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T2 weighting is particularly sensitive, but notoriously unspecific, to a wide range of brain pathologies. However, careful measurement and analysis of the T2 decay curve from brain tissue promise to provide much improved pathological specificity. In vivo T2 measurement requires accurate 180 pulses and appropriate manipulation of stimulated echoes; the most common approach is to acquire multiple echoes from a single slice. The T2 distribution, a plot of component amplitude as a function of T2, can be estimated using an algorithm capable of fitting a multi-exponential T2 decay with no a priori assumptions about the number of exponential components. T2 distributions from normal brain show peaks from myelin water, intra/extracellular water and cerebral spinal fluid; they can be used to provide estimates of total water content (total area under the T2 distribution) and myelin water fraction (MWF, fractional area under the myelin water peak), a measure believed to be related to myelin content. Experiments on bovine brain suggest that magnetization exchange between water pools plays a minor role in the T2 distribution. Different white matter structures have different MWFs. In normal white matter (NWM), MWF is not correlated with the magnetization transfer ratio (MTR) or the diffusion tensor fractional anisotropy (FA); hence it provides unique information about brain microstructure. Normal-appearing white matter (NAWM) in multiple sclerosis (MS) brain possesses a higher water content and lower MWF than controls, consistent with histopathological findings. Multiple sclerosis lesions demonstrate great heterogeneity in MWF, presumably due to varying myelin contents of these focal regions of pathology. Subjects with schizophrenia were found to have significantly reduced MWF in the minor forceps and genu of the corpus callosum when compared to controls, suggesting that reduced frontal lobe myelination plays a role in schizophrenia. In normal controls, frontal lobe myelination was positively correlated with both age and education; this result was not observed in subjects with schizophrenia. A strong correlation between MWF and the optical density from the luxol fast blue histological stain for myelin was observed in formalin-fixed brain, supporting the use of the MWF as an in vivo myelin marker.

Focal lesions of brainstem, thalamus, and subcortical white matter may cause movement disorders that are clinically indistinguishable from cerebellar symptoms. It is suspected that ataxia in these cases is due to damage of efferent or afferent pathways of the cerebellum. However, the precise anatomical correlate often remains undefined. We used deterministic diffusion tensor magnetic resonance imaging (DTI) tractography to study the anatomical relationship between lesions causing ataxia and efferent cerebellar pathways. Study subjects were six male patients with focal lesions of different etiology (demyelination, hemorrhage, ischemia, neoplasm) outside the cerebellum. Five patients had cerebellar-like ataxia with prominent contralateral upper limb involvement. One patient with an almost midline mesencephalic lesion had a symmetrical ataxic syndrome. We used 3T MRI (Intera, Philips Medical Systems, Best, Netherlands) and DTI tractography (32 directions, StealthViz DTI, Medtronic Navigation, Louisville, USA) to delineate the dentato-rubro-thalamo-cortical tract (DRT). In all patients, tractography demonstrated focal lesions affecting the DRT in different locations. We conclude that in vivo mapping of cerebral pathways using DTI tractography in patients with focal extracerebellar brain lesions may provide direct evidence of circumscribed damage to the DRT, causing unilateral cerebellar-like ataxia. Also, a unilateral mesencephalic lesion at the level of the crossing of the DRT may cause bilateral ataxia.

Introduction The histopathological basis of “unidentified bright objects” (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide measures relating to microstructural change. We combined these methods and present previously unreported data on in vivo UBO microstructure in NF1. Methods 3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density imaging parameters were calculated within UBO sites and in contralateral normal appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24 UBO–cNAWM pairs. Results No significant alterations in the myelin water fraction and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE water was significantly higher in UBOs. UBOs furthermore showed increased axial, radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis and neurite density index compared to cNAWM. Neurite orientation dispersion and isotropic fluid fraction were unaltered. Conclusion Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in ‘extracellular-like’, intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo., Highlights • We examine MRI white matter T2-weighted hyperintense lesions, “UBOs” in NF1. • Myelin water and intra- and extracellular water fractions are unchanged in UBOs. • Diffusivity is higher, while mean kurtosis and neurite density are lower in UBOs. • The combined measures suggest that UBOs may arise from intramyelinic edema. • Combining diffusion MRI and multi-exponential T2 relaxation has added value.

