Effects of trifluoperazine on function and structure of toad urinary bladder. Role of calmodulin vasopressin-stimulation of water permeability.

Calcium ion plays a major regulatory role in many hormone-stimulated systems. To determine the site of calcium's action in the toad urinary bladder, we examined the effect of trifluoperazine, a compound that binds specifically to the calcium binding protein, calmodulin, and thereby prevents activation of enzymes by the calcium- calmodulin complex. 10 microM trifluoperazine inhibited vasopressin stimulation of water flow, but did not alter vasopressin's effects on urea permeability or short-circuit current. Trifluoperazine also blocked stimulation of water flow by cyclic AMP and methylisobutylxanthine, implying a "postcyclic AMP" site of action. Consistent with these results, trifluoperazine did not decrease epithelial cyclic AMP content or the cyclic AMP-dependent protein kinase activity ratio. Assay of bladder epithelial supernate demonstrated calmodulin-like activity of 1.5 U/microgram protein. Morphologic studies of vasopressin-treated bladders revealed that trifluoperazine did not alter the volume density of cytoplasmic microtubules or significantly decrease the number of fusions between cytoplasmic, aggregate-containing, elongated vesicles and the luminal membrane. Nonetheless, the frequency of luminal membrane aggregates, structures that correlate well with luminal membrane water permeability, was decreased by greater than 50%. Thus, trifluoperazine appears to inhibit the movement of intramembranous particle aggregates from the fused intracellular membranes to the luminal membrane, perhaps by blocking an effect of calcium on microfilament function.

An fMRI study of the effect of amphetamine on brain activity.

Functional magnetic resonance imaging was used to evaluate the effects of oral d-amphetamine on brain activation elicited by auditory and simple motor tasks in ten normal right-handed subjects. We measured the percent signal change and number of voxels activated by a tone discrimination task and a right hand finger-tapping task after 20 mg of d-amphetamine and after placebo. Compared to placebo, amphetamine significantly increased the number of activated voxels in the left and right primary auditory cortices during the tone discrimination task and increased the number of activated voxels in the ipsilateral primary sensorimotor cortex and right middle frontal area during the motor task. Although highly specific vascular effects of drug cannot be ruled out as an explanation, these results could also mean that amphetamine increases the neuronal activity associated with each of these two tasks.

A frameless stereotactic approach to neurosurgical planning based on retrospective patient-image registration. Technical note.

A frameless stereotactic device interfacing an electromagnetic three-dimensional (3-D) digitizer to a computer workstation is described. The patient-image coordinate transformation was found by retrospectively registering a digitizer-derived model of the patient's scalp with a magnetic resonance (MR) imaging-derived model of the same surface. This procedure was performed with routine imaging data, eliminating the need to obtain special-purpose MR images with fiducial markers in place. After patient-image fusion was achieved, a hand-held digitizing stylus was moved over the scalp and tracked in real time on cross-sectional and 3-D brain images on the computer screen. This device was used for presurgical localization of lesions in 10 patients with meningeal and superficial brain tumors. The results suggest that the system is accurate enough (typical error range 3 to 8 mm) to enable the surgeon to reduce the craniotomy to one-half the size advisable with conventional qualitative presurgical planning.

Frameless stereotaxy with real-time tracking of patient head movement and retrospective patient-image registration.

The accuracy of a novel frameless stereotactic system was determined during 10 surgeries performed to resect brain tumors. An array of three charge-coupled device cameras tracked the locations of infrared light-emitting diodes on a hand-held stylus and on a reference frame attached to the patient's skull with a single bone screw. Patient-image registration was achieved retrospectively by digitizing randomly chosen scalp points with the system and fitting them to a scalp surface model derived from magnetic resonance (MR) images. The reference frame enabled continual correction for patient head movements so that registration was maintained even when the patient's head was not immobilized in a surgical clamp. The location of the stylus was displayed in real-time on cross-sectional and three-dimensional MR images of the head; this information was used to predict the locations of small intracranial lesions. The average distance (and standard deviation) between the actual position of the mass and its stereotactically predicted location was 4.8 +/- 3.5 mm. The authors conclude that frameless stereotaxy can be used for accurate localization of intracranial masses without resorting to using fiducial markers during presurgical imaging and without immobilizing the patient's head during surgery.

