The short-T1 fraction is interpreted as the water resident in myelin. Its detection is facilitated by longer T1 of axoplasmic water at higher magnetic field.

Background Bipolar I disorder is defined by the occurrence of mania. The presence of mania, coupled with a course of illness characterized by waxing and waning of affective symptoms, suggests that bipolar disorder arises from dysfunction of neural systems that maintain emotional arousal and homeostasis. We used functional magnetic resonance imaging (fMRI) to study manic bipolar subjects as they performed a cognitive task designed to examine the ventrolateral prefrontal emotional arousal network. Methods We used fMRI to study regional brain activation in 40 DSM-IV manic bipolar I patients and 36 healthy subjects while they performed a continuous performance task with emotional and neutral distracters. Event-related region-of-interest analyses were performed to test the primary hypothesis. Voxelwise analyses were also completed. Results Compared with healthy subjects, the manic subjects exhibited blunted activation to emotional and neutral images, but not targets, across most of the predefined regions of interest. Several additional brain regions identified in the voxelwise analysis also exhibited similar differences between groups, including right parahippocampus, right lingual gyrus, and medial thalamus. In addition to these primary findings, the manic subjects also exhibited increased activation in response to targets in number of brain regions that were primarily associated with managing affective stimuli. Group differences did not appear to be secondary to medication exposure or other confounds. Conclusions Bipolar manic subjects exhibit blunted brain fMRI response to emotional cues throughout the ventrolateral prefrontal emotional arousal network. Disruption of this emotional network may contribute to the mood dysregulation of bipolar disorder.

The standard pharmacokinetic model for the analysis of MRI contrast reagent (CR) bolus-tracking (B-T) data assumes that the mean intracellular water molecule lifetime (tau(i)) is effectively zero. This assertion is inconsistent with a considerable body of physiological measurements. Furthermore, theory and simulation show the B-T time-course shape to be very sensitive to the tau(i) magnitude in the physiological range (hundreds of milliseconds to several seconds). Consequently, this standard model aspect can cause significant underestimations (factors of 2 or 3) of the two parameters usually determined: K(trans), the vascular wall CR transfer rate constant, and v(e), the CR distribution volume (the extracellular, extravascular space fraction). Analyses of animal model data confirmed two predicted behaviors indicative of this standard model inadequacy: (1) a specific temporal pattern for the mismatch between the best-fitted curve and data; and (2) an inverse dependence of the curve's K(trans) and v(e) magnitudes on the CR dose. These parameters should be CR dose-independent. The most parsimonious analysis allowing for realistic tau(i) values is the 'shutter-speed' model. Its application to the experimental animal data essentially eliminated the two standard model signature inadequacies. This paper reports the first survey for the extent of this 'shutter-speed effect' in human data. Retrospective analyses are made of clinical data chosen from a range of pathology (the active multiple sclerosis lesion, the invasive ductal carcinoma breast tumor, and osteosarcoma in the leg) that provides a wide variation, particularly of K(trans). The signature temporal mismatch of the standard model is observed in all cases, and is essentially eliminated by use of the shutter-speed model. Pixel-by-pixel maps show that parameter values from the shutter-speed analysis are increased by more than a factor of 3 for some lesion regions. This endows the lesions with very high contrast, and reveals heterogeneities that are often not seen in the standard model maps. Normal muscle regions in the leg allow validation of the shutter-speed model K(trans), v(e), and tau(i) magnitudes, by comparison with results of previous careful rat leg studies not possible for human subjects.

A general picture is presented of the implications for diffusionweighted NMR signals of the parsimonious two-site-exchange (2SX) paradigm. In particular, it is shown that the diffusigraphic "shutter-speed," -1 ϵ ͦq 2 (D A -D B )ͦ, is a useful concept. The "wave-number" q has its standard definition (given in the text), and D A and D B are the apparent diffusion coefficients (ADCs) of molecules in the two "sites," A and B, if there is no exchange between them. At low gradient strengths (center of q-space), -1 is less than rate constants for intercompartmental water molecule exchange in most tissue cases. Thus, the exchange reaction appears fast. However, q is increased during the course of most experiments and, as it is, the shutter-speed becomes "faster" and the exchange reaction, the kinetics of which do not change, appears to slow down. This causes a multiexponential behavior in the diffusion-weighting dimension, b, which also has its standard definition. This picture is found to be in substantial agreement with a number of different experimental observations. It is applied here to literature 1 H 2 O data from a yeast cell suspension and from the human and the rat brain. Since the equilibrium transcytolemmal water exchange reaction appears to be in the fast-exchange-limit at small b, the initial slope represents the weighted-average of the ADCs of intra-and extracellular water. Of course, in tissue the former is in the significant majority. Furthermore, a consideration of reasonable values for the other 2SX parameters suggests that, for resting brain tissue, the intracellular water ADC may be larger than the extracellular water ADC. There are some independent inferences of this, which would have ramifications for many applications of diffusion-weighted MRI. Stejskal and Tanner (1) showed that the judicious use of pulsed magnetic field gradients (PFGs) can encode an NMR signal with sensitivity to translational diffusion of the spin-bearing molecule. In combination with spatial encoding, powerful applications of this concept to in vivo brain 1 H 2 O MRI continue to grow dramatically. Recent examples include: monitoring the immediate stroke aftermath and the prognosis of its consequences (2), discriminating tissue affected by multiple sclerosis (3), tracing of nerve fiber tracts in white matter (WM) (4,5), and detection of brain function (6). A number of results in the human (7,8) and rat (9 -11) brain suggest that water populations contributing to these phenomena are diffusionally distinct. The evidence for this is a non-monoexponential decay of diffusion-weighted magnetization. Unfortunately, analytical interpretation of these results has so far proven problematic.Translational diffusion has manifestations both in space and in time: the diffusion coefficient (D) has dimensions (length) 2 /(time). The most sophisticated recent analyses of diffusion-weighted NMR (12-15) have focused heavily on the spatial domain. Besides its compartmentalization, however, tissue water has also a decidedly dynamic aspect. If the...

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