Structural characteristics of the palmitoyl and dodecyl chains as well as of the headgroups of POPC and C12E4, respectively, were determined at 25 °C in the pure and mixed (surfactant lipid molar ratios RS/L = 0.2 and 1) membranes hydrated at the same relative humidity of 97% by deuterium NMR using partially deuterated lipids (POPC-d31 and POPC-d4) and surfactants (C12E4-d25 and C12E4-d16). At RS/L = 0.2 the surfactant causes a rigidization of the membrane evidenced by the reduction of the cross-sections of the hydrocarbon chains, mainly of that of the surfactant dodecyl chain, whereas at RS/L = 1 fluidization of the membrane occurs due to the mismatch of the hydrocarbon chain lengths. The surfactant dodecyl chain penetrates the membrane to the same depth as the first twelve methylene segments of the lipid palmitoyl chain. Experiment and Monte Carlo simulation show that the mean orientation of the lipid headgroup simultaneously changes toward the membrane director whereas the headgroup structure adopts a ...

The partial orientation of multilamellar vesicles (MLVs) in high magnetic fields is known to affect the shape of 2H NMR spectra. There are numerical methods for extracting either the orientational order parameters of lipid molecules for a random distribution of domain orientations in the sample, or the distribution of orientations for a known set of spectral anisotropies. A first attempt at determining the orientational order parameters in the presence of an unknown nonrandom distribution of orientations is presented. The numerical method is based on the Tikhonov regularization algorithm. It is tested using simulated partially oriented spectra. An experimental spectrum of a phospholipid-ether mixture in water is analyzed as an example. The experimental spectrum is consistent with an ellipsoidal shape of MLVs with a ratio of semiaxes of approximately 3.4.

Background context Magnetic resonance imaging (MRI) is a very useful diagnostic test for cervical spondylotic myelopathy (CSM) because it can identify degenerative changes within the spinal cord (SC), disclose the extent, localization, and the kind of SC compression, and help rule out other SC disorders. However, the relationships between changes in cerebrospinal fluid (CSF) flow, cord motion, the extent and severity of spinal canal stenosis, and the development of CSM symptoms are not well understood. Purpose To evaluate if changes in the velocity of CSF and SC movements provide additional insight into the pathophysiological mechanisms underlying CSM beyond MRI observations of cord compression. Study design Prospective radiologic study of recruited patients. Patient sample Thirteen CSM subjects and 15 age and gender matched controls. Outcome measures Magnetic resonance imaging measures included CSF and SC movement. Cervical cord condition was assessed by the Japanese Orthopaedic Association (JOA) score, compression ratio (CR), and somatosensory evoked potentials (SSEPs) of the tibial and ulnar nerves. Methods Phase-contrast imaging at the level of stenosis for patients and at C5 for controls and T 2 -weighted images were compared with clinical findings. Results Cerebrospinal fluid velocity was significantly reduced in CSM subjects as compared with controls and was related to cord CR. Changes in CSF velocity and cord compression were not correlated with clinical measures (JOA scores, SSEP) or the presence of T 2 hyperintensities. Spinal cord movements, that is, cord displacement and velocity in the craniocaudal axis, were increased in CSM patients. Increased SC movements (ie, total cord displacement) both in the controls and CSM subjects were associated with altered spinal conduction as assessed by SSEP. Conclusions This study revealed rather unexpected increased cord movements in the craniocaudal axis in CSM patients that may contribute to myelopathic deteriorations in combination with spinal canal compression. Understanding the relevance of cord movements with respect to supporting the clinical CSM diagnosis or disease monitoring requires further long-term follow-up studies.

Diffusion tensor imaging (DTI) is more than just a useful adjunct to invasive techniques like optogenetics which recently have tremendously influenced our understanding of the mechanisms of deep brain stimulation (DBS). In combination with other technologies, DTI helps us to understand which parts of the brain tissue are connected to others and which ones are truly influenced with neuromodulation. The complex interaction of DBS with the surrounding tissues-scrutinized with DTI-allows to create testable hypotheses that can explain network interactions. Those interactions are vital for our understanding of the net effects of neuromodulation. This work naturally was first done in the field of movement disorder surgery, where a lot of experience regarding therapeutic effects and only a short latency between initiation of neuromodulation and alleviation of symptoms exist. This chapter shows the journey over the past 10 years with first applications in DBS toward current research in affect regulating network balances and their therapeutic alterations with the neuromodulation technology.

