Ken Maravilla

Hierarchical clustering to measure connectivity in fMRI resting-state data

Low frequency oscillations, which are temporally correlated in functionally related brain regions, characterize the mammalian brain, even when no explicit cognitive tasks are performed. Functional connectivity MR imaging is used to map regions of the resting brain showing synchronous, regional and slow fluctuations in cerebral blood flow and oxygenation. In this study, we use a hierarchical clustering method to detect similarities of low-frequency fluctuations. We describe one measure of correlations in the low frequency range for classification of resting-state fMRI data. Furthermore, we investigate the contribution of motion and hardware instabilities to resting-state correlations and provide a method to reduce artifacts. For all cortical regions studied and clusters obtained, we quantify the degree of contamination of functional connectivity maps by the respiratory and cardiac cycle. Results indicate that patterns of functional connectivity can be obtained with hierarchical clustering that resemble known neuronal connections. The corresponding voxel time series do not show significant correlations in the respiratory or cardiac frequency band.

Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulus

Objective:To develop a non-invasive method of studying brain mechanisms involved in energy homeostasis and appetite regulation in humans by using visual food cues that are relevant to individuals attempting weight loss.Design:Functional magnetic resonance imaging (fMRI) was used to compare brain activation in regions of interest between groups of food photographs.Participants:Ten healthy, non-obese women who were not dieting for weight loss.Measurements:Independent raters viewed food photographs and evaluated whether the foods depicted should be eaten by individuals attempting a calorically-restricted diet. Based on their responses, we categorized photographs into ‘non-fattening’ and ‘fattening’ food groups, the latter characterized by high-caloric content and usually also high-fat or high-sugar content. Blood oxygen level-dependent (BOLD) response was measured by fMRI while participants viewed photographs of ‘fattening’ food, ‘non-fattening’ food, and non-food objects.Results:Viewing photographs of fattening food compared with non-food objects resulted in significantly greater activation in the brainstem; hypothalamus; left amygdala; left dorsolateral prefrontal cortex; left orbitofrontal cortex; right insular cortex; bilateral striatum, including the nucleus accumbens, caudate nucleus, and putamen; bilateral thalamus; and occipital lobe. By comparison, only the occipital region had greater activation by non-fattening food than by object photographs. Combining responses to all food types resulted in attenuation of activation in the brainstem, hypothalamus, and striatum.Conclusion:These findings suggest that, in non-obese women, neural circuits engaged in energy homeostasis and reward processing are selectively attuned to representations of high-calorie foods that are perceived as fattening. Studies to investigate hormonal action or manipulation of energy balance may benefit from fMRI protocols that contrast energy-rich food stimuli with non-food or low-calorie food stimuli.

Magnetic resonance neurography of peripheral nerve lesions in the lower extremity

OBJECTIVE We describe the clinical application and utility of high-resolution magnetic resonance neurography (MRN) techniques to image the normal fascicular structure of peripheral nerves and its distortion by mass lesions or trauma in the lower extremity. METHODS MRN images were obtained using a standard 1.5 Tesla magnet and custom built phased-array coils. Patients were imaged using T1-weighted spin echo without and with gadolinium, T2-weighted fast spin echo with fat peripheral nerve tumors (three neurofibromas and one schwannoma), two with intraneural cysts, and three with traumatic peripheral nerve lesions. Six patients with peripheral nerve mass lesions underwent surgery, thereby allowing MRN images to be correlated with intraoperative and pathological findings. RESULTS Preoperative MRN accurately imaged the normal fascicular anatomy of peripheral nerves and precisely depicted its relation to tumor and cystic lesions. Increased signal on T2-weighted fast spin-echo and short tau inversion recovery fast spin-echo pulse sequences was seen in the peripheral nerve fascicles of patients with clinical and electrodiagnostic evidence of nerve injury. CONCLUSION MRN proved useful in the preoperative evaluation and planning of surgery in patients with peripheral nerve lesions.

Tract-Based Spatial Statistics of Diffusion Tensor Imaging in Adults with Dyslexia

BACKGROUND AND PURPOSE: Diffusion tensor imaging is a tool that can be used to study white matter microstructure in dyslexia. We tested the hypothesis that dyslexics have a white matter structural change (as measured by directional diffusion of water, which can be affected by disruption in white matter tracts) between brain regions that previous functional connectivity studies showed were associated with phonologic processing. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) scans were acquired from 7 healthy adult normal readers and from 14 adults with dyslexia on a 1.5T scanner. Voxelwise statistical analysis of the fractional anisotropy data were carried out by using Tract-Based Spatial Statistics to compare dyslexic subjects versus control subjects in white matter tracts. RESULTS: Significant group difference map clusters (comparing adults with and without dyslexia) occurred in specific bilateral white matter tracts within the frontal lobe, temporal lobe, occipital lobe, and parietal lobe. CONCLUSION: The DTI fractional anisotropy results in the bilateral white matter showing higher fractional anisotropy in adult control subjects compared with adults with dyslexia (relating to white matter fiber tract integrity) are consistent with our previous functional connectivity results from seed points in the bilateral inferior frontal gyrus.