Three-dimensional magnetic resonance images of the brain: application to neurosurgical planning.

Data from single 10-minute magnetic resonance scans were used to create three-dimensional (3-D) views of the surfaces of the brain and skin of 12 patients. In each case, these views were used to make a preoperative assessment of the relationship of lesions to brain surface structures associated with movement, sensation, hearing, and speech. Interactive software was written so that the user could "slice" through the 3-D computer model and inspect cross-sectional images at any level. A surgery simulation program was written so that surgeons were able to "rehearse" craniotomies on 3-D computer models before performing the actual operations. In each case, the qualitative accuracy of the 3-D views was confirmed by intraoperative inspection of the brain surface and by intraoperative electrophysiological mapping, when available.

Using an image database to constrain the acquisition and reconstruction of MR images of the human head.

A training set of MR images of normal and abnormal heads was used to derive a complete set of orthonormal basis functions which converged to head-like images more rapidly than Fourier basis functions. The new image representation was used to reconstruct MR images of other heads from a relatively small number of phase-encoded signal measurements. The training images also determined exactly which phase-encoded signals should be measured to minimize image reconstruction error. These signals were nonuniformly scattered throughout k-space. Experiments showed that head images reconstructed with the new method had less serious truncation artifacts than conventional Fourier images reconstructed from the same number of signals. The resulting images were characterized by spatially variable spatial resolution and were particularly well-resolved in regions where the training images had structural detail.

Oscillating intensity display of soft tissue lesions in MRI.

A new postprocessing method for improving visualization of soft tissue lesions in MR images is described. Abnormal tissues are detected by a computerized tissue characterization algorithm which is based on measurements of intensity in a spatially matched pair of T1- and T2-weighted images. Simultaneous display of information from this pair of static images is achieved by using a temporal parameter (amplitude or frequency of intensity oscillation) to encode abnormal pixels. Specifically, a movie is created in which pixel intensities of abnormal tissues are made to oscillate so that the amplitude (or frequency) of oscillation is proportional to an abnormality index which depends on the difference between intensities of normal and abnormal tissues in the original image pair. The visual effect is that of a churning motion within the lesion, while surrounding normal tissues are displayed as stable structures. This technique increases the conspicuity of the lesion by exploiting the eye's great sensitivity to motion.

Using prior knowledge of human anatomy to constrain MR image acquisition and reconstruction: half k-space and full k-space techniques.

In this note, we demonstrate how to utilize prior knowledge of human cranial anatomy to constrain full k-space and half k-space acquisition and reconstruction of 128 times 128 images. We used a database of magnetic resonance head images to derive new basis functions which represent the most important features of the head. the "training" images were also used to derive formulas for reconstructing head images from a subset of the usual 128 phase-encoded signals and to determine the optimal k-space locations of those signal measurements. We used this algorithm, called Feature-Recognizing MRI, to reconstruct 128 times 128 head images from 50-60% of the signals filling the full k-space. Furthermore, we combined the algorithm with a conventional half k-space technique to create 128 times 128 images from only 60% of the 80 signals required by the usual unconstrained half k-space imaging. Thus, the prior knowledge represented by the image database, together with a half k-space technique, made it possible to construct accurate magnetic resonance images from only 30-40% of the complete set of 128 signals. In other words, a database of head images was used to devise a 1/3 k-space method for imaging the head.

Assessment of the biomechanical state of intracranial tissues by dynamic MRI of cerebrospinal fluid pulsations: a phantom study.

We used a cranial phantom to investigate how intracranial mechanical factors [brain compliance and the resistance to the flow of cerebrospinal fluid (CSF)] affect the way in which CSF pulsations are driven by pulsatile transcranial blood flow. Dynamic phase-contrast magnetic resonance imaging (MRI) was used to measure the transfer function between vascular pulsations and pulsatile response of the CSF below the foramen magnum of the phantom. We found that the coupling between the high frequency components of cervical CSF flow and transcranial blood flow was decreased when the phantom was modified to simulate increased brain compliance and increased resistance to CSF flow.