To assess the reproducibility of myelin water fraction (MWF) and geometric mean T2 (GMT2 ), which are in vivo markers of pathological changes underlying disability and progression in diseases such as multiple sclerosis.Five healthy volunteers were scanned twice within 24 hours at six different sites using the same manufacturer's 3T magnetic resonance (MR) system. T2 distributions were produced by fitting multiecho 3D T2 data using non-negative least squares, with stimulated echo correction. MWF, the fraction of signal with T2 between 15 and 40 msec to the entire signal, and GMT2 , the mean T2 on a logarithmic scale from T2 between 40 and 200 msec, were examined in white matter.Intrasite coefficients of variation (COVs) were low (mean 3.99% for MWF and 0.51% for GMT2 ), as were intersite COVs (mean 4.68% for MWF, 0.31% for GMT2 ). Scan-rescan intraclass correlation coefficients (ICCs) (0.76 for MWF and 0.93 for GMT2 ) and Bland-Altman plots indicated good agreement between single site scans. Intersite ICCs were relatively high (0.69 for MWF and 0.92 for GMT2 ), revealing good intersite reliability.MWF and GMT2 measures are reproducible between scans and across sites with an equivalent MR scanner and sequence protocol. Multicenter clinical trials using quantitative T2 relaxation are feasible.

Background Treatment-resistant major depressive disorder is a prevalent and debilitating condition. Deep brain stimulation to different targets has been proposed as a putative treatment. Methods In this pilot study, we assessed safety and efficacy of deep brain stimulation to the supero-lateral branch of the medial forebrain bundle in seven patients with highly refractory depression. Primary outcome criterion was severity of treatment-resistant major depressive disorder as assessed with the Montgomery-Asberg Depression Rating Scale. General psychopathologic parameters, social functioning, and tolerance were assessed with standardized scales, the Global Assessment of Functioning scale, quality of life (Short-Form Health Survey Questionnaire), and neuropsychological tests. Results All patients showed strikingly similar intraoperative effects of increased appetitive motivation. Six patients attained the response criterion; response was rapid—mean Montgomery-Asberg Depression Rating Scale of the whole sample was reduced by>50% at day 7 after onset of stimulation. At last observation (12–33 weeks), six patients were responders; among them, four were classified as remitters. Social functioning (Global Assessment of Functioning) improved in the sample as a whole from serious to mild impairment. Mean stimulation current was 2.86 mA; all side effects (strabismus at higher stimulation current, one small intracranial bleeding during surgery, infection at the implanted pulse generator site) could be resolved at short term. Conclusions These preliminary findings suggest that bilateral stimulation of the supero-lateral branch of the medial forebrain bundle may significantly reduce symptoms in treatment-resistant major depressive disorder. Onset of antidepressant efficacy was rapid (days), and a higher proportion of the population responded at lower stimulation intensities than observed in previous studies.

BACKGROUND AND PURPOSE: Although progress has been made in understanding the optimal anatomic structures as target areas for DBS, little effort has been put into modeling and predicting electromagnetic field properties of activated DBS electrodes and understanding their interactions with the adjacent tissue. Currently, DBS is performed with the patient awake to assess the effectiveness and the side effect spectrum of stimulation. This study was designed to create a robust and rather simple numeric and visual tool that provides sufficient and practical relevant information to visualize the patient9s individual VAT. MATERIALS AND METHODS: Multivariate polynomial fitting of previously obtained data from a finite-element model, based on a similar DBS system, was used. The model estimates VAT as a first-approximation sphere around the active DBS contact, using stimulation voltages and individual tissue-electrode impedances. Validation uses data from 2 patients with PD by MR imaging, DTI, fiber tractography, and postoperative CT data. RESULTS: Our model can predict VAT for impedances between 500 and 2000 Ω with stimulation voltages up to 10 V. It is based on assumptions for monopolar DBS. Evaluation of 2 DBS cases showed a convincing correspondence between predicted VAT and neurologic (side) effects (internal capsule activation). CONCLUSIONS: Stimulation effects during DBS can be readily explained with this simple VAT model. Its implementation in daily clinical routine might help in understanding the types of tissues activated during DBS. This technique might have the potential to facilitate DBS implantations with the patient under general anesthesia while yielding acceptable clinical effectiveness.

Krabbe disease is an autosomal recessive demyelinating lysosomal storage disorder caused by a deficiency of galactocerebrosidase. The adult-onset variant is very rare. Hematopoietic stem cell transplantation (HSCT) is reported to be successful in treating infants with Krabbe disease prior to the onset of symptoms, but there are no reported cases of its use for adult-onset disease. We report the first follow-up data for a patient with adult-onset Krabbe disease who underwent HSCT at age 41, 16 years after the onset of symptoms. HSCT resulted in a sustained normalization of peripheral GALC enzyme activity, halted the progression of symptoms at 24 months post-allograft, and led to improvements in gait and balance. Serial imaging also confirmed that no significant progression of demyelination has occurred. Although long-term follow-up is needed to confirm the effects of HSCT, our 24-month results suggest that HSCT is a viable therapeutic option for symptomatic patients with adult-onset Krabbe disease.

