different areas of white matter in normal volunteers and in the wall and cavity of cystic lesions in patients was carried out for calculating the ADC values. We found a significant increase (P<.05) in the ADC values in brain parenchyma and cavity of those intracranial cystic lesions having considerable amount of proteins after the application of MT preparation pulse except for arachnoid cysts. This is due to the size of the macromolecules present in the normal and abnormal tissue. Our studies suggest that this technique is likely to give a novel image contrast and may be of value in improving the tissue specificity in pathologies associated with variable macromolecular size.

Role of diffusion-weighted imaging and in vivo proton magnetic resonance spectroscopy in the differential diagnosis of ring-enhancing intracranial cystic mass lesions.

OBJECTIVES: Proton magnetic resonance spectroscopy (PMRS) and diffusion-weighted imaging (DWI) were compared to determine which technique is more effective in the differential diagnosis of cystic intraparenchymal ring-enhancing lesions with variable perifocal edema. METHODS: Fifty-two patients (abscesses [n = 29], tumor cysts [n = 20], and benign cysts [n = 3]) formed the basis for comparative evaluation in this study. The criteria for abscess diagnosis were apparent diffusion coefficient (ADC) values less than 0.9 +/- 1.3 x 10 mm/s and presence of lactate cytosolic amino acids (AAs) with/without succinate, acetate, alanine, and glycine on PMRS. Criteria for nonabscess cyst identification were ADC values of 1.7-3.8 x 10 mm/s and presence of lactate and choline on PMRS. On the basis of these criteria, patients were categorized into abscess (n = 29) and nonabscess (n = 23) groups. Sensitivity and specificity of PMRS and DWI with respect to the final diagnosis were calculated based on the efficacy of these techniques. RESULTS: : Apparent diffusion coefficient values in 21 patients with abscesses were observed within the range of defined criteria, whereas in 8 patients, ADC values were beyond the range of defined criteria. Lactate and AAs with or without other metabolites were observed in 25 of 29 cases of abscesses on PMRS. In the nonabscess group, ADC values of cystic lesions in all patients were consistent with respect to the defined criteria. Only lactate was seen in 14 of 23 patients, whereas both lactate and choline were visible in 6 patients. In 3 patients with neurocysticercosis, AAs (n = 2), lactate (n = 3), acetate (n = 1), succinate (n = 3), choline (n = 2), and alanine (n = 3) were seen. The sensitivity of DWI and PMRS for differentiation of brain abscess from nonbrain abscess was 0.72 and 0.96, respectively, whereas the specificity was 1 for both techniques. CONCLUSION: Demonstration of restricted diffusion on DWI with reduced ADC is highly suggestive of brain abscess; however, in the absence of restriction, PMRS is mandatory to distinguish brain abscesses from cystic tumors.