The mechanical state of intracranial tissues in elderly subjects studied by imaging CSF and brain pulsations.

The biomechanical properties of intracranial tissues influence the mechanical coupling of brain and CSF oscillations to the driving vascular pulsations. Dynamic phase contrast MRI was used to measure the transfer functions that characterize these couplings in normal elderly subjects and patients with Alzheimer's disease. The transfer functions of both groups were significantly different from the previously reported transfer functions of normal young subjects. The data show that vascular pulsations tend to cause greater spinal cord movements and smaller CSF oscillations in the older subjects than in the younger ones. These results are likely to be due to age-related changes in the mechanical state of intracranial tissues.

Integrated 3D display of brain surface anatomy and MR spectral data.

We describe a method of displaying the relationship between MR spectral data and an MRI-derived three-dimensional (3D) model of the same subject's brain surface. In this way, biochemical abnormalities in the MR spectra can be localized with respect to specific gyral convolutions (e.g., those associated with movement and sensation), which are best identified on 3D brain models. This was accomplished by retrospectively registering spectral data and MR images, acquired with different head coils. The highly resolved MR images were used to identify the brain surface in the poorly resolved spectral data and to produce a 3D rendition of brain surface metabolite distributions. This was then integrated with an MRI-derived 3D model of brain gyral anatomy. The method was tested on P31 spectral data from a phantom and from a human volunteer.

Unit membrane parameters of electrically syncytial tissues.

A change in the holding voltage, exposure to channel-blocking agents, and similar interventions will induce changes in the membrane properties of electrically syncytial tissues. The altered membrane characteristics will produce changes in the input resistance (RIN) and the phase angle (phi) of the complex admittance of the whole preparation. Exact geometry-independent formulas are derived that give the intervention-induced changes in the membrane capacitance and conductance in terms of the measured changes in RIN and phi. The formulas automatically account for the effects of extracellular resistance in tissues such as skeletal muscle fibers, cardiac Purkinje fibers, and small cardiac "aggregates." The size, shape, and resistance of the extracellular space may be arbitrary and need not be measured. The surface (invaginated) membranes, which face the bath (extracellular space), are assumed to be characterized by an RC circuit with specific capacity Cme (Cmi) and specific conductivity gme (gmi). It is assumed that the intracellular voltage gradient between the electrodes and the membranes is negligible or reliably calculable. The intervention is assumed to leave the geometry and resistivity of the extracellular space unchanged. Under these circumstances the intervention-induced changes in Cme, Cmi, gme, and gmi are determined exactly in terms of the corresponding changes in RIN and certain frequency domain integrals over phi. The technique is illustrated by synthetic data for RIN and phi generated by the "disk" model of a skeletal muscle fiber in which Cme and Cmi depend upon holding voltage. The corresponding voltage dependence of RIN and phi is successfully "inverted" to expose the underlying voltage dependence of Cme and Cmi. These computations suggest that the formulas for Cme and Cmi will be useful in realistic situations, since they are not too sensitive to experimental error in the data for RIN and phi. This method makes it possible to detect voltage-dependent capacity changes due to unit membrane processes (e.g., charge movement) as long as the intrinsic time constant of that process is very small (e.g., less than 1/30 ms). As a second example I consider a disk model that is exposed to increasing concentrations of a channel-blocking agent. The drug dependence of RIN and phi is used to calculate the drug dependence of the total membrane conductivity (the sum of gme and gmi, weighted by the areas of surface and invaginated membranes, respectively).

Surface capacity of electrically syncytial tissues.