Diffusion tensor imaging (DTI) is more than just a useful adjunct to invasive techniques like optogenetics which recently have tremendously influenced our understanding of the mechanisms of deep brain stimulation (DBS). In combination with other technologies, DTI helps us to understand which parts of the brain tissue are connected to others and which ones are truly influenced with neuromodulation. The complex interaction of DBS with the surrounding tissues-scrutinized with DTI-allows to create testable hypotheses that can explain network interactions. Those interactions are vital for our understanding of the net effects of neuromodulation. This work naturally was first done in the field of movement disorder surgery, where a lot of experience regarding therapeutic effects and only a short latency between initiation of neuromodulation and alleviation of symptoms exist. This chapter shows the journey over the past 10 years with first applications in DBS toward current research in affect regulating network balances and their therapeutic alterations with the neuromodulation technology.

The presence of diffuse and widespread abnormalities within the ‘normal appearing’ white matter (NAWM) of multiple sclerosis (MS) brain has been established. T 1 histogram analysis has revealed increased T 1 (related to water content) in segmented NAWM, while quantitative assessment of T 2 relaxation measures has demonstrated decreased myelin water fraction (MWF, related to myelin content) and increased geometric mean T 2 (GMT2) of the intra/extracellular water pool. Previous studies with follow-up periods of 1–5 years have demonstrated longitudinal changes in T 1 histogram metrics over time; however, longitudinal changes in MWF and GMT2 of segmented NAWM have not been examined. We examined the short-term evolution of MWF, GMT2 and T 1 in MS NAWM based on monthly scanning over 6 months in 18 relapsing remitting (RR) MS subjects. Histogram metrics demonstrated short-term stability of T 1, MWF and remitting (RR) MS subjects. We observed no change in MWF, GMT2 or T 1 histogram metrics in NAWM in RRMS over the course of 6 months. Longer follow-up periods may be required to establish demonstrable changes in NAWM based on of MWF, GMT2 and T 1 metrics.

Essential tremor (ET) is a neurological disorder that can be treated effectively by means of bilateral thalamic ventral intermediate nucleus (VIM) deep brain stimulation (DBS). We present a rare case of stimulation-dependent reversible ageusia that poses a therapeutic dilemma on the one hand and serves as an instructive example to elucidate the as yet incompletely defined gustatory pathways on the other. A 69-year-old patient with successful reduction of his disabling upper extremity ET experienced an almost complete but during stimulation cessation reversible ageusia under bilateral VIM DBS. An evaluation of diffusion tensor (DTI) neuroimaging studies was performed in order to detect effective electrode positions and volumes of activated tissue (VTA) in relation to the medial lemniscus (ML) and dentato-rubro-thalamic tract (DRT). Repeated subjective gustometry was conducted with differential manipulation of stimulation settings. This case report stresses the importance of fiber tracts for DBS surgery. Reconciled with previous findings in lesion cases, we assume the coexistence of decussating and non-decussating fibers in the gustatory tract combined with hemispheric dominance in the processing of gustatory information. A therapeutic option for this dilemma may be a patient-selectable stimulation program or bipolar stimulation establishing a smaller ovoid VTA.

Objective To examine the relation between diffusion tensor imaging (DTI) of the corpus callosum and postconcussion symptom reporting following mild traumatic brain injury (MTBI). Participants Sixty patients with MTBI and 34 patients with orthopedic/soft-tissue injuries (Trauma Controls) prospectively enrolled from consecutive admissions to a level 1 trauma center. Procedure Diffusion tensor imaging of the corpus callosum was undertaken using a Phillips 3T scanner at 6 to 8 weeks postinjury. Participants also completed a postconcussion symptom checklist. The MTBI group was divided into 2 subgroups based on the International Classification of Diseases, Tenth Revision symptom criteria for postconcussion disorder (PCD): PCD Present (n = 21), PCD Absent (n = 39). Main outcome measures Measures of fractional anisotropy and mean diffusivity for the genu, body, and splenium of the corpus callosum. Participants also completed the British Columbia Post-Concussion Symptom Inventory. Results The MTBI group reported more postconcussion symptoms than the trauma controls. There were no significant differences between MTBI and trauma control groups on all DTI measures. In the MTBI sample, there were no significant differences on all DTI measures between those who did and did not meet the International Classification of Diseases, Tenth Revision research criteria for postconcussion disorder. Conclusions These data do not support an association between white matter integrity in the corpus callosum and self-reported postconcussion syndrome 6 to 8 weeks post-MTBI.