Activity of P-Glycoprotein, a β-Amyloid Transporter at the Blood–Brain Barrier, Is Compromised in Patients with Mild Alzheimer Disease

Studies in animals and postmortem human brain tissue support a role for P-glycoprotein in clearance of cerebral β-amyloid across the blood–brain barrier (BBB). We tested the hypothesis that BBB P-glycoprotein activity is diminished in Alzheimer disease (AD) by accounting for an AD-related reduction in regional cerebral blood flow (rCBF). Methods: We compared P-glycoprotein activity in mild-AD patients (n = 9) and cognitively normal, age-matched controls (n = 9) using PET with a labeled P-glycoprotein substrate, 11C-verapamil, and 15O-water to measure rCBF. BBB P-glycoprotein activity was expressed as the 11C-verapamil radioactivity extraction ratio (11C-verapamil brain distributional clearance, K1/rCBF). Results: Compared with controls, BBB P-glycoprotein activity was significantly lower in the parietotemporal, frontal, and posterior cingulate cortices and hippocampus of mild AD subjects. Conclusion: BBB P-glycoprotein activity in brain regions affected by AD is reduced and is independent of rCBF. This study improves on prior work by eliminating the confounding effect that reduced rCBF has on assessment of BBB P-glycoprotein activity and suggests that impaired P-glycoprotein activity may contribute to cerebral β-amyloid accumulation in AD. P-glycoprotein induction or activation to increase cerebral β-amyloid clearance could constitute a novel preventive or therapeutic strategy for AD.

Gadolinium Contrast Agents for CNS Imaging: Current Concepts and Clinical Evidence

SUMMARY: The aim of this article was to review the properties of the various gadolinium-based contrast agents used for CNS imaging along with the clinical evidence and published data that highlight the impact these different properties can have on diagnostic performance. In addition, approaches to optimizing image acquisition that take into account the different properties of specific gadolinium-based contrast agents and an extensive review of the safety profiles of the various agents are presented.

Phase I study of a humanized anti‐CD11/CD18 monoclonal antibody in multiple sclerosis

To evaluate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of a humanized anti‐CD11/CD18 monoclonal antibody (Hu23F2G) in patients with multiple sclerosis.

Central nervous system manifestations in human immunodeficiency virus infection without AIDS.

To characterize neurological and neuropsychological findings associated with human immunodeficiency virus type-I (HIV) infection, 77 seropositive homosexual or bisexual males with no or minor symptoms of HIV were compared prospectively to 44 HIV seronegative men by observers blinded to serological status of the subjects. Neurological symptoms and examination findings were not significantly different between seropositives and seronegatives except for cranial nerve findings, predominately mild hearing impairment. Mean performance scores for a 15-test neuropsychological battery were within an unimpaired range for both groups, although for five tests, mean scores were significantly poorer in seropositives. After adjustment for vocabulary score, and demographic and psychosocial variables, the mean score of seropositives was significantly worse only for the Benton Visual Retention Test. Magnetic resonance (MR) images of brain were abnormal in 14 (27%) of 52 seropositives and one of 10 seronegatives (value was not significant). HIV was isolated from cerebrospinal fluid (CSF) in 31 (61%) of 51 seropositives. The only clinical or laboratory difference between CSF culture positives and negatives was a higher CSF immunoglobulin synthesis rate in the former subjects (medians of 10.3 versus 0.1 mg/day; p = 0.03). An additional 13 seropositive subjects had immunologic evidence of central nervous system HIV infection, defined by a serum-to-CSF HIV antibody ratio of <5.5. Intracranial abnormalities on MR imaging were associated with CSF immunologic responses to HIV. Nervous system involvement occurred in the vast majority of men with early HIV infection, but clinically significant impairment was uncommon.

In vivo manganese MR imaging of calcium influx in spontaneous rat pituitary adenoma.

BACKGROUND AND PURPOSE: Rapid uptake of the calcium analog manganese (Mn2+) into spontaneous pituitary adenoma during MR imaging of aged rats generated the hypothesis that neuroendocrine tumors may have a corresponding increase in calcium influx required to trigger hormonal release. A goal of this study was to investigate the potential for clinical evaluation of pituitary adenoma by MR imaging combined with administration of Mn2+ (Mn-MR imaging). MATERIALS AND METHODS: Mn-MR imaging was used to characterize the dynamic calcium influx in normal aged rat pituitary gland as well as spontaneous pituitary adenoma. To confirm the validity of Mn2+ as a calcium analog, we inhibited Mn2+ uptake into the olfactory bulb and pituitary gland of normal rats by using the calcium channel blocker verapamil. Rats with adenomas received fluorodeoxyglucose–positron-emission tomography (FDG-PET) scanning for characterization of tumor metabolism. Mn2+ influx was characterized in cultured pituitary adenoma cells. RESULTS: Volume of interest analysis of the normal aged pituitary gland versus adenoma indicated faster and increased calcium influx in adenoma at 1, 3, 11, and 48 hours. Mn2+ uptake into the olfactory bulb and pituitary gland of normal rats was inhibited by calcium channel blockers and showed dose-dependent inhibition on dynamic MR imaging. FDG-PET indicated correlation between tumor energy metabolism and Mn2+ influx as well as tumor size. CONCLUSION: These results indicate that adenomas have increased activity-dependent calcium influx compared with normal aged pituitary glands, suggesting a potential for exploitation in the clinical work-up of pituitary and other neuroendocrine tumors by developing Mn-MR imaging for humans.

Functional magnetic resonance imaging sequential-finger movement activation differentiating good and poor writers

Good and poor fifth-grade writers differed, after controlling for multiple comparisons, in 42 brain regions on group maps and then individual brain analyses for functional magnetic resonance imaging (fMRI) contrast between tapping adjacent fingers sequentially and same finger repeatedly. Of these, 11 regions were correlated with both handwriting and spelling (transcription). Gender differences on the fMRI contrast, with girls more activated, occurred only in left superior parietal, which was correlated with handwriting and spelling. Significance of serial organization of fingers for handwriting and spelling is discussed.