An exact geometry-independent formula is derived that gives the total surface membrane capacity of an electrical syncytium in terms of its input resistance (RIN) and the phase angle (phi) of its complex admittance. The formula strips off the effects of resistance in the extracellular space and exposes the true capacity of the external surface of preparations such as skeletal muscle fibers, cardiac Purkinje fibers, or spherical cardiac aggregates. The shape, extent, and resistivity of the extracellular space may be arbitrary and need not be measured. The medium in this space may have an arbitrary and nonuniform resistivity. It is assumed that the tissue is impaled with current and voltage electrodes, so that the intracellular resistance between the electrodes and membranes is negligible or can de dealth with by theoretical calculations. Under these circumstances the total surface membrane capacity at high frequency is determined exactly by RIN and a frequency domain integral over phi. The method is tested with synthetic data for RIN and phi generated by the "disk" model of skeletal muscle fibers and the "pie" model of cardiac Purkinje fibers. The formula allows the "inversion" of these data and the deduction of the correct value of the total surface membrane capacity.

On the relationship between feature-recognizing MRI and MRI encoded by singular value decomposition.

This paper describes the similarity between two methods of non-Fourier MRI: feature-recognizing MRI (FR MRI) and MRI with encoding by singular value decomposition (SVD MRI). Both methods represented images as truncated expansions of non-Fourier basis functions; these basis images were derived from prior image data by using closely-related mathematical techniques: the Karhunen-Loeve decomposition (or principal components analysis) and singular value decomposition, respectively. We demonstrate that FR and SVD MRI are equivalent in the following sense: given the same prior image data, they lead to exactly the same basis functions. FR MRI utilized prior images of the same body part in many "training" subjects, thought to be similar to the "unknown" subject to be imaged. SVD MRI utilized a single prior image of one subject in order to perform dynamic imaging of that subject. We demonstrate that the basis function expansion derived from a single prior image may not be capable of representing new features (features not found in the prior image). Therefore, the SVD basis functions may be inappropriate for dynamic imaging.

Feature-recognizing MRI.

We describe a new theory of MR imaging that utilizes prior information in the form of a set of "training" images thought to be similar to the "unknown" objects to be scanned. First, the training images are processed to find an orthonormal series representation of these images that is more convergent than the usual Fourier series. The coefficients in this new series can be calculated from a subset of the phase-encoded signals needed to construct the Fourier image representation. The characteristics of the training images also determine exactly which phase-encoded signals should be measured in order to minimize error in the image reconstruction. The optimal phase-encodings are usually scattered nonuniformly in kappa-space. Good results were obtained when this theory was applied to imaging data from simulated objects and to experimental data from phantom scans. This theory provides the basis for developing efficient scanning and image reconstruction techniques that are "tailored" to each body part or to particular disease states.

MR imaging with spatially variable resolution.

In some situations it may be advantageous to produce "locally focused" magnetic resonance images that have nonuniform spatial resolution matching the expected local rate of spatial variation in the object. Because such an image has fewer pixels than a conventional image with uniformly high resolution, it can be reconstructed from fewer signals, acquired in less time. This can be done by using a highly convergent representation of the image as a sum of orthonormal functions with slow (fast) spatial variation in relatively homogeneous (heterogeneous) parts of the object. Since this series is shorter than a conventional truncated Fourier series, its terms can be calculated from a subset of the usual array of phase-encoded signals. The optimal choice of these phase encodings, which are usually scattered nonuniformly in k space, results in minimization of noise in the reconstructed image. The technique is illustrated by applying it to simulated data and to data from images of phantoms.

A cleft model for cardiac Purkinje strands.

Conduction of the action potential in cardiac muscle is complicated by its multicellular structure, with narrow intercellular clefts and cell-to-cell coupling. A model is developed from anatomical data to describe cardiac Purkinje strands of variable diameter and different internal arrangements of cells. The admittance of the model is solved analytically and fit to results of cable analysis. Using the extracted specific membrane and cell electrical parameters (Rm = 13 K omega cm2, Cm = 1.5 mu F/cm2, Ri = 100 mu cm, and Re = 50 omega cm), the model correctly predicted conduction velocity and filling of capacitance at the onset of a voltage step. The analysis permits more complete studies of the factors controlling conduction velocity; for instance, the effect on conduction velocity of a capacity in the longitudinal current circuit is discussed. Predictions of the impedance and phase angle were also made. Measurements of the frequency dependence of phase angle may provide a basis for separating cleft membrane properties from those of the surface membrane and may aid the measurement of nonlinear membrane properties in muscle.