We propose a multicomponent fitting algorithm for multiecho T(2) data which allows for correction of T(2) distributions in the presence of stimulated echoes. Tracking the population of spins in many coherence pathways via the iterated method of the Extended Phase Graph algorithm allows for accurate quantification of echo magnitudes. The resulting decay curves allow for correction of errors due to nonideal refocusing pulses as a result of inhomogeneities in the B(1) transmit field. Non-Negative Least Squares fitting is used to quantify the magnitude of T(2) components at various T(2) values. This method, allowing calculation of the T(2) distribution with simultaneous extraction of the refocusing pulse flip angle, requires no change to image acquisition procedures and no extra data input. Validation by means of both simulations and in vivo data shows excellent interscan reproducibility while vastly improving the accuracy of extracted T(2) parameters in voxels where poor B(1) homogeneity leads to refocusing pulse flip angles significantly less than 180°. Most notably, myelin water fraction values in these regions are found to have increased consistency and accuracy.

Deep brain stimulation (DBS) can alleviate tremor of various origins. A number of regions are targeted. In recent work our group was able to show the involvement of the dentato-rubro-thalamic tract (drt) in tremor control with fiber tracking techniques. Here we report for the first time the successful use of magnetic resonance tractography in combination with traditional landmark-based targeting techniques to perform the implantation of a bilateral DBS system in a patient with dystonic head tremor.We report on a 37-year-old female with long-standing pure head tremor from myoclonus dystonia. She was identified as a candidate for thalamic DBS. The use of head fixation in a stereotactic frame would blur target symptoms (head tremor) during surgery and was therefore avoided. Her dentate-rubro-thalamic tracts were visualized with preoperative diffusion tensor imaging (DTI) and tractography, and then directly targeted stereotactically with DBS electrodes.Three months after implantation, tremor control was excellent (90%). A close evaluation of the active electrode contact positions revealed clear involvement of the drt.This is the first time that direct visualization of fiber tracts has been employed for direct targeting and successful movement disorder tremor surgery. In the reported case, additional knowledge about the position of the drt, which previously has been shown to be a structure for modulation to achieve tremor control, led to a successful implantation of a DBS system, although there was a lack of intra-operatively testable tremor symptoms. In concordance with studies in optogenetic neuromodulation, fiber tracts are the emerging target structures for DBS. The routine integration of DTI tractography into surgical planning might be a leading path into the future of DBS surgery and will add to our understanding of the pathophysiology of movement disorders. Larger study populations will have to prove these concepts in future research.

BACKGROUND: Cam deformities cause femoroacetabular impingement and damage the acetabular labral-chondral complex. The aims of this study were to investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to detect cartilage disease in asymptomatic hips with cam deformities compared with morphologically normal hips, establish whether dGEMRIC could identify advanced disease in hips with positive clinical findings, and establish whether cartilage damage correlated with the severity of the cam deformity. METHODS: Subjects were recruited from a prospective study of individuals with a family history of osteoarthritis and their spouses who served as control subjects. Their symptoms and impingement test results were recorded. Asymptomatic hips with normal radiographic joint-space width were placed in a subgroup according to the presence of a cam deformity and the impingement test result. dGEMRIC was performed on a 3-T system, studying two regions of interest: the anterosuperior aspect of the acetabular cartilage (T1(acet)) and the total femoral and acetabular cartilage (T1(total)). The ratio T1(acet)/T1(total) gave the relative glycosaminoglycan content in the anterosuperior aspect of the acetabular cartilage. The cohort was placed in subgroups by joint morphology, impingement test status, and genetic predisposition; the mean T1 scores were compared, and the alpha angle and T1 were correlated. RESULTS: Of thirty-two subjects (mean age, fifty-two years), nineteen had cam deformities. Hips with a cam deformity had reduced acetabular glycosaminoglycan content compared with normal hips (mean T1(acet)/T1(total), 0.949 and 1.093, respectively; p = 0.0008). Hips with a positive impingement test result had global depletion of glycosaminoglycan compared with hips with a negative result (mean T1(total), 625 ms versus 710 ms; p = 0.0152). T1(acet) inversely correlated with the magnitude of the alpha angle (r = -0.483, p = 0.0038), suggesting that the severity of cartilage damage correlates with the magnitude of the cam deformity. All of these differences occurred irrespective of genetic predisposition. CONCLUSIONS: The dGEMRIC technique can detect cartilage damage in asymptomatic hips with cam deformities and no radiographic evidence of joint space narrowing. This damage correlates with cam deformity severity. Further study of the application of dGEMRIC as an imaging biomarker of early osteoarthritis is justified to validate its prognostic accuracy, identify subjects for clinical trials, and evaluate the effectiveness of surgical procedures.

