Streamline density and lesion volume reveal a postero-anterior gradient of corpus callosum damage in multiple sclerosis.

BACKGROUND AND PURPOSE: Although interhemispheric disconnection significantly contributes to disability in multiple sclerosis (MS), the topography, timeline and relationship of callosal damage accrual with hemispheric damage are still unclear. METHODS: Streamline density and the presence of focal lesions in five callosal subregions were computed in 55 people with MS [13 relapsing-remitting (RRMS), 20 secondary progressive (SPMS), 22 primary progressive (PPMS)] and 24 healthy controls. RESULTS: Streamline density decrease was identified in SPMS in all corpus callosum (CC) subregions, in PPMS in the posterior CC and mid-posterior CC and in RRMS in the posterior CC. CC density was independently predicted by CC lesion volume and hemispheric lesion volume and independently predicted visuospatial memory, Expanded Disability Status Scale, manual dexterity and ambulation. CONCLUSIONS: The reduction in CC density across phenotypes suggests an earlier involvement of the posterior regions, followed only at a later stage by involvement of the anterior portions of the CC. Such interhemispheric disconnection seems to develop as a consequence of white matter macroscopic damage and exerts a relevant impact on motor and, to a lesser extent, cognitive disability.

Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia.

BACKGROUND AND PURPOSE: Spasmodic dysphonia (SD), or laryngeal dystonia, is a task-specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers. METHODS: We used a combination of independent component analysis and linear discriminant analysis of resting-state functional magnetic resonance imaging data to investigate brain organization in different SD phenotypes (abductor versus adductor type) and putative genotypes (familial versus sporadic cases) and to characterize neural markers for genotype/phenotype categorization. RESULTS: We found abnormal functional connectivity within sensorimotor and frontoparietal networks in patients with SD compared with healthy individuals as well as phenotype- and genotype-distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortices. When categorizing between different forms of SD, the combination of measures from the left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms. CONCLUSIONS: Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder.

Brain Charts for the Rhesus Macaque Lifespan.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Brain-mimicking phantom for biomechanical validation of motion sensitive MR imaging techniques.

Motion sensitive MR imaging techniques allow for the non-invasive evaluation of biological tissues by using different excitation schemes, including physiological/intrinsic motions caused by cardiac pulsation or respiration, and vibrations caused by an external actuator. The mechanical biomarkers extracted through these imaging techniques have been shown to hold diagnostic value for various neurological disorders and conditions. Amplified MRI (aMRI), a cardiac gated imaging technique, can help track and quantify low frequency intrinsic motion of the brain. As for high frequency actuation, the mechanical response of brain tissue can be measured by applying external high frequency actuation in combination with a motion sensitive MR imaging sequence called Magnetic Resonance Elastography (MRE). Due to the frequency-dependent behavior of brain mechanics, there is a need to develop brain phantom models that can mimic the broadband mechanical response of the brain in order to validate motion-sensitive MR imaging techniques. Here, we have designed a novel phantom test setup that enables both the low and high frequency responses of a brain-mimicking phantom to be captured, allowing for both aMRI and MRE imaging techniques to be applied on the same phantom model. This setup combines two different vibration sources: a pneumatic actuator, for low frequency/intrinsic motion (1 Hz) for use in aMRI, and a piezoelectric actuator for high frequency actuation (30-60 Hz) for use in MRE. Our results show that in MRE experiments performed from 30 Hz through 60 Hz, propagating shear waves attenuate faster at higher driving frequencies, consistent with results in the literature. Furthermore, actuator coupling has a substantial effect on wave amplitude, with weaker coupling causing lower amplitude wave field images, specifically shown in the top-surface shear loading configuration. For intrinsic actuation, our results indicate that aMRI linearly amplifies motion up to at least an amplification factor of 9 for instances of both visible and sub-voxel motion, validated by varying power levels of pneumatic actuation (40%-80% power) under MR, and through video analysis outside the MRI scanner room. While this investigation used a homogeneous brain-mimicking phantom, our setup can be used to study the mechanics of non-homogeneous phantom configurations with bio-interfaces in the future.

Ultra-High-Field MRI Visualization of Cortical Multiple Sclerosis Lesions with T2 and T2*: A Postmortem MRI and Histopathology Study.

