Evaluating brain damage in multiple sclerosis with simultaneous multi-angular-relaxometry of tissue

OBJECTIVE: Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination. METHODS: Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric was determined in normal-appearing cortical gray matter (NAGM), normal-appearing subcortical white matter (NAWM), and demyelinating lesions. MPF metric was evaluated for correlations with physical and cognitive test scores. Comparisons were made between HC and MS and between MS subtypes. Furthermore, correlations were determined between MPF and neuropathology in the biopsied person. RESULTS: SMART-derived MPF in NAGM and NAWM were lower in MS than HC (p \u3c 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively) and nine-hole peg test (p \u3c 0.001, p \u3c 0.001, p \u3c 0.01, respectively). MPF was lower in the histopathologically confirmed inflammatory demyelinating lesion than the contralateral NAWM and increased in the biopsied lesion over time, mirroring improved clinical performance. INTERPRETATION: SMART-derived MPF metric holds potential as a quantitative imaging biomarker of demyelination and remyelination

Broken symmetries and directed collective energy transport

We study the appearance of directed energy current in homogeneous spatially extended systems coupled to a heat bath in the presence of an external ac field E(t). The systems are described by nonlinear field equations. By making use of a symmetry analysis we predict the right choice of E(t) and obtain directed energy transport for systems with a nonzero topological charge Q. We demonstrate that the symmetry properties of motion of topological solitons (kinks and antikinks) are equivalent to the ones for the energy current. Numerical simulations confirm the predictions of the symmetry analysis and, moreover, show that the directed energy current drastically increases as the dissipation parameter $\alpha$ reduces. Our results generalize recent rigorous theories of currents generated by broken time-space symmetries to the case of interacting many-particle systems.Comment: 4 pages, 2 figure

Random walk with barriers: Diffusion restricted by permeable membranes

Restrictions to molecular motion by barriers (membranes) are ubiquitous in biological tissues, porous media and composite materials. A major challenge is to characterize the microstructure of a material or an organism nondestructively using a bulk transport measurement. Here we demonstrate how the long-range structural correlations introduced by permeable membranes give rise to distinct features of transport. We consider Brownian motion restricted by randomly placed and oriented permeable membranes and focus on the disorder-averaged diffusion propagator using a scattering approach. The renormalization group solution reveals a scaling behavior of the diffusion coefficient for large times, with a characteristically slow inverse square root time dependence. The predicted time dependence of the diffusion coefficient agrees well with Monte Carlo simulations in two dimensions. Our results can be used to identify permeable membranes as restrictions to transport in disordered materials and in biological tissues, and to quantify their permeability and surface area.Comment: 8 pages, 3 figures; origin of dispersion clarified, refs adde

Regional pressure and temperature differences across the injured human brain : comparisons between intraparenchymal and ventricular measurements

Introduction: Intraparenchymal, multimodality sensors are commonly used in the management of patients with severe traumatic brain injury (TBI). The ‘gold standard’, based on accuracy, reliability and cost for intracranial pressure (ICP) monitoring is within the cerebral ventricle (external strain gauge). There are no standards yet for intracerebral temperature monitoring and little is known of temperature differences between brain tissue and ventricle. The aim of the study therefore was to determine pressure and temperature differences at intraparenchymal and ventricular sites during five days of continuous neurominitoring. Methods: Patients with severe TBI requiring emergency surgery. Inclusion criteria: patients who required ICP monitoring were eligible for recruitment. Two intracerebral probe types were used: a) intraventricular, dual parameter sensor (measuring pressure, temperature) with inbuilt catheter for CSF drainage: b) multiparameter intraparenchymal sensor measuring pressure, temperature and oxygen partial pressure. All sensors were inserted during surgery and under aseptic conditions. Results: Seventeen patients, 12 undergoing neurosurgery (decompressive craniectomy n=8, craniotomy n=4) aged 21–78 years were studied. Agreement of measures for 9540 brain tissue-ventricular temperature ‘pairs’ and 10,291 brain tissue-ventricular pressure ‘pairs’ were determined using mixed model to compare mean temperature and pressure for longitudinal data. There was no significant overall difference for mean temperature (p=0.92) or mean pressure readings (p=0.379) between tissue and ventricular sites. With 95.8% of paired temperature readings within 2SD (−0.4 to 0.4°C) differences in temperature between brain tissue and ventricle were clinically insignificant. For pressure, 93.5% of readings pairs fell within the 2SD range (−9.4756 to 7.8112 mmHg) (Fig. 2). However, for individual patients, agreement for mean tissue-ventricular pressure differences was poor on occasions. Conclusions: There is good overall agreement between paired temperature measurements obtained from deep white matter and brain ventricle in patients with and without early neurosurgery. For paired ICP measurements, 93.5% of readings were within 2SD of mean difference. Whilst the majority of paired readings were comparable (within 10mmHg) clinically relevant tissue-ventricular dissociations were noted. Further work is required to unravel the events responsible for short intervals of pressure dissociation before tissue pressure readings can be definitively accepted as a reliable surrogate for ventricular pressure.</p

In vivo evaluation of heme and non-heme iron content and neuronal density in human basal ganglia

Non-heme iron is an important element supporting the structure and functioning of biological tissues. Imbalance in non-heme iron can lead to different neurological disorders. Several MRI approaches have been developed for iron quantification relying either on the relaxation properties of MRI signal or measuring tissue magnetic susceptibility. Specific quantification of the non-heme iron can, however, be constrained by the presence of the heme iron in the deoxygenated blood and contribution of cellular composition. The goal of this paper is to introduce theoretical background and experimental MRI method allowing disentangling contributions of heme and non-heme irons simultaneously with evaluation of tissue neuronal density in the iron-rich basal ganglia. Our approach is based on the quantitative Gradient Recalled Echo (qGRE) MRI technique that allows separation of the total R2* metric characterizing decay of GRE signal into tissue-specific (R2t*) and the baseline blood oxygen level-dependent (BOLD) contributions. A combination with the QSM data (also available from the qGRE signal phase) allowed further separation of the tissue-specific R2t* metric in a cell-specific and non-heme-iron-specific contributions. It is shown that the non-heme iron contribution to R2t* relaxation can be described with the previously developed Gaussian Phase Approximation (GPA) approach. qGRE data were obtained from 22 healthy control participants (ages 26–63 years). Results suggest that the ferritin complexes are aggregated in clusters with an average radius about 100nm comprising approximately 2600 individual ferritin units. It is also demonstrated that the concentrations of heme and non-heme iron tend to increase with age. The strongest age effect was seen in the pallidum region, where the highest age-related non-heme iron accumulation was observed