Multiecho T(2) relaxation measurements offer specific information about myelin content through the myelin water fraction (MWF), as well as about the water environments through the intra- and extra-cellular (IE), and global, geometric mean T(2) (GMT(2)) times. While these measurements have yielded new insights into brain development and pathologies, they have yet to be thoroughly investigated in the spinal cord. The goals of this study were: (1) to apply a new 3D multiecho T(2) relaxation measurement in the cervical spine with sufficient axial resolution to distinguish grey and white matter; (2) to perform a pilot reliability assessment of the resulting MWF and GMT(2) measures in a target population; and (3) to detect differences in these measures between a younger cohort (20-30 years of age) and an older cohort (50-75 years of age) of healthy adults. The results demonstrated that the MWF in younger healthy adults follows the known pattern of lower myelin content in grey matter (mean (95% confidence interval)) (0.049 (0.030-0.067)) as compared to white matter (0.296 (0.275-0.317), p

Objective Hypomania accounts for approximately 4% to 13% of psychotropic adverse events during subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease. Diffusion of current into the inferior and medial "limbic" STN is often reported to be the cause. We suggest a different explanation, in which the coactivation of the medial forebrain bundle (MFB), outside the STN, leads to hypomania during STN DBS. Methods Six patients with advanced Parkinson's disease (age, 54 +/- 11 years) underwent bilateral STN DBS surgery. Preoperative diffusion tensor imaging scans for fiber tracking of the MFB were conducted on a 3T magnetic resonance imaging scanner. After implantation, the electrode positions were determined with computed tomography and integrated in a diffusion tensor imaging software environment. Results The medial STN was shown to send tributaries to the MFB using it as a pathway to connect to the reward circuitry. One patient, who had a transient, stimulation-induced acute hypomanic episode, showed a direct contact between 1 active electrode contact and these putative limbic STN tributaries to the MFB unilaterally on the left. In 5 asymptomatic patients, the active contacts were between 2.9 and 7.5 mm distant from the MFB or its limbic STN tributaries. Conclusion We hypothesize that STN DBS-induced reversible acute hypomania might be elicited by inadvertent and unilateral coactivation of putative limbic STN tributaries to the MFB. These findings may provide insight into the neural pathways of hypomania and may facilitate future investigations of the pathophysiology of mood disorders.

The prefrontal cortex (PFC) plays a crucial role in cognitive control and higher mental functions by maintaining working memory representations of currently relevant information, thereby inducing a mindset that facilitates the processing of such information. Using fMRI, we examined how the human PFC implements mindsets for information at varying levels of abstraction. Subjects solved anagrams grouped into three kinds of blocks (concrete, moderately abstract, and highly abstract) according to the degree of abstraction of their solutions. Mindsets were induced by cuing subjects at the beginning of every block as to the degree of abstraction of solutions they should look for. Different levels of abstraction were matched for accuracy and reaction time, allowing us to examine the effects of varying abstraction in the absence of variations in cognitive complexity. Mindsets for concrete, moderately abstract, and highly abstract information were associated with stronger relative recruitment of ventrolateral, dorsolateral, and rostrolateral PFC regions, respectively, suggesting a functional topography whereby increasingly anterior regions are preferentially associated with representations of increasing abstraction. Rather than being a structural property of the neurons in different prefrontal subregions, this relative specialization may reflect one of the principles according to which lateral PFC adaptively codes and organizes task-relevant information.

Immobility in bed and decreased mobility cause adaptations to most human body systems. The effect of immobility on fat accumulation in hemopoietic bone marrow has never been measured prospectively. The reversibility of marrow fat accumulation and the effects on hemopoiesis are not known. In the present study, 24 healthy women (age: 25–40 yr) underwent −6° head-down bed rest for 60 days. We used MRI to noninvasively measure the lumbar vertebral fat fraction at various time points. We also measured hemoglobin, erythropoietin, reticulocytes, leukocytes, platelet count, peripheral fat mass, leptin, cortisol, and C-reactive protein during bed rest and for 1 yr after bed rest ended. Compared with baseline, the mean (± SE) fat fraction was increased after 60 days of bed rest (+2.5 ± 1.1%, P < 0.05); the increase persisted 1 yr after the resumption of regular activities (+2.3 ± 0.8%, P < 0.05). Mean hemoglobin levels were significantly decreased 6 days after bed rest ended (−1.36 ± 0.20 g/dl, P < 0.05) but had recovered at 1 yr, with significantly lower mean circulating erythropoietin levels (−3.8 ± 1.2 mU/ml, P < 0.05). Mean numbers of neutrophils and lymphocytes remained significantly elevated at 1 yr (+617 ± 218 neutrophils/μl and +498 ± 112 lymphocytes/μl, both P < 0.05). These results constitute direct evidence that bed rest irreversibly accelerated fat accumulation in hemopoietic bone marrow. The 2.5% increase in fat fraction after 60 days of bed rest was 25-fold larger than expected from historical ambulatory controls. Sixty days of bed rest accelerated by 4 yr the normal bone marrow involution. Bed rest and marrow adiposity were associated with hemopoietic stimulation. One year after subjects returned to normal activities, hemoglobin levels were maintained, with 43% lower circulating erythropoietin levels, and leukocytes remained significantly elevated across lineages. Lack of mobility alters hemopoiesis, possibly through marrow fat accumulation, with potentially wide-ranging clinical consequences.