BACKGROUND AND PURPOSE: At 7T MR imaging, T2*-weighted gradient echo has been shown to provide high-resolution anatomic images of gray matter lesions. However, few studies have verified T2*WI lesions histopathologically or compared them with more standard techniques at ultra-high-field strength. This study aimed to determine the sensitivity of T2WI and T2*WI sequences for detecting cortical GM lesions in MS. MATERIALS AND METHODS: At 7T, 2D multiecho spin-echo T2WI and 3D gradient-echo T2*WI were acquired from 27 formalin-fixed coronal hemispheric brain sections of 15 patients and 4 healthy controls. Proteolipid-stained tissue sections (8 µm) were matched to the corresponding MR images, and lesions were manually scored on both MR imaging sequences (blinded to histopathology) and tissue sections (blinded to MR imaging). The sensitivity of MR imaging sequences for GM lesion types and white matter lesions was calculated. An unblinded retrospective scoring was also performed. RESULTS: If all cortical GM lesions were taken into account, the T2WI sequence detected slightly more lesions than the T2*WI sequence: 28% and 16%, respectively (P = .054). This difference disappeared when only intracortical lesions were considered. When histopathologic information (type, location) was revealed to the reader, the sensitivity went up to 84% (T2WI) and 85% (T2*WI) (not significant). Furthermore, the false-positive rate was 8.6% for the T2WI and 10.5% for the T2*WI sequence. CONCLUSIONS: There is no strong advantage of the T2*WI sequence compared with a conventional T2WI sequence in the detection of cortical lesions at 7T. Retrospectively, a high percentage of lesions could be detected with both sequences. However, many lesions are still missed prospectively. This could possibly be minimized with better a priori observer training.

Neural correlates of ankle movements during different motor tasks: A feasibility study.

This ongoing study investigates the neural correlates of ankle dorsi-plantar flexion in active, passive, and proprioceptive tasks. Specifically, we investigated two proprioceptive matching tasks that required a simple combination of active and passive ankle movements: (1) a memory-based ipsilateral matching task and (2) a contralateral concurrent matching task. As expected, during the passive tasks, subjects recruited the same brain areas involved in the correspondent active movements (primary motor cortex (M1), premotor cortex (PM) supplementary motor cortex (SMA) and primary somatosensory cortex (S1)), but the activations were lower. Instead, in both the proprioceptive matching tasks, subjects recruited more motor and sensory-motor areas of the brain and the activations were greater.

Sodium imaging as a marker of tissue injury in patients with multiple sclerosis.

Recent studies have suggested that intra-axonal sodium accumulation contribute to axonal degeneration in patients with MS. Advances in MRI hardware and software allow acquisition of brain sodium signal in vivo. This review begins with a summary of the experimental evidence for impairment of sodium homeostasis in MS. Then, MRI methods for sodium acquisition are reviewed and the application of the techniques in patients with MS is discussed. Sodium imaging and ultra-high field MRI have the potential to provide tissue-specific markers of neurodegeneration in MS.

Discovery of localized regions of excess 10-TeV cosmic rays.

The 7 year data set of the Milagro TeV observatory contains 2.2 x 10(11) events of which most are due to hadronic cosmic rays. These data are searched for evidence of intermediate scale structure. Excess emission on angular scales of approximately 10 degrees has been found in two localized regions of unknown origin with greater than 12sigma significance. Both regions are inconsistent with pure gamma-ray emission with high confidence. One of the regions has a different energy spectrum than the isotropic cosmic-ray flux at a level of 4.6sigma, and it is consistent with hard spectrum protons with an exponential cutoff, with the most significant excess at approximately 10 TeV. Potential causes of these excesses are explored, but no compelling explanations are found.

Evidence for TeV gamma-ray emission from a region of the galactic plane.

Gamma-ray emission from a narrow band at the galactic equator has previously been detected up to 30 GeV. We report evidence for a TeV gamma-ray signal from a region of the galactic plane by Milagro, a large-field-of-view water Cherenkov detector for extensive air showers. An excess with a significance of 4.5 standard deviations has been observed from the region of galactic longitude l E (40 degrees, 100 degrees) and latitude /b/ < 5 degrees. Under the assumption of a simple power law spectrum, with no cutoff in the EGRET-Milagro energy range, the measured integral flux is phi gamma(>3.5 TeV) = (6.4 +/- 1.4 +/- 2.1) x 10(-11) cm(-2) s(-1) sr(-1). This flux is consistent with an extrapolation of the EGRET spectrum between 1 and 30 GeV in this galactic region.

Evidence for TeV Emission from GRB 970417a.

Milagrito, a detector sensitive to very high energy gamma rays, monitored the northern sky from 1997 February through 1998 May. With a large field of view and a high duty cycle, this instrument was well suited to perform a search for TeV gamma-ray bursts (GRBs). We report on a search made for TeV counterparts to GRBs observed by BATSE. BATSE detected 54 GRBs within the field of view of Milagrito during this period. An excess of events coincident in time and space with one of these bursts, GRB 970417a, was observed by Milagrito. The excess has a chance probability of 2.8x10-5 of being a fluctuation of the background. The probability for observing an excess at least this large from any of the 54 bursts is 1.5x10-3. No significant correlations were detected from the other bursts.

TeV Observations of Markarian 501 with the Milagrito Water Cerenkov Detector.

The Milagrito water Cerenkov detector near Los Alamos, New Mexico, was operated as a sky monitor at energies of a few TeV between 1997 February and 1998 May, including the period of the strong, long-lasting 1997 flare of Markarian 501. Milagrito served as a test run for the full Milagro detector. An event excess with a significance of 3.7 sigma from Markarian 501 was observed, in agreement with expectations.