This article provides an overview of relaxation times and their application to normal brain and brain and cord affected by multiple sclerosis. The goal is to provide readers with an intuitive understanding of what influences relaxation times, how relaxation times can be accurately measured, and how they provide specific information about the pathology of MS. The article summarizes significant results from relaxation time studies in the normal human brain and cord and from people who have multiple sclerosis. It also reports on studies that have compared relaxation time results with results from other MR techniques.

This study compared region of interest (ROI) and voxel-based analysis (VBA) methods to determine the optimal method of myelin water fraction (MWF) analysis. Twenty healthy controls were scanned twice using a multi-echo T(2) relaxation sequence and ROIs were drawn in white and grey matter. MWF was defined as the fractional signal from 15 to 40 ms in the T(2) distribution. For ROI analysis, the mean intensity of voxels within an ROI was fit using non-negative least squares. For VBA, MWF was obtained for each voxel and the mean and median values within an ROI were calculated. There was a slightly higher correlation between Scan 1 and 2 for the VBA method (R(2)=0.98) relative to the ROI method (R(2)=0.95), and the VBA mean square difference between scans was 300% lower, indicating VBA was the most consistent between scans. For the VBA method, mean MWF was found to be more reproducible than median MWF. As the VBA method is more reproducible and gives more options for visualization and analysis of MWF, it is recommended over the ROI method of MWF analysis.

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons in the brain, brainstem, and spinal cord. It has been proposed that bone marrow (BM)-derived cells might supply motor neurons and other cells with a cellular milieu more conducive to survival in ALS. Direct injection of stem cells in ALS is problematic because of the large expanse of the neuraxis that would need to be injected. We reasoned that transiently increasing the number of circulating hematopoietic stem cells might be a useful therapeutic approach. However, agents stimulating the activation and mobilization of hematopoietic stem cells may have adverse effects such as activation of microglial cells. We conducted a small pilot trial of the collection and reinfusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) in ALS patients and found no adverse effects, paving the way for a properly powered therapeutic trial with an optimized regimen of G-CSF.

This review discusses how magnetic resonance techniques are used to provide specific information about the pathology of multiple sclerosis.

We compare T2-relaxation and diffusion tensor data from normal human brain. The relationships between myelin-water fraction (MWF) and various diffusion tensor measures [e.g., fractional anisotropy (FA), perpendicular diffusivity (ADC perpendicular) and mean diffusivityD] in white matter (WM) and gray matter (GM) structures in the brain were examined in 16 normal volunteers at 1.5 T and 6 normal subjects at 3.0 T and mean diffusivity. We found some degree of linear correlation between these measurements, but by using region of interest (ROI)-based analysis, we also observed several structures which seemed to deviate significantly from a linear relationship. From all investigated relationships between various diffusion tensor measures and myelin-water content, FA and ADC perpendicular yielded the highest correlation coefficients with MWF. However, diffusion anisotropy was also significantly influenced by factors other than myelin-water content. The less operator-dependent voxel-based analysis (VBA) between myelin-water and diffusional anisotropy measures is proposed as an innovative alternative to ROI-based analysis. We confirmed that WM structures, in general, have higher diffusional anisotropy than GM structures and also have higher myelin-water content. However, our findings suggest that in the highly organized fibre arrangement of compact WM structures such as the genu of the corpus callosum, elevated degrees of diffusional anisotropies are measured, which do not necessarily correspond to an elevated myelin content but more likely reflect the highly organized directionality of fibre bundles in these areas (low microscopic and macroscopic tortuosity) as well as strongly restricted diffusion in the interstitial space between the myelinated axons. Conversely, in structures with disorganized fibre bundles and multiple fibre crossings, such as the minor and major forceps, low FA values were measured, which does not necessarily reflect a decrease myelin-water content.

Purpose To describe what, if any, specific long T2-related abnormalities occur in the white matter of subjects with either phenylketonuria (PKU) or multiple sclerosis (MS). Materials and Methods The 48-echo T2 relaxation data (maximum TE = 1.12 sec) were acquired from 15 PKU subjects, 20 MS subjects, and 15 healthy volunteers. Regions of interest were drawn in diffuse white matter hyperintensities (DiffWM), lesions, normal-appearing white matter (NAWM), and normal white matter. Long T2 maps (200 msec < T2 < 800 msec) were created for each subject. Results A new water reservoir with a markedly prolonged T2 peak was identified in DiffWM and NAWM in 12 out of 15 subjects with PKU and a long T2 signal was also seen in 23/97 lesions in 50% of subjects with MS. Additionally, a long T2 component was observed in the corticospinal tracts of 10 healthy volunteers. The characteristics of the long T2 signal were unique for each subject group. Potential sources of this signal include vacuolation and increases in extracellular water. Conclusion This study supports the usefulness of increasing the data acquisition window of the multiecho T2 relaxation sequence to better characterize the T2 decay from pathological brain. J. Magn. Reson. Imaging 2007;26:1117–1121. © 2007 Wiley-Liss, Inc.

A PRESS (Point RESolved Spectroscopy) sequence for the improved detection of the C 2 protons of Glx (glutamate and glutamine) at ≈3.75 ppm is presented in this work. It is shown that for spins like the C 2 protons of Glx which are involved solely in weak coupling interactions, the chemical shift displacement effect can be turned to advantage by exploiting PRESS refocusing pulses with bandwidths less than the chemical shift difference between the target spins and the spins to which they are weakly coupled. The narrow-bandwidth PRESS sequence allows refocusing of the J -coupling evolution of the target protons in the voxel of interest independently of echo time yielding signal equivalent to that which can be obtained with a one-pulse acquire sequence (assuming ideal pulses and ignoring T 2 relaxation). The total echo time of PRESS was set long enough for the decay of macromolecule signal and the two echo times were empirically optimized so that the Glx signal at 3.75 ppm suffered minimal contamination from myo-inositol. The efficacy of the method was verified on phantom solutions of Glx and on brain in vivo .

While conventional magnetic resonance imaging (MRI) has long been used to study multiple sclerosis (MS), more sensitive and specific approaches to studying both MS lesions and normal appearing white matter (NAWM) are needed to gain a better understanding of the pathogenesis of the disease. Two MRI techniques thought to offer insight regarding myelin and axonal integrity are T(2) relaxation and diffusion tensor imaging (DTI). In this study, metrics obtained from T(2) relaxation (specifically myelin water content (MWC) and long-T(2) fraction) and DTI experiments (in particular the fractional anisotropy, mean diffusivityD, parallel diffusivity lambda(||), and perpendicular diffusivity lambda(perpendicular)) were compared for 19 MS patients within both lesion and contralateral NAWM with the goal of better understanding how each of the measures are affected by pathology. In particular, it was successfully determined that the detection of a long-T(2) signal within an MS lesion is indicative of a different underlying pathology than is present in lesions without long-T(2) signal. All of the diffusion metrics were significantly different in lesions with a long-T(2) signal than in those without. While no significant correlations were found between MWC andD, lambda(||) or lambda(perpendicular) in NAWM (R(2)=0.02-0.04, p0.07), and only weak correlations were found in lesions without long-T(2) signal (R(2)=0.05-0.14, p0.04), strong correlations were observed in lesions exhibiting long-T(2) signal (R(2)=0.54-0.61, p0.0001).

Ternary systems of palmitoyl-oleoyl-phosphatidylcholine (POPC) and the non-ionic surfactant C12EO2 (di-ethylene-oxide-mono-dodecyl-ether) in water have been studied with optical microscopy, NMR, DSC and X-rays from ambient temperatures to 45 °C. Below 29 °C the system is in the lamellar liquid crystalline state. Between 30 and 32 °C it transforms into a cubic Ia3d structure which converts into the cubic Pn3m phase at 39 °C. The transitions are fully reversible. An epitaxial relationship between all three phases was found, which is an elegant and convenient way to rearrange molecules from lamellar bilayers to a network of curved surfaces. The la3d (Q230) to Pn3m (Q224) transition occurs without measurable enthalpy change. This, together with the metric relation of 1.60 between the cubic lattice constants is strong evidence for a Bonnet transformation, where the structural changes occur without change in curvature. The potential significance of the cubic phases as intermediate structures for biological processes, e. g. transport across a bilayer or fusion of membranes